Experimental Study: The Effect Of 20% Intralipid Emulsion Therapy In Cerebral Ischemic Reperfusion.

BACKGROUND: This experimental study was conducted to investigate the effect of 20% Intralipid Emulsion (ILE) treatment on Cerebral Ischemia Reperfusion Injury (CIRI) after reperfusion in acute ischemic stroke. METHODS: In this experimental study, seven rats without any intervention (control group), seven rats (sham group) for which CIRI was created after the common carotid artery was ligated for 2 hours, and seven rats who were treated with 20% ILE after CIRI (CIRI + ILE group) were sacrificed after 24 hours, and histopathological findings were investigated. RESULTS: In rats that were not treated after CIRI, 52.7% had level-1, 32.7% had level-2. and 14.5% had level-3. histopathological findings. While 72.2% of the rats treated with ILE had level-1 and 27.8% had level-2 findings, no level-3 histopathological findings were detected in any of the rats. While no signs of coagulative necrosis, spongiosis of surrounding tissue and polymorphonuclear leukocytes were observed histopathological in any of the rats given ILE, there was no macrophages finding in 85.6% of the rats. ILE treatment also reduced the histopathological findings of eosinophilic neurons, astrogliosis, neovascularization, vascular thrombosis and mononuclear inflammatory cells. CONCLUSION: This study showed that 20% ILE treatment reduces the histopathological damage seen in cerebral ischemia and CIRI.

Large nested urothelial carcinoma: A clinicopathological study of 22 cases on transurethral resection materials.

Large nested urothelial carcinoma (LNUC) is a recently recognized variant of urothelial carcinoma (UC), which is characterized with inverted growth pattern and bland cytology. Diagnosis can be extremely challenging, especially in transurethral resection (TUR) materials. Haematoxylin-eosin stained slides of TUR materials with UC, submitted to our department between 2008 and 2017 were re-examined. Twenty-two LNUC cases were found. LNUC frequency was 0.7%. Mean age was 69.9, 82% were male. Mean tumor diameter was 4.9 cm. Non-invasive UC was present in all cases; low-grade in 6, high-grade in 1, low and high-grade in 15. Five and 16 cases were pT1 and pT2, respectively, no invasion was detected in one case. In addition to medium-large nests, small nests and conventional UC areas was present in 2 and 3 cases, respectively. Stroma-tumor interface was irregular in 19 cases and 3 cases had invasive nests with rounded contours. Fibrous stromal reaction and/or stromal lymphoid infiltration were present in 21 cases. Budding, described as small nests in stromal interface of medium-large nests was found in 16 cases. Follow-up was available for 18 cases with an average of 59 months. Four cases had metastasis, 1 patient died of disease. LNUC causes diagnostic difficulty, especially in TUR materials. Large size of tumor, irregularity of nests, presence of stromal reaction and budding can be clues for correct diagnosis.

Atypical spindle cell/pleomorphic lipomatous tumor: A clinicopathologic, immunohistochemical, and molecular study of 20 cases.

Lipomatous tumors accompanied by spindle cell component are not frequently encountered, and there are still problems regarding their differential diagnosis, nature, and nomenclature. To contribute to ongoing efforts, we present the clinical, histologic, and immunohistochemical characteristics of 20 cases of spindle cell lipomatous tumors with atypical features that may also be called atypical spindle cell/pleomorphic lipomatous tumors. Of the patients, 13 were men and 7 were women with an average age of 57.5 years. The most commonly affected site was the extremities. Twelve tumors arose in the subcutaneous tissue, while eight cases were located in the deep soft tissues. Tumor margins were often ill-defined with invasion into the surrounding tissues. Microscopic examination revealed a wide spectrum of histologic features. All cases consisted of poorly marginated proliferation of mildly atypical spindle cells set in a fibrous or myxoid stroma with a variable amount of adipocytic component showing variation in adipocyte size and scattered nuclear atypia and frequent univacuolated or multivacuolated lipoblasts. Tumor cellularity and the relative proportion of the components were highly variable. One tumor showed morphologic features evocative of dedifferentiation and another one exhibited histological features resembling pleomorphic liposarcoma. None of the patients had recurrence or metastasis at follow-up.

