Lung tumors
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Last revised 3 February 2008
Last major update November 2003
Copyright (c) 2003-2007, PathologyOutlines.com, Inc.
See also Lung-nontumor, Mediastinum, Pleura, Trachea
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Benign tumors: adenoma, benign metastasizing leiomyoma, clear cell (sugar) tumor, diffuse pulmonary lymphangiomatosis, granular cell tumor, hamartoma, hemangioma, hemangiomatosis, inflammatory pseudotumor, Langerhans cell histiocytosis, leiomyoma, lipoma, lymphangiomyomatosis, micronodular pneumocyte hyperplasia, paraganglioma, sclerosing hemangioma, solitary fibrous tumor, squamous papilloma
Dysplasia/CIS: general, bronchioalveolar atypical adenomatous hyperplasia
Carcinoma: general, acinic cell, adenocarcinoma, adenocarcinoma-fetal lung type, adenocarcinoma-well differentiated fetal, adenocarcinoma vs mesothelioma, adenoid cystic, adenosquamous, bronchioloalveolar, epithelial-myoepithelial, giant cell, large cell, large cell neuroendocrine, lymphoepithelioma-like, metastatic, metastatic endometrial stromal sarcoma, micropapillary, mucoepidermoid, papillary, pleomorphic, pleuropulmonary blastoma, pulmonary blastoma, sebaceous, small cell, spindle cell, squamous cell
Carcinoid and related tumors: carcinoid, atypical carcinoid, tumorlet
Hematologic: BALT lymphoma, Burkitt’s lymphoma, diffuse large B cell lymphoma, follicular bronchitis, Hodgkin’s lymphoma, lymphomatoid granulomatosis, MALT lymphoma, Nasal type NK/T cell lymphoma, plasmacytoma, SLL/CLL, Waldenström macroglobulinemia
Other malignancies: angiosarcoma, desmoplastic small round cell tumor, epithelioid hemangioendothelioma, histiocytic-dendritic, HIV lymphoproliferative, Kaposi’s sarcoma, leiomyosarcoma, melanoma, rhabdomyosarcoma, synovial sarcoma
Other: staging, features to report, cytology, grossing, frozen section
Go to Lung: non-tumors (separate page)
Benign tumors
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Pleomorphic adenoma
Very rare (< 20 cases reported), ages 35-74 years
Usually in trachea and major bronchi, rarely in distal bronchi
Case report in 56 year old woman with incidental lesion, Archives 2003;127:621
Treatment: surgical excision, but may recur many years later
Gross: well circumscribed, no capsule, 2-16 cm, gray-white cut surface, may have tumor tongues outside their fibrous capsules
Micro: nests and trabeculae of epithelial cells in chondromyxoid stroma; lumina may contain PAS+ eosinophilic secretions; 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
Positive stains: epithelium - CK7, CAM5.2, AE1/AE3, alpha-1-antitrypsin, lysozyme; myoepithelial cells - S100, vimentin
DD: primary salivary gland tumors (have ducts with single layer of cells, lack PAS+ material in lumens, lack S100+ / vimentin+ myoepithelial layer)
Alveolar adenoma: usually in peripheral lung, consists of small cystic spaces lined by type II pneumocytes and containing fluid
Bronchial gland adenomas: include oncocytoma and mucus gland adenoma
Papillary adenomas: arise in peripheral lung, composed of type II pneumocytes or Clara cells
Benign metastasizing leiomyoma
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Rare, <60 cases reported through April 2003
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
Usually no symptoms or mild cough and shortness of breath; nodule(s) on chest Xray
Good prognosis
Case report in 76 year old woman, Archives 2003;127:501
Treatment: hysterectomy, bilateral salpino-oophorectomy, long term hormonal therapy
Micro: 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; no atypia, no vascular invasion, no mitotic figures; may contain cysts
DD: hamartoma, low grade leiomyosarcoma
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Usually adults, may occur in children
Derived from perivascular epithelioid cells (also angiomyolipomas, lymphangioleiomyomas)
Treatment: simple excision
Gross: small, sharply outlined, red-tan mass, usually in peripheral lung
Micro: 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
Positive stains: HMB45, S100 (focal)
EM: membrane bound glycogen in lysosome-like organelles, intracytoplasmic filaments
DD: carcinoma with clear cell pattern, metastatic renal cell carcinoma
Diffuse pulmonary lymphangiomatosis
Men, women or children with wheezing and shortness of breath
No cysts, no pneumothorax
May be progressive and fatal
Micro: prominent lymphatics in pleura and alveolar septa, variable smooth muscle proliferation that may appear kaposiform
Negative stains: HMB45
Polypoid intrabronchial mass that may cause obstruction
May be multicentric
Also called pulmonary chondroma
Benign, occurs in adults
Usually solitary, subpleural
Common, presents as incidental coin lesion (rounded abnormality) with popcorn pattern of calcification on chest Xray
May present as intrabronchial polypoid mass causing obstruction
Treatment: excision
Nonfamilial syndrome: pulmonary chondroma, gastric epithelioid leiomyosarcoma, functional extra-adrenal paraganglioma
Gross: 4 cm or less, sharply delineated and lobulated, glistening cut surface (cartilage) with ill defined clefts
