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Lung tumor

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Revised: 24 January 2013
Copyright: (c) 2001-2013, PathologyOutlines.com, Inc.

Benign tumors

Pleomorphic adenoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 6 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Very rare (< 20 cases reported), ages 35-74 years
● Usually in trachea and major bronchi, rarely in distal bronchi

Related entities
=========================================================================

Alveolar adenoma:
● Benign tumor in asymptomatic patients
● Presents as coin lesion, usually in peripheral lung, consisting of small cystic spaces lined by type II pneumocytes and containing fluid
● Interstitial cellular component consists of epithelioid and spindle shaped cells

Bronchial gland adenoma:
● Includes oncocytoma and mucus gland adenoma, a rare, solitary, benign, well-circumscribed, multicystic, predominately exophytic bronchial tumor

Carcinoma ex pleomorphic adenoma:
● Malignant cases arising from pleomorphic adenoma (Am J Clin Pathol 2011;136:793)




Various images

Intracapsular carcinoma ex pleomorphic adenoma:
● Malignant component does not breach the capsule of the parent tumor, no metastatic potential

Papillary adenoma:
● Arises in peripheral lung, composed of type II pneumocytes (Clara cells), TTF1+; rarely has infiltrative features (Virchows Arch 2000;436:289)

Case reports
=========================================================================

● 56 year old woman with incidental lesion (Arch Pathol Lab Med 2003;127:621)

Treatment
=========================================================================

● Surgical excision, but may recur many years later

Gross description
=========================================================================

● Well circumscribed, no capsule, 2-16 cm, gray-white cut surface, may have tumor tongues outside circumscribed margin

Micro description
=========================================================================

● Nests and trabeculae of epithelial cells in chondromyxoid stroma
● Mixture of epithelial cells with small branching ductules, myoepithelial cells and fibromyxoid stroma with focal hyalinization
● Mild nuclear atypia, occasional multinucleated giant cells, no/rare mitosis
● Lumina may contain PAS+ eosinophilic secretions
● High proliferation index, p16+ (INK4A) (Arch Pathol Lab Med 2003;127:621)

Micro images
=========================================================================



Various images


Metastasizing tumor with benign features

Positive stains
=========================================================================

● Epithelium: CK7, CAM5.2, AE1/AE3, alpha-1-antitrypsin, lysozyme
● Myoepithelial cells: S100, vimentin

Differential diagnosis
=========================================================================

● Primary salivary gland tumors: have ducts with single layer of cells, lack PAS+ material in lumens, no S100+ / vimentin+ myoepithelial layer



Benign tumors

Benign metastasizing leiomyoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 6 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Benign appearing leiomyoma in lung, clonally derived from benign-appearing uterine leiomyomas (Mod Pathol 2006;19:130)
● Rare, ~100 cases reported to date
● Usually women ages 36-64 years, mean 44 years, often with prior history of uterine leiomyomas
● Regress during pregnancy or after oophorectomy
● May represent a well differentiated leiomyosarcoma of low malignant potential, metastatic to lung
● Nodule on chest Xray, but usually only mild cough and shortness of breath or no symptoms
● Good prognosis

Case reports
=========================================================================

● 48 year old woman with incidental retroperitoneal mass and multiple lung nodules (Clin Exp Reprod Med 2011;38:174)
● 76 year old woman with bilateral pulmonary nodules (Arch Pathol Lab Med 2003;127:501)
● Presenting as cystic lung disease (Histopathology 2011;59:786)

Treatment
=========================================================================

● Hysterectomy, bilateral salpino-oophorectomy, long term hormonal therapy

Gross images
=========================================================================



Retroperitoneal and lung masses

Micro description
=========================================================================

● Well circumscribed, single or multiple nodules of smooth muscle, composed of elongated cells with abundant eosinophilic cytoplasm, oval nuclei, inconspicuous nucleoli
● Large, irregularly shaped thick walled vessels
● May contain cysts
● No atypia, no vascular invasion, no mitotic figures

Micro images
=========================================================================



Various images


Comparison with leiomyosarcoma

Cytogenetics description
=========================================================================

● Genetically distinct entity with consistent chromosomal aberrations (19q and 22q terminal deletion in all cases, Am J Surg Pathol 2007;31:737)

Differential diagnosis
=========================================================================

Hamartoma
Low grade leiomyosarcoma: miR-221 expression differentiates leiomyosarcoma from benign metastasizing leiomyoma, Diagn Mol Pathol 2008;17:145)



Benign tumors

Clear cell (sugar) tumor


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 6 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Benign tumor derived from perivascular epithelioid cells, sheets of large cells with clear to eosinophilic granular cytoplasm and numerous PAS+ glycogen granules (similar tumors: angiomyolipoma, lymphangioleiomyoma, PEComa)
● Usually adults, may occur in children

Treatment
=========================================================================

● Simple excision

Gross description
=========================================================================

● Small, sharply outlined, red-tan mass, usually in peripheral lung

Gross images
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4 cm, gray-white, circumscribed tumor confined to the lower lobe under the pleura


Well circumscribed tumors

Micro description
=========================================================================

● Sheets of large cells with clear to eosinophilic granular cytoplasm and numerous PAS+ glycogen granules
● Small uniform nuclei, prominent vasculature, may have extracellular amorphous eosinophilic material with variable calcification, minimal stroma
● No fat, no mitotic figures
● Rarely reported with malignant histologic features (J Clin Oncol 2010;28:e626, Histopathology 2011;58:498)

Micro images
=========================================================================



Various images


(A) Core-needle biopsy shows neoplastic cells in nested and insular pattern surrounding numerous thinned wall sinusoid-like vessels; (B) intranuclear cytoplasmic invaginations (C) HMB45+ staining


Tumor with malignant histiology

Cytology images
=========================================================================



(A) Large, irregular, cohesive clusters of columnar and spindle-shaped cells in background of single naked nuclei (Pap); (B) several large clusters with open cribriform-like spaces (Pap); (C) spindle-shaped and polygonal cells with round to oval nuclei and vacuolated ill-defined cytoplasm(Pap); (D) cell block shows neoplastic cells arranged in a nested and insular pattern surrounding sinusoid-like vessels; inset shows sinusoid-like vessel amidst tumor

Positive stains
=========================================================================

● HMB45, S100 (focal)

Electron microscopy description
=========================================================================

● Membrane bound glycogen in lysosome-like organelles, intracytoplasmic filaments

Cytogenetics description
=========================================================================

● TFE3 gene fusions in some cases (Am J Surg Pathol 2010;34:1395)

Differential diagnosis
=========================================================================

● Carcinoma with clear cell pattern
Langerhans cell histiocytosis: cleaved nuclei, CD1a+ (see Pathol Int 2006;56:453-unclear how to best classify this tumor)
● Metastatic renal cell carcinoma



Benign tumors

Diffuse pulmonary lymphangiomatosis


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 6 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Diffuse proliferation of abnormal pulmonary lymphatic channels in men, women or children, causing wheezing and shortness of breath (Lymphat Res Biol 2011;9:191)
● No cysts, no pneumothorax
● May be progressive and fatal

Case reports
=========================================================================

● 4 year old girl with recurrent hemorrhagic pericardial effusion (J Med Case Rep 2010;4:62)

Micro description
=========================================================================

● Diffuse proliferation of abnormal pulmonary lymphatic channels, prominent lymphatics in pleura and alveolar septa, variable smooth muscle proliferation that may appear kaposiform

Micro images
=========================================================================



Various images

Negative stains
=========================================================================

● HMB45



Benign tumors

Granular cell tumor


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 6 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Polypoid intrabronchial mass, similar to granular cell tumors at other sites, that may cause obstruction
● May be multicentric

Case reports
=========================================================================

● 32 year old woman with malignant tumor (World J Surg Oncol 2003 Oct 21;1:22)
● Malignant granular cell tumor of thigh with metastases to abdominal wall and both lungs (Ann Diagn Pathol 2010;14:273)

Gross images
=========================================================================



Bronchial tumor

Micro images
=========================================================================



Various images-not lung


Malignant tumor



Benign tumors

Hamartoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 8 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Solitary, subpleural islands of mature hyaline cartilage, fat, smooth muscle and clefts lined by respiratory epithelium
● Also called pulmonary chondroma, although chondromas in Carney triad have thin fibrous pseudocapsule, frequent bone metaplasia, calcification, and lack entrapped epithelium and fat (Am J Surg Pathol 2007;31:1844)
● Benign, occurs in adults
● Common, presents as incidental coin lesion (rounded abnormality) with popcorn pattern of calcification on chest Xray
● May present as intrabronchial polypoid mass causing obstruction
Nonfamilial syndrome: pulmonary chondroma, gastric epithelioid leiomyosarcoma, functional extra-adrenal paraganglioma

Case reports
=========================================================================

● Pulmonary hamartoma with salivary gland-type tumors showing myoepithelial differentiation (Am J Surg Pathol 2006;30:375)

Treatment
=========================================================================

● Excision is curative

Radiologic images
=========================================================================



Chest Xray contributed by Dr. Hanni Gulwani, New Delhi (India)


CT scan contributed by Dr. Hanni Gulwani, New Delhi (India)

Gross description
=========================================================================

● 4 cm or less, sharply delineated and lobulated, glistening cut surface (cartilage) with ill defined clefts

Gross images
=========================================================================



Various images


Lobulated tumor contributed by Dr. Hanni Gulwani, New Delhi (India)

Micro description
=========================================================================

● Principally composed of islands of mature hyaline cartilage, fat, smooth muscle and clefts lined by respiratory epithelium (ciliated or not)
● Cartilage may be calcified or ossified
● Periphery of cartilage may contain immature myxomatous tissue
● Resembles breast fibroadenoma if no cartilage present
● 15% have papillary projections resembling immature placental villi (placental transmogrification), with stromal macrophages and lymphocytes and abundant mast cells (Arch Pathol Lab Med 2002;126:562)

Micro images
=========================================================================



Various images


Placental transmogrification


Lung hamartoma contributed by Dr. Hanni Gulwani, New Delhi (India)

Virtual slides
=========================================================================



Various images

Differential diagnosis
=========================================================================

Benign metastasizing leiomyoma
Leiomyosarcoma
Lymphangioleiomyomatosis
● Native pulmonary muscle proliferation
Mesenchymal cystic hamartoma
● Chronic interstitial pneumonitis-reactive smooth muscle proliferation


Multiple pulmonary leiomyomatous hamartomas

General
=========================================================================

● Very rare, almost always asymptomatic middle-aged women

Case reports
=========================================================================

● 31 year old woman whose tumors had secondary ossification (Pathol Int 1999;49:222)
● 46 year old man associated with bronchogenic cyst (Arch Pathol Lab Med 2003;127:e194)

Micro description
=========================================================================

● Excessive smooth muscle, not associated with tumor nodules

Micro images
=========================================================================



Smooth muscle proliferations

Negative stains
=========================================================================

● HMB45



Benign tumors

Hemangioma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 8 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

See also Sclerosing hemangioma

General
=========================================================================

● Benign capillary proliferation with numerous thin-walled capillary vessels, usually solitary (Am J Surg Pathol 2006;30:750)
● Endobronchial or peripheral parenchyma
● Often in children

Micro images
=========================================================================



Various images

Differential diagnosis
=========================================================================

Pulmonary capillary hemangiomatosis: multiple hemangiomas, often associated with veno-occlusive disease



Benign tumors

Pulmonary capillary hemangiomatosis (PCH)


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 8 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Proliferation of benign-appearing capillaries in alveolar septa that appear to compress pulmonary veins; may represent a secondary angioproliferative process of veno-occlusive disease caused by postcapillary obstruction rather than a distinct entity (Am J Surg Pathol 2006;30:850)
● May present with pulmonary hypertension or interstitial lung disease
● Mean age 30 years, range 2-71 years
● Poor prognosis

Treatment
=========================================================================

● Lung transplantation

Micro description
=========================================================================

● Proliferation of benign-appearing capillaries in alveolar septa that appear to compress pulmonary veins
● Also hemorrhage, hemosiderosis
Vascular transformation of sinuses in lobar, hilar and mediastinal lymph nodes is common, with intra-sinusal hemorrhage, erythrophagocytosis, lymphoid follicular hyperplasia (Virchows Arch 2008;453:171)

Micro images
=========================================================================



Various images


A-small veins demonstrate marked myointimal thickening; adjacent alveolar septa are thickened by endothelial cell proliferation of pulmonary capillary hemangiomatosis; (B) CD31 highlights endothelial cell proliferation

Positive stains
=========================================================================

● CD31, CD34

Differential diagnosis
=========================================================================

Veno-occlusive disease: associated with PCH; eccentric intimal thickening of venules in lobular septa with some septal veins completely occluded, increased elastic fibers in venous media (highlighted with elastin stain); intimal fibrosis narrows and occludes the pulmonary veins, causing dilatation of capillaries



Benign tumors

Inflammatory pseudotumor


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 7 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Also called inflammatory myofibroblastic tumor, plasma cell granuloma
Neoplastic: clonal cytogenetic abnormalities involving 2p23 that encodes ALK gene, typically occurs in children and young adults, well-demarcated but nonencapsulated, usually solitary mass that replaces underlying lung tissue
Nonneoplastic: older age, ill-defined or irregular contour due to prominent organizing pneumonia component and fibrosis at edge (Arch Pathol Lab Med 2010;134:417)
● IgG4-related immunopathologic processes may be involved
● Usually age < 30 years; most common lung tumor in children age 16 and younger

Poor prognostic factors
=========================================================================

● Metastases, necrosis >15% of surface area examined, local recurrence, bizarre giant cells, > 3 mitotic figures/50 HPF, advanced stage, high cellularity, poor circumscription

Treatment
=========================================================================

● Excision
● Rarely causes death due to local extension

Gross description
=========================================================================

