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Sarcomatoid urothelial carcinoma is a rare aggressive malignant neoplasm of the urinary bladder. It usually presents at an advanced stage and thus carries a poor prognosis. These tumours are usually managed with multimodal therapies such as cystectomy and chemotherapy. In the present case, a 72-year-old man presented with gross haematuria and was diagnosed as sarcomatoid urothelial carcinoma with chondrosarcomatous differentiation and extensive stromal osseous metaplasia. The patient was managed with transurethral resection of bladder tumour (TURBT), followed by intravesical chemotherapy. The patient is doing well post 14 months follow-up. Hence, complete TURBT with chemotherapy is also a viable option for patients who prefer to preserve bladder.

As gender-affirming surgery is becoming more common, it is important for pathologists to recognize potential benign findings to avoid misinterpretation. Cervical transitional cell metaplasia and superficial clusters of small basophilic cells have been described in the context of gender-affirming testosterone therapy; these findings may be misdiagnosed as high-grade squamous intraepithelial lesions or endometrial cells on Pap smears. Prostatic metaplasia has been reported in the surface squamous epithelium of the vagina and the uterine cervix in individuals undergoing gender-affirming androgen therapy; this finding is often associated with NKX3.1-positive basal keratinocytes. The aim of this study was to assess the morphological and immunohistochemical features of the uterine cervix in gender-affirming hysterectomies in comparison with benign hysterectomies from cisgender women.We assessed the morphological and immunohistochemical features of the uterine cervix in 49 gender-affirming hysterectomies as compared with 57 hysterectomies from cisgender patients to establish the relative prevalences of surface prostatic metaplasia, NKX3.1-positive basal keratinocytes, transitional cell metaplasia, and small basophilic cells in the cervical squamous epithelium. The cervical tissue from the gender-affirming therapy cohort showed significantly higher prevalences of NKX3.1-positive basal keratinocytes (86% versus 1.8%), transitional cell metaplasia (80% versus 3.5%), superficial clusters of small basophilic cells (67% versus 7%), and surface prostatic metaplasia (43% versus 3.5%).NKX3.1-positive basal keratinocytes, transitional cell metaplasia, small basophilic cells and surface prostatic metaplasia are all more prevalent in the cervices of individuals receiving gender-affirming testosterone therapy; awareness of this fact allows pathologists to avoid the overdiagnosis of dysplasia or the recommendation of unnecessary follow-up procedures.

With the increasing practice of gender-affirming mastectomy as a therapeutic procedure in the setting of gender dysphoria, there has come a profusion of literature on the pathologic findings within these specimens. Findings reported in over 1500 patients have not included either prostatic metaplasia or pilar metaplasia of breast epithelium. We encountered both of these findings in the course of routine surgical pathology practice and therefore aimed to analyze these index cases together with a retrospective cohort to determine the prevalence, anatomic distribution, pathologic features, and associated clinical findings of prostatic metaplasia and pilar metaplasia in the setting of gender-affirming mastectomy. In addition to the 2 index cases, 20 additional archival gender-affirming mastectomy specimens were studied. Before mastectomies, all but 1 patient received testosterone cypionate, 6/22 patients received norethindrone, and 21/22 practiced breast binding. Prostatic metaplasia, characterized by glandular proliferation along the basal layer of epithelium in breast ducts, and in one case, within lobules, was seen in 18/22 specimens; 4/22 showed pilar metaplasia, consisting of hair shafts located within breast ducts, associated with squamoid metaplasia resembling hair matriceal differentiation. By immunohistochemistry, prostatic metaplasia was positive for PSA in 16/20 cases and positive for NKX3.1 in 15/20 cases. Forty-three reduction mammoplasty control cases showed no pilar metaplasia and no definite prostatic metaplasia, with no PSA and NKX3.1 staining observed. We demonstrate that prostatic metaplasia and pilar metaplasia are strikingly common findings in specimens from female-assigned-at-birth transgender patients undergoing gender-affirming mastectomy. Awareness of these novel entities in the breast is important, to distinguish them from other breast epithelial proliferations and to facilitate accrual of follow-up data for better understanding their natural history.

The mucosa of the body of the stomach (ie, the gastric corpus) uses 2 overlapping, depth-dependent mechanisms to respond to injury. Superficial injury heals via surface cells with histopathologic changes like foveolar hyperplasia. Deeper, usually chronic, injury/inflammation, most frequently induced by the carcinogenic bacteria Helicobacter pylori, elicits glandular histopathologic alterations, initially manifesting as pyloric (also known as pseudopyloric) metaplasia. In this pyloric metaplasia, corpus glands become antrum (pylorus)-like with loss of acid-secreting parietal cells (atrophic gastritis), expansion of foveolar cells, and reprogramming of digestive enzyme-secreting chief cells into deep antral gland-like mucous cells. After acute parietal cell loss, chief cells can reprogram through an orderly stepwise progression (paligenosis) initiated by interleukin-13-secreting innate lymphoid cells (ILC2s). First, massive lysosomal activation helps mitigate reactive oxygen species and remove damaged organelles. Second, mucus and wound-healing proteins (eg, TFF2) and other transcriptional alterations are induced, at which point the reprogrammed chief cells are recognized as mucus-secreting spasmolytic polypeptide-expressing metaplasia cells. In chronic severe injury, glands with pyloric metaplasia can harbor both actively proliferating spasmolytic polypeptide-expressing metaplasia cells and eventually intestine-like cells. Gastric glands with such lineage confusion (mixed incomplete intestinal metaplasia and proliferative spasmolytic polypeptide-expressing metaplasia) may be at particular risk for progression to dysplasia and cancer. A pyloric-like pattern of metaplasia after injury also occurs in other gastrointestinal organs including esophagus, pancreas, and intestines, and the paligenosis program itself seems broadly conserved across tissues and species. Here we discuss aspects of metaplasia in stomach, incorporating data derived from animal models and work on human cells and tissues in correlation with diagnostic and clinical implications.

BACKGROUND & AIMS: A non-endoscopic approach to Barrett’s esophagus (BE) surveillance after radiofrequency ablation (RFA) would offer a less invasive method for monitoring. We assessed the test characteristics and cost-effectiveness of the Cytosponge® in post-RFA patients. METHODS: We performed a multicenter study of dysplastic BE patients after at least one round of RFA. A positive Cytosponge® before endoscopy was defined as intestinal metaplasia (IM) on cytological assessment and/or TFF3 immunohistochemistry. Sensitivity, specificity, and receiver operator characteristic (ROC) curves were calculated. Multivariable regression was used to estimate the odds of a positive Cytosponge® in BE. A microsimulation cost-effectiveness model was performed to assess outcomes of various surveillance strategies: endoscopy-only, Cytosponge®-only, and alternating endoscopy/Cytosponge®. RESULTS: Of 234 patients, Cytosponge® adequately sampled the distal esophagus in 175 (75%). Of the 142 with both endoscopic and histologic data, 19 (13%) had residual/recurrent BE. For detecting any residual Barrett’s, Cytosponge® had a sensitivity of 74%, specificity of 85%, accuracy of 84%, and ROC curve showed an area under the curve of 0.74. The adjusted odds of a positive Cytosponge® in BE were 17.1 (95% CI: 5.2–55.9). Cytosponge®-only surveillance dominated all the surveillance strategies, being both less costly and more effective. Cytosponge®-only surveillance required

Cutaneous syncytial myoepithelioma (CSM) is a recently recognized variant of myoepithelial neoplasms. CSM is characterized by an intradermal syncytial proliferation of spindled, ovoid, and histiocytoid cells. Immunohistochemically, tumor cells usually show strong positivity for S-100 and EMA. Here, we report a case of CSM in the thigh of a 51-year-old Japanese woman. Histopathological findings showed a sheet-like growth of ovoid cells and histiocytoid cells with an eosinophilic syncytial cytoplasm, and adipocytic metaplasia was widely observed in the tumor. Immunohistochemical staining revealed a diffuse strong pattern for EMA, smooth muscle actin (SMA), and HHF35 and variable positivity for S-100 protein and p63 in ovoid and histiocytoid cells without significant mitotic figures or pleomorphism. In addition, EWSR1-PBX3 gene fusion, which is characteristic of CSM, was observed in the tumor. Based on these findings, we diagnosed the patient as having CSM. Our case suggests that CSM could show extensive adipocytic metaplasia, which could make its histopathological diagnosis challenging. This article is protected by copyright. All rights reserved.

