Faculty Bibliography

Background: Entrapped cells or tubules within the fibrous stroma/central scar (fibrous epithelial cellular component = FECC) of oncocytoma have been previously reported although not to date studied in detail. While benign, the varied features of these cells may at times pose a diagnostic challenge. Although these have been attributed as entrapped tubules of oncocytoma, the underlying nature and differentiation of the fibrous epithelial cellular component (FECC) remains unexplored.
Design(s): We evaluated cases of renal oncocytoma for cellular components in the fibrous stroma ('entrapped tubules') and describe their morphologic variation and immunohistochemical features in comparison to the surrounding oncocytoma.
Result(s): We examined twelve oncocytoma cases with fibrous stroma ('central scar') containing FECC which were evaluated further by immunohistochemical studies, including CD117 and CK7. In select cases, additional immunohistochemical stains were performed depending on the renal tumor differential diagnosis. These included carbonic anhydrase IX (CA-9), 34Be12 and AE1/AE3 in select cases. The fibrous stroma of the oncocytoma ('central scar') was noted to represent from 10% to 50% of the tumor area and while predominantly central also extended peripherally as short septa. FECC was predominantly in the stroma immediately subjacent to the usual oncocytoma component. The architecture varied as tubular, trabecular, to diminutive acini with adjacent single cells and showed mixed pattern in majority. Cytologically the FECC had cleared cytoplasm, and slightly larger and vesicular nuclei than oncocytoma cells. Some cases demonstrated an area of transition between oncocytoma and the fibrous cellular component with trabecular bands containing scattered oncocytic intermingled with clear cells. Immunohistochemical studies showed FECC positive for CK7 and CA-9 and negative for CD117 (CK7 +/ CA- 9 +/CD117 -), whereas oncocytoma cells showed the reverse pattern (CK7 -/ CA-9 -/CD117 +). Immunostains for 34betaE12 and AE1/AE3 performed in a subset of cases showed positive staining of in contrast to the nonreactivity in the oncocytoma. (Figure Presnted)
Conclusion(s): FECC or 'entrapped tubules' likely represents a fibrous stromal component of oncocytoma with different microscopic appearance and immunohistochemical profile. It is important to be aware of the variant histological pattern and immunohistochemical profile of oncocytoma as may pose diagnostic difficulty in limited sampling by core needle biopsy. The clear appearance and narrowed trabecular/ tubular pattern is suggestive of an atrophic/ entrapped tumor component, however its varied immunoprofile also raises question as to whether this represents a different differentiation of tumor in an altered microenvironment

Background: Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in the genes encoding polycystin 1 and polycystin 2 (PKD1 and PKD2, respectively), leading to florid cystic change of the renal parenchyma. The incidence of carcinoma associated with ADPKD remains unclear although there are studies to suggest that the incidence may be higher.
Design(s): We queried our department pathology database for surgical specimens with ADPKD from 1990 to 2020. We evaluated these cases for the presence of associated malignant or benign neoplasia, as well as pathological and clinical parameters.
Result(s): The majority of the surgical specimens are kidney explants with a clinical diagnosis of ADPKD and the status of end stage kidney diseases. All specimens showed radiological, gross and microscopic features of ADPKD. Eight of 33 ADPKD patients with kidney resection specimens examined contained a malignant neoplasm, including 2 patients with bilateral malignancy. The types of renal cell carcinoma (RCC) associated with the following types: four cases of clear cell RCC, two cases of papillary RCC, type 2, two cases of unclassified high grade RCC, one case of unclassified low grade, as well as one case of TFE3 translocated RCC. Associated carcinomas ranged in size from less than 1 cm to 12 cm. One case with a concurrent oncocytoma and several cases with associated papillary adenoma were also reported.
Conclusion(s): In this cohort, a wide distribution of renal cell carcinoma subtypes were observed, with clear cell RCC being the most common type. The incidence of associated malignancy (24%) is higher than previously reported by Jilg et al. 2013 (5%), possibly due to differences in patient management or patient populations between the institutions. This case series highlights the high occurrence of carcinoma in APKD nephrectomies suggesting a clinical risk of malignancy in patients with ADPKD. Additionally this case series reports the first case of a TFE3 translocated renal cell carcinoma arising synchronously with a contralateral clear cell renal cell carcinoma in a patient with ADPKD. The heterogeneity of renal carcinoma subtypes within the group (and within contralateral kidneys in one patient with bilateral involvement) suggests that stimuli for tumorigenesis arise at the kidney microenvironment level rather than on the basis of gene mutation alone. Accrual of an expanded cohort of patients is planned to enable confirmation of differences between carcinomas arising in the setting of ADPKD versus those arising in end stage renal disease due to other causes, and in the sporadic setting. Furthermore a role for molecular studies is suggested to evaluate if any of the ADPKD causing mutations (PKD1, PKD2, or other) is associated with the development of carcinoma

Gastric cancer is a rare long-term complication in gastrocystoplasty. We report 2 cases of gastric adenocarcinoma and review the literature for similar cases. A total of 14 cases are identified. The majority of patients are males, presented with hematuria, and developed cancer at a younger age, more than 10 years after gastrocystoplasty. Long-term follow up information was limited, but 5 patients (36%) died within 5 years of diagnosis. Annual surveillance for malignancy may not be effective due to its rarity. However, symptomatic patients, particularly those 10 years after the surgery, warrant detailed evaluation to rule out neoplastic transformation.

