Villoglandular Differentiation Research Articles

Variant morphology and random chromosomal integration of BK polyomavirus in posttransplant urothelial carcinomas.

BK polyomavirus (BKPyV) causes major complications in solid organ transplant recipients but little is known about its role in the development of urothelial carcinoma (UC) during immunosuppression. Immunohistochemistry (IHC) screening for polyomavirus large T antigen (LTag) was performed in 94 micropapillary UC (MPUC), 480 unselected UC, 199 muscle invasive UC (including 83 UC with variant differentiation), 76 cases of plasmocytoid, nested and large nested UC and 15 posttransplant UC. LTag expressing UC were reevaluated regarding their histomorphological features and characterized by IHC for p53 and HER2, chromogenic in situ hybridization for HER2 and SNaPshot analysis of the TERT promoter and HRAS. Real-time PCR and next generation sequencing (NGS) were performed to search for BKPyV-DNA and for variants in the tumor and viral genomes. We detected five LTag expressing UC which were diagnosed between 2 and 18 years after kidney (n = 4) or heart (n = 1) transplantation. 89 MPUC without history of organ transplantation and overall 755 UC (including cases with variant histology) were LTag negative. Of the five LTag expressing UC, three were MPUC, one showed extensive divergent differentiation with Mullerian type clear cell carcinoma, and one displayed focal villoglandular differentiation. All five tumors had aberrant nuclear p53 expression, 2/5 were HER2-amplified, and 3/5 had TERT promoter mutations. Within the 50 most common cancer related genes altered in UC we detected very few alterations and no TP53 mutations. BKPyV-DNA was present in 5/5 UC, chromosomal integration of the BKPyV genome was detectable in 4/5 UC. Two UC with BKPyV integration showed small deletions in the BKPyV noncoding control region (NCCR). The only UC without detectable BKPyV integration had a high viral load of human herpesvirus 6 (HHV-6). Our results suggest that LTag expression of integrated BKPyV genomes and resulting p53 inactivation lead to aggressive high-grade UC with unusual, often micropapillary morphology.

Villous Morphology in Urinary Bladder Biopsy: An Approach to Diagnosis.

Villous morphology in urinary bladder biopsy is a relatively uncommon finding. Villi are slender, finger-like structures that are commonly seen in the small intestine or in neoplastic lesions of gastrointestinal lineage/differentiation. Importantly, placenta also exhibits villi that are morphologically and functionally different from the intestinal one. Majority of the neoplastic lesions of urinary bladder are urothelial in origin with a minor subset showing glandular differentiation. While the presence of benign villi in urinary bladder biopsy necessitates a search for an occult perforation, provided a sample mismatch is ruled out, cytoarchitecturally abnormal/dysplastic villi indicate a neoplastic lesion of the urinary bladder encompassing villous adenoma and adenocarcinoma and urothelial carcinoma with villoglandular differentiation. The dysplastic villi in urinary bladder also imply a lower gastrointestinal endoscopy to rule out a colorectal primary. The development of the villous lesions in the urinary bladder and the colorectum are embryologically related and pose a major diagnostic challenge to the clinicians and surgical pathologists due to identical histomorphology and immunohistochemistry. We tend to discuss the morphological differentials and diagnostic approach to the villous lesions in the urinary bladder biopsy.

Urothelial tumors with villous morphology: Histomorphology and role of immunohistochemistry in diagnosis.

Villous adenoma and urothelial carcinoma with villoglandular differentiation (UCVGD) are rare urothelial tumours showing villous morphology, the former being a preneoplastic entity and the latter being a malignant one. The detailed immunohistochemistry of these entities is previously not described in the literature. Moreover, a limited biopsy sample of UCVGD or a villous adenoma with or without adenocarcinoma may be difficult to distinguish on the basis of the histomorphology alone. An immunohistochemical panel comprising of GATA3, p63, β-catenin, CK7 and CK20 was performed on five cases of UCVGD and three cases of villous adenoma with the aim of studying the expression of the proteins thereby aiding in the diagnosis of these entities in a limited surgical pathology specimen. The mean age of UCVGD was 66.8 years and all the patients were male. All the cases of UCVGD were associated with high grade papillary urothelial carcinoma with lamina propria invasion. The immunohistochemical panel showed strong nuclear GATA3 expression in the urothelial component of UCVGD. Interestingly, the high grade and the low grade villoglandular components of UCVGD also expressed GATA3 (nuclear) with a progressive loss of expression from the high grade to the low grade component. The villous adenomas showed negativity or aberrant cytoplasmic positivity for GATA3. The β-catenin showed a gradual loss of membranous expression from villous adenoma to low grade and high grade villoglandular components of UCVGD with a patchy membranous expression in the urothelial component of the UCVGD. p63 showed strong nuclear positivity in the urothelial component and uniform negativity in the villous adenoma and villoglandular component of UCVGD irrespective of its grade, thereby distinguishing the villoglandular component from the urothelial component. The urothelial component of UCVGD showed strong membranous CK7 expression and was higher than the CK20 expression in the urothelial component. In contrast, CK20 expression was higher in villous adenoma as compared to CK7. There was no difference in the expression of CK7 and CK20 in the villoglandular components and low grade and high grade villoglandular areas. The above-mentioned immunohistochemical pattern may help to distinguish the UCVGD from the villous adenoma.

