Ovary tumor
Germ cell tumors
Dysgerminoma

Senior Author: M. Carolina Reyes, M.D.
Editor-in-Chief: Debra Zynger, M.D.

Topic Completed: 26 December 2018

Revised: 8 February 2019

Revised: 26 December 2018

Copyright: (c) 2002-2018, PathologyOutlines.com, Inc.

PubMed Search: Ovarian dysgerminoma[title] germ cell
Page views in 2018: 12,817
Page views in 2019 to date: 3,652
Cite this page: Song S, Reyes MC. Dysgerminoma. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/ovarytumordysgerminoma.html. Accessed March 20th, 2019.
Definition / general
  • Malignant primitive germ cell tumor with no specific type of differentiation
Essential features
  • Most common malignant ovarian germ cell tumor
  • Female counterpart to testicular seminoma
  • Most common in children and young women
  • Excellent prognosis with chemotherapy
  • Composed of sheets or nests of uniform cells with clear or eosinophilic cytoplasm and distinct, squared off cell membranes
  • Tumor often separated by fibrous septae containing cytotoxic lymphocytes that can spill out into tumor
  • Positive for SALL4, OCT3/4, D2-40, CD117, PLAP
ICD coding
  • ICD-10: C56 - malignant neoplasm of ovary
Epidemiology
  • Constitutes 1 - 2% of all malignant ovarian tumors
  • Most common malignant germ cell tumor of ovary (50%)
  • Most common in children and young women
Sites
  • Ovary
Pathophysiology
Etiology
  • Arises from primordial germ cells of the ovary
Clinical features
  • Most common in children and young women
  • May present in pure form or as a component of a malignant mixed germ cell tumor
  • Patients clinically present with abdominal pain or distention
  • Bilateral ovarian involvement occurs in 10 - 15% of patients (Cancer Treat Rev 2008;34:427); involvement of contralateral ovary may be microscopic
  • One of the most common neoplasms in pregnancy (Cancer Treat Rev 2008;34:427)
  • Rare association with gonadal dysgenesis and chromosome Y abnormalities; may arise from gonadoblastoma
  • Rare estrogenic manifestations
Laboratory
  • Serum lactic dehydrogenase (LDH) is often elevated (95%)
  • A rare subset (3 - 5%) shows low level hCG production related to the presence of multinucleated syncytiotrophoblastic giant cells that are not associated with cytotrophoblasts (Cancer Treat Rev 2008;34:427)
  • Serum placental alkaline phosphatase (PLAP) may be elevated (Cancer Treat Rev 2008;34:427)
  • Hypercalcemia may develop as a paraneoplastic syndrome
Radiology description
  • On ultrasound, tends to appear as a highly vascularized, large, solid, lobulated adnexal mass with irregular internal echogenicity (Ultrasound Obstet Gynecol 2011;37:596)
  • Enhancing septa and areas of cystic change that may represent necrosis or hemorrhage may be seen; calcifications may manifest as a speckled pattern (Radiographics 2014;34:777)
Prognostic factors
  • Most tumors are stage I at diagnosis
  • Recurrence rate is low
  • KIT mutations are associated with advanced stage at presentation
  • With treatment, excellent prognosis and overall survival > 90%
Case reports
Treatment
Gross description
  • Usually > 10 cm
  • Solid and lobulated with fleshy tan-white cut surface
  • Hemorrhage and necrosis with cystic degeneration may be present
Gross images

Contributed by AFIP

Solid, fleshy, lobulated

Cystic degeneration



Images hosted on other servers:

Various images

Frozen section description
  • May favor diagnosis of high grade malignant germ cell tumor on frozen section; however, final diagnosis should be deferred to permanent
  • Distinguishes dysgerminoma from large cell lymphoma, both of which share similar gross appearance, large neoplastic nuclei and infiltrating background lymphocytes
    • Features favoring dysgerminoma include presence of fibrous septae and squared off nuclei
    • Thickening of the fallopian tube is more suggestive of lymphoma (Int J Gynecol Pathol 2008;27:353)
Microscopic (histologic) description
  • Histomorphology identical to that of testicular seminoma
  • Sheets or nests of large, uniform polygonal cells with clear or eosinophilic cytoplasm and distinct squared off cell membranes
  • May also grow as cords, microcysts, tubules, pseudoglandular spaces or trabeculae (Arch Pathol Lab Med 2014;138:351)
  • Rarely may show pseudopapillary or macrofollicular growth pattern (Iran J Pathol 2018;13:94)
  • Tumor separated by fibrous septae containing cytotoxic lymphocytes and epithelioid histiocytes, often with spillover into tumor; non caseating granulomas or lymphoid follicles with germinal centers may be present
  • Stroma is usually loose and delicate but in some cases may be hyalinized, myxoid or luteinized
  • Numerous mitotic figures
  • Rare cases show syncytiotrophoblastic cells, singly or in clusters, without cytotrophoblastic cells; sample tumor thoroughly to exclude choriocarcinoma
  • Extensive hemorrhage and necrosis may be present with dystrophic calcification; if large areas of dystrophic calcification seen in the absence of necrosis, may be a gonadoblastoma
    • As gonadoblastomas give rise to dysgerminomas, thorough sampling indicated to rule out its presence
Microscopic (histologic) images

