Mediastinum is the central portion of the thoracic cavity (between the pleural cavities, from sternum to spine and thoracic inlet to diaphragm), which contains the heart, great vessels, esophagus, trachea and thymus as well many other vessels and neural components; it can be divided into 4 regions
Thymus is a partially lobulated, encapsulated, primary lymphoid organ that plays a central role in the development of cell mediated immunity and T cell differentiation
Essential features
Mediastinum is the centrally located portion of thorax, which notably contains the heart, aorta, vena cava, esophagus, trachea, thymus, thoracic duct, sympathetic trunk, phrenic and vagus nerves, internal thoracic arteries, azygos and hemiazygos veins
Mediastinum can be divided into 4 regions: superior, anterior, middle and posterior
Thymus is a partially lobulated, encapsulated, primary lymphoid organ that plays a central role in the development of cell mediated immunity and T cell differentiation
Thymus is active before birth and in childhood; after puberty the cortex involutes and is replaced by adipose tissue
Terminology
Mediastinal cavity
Gross anatomy - mediastinum
Mediastinum is the anatomical compartment that runs the length of the thoracic cavity (longitudinally from the thoracic inlet to the diaphragm) and comprises the area between the lungs / pleura; it is further divided into 4 compartments
Superior mediastinum
Area inferior to the thoracic outlet (~first rib) and superior to the thoracic plane (sternal angle ventrally and the T4 - T5 junction dorsally)
Contains the aortic arch (including brachiocephalic trunk, left common carotid and left subclavian arteries), esophagus, trachea, thymus, phrenic and vagus nerves
Anterior mediastinum
Area that is ventral to anterior cardiac border and aortic root and dorsal to the body of the sternum
Contains the internal thoracic arteries and transversus thoracis muscles
Middle mediastinum
Area inferior to the thoracic plane, medial to the pleural sacs and superior to the diaphragm
Contains the heart, ascending aorta and superior vena cava, pulmonary trunk and veins, trachea and bronchi
Posterior mediastinum
Area ventral to the posterior thoracic body wall and dorsal to the posterior surface of the heart (base)
Contains the descending aorta, esophagus, thoracic duct, sympathetic trunk, azygos and hemiazygos veins
Thymus arises from the endoderm of the third and fourth branchial clefts (Br Med J 1963;2:459)
At week 6, it develops as 2 separate lobes and at week 8, the lobes migrate to fuse in the anterior superior mediastinum; however, the blood supply, lymphatic drainage and innervation of each lobe remain separate
At week 10, lobules begin to form as a result of the migration of hematopoietic cells from the liver
Differentiation into cortex and medulla occurs at 14 - 16 weeks
Thymus reaches maturity in utero
Ratio of thymus to body weight is its greatest before birth; however, the thymus reaches its maximum weight just before puberty, before undergoing involution
Mature thymus
Located in the anterior superior mediastinum, retrosternally
Bilobed organ with a cortex and medulla
It is supplied with blood via the internal thoracic and inferior thyroid arteries
Has no afferent lymphatic vessels
Has a blood thymus barrier that prevents the transport of macromolecules from the vasculature into the thymic cortical parenchyma
Involution of the thymus involves its cellular structure being replaced with adipose tissue; this also is related to a decrease in function
Thymic remnants may be present in adult prepericardial or retrocarinal fat
Primary organ responsible for the production and maturation of lymphocytes and development of the immune system (Adv Clin Exp Med 2016;25:369)
It has an important role in development of cell mediated immunity and T cell differentiation
Positive selection of self antigen recognizing T cells induces apoptosis; surviving T cells do not react with self antigen
Negative selection of lymphocytes that have high affinity binding with the antigen; these also undergo apoptosis
Lymphocytes that pass both positive and negative selection can travel outside the thymus, where they are activated by bacteria, viruses or other foreign antigens
In thymus, 95% of all T cells undergo apoptosis due to their ability to recognize self antigen presented by the major histocompatibility complex (MHC) system
Clonal selection / activation of only those cells that can recognize antigen; this leads to secretion of antibodies, mitosis of T cells and a resulting increase in T cells that recognize the antigen to a pathogen
Once the pathogen is eliminated, most of the activated cells undergo apoptosis, with a few surviving as memory cells
Normal age related loss of organized architecture with increased adipose cell deposition, resulting in a replacement of functional cells with fat throughout the organ
Scarcity of T cell precursors from bone marrow and effects of circulating cytokines and hormones (e.g., hypothesized sex hormone dependent involution) contribute to involution
Involution is thought to contribute to immunosenescence, which increases susceptibility to neoplasia, infection and autoimmune diseases
Undernutrition / malnutrition can affect thymic microenvironment and immune function (Front Nutr 2022;9:948488)
Early programming of thymus, sexual dimorphism, specific T cell progenitors and thymic microenvironment may influence long term immunity and determine progression of involution at older ages (Aging Dis 2012;3:280)
ABH histoblood group antigens are heterogenically expressed in the epithelial cells and lymphocytes of normal thymus and may become immunoreactive in myasthenia gravis and thymoma (APMIS 2006;114:669)
Diagrams / tables
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Mediastinum anatomy, sagittal
Mediastinum anatomy, transverse
Histological structure of thymus
Thymus, hyperplasia, thymoma
Clinical features
Superior mediastinum: lymphoma, thyroid lesions, parathyroid adenoma
Superior vena cava syndrome: partial blockage or compression of the superior vena cava; affects superior and middle mediastinum
Mediastinal fibrosis / sclerosing mediastinitis: benign, progressive proliferation of fibrous tissue within the mediastinum (BJR Case Rep 2016;2:20150274)
Laboratory
Percutaneous needle biopsy with imaging guidance allows for extrapleural access (Radiographics 2005;25:763)
Parasternal approach for anterior or middle mediastinal lesions
Paravertebral approach for subcarinal and posterior mediastinal lesions
Transsternal approach for anterior or middle lesions that are not accessible by the parasternal approach
Suprasternal approach for superior mediastinal lesions
Ultrasound guided transthoracic biopsy has been shown to be a viable approach in countries without ready access to video assisted procedures (Cureus 2021;13:e13914)
Diagnosis of thymoma is usually via clinical and radiological findings; laboratory blood tests are not indicated
However, laboratory studies may be helpful in those suspected to have myasthenia gravis or another autoimmune condition or to rule out germ cell tumor