Micro: 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
References: Archives 2002;126:562
Multiple pulmonary leiomyomatous hamartomas
Very rare, almost always in asymptomatic middle-aged women
Case report in 46 year old man associated with bronchogenic cyst, Archives 2003;127:e194
Micro: excessive smooth muscle, not associated with tumor nodules
Negative stains: HMB45
DD: reactive smooth muscle proliferation in chronic interstitial pneumonitis, benign metastasizing leiomyoma, leiomyosarcomas, lymphangioleiomyomatosis, native pulmonary muscle proliferation
Hemangioma
Usually children
Endobronchial or parenchyma
May present with symptoms of pulmonary hypertension or interstitial lung disease
Poor prognosis; may be a variant of veno-occlusive disease
Micro: proliferation of benign-appearing capillaries in alveolar septa that appear to compress pulmonary veins; also hemorrhage, hemosiderosis
DD: veno-occlusive disease
Also called inflammatory myofibroblastic tumor, plasma cell granuloma
Often children and adults age 30 or less; most common lung tumor in children age 16 and younger
Treatment: excision; rarely causes death due to local extension
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
Gross: well circumscribed, non-encapsulated, usually solitary, white, firm, parenchymal nodule; 3% bilateral; may have hemorrhage, necrosis or calcification
Micro: 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
Positive stains: spindle cells - vimentin, smooth muscle actin
EM: elongated cytoplasmic processes with pinocytotic vesicles, subplasmalemmal plaques, thin filaments, abundant endoplasmic reticulum
DD: hemangiopericytoma, carcinoid tumor, plasmacytoma, amyloid tumor, metastatic carcinoma, TB in immunosuppressed patients, organizing pneumonia, lipid pneumonia, benign and malignant fibrous histiocytoma, other spindle cell tumors, mycobacterial pseudotumor
Childhood inflammatory pseudotumor
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: solitary, small peripheral nodules, yellow, firm, covered by intact pleura or polypoid bronchial mass
Micro: see above; often rich in plasma cells
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
20% with multicentric disease (bone, skin, lymph nodes, spleen, pituitary) have lung involvement
50% of cases only involve lung
Often associated with pneumothorax, Pneumocystis carinii pneumonia
Usually lung disease resolves or stabilizes, but 10-20% may progress to respiratory failure
Case report of 40 year old woman with Stage IV diffuse large B cell lymphoma, Archives 2002;126:747
Gross: lesion of upper lobes, local or diffuse, with nodules and cavitary lesions and late honeycombing
Micro: interstitial scarring with nodular aggregates of Langerhans cells with a bronchiolocentric distribution; also prominent eosinophils and mesothelial cells; Langerhans cells have abundant eosinophilic cytoplasm and grooved nuclei with indented nuclear membranes; 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
Positive stains: CD1a, S100, HLA-DR
EM: Birbeck’s granules (pentilaminar intracytoplasmic structures, tennis racket shaped)
DD: eosinophilic pleuritis (no Langerhans cells although mesothelial cells may appear similar), reactive Langerhans cells in inflammatory conditions (no sheets or groups of Langerhans cells), desquamative interstitial pneumonitis
Rare, associated with HIV-infected children
See also benign metastasizing leiomyoma (above)
DD: spindle cell carcinoma
Usually endobronchial, usually men ages 50+
Also called lymphangioleiomyomatosis
Rare, unknown etiology, may diffusely involve both lungs
Almost always in women, usually white and of reproductive age; rare cases in men or postmenopausal women on hormone replacement
Associated with tuberous sclerosis, renal angiomyolipomas
May involve mediastinal or periaortic lymph nodes
Derived from perivascular epithelioid cells (also angiomyolipomas, clear cell [sugar] tumor of lung)
Symptoms: dyspnea with pneumothorax or emphysema, without a smoking history
Have severe impairment of diffusion with air trapping and expanding lung volumes
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; may be due to metastases or migration of progenitor cells
Treatment: oophorectomy, hormone manipulation (progesterone or antiestrogens), lung transplantation (but may recur in lung allografts, Hum Path 2003;34:95)
Gross: emphysematous-like changes to widespread cystic spaces separated by thick, gray-white septa
Micro: 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
Positive stains: HMB45, ER, PR
DD: metastatic endometrial sarcoma, benign metastasizing leiomyoma, idiopathic pulmonary hemosiderosis (all HMB45 negative), micronodular pneumocyte hyperplasia
Micronodular pneumocyte hyperplasia
Associated with tubular sclerosis; may coexist with lymphangioleiomyomatosis
Usually women with shortness of breath
Considered a hamartoma
Not progressive
Micro: bland multifocal proliferation of alveolar type II pneumocytes
Negative stains: HMB45, ER, PR
DD: lymphangioleiomyomatosis
Rare in lung
Usually benign; rarely malignant