Accurate diagnosis of cribriform Gleason pattern 4 (CrP4) prostate adenocarcinoma (PCa) is important due to its independent association with adverse clinical outcomes and as a growing body of evidence suggests that it impacts clinical decision making in PCa management. To identify reproducible features for diagnosis of CrP4, we assessed interobserver agreement among 27 experienced urologic pathologists of 60 digital images from 44 radical prostatectomies (RP) that represented a broad spectrum of potential CrP4. The following morphologic features were correlated with the consensus diagnosis (defined as 75% agreement) for each image: partial vs. transluminal glandular bridging, intraglandular stroma, <12 vs. ≥12 lumina, well vs. poorly formed lumina, mucin (mucinous fibroplasia, extravasation, or extracellular pool), size (compared to benign glands and number of lumina), number of attachments with gland border by tumor cells forming a "glomeruloid-like" pattern, a clear luminal space along the periphery of gland occupying <50% of glandular circumference, central nerve, dense (cell mass occupying >50% of luminal space) vs. loose, and regular vs. irregular contour. Interobserver reproducibility for the overall diagnostic agreement was fair (k=0.40). Large CrP4 had better agreement (k=0.49) compared to small CrP4 (k=0.40). Transluminal bridging, dense cellular proliferation, a clear luminal space along the periphery of gland occupying <50% of gland circumference, lack of intraglandular mucin, and lack of contact between the majority of intraglandular cells with stroma were significantly associated with consensus for CrP4. In contrast, partial bridging, majority of intraglandular cells in contact with stroma, mucinous fibroplasia, only one attachment to the gland border by tumor cells forming a "glomeruloid-like" pattern, and a clear luminal space along the periphery of gland accounting for >50% of the glandular circumference were associated with consensus against CrP4. In summary, we identified reproducible morphological features for and against CrP4 diagnosis, which could be used to refine and standardize the diagnostic criteria for CrP4.

PURPOSE/OBJECTIVE:A benign MRI-targeted prostate biopsy (MRF-TB) in the setting of a PI-RADS 4/5 abnormality presents a clinical dilemma for future management. We evaluated benign histologic features on MRF-TB to determine if they predict the likelihood of missed cancer on subsequent biopsy. MATERIALS AND METHODS/METHODS:Between 6/2012 and 9/2016, 1595 men were enrolled in a prospective study of MRI-targeted and systematic biopsy outcomes. We re-reviewed pathology from benign MRF-TB of PI-RADS 4/5 abnormalities and divided into 5 groups for comparison to outcomes of clinical follow-up: inflammation (38%), stroma/glandular hyperplasia (9%), normal prostate tissue (28%), ASAP/HGPIN (9%), and cancer in adjacent systematic cores (16%). RESULTS:88/497 (18%) men with PI-RADS 4/5 abnormality prior to initial biopsy had no cancer on MRF-TB. In follow-up, 45 men underwent repeat MRI: 12 (27%) had persistent PI-RADS 4/5 abnormalities, 17 (38%) had PI-RADS 2/3, 16 (35%) had PI-RADS 1. On repeat MRF-TB, cancer was found in 62.5% of men with PI-RADS 4/5 and 23% of men with PI-RADS 2/3. Histologic groups on initial MRF-TB were not predictive of the likelihood of PI-RADS downgrade on repeat MRI or cancer detection on repeat biopsy. CONCLUSIONS:Among men with no cancer on MRF-TB performed for PI-RADS abnormality, downgrade of PI-RADS score is noted in 73% on repeat MRI. Persistence of PI-RADS 4/5 predicts a higher risk of missed cancer, warranting prompt re-biopsy. While histologic findings such as inflammation may underlie some PI-RADS 4/5 abnormalities, initial histology is a poor predictor of cancer likelihood on repeat biopsy.

PURPOSE/OBJECTIVE:To demonstrate the generalizability of PRECISION findings and apply the PRECISION biopsy strategy to a contemporary cohort to characterize cancers missed by employing this strategy. MATERIALS AND METHODS/METHODS:629 men biopsied between 2/2015-9/2018 met PRECISION inclusion criteria. Men with PI-RADS 1-2 MRI were only biopsied if high clinical suspicion for cancer. Missed cancers were defined as prostate cancer (PCa) identified uniquely on systematic biopsy (SB) in men with PI-RADS 3-5 MRI, or on either SB or MRI-targeted prostate biopsy (MRI-TB) in men with PI-RADS 1-2 MRI. Outcomes included 1) clinically-significant PCa (csPCa), ≥Gleason grade group (GG) 2, detection rate (CDR), 2) missed csPCa rate upon application of PRECISION biopsy strategy, 3) GG distribution, core size, spatial orientation, and oncologic risk among missed cancers. RESULTS:Application of the PRECISION biopsy strategy to the study cohort resulted in avoidance of biopsy in 28%, similar MRI-TB CDR to PRECISION, reduction of GG1 CDR by 60%, and reduction of csPCa CDR by 19%. Missed csPCa were often <6 mm (54.5%), GG2 (67.3%), and low-risk by clinical nomogram (74.6%). GG1 cancers identified uniquely on SB were often contralateral to MRI target (46.4%), while missed csPCa was predominantly ipsilateral (81%). Limitations include biopsy of only men with high-risk clinical features among PIRADS 1-2 MRI, potentially overestimating the csPCa CDR. CONCLUSIONS:The study cohort demonstrated generalizability of PRECISION findings. Applying the PRECISION biopsy strategy greatly reduces GG1 CDR, while missing a small number of csPCa, typically small volume, low-risk, and GG2. Missed csPCa are predominantly ipsilateral to MRI target, possibly representing targeting error.