Urothelial Carcinoma With Villoglandular Differentiation

Urothelial neoplasms are the commonest neoplasms of the urinary bladder. Many variants of urothelial neoplasms have been described in the literature with diagnostic, therapeutic, and prognostic significance. We describe a rare case of urothelial neoplasm with villoglandular differentiation along with its immunohistochemical profile arising in an elderly male. Its poor prognosis signifies its need to be recognized.

Urothelial carcinoma with villoglandular differentiation

The patient is a 72-year-old man who presented with hematuria. On cystoscopy, a large friable mass was identified involving the left bladder wall. A transurethral resection of the bladder tumor was performed. Histologically, the tumor was composed of superficial finger-like processes lined by epithelium with true glandular lumina with intraluminal mucin, intimately admixed with invasive high grade urothelial carcinoma. Several glands also had cribriform features and some were lined by non-mucin producing cuboidal to columnar cells. Variable amounts of intraluminal necrosis, apoptotic bodies, and eosinophilic secretions were also present. The tumor invaded the muscularis propria (Detrusor muscle). A diagnosis of urothelial carcinoma with villoglandular differentiation with made. Urothelial carcinoma with villoglandular differentiation is a relatively recently described aggressive variant of urothelial carcinoma. Mean patient age at presentation is 70 years (range: 4684 years) with a male predominance (5:1). Other aggressive variants of urothelial carcinoma have also been associated with this tumor including, micropapillary urothelial carcinoma, plasmacytoid urothelial carcinoma, sarcomatoid urothelial carcinoma and small cell carcinoma. Tumors that may mimic urothelial carcinoma with villoglandular differentiation include colorectal adenocarcinoma, prostatic ductal adenocarcinoma, urachal carcinoma, villous adenoma and other entities.

Prognostic significance and clinical importance of estrogen receptor α and β in human endometrioid adenocarcinomas

Human endometrial cancer expresses both the known estrogen receptors (ER-alpha and ER-beta). The significance of the relative expression of both ER subtypes in endometrial adenocarcinomas remains to be clarified and the usefulness of the determination of the receptor status in endometrial cancer patients is still controversially discussed. Therefore, the aims of this study were the evaluation of the expression patterns of ER-alpha and ER-beta with the characterization of the prognostic significance in uterine endometrioid adenocarcinomas. Pathological and surgical records of 214 patients who were diagnosed with an endometrioid adenocarcinoma without other histological types (including mucinous, mixed, squamous or villoglandular differentiation) were reviewed for both estrogen receptors. The expression of both estrogen receptors was demonstrated in malignant endometrioid adenocarcinomas. ER-alpha was associated with histological differentiation, while ER-beta demonstrated an association with ovarial invasion. The loss of receptor positivity for ER-alpha resulted in a poorer cause-specific survival in endometrial cancer patients, while ER-beta did not affect survival. Interestingly, metastatic patients who expressed ER-alpha or ER-beta had a better survival outcome than estrogen receptor negative patients. Moreover, when tumor samples of affected patients expressed ER-alpha, they had a better cause-specific survival compared to negative findings regarding both estrogen receptors. However, ER-alpha and ER-beta were not independent factors with survival in endometrial adenocarcinoma patients. Therefore, the analysis of both estrogen receptors might be used as a marker to identify high-risk patients only in a subset of patients with endometrioid adenocarcinoma.

Urothelial carcinoma with villoglandular differentiation: a study of 14 cases

Tumors of the urinary bladder may have a variety of histological patterns. Tumors with either glandular or villous features, such as villous adenomas, in situ adenocarcinomas, invasive adenocarcinomas, and variants of urothelial carcinoma such as micropapillary carcinomas have been described. However, urothelial carcinomas with both villous and glandular features have not been well characterized. We identified 14 cases of urothelial carcinoma with villoglandular differentiation. These cases were defined as having villoglandular features if they contained superficial finger-like processes lined by epithelium having true glandular lumina. Mean patient age at presentation was 70 years (range: 46–84 years) with a male predominance (5:1). A total of 3 cases (21%) were non-invasive, five cases (36%) had lamina propria invasion, five cases (36%) had muscularis propria invasion and one case (7%) had extravesicular extension. A concurrent high-grade papillary urothelial carcinoma component was identified in 11 cases (79%), micropapillary component in 5 (36%) cases, in-situ urothelial carcinoma component in 3 cases (21%), plasmacytoid component in 3 cases (21%), invasive adenocarcinoma in 2 cases, sarcomatoid carcinoma component in one case (14%), and small-cell carcinoma component in 1 case (7%). Cystitis cystica et glandularis was present in 3 cases (21%). Angiolymphatic invasion was identified in 3 cases (21%). Histologically, the villoglandular components were composed of finger-like processes lined by glands intimately admixed with high-grade urothelial carcinoma. Many of the glands had cribriform features lined by non-mucin producing cuboidal to columnar cells. Urothelial carcinoma with villoglandular differentiation are high-grade tumors typically seen in elderly males, characterized by superficial filliform processes lined by glands intimately admixed with high-grade urothelial carcinoma (in situ or invasive) and other aggressive variants of urothelial carcinoma. These relatively rare tumors should be recognized as a variant of urothelial carcinoma.