Cortex: densely packed T cells, basophilic, early T cell development, partially lobulated by connective tissue septa
Medulla: Hassall corpuscles, T cell later development, continuous appearance and lighter staining on H&E
Thymus has no nodules (B cells), no hilus (only efferent lymphatics) and no subcapsular sinus
Mature adult thymic cortex is mostly adipose tissue, where most of the lymphocytes have been replaced by fat; in this case, the most prominent features are Hassall corpuscles
Gross images
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Morphology of thymus
Adult persistent thymus, cadaver
Normal thymus, 29 weeks gestation
Frozen section description
In one study, intraoperative frozen section of mediastinal neoplasm without preoperative cytological or histological diagnosis resulted in the correct diagnosis of benign lesions 91% of the time (Eur J Cardiothorac Surg 1990;4:584)
However, in 35.5% of cases, intraoperative classification was not possible and in 27.6% of cases, the diagnosis was wrong, resulting in surgical overtreatment for lymphoma in 3 cases
Microscopic (histologic) description
Thymus has a connective tissue capsule with septa that extend into the organ, forming partial lobules
Lymphocyte nuclei are numerous in the cortex, giving it a generally darker microscopic appearance (on H&E) and a lighter appearing medulla
Parenchyma consists of T cells (of varying phenotypes) and B cells within the medulla and perivascular space (which increase with age) (Hum Pathol 2001;32:926)
Thymus of children ages 3 - 6 seem to be the most active, demonstrating high numbers of total thymocytes and many CD34+ progenitors (J Allergy Clin Immunol 2005;115:834)
Thymic stroma consists of all of the nonhematopoietic components of the thymus and is arranged into 2 regions, the cortex and medulla
Stromal components comprise the thymic structure and provide a matrix for thymocyte development
Keratin negative cells: fibroblasts, nonfibroblastic mesenchymal cells, endothelial cells of the vasculature and connective tissue that forms the capsule and septa
Other stromal cells: Hassall corpuscles, dendritic cells, macrophages and CD45+ hematopoietic cells
Mature thymus will show many clusters of adipose cells where the process of involution has replaced the thymic parenchyma with fat (Gerontology 2005;51:14)
Hassall corpuscles are unique to the thymus and are involved in thymocyte maturation, clearing of apoptotic cells and lymphopoiesis (Age (Dordr) 2014;36:313)
Concentrically arranged type VI epithelial reticular cells
Contributed by Nicole Stringham, Ph.D. (source: University of Michigan virtual slide box and Duke University virtual slide collection)
Neonatal thymus, lobule
Neonatal thymus, cortex / medulla
Neonatal thymus, Hassall corpuscle
Adult thymus, involuted
Adult thymus, medulla
Adult thymus, Hassall corpuscle
Virtual slides
Images hosted on other servers:
Thymus, adult
Thymus, young
Cytology description
Hallmark cytology of thymus includes 2 cell types, lymphocytes and epithelial cells (Cancers (Basel) 2022;14:2013)
Diagnosis of thymic hyperplasia is challenging on cytology due to the difficulty of identifying Hassall corpuscles and because smear cellularity can affect the size and density of epithelial clusters
Thymic hyperplasia: epithelial cell clusters are more sparse and smaller than those of thymoma and can mimic lymphoid tangles in lymph node aspirates
Presence of Hassall corpuscles favors hyperplasia over thymoma (although they may be seen in B1 thymoma)
Which anatomical compartment contains the aortic arch, brachiocephalic trunk, left common carotid and left subclavian arteries?
Anterior mediastinum
Middle mediastinum
Posterior mediastinum
Superior mediastinum
Board review style answer #1
D. Superior mediastinum contains aortic arch, brachiocephalic trunk, left common carotid and left subclavian arteries as well as the esophagus, trachea, thymus, phrenic and vagus nerves. Answer A is incorrect because anterior mediastinum notably contains the internal thoracic arteries and transversus thoracis muscles. Answer B is incorrect because middle mediastinum contains the heart and ascending aorta but not the arch. Answer C is incorrect because posterior mediastinum contains the descending aorta and other structures that pass from the thorax into the abdomen.
The micro image shown above is in need of evaluation. Features that are present, both in the image and in adjacent areas, include a connective tissue capsule, cortex and medulla, efferent lymphatics (only) and concentrically arranged epithelial reticular cells within the medulla. What is the anatomical origin of this sample?
Lymph node
Spleen
Thymus
Thyroid
Tonsil
Board review style answer #2
C. Thymus. The thymus is the only listed option that has numerous lymphocytes (shown in the image) in addition to all of the other listed features. Additionally, the concentrically arranged epithelial reticular cells (i.e., Hassall corpuscles) are unique to the medulla of the thymus. Answer A is incorrect because although lymph nodes have many of these features, including a cortex / medulla arrangement, they do not have Hassall corpuscles. Answer B is incorrect because spleen is histologically arranged as red pulp and white pulp, with nodules throughout the organ, not as a cortex and medulla. Answer E is incorrect because tonsils contain aggregates of lymphocytes but do not have many of the features listed. Answer D is incorrect because thyroid histomorphology would show simple columnar epithelium arranged in spheres around colloid rather than a parenchyma of lymphocytes.
A 1 month old girl presents with acute respiratory distress and failure to thrive. Imaging studies reveal a 3.5 cm cystic mediastinal mass compressing her trachea. The lesion is excised and shown above.
Which of the following statements accurately describes this lesion?
Congenital cyst arising from abnormal budding of the primitive ventral foregut
Congenital cyst derived from remnants of the second branchial apparatus
Congenital cyst derived from the thyroglossal duct
Mature germ cell tumor derived from all 3 germ cell layers
Board review style answer #1
A. Congenital cyst arising from abnormal budding of the primitive ventral foregut. The lesion shown is a bronchogenic cyst. Teratomas are mature germ cell tumors derived from all 3 germ cell layers (answer D); branchial cleft cysts are derived from remnants of the second branchial apparatus (answer B); thyroglossal duct cysts are derived from the thyroglossal duct (answer C).
Each of the following immunohistochemical markers may be positive in cystic teratomas of the mediastinum. Which is most reliably negative in bronchogenic cysts and therefore useful in the distinction between these 2 entities?
CDX2
Cytokeratin 7
Cytokeratin 20
TTF1
Board review style answer #2
A. CDX2. Based on one series of 22 bronchogenic cysts, CDX2 was negative in all 22 cases. The other listed immunohistochemical stains had varying levels of positivity in this cohort (from positivity with CK7 in 100% of cases to positivity with TTF1 in 18% of cases) (Am J Clin Pathol 2008;130:265).
