Paragangliomas Arising From the Laryngeal Paraganglia: Thyroid and Laryngeal Paragangliomas With Radiology-Pathology Correlation.

Paragangliomas are neuroendocrine tumors that arise from the embryonic neural crest cells of the extra-adrenal chromaffin and non-chromaffin cellular system. Paragangliomas arising from the laryngeal paraganglia, which occur in the thyroid and larynx, are a rare subset of paragangliomas compared to the more common locations of the carotid body, vagale, jugular, and tympanic paragangliomas. The preoperative diagnosis of both thyroid and laryngeal paragangliomas may pose a challenge due to cytological, pathological, and imaging non-specificity that overlaps with many other neoplasms. These lesions may be associated with significant intraoperative bleeding and complicated excision with adherence to nearby structures, including the recurrent laryngeal nerve. This article discusses the imaging appearance, pathological features, clinical and operative considerations and manifestations, and management of head and neck paragangliomas, as seen in two patients at our institution.

A Low-grade Sinonasal Sarcoma Harboring EWSR1::BEND2: Expanding the Differential Diagnosis of Sinonasal Spindle Cell Neoplasms.

BACKGROUND: Molecular diagnostics has greatly refined sinonasal tumor pathology over the past decade. While much of the attention has focused on carcinomas, it is becoming clear that there are emerging mesenchymal neoplasms which have previously defied classification. METHODS: Here, we present a 33-year-old woman with a multiply recurrent sinonasal spindle cell tumor exhibiting distinctive features, and not easily classifiable into a specific category. RESULTS: The hypercellular tumor was composed of plump spindled cells, with uniform vesicular chromatin arranged as vague fascicles around a prominent hemangiopericytoma-like vasculature. The mitotic rate was brisk at 10 per 10 high power fields. By immunohistochemistry, it was only positive for EMA (focal) and SATB2 (diffuse, weak). Fusion analysis uncovered EWSR1::BEND2, a fusion which is best known for being seen in astroblastoma, but which has not yet been reported in sarcomas. CONCLUSION: This case underscores the utility of fusion analysis when confronted with a sinonasal spindle cell neoplasm which does not neatly fit into any specific category. It remains to be seen if EWSR1::BEND2 sinonasal sarcoma represents a distinct entity.

High-risk human papillomavirus testing in cytology aspiration samples from the head and neck part 1: a review of the literature on available testing options.

Human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma is increasing in incidence and is often first diagnosed on a cytology fine needle aspiration (FNA) specimen of metastatic nodal disease of the neck. In the setting of oropharyngeal squamous cell carcinoma, HPV status defines the disease with HPV-associated tumors having better overall prognosis than those that are HPV negative. Furthermore, metastatic squamous cell carcinoma of the neck of unknown origin requires testing for HPV as a positive result suggests an oropharyngeal primary. As a result, HPV testing in aspirate samples is increasingly important for the proper diagnosis and treatment of patients with head and neck squamous cell carcinoma. Although HPV testing in cervicovaginal cytology specimens is common and well-established, testing in head and neck FNA samples remains challenging. p16 immunohistochemistry is an excellent surrogate marker for HPV in tumors of known or suspected oropharyngeal origin, but the criteria used in histologic specimens may not be appropriate in cytology samples. FNA samples are more frequently hypocellular, and cytology cell blocks have variable fixation and processing steps, limiting the utility of p16 immunohistochemistry. Other potential testing options have been reported in the literature including staining of aspirate smears and molecular testing of liquid-based samples. The American Society of Cytopathology Clinical Practice Committee recently surveyed the American Society of Cytopathology membership to determine the current state of HPV testing in aspirate samples, and this review article is designed to provide a summary of the current literature on various testing options in FNA samples.

High-risk human papillomavirus testing in cytology aspiration samples from the head and neck part 2: a survey of the American Society of Cytopathology community.

