Case Report: The Complete Remission of a Mixed Germ Cell Tumor With Somatic Type Malignancy of Sarcoma Type With a GCT-Oriented Therapy: Clinical Findings and Genomic Profiling

Abstract

Somatic malignant transformation in a germ cell tumor (GCT) is the development of non-germ malignancies; much of available literature refers to teratoma with malignant transformation (TMT). There are various transformation histologies such as sarcoma, adenocarcinoma, primitive neuroectodermal tumors, and more rarely carcinoid tumors, hemangioendothelioma, lymphoma, or nephroblastoma. The treatments of these entities include surgery and/or chemotherapy. A standard approach in choosing chemotherapy in TMT cases has not yet been established. Many authors suggest using chemotherapeutic agents based on the transformed histology, while others recommend GCT-oriented therapy combined with surgery as the primary treatment, reserving histology-driven chemotherapies for metastatic relapse. We report the clinical findings and the genomic profile of a mixed GCT case with somatic-type malignancy of sarcoma type. We achieved a complete radiological response with GCT-oriented chemotherapy performed as salvage therapy after sarcoma-histology therapy. In addition, molecular profiles with RNA-sequencing and exome sequencing analyses of the primary tumor and the tumor with somatic-type malignancy of sarcoma type were explored.

A Case of Mediastinal Carcinosarcoma With Beta-HCG Production and KRAS Mutation

“… 9 , 10 With rare exceptions germ cell tumors with somatic type malignancy occur in adult males and manifest as a spectrum of malignant tumors including chondrosarcoma and adenocarcinoma. 11 – 13 While the possibility of germ cell tumor with somatic type malignancy cannot be completely excluded, the patient's sex, the lack of conventional germ cell tumor morphology, the low levels of beta-HCG production, and the tumor's immunoprofile with negative germ cell tumor markers (SALL4 and OCT3/4) make that diagnosis unlikely.…”

Germ Cell Tumor With Somatic-Type Malignancy: A Case Report and Review of the Literature

“…At present, the optimal strategy for the management of SMs is unclear. Several studies have shown resistance of SMs to GCT-oriented chemotherapy with the exception of one report from Pantaleo et al of successful treatment of a mixed GCT with SM of sarcoma type with a GCT-oriented treatment [ 17 - 19 ]. A study of 121 patients with SM treated at Indiana University demonstrated a clinical complete remission (CR) rate of 12.8% with cisplatin-based chemotherapy, which is significantly lower than the 70-80% rate of CR that would be expected with cisplatin-based chemotherapy in patients with metastatic GCT [ 18 ].…”

Testicular Germ Cell Tumors with Somatic-type Malignancy

“…The positive staining of spalt-like transcription factor 4 suggests a germ cell origin, especially with a history of GCTs. 14,17 The strong expression of desmin, myogenin (Fig. 1c), and myoblast determination protein 1 can confirm the diagnosis of rhabdomyosarcoma in a GCT.…”

“…Based on their morphological and immunohistochemical characteristics, GCTs with SM can be classified as sarcoma, adenocarcinoma, ENTs, or other rare tumors, such as carcinoid tumors, hemangioendothelioma, lymphoma, or nephroblastoma. 10,14…”