Also called well differentiated neuroendocrine carcinoma
Sites
Usually of thymic origin in anterior mediastinum, occasionally in middle or posterior mediastinum
Diagrams / tables
Images hosted on other servers:
Features of 4 patients (tables 1 and 3)
Clinical features
Mean age 48 years old, 80% men
20% occur in MEN1 or MEN2 patients
One - third have paraneoplastic Cushing syndrome, syndrome of inappropriate antidiuretic hormone, Eaton-Lambert syndrome or rarely PTH production (Ann Thorac Surg 2002;73:675)
Coexisting carcinoid syndrome is very unusual
Behavior similar to atypical carcinoid at other sites; must be considered to have metastatic potential with metastasis to mediastinal lymph nodes, bone, liver, skin
Aggressive, presents at advanced stage; complete surgical resection with postoperative radiotherapy to tumor bed is recommended (Interact Cardiovasc Thorac Surg 2010;11:732)
Radiation therapy and chemotherapy are ineffective
Gross description
Well circumscribed but unencapsulated, firm, gray-pink, fleshy, gritty on cut section, hemorrhage, necrosis, no internal fibrous septa
Microscopic (histologic) description
Organoid pattern with islands, ribbons, festoons, trabeculae, rosettes of small round cells with minimal cytoplasm, salt and pepper chromatin, no / rare mitotic activity
Cellular nests may become detached from septa during processing and contain foci of central geographic necrosis with dystrophic calcification
Marked vascularization, frequent angiolymphatic invasion, may have amyloid type stroma, sclerotic (desmoplastic type) stroma, melanin pigment, mucin
May coexist with sarcomatoid carcinoma, thymoma, thymic cyst
2 - 10 cm, rounded or irregular, with fibromuscular wall of variable thickness
Usually unilocular but may be multiloculated
Smooth inner lining, often mucoid contents
Microscopic (histologic) description
Squamous, simple columnar, pseudostratified columnar or mixed epithelial lining, usually with some gastric glandular mucosa, overlying a double layer of smooth muscle
Among NSGCTs, choriocarcinoma and embryonal carcinoma have the worst prognosis (J Surg Res 2021;267:25)
Case reports
25 year old man presented with cutaneous metastasis of primary mediastinal choriocarcinoma (J Cutan Pathol 2021;48:81)
26 year old man with primary mediastinal choriocarcinoma with diffuse metastasis to both lungs and multiple brain metastases (Medicine (Baltimore) 2019;98:e16411)
71 year old man on goserelin treatment for metastatic prostatic adenocarcinoma developed mediastinal choriocarcinoma with lung and vertebral metastases (Case Rep Pathol 2019;2019:2734815)
Treatment
Chemotherapy, radiotherapy and surgery
Treatment with cisplatin based therapy may improve the outcome
Gross description
Large, soft, friable, extensively hemorrhagic and with foci of necrosis
Microscopic (histologic) description
Intermingled syncytiotrophoblasts and cytotrophoblasts in a plexiform pattern or in disordered sheets
Syncytiotrophoblasts, large multinucleated cells with numerous, pleomorphic, dark staining nuclei, variably distinct nucleoli and abundant densely eosinophilic or amphophilic cytoplasm
Cytotrophoblasts, uniform, polygonal cells with round nuclei, prominent nucleoli and clear or eosinophilic cytoplasm
Germ cell tumor with morphological and immunohistochemical profile favoring choriocarcinoma (see comment)
Comment: A possibility of mixed germ cell tumor in the vicinity cannot be excluded.
Differential diagnosis
Sarcomatous carcinoma with giant cells:
Shows small to medium sized tumor cells with larger giant cells; this is in contrast with choriocarcinomas that show 2 cell populations of cytotrophoblasts and syncytiotrophoblasts
Embryonal carcinoma
Definition / general
Malignant nonseminomatous germ cell tumor characterized by embryonal type cells
Among NSGCTs, choriocarcinoma and embryonal carcinoma have the worst prognosis (J Surg Res 2021;267:25)
Case reports
12 year old boy with large soft tissue mass in mediastinum and left thoracic cavity, diagnosed as malignant mixed germ cell tumor with yolk sac tumor, immature teratoma and embryonal carcinoma components (Open Med (Wars) 2021;16:892)
23 year old man with anterior mediastinal mass and right pleural effusion developed pericardial effusion and cardiac tamponade (AJR Am J Roentgenol 1998;170:722)
25 year old man with an unresectable embryonal carcinoma of the anterior mediastinum that developed a bronchial fistula after systemic chemotherapy (Case Rep Radiol 2020;2020:7650206)
29 year old man with primary mediastinal embryonal carcinoma presented with pulmonary artery stenosis (Pneumonol Alergol Pol 2015;83:151)
12 year old boy with mixed germ cell tumor of the mediastinum diagnosed on core biopsy (Open Med (Wars) 2021;16:892)
16 year old boy with huge mediastinal mass diagnosed as mixed germ cell tumor with possible combination of embryonal carcinoma, yolk sac and teratoma (Case Rep Surg 2016;2016:7615029)
26 year old man with mixed germ cell tumor comprising of immature teratoma and seminoma diagnosed due to massive organ displacing tumor in right chest on chest Xray (Pathol Res Pract 2009;205:572)
29 year old man with disease progression despite systemic chemotherapy, diagnosed as mixed germ cell tumor on en bloc resection (J Surg Case Rep 2021;2021:rjab416)
Treatment
Resected after chemotherapy
Gross description
Heterogeneous cut surface
Solid, fleshy tumor with areas of hemorrhage and necrosis
Cystic spaces indicate presence of a teratomatous component
Gross images
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4.6 kg mediastinal mixed GCT, mostly teratoma
Microscopic (histologic) description
Morphology identical to pure germ cell component
Please refer to the sections above for microscopic description of individual components
Cytology description
Please refer to the sections above for cytological description of individual components
Positive stains
Please refer to the sections above for individual components
Negative stains
Please refer to the sections above for individual components
Sample pathology report
Anterior mediastinal mass, biopsy:
Malignant mixed germ cell tumor with seminoma (~50%), yolk sac tumor (~30%) and embryonal carcinoma (~20%) components (see comment)
Comment: The findings show majority of tumor comprised of sheets of polygonal cells with vesicular nuclei and prominent nucleoli. Intervening fibrous septa show lymphocytic infiltration. This component stains positive for immunohistochemical stains SALL4 and OCT3/4 while staining negative for CD30 and glypican 3. Another admixed component shows reticular pattern and Schiller-Duval bodies of cuboidal cells which stain positive for SALL4 and glypican 3 while staining negative for OCT3/4 and CD30. A small component comprised of large polygonal cells with pleomorphic nuclei, prominent nucleoli, numerous mitoses and necrosis is seen. This component stains positive for SALL4 and OCT3/4 and CD30 while staining negative for glypican 3.
See synoptic reporting for resection specimen.
