Iatrogenic pathology of the urinary bladder

Intravesical immunotherapy, chemotherapy, and neoadjuvant systemic chemotherapy are among the most frequent therapeutic procedures to treat malignancies of the urinary bladder. These treatment modalities produce reactive morphologic changes in the urothelium that can mimic urothelial carcinoma in situ, urothelial dysplasia or true invasive urothelial neoplasia. Mitomycin C used after transurethral resection of bladder tumor to reduce recurrences, BCG intravesical immunotherapy to treat high risk non-muscle invasive bladder cancer and urothelial carcinoma in situ, and platinum-based systemic chemotherapy to improve post-cystectomy disease-specific survival some of the causes of therapy related atypia in urinary bladder. In addition, a number of systemic drugs in use to treat other systemic diseases, such as cyclophosphamide used to treat certain auto-immune disorders or hematologic malignancies, or the anesthetics ketamine increasingly used as illegal recreational drug, may produce similarly relevant atypical changes in the urothelium, and therefore, need to be differentiated from intraepithelial neoplasia. Immunohistochemical approach to reactive urothelium from CIS using CK20, p53, and CD44 may also be of utility in the pos-therapy scenario

Inherited Forms of Bladder Cancer: A review of Lynch Syndrome and Other Inherited Conditions

Environmental factors that play a role in the urothelial carcinogenesis have been well characterized. Current research is continuously exploring potential heritable forms of bladder cancer. Lynch syndrome is a well-known inheritable disease that increases the risk for a variety of cancers, including urothelial carcinomas. Screening of patients with known Lynch syndrome is important to evaluate for development of new primary tumors. Further study may provide more information on what level of follow-up each patient needs. Recent data suggest that mismatch repair mutations confer a greater risk for urothelial cancer. Additional large patient series as well as advancement of molecular testing may provide triage for Lynch syndrome patients in regards to the frequency and type of screening best suited for individual patient

PreImplantation Factor immunohistochemical expression correlates with prostate cancer aggressiveness

Background: The PreImplantation Factor (PIF)—a peptide secreted by viable embryos—exerts autotrophic protective effects, promotes endometrial receptivity and controls trophoblast invasion. Synthetic PIF (sPIF) has both immune-protective and regenerative properties, and reduces oxidative stress and protein misfolding. PIF is detected by immunohistochemistry (IHC) in hyperplastic endometriotic lesions and advanced uterine cancer. sPIF reduces graft-versus-host disease while maintaining a graft-versus-leukemia effect. Methods: PIF detection in prostate cancer was assessed in 50 human prostate samples following radical prostatectomy using tumor-microarray-based IHC correlating PIF immune staining with Gleason score (GS) and cancer aggressiveness. Results: PIF was detected in moderate-to-high risk prostate cancer (GS 4+3 and beyond, prognostic groups 3 to 5). In prostate cancer (GS (WHO Grade Group (GG)5), PIF was detected in 50% of cases; in prostate cancer (GS 4+4 GG4), PIF was observed in 62.5% of cases; in prostate cancer (GS 4+3 GG3), PIF immunostaining was observed in 57.1% of cases. In prostate cancer, (GS 3+4 GG2) and (GS 3+3 GG1) cases where PIF staining was negative to weak, membranous staining was observed in 20% of cases (staining pattern considered negative). High-grade prostate intraepithelial neoplasia PIF positive stain in 28.57% of cases (6 of 21) was observed. In contrast, PIF was not detected in normal prostate glands. Importantly, sPIF added to the PC3 cell line alone or combined with prostate cancer fibroblast feeder-cells did not affect proliferation. Only when peripheral blood mononuclear cells were added to the culture, a minor increase in cell proliferation was noted, reflecting local proliferation control. Conclusions: Collectively, PIF assessment could be a valuable, simple-to-use immunohistochemical biomarker to evaluate aggressiveness/prognosis in specimens from prostate cancer patients

The 2022 World Health Organization Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours.

The fifth edition of the World Health Organization (WHO) classification of urogenital tumours (WHO "Blue Book"), published in 2022, contains significant revisions. This review summarises the most relevant changes for renal, penile, and testicular tumours. In keeping with other volumes in the fifth edition series, the WHO classification of urogenital tumours follows a hierarchical classification and lists tumours by site, category, family, and type. The section "essential and desirable diagnostic criteria" included in the WHO fifth edition represents morphologic diagnostic criteria, combined with immunohistochemistry and relevant molecular tests. The global introduction of massive parallel sequencing will result in a diagnostic shift from morphology to molecular analyses. Therefore, a molecular-driven renal tumour classification has been introduced, taking recent discoveries in renal tumour genomics into account. Such novel molecularly defined epithelial renal tumours include SMARCB1-deficient medullary renal cell carcinoma (RCC), TFEB-altered RCC, Alk-rearranged RCC, and ELOC-mutated RCC. Eosinophilic solid and cystic RCC is a novel morphologically defined RCC entity. The diverse morphologic patterns of penile squamous cell carcinomas are grouped as human papillomavirus (HPV) associated and HPV independent, and there is an attempt to simplify the morphologic classification. A new chapter with tumours of the scrotum has been introduced. The main nomenclature of testicular tumours is retained, including the use of the term "germ cell neoplasia in situ" (GCNIS) for the preneoplastic lesion of most germ cell tumours and division from those not derived from GCNIS. Nomenclature changes include replacement of the term "primitive neuroectodermal tumour" by "embryonic neuroectodermal tumour" to separate these tumours clearly from Ewing sarcoma. The term "carcinoid" has been changed to "neuroendocrine tumour", with most examples in the testis now classified as "prepubertal type testicular neuroendocrine tumour"

WHO Classification of Tumours fifth edition: evolving issues in the classification, diagnosis, and prognostication of prostate cancer

The fifth edition of the WHO Classification of Tumours of the Urinary and Male Genital Systems encompasses several updates to the classification and diagnosis of prostatic carcinoma as well as incorporating advancements in the assessment of its prognosis, including recent grading modifications. Some of the salient aspects include: (1) recognition that prostatic intraepithelial neoplasia (PIN)-like carcinoma is not synonymous with a pattern of ductal carcinoma, but better classified as a subtype of acinar adenocarcinoma; (2) a specific section on treatment-related neuroendocrine prostatic carcinoma in view of the tight correlation between androgen deprivation therapy and the development of prostatic carcinoma with neuroendocrine morphology, and the emerging data on lineage plasticity; (3) a terminology change of basal cell carcinoma to "adenoid cystic (basal cell) cell carcinoma" given the presence of an underlying MYB::NFIB gene fusion in many cases; (4) discussion of the current issues in the grading of acinar adenocarcinoma and the prognostic significance of cribriform growth patterns; and (5) more detailed coverage of intraductal carcinoma of prostate (IDC-P) reflecting our increased knowledge of this entity, while recommending the descriptive term atypical intraductal proliferation (AIP) for lesions falling short of IDC-P but containing more atypia than typically seen in high-grade prostatic intraepithelial neoplasia (HGPIN). Lesions previously regarded as cribriform patterns of HGPIN are now included in the AIP category. This review discusses these developments, summarising the existing literature, as well as the emerging morphological and molecular data that underpins the classification and prognostication of prostatic carcinoma. Keywords: WHO Classification; pathology; prostate carcinoma