[Pathology] Atlas of Thymic Carcinoma

Thymic Carcinoma, Atlas of Thymic Carcinoma, [Pathology] Atlas of Thymic Carcinoma, Atlas of Mediastinal Pathology, Free medical atlases

Thymic carcinoma corresponds to the most aggressive end of the spectrum of primary thymic epithelial neoplasms. Two features of thymic carcinoma deserve special attention: (1) there are no specifi c morphologic features that permit making an a priori diagnosis of thymic carcinoma based solely on their histology (these tumors usually resemble a variety of carcinomas commonly seen at other organs) and (2) the diagnosis of thymic carcinoma is a diagnosis of exclusion that requires strict clinicopathologic correlation and demonstration of the absence of a primary tumor elsewhere on thorough clinical, endoscopic, and radiographic examination. Thymic carcinoma is easily distinguishable from thymoma by the lack of any of the organotypical features of thymic differentiation associated with the latter. Also, thymic carcinomas are not generally associated with autoimmune disorders or other paraneoplastic syndromes. A large number of histologic variants of thymic carcinoma have been described (Table 2.4).

Table 2.4 Histologic variants of thymic carcinoma  

Fig. 2.98 Gross appearance of well-differentiated squamous cell carcinoma 

of the thymus. The tumor is composed of a well-circumscribed

mass surrounded by a partial fibrous capsule and shows a variegated cut

surface, with gray-white, rubbery tissue containing areas of hemorrhage and necrosis  

Fig. 2.99 Histologic appearance of squamous cell carcinoma of the

thymus. The tumor is composed of infiltrative, irregular islands 

of atypical tumor cells with well-defined cell borders and marked cytologic

atypia. The infi ltrative appearance of the tumor cell islands serves to

separate this tumor from an atypical thymoma (WHO type B3)  

Fig. 2.100 Well-differentiated mucoepidermoid carcinoma of the 

thymus shows sheets of squamoid intermediate cells admixed with 

scattered mucocytes. Mucin-filled cysts can also be seen  

Fig. 2.101 Mucicarmine stain shows intraepithelial mucin within 

scattered mucocytes as well as lakes of mucin within cystlike spaces

Fig. 2.102 Gross appearance of a mucoepidermoid carcinoma of the

thymus with cystic changes; this is one of the histologic variants of

thymic carcinoma that has been associated more often with cystic

changes. Tumors with extensive cystic degeneration can be mistaken

for acquired multilocular thymic cysts; thorough sampling is always

advised in such cases to identify the neoplastic elements 

  

Fig. 2.103 Histologic appearance of mucoepidermoid carcinoma of the

thymus with cystic degeneration. Notice the cystic space on the right

surrounded by lymphoid infiltrates with hyperplastic lymphoid follicles

Fig. 2.104 Poorly differentiated, nonkeratinizing (lymphoepitheliomalike) 

