Immune Checkpoint Inhibitor-Induced Hemorrhagic Gastritis.

Immune checkpoint inhibitors (ICIs) have been increasingly used in the treatment of several malignancies and may target cytotoxic T-lymphocyte-associated antigen-4, programmed cell death-1, and programmed cell death ligand 1, which work on maintaining peripheral immune tolerance. ICIs inhibit these ligands causing an immune-enhancing effect, leading to a wide spectrum of complications from mild mucositis to life-threatening pneumonitis or hepatitis. These complications are collectively called immune-related adverse events. Their prevalence has increased with a rise in ICI use, with rare manifestations being reported in popular literature. We present a case of hemorrhagic gastritis due to the anti-programmed cell death-1 antibody, pembrolizumab.

Benign metastasizing leiomyoma in retroperitoneal lymph nodes with concurrent early stage cervical cancer.

Extrauterine leiomyomas can present as benign metastasizing leiomyoma involving lymph nodes, which can be mistaken for metastatic malignancy. We report a case of a 52-year-old female who presented with postmenopausal bleeding and was found to have an endocervical mass. Imaging demonstrated retroperitoneal lymphadenopathy and biopsy of the cervical mass showed adenocarcinoma of either uterine or cervical origin. Patient underwent hysterectomy, bilateral salpingo-oophorectomy and lymphadenectomy for bulky pelvic and para-aortic lymph nodes. Final pathology was consistent with FIGO 2019 stage IB2 adenocarcinoma of the cervix with concurrent and benign metastasizing leiomyomas involving retroperitoneal lymph nodes.

A Case of Sclerosing Polycystic Adenoma of the Parotid Gland.

Sclerosing polycystic adenoma (SPA) is a rare salivary gland tumor with about 100 cases reported in the literature. We describe a case of SPA in the parotid gland and review the diagnostic tools used for identifying SPA. A 24-year-old male with a two-year history of right-sided face mass, initially thought to be pleomorphic adenoma of the parotid gland after fine needle aspiration (FNA). Following superficial parotidectomy, histologic features were consistent with SPA. This case illustrates the challenge of pre-operative assessment for SPA. Recent study has suggested SPA is a neoplasm and definitive treatment is surgical excision.

Analysis and Comparison of Tissue-Marking Dye Detection via Light Microscopy, Telemicroscopy, and Virtual Microscopy.

Objectives: To examine the fidelity of ink color identification using light microscopy (LM), telemicroscopy (TM), and virtual microscopy (VM). Methods: Twenty H&E-stained frozen section slides, prepared after tissue inking with five stain combinations, were assessed by three pathologists using LM, TM, and VM. TM was performed using Mikroscan D2 slide scanner/LiveQ software with various objectives. VM was performed using Mikroscan D2 scanner/Qumulus software, specimens digitized at20×. Results: Sensitivity/specificity by LM was 100%/100% for all colors. TM showed high overall specificity but poor sensitivity, particularly red (54%). VM showed high specificity for all colors except black (69%) and, consequently, poor sensitivity for all colors except black (96%). Conclusions: TMD identification via telepathology showed loss of sensitivity/specificity vs LM and highlighted the need for caution when interpreting TMDs with digital technologies and the need for validation protocols.

Prevalence of vitamin D deficiency in infertile women with polycystic ovarian syndrome and its association with metabolic syndrome - A prospective observational study.

OBJECTIVE: The main purpose of this study was to determine the prevalence of vitamin D deficiency in infertile women with polycystic ovarian syndrome (PCOS) and to explore the association of hypovitaminosis D with metabolic syndrome in women with PCOS. STUDY DESIGN: A prospective observational study was conducted in a tertiary care, infertility centre from March 2016 to March 2017. The primary outcome was estimation of the prevalence of vitamin D deficiency in infertile PCOS women. Secondary outcomes were to study the association of hypovitaminosis D with metabolic syndrome, obesity and hypercholesterolemia in PCOS patients. RESULTS: A total of 256 infertile women with PCOS were included in the study. Vitamin D deficiency was observed in 70.3% women, 20.3% were vitamin D insufficient and only 9.4% were vitamin D sufficient. Metabolic syndrome was seen in 80/256 (31.25%) women. There was no evidence of an association between hypovitaminosis D and metabolic syndrome, obesity or hyperlipidemia. There was a strong evidence of an association between waist circumference of >80 cm and vitamin D deficiency (p = 0.02). CONCLUSION: Vitamin D deficiency is highly prevalent in infertile PCOS women and there seems to be no association between hypovitaminosis D and the metabolic syndrome in the same population.