INTRODUCTION: High-risk human papillomavirus (HR-HPV) status is critical in the diagnosis of oropharyngeal squamous cell carcinoma, informing prognosis and choice of therapy. HR-HPV status additionally plays a key role in the evaluation of squamous cell carcinoma of unknown origin metastatic to cervical lymph nodes. Thus, HR-HPV testing of fine needle aspirate (FNA) specimens from the head and neck is invaluable for accurate diagnosis, prognostication, and treatment planning. MATERIALS AND METHODS: American Society of Cytopathology members were surveyed to understand the current state of HR-HPV testing on FNA samples from the head and neck. The survey focused on 3 main topic areas: practice setting of respondents, methods of collection and processing of aspirate specimens for HR-HPV testing, and validation of HR-HPV testing methodologies on aspirate samples. RESULTS: The survey reveals that laboratories employ various methods to detect HR-HPV in FNA samples, most commonly p16 immunohistochemical staining of cell block sections. Although some laboratories have independently validated their HR-HPV detection method, such validation is not universal. Finally, not all respondents currently have HR-HPV testing available, but approximately half of those without a testing method desire to make HR-HPV testing of FNA samples available. CONCLUSIONS: Survey responses highlight that various testing modalities are utilized for HR-HPV detection in aspirate samples. However, internal laboratory validation of HR-HPV testing for FNA specimens is not ubiquitous despite professional society recommendations.

Multi-institutional validation of a modified scheme for subcategorizing salivary gland neoplasm of uncertain malignant potential (SUMP).

BACKGROUND: The salivary gland neoplasm of uncertain malignant potential (SUMP) category in the Milan System is diagnostically challenging. This study aims to validate a modified scheme for subcategorizing SUMP in a large multi-institutional cohort. METHODS: Retrospective review of salivary gland fine-needle aspirations (FNAs) from 10 institutions were classified based on the Milan System. Cases diagnosed as SUMP with available cytology slides and surgical follow-up were retrieved for review and subcategorized based on a modified scheme as follows: basaloid SUMP (B1: absent/scant nonfibrillary matrix; B2: presence of nonfibrillary/mixed-type matrix), oncocytic/oncocytoid SUMP (O1: with mucinous background; O2: without mucinous background), and SUMP not otherwise specified (NOS). RESULTS: A total of 742 (7.5%) cases from 9938 consecutive salivary gland FNAs were classified as SUMP. Among them, 525 (70.8%) had surgical follow-up and 329 (62.7%) were available for review. The overall risk of malignancy (ROM) of SUMP was 40.4%. There were 156 cases (47.4%) subcategorized as basaloid SUMP with a ROM of 36.5%, 101 (30.7%) as oncocytic/oncocytoid SUMP with a ROM of 52.5%, and 72 (21.9%) as SUMP NOS with a ROM of 31.9%. The ROM of oncocytic/oncocytoid SUMP was significantly higher than basaloid SUMP (P = .0142) and SUMP NOS (P = .0084). No significant differences in ROM were noted between B1 and B2 (36.7% vs 36.4%, P = 1.0000) and O1 and O2 (65.2% vs 48.7%, P = .2349). CONCLUSIONS: The ROM of oncocytic/oncocytoid SUMP was 52.5% and significantly higher than that of basaloid SUMP (36.5%, P = .0142) and SUMP NOS (31.9%, P = .0084), whereas no significant differences in ROM were noted for cases with different types of extracellular matrix or background material.

Granulomas associated with renal neoplasms: A multi-institutional clinicopathological study of 111 cases.

AIMS: Formal depiction of granulomatous inflammation associated with renal neoplasms has mainly consisted of case reports. Herein, we investigate the clinicopathological features and potential significance of granulomas associated with renal tumours from a large multi-institutional cohort. METHODS AND RESULTS: One hundred and eleven study cases were collected from 22 institutions, including 57 partial nephrectomies and 54 radical nephrectomies. Patient ages ranged from 27 to 85 years (average = 60.1 years; male = 61%). Renal neoplasms included clear cell renal cell carcinoma (RCC; 86%), papillary RCC (8%), chromophobe RCC (3%), clear cell papillary RCC (1%), mixed epithelial stromal tumour (1%) and oncocytoma (1%). Granulomas were peritumoral in 36%, intratumoral in 24% and both in 40% of cases. Total granuloma count per case ranged from one to 300 (median = 15) with sizes ranging from 0.15 to 15 mm (mean = 1.9 mm). Necrotising granulomas were seen in 14% of cases. Histochemical stains for organisms were performed on 45% of cases (all negative). Sixteen cases (14%) had a prior biopsy/procedure performed, and eight patients had neoadjuvant immunotherapy or chemotherapy. Eleven patients (10%) had a confirmed diagnosis of sarcoidosis, including five in whom sarcoidosis was diagnosed after nephrectomy. CONCLUSION: Based on this largest case-series to date, peri-/intratumoral granulomas associated with renal neoplasms may be more common than initially perceived. The extent of granulomatous inflammation can vary widely and may or may not have necrosis with possible aetiologies, including prior procedure or immunotherapy/chemotherapy. Although a clinical association with sarcoidosis is infrequent it can still occur, and the presence of granulomas warrants mention in pathology reports.