The histological diagnosis of type 1 autoimmune pancreatitis (AIP) based on the findings obtained by an endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is feasible, but the diagnostic consistency of this method has not been confirmed. We determined the interobserver agreement among 20 pathologists regarding the diagnosis of type 1 AIP, including the distinction from pancreatic ductal adenocarcinoma (PDAC) using large tissue samples obtained by EUS-FNB. After guidance for diagnosing AIP with biopsy tissues was provided, a round 2 was performed. The median sensitivity and specificity for diagnosing PDAC vs. non-neoplastic diseases were 95.2% and 100%, respectively. In groups of specialists (n = 7) and the generalists (n = 13), Fleiss’ к-values increased from 0.886 to 0.958 and from 0.750 to 0.816 in round 2. The concordance was fair or moderate for obliterative phlebitis and storiform fibrosis but slight for ductal lesion of type 1 AIP. Discordant results were due to ambiguous findings and biopsy tissue limitations. Among the specialists, the ratio of cases with perfect agreement regarding the presence of storiform fibrosis increased in round 2, but agreement regarding obliterative phlebitis or ductal lesions was not improved. Although the histological definite diagnosis of type 1 AIP was achieved by most observers in > 60% of the cases, the confidence levels varied. Because some ambiguities exist, the histological diagnostic levels based on the diagnostic criteria of type 1 AIP should not be taken for granted. Guidance is effective for improving accurate PDAC diagnoses (notably by recognizing acinar-ductal metaplasia) and for evaluating storiform fibrosis.

Family history is an important risk factor of gastric cancer. No guidelines have been developed that target gastric cancer with a family history; only hereditary familial gastric cancer is targeted. We review the available evidence regarding the familial aggregation mechanisms of gastric cancer and a strategy of screening and surveillance for gastric cancer in individuals with a positive family history of the disease. As there is a synergic effect of Helicobacter pylori infection and family history on the increased risk of gastric cancer, Helicobacter pylori eradication should be considered in all infected individuals with a family history of gastric cancer. Currently, there is weak evidence indicating that suitable timing to initiate eradication therapy is at the age of 20, when precancerous lesions, including significant gastric atrophy and intestinal metaplasia, have not been established. Reasonable timing to initiate screening for gastric cancer in individuals with a family history of gastric cancer is 10 years prior to the age of onset of gastric cancer in affected relatives. A 2-year surveillance interval, instead of the 3-year interval recommended in the present guidelines, may be better to detect early gastric cancer in those individuals who have already developed precancerous gastric lesions.

Objectives The Kyoto classification of gastritis was established for diagnosing Helicobacter pylori (H. pylori) infection via endoscopic findings. We investigated the role of the Kyoto classification of gastritis in the diagnosis of H. pylori infection and histological gastritis in Japanese individuals. Moreover, the histological findings of gastritis in H. pylori infection were examined based on age and sex differences. Methods We selected 561 patients aged 20-79 years who underwent gastroduodenal endoscopy at our hospital between 2010 and 2018. Endoscopic biopsy specimens from the antrum and corpus were used to investigate H. pylori infection and histology. Endoscopic findings were based on the Kyoto classification of gastritis, and histological findings were based on the updated Sydney System. Results Endoscopic findings based on the Kyoto classification of gastritis (H. pylori positive, 303 patients; H. pylori negative, 258 patients, based on endoscopic findings) had 98.7% sensitivity and 98.4% specificity for histological gastritis. In addition, endoscopic findings in the three age groups (20-39, 40-59, and 60-79 years) had high sensitivity and specificity. Atrophy and intestinal metaplasia were found only in the H. pylori-positive group and progressed with age. Histological inflammation of pyloric mucosa in the younger age group of H. pylori-positive patients was significantly higher than that in the elderly group. Significant inflammation was observed in young women. Conclusions The Kyoto classification of gastritis can not only diagnose H. pylori infection but also detect histological gastritis. Histological gastritis has varying characteristics of inflammation, atrophy, and intestinal metaplasia, depending on age and sex.

Sclerodermatous graft-versus-host disease (GVHD) is one of the many clinicopathological variants of chronic GVHD. One of the rarest forms of this variant is GVHD-associated angiomatosis (GVHD-AA). We describe the case of a 62-year-old male with sclerodermatous GVHD who presented, in consecutive years, two different lesions that showed characteristics of GVHD-AA. The first lesion fitted perfectly with the previously known features of this rare entity. However, the second lesion, was more interesting as the angiomatoid lesion was surrounded by newly appeared adipocytes, something not previously described. The appearance of this peculiar adipose tissue may be explained as related to an important dermal atrophy, as a concomitant appearance of a lipomatous nevus and GVHD-AA or finally, as mature adipose tissue related to a previous inflammatory process, that is lipomatous metaplasia. Both lesions were diagnosed as GVHD-AA, and the second one was considered to be associated with dermal lipomatous metaplasia. We also considered that hypoxia could be related to both lesions. In the present report we review previously published cases of GVHD-AA and discuss the different hypothesis that could explain the appearance of metaplasia associated to the second lesion. This article is protected by copyright. All rights reserved.

PURPOSE: Gastric cancers are classified as diffuse-type (DTGC) or intestinal-type (ITGC). DTGCs have distinct clinical and histopathologic features, and carry a worse overall prognosis compared to ITGCs. Atrophic gastritis (AG) and intestinal metaplasia (IM) are known precursors to ITGC. It is unknown if AG and IM increase risk for DTGC. METHODS: We performed a systematic review to identify studies reporting on the association of AG/IM and DTGC. We extracted the odds ratio (OR) of the association from studies, and performed pool analysis. Subgroup analysis was performed on studies reporting histologic severity (using operative link systems) to assess if histologic severity of AG/IM was associated with higher risk. RESULTS: We identified six case-control and eight cohort studies for inclusion. Both AG (pooled OR=1.9, 95% CI 1.5 to 2.4, p

Screening for gastric intestinal metaplasia (GIM) may lead to early gastric cancer detection. We developed and validated a pre-endoscopy risk prediction model for detection of GIM based on patient-level risk factors in a U.S. population. We used data from 423 GIM cases and 1796 controls from a cross-sectional study among primary care and endoscopy clinic patients at the Houston VA. We developed the model using backwards stepwise regression and assessed discrimination using area under the receiver operating characteristic (AUROC). The model was internally validated using cross-validation and bootstrapping. The final expanded model was compared to a model including H. pylori infection alone and a baseline model including remaining terms without H. pylori. Male sex, older age, non-white race/ethnicity, smoking status, and H. pylori were associated with GIM risk. The expanded model including these terms had AUROC 0.73 (95%CI 0.71–0.76) for predicting GIM and AUROC 0.82 (95%CI 0.79–0.86) for extensive GIM. This model discriminated better than a model including only H. pylori (AUROC 0.66; 95%CI 0.63–0.68) and the baseline model (AUROC 0.67; 95%CI 0.64–0.70). The expanded model performed similarly among primary care (AUROC 0.75) and endoscopy (AUROC 0.73) patients. The expanded model showed sufficient internal validity (cross-validation AUROC 0.72) with little evidence of over-fitting. We develop and validate a non-invasive risk model for GIM detection in a U.S. population that included terms for sex, age, race/ethnicity, smoking status, and H. pylori infection. Validated risk models would identify individuals with GIM who should be referred for endoscopic screening.

Endoscopic mucosal resection (EMR) and radiofrequency ablation (RFA) for Barrett’s esophagus (BE)-related high-grade dysplasia (HGD) and early esophageal adenocarcinoma (EAC) are considered effective treatments for eradication of BE. Little is known about the impact of achieving complete eradication of intestinal metaplasia (CE-IM) following the complete eradication of neoplasia (CE-N), specifically if CE-IM reduces the risk of recurrent dysplasia. Retrospective cohort study of consecutive patients with BE and HGD or intramucosal cancer (IMC)-treated endoscopically at a tertiary referral center between 2001 and 2019. Association between CE-IM and recurrent dysplasia after CE-N was evaluated. A total of 433 patients treated with EMR and/or RFA were included. Of these, 381 (88%) achieved CE-N, of which 345 (80%) had adequate follow-up for inclusion in the analysis. A total of 266 (77%) patients achieved CE-IM; with a median follow-up since initial treatment for HGD/IMC of 45.9 months (IQR 25.9, 93.1); 20 patients (5.8%) had recurrent dysplasia after achieving CE-N. Kaplan Meier survival curves revealed that time free of recurrence in those who achieved CE-IM was significantly higher (p = 0.002). In the multivariable analysis, CE-IM was associated with a significant lower hazard of recurrence (HR 0.2, 95% CI 0.1, 0.6), whereas the number of endoscopic treatments to achieve CE-N was associated with a significant higher hazard of recurrence (HR 1.1, 95% CI 1.0, 1.2). Achieving CE-IM following CE-N reduces the risk of recurrent dysplasia and should be considered a treatment target among patients with BE undergoing endoscopic therapies for HGD or EAC.