Effectiveness of Anti-Mullerian Hormone-tailored Protocol Compared to Conventional Protocol in Women Undergoing In vitro Fertilization: A Randomized Controlled Trial.

BACKGROUND: Assessment of ovarian reserve before an in vitro fertilization cycle (IVF) is one among the many factors that predicts a successful cycle. Individualized protocol based on ovarian reserve is designed to optimize the pregnancy outcome without compromising the patient safety. Although authors have shown that anti-Mullerian hormone-tailored (AMH) protocols have reduced the treatment burden and improved pregnancy rates, a few others have questioned its efficacy. AIMS: The aim of this study was to decide whether the AMH-tailored protocol or the conventional protocol better decides IVF outcomes. SETTING AND DESIGN: Prospective randomized controlled trial conducted at a tertiary level university hospital. MATERIALS AND METHODS: Patients undergoing theirfirst IVF cycle who fulfilled the inclusion criteria were recruited and randomized to each group. Serum follicle-stimulating hormone was done for the patients on day 2 or 3 of a prior menstrual cycle, and serum AMH was done in the preceding cycle. STATISTICAL ANALYSIS: Analysis was performed using SPSS software version 16. RESULTS AND CONCLUSION: There were 100 patients in each group. A total of 83 patients underwent embryo transfer in the conventional group and 78 patients in the AMH group. The clinical pregnancy rates per initiated cycle (36.4% vs. 33.3%) and per embryo transfer (45.1% vs. 41.3%) were similar in both the groups. There was no statistical difference in the number of cycles cancelled due to poor response or the risk of ovarian hyperstimulation syndrome in both the groups. Hence, this study showed the similar effectiveness of AMH-tailored protocol and conventional protocol in women undergoing IVF.

A case report of mesenteric heterotopic ossification: Histopathologic and genetic findings.

Mesenteric heterotopic ossification (MHO) is very rare and occurs in mid- to late-adulthood, usually in the context of prior abdominal surgery. The mechanisms of MHO are unknown. Here we describe the case of a 72-year-old man with MHO. Standard histological staining revealed that MHO occurred through an endochondral process. By comparison to known mutations in genetic conditions of HO such as fibrodysplasia ossificans progressiva (FOP) and progressive osseous heteroplasia (POH), DNA sequencing analysis demonstrated the presence of a commonly occurring heterozygous synonymous polymorphism (c.690G>A; E230E) in the causative gene for FOP (ACVR1/ALK2). However, no frameshift, missense, or nonsense mutations in ACVR1, or in the causative gene for POH (GNAS), were found. Although genetic predisposition may play a role in MHO, our data suggest that mutations which occur in known hereditary conditions of HO are not the primary cause.

Clear Cell Carcinoma of the Endometrium: Evaluation of Prognostic Parameters in a Multi-institutional Cohort of 165 Cases.