May be hyperplastic, not neoplastic
Gross: solitary or multiple, usually peripheral mass, often microscopic
Micro: zellballen pattern (islands of cells) with sustentacular cells at periphery of nests
Positive stains: neuroendocrine markers; S100 (sustentacular cells)
Negative stains: keratin, mucin, CEA
EM: resembles meningeal arachnoid granulations
DD: carcinoid tumor (ribbons, festoons, rosettes)
Also called sclerosing pneumocytoma
Usually adult women, ages 30-50 years, with incidental solitary nodule on chest Xray
Apparently derived from type II pneumocytes or with differentiation towards these cells
Almost always benign, 2-4% have nodal metastases that don’t appear to affect prognosis (Archives 2003;127:321)
Sclerosis and hemorrhage are probably secondary changes
Gross: well circumscribed, non-encapsulated, easily shelled out, tan-yellow, may be hemorrhagic, usually peripheral lung
Micro: papillary pattern or islands filled with bland polygonal cells 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
Positive stains: EMA, keratin (focal), LeuM1, TTF1, PR, ER (weak), surfactant proteins
Negative stains: CEA, S100, smooth muscle actin, chromogranin, CD34
DD: primary and metastatic carcinoma, clear cell (“sugar”) tumor, carcinoid tumor, papillary adenoma, alveolar adenoma, epithelioid hemangioendothelioma, Langerhans cell histiocytosis, meningiomas, meningothelial-like nodules
References: Archives 2003;127:377
May be intrapulmonary and not pleural
Peaks at ages 50-69 years
Larger tumors associated with hypoglycemia, pleural effusion, pulmonary osteoarthropathy (particularly if tumors 7cm+)
Gross: firm, rounded, lobulated; variable cysts, hemorrhage, necrosis
Micro: highly variable cellularity, markedly collagenous stroma with irregularly distributed thick walled vessels; may have myxoid stroma; often has malignant features (pleomorphism, tumor giant cells, mitotic figures); may have MFH, hemangiopericytoma, fibrosarcoma or neural patterns
Positive stains: CD34, vimentin; variable smooth muscle actin
Occur in large bronchi, often with associated tracheal or laryngeal lesions
Due to HPV
Often associated with dysplasia, carcinoma in situ or invasive squamous cell carcinoma
May contain mucus cells
Micro: papillary lesion covered by squamous epithelium
DD: mucoepidermoid carcinoma (for papillomas with mucus cells)
Dysplasia/carcinoma in situ
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: either unremarkable or papillary, granular with loss of folds
Micro: 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
Bronchioalveolar atypical adenomatous hyperplasia
Diagnostic variability exists - also called adenoma, well differentiated bronchioalveolar carcinoma of Clara cell or type II pneumocyte type
Associated with coexisting bronchioloalveolar carcinoma and papillary adenocarcinoma
If malignant appearing but noninvasive, recommended to call bronchioloalveolar carcinoma of nonmucinous type
Gross: focal
Micro: alveolar lining cells replaced by cuboidal cells with uniform, mildly to highly atypical nuclei, scanty cytoplasm, minimal mitotic figures
References: Hum Path 2002;33:697 (telomerase expression).
Carcinoma
95% of lung tumors are bronchogenic carcinoma; also bronchial carcinoids, mesenchymal, miscellaneous neoplasms
In US, lung cancer is #1 cause of cancer death in men and women; causes 30% of cancer deaths in men
In 2002, 164,000 new cases in US; 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
Young patients (age 40 or less) have higher incidence of 20q gains/amplifications compared to older patients (56% vs. 8%), Mod Path 2002;15:372
Cigarette smoking: causes most cases of lung cancer; relative risk of smokers vs. nonsmokers is 10:1; increases to 20:1 for >40 cigarettes/day; risk is strongly related to number of cigarettes smoked, described in pack years (number of packs per day x number of years 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: radiation exposure, uranium (RR with uranium exposure is 4:1 for nonsmokers, 10:1 for smokers vs. general population); asbestos (RR with asbestos exposure is 5:1 for nonsmokers, 50-90:1 for smokers vs. general population), exposure to nickel, chromate, coal, mustard gas, arsenic, beryllium, iron, vinyl chloride, radon radiation, gold miners
Causes of death for asbestos workers are: 20% lung cancer, 10% mesothelioma, 10% GI carcinomas
Symptoms: cough, weight loss, chest pain, shortness of breath, increased sputum production
Systemic symptoms: Lambert-Eaton myasthenic syndrome (muscle weakness due to antibodies to neuronal calcium channel), sensory peripheral neuropathy, acanthosis nigricans, leukemoid reaction, hypertrophic pulmonary osteoarthropathy (clubbing), superior vena cava syndrome (compression/invasion of SVC causes venous congestion, circulatory compromise, dusky head, arm edema), pain in distribution of ulnar nerve and Horner’s syndrome (enophthalmos, ptosis, miosis, anhidrosis) due to apical lung tumors called Pancoast tumors
Classification: broad classification is non-small cell carcinoma (80%) versus small cell carcinoma (20%)