Background and Aims Crohn’s disease [CD] is characterised by a heterogeneous disease course. Patient stratification at diagnosis using clinical, serological, or genetic markers does not predict disease course sufficiently to facilitate clinical decision making. The current study aimed to investigate the additive predictive value of histopathological features to discriminate between a long-term mild and severe disease course. Methods Diagnostic biopsies from treatment-naïve CD patients with mild or severe disease courses in the first 10 years after diagnosis were reviewed by two gastrointestinal pathologists after developing a standardised form comprising 15 histopathological features. Multivariable logistic regression models were built to identify predictive features and compute receiver operating characteristic [ROC] curves. Models were internally validated using bootstrapping to obtain optimism-corrected performance estimates. Results In total, 817 biopsies from 137 patients [64 mild, 73 severe cases] were included. Using clinical baseline characteristics, disease course could only moderately be predicted (area under receiver operating characteristic curve [AUROC]: 0.738 [optimism 0.018], 95% confidence interval [CI] 0.65–0.83, sensitivity 83.6%, specificity 53.1%). When adding histopathological features, in colonic biopsies a combination of [1] basal plasmacytosis, [2] severe lymphocyte infiltration in lamina propria, [3] Paneth cell metaplasia, and [4] absence of ulcers were identified and resulted in significantly better prediction of a severe course (AUROC: 0.883 [optimism 0.033], 95% CI 0.82–0.94, sensitivity 80.4%, specificity 84.2%). Conclusions In this first study investigating the additive predictive value of histopathological features in biopsies at CD diagnosis, we found that certain features of chronic inflammation in colonic biopsies contributed to prediction of a severe disease course, thereby presenting a novel approach to improving stratification and facilitating clinical decision making.

Introduction: Gallbladder diseases are prevalent worldwide and present with a diverse histopathological spectrum. Mucosal irritation and chronic inflammation is considered as an important etiological factor for the mechanical or functional dysfunction of emptying of the gallbladder. This study aims to find the prevalence of non-neoplastic lesions of gallbladder among cholecystectomy specimens of a tertiary care center. Methods: A descriptive cross-sectional study was conducted in the Department of Pathology, of a tertiary care center from January 2005 to December 2020. Ethical approval was taken from the Institutional Review Committee. All the patients who had undergone cholecystectomy procedures which showed non-neoplastic lesions were enrolled in the study. Convenient sampling was done. Statistical Package for Social Sciences version 21 and Microsoft Excel were used for data analysis. Point estimate at 95% Confidence Interval was calculated along with frequency and proportion forbinary data. Results: Out of 4914 cholecystectomy specimens, 4852 (98.73%) (95% Confidence Interval= 98.42- 99.04) were non-neoplastic lesions. There were 1252 (25.8%) males and 3600 (74.2%) females with a male to female ratio of 1:2.87. Age ranged from 2 to 89 years with a mean age of 45±14.48 years. Gallbladder lesions were observed maximum in age group 41-50 years with 1200 (24.7%) cases. Among the non-neoplastic lesions, cholecystitis without any specific finding was the most common finding with 3028 (62.4%) cases followed by cholelithiasis with 1478 (30.5%) cases. Conclusions: The prevalence of non-neoplastic lesions of gallbladder is similar to other studies done in similar setings. Female predominance was noted in non-neoplastic lesions.

Summary Autoimmune gastritis is a well-known pathologic entity, but there are few studies that examine its clinical and histologic presentation in children. This is a single institution, retrospective study performed on patients diagnosed from 2011 through 2019. Patients were identified by their pathologic diagnosis within the laboratory information system. The electronic medical record and archived slides were reviewed. Twenty-two children (3 months to 18 years; median, 10.9 years) with autoimmune gastritis were diagnosed of a total of 14,257 nonconsultation gastric biopsies from unique patients (0.15% prevalence). Patients with autoimmune gastritis were diagnosed at an average age of 10.9 years and were mostly female (68.2% women, 31.8% men). The majority had extragastric immune disorders (13/22; 59.1%). All patients in the study had gastric body mucosa with enterochromaffin-like cell hyperplasia, atrophy, and histologic features of chronic injury. Most biopsies showed gastric body metaplasia (n = 19) or active gastric inflammation. However, antral atrophy was also observed in 12 patients, and antral metaplasia was identified in one patient; four patients had active chronic antral gastritis. All biopsies were negative for Helicobacter pylori. Pediatric autoimmune gastritis is a rare disorder that should be recognized because of its systemic effects with long-term morbidity. In addition, the possibility of tandem extragastric immune disorders should be considered when a diagnosis of pediatric autoimmune gastritis is established.

Background The role of the subacromial bursa in the development or healing of shoulder pathologies is unclear. Due to this limited knowledge, we aimed to understand specific reactions of the subacromial bursa according to rotator cuff (RC) pathologies compared to non-tendon defects of the shoulder. We hypothesized that the tissue composition and inflammatory status of the bursa are likely to vary between shoulder pathologies depending on the presence and the extent of RC lesion. Method Bursa samples from patients with either 1) shoulder instability with intact RC (healthy bursa, control), 2) osteochondral pathology with intact RC, 3) partial supraspinatus (SSP) tendon tear, or 4) full-thickness SSP tear were investigated histologically and on gene expression level. Result Bursae from SSP tears differed from non-tendon pathologies by exhibiting increased chondral metaplasia and TGFβ1 expression. MMP1 was not expressed in healthy bursa controls, but strongly increased with full-thickness SSP tears. Additionally, the expression of the inflammatory mediators IL1β, IL6, and COX2 increased with the extent of SSP tear as shown by correlation analysis. In contrast, increased angiogenesis and nerve fibers as well as significantly upregulated IL6 and COX2 expression were features of bursae from patients with osteochondral pathology. Using immunohistochemistry, CD45+ leukocytes were observed in all examined groups, which were identified in particular as CD68+ monocytes/macrophages. Conclusion In summary, besides the strong increase in MMP1 expression with SSP tear, molecular changes were minor between the investigated groups. However, expression of pro-inflammatory cytokines correlated with the severity of the SSP tear. Most pronounced tissue alterations occurred for the osteochondral pathology and full-thickness SSP tear group, which demonstrates that the bursal reaction is not exclusively dependent on the occurrence of an SSP tear rather than longstanding degenerative changes. The present bursa characterization contributes to the understanding of specific tissue alterations related to RC tears or non-tendon shoulder pathologies. This pilot study provides the basis for future studies elucidating the role of the subacromial bursa in the development or healing of shoulder pathologies.

Background Intraocular osseous metaplasia is a rare histological finding associated with benign cellular transformation. Its development requires inflammatory cytokines and the process takes many years. Previous case reports of intraocular ossification manifested as linear calcification or white plaques. In contrast, our case presented with a tumor-like solid mass, in which a long-standing chronic inflammatory stimulation may contribute to the stunning appearance. Case presentation This is a 48-year-old woman with past history of advanced Coat’s-like retinopathy and chronic retinal detachment in the left eye for 12 years. She underwent vitreoretinal surgery to prevent phthisis bulbi. During the operation, a 9 mm solid mass was found embedded within the proliferative tissue above the retina and was removed. Pathological findings revealed bone formation in the center of the mass surrounded by fibrous metaplasia and focal gliotic changes. Layers of cohesive cells were found lining on the external side of the mass, and further immuno-histochemical study suggested them retinal pigment epithelial cells. Postoperatively, the retina was attached with stable visual acuity and normal intraocular pressure. Conclusion To our knowledge, the appearance of a tumor-like mass representing intraocular osseous metaplasia in eyes with chronic inflammation or retinal detachment has not been reported in previous case reports. This case emphasizes the importance of considering osseous metaplasia as one of the differential diagnoses of an unknown intraocular mass, especially in eyes with great severity of chronic inflammation. Also, our immuno-histochemical study provided more evidence on the pathological role of retinal pigment epithelial cells in developing ossification.