OBJECTIVES: Clear cell carcinoma (CCC) comprises a rare yet an aggressive subtype, accounting for less than 5% of all uterine carcinomas. Several clinicopathologic features have been predictive of poor prognosis; however, data remain controversial. The aim of this study was to evaluate the clinicopathologic features of a multi-institutional cohort of endometrial CCC in order to identify which, if any, have prognostic significance. METHODS: Retrospective review of endometrial CCC diagnosed between 1995 and 2012 at 3 institutions was conducted to evaluate clinicopathologic parameters: age, race, tumor size, stage, myometrial invasion (MI), lymphovascular invasion, lymph node and adnexal involvement, adjuvant therapy, and outcomes. Data were analyzed using Fisher exact, Cox regression, and Kaplan-Meier analyses. RESULTS: Patients' ages ranged from 36 to 90 years (median, 67 years). The median tumor size was 3.6 cm. Inner-half MI was present in 44%, lymphovascular invasion in 34%, adnexal involvement in 16%, and lymph node metastasis in 30% of cases. Fifty-eight percent of the patients presented with early-stage disease. The 5-year overall survival (OS) was 58%. Shorter disease-free interval (DFI) was significantly associated with older age at diagnosis (>70 years), advanced-stage disease, adnexal involvement, and deep MI (P = 0.005, P = 0.001, P = 0.001, and P = 0.003, respectively). Patients who received adjuvant chemotherapy had a significantly worse DFI and 5-year OS (P = 0.001 and P = 0.001, respectively). A significantly shorter 5-year OS was noted with advanced stage (III-IV) and presence of adnexal involvement (P = 0.001 and P = 0.021, respectively). On Cox regression analysis, advanced-stage disease, older age, and adnexal involvement were significant independent predictors of worse DFI (P = 0.001, P = 0.005, and P = 0.019, respectively), whereas inner-half MI was a significant independent predictor of longer DFI (P = 0.004). Adjuvant radiotherapy alone was a significant independent predictor of better 5-year OS (P = 0.012). CONCLUSIONS: In our series of endometrial CCC, older age at diagnosis, advanced stage, deep MI, and adnexal involvement were independent poor prognostic factors. Adjuvant radiotherapy had a significant positive impact on 5-year OS.

Granulosa Cell Tumors: Novel Predictors of Recurrence in Early-stage Patients.

Granulosa cell tumors (GCTs) comprise 2% to 5% of ovarian neoplasms, with unpredictable patterns of recurrence. The HER family, GATA4, and SMAD3 genes are reportedly involved in GCT proliferation and apoptosis and may serve as new predictors of recurrence. The aim of the study was to evaluate novel predictors of recurrence in GCT from a large single institution cohort. Patients diagnosed with GCTs (n=125) between 1975 and 2014 were identified. Clinicopathologic parameters were obtained and immunohistochemical evaluation was performed of calretinin, inhibin, HER2, CD56, SMAD3, and GATA4. Statistical analyses were conducted using Fisher exact test and Kaplan-Meier survival curves and Cox regression analysis. The median follow-up period was 120 months (range, 1-465 mo). Recurrence was noted in 12/125 (9.6%) patients. Kaplan-Meier analysis showed a shorter mean disease-free interval in whites versus blacks (P=0.001), stage III-IV versus stage I-II (P=0.0001), patients treated with surgery+chemotherapy versus surgery (P=0.0001), mitotic rate ≥4 (P=0.005), severe nuclear pleomorphism (P=0.013), high HER2 expression (P=0.001), high CD56 expression (P=0.001), and high SMAD3 expression (P=0.001). On Cox regression analysis, SMAD3 and type of treatment received were the only 2 independent prognostic factors for disease-free interval (P=0.03 and P=0.007, respectively). On subanalysis for early-stage (stage I) GCTs, the need for adjuvant chemotherapy and high expression of SMAD3 continued to be independent predictors of recurrence (HR=10.2, P=0.01 and HR=8.9, P=0.001, respectively).

Patients' perception towards directly observed treatment - A qualitative study from Kollam district, Kerala, southern India.

BACKGROUND: The Direct Observation of Treatment (DOT) is an important component of the country's TB Control strategy. Standards of TB care in India and the End TB strategy emphasised the importance of a patient-centered approach to foster adherence. A qualitative study was conducted to explore the perception of people with Tuberculosis in Kerala regarding DOT, mechanisms to make the treatment of TB more patients centered and to identify the preferable mechanisms to ensure adherence. METHODS: Six focus group discussions were conducted - two among people with TB from rural area, two among people with TB in urban area, one among multipurpose health workers of rural area and one among key field staff of TB control in urban area. RESULTS: Patients who were on a strict DOT were unhappy about the issues of confidentiality, patient inconvenience and provider centered approach. A flexible, patient centered approach were a family member can act as the DOT provider with guidance from a trained health worker was evolved as the most acceptable and comfortable mode of treatment to majority of the TB patients. They felt that a strict external monitor as a DOT provider was not a necessity in majority of the cases. Only practical way to effectively incorporate ICT in monitoring patient compliance in current scenario was identified as daily phone call reminders. Patients also expressed their concerns in keeping the medicines for entire duration at home. CONCLUSION: A flexible patient wise individualized system based on patient's behavior, literacy and awareness along with attitude of family members is needed to ensure adherence to anti TB drugs.

