Diagnostic Challenges and Long-term Outcomes of Neuroendocrine Carcinoma of the Cervix: A Case Series.

Neuroendocrine carcinomas (NECs) of the cervix are rare, aggressive malignancies that are challenging to diagnose and treat. They are high-grade lesions that often share features with poorly differentiated adenocarcinoma and squamous cell carcinoma. NECs are classified into large-cell or small-cell subtypes but can often have a mixed appearance or occur concurrently with a squamous or adenocarcinoma. Diagnosis is dependent on tissue sampling, histomorphology, and immunohistochemistry. Eight cases of NEC were retrieved from the Department of Pathology at our institution from 2008 to 2022. Tumor slides were reviewed and evaluated by 2 independent pathologists. Seven of 8 patients tested positive for neuroendocrine markers, including CD56, synaptophysin, and chromogranin. We discuss the diagnostic challenges, review the histopathology, and describe the treatment courses and clinical outcomes. This case series reveals that traditional markers, such as p16, p63, and p40, may be focally positive in NEC and should not be considered a confirmation of squamous cell carcinoma. Patient outcomes can be affected by delays in diagnosis, misdiagnosis, and inadequate treatment when NEC is not considered in the initial differential diagnosis.

Ewing's sarcoma of the male external genitalia: a case report and review of the literature.

BACKGROUND: Ewing's sarcoma (ES) within the genitourinary tract are relatively unheard of and those within the external male genitalia are even rarer. To our knowledge, this is the first known case of primary ES within the paratesticular region in an adult. CASE PRESENTATION: We present a case of a 24-year-old man with a right sided testicular mass on examination that was initially characterized as an adenomatoid tumor on ultrasound. After the patient was lost to follow up over the course of 9 months, the testicular mass grew significantly and was excised with pathology revealing primary paratesticular Ewing's sarcoma. This rare case emphasizes the importance of elucidating between the broad differentials of paratesticular masses, including the rare presentation of primary ES and adds a review of the literature of ES in the external male genitalia. CONCLUSIONS: Rare differentials such as this case should be considered in patients with paratesticular masses. Further diagnostic and management algorithms for extraosseous Ewing Sarcoma, particularly in the adult population, are warranted.

Lymph node ratio as best prognostic factor in triple-negative breast cancer patients with residual disease after neoadjuvant chemotherapy.

Although lymph node status (ypN) is one of the most important prognostic factors of survival, the lymph node ratio (LNR) has emerged as an equitable factor. We aimed to compare the prognostic value of both ypN and LNR in patients with residual triple-negative breast cancer (TNBC) after neo-adjuvant chemotherapy (NAC). This was a retrospective cohort study of patients treated in a tertiary care center during the period 2000-2014. We stratified the population based on LNR (≤0.20, 0.20-0.65, and >0.65) and ypN (N1, N2, and N3) status. The overall survival (OS) and progression-free survival (PFS) were estimated with Kaplan-Meier curves and the log-rank + test. We further compared patient mortality and disease recurrence using multivariate Cox regression analysis. We evaluated 169 patients with a median follow-up of 87 months. At 2 years of follow-up, patients with low-risk LNR compared to those with moderate and high risk had a higher PFS (54% vs 31% vs 18%, respectively; P < .001) and OS (74% vs 64% vs 45%, respectively; P < .001). Moreover, ypN1 patients compared to ypN2 and ypN3 showed similar results in PFS (53% vs 35% vs 19%, respectively; P = .001) and OS (73% vs 69% vs 43%, respectively; P < .001). Compared to the low-risk population, patients with moderate (hazard ratio [HR]: 3.50; 95% confidence interval [CI]: 1.41-8.71) and high risk (HR: 6.90; 95% CI: 2.29-20.77) had a worse PFS. Regarding OS, moderate-risk (HR: 2.85; 95% CI: 1.10-7.38) and high-risk patients (HR: 6.48; 95% CI: 2.13-19.76) showed considerably worse outcomes. On the other hand, ypN staging was not associated with PFS or OS in the multivariate analysis. The LNR is a better prognostic factor of survival than ypN. The LNR should be considered in the stratification of risk after NAC in patients with TNBC.

Focal Laser Ablation of Prostate Cancer: Results in 120 Patients with Low- to Intermediate-Risk Disease.

