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Surgical Pathology Criteria

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Germ Cell Tumors of the Mediastinum / Thymus


  • Neoplasms exhibiting features of gonadal germ cell neoplasms arising in the mediastinum

Diagnostic Criteria

  • All types of gonadal germ cell tumors (GCT) may be seen in the mediastinum
    • Mature teratoma is by far the most common type
      • Occurs roughly equally in males and females
    • Immature teratoma and all other types of GCT occur virtually only in males
  • Histologic patterns are essentially the same as in their gonadal counterparts
    • Seminoma may be obscured by inflammatory response, thymic epithelial hyperplasia and cyst formation
  • Hematologic malignancy may rarely be associated with mediastinal GCT
    • Most common types are:
      • Acute myelogenous leukemia
      • Acute megakaryocytic leukemia
      • Rare cases reported as malignant histiocytosis
        • Probably really anaplastic large cell lymphoma
    • Most frequently associated with yolk sac tumor
    • May be synchronous, appears not to be related to therapy
  • Somatic malignancy may rarely be associated with mediastinal GCT
    • Most common types:
      • Embryonal rhabdomyosarcoma
      • Angiosarcoma
      • Myxoid liposarcoma
    • May occur in both males and females
  • Almost all mediastinal GCT directly involve or are adjacent to the thymus
  • Metastasis from a gonadal primary must be ruled out

Robert V Rouse MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342

Original posting/updates: 9/24/10, 10/22/10, 12/1/13

Supplemental studies


  • Germ cell tumor markers may be useful
      Seminoma Embryonal Carcinoma Yolk Sac Tumor
    SALL4 100% 100% 100%
    OCT3/4 100% 100% 0%
    Glypican3 0% 0-8% 100%
    CD117 90% 0% 0%
    CD30 5% 90% 20%
    These markers are superior to placental alkaline phosphatase and alpha fetoprotein
  • (Serum test for alpha fetoprotein is much more sensitive than immunohistochemistry)

Differential Diagnosis

  • Most germ cell tumors are recognizable easily by their patterns
    • Essentially the same as in the gonads
  • Immunohistochemistry (see Supplemental Studies) may help in difficult cases
  • Lymphoma can be identified with CD45a and B or T cell markers and lacks SALL4 and OCT3/4
    • CD30 stains both embryonal carcinoma and some lymphomas
      • Anaplastic large cell lymphoma and some mediastinal large B cell lymphomas
  • Lymphoepithelioma-like carcinoma can be distinguished from seminoma and embryonal carcinoma as it is EMA positive and negative for SALL4 and OCT3/4
  • Adenomatoid/reticular pattern Type A thymoma can be distinguished from yolk sac tumor by its lack of mitotic activity, Schiller-Duval bodies and hyaline globules
    • SALL4 and glypican 3 not tested

Grading / Staging


  • Not applicable


  • TNM has been proposed

Classification / Lists

Extragonadal Germ Cell Tumors (excluding CNS)

Age Site Histology Comments
Congenital / Neonatal Primarily sacrococcygeal, others midline Teratoma with or without YST Immaturity and histologic type not critical; may recur post resection but curable with chemotherapy
Childhood (7 mo - puberty) Various midline Usually YST Rare but frequently aggressive
Adult Cervical / thyroid / mediastinum / thymus Mature teratoma Benign
    Immature teratoma, YST, others Potentially aggressive; mediastinal tumors may be associated with hematologic malignancy
  Sacrococcygeal Mature Teratoma Benign
    Immature teratoma Probably benign, has not been shown to be aggressive
    Other germ cell tumors Rare, aggressive
  Retroperitoneum Any type Most should be considered metastases from gonadal primary
YST = yolk sac tumor; table based on McKenney JK, Heerema-McKenney A, Rouse RV. Extragonadal germ cell tumors: a review with emphasis on pathologic features, clinical prognostic variables and differential diagnostic features. Adv Anat Pathol 2007, 14:69-92.


Non-Thymic Neoplasms that May Arise Primarily in the Thymus

  • Hematopoietic
    • Primary mediastinal large B cell lymphoma
    • Extranodal marginal zone lymphoma
    • Precursor T lymphoblastic lymphoma/leukemia
    • Hodgkin lymphoma
  • Germ cell tumors
    • Seminoma (Germinoma)
    • Embryonal carcinoma
    • Yolk sac tumor
    • Teratoma
    • Choriocarcinoma
    • With associated somatic type malignancy
      • Embryonal rhabdomyosarcoma
      • Angiosarcoma
      • Others
    • With associated hematologic malignancy
      • Acute myelogenous leukemia
      • Acute megakaryoblastic leukemia
      • Others

Miscellaneous Thymic Lesions and Conditions

Intrinsic Tumors of the Thymus


  • Shimosato Y, Mukai K, Matsuno Y. Tumors of the Mediastinum, Atlas of Tumor Pathology, AFIP Fourth Series, Fascicle 11, 2010
  • Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC eds. World Health Organization Classification of Tumors. Pathology and genetics of tumors of the lung, pleura, thymus and heart. IARC Press: Lyon 2004.
  • McKenney JK, Heerema-McKenney A, Rouse RV. Extragonadal germ cell tumors: a review with emphasis on pathologic features, clinical prognostic variables and differential diagnostic features. Adv Anat Pathol 2007, 14:69-92.
  • den Bakker MA, Oosterhuis JW. Tumours and tumour-like conditions of the thymus other than thymoma; a practical approach. Histopathology. 2009 Jan;54(1):69-89
  • deMent SH, Eggleston JC, Spivak JL. Association between mediastinal germ cell tumors and hematologic malignancies. Report of two cases and review of the literature. Am J Surg Pathol. 1985 Jan;9(1):23-30
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  • Ikdahl T, Josefsen D, Jakobsen E, Delabie J, Fosså SD. Concurrent mediastinal germ-cell tumour and haematological malignancy: case report and short review of literature. Acta Oncol. 2008;47(3):466-9
  • Lachman MF, Kim K, Koo BC. Mediastinal teratoma associated with Klinefelter's syndrome. Arch Pathol Lab Med. 1986 Nov;110(11):1067-71
  • Zhao GQ, Dowell JE. Hematologic malignancies associated with germ cell tumors. Expert Rev Hematol. 2012 Aug;5(4):427-37.
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