Aim: To evaluate the prevalence of Helicobacter pylori (H. pylori) and related histopathological lesions in gastric mucosa samples in this single-center study. Methods: Esophagogastroduodenoscopy and endoscopic biopsy reports of 1605 elective cases were retrospectively evaluated. Histopathological examination was evaluated according to the Sydney classification. The data were analyzed according to the prevalence of H. pylori, age, gender, gastric atrophy and intestinal metaplasia rates, and the distribution of the study group in the population below 40 years old and over 40 years old. Results: 584 males (Mean age 51.5 ± 16.5 years) and 1021 females (mean age 49.6 ± 16 years), (p = 0.03), a total of 1605 cases were included in the study. The rate of atrophy, metaplasia and H. pylori positivity in total study population were 0.2%, 16%, 71%, respectively. The rate of atrophy in men and women were 1.2% and 0.8%, respectively (p = 0.006). The rate of metaplasia in men and women were 20.9% and 13.7%, respectively (p

Background The precursors of clear cell endometrial carcinoma (CC-EC) are still undefined. Here, we deal with the diagnostic issues related to CC-EC precursors by presenting a morphological, immunophenotypical and molecular study of two representative cases and discussing the relevant literature. Case presentation Our and previous cases suggest that clear cell endometrial intraepithelial carcinoma (CC-EIC) is a real entity, which may be distinguished from metaplastic/reactive changes and from its serous counterpart. CC-EIC appears associated with atrophic polyps and may be diagnosed based on morphological and immunophenotypical features of CC-EC in the absence of invasive disease. We described a p53-mutant putative precursor characterized by high-grade nuclei in the absence of other distinctive features. Two putative low-grade precursors resembled atypical tubal metaplasia and endometrial intraepithelial neoplasia, although immunohistochemistry could not support their relationship with CC-EC. Conclusions In conclusion, pathologists should be aware of the existence of CC-EIC, since its correct diagnosis may be crucial for a correct patient management. Although several putative earlier precursors have been described, they does not show univocal features that allow their recognition in the common practice. Further studies are necessary in this field.

Aims: To highlight the pathogenesis of endometrial osseus metaplasia, its importance as a rare cause of infertility and the benefit of hysteroscopic evaluation of infertile women with risk factors for osseus metaplasia. Presentation of Case: A diagnosis of endometrial osseus metaplasia was confirmed histologically in three women undergoing diagnostic hysteroscopy as part of infertility evaluation. They all had chronic vaginal discharge and a preceding history of induced second trimester abortion. Two of the patients were referred for evaluation before in-vitro-fertilization (IVF). Hysteroscopy was done with a 30° telescope, initially using a 2-channel diagnostic sheath, which was later replaced with a 4-channel operating sheath for tissue retrieval. Discussion: Endometrial osseus metaplasia is a rare condition characterized by the presence of mature or immature bone in the endometrial cavity. Endometrial retention of embryonic tissue following an abortion is the commonest theory of etio-pathogenesis. It is an important cause of infertility and while other causes of infertility can be easily by-passed in an IVF cycle, endometrial factors may not be addressed by IVF alone, as a defective endometrium is a risk for failure. Although there is no consensus on routine hysteroscopy for women undergoing IVF, it is the mainstay of evaluation and treatment of women with endometrial osseus metaplasia. Conclusion: Only complete removal of metaplastic tissue would restore fertility, in patients with osseus metaplasia. Hysteroscopy done in infertile women with risk factors for endometrial osseus metaplasia may enhance early treatment and ultimately increase successful spontaneous and IVF pregnancy rates.

Necrotizing infundibular crystalline folliculitis is a rare entity, which is a distinctive clinical and histopathological entity. Eruptive yellow waxy umbilicated folliculocentric plugs clinically correspond to pale crystalline filaments embedded in an amorphous sebum-rich material. Remarkably, only the superficial infundibular ostia remain, and the distended cavity is devoid of a follicular or sebaceous gland remnant. The pathogenesis of this enigmatic event remains to be established. The emergence of necrotizing infundibular crystalline folliculitis (NICF) as a paradoxical side effect of antitumor inhibitors epidermal growth factor receptor vascular endothelial growth factor and more recently programmed death-1 represents the expression of altered molecular pathways that underpin the pathogenesis of NICF. To explore these pathways, it is necessary to explore the hierarchy of follicular stem cells, particularly the potential role of committed infundibular stem cells that play a key role in wound healing. Committed infundibular stem cells are closely linked to the sebaceous gland stem cell axis, and this has relevance in the process of homeostatic repair of sebaceous follicles in the wake of folliculitis. The unscheduled modulation of this infundibular homeostatic sebaceous repair axis by epidermal growth factor receptor vascular endothelial growth factor, and programmed death-1 may lead to an aberrant outcome with metaplasia of infundibular keratinocytes to sebocytes. In the absence of sebaceous gland differentiation, these metaplastic infundibular sebocyte cells would lead to the consumption and loss of the infundibulum as a result of holocrine sebum production. This conceptual pathogenic pathway for NICF is constructed by incorporating recent advances in the fields of follicular stem cells, wound repair, follicular homeostasis, regulatory T cells, and molecular pathways linked to the biologicals inducing NICF.

Squamous metaplasia of the breast is a rare and unusual finding. A number of benign and malignant differential entities exist when squamous cells are present in a breast lesion. Our patient was found to have pronounced squamous metaplasia and keratin cysts arising in a complex fibroadenoma. The rare nature of squamous metaplasia arising in such a lesion poses some diagnostic challenges, as squamous epithelium and squamous metaplasia in the breast may raise suspicion for malignancy. Herein we present a unique case and discussion of benign and malignant differential entities. We also retrospectively reviewed a series of complex fibroadenomas in our institution, including the demographic and histologic features, and more importantly the associated breast cancer risk.