Primary breast carcinomas with neuroendocrine features: Clinicopathological features and analysis of tumor growth patterns in 36 cases.

Primary breast carcinoma with neuroendocrine features (NEBC) is an uncommon tumor. In the classification of WHO 2012, these tumors were categorized as: 1- neuroendocrine tumor, well-differentiated; 2- neuroendocrine carcinoma, poorly differentiated/small cell carcinoma; and 3- invasive breast carcinoma with neuroendocrine differentiation. In this study, we reviewed NEBC except poorly differentiated/small cell carcinoma variant in order to define the morphological growth patterns and cytonuclear details of these tumors. All breast surgical excision materials between 2007 and 2016 were re-evaluated in terms of neuroendocrine differentiation. Thirty-six cases showing positive staining for synaptophysin and/or chromogranin A in ≥50% of tumor cells were included in the study. All cases were female with a mean age of 67.4. Mean tumor diameter was 26 mm. Multifocality was noted in 5 cases. Grossly, they were mostly infiltrative mass lesions. T stages, identified in 34 cases, were as follows: 13 cases with pT1; 19 pT2 and 2 pT3. We described schematically 4 types of patterns depending on predominant growth pattern, except one case: 1) Large-sized solid cohesive groups (6 cases), 2) Small- to medium-sized solid cohesive groups with trabeculae/ribbons and glandular structures (6 cases), 3) Mixed growth patterns (20 cases), 4) Invasive tumor with prominent extracellular and/or intracellular mucin (3 cases). The tumor cells were mostly polygonal-oval with eosinophilic/eosinophilic-granular cytoplasm. The nuclei of tumor cells were mostly round to oval with evenly distributed chromatin. Only 5 cases showed high grade nuclear and histological features. Molecular subtypes of the cases were as follows: 33 luminal A, 2 luminal B, and 1 triple negative. NEBC should come to mind when a tumor display one of the morphological patterns described above, composed of monotonous cells with mild to moderate nuclear pleomorphism and abundant eosinophilic/eosinophilic granular or clear cytoplasm, especially in elderly patients.

Cytologic predictors of malignancy in bile duct brushings: a multi-reviewer analysis of 60 cases.

Diagnosing malignancy in bile duct brushings is highly challenging. Seven reviewers of variable backgrounds and levels of participation in bile duct brushing sign out blindly reviewed 60 specimens (30 malignant with histologic confirmation and 30 benign (15 stented) with resection or ≥18 months of uneventful follow-up), testing the utility of 14 malignant characteristics. Eleven characteristics were statistically significantly associated with malignancy including 3-dimensional clusters (63% in malignant vs 3% in benign, odds ratio 50, P=0.0003), pleomorphism (62 vs 3, odds ratio 48, P=0.0004), 2-cell population (60% vs 3, odds ratio 44, P=0.0005), chromatin pattern (hypo/hyperchromasia) changes (70% vs 7%, odds ratio 33, P<0.0001), high nuclear-to-cytoplasmic ratio (48 vs 3%, odds ratio 27, P=0.0023), cytoplasmic vacuoles (43 vs 3%, odds ratio 22, P=0.0042), nuclear irregularity (70 vs 10%, odds ratio 21, P<0.0001), cellular discohesion (38 vs 3%, odds ratio 18, P=0.0082), hypercellularity (23% vs 0), nuclear molding (20% vs 0) and prominent nucleoli (21% vs 0). Necrosis and infiltrating inflammation were not helpful in identifying malignancy ('neutrophil cannibalism' was noted in 43% malignant); 21/30 (70%) malignant brushings had ≥3 malignant characteristics, while 23 (77%) benign brushings had none. Of 20 brushings with ≥4 characteristics, 1(5%) proved benign and showed detachment atypia, a close malignant mimicker in brushings. Identification of 3 characteristics maximized the combined sensitivity (70%), specificity (97%) and accuracy (83%), but sensitivity dropped as number of characteristics increased. Identification of 3/11 characteristics (3-dimensional clusters, pleomorphism, high nuclear-to-cytoplasmic ratio, nuclear irregularity, hypercellularity, discohesion, chromatin changes, vacuoles, prominent nucleoli, molding and 2-cell population) improves pathologists' overall performance greatly.