Prevalence of chromosomal abnormalities and Y chromosome microdeletion among men with severe semen abnormalities and its correlation with successful sperm retrieval.

AIM: To estimate the prevalence of chromosomal abnormalities and Y chromosome microdeletion among men with azoospermia and severe oligozoospermia and its correlation with successful surgical sperm retrieval. SETTING AND DESIGN: A prospective study in a tertiary level infertility unit. MATERIALS AND METHODS: In a prospective observation study, men with azoospermia and severe oligozoospermia (concentration <5 million/ml) attending the infertility center underwent genetic screening. Peripheral blood karyotype was done by Giemsa banding. Y chromosome microdeletion study was performed by a multiplex polymerase chain reaction. RESULTS: The study group consisted of 220 men, 133 of whom had azoospermia and 87 had severe oligozoospermia. Overall, 21/220 (9.5%) men had chromosomal abnormalities and 13/220 (5.9%) men had Y chromosome microdeletions. Chromosomal abnormalities were seen in 14.3% (19/133) of azoospermic men and Y chromosome microdeletions in 8.3% (11/133). Of the 87 men with severe oligozoospermia, chromosomal abnormalities and Y chromosome microdeletions were each seen in 2.3% (2/87). Testicular sperm aspiration was done in 13 men and was successful in only one, who had a deletion of azoospermia factor c. CONCLUSIONS: Our study found a fairly high prevalence of genetic abnormality in men with severe semen abnormalities and a correlation of genetic abnormalities with surgical sperm retrieval outcomes. These findings support the need for genetic screening of these men prior to embarking on surgical sperm retrieval and assisted reproductive technology intracytoplasmic sperm injection.

Interobserver Variability in the Diagnosis of Uterine High-Grade Endometrioid Carcinoma.

CONTEXT: -Low interobserver diagnostic agreement exists among high-grade endometrial carcinomas. OBJECTIVE: -To evaluate diagnostic variability in International Federation of Gynecology and Obstetrics (FIGO) grade 3 endometrioid adenocarcinoma (G3EC) in 2 different sign-out practices. DESIGN: -Sixty-six G3EC cases were identified from pathology archives of Wayne State University (WSU, Detroit, Michigan) (general surgical pathology sign-out) and 65 from Memorial Sloan Kettering Cancer Center (MSK, New York, New York) (gynecologic pathology focused sign-out). Each case was reviewed together by 2 gynecologic pathologists, one from each institution, and classified into the G3EC group or a reclassified group. Clinicopathologic parameters were compared. RESULTS: -Twenty-five WSU cases (38%) were reclassified as undifferentiated (n = 2), serous (n = 4), mixed endometrioid and serous carcinomas (n = 12), and FIGO grade 2 endometrioid adenocarcinomas with focal marked nuclear atypia (n = 7). Eleven MSK cases (17%) were reclassified as undifferentiated (n = 5), serous (n = 1), mixed endometrioid and serous carcinomas (n = 4), and mixed endometrioid and clear cell carcinomas (n = 1). Agreement rate between original and review diagnosis was 83% (54 of 65) at MSK and 62% (41 of 66) at WSU (P = .01) with an overall rate of 73% (95 of 131). There were more undifferentiated carcinomas at MSK than there were at WSU (45% [5 of 11] versus 8% [2 of 25]; P = .02). There were more grade 2 endometrioid adenocarcinomas with focal, marked nuclear atypia at WSU (28%; 7 of 25) than there were at MSK (0%) (P = .03). Mixed endometrioid and serous carcinoma was the most common misclassified subtype (44%; 16 of 36). CONCLUSION: -Moderate interobserver variability exists in the diagnosis of G3EC with a significantly greater diagnostic agreement rate in gynecologic pathology-focused sign-out than in general sign-out practice.