Frankly Invasive Carcinoma Ex-intraductal Carcinoma: Expanding on an Emerging and Perplexing Concept in Salivary Gland Tumor Pathology.

Intraductal carcinoma (IDC) of the salivary glands is an uncommon and enigmatic tumor, our understanding of which is rapidly evolving. Recent studies have demonstrated multiple IDC subtypes and consistent gene fusions, most frequently involving RET. Because IDC is a ductal proliferation surrounded by flattened myoepithelial cells, it was previously presumed to be analogous to breast ductal carcinoma in situ, but recent evidence has shown that the myoepithelial cells of fusion-positive IDC harbor the same genetic alterations of the ductal cells and are therefore neoplastic. In addition, there are rare reports of fusion-positive IDC with overt areas of irregular invasion lacking myoepithelial cells, but this phenomenon is not well documented or understood. This study aims to better characterize these frankly invasive carcinoma ex-IDC. All cases of frankly invasive carcinoma ex-IDC were obtained from the authors' files. Inclusion criteria included a component of concurrent or antecedent IDC and/or a fusion known to be associated with IDC. Immunohistochemistry (S100, SOX10, mammaglobin, androgen receptor, p63, p40) and molecular analysis (targeted RNA sequencing or large panel DNA next generation sequencing) was performed. Clinical follow-up was obtained from medical records. Ten cases of frankly invasive carcinoma ex-IDC were identified. The tumors occurred in 8 men and 2 women ranging from 33 to 82 years (mean, 66.3). All but one case arose in the parotid gland. In 4 cases, the IDC component was intercalated duct type. It was mixed apocrine/intercalated duct in two, and in the remaining 4 cases, no residual IDC was identified. The frankly invasive carcinomas were remarkably heterogeneous, ranging from minimally to widely invasive beyond the confines of the IDC, low-grade to high-grade, with morphologies that varied from duct-forming to those having clear cell or sarcomatoid features, to frankly apocrine. The original diagnoses for these cases were (adeno) carcinoma, not otherwise specified (n = 6), salivary duct carcinoma (n = 3), and secretory carcinoma (n = 1). All cases harbored fusions: NCOA4::RET (n = 6), TRIM33::RET (n = 2), TRIM27::RET (n = 1), and STRN::ALK (n = 1). Clinically, one tumor recurred locally, cervical lymph node metastases occurred in five patients, and distant metastasis later developed in four of these patients. Our findings highlight striking diversity in frankly invasive carcinomas that arise from fusion-positive IDC, a tumor which may serve as a precursor neoplasm like pleomorphic adenoma. These carcinomas vary in their extent of invasion, grade, histologic appearances, and clinical behavior. Importantly, in contrast to pure IDC, which is believed to be indolent, many frankly invasive cases were aggressive. Because RET and ALK fusions are targetable, it is important to recognize the broad spectrum of frankly invasive carcinomas that can arise from IDC, particularly because some cases are completely overrun or recur without any recognizable IDC component. These results suggest fusion analysis may be of clinical benefit on any salivary gland (adeno) carcinoma, not otherwise specified or salivary duct carcinoma.

Analysis of the risk of malignancy associated with the basaloid and oncocytic subtypes of the salivary gland neoplasm of unknown malignant potential (SUMP) category in the Milan system.