50% of non-small cell carcinomas are metastatic at diagnosis vs. 80% of small cell carcinomas
Many have mixed histologic subtypes
Scar cancers: scar is desmoplastic response to tumor
Spread: along bronchus distally and proximally, into lung parenchyma to mediastinum or pleura, causing pleural seeding, pleural effusion, involvement of diaphragm and chest wall
Metastases: 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
Treatment: complete excision for non-small cell lung carcinoma; radiation therapy (usually non-curative), chemotherapy (rarely curative, even for small cell carcinoma)
Survival: 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 are p53+, HER2+, angiolymphatic invasion or tumor size > 3 cm, Hum Path 2002;33:105
Poor prognostic factors (clinical): 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
Favorable subtypes: non-mucinous bronchioloalveolar, well differentiated squamous cell
Gross: arise near hilus; hemorrhage, necrosis, cavities are common; 2-5% are multiple; peripheral tumors are usually adenocarcinomas
Micro (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
Positive stains (see also specific subtypes): 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, AJSP 2003;27:141), Hep Par1 (hepatocyte marker, Mod Path 2003;16:137)
Molecular: dominant oncogenes are K-ras (adenocarcinomas), c-myc (small cell carcinomas), p53, Rb, 3p suppressor gene; non-small cell carcinogenesis may be related to loss of Cables protein expression at 18q11-12, Hum Path 2003;34:143
Bronchial gland tumor with low grade malignancy
Very rare at this site, usually in parotid gland, less commonly in submandibular and sublingual glands
Case report in 30 year old woman, Archives 2003;127:e216
May arise from pluripotent cells of tracheobronchial submucosal serous and mucus glands
Treatment: surgical excision
Micro: predominantly acinar cells, also ductal cells, myoepithelial cells, reserve/stem cells; solid areas recapitulate salivary gland acinar differentiation with large polyhedral cells containing round, bland nuclei and abundant granular cytoplasm; microcystic areas recapitulate terminal duct-acinar unit; no/rare perineural invasion (unlike salivary gland tumor)
Positive stains: cytokeratin, EMA
Negative stains: amylase
EM: no melanosomes, no abundant cytoplasmic glycogen, no neurosecretory granules, no abundant mitochondria or fat globules
DD: metastastic salivary gland tumor, primary lung adenocarcinoma, clear cell (sugar) tumor of lung, oncocytic carcinoma, bronchial oncocytoma, bronchial granular cell tumor, metastatic renal cell carcinoma
Arises from terminal bronchioles
In US, 50% of lung carcinomas in women are adenocarcinoma; is the most common subtype in nonsmokers
80% contain mucin
Grow slower than squamous cell; may be associated with scarring
5 year survival: stage I - 69%, II - 40%, IIIA - 17%, IIIB - 5%, IV - 8%
Peripheral tumors with bronchioloalveolar and invasive areas < 5 mm had low rates of vascular and pleural invasion and no nodal involvement, AJSP 2003;27:937
More likely TTF1 negative in males or smokers
Gross: 77% involve visceral pleura producing puckering/pleural retraction, 65% are peripheral; poorly circumscribed gray-yellow lesions, single or multiple, may be mucoid; usually not cavitary; often is 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
Micro: glandular differentiation with tubules or papillae and mucin secretion; bronchioloalveolar (BAC), colloid, hepatoid, signet ring and undifferentiated subtypes; 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
Positive stains: mucin, low molecular weight keratin (CK7), EMA, CEA, TTF1 (72%), surfactant apoprotein (50%), mesothelin (50%), vimentin (9%), S100 (Langerhans cells), p53, CD57/Leu7 (50% of well/moderately differentiated tumors), calretinin (11%)
Negative stains: CK20, vimentin (usually), keratin 5 (usually), P504S
EM: goblet cells, mucus cells, nonciliated bronchiolar cells, Clara cells
DD: melanoma (may be mucin positive)
References: AJSP 2003;27:150, AJSP 2002;26:767 (TTF1)
Subtypes:
Bronchial surface cell type with little/no mucin
8% of adenocarcinoma cases
Gross: cartilage bearing bronchus with polypoid growth or in distal airways
Micro: papillary or tubular groups of tall columnar cells resembling ciliated columnar cells, but without cilia
EM: numerous mitochondria and smooth surfaced vesicles, basal bodies but usually no cilia, no secretory granules
Goblet cell type
Gross: lobar pneumonia-like or nodular
Micro: tumor cells resemble goblet cells, with cytoplasmic mucin displacing the nuclei to basal portion; usually in bronchioloalveolar pattern, rarely in papillary pattern
Positive stains: lysozyme
Bronchial gland cell type
5% of adenocarcinoma cases
Gross: cartilage bearing bronchus with polypoid growth or in distal airways as nodular tumor
Micro: acini, tubules, ducts, cribriform patterns or solid nests of cuboidal or polygonal cells, often with mucin; may have signet ring cells; resemble bronchial glands; nests surrounded by myoepithelial type cells
Clara cell type
50% of adenocarcinoma cases
Gross: pleura indented toward area of central fibrosis
