Cell polarity (the 'four lines') distinguishes gastric dysplasia from epithelial changes in reactive gastropathy.

AIMS: Gastric dysplasia is a risk factor for synchronous and subsequent gastric carcinoma. Distinguishing gastric dysplasia from reactive changes is subject to interobserver disagreement and is a frequent reason for expert consultation. We previously used assessment of surface cell polarity (the 'four lines') as a key feature to decrease equivocal diagnoses in Barrett oesophagus. In the current study, we examined for the presence or absence of the four lines in gastric dysplasia and reactive gastropathy. MATERIALS AND METHODS: The study includes all (n = 91) in-house biopsies with at least gastric dysplasia from the surgical pathology archives of two academic institutions during a 5-year period from 2008 to 2012. A reactive gastropathy group (n = 60) was created for comparison. RESULTS: The dysplasia/neoplasia group was comprised of 14 biopsies of gastric foveolar-type dysplasia, 59 of intestinal-type dysplasia, 14 with dysplasia in fundic gland polyps, three pyloric gland adenomas and one oxyntic gland adenoma. Loss of surface cell polarity was seen in all 88 dysplasia cases with evaluable surface epithelium. All 57 reactive gastropathy cases with evaluable surface epithelium showed intact surface cell polarity except in focal areas directly adjacent to erosions in 17 cases, where the thin wisp of residual surface mucin could not be appreciated on haematoxylin and eosin. CONCLUSION: Surface cell polarity (the four lines) was lost in all gastric dysplasia biopsies with evaluable surface epithelium and maintained in all biopsies of reactive gastropathy. Caution should be taken in using this feature adjacent to erosions in reactive gastropathy.

Lymphocytic and collagenous colitis in children and adolescents: Comprehensive clinicopathologic analysis with long-term follow-up.

Microscopic colitis (MC) is characterized by chronic watery diarrhea, endoscopically normal findings, and abnormal histology. While mostly encountered in adults, pediatric cases are rare and may show varying presentations. Our pathology data system was searched from 1984 to 2019 for patients ≤18 years of age with a lymphocytic colitis (LC) or collagenous colitis (CC) pattern of injury. Twenty-seven cases (23 LC and 4 CC) were retrieved. LC was more prevalent than CC (85% vs 15%, respectively) and affected slightly younger individuals (mean, 9.8 years versus 12.25 years). Immune dysregulation was documented in 11 (41%) patients. Most patients presented with watery diarrhea (n = 26, 96%) and either abdominal pain (n = 18, 67%), nausea/vomiting (n = 5, 19%), flatulence (n = 6, 22%), and/or weight loss (n = 1, 4%). A subset of patients (n = 10, 37%) demonstrated endoscopic abnormalities. Histologically, some patients with LC and CC displayed focal cryptitis or crypt abscess formation (n = 7, 26%) and focally increased crypt apoptosis (n = 9, 33%) in the absence of chronic injury. Clinical follow-up data were available for 23 (85%) patients with variable clinical responses recorded. Only 8 patients experienced complete symptom resolution. Twelve patients (11 LC and 1 CC) had subsequent biopsy material; of which, one developed histologic features of inflammatory bowel disease and another was found to have a CTLA-4 deficiency. Our study shows that pediatric patients with MC may have atypical clinical, histologic, and endoscopic findings and variable clinical responses. Underlying inflammatory and/or genetic conditions may be eventually unmasked, and genetic testing may be helpful in a small subset of patients.

The "Race" Toward Diversity, Inclusion, and Equity in Pathology: The Johns Hopkins Experience.

With 3.8% black trainees in 2012, pathology had significantly fewer trainees from groups underrepresented in medicine compared to other specialties. To address this, faculty in the Johns Hopkins Department of Pathology established an outreach program and funded rotation for students underrepresented in medicine and from disadvantaged groups. The aims were to increase exposure to the field and improve diversity, inclusion, and equity in pathology. A 1-month rotation for students underrepresented in medicine was established in 2013. Rotation schedules tailored to each rotator's interests included resident conferences and individual faculty meetings. In 2016, a proactive outreach program was established. Faculty visited historically black medical schools and underrepresented in medicine student groups at other institutions, where they gave a "Careers in Pathology" presentation targeted to second- and third-year medical students. Faculty also attended underrepresented in medicine student conferences and participated in high school student programs to further expand the underrepresented in medicine pipeline into medicine and pathology. Since 2016, fourteen outreach presentations have been delivered. The number of rotators increased from 1 in 2013 to 18 in July 2019. Rotators self-identified as African, African American, Hispanic, and Native American. Most were second- to fourth-year medical students, and 1 was a pathology resident. Six rotators are currently pathology residents, and others are strongly considering applying to pathology. The outreach efforts account for the success of our rotation, which, in turn, has had a positive impact on interest in pathology. However, we recognize barriers to retention and intend to incorporate additional professional development activities to further address equity.