● Well circumscribed, non-encapsulated, usually solitary, white, firm, parenchymal nodule
● 3% bilateral
● May have hemorrhage, necrosis or calcification

Micro description
=========================================================================

● Plasma cells, lymphocytes, histiocytes and myofibroblasts
● May have vascular proliferation, collagenous or hyalinized stroma, myxoid change, xanthoma cells, hemosiderin
● May resemble nodular fasciitis, fibrous histiocytoma or fibromatosis

Micro images
=========================================================================



Various images


Spindle cells in collagenous stroma

Positive stains
=========================================================================

● Spindle cells: vimentin, smooth muscle actin

Electron microscopy description
=========================================================================

● Elongated cytoplasmic processes with pinocytotic vesicles, subplasmalemmal plaques, thin filaments, abundant endoplasmic reticulum

Differential diagnosis
=========================================================================

Amyloid tumor
● Benign and malignant fibrous histiocytoma
Carcinoid tumor
● Hemangiopericytoma
Histoplasmosis see Am J Clin Pathol 2011;136:410
Lipoid pneumonia
Metastatic carcinoma
● Mycobacterial pseudotumor
Organizing pneumonia
Plasmacytoma
Tuberculosis (immunosuppressed patients)
● Other spindle cell tumors


Childhood inflammatory pseudotumor

General
=========================================================================

● Most common isolated lung lesion in children, usually asymptomatic
● Benign, although rare cases of malignant behavior have been reported

Treatment
=========================================================================

● Excision or radiation therapy

Gross description
=========================================================================

● Solitary, small peripheral nodules, yellow, firm, covered by intact pleura or polypoid bronchial mass

Micro description
=========================================================================

● Plasma cells (often abundant), lymphocytes, histiocytes and myofibroblasts
● May have vascular proliferation, collagenous or hyalinized stroma, myxoid change, xanthoma cells, hemosiderin
● May resemble nodular fasciitis, fibrous histiocytoma or fibromatosis

Micro images
=========================================================================



3 year old child



Benign tumors

Langerhans cell histiocytosis


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 7 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Neoplastic disorder of Langerhans cells; most common pulmonary histocytic lesion (Arch Pathol Lab Med 2008;132:1171)
● Also called eosinophilic granuloma, Langerhans cell granulomatosis, histiocytosis X (“H-X”), Hand-Schuller-Christian disease, Letterer-Siwe disease
● Usually ages 20-39 years
● Strongly associated with smokers
● 50% of cases only involve lung; 20% with multicentric disease (bone, skin, lymph nodes, spleen, pituitary) have lung involvement
● Often associated with pneumothorax, Pneumocystis carinii pneumonia
● Lung biopsy is necessary for a definitive diagnosis, although may not be required if imaging findings are highly characteristic (Orphanet J Rare Dis 2012 Mar 19;7:16)
● Usually lung disease resolves or stabilizes, but 10-20% may progress to respiratory failure

Case reports
=========================================================================

● 40 year old woman with Stage IV diffuse large B cell lymphoma (Arch Pathol Lab Med 2002;126:747)

Gross description
=========================================================================

● Lesion of upper lobes, local or diffuse, with nodules and cavitary lesions and late honeycombing

Micro description
=========================================================================

● Interstitial scarring with nodular aggregates of Langerhans cells with a bronchiolocentric distribution
● Langerhans cells have abundant eosinophilic cytoplasm and grooved nuclei with indented nuclear membranes
● Also prominent eosinophils and mesothelial cells
● Frequent hemosiderin, necrosis, alveolar lining cell hyperplasia, pigmented alveolar macrophages
● Variable vasculitis
● Older lesions have fewer eosinophils and more interstitial fibrosis
● Sarcomatous variant has significant atypia and mitotic figures

Micro images
=========================================================================





Various images


Fibrotic nodule with histiocyte-like cells

Positive stains
=========================================================================

● CD1a, S100, HLA-DR

Electron microscopy description
=========================================================================

● Birbeck’s granules (pentilaminar intracytoplasmic structures, tennis racket shaped)

Electron microscopy images
=========================================================================



Birbeck granules, not necessary from lung


Binucleated Langerhans cells, from orbit

Differential diagnosis
=========================================================================

● Eosinophilic pleuritis: no Langerhans cell, although mesothelial cells may appear similar
● Reactive Langerhans cells in inflammatory conditions: no sheets or groups of Langerhans cells
Desquamative interstitial pneumonitis



Benign tumors

Leiomyoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 7 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Extremely rare (<100 cases reported)
● Associated with HIV+ children
● See also benign metastasizing leiomyoma

Case reports
=========================================================================

● 62 year old woman with vascular leiomyoma of lung arising from pulmonary artery (Int J Clin Exp Pathol 2013;6:97)

Gross images
=========================================================================



Bronchial leiomyomas

Micro images
=========================================================================



Bronchial leiomyomas


Vascular leiomyoma

Differential diagnosis
=========================================================================

Spindle cell carcinoma



Benign tumors

Lipoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 7 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Very rare; usually endobronchial, usually men ages 50+ (Chest 2003;123:293)
● Treatment of choice is bronchoscopic removal

Case reports
=========================================================================

● 54 year old women (Tuberk Toraks 2006;54:374, Br J Radiol 2004;77:60)



Benign tumors

Lymphangioleiomyomatosis


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 7 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare progressive lung disease in women due to mutations in tuberous sclerosis genes, resulting in activation of the mTOR complex 1 signaling network (J Clin Invest 2012;122:3807)
● Also called lymphangiomyomatosis
● May be due to metastases or migration of smooth muscle progenitor cells from uterus, since uterine involvement is a common manifestation (Am J Surg Pathol 2011;35:1776)
● Have severe impairment of diffusion with air trapping and expanding lung volumes (dyspnea with pneumothorax or emphysema, without a smoking history)

Clinical features
=========================================================================

● Almost always women, usually white and of reproductive age
● Rare cases in men or postmenopausal women on hormone replacement
● Associated with tuberous sclerosis, renal angiomyolipomas
● May diffusely involve both lungs; may also involve mediastinal or periaortic lymph nodes
● Disease is progressive, prognosis poor, death due to respiratory failure or cor pulmonale
● Disease worsened by pregnancy or menstruation, improved post-menopause
● Complications: respiratory insufficiency and death, spontaneous pneumothorax, chylous pleural effusion

Treatment
=========================================================================

● Oophorectomy, hormone manipulation (progesterone or antiestrogens), lung transplantation (but may recur in lung allografts, Hum Pathol 2003;34:95)

Gross description
=========================================================================

● Emphysematous-like changes to widespread cystic spaces separated by thick, gray-white septa

Micro description
=========================================================================

● Cystic air spaces and patchy disordered nodular proliferation of bland smooth muscle around airways, lymphatics, blood vessels
● Proliferating smooth muscle cells expand lung parenchyma
● Resembles renal angiomyolipoma in that smooth muscle appears to spin off muscle coats of these structures, extending towards adjacent alveoli
● Muscle cells have optically clear cytoplasm, intracytoplasmic glycogen
● Hemosiderin pigment is common

Gross images
=========================================================================



Various images

Micro images
=========================================================================





Various images

Positive stains
=========================================================================

● HMB45, ER, PR, beta catenin (Am J Clin Pathol 2011;135:776)

Differential diagnosis
=========================================================================

Benign metastasizing leiomyoma: well circumscribed, single or multiple nodules of smooth muscle, composed of elongated cells with abundant eosinophilic cytoplasm, oval nuclei, inconspicuous nucleolioften focal, HMB45-
Idiopathic pulmonary hemosiderosis: hemosiderin laden macrophages in alveolar lumina, shedding and hyperplasia of alveolar epithelial cells and marked alveolar capillary congestion; HMB45-
● Metastatic endometrial sarcoma
Micronodular pneumocyte hyperplasia



Benign tumors

Micronodular pneumocyte hyperplasia


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 8 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Associated with tubular sclerosis
● Due to loss of heterozygosity on TSC gene (Mod Pathol 2010;23:1251), may coexist with lymphangioleiomyomatosis
● Usually women with shortness of breath
● Considered a hamartoma
● Not progressive

Case reports
=========================================================================

● 16 year old girl with respiratory failure (Histopathology 2002;41:263)
● 51 year old woman with tuberous sclerosis complex but no classical clinical findings (J Med Case Rep 2012 Oct 16;6:352)

Micro description
=========================================================================

● Bland, papillary or tubular, multifocal proliferation of alveolar type II pneumocytes lining thickened alveolar septa; lymphocyte infiltration, clear cell micronodules, no nuclear atypia (Int J Surg Pathol 2010;18:522)

Micro images
=========================================================================



Various images

Positive stains
=========================================================================

● Cytokeratin, surfactant proteins A and B

Negative stains
=========================================================================

● HMB45, ER, PR, SMA, P53, CEA

Differential diagnosis
=========================================================================

Lymphangioleiomyomatosis



Benign tumors

Paraganglioma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 8 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare neuroendocrine tumor in lung; usually benign behavior
● May be hyperplastic, not neoplastic

Case reports
=========================================================================

● 37 year old woman (Korean J Radiol 2008;9:87)
● 69 year old woman with lung metastasis from bilateral carotid body paragangliomas (Interact Cardiovasc Thorac Surg 2004;3:578)

Gross description
=========================================================================

● Solitary or multiple, usually peripheral mass, often microscopic

Micro description
=========================================================================

● Zellballen pattern (islands of cells) with sustentacular cells at periphery of nests (Am J Surg Pathol 2004;28:825)

Micro images
=========================================================================



60 year old woman with primary pulmonary paraganglioma (left to right): H&E, chromogranin, synaptophysin, NSE, S100


Carotid body paragangliomas

Positive stains
=========================================================================

● Neuroendocrine markers
● S100 (sustentacular cells)

Negative stains
=========================================================================

● Keratin, mucin, CEA

Electron microscopy description
=========================================================================

● Resembles meningeal arachnoid granulations, dense core granules with an eccentric halo ("norepinephrine-type" granules)

Differential diagnosis
=========================================================================

Carcinoid tumor: ribbons, festoons, rosettes



Benign tumors

Sclerosing hemangioma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 8 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Papillary pattern or islands filled with bland polygonal cells with abundant eosinophilic cytoplasm and indistinct cell borders, with sclerotic stroma
● Also called pneumocytoma, sclerosing pneumocytoma, papillary pneumocytoma (Arch Pathol Lab Med 2009;133:820)
● 80% women, ages 30-50 years, present with incidental solitary nodule on chest Xray
● Apparently derived from type II pneumocytes or with differentiation towards these cells
● Almost always benign, although 2-4% have nodal metastases that don’t appear to affect prognosis (Arch Pathol Lab Med 2003;127:321)
● Sclerosis and hemorrhage are probably secondary changes

Case reports
=========================================================================

● 23 year old woman with dry cough and dyspnea (Arch Pathol Lab Med 2003;127:377)
● Metastatic spread to stomach (Histopathology 2012;60:1162)

Gross description
=========================================================================

● Well circumscribed, non-encapsulated, easily shelled out, tan-yellow, may be hemorrhagic, usually peripheral lung

Gross images
=========================================================================



Tan-yellow tumor

Micro description
=========================================================================

● Papillary, sclerotic, solid or hemorrhagic patterns of bland polygonal or surface cuboidalcells with abundant eosinophilic cytoplasm and indistinct cell borders
● May have sclerotic stroma, may be continuous with bronchial epithelium
● Frequent hemorrhage, aggregates of histiocytes
● No/rare granulomatous reaction, no/rare mitotic figures
● No angiolymphatic invasion, no necrosis

Micro images
=========================================================================





Various images


Young Asian woman with lung tumor (images contributed by anonymous)

Positive stains
=========================================================================

● EMA, keratin (focal), LeuM1, TTF1, PR, ER (weak), surfactant proteins, Napsin A (Histopathology 2012;60:361), p53 mutation higher in polygonal cells (J Clin Pathol 2008;61:192)
● Distinct expression of B-catenin, Axin, and C-myc in 2 cell types (Virchows Arch 2012;461:59, Histopathology 2012;61:178)

Negative stains
=========================================================================

● CEA, S100, smooth muscle actin, chromogranin, CD34

Differential diagnosis
=========================================================================

Alveolar or papillary adenoma
Carcinoid tumor
● Carcinoma (primary or metastatic)
Clear cell (“sugar”) tumor
Epithelioid hemangioendothelioma
Langerhans cell histiocytosis
● Meningioma
● Meningothelial-like nodules



Benign tumors

Solitary fibrous tumor


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 8 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

See also Kidney tumor-benign chapter for more images

General
=========================================================================

● Tumor with markedly collagenous stroma and irregularly distributed thick walled vessels; common at many sites; may be intrapulmonary and not pleural
● Peaks at ages 50-69 years
● Larger tumors (> 7 cm) associated with hypoglycemia, pleural effusion, pulmonary osteoarthropathy
● Even bland tumors may have aggressive behavior

Gross description
=========================================================================

● Firm, rounded, lobulated
● Variable cysts, hemorrhage, necrosis

Micro description
=========================================================================

● Markedly collagenous stroma (ropey collagen) with irregularly distributed thick walled vessels and cellular bland spindle cells
● May have myxoid stroma
● Low grade: <5 mitoses per 10 HPF with bland spindle cells, no atypia
● Often has malignant features (pleomorphism, tumor giant cells, mitotic figures)
● Patterns: adenofibroma (Int J Surg Pathol 2005;13:79), fibrosarcoma, hemangiopericytoma, MFH-like, neural

Micro images
=========================================================================



Benign and malignant tumors

Positive stains
=========================================================================

● CD34, CD99, BCL2 (Am J Surg Pathol 2012 Oct 26 [Epub ahead of print])
● Vimentin, nuclear and cytoplasmic beta catenin (Arch Pathol Lab Med 2006;130:1503)
● p53 expression related to prognosis (Am J Surg Pathol 2008;32:1627)