Seminoma
Definition / general
Malignant germ cell tumor composed of seminomatous germ cells
A seminoma with any component of a nonseminomatous tumor is considered a nonseminomatous germ cell tumor (NSGCT)
Prominent eosinophilic nucleoli, pigment if present and a characteristic immunoprofile
Teratoma
Definition / general
Neoplasm of pluripotent cell origin that forms differentiated somatic type tissues, which may be exclusively mature (adult type), exclusively immature (embryonal or fetal) or a combination of both
Essential features
Tumor composed entirely of differentiated somatic type tissue, may be mature, immature or combined
24 year old man with multilocular thymic cyst and mature teratoma with a carcinoid component (Surg Case Rep 2022;8:24)
30 year old woman with mature mediastinal teratoma and somatic type malignancy including neuroblastoma and intestinal type adenocarcinoma (Int J Surg Case Rep 2021;80:105680)
Treatment
Complete surgical excision in cases of benign teratoma
Clinical images
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En bloc tumor resection
Gross description
Encapsulated masses with variegated cut surface and unilocular or multilocular cysts
Cyst contents may include clear fluid, mucoid material, sebaceous and keratinaceous debris, hair, fat, cartilage and rarely teeth or bone
Immature teratomas have soft to fleshy consistency or are extensively fibrous or cartilaginous
Hemorrhage and necrosis common
Gross images
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Excised tumor with rib
Microscopic (histologic) description
Haphazard distribution of mature somatic tissue is hallmark
Skin and cutaneous appendages are common, often lining cysts
Bronchial mucosa, glands, gastrointestinal mucosa, nerves and mature brain tissue
Large solid - cystic mass with intratumoral hemorrhage, capsular tear, marked heterogeneous enhancement and enlarged intratumoral vessels on CT scan (Acta Radiol 2016;57:98)
Radiology images
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CT scan of chest
Prognostic factors
No significant difference between yolk sac tumor and mixed germ cell tumor
Complete surgical resection is the most favorable prognostic factor
Case reports
15 year old boy with mediastinal yolk sac tumor infiltrating the heart (Exp Oncol 2018;40:82)
20 year old man with yolk sac tumor of anterior mediastinum presenting as acute pericarditis (Am J Case Rep 2022;23:e932616)
47 year old man presented with conus medullaris syndrome due to metastatic primary mediastinal yolk sac tumor (Int J Spine Surg 2015;9:59)
A 35 year old man presented with signs and symptoms of superior vena cava syndrome. On radiology, a mass was found in the anterior mediastinum, pushing on to the great vessels. It was resected. The photomicrograph above shows the histologic features. The tumor stained with SALL4 and OCT3/4 and was negative for CD30. What is the most likely diagnosis in this case?
Embryonal carcinoma
Seminoma
Teratoma
Yolk sac tumor
Board review style answer #1
B. Seminoma. The microscopic image shows sheets of tumor cells with fibrous septa infiltrated by lymphocytes. The cells are round to polygonal, uniform epithelioid cells with round to oval nuclei and vesicular chromatin. These features plus the IHC pattern are typical for seminoma. The morphology is not typical for the other germ cell tumors. Answer A is incorrect because embryonal carcinoma is positive for CD30 in addition to the other 2 markers given. Answer C is incorrect because teratoma is negative for all 3 markers. Answer D is incorrect because yolk sac tumor shows only SALL4 positivity. Therefore, the correct answer is seminoma.
A 24 year old man presented with shortness of breath, cough and dysphagia. Radiological examination shows a well demarcated, multilocular cystic mediastinal mass with fat, bone and areas of calcification. On resection, microscopic examination shows cystic cavities lined by stratified squamous keratinized epithelium with adnexal structures underneath. Foci showing undifferentiated mesenchyme, primitive cartilage, neuroectodermal tissue and mature bone are also seen. What is the most likely diagnosis in this case?
Embryonal carcinoma
Immature teratoma
Mature teratoma
Seminoma
Yolk sac tumor
Board review style answer #2
B. Immature teratoma. The radiological findings of the presence of fat, bone and calcification are typical of teratoma. Based on the presence of immature cartilage, mesenchyme and neuroectodermal tissue on microscopy, this represents immature teratoma. Answer C is incorrect because a mature teratoma will not show any such immature components. Answer A is incorrect because embryonal carcinoma does not show derivatives of all 3 germ cell layers; neither do seminoma or yolk sac tumor. Embryonal carcinoma shows uniform population of large polygonal cells with nuclei showing prominent nucleoli, many mitoses and necrosis. Answer D is incorrect because seminoma shows cells divided by incomplete fibrous septae with lymphocytic sprinkling and cells having eosinophilic nucleoli. Answer E is incorrect because yolk sac tumor shows many growth patterns but characteristic endodermal sinus-like formations (also known as Schiller-Duval bodies) can be identified in most cases.
Also known as poorly differentiated, nonkeratinizing, squamous cell thymic carcinoma or lymphoepithelioma-like thymic carcinoma
Originates from thymic epithelial cells and shows histologic and immunophenotypic evidence of squamous differentiation
WHO classification: lymphoepithelial carcinoma of the thymus
Essential features
Defined as a primary thymic epithelial neoplasm displaying overt cytologic evidence of malignancy with loss of organotypical features of thymic differentiation
Diagnosis of exclusion
Invasive growth pattern of nests and cords of tumor cells, which grow in sheets with a syncytial growth pattern and have vesicular nuclei with prominent nucleoli
Often have prominent associated lymphoid infiltrate within fibrous stroma
No pathognomonic molecular alterations have been identified
Clinical features
Presents with anterior mediastinal masses, often found incidentally
When symptomatic, clinical symptoms include chest pain, shortness of breath and weight loss (Am J Surg Pathol 2018;42:1224)
Diagnosis
Diagnosis of exclusion
Requires the presence of a poorly differentiated carcinoma primary to the thymus with an invasive growth pattern of nests and cords of tumor cells with syncytial growth and vesicular nuclei with prominent nucleoli
Radiology description
Typically appears as well demarcated anterior mediastinal masses
Positron emission tomography (PET) usually shows mild to moderate PET avidity
Prognostic factors
Staging at time of diagnosis is the most important prognostic factor
Staging performed using the AJCC 8th edition staging system for thymic carcinoma (J Thorac Oncol 2022;17:838)
52 year old man and 64 year old woman underwent complete surgical resection for thymic lymphoepithelioma-like carcinoma (Am J Transl Res 2021;13:1896)
60 year old man with right sided neck mass found to be an intrathyroidal lymphoepithelioma-like thymic carcinoma (APMIS 1996;104:419)
65 year old woman with chest pain and 81 year old woman with abnormal shadow on chest Xray (Surg Case Rep 2019;5:158)
Treatment
Surgical resection is still the predominant treatment
Radiotherapy may increase local regional relapse free survival with mild toxicities in advanced stage patients (Ann Thorac Surg 2017;104:1718)
In the largest study, 14 of 20 patients had no evidence of disease between 1.5 and 16 years after diagnosis (median survival: 4 years; mean survival: 5.5 years) (Oncol Lett 2014;8:2183)
Microscopic (histologic) description
Invasive growth pattern of cords, nests and trabeculae separated by fibrous stroma with variable prominent mature lymphoid infiltrates
Lymphoepithelioma-like pattern: irregular cords and islands of tumor cells separated by connective tissue stroma containing dense lymphoplasmacytic infiltrates
Desmoplastic pattern: irregular cords and nests of tumor cells separated by fibrous stroma with minimal inflammatory infiltrates
Can have both patterns
Can show focal areas of abrupt keratinization
Prominent areas of comedonecrosis
Uniform, poorly differentiated tumor cell population with round to oval nuclei, vesicular chromatin, prominent round eosinophilic nucleoli and an indistinct rim of eosinophilic cytoplasm
Syncytial growth pattern of tumor cells with rare pleomorphic and multinucleated cells
Cohesive population of large cells with round to oval nuclei containing a single nucleolus and scattered heterochromatin (Am J Surg Pathol 2018;42:1224)
Abundant junctional complexes, with dense plaques and well formed desmosomes containing attached short tonofilaments (Am J Surg Pathol 2018;42:1224)
Molecular studies reveal a heterogeneous group of variants with low numbers of mutations, similar to other molecular studies done on thymic carcinoma
5 patients had somatic variants in 6 genes known to play a significant role in tumor development and growth, including IDH1, CDKN2A, FGFR3 and others (Am J Surg Pathol 2018;42:1224)
Sample pathology report
Thymus, resection:
Poorly differentiated thymic squamous cell carcinoma, predominantly nonkeratinizing (lymphoepithelial carcinoma) (see synoptic report and comment)
Comment: The tumor cells are positive for p40, CD117, CD5 and PDL1.