Micro: papillary, tubular or bronchioloalveolar patterns of peg-shaped cells or low columnar cells with tongue-shaped projections; fibrotic focus representing collapsed alveoli may be present; variable nuclear atypia and mitotic activity; frequent intranuclear eosinophilic inclusion bodies
EM: microvilli on free cell surface of peg cells, scattered rough endoplasmic reticulum, 200-900 nm round, dense, neurosecretory granules
DD: type II alveolar epithelial cell type
Type II alveolar epithelial cell type
Gross: solitary nodular of rarely diffusely distributed tumor
Micro: papillary or bronchioloalveolar patterns of cuboidal to low columnar cells with dome-shaped free cell border; finely vacuolated cytoplasm
EM: cytoplasmic lamellar inclusion bodies
Hepatoid
Resembles hepatocellular carcinoma (HCC); more common in gastric adenocarcinomas
Old age, high serum AFP, aggressive behavior, often with liver metastases
Micro: tubular and papillary adenocarcinoma with hepatic morphology; liver metastases are difficult to distinguish from HCC
Positive stains: same as HCC - AFP, CK8, CK18, canalicular staining with polyclonal CEA
Positive stains: different from HCC - CK19, CK20, negative for HepPar1, negative for CK7
Molecular: 4q-, 8p-, Xq+ (seen in hepatocellular carcinoma and hepatoblastoma)
References: AJSP 2003;27:1302
Adenocarcinoma of fetal lung type
Rare, high grade variant is very aggressive
May be a variant of pulmonary blastoma without malignant mesenchymal components
Associated with upregulation of Wnt signaling pathway, Mod Path 2002;15:617
Micro: 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; fibrous stroma without atypia; no morules
DD: well-differentiated fetal adenocarcinoma (has morules)
Adenocarcinoma - well differentiated fetal type
Mean ~40 years
Better prognosis than pulmonary blastoma
Variant of bronchioloalveolar carcinoma
Associated with upregulation of Wnt signaling pathway, Mod Path 2002;15:617
Gross: well-defined, non-encapsulated, not related to visible bronchi
Micro: irregular tubular structures of columnar epithelial cells with clear cytoplasm and oval nuclei, continuous with morular structures; nuclei in morules are optically clear and rich in biotin; fibrous stroma without atypia
Positive stains: chromogranin A, synaptophysin, N-CAM
Negative stains: p53
DD: adenocarcinoma of fetal type (no morules)
Adenocarcinoma vs. mesothelioma
Difficult to differentiate histologically if adenocarcinoma does not produce mucin
Stains recommended to differentiate these 2 tumors: calretinin, cytokeratin 5/6 or WT1 and CEA, MOC31 (or B72.3, Ber-EP4 or BG8), AJSP 2003;27:1031
Stains that are specific for adenocarcinoma vs. mesothelioma: MOC31 (100% vs. 8%), Ber-EP4 (100% vs. 18%), BG8 (96% vs. 7%), CEA (88% vs. 0%), B72.3 (84% vs. 0%), TTF1 (74% vs. 0%), CD15/LeuM1 (72% vs. 0%)
Stains that are specific for mesothelioma vs. adenocarcinoma: calretinin (100% vs. 8%), cytokeratin 5/6 (100% vs. 2%), WT1 (93% vs. 0%), thrombomodulin (77% vs. 14%), N-cadherin (73% vs. ?)
Stains frequently positive in both tumors: EMA, E-cadherin, HBME, CD44S, mesothelin, vimentin
EM: long, slender microvilli in mesothelioma
May arise from submucus bronchial glands
Usually in large bronchi, may involve the trachea
Frequent metastases to regional lymph nodes and lung parenchyma
Prolonged course, but overall prognosis is poor
Treatment: radiation therapy (palliative)
Gross: large, polypoid, intrabronchial mass or may grow subepithelially along the bronchi causing thickened bronchial wall
DD: basaloid carcinoma with adenoid cystic carcinoma-like pattern (microcystic spaces containing mucin, surrounded by small tumor cells)
Substantial amounts of squamous and glandular differentiation
Don’t diagnose if one component is clearly minor
<10% of lung carcinomas
90% peripheral, often associated with scars
Metastases may have different histology
Poorer prognosis than either component alone
Arises from alveolar walls; similar to jagziekte, a disease of South African sheep, but jagziekte DNA not identified in human tumors
1-9% of all lung carcinomas; M=F
Solitary lesions can be resected (5 year survival 50%), but overall 5 year survival is 25%
Late metastases
More favorable prognosis: non-mucinous histology (hobnail cells, Clara cells), localized disease
This diagnosis is usually limited to non-invasive tumors with lepidic spread (along alveolar septa); if stromal, vascular or pleural invasion is seen, tumor is classified as adenocarcinoma, mixed subtype
Gross: peripheral lung, one or more nodules (nodules may coalesce) or pneumonia-like infiltrate
Micro: tall, columnar cells line up along alveolar septa, project into spaces with papillary projections, but underlying lung architecture is preserved; variable anaplasia but usually well differentiated
Composed of mucus-producing goblet cells, Clara cells or type II alveolar epithelial cells
Mucinous type - composed of well differentiated columnar cells containing mucin that line respiratory spaces; tumor cells are associated with bronchioles, not bronchi; usually sharp demarcation between normal and tumor cells