Negative stains
=========================================================================

● D2-40 (usually, Appl Immunohistochem Mol Morphol 2010;18:411), smooth muscle actin



Benign tumors

Squamous papilloma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 8 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Papillomas are HPV related benign tumors, uncommon in lower bronchial tree
● 3 types: squamous, glandular, mixed (Am J Surg Pathol 1998;22:1328)
● Usually occur in large bronchi, often with associated tracheal or laryngeal lesions
● Often associated with dysplasia, carcinoma in situ or invasive squamous cell carcinoma

Case reports
=========================================================================

● 42 year old woman (Kyobu Geka 2012;65:808)
● 70 year old man with spindle and squamous cell carcinoma arising in peripheral mixed squamous and glandular papilloma (Arch Pathol Lab Med 2011;135:1353)
● 79 year old woman with HPV11 in tumor (Intern Med 1999;38:817)

Micro images
=========================================================================



23 year old nonsmoking woman

Micro description
=========================================================================

● Papillary lesion covered by squamous epithelium; may contain glandular areas (with mucus)

Micro images
=========================================================================



Various images


Pulmonary inverted schneiderian papilloma

Differential diagnosis
=========================================================================

Mucoepidermoid carcinoma: for papillomas with mucus cells



Dysplasia / carcinoma in situ

Dysplasia-general


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 8 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Pulmonary preneoplastic changes include (1) bronchial squamous dysplasia and in situ carcinoma preceding invasive squamous cell carcinoma and basaloid carcinoma, (2) atypical adenomatous hyperplasia preceding bronchioloalveolar carcinoma, and (3) diffuse idiopathic pulmonary neuroendocrine cell hyperplasia, a proposed precursor for carcinoid tumor
● Usually associated with bronchial lesions
● Often present in uninvolved bronchus near carcinoma
● No distinct criteria for dysplasia versus carcinoma in situ - expert confirmation recommended before signing out case as carcinoma in situ

Gross description
=========================================================================

● Either unremarkable or papillary and granular with loss of folds

Micro description
=========================================================================

● Squamous dysplasia: focal to full thickness replacement of epithelium by squamous cells with increased nuclear to cytoplasmic ratio, nuclear pleomorphism, mitotic activity but intact basement membrane
● No invasive growth although may extend into ducts of submucosal glands

Micro images
=========================================================================



Various images

Virtual slides
=========================================================================



Bronchial squamous cell carcinoma in situ



Dysplasia / carcinoma in situ

Bronchioalveolar atypical adenomatous hyperplasia


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 8 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● WHO: adenomatous lesion no more than 0.5 cm in diameter
● Also called adenoma, well differentiated bronchioalveolar carcinoma of Clara cell type / type II pneumocyte type
● Associated with coexisting bronchioloalveolar carcinoma and papillary adenocarcinoma
● May be precursor of bronchioloalveolar carcinoma of nonmucinous type (Hum Pathol 2002;33:697, Exp Ther Med 2012;4:1032, Am J Surg Pathol 1996;20:553); recommended to diagnose as such if malignant appearing but noninvasive

Gross description
=========================================================================

● Focal lesion

Micro images
=========================================================================



4 mm nodule

Micro description
=========================================================================

● Alveolar lining cells replaced by cuboidal cells with uniform, mildly to highly atypical nuclei, scanty cytoplasm, minimal mitotic figures

Micro images
=========================================================================



Various images

Cytology images
=========================================================================



FNA shows sheet-like collection of monotonous pneumocytes with no overt features of malignancy (Pap)



Adenocarcinoma-general


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 12 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

See revised Adenocarcinoma classification system

General
=========================================================================

● Arises from terminal bronchioles
● Most common subtype in nonsmokers
● In US, 50% of lung carcinomas in women are adenocarcinoma
● 80% contain mucin

Clinical features
=========================================================================

● May be associated with scarring
● Grows slower than squamous cell
● 5 year survival: stage I - 69%, II - 40%, IIIA - 17%, IIIB - 5%, IV - 8%
● More likely TTF1 negative in males or smokers

Gross description
=========================================================================

● Poorly circumscribed gray-yellow lesions, single or multiple, may be mucoid
● 77% involve visceral pleura producing puckering/pleural retraction, 65% are peripheral
● Usually not cavitary
● Often associated with a peripheral scar or honeycombing (scar appears to be response to tumor)
● Rarely spreads into pleural space to coat visceral and parietal pleura and resemble diffuse mesothelioma

Gross images
=========================================================================



Peripheral tumor

Micro description
=========================================================================

● Glandular differentiation with tubules or papillae and mucin secretion
● Either in situ, minimally invasive or invasive (mucinous or serous)
● Subtypes indicated below
● Tumors 1.5 cm or less are usually one cell type, larger tumors are often mixed
● Vascular invasion common
● Rarely choriocarcinoma foci, pagetoid spread along bronchial mucosa, eosinophilic intracytoplasmic globules, clear cell change (glycogen)
● Periphery of tumor often has minimal atypia, with marked atypia centrally
● Ciliated / non-terminal respiratory unit type: see Mod Pathol 2012;25:1265

Cytology images
=========================================================================



Pleomorphic cells with cytoplasmic intranuclear inclusion

Virtual slides
=========================================================================



Peripheral tumor


Moderately differentiated adenocarcinoma

Positive stains
=========================================================================

● Mucin, low molecular weight keratin (CK7), EMA, CEA, TTF1 (72%, Am J Surg Pathol 2002;26:767)
● Also surfactant apoprotein (50%), mesothelin (50%), vimentin (9%), S100 (Langerhans cells), p53, CD57/Leu7 (50% of well/moderately differentiated tumors), calretinin (11%, Am J Surg Pathol 2003;27:150)
● Also EGFR mutation specific antibodies (variable, Lung Cancer 2012;77:299)

Negative stains
=========================================================================

● CK20, keratin 5 (usually), P504S, p63 (cytoplasmic expression associated with bad prognosis, Histopathology 2006;49:349)

Electron microscopy description
=========================================================================

● Goblet cells, mucus cells, nonciliated bronchiolar cells, Clara cells

Molecular description
=========================================================================

● EGFR mutation: exon 21 L858R and exon 19 deletion (predictor of response to tyrosine kinase inhibitors, Arch Pathol Lab Med 2012;136:504), Kras mutation (with mucinous adenoca), ALK-1 mutation (extensive signet ring morphology)

Differential diagnosis
=========================================================================

● Melanoma (may be mucin positive)



Adenocarcinoma

Adenocarcinoma-classification


Reviewers: Fulvio Lonardo, M.D. (see Reviewers page)
Revised: 11 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● In February 2011, Travis et al. reported, on behalf of multiple agencies, a revised classification (J Thorac Oncol 2011;6:244, PDF)

Differences from 2004 WHO classification of Lung-Adenocarcinoma
=========================================================================

● Mixed subtype is mostly dropped (previously included 95% of all cases so not that helpful); call "mixed mucinous and non mucinous" if at least 10% of each component is present
● Concept of “predominant” growth pattern is added (predominant: largest percentage, even if <50%)
● Minimally Invasive Adenocarcinoma (MIA) type is added; predominant lepidic growth pattern; excellent prognosis if invasion of 5 mm or less
● Lepidic predominant and mucinous adenocarcinoma are added as variants; lepidic is defined as “growth restricted to neoplastic cells, along preexisting alveolar structures, lacking stroma, vascular or pleural invasion, with no papillary or micropapillary patterns, and no intra-alveolar tumor cells
● Bronchioloalveolar carcinoma (BAC) is dropped; BAC growth pattern regarded as pre-invasive lesion; entities formerly known as BAC, i.e. tumors with a prominent or exclusive lepidic growth pattern, are reclassified based on size and morphological features
● Adenocarcinoma in situ (AIS) is subdivided into nonmucinous and mucinous variants, but virtually all cases are non-mucinous, consisting of type II pneumocytes or Clara cells; considered an intermediate step between normal and invasive adenocarcinoma; has lepidic growth pattern; no papillary or micropapillary patterns, no intra-alveolar tumor cells

Bronchioloalveolar carcinoma: how to classify tumors now
=========================================================================

1. <=3cm, NO stromal, lymphatic, vascular or pleural invasion, no necrosis, no growth patterns other than lepidic:
● Adenocarcinoma in situ, either serous or mucinous

2. <=3cm, with <=5mm area of stromal invasion or growth pattern(s) other than lepidic:
● Minimally Invasive Adenocarcinoma (MIA)

3. >3cm OR lymphatic, vascular or pleural invasion OR necrosis OR >5mm area of stromal invasion OR growth pattern(s) other than lepidic:
● Serous: invasive adenocarcinoma, lepidic predominant or
● Mucinous: invasive mucinous adenocarcinoma

● Invasion defined as histological subtypes other than lepidic or presence of a myofibroblastic stroma associated invasive tumor
● For tumors with multiple foci, measure largest dimension on a single slide; do NOT sum invasive foci on all slides

Entities in which the term BAC was used
=========================================================================

● Adenocarcinoma in situ (AIS): usually nonmucinous, rarely mucinous
● Minimally invasive adenocarcinoma (MIA): usually nonmucinous, rarely mucinous
● Lepidic predominant adenocarcinoma (LPA): nonmucinous
● Adenocarcinoma, predominantly invasive, with some nonmucinous lepidic component: includes some resected tumors formerly classified as mixed subtype and some clinically advanced adenocarcinomas formerly classified as nonmucinous BAC
● Invasive mucinous adenocarcinoma: formerly mucinous BAC

Clinical features
=========================================================================

● Multifocal / lobal / bilateral involvement is frequent in invasive mucinous, rare in nonmucinous (AIS/MIA/LPA)

Micro description
=========================================================================

● Invasive mucinous: composed primarily of mucin filled columnar goblet cells
● Non mucinous tumors (AIS, MIA, LPA): composed primarily of Type II pneumocytes or Clara cells
● Note: invasive adenocarcinomas that secrete mucin but lack goblet cells or columnar cells should not be classified as mucinous adenocarcinoma, but are classified based on the predominant growth pattern adding “with mucinous features” or “with mucin production”
● Note: tumors with a lepidic growth pattern may represent metastatic mucinous tumors of pancreas, ovary, other

Staining patterns
=========================================================================

● Invasive mucinous: CK7 (90%), CK20 (54%), TTF1 (17%)
● Non mucinous tumors (AIS/MIA/LPA): CK7 (98%), CK20 (5%), TTF1 (67%)



Adenocarcinoma

Acinar cell carcinoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 13 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Malignant glandular epithelial neoplasm consisting of secretory cells forming acinar patterns (WHO)
● Bronchial gland tumor resembling salivary gland tumor, well circumscribed, 1-5 cm, with predominantly low grade malignant acinar cells (note difference from WHO definition)
● Very rare at this site, usually in parotid gland, less commonly in submandibular and sublingual glands
● Also known as Fechner tumor
● May arise from pluripotent cells of tracheobronchial submucosal serous and mucus glands

Case reports
=========================================================================

● 30 year old woman with primary acinic cell carcinoma of lung with lymph node metastasis (Arch Pathol Lab Med 2003;127:e216)

Treatment
=========================================================================

● Surgical excision

Micro description
=========================================================================

● Low grade tumor with acinar, oncocytic, papillocystic patterns (Am J Surg Pathol 1992;16:1039)
● Predominantly acinar cells, also ductal cells, myoepithelial cells, reserve/stem cells
● Solid areas recapitulate salivary gland acinar differentiation with large polyhedral cells containing abundant granular cytoplasm, round bland nuclei
● Microcystic areas recapitulate terminal duct-acinar unit
● In contrast to salivary gland tumor, no/rare perineural invasion
● No nuclear pleomorphism, no mitotic activity

Micro images
=========================================================================



Acinic cell carcinoma: primary and recurrent tumor


Salivary gland acinic cell carcinoma: various images

Positive stains
=========================================================================

● Cytokeratin, EMA

Negative stains
=========================================================================

● Amylase

Electron microscopy description
=========================================================================

● No melanosomes, no abundant cytoplasmic glycogen, no neurosecretory granules, no abundant mitochondria or fat globules

Differential diagnosis
=========================================================================

Clear cell (sugar) tumor of lung
Granular cell tumor
● Oncocytic carcinoma
● Oncocytoma
● Metastatic renal cell carcinoma
● Metastastic salivary gland tumor
● Primary lung adenocarcinoma



Adenocarcinoma

Fetal lung type


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 11 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare tumor resembling fetal lung in pseudoglandular stage
● Either high grade or low grade
● May be a variant of pulmonary blastoma without malignant mesenchymal components
● Low grade tumors associated with upregulation of Wnt signaling pathway (Mod Pathol 2002;15:617)
● High grade variant is very aggressive

Micro description
=========================================================================

● Irregular tubular structures of columnar epithelial cells with clear cytoplasm and oval nuclei, optically clear nuclei rich in biotin
● Resembles fetal lung in pseudoglandular stage
● High grade: disorganized glands, large vesicular nuclei, prominent nucleoli, pronounced anisonucleosis, transition to conventional adenocarcinoma, broad areas of necrosis, desmoplastic stroma, p53+, AFP+, no morules (Am J Surg Pathol 1998;22:399)

Micro images
=========================================================================



Low grade (left), high grade (right)


Well differentiated tumor

Cytology description
=========================================================================

● Low grade tumors: subnuclear vacuoles with tigroid features, small, uniform, round nuclei, morules, neuroendocrine differentiation in glandular epithelial cells (Am J Clin Pathol 2010;134:894)

Cytology images
=========================================================================







Various images



Adenocarcinoma

Hepatoid adenocarcinoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised:11 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Resembles hepatocellular carcinoma (HCC)
● More common in gastric than pulmonary adenocarcinoma
● Usually older men (range, 35-82 years)
● High serum AFP
● Aggressive behavior, often with liver metastases

