Ovary
Mixed germ cell - sex cord stromal tumors
Mixed germ cell - sex cord stromal tumor, unclassified
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PubMed Search: Mixed germ cell - sex cord stromal tumor
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Laboratory | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Positive stains | Negative stains | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Simsek ZC, Andersen JD. Mixed germ cell - sex cord stromal tumor, unclassified. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/ovarymixedgermcellsexcordstromal.html. Accessed March 30th, 2025.
Definition / general
- Mixed lineage neoplasm composed of germ cells and sex cord cells; occurs in normal gonads in patients without sex chromosomal abnormalities but lacks the distinctive appearance of a gonadoblastoma (Int J Gynecol Pathol 2007;26:313)
- ~10% of tumors have malignant germ cell components (Int J Clin Exp Pathol 2014;7:5259)
Essential features
- Ovarian tumors that are characterized by an irregular mix of dysgerminoma-like germ cells and sex cord cells and lack the characteristic features of gonadoblastoma
- Distinct from gonadoblastoma in macroscopic appearance, histology, absence of regressive changes and occurrence in normal gonads of phenotypically and genetically normal female patients (Int J Gynecol Pathol 1992;11:227)
Terminology
- Mixed germ cell sex cord - stromal tumor (MGSCT)
ICD coding
- ICD-O: 8594/1 - mixed germ cell - sex cord stromal tumor, NOS
- ICD-11: 2C73.Y & XH27A8 - other specified malignant neoplasms of the ovary & mixed germ cell - sex cord stromal tumor, unclassified
Epidemiology
- Extremely rare; < 100 cases reported
- Less common than gonadoblastoma; true frequency is unknown (Int J Gynecol Pathol 2007;26:313)
- More common in the ovaries than in the testes (Int J Gynecol Pathol 2007;26:313)
- Occurs in female patients with a normal phenotype, normal anatomical and gonadal development and normal 46,XX karyotype (Int J Gynecol Pathol 2007;26:313)
- Typically found in infants or girls younger than 10 years but may be seen in postmenarchal girls and women of reproductive age (Int J Gynecol Pathol 2007;26:313)
Sites
- Ovary
Pathophysiology
- Unknown at this time
Etiology
- Unknown at this time
Clinical features
- Most tumors occur in infants or children aged < 10 years
- Occasionally, tumors are associated with isosexual pseudoprecocity
- References: Int J Gynecol Pathol 2007;26:313, Cancer 1988;61:2122
Diagnosis
- Intraoperative consultation / frozen section
- Resection of tumor
Laboratory
- Elevation of germ cell serological markers
- Alpha fetoprotein (AFP)
- Inhibin
- Lactate dehydrogenase (LDH)
- Beta human chorionic gonadotropin (βhCG)
Radiology description
- Unilateral, solid pelvic / adnexal / abdominal mass
Radiology images
Images hosted on other servers:
Computed tomography of ovarian mass
Computed tomography of pelvic mass
Prognostic factors
- Most tumors are clinically benign, with rare cases of dysgerminoma or other malignant germ cell tumors and metastasis; ~10% more frequent in postpubertal patients (Int J Gynecol Pathol 2007;26:313)
- Malignant germ cell tumors are less common in mixed germ cell - sex cord stromal tumors than in gonadoblastoma but metastasis can occur without a secondary malignant component (~20%) (Int J Gynecol Pathol 2007;26:313)
- Female patients with this tumor have had normal full term pregnancies (Fox: Haines & Taylor Obstetrical and Gynaecological Pathology, 5th Edition, 2002)
- Prognosis is favorable without secondary malignant tumors; platinum based chemotherapy is effective when such tumors are present (Int J Gynecol Pathol 2007;26:313)
- 2 patients developed metastasis or recurrence without secondary malignancy, successfully treated with surgery and chemotherapy (Cancer 1988;61:2122, Int J Gynecol Pathol 1998;17:281)
Case reports
- 4 year old girl with precocious puberty and MGSCT with yolk sac tumor (J Med Case Rep 2012;6:162)
- 14 year old girl with precocious puberty and normal phenotype (Cureus 2020;12:e9350)
- 28 year old woman with a right adnexal mass measuring 8 cm in greatest dimension, containing areas with both germ cell and sex cord components (Int J Clin Exp Pathol 2014;7:5259)
Treatment
- Cisplatin based chemotherapy and tumor markers have significantly improved outcomes for patients with secondary malignant germ cell neoplasms (Int J Gynecol Pathol 2007;26:313)
- Unlike gonadoblastoma, removing a normal appearing contralateral gonad is contraindicated (Int J Gynecol Pathol 2007;26:313)
Gross description
- Tumors are typically large, unilateral, solid masses with a grayish pink or yellow to pale brown cut surface and measuring >10 cm (Int J Gynecol Pathol 2007;26:313)
Gross images
Images hosted on other servers:
Firm, solid and cystic
Microscopic (histologic) description
- Variable and irregular mix of germ cells and sex cord cells
- Germ cells are large, with pleomorphic nuclei and clear, PAS positive cytoplasm, resembling dysgerminoma cells
- Sex cord cells may form cords, trabeculae, hollow or solid tubules, cysts or diffuse growth patterns
- Solid, though small spaces or clefts may be present; occasionally, the sex cord element forms a cystic or retiform pattern or annular tubules, similar to features seen in sex cord stromal neoplasms (Int J Gynecol Pathol 1985;4:161, Int J Gynecol Pathol 1998;17:281)
- Germ cell component appears immature with high mitotic activity
- Infrequently, tumors have larger cystic spaces lined by sex cord elements or lack an epithelial lining, sometimes resembling serous epithelium (Int J Gynecol Pathol 2007;26:313)
Microscopic (histologic) images
Contributed by Russell Vang, M.D. and Kyle Devins, M.D.