Can sometimes have areas suspicious for invasion; however, they are generally well circumscribed with thick fibrous septa (not very inflammatory) and no obvious invasion or necrosis
Lymphoepithelial carcinoma may arise in extramediastinal locations as a primary tumor
Outside the mediastinum these tumors tend to be strongly correlated with EBV positivity
Strict clinical correlation and detailed history required to rule out metastasis
Board review style question #1
A 62 year old patient presented with a 9 cm anterior mediastinal mass (see image above). What would help differentiate this lesion from a metastasis from a head and neck lymphoepithelioma-like thymic carcinoma?
Detailed clinical history
Immunohistochemistry for p63 and cytokeratins
In situ hybridization for EBER
In situ hybridization for HPV
Next generation sequencing
Board review style answer #1
A. Detailed clinical history. Immunohistochemistry and in situ hybridization in general are unhelpful in distinguishing lymphoepithelial carcinomas from different sites. Although a much lower percentage of lymphoepithelial carcinomas test positive for EBV compared to other primary sites, a significant proportion are still reported to express EBV. HPV ISH would not be helpful as it would be expected to be negative. The most useful way to separate these tumors is through a detailed clinical history, including thoracic and head and neck radiologic studies.
Which immunohistochemical stains would be most helpful in distinguishing a primary squamous cell thymic carcinoma from metastatic lesions from other primary sites?
CD5 and CD117
Cytokeratins
p16
p63
Board review style answer #2
A. CD5 and CD117 would be the most helpful in establishing thymic origin in this scenario. While primary lymphoepithelioma-like thymic carcinoma will express keratins, p16 and p63, so would poorly differentiated squamous cell carcinomas elsewhere in the body; however, few lesions outside the body would have CD5 and CD117 positivity.
Also called idiopathic mediastinal fibrosis, fibrosing mediastinitis
Fibroinflammatory lesion, usually anterosuperior mediastinum, often presenting with superior vena cava syndrome or cardiorespiratory compromise
All ages
Clinical features
Associated with other idiopathic fibrosing conditions such as inflammatory pseudotumor of orbit, retroperitoneal fibrosis, Riedel struma, sclerosing cholangitis
Also associated with pulmonary or mediastinal nodal infection due to fungi (Histoplasma), methysergide treatment, phlebitis, syphilis, trauma
Radiology description
Asymmetric mediastinal widening with projection of mass into upper lung field
Radiologically divided into 2 types: focal (common) and diffuse
Focal: localized and calcified mass in paratracheal or subcarinal compartments of mediastinum or in pulmonary hilum
Diffuse: diffusely infiltrating, noncalcified mass affecting multiple mediastinal compartments
Additional pulmonary findings includes infiltrates, consolidation and pleural effusion
Prognostic factors
Prognosis depends mainly on location of fibrosis and structures involved
Case reports
30 year old man with idiopathic mediastinal fibrosis presenting as mediastinal compression syndrome
(Indian J Med Sci 2005;59:268)
46 year old woman with tracheobronchial narrowing, severe hyperemia and mucosal edema
(Rev Pneumol Clin 2009;65:159)
70 year old woman with multifocal fibrosclerosis with intracardiac solid masses
(Hum Pathol 2006;37:493)
Defect in nicotinic acetylcholine receptor (AChR) present in subsynaptic membrane of neuromuscular junction (at motor end plate), due to circulating autoantibodies to receptor
Acetylcholine receptor also present in normal thymus, in myoid type cells
Thymus may contain ectopic germinal centers with B cells producing pathogenic antiacetylcholine receptor antibodies (Ann N Y Acad Sci 2008;1132:135)
Pathophysiology
May be due to T cells attacking myoid cells, then T cells induce B cells to produce autoantibodies; physiological connection with thymomas is unclear
Two step hypothesis: hyperplastic medullary thymic epithelial cells are involved in provoking infiltration and thymic myoid cells (with intact AChR) are involved in germinal center formation (Am J Pathol 2007;171:893)
MG patients have high number / ratio and abnormal distribution of thymic dendritic cells, which may be actively involved in pathogenesis (Zhonghua Yi Xue Za Zhi 2008;88:3349)
Autoimmunity may be related to increased toll-like receptor 4 expression in thymus of some myasthenic patients (Am J Pathol 2005;167:129)
Clinical features
12% of myasthenia gravis (MG) patients have other autoimmune diseases, including Graves disease, rheumatoid arthritis
MG patients with thymomas may have autoantibodies to titin or other striated muscle antigens
65% of patients have thymic hyperplasia, 25% normal thymus, 10% thymomas; risk factors for thymoma are males with initial MG symptoms age 50+ years
Present or develops in 30 - 45% of patients with thymomas, usually months / years after excision of thymoma
Lymphoid follicles in thymoma or adjacent thymus indicates higher risk for MG
MG associated thymomas are morphologically similar to non-MG associated thymomas
Due to stress (chronic debilitating disease), HIV or other infections, prolonged protein malnutrition and immunosuppressive or cytotoxic drugs, graft versus host reaction
Seen in newborn infants with chorioamnionitis and sepsis
Thymus size is significantly reduced in preterm infants born to mothers with subclinical, histologically proven chorioamnionitis
(Hum Pathol 2000;31:1121)
Microscopic (histologic) description
Preservation of lobular architecture and Hassall corpuscles but marked lymphocyte depletion (particularly with HIV)
Vessels are large compared to size of lobules
Frequent plasma cells, fibrohyaline changes of basement membrane of vessels and thymic epithelium
HIV patients also have effacement of corticomedullary junction and inconspicuous Hassall corpuscles
Descending necrotizing mediastinitis: rare spreading of cervical infection to mediastinum (Clin Imaging 2005;29:138)
Microscopic (histologic) images
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Extensive acute inflammation
Fibrinoinflammatory exudate
Mediastinitis, chronic
Definition / general
May compress superior vena cava and simulate malignancy
Usually anterior to tracheal bifurcation
Some cases may represent fibrosing mediastinitis
Microscopic (histologic) description
Granulomas, fibrosis; may be fungus, Histoplasma (with thick fibrous capsule), mycobacteria (thin fibrous capsule)
Thymic dysplasia
Definition / general
Congenital thymic alteration due to developmental arrest