Comparison of World Health Organization 2000/2004 and World Health Organization 2010 classifications for gastrointestinal and pancreatic neuroendocrine tumors.

Gastroenteropancreatic neuroendocrine tumors (GEPNETs) were divided into 4 groups based on tumor diameter and stage in World Health Organization (WHO) 2000/2004 classification as well-differentiated endocrine tumor benign (WDETB), well-differentiated endocrine tumor with uncertain behavior (WDETUB), well-differentiated endocrine carcinoma (WDEC), and poorly differentiated endocrine carcinoma (PDEC). World Health Organization 2000/2004 was not widely accepted because of stage-related classification and the category of "uncertain behavior." The European NET Society proposed a grading classification and site-specific staging system in 2010. Gastroenteropancreatic NETs were divided into 3 groups as NET grade 1 (G1), NET grade 2 (G2), and neuroendocrine carcinoma (NEC) grade 3 (G3) based on mitoses and the Ki-67 index. We evaluated 63 GEPNET cases according to both classifications. We compared two classifications and the tumor groups in terms of prognostic parameters (diameter, mitosis, Ki-67 index, angioinvasion, perineural invasion, necrosis, and metastasis) and pathologic stage. All 14 cases diagnosed as PDEC were included in the NEC G3 according to WHO 2010. Seventeen cases were diagnosed as WDETB, 9 as WDETUB, and 23 as WDEC. There was statistically significant difference between these groups in terms of all prognostic parameters except for necrosis, mitosis, Ki-67 index, and grade. All WDETB cases, 89% of WDETUBs, and 87% of WDECs were included in the NET G1. There were 45 cases evaluated as NET G1 and 4 cases as NET G2 according to WHO 2010. Metastasis and perineural invasion were more common in NET G2, no significant differences in other parameters. In conclusion, WHO 2010 is easier to use, whereas WHO 2000/2004 shows higher correlation with prognosis. However, it includes benign and uncertain behavior categories, although small tumors with low proliferative activity can also cause metastases. All GEPNETs should be considered potentially malignant.

PD-L1 Assessment in Needle Core Biopsies of Non-Small Cell Lung Cancer: Interpathologist Agreement and Potential Associated Histopathological Features.

OBJECTIVE: Immune checkpoint inhibitors are used in the treatment of non-small cell lung cancer (NSCLC). Programmed cell death-ligand 1 (PD-L1) immunohistochemistry (IHC) assessed by pathologists is subject to interobserver variability. In advanced/metastatic disease and inoperable patients, PD-L1 assessment relies on biopsy specimens, commonly needle core biopsies (NCB). We aimed to determine the interobserver agreement for PD-L1 tumor proportion score (TPS) in NSCLC NCBs and identify histopathological features that may be related to interobserver variability. MATERIAL AND METHODS: Sixty NSCLC NCBs with PD-L1 IHC were evaluated independently by four pathologists from different institutions. PD-L1 TPS was evaluated in three categories: no/low expression ( < 1%), intermediate expression (1%49%), and high expression (≥50%). Histological tumor type, necrosis, tumor-infiltrating lymphocytes, tumor length/percentage in the biopsy, and crush/squeeze artifact was evaluated. RESULTS: The statistical analysis of the three PD-L1 TPS categories demonstrated moderate agreement (Fleiss Kappa 0.477) in the no/low category, fair agreement (Fleiss Kappa 0.390) in the intermediate category, and almost perfect agreement (Fleiss Kappa 0.952) in the high category. A significant correlation (p=0.003) was found between the crush/squeeze artifact in NCB and rate of discordant TPS categories. There was no significant correlation between pathologists' agreement in the TPS categories and histological tumor type, tumor length, tumor ratio, necrosis, and tumor-infiltrating lymphocytes. CONCLUSION: Our results demonstrated moderate agreement among pathologists for the PD-L1 TPS 1% cut-off in NSCLC NCB, which is lower than that reported in resection materials. The presence of crush/squeeze artifact in NCBs is significantly related to the rate of discordant TPS categories, suggesting that PD-L1 assessment of pulmonary NCBs requires an awareness of this artifact.

