Case Report: From teratoma to adenocarcinoma: molecular insights into somatic-type malignancy in testicular germ cell tumors - two case reports and review of the literature

Testicular germ cell tumors (TGCTs), though typically responsive to therapy, may rarely develop somatic-type malignancy (STM), a transformation associated with poor prognosis and chemoresistance. This study presents two cases of postpubertal-type teratoma with intestinal-type adenocarcinoma as STM, offering insights into their clinical, histopathological, immunophenotypic, and molecular profiles. The first patient, a 63-year-old male, presented with pulmonary and retroperitoneal metastases and underwent orchiectomy, revealing an intratesticular intestinal-type adenocarcinoma. Molecular testing confirmed 12p overrepresentation and pathogenic mutations in <i>CTNNB1</i>, <i>STK11</i>, and <i>MDM2</i>. The second patient, initially diagnosed at age 35 with a mixed TGCT, developed STM as a late recurrence 16 years post-orchiectomy, manifesting as a retroperitoneal mass with vertebral invasion. Histology again confirmed intestinal-type adenocarcinoma, and molecular testing revealed amplification of <i>ERBB2</i>, <i>KRAS</i>, along with mutations in <i>TP53</i> and <i>PIK3CA</i>. Both cases were managed with capecitabine-oxaliplatin plus bevacizumab, followed by maintenance therapy, achieving disease stabilization for at least 9 months. These cases illustrate the diagnostic and therapeutic complexities of STM, particularly with adenocarcinoma morphology that may mimic primary gastrointestinal neoplasms. Accurate diagnosis required exclusion of alternate primary sites and demonstration of chromosome 12 aberrations using FISH and next-generation sequencing. Our findings emphasize the importance of long-term follow-up in TGCT patients, particularly those with teratomatous elements, and highlight the value of cytogenetic and molecular profiling in confirming STM and identifying potential therapeutic targets. Given the rarity of STM, especially in metastatic or recurrent settings, there is an urgent need for standardized diagnostic protocols and evidence-based treatment strategies. These cases support the use of tumor-specific chemotherapy regimens guided by the histological and molecular characteristics of STM.