Non-mucinous type - cuboidal cells with bright eosinophilic cytoplasm, prominent nucleoli and nuclear atypia; apical spouts and hobnail cells often present; cilia are rare; also PAS+ intranuclear inclusions; associated with interstitial fibrosis (may be severe) and chronic inflammatory infiltrate; 13% have psammoma bodies
Positive stains: alpha-1-antitrypsin for Clara cells in non-mucinous type, surfactant for type 2 pneumocytes in non-mucinous type, TTF1 (80% of non-mucinous, 0% of mucinous), CK7 (94-100%)
Negative stains: CK20 (but 25-90% of mucinous are CK20+)
EM: mucinous - resemble bronchiolar goblet cells; non-mucinous - resemble Clara cells or type 2 pneumocytes
DD: metastatic mucinous carcinoma
References: Mod Path 2002;15:538 (TTF1, CK7, CK20), Hum Path 2002;33:915 (CK7, CK20)
DD: metastatic adenocarcinoma
Epithelial-myoepithelial carcinoma
Arises from submucosal bronchial glands, mimics the similar salivary gland tumor
Very rare, < 10 cases reported through April 2003
Ages 40-69 years
Low grade malignancy; long interval to recurrence or metastasis
Case report of 73 year old man with bronchial tumor, Archives 2003;127:e177
Gross: intraluminal polypoid mass in bronchus; may invade pulmonary parenchyma
Micro: well circumscribed mass, pushing margin; tumor consists of ductlike structures with inner epithelial cells and outer clear myoepithelial cells; no myxoid/chondroid stroma, no perineural invasion
Positive stains: epithelial cells - cytokeratin, EMA; myoepithelial cells - S100, muscle specific actin
Negative stains: HMB45
DD: mucoepidermoid carcinoma, acinic cell carcinoma, pleomorphic adenoma, adenoid cystic carcinoma with a tubular pattern, myoepithelioma, myoepithelial carcinoma, clear cell (“sugar”) tumor, metastatic epithelial-myoepithelial carcinoma (usually parenchymal, not endobronchial), metastatic clear cell carcinoma
Included in WHO classification of “carcinomas with pleomorphic, sarcomatoid, or sarcomatous elements”
<1% of all primary lung carcinomas
Micro: neoplastic, highly pleomorphic giant cells, often in inflammatory stroma with emperipolesis; giant cells are multinucleated, may resemble syncytiotrophoblasts
Positive stains: calretinin (67%)
Negative stains: surfactant apoprotein A
Large cell undifferentiated carcinoma
May be undifferentiated squamous cell or adenocarcinomas
Diagnosis of exclusion; cannot diagnose on small biopsies or in lymph node metastases
80% men
Often associated with peripheral eosinophilia and leukocytosis, due to tumor production of colony stimulating factor
Behavior is similar to adenocarcinoma
5 year survival: stage I - 65%, II - 26%, IIIA - 18%, IIIB - 15%, IV - 6%
Gross: usually peripheral lung, spherical tumor with well-defined borders and bulging, fleshy, homogenous gray-white cut surface; no anthracosis; frequently involves thoracic wall
Micro: large polygonal cells and anaplastic cells growing in solid nests without obvious squamous or glandular differentiation; vesicular nuclei, prominent nucleoli, moderately abundant cytoplasm, well defined cell borders
Positive stains: keratin5 (56%), calretinin (38%), thrombomodulin (25%), mesothelin (13%), TTF1 (variable reports of staining)
EM: glandular (intracellular and extracellular lumina) and squamous (desmosomes, tonofilaments) features often present although not obvious with H & E staining
Large cell neuroendocrine carcinoma
Diagnostic criteria (Rosai): resembles a non-small cell carcinoma, but on closer inspection has a hint of neuroendocrine architecture confirmed by special stains
Micro: larger tumor cells than atypical carcinoid, high nuclear grade, increased mitotic activity (11+ per 10 HPF) and necrosis; poorly developed neuroendocrine architecture with some pallisading or rosette-like structures present
Positive stains: neuroendocrine markers, CD117 (60%), TTF1 (50%)
Lymphoepithelioma-like carcinoma
Rare, ~ 100 cases reported
In Taiwan study, most patients were women, Chinese, non-smokers, AJSP 2002;26:715
Case report of EBV+ tumor in 25 year old Italian man, Hum Path 2003;34:623
Otherwise rare in Caucasians, and usually EBV-
Tumor size may correlate with EBV serology titer
May have better prognosis than other nonsmall cell carcinomas of lung
Gross: well circumscribed nodules
Micro: 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
Positive stains: EBV, EBER-1, LMP (EBV latent membrane protein), bcl2, patchy keratin
Negative stains: CD45/LCA (in tumor cells)
DD: metastatic nasopharyngeal carcinoma, lymphoma, inflammatory pseudotumor
Metastastic tumors to lung
Lung is a common site of metastases
Usually multiple, bilateral, sharply outlined, rapidly growing, more pleomorphic and necrotic than lung primaries, negative for TTF1
Often multiple discrete nodules in periphery of lung; also lymphangitis carcinomatosa (peribronchial and perivascular patterns via lymphatics); rarely intralymphatic microscopic foci that may cause pulmonary hypertension
Treatment: excision of isolated nodules
Nodular metastases: breast, GI tract, kidney, sarcoma, melanoma