PURPOSE: Can focal laser ablation (FLA) of low to intermediate risk prostate cancer preserve sexual and urinary function with low morbidity while providing adequate oncologic outcomes. MATERIALS AND METHODS: Transrectal FLA was done in 120 patients with low- to intermediate-risk prostate cancer. MR imaging thermometry controlled ablation. At 6 and 12 months, patients had clinical and MR imaging follow-up with biopsy of suspicious areas. Patients submitted surveys of sexual and urinary function. Multivariate logistic regression identified determinants of positive imaging and biopsies. Two-sided Wilcoxon signed rank test evaluated scores and laboratory values. RESULTS: Median patient age was 64 years, and median prostate-specific antigen (PSA) was 6.05 ng/mL. Median follow-up period was 34 months (range, 17-55 months). Gleason score was 3+3=6 in 37 (30.8%), 3+4=7 in 56 (46.7%), and 4+3=7 in 27 (22.5%) patients. Tumor stage was T1c in 89 (74.2%), T2a in 26 (21.7%), and T2b in 5 (4.2%) patients. Twenty (17%) patients had additional oncologic therapy 1 year after FLA when biopsy confirmed cancer following abnormal MR imaging. There was no difference between functional scores before and after ablation. Median PSA decreased to 3.25 at 12 months (P < .001). Tumor diameter above the median (odds ratio = 3.36; 95% confidence interval, 1.41-7.97) was the only significant predictor for positive MR imaging after treatment. CONCLUSIONS: One year after FLA, selected patients had low morbidity, no significant changes in quality of life, and 83% freedom of retreatment rate. Sexual and urinary function did not significantly change after FLA.

Initial series of magnetic resonance imaging (MRI)-fusion targeted prostate biopsy using the first transperineal targeted platform available in the USA.

OBJECTIVES: To describe a step-by-step guide for using the first transperineal targeted prostate biopsy platform available in the USA. PATIENTS AND METHODS: A total of 32 men with elevated prostate-specific antigen (PSA) levels were diagnosed with a region of interest on multiparametric magnetic resonance imaging (mpMRI) between February 2017 and January 2018. The transperineal targeted prostate biopsy procedure was accomplished via a transperineal approach and used a stepper, combined with advanced mpMRI/transrectal ultrasound fusion software, to perform targeted prostate biopsy. The detection of overall and clinically significant prostate cancer (PCa) was assessed as well as the rate of complications. RESULTS: The median patient age was 68.0 years and the median PSA was 8.0 ng/mL. Two patients (6%) were active surveillance candidates and 16 (50%) had a prior negative prostate biopsy. The detection rates for overall and clinically significant PCa were 81% and 59%, respectively. The two candidates for active surveillance and eight of the patients with a prior negative prostate biopsy had clinically significant PCa confirmed on targeted biopsy. There were no peri-operative complications. CONCLUSION: These results demonstrate the promising potential of the first transperineal targeted prostate biopsy platform in the USA as an alternative diagnostic method for PCa.

CD8 + T cell response promotes viral clearance and reduces chances of severe testicular damage in mouse models of long-term Zika virus infection of the testes.

Zika virus (ZIKV) causes human testicular inflammation and alterations in sperm parameters and causes testicular damage in mouse models. The involvement of individual immune cells in testicular damage is not fully understood. We detected virus in the testes of the interferon (IFN) α/ß receptor -/- A129 mice three weeks post-infection and found elevated chemokines in the testes, suggesting chronic inflammation and long-term infection play a role in testicular damage. In the testes, myeloid cells and CD4 + T cells were absent at 7 dpi but were present at 23 days post-infection (dpi), and CD8 + T cell infiltration started at 7 dpi. CD8 -/- mice with an antibody-depleted IFN response had a significant reduction in spermatogenesis, indicating that CD8 + T cells are essential to prevent testicular damage during long-term ZIKV infections. Our findings on the dynamics of testicular immune cells and importance of CD8 + T cells functions as a framework to understand mechanisms underlying observed inflammation and sperm alterations in humans.

Paratesticular Ewing's sarcoma.

This case report follows a 23-year-old man who presented with a painful right scrotal mass which was found to be a paratesticular vascular solid mass on ultrasound, and after uncomplicated orchiectomy, was revealed to be a high-grade extraskeletal Ewing's sarcoma. Diagnosis leading up to the orchiectomy was primarily clinical with only ultrasound used in identification and characterization of the paratesticular mass. Paratesticular masses are more commonly benign, and ultrasound is the first modality, with computed tomography and magnetic resonance imaging providing more definitive findings. We discuss imaging findings and histopathology of this rare tumor with an uncommon presentation.

p16 Immunohistochemical Expression in Nephrogenic Adenoma.

