Sex cord stromal tumors
2023-05-02 Andres M. Acosta, MD Affiliation1.Department of Pathology, Indiana University, Indianapolis, IN
Classification
Definition
Sex cord stromal tumors (SCSTs) constitute ~5% of all testicular neoplasms and comprise a heterogeneous group of lesions with sex-cord and/or stromal phenotype that may arise in pediatric or adult patients. 1 The most common testicular SCSTs are Leydig cell tumor and Sertoli cell tumors, with other types being relatively rare. Overall, ~90% of these neoplasms are indolent and the remaining ~10% are clinically malignant. Because SCSTs are typically resistant to systemic treatment, management of patients with metastatic disease is often challenging and overall prognosis of malignant testicular SCSTs is worse than that of testicular germ cell tumors. 2 Subsets of Leydig cell tumors harbor mutations in LHGCR, FH, CTNNB1, and recurrent TERT fusions and MDM2 amplifications have been identified in metastasizing cases. 3-6 Sertoli cell tumors, not otherwise specified are typically associated with gain-of-function CTNNB1 mutations, and large cell calcifying Sertoli cell tumors are characterized by PRKAR1A inactivation. 7-10 Other subtypes of sex cord-stromal tumors their molecular features have been less extensively studied.
| Sex cord stromal tumors (SCSTs) | Genetics Events |
|---|---|
| Leydig cell tumor of the testis | Pediatric Leydig cell tumors are associated with gain-of-function LHCGR mutations. 11 Adult cases may also demonstrate activating GNAS mutations, activating CTNNB1 mutations and FH inactivation. 3,4,6,12 Malignant behavior and/or aggressive features seem to be asscoiated with FH deficiency and alterations of genes of the p53 pathway such as MDM2 amplifications and TP53 mutations. 3,4,6 |
| Sertoli cell tumor of the testis | Gain of the X chromosome, and less commonly entire or partial losses of chromosomes 2 and 19 have been reported in this tumor type. 13 Most benign and ~50% of metastasizing cases harbor gain-of-function CTNNB1 mutations. 7,14 These most commonly affect mutational hotspots in exon 3. Alternatively, activation of the Wnt pathway may be secondary to loss of APC in rare cases. 14 A subset of malignant neoplasms may represent biologic progression of CTNNB1-mutant Sertoli cell tumors that acquire additional genomic lesions such chromosomal imbalances. 14 Another subset of malignant cases with unique morphologic features that partially overlap with those seen in seminoma are driven by EWSR1::ATF1. 15 |
| Large cell calcifying Sertoli cell tumor of testis (LCCSCT) | About 10-40% of LCCSCT present in the context of Carney complex 16, and rare cases have been descibed in patients with NF1 17 and Peutz-Jeghers syndrome. 18 Both sporadic and syndromic cases demonstrate pathogenic PRKAR1A variants with loss of heterozygosity, resulting in functional loss of the gene. 9,10,19 |
| Granulosa cell tumors of the testis (TGCT) | Unlike their ovarian counterparts, adult granulosa cell tumors of the testis only rarely harbor hotspot FOXL2 p.C134W mutations.20,21 Recurrent loss of 22q is seen in ~70% of adult granulosa cell tumors. Juvenile granulosa cell tumors of the testis are also diferent from their ovarian counterparts in that they lack internal tandem duplications in AKT1 and hotspot GNAS mutations. 22 Monosomy 10 is a recurrent finding in 50-60% of testicular juvenile granulosa cell tumors. 22 |
| Tumors in the fibroma family of tumors | No specific molecular abnormalities described so far. |
Article Bibliography
| Reference Number | Pubmed ID | Last Year | Title | Authors |
|---|---|---|---|---|
| 1 | 29382456 | 2017 | A contemporary population-based study of testicular sex cord stromal tumours: Presentation, treatment patterns, and predictors of outcome. | Yuh LM et al |