Lymphangitis carcinomatosis: stomach, breast, choriocarcinoma, pancreas, prostate; case report with hepatocellular carcinoma, Archives 2003;127:e11
Central cavitation: squamous cell carcinoma of upper aerodigestive tract, colonic adenocarcinoma, leiomyosarcoma
Intrabronchial masses: breast, kidney, colon
Tumor emboli: breast, stomach, liver, choriocarcinoma
Lepidic pattern: colon, pancreas
Positive stains: CDX2 (colorectal carcinoma, AJSP 2003;27:141)
Negative stains: surfactant apoprotein
Metastatic endometrial stromal sarcoma
Metastases to lung are rare, reports at AJSP 2002;26:440, AJSP 2002;26:1142
Metastases occur a mean 10 years after diagnosis of uterine endometrial stromal sarcoma
Excellent prognosis; patients only rarely die of disease
Note: uterine diagnosis often not disclosed to pathologist
Micro: well circumscribed, solid tumor composed of plump spindle cells in short fascicles, often with hyalinized areas; may have cystic or sex cord-like areas
Positive stains: vimentin, ER, PR, CD10; variable smooth muscle actin, desmin and keratin
Negative stains: chromogranin, HMB45
DD: sclerosing hemangioma, carcinoid tumor, lymphangioleiomyomatosis, endometriosis, hemangiopericytoma, lymphoma
Associated with nodal metastases of similar histology, intrapulmonary metastases, non-smokers
Poorer survival than non-papillary for stage I (79% vs. 93%), AJSP 2003;27:101, AJSP 2002;26:358
Case report of incidental brain metastases with micropapillary structures, Archives 2003;127:e313
Micro: small papillary tufts without a fibrovascular core; associated with varied other histologic subtypes
Positive stains: CK7 (93%), TTF1 (80%), CK20 (13%)
May arise from submucus 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
Gross: polypoid growth in major bronchi
Micro: low grade or high grade; mucus secreting cells, squamous cells, intermediate type cells
DD: adenosquamous carcinoma arising from bronchial epithelium
Includes goblet cell (mucin producing) type, Clara cell type, type II pneumocyte type and bronchial surface epithelial cell type with or without mucin production
Micro: papillary structures with true fibrovascular core should comprise at least 75% of tumor
Pleomorphic carcinoma
Also called sarcomatoid carcinoma, spindle cell carcinoma, giant cell carcinoma, pseudosarcoma, pulmonary blastoma, and carcinosarcoma
Included under recent WHO classification of “carcinomas with pleomorphic, sarcomatoid, or sarcomatous elements”
<1% of all carcinomas
Mean age 65 years, range 42-81 years, >90% men, 92% smokers
Diagnosis is based on histology, not immunostains
Presumed epithelial origin, although epithelial and sarcomatous components express common markers differently, AJSP 2003;27:1203
Nodal metastases common
Stage 1 tumors have same prognosis as other stage 1 non-small cell carcinomas; pleomorphic tumors at higher stages may have worse prognosis by stage than other non-small cell carcinomas, AJSP 2003;27:311
Giant cell tumors frequently metastasize to small intestine
Carcinosarcoma: carcinoma component is combined with a sarcoma, the latter consisting of heterologous elements, such as malignant cartilage, bone, or muscle; both components appear to have a common origin, AJSP 2002;26:510
Gross: 2-17 cm, necrosis and hemorrhage common
Micro: 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; 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; 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
Molecular: extensive allelic loss in carcinosarcomas at 3p, 5q, 17p
Children less than age 10 years
Micro: cystic or solid sarcoma, with cysts lined by metaplastic epithelium; has features of chondrosarcoma, leiomyosarcoma, rhabdomyosarcoma, liposarcoma, undifferentiated sarcoma
Also called embryoma
Considered a subtype of pleomorphic carcinoma / carcinosarcoma
Usually in adults (mean age 43 years), 20% less than 20 years old
Metastases common; 2/3 die within 2 years
In infants/children, epithelial component is benign appearing or minimal; stroma may be rhabdomyoblastic or chondroid; tumors may be cystic and may involve pleura and lung
Case report of 16 year old white boy, Archives 2002;126:875
Gross: peripheral, solitary, well circumscribed, large
Micro: 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
Positive stains: PAS (glycogen in epithelial cells)
Case report of 78 year old man with slow growing, endobronchial tumor, AJSP 2002;26:795
Micro: 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
DD: metastatic tumor from head and neck, mucoepidermoid carcinoma, squamous cell carcinoma with sebaceous differentiation
Also called undifferentiated carcinoma, 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 ADH (hyponatremia), ACTH (Cushing’s syndrome), parathyroid hormone (hyperparathyroidism), calcitonin (hypocalcemia), gonadotropins (gynecomastia), serotonin (carcinoid syndrome), encephalomyelitis, sensory neuropathy, Lambert-Eaton syndrome
Diagnosis is based on H & E staining, not the presence of neuroendocrine markers