Nephrogenic adenoma (NA) is a rare metaplastic entity commonly associated with a prior urothelial injury. Most are seen in the urinary bladder and a minority involve the urethra. In this study, we evaluated the expression of p16 as a surrogate marker of this entity and correlated it with clinical pathological parameters. A total of 17 cases of NA were retrospectively studied to assess the immunohistochemical expression of p16 and its value for the diagnosis of this entity.

Nephrogenic Adenoma Arising From a Female Urethral Diverticulum: A Case Report and Potential Diagnostic Pitfalls.

Nephrogenic adenoma is a benign lesion of the urothelial tract characterized by tubules surrounded by thick, hyalinized basement membranes. There is a great variety of architectural patterns within nephrogenic adenomas, including patterns that mimic malignancy, such as focal clear or hobnail cells, areas of significant nuclear atypia, mitosis, and isolated cystic changes. This represents a diagnostic pitfall, where a malignant lesion can be mistaken for a nephrogenic adenoma, leading to a delay in diagnosis and treatment that adversely affects the outcome. In this case report, we describe a nephrogenic adenoma arising in a female urethral diverticulum and discuss the differential diagnosis, which includes clear cell carcinomas, microcystic variant urothelial carcinomas, and Skene's gland cysts.

Postmenopausal Tubular Adenoma of the Breast: A Case Report.

Tubular adenoma (TA) of the breast is a rare, benign proliferative breast lesion that is predominantly composed of closely compacted tubules with an inner layer of epithelial cells and an outer layer of myoepithelial cells. They are regarded as residing on the opposite end of a spectrum of proliferative breast lesions from fibroadenomas, which are predominantly stromal. The majority of TAs are found in premenopausal women and the reason for this demographic predilection is not yet known. It is generally not possible to distinguish between TA and other, higher-risk breast lesions prior to biopsy or resection because the clinical and radiographic findings overlap. In this article, we present the case of a TA in a postmenopausal patient and review the epidemiology, histology, carcinogenic potential, and management of such lesions.

Characterizing molecular subtypes of high-risk non-muscle-invasive bladder cancer in African American patients.

BACKGROUND: We sought to determine whether differences in subtype distribution and differentially expressed genes exist between African Americans (AAs) and European Americans (EAs) in patients with high-risk nonmuscle-invasive bladder cancer (NMIBC). METHODS: We performed a retrospective cohort study including 26 patients (14 AAs and 12 EAs) from the University of Texas Medical Branch and the Durham Veterans Affair Health Care System from 2010 to 2020 among treatment naïve, high-risk NMIBC. Profiled gene expressions were performed using the UROMOL classification system. RESULTS: UROMOL racial subtype distributions were similar with class 2a being most common with 10 genes commonly upregulated in AAs compared to EAs including EFEMP1, S100A16, and MCL1 which are associated with progression to muscle-invasive bladder cancer, mitomycin C resistance, and bacillus Calmette-Guérin durability, respectively. We used single nuclei analysis to map the malignant cell heterogeneity in urothelial cancer which 5 distinct malignant epithelial subtypes whose presence has been associated with different therapeutic response prediction abilities. We mapped the expression of the 10 genes commonly upregulated by race as a function of the 5 malignant subtypes. This showed borderline (P = 0.056) difference among the subtypes suggesting AAs and EAs may be expected to have different therapeutic responses to treatments for bladder cancer. AAs were enriched with immune-related, inflammatory, and cellular regulation pathways compared to EAs, yet appeared to have reduced levels of the aggressive C3/CDH12 bladder tumor cell population. CONCLUSIONS: While premature, gene expression differed between AAs and EAs, supporting potential race-based etiologies for muscle-invasion, response to treatments, and transcriptome pathway regulations.

SARS-CoV-2 Infects Hamster Testes.

The COVID-19 pandemic continues to affect millions of people worldwide. Although SARS-CoV-2 is a respiratory virus, there is growing concern that the disease could cause damage and pathology outside the lungs, including in the genital tract. Studies suggest that SARS-CoV-2 infection can damage the testes and reduce testosterone levels, but the underlying mechanisms are unknown and evidence of virus replication in testicular cells is lacking. We infected golden Syrian hamsters intranasally, a model for mild human COVID-19, and detected viral RNA in testes samples without histopathological changes up to one month post-infection. Using an ex vivo infection model, we detected SARS-CoV-2 replication in hamster testicular cells. Taken together, our data raise the possibility that testes damage observed in severe cases of COVID-19 could be partly explained by direct SARS-CoV-2 infection of the testicular cells.

EGFR and HER-2/neu expression in invasive apocrine carcinoma of the breast.