Lack of differentiation of thymic epithelium, responsible for absence of Hassall corpuscles, is main feature (Histopathology 1992;21:499)
Clinical features
Associated with severe combined immunodeficiency syndrome, ataxia telangiectasia, chromosomal instability syndromes, Nezelof syndrome (Arch Pathol Lab Med 1987;111:1118)
Incomplete form of DiGeorge syndrome is congenital anomaly with a constellation of findings that includes thymic hypoplasia
(J Cutan Pathol 2008;35:380); complete form has absent thymus
Gross description
Small thymus (< 5 g)
Microscopic (histologic) description
Tubules and rosettes of primitive appearing epithelium without segregation into cortical and medullary regions
Fibrous tissue lined by bland mesothelium, rarely with papillary hyperplasia, no cholesterol granulomas, no smooth muscle, no cartilage, no specialized epithelium
AJCC/TNM staging is used for predicting outcomes of thymic tumors, such as recurrence (in the lower stages) and disease specific survival (in the higher stages); reference numbers are available (J Thorac Oncol 2014;9:S65)
Pre operative clinical staging is based on physical examination and imaging; post operative clinical staging may be supplemented by pathological findings
Stage is determined primarily by levels of local invasion of a thymic malignancy into surrounding mediastinal structures (T classification) while nodal involvement and metastatic spread are much rarer events
There is no recommended histologic grading system for thymic tumors
AJCC 7th edition staging was sunset on December 31, 2017; as of January 1, 2018, use of the 8th edition is mandatory
T, N and M categories are the mainstay for predicting recurrence and survival in patients with thymic tumors
Local invasion (T category) is the primary determinant of staging
Primary tumor (T)
TX: primary tumor cannot be assessed
T0: no evidence of primary tumor
T1: tumor encapsulated or extending into the mediastinal fat, may involve the mediastinal pleura
T1a: tumor with no mediastinal pleura involvement
T1b: tumor with direct invasion of mediastinal pleura
T2: tumor with direct invasion of the pericardium (either partial or full thickness)
T3: tumor with direct invasion into any of the following: lung, brachiocephalic vein, superior vena cava, phrenic nerve, chest wall or extrapericardial pulmonary artery or veins
T4: tumor with invasion into any of the following: aorta (ascending, arch or descending), arch vessels, intrapericardial pulmonary artery, myocardium, trachea, esophagus
Notes:
Involvement must be microscopically confirmed in pathological staging, if possible
T categories are defined by levels of invasion; they reflect the highest degree of invasion regardless of how many other (lower level) structures are invaded
N1: metastasis in anterior (perithymic) lymph nodes
N2: metastasis in deep intrathoracic or cervical lymph nodes
Note:
Involvement must be microscopically confirmed in pathological staging, if possible
Distant metastasis (M)
M0: no pleural, pericardial or distant metastasis
M1: pleural, pericardial or distant metastasis
M1a: separate pleural or pericardial nodule(s)
M1b: pulmonary intraparenchymal nodule or distant organ metastasis
AJCC prognostic stage grouping
Stage I:
T1a, T1b
N0
M0
Stage II:
T2
N0
M0
Stage IIIA:
T3
N0
M0
Stage IIIB:
T4
N0
M0
Stage IVA:
any T
N1
M0
any T
N0, N1
M1a
Stage IVB:
any T
N2
M0, M1a
any T
any N
M1b
Board review style question #1
A 62 year old man presented with a large thymic carcinoma directly invading pericardium and no
metastatic spread. What is the pT category per the AJCC/TNM 8th edition?
May involve any mediastinal compartment including anterior (prevascular), posterior (paravertebral), middle (visceral) and superior mediastinum (Am J Surg Pathol 2018;42:761)
Clinical features
Typically presents with symptoms related to a large mediastinal mass, which may include pain (chest, back, epigastric, shoulder), chest tightness, dyspnea, cough, dysphagia, hemoptysis, Horner syndrome, hemothorax, obstructive pneumonia or syncope (Am J Surg Pathol 2018;42:761)
Aggressive clinical course is probably due to site specific factors, such as proximity to critical anatomic structures as well as late detection with large tumor size at diagnosis
Adverse outcome may also be related to the high rate of poorly differentiated morphology
No known differences are noted in the clinical behavior of monophasic and biphasic synovial sarcoma; therefore, this distinction is not important for clinical management purposes
Poorly differentiated morphology is associated with older age at presentation and poor prognosis
Tumors are grossly tan-white, soft to rubbery cut surface with hemorrhage and necrosis
May show cystic degeneration and gelatinous change
Often appear grossly well circumscribed / lobulated but usually show subtle invasive growth into adjacent structures, including chest wall, great vessels, heart, pericardium, pleura, ribs or vertebra (Mod Pathol 2007;20:760, Am J Surg Pathol 2005;29:569)
Immunohistochemistry with antibodies directed against the SS18::SSX fusion protein and the C terminus of SSX are sensitive and specific markers of synovial sarcoma, especially when performed together
If positive in the correct morphological context, molecular confirmation is usually not required
Highly sensitive nuclear marker of synovial sarcoma
Not specific, since other tumors can show staining
Most valuable to identify cases in which molecular genetic testing is likely to be positive (i.e. a negative stain is a good "rule out" marker but positive stain should be confirmed by molecular studies if the diagnosis is in doubt)
Can be focally positive, which may make the differential diagnosis with malignant peripheral nerve sheath tumor (MPNST) quite difficult; this distinction may require molecular analysis
In the absence of SS18::SSX and SSX C terminus immunohistochemistry, definitive diagnosis often requires ancillary molecular genetic testing due to the rare primary site; these tests are possible even on small biopsies
t(X;18)(p11;q11)
Present in > 95%
Leads to the fusion of SS18 (also known as SYT or SST) with one of the SSX genes (Oncogene 2001;20:5755)
Can be detected by next generation sequencing assays, reverse transcription polymerase chain reaction (RT-PCR) or fluorescence in situ hybridization (FISH) (Appl Immunohistochem Mol Morphol 2008;16:246)
SS18::SSX1 fusion is the most common fusion gene, present in 67% of cases, including most biphasic tumors
A 37 year old man presented with shortness of breath and dull chest pain. He was found to have a 15 cm mass in the anterior mediastinum. Representative photomicrographs from the needle biopsy are shown below. What is the most likely molecular alteration in this tumor?
