The Utility of ERBB4 and RB1 Immunohistochemistry in Distinguishing Chromophobe Renal Cell Carcinoma From Renal Oncocytoma.

Objectives. Differentiating renal oncocytoma (RO) from chromophobe renal cell carcinoma (ChRCC) can occasionally be challenging. We evaluated the expression of RB1 and ERBB4 in RO and ChRCC, and compared the immunohistochemistry (IHC) results to RB1 and ERBB4 gene abnormalities detected by fluorescence in situ hybridization (FISH). Materials and Methods. Fifty-three kidney resections (ChRCC, n=28; RO, n=25) were stained for RB1 and ERBB4 IHC and FISH was performed to evaluate gene copy number analysis. Results. A loss of RB1 staining was identified in 64% (18/28) of ChRCCs, which was not found in any ROs (0/25; P <.001). FISH analysis revealed 36% (10/28) of ChRCCs contained a RB1 hemizygous deletion with a concordance of 56% (10/18) between the IHC and FISH findings. No RB1 gene copy number variations were detected in any of the ROs (0/25; P <.001) and retained expression of RB1 by IHC. ERBB4 showed cytoplasmic/membranous staining in all ROs and ChRCCs. However, 75% (21/28) of ChRCCs also contained nuclear positivity for ERBB4, which was uncommonly seen in ROs (3/25, 12%; P < .001). A hemizygous ERBB4 gene deletion was detected in 46% of ChRCCs (13/28), but none of the ROs (0/25; 0%). Loss of labeling by RB1 or nuclear staining for ERBB4 IHC identified 25 of 28 (89%) of ChRCCs. Conclusion. In summary, the loss of RB1 expression is a highly specific diagnostic biomarker in distinguishing ChRCC from RO. Nuclear ERBB4 expression also appears to be a sensitive diagnostic biomarker for ChRCC, albeit the mechanism is unknown.

How Are Gleason Scores Categorized in the Current Literature: An Analysis and Comparison of Articles Published in 2016-2017.

BACKGROUND: A new prostate cancer grading system was proposed in 2013 and endorsed by major journals and societies in 2014, in part because of anecdotal evidence that Gleason scores (GSs) were incorrectly combined in the literature. OBJECTIVE: To examine how published studies categorized GSs in current practice. DESIGN, SETTING, AND PARTICIPANTS: A PubMed search was conducted on articles published in 2016-2017 using the search terms "Gleason" and "prostate". This literature review included 1576 articles after exclusions. RESULTS: (1) Separating GS 7: pathology journals were more likely than non-pathology journals to grade GS 7 separately (56.9% vs 40.0%, p<0.05). Articles co-authored by a pathologist separated GS 7 more than those without a pathologist (53.2% vs 32.9%, p<0.001). North American and European studies separated GS 7 more than Asian studies (47.6% and 44.1% vs 24.1%, p<0.001). Clinical articles separated GS 7 more than research articles (43.7% vs 32.9%, p<0.001). (2) Separating GS 8 from GS 9-10: pathology journals separated GS 8 from GS 9-10 more than non-pathology journals (55.2% vs 34.4%, p=0.001). Articles co-authored by a pathologist separated GS 8 from GS 9-10 more often than those without a pathologist (44.9% vs 29.5%, p<0.001). (3) Using grade groups as "ideal" with all other groupings "non-ideal": pathology journals used ideal more than non-pathology journals (32.2% vs 15.9%, p<0.001). Ideal grouping is more likely in articles co-authored by a pathologist than in those without a pathologist (20.6% vs 11.0%, p<0.001). North American and European studies used ideal grouping more than Asian studies (17.6% and 14.0% vs 9.1%, p<0.05). (4) Arranging groupings in decreasing order from ideal to non-ideal: pathology journals were closer to ideal than non-pathology journals (p=0.002). Articles co-authored by a pathologist were classified closer to ideal than those without a pathologist (p<0.001). North American (p<0.001) and European (p=0.02) studies were closer to ideal than Asian studies. CONCLUSIONS: There is still wide variation in how GSs are grouped world-wide. Only a minority of published articles group GSs accurately. PATIENT SUMMARY: In this report, we looked at how GSs were grouped world-wide. We found that only a minority of published articles on prostate cancer were grouping GSs accurately, which could lead to inaccurate results and affect patient care with different prostate cancer grades. Our study calls for more widespread adoption of the new prostate cancer grading system composed of five grade groups to minimize incorrect grouping for future studies.