squamous cell carcinoma of the thymus is characterized by irregular 

islands of tumor cells that often display central, comedo-like foci of

necrosis. The tumors can contain a prominent lymphoplasmacytoid

stromal component similar to that observed in their nasopharyngeal

counterparts, or they can show an extensively fi brotic stroma, such as in

the current example  

Fig. 2.105 Another example of a poorly differentiated, nonkeratinizing 

(lymphoepithelioma-like) squamous cell carcinoma of the thymus

showing the classic dense lymphoplasmacellular stroma surrounding

the tumor cell islands  

Fig. 2.106 Higher magnification of lymphoepithelioma-like carcinoma

 of the thymus shows sheets of cells with vesicular nuclei and

frequent mitotic figures  

Fig. 2.107 High-power image of the cells in lymphoepithelioma-like

carcinoma of the thymus. The cytologic appearance of these cells is

quite distinctive; they are round to oval, with indistinct cytoplasm and

dispersed nuclear chromatin but with single prominent eosinophilic

nucleoli. Some cases, particularly those in children and Asian patients,

have been shown to be associated with Epstein-Barr virus infection  

Fig. 2.108 This desmoplastic variant of lymphoepithelioma-like

 carcinoma of the thymus is characterized by short strands and islands of

tumor cells surrounded by abundant fibrous stroma  

Fig. 2.109 Gross image showing invasion of the lung by

lymphoepithelioma- like carcinoma of the thymus. Lymphoepitheliomalike 

carcinoma of the thymus is a highly aggressive tumor that is associated

with a poor prognosis. The tumors are often widely invasive at the time of

diagnosis and can metastasize to the lymph nodes and extrathoracic sites  

Fig. 2.110 Clear cell carcinoma of the thymus is characterized by 

lobules composed of cells with abundant clear cytoplasm. The tumors can

resemble metastases from renal cell carcinoma or other types of clear

cell cancers arising at other organs  

Fig. 2.111 Higher magnification of clear cell carcinoma of the thymus

shows large cells with abundant water-clear cytoplasm and scattered

mitotic fi gures. Clinical correlation is required in these cases to rule out

the possibility of a metastasis from an occult primary tumor  

Fig. 2.112 Clear cell carcinoma of the thymus can sometimes be the

result of secondary clear cell changes in well-differentiated squamous

cell carcinoma caused by intracytoplasmic accumulation of glycogen  

Fig. 2.113 Basaloid carcinoma of the thymus is characterized by

strands and sheets of hyperchromatic round to oval cells displaying

prominent peripheral palisading of nuclei. The tumor cells have

increased nuclear chromatin and prominent nucleoli, and scattered

mitotic figures are commonly seen  

Fig. 2.114 Higher magnification of basaloid carcinoma of the thymus

shows small, oval, and spindle cells with hyperchromatic nuclei and an

inconspicuous rim of cytoplasm. The tumors are very cellular and display 

high mitotic activity and apoptosis. Notice the prominent peripheral 

palisading of cells at the borders of the tumor cell islands  

Fig. 2.115 Basaloid carcinoma of the thymus can occasionally contain

large, myoid cells scattered within the tumor. In such instances, the

myoid cells are strongly positive for skeletal muscle markers, such as

desmin, myogenin, and Myo-D1 

  

Fig. 2.116 Primary adenocarcinoma of the thymus is extremely rare

and resembles adenocarcinomas arising in the gastrointestinal tract;

they can be of either mucinous or nonmucinous types. Thorough clinical, 

endoscopic, and radiographic correlation is indicated to rule out the

possibility of a metastasis from an occult primary tumor in such cases  

Fig. 2.117 Mucinous adenocarcinoma of the thymus shows small

glands floating in pools of mucin similar to what is observed in socalled 

“colloid” carcinoma arising from various organs (such as the

breast, colon, and gallbladder). Signet-ring cells can also be commonly

seen in such instances. In such cases, thorough endoscopic and radiologic 

studies are indicated to rule out the possibility of a metastasis

from an occult primary tumor  

Fig. 2.118 Spindle-cell (sarcomatoid) carcinoma of the thymus is a

rare variant of thymic carcinoma characterized by an infiltrative atypical 

spindle-cell proliferation. A preexisting conventional spindle-cell

thymoma component can often be appreciated in these tumors. They are

generally widely invasive at the time of initial diagnosis and capable of

distant metastases  

Fig. 2.119 Higher magnification of spindle-cell thymic carcinoma

shows oval to spindle cells with hyperchromatic nuclei, prominent

nucleoli, and frequent mitotic figures. The tumor cells are positive for

cytokeratin and focally for p63 and show a high proliferation index with

Ki-67  

Fig. 2.120 Anaplastic carcinoma of the thymus shows poorly differentiated 

tumor cell proliferation with striking nuclear pleomorphism

resembling a high-grade pleomorphic sarcoma. The diagnosis is one of

exclusion and requires demonstration of reactivity of the tumor cells for

epithelial markers by immunohistochemistry or evidence of epithelial

differentiation on electron microscopic examination  

Suggested Reading

Chalabreysse L, Roy P, Cordier J-F, Loire R, Gamondes JP, ThivoletBejui F. Correlation of the WHO schema for the classification of thymic epithelial neoplasms with prognosis: a retrospective study of 90 tumors. Am J Surg Pathol. 2002;26:1605–11.

Choi WWL, Lui YH, Lau WH, Crowley P, Khan A, Chan JK. Adenocarcinoma of the thymus: report of two cases, including a previously undescribed mucinous subtype. Am J Surg Pathol. 2003;27:124–30.

Hasserjian RP, Klimstra DS, Rosai J. Carcinoma of the thymus with clear cell features: report of eight cases and a review of the literature. Am J Surg Pathol. 1995;19:835–41.

Kalhor N, Suster S, Moran CA. Spindle cell thymoma with prominent papillary and pseudopapillary features: A clinicopathologic study of 10 cases. Am J Surg Pathol. 2011;35:372–7.

Koga K, Matsuno Y, Noguchi M, Mukai K, Asamura H, Goya T, Shimosato Y. A review of 79 thymomas: modification of staging system and reappraisal of conventional division into invasive and non-invasive thymoma. Pathol Int. 1994;44:359–67.

Matsuno Y, Morozumi N, Hirosashi S, Shimosato Y, Rosai J. Papillary carcinoma of the thymus. Report of four cases of a new microscopic type of thymic carcinoma. Am J Surg Pathol. 1998;22:873–80.

