What’s new in genitourinary pathology 2023: WHO 5th edition updates for urinary tract, prostate, testis, and penis

The 5th edition WHO Classification of Urinary and Male Genital Tumours (2022) introduced many significant changes relevant to urologic daily practice, mainly to renal tumors which was covered in the What’s New newsletter in September 2022. In this newsletter, we summarize the notable changes to bladder, prostate, testis, and penis based on the 5th edition of the WHO

Expression of glypican 3 in placental site trophoblastic tumor

<p>Abstract</p> <p>Background</p> <p>Glypican-3 (GPC3) is a membrane-bound heparan sulfate proteoglycan that functions in embryonic cell growth and differentiation and is highly expressed in the placenta. GPC3 is mutated in Simpson-Golabi-Behmel syndrome, which is characterized by tissue overgrowth and an increased risk of embryonal malignancies. GPC3 has also been implicated in sporadic cancer, particularly hepatocellular carcinoma, for which it has been shown to be a useful diagnostic marker. Although GPC3 expression has been studied in non-neoplastic placental tissue, its presence in gestational trophoblastic diseases has not been previously explored. The purpose of this study was to investigate the immunohistochemical expression of GPC3 in placental site trophoblastic tumor (PSTT), a very rare gestational trophoblastic neoplasm which may be morphologically confused with non-trophoblastic tumors, and to assess its possible utility as a diagnostic marker.</p> <p>Methods</p> <p>Fifteen cases of PSTT, as well as samples from placental site nodule (PSN) (n = 2), leiomyosarcoma (n = 1), leiomyoma (n = 1), invasive cervical squamous cell carcinoma (n = 7) and endometrial adenocarcinoma (n = 11) were examined. Immunoreactivity was semi-quantitatively evaluated as negative (0, < 5% of cells stained), focally positive (1+, 5-10% of cells stained), positive (2+, 11-50% of cells stained) or diffusely positive (3+, > 50% of cells stained). Staining intensity for each subtype was graded from 0 to 3 and a mean intensity was calculated.</p> <p>Results</p> <p>Eighty percent of PSTT (12/15) were immunoreactive for GPC3 (0, 20; 1+, 20%; 2+, 40%; 3+, 20%) with a mean intensity of 1.3. Stronger, predominately cytoplasmic staining was seen in larger multi- and mononucleated cells with smaller mononucleate cells showing weak muddy cytoplasmic staining. Both PSN cases were positive (1+, 50%; 2+, 50%) and two of nine invasive cervical squamous cell carcinomas showed staining (0, 57%; 1+, 29%; 2+, 14%), predominately in a basal distribution. Other uterine tumors and non-neoplastic tissues were negative.</p> <p>Conclusions</p> <p>Identification of GPC3 in PSTT and PSN is consistent with the derivation of these lesions from intermediate trophoblasts, which have been described to express GPC3. GPC3 may be a useful adjunct immunohistochemical marker in differentiating PSTT from non-trophoblastic tumors.</p

von Brunn's Nests and Follicular Cystitis Following Intradetrusor OnabotulinumtoxinA Injections for Overactive Bladder

A 67-year-old female with refractory OAB was treated with intradetrusor Botox. She subsequently developed multiple papillary bladder lesions with tissue biopsy showing Von Brunn's nests. Von Brunn’s nests are benign bladder lesions similar in appearance to a rare urothelial tumor called Nested Variant of Urothelial Carcinoma (NVUC). It is critical that patients with these findings undergo evaluation to rule out the presence of carcinoma. This finding suggests the possibility of a previously unreported adverse reaction in association with intradetrusor Botox

Concordance of lymphovascular invasion diagnosed in penile carcinoma with and without the immunohistochemical markers ERG and CD31

Lymphovascular invasion (LVI) is an independent predictor of metastatic lymph node disease in penile carcinoma and is one factor used to guide clinical management. The presence of LVI with and without the use of the endothelial immunohistochemical (IHC) markers, ERG and CD31, was retrospectively assessed in 46 penectomy cases containing invasive penile carcinoma (43 squamous cell carcinoma and 3 non-squamous cell carcinoma). Concordance for the detection of LVI between the original report, upon pathology review, and with the use of IHC was determined and histologic pitfalls were identified. For penile squamous cell carcinoma, LVI was diagnosed in 27.9% of tumors in the original reports, 16.3% upon pathology review, and in 16.3% with use of ERG and CD31. Concordance of LVI identification in the original report compared to IHC was 74.4% while concordance of review compared to IHC was 95.3%. Using IHC data as the reference, false positive LVI diagnoses were more common in the original report than false negatives. Histologic mimickers of LVI including involvement of the penile corpora cavernosum or spongiosum vasculature, seromucinous colonization, and a nested pattern of tumor invasion were identified. We demonstrated that it was not uncommon for LVI in penile carcinoma to be overdiagnosed or underdiagnosed. The use of endothelial IHC markers, such as ERG or CD31, or additional pathology consultation is recommended for penectomy cases in which LVI is difficult to histologically discern

Research and applications: Identifying survival associated morphological features of triple negative breast cancer using multiple datasets

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Alterations of Histone H1 Phosphorylation During Bladder Carcinogenesis

There is a crucial need for development of prognostic and predictive biomarkers in human bladder carcinogenesis in order to personalize preventive and therapeutic strategies and improve outcomes. Epigenetic alterations, such as histone modifications, are implicated in the genetic dysregulation that is fundamental to carcinogenesis. Here we focus on profiling the histone modifications during the progression of bladder cancer. Histones were extracted from normal human bladder epithelial cells, an immortalized human bladder epithelial cell line (hTERT), and four human bladder cancer cell lines (RT4, J82, T24, and UMUC3) ranging from superficial low-grade to invasive high-grade cancers. Liquid chromatography–mass spectrometry (LC–MS) profiling revealed a statistically significant increase in phosphorylation of H1 linker histones from normal human bladder epithelial cells to low-grade superficial to high-grade invasive bladder cancer cells. This finding was further validated by immunohistochemical staining of the normal epithelium and transitional cell cancer from human bladders. Cell cycle analysis of histone H1 phosphorylation by Western blotting showed an increase of phosphorylation from G₀/G₁ phase to M phase, again supporting this as a proliferative marker. Changes in histone H1 phosphorylation status may further clarify epigenetic changes during bladder carcinogenesis and provide diagnostic and prognostic biomarkers or targets for future therapeutic interventions