EWSR1::FLI1
FUS::DDIT3
NAB2::STAT6
SS18::SSX1
WWTR::CAMTA
Board review style answer #1
D.SS18::SSX1. t(X;18)(p11;q11) is characteristically seen in synovial sarcoma and leads to the fusion of SS18 (also known as SYT or SST) with one of the SSX genes. It can be detected by next generation sequencing, RT-PCR or FISH. SYT::SSX1 is the most common fusion in synovial sarcoma, present in 67% of cases. The tumors characterized by the other fusion genes listed would not be expected to show the cellular monomorphic spindle cell sarcoma observed in the photomicrograph. EWSR1::FLI occurs in Ewing sarcoma; FUS::DDIT3 is observed in myxoid liposarcoma; NAB2::STAT6 fusion characterizes solitary fibrous tumor; and WWTR::CAMTA fusion is present in epithelioid hemangioendothelioma.
Which of the following features essentially excludes a monophasic synovial sarcoma from the differential diagnosis in a mediastinal needle biopsy of a spindle cell tumor?
Focal CD99 expression
Focal S100 expression
Lack of keratin expression
Marked nuclear pleomorphism
Small round blue cell morphology
Board review style answer #2
D. Marked nuclear pleomorphism. Monophasic synovial sarcomas are spindle cell sarcomas with striking nuclear monotony and generally should not show marked nuclear pleomorphism, even in poorly differentiated examples. The lack of keratin expression, especially on small biopsies, does not exclude the diagnosis if the correct morphology is observed and molecular confirmation could be considered in this context. Focal S100 expression can be observed in synovial sarcoma and in this setting, molecular analysis may be needed to differentiate it from malignant peripheral nerve sheath tumor. Poorly differentiated examples of synovial sarcoma can show small round blue cell morphology, often resembling Ewing sarcoma, which also may require molecular analysis since both entities can express CD99.
59 year old man with tumor demonstrating papillary, acinar and cribriform structure and which produced abundant extracellular mucin
(Hum Pathol 2005;36:219)
61 year old woman with tumor with numerous psammoma bodies and 82 year old woman with case arising from thymic cyst with areas of transition from benign to dysplastic epithelium
(Am J Surg Pathol 2007;31:1330)
Irregular fascicles of fusiform and pleomorphic cells with amphophilic or eosinophilic cytoplasm, hyperchromatic nuclei, prominent nucleoli (at least focally), brisk mitotic activity, often atypical mitotic figures
May have epithelioid foci
Usually transitional areas with spindle cell thymoma
May also have lymphoepithelioma-like or anaplastic areas
Rarely rhabdomyogenic foci with cross striations
Microscopic (histologic) images
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Atypical population
of spindle cells
with frequent
mitotic figures
Positive stains
EMA (may be focal), keratin (including CAM5.2), vimentin, muscle markers in areas of myogenic differentiation
Resembles cutaneous proliferating epidermoid cyst and proliferating trichilemmal cyst
Microscopic (histologic) description
Pseudoepitheliomatous hyperplasia of cyst lining cells (narrow tongues of squamoid epithelium extending deeply into fibrous cyst wall) with reactive changes but no dysplasia
May be idiopathic or seen in association with other autoimmune disorders, including myasthenia gravis, Graves disease, systemic lupus erythematosus, rheumatoid arthritis, scleroderma and allergic vasculitis
Comment: Thymic tissue, consisting of thymic epithelial cells and associated small mature lymphocytes, in addition to occasional lymphoid follicles with prominent germinal centers. Hassall corpuscles are also noted. These histopathologic findings represent thymic follicular hyperplasia, a condition present in association with myasthenia gravis. Defining morphologic features of thymoma are not present.
Distorted architecture with desmoplasia and often increased cytologic atypia
Board review style question #1
Which of the following is a feature seen in thymic follicular hyperplasia?
Diffuse meshwork of epithelial cells
Effacement of normal thymic architecture
Lack of reactive secondary follicles
Large lobules separated by fibrous bands
Normal distribution of cortex and medulla
Board review style answer #1
E. Normal distribution of cortex and medulla. Answers A - D are incorrect because effacement of normal thymic architecture, large lobules separated by fibrous bands, lack of reactive secondary follicles and diffuse meshwork of epithelial cells are features of thymoma.
Which of the following is the most common thymic entity found in patients with myasthenia gravis?
Lymphoma
Thymic follicular hyperplasia
Thymoma
True thymic hyperplasia
Board review style answer #2
B. Thymic follicular hyperplasia. Thymic follicular hyperplasia may be seen in association with autoimmune disorders, including myasthenia gravis, Graves disease, systemic lupus erythematosus, rheumatoid arthritis, scleroderma and allergic vasculitis.
Suggested on chest Xray, confirmed by CT; possibly MRI
Preresection biopsy usually not performed or necessary
Laboratory
None for thymoma
Acetylcholine receptor binding antibodies if myasthenia gravis
Possibly workup for other paraneoplastic / autoimmune syndromes if clinically suspicious
Radiology description
Chest Xray: usually ovoid or lobulated, smooth, well marginated mass, projecting over the mediastinum, more commonly protruding unilaterally (J Thorac Oncol 2010;5:S296)
Chest CT: typically well defined, round or lobulated, homogeneous lesion that enhances after contrast injection
Can be heterogeneous or cystic
Used to evaluate for invasion
MRI increasingly utilized, specifically in differentiating thymoma from thymic cyst or thymic hyperplasia, to identify phrenic nerve involvement or to evaluate for invasion in patients with contraindication to iodinated contrast (Magn Reson Imaging Clin N Am 2015;23:165, J Cancer 2019;10:3208)
Radiology images
Contributed by Anja C. Roden, M.D.
WHO type A thymoma
Prognostic factors
Stage (TNM stage; previously Masaoka-Koga stage), in some studies independent of resection status and WHO subtype (J Thorac Oncol 2015;10:691)
Complete resection associated with overall survival
WHO subtype associated with overall and disease free survival
Size of thymoma, age, weight loss are associated with outcome in some studies
Thymectomy with or without resection of adjacent structures depending on extent of tumor, whenever possible
Possibly neoadjuvant chemotherapy or radiation or postoperative chemotherapy or radiation, depending on stage and involvement of margins
Immune checkpoint inhibitors: prospective trials have shown durable responses and appears to improve survival in patients with relapsed thymoma
Controversial, possibly contraindicated; severe and life threatening immune toxicity can occur and therefore extreme caution is necessary while using immunotherapy in patients with thymoma
Currently, this treatment is only recommended in the setting of clinical trials with close monitoring (Mediastinum 2021;5:23)
Sampling of perithymic lymph nodes important for staging
Gross images
Contributed by Anja C. Roden, M.D.
