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Thymic Carcinoma

Synonyms: Thymoma Type C

Definition

Primary epithelial tumor of the thymus exhibiting clearcut cytologic features of malignancy and with lack of organotypic features.

Clinical Features

  • Rare

Histopathology

  • Thymic epithelial tumor (i.e. a thymoma) with clearcut cytologic features of malignancy1,2 (Fig. 1
    Gross appearance of thymic carcinoma (type C thymoma). The tumor is invasive and shows foci of necrosis.

    Fig. 1: Gross appearance of thymic carcinoma (type C thymoma). The tumor is invasive and shows foci of necrosis.

    )
  • Variety of microscopic patterns
  • >90% of cases squamous cell and nonkeratinizing carcinoma

Microscopic Types Recognized by WHO Committee for the Histologic Typing of Tumors of the Thymus3

Epidermoid Keratinizing Carcinoma
  • Rich in atypical epithelial cells, many of which undergo keratinization4,5 (Figs 2 and 3
    Low-power appearance of thymic carcinoma of keratinizing squamous type. Note distinct lobulation.

    Fig. 2: Low-power appearance of thymic carcinoma of keratinizing squamous type. Note distinct lobulation.

    High-power appearance of thymic carcinoma of keratinizing squamous type. Note distinct lobulation.

    Fig. 3: High-power appearance of thymic carcinoma of keratinizing squamous type. Note distinct lobulation.

    )
  • Appearance similar to squamous cell carcinoma at other sites, but:
    • lobular pattern of growth generally maintained
    • tumor lobules even more widely separated from each other by fibrous bands than in other thymoma types6 (Fig. 4
      Low-power view of thymic carcinoma (type C thymoma). The tumor lobules are more widely separated by fibrous tissue and smaller than in conventional thymoma.

      Fig. 4: Low-power view of thymic carcinoma (type C thymoma). The tumor lobules are more widely separated by fibrous tissue and smaller than in conventional thymoma.

      )
Epidermoid Nonkeratinizing Carcinoma
  • Overall appearance similar to epidermoid keratinizing carcinoma, but
    • lobulation less developed
    • no overt signs of keratinization
Lymphoepithelioma-like Carcinoma
  • Appearance of tumor approaches and sometimes indistinguishable from lymphoepithelioma of tonsil and nasopharynx
  • Hallmark:
    • large, deeply acidophilic, sharply outlined and perfectly round nucleoli
  • Syncytial appearance (Fig. 5
    Nonkeratinizing undifferentiated type of thymic carcinoma. The tumor has a lymphoepithelioma-like quality.

    Fig. 5: Nonkeratinizing undifferentiated type of thymic carcinoma. The tumor has a lymphoepithelioma-like quality.

    )
  • No keratinization and intercellular bridges
  • Tumor cells consistently immunoreactive for keratin
  • Lymphocytes:
    • can be very numerous
    • phenotype of mature peripheral T cells rather than immature thymocytic phenotype of ordinary thymoma
  • Epstein–Barr virus (EBV) genome in several cases suggests similarity with nasopharyngeal carcinoma beyond morphologic parameters:7–9
Sarcomatoid Carcinoma
Clear Cell Carcinoma
  • Rare
  • Large amounts of glycogen-rich clear cytoplasm in tumor cells (Fig. 7
    Thymic carcinoma of clear cell type. This tumor needs to be distinguished from metastatic carcinoma, particularly from the kidney.

    Fig. 7: Thymic carcinoma of clear cell type. This tumor needs to be distinguished from metastatic carcinoma, particularly from the kidney.

    )
  • Striking resemblance with renal cell carcinoma13,15,16
Mucoepidermoid Carcinoma
  • Alternating areas of squamous and mucin-producing glandular differentiation
  • Some mucin may become extracellular and elicit an inflammatory reaction13,19,20 (Fig. 9
    Thymic carcinoma of mucoepidermoid type.

    Fig. 9: Thymic carcinoma of mucoepidermoid type.

    )
Papillary Carcinoma
  • Resembles papillary thyroid carcinoma due to its:
    • complex arborizing structure
    • psammoma bodies21
  • However, it:
    • lacks optically clear nuclei
    • is positive for CD5
    • shows no reactivity for thyroglobulin or TTF-122
  • Most cases have arisen from type A (spindle cell, medullary) thymomas22
Mucinous Adenocarcinoma23 Small Cell Carcinoma and Small Cell–Squamous Cell Carcinoma Undifferentiated Carcinoma
  • No detectable differentiation in any specific direction
  • Tends to exhibit considerable pleomorphism

Special Stains and Immunohistochemistry

Differential Diagnosis

Differences From All Other Types Of Thymomas

  • Very rarely associated with myasthenia gravis or other immune-mediated systemic diseases
  • Generally lack all ancillary features of thymoma, such as:
    • perivascular spaces
    • foci of medullary differentiation
    • abortive Hassall's corpuscles
    • rosettes
    • glandlike spaces
  • Lack immature T lymphocytes
  • Lymphocytes:
    • may be present and numerous
    • phenotype of mature T or (rarely) B cells
  • Rarely intermediate or hybrid forms (Fig. 11
    Thymic tumor bridging the gap between thymoma and thymic carcinoma. The degree of atypia in the neoplastic cell is such as to justify a diagnosis of thymic carcinoma (type C thymoma), but the overall configuration of the tumor and the phenotype of the lymphocytes were those of conventional thymoma.