Moran CA, Suster S. Mucoepidermoid carcinomas of the thymus. Clinicopathologic study of 6 cases. Am J Surg Pathol. 1995;19:826–34.

Moran CA, Suster S. Thymoma with prominent cystic and hemorrhagic changes and areas of necrosis and infarction. A clinicopathologic study of 25 cases. Am J Surg Pathol. 2001;25:1086–90.

Moran CA, Suster S. Ancient (sclerosing) thymomas. A clinicopathologic study of 10 cases. Am J Clin Pathol. 2004;121:867–71.

Moran CA, Suster S. Thymic carcinoma: current concepts and histologic features. Hematol Oncol Clin North Am. 2008;22:393–407.

Moran CA, Kalhor N, Suster S. Invasive spindle cell thymomas (WHO type A): a clinicopathologic correlation of 41 cases. Am J Clin Pathol. 2010;134:793–8.

Pan CC, Chen WY, Chiang H. Spindle cell and mixed spindle/lymphocytic thymomas: an integrated clinicopathologic and immunohistochemical study of 81 cases. Am J Surg Pathol. 2001;25:111–20.

Rieker RJ, Hoegel J, Morresi-Hauf A, Hofmann WJ, Blaeker H, Penzel R, Otto HF. Histologic classification of thymic epithelial tumors: comparison of established classifications schemes. Int J Cancer. 2002;98:900–6.

Shimosato Y, Kameya T, Nagai K, Suemasu K. Squamous cell carcinoma of the thymus: an analysis of 8 cases. Am J Surg Pathol. 1997;1:109–21.

Snover DC, Levine GD, Rosai J. Thymic carcinoma: five distinctive histological variants. Am J Surg Pathol. 1982;6:451–70.

Suster S, Rosai J. Thymic carcinoma: a clinicopathologic study of 60 cases. Cancer. 1991;67:1025–32.

Suster S, Rosai J. Cystic thymomas: clinicopathologic study of 10 cases. Cancer. 1992;69:92–7.

Suster S, Moran CA. Primary thymic epithelial neoplasms with combined features of thymoma and  thymic carcinoma. A clinicopathologic study of 22 cases. Am J Surg Pathol. 1996;20:1469–80. 

Suster S, Moran CA, Chan JKC. Thymoma with pseudosarcomatous stroma. Report of an unusual histologic variant of thymic epithelial neoplasms that may simulate carcinosarcoma. Am J Surg Pathol. 1997;21:1316–23.

Suster S, Moran CA. Thymic carcinoma: spectrum of differentiation and histologic types. Pathology. 1998;30:111–22. 

Suster S, Moran CA. Thymoma, atypical thymoma and thymic carcinoma. A novel conceptual approach to the classifi cation of neoplasms of thymic epithelium. Am J Clin Pathol. 1999a;111:826–33.

Suster S, Moran CA. Spindle cell carcinoma of the thymus. Clinicopathologic and immunohistochemical study of 15 cases of a novel form of thymic carcinoma. Am J Surg Pathol. 1999b;23:691–700.

Suster S, Moran CA. Micronodular thymoma with lymphoid B-cell hyperplasia. Clinicopathologic and immunohistochemical study of 18 cases of a distinctive morphologic variant of thymic epithelial

neoplasm. Am J Surg Pathol. 1999c;23:955–62.

Suster S, Moran CA. Primary thymic epithelial neoplasms: spectrum of differentiation and histologic features. Semin Diagn Pathol. 1999d;16:2–17.

Suster S. Thymic carcinoma: update of current diagnostic criteria and histologic types. Semin Diagn Pathol. 2005;22:198–212. 

Suster S, Moran CA. Thymoma classification: current status and future trends. Am J Clin Pathol. 2006;125:542–54.

Suster S, Moran CA. Classification of thymoma: the WHO and beyond. Hematol Oncol Clin North Am. 2008;22:381–92. 

Suster S, Moran CA. The mediastinum. In: Weidner N, Cote R, Suster S, Weiss LM, editors. Modern surgical pathology. 2nd ed. Philadelphia: W.B. Saunders; 2009. p. 454–516.

Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG. Pathology and genetics. Tumors of the lung, pleura, thymus, and heart. In: World Health Organization classification of tumors. Lyon: IARC

Press; 2015.

Wu T-C, Kuo T-T. Study of Epstein-Barr virus RNA (EBER-1) expression by in-situ hybridization in thymic epithelial tumors of Chinese patients in Taiwan. Hum Pathol. 1993;24:235–8.