Some pathologists report the presence of a large cell component or classify as undifferentiated or squamous cell carcinoma of small cell type if small tumor cells with hyperchromatic, coarsely granular or vesicular nuclei, small but distinct nucleoli, scanty but identifiable cytoplasm, distinct cell border, primarily negative for neuroendocrine stains
5 year survival (n=55): stage I - 33%, II - 44%, IIIA - 22%, IIIB - 0%, IV - 12%
Biopsies often crushed; cytology may be helpful
Flow cytometry: CD56+ (neural cell adhesion molecule), CD45-, which differentiates from lymphoma, Archives 2003;127:461
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
Poor prognostic factors: elevated serum LDH, alkaline phosphatase, albumin, hemoglobin, white blood count
Gross: usually central/hilar; white-tan, soft, friable, extensive necrosis; peripheral nodules have fairly well-defined border and fleshy cut surface
Micro: 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; rarely scattered giant cells, prominent nucleoli
Positive stains: pan-keratin (100%, dot like pattern), CK-BB (91%), TTF1 (89%), histamine decarboxylase (78%, Mod Path 2003;16:72), neuron specific enolase (77%), CD117 (75%, 50% after chemotherapy), chromogranin (58%, may be weak), synaptophysin (57%), calretinin (49%), thrombomodulin (27%), keratin5 (27%), CD57/Leu7 (variable), gastrin releasing peptide, N-CAM, bcl-2 (variable)
Negative stains: CD3, CD20, CD45, CD99/MIC2, pancreatic polypeptide, vimentin, mesothelin, p63
EM: occasional round, membrane bound, dense core neurosecretory granules, 100-200 nm in diameter; may have bundles of tonofibrils; may form glandular spaces
DD: atypical carcinoid tumor (less nuclear atypia, <20 mitotic figures per 10 HPF, no extensive necrosis, more intense neuroendocrine staining)
References: Mod Path 2003;16:1041 (CD117 expression), AJSP 2002;26:1184, Hum Path 2002;33:1182 (CD117 expression);
Included under recent WHO classification of “carcinomas with pleomorphic, sarcomatoid, or sarcomatous elements”
<1% of all primary lung carcinomas
Micro: carcinoma composed exclusively of spindle-shaped tumor cells; tumor cells often obliterate vessels
Negative stains: surfactant apoprotein A
Usually men, closely correlated with smoking history, most common type of lung cancer in Western countries although rates are declining due to reduction in tobacco use
Important to examine margins carefully for intraepithelial spread
May spread to thoracic wall, diaphragm, mediastinum; associated pleural effusions usually do NOT contain tumor
Hypercalcemia in a lung tumor not due to bone metastases is usually due to squamous cell carcinoma production of parathyroid hormone-related protein
Central cases appear to arise from bronchial epithelial dysplasia; peripheral cases usually lack dysplasia
Peripheral cases with alveolar space filling pattern have better prognosis, no lymphatic invasion or nodal metastases, AJSP 2003;27:978
Symptoms: bronchial obstruction (pneumonitis, atelectasis)
Cytology: often positive in sputum
5 year survival after resection: stage I-64%, stage II-48%, stage IIIA-28%, stage IIIB-6%, stage IV-0%
Gross: 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
Micro: 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 spread 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
Variants: small cell (small tumor cells with focal keratinization, distinct nucleoli, sharply outlined tumor nests, less necrosis than small cell carcinoma), clear cell (numerous clear tumor cells containing glycogen), well-differentiated papillary, basaloid (see below), spindle cell (see below)
Positive stains: keratin, keratin5 (87-100%), EMA, thrombomodulin (87-100%), S100, CD15, CEA, p53, p63, HPV, mesothelin (16-31%)
Negative stains: vimentin (usually), TTF1 (usually)
EM: abundant tonofilaments, complex desmosomes, basal lamina
DD: squamous metaplasia with atypia (Hum Path 2002;33:1052)
References: Hum Path 2002;33:921 (p63)
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
Are usually squamous cell carcinomas
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 clinical course
Spindle cell squamous cell carcinoma
Also called sarcomatoid carcinoma
Carcinoid and related tumors
Also called well-differentiated neuroendocrine carcinoma
<5% of primary lung tumors
Locally invasive, rarely metastasizes
Usually ages 40 years or younger; 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, involve lung or liver, may metastasize regardless of histology or classification as carcinoid vs. neuroendocrine carcinoma, Archives 2003;127:1200
Gross: either central (polypoid and endobronchial in major bronchi) or peripheral (solid/nodular); usually well defined, smooth, ivory to pink cut surface, no necrosis
Micro: nests or trabeculae of medium sized polygonal cells of low nuclear grade, round to oval finely granular nuclei and lightly eosinophilic cytoplasm, may have rosettes or small acinar structures with variable mucin; scanty vascular stroma, occasionally amyloid stroma with bone; no/minimal mitotic activity or necrosis
Central carcinoid tumor
Most common type, usually slow growing, associated with obstruction, infection, hemorrhage
Usually adults, but also most common lung tumor of children