Paratesticular/inguinal SMARCB1/INI1 deficient carcinomas with yolk sac tumour-like differentiation are aggressive...

Extragonadal yolk sac tumour (YST) is rare, and may present a diagnostic challenge. YST differentiation was recently reported in some somatically derived tumours in the sinonasal location and in the female genital tract, together with a SMARCB1/INI1 loss. We report two paratesticular/inguinal tumours with striking morphological and immunohistochemical similarities with YST, further expanding the spectrum of extragonadal tumours with YST-like morphology and SMARCB1/INI1 loss.

Patients were 13- and 27-year-old males who presented with a 1-cm inguinal mass and a 4.6-cm spermatic cord mass, respectively. Both neoplasms showed histological and immunohistochemical features in keeping with YST. Immunohistochemically, the neoplastic cells were diffusely positive for AE1/AE3, spalt-like transcription factor 4 (SALL4) and glypican-3; alpha-fetoprotein (AFP) was positive in one of two tumours. S100, SMA, CD34 and brachyury were negative in both tumours. Pre-operative serum AFP levels were normal in both patients. Although the initial diagnostic consideration was extragonadal YST, the diagnostic work-up revealed complete loss of SMARCB1/INI1 on immunohistochemistry and absence of isochromosome 12p by fluorescence in-situ hybridisation. Both patients had an aggressive clinical course with rapid disease progression and widespread metastatic spread.

Somatically derived tumours with YST-like morphology at an extragonadal location present a potential diagnostic pitfall. This type of neoplasm has not been previously reported in males at this location. Therefore, SMARCB1/INI1 should be included in the immunohistochemistry work-up of any neoplasm that morphologically resembles YST at an extragonadal site, even in the setting of positive germ cell tumour markers, as the correct diagnosis has prognostic and therapeutic implications.