| 2 | 32303266 | 2020 | A comparison of stage-specific all-cause mortality between testicular sex cord stromal tumors and germ cell tumors: results from the National Cancer Database. | Zuniga KB et al |
| 3 | 34103665 | 2021 | Comparative molecular analysis of testicular Leydig cell tumors demonstrates distinct subsets of neoplasms with aggressive histopathologic features. | Rizzo NM et al |
| 4 | 31147264 | 2019 | Genomic Features of Metastatic Testicular Sex Cord Stromal Tumors. | Necchi A et al |
| 5 | 33741265 | 2021 | TERT Gene Fusions Characterize a Subset of Metastatic Leydig Cell Tumors. | Kruslin B et al |
| 6 | 32757426 | 2021 | The Leydig cell tumour Scaled Score (LeSS): a method to distinguish benign from malignant cases, with additional correlation with MDM2 and CDK4 amplification. | Colecchia M et al |
| 7 | 24061522 | 2014 | Frequent mutation and nuclear localization of β-catenin in sertoli cell tumors of the testis. | Perrone F et al |
| 8 | 20004940 | 2010 | Large cell calcifying Sertoli cell tumor: a clinicopathologic study of 1 malignant and 3 benign tumors using histomorphology, immunohistochemistry, ultrastructure, comparative genomic hybridization, and polymerase chain reaction analysis of the PRKAR1A gene. | Petersson F et al |
| 9 | 31286102 | 2019 | Somatic PRKAR1A Gene Mutation in a Nonsyndromic Metastatic Large Cell Calcifying Sertoli Cell Tumor. | Tatsi C et al |
| 10 | 34780072 | 2022 | Large cell calcifying Sertoli cell tumour: a contemporary multi-institutional case series highlighting the diagnostic utility of PRKAR1A immunohistochemistry. | Anderson WJ et al |
| 11 | 10580072 | 1999 | Leydig-cell tumors caused by an activating mutation of the gene encoding the luteinizing hormone receptor. | Liu G et al |
| 12 | 22016347 | 2012 | A rare cause of hypertestosteronemia in a 68-year-old patient: a Leydig cell tumor due to a somatic GNAS (guanine nucleotide-binding protein, alpha-stimulating activity polypeptide 1)-activating mutation. | Libé R et al |
| 13 | 17333264 | 2007 | Molecular-cytogenetic characterisation of sex cord-stromal tumours: CGH analysis in sertoli cell tumours of the testis. | Verdorfer I et al |
| 14 | 36906070 | 2023 | Molecular Correlates of Aggressive Behavior and Biological Progression in Testicular Sertoli Cell Tumors. | Rizzo NM et al |
| 15 | 36791251 | 2023 | Inflammatory and Nested Testicular Sex Cord Tumor: A Novel Neoplasm With Aggressive Clinical Behavior and Frequent EWSR1::ATF1 Gene Fusions. | Acosta AM et al |
| 16 | 160980 | 1979 | The mixed lymphocyte culture test. | |
| 17 | 162200 | 1979 | Physiological functional position of the mandible. | May W et al |
| 18 | 175200 | 1975 | [Bone imaging with 99m Tc-pyrophosphate]. | Fujiwara K et al |
| 19 | 36929593 | 2023 | Large cell calcifying Sertoli cell tumour: molecular and immunohistochemical assessment of a series comprising non-metastasising and metastasising neoplasms. | Yu S et al |
| 20 | 22742556 | 2012 | FOXL2 mutations in granulosa cell tumors occurring in males. | Lima JF et al |
| 21 | 34845303 | 2022 | Molecular assessment of testicular adult granulosa cell tumor demonstrates significant differences when compared to ovarian counterparts. | Siegmund S et al |
| 22 | 36813116 | 2023 | Testicular Juvenile Granulosa Cell Tumors Demonstrate Recurrent Loss of Chromosome 10 and Absence of Molecular Alterations Described in Ovarian Counterparts. | Collins K et al |
Citation
Andres M. Acosta, MD
Sex cord stromal tumors
Atlas Genet Cytogenet Oncol Haematol. 2023-05-02
Online version: http://atlasgeneticsoncology.org/solid-tumor/209121/sex-cord-stromal-tumors