BACKGROUND: The salivary gland neoplasm of unknown malignant potential (SUMP) category reflects the cytomorphologic overlap and complexity of reporting salivary gland cytology in the Milan system. It includes neoplasms for which a diagnosis of a specific entity cannot be made and, more importantly, for which a carcinoma cannot be entirely excluded. For risk stratification, the subcategorization of SUMP based on the predominant cell type is recommended. This study was aimed at evaluating the risk of neoplasm (RON) and the risk of malignancy (ROM) of the basaloid and oncocytic subtypes of the SUMP category. METHODS: A retrospective analysis of 482 salivary gland fine-needle aspirations from 2012 to 2019 resulted in 48 SUMP cases. The cytology of these cases was reviewed and reclassified as the basaloid or oncocytic subtype. Surgical follow-up was available for 36 cases. The RON and ROM for each subtype were calculated. RESULTS: The RON and ROM were 100% and 23%, respectively, for monomorphic basaloid tumors and 88% and 58.8%, respectively, for monomorphic oncocytic tumors. The ROM for basaloid tumors was 8.3% without matrix/with minimal matrix and 60% with an nonfibrillary matrix. The ROM for oncocytic tumors was 50% without a cystic background and 60% with a cystic or mucinous background. The difference was not statistically significant for either of the subgroups. CONCLUSIONS: Even though statistically not significant in our study, the differential ROMs within the oncocytic and basaloid subgroups help in the risk stratification of SUMP cases. Further subcategorization based on the stroma and background helps in limiting the differential diagnosis but does not necessarily add to the value of the risk stratification.

Impact of the Milan System for Reporting Salivary Gland Cytology on risk assessment when used in routine practice in a real-time setting.

INTRODUCTION: Several retrospective studies across the world have validated the role of the Milan System for Reporting Salivary Gland Cytology (MSRSGC) in improving communication between pathologists and clinicians. In this study, we evaluated the applications of MSRSGC in a real-time setting for 2 years. MATERIALS AND METHODS: All salivary gland lesions that underwent fine-needle aspiration (FNA) from January 2018 to December 2020 were categorized according to MSRSGC guidelines. The risk of malignancy (ROM) was calculated for each category and compared with the ROM proposed by MSRSGC and recent retrospective studies. RESULTS: A total of 160 FNA of salivary gland lesions were categorized as: nondiagnostic (ND) 30 (18%), non-neoplastic (NN) 7 (10.6%), atypia of undetermined significance (AUS) 5 (3.1%), benign neoplasm (BN) 59 (36.8%), salivary gland of uncertain malignant potential (SUMP) 21 (13%), suspicious for malignancy (SM) 3 (1.84%), and malignant (M) 25 (15.6%). Histopathologic follow-up was available for 94 (57.5%) cases. The ROM for each category was ND 54%, NN 0%, AUS 66%, BN 0%, SUMP 37.56%, SM 100%, and M 100%. CONCLUSION: With strict adherence to the diagnostic criteria and MSRSGC guidelines, a ROM of 100% in SM and M categories and a ROM of 0% in NN can be achieved in a real-time setting. The high ROM in the ND category in our study highlights the value of repeat FNA/biopsy for this category. High ROM for AUS indicates the tendency to classify high-grade tumors as AUS, calling for refinement in its criteria.

Threshold for interpretation of p16 immunostaining in fine-needle aspirate specimens of metastatic oropharyngeal squamous cell carcinoma.

INTRODUCTION: Human papilloma virus (HPV)-associated oropharyngeal squamous cell carcinoma (HPV-OPSCC) has been recognized to have an excellent response to treatment and has a distinct pathologic staging. For this reason, HPV testing is recommended in cytology specimens of metastatic OPSCC, although the guidelines for testing are not clearly defined. The aim of the current study was to establish a threshold for interpretation of p16 in aspirates from metastatic OPSCC. MATERIALS AND METHODS: Cases diagnosed as metastatic SCC by cytology in neck lymph nodes with concurrent p16 on cytology and on paired surgical specimen or an in situ hybridization (ISH) for HPV were included in the study. Stain intensity and percentage positive cells for p16 was compared with p16 on paired surgical pathology specimens and/or ISH RNA for HPV on cytology specimens. RESULTS: Of the 52 cases diagnosed as metastatic SCC on neck aspirates, paired surgical pathology specimens and/or ISH HPV was available in 17 cases. A p16 expression in ≥10%-15% cells resulted in a sensitivity and negative predictive value of 66% and 37%, respectively. However, when even minimal expression in tumor fragments is considered positive, the negative predictive value increases to 100%. CONCLUSIONS: We recommend that even minimal nuclear expression for p16 in viable tumor fragments must be considered as positive in cytology specimens. Expression limited to only background single tumor cells or in a necrotic specimen must be interpreted with caution.

Clinicopathologic Diagnostic Approach to Aggressive Variant Prostate Cancer.

