Background

This is the ovarian counterpart for the male testicular seminoma germ cell tumor. Histologically, this tumor is indistinguishable from the seminoma. The most common presentation is an abdominal mass and selected patients may have a gonadoblastoma, a rare tumor usually associated with abnormal gonadal development.

OUTLINE

Epidemiology
Disease Associations
Pathogenesis
Laboratory/Radiologic/ Other Diagnostic Testing
Gross Appearance and Clinical Variants
Histopathological Features and Variants
Special Stains/ Immunohistochemistry/ Electron Microscopy
Differential Diagnosis
Prognosis
Treatment
Commonly Used Terms
Internet Links

EPIDEMIOLOGY	CHARACTERIZATION
SYNONYMS
INCIDENCE	Most common malignant germ cell tumor of the ovary 1% of all ovarian cancers
AGE RANGE-MEDIAN	5-10% of ovarian cancers in first two decades of life 20-30% of ovarian cancers during pregnancy 80% occur during 2-3rd decades Mean and median in late teens and early 20's 5%<10 years Rare >50 years
GEOGRAPHY	Higher in Japan than in Western countries

 

DISEASE ASSOCIATIONS	CHARACTERIZATION
Phenotypic females with gonadal dysgenesis	Usually arise from gonadoblastomas
Arising in testis of females with androgen insensitivity syndrome
Ataxia-telangiectasia

PATHOGENESIS	CHARACTERIZATION
CHROMOSOMAL ABNORMALITIES
Chromosome 12p abnormalities in dysgerminoma of the ovary: a FISH analysis. Cossu-Rocca P, Zhang S, Roth LM, Eble JN, Zheng W, Karim FW, Michael H, Emerson RE, Jones TD, Hattab EM, Cheng L. [1] 1Departments of Pathology and Laboratory Medicine, Indiana University, Indianapolis, IN, USA [2] 2Dipartimento di Patologia, Universita di Sassari, Sassari, Italy.	Mod Pathol. 2006 Apr;19(4):611-5. Abstract quote   Dysgerminoma is the most common malignant ovarian germ cell tumor and shares histological and immunophenotypical features with its testicular counterpart, seminoma. Chromosome 12p abnormalities are genetic hallmarks of testicular seminomas. Little is known about these genetic changes in dysgerminoma. We performed dual color fluorescence in situ hybridization (FISH) analyses with a centromeric alpha-satellite probe for chromosome 12 and a subtelomeric probe for 12p on paraffin-embedded tissue sections from 21 dysgerminomas and two gonadoblastomas. Chromosome 12p abnormalities were detected in 81% of dysgerminomas. In all, 57% of cases had only isochromosome 12p and 5% had only 12p overrepresentation. In all, 19% had both isochrome 12p and 12p overrepresentation. Gonadoblastomas were negative for isochromosome 12p or 12p overrepresentation. Chromosome 12p abnormalities are common in dysgerminoma of the ovary. FISH analyses for chromosome 12p abnormalities may be a useful diagnostic adjunct for confirming the diagnosis of dysgerminoma and for distinguishing it from nongerm cell malignancies that enter into the differential diagnosis.

LABORATORY/ RADIOLOGIC/ OTHER TESTS	CHARACTERIZATION
Laboratory Markers
Elevated serum hCG	3% of patients
Elevated serum lactic dehydrogenase	95% of patients
Other elevated serum enzymes	Alkaline phosphatase Neuron specific enolase CA125

 

GROSS APPEARANCE/ CLINICAL VARIANTS	CHARACTERIZATION
General	Solid tumors with median diameter of 15 cm Smooth or bosselated external surface Cysts, hemorrhage, and necrosis may be present Bilateral in 10% 10% have microscopic foci of tumor in the grossly normal contralateral ovary

 

HISTOLOGICAL TYPES

CHARACTERIZATION

General

Uniform cells with discrete membranes with a clear glycogen rich cytoplasm Central large nucleus with coarsely clumped chromatin and several nucleoli Arranged in several patterns: Diffuse Insular Trabecular Cord-like Numerous mitotic figures Thin to fibrous bands of stroma with mature lymphocytes (T-cells) Caseation like necrosiis frequent Sarcoidal granulomas in 20% 3% with syncytiotrohoblastic giant cells positive for hCG Occasionally luteinized stromal cells Calcifications may indicate an underlying or previous gonadoblastoma