Case reports
=========================================================================

● 36 year old man with AFP producing tumor (Am J Surg Pathol 1997;21:1113)
● 55 year old man with smoking history (Lung Cancer 2002;38:211)

Gross images
=========================================================================



5 cm tumor with firm-white and necrotic parts

Micro description
=========================================================================

● Liver metastases resemble HCC

Micro images
=========================================================================



Papillary or trabecular pattern of HCC-like cells (A/B), with hyaline globules (C) and AFP+ cells (D)


Various images

Immunohistochemistry
=========================================================================

● Same as HCC: AFP+, CK8/CK18+, canalicular staining with polyclonal CEA (Am J Surg Pathol 2003;27:1302)
● Different from HCC: CK19+, CK20+ (HCC is rarely CK20+ Eur J Histochem 2009;53:e32) , negative for HepPar1, negative for CK7

Molecular description
=========================================================================

● 4q-, 8p-, Xq+ (seen in HCC and hepatoblastoma)

Differential diagnosis
=========================================================================

● Metastatic hepatocellular carcinoma, metastatic hepatoid adenocarcinoma from stomach, gallbladder or other site



Adenocarcinoma

Micropapillary


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 12 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Associated with nodal metastases of similar histology, intrapulmonary metastases, non-smokers
● Poorer survival than non-papillary for stage I (79% vs. 93%, Am J Surg Pathol 2003;27:101, Am J Surg Pathol 2002;26:358)

Case reports
=========================================================================

● 68 year old woman with incidental brain metastases with micropapillary structures (Arch Pathol Lab Med 2003;127:e313)

Gross images
=========================================================================



Various images

Micro description
=========================================================================

● Small papillary tufts without a fibrovascular core
● Associated with other histologic subtypes, small cluster invasion / stromal invasion which is defined as acinar-papillary tumor structures with single or small clusters of carcinoma cells invading stroma within fibrotic foci
● May have "aerogenous" micropapillary component of tumor cells floating within alveolar spaces (Diagn Pathol 2012 Jan 6;7:3)

Micro images
=========================================================================





Various images


Papillary and micropapillary structures

Positive stains
=========================================================================

● CK7 (93%), TTF1 (80%), CK20 (13%)

Molecular description
=========================================================================

● Kras, EGFR, BRAF mutations (Am J Clin Pathol 2009;131:694)

Additional references
=========================================================================

Hum Pathol 2008;39:324, Mod Pathol 2007;20:638, Mod Pathol 2007;20:514
Mod Pathol 2011;24:653, Histopathology 2005;46:677, Histopathology 2011;59:1204)



Adenocarcinoma

Papillary adenocarcinoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 16 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Malignant epithelial neoplasm composed of glandular cells and characterized by a papillary growth pattern (WHO)
● Includes goblet cell (mucin producing) type, Clara cell type, type II pneumocyte type and bronchial surface epithelial cell type with or without mucin production (Am J Surg Pathol 1997;21:43)

Micro description
=========================================================================

● Papillary structures with true fibrovascular core comprise 75%+ of tumor

Micro images
=========================================================================



Various images



Other carcinoma

Carcinoma-general


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 12 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● 95% of lung tumors are bronchogenic carcinoma
● Others are bronchial carcinoid, mesenchymal, miscellaneous neoplasms
● In US, lung cancer is #1 cause of cancer death in men and women; causes 30% of cancer deaths in men
● 2012: estimated 226,160 new cases in US, 160,000 deaths (National Cancer Institute)
● Incidence in men is 74 per 100,000 vs. 31 per 100,000 for women
● Peaks at ages 50-69 years; 2% occur before age 40 years

Cigarette smoking
=========================================================================

● Causes most cases of lung cancer
● Relative risk of smokers vs. nonsmokers is 10:1, but is 20:1 for >40 cigarettes/day
● Risk strongly related to number of cigarettes smoked, described in pack years (number of packs per day x number of years smoking)
● Cigarette smoking also associated with carcinomas of lip, tongue, pharynx, larynx, esophagus, bladder, pancreas, kidney, floor of mouth
● 10% of smokers have atypia or hyperplasia of bronchial epithelium
● Carcinogens in tobacco smoke are benzo [a] pyrene (an initiator) and phenol derivatives (promoters)
● Usually associated with squamous cell and small cell carcinoma, less likely with adenocarcinoma

Other causes of lung cancer
=========================================================================

● Radiation exposure, uranium (RR with uranium exposure is 4:1 for nonsmokers, 10:1 for smokers vs. general population)
● Asbestos (RR is 5:1 for nonsmokers, 50-90:1 for smokers vs. general population); causes of death for asbestos workers are: 20% lung cancer, 10% mesothelioma, 10% GI carcinomas
● Also exposure to arsenic, beryllium, chromate, coal, gold ore, iron, mustard gas, nickel, radon, vinyl chloride

Symptoms
=========================================================================

● Cough, weight loss, chest pain, shortness of breath, increased sputum production
● Also acanthosis nigricans, hypertrophic pulmonary osteoarthropathy (clubbing), Horner’s syndrome (enophthalmos, ptosis, miosis, anhidrosis) due to apical lung tumors called Pancoast tumors, Lambert-Eaton myasthenic syndrome (muscle weakness due to antibodies to neuronal calcium channel), leukemoid reaction, pain in distribution of ulnar nerve, sensory peripheral neuropathy, superior vena cava syndrome (compression/invasion of SVC causes venous congestion, circulatory compromise, dusky head, arm edema)

Spread and classification
=========================================================================

● Spreads along bronchus distally and proximally, into lung parenchyma to mediastinum or pleura, causing pleural seeding, pleural effusion, involvement of diaphragm and chest wall
● 50% have nodal involvement at resection (usually hilar, mediastinal and supraclavicular)
● Also metastases to adrenals (50%), liver (30%), brain, bone
● Also opposite lung, pericardium, kidneys

Survival (pre-EGFR inhibitors)
=========================================================================

● Overall 5 year survival is 10-15%
● Only 30% have limited disease at diagnosis making resection for cure an option
● For stage I non-small cell carcinoma, 5 year survival is 60%
● Poor prognostic factors: high TNM stage, weight loss >10% of body weight, age < 40 years or women (usually are high stage), small cell or giant cell subtypes, angiolymphatic invasion, pleural effusion, lack of lymphoplasmacytic reaction

Gross description
=========================================================================

● Arise near hilus
● Hemorrhage, necrosis, cavities are common
● 2-5% are multiple
● Peripheral tumors are usually adenocarcinomas

Micro description
=========================================================================

● See also specific subtypes
● Begins with atypia, then warty excrescence, then fungates into lumen, penetrates wall of bronchus growing along broad front to produce a cauliflower like intraparenchymal mass
● 80% have vascular invasion

Virtual slides
=========================================================================



Tumor emboli

Positive stains
=========================================================================

● May be positive for neuroendocrine markers but with no neuroendocrine morphology - recommended to either ignore neuroendocrine stain results or to diagnose as tumor with neuroendocrine features

Negative stains
=========================================================================

● CDX2 (marker of intestinal origin, Am J Surg Pathol 2003;27:141), Hep Par1 (hepatocyte marker, Mod Pathol 2003;16:137)

Molecular description
=========================================================================

● Dominant oncogenes are Kras (see below), c-myc (small cell carcinomas), p53, Rb, 3p suppressor gene
● High Kras mutation rate in Western countries in lung adenocarcinoma / nonsmall cell lung cancer (25%) but less in Asian countries (0% in China, Onkologie 2008;31:174, 5% in Taiwan, Cancer 2008;113;3199, 11% in Japan, Oncol Rep 2007;18:623)
● Kras mutations are associated with mucinous versus nonmucinous adenocarcinoma (J Mol Diagn 2007;9:320)
● In Western patients, similar rate of Kras mutations between never, former and current smokers, although mutations were different (Clin Cancer Res 2008;14:5731)
● Kras mutations are associated with poor prognosis and EGFR tyrosine kinase resistance (Curr Opin Pharmacol 2008;8:413)

Molecular images
=========================================================================



H&E and FISH of Kras mutation



Other carcinoma

Adenoid cystic carcinoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 9 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● #2 most common salivary gland tumor of lung, may arise from submucus bronchial glands
● Usually in large bronchi, may involve the trachea
● M:F 2:1
● Prolonged course, but overall prognosis is poor
● Frequent metastases to regional lymph nodes and lung parenchyma

Treatment
=========================================================================

● Radiation therapy (palliative)

Gross description
=========================================================================

● Large, centrally located, polypoid, intrabronchial mass, or may grow subepithelially along bronchi causing thickened bronchial wall

Gross images
=========================================================================



75 year old woman with 1 cm lung lesion

Micro description
=========================================================================

● Cylindromatous, tubular, and solid patterns of microcystic spaces containing mucin, surrounded by small tumor cells
● Defining features are pseudocysts (rounded extracellular space containing basal lamina), intercellular spaces, basal lamina, and true glandular lumens (Hum Pathol 1982;13:916)

Micro images
=========================================================================



14 year old girl with 11 cm lung mass


75 year old woman with 1 cm lung lesion: H&E, TTF1


Various images


Lung metastases

Differential diagnosis
=========================================================================

Basaloid squamous cell carcinoma: may have adenoid cystic carcinoma-like pattern of microcystic spaces containing mucin, surrounded by small tumor cells
Epithelial-myoepithelial carcinoma
● Metastatic disease



Other carcinoma

Adenosquamous carcinoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 10 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Substantial amounts of squamous and glandular differentiation (at least 5-10% each component of entire tumor)
● Don’t diagnose if one component is clearly minor
● Uncommon; <10% of lung carcinomas
● 90% peripheral, often associated with scars
● Metastases may have different histology
● Poorer prognosis than either component alone

Micro images
=========================================================================



Various images

Positive stains
=========================================================================

● TTF1 in adenocarcinoma component and p63 in squamous component (Pathol Int 2011;61:717)

Molecular images
=========================================================================



With KRas and EGFR mutations



Other carcinoma

Bronchioloalveolar carcinoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 12 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Refers to growth pattern called lepidic, which arises from and spreads along alveolar walls without invasion
● Similar to jagziekte, a disease of South African sheep, but jagziekte DNA not identified in human tumors
● IASLC/ATS/ERS classification (Mod Pathol 2011;24:653): BAC no longer a valid diagnosis
● WHO definition: adenocarcinoma with bronchioloalveolar pattern and no evidence of stromal, vascular, or pleural invasion, based on complete resection specimen

Bronchioloalveolar carcinoma: how to classify tumors now
=========================================================================

1. <=3cm, NO stromal, lymphatic, vascular or pleural invasion, no necrosis, no growth patterns other than lepidic:
● Adenocarcinoma in situ, either serous or mucinous

2. <=3cm, with <=5mm area of stromal invasion or growth pattern(s) other than lepidic:
● Minimally Invasive Adenocarcinoma (MIA)

3. >3cm OR lymphatic, vascular or pleural invasion OR necrosis OR >5mm area of stromal invasion OR growth pattern(s) other than lepidic:
● Serous: invasive adenocarcinoma, lepidic predominant or
● Mucinous: invasive mucinous adenocarcinoma

● Invasion defined as histological subtypes other than lepidic or presence of a myofibroblastic stroma associated invasive tumor
● For tumors with multiple foci, measure largest dimension on a single slide; do NOT sum invasive foci on all slides

Micro images
=========================================================================



Noninvasive


Mucinous: H&E, TTF1, CK7, CK20


Nonmucinous (H&E, TTF1, CK7, CK20)



Other Carcinoma

Carcinosarcoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 13 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Subtype of sarcomatoid carcinoma (WHO); monoclonal tumor with divergent lines of differentiation, leading to mixture of carcinomatous and sarcomatous elements (WHO, Am J Surg Pathol 2002;26:510)

Micro description
=========================================================================

● Mixture of carcinomatous and sarcomatous elements

Micro images
=========================================================================



Various images


Initially presenting as invasive aspergillosis


Blastomatoid variant



Other Carcinoma

Epithelial-myoepithelial carcinoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 12 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Low grade malignancy that arises from submucosal bronchial glands, mimics similar salivary gland tumor
● Very rare, < 20 cases reported through 2009
● Ages 40-69 years
● Long interval to recurrence or metastasis

Case reports
=========================================================================

● 57 year old man with incidental endobronchial tumor (Case Report Pathol 2012;2012:319434)
● 73 year old man with bronchial tumor (Arch Pathol Lab Med 2003;127:e177)

Gross description
=========================================================================

● Intraluminal polypoid mass in bronchus; may invade pulmonary parenchyma

Gross images
=========================================================================



Incidental endobronchial mass

Micro description
=========================================================================

● Well circumscribed mass, pushing margin
● Biphasic proliferation of epithelial and myoepithelial cells with formation of bilayered ductlike structures
● Tumor consists of ductlike structures with inner epithelial cells and outer clear myoepithelial cells
● No myxoid/chondroid stroma, no perineural invasion (Hum Pathol 2009;40:366)

Micro images
=========================================================================



Various images




Incidental endobronchial mass

Positive stains
=========================================================================

● Epithelial cells: cytokeratin, EMA
● Myoepithelial cells: S100, muscle specific actin, weak keratin

Negative stains
=========================================================================

● Epithelial cells: S100, HMB45

Differential diagnosis
=========================================================================

Acinic cell carcinoma
Adenoid cystic carcinoma with a tubular pattern
Clear cell (“sugar”) tumor
● Metastatic clear cell carcinoma
● Metastatic epithelial-myoepithelial carcinoma (usually parenchymal, not endobronchial)
Mucoepidermoid carcinoma
● Myoepithelial carcinoma
● Myoepithelioma
Pleomorphic adenoma
● Pneumocytic adenomyoepithelioma: has bronchial minor salivary gland origin; shows myoepithelial and pneumocytic differentiation (Am J Surg Pathol 2007;31:562)



