Spontaneous regression of testicular germ cell tumors: an analysis of 42 cases

Spontaneous regression of testicular germ cell tumors (GCTs) is a well-recognized phenomenon but has been incompletely characterized. Many pathologists are not familiar with the findings that support a diagnosis of a "burnt-out" primary in a patient with metastatic GCT. We therefore report the clinical, gross, and histologic findings in 42 cases of testicular GCT that showed either complete (26) or greater than 50% scarring (16). Thirty-seven patients (88%) had either known GCT metastasis or some residual testicular GCT, and none had treatment before orchiectomy. The patients were 17 to 67 years old, with a median of 32. Thirty presented with symptoms of metastasis, 7 with a testicular mass, 2 with elevated human chronic gonadotropin, and 1 with testicular pain. In 2 patients the presentation was unknown. Two patients had prior orchiopexy; another had an intraabdominal testis, and 2 others had prior contralateral seminoma (20 and 42 years previously). Gross descriptions in 37 cases identified white to tan scars, 0.6 to 2.4 cm, in 33. These were circumscribed in 16, with 15 of these having nodular or multinodular configurations and 1 a band-like appearance. In 9 cases the scar was ill defined or stellate, and in 8 cases no further details concerning the scar configuration were available. In 4 cases no scar was apparent; 2 of these had received intraoperative biopsy. Microscopically, all cases showed circumscribed to irregular foci of scarring, distinct from the adjacent parenchyma, in association with widespread testicular atrophy. Other common features were lymphoplasmacytic infiltrates in the scars (37/42) and "ghost" tubules in scars (31/42). Less common features in the scars included angiomatous foci (22/42), siderophages (15/42), and coarse intratubular calcifications (6/42); in the surrounding testis they included intratubular germ cell neoplasia, unclassified (IGCNU) (22/42), Leydig cell prominence (18/42), and necrosis (5/42). Tubular microliths occurred in 13 cases, 12 peripheral to the scar and 1 within it. Metastases in 31 cases were: pure seminoma (17, 3 with residual testicular seminoma), mixed GCT with seminoma (4, 3 with residual testicular seminoma), mixed nonseminomatous GCT (4, 3 with residual testicular GCT), pure embryonal carcinoma (2), pure teratoma (2, 1 with residual testicular teratoma), and pure yolk sac tumor (2). In 5 cases with clinically diagnosed metastases, there was no histologic documentation of the nature of the metastatic tumor. Testicular tumors in the remaining 6 cases having residual primaries without concomitant metastases were pure seminoma (3), mixed GCT with seminoma (2), and pure embryonal carcinoma (1). The most specific histologic findings of a regressed GCT are a distinct scar in association with either IGCNU or coarse intratubular calcifications; however, many cases lack the latter 2 features. In such cases additional features supportive of regressed GCT include testicular atrophy, microlithiasis and, in the scar, lymphoplasmacytic infiltrates and prominent vascularity. Ghost tubules in many scars are not evidence of a non-neoplastic process but likely reflect regression of tumors with intertubular growth. Intertubular growth is a common finding in seminoma, which is the single most frequent type of regressed GCT, occurring either in pure or mixed form in the metastases of 68% (21/31) of the cases and identifiable in 62% (10/16) of persistent testicular tumors. We conclude that regression of testicular GCTs shows a distinctive constellation of findings that usually permits its recognition. In contrast, nonspecific atrophy lacks distinct scars, and scars from non-neoplastic causes lack most of the associated findings seen in our cases.