    Fig. 11: Thymic tumor bridging the gap between thymoma and thymic carcinoma. The degree of atypia in the neoplastic cell is such as to justify a diagnosis of thymic carcinoma (type C thymoma), but the overall configuration of the tumor and the phenotype of the lymphocytes were those of conventional thymoma.

    )

Sarcomatoid Carcinoma

  • Germ cell tumors
  • Malignant schwannoma (triton tumor)
  • Low-grade thymic tumor cured by surgical excision characterized by a biphasic epithelial and spindle cell morphology with absence of significant atypia in both components variously reported as:
    • thymoma with pseudosarcomatous stroma31
    • low-grade metaplastic thymic carcinoma32

Undifferentiated Carcinoma

  • Consider alternative possibilities more seriously the more undifferentiated the neoplasm, especially:
    • large cell malignant lymphoma
    • germ cell tumors

Genetics

  • Several cases with same chromosomal translocation (15;19)33

Management

  • Surgery plus radiation therapy:
    • for thymic carcinomas of epidermoid (keratinizing or nonkeratinizing) or lymphoepithelioma-like types
  • Additional chemotherapy:
    • if massive local disease or distant spread34

References

1 Ritter JH, Wick MR. Primary carcinomas of the thymus gland. Semin Diagn Pathol. 1999;16:18–31.

2 Wick MR, Scheithauer BW, Weiland LH, Bernatz PE. Primary thymic carcinomas. Am J Surg Pathol. 1982;6:613–630.

3 Rosai J. Histological typing of tumours of the thymus. Berlin: Springer; 1999;.

4 Kuo T-t, Chang J-P, Lin F-J, Wu W-C, Chang C-H. Thymic carcinomas: Histopathological varieties and immunohistochemical study. Am J Surg Pathol. 1990;14:24–34.

5 Shimosato Y, Kameya T, Nagai K, Suemasu K. Squamous cell carcinoma of the thymus. An analysis of eight cases. Am J Surg Pathol. 1977;1:109–121.

6 Suster S, Rosai J. Thymic carcinoma. A clinicopathologic study of 60 cases. Cancer. 1991;67:1025–1032.

7 Fujii T, Kawai T, Saito K, Fukushima K, Hasegawa T, Tokunaga M, et al. EBER-1 expression in thymic carcinoma. Acta Pathol Jpn. 1993;43:107–110.

8 Leyvraz S, Henle W, Chahinian AP, Perlman C, Klein G, Gordon RE, et al. Association of Epstein-Barr virus with thymic carcinoma. N Engl J Med. 1985;312:1296–1299.

9 Mann RB, Wu T-C, MacMahon EM, Ling Y, Charache P, Ambinder RF. In situ localization of Epstein-Barr virus in thymic carcinoma. Mod Pathol. 1992;5:363–366.

10 Chan JKC, Yip TTC, Tsang WYW, Seneviratne S, Poon YF, Wong CSC, et al. Lack of evidence of pathogenetic role of Epstein-Barr virus in thymic lymphoid hyperplasia and thymomas in the Chinese population of Hong Kong. Int J Surg Pathol. 1994;2:17–22.

11 Inghirami G, Chilosi M, Knowles DM. Western thymomas lack Epstein-Barr virus by Southern blotting analysis and by polymerase chain reaction. Am J Pathol. 1990;136:1429–1436.

12 Wu T-C, Kuo T-T. Study of Epstein-Barr virus early RNA1 (EBER1) expression by in situ hybridization in thymic epithelial tumors of Chinese patients in Taiwan. Hum Pathol. 1993;24:235–238.

13 Snover DC, Levine GD, Rosai J. Thymic carcinoma. Five distinctive histologic variants. Am J Surg Pathol. 1982;6:451–470.

14 Eimoto T, Kitaoka M, Ogawa H, Niwa H, Murase T, Tateyama H, et al. Thymic sarcomatoid carcinoma with skeletal muscle differentiation: report of two cases, one with cytogenetic analysis. Histopathology. 2002;40:46–57.

15 Hasserjian RP, Klimstra DS, Rosai J. Carcinoma of the thymus with clear-cell features. Report of eight cases and review of the literature. Am J Surg Pathol. 1995;19:305–310.

16 Wick MR, Ritter JH, Humphrey PA, Nappi O. Clear cell neoplasms of the endocrine system and thymus. Semin Diagn Pathol. 1997;14:183–202.

17 Iezzoni JC, Nass LB. Thymic basaloid carcinoma: A case report and review of the literature. Mod Pathol. 1996;9:21–25.

18 Kawashima O, Kamiyoshihara M, Sakata S, Kurihara T, Ishikawa S, Morishita Y. Basaloid carcinoma of the thymus. Ann Thorac Surg. 1999;68:1863–1865.

