Germ Cell Tumors of the Mediastinum / Thymus

Definition

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

Immunohistology

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

Grading

Not applicable

Staging

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

Atrophy
Cysts
- Most are non-specific
- Neoplasms most commonly associated with cysts
Castleman disease
Dysplasia
Hyperplasia
- B cell/lymphoid/germinal center
- Rebound
- True thymic
Microscopic thymoma / nodular hyperplasia of thymic epithelium
(Ectopic hamartomatous thymoma)

Intrinsic Tumors of the Thymus

Thymoma
- Type A
- Type AB
- Type B1
- Type B2
- Type B3
- Other types
  - Micronodular with lymphoid stroma
  - Metaplastic
  - Sclerosing
  - With prominent signet ring like features
Thymic carcinoma
- Low grade
  - Well differentiated squamous
  - Basaloid
  - Adenocarcinoma
  - Adenosquamous
  - Low grade mucoepidermoid
  - Micronodular
- High grade
  - Lymphoepithelial-like
  - Large cell undifferentiated
  - Clear cell
  - Sarcomatoid
  - Midline carcinoma with t(15;19)
Thymic neuroendocrine carcinoma
- Well differentiated (carcinoid)
- Poorly differentiated
  - Small cell
  - Large cell
Miscellaneous
- Thymolipoma
- Microscopic thymoma / nodular hyperplasia of thymic epithelium

Bibliography

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
deMent SH. Association between mediastinal germ cell tumors and hematologic malignancies: an update. Hum Pathol. 1990 Jul;21(7):699-703
Nichols CR, Roth BJ, Heerema N, Griep J, Tricot G. Hematologic neoplasia associated with primary mediastinal germ-cell tumors. N Engl J Med. 1990 May 17;322(20):1425-9
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.

Printed from Surgical Pathology Criteria: http://surgpathcriteria.stanford.edu/


© 2009 Stanford University School of Medicine

Germ Cell Tumors of the Mediastinum / Thymus