Optimizing decellularization protocols for human thyroid tissues: a step towards tissue engineering and transplantation.

Hypothyroidism is caused by insufficient stimulation or disruption of the thyroid. However, the drawbacks of thyroid transplantation have led to the search for new treatments. Decellularization allows tissue transplants to maintain their biomimetic structures while preserving cell adhesion, proliferation, and differentiation. This study aimed to decellularize human thyroid tissues using a structure-preserving optimization strategy and present preliminary data on recellularization. Nine methods were used for physical and chemical decellularization. Quantitative and immunohistochemical analyses were performed to investigate the DNA and extracellular matrix components of the tissues. Biomechanical properties were determined by compression test, and cell viability was examined after seeding MDA-T32 papillary thyroid cancer (PTC) cells onto the decellularized tissues. Decellularized tissues exhibited a notable decrease (<50 ng mg-1DNA, except for Groups 2 and 7) compared to the native thyroid tissue. Nonetheless, collagen and glycosaminoglycans were shown to be conserved in all decellularized tissues. Laminin and fibronectin were preserved at comparatively higher levels, and Young's modulus was elevated when decellularization included SDS. It was observed that the strain value in Group 1 (1.63 ± 0.14 MPa) was significantly greater than that in the decellularized tissues between Groups 2-9, ranging from 0.13 ± 0.03-0.72 ± 0.29 MPa. Finally, viability assessment demonstrated that PTC cells within the recellularized tissue groups successfully attached to the 3D scaffolds and sustained metabolic activity throughout the incubation period. We successfully established a decellularization optimization for human thyroid tissues, which has potential applications in tissue engineering and transplantation research. Our next goal is to conduct recellularization using the methods utilized in Group 1 and transplant the primary thyroid follicular cell-seeded tissues into anin vivoanimal model, particularly due to their remarkable 3D structural preservation and cell adhesion-promoting properties.

Production of parathyroid-like cells from thyroid stem cells in co-culture environment.

BACKGROUND: Parathyroid-like cells were aimed to be developed using cells isolated from thyroid since their embryological origins are the same. METHOD: Activin A and sonic hedgehog (Shh) are the proteins used in differentiation (dif) medium. Parathyroid and thyroid cells were cultured in a 3-dimensional environment and divided into five groups: thyroid standard (st) medium, thyroid dif medium, parathyroid st medium, thyroid-parathyroid co-culture st medium, and thyroid-parathyroid co-culture dif medium. Throughout 28 days of incubation, groups were investigated by carrying out the live dead assay, confocal microscopy, real-time PCR, immunohistochemistry and biochemical assays. RESULTS: Thyroid-parathyroid co-culture cells grown in dif medium exhibited upregulated expressions of parathormone (PTH) (5.1-fold), PTH1R (3.6-fold), calcium sensing receptor (CaSR) (8.8-fold), and loss of thyroid-specific thyroid transcription factor 1 (TTF1) expression when compared to the thyroid st medium group. PTH secretion decreased by 35% in the parathyroid st medium group and 99.9% in the thyroid-parathyroid co-culture st medium group but decreased only 3.5% in the thyroid-parathyroid co-culture dif medium group on day 28. CONCLUSION: Using Activin A and Shh proteins, thyroid stem/progenitor cells were differentiated to parathyroid-like cells successfully in a co-culture environment. A potentially effective novel method for cell differenatiation is co-culture of cells having the same embryological origin.

Lymphoepithelioma like carcinoma of the urinary bladder, treated with transurethral resection and intravesical Bacillus Calmette Guerin therapy only: A case report.