19 Moran CA, Suster S. Mucoepidermoid carcinomas of the thymus. A clinicopathologic study of six cases. Am J Surg Pathol. 1995;19:826–834.

20 Tanaka M, Shimokawa R, Matsubara O, Aoki N, Kamiyama R, Kasuga T, et al. Mucoepidermoid carcinoma of the thymic region. Acta Pathol Jpn. 1982;32:703–712.

21 Chilosi M, Zamò A, Brighenti A, Malpeli G, Montagna L, Piccoli P, et al. Constitutive expression of ΔN-p63α isoform in human thymus and thymic epithelial tumours. Virchows Arch. 2003;443:175–183.

22 Matsuno Y, Morozumi N, Hirohashi 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;22:873–880.

23 Choi WWL, Lui YH, Lau WH, Crowley P, Khan A, Chan JKC. Adenocarcinoma of the thymus: report of two cases, including a previously undescribed mucinous subtype. Am J Surg Pathol. 2003;27:124–130.

24 Kornstein MJ, Rosai J. CD5 labeling of thymic carcinomas and other nonlymphoid neoplasms. Am J Clin Pathol. 1998;109:722–726.

25 Tateyama H, Eimoto T, Tada T, Hattori H, Murase T, Takino H. Immunoreactivity of a new CD5 antibody with normal epithelium and malignant tumors including thymic carcinoma. Am J Clin Pathol. 1999;111:235–240.

26 Hishima T, Fukayama M, Hayashi Y, Fujii T, Ooba T, Funata N, et al. CD70 expression in thymic carcinoma. Am J Surg Pathol. 2000;24:742–746.

27 Pan C-C, Chen PC-H, Wang L-S, Lee J-Y, Chiang H. Expression of apoptosis-related markers and HER-2/neu in thymic epithelial tumours. Histopathology. 2003;43:165–172.

28 Hishima T, Fukayama M, Hayashi Y, Fujii T, Arai K, Shiozawa Y, et al. Neuroendocrine differentiation in thymic epithelial tumors with special reference to thymic carcinoma and atypical thymoma. Hum Pathol. 1998;29:330–338.

29 Kuo T-t. Frequent presence of neuroendocrine small cells in thymic carcinoma: a light microscopic and immunohistochemical study. Histopathology. 2000;37:19–26.

30 Lauriola L, Erlandson RA, Rosai J. Neuroendocrine differentiation is a common feature of thymic carcinoma. Am J Surg Pathol. 1998;22:1059–1066.

31 Suster S, Moran CA, Chan JK. Thymoma with pseudosarcomatous stroma: report of an unusual histologic variant of thymic epithelial neoplasm that may simulate carcinosarcoma. Am J Surg Pathol. 1997;21:1316–1323.

32 Yoneda S, Marx A, Heimann S, Shirakusa T, Kikuchi M, Muller-Hermelink HK. Low-grade metaplastic carcinoma of the thymus. Histopathology. 1999;35:19–30.

33 Lee ACW, Kwong Y-I, Fu KH, Chan GCF, Ma L, Lau Y-I. Disseminated mediastinal carcinoma with chromosomal translocation (15;19). Cancer. 1993;72:2273–2276.

34 Ogawa K, Toita T, Uno T, Fuwa N, Kakinohana Y, Kamata M, et al. Treatment and prognosis of thymic carcinoma: a retrospective analysis of 40 cases. Cancer. 2002;94:3115–3119.

35 Bedini AV, Andreani SM, Tavecchio L, Fabbri A, Giardini R, Camerini T, Bufalino R, Rosai J. Proposal of a novel TNM-based system to stage thymic epithelial tumors according to the World Health Organization pathologic classification (submitted for publication).

36 Begg CB, Cramer LD, Venkatraman ES, Rosai J. Comparing tumour staging and grading systems: a case study and a review of the issues, using thymoma as a model. Statist Med. 2000;19:1997–2014.

37 Blumberg D, Weksler B, Delgado R, Rosai J, Bains MS, Ginsberg RJ, et al. Thymoma. A multivariate analysis of factors predicting survival. Ann Thorac Surg. 1995;60:908–913.

38 Kuo T-T, Chang J-P, Lin F-J, Chang C-H. Thymic carcinomas. Histopathological varieties and immunohistochemical study. Am J Surg Pathol. 1990;14:24–34.

39 Lewis JE, Wick MR, Scheithauer BW, Bernatz PE, Taylor WF. Thymoma. A clinicopathologic review. Cancer. 1987;60:2727–2743.

40 Suster S, Rosai J. Thymic carcinoma. A clinicopathologic study of 60 cases. Cancer. 1991;67:1025–1032.

41 Truong LD, Mody DR, Cagle PT, Jackson York GL, Schwartz MR, Wheeler TM. Thymic carcinoma. A clinicopathologic study of 13 cases. Am J Surg Pathol. 1990;14:151–166.

42 Wick MR, Scheithauer BW, Weiland LH, Bernatz PE. Primary thymic carcinomas. Am J Surg Pathol. 1982;6:613–630.

Last updated: 9 Mar 2006

Thymic Carcinoma

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