Background. Chronic pancreatitis (CP) is characterized by a number of specific changes in the structure and function of the pancreas, including atrophy of functional tissue, fibrosis and ductal degeneration, a decrease in the number of islets. Despite a large number of possible etiological factors, the main pathophysiological mechanisms of CP development have much in common. Thus, with the preservation of secretory activity under obstruction of the ducts and their compensatory expansion, pancreatic secret infiltrates the surrounding tissue with the formation of edema, followed by intrapancreatic activation of digestive enzymes, in particular trypsinogen, which initiates proteolytic necrobiosis of the pancreocytes. The duct cells make up to 30 % of the human pancreas, compared to 1–2 % of endocrine cells. One of the first signs of CP is the abnormal increase in the number of ductal branches. It has also been shown that in the ducts of CP patients, the number of cells containing insulin increases, as well as cells that contain other endocrine and exocrine markers. Modeling chronic, acute and complicated pancreatitis in rats also confirmed that epithelial cells are involved in the regulation of extracellular matrix of the pancreas. Materials and methods. Comprehensive histopathological and immunohistochemical (IHC) study was performed in the laboratory of histological and immunohistochemical diagnosis of the university hospital of Zaporizhia State Medical University on postoperative material of 40 patients with CP aged 28 to 74 years, who were opera­ted at the clinic of surgery and minimally invasive technologies of Zaporizhia State Medical University. Immunohistochemical exa­mination was carried out according to standard procedures using a mouse monoclonal antibody Alpha Smooth Muscle Actin (Clone 1A4) against the a-isoform of smooth muscle actin (a-SMA) and Desmin (Clone D33) against desmin (DAKO, USA), monoclonal rabbit antibody against collagen I (Clone RAH C11) anti-collagen type 1 (Imtek, RF) and rabbit polyclonal antibodies against fibronectin (DAKO, USA). Quantitative determination of the intensity and the relative area of the markers’ stromal expression was reproduced using the program for medical digital image processing ImageJ v.1.48, embedded plugin Colour Deconvolution analysis circuit and coloring H DAB (hematoxylin + DAB) for determi­ning the area occupied by immunopositive structure in immunohistochemical preparations and optical (densitometric) intensity of immunostaining by patented procedure. Results. Pathohistological study of biopsies with a specific staining of collagen (by Van Gieson and Masson’s trichrome) showed that fibrotic changes in all the patients with CP were characterized by a combination of pronounced perilobular fibrosis, which covered all lobules, widespread intralobular fibrosis, and significant periductal fibrosis near large, sharply defined narrowed and cystically dilated ducts. There was also a pronounced expansion of interlobular fibrosis, a noticeable thickening of intralobular connective tissue strands directed deep into the lobules and connective tissue strands that surrounded some acini, as well as a significant tortuosity and widening of the ducts with retention cysts. In most cases, the deformation of the ductal system was one of the most significant structural changes. Thus, 87.5 % of cases were characterized by the unevenly narrowed and cystic-altered interlobular ducts, pronounced concentric fibrosis, protein plugs and concrements observed in the ducts. In 7.5 % of the cases, in the main pancreatic duct, foci of the epithelium atrophy were present, which alternated with foci of papillary intraepithelial hyperplasia, identified as pancreatic intraepithelial neoplasia. The parenchyma of the pancreas was thus constituted small, atrophic acini, surrounded by dense fibrous strands, with an increased number of gaping ducts of different diameters. Also, in 17.5 % of cases, phenomena of acinar-ductal metaplasia were observed. In the centers of the acinar-ductal metaplasia zones, the transformation of some acinar cells into ductal cells was determined with the formation of small duct-like structures, the so-called tubular complexes, which, according to the literature, are the primary focus of acinar tissue regeneration. In particular, a large number of activated a-SMA + pancreatic stellate cells (PSC) is detected in the zones of fibrosis. The pattern of expression of this marker is characterized by pronounced a-SMA-immunopositive staining of both PSC and their processes, and, in part, of the fibrillar component. Primary statistical processing of morphometry data revealed a direct relationship between the expression of a-SMA and the area of collagen I type, but this relationship was not significant (r = +0.321, p > 0.05). In order to further objectify the statistical studies, we isolated a group of cases characterized by low a-SMA expression (n = 9). A further study using medical statistics methods showed that the average area of type I collagen and the intensity of its expression in this group was significantly lower than in the other biopsy specimens (p < 0.05). In contrast, desmin expression was identified both in connective tissue, which was characterized by a lower intensity of immunostaining, in acinar tissue and in the epithelium of the pancreatic ducts. The pattern of its expression in fibrosis zones in CP was similar to that of a-SMA, but in 27.5 % of cases, the intensity of staining was below the threshold for determination by morphometric methods. We isolated a group of cases characterized by high expression of fibronectin (n = 9). A further study using medical statistics showed that the average area of type I collagen and the intensity of its expression in this group was significantly higher than in the other biopsy specimens (p < 0.05). Thus, IHC study of the material obtained from patients with CP showed that a large number of activated PSC expressing a-SMA and desmin are concentrated in the pancreatic ductal zones. Also, in these zones, a significant accumulation of fibronectin was found, which is synthesized in excess by activated PSC. The pattern of IHC staining of type I collagen in the zones of severe pancreatic fibrosis is characterized by a weak and moderate intensity with a average level of its expression. Conclusions. A characteristic morphological picture of the CP development is a combination of fibrosis with deformation of the ductal system due to periductal fibrosis with the expansion of interlobular fibrosis, thickening of intralobular connective tissue strands, as well as considerable tortuosity and widening of the ducts with retention cysts. Significant structural reorganization of the pancreatic duct system in patients with CP was observed in 87.5 % of cases, in 17.5 % of cases, the picture was supplemented by phenomena of acinar-ductal metaplasia with the transformation of acinar cells into ductal cells and the formation of small duct-like structures, the so-called tubular complexes. In 7.5 % of cases, in the main pancreatic duct, foci of atrophy of the epithelium were identified, which alternated with foci of papillary intraepithelial epithelial hyperplasia (PanIN). The development of pancreatic fibrosis in CP is facilitated by the accumulation of a-SMA+ activated pancreatic stellate cells synthesizing an excess of components of the extra-cellular matrix, in particular type I collagen. The mean area of type I collagen and the intensity of its expression were significantly lower with reduced a-SMA expression (p < 0.05), and significantly higher in cases of pronounced fibronectin expression (p < 0.05).

Background. The study of the cytokine balance is important due to searching the general links of the pathogenesis of comorbidity in precancerous gastric lesions and thyroid diseases. The purpose was to determine the peculiarities of the cytokine balance in terms of the level of vascular endothelial growth factor (VEGF), tumor necrotizing factor (TNF) α, interleukins (IL) 8 and IL-18 in patients with precancerous gastric lesions depending on the changes in the structure of the thyroid gland. Materials and methods. Forty-five patients with precancerous gastric lesions were examined. Inclusion criteria were as follows: intestinal metaplasia in the body and/or antrum, atrophy in the body of the stomach. According to the results of an ultrasound examination of the thyroid gland, patients are divided into the groups: group I — 19 patients with nodular changes, group II — 18 patients with diffuse changes, and group III — 8 patients without changes. The control group included 10 healthy individuals. The level of IL-8, IL-18, TNF-α, VEGF was determined in the blood serum by the enzyme immunoassay using reagent kits of the Vector-BEST company, Novosibirsk, Russia. Results. 82.2 % patients with precancerous gastric lesions developed the changes in the structure of the thyroid gland (n = 37), 42.2 % (n = 19) had nodular changes in. The concentration of IL-8 in patients of group I was higher compared with group II, III and control group by 2.0 (p

Native cardiac valves may undergo calcification in the setting of chronic injury, subsequently impeding normal valve structure and function. In the same setting, there may be evidence of metaplasia-specifically osseous metaplasia-with lamellar bone admixed with dystrophic calcification. In this study, the histologic features of 123 native aortic valves (identified from 1094 sequentially reviewed native valves of all types that included a total of 754 aortic valves) with osseous metaplasia are focused upon, as well as correlation with other histopathologic features, and clinical and echocardiographic findings. Osseous metaplasia was identified in aortic and significantly less frequently in mitral valves, and never in tricuspid or pulmonic valves. Notable observations included that osseous metaplasia in aortic valves were seen in patients with greater body mass index, and less commonly identified in patients with a history of autoimmune disease. Aortic valves with osseous metaplasia were more commonly tricuspid (as opposed to bicuspid), and with smaller aortic valve area and greater peak and mean gradients. The rate of osseous metaplasia in aortic valves increased with increasing degree of stenosis and decreasing degree of regurgitation. The rates of the presence of chondromatous metaplasia, smooth muscle, arterial vessels, capillary bed formation, chronic inflammation, and hemosiderin laden macrophages were greater in aortic valves with osseous metaplasia compared to valves without osseous metaplasia. Further investigation is required to determine potential physiologic and/or pathologic consequence of the presence of valvular osseous metaplasia.

Objective Esophageal white lesions (EWL) are commonly observed under upper endoscopy, while their clinical significance remains undetermined. The aim of this study was to identify the endoscopic characteristics of EWL and distinguish between different types of EWL. Methods Consecutive patients with upper gastrointestinal complaints and participants admitted for health check-up who underwent esophagogastroduodenoscopy from October 2018 to August 2019 in a tertiary hospital were prospectively screened. EWL were detected under endoscopy and biopsy was performed for histological analysis. Participants' characteristics, lifestyle, esophageal motility and reflux monitoring variables were analyzed. Results Of the 3641 consecutive participants screened, 303 of them aged 56.12 ± 10.95 years were found to have EWL (detection rate of 8.3%). More than one-third of them preferred hot drinks, eating pickled or spicy food, smoking and alcohol consumption and 5.3% had current or former upper gastrointestinal or head and neck cancers. The common endoscopic appearance of the EWL (2.9 mm ± 1.2 mm in diameter) included slightly elevated plaque, translucent white in color, with a clear border, round or oval in shape, and a scaly, rough or smooth surface. Histology showed low-grade intraepithelial dysplasia in 13 cases, leukoplakia in 10 and intestinal metaplasia in one. No significant differences were found between the histological findings and endoscopic manifestations of EWL. Conclusions EWL are not uncommon in daily endoscopic examination, with some of them being precancerous lesions. Conventional white-light endoscopy is insufficient to identify EWL, while histological assessment is important. Further studies using advanced endoscopic techniques with long-term follow-up are needed.

INTRODUCTION: squamous cell metaplasia in the rectum is found in patients with longstanding inflammation or infectious lesions [1]. Colonoscopy plays a major role in the diagnostic of squamous cell metaplasia, especially with the use of Narrow Band Imaging (NBI) or Blue Light Imagining (BLI), which allows for targeted visualization of intraepithelial capillary loopspeculiar for the squamous epithelium [1,2]. The final conclusion cannot be reached without morphological diagnostics. We would like to show on two clinical cases of patients with a longstanding ulcerative colitis the occurrence of squamous cell metaplasia in the rectum. These areas of metaplasia may be the source of squamous cell cancer.CLINICAL CASES: a clinical cases of squamous cell metaplasia in the rectum in two patients with a longstanding ulcerative colitis (9 and 14 years) are presented. The total ulcerative colitis was verified in both patients by colonoscopy. Against the background of endoscopic remission, flat whitish areas of irregular shape, up to 3 cm in size, in the form of “tongues” of metaplastic epithelium with clear boundaries were found in the low rectum. When examined in a Narrow Band Imaging (NBI) and Blue Light Imagining (BLI), the microvascular pattern in the detected areas was identical in structure to the microvascular pattern of the squamous epithelium. The biopsies confirmed the presence of squamous cell epithelium.CONCLUSION: patients with a longstanding ulcerative colitis may have squamous cell metaplasia of the rectal mucosa, which can be detected by colonoscopy in white light. Using a Narrow Band Imaging (NBI) followed by a targeted biopsy allows the most accurate diagnosis to be established. Patients of this group require repeated colonoscopies using the above methods, since areas of metaplasia can be a source of squamous cell cancer of the rectum.