Can problematic fibroepithelial lesions be accurately classified on core needle biopsies?

Fibroepithelial lesions (FEL) of the breast are notoriously difficult to classify on core needle biopsies. The goal of this study was to evaluate interobserver variability and accuracy of subclassifying difficult FELs into fibroadenoma (FA) and phyllodes tumors (PTs). We identified 50 breast core needle biopsies, initially diagnosed generically as FEL, with subsequent excision and final diagnosis of either FA or benign PT. Five surgical pathologists from one institution independently reviewed these in 3 rounds. The pathologists were blinded to the final excisional diagnosis. Two diagnostic categories were allowed: FA and PT. A set of histologic criteria was provided including the presence of subepithelial condensation, stromal heterogeneity, overgrowth, pleomorphism, fragmentation, cellularity, adipose tissue entrapment, and mitotic count and asked to review the slides for the second round. A third round of interpretations was conducted after each criterion was defined. Interobserver agreement for the diagnosis and each criterion was evaluated using the κ level of agreement. Accuracy of ratings to final diagnosis was calculated using Wilcoxon signed-rank test. κ Values for interobserver agreement were fair for the first and second rounds varying from 0.20 to 0.22, respectively. This increased to 0.27 in round 3. When considering each category, the κ value varied from 0.26 to 0.29 for FA and 0.28 to 0.14 for PT. Overall, there was fair agreement between the pathologists in all categories. The rate of correctly diagnosed cases ranged from 40% in the first round, to 48% in the second round, to 67% in round 3. Overall the pathologists performed better in identifying FA than PT. The accuracy of interpretations was significantly different between the first (40%), second (48%), and third rounds (67%).

The prognostic significance of histologic type in early stage cervical cancer - A multi-institutional study.

BACKGROUND: Cervical adenocarcinomas (ADC) have been viewed as more aggressive than squamous cell carcinoma (SCC). We analyzed an international cohort of early stage cervical cancer to determine the impact of histologic type. METHODS: Retrospective analysis of patients with SCC (148 patients) and ADC (130 patients) stages IA1-IB2 who underwent surgery at our three institutions (two from Detroit, one from Mexico) from 2000-2010 was performed for: age, stage, tumor size, lymphovascular invasion (LVI), invasion depth, lymph node status (LN), recurrence and survival. Pathologic review proceeded inclusion. RESULTS: In the Latino population, ADC's tended to be higher grade (p=0.01), while SCC's were larger with deeper invasion (p<0.001). LVI and LN were not significantly different. Recurrence rate (RR) was 8% (8/101) in ADC and 11.8% (9/76) in SCCs. 5 year survival (OS) was equivalent (98.2% and 95.2% for ADC and SCC respectively, p=0.369). In the Detroit cohort, we noted no difference in size, grade, depth of invasion, LVI, LN. RR was 8/72 (13.7%) for SCC and 4/29 (13.7%) but not statistically different between the tumor types (p=0.5). 5 year survival was 91% and 92% for ADC and SCC, respectively. In this population 33% of the patients with SCC and 34% of the patients with ADC received adjuvant chemo-radiation (p=0.4). Histologic type demonstrated no significant outcome difference for any type of adjuvant therapy. CONCLUSION: Comparing early stage disease cervical ADC and SCC suggests equivalent recurrence and survival. Therefore, the paradigm of more aggressive management of early stage cervical ADC warrants further investigation.

Imprint cytopathology of core needle biopsies: a "first responder" role for cytotechnologists.