Lymphoepithelioma-like urotehelial carcinoma which was first identified by Zukerberg, constitutes 0,4-1,3% of all urothelial carcinomas and has similar histomorphological features with nasopharyngeal lymphoepithelioma. We report a case of predominant lymphoepithelioma like bladder carcinoma in a 72 years old male patient. Transuretheral resection of the bladder and adjuvant intravesical Bacillus Calmette Guerin treatment was applied. The patient is currently at the 16th month after diagnosis and no recurrence or metastasis has been observed in cystoscopic and radiological examinations.

Stromal Lymphoid Response Status in Micropapillary Urothelial Carcinomas Diagnosed in Bladder Transurethral Resections and its Comparison with Conventional Urothelial Carcinomas.

OBJECTIVE: Micropapillary urothelial carcinoma is an aggressive variant of urothelial carcinoma. Evidence suggests that the relationship between the tumor and inflammatory cells is important in tumor progression and the treatment response. We evaluated the stromal lymphoid response in micropapillary urothelial carcinomas and compared it with conventional urothelial carcinomas. MATERIAL AND METHOD: Among bladder transurethral resection materials diagnosed as 'invasive urothelial carcinoma' between January 2010-March 2017, cases with at least 5% micropapillary urothelial carcinoma were evaluated for age, gender, grade, stage, micropapillary urothelial carcinoma percentage, presence/percentage of accompanying conventional urothelial carcinoma/urothelial carcinoma variants, in situ urothelial carcinoma/micropapillary urothelial carcinoma, lymphovascular invasion, necrosis, and stromal lymphoid response. Stromal lymphoid response was scored as 0-1-2-3. All parameters were evaluated in 50 pure conventional urothelial carcinomas. RESULTS: Among 47 micropapillary urothelial carcinomas, 41 were male. The mean age was 69 years. pT1/pT2 was 23/24. Six cases were pure MPUC. Lymphovascular invasion was present in 8, necrosis in 9 cases. Stromal lymphoid response was present and scored as 1-2-3 in 32 micropapillary urothelial carcinomas (68.1%) and 48 conventional urothelial carcinomas (96%). Micropapillary urothelial carcinomas had significantly higher lymphovascular invasion and pT2 rates and lower stromal lymphoid response. CONCLUSION: Low stromal lymphoid response in micropapillary urothelial carcinomas can be responsible for the poor clinical outcome and impaired response to treatment of these tumors. This is the first study in the English literature to demonstrate a lower stromal lymphoid response rate in micropapillary urothelial carcinomas compared to conventional urothelial carcinomas.

Invasive Breast Carcinoma with Abundant Collagenous Stroma Shows Lower Level of CD68-Positive Tumor Associated Macrophages than Those of Invasive Carcinoma without Abundant Collagenous Stroma.

BACKGROUND AND AIM OF THE WORK: The significance of association between cancer and its stromal microenvironment has been recognized. We aimed to investigate the immunohistochemical staining features of D2-40 (podoplanin), SMA (smooth muscle actin) and CD68 (pan-macrophage marker) in patients with early stage invasive breast cancer with/out peritumoral PASH-like stroma. METHODS: The H&E sections of core needle biopsy specimens of invasive breast carcinomas diagnosed during one-year time period were reviewed in terms of the presence of accompanying PASH-like stroma retrospectively. Cases with similar pattern of growth in their surgical excision materials were included. Eight cases were grouped as 'Invasive tumor with PASH-like stroma' and 21 cases as 'Invasive tumor without PASH-like stroma', consecutively. The results of immunohistochemical staining for D2-40, SMA and CD68 were noted semiquantitatively as 'negative','weak', moderate' or 'strong'. RESULTS: CD68 was found significantly lower in invasive tumor with peritumoral PASH-like stroma than those of tumor without PASH-like stroma. No significant differences were found for SMA and D2-40 between two groups.  Conclusions: Tumor-associated macrophages (CD68 positive) in tumor stroma have been demonstrated in association with tumor behavior in several studies. The presence of peritumoral PASH-like stroma, which is poorly staining for CD68, might be a morphological clue for the behavior of tumor.