Other Carcinoma

Giant cell carcinoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 12 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Malignant epithelial neoplasm predominantly composed of giant, pleomorphic cells (WHO)
● First described in 1958 (Cancer 1958;11:369)
● <1% of all primary lung carcinomas

Case reports
=========================================================================

● 51 year old man with small intestinal metastases (World J Surg Oncol 2005 Jun 2;3:32)
● 56 year old man with hemoptysis (J Cancer Res Ther 2011;7:363)

Gross images
=========================================================================



8 x 7 cm tumor

Micro description
=========================================================================

● Neoplastic, highly pleomorphic giant cells, often in inflammatory stroma with emperipolesis (Arch Pathol Lab Med 2010;134:1645)
● Giant cells are multinucleated, may resemble syncytiotrophoblasts and produce human chorionic gonadotropin, but are usually fewer than in primary choriocarcinoma of lung (Histopathology 2000;36:17)
● No sarcomatoid component present

Micro images
=========================================================================



8 x 7 cm tumor


Diffuse proliferation of atypical, giant and bizarre cells


Emperipolesis

Positive stains
=========================================================================

● Calretinin (67%)



Other Carcinoma

Large cell undifferentiated carcinoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 12 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Malignant epithelial neoplasm composed of large, atypical cells; subtypes include Basaloid carcinoma, Large cell neuroendocrine carcinoma, Large cell carcinoma with rhabdoid phenotype, Lymphoepithelial carcinoma (WHO)
● Tumor with solid nests of large polygonal and anaplastic cells without obvious squamous or glandular differentiation; may be undifferentiated squamous cell carcinoma or adenocarcinoma
● Diagnosis of exclusion - cannot diagnose on small biopsies or in lymph node metastases
● Extended panel of immunohistochemical markers can reclassify 60%; miRNA-based analysis can reclassify the balance, but clinical relevance is unknown (Am J Clin Pathol 2011;136:773)
● 80% men
● Often associated with peripheral eosinophilia and leukocytosis, due to tumor production of colony stimulating factor
● Behavior is similar to adenocarcinoma

Case reports
=========================================================================

● 58 year old man presenting with paroxysmal abdominal pain (World J Surg Oncol 2012 Jan 29;10:26)

Gross description
=========================================================================

● Usually peripheral lung; spherical tumor with well-defined borders and bulging, fleshy, homogenous gray-white cut surface
● No anthracosis
● Frequently involves thoracic wall

Micro description
=========================================================================

● Large polygonal cells and anaplastic cells growing in solid nests without obvious squamous or glandular differentiation
● Moderately abundant cytoplasm, well defined cell borders, vesicular nuclei, prominent nucleoli

Micro images
=========================================================================



Rhabdoid cells


Various images


Tumors reclassified and unable to be reclassified with extended IHC panel

Virtual slides
=========================================================================



Anaplastic tumor cells

Positive stains
=========================================================================

● CK5 (56%), calretinin (38%), thrombomodulin (25%), mesothelin (13%), TTF1 (variable)

Electron microscopy description
=========================================================================

● Glandular (intracellular and extracellular lumina) and squamous (desmosomes, tonofilaments) features often present although not obvious with H & E staining



Other Carcinoma

Large cell neuroendocrine carcinoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 12 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Aggressive carcinoma composed of large malignant cells which display neuroendocrine characteristics; characterized by high mitotic activity and necrotic change (WHO)
● Rosai: resembles non-small cell carcinoma, but on closer inspection has a hint of neuroendocrine architecture confirmed by special stains
● More likely to develop recurrent lung cancer and have shorter actuarial survival than patients with other histologic types of NSCLC, even in those with stage I disease (Cancer Control 2006;13:270)

Micro description
=========================================================================

● Larger tumor cells than atypical carcinoid, high nuclear grade, increased mitotic activity (11+ per 10 HPF) and necrosis (Arch Pathol Lab Med 2010;134:1628)
● Poorly developed neuroendocrine architecture with some pallisading or rosette-like structures present
● Oncocytic neuroendocrine tumor: low grade or high grade; oncocytic features, but similar clinically to nononcocytic tumors (Hum Pathol 2011;42:578)

Micro images
=========================================================================



Large cell neuroendocrine versus small cell neuroendocrine carcinoma


CD117, HER2, EGFR


Phosphohistone H3


Metastases from lung primaries

Positive stains
=========================================================================

● Neuroendocrine markers, CD117 (60%), TTF1 (50%)
● Phosphohistone H3 recommended for counting mitotic figures (Am J Clin Pathol 2011;136:252)
● GLUT1 (74%, Mod Pathol 2009;22:633)
● Enhancer of zeste homolog 2 (EZH2): diffusely and strongly positive in all small-cell carcinomas and large-cell neuroendocrine carcinomas (Hum Pathol 2011;42:867)



Other Carcinoma

Lymphoepithelioma-like carcinoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 12 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare tumor in lung, more commonly in Asians
● In Asians, usually women, non-smokers, with EBV+ tumors (Am J Surg Pathol 2002;26:715)
● In Caucasians, usually EBV-
● Tumor size may correlate with EBV serology titer
● May have better prognosis than other nonsmall cell carcinomas of lung (Cancer 2012;118:4748)

Case reports
=========================================================================

● 25 year old Italian man with EBV+ tumor (Hum Pathol 2003;34:623 )

Gross description
=========================================================================

● Well circumscribed nodules

Micro description
=========================================================================

● Syncytial growth of epithelial cells with large vesicular nuclei, prominent eosinophilic nucleoli, accompanied by marked CD8+ lymphocytic infiltration
● Predominantly pushing borders, permeative interface with adjacent lung
● Occasional amyloid deposition

Micro images
=========================================================================



Various images

Positive stains
=========================================================================

● EBV, BCL2; variable EBER-1, LMP; patchy keratin

Negative stains
=========================================================================

● CD45/LCA (in tumor cells)
● Microsatellite instability is uncommon (Am J Clin Pathol 2007;127:282)

Differential diagnosis
=========================================================================

Inflammatory pseudotumor
● Lymphoma
● Metastatic nasopharyngeal carcinoma



Other Carcinoma

Metastastic tumors to lung


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 12 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Lung is a common site of metastases - usually multiple, bilateral, sharply outlined, rapidly growing, more pleomorphic and necrotic than lung primaries, negative for TTF1
● May appear as multiple discrete nodules in periphery of lung, or as lymphangitis carcinomatosa (peribronchial and perivascular patterns via lymphatics)
● Rarely appear as intralymphatic microscopic foci that cause pulmonary hypertension
● Note: metastases can also be from other lung primaries (Am J Surg Pathol 2009;33:1752)

Patterns associated with specific primaries
=========================================================================

● Central cavitation: colonic adenocarcinoma, leiomyosarcoma, squamous cell carcinoma of upper aerodigestive tract
● Intrabronchial masses: breast, colon, kidney
● Lepidic pattern: colon, pancreas
● Lymphangitis carcinomatosis: breast, choriocarcinoma, pancreas, prostate, stomach
● Nodular metastases: breast, GI, kidney, melanoma., sarcoma
● Tumor emboli: breast, choriocarcinoma, liver, stomach

Case reports
=========================================================================

● 48 year old man with lymphangitic spread of hepatocellular carcinoma (Arch Pathol Lab Med 2003;127:e11)

Treatment
=========================================================================

● Excision of isolated nodules

Gross images
=========================================================================



Osteosarcoma


Multiple tumor nodules

Micro images
=========================================================================



Bladder, urothelial carcinoma


Breast, invasive ductal carcinoma


Chondrosarcoma, dedifferentiated


Colon: adenocarcinoma


Kidney: renal cell carcinoma


Liver: hepatocellular carcinoma


Oropharyngeal carcinoma


Prostate: adenocarcinoma


Testis: choriocarcinoma

Virtual slides
=========================================================================



Metastatic adenocarcinoma


Metastatic small cell carcinoma

Positive stains
=========================================================================

● CDX2 (colorectal carcinoma, Am J Surg Pathol 2003;27:141)



Other Carcinoma

Mucoepidermoid carcinoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 12 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Low grade or high grade salivary gland type tumor with mucus secreting cells, squamous cells, intermediate type cells
● May arise from submucous bronchial glands, usually in large bronchi
● May occur in children
● Usually considered to have low malignant potential with recurrence but only rarely aggressive
● Excellent prognosis after surgical removal

Case reports
=========================================================================

● 22 year old man (Diagn Pathol 2012 Oct 8;7:137)

Gross description
=========================================================================

● Polypoid growth in major bronchi

Micro description
=========================================================================

● Low grade or high grade
● Mucus secreting cells, squamous cells, intermediate type cells
● May have dense lymphoplasmacytic infiltrate (Am J Surg Pathol 2005;29:407)

Micro images
=========================================================================



Various images


Series of images - high grade tumor


Series of images - low grade tumor

Positive stains
=========================================================================

● Cyclin D1 overexpression in 20%

Differential diagnosis
=========================================================================

Adenosquamous carcinoma: usually peripheral in lung, not centered on bronchi; large tumors, no intermediate cells



Other Carcinoma

Pleomorphic carcinoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 22 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Subtype of sarcomatoid carcinoma; usually aggressive, malignant epithelial neoplasm composed of cells with significant cytologic atypia and nuclear pleomorphism (WHO)
● Contains at least 10% spindle cells and/or giant cells
● Included under recent WHO classification of “carcinomas with pleomorphic, sarcomatoid, or sarcomatous elements”

Clinical features
=========================================================================

● <1% of all carcinomas
● Mean age 65 years, range 42-81 years, >90% men, 92% smokers
● Presumed epithelial origin, although epithelial and sarcomatous components express common markers differently (Am J Surg Pathol 2003;27:1203)
● Classified as carcinomas despite presence of sarcomatoid features (Arch Pathol Lab Med 2010;134:1645)
● Nodal metastases common
● Stage 1 tumors have same prognosis as other stage 1 non-small cell carcinomas; at higher stages, may have worse prognosis than other non-small cell carcinomas of similar stage (Am J Surg Pathol 2003;27:311)
● Giant cell tumors frequently metastasize to small intestine

Gross description
=========================================================================

● 2-17 cm, necrosis and hemorrhage common

Micro description
=========================================================================

● Non small cell lung carcinoma with at least 10% neoplastic spindle or giant cells, usually with epithelial cells
● Epithelial component 10-85%, usually adenocarcinoma or large cell carcinoma, also squamous cell carcinoma (Am J Surg Pathol 2008;32:1727)
● Usually poorly differentiated
● Spindle cells resemble MPNST, MFH or fibrosarcoma
● Giant cells usually bizarre with multilobulated nuclei, abundant eosinophilic cytoplasm accompanied by heavy neutrophilic infiltrate with occasional ingested white blood cells
● Stroma often myxoid, frequent inflammatory infiltrate, collagen fibers
● Numerous mitotic figures
● Massive necrosis common
● Vascular invasion in 58%

Positive stains
=========================================================================

Sarcomatoid component - CK7 (63%), TTF1 (43%), surfactant protein A (6%)
Epithelial component - CK7 (76%), TTF1 (59%), surfactant protein A (39%)

Negative stains
=========================================================================

● CK20



Other Carcinoma

Sebaceous carcinoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 23 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

See also Skin - Nonmelanocytic tumors chapter

Case reports
=========================================================================

● 78 year old man with slow growing, endobronchial tumor (Am J Surg Pathol 2002;26:795)

Micro description
=========================================================================

● Sebaceous differentiation with lobulated and infolded architecture, light and dark zones composed of basaloid cells with sharp cytoplasmic borders, vesicular nuclei and cytoplasm varying from scant to abundant with small vesicles

Positive stains
=========================================================================

● Oil red O (lipid)

Negative stains
=========================================================================

● PAS-diastase, mucicarmine

Differential diagnosis
=========================================================================

● Metastatic tumor from head and neck
Mucoepidermoid carcinoma
Squamous cell carcinoma with sebaceous differentiation



Other Carcinoma

Small cell carcinoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 23 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Also called oat cell carcinoma
● 10-20% all of lung carcinoma, 45,000 new cases per year in US
● Usually men, median age 60 years, 99% occur in smokers, very aggressive with early mediastinal lymph node involvement
● Apparently derived from primitive cells of basal bronchial epithelium with partial differentiation towards neuroendocrine cells
● Associated with paraneoplastic syndromes due to production of ACTH (Cushing’s syndrome), ADH (hyponatremia), calcitonin (hypocalcemia), gonadotropins (gynecomastia), parathyroid hormone (hyperparathyroidism), serotonin (carcinoid syndrome); also encephalomyelitis, Lambert-Eaton syndrome, sensory neuropathy
● Two subtypes: pure or combined (Mod Pathol 2012;25:S18)
● Biopsies often crushed
● Cytology may be helpful
● Diagnosis based on H&E, not the presence of neuroendocrine markers

Prognostic factors
=========================================================================

Poor prognostic factors: elevated serum LDH, alkaline phosphatase, albumin, hemoglobin, white blood count

Treatment
=========================================================================

● Chemotherapy, radiation
● Cure rates of 15-25% for limited disease
● Most live 1 year
● Preoperative chemotherapy and surgery if T1-2, N0-1, M0

Gross description
=========================================================================

● Usually central/hilar
● White-tan, soft, friable, extensive necrosis
● Peripheral nodules have fairly well-defined border and fleshy cut surface

Gross images
=========================================================================



Central tumor


Spreading along bronchi

Micro description
=========================================================================

