Bich N. Nguyen

Focal nodular hyperplasia of the liver: a comprehensive pathologic study of 305 lesions and recognition of new histologic forms.

Atypical histologic variants of focal nodular hyperplasia have been reported and are sometimes difficult to recognize. To characterize the morphologic spectrum of focal nodular hyperplasia, we studied 305 lesions surgically resected from 168 patients. Clinicomorphologic correlations were established by statistical analyses. The patients included 150 women and 18 men (sex ratio, 8:1; median age, 38 years). One hundred twenty-eight (76.2%) patients had solitary lesions, and 40 (23.8%) had 2 to 30 lesions. All 305 lesions measured 1 mm to 19 cm in diameter. Only 49% of these lesions had one to three macroscopic scars. Histologically, 245 (80.3%) lesions were of classical form, and 60 (19.7%) lesions were nonclassical. The latter were classified as focal nodular hyperplasia of telangiectatic form (47 lesions), of mixed hyperplastic and adenomatous form (five lesions), and with atypia of large cell type (eight lesions). Several benign or malignant tumors were found in association with these lesions. This large retrospective series of focal nodular hyperplasia shows the relative incidence of its classical and nonclassical forms. The absence of a central scar could explain the difficult preoperative diagnosis of some of the cases. The morphologic diagnostic criteria in this study require further prospective evaluation.

Renal epithelioid angiomyolipoma: a study of six cases and a meta-analytic study. Development of criteria for screening the entity with prognostic significance

Aims:  Renal epithelioid angiomyolipoma (EAML) is only described in case reports or in multi‐institutional small series. The aim was to report cases seen at our institution and to perform a meta‐analysis based on a literature review.

Utility of cytokeratin 5/6, cytokeratin 20, and p16 in the diagnosis of reactive urothelial atypia and noninvasive component of urothelial neoplasia.

Background:The utility of cytokeratin (CK)5/6 in distinguishing reactive urothelial atypia (RA) from urothelial carcinoma in situ (CIS) and from noninvasive component of high-grade papillary urothelial carcinoma (PUC) is unknown. Design:Twenty RA with or without papillary hyperplasia and 90 noninvasive components of neoplastic urothelial lesions were submitted for immunostaining with CK5/6, CK20, and p16. Results:Diffuse and strong reactivity involving the full or nearly full thickness of urothelium was observed with CK5/6 in 90% of RA cases. CK20 and p16 were negative in 90% and 85% of the RA cases, respectively. For CIS and noninvasive components of high-grade PUC without squamous differentiation, there was no CK5/6 staining or reactivity in the basal layer only. CK20 and p16 showed strong positivity in full thickness of urothelium in 75% to 85% of cases. CIS with weak/focal or negative reactivity for p16 or CK20 exhibited moderate cytologic atypia. Low-grade PUC displayed variable reactivity for CK5/6, CK20, and p16. Urothelial lesions with squamoid or basaloid features showed positive reactivity for CK5/6. Urothelial lesions with glandular differentiation showed negative reactivity for CK5/6. Conclusions:Diffuse CK5/6 reactivity in RA and negative CK5/6 reactivity in CIS and PUC may be helpful in distinguishing between these 2 entities.

Detection of Steatohepatitis in a Rat Model by Using Spectroscopic Shear-Wave US Elastography