The Effect of the Extent of Neuroendocrine Differentiation on Cytopathological Findings in Primary Neuroendocrine Neoplasms of the Breast.

OBJECTIVE: This study aimed to describe the cytological features of neuroendocrine breast tumors and to show the effect of the extent of neuroendocrine differentiation on cytological features. METHODS: Breast tumor excision materials showing immunostaining with neuroendocrine markers (Synaptophysin or Chromogranin A) were determined and divided into two groups: cases with focal (10%-50% of tumor cells) staining and cases with diffuse (>50% of tumor cells) staining. A group of cases without neuroendocrine features/staining was used as control group. Fine needle aspiration biopsy specimens of the tumor mass or metastatic lymph nodes were examined and compared. RESULTS: Twenty cases with neuroendocrine differentiation were included. Eleven cases were in the diffuse group, nine cases were in the focal group. Clean background, high cellularity, loosely cohesive cell groups with monotonous appearance, and naked nuclei were more common in the diffuse group. On the contrary, tight cohesive cell groups, the proportion of large cells, nuclear pleomorphism, and nucleolar prominence were higher in the group with focal staining. Plasmocytoid appearance, isolated cell groups, and binucleation were in similar distribution in both groups. Although round-oval nuclei were dominant in both groups, round nuclei were observed to be slightly more in the diffuse group. Only two cases in diffuse group showed cytoplasmic granularity and one case in focal group showed necrosis and mitosis. In the control group, tight cohesive groups, large cell size, pleomorphism, prominent nucleoli, and coarse chromatin were more commonly encountered. CONCLUSIONS: Clean background, hypercellularity, loss of cohesion, naked nuclei, monotonous cells with round nucleus, and granular cytoplasm were more prominent in cases showing diffuse staining with neuroendocrine markers. Suspecting neuroendocrine differentiation in tumors that show focal staining with neuroendocrine markers can be challenging in cytological preparations.

Evaluation and Pathologic Classification of Choledochal Cysts: Clinicopathologic Analysis of 84 Cases From the West.

Choledochal cyst (CC) is believed to be a mostly Asian disorder. As a clinically defined entity, its pathologic correlates are poorly characterized. Eighty-four resected CCs from the West were reanalyzed. After applying established Japanese criteria, 9/66 with available imaging were disqualified and 10/39 with preoperative cyst typing had to be recategorized. None had been diagnosed with, or evaluated for, pancreatobiliary maljunction, but on retrospective analysis of radiologic images, 12/66 were found to have pancreatobiliary maljunction. The clinical findings were: F/M=5.7; mean age, 48; most (77%) presented with abdominal pain; mean size, 2.9 cm; choledocholithiasis 11%. Gross/histologic examination revealed 3 distinct pathology-based categories: (I) Cystic dilatation of native ducts (81%). (II) Double bile duct (13%), almost all of which were found in women (10/11); all were diagnosed by pathologic examination, and not preoperative diagnosis. (III) Gastrointestinal (GI) duplication type (6%). Microscopic findings of the entire cohort included mucosal-predominant lymphoplasmacytic inflammation (50%), follicular cholangitis (7%), mucosal hyperplasia (43%; 13% with papillae), intestinal metaplasia (10%), BilIN-like hyperplasia (17%), erosion/ulceration (13%), and severe dysplasia-mimicking atypia including "detachment atypia" and micropapillary degeneration (11%). Carcinomatous changes were seen in 14 cases (17%) (high-grade dysplasia/carcinoma in situ in 7, intraductal papillary neoplasm 1, and invasive carcinoma 6); and 13/14 of these occurred in pathologic category I, all with cyst size >1 cm. In conclusion, diagnostic imaging guidelines used in Asia are not routinely used (but should be adopted) in the West. Pathologically, cases designated as CC are classifiable in 3 groups: category 1 (dilated native duct type), more prone to carcinomatous change; category 2, double-duct phenomenon (all but 1 being female in this study); and category 3, GI-type duplication. Overall, 17% of CCs show carcinomatous change (50% of them invasive). CC specimens should be carefully examined with this classification and submitted entirely for assessment of at-risk mucosa and cancerous transformation.