● Sheets, ribbons, clusters, rosettes or peripheral pallisading of small to medium sized (2-4x neutrophils) round/oval cells with minimal cytoplasm, salt and pepper chromatin without prominent clumps, hyperchromatic, indistinct nucleoli, nuclear molding, smudging, frequent mitotic figures
● Azzopardi phenomena (basophilic nuclear chromatin spreading to wall of blood vessels), indistinct cell borders
● Stroma is scanty, vascular, delicate
● No glands, replacement of epithelium is less common than subepithelial growth
● Necrosis and apoptotic debris are common
● More cytoplasm is present in cells in metastases or resections than in small biopsies
● May have larger cells with similar morphology, small mixtures of squamous cell carcinoma or adenocarcinoma (Am J Surg Pathol 2002;26:1184)
● Rarely scattered giant cells, prominent nucleoli

Micro images
=========================================================================



Flow, H&E, stains (not necessarily lung)

Virtual slides
=========================================================================



Various slides

Positive stains
=========================================================================

● Pan-keratin (100%, dot like pattern), TTF1 (89%); also neuron specific enolase (77%), CD117 (75%, 50% after chemotherapy, Mod Pathol 2003;16:1041), chromogranin (58%, may be weak), synaptophysin (57%), calretinin (49%), thrombomodulin (27%), keratin5 (27%), CD57/Leu7 (variable), gastrin releasing peptide, N-CAM/CD56, bcl-2 (variable)

Negative stains
=========================================================================

● CD3, CD20, CD45, CD99/MIC2, pancreatic polypeptide, vimentin, mesothelin, p63

Flow cytometry description
=========================================================================

● CD56+ (neural cell adhesion molecule), CD45-, which differentiates from lymphoma (Arch Pathol Lab Med 2003;127:461)

Electron microscopy description
=========================================================================

● Occasional round, membrane bound, dense core neurosecretory granules, 100-200 nm in diameter
● May have bundles of tonofibrils
● May form glandular spaces

Differential diagnosis
=========================================================================

Atypical carcinoid tumor: less nuclear atypia, <20 mitotic figures per 10 HPF, no extensive necrosis, more intense neuroendocrine staining
● Metastatic small cell carcinoma



Other Carcinoma

Spindle cell carcinoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 23 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Subtype of Sarcomatoid carcinoma (WHO)
● <1% of all primary lung carcinomas

Micro description
=========================================================================

● Carcinoma composed exclusively of spindle-shaped tumor cells
● Tumor cells often obliterate vessels

Negative stains
=========================================================================

● Surfactant apoprotein A



Other Carcinoma

Squamous cell carcinoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 22 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Carcinoma arising from squamous epithelial cells, morphologically characterized by proliferation of atypical, often pleomorphic squamous cells; graded as well, moderately, or poorly differentiated; well differentiated carcinomas are usually associated with keratin production and presence of intercellular bridges between adjacent cells; subtypes include basaloid, clear cell type, papillary, small cell nonkeratinizing (WHO)

Terminology
=========================================================================

Early lung carcinoma of hilar type
● Arises proximal to sub segmental bronchi (i.e. major bronchi), confined to bronchial wall with no lymph node metastases
● Usually squamous cell carcinoma; may be polypoid, nodular, superficially infiltrating or mixed
● Longitudinal mucosal folds show changes at tumor border
● Superficial tumor has thickened and fused folds
● Five year survival is 90% or more if no second squamous cell carcinoma present

Early squamous cell carcinoma of peripheral type
● Defined as tumor 2 cm or less in peripheral lung with no lymph node or distal metastases
● Only rarely identified in practice, since these tumors grow rapidly
● Often have glandular cell characteristics

Basaloid squamous cell carcinoma
● Very aggressive subtype

Spindle cell squamous cell carcinoma
● Also called sarcomatoid carcinoma

Clinical features
=========================================================================

● Most common type of lung cancer in Western countries, although rates are declining due to reduction in tobacco use
● Usually men, closely correlated with smoking history
● Central cases appear to arise from bronchial epithelial dysplasia; peripheral cases usually lack dysplasia
● Symptoms: bronchial obstruction (pneumonitis, atelectasis)
● Associated pleural effusions usually do NOT contain tumor
● May spread to thoracic wall, diaphragm, mediastinum
● Hypercalcemia in a lung tumor not due to bone metastases is usually due to squamous cell carcinoma production of parathyroid hormone-related protein

Gross description
=========================================================================

● Usually central portion of lung affecting larger bronchi but may be peripheral
● Invades peribronchial soft tissue, lung parenchyma and nearby lymph nodes
● May compress pulmonary artery and vein
● Peripheral tumors often have nodular growth with central necrosis and cavitation
● Surrounding lung may exhibit lipid pneumonia, bronchopneumonia, atelectasis
● Calcification is unusual

Gross images
=========================================================================



Central cavitation


Tumor obstructing bronchus


Tumor extending to pleura

Micro description
=========================================================================

● Sheets or islands of large polygonal malignant cells containing keratin (individual cells or keratin pearls) and intercellular bridges
● Adjacent bronchial dysplasia or carcinoma in situ is common
● At advancing tumor border, tumor cells usually destroy alveoli or fill alveolar spaces
● Rarely spreads beneath basement membrane
● May have focal areas of intracytoplasmic mucin
● Rarely oncocytes, foreign body giant cells (reacting to keratin), pallisading granulomas, extensive neutrophilic infiltration, lepidic growth pattern at tumor periphery, clear cell change (glycogen)
● Classify as well, moderately or poorly differentiated based on amount of keratinization present in predominant component
Peripheral tumor types: alveolar space filling (tumor cells fill alveoli but don’t destroy elastic septa), expanding type (growth destroys elastic septa) or mixture
Subtypes: basaloid, clear cell (numerous clear tumor cells containing glycogen), small cell (small tumor cells with focal keratinization, distinct nucleoli, sharply outlined tumor nests, less necrosis than small cell neuroendocrine carcinoma), papillary
● Important to examine margins carefully for intraepithelial spread

Micro images
=========================================================================



Well differentiated


Moderately differentiated


Mixed, with keratin pearls and mitotic figures

Virtual slides
=========================================================================



Cavitating tumor


Endobronchial and bronchial tumors


Keratinizing-moderately differentiated


Esophageal metastasis

Cytology description
=========================================================================

● Often positive in sputum

Cytology images
=========================================================================



Sheets of atypical cells with jagged cell borders, basophilic cytoplasm, irregular nuclear contours, nuclear hyperchromasia

Positive stains
=========================================================================

● p63 most common (Arch Pathol Lab Med 2012;136:155, Hum Pathol 2002;33:921); also CK5/6 (87-100%), EMA, thrombomodulin (87-100%)
● Variable CD15, CEA, HPV, mesothelin (16-31%), p53, p40, S100

Negative stains
=========================================================================

● Vimentin (usually), TTF1 (usually), Napsin A

Electron microscopy description
=========================================================================

● Abundant tonofilaments, complex desmosomes, basal lamina

Differential diagnosis
=========================================================================

● Squamous metaplasia with atypia (Hum Pathol 2002;33:1052)



Other Carcinoma

Papillary squamous cell carcinoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 16 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare, well differentiated squamous cell carcinoma characterized by papillary, exophytic growth pattern and hyperkeratosis (WHO)

Case reports
=========================================================================

● 75 year old woman with endobronchial tumor (Ann Diagn Pathol 2005;9:284)

Micro images
=========================================================================



Head and neck (not lung): papillary squamous cell carcinoma with individual, delicate finger-like projections with fibrovascular cores (left); cytologically atypical epithelium lines the papillary projections (right upper); ‘koilocytic atypia’ and keratosis are common (right lower)



Carcinoid and related tumors

Carcinoid tumor


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 22 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● World Health Organization classification recognizes 4 histologic subtypes of pulmonary neuroendocrine carcinomas (NECs), which include typical carcinoids (TCs), atypical carcinoids (ACs), small cell carcinomas (SCCs), and large cell NECs (LCNECs)
● Also called well-differentiated neuroendocrine carcinoma
● <5% of primary lung tumors
● Locally invasive, rarely metastasizes
● Usually age <40 years old
● No gender predilection, not related to smoking
● Occasionally occurs as part of MEN syndrome
● May infiltrate or spread to local lymph nodes, but doesn’t affect prognosis
● Rarely produces carcinoid syndrome (flushing, diarrhea, cyanosis)
● 10 year survival is 50%
● In children, involves lung or liver, may metastasize regardless of histology (Arch Pathol Lab Med 2003;127:1200)

Gross description
=========================================================================

● Either central (polypoid and endobronchial in major bronchi) or peripheral (solid/nodular)
● Usually well defined, smooth, ivory to pink cut surface, no necrosis

Micro description
=========================================================================

● Nests or trabeculae of medium sized polygonal cells with lightly eosinophilic cytoplasm, low nuclear grade, round to oval finely granular nuclei; may have rosettes or small acinar structures with variable mucin
● Scanty vascular stroma, occasionally amyloid stroma with bone
● No / minimal mitotic activity (<2/10HPF), no necrosis

Micro images
=========================================================================



Left: figure B; right: figure A

Positive stains
=========================================================================

● TTF1 (43-53%, Appl Immunohistochem Mol Morphol 2007;15:407, Am J Clin Pathol 2005;123:394)
● Secretin receptor overexpression (Mod Pathol 2008;21:387)


Central carcinoid tumor

General
=========================================================================

● Most common type, usually slow growing, associated with obstruction, infection, hemorrhage
● Usually adults, but also most common lung tumor of children
● 5% metastasize, usually to regional lymph nodes
● Rarely distant osteoblastic metastases to bone
● 10 year survival 70%
● Cytology often negative since tumor is covered by mucosa

Treatment
=========================================================================

● Surgical resection

Gross description
=========================================================================

● Solitary, intrabronchial polypoid mass that may infiltrate bronchial wall, covered by intact mucosa
● Gray-yellow cut surface, cartilage may be present

Micro description
=========================================================================

● Nests or cords of uniform, bland cells with central nuclei and moderate granular cytoplasm, prominent vasculature, stroma may be delicate fibrovascular, hyalinized or exhibit calcification
● Angiolymphatic invasion common
● Rarely mitotic figures, rosettes or papillary architecture, endocrine atypia, melanin granules
● May have paraganglioma appearance with S100+ sustentacular cells
● Sox10+ sustentacular cells observed in carcinoid tumours but not in high-grade NECs (Histopathology 2011;58:276)
● May have oncocytic features (abundant granular eosinophilic cytoplasm with numerous mitochondria by EM, Hum Pathol 2011;42:578)

Virtual slides
=========================================================================



Bronchial carcinoid

Positive stains
=========================================================================

● Keratin, serotonin, neuron-specific enolase, chromogranin A and B, synaptophysin, CD57/Leu7, pancreatic polypeptide, N-CAM

Negative stains
=========================================================================

● Mucin (except in glandular lumina), TTF1 (usually, Hum Pathol 2004;35:825)

Molecular description
=========================================================================

● 1/3 are aneuploid, which doesn’t appear to affect prognosis

Electron microscopy description
=========================================================================

● Dense core secretory granules that vary in shape and size

Differential diagnosis
=========================================================================

Small cell neuroendocrine carcinoma: may to difficult to distinguish if extensively crushed, but PAX5 discriminates low/intermediate grade from high-grade neuroendocrine carcinomas (Am J Clin Pathol 2008;129:556)


Peripheral carcinoid tumor

General
=========================================================================

● Arise in peripheral lung, often beneath the pleura
● Usually asymptomatic and incidental
● Excellent prognosis
● Rare nodal metastases are usually cured by excision

Treatment
=========================================================================

● Lobectomy (since multiple tumors are common)

Gross description
=========================================================================

● Multiple, nonencapsulated, gray-tan nodules, bulging, brown-tan cut surface, not associated with a bronchus

Micro description
=========================================================================

● Disorderly spindle cells resembling smooth muscle
● Moderate pleomorphism and mitotic activity
● Prominent stroma
● Amyloid and melanin often present (Histopathology 2011;59:526)

Positive stains
=========================================================================

● Congo Red (amyloid), TTF1 (usually), calcitonin (often)



Carcinoid and related tumors

Atypical carcinoid tumor


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 9 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Also called moderately differentiated neuroendocrine carcinoma
● Diagnostic criteria (Rosai): resembles a carcinoid but with atypical features
● More aggressive than typical carcinoid tumors: nodal metastases in 70% vs. 5%
● 5 year survival is 49-69%

Micro description
=========================================================================

● Carcinoid tumors with increased mitotic activity (2-10 per 10 HPF), nuclear pleomorphism or foci of necrosis

Micro images
=========================================================================



Various images


Various immunostains with various tumors


Atypical carcinoid tumor of lung metastatic to adrenal gland

Positive stains
=========================================================================

● More intense neuroendocrine staining than small cell carcinoma
● Also positive for pancreatic polypeptide
● FoxM1(+), p27/kip1 (high, Histopathology 2012;60:731)
● Coexpression of PAX5 with c-Met (Arch Pathol Lab Med 2010;134:1702)

Negative stains
=========================================================================

● Enhancer of zeste homolog 2 (Hum Pathol 2011;42:867)
● Collapsin response mediator protein (CRMP5, Am J Surg Pathol 2008;32:1699)

Electron microscopy description
=========================================================================

● Numerous large neurosecretory granules

Differential diagnosis
=========================================================================

Carcinoid tumor: lacks comedo-like necrosis, has < 0.2 mitotic figures/HPF (Lung Cancer 2011;71:34)



Carcinoid and related tumors

Tumorlet


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 22 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Nodular proliferation of small spindle cells near bronchioles
● May be associated with bronchiectasis or other causes of scarring
● Almost always benign
● By definition, 5 mm or less

Positive stains
=========================================================================

● Same as carcinoid

Electron microscopy description
=========================================================================

● Same as carcinoid



Lymphoma and lymphoid infiltrates

BALT lymphoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 22 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Lymphoma of Bronchus Associated Lymphoid Tissue
● Rare type of low-grade, primary pulmonary MALT lymphoma
● Often need gene rearrangement studies to diagnose
● Indolent with good prognosis