CONTEXT.­: Aggressive variant prostate cancer (AVPCa) develops in a subset of patients with metastatic castration-resistant prostate cancer. The clinical and histologic overlap of AVPCa with other neuroendocrine carcinomas of the prostate has resulted in a lack of consensus on its terminology and treatment. OBJECTIVE.­: To review AVPCa to familiarize pathologists with this entity so they can actively participate in the detection, ongoing research, and evolving management of AVPCa. DATA SOURCES.­: The English language literature was reviewed. CONCLUSIONS.­: The current review summarizes the pathologic features of AVPCa, describes how it has been defined clinically, and discusses how biomarkers may inform treatment strategies in the future.

Rapid On-site Evaluation of Spine Lesions.

Fine-needle aspiration (FNA) and core needle biopsy are the primary diagnostic modalities for assessing mass lesions. Any superficial or deep-seated lesion occurring anywhere in the body, including bone and soft tissue, can undergo this procedure to pathologically characterize it. The outcomes of FNA, performed either alone or in combination with core biopsy, are best when performed and interpreted by skilled individuals. The roles of interventional radiologists and cytologists are pivotal in ensuring adequacy of the specimen and leading the clinical team in making the diagnosis and avoiding repeat diagnostic procedures or a more invasive open surgical biopsy.

Race-associated expression of MHC class I polypeptide-related sequence A (MICA) in prostate cancer.

Despite the lack of a complete understanding of the disparities involved, prostate cancer (PCa) has both higher incidence and death rates in African American Men (AAM) relative to those of Caucasian American Men (CAM). MHC class I polypeptide related sequence A (MICA) is an innate immunity protein involved in tumor immunoevasion. Due to a lack of reports of race-specific expression of MICA in PCa, we evaluated MICA expression in patients' tumors and in cell lines from a racially diverse origin. Immunohistochemistry was done on a tissue microarray (TMA) with antibodies against MICA. Tumor MICA mRNA was assessed by data mining using Oncomine and PROGeneV2. Surface MICA and release rate of soluble (s) MICA was evaluated in PCa cell lines originally derived from African American (MDA-PCa-2b) or Caucasian (LNCaP and DU-145) PCa patients. Prostate tumor tissue had a 1.7-fold higher MICA expression relative to normal tissue (p < .0001). MICA immunoreactivity in PCa tissue from AAM was 24% lower (p = .002) compared to CAM. Survival analysis revealed a marginal association of low MICA with poor overall survival (OS) (p = .058). By data mining analysis, a 2.9-fold higher level of MICA mRNA was evidenced in tumor compared to normal tissue (p < .0001). Tumors from AAM had 24% lower levels of MICA mRNA compared to tumors from CAM (p = .038), and poor prognosis was found for patients with lower MICA mRNA (p = .028). By flow cytometry analysis, cell fraction positive for surface MICA was of 3% in MDA-PCa-2b cells, 54% in DU-145 cells, and 67% in LNCaP cells (p < .0001). sMICA was detected in DU-145 and LNCaP cells, but was not detected in MDA-PCa-2b cells. Both LNCaP and DU-145 cells were sensitive to cytolysis mediated by Natural killer (NK) cells. MDA-PCa-2b cells, however were between 1.3-fold at 10:1 Effector:Target (E:T) ratio (p < .0001) and 2-fold at 50:1 E:T ratio (p < .0001) more resistant to NK-mediated cytolysis relative to cells from Caucasian origin. These results suggest that MICA expression may be related to the aggressive nature of PCa. Our findings also demonstrate for the first time that there are variations in MICA expression in the context of racial differences. This study establishes a rationale for further investigation of MICA as a potential race-specific prognostic marker in PCa.

Role of cytology and immunochemistry in diagnosis of metastatic malignancies in the lung: A critical appraisal.

