Urothelial Carcinomas With Trophoblastic Differentiation, Including Choriocarcinoma

Abstract

Trophoblastic differentiation (including choriocarcinoma) arising in urothelial carcinoma has been described in numerous case reports, but never in a single series. We present a series of these tumors, describing the morphologic spectrum, applying traditional and novel immunohistochemical stains, and characterizing clinical follow-up. We identified 16 cases, arising predominantly in the bladder (N=14), but also the ureter (N=1) and prostatic urethra (N=1). Six of our cases (38%) contained invasive urothelial carcinoma with admixed syncytiotrophoblasts, 8 cases (50%) consisted of invasive urothelial carcinoma with choriocarcinoma, 1 case (6%) showed urothelial carcinoma in situ with associated choriocarcinoma, and 1 case (6%) consisted of pure choriocarcinoma. Other subtypes of variant morphology were seen in 5 of our cases (31%) and included squamous, glandular, lipoid, chordoid/myxoid, and sarcomatoid features. Given the limited specificity of human chorionic gonadotropin immunohistochemistry, we also studied the expression of a novel specific trophoblastic marker, hydroxyl-δ-5-steroid dehydrogenase, as well as Sal-like protein 4. Human chorionic gonadotropin expression was seen in nearly all cases (93%) but was often not limited to the trophoblastic component, staining the urothelial component also in 85% of the cases. Expression of hydroxyl-δ-5-steroid dehydrogenase was more sensitive and more specific, staining 100% of the cases and limited to trophoblasts in all but 1 case. Sal-like protein 4 expression was variable, staining trophoblast in only 50% of cases and staining the urothelial carcinoma component in 43% of those positive cases. Most of our tumors presented at a high stage and were associated with poor clinical outcomes, with at least muscle-invasive disease (pT2) in 10 of the 14 bladder tumors (71%), periureteric fat invasion in the ureter tumor (pT3), distant metastases in 7 of 16 cases (44%) and death of disease in 3 of the 15 patients with follow-up (20%). Our study describes a series of urothelial carcinomas with trophoblastic differentiation, demonstrating the morphologic spectrum of this entity, its frequent association with other subtypes of variant morphology, its characteristic immunoprofile, and its aggressive clinical behavior.

Urothelial carcinoma of the prostate with raised β-hCG levels: a case report

“…Moreover, repeatedly measured β-hCG provided an occasion to observe how its serum concentration correlates with gradual disease progression. To our knowledge, urothelial prostate cancer has been reported in the literature only once, but this is the first report of such clinical presentation with increased concentration of β-hCG and testis enlargement [ 2 ]. We hope that our case will lead to the widening of the clinical perception of urothelial prostate cancer and the extension of the differential diagnosis of neoplasms with a high β-hCG level to include urothelial prostate cancer with trophoblastic differentiation.…”

“…Overall survival does not exceed 2 years as it tends to recur and metastasize quickly [ 1 ]. As trophoblastic transformation in prostatic urothelial carcinoma is extremely rare, the prognostic significance of β-subunit human chorionic gonadotropin (β-hCG) has not been investigated yet [ 2 ]. Trophoblastic differentiation results in the presence of syncytiotrophoblastic cells and in some cases in increased β-hCG levels in serum [ 3 ].…”

Unusual Faces of Bladder Cancer

“…GATA3 positivity has been detected in more than 70% of trophoblastic tumors in a large series [59] and appears as a useful marker to be included in the diagnostic panel. SALL4 is focally positive in less than 50% of the cases [57] and is negative in the larger syncytiotrophoblastic cells [60]. HSD3B1, a novel marker specific to trophoblastic differentiation [61], has been detected in 100% of the cases [57].…”

“…SALL4 is focally positive in less than 50% of the cases [57] and is negative in the larger syncytiotrophoblastic cells [60]. HSD3B1, a novel marker specific to trophoblastic differentiation [61], has been detected in 100% of the cases [57].…”

“…Trophoblastic differentiation is a rare event in UC that has been recently reviewed by Przybycin et al in a series of 16 cases [57]. The spectrum includes isolated syncytiotrophoblast cells interspersed in a conventional UC, mixed choriocarcinoma and UC, and pure choriocarcinoma.…”