The impact of noninvasive follicular thyroid neoplasm with papillary-like nuclear features on the rate of malignancy for atypia of undetermined significance subcategories.

BACKGROUND: The recent revision in terminology, with noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) replacing noninvasive follicular variant of papillary thyroid carcinoma, has reclassified the clinically indolent tumor as nonmalignant. The objective of this study was to evaluate the impact of this change on the rate of malignancy (ROM) for subcategories of an atypia of undetermined significance (AUS) diagnosis on fine-needle aspiration (FNA) cytology. METHODS: Consecutive thyroid FNAs interpreted as AUS over a period of 4 years were retrospectively analyzed. The ROM for AUS subcategories, including atypia of undetermined significance with nuclear atypia (AUS-N), atypia of undetermined significance with a microfollicular pattern (AUS-F), atypia of undetermined significance with nuclear atypia and a microfollicular pattern (AUS-N/F), atypia of undetermined significance with Hürthle cells (AUS-H), and atypia of undetermined significance, not otherwise specified (AUS-NOS), were analyzed. RESULTS: Of the 426 nodules interpreted as AUS, 244 were surgically excised. The incidence of NIFTP in each subcategory was as follows: 18% for AUS-N, 18% for AUS-F, 9% for AUS-N/F, 3% for AUS-H, and 0% for AUS-NOS. After the reclassification of NIFTP as nonmalignant, the ROM based on histologic follow-up significantly decreased from 43% to 26% for AUS-N (P < .001) and from 29% to 10% for AUS-F (P = .008). The ROM for AUS-N remained significantly higher than the ROM for AUS-F (P = .030). CONCLUSIONS: A subset of resected AUS nodules can be reclassified as NIFTP, and that significantly decreases the ROM, especially for AUS-N and AUS-F. Nonetheless, AUS-N still harbors a substantially higher ROM than AUS-F. Cancer Cytopathol 2018;126:309-16. © 2018 American Cancer Society.

Performance of ovarian cyst fluid fine-needle aspiration cytology.

BACKGROUND: Although ovarian fine-needle aspiration (FNA) cytology is not commonly used as a primary modality of diagnosis for patients with ovarian lesions, many ovarian cysts are aspirated intraoperatively and occasionally for diagnostic purposes. Therefore, the ability to interpret these specimens remains critical. Previous studies have suggested a high specificity but low sensitivity as a limitation. The objective of the current study was to further explore the use and performance of ovarian cyst FNA for diagnosing malignancy at the study institution. METHODS: The electronic database was searched from 1998 through 2016 for ovarian cyst fluid cytology specimens; any concurrent or follow-up surgical pathology; and clinical information including patient age, radiology findings, and procedure type. Test performance was calculated using the surgical pathology diagnosis as the gold standard. RESULTS: A total of 459 ovarian cyst FNA specimens had the following diagnoses: 416 (90.6%) were diagnosed as benign, 32 (7.0%) as atypical, 4 (0.9%) as suspicious, and 7 (1.5%) as malignant. Overall, 300 specimens (65.4%) had a corresponding surgical pathology specimen. On follow-up, the rate of malignancy (including borderline neoplasms) for benign FNA was 10 of 264 specimens (3.8%), that for atypical FNA was 0 of 24 specimens (0%), that for suspicious FNA was 5 of 5 specimens (100%), and that for malignant FNA was 7 of 7 specimens (100%). Test sensitivity was 54.0% and test specificity was 100%. The positive predictive value was 1.00 and the negative predictive value was 0.97, with a disease (malignancy) prevalence of 7.33%. CONCLUSIONS: Ovarian cyst fluid cytology is highly specific and moderately sensitive for the detection of ovarian malignancies. A negative FNA is reassuring for patients with a low pretest probability of malignancy. Cancer Cytopathol 2018;126:112-21. © 2017 American Cancer Society.