Case reports
=========================================================================

● 41 year old woman with clonality by gene rearrangement but not by flow cytometry (Arch Pathol Lab Med 2003;127:115)

Micro description
=========================================================================

● Centrocyte-like lymphocytic proliferation in bronchiolar submucosa with lymphoepithelial lesions, reactive lymphocytes and plasma cells
● Bland appearance

Micro images
=========================================================================



H&E with lymphoepithelial lesions

Differential diagnosis
=========================================================================

● Reactive hyperplasia



Lymphoma and lymphoid infiltrates

Burkitt lymphoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 22 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Case reports
=========================================================================

● 33 year old man with cystic fibrosis and Burkitt’s lymphoma after double lung transplant (Am J Surg Pathol 2003;27:818)



Lymphoma and lymphoid infiltrates

Diffuse large B cell lymphoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 22 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Presents as large parenchymal mass accompanied by necrosis, occasionally by intrabronchial mass
● May evolve from MALT lymphoma or arise without preexisting lesions
● 5 year survival is 50%

Micro description
=========================================================================

● Pleomorphic large lymphoid cells, usually noncleaved
● Various patterns of infiltration (Am J Clin Pathol 2004;121:718)

Positive stains
=========================================================================

● CD20

Negative stains
=========================================================================

● CD3, CD5, CD26



Lymphoma and lymphoid infiltrates

Follicular bronchitis / bronchiolitis


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 22 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Lymphoid follicles and plasma cells around distal bronchi and bronchioles that infiltrate fibromuscular wall and may compress the lumen
● Associated with immunodeficiency (congenital, AIDS), rheumatoid arthritis and Sjogren’s syndrome
● Causes mild shortness of breath

Treatment
=========================================================================

● Steroids, uncertain if chemotherapy if helpful

Micro description
=========================================================================

● Lymphoid follicles and plasma cells around distal bronchi and bronchioles that infiltrate fibromuscular wall and may compress the lumen (Arch Pathol Lab Med 2010;134:691)
● Alveoli relatively unaffected



Lymphoma and lymphoid infiltrates

Hodgkin lymphoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 22 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Very rare (<100 cases reported) as primary tumor of lung; secondary involvement more common
● By definition, primary lung disease is restricted to lung with no involvement of hilar nodes
● Usually good prognosis, but fatal cases occur

Case reports
=========================================================================

● 21 year old woman with localized consolidation (Arch Pathol Lab Med 2003;127:e49)

Gross description
=========================================================================

● Nodular or multinodular lesions in upper lung

Micro description
=========================================================================

● Typical Reed-Sternberg cells, mononuclear cells, lacunar variants in background of mixed inflammatory infiltrate
● Rarely granulomatous inflammation simulating tuberculosis

Micro images
=========================================================================



Figure 3A: CD15; Figure 3B: CD30

Positive stains
=========================================================================

● CD15, CD30

Negative stains
=========================================================================

● Reed-Sternberg like cells: CD45, CD20, CD3, EMA

Differential diagnosis
=========================================================================

● Anaplastic lymphoma
Organizing pneumonia
● T cell lymphoma
Tuberculosis
Wegener’s granulomatosis



Lymphoma and lymphoid infiltrates

Lymphomatoid granulomatosis


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 22 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Also called angioimmunoproliferative lesion
● Lymphoproliferative disorder that is malignant per se or likely to become malignant, resembles post-transplant lymphoproliferative disorders

Clinical features
=========================================================================

● Middle aged men and women with well defined, bilateral rounded mass densities on chest Xray
● Associated with transplant-related immunosuppression, Sjogren’s syndrome, HIV
● 80% of cases have extrapulmonary involvement (skin, CNS, kidneys, liver, spleen, adrenal glands, heart, GI tract); rarely, there is only extrapulmonary involvement
● Usually no hilar or mediastinal lymph node involvement
● May be an EBV related, B cell proliferation; T cells present are usually reactive; may have reversal of T helper / suppressor ratio
● Large number of atypical lymphoid cells is a poor prognostic factor
● Median survival 14 months; death due to sepsis, destruction of lung tissue

Treatment
=========================================================================

● Chemotherapy

Micro description
=========================================================================

● Nodular inflammatory infiltrate of large atypical lymphoid cells (prominent nuclei, mitotic activity), plasma cells, immunoblasts, involving walls of pulmonary vessels (angioinvasive, angiocentric, angiodestructive)
● No multinucleated giant cells
● Similar infiltrates found in other organs

Positive stains
=========================================================================

● EBV (50-70%)

Differential diagnosis
=========================================================================

Wegener’s granulomatosis: giant cells, necrosis



Lymphoma and lymphoid infiltrates

MALT lymphoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 22 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Lymphoma of Mucosal Associated Lymphoid Tissue - a type of marginal zone lymphoma
● See also lymphoma of bronchial associated lymphoid tissue (BALT)
● Called pseudolymphoma in older literature
● In adults, lung MALT is usually low-grade, median age 68 years (range 34-88), often associated with autoimmune disorders, monoclonal gammopathies, hepatitis C, Helicobacter pylori gastritis
● 44% involve mediastinal nodes
● Usually indolent with excellent prognosis (Am J Surg Pathol 2001;25:997)
● May recur locally, rarely transforms, few die of disease
● 20% have monoclonal gammopathy, 30% have pleural effusions
● Flow cytometry of tumor cells is useful in phenotyping; may even be helpful on peripheral blood

Etiology
=========================================================================

● In pediatric HIV patients with lymphoid interstitial pneumonitis, chemokines and cytokines may recruit inflammatory cells, either representing an early stage of MALT or providing a microenvironment for the evolution of a monoclonal B-cell population (Mod Pathol 2001;14:929)

Case reports
=========================================================================

● 41 year old woman with multiple lung nodules, negative flow cytometry but clonal IgH gene rearrangement (Arch Pathol Lab Med 2003;127:115)

Treatment
=========================================================================

● Local resection for limited disease, chemoradiotherapy for advanced disease

Gross description
=========================================================================

● Solitary discrete mass, occasionally multiple nodules

Gross images
=========================================================================



Discrete tan mass (contributed by anonymous)

Micro description
=========================================================================

● Nodular pattern of monotonous, mature lymphocytes with germinal centers that infiltrate overlying epithelium (lymphoepithelial lesions) and around vessels, pleura and alveolar septa
● Cells may be monocytoid or resemble centrocytes
● Also reactive plasma cells, variable fibrosis and epithelioid granulomas
● Also colonization of germinal centers by tumor cells
● Rarely granulomatous vasculitis

Micro images
=========================================================================



Monotonous population of small-intermediate cells (contributed by anonymous)


Lymphoepithelial lesion (contributed by anonymous)


Figure 1-CT with multiple pulmonary nodules; 2A-lymphocytic proliferations with some germinal centers; 2B-lymphoepithelial lesions associated with bronchial mucosa

Positive stains
=========================================================================

● CD20, CD43

Negative stains
=========================================================================

● CD5, CD10, CD23

Differential diagnosis
=========================================================================

● Benign lymphoid aggregates / reactive disorder: architecture is preserved, associated with immunosuppression and collagen vascular disease; not monoclonal by flow cytometry or PCR (Am J Surg Pathol 2002;26:76)



Lymphoma and lymphoid infiltrates

Nasal type NK-T cell lymphoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 22 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Epstein-Barr virus associated lymphoma that usually involves nasal cavity and upper respiratory tract, and only rarely lung

Case reports
=========================================================================

● 41 year old man with retroperitoneal tumor and massive lung involvement (J Hematop 2010;3:19)
● Orbital tumor with lung metastases (Hum Pathol 2003;34:290)



Lymphoma and lymphoid infiltrates

Plasmacytoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 22 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Associated with nodal or bone involvement and myeloma

Micro description
=========================================================================

● Mature and atypical plasma cells



Lymphoma and lymphoid infiltrates

SLL/CLL


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 22 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Small lymphoblastic lymphoma / chronic lymphocytic leukemia
● Usually asymptomatic pulmonary nodules or infiltrates in elderly
● Involves the lung at autopsy in 30% of cases, may cause significant pulmonary impairment

Gross description
=========================================================================

● Well defined, encapsulated mass, homogenous gray cut surface

Micro description
=========================================================================

● Monomorphic low grade lymphocytic infiltrate with pseudofollicles

Differential diagnosis
=========================================================================

● Reactive lymphoid infiltrate: polymorphic lymphocytes, germinal centers, other inflammatory cells



Lymphoma and lymphoid infiltrates

Waldenström macroglobulinemia


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 22 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● B cell neoplasm (usually lymphoplasmacytic lymphoma) plus serum IgM monoclonal paraprotein
● Usually elderly patients with indolent clinical course
● Median survival 5 years
● Involves bone marrow (100%), liver, spleen, lymph nodes (15-20%); lung is an unusual site (Am J Surg Pathol 2003;27:1104)
● Hyperviscosity syndrome in 15%

Diagnosis
=========================================================================

● Serum protein electrophoresis to detect monoclonal paraprotein



Other malignancies

Angiosarcoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 10 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Presents as mass or diffuse pulmonary infiltrates, usually in adult men (Ann Diagn Pathol 2010;14:296)
● Almost all cases in lung represent metastatic disease

Case reports
=========================================================================

● 83 year old man with epithelioid tumor of lungs (Arch Pathol Lab Med 2005;129:e7)

Gross description
=========================================================================

● Diffusely hemorrhagic lungs with multiple dark red nodules
● Involves interlobar septa and bronchovascular bundles
● Grows along lymphatics or venous routes

Gross images
=========================================================================



Metastatic tumor at autopsy has multiple cystic nodules

Micro images
=========================================================================



Primary angiosarcoma of lung shows (left to right): interanastomosing vascular spaces, tumor cells with atypia and hobnailing that dissect vascular spaces, solid sheets of epithelioid cells, primitive vessel formation


Primary epithelioid (left) and metastatic (right) disease


Post Lucite plombage treatment of pulmonary TB

Differential diagnosis
=========================================================================

● Metastatic angiosarcoma



Other malignancies

Desmoplastic small round cell tumor


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 22 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Case reports
=========================================================================

● 22 year old man (Arch Pathol Lab Med 2002;126:1226)

Micro description
=========================================================================

● Nests of small round tumor cells within a cellular and vascular collagenous stroma

Micro images
=========================================================================



H&E, stains

Positive stains
=========================================================================

● AE1/AE3, EMA, CAM5.2, vimentin, desmin, neuron-specific enolase, WT1

Negative stains
=========================================================================

● Thrombomodulin, calretinin

Electron microscopy description
=========================================================================

● Intracytoplasmic whorls of intermediate filaments

Electron microscopy images
=========================================================================



Cytoplasmic perinuclear aggregates of intermediate filaments

Molecular description
=========================================================================

● t(11;22)(p13;q12) [EWS-WT1 gene fusion]

Molecular images
=========================================================================



RT-PCR



Other malignancies

Epithelioid hemangioendothelioma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 22 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Formerly called intravascular bronchioloalveolar tumor
● 80% women, usually young adults
● Neoplastic, but usually not metastatic
● Progressive growth, usually remains within thoracic cavity, may cause death from respiratory insufficiency
● Other sites: liver, bone
● 10% have peripheral eosinophilia
● Poor prognosis if vascular spread, pleural involvement, severe symptoms

Case reports
=========================================================================

● 54 year old man with multiple pulmonary nodules (Arch Pathol Lab Med 2003;127:e319)

Gross description
=========================================================================

● Multiple round, well demarcated nodules < 2 cm, often in lower lung, with a gray-white peripheral rim and chondroid appearance
● Resembles metastasis, granulomatous disease or interstitial lung disease
● May spread along pleura or pericardium and resemble mesothelioma

Micro description
=========================================================================

● Central hyalinized stroma, eosinophilic amorphous material or coagulative necrosis with variable calcification surrounded by thin rim of plump eosinophilic endothelial cells
● Clusters fill alveoli, apparently through pores of Kohn, and occasionally bronchioles, arteries, veins
● Nuclei are bland, round/oval, may have cytoplasmic vacuoles
● No/minimal mitoses
● Lung architecture preserved

Micro images
=========================================================================



H&E, Factor VIII (figure D)

Positive stains
=========================================================================

● CD10 (Arch Pathol Lab Med 2009;133:1965); Factor VIII, CD31, CD34
● Variable ER and PR

Electron microscopy description
=========================================================================

● Endothelial features: well developed basal lamina, pinocytotic vesicles, occasional Weibel-Palade bodies

Differential diagnosis
=========================================================================

● Metastatic tumor from liver or other sites: destroy lung architecture, high mitotic rate
Sclerosing hemangioma: destroys lung architecture, negative for vascular markers



Other malignancies

Hemangiopericytoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 22 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare tumor at any site, often a misdiagnosis
● Lipomatous variant (Ultrastruct Pathol 2007;31:51)

Micro description
=========================================================================

● Blunt spindle cells with scant cytoplasm, separated by arborizing vascular spaces arranged in a staghorn pattern

Differential diagnosis
=========================================================================

● Metastatic endometrial stromal sarcoma



Other malignancies

HIV associated polymorphic lymphoproliferative disorders


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 22 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Resemble posttransplant lymphoproliferative disorders in solid organ transplant recipients (Am J Surg Pathol 2003;27:293)
● Case report: HIV+ patient with EBV associated polymorphic lymphoproliferation (Virchows Arch 2012;461:93)



Other malignancies

Kaposi sarcoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 22 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Usually associated with AIDS, HHV8 infection; also immunocompromise, organ transplant
● Diffuse reticulonodular pulmonary infiltrates, solitary lung nodules, or pleural effusions
● Tumor follows lymphatic channels
● Detection of HHV8 DNA is highly specific and sensitive for diagnosis of pulmonary Kaposi sarcoma

Gross description
=========================================================================