This study was undertaken to investigate epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER-2)/neu expression in a cohort of apocrine carcinomas of the breast with emphasis on the classification of the breast tumors with apocrine morphology. In total, 55 breast carcinomas morphologically diagnosed as apocrine were evaluated for the steroid receptor expression profile characteristic of normal apocrine epithelium (androgen receptor positive/estrogen receptor (ER) negative/progesterone receptor (PR) negative), and for the expression of EGFR and Her-2/neu proteins, and the copy number ratios of the genes EGFR/CEP7 and HER-2/CEP17. On the basis of the results of steroid receptors expression, 38 (69%) cases were classified as pure apocrine carcinoma (androgen receptor positive/ER negative/PR negative), whereas 17 (31%) were re-classified as apocrine-like carcinomas because they did not have the characteristic steroid receptor expression profile. Her-2/neu overexpression was observed in 54% of the cases (57% pure apocrine carcinomas vs 47% apocrine-like carcinomas). HER-2/neu gene amplification was demonstrated in 52% of all cases (54% pure apocrine carcinomas vs 46% apocrine-like carcinomas). EGFR protein (scores 1 to 3+) was detected in 62% of all cases and was expressed in a higher proportion of pure apocrine carcinomas than in the apocrine-like carcinomas group (76 vs 29%, P=0.006). In the pure apocrine carcinoma group, Her-2/neu and EGFR protein expression were inversely correlated (P=0.006, r=-0.499). EGFR gene amplification was observed in two pure apocrine carcinomas and one apocrine-like carcinoma. Polysomy 7 was commonly present in pure apocrine carcinomas (61 vs 27% of apocrine-like carcinomas; P=0.083) and showed a weak positive correlation with EGFR protein expression (P=0.025, r=0.326). Our study showed that apocrine breast carcinomas are molecularly diverse group of carcinomas. Strictly defined pure apocrine carcinomas are either HER-2-overexpressing breast carcinomas or triple-negative breast carcinomas, whereas apocrine-like carcinomas predominantly belong to the luminal phenotype. Pure apocrine carcinomas show consistent overexpression of either EGFR or HER-2/neu, which could have significant therapeutic implications.

Clear Cell Papillary Renal Cell Carcinoma.

Clear cell papillary renal cell carcinoma (ccpRCC) is a recently recognized entity and represents the fourth most common variant of renal cell carcinoma (RCC). It has unique morphologic and immunohistochemical features and demonstrates an indolent clinical behavior. Microscopically, it may mimic other RCCs with clear cell features, such as clear cell RCC, translocation RCC, and papillary RCC with clear cell changes. A high index of suspicion is required to keep ccpRCC in the differential diagnosis of RCCs with features of clear cell and/or papillary architecture. In equivocal cases, immunohistochemistry is generally sufficient to substantiate the diagnosis of ccpRCC. In this review, we discuss the clinical, gross, and histopathologic features, immunohistochemical and genetic profiling, and prognosis of ccpRCC.

Memy I: a novel murine model for uterine leiomyoma using adenovirus-enhanced human fibroid explants in severe combined immune deficiency mice.

OBJECTIVE: This study was undertaken to develop a representative murine model for human leiomyoma. STUDY DESIGN: Human fibroid tumor tissues were cut into small pieces and treated with medium alone, adenoviral-beta-galactosidase, adenoviral-vascular endothelial growth factor-A, adenoviral-cyclooxygenase-2, or both adenoviral-vascular endothelial growth factor-A and adenoviral- cyclooxygenase-2. Tissue pieces were inserted subcutaneously in the flank of each severe combined immunodeficient mouse. The developed lesion was measured twice per week. Xenograft tissues were harvested after 30 days and analyzed. RESULTS: Tissue pieces transfected with both adenoviral-cyclooxygenase-2 and adenoviral-vascular endothelial growth factor-A continued to grow up to 30 days postimplantation. The number of proliferating and apoptotic cells, as well as the expression of smooth muscle actin, desmin, vimentin, estrogen receptors, and progesterone receptors was similar between retrieved grafts from that group and the original patient tissue. Furthermore, hematoxylin and eosin and Masson's Trichrome stains confirmed this similarity. CONCLUSION: Human uterine leiomyoma xenografts, pretreated with both adenoviral- cyclooxygenase-2 and adenoviral-vascular endothelial growth factor-A and implanted subcutaneously in severe combined immunodeficient mice, represent a novel model for human uterine leiomyoma.