Admixed germ cell and sex cord components
Atypical and proliferative plump germ cells
Poorly formed nests
Small, dark sex cord cells
SALL4
SF1
Positive stains
- Sex cord elements: inhibin, calretinin, SF1, WT1 (Virchows Arch 2006;448:612)
- Germ cell component
- PLAP, OCT 3/4, CD117 (Virchows Arch 2006;448:612)
- High proliferative index as measured by MIB1 (Virchows Arch 2006;448:612)
- PAS (cytoplasm) (Virchows Arch 2006;448:612)
- Neuron specific enolase (NSE) (Virchows Arch 2006;448:612)
- Cytokeratin AE1 / AE3: perinuclear staining pattern (Virchows Arch 2006;448:612)
Negative stains
- Staining pattern of admixed germ cell and sex cord stromal cell markers highlighting their respective component
Molecular / cytogenetics description
- No mutation in the KIT and PDFGRA genes (Virchows Arch 2006;448:612)
Sample pathology report
- Ovary, right, unilateral oophorectomy:
- Mixed germ cell - sex cord stromal tumor, unclassified (see comment)
- Comment: Mixed germ cell - sex cord stromal tumor components include germ cells resembling dysgerminoma (80%) and sex cord cells reminiscent of sex cord tumor with annular tubules (20%).
Differential diagnosis
- Gonadoblastoma:
- Typically occurs in the dysgenetic gonads of intersex patients with a Y chromosome (Int J Gynecol Pathol 2007;26:313)
- Frequent foci of calcifications (Mulberry-like)
- Anti-Müllerian hormone focally (Hum Pathol 2000;31:1202)
- Positive SALL4 and SF1 (Int J Gynecol Pathol 2013;32:379)
- Occasional KIT mutations (PLoS One 2012;7:e43952)
- Dysgerminoma:
- Absence of admixed sex cord stromal elements
- Positive for CD117 (membranous), OCT 3/4, SALL4, PLAP (PLoS One 2012;7:e43952)
- 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 ~33% of cases and associated with advanced stage at presentation (Cancer 2011;117:2096)
- Sex cord stromal tumors:
- Absence of admixed germ cells
- SF1: sensitive marker (Am J Surg Pathol 2009;33:354)
- Inhibin A: more specific marker
- Adult granulosa cell tumor:
- FOXL2 mutation FOXL2 402C → G (C134W) (N Engl J Med 2009;360:2719, PLoS One 2009;4:e7988, Am J Surg Pathol 2011;35:484)
- Sertoli-Leydig cell tumor:
- DICER1 hotspot sequences
- 3 molecular subtypes (Am J Surg Pathol 2019;43:628)
- Other mutations identified: MET, CTNNB1, TP53, GNAS (Pathology 2020;52:686)
- DICER1 hotspot sequences
Board review style question #1
The tumor shown above is found in the ovary of a 10 year old girl. Which of the following statements accurately distinguishes this tumor from a gonadoblastoma?
- Both mixed germ cell - sex cord stromal tumors and gonadoblastomas typically present with malignant germ cell components in > 50% of cases
- Gonadoblastomas are characterized by the presence of both germ cells and sex cord stromal cells in patients with normal karyotypes
- Mixed germ cell - sex cord stromal tumors exclusively occur in patients with abnormal sex chromosomes
- Mixed germ cell - sex cord stromal tumors occur in normal gonads of phenotypically and genetically normal patients and lack the characteristic features of a gonadoblastoma
Board review style answer #1
D. Mixed germ cell - sex cord stromal tumors occur in normal gonads of phenotypically and genetically normal patients and lack the characteristic features of a gonadoblastoma. A unique classification of mixed germ cell - sex cord stromal tumor (MGSCT) is that it occurs in patients without chromosomal aberrations, unlike gonadoblastoma. Answer C is incorrect because ovarian MGSCT occurs in patients without chromosomal aberrations. Answer B is incorrect because gonadoblastomas occur in patients with chromosomal aberrations / abnormal karyotypes. Answer A is incorrect because the percentage of MGSCT with a malignant germ cell component is 10%, significantly < 50%.
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Reference: Mixed germ cell - sex cord stromal tumor, unclassified
Comment Here
Reference: Mixed germ cell - sex cord stromal tumor, unclassified
Board review style question #2
Why is it clinically important to accurately distinguish a mixed germ cell - sex cord stromal tumor from a gonadoblastoma in a patient with an ovarian mass?
- Both tumors have a high risk of metastasis, so aggressive chemotherapy is required in all cases
- Both tumors require removal of the contralateral gonad, even if it appears normal
- Gonadoblastomas typically occur in dysgenetic gonads with a Y chromosome, whereas mixed germ cell - sex cord stromal tumors occur in phenotypically and genetically normal patients, impacting treatment decisions
- Mixed germ cell - sex cord stromal tumors often occur in patients with sex chromosomal abnormalities, influencing genetic counseling
Board review style answer #2
C. Gonadoblastomas typically occur in dysgenetic gonads with a Y chromosome, whereas mixed germ cell - sex cord stromal tumors (MGSCTs) occur in phenotypically and genetically normal patients, impacting treatment decisions. MGSCT occurs in patients without chromosomal aberrations, which impacts treatment decisions. Answer B is incorrect because the typical management for MGSCT is unilateral oophorectomy with conservation of the contralateral ovary. Answer D is incorrect because MGSCT does not demonstrate typical chromosomal aberrations. Answer A is incorrect because MGSCTs have a low risk of metastasis. Aggressive treatment is not required.
Comment Here
Reference: Mixed germ cell - sex cord stromal tumor, unclassified
Comment Here
Reference: Mixed germ cell - sex cord stromal tumor, unclassified