Gross specimen of thymoma
Frozen section description
Lobulated neoplasm with fibrous bands and cellular lobules
Sometimes only a few fibrous bands present
Cellular lobules comprised of (i) a mixture of lymphocytes and large polygonal (epithelial neoplastic) cells, (ii) polygonal cells only without or only with a few lymphocytes or (iii) bland short spindle cells
Associated cyst(s) possible
Evaluation of margins: discussion with surgeon important to identify true surgical margin as not the entire specimen surface is considered surgical margin
Invasion into adjacent structures (mediastinal pleura, pericardium, phrenic nerve, lung, great vessels, among others)
Frozen section images
Contributed by Anja C. Roden, M.D.
Lobulated architecture
Abundant lymphocytes
Hassall corpuscle-like elements
Surgical margin negative
Microscopic (histologic) description
Low magnification: lobulated architecture with cellular lobules and intersecting fibrous bands; usually at least partially encapsulated
High magnification: neoplastic epithelial cells (polygonal or spindled), various numbers of lymphocytes (thymocytes)
Sometimes associated with cyst(s) or focal cystic changes
Thymomas may be almost entirely necrotic, sclerosed or ossified
Entities that have been obsoleted in the 2021 WHO: microscopic thymoma (small thymic epithelial cell nests unlikely to be neoplastic; do not appear to be precursors of thymoma), sclerosing thymoma (appears to be sclerotic change of existing thymoma rather than distinct form of thymoma)
Lipofibroadenoma:
Resembles fibroadenoma of the breast
Fibrotic and hyaline stroma, focal adipose tissue, strands of bland appearing epithelial cells and a few lymphocytes
WHO type A thymomas, various patterns and atypical type A variant
WHO type A thymomas, various patterns and atypical type A variant
WHO type AB thymoma
WHO type AB thymoma
WHO type B1 thymoma
WHO type B2 thymoma
Thymoma: core needle biopsy
Thymoma: core needle biopsy
Thymoma: core needle biopsy
Micronodular thymoma with lymphoid stroma
Metaplastic thymoma
Lipofibroadenoma
Lipofibroadenoma
Thymoma with extensive sclerosis and ossification
Small thymic epithelial cell nest
Cytology description
Dual cell population: small lymphocytes and polygonal epithelial cells (isolated or clustered); possibly sheets of bland, elongated or spindled cells or polygonal epithelial cells
Loss of heterozygosity in 6q25.2-25.3: most common chromosomal deletion, FOXC1 is potential target (tumor suppressor gene) (Clin Cancer Res 2013;19:1960)
GTF2I missense mutations (codon L424H) in 74 - 82% of type A and AB thymomas and 21 - 32% of B1 - B3 thymomas, appears thymoma specific oncogene (Cancer Cell 2018;33:244, Nat Genet 2014;46:844)
No diffuse meshwork of keratin positive neoplastic cells
Effaced architecture in lymphoma versus lobulated architecture in thymoma
LMO2 expressed in neoplastic lymphoblasts of T acute lymphoblastic leukemia (T ALL) and absent in thymoma (Am J Clin Pathol 2016;145:180)
CD20 positive B cells in small B cell lymphomas; classic Hodgkin lymphoma can show lobulated architecture but is comprised of mixed chronic inflammation often with eosinophils and scattered large Reed-Sternberg cells and Hodgkin cells
Lacks lobulated architecture and lacks the diffuse meshwork of keratin positive neoplastic cells (although there are keratin positive epithelial cells scattered throughout the benign thymic gland)
Usually intimately associated with adipose tissue without capsule
Lymphoid follicles in thymic follicular hyperplasia (caveat: can also be seen in micronodular thymoma with lymphoid stroma or on rare occasions in thymoma)
A. Epithelial cell. In thymomas, epithelial cells are the neoplastic cells.
(B) Incorrect. A few scattered benign histiocytes might be present in
these tumors.
(C) Incorrect. Lymphocytes, which are predominantly thymocytes, are considered reactive.
(D) Incorrect. Although classic Hodgkin lymphomas can exhibit a lobulated architecture, usually they do not have so sharply demarcated fibrous bands. Reed-Sternberg cells or Hodgkin cells are not identified.
(E) Incorrect. Thymocytes are considered reactive in these tumors.
What is an important prognostic parameter in thymomas?
Association with a cyst
Male sex
Presence of fibrous bands
Surgical resection margin
Thymic follicular hyperplasia
Board review style answer #2
D. Surgical resection margin. Complete resection is an important prognostic parameter in thymomas.
(A) Incorrect. Cystic changes have no impact on prognosis.
(B) Incorrect. Sex is not associated with prognosis.
(C) Incorrect. The presence of fibrous bands is not associated with prognosis.
(E) Incorrect. Thymic follicular hyperplasia in the background thymic gland has no prognostic implication.
Comment: Sections show thymic tissue, characterized by lobular architecture featuring small cortical thymocytes that border interconnecting medullary tissue containing many Hassall corpuscles. The lobules are separated by mature fibroadipose tissue. There is no evidence of lymphoid hyperplasia. The average weight of the thymus gland in this age group is ~25 - 35 g. The thymus in this case weighs 90 g. These findings are consistent with true thymic hyperplasia.
Usually morphology is different; however, seminoma can have lymphoid hyperplasia and remnant thymic tissue
Board review style question #1
Which of the following statements most correctly describes true thymic hyperplasia?
Effacement of normal thymic architecture
Expansion of the normal component of the thymic gland
Increased number of reactive secondary follicles
Large lobules separated by fibrous bands
Board review style answer #1
B. Expansion of the normal component of the thymic gland. Answers A and D are incorrect because effacement of normal thymic architecture and large lobules separated by fibrous bands are features of thymoma. Answer C is incorrect because reactive secondary follicles are features of thymic follicular hyperplasia.
Which type of thymoma can resemble the morphologic features of true thymic hyperplasia?
Type A
Type AB
Type B1
Type B2
Type B3
Board review style answer #2
C. Type B1. Thymoma type B1 can closely resemble true thymic hyperplasia particularly in small biopsies; however, thymoma type B1 has larger lobules, thicker fibrous capsule and septa and predominance of cortical over medullary areas. There are no or very few Hassall corpuscles in type B1 thymoma in comparison to true thymic hyperplasia. Scattered large neoplastic epithelial cells (keratin+) obscured by a diffuse, small lymphocytic background are present.