“Somatic-type” Malignancies Arising From Testicular Germ Cell Tumors

Abstract

Somatic-type malignancies (SMs) in patients with testicular germ cell tumors (GCT) are rare and mostly attributed to "transformation" of teratoma, although yolk sac tumor (YST) origin has also been proposed. We studied 124 cases of "SM" of testicular GCT origin from 106 patients to evaluate their morphology, immunohistochemical features (especially the utility of SALL4), and relationship to YST. Primitive neuroectodermal and nephroblastomatous tumors were excluded because of prior studies. Patients ranged in age from 15 to 68 years (mean, 33 y). The tumors ranged from 0.7 to 30 cm (mean, 7.6 cm) and involved the retroperitoneum (64%), abdomen/pelvis (10%), lung (10%), mediastinum (6%), supraclavicular region/neck (4%), testis (4%), and thigh (1%). Most initial diagnoses were sarcomas (n=68) or carcinomas (n=51). On review and immunohistochemical analysis, 7 of 45 adenocarcinomas were reclassified as glandular YSTs (GYST) on the basis of glypican-3 (GPC3) and/or α-fetoprotein positivity and scant/absent reactivity for EMA and CK7. These occasionally (29%) had subnuclear and sometimes supranuclear vacuoles (endometrioid-like), whereas adenocarcinomas were more frequently mucinous (17%) or enteric-type (11%) than endometrioid-like (9%). Both expressed CDX2 frequently (83% and 63%, respectively). MUC protein 2, 4, 5, and 6 expression was more common in adenocarcinomas (7% to 36%) than in GYSTs (0% to 20%) but was infrequent. Both were often positive for SALL4, BerEP4, and MOC31; all were negative for TTF-1. On follow-up (GYST: range, 23 to 169 mo; mean, 81mo; adenocarcinoma: range, 1 to 170 mo; mean, 55 mo), 50% and 33% of patients with GYST and adenocarcinoma, respectively, died of disease. We reclassified 26 of 76 sarcomatoid tumors as sarcomatoid YSTs (SYST) on the basis of positive reactivity for both AE1/3 and GPC3. These tumors often had spindled and epithelioid cells in a fibromyxoid stroma. SYSTs were often (60%) SALL4 positive, whereas sarcomas were all negative. On follow-up (SYST: range, 1 to 259 mo; mean, 62 mo; sarcoma: range, 1 to 327 mo; mean, 70 mo), 50% and 29% of patients with SYST and sarcoma, respectively, died of disease, with most mortality occurring in those with high-grade tumors. We conclude that, on the basis of a panel of immunoreactivities, a significant number of "SMs" in testicular GCT patients are more accurately classified as either GYSTs or SYSTs. Ambiguous glandular tumors should be evaluated for GPC3, α-fetoprotein, CK7, and EMA reactivity and sarcomatoid ones for GPC3, AE1/3, and SALL4 reactivity.

Clinicopathology Illustration Treatment Options and Survival in the Patients with Testicular Germ Cell Tumors in Kermanshah Province, Iran

“…In a study, the mean age for TGCT patients was 33 years (14). Assi et al (12) reported that the mean age for testicular tumors was 32 years.…”

Testicular Germ Cell Tumors

“…Somatic-type malignancy: While the development of somatic-type malignancy is not a phenomenon exclusively found in post-chemotherapy specimens, it is more commonly seen in this setting [135]. The most common histologies are peripheral neuroectodermal tumors, rhabdomyosarcoma and other sarcomas, and adenocarcinomas; however, a wide spectrum of somatic histologic types has been described.…”

“…The term sarcomatoid YST has been used to describe tumors with spindled cellular stroma that retains cytokeratin reactivity. A recent study [135] has proposed that some somatic sarcomatoid malignancies may actually represent sarcomatoid YST. Hepatoid YST consists of cells with abundant eosinophilic cytoplasm, large central nucleus, and prominent nucleolus arranged in nests, cords, or trabeculae.…”

“…The rationale for separating teratomatous and non-teratomatous elements resides in the fact that teratoma response to chemotherapy is not expected, and thus, the presence of teratoma does not imply ineffective or insufficient chemotherapy. Surgical removal of teratoma elements is required, as teratomas may grow and impinge on vital structures ("growing teratoma syndrome") [145,146] or may undergo development of somatic malignancy [135]. The presence of teratoma and YST in the primary tumor is a predictor of teratoma in PC-RPLND specimen [168].…”

“…7.25). The presence of these elements does not impact prognosis or diagnostic terminology, unless frank overgrowth is present, in which case one must consider the possibility of a secondary malignancy [135] (see Chap. 12).…”