INTRODUCTION: squamous cell metaplasia in the rectum is found in patients with longstanding inflammation or infectious lesions [1]. Colonoscopy plays a major role in the diagnostic of squamous cell metaplasia, especially with the use of Narrow Band Imaging (NBI) or Blue Light Imagining (BLI), which allows for targeted visualization of intraepithelial capillary loopspeculiar for the squamous epithelium [1,2]. The final conclusion cannot be reached without morphological diagnostics. We would like to show on two clinical cases of patients with a longstanding ulcerative colitis the occurrence of squamous cell metaplasia in the rectum. These areas of metaplasia may be the source of squamous cell cancer.CLINICAL CASES: a clinical cases of squamous cell metaplasia in the rectum in two patients with a longstanding ulcerative colitis (9 and 14 years) are presented. The total ulcerative colitis was verified in both patients by colonoscopy. Against the background of endoscopic remission, flat whitish areas of irregular shape, up to 3 cm in size, in the form of “tongues” of metaplastic epithelium with clear boundaries were found in the low rectum. When examined in a Narrow Band Imaging (NBI) and Blue Light Imagining (BLI), the microvascular pattern in the detected areas was identical in structure to the microvascular pattern of the squamous epithelium. The biopsies confirmed the presence of squamous cell epithelium.CONCLUSION: patients with a longstanding ulcerative colitis may have squamous cell metaplasia of the rectal mucosa, which can be detected by colonoscopy in white light. Using a Narrow Band Imaging (NBI) followed by a targeted biopsy allows the most accurate diagnosis to be established. Patients of this group require repeated colonoscopies using the above methods, since areas of metaplasia can be a source of squamous cell cancer of the rectum.

Ovarian primary mucinous tumours (OPMTs) show an adenoma-borderline-carcinoma sequence with gastrointestinal metaplasia. Gastric gland mucin-specific O-glycans are unique with an α1,4-linked N-acetylglucosamine (αGlcNAc) residue attached to mucin 6 (MUC6). Although αGlcNAc is expected to be expressed in OPMTs, the relationship between αGlcNAc expression and OPMT progression remains unknown. Here, we analysed 104 areas of benign mucinous tumours (benign), 55 areas of borderline mucinous tumours (borderline), and 18 areas of malignant mucinous tumours (malignant) to investigate the expression patterns of αGlcNAc, mucin 2 (MUC2), mucin 5AC (MUC5AC), and MUC6 during the progression of OPMT from benign to malignant. MUC5AC expression was observed in all areas. The frequencies of MUC6- and αGlcNAc-positive areas were decreased with tumour progression. In particular, the decrease in αGlcNAc-positive areas was remarkable. Furthermore, αGlcNAc expression was lower than MUC6 expression at all grades (benign, p < 0.0001; borderline, p = 0.0014; malignant, p = 0.0039). Conversely, there was no difference in the expression frequency or level of MUC2 among the three grades. These results suggest that decreased expression of αGlcNAc relative to MUC6 occurs early in tumour development and marks the initiation of OPMT progression.

Summary A 10-year-old spayed female Border Collie developed a ductal adenocarcinoma in the spleen. Clinically, the spleen was enlarged and a small liver nodule was present but there were no other abnormalities. Most of the splenic parenchyma was diffusely infiltrated by variably shaped atypical neoplastic cells that formed small clusters or larger nests, arranged as duct or duct-like structures within a fibrous matrix. There was acinar differentiation in a few portions of the tumour with a sheet-like solid growth pattern and occasional squamous metaplasia or exocrine acinus-like structures. Mitotic figures were frequent. Neoplastic cells with ductal differentiation were diffusely immunoreactive for AE1/AE3, CAM5.2 and CK7 cytokeratins but negative for CK20, while cells with acinar differentiation were immunolabelled only for AE1/AE3 cytokeratins and were also immunopositive for mucin-1 and trypsin. A few regions of tumour with ductal or acinar differentiation were immunopositive for pancreatic lipase. All neoplastic cells were negative for mucin-2, vimentin, smooth muscle actin, chromogranin A, CD31, hepatocyte paraffin 1 and thyroglobulin antigens. Because of the formation of exocrine acinus-like structures and an immunolabelling pattern consistent with exocrine pancreas tissue, an adenocarcinoma of ectopic exocrine pancreas within the spleen was diagnosed.

Capsular contracture is a severe complication to breast surgery with implants. Previous studies suggest multiple risk factors are associated with capsular contracture, but the etiology is still unknown. We performed a literature review to investigate existing studies on histological analyses of breast implant capsules and how clinical risk factors impact the capsule morphology. The literature search was conducted in PubMed. Studies that performed histological analyses of breast implant capsules were included. Animal studies or studies with a study population of less than five patients were excluded. Fifty-two studies were included. The histological analyses showed that the breast implant capsules were organized in multiple layers with an inner layer of synovial-like metaplasia which was reported to diminish in capsules with capsular contracture. The remaining layers of the capsule mostly consisted of collagen. The alignment of the collagen fibers differed between contracted and non-contracted capsules, and capsules with higher Baker grade were generally thickest and contained more tissue inflammation. Studies investigating capsules affected by radiotherapy found a more pronounced inflammatory response and the capsules were generally thicker and fibrotic compared with nonirradiated capsules. The included studies offer valuable insights into the histological changes caused by capsular contracture and their relation to clinical risk factors. Further studies with larger sample sizes and more strict inclusion criteria are needed to further investigate implant capsules and the role of the synovial-like metaplasia for the development of capsular contracture. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors https://www.springer.com/00266 .

We herein report a patient who presented with follicular lymphoma. Although the stomach was initially intact, mucosal redness and multiple erosions appeared in the gastric body owing to infiltration of the follicular lymphoma cells. Subsequently, a slightly depressed, white area lacking gastric mucosal structure was detected in the lesser curvature of the gastric cardia and body, where lymphoma cell infiltration was also pathologically observed beneath the stratified squamous epithelium. This case indicated that, although infrequent, prolonged mucosal injury owing to lymphoma infiltration can cause squamous metaplasia in the stomach.

A 130-week-old male Royal College of Surgeons rat kept as a non-treated animal in a long-term animal study presented with a mass in the hepatic portal region that adhered to a dilated common bile duct and the duodenum. Histopathologically, the solitary mass showed expansive growth with no apparent compression and continued to dilate the common bile duct, which had a hyperplastic epithelium with intestinal metaplasia. The mass mainly consisted of small to large dilated and/or tortuous ducts with abundant dense connective tissue and many inflammatory cells. The single-layer lining epithelium of the duct changed from cuboidal to columnar. Immunohistochemically, the lining cells were positive for cytokeratin 7, cytokeratin 19, and OV-6, which are bile duct markers. Based on the pathological characteristics, the rat was diagnosed as spontaneous cholangiofibrosis adjacent to a dilated common bile duct with intestinal metaplasia.

The association of Brenner tumor (BT) with rete ovarii (RO) has been rarely alluded to in the literature. Both entities have debatable histogenesis. In this study of six cases of BT associated with RO, we describe the morphologic features and performed immunohistochemical staining for markers of Mullerian, Wolffian, mesothelial, and sex cord stromal derivation to explore the relationship between these entities. Histologically, all BTs were benign, microscopic, and incidental. RO was prominent and hyperplastic with gradual or abrupt transition to BT. In addition, focal areas of rete entrapped between BT nests were seen. All BTs were positive for GATA-3 and negative for PAX-8. Conversely, the RO in all cases was negative for GATA-3 and positive for PAX-8. WT-1 was positive in both entities. Sex cord stromal and mesothelial markers (other than WT-1) were negative in BT and RO. Although morphologically, BTs seem to arise from RO in these cases, they have a distinct immunophenotype. It is possible that at least some BTs arise from metaplastic changes in RO epithelium.