Contributed by Sharon Song, M.D.

Medium sized cells

Eosinophilic cytoplasm

Cells growing as cords

Varied growth pattern


OCT3/4

SALL4

CD117



Contributed by AFIP

Lymphocytes

Cords

Solid tubular pattern

Syncytiotrophoblasts

Cytology description
  • Uniformly medium sized, round to oval and centrally located nuclei with vesicular or finely granular chromatin
  • Prominent single or multiple nucleoli
  • Nuclear membrane shows angulated, squared off borders
  • Cytoplasm may be scant and eosinophilic due to poor fixation, mimicking cells of embryonal carcinoma
Positive stains
  • OCT3/4 (nuclear), CD117 (c-KIT; membranous), D2-40 (membranous and cytoplasmic) (Histopathology 2013;62:71)
  • NANOG (nuclear) and SALL4 (nuclear) stem cell markers
  • PLAP (membranous and cytoplasmic)
  • May focally express keratins with cytoplasmic dot or rim-like staining: CAM 5.2 (positive in up to 10% of tumor cells in < 50% of dysgerminomas); AE1 / AE3 and CK7 (positive in up to 10% of tumor cells in < 25% of dysgerminomas)
  • hCG, inhibin, Glypican 3 and CK7 can highlight syncytiotrophoblastic giant cells; can search for these cells in patients with moderate serum hCG elevation (Histopathology 2013;62:71)
Negative stains
Molecular / cytogenetics description
  • Isochromosome 12p in 81% (Pathol Res Pract 2012;208:628, Mod Pathol 2006;19:611)
  • KIT mutations in exon 17 codon 816 or KIT amplification detected in approximately 1/3 of cases and associated with advanced stage at presentation (Cancer 2011;117:2096)
    • As this KIT mutation involves exon 17, not exon 11 as in gastrointestinal stromal tumors, these cases are not responsive to KIT receptor inhibitors
Videos


Histopathology Ovary - Dysgerminoma
Differential diagnosis
  • Important to rule other types of mixed germ cell tumor
    • Embryonal carcinoma
      • Mimicker especially in poorly fixed specimens
      • Nuclei are more pleomorphic with amphophilic cytoplasm and frequent apoptotic cells
      • Lack fibrous septae containing lymphocytes
      • CD30+, SOX2+, NANOG+, OCT3/4+, CD117-, D2-40-
  • Lymphoma
    • Lacks fibrous septae
    • May be associated with thickened fallopian tube
    • Positive lymphoid markers and IgH clonality
Board review question #1
    If patient with dysgerminoma has elevated hCG levels, all of the following are likely possibilities except:

  1. Mixed germ cell tumor with a component of choriocarcinoma
  2. Mixed germ cell tumor with a component of yolk sac tumor
  3. The patient is also pregnant
  4. Presence of syncytiotrophoblastic cells in dysgerminoma
Board review answer #1
B. The presence of syncytiotrophoblastic giant cells without an associated component of cytotrophoblasts can lead to low-level hCG production in dysgerminomas. In addition to dysgerminomas being the most common neoplasm seen in pregnancy, an elevated level of hCG should always lead one to consider pregnancy. Elevated hCG levels are seen in choriocarcinomas.

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Board review question #2
    Which of the following immunostains are typically positive in dysgerminoma and can confirm the diagnosis?

  1. AFP, SALL4, OCT3/4, hCG
  2. D2-40, CD117, OCT3/4, SALL4
  3. OCT3/4, EMA, hCG, SALL4
  4. PLAP, AFP, hCG, AE1/3
Board review answer #2
B. SALL4 is positive in germ cell tumors. OCT3/4 positivity narrows the differential of germ cell tumors to dysgerminomas and embryonal carcinomas. Dysgerminomas are positive for CD117 and D2-40.

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