 

SPECIAL STAINS/ IMMUNOPEROXIDASE/ OTHER	CHARACTERIZATION
Special stains	PAS positive diastase sensitive glycogen rich cytoplasm
Immunoperoxidase	Positive for: PLAP Vimentin c-kit (92%) hCG focally within giant cells Some positivity for: LDH NSE Leu-7 Cytokeratin Desmin GFAP
CD30
Cytokeratin and CD30 expression in dysgerminoma . Cossu-Rocca P, Jones TD, Roth LM, Eble JN, Zheng W, Karim FW, Cheng L. Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, IN 46202, USA.	Hum Pathol. 2006 Aug;37(8):1015-21. Abstract quote Dysgerminoma is a malignant germ cell tumor of the ovary that shares morphological, immunophenotypic, and genetic features with its testicular counterpart, seminoma. Recent evidence supports the hypothesis that seminoma can differentiate into non-seminomatous germ cell tumor types. The progression of these tumors can be measured by their acquisition of the potential to express cytokeratin intermediate filaments, a characteristic specific to epithelial differentiation. Although testicular seminomas have been widely investigated, little is known about cytokeratin or E-cadherin expression in dysgerminomas. We investigated 26 formalin-fixed, paraffin-embedded ovarian dysgerminomas with immunohistochemical stains for CAM5.2, AE1/AE3, epithelial membrane antigen, cytokeratin 7, cytokeratin 20, high-molecular-weight keratin, and E-cadherin. In addition, we investigated the CD30 and vimentin immunoreactivity of these tumors. Immunoreactivity for CAM5.2 and for AE1/AE3 was present in more than 10% of neoplastic cells in 5 (19.2%) of 26 cases and in 2 (7.7%) of 26 cases, respectively. Cytokeratin 7 showed only focal positivity and never showed positive staining in greater than 10% of dysgerminoma cells. E-cadherin staining was positive in 2 cases showing weak membranous immunostaining in more than 10% of cells. Vimentin immunoreactivity was observed in only 2 dysgerminomas, both of which had less than 10% of the neoplastic cells staining. Cytokeratin 20, epithelial membrane antigen, high-molecular-weight keratin, and CD30 were consistently negative in all cases. Our study demonstrates that cytokeratin expression in dysgerminomas is not unusual and is consistent with the hypothesis that dysgerminomas have the capacity to differentiate along epithelial lines. Furthermore, the immunohistochemical staining patterns for cytokeratins, E-cadherin, and CD30 in dysgerminomas need to be considered when assessing differential diagnoses in difficult cases of primary ovarian tumors.
CD117
Expression of CD117 (c-kit) receptor in dysgerminoma of the ovary: diagnostic and therapeutic implications. Sever M, Jones TD, Roth LM, Karim FW, Zheng W, Michael H, Hattab EM, Emerson RE, Baldridge LA, Cheng L. 1Department of Pathology and Laboratory Medicine, Indiana University, Indianapolis, IN, USA.	Mod Pathol. 2005 Nov;18(11):1411-6. Abstract quote   The proto-oncogene c-kit encodes a tyrosine kinase receptor, c-kit (CD117), which has been implicated in the development of a number of human malignancies. While the preferential expression of this protein has been well documented in testicular seminomas, there is little data concerning its expression in dysgerminomas of the ovary. We examined the expression of c-kit in 30 cases of ovarian dysgerminomas using immunohistohemical staining with a polyclonal anti-CD117 antibody. Staining was graded in a semiquantitative manner as follows: negative (no staining), 1+ (1-10% staining), 2+ (10-29% staining), 3+ (30-50% staining), or 4+ (>50% staining). Of the 30 cases examined, 26 (87%) demonstrated immunoreactivity for CD117. In total, 10 (33%) demonstrated 4+ staining; 9 (30%) demonstrated 3+ staining; 3 (10%) demonstrated 2+ staining; 4 (13%) demonstrated 1+ staining; and 4 (13%) demonstrated no staining. In conclusion, CD117 immunoreactivity was detected in 87% of ovarian dysgerminomas, a finding that correlates with previously reported frequencies of CD117 expression in seminomas (78-100%). Thus, antibodies to c-kit may be a useful diagnostic marker for ovarian dysgerminoma. Although the prognosis of patients with dysgerminoma is generally good, this receptor could potentially serve as a target for site-specific immunotherapy as an alternative and/or complement to conventional treatment options.
OCT4
OCT4: A Novel Biomarker for Dysgerminoma of the Ovary. Cheng L, Thomas A, Roth LM, Zheng W, Michael H, Karim FW. *Departments of Pathology and Laboratory Medicine, Indiana University, Indianapolis, IN; daggerDepartment of Pathology, Case Western Reserve University, Cleveland, OH; and double daggerDepartment of Pathology, Yale University, New Haven, CT.	Am J Surg Pathol. 2004 Oct;28(10):1341-1346. Abstract quote The prognosis and therapy for dysgerminomas are different from those of other ovarian tumor types, making accurate diagnosis imperative for patient care. OCT4 (POU5F1) is a transcription factor involved in the regulation of pluripotency during embryonic development. It can be detected in both pluripotent cells and other early germ cells. This study examines the expression of OCT4 in both dysgerminoma and nondysgerminomatous neoplasms involving the ovary. Formalin-fixed, paraffin-embedded cell blocks of 33 cases of dysgerminoma including 2 cases of gonadoblastoma associated with dysgerminoma and 3 cases of metastatic dysgerminoma, and 111 cases of nondysgerminomatous neoplasms involving the ovary were stained using the antibody against OCT4. All cases of dysgerminomas and gonadoblastomas were positive for OCT4 with strong nuclear staining. More than 90% of dysgerminoma cells in each case showed diffuse strong nuclear staining. In addition, 3 metastatic dysgerminomas also showed uniform strong nuclear staining. All nondysgerminomatous tumors (mature teratoma, 14; yolk sac tumor, 4; Sertoli-Leydig cell tumor, 15; granulosa cell tumor, 22; Brenner tumor, 3; carcinoid tumor, 4; struma ovarii, 2; fibroma, 5; thecoma, 1; serous adenocarcinoma, 5; endometrioid adenocarcinoma, 4; small cell carcinoma, 6; stromal sarcoma, 1; malignant lymphoma, 6; metastatic malignant melanoma, 1; metastatic carcinoid, 2; metastatic small cell carcinoma, 1; and metastatic lobular carcinoma of the breast, 1) were negative for OCT4, except for some cases of clear cell adenocarcinoma of the ovary. Four of 14 clear cell adenocarcinomas showed focal positive nuclear immunoreactivity for OCT4. OCT4 is a sensitive and relatively specific biomarker for the detection of dysgerminoma. It may also be useful in the diagnosis of gonadoblastoma, which contains similar cells and may be associated with dysgerminoma. OCT4 may aid in the detection of small foci of metastatic dygerminoma in extraovarian sites and may also help distinguish dysgerminoma from other primary and metastatic tumors of the ovary.