INTRODUCTION: Imprint cytopathology (IC) of image-guided core needle biopsies (CNBs) is used to ensure adequate sampling. In our institution, cytotechnologists (CyTs) are the "first responders" for on-site adequacy assessment (OSAA) of image-guided CNBs. We report our experience with this expanded and relatively unexplored role for CyT. MATERIALS AND METHODS: We reviewed all image-guided CNBs performed over a 12-month period that required OSAA. OSAA was provided primarily by CyT. Interpretation between all IC specimens and tissue diagnoses (concordance) and between adequate IC specimens and tissue diagnoses (accuracy) were analyzed. Performance was compared using the Fisher exact test. We retrospectively reviewed discrepant cases to deduce the reasons for discordance. RESULTS: We evaluated 255 CNBs: 179 computed tomography-guided, 74 ultrasonography-guided, 2 endoscopy-guided. Lung (39%) followed by liver (16%) and lymph node (11%) were the most frequent sites of OSAA IC. Overall adequacy and accuracy rates were 80.8% and 87.9%, respectively, with a concordance rate of 81.2%. The performance for CyT alone, CyT/cytopathology fellow, and CyT/cytopathologist were comparable (P > 0.05). Review of discordant cases showed agreement with 91% of OSAA IC cases originally interpreted as inadequate, but with only 19% interpreted as adequate. CONCLUSIONS: OSAA IC of CNBs expands the CyT's role in an effort to ensure adequate sampling. CyT performance was high in recognition of adequate versus inadequate IC slides when compared with the tissue. Reasons for discrepancy included sampling error and overinterpretation of atypia as being sufficient evidence of adequacy. Organ-specific cytologic criteria to assess adequacy are required to reduce interpretation error.

Postpartum pemphigoid gestationis.

Pemphigoid gestationis (PG) or herpes gestationis is a rare autoimmune subepidermal blistering disorder associated with pregnancy. The condition typically develops during the second or third trimester of pregnancy, but has been rarely reported in the first trimester and postpartum period. Here, we report a case of PG that presented for the first time in the postpartum period, associated with a low birth weight baby.

AIDS associated Kaposi's sarcoma.

Epidemic Kaposi's sarcoma (KS) is the most common malignant neoplasm occuring in HIV patients. Although the prevalence of HIV infection is high in Asian countries, KS is rarely reported. We report a case of fatal KS involving the skin and mucous membranes in a homosexual male.

Localized psoriasis herpeticum: Case report and review of literature.

Kaposi's varicelliform eruption (KVE) is a widespread cutaneous eruption caused by viruses, especially herpes simplex virus in patients with pre-existing dermatoses. "Psoriasis herpeticum" refers to the rare occurrence of KVE in patients with psoriasis. We report a case of KVE localized to the face in a patient with exfoliative dermatitis secondary to psoriasis. This case is being reported to make the treating clinician aware of the possibility of KVE in patients with psoriatic erythroderma.

Purpuric macules with vesiculobullous lesions: a novel manifestation of Chikungunya.

BACKGROUND: Chikungunya (CHIK) is an emerging viral disease with a myriad of cutaneous manifestations. AIMS: The aim of our study was to document the morphology and evolution of skin lesions in cases presenting with fever, purpuric macules and vesiculobullous lesions, to confirm its causative relationship with CHIK, and to investigate further in order to delineate possible mechanisms of bulla formation in these cases. MATERIALS AND METHODS: A prospective, descriptive hospital-based study was carried out at a tertiary health care centre in Kerala. A total of 10 patients were enrolled in the study and investigated. RESULTS: All cases had morbilliform eruption prior to onset of purpuric macules. Eight cases developed vesiculobullous lesions that arose either de novo or over a part or whole of the purpuric macules. Skin lesions resolved within an average of 7.6 days leaving post-inflammatory hypopigmentation. IgM CHIK enzyme-linked immunosorbent assay (ELISA) was positive in all 10 patients. Tzanck smear from the bullae showed lymphocytes in most cases along with acantholytic cells, necrotic keratinocytes or occasional neutrophils. Skin biopsy showed intraepidermal or subepidermal bullae. Immunohistochemistry revealed predominantly CD8 positive T lymphocytes in the infiltrate. The prognosis was good with supportive management alone. DISCUSSION: The clinical features in our cases are comparable to the 3 previous reports of vesiculobullous lesions in CHIK affected infants. Based on the current evidence, we hypothesize that at least 2 mechanisms are at play for these skin lesions; CHIK virus induced keratinocyte necrosis followed by a cytotoxic immune response, and possible modulation of rash by drugs. CONCLUSION: With severe epidemics of CHIK spreading from Asia and Africa to the Western hemisphere, we must consider bullous CHIK as a differential diagnosis in cases with fever and purpuric and vesiculobullous lesions.