Background and Aims Buried Barrett’s mucosa is defined as intestinal metaplasia that is “buried” under the normal-appearing squamous epithelium. This can occur in Barrett’s esophagus with or without previous endoscopic therapy. Dysplasia and neoplasia within buried Barrett’s mucosa have also been reported. However, endoscopic features of buried Barrett’s mucosa have not been described. At our tertiary referral center for Barrett’s esophagus, several endoscopic features have been observed in patients who were found to have buried Barrett’s mucosa on histology. These features are squamous epithelium which is (1) darker pink on white-light and darker brown on narrow-band imaging and/or (2) has a slightly raised or nodular appearance. It was also observed that either of these 2 features is frequently seen adjacent to a Barrett’s mucosa island. This study aimed to (1) evaluate the diagnostic accuracy of these endoscopic features, and (2) evaluate the frequency of endoscopically identifiable buried Barrett’s mucosa in patients with dysplastic Barrett’s esophagus, before and after endoscopic eradication therapy. Methods This was a retrospective analysis of a prospectively observed cohort of all cases of dysplastic Barrett’s esophagus referred to St Vincent’s Hospital, Melbourne. Endoscopy documentation software and histopathology reports of esophageal biopsy and EMR specimens between March 2013 and March 2019 were searched for terms “buried” or “subsquamous” Barrett’s mucosa. Endoscopic reports, images, and histopathology reports of suspected buried Barrett’s mucosa were then reviewed to apply the endoscopic features and correlate with the histologic diagnosis. Results In a cohort of 506 patients with dysplastic Barrett’s esophagus, 33 (7%) patients (73% male, median age at referral 70.5 years) had buried Barrett’s mucosa on histology. Twenty-seven (82%) patients had previous treatment for dysplastic Barrett’s esophagus; radiofrequency in 2 (6%), EMR in 4 (12%), and both modalities in 21 (64%). Six (18%) had no previous treatment. Histologically confirmed buried Barrett’s mucosa was suspected at endoscopy in 26 patients (79%). Endoscopic features were (1) darker pink or darker brown mucosa underneath squamous epithelium (24%), (2) raised areas underneath squamous mucosa (27%), and both features present concurrently (27%). These features were associated with adjacent islands of Barrett’s esophagus in 48%. Forty-four cases of buried Barrett’s mucosa were suspected endoscopically, and these were sampled by biopsy (50%) and EMR (50%). Buried Barrett’s mucosa was confirmed in 26 cases, with a positive predictive value of endoscopic suspicion of 59%. Eighteen cases of endoscopically suspected buried Barrett’s mucosa had no buried Barrett’s mucosa on histology; inflammation or reflux was identified in 12 (67%) patients. Dysplasia was identified within buried Barrett’s mucosa in 12 (36%) patients; 5 intramucosal adenocarcinoma, 1 high-grade dysplasia, and 6 low-grade dysplasia. Endoscopic features of buried Barrett’s mucosa were observed in 11 of 12 cases harboring dysplasia or neoplasia, compared with 15 of 21 cases of buried Barrett’s mucosa without dysplasia. Conclusions In this retrospective analysis of prospectively observed patients with dysplastic Barrett’s esophagus, buried Barrett’s mucosa was identified in 7%, including treatment-naive patients. The proposed endoscopic features of buried Barrett’s mucosa were seen in 79% of patients with histology confirmed disease. These endoscopic features may predict the presence of buried Barrett’s mucosa, which may contain dysplasia or neoplasia. An overlap between the endoscopic features of inflammation, reflux, and buried Barrett’s mucosa was observed. Future prospective studies are required to develop and validate endoscopic criteria for identifying buried Barrett’s mucosa.

We evaluated keratin 7 (K7) hepatocellular expression in 92 patients with common types of acute and chronic cholestatic diseases caused by bile duct obstruction/destruction or parenchymal lesions [acute hepatitis (n=20), mixed/pure cholestasis (n=16), primary biliary cholangitis-PBC (n=35), primary sclerosing cholangitis-PSC (n=10), vanishing bile duct syndrome (n=3), complete large bile duct obstruction due to space-occupying lesions (n=8)]. K7 immunohistochemical hepatocellular expression and ductular reaction (DR) were semi-quantitatively assessed. Results were correlated with liver enzyme serum levels, cholestasis type, histological features, hepatocellular Ki67 labelling index (LI) and HepPar1 expression. Hepatocellular K7 expression was detected in 87% (81/92) cases and in all cholestatic disease types with lowest incidence in pure/mixed cholestasis and highest in incomplete bile duct obstruction (iBDO), reaching 100% in PSC. K7-positive hepatocytes had low Ki67 LI (0-5%) retaining HepPar1 expression, irrespective of disease type. PSC cases had high K7 hepatocellular expression even with intact bile ducts, a feature that may aid differential diagnosis of cholestatic syndromes. K7 hepatocellular expression significantly correlated with cholestasis type, bile duct loss and fibrosis stage. It was higher in milder acute cholestatic hepatitis showing inverse correlation with hepatocyte proliferation and serum transaminase levels. In iBDO, younger age independently correlated with high K7 expression, while serum GGT levels showed a nearly significant correlation. Correlation with DR findings implied that K7-positive hepatocytes may result through metaplasia. In conclusion, K7 hepatocellular expression is a sensitive though non-specific marker of cholestasis. It may represent a cytoprotective reaction of resting hepatocytes in cholestasis of longer duration especially in younger patients.

Annotation. Barrett’s esophagus is an acquired condition that develops as a result of the replacement of normal stratified squamous epithelium in the lower part of the esophagus by columnar epithelium. Barrett’s esophagus is considered a complication of gastroesophageal reflux disease (GERD). It has been shown and proven that various endoscopic methods are successful in treating this condition. However, long-term success in preventing further metaplasia and dysplasia is incompletely studied. Biological welding – controlled action of high frequency current on living tissues. It is used to stop gastrointestinal bleeding, ablation of small intestinal metaplasia of the esophageal mucosa. The aim of this study was to evaluate the success of endoscopic treatments for Barrett's esophagus and the need for further surgery in patients with GERD complicated by Barrett’s esophagus. Patients with Barrett’s esophagus C1-3M2-4 (Prague classification 2004) and severe dysplasia without nodule, as well as confirmed GERD without esophageal hernia were included. A total of 98 patients were included in the study, of whom 89 were re-consulted and examined after primary Barrett's esophageal ablation. Endoscopic treatment was performed by argon-plasma coagulation (APC) and high-frequency welding of living tissues (HFW). In the dynamics of patients were re-examined. Patients with recurrent metaplasia and a high DeMeester index (˃100) underwent antireflux surgery – crurography (if necessary) and Nissen fundoplication with a soft and short cuff. Recurrence of small bowel metaplasia was recorded in 15 patients. 12 patients underwent a two-stage treatment: first a second session of esophageal ablation, and in the second stage - antireflux surgery. 2 patients refused surgical treatment and underwent only the second session of ablation. All patients received drug therapy – prokinetics and proton pump inhibitors. Three months after surgery, pH metry was performed again, which showed normalization of the DeMeester index, as a result of which patients had no complaints such as heartburn, chest pain, dysphagia, which significantly improved their quality of life. Esophagogastroduodenoscopy and biopsy of the mucous membrane of the lower third of the esophagus according to the Seattle protocol was also performed. After examination of the histological material of metaplasia zones were not recorded. It is concluded that antireflux surgery is required as part of Barrett’s esophageal treatment to prevent further dysplasia and the development of esophageal cancer.

BACKGROUND AND AIMS Gastric intestinal metaplasia (GIM), a precursor of gastric adenocarcinoma, is challenging to diagnose with white light endoscopy (WLE) and can be missed by random gastric biopsies. Narrowband imaging (NBI) may potentially improve the detection of GIM. However, pooled estimates from prospective studies are lacking. METHODS Electronic databases were searched for studies comparing NBI and WLE alone for detection of GIM and synchronous dysplasia. Primary outcome was pooled detection rate of GIM by NBI compared with WLE in prospective studies. The secondary outcome was concurrent dysplasia detection. RESULTS Ten studies were found eligible from 306 articles screened. Eight prospective studies were found eligible for primary endpoint of GIM detection. Two other retrospective studies were included for dysplasia detection. A total of 1366 subjects (694 males, 54.4 ± 5.08 years) underwent upper endoscopy. GIM was detected in 482 (35.3%) subjects. NBI detected GIM in 32% additional subjects (70% vs 38%, RR 1.79; 95% CI 1.34-2.37; P

To care and treat patients with esophageal cancer, one must first understand the epidemiology of Barrett's esophagus (BE). BE is defined as the intestinal metaplasia occurring within the esophagus from normal squamous epithelium to abnormal specialized columnar epithelium. BE, while first described by Allison in 1948, was attributed to Norman Barrett in 1950, who reported a case of chronic peptic ulcer in the lower esophagus that was covered by columnar epithelium.