 

DIFFERENTIAL DIAGNOSIS	KEY DIFFERENTIATING FEATURES
Yolk sac tumor-solid pattern
Embryonal carcinoma
Clear cell carcinoma
Granulosa cell tumors
Metastatic carcinomas with clear cell changes

 

PROGNOSIS AND TREATMENT	CHARACTERIZATION
Prognostic Factors	65% present in stage Ia
Treatment	Stage Ia unilateral tumors are treated conservatively Unilateral salpingo-oophorectomy with radiation

Henry JB. Clinical Diagnosis and Management by Laboratory Methods. Twentieth Edition. WB Saunders. 2001.
Rosai J. Ackerman's Surgical Pathology. Ninth Edition. Mosby 2004.
Sternberg S. Diagnostic Surgical Pathology. Fourth Edition. Lipincott Williams and Wilkins 2004.
Robbins Pathologic Basis of Disease. Seventh Edition. WB Saunders 2005.
DeMay RM. The Art and Science of Cytopathology. Volume 1 and 2. ASCP Press. 1996.
Weedon D. Weedon's Skin Pathology Second Edition. Churchill Livingstone. 2002
Fitzpatrick's Dermatology in General Medicine. 6th Edition. McGraw-Hill. 2003.
Weiss SW and Goldblum JR. Enzinger and Weiss's Soft Tissue Tumors. Fourth Edition. Mosby 2001.

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Last Updated August 28, 2006

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