BACKGROUND: Lung is one of the most common sites for primary and metastatic malignancies and a challenging site to diagnose primary versus a metastatic origin of the tumor on cytology. Pathologic diagnosis of the site of origin of cancer has major implications in the management and staging purposes and may have to be followed by testing for predictive/prognostic markers. The clinical history of a known extrapulmonary primary and the radiologic findings of multiple nodules in the lung are useful in arriving at the right diagnosis but is not always available. Rarely pulmonary metastasis may be the first manifestation of an extrapulmonary tumor or may even present as a single nodule. METHOD: In this study, we reviewed cytomorphologic features of tumors metastatic to the lung (2014-2017) in conjunction with immunochemistry and evaluation of needle core biopsy when available. The review of the slides was performed with an emphasis on our ability to identify the site of origin in the tumors. RESULTS: We identified 47 cases of metastatic tumors in the lung diagnosed on cytology. Clinical history was available in 83% cases and with aid of immunostains, a definitive diagnosis on the origin of the tumor was made in all these cases. In the remaining 8 cases, a primary origin could only be suggested. The use of immunochemistry facilitated the diagnosis but could be misleading. CONCLUSION: The approach to the diagnosis of metastatic tumors in the lung on cytology should be largely guided by the previous clinical history and comparison with previous tissue/cellular material if available.

Cyto-histological correlation of Xp11.2 translocation/TFE3 gene fusion associated renal cell carcinoma: Report of a case with review of literature.

The MiT family translocation renal cell carcinomas (RCCs) are relatively rare in comparison to the conventional RCC. The cytologic features overlap with conventional clear cell RCC and papillary RCCs, thereby making the diagnosis extremely challenging. Here, we describe a case of TFE3 translocation associated RCC in a 58-year-old patient, with emphasis on cytomorphologic features and clues toward this diagnostic entity. Correlating the cytohistologic findings and review of touch imprints revealed that presence of hyaline nodules resembling leisegang rings and psammoma bodies in cytologic smears from kidney tumors serve as an important clue in raising a suspicion for the diagnosis of MiT family translocation RCCs.

Changing Trends and Practices in Cytopathology.

OBJECTIVE: To explore the current and anticipated changes in the practice of cytopathology. STUDY DESIGN: The present review is based on a review of recent literature and an evaluation of the authors' personal experiences. RESULTS AND CONCLUSION: In recent years the practice of cytopathology, nationwide and in our institute, has witnessed a major change affecting gynecologic and nongynecologic cytology. There has been a decline in the number of Papanicolaou tests which has affected the utilization of cytotechnologists and provoked a reorganization of their work flow. The "need to do more with less" in the era of targeted therapy/personalized medicine has resulted in an increasing preference for needle core biopsy when performing a rapid on-site evaluation. We feel that this change is unavoidable. It is pertinent that cytopathologists as a group recognize this change and prepare themselves and the trainees not only to become adapt but also to use this as an opportunity to discover the yet unexplored world of cytology.

Histiocytic Sarcoma in a Kidney Transplant Patient: A Case Report and Review of the Literature.

Objective. Histiocytic sarcoma (HS) is an aggressive neoplasm with only limited number of reported series of cases and rare case reports of occurrence as a posttransplant neoplastic disorder. The etiology and pathogenesis of the disease is unknown and the optimal treatment is still under investigation. We describe an unusual case of HS in a patient with a remote history of kidney transplant. Method and Results. A 54-year-old male with a remote history of renal transplantation under maintenance immunosuppression presented with features of sepsis. CT abdomen revealed multiple heterogeneous masses in bilateral native kidneys and liver and enlarged abdominal and retroperitoneal lymph nodes. Viral serology work-up was negative. Needle core biopsy revealed a highly undifferentiated neoplasm comprised of highly atypical large cells with eosinophilic to vacuolated cytoplasm and hemophagocytosis. Extended panel of immunohistochemistry proved histiocytic lineage for the tumor cells. The patient expired 2 weeks following the diagnosis. Conclusion. Our case along with three previously published case reports raised the possibility of HS as a treatment-related neoplasm or a posttransplantation neoplastic disorder in solid organ transplant recipients.

Villous Adenoma of the Urinary Bladder: A Brief Review of the Literature.

Villous adenoma is a rare neoplasm in the urinary tract. It usually occurs in patients older than 50 years with a male predominance. The affected patients typically present with hematuria, irritative voiding symptoms, and mucosuria. The malignant potential of this entity has not been established, but some of the case series studies on bladder villous adenoma do suggest a possible association with malignant tumors. Findings on ultrasonography, computed tomographic scanning, magnetic resonance imaging, or on cystoscopic examination are nonspecific. Therefore, villous adenoma of the bladder is primarily a histologic diagnosis. This review will highlight the current theories on its pathogenesis and discuss its main histologic and immunohistochemical features to aid the diagnosis.