Testicular germ cell tumors with somatic-type malignancy
image: (a) Overgrowth of round cells with eosinophilic cytoplasm in a sheet-like growth pattern. Note the residual teratomatous (glandular) component in the right upper corner. (b) High-power view of the tumor showing medium-to-large round cells with eosinophilic cytoplasm, eccentric atypical nuclei, and prominent nucleoli. (c) The tumor cells are strongly positive for myogenin.
Credit: Gang Wang, Yong Guan
Testicular germ cell tumors (GCTs) are the most common malignancies in young men aged 15–35. Despite the high cure rate of over 90%, the prognosis drastically worsens when somatic-type malignancy (SM) arises within these tumors. This review explores the diagnostic criteria, histopathology, molecular features, and clinical management of GCTs with SM, emphasizing the importance of recognizing and treating these rare yet aggressive tumors.
Histopathology
Diagnostic Criteria
GCT with SM is diagnosed when there is an expansile or infiltrative growth of epithelial or mesenchymal components measuring at least 5 mm. The tumor must exhibit a pure population of atypical cells, occupying at least one low-power field (4× objective). If the overgrowth involves less than one low-power field, it is considered a teratoma rather than SM. However, clinical practice may apply less stringent criteria, focusing on the overall amount of tumor exceeding 5 mm in contiguous sections.
Histological Subtypes
GCTs with SM exhibit a broad spectrum of histological types resembling non-GCT malignancies in other organs. These include sarcomas, carcinomas, and other rare tumors.
Sarcoma
Sarcomas are the most common type of SM, with various forms including rhabdomyosarcoma, leiomyosarcoma, angiosarcoma, and myxofibrosarcoma. Rhabdomyosarcoma, characterized by rhabdomyoblasts at various stages of myogenesis, is the most frequently reported. Leiomyosarcoma exhibits a fascicular growth pattern with high-grade atypical spindle cells, while angiosarcoma shows pleomorphic atypical cells with irregular vascular spaces.
Carcinoma
Approximately 90% of carcinomas in SMs are adenocarcinomas. These can present as enteric, mucinous, endometrioid-like, or not-otherwise-specified types, characterized by high-grade cytologic atypia and an infiltrative growth pattern. Differentiating SM adenocarcinoma from yolk sac tumor (YST) is crucial due to differences in prognosis and treatment. Adenocarcinoma typically shows strong expression of carcinoembryonic antigen and caudal-type homeobox 2, but is negative for alpha-fetoprotein.
Embryonic-Type Neuroectodermal Tumor (ENT)
ENTs, previously known as primitive neuroectodermal tumors, result from malignant transformation along mesodermal lines. They are characterized by small, round, blue malignant cells in diffuse sheets, occasionally forming tubules or pseudorosettes. Differentiating ENT from other small round cell tumors like Ewing sarcoma is critical.
Neuroglial Neoplasms
Neuroglial neoplasms in GCTs are extremely rare. They include low-grade astrocytoma, ganglioglioma, and anaplastic astrocytoma, among others. These tumors are confirmed by immunohistochemistry for glial fibrillary acidic protein.
Molecular Features
The molecular features of GCTs with SM remain under investigation. Recent studies suggest that the presence of SM in GCT metastasis may be a high-risk factor for prognosis. Molecular analyses have shown various genetic alterations, including those involving the p53 pathway, which are associated with poor outcomes.
Management and Outcomes
Surgical Treatment
The primary treatment for GCT with SM is radical surgical extirpation. The feasibility of complete resection significantly impacts the prognosis. In cases where SM is confined to the testis or retroperitoneum, surgical resection can lead to favorable outcomes.
Chemotherapy and Radiotherapy
The role of chemotherapy and radiotherapy in treating GCT with SM is less well-defined. While traditional GCTs respond well to platinum-based chemotherapy, SM components may be resistant, necessitating alternative therapeutic strategies. Radiotherapy may be considered for certain histological subtypes, such as sarcomas and neuroglial tumors.
Prognosis
The prognosis for patients with GCT and SM is generally poor, with cancer-specific survival rates of 50–60%. The extent of the disease at onset and the feasibility of radical resection are critical factors influencing outcomes. Regular follow-up and monitoring for late recurrences are essential for managing these patients.
Conclusions
GCTs with SM represent a rare and aggressive subset of testicular tumors. Early recognition and appropriate management are crucial for improving patient outcomes. Ongoing research into the molecular characteristics and treatment responses of these tumors will likely provide new insights and therapeutic options in the future.
Full text
https://www.xiahepublishing.com/2771-165X/JCTP-2022-00028
The study was recently published in the Journal of Clinical and Translational Pathology.
Journal of Clinical and Translational Pathology (JCTP) is the official scientific journal of the Chinese American Pathologists Association (CAPA). It publishes high quality peer-reviewed original research, reviews, perspectives, commentaries, and letters that are pertinent to clinical and translational pathology, including but not limited to anatomic pathology and clinical pathology. Basic scientific research on pathogenesis of diseases as well as application of pathology-related diagnostic techniques or methodologies also fit the scope of the JCTP.
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