The presence of atrophic gastritis (AG) and intestinal metaplasia (IM) is associated with an increased risk of gastric cancer (GC). Thus, the development of new strategies to improve AG/IM is essential for reducing the incidence of GC.We aimed to evaluate the efficacy of rebamipide for improving AG/IM.This was a prospective, randomized, pilot study from a single tertiary referral center. Fifty-three (rebamipide, n = 34 vs. placebo, n = 19) patients, who underwent endoscopic resection for gastric dysplasia or early GC, were analyzed. We obtained tissue samples from the antrum and corpus of the stomach, at the time of screening and 1-year later. The histologic grading of inflammation was performed by histopathologists RESULTS: The AG grade in the antrum improved significantly after rebamipide treatment (pre-administration, 1.870 ± 0.932 vs. post-administration, 1.430 ± 0.986; P = 0.013). Additionally, the severity of IM in the antrum was significantly improved (pre-administration, 1.750 ± 0.963 vs. post-administration, 1.370 ± 1.032; P = 0.038). The rebamipide subgroup analysis revealed that patients with no Helicobacter pylori (HP) infection showed significant improvements in AG in the antrum (pre-administration, 1.880 ± 1.040 vs. post-administration, 1.250 ± 0.894; P = 0.028) and IM in antrum (pre-administration, 1.840 ± 1.012 vs. post-administration, 1.180 ± 0.912; P = 0.020).This study demonstrated that the administration of rebamipide improves AG and IM in the antrum, especially in patients with HP non-infection (KCT0001915).

Background: Calculous cholecystitis is the most common lesion of the gallbladder. Pain abdomen is the common clinical presentation.Calculous and acalculous cholecystitis are the most common indications for cholecystectomy. Gross and microscopic examination of the gall bladder indicates the outcome of the lesions. The various histological findings will reveal the type of the disease entity and prognosis. Materials and Methods: Retrospective study was done, total 120 cases of cholecystectomy specimens were received in pathology department. Formalin fixed specimens were analysed. After processing, H&E stained sections were studied. Results: Chronic calculous cholecystitis is the most common non-neoplastic lesion. calculous cholecystitis(92 cases), acalculous cholecystitis (21 cases), follicular cholecystitis (4 cases), empyema gallbladder (1 case), xanthogranulomatous cholecystitis (1 case), eosinophilic cholecystitis (1 case). Among premalignant lesions, cholecystitis with metaplasia was seen in 40 (33.3%) cases. Pyloric metaplasia (25 cases), Intestinalmetaplasia (15 cases). Conclusion: Chronic calculous cholecystitis was the most common lesion. Histopathological evaluation plays an important role in identifying the metaplastic, dysplastic and incidental carcinoma of the gallbladder. Keywords: Chronic Calculous Cholecystitis, Cholecystectomy, Metaplasia.

Helicobacter pylori is the most prevalent bacteria infecting humans resulting in a variety of gastrointestinal and extra gastrointestinal complications. Although most of the infected adults are asymptomatic, the prevalence varies in different parts of the world it is higher in Eastern and Southern Europe. Eradication of Helicobacter pylori is necessary to prevent precancerous conditions like gastric atrophy, gastric intestinal metaplasia and gastric dysplasia. This comprehensive review addresses briefly on: whom and how to test and treat including recommended first line therapies, salvage therapies, testing for eradication and strategy to be used in primary care clinics.

A 40-year-old man with slightly depressed (0-IIc) type gastric cancer of the pyloric anterior gastric area underwent pre-operative screening for tetralogy of Fallot and endoscopic submucosal dissection (ESD) and was tested for Helicobacter pylori antigens and antibodies. Both tests were negative. He did not have a history of eradication. Pathological diagnosis of ESD showed a well-differentiated adenocarcinoma. The tumor was CD10-positive, MUC5AC-negative, and MUC6-confocal positive; it showed differentiation with gastrointestinal phenotype. Moreover, the tumor cells were lysozyme-positive, resembling Paneth cells. Mucosal glands exhibited intestinal metaplasia on the anal side of the tumor lesion. On the oral side of the tumor, metaplasia was non-existent, with normal pyloric glands present in the mucosal layer. The patient was not infected with H. pylori; however, intestinal metaplasia existed around the early gastric cancer. This suggested that the intestinal metaplasia occurred due to bile reflux, and the gastric neoplasia arose with the metaplasia without an H. pylori infection. This case may potentially help explain gastric cancer development in the absence of H. pylori infection.

SUMMARY Current controversies surrounding breast implants are focused not only on the implant but also on the capsule. There has been tremendous discussion regarding how much of the capsule, if any, should be removed during explantation for benign conditions. The appearance of benign capsules is highly variable ranging from a thin membrane to densely fibrotic with calcifications. The options for capsulectomy include none, partial, complete, complete-intact, and en bloc. Some patients are requesting en bloc capsulectomy even in the absence of anaplastic large cell lymphoma; however, the scientific evidence only supports this for patients with capsular malignancies. The purpose of this article is to review the old and new evidence to answer the question regarding how much capsule should be removed during explantation for benign conditions.

Background Some thyroid nodules cytologically presenting as follicular neoplasm, Hurthle cell (Oncocytic) type (FNHCT), are not oncocytic tumors and represent autonomously functioning thyroid nodules (AFTNs) with TSHR, GNAS, and EZH1 mutations or oncocytic metaplasia. A to be defined subset of FNHCT harbors genome haploidisation-type DNA copy number alterations (GH-CNA). Molecular profiling of FNHCT may distinguish oncocytic neoplasms from its mimics. Methods Consecutive fine-needle aspirates of 180 thyroid nodules over 37 months diagnosed as FNHCT and tested by ThyroSeq v3 were identified. Histologic follow-up was available for 79 of 180 nodules (44%). Results No molecular alterations were found in 76 of 180 nodules (42%), of which 15 were resected (oncocytic metaplasia, n = 7; follicular oncocytic adenoma, n = 8). Of nodules followed without surgery, 17 of 101 (17%) showed TSHR, EZH1, and GNAS mutations of AFTNs. Papillary thyroid carcinoma was identified by BRAF V600E (n = 2) and hyalinizing trabecular adenoma by PAX8-GLIS3 (n = 1). GH-CNA alone was detected in 42 of 180 FNHCT nodules (23%), of which 29 were resected and histologically diagnosed as follicular oncocytic neoplasms. All remaining resected nodules were histologically proven oncocytic neoplasms: 1) RAS-like alterations without GH-CNA (n = 25) and 2) TERT and/or TP53 mutations co-occurring with GH-CNA (n = 6), including anaplastic thyroid carcinoma arising from follicular oncocytic carcinoma with TP53, TERT mutations with GH-CNA (n = 2). Conclusions A proportion of FNHCT nodules are AFTNs and oncocytic metaplasias, which can be suspected based on characteristic mutations or lack of alterations on molecular testing. Among resected FNHCTs, GH-CNAs characterize approximately half of histologically confirmed follicular oncocytic neoplasms.

Pleomorphic adenoma (PA) is the most common salivary gland neoplasm, and its diagnosis is straightforward in the majority of cases. However, not infrequently, PA shows unusual and uncommon histological features that can be confused with those of malignancy. The difficulties in diagnosing PA arise from its ability to mimic invasion, show atypical or metaplastic cytomorphology, and show morphological features that overlap with those of established salivary gland carcinomas. In addition, recognising early malignant transformation to carcinoma ex-pleomorphic adenoma continues to be a frequent challenge. This review describes the diagnostic pitfalls of PA, and offers a systematic approach to avoid them by combining classic histopathology with novel immunohistochemical and molecular tests.

Anaplastic thyroid cancer is the most advanced and aggressive thyroid cancer. It is very rare and isfound in less than 2% of patients with thyroid cancer. It most commonly occurs in people over theage of 60 years. It is usually diagnosed at later stages when the disease has already spread tosurrounding structures or has grown large enough to compress the trachea or esophagus causingpressure symptoms. The patient here, a 75-year-old female, presented with a large swelling in thefront of the neck in euthyroid status which was diagnosed as anaplastic thyroid cancer and wasmanaged surgically and the surgical specimen was sent for histopathological examination. Thepresence of osseous metaplasia with mature bone formation in anaplastic thyroid carcinoma is a rareentity and has been discussed in this case report.