Mixed Adenocarcinomatous and Neuroendocrine Tumor of the Urinary Bladder With Concomitant Carcinoma In Situ: A Case Report With a Comprehensive Immunohistochemical Analysis and Review of the Literature

Abstract

Mixed adenoneuroendocrine carcinomas are rare and usually occur in the gastrointestinal tract. Although there have been several investigations regarding their developmental mechanism, the molecular origin of these tumors remains unclear. In this article, we present an exceedingly rare case of a mixed tumor of the urinary bladder with an adenocarcinomatous and a neuroendocrine component and a concomitant urothelial carcinoma in situ (CIS). Due to this extraordinary combination of tumor components, our goal was to extensively examine the 3 tumor components with regard to a representable common origin. Therefore, a comprehensive immunohistochemical analysis and review of the literature was performed. Besides expected outcome, our examination also revealed surprising staining results. Urothelial CIS, like the adenocarcinomatous component, showed strong staining for CDX2. In addition, parts of the adenocarcinoma were positive for synaptophysin like the neuroendocrine tumor component. All 3 components showed a significant overexpression of p53 and a moderate to strong membranous and cytoplasmatic staining for β-catenin. To our knowledge, we are the first to describe a case of a mixed tumor of the urinary bladder with an adenocarcinomatous and a neuroendocrine component and a concomitant CIS. The components share striking molecular features that argue for a common clonal origin and a development of the invasive tumor via the urothelial precursor lesion.

Ureter mixed neuroendocrine-non-neuroendocrine neoplasm: a case report and literature review

“…Over half of the primary urinary NECs are mixed with other histological components (5,6), and more than 90% of these reports of non-neuroendocrine components were of urothelial carcinoma, followed by squamous cell carcinoma, lymphoma, sarcoma, and adenocarcinoma, in order of frequency. We summarized published cases of mixed neuroendocrine and adenocarcinomatous tumor of the urinary system between 1990 and 2023 (Table 1) (7)(8)(9)(10)(11)(12)(13). The male-tofemale ratio was 7:1, with a median of 61 years, and it can occur in the bladder, ureter and urethra.…”

“…At present, many scholars support the theory of MiNEN is hypothesized to originate from monoclonal pluripotent stem cells that differentiate bidirectionally when stimulated with certain factors, which could explain the mixed histological features in urogenital NECs (19). Tränkenschuh et al (11) reported the case of a patient with primary adenoneuroendocrine carcinoma of the bladder combined with in situ urothelial carcinoma and observed significant similarities in the molecular features between these carcinomas, thereby highlighting their common clonal origin. Another postulated theory is that ureteral MiNEN may be caused by conversion of non-neuroendocrine to neuroendocrine components during tumor progression, including originating from residual urachus epithelium, or cystitis glandularis and intestinal anisocytosis, which would seem to explain the mix of adenocarcinoma components in MiNEN.…”