Urinary tract washing specimens containing atypical urothelial tissue fragments are significantly associated with urothelial neoplasia.

BACKGROUND: We previously found that the presence of atypical urothelial tissue fragments (AUTF) was associated with an increased risk of high-grade urothelial carcinoma (HGUC) but not low-grade urothelial neoplasia (LGUN) in voided urine (VU) specimens. However, we subsequently found that patients with LGUN were more likely to have cytologic atypia in urinary washing (UW) specimens, suggesting that cytologic atypia found in UW specimens might be associated with both LGUN and HGUC. In this study, we retrospectively examined UW specimens containing AUTF to determine whether they were associated with HGUC, LGUN, or both HGUC and LGUN. METHODS: 1173 UW specimens and any follow up biopsies were identified over a 10-year period and the presence of AUTF was recorded based on the original clinical diagnosis. RESULTS: The presence of AUTF in UW specimens was significantly associated with high-risk indeterminate diagnosis or definitive diagnosis of HGUC (P < .001). In addition, AUTF specimens were significantly associated with a neoplastic diagnosis of low-grade urothelial carcinoma (LGUC) or HGUC on subsequent biopsies when compared to specimens lacking AUTF (P = .047). The overall rate of CIS/HGUC in specimens with AUTF was 33.0 vs. 13.5% for specimens without AUTF (P = .051). CONCLUSIONS: Urothelial tissue fragments (UTF) found in UW specimens should be examined for the presence of cytomorphological atypia, as the presence of AUTF almost triples the risk of HGUC. As opposed to what has been found in VU specimens, AUTF in UW specimens is also associated with an increased risk of LGUN.

Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP).

Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a new term replacing what was previously known as non-invasive encapsulated follicular variant of papillary thyroid carcinoma (FVPTC). These tumors show benign/indolent clinical behavior when compared with invasive FVPTC, which led to their reclassification as a "non-malignant" neoplasm. NIFTP shares essentially similar cytomorphologic features as FVPTC, and can only be definitively diagnosed on surgical excision specimens. This article provides an update on morphologic characteristics of NIFTP, along with pertinent molecular studies and management algorithms.

Mass Forming Eosinophilic Cystitis in Pediatric Patients.

Eosinophilic cystitis (EC) is an uncommon inflammatory disorder of uncertain etiology that has been described in adult and pediatric populations. We describe 3 recent cases of EC that presented as a mass lesion in pediatric patients from the New England region of the United States. All patients were initially suspected to have a malignancy, and biopsy was performed, which ultimately led to the diagnosis of EC. We propose the use of eosinophil density of >25 eosinophils per high-power field and myocyte degeneration as supportive histopathologic features to make this diagnosis. It is of utmost importance to consider EC in the differential diagnosis when approaching a pediatric patient with a bladder mass.

Role of Tetrasomy for the Diagnosis of Urothelial Carcinoma Using UroVysion Fluorescent In Situ Hybridization.

CONTEXT: -UroVysion fluorescent in situ hybridization (FISH) is routinely used to detect urothelial carcinoma (UC). A positive threshold is defined as chromosome polysomy in 4 or more cells, which also includes tetrasomy, a natural product of cell division. OBJECTIVES: -To evaluate tetrasomy for UC detection and explore the relation to the surgical diagnosis or patient history. DESIGN: -The FISH was performed on 1532 urine samples from patients with cytology results and 4 or more years of follow-up. We created separate polysomy and tetrasomy categories and constructed receiver operating curves to determine appropriate thresholds using biopsy (n = 194) as the gold standard. Standard FISH and a novel assay integrating cytomorphology and FISH (Target-FISH) were compared. Matching tissue biopsies of urine samples with 10 or more tetrasomy cells were analyzed. RESULTS: -No significant threshold was found for tetrasomy cells. Exclusion of tetrasomy from the polysomy category changed the threshold from 8.5 to 4.5 cells, increased specificity (59.2% to 78.9%), but reduced sensitivity (78.9% to 65.9%). In Target-FISH, the same approach yielded a specificity of 93.7% and sensitivity of 65.2%. Similarly, specificity improved significantly for low- and high-grade UC, but sensitivity decreased for low-grade UC. No evidence of UC was observed in 95% (52 of 55) of the patients referred for screening who had 10 or more tetrasomy cells by FISH. Matching biopsies for urines containing 10 or more tetrasomy cells showed few or no tetrasomy cells. CONCLUSIONS: -Tetrasomy is a nonspecific finding frequently encountered in urine FISH and should be excluded from the polysomy classification. Target-FISH is an optimal approach, offering the ability to detect rare tetrasomy tumors.