Epstein-Barr virus infection in patients with chronic gastritis without Helicobacter pylori infection.

BACKGROUND/AIMS: The association of Epstein-Barr virus (EBV) with gastric malignancies has been proven by many studies in the literature. However, information about EBV-associated inflammation/gastritis remains limited. The aim of this study is to establish the prevalence of latent EBV infection in patients with chronic gastritis without H. pylori infection. MATERIALS AND METHODS: In this study, 119 patients with gastritis without H. pylori infection were included. Furthermore, 28 patients with H. pylori gastritis were included in the study as a control group. Chromogenic in situ hybridization (EBV-encoded RNA) and immunohistochemistry (LMP-1 antibody) were performed in all 147 cases. The prevalence of EBV and its relationship with age, sex, the affected part of the stomach, the density of inflammation, inflammatory activity, intestinal metaplasia, and atrophy were analyzed. RESULTS: In this study, 14 cases showed positive immunostaining for EBV. EBV positivity was seen mostly in the lymphoid tissue (13 cases), but it was also detected at the gastric epithelium (7 cases). The mean age of the patients was 44 years, which was slightly younger than that of the EBV-negative cases (48 years). The inflammation density was higher in EBV-positive cases than the EBV-negative gastritis cases (p=0.002). Intestinal metaplasia was detected in 7% of the cases. EBV-positive cases had a higher incidence of atrophy without intestinal metaplasia (21% vs 3.8% without EBV). CONCLUSION: EBV was detected in 12% of the cases with gastritis without H. pylori infection. Endoscopic follow-up may be appropriate for patients with gastritis, who have atrophy without intestinal metaplasia and are H. pylori negative but EBV positive.

Factors Impacting the Performance Characteristics of Bile Duct Brushings: A Clinico-Cytopathologic Analysis of 253 Patients.

CONTEXT: - Literature on factors impacting bile duct brushings (BDBs) performance characteristics remain limited. OBJECTIVE: - To capture the current state of daily practice with BDB sign-out. DESIGN: - Two hundred fifty-three of 444 BDBs signed out by more than 7 cytopathologists, with histopathologic and/or clinical follow-up of at least 18 months, were examined. RESULTS: - One hundred thirty-five of 253 BDBs (53%) had histologically confirmed malignancies, 22 (9%) had cancer-related deaths, and 96 (38%) were benign. Cytologic diagnoses in the 444 BDBs were nondiagnostic (11 [2.5%]), negative (284 [64%]), atypical (62 [13.9%]), suspicious (34 [7.7%]), and malignant (53 [11.9%]). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of malignancy detection were 35%, 100%, 100%, 58%, and 66%, respectively. When atypical, suspicious, and malignant (ASM) categories were combined, sensitivity increased (58%), specificity and PPV dropped (97%), and accuracy increased (73%). Carcinoma type (bile-duct versus pancreatic-ductal) had no effect on accuracy ( P = .60) or diagnostic class ( P = .84), nor did time of performance (first 7.5 versus latter 7.5 years, P = .13). Interestingly, ThinPrep + cell block (n = 41) had higher sensitivity (61%) and lower specificity (80%) than ThinPrep only (versus 51% and 100%, respectively). Sensitivity and specificity were higher (47% and 100%) in nonstented than stented specimens (59% and 97%). Relative risk of malignancy for "suspicious" (2.30) and "atypical" (2.28) categories was lower but not very different from that of "malignant" category (2.41). CONCLUSIONS: - Bile duct brushings had fairly low sensitivity but high specificity and PPV with no false positives. Sensitivity almost doubled and specificity dipped minimally when ASM categories were combined, highlighting the need for better classification criteria for atypical/suspicious cases. Higher specificity, PPV, NPV, and accuracy but lower sensitivity in stented BDBs suggest that they be called malignant only when evidence is overwhelmingly convincing.

Pseudoangiomatous Stromal Hyperplasia in Core Needle Biopsies of Breast Specimens.

