Improving Diagnostic Accuracy for Plasmacytoid Urothelial Carcinoma: Insights from Cytological Evaluation of Fine Needle Aspiration (FNA) Smears and Urine Samples

Summary: Introduction: Plasmacytoid urothelial carcinoma (PUC) is a rare and aggressive variant of high-grade urothelial carcinoma (HGUC), demanding precise identification for effective clinical management. PUC manifests with a distinct plasmacytoid appearance, presenting diagnostic challenges in distinguishing it from conditions such as multiple myeloma, lobular breast carcinoma, melanoma, and neuroendocrine tumors. Diagnostic evaluation of PUC cases through urine cytology is notably challenging due to factors like sparse tumor cellularity and relatively unremarkable nuclear features. This study aims to explore the cytological characteristics of PUC using fine needle aspiration (FNA) smears in conjunction with concurrent core needle biopsies (CNB), supplemented by pathology reports from cystectomy and Thin Prep urine preparations. Materials and Methods: Institutional cytopathology records were examined for confirmed cases of PUC where both FNA and CNB were available, between 2021 and 2023. Additionally, pathology/cytology reports from cystectomy procedures and urine samples collected within one month before cystectomy were reviewed for these cases. Results: We identified 8 cases of PUC (table 1). One originated from bladder and 7 as locoregional or distant metastases. Biopsy sites included lymph nodes, bone/ soft tissue, and bladder. Cytological diagnoses varied, with 2/8 positive for malignancy, 1/8 positive for neoplasm, 2/8 suspicious for malignancy, 2/8 nondiagnostic, and 1/8 negative. PUC cytomorphology (Fig. 1) depicted single cells, loosely cohesive sheets of cells, plasmacytoid appearance, prominent cytoplasmic vacuoles, high nuclear-to-cytoplasmic ratio, coarse chromatin, smooth nuclear contours, and ""grungy"" cytoplasm. Similar features were seen in some CNB samples (Fig. 2). Immunohistochemistry consistently indicated pan-cytokeratin, CD138, and GATA3 expression, with loss of E-cadherin. Only two cases (2/6) reported plasmacytoid features in surgical specimens. Cytology of urine collected within 1 month before cystectomy showed HGUC (1/8), atypical urothelial cells (2/8), or findings suspicious (3/8) or negative (2/8) for HGUC. Conclusions: The primary cytological features of PUC observed on FNA included single cells and loosely cohesive cell nests displaying plasmacytoid morphology, often accompanied by prominent cytoplasmic vacuoles. These features correlated with histological findings in corresponding CNB samples, but only 1/3 of the pathology reports of surgical specimens. Cytological assessment for PUC cases provides valuable diagnostic insights. A cytology preparation may serve as the initial indication of PUC, sometimes less apparent on resection specimens. In urine cytology cases of PUC, only half exhibit positivity or suspicion for HGUC, underscoring the challenge in detecting PUC tumor cells in urine samples.