Papillary renal cell carcinoma: correlation of tumor grade and histologic characteristics with clinical outcome.

Histologic prognostic parameters in papillary renal cell carcinoma (PRCC) are unclear. The aims were to review the clinicopathological features of PRCC, including Fuhrman grade and International Society of Urological Pathology (ISUP) nucleolar grade, and to identify parameters that may be independent prognostic indicators. PRCCs in patients treated by nephrectomy were retrieved from the pathology files from 1984 to 2010. Parameters studied included tumor multifocality, size, PRCC type (1 or 2), Fuhrman grade, ISUP nucleolar grade, presence of necrosis, lymphovascular invasion, and stage at presentation. Cancer-specific survival (CSS) and overall survival (OS) were used as prognostic measures. Of 154 PRCCs, 112 (73%) were type 1, and 42 (27%), type 2. A total of 125 patients were male, and 29, female, with ages from 26 to 86 (mean, 62.7) years. Fuhrman grade was 1 in 8 (5%), 2 in 95 (62%), 3 in 49 (32%), and 4 in 2 (1%) tumors, respectively. ISUP nucleolar grade was 1 in 47 (31%), 2 in 56 (36%), 3 in 49 (32%), and 4 in 2 (1%) tumors, respectively. Mean follow-up interval was 73.9 months (0.13-222 months). ISUP nucleolar grade was a significant predictor of both CSS and OS in univariate (CSS, P = .001; OS, P = .004) and multivariate (CSS, P = .04; OS, P = .008) analyses, whereas Fuhrman grade was only predictive of CSS in univariate (P = .001) and multivariate (P = .04) analyses. Only ISUP nucleolar grade and lymphovascular invasion were independently prognostic for CSS and OS in univariate and multivariate analyses. Therefore, the ISUP nucleolar grade appears to be superior in predicting survival in patients with PRCC.

Urine Cytopathology and Ancillary Methods.

Urothelial carcinoma (UC) is the most common malignancy of the urinary tract. Cytology and cystoscopy are two of the most commonly used tests for screening and diagnosis of UC. However, the sensitivity of cytology for UC is less than ideal, while cystoscopy is an invasive and expensive procedure. The search for an accurate, sensitive, noninvasive, and cost-effective method for detecting UC has led to the development of ancillary studies using immunological and molecular methods.

Clinical implications of current developments in genitourinary pathology.

CONTEXT: Several developments in genitourinary pathology are likely to change our understanding and management of some genitourinary cancers considerably. OBJECTIVE: To review 5 stories in genitourinary pathology: (1) fusion in the ETS (E26) gene family in prostatic adenocarcinoma; (2) insulin-like growth factor II messenger RNA-binding protein 3 (IMP3), an important prognostic biomarker for kidney and bladder cancers; (3) translocation renal cell carcinoma; (4) UroVysion fluorescence in situ hybridization test in urine cytology for detection of bladder cancer; and (5) the use of triple immunostaining for diagnosis of prostate cancer. DATA SOURCES: Literature review and authors' personal experiences. CONCLUSIONS: Many scientific findings have contributed recently to the understanding of the natural pathogenesis and progression of genitourinary cancers. This translational research helps in diagnosing, predicting, and potentially, treating genitourinary cancers.