Vaginal Bleeding as Initial Presentation of an Aggressive Renal Cell Carcinoma: A Case Report and Review of the Literature.

INTRODUCTION: Renal cell carcinoma is the third most common urogenital cancer. In some patients, it can metastasize to distant organs. Metastasis to the vagina is extremely rare. CASE PRESENTATION: A 54-year-old female with unremarkable history presented to the clinic with a chief complaint of vaginal bleeding. Further examination identified a pedunculated mass on the vaginal wall. Histologic examination revealed a metastatic clear cell renal cell carcinoma. Radiological studies then revealed a left renal mass and bilateral adrenal masses. The patient underwent a nephrectomy, adrenalectomy, and resection of the vaginal mass. The mass in the vagina has since recurred. CONCLUSION: We report the first known case of vaginal metastasis as initial presentation of a renal cell carcinoma with rhabdoid features. Postmenopausal women with renal cell carcinoma who present with vaginal bleeding should undergo a thorough inspection of the vaginal wall for the potential of metastatic neoplasms.

A Rare Case of Multifocal Prostatic Blue Nevus.

Prostatic blue nevus is a rare benign pathologic diagnosis most commonly diagnosed incidentally on many different types of prostate specimens. Blue nevus is the deposition of stromal melanin characterized by spindle cells within the fibromuscular stroma which stains positive for melanin-specific stains Fontana-Masson and S100 and stains negative for CD68, HMB45, and iron stains. We report the case of a multifocal and bilateral blue nevus in a 52-year-old Hispanic male who presented with an elevated prostate-specific antigen of 4.3 and mild obstructive lower urinary tract symptoms, found by transrectal ultrasound-guided prostate needle biopsy. The biopsy also revealed benign prostatic tissue with postatrophic hyperplasia and chronic inflammation. This is the 35th reported case of prostatic blue nevus and the third to show multifocal blue nevus.

Atypical small acinar proliferation at index prostate biopsy: rethinking the re-biopsy paradigm.

PURPOSE: Guidelines for atypical small acinar proliferation (ASAP) diagnosed on prostate biopsy recommend repeat biopsy within 3-6 months after diagnosis. We sought to discern the rate of detecting clinically significant prostate cancer on repeat biopsy and predictors associated with progression. MATERIALS AND METHODS: We performed a retrospective chart review of patients who underwent prostate biopsy at our institution from January 1, 2008, to December 31, 2015. Gleason grade group (GGG) system and D'Amico stratification were used to report pathology and risk stratification, respectively. Logistic and linear regression analyses were performed. RESULTS: A total of 593 patients underwent transrectal ultrasound-guided prostate biopsy, of which 27 (4.6%) had the diagnosis of ASAP. Of these, 11 (41%) had a repeat biopsy. Median time from diagnosis to repeat biopsy was 147 days (IQR 83.5-247.0). Distribution across the GGG system on repeat biopsy was as follows: 7 (63.6%) benign, 3 (27.3%) GG1, and 1 (9.1%) GG2. ASAP was not associated with subsequent diagnosis of clinically significant prostate cancer (OR 0.46, 95% CI 0.064-3.247, P = 0.432). There was no association between ASAP and high cancer risk (ASAP: ß = - 0.12; P = 0.204). CONCLUSIONS: Patients diagnosed with ASAP managed according to guideline recommendations are more likely diagnosed with benign pathology and indolent prostate cancer on repeat biopsy. These findings support prior studies suggesting refinement of guidelines in regard to the appropriateness and timeliness of repeat biopsy among patients diagnosed with ASAP.

Acquired Cystic Disease-Associated Renal Cell Carcinoma: Review of Pathogenesis, Morphology, Ancillary Tests, and Clinical Features.

Acquired cystic disease-associated renal cell carcinoma (ACD-RCC) is a recently described subtype of RCC found in individuals with ACD of the kidney. Because of underrecognition, information regarding this lesion is sparse but continues to accumulate with each new report. Herein, a thorough literature review amassing the current understanding of this unique neoplasm is presented. Discussion focuses on clinical features, pathogenesis, disease outcome, and relation to the duration of dialysis. The macroscopic and characteristic microscopic features are described with illustrations. Compared with previous opinion, compiled immunohistochemical data may now allow for recognition of a unique immunophenotypic pattern of ACD-RCC. Distinction of ACD-RCC from clear cell and papillary RCCs based on molecular genetic information is deliberated, including a summary of the most frequently detected cytogenetic abnormalities. The key morphologic and immunophenotypic patterns used to distinguish this entity from a comprehensive differential diagnosis are provided.