● Discrete dark red hemorrhagic nodules with growth along septa and infiltration of small airways, pulmonary arteries, veins



Other malignancies

Leiomyosarcoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 22 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Usually metastatic, not primary
● Endobronchial site is also rare (J Clin Imaging Sci 2012;2:35)



Other malignancies

Melanoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 22 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare as primary, must rule out metastatic disease
● Primaries probably arise from residual melanoblasts
● Frequently endobronchial



Other Carcinoma

Metastatic endometrial stromal sarcoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 12 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Metastases to lung are rare; occur a mean 10 years after diagnosis of uterine tumor
● Excellent prognosis - patients only rarely die of disease (Am J Surg Pathol 2002;26:440, Am J Surg Pathol 2002;26:1142)
● Note: uterine diagnosis often not disclosed to pathologist

Micro description
=========================================================================

● Well circumscribed, solid tumor composed of plump spindle cells in short fascicles, often with hyalinized areas
● May have cystic or sex cord-like areas

Micro images
=========================================================================



Various images

Positive stains
=========================================================================

● Vimentin, ER, PR, CD10
● Variable smooth muscle actin, desmin and keratin

Negative stains
=========================================================================

● Chromogranin, HMB45

Differential diagnosis
=========================================================================

Carcinoid tumor
Endometriosis
● Hemangiopericytoma
Lymphangioleiomyomatosis
● Lymphoma
Sclerosing hemangioma



Other malignancies

Pleuropulmonary blastoma


Reviewer: Nat Pernick, M.D. (see Reviewers page)
Revised: 23 January 2013, last major update February 2010
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Definition
=========================================================================

● Pleuropulmonary blastoma (PPB) is a childhood tumor of the lung or pleura that usually occurs in children age 4 years or younger
● First described in 1988 (Cancer 1988;62:1516)

Epidemiology
=========================================================================

● Rare overall, but one of the most common primary lung malignancies in children (Arch Pathol Lab Med 2008;132:1079)

Clinical features
=========================================================================

● International registry is at http://www.ppbregistry.org
● Children usually present with difficulty breathing or other respiratory problems
● MRI or CT can help diagnose, but biopsy is suggested (Pediatr Radiol 2007;37:337)
● Gross total resection is necessary for cure, and selected patients do not require radiation therapy (J Pediatr Hematol Oncol 2012;34:e182)
● Classified into three types:
  - Type I is multicystic, and may progress into types II or III
  - Type II shows thickened areas within the cysts
  - Type III shows solid masses

Case reports
=========================================================================

● 8 month old infant with shortness of breath (Case of the Week #166)

Treatment
=========================================================================

● Radical surgery to excise the cyst or mass, with extensive follow up to detect relapses
● Chemotherapy is usually provided for types II and III; 11% of type II and 54% of type III patients develop cerebral metastases (Pediatr Blood Cancer 2007;49:266)

Gross images
=========================================================================



Case of the Week #166

Micro description (Histopathology)
=========================================================================

● Mixed blastematous and sarcomatous appearance and primitive cells (Singapore Med J 2007;48:e190)
● Primitive, undifferentiated blastema cells and sarcomatous elements of different types of differentiation, including lipoblastic, chondroblastic, rhabdomyoblastic and giant cell undifferentiated sarcomas
● Cystic and slit-like spaces lined by the primitive or sarcomatous cells
● Multiple foci of necrosis
● Type I is multicystic, and may progress into types II or III
● Type II shows thickened areas within the cysts
● Type III shows solid masses

Micro images
=========================================================================





Case of the Week #166

Molecular / cytogenetics description
=========================================================================

● Frequently gains in chromosome 8q (Mod Pathol 2007;20:1191)

Differential diagnosis
=========================================================================

● Many type III tumors resemble embryonal rhabdomyosarcoma, but this tumor is rare in lungs/pleura, and PPB also has cystic architectural, blastema tissue and other mesenchymal components such as cartilage
● Other tumors to consider include monophasic synovial sarcoma, malignant peripheral nerve sheath tumor, mesothelioma, malignant teratoma and undifferentiated sarcoma
● Immunostains are typically not helpful in differentiating these entities



Other malignancies

Pulmonary blastoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 22 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare tumor composed of mixture of immature epithelial and mesenchymal tissue resembling fetal lung tissue
● Also called embryoma
● Usually adults (mean age 43 years), 20% occur in patients < age 20 years
● Metastases common
● 2/3 die within 2 years
● See also pleuropulmonary blastoma - cystic tumor of pleura and lung

Case reports
=========================================================================

● 16 year old boy with biphasic tumor (Arch Pathol Lab Med 2002;126:875)
● 16 year old girl (Case Report Med 2012;2012:471613)

Gross description
=========================================================================

● Peripheral, solitary, well circumscribed, large
● Type I (purely cystic), type II (cystic and solid), type III (purely solid)

Micro description
=========================================================================

● Biphasic tumor in which epithelial and mesenchymal components have a primitive, “fetal-type” appearance
● Well formed tubular glands surrounded by cellular stroma of “embryonal” appearance
● Resembles Wilm’s tumor and fetal lung at 10-16 weeks
● Glandular cells are tall, columnar, often with clear cytoplasm and subnuclear and supranuclear cytoplasmic vacuoles
● Morules with ground-glass nuclei are common
● Stroma may differentiate towards striated muscle, smooth muscle, cartilage
● In infants/children, epithelial component is benign appearing or minimal
● Stroma may be rhabdomyoblastic or chondroid

Micro images
=========================================================================



Biphasic tumor

Positive stains
=========================================================================

● PAS (glycogen in epithelial cells)

Molecular description
=========================================================================

● CTNNB1 mutation (J Clin Pathol 2011;64:349), DICER1 mutation

Differential diagnosis
=========================================================================

● Fetal lung interstitial tumor (FLIT): see Am J Surg Pathol 2010;34:1762



Other malignancies

Rhabdomyosarcoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 22 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Pleomorphic subtype more common in adults, embryonic subtype more common in children



Other malignancies

Synovial sarcoma


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 22 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Rare tumor in lung
● Associated with chest pain, hemoptysis, dyspnea, cough, fever
● Rarely is cystic (Am J Surg Pathol 2010;34:1176)
● 40-55% die of disease after 20 years follow-up, due to metastases to bone, CNS, liver, or invasion of adjacent organs
● Tumors with SYT-SSX2 fusion proteins have 89% 5 year survival vs. 42% for tumors with SYT-SSX1 fusion protein

Case reports
=========================================================================

● 45 year old woman with SYT-SSX2 and rapidly progressive course (Arch Pathol Lab Med 2003;127:e201)
● 72 year old white man with poorly differentiated tumor with rhabdoid features (Arch Pathol Lab Med 2003;127:e160)

Micro description
=========================================================================

● Monophasic spindle cells or biphasic with epithelial and spindle cell component
● Monophasic tumors have compact fascicles of hyperchromatic spindle cells with hemangiopericytoma-like areas, often punctuated by small arteries and capillaries in an irregular distribution
● Poorly differentiated tumors have small, round blue cells resembling Ewing sarcoma/PNET
● Rarely rhabdoid features

Micro images
=========================================================================



H&E, BCL2, CD99, CD117


Poorly differentiated tumor: H&E and vimentin

Positive stains
=========================================================================

● TLE1 highly specific (Virchows Arch 2011;459:615)

Negative stains
=========================================================================

● CD117 (most cases)

Molecular description
=========================================================================

● t(X;18)(p11.2;icq11.2)
● Produces either SYT-SSX1 or SYT-SSX2 fusion genes

Differential diagnosis
=========================================================================

● Monophasic tumor resembles fibrosarcoma
Carcinosarcoma: may be primary or metastatic
Hemangiopericytoma
Leiomyosarcoma
Spindle cell carcinoma



Other

Staging


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 17 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

Primary tumor (T)
=========================================================================

TX: Primary tumor cannot be assessed, or tumor proven by the presence of malignant cells in sputum or bronchial washings but not visualized by imaging or bronchoscopy
T0: No evidence of primary tumor
Tis: Carcinoma in situ
T1: Tumor 3 cm or less in greatest dimension, surrounded by lung or visceral pleura, without bronchoscopic evidence of invasion more proximal than the lobar bronchus (i.e. not in the main bronchus); also includes the uncommon, superficial tumor of any size with its invasive component limited to the bronchial wall, which may extend proximally to the main bronchus
T1a: Tumor 2 cm or less in greatest dimension
T1b: Tumor more than 2 cm but 3 cm or less in greatest dimension
T2: Tumor more than 3 cm but 7 cm or less or tumor with any of the following features (T2 tumors with these features are classified T2a if 5 cm or less):
- Involves main bronchus
- 2 cm or more distal to the carina
- Invades visceral pleura (PL1 or PL2)
- Associated with atelectasis or obstructive pneumonitis that extends to the hilar region but does not involve the entire lung
T2a: Tumor more than 3 cm but 5 cm or less in greatest dimension
T2b: Tumor more than 5 cm but 7 cm or less in greatest dimension
T3: Tumor more than 7 cm or one that directly invades any of the following: parietal pleura (PL3), chest wall (including superior sulcus tumors), diaphragm, phrenic nerve, mediastinal pleura, parietal pericardium; or tumor in the main bronchus (less than 2 cm distal to the carina but without involvement of the carina); or associated atelectasis or obstructive pneumonitis of the entire lung or separate tumor nodule(s) in the same lobe
T4: Tumor of any size that invades any of the following: mediastinum, heart, great vessels, trachea, recurrent laryngeal nerve, esophagus, vertebral body, carina; separate tumor nodule(s) in a different ipsilateral lobe

Regional lymph nodes (N)
=========================================================================

NX: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Metastasis in ipsilateral peribronchial or ipsilateral hilar lymph nodes and intrapulmonary nodes, including involvement by direct extension
N2: Metastasis in ipsilateral mediastinal or subcarinal lymph node(s)
N3: Metastasis in contralateral mediastinal, contralateral hilar, ipsilateral or contralateral scalene, or supraclavicular lymph node(s)

Distant metastasis (M)
=========================================================================

M0: No distant metastasis
M1: Distant metastasis
M1a: Separate tumor nodule(s) in a contralateral lobe tumor with pleural nodules or malignant pleural (or pericardial) effusion
M1b: Distant metastasis

Notes:
● Most pleural (and pericardial) effusions are due to tumor
● In a few patients, however, multiple cytopathologic examinations of pleural (pericardial) fluid are negative for tumor, and the fluid is nonblood and is not an exudate
● Where these elements and clinical judgment dictate that the effusion is not related to the tumor, the effusion should be excluded as a staging element and the patient should be classified as M0

Stage grouping
=========================================================================

Occult carcinoma: TX N0 M0
Stage 0: Tis N0 M0
Stage IA: T1a-b N0 M0
Stage IB: T2a N0 M0
Stage IIA: T2b N0 M0 or T1a-T2a N1 M0
Stage IIB: T2b N1 M0 or T3 N0 M0
Stage IIIA: T1a-T2b N2 M0 or T3 N1-N2 M0 or T4 N0-N1 M0
Stage IIIB: Any T N3 M0 or T4 N2-N3 M0
Stage IV: Any T any N M1a-b

Additional references
=========================================================================

AJCC Cancer Staging Manual (7th ed)



Other

Features to report


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 13 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Specimen type and site (involved bronchi or segments, laterality, intact or fragmented)
● Procedure
● Histologic type
● Histologic grade (incorporating nuclear atypia, mitotic index)
● Tumor size
● Surgical resection margins (bronchi, peribronchial and perivascular soft tissue)
● Involvement of bronchi, surfaces covering tumor (pleura, thoracic wall, diaphragm), adjacent structures
● Angiolymphatic invasion
● Presence of multiple tumors (intrapulmonary metastases)
● Pleural dissemination
● Lymph node involvement (site of lymph nodes, number obtained, number positive, size of largest metastasis, extracapsular invasion)
● Presence of disease in uninvolved lung/bronchi
● Presence of histologic treatment effect (if prior chemoradiation therapy)
● Molecular studies, as appropriate

Micro images
=========================================================================



Visceral pleural invasion

Additional references
=========================================================================

Arch Pathol Lab Med 2009;133:1552



Other

Cytology


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 16 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● Sputum or bronchial brushings are 80-90% sensitive for lung carcinoma if examine 5+ sputum samples
● Fine needle aspirate is superior to bronchoalveolar lavage for diagnosis of pathologic pathology (Mod Pathol 2002;15:1259)
● False positives: due to misidentification of macrophages or pneumocytes - includes bronchiectasis, fungal infections, infarct, lipoid pneumonia, post-radiation changes, viral pneumonia
● False negatives: often due to sampling (Diagn Cytopathol 2012;40:556); pleural fluid cytology is often falsely negative for small cell carcinoma
● Also useful for mutation analysis (Acta Cytol 2012;56:661)

Micro images
=========================================================================



Adenocarcinoma


Squamous cell carcinoma



Other

Grossing lung tumors


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 12 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

● 1 section per cm of tumor diameter, representative of grossly distinct areas
● Margins (bronchial, pulmonary artery/vein, visceral pleura, other surgical margins)
● Tumor and adjacent lung
● Tumor and bronchial wall
● Tumor and pleura
● Bronchial mucosa proximal to tumor



Other

Frozen section


Reviewer: Deepali Jain, M.D. (see Reviewers page)
Revised: 11 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

General
=========================================================================

May be difficult to distinguish between the following:
● In situ and invasive carcinoma of bronchial mucosa (Arch Pathol Lab Med 2012;136:1515)
● Bronchioloalveolar hyperplasia and carcinoma
● Primary and metastatic disease

● Touch preparation cytology recommended to supplement frozen section findings (J Clin Pathol 2010;63:675)

Micro images
=========================================================================



Frozen section challenges


Lung versus breast carcinoma at frozen section


Squamous cell carcinoma


Various images

End of Lung tumor > Superpage


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