BACKGROUND: Pseudoangiomatous stromal hyperplasia (PASH) is a benign lesion of myofibroblasts that is composed of a network of slit-like channels that resemble vascular spaces. The aims of this study were to document the frequency of PASH in core needle biopsy specimens (CNBS) of the breast, to describe which histopathologic findings coexist with PASH and to examine any endothelial cell differentiation. MATERIALS AND METHODS: We reevaluated hematoxylin and eosin-stained sections of all CNBS that were obtained during a 1-year period. First, we performed CD34 and CD31 immunostainings to highlight the areas of PASH, then performed D2-40/podoplanin (lymphatic endothelial marker) and Fli-1 (vascular endothelial cell marker) immunostains. RESULTS: The total number of CNBS was 412. Areas of PASH were noted in 37 of the 412 cases (9%), with a mean age of 38.5 years. The lesions that were described in association with PASH were "benign breast parenchyma with stromal fibrosis" (17/37; 46%), "fibroepithelial tumors" (17/37; 46%), "columnar cell changes (CCC)" (2/37; 5%), and "invasive carcinoma" (1/37; 3%). There were 2 cases of CCC within the foci of PASH (direct contact with PASH), and 8 additional cases of CCC that coexisted in the same specimen but were not in direct contact. There was no staining for D2-40 or Fli-1 within PASH foci. CONCLUSION: PASH lesions occurred with a frequency of 9% in CNBS and were mostly in association with benign breast lesions in premenopausal women. CCC was determined as an accompanying epithelial lesion within or near PASH areas. No obvious immunopositivity compatible with endothelial cell differentiation was revealed.

Immunohistochemical Classification of Ampullary Carcinomas: Critical Reappraisal Fails to Confirm Prognostic Relevance for Recently Proposed Panels, and Highlights MUC5AC as a Strong Prognosticator.

Recently, immunohistochemistry-based classifications of ampullary carcinomas have been proposed (Ang and colleagues [PMID: 24832159]; Chang and colleagues [PMID: 23439753]). In this study, the prognostic value of Ang/Chang panel markers (CK20, MUC1, MUC2, CDX2) as well as other markers (CK7, MUC5AC, and MUC6) were tested on full-faced sections of 136 ampullary carcinoma resections with substantial (>5 mm) invasion. Immunohistochemistry was correlated with both histologic classification (intestinal [INT], pancreatobiliary [PB], or nontubular based on ≥3/5 observer agreement) and clinical outcome. No prognostic correlation was found with MUC1, CDX2, MUC2 or CK20 despite testing with different quantitative cutoffs. CK7 and CK20 were nonspecific. Ang classification had reasonable correlation with histologic subclassification of tubular cases as INT versus PB with high specificity but low sensitivity and ambiguous category was large (29%) and included also some classical cases. Prognostically, Ang classification approached but did not reach statistical significance, even when their large "ambiguous" group was eliminated and only tubular cases were analyzed (Ang-INT vs. Ang-PB; P=0.08). The Chang panel, in which the definition of the INT subcategory is not clearly defined, only marginally reached prognostic significance when tested as MUC1+/CDX2- versus MUC1-/CDX2+ and only by Wilcoxon test (P=0.0485) but 31% of the cases were "unclassifiable." The only individual marker that was found to have direct and strong correlation with the clinical outcome was MUC5AC (not used in the Ang or Chang panels), with statistically significant survival differences found with various cutoffs tested (for 20% cutoff, 5-y survival, 68% vs. 31%; P=0.0002). In addition, MUC5AC significantly stratified the histologically PB and INT cases (P=0.01 and 0.03, respectively), as well as Ang's ambiguous and Chang's unclassified cases (P=0.006 and 0.007, respectively). In conclusion, the widely used putative lineage markers, MUC1/MUC2/CK7/CK20/CDX2, do not seem to have direct/significant prognostic correlation either individually or in combination of Ang and Chang panels. Ang panel is helpful as an adjunct in determining the cell lineage with a few caveats. MUC5AC proves to be a significant independent prognosticator and should be incorporated into evaluation of ampullary carcinomas.