Purpose To compare low- versus high-frequency ultrasonographic (US) elastography for detection of steatohepatitis in rats by using histopathologic findings as the reference standard. Materials and Methods Between March and September 2014, after receiving approval from the institutional animal care committee, 60 male Sprague-Dawley rats were fed either a standard chow for 4 weeks or a methionine- and choline-deficient diet for 1, 4, 8, or 12 weeks to induce a continuum of steatohepatitis severity. Liver shear stiffness was assessed in vivo by using US elastography at low (40-130-Hz) and high (130-220-Hz) frequencies. Histologic features (steatosis, inflammation, and fibrosis) and modified nonalcoholic steatohepatitis categories were used as reference standards. Definite steatohepatitis was divided into steatohepatitis with fibrosis stage 1 or lower and stage 2 and higher. Analyses included the Kendall τ correlation, multivariable linear regression analyses, Kruskal-Wallis rank sum test, and post hoc Dunn test with Holm correction. Results Correlations between liver shear stiffness and histologic features were higher at high frequencies than at low frequencies (low frequency: 0.08, 0.24, and 0.20 for steatosis, inflammation, and fibrosis, respectively; high frequency: 0.11, 0.35, and 0.50, respectively). The absolute value of multivariable regression coefficients was higher at high frequencies for the presence of steatosis, inflammation grade, and fibrosis stage (low frequency: -0.475, 0.157, and 0.209, respectively; high frequency: -0.893, 0.357, and 0.447, respectively). The model fit was better at high frequencies (adjusted R2 = 0.57) than at low frequencies (adjusted R2 = 0.21). There was a significant difference between steatohepatitis categories at both low and high frequencies (P = .022 and P < .001, respectively). Conclusion Liver shear stiffness measured with US elastography provided better distinction of steatohepatitis categories at high frequencies than at low frequencies. Further, liver shear stiffness decreased with steatosis and increased with inflammation and fibrosis at both low and high frequencies.

Low-grade versus high-grade chromophobe renal cell carcinoma.

To the Editor: We read the article by Paner et al with interest. As pointed out by the authors, the Fuhrman nuclear grading that is useful in predicting the prognosis of clear cell renal cell carcinoma (RCC) is not applicable to chromophobe RCC. The authors have proposed a novel 3-tiered tumor grading system that seems to be associated with tumor volume and clinical outcome. As reported in earlier studies, a majority of chromophobe RCC show common features including trabeculae, low nuclear/cytoplasmic ratio, absence of tumoral necrosis, and absence of vascular invasion. These tumors are associated with a favorable prognosis. A study of the aggressive variant of chromophobe RCC described metastasizing chromophobe RCC, including 1 tumor with features of renal oncocytoma (oncocytic variant of chromophobe RCC associated with low nuclear grade). Paner et al state that chromophobe RCC with novel nuclear grade 3 features are associated with an adverse outcome. In practice, however, a 3-tiered grading system is currently difficult to apply for the following reasons: (1) Most grading schemes in surgical pathology are currently based on a low-grade versus high-grade system. (2) Some novel nuclear grade 2 chromophobe RCCs are likely difficult to distinguish from novel nuclear grade 1 tumors, as there are frequently degenerative changes associated with chromophobe RCC. (3) Pathologists in our region and investigators in most reports of chromophobe RCC rarely, if ever, use Fuhrman grading to grade chromophobe RCC. Chromophobe RCCs are commonly reported as the common variant (low grade), with additional details provided when indicated (ie, tumor necrosis, increased mitotic figures or sarcomatoid changes), which likely represent the high-grade chromophobe RCC that may be associated with aggressive behavior. In view of the authors’ study, tumors with novel nuclear grade 3 and some grade 2 may be added to this group of high-grade chromophobe RCC. Given the trend in pathology toward 2-tiered grading systems, we invite the authors to comment on the use of a 2-tiered system rather than a 3-tiered system for chromophobe RCC using the relevant criteria they have identified.

Comparative immunohistochemical study of the stroma of serous and mucinous cystic neoplasms: possible histopathogenetic relationship of the 2 entities.

Objectives: Serous and mucinous cystic neoplasms (SCNs/MCNs) are the most common true cystic neoplasms of the pancreas and occur more frequently in women. The aim of this study was to characterize the stroma of SCNs to compare its phenotype with that of MCNs. Methods: A total of 12 SCNs and 5 MCNs were analyzed immunohistochemically using the following antisera: progesterone receptor (PR), estrogen receptor (ER), inhibin, CD10, and vimentin. Normal pancreatic tissue (17 cases) and ductal adenocarcinomas of the pancreas (3 cases) were used as controls. Results: Eight of 12 patients with SCNs and all 5 patients with MCNs were women. For SCNs, the stroma was sclerotic and paucicellular and showed focal moderate to strong reactivity for PR. Estrogen receptor, CD10, and inhibin were virtually negative. For MCNs, the stroma was more cellular and ovarianlike and showed a larger number of PR-positive cells with focal expression of ER and inhibin. Vimentin was expressed in all stromal cells in both groups. Conclusions: Both SCNs and MCNs contain PR-positive stromal cells. In view of the aforementioned clinical and immunophenotypical similarities, we suggest that in SCNs and MCNs, the stromal framework is similar in origin and/or differentiation.

