Testicular sertoli cell tumour in a patient with familial adenomatous polyposis: A not-so-incidentaloma?

Germline APC Alterations May Predispose to Testicular Sex Cord-Stromal Tumors

“…7,9 Although there have been 2 occasional reports of TSCSTs arising in patients with FAP, this association remained largely anecdotal due to the lack of evidence that germline APC variants had a role in oncogenesis. 4,5 Hence, these cases could potentially represent a coincidental occurrence of typical CTNNB1-altered Sertoli cell tumors arising in patients with FAP. In this study, we demonstrate that TSCSTs in patients with pathogenic germline APC variants (including some with known FAP) lacks gainof-function CTNNB1 variants, being driven by functional inactivation of APC likely secondary to LOH events.…”

“…Of note, a subset of these tumors have demonstrated malignant clinical behavior 7,9 . Although there have been 2 occasional reports of TSCSTs arising in patients with FAP, this association remained largely anecdotal due to the lack of evidence that germline APC variants had a role in oncogenesis 4,5 . Hence, these cases could potentially represent a coincidental occurrence of typical CTNNB1 -altered Sertoli cell tumors arising in patients with FAP.…”

“…Consequently, the detection of nongastrointestinal neoplasms that may arise or progress later in life has become increasingly relevant in patients with germline pathogenic APC variants. Testicular Sertoli cell tumor, a neoplasm commonly driven by gain-of-function CTNNB1 mutations, has anecdotally been reported twice in the context of FAP, but it remained uncertain whether this represented an incidental occurrence given the absence of molecular data to support the pathogenic role of APC in these cases 3–5 . Our group and others have recently identified APC mutations in testicular sex cord-stromal tumors (TSCST) with different phenotypes, prompting us to further investigate their potential association with germline APC variants 6–9 …”

“…Testicular Sertoli cell tumor, a neoplasm commonly driven by gain-of-function CTNNB1 mutations, has anecdotally been reported twice in the context of FAP, but it remained uncertain whether this represented an incidental occurrence given the absence of molecular data to support the pathogenic role of APC in these cases. [3][4][5] Our group and others have recently identified APC mutations in testicular sex cord-stromal tumors (TSCST) with different phenotypes, prompting us to further investigate their potential association with germline APC variants. [6][7][8][9] In this study, we evaluated 4 TSCSTs with known pathogenic APC variants and/or a known clinical association with FAP to determine the link between germline APC alterations and oncogenesis in these tumors.…”

Contemporary Updates on Sex Cord–stromal Tumors of the Testis

“…30,44 Until recently, only 2 cases of Sertoli cell tumor, NOS arising in patients with familial adenomatous polyposis (FAP) had been documented, but the association was largely anecdotal, because there was no evidence that a germline APC variant was implicated in the oncogenesis of these neoplasms. 46,47 This year, Siegmund and colleagues analyzed 3 Sertoli cell tumors, NOS (including 2 occurring in patients with a clinical history of FAP) and 1 malignant unclassified TSCST with APC variants, demonstrating that germline loss-of-function APC variants with loss-of-heterozygosity were the underlying oncogenic mechanism in these tumors 48 . This suggests that FAP and variants thereof may predispose patients to develop TSCSTs in general, and Sertoli cell tumor, NOS in particular.…”