Histopathogenesis of endometrium with asynchronous glands in dysfunctional uterine bleeding

presence of parasitized cells, randomly scattered in the centrofollicular areas. The cells were confirmed as macrophages rather than follicular dendritic cells by positivity for CD68 and negativity for CD23 and CD35 on immunohistochemistry. To our knowledge, this surprising finding has not been previously reported. We report this case to highlight the existence of this unusual clinicopathological presentation of leishmaniasis in an immunocompetent patient. Leishmanial lymphadenitis must be systematically considered when confronted with any adenopathy of unknown origin in endemic areas.

Fluorescent In-situ Hybridization Study of Non-papillary Oncocytic/Eosinophilic Renal Cell Carcinoma.

AimsPapillary renal cell carcinoma (PRCC) and clear cell RCC (CRCC) can display extensive areas with oncocytic/eosinophilic changes and may be associated with either minimal papillary architecture. These nonpapillary oncocytic/eosinophilic RCC often mimic renal oncocytoma (RO). We investigated numeric changes of chromosomes 7, 17, and Y and loss of the small arm of chromosome 3 in the above-mentioned oncocytic RCC by using the florescent in-situ hybridization (FISH). Materials and MethodsArchival cases of oncocytic RCC previously screened by immunohistochemical study were submitted for FISH. ResultsThere were a total of 9 cases out of a total of 650 renal carcinomas surgically resected. Seven tumors displayed an immunoprofile of CRCC or PRCC with RCC(+)/CD117(−) and variable reactivity for CK7 and &agr;-methylacyl-CoA racemase. FISH showed trisomies 7/17 with or without loss of Y in 5 tumors. Loss of loci 3p25 and 3p14 was identified in another 2 cases. The remaining 2 carcinomas previously reported as malignant RO owing to cytological atypia and lymph node metastasis showed immunoprofile of RCC(−)/CD117(+) and absence of numeric changes for chromosomes 7, 17, and Y or loss of loci 3p25 or 3p14. ConclusionsIn this uncommon variant of RCC, FISH for chromosomes 7, 17, and Y lend more support for the role of immunostaining in distinguishing RO and chromophobe RCC from the nonchromophobe RCC. FISH for chromosomes 7, 17, Y, and loci 3p25 and 3p14, and not immunostaining for &agr;-methylacyl-CoA racemase and CK7 is helpful in distinguishing CRCC from PRCC.

Urinary bladder sinuses: a novel morphologic lesion with clinical and pathologic significance.

Background:We described urinary bladder sinuses (UBS) in the urinary bladder, characterized by segmental mucosal with muscularis mucosa invaginations into the submucosa (superficial UBS) and muscularis propria (deep UBS). Materials:Radical cystectomy specimens and transurethral resections of the bladder were reviewed. Results:Superficial UBS (extending up to the submucosa) were distinguished from cystitis cystica, and deep UBS differed from embryonic remnants, intramural ureters, and diverticulum by their cleft-like structures lined by the urothelium. In transurethral resections of the bladder specimens and bladder biopsy specimens, superficial UBS were identified in 13/20 cases. In radical cystectomy specimens, superficial UBS were identified in 15/50 cases, whereas deep UBS (all with associated superficial UBS) were seen in 23/50 additional cases. Deep UBS limited to the inner quarter of the muscularis propria and only reached the level of the inner third outer/middle third of the muscularis propria in 5 cases. Intraepithelial neoplasia involved the mucosa of UBS in 10 cases; this may pose diagnostic problems with invasive carcinoma. Furthermore, UBS were often associated with mucosal redundancy and hypertrophy of the muscularis propria, therefore mimicking muscle invasive cancer on pelvic examination and imaging techniques. Conclusions:Recognition of UBS is important to pathologically and clinically avoid over-staging of bladder malignancies.