A KRAS wild type mutational status confers a survival advantage in pancreatic ductal adenocarcinoma.

BACKGROUND: The KRAS oncogene is a driver mutation and is present in greater than 90% of pancreatic ductal adenocarcinomas (PDAC). A subset of these tumors, however, do not harbor mutations in KRAS (wild type KRAS). Studies have shown that patients with mutated KRAS have a poorer survival on first-line gemcitabine-based chemotherapy compared to wild type KRAS. In this study, we examined a cohort of patients with PDAC at our institution who were either wild type or mutant for the KRAS gene and assessed for differences in survival and response to different chemotherapeutic regimens. METHODS: We examined clinical records of patients treated at the Abramson Cancer Center of the University of Pennsylvania from 2013 to 2017. Patients with a pancreatic mass and a histologic diagnosis of pancreatic or pancreaticobiliary adenocarcinoma were identified. Thirty-nine patients with PDAC who underwent tumor sequencing at Penn Medicine's Center for Personalized Diagnostics (CPD) were selected for further study. Twelve patients were identified whose tumors were KRAS wild type. Twenty-seven patients with PDAC whose tumors harbored KRAS mutations were selected as controls (KRAS mutant). RESULTS: We noted a longer overall survival (OS) among KRAS wild type patients compared to KRAS mutant patients (P=0.026). This was independent of the age at diagnosis, patient gender, stage of diagnosis, tumor morphology, mismatch repair (MMR) status, and chemotherapeutic regimen. CONCLUSIONS: Similar to previously reported studies, PDAC with a KRAS wild type mutational profile has a better prognosis with a longer OS. This improved prognosis is independent of the protocol utilized in therapy for these patients. Our findings suggest that future clinical trials in pancreatic cancer should take into consideration the presence of KRAS mutations in their pre-planned analysis when assessing the efficacy of a novel therapeutic approach. This may be a crucial factor in trial concepts and outcomes.

Erythropoietic protoporphyria in an adult with sequential liver and hematopoietic stem cell transplantation: A case report.

Erythropoietic protoporphyria (EPP) is a rare inherited disorder of the heme biosynthesis pathway resulting in the accumulation of protoporphyrins in the blood, erythrocytes, and other tissues. Because of a gene mutation in the FECH gene, ferrochelatase, the enzyme involved in the final step of heme synthesis, is deficient in these patients. Although the major symptom of this disorder is photosensitivity, rarely, it can cause progressive liver disease requiring liver transplantation (LT). However, LT is not curative and only bone marrow transplantation (BMT) can correct the underlying enzymatic defect. Because liver disease results from accumulation of protoporphyrin in the liver, LT without hematopoietic stem cell transplantation leaves the new liver at risk for similar EPP-related damage. A handful of pediatric patients undergoing sequential LT and stem cell transplantation have been described in the literature; however, to date none has been described in detail in adults. We report a case of an adult male with EPP and liver failure who successfully underwent a sequential liver and hematopoietic stem cell transplantation (HSCT).

Iatrogenic Kaposi's Sarcoma in an HIV-Negative Young Male With Crohn's Disease and IgA Nephropathy: A Case Report and Brief Review of the Literature.

BACKGROUND: Kaposi's sarcoma (KS) is a vascular tumor arising in association with human herpesvirus-8 (HHV-8) infection, and different variants show different clinical presentations. Isolated intestinal KS in the background of Crohn's disease (CD) is exceedingly rare with only 3 cases reported in the English literature (from 1966 to 2016). CASE PRESENTATION: Herein, we report a case of intestinal KS in a 21-year-old HIV-negative Ethiopian male with a long-standing history of steroid therapy for his underlying IgA nephropathy. Recent gastrointestinal biopsies confirmed an additional diagnosis of CD. Despite the addition of Infliximab to his therapy, his CD remained refractory, and a laparoscopic-assisted ileocolectomy was performed to alleviate a partial small bowel obstruction. Examination of his terminal ileum demonstrated a polypoid mass with adjacent incidental ileal submucosal nodules. These nodules were composed of plump spindle cells with scattered mitoses and vascular channels with extravasated red blood cells. Intratumoral hyaline globules were also noted. Immunohistochemistry revealed HHV-8 positivity, confirming the histologic impression of KS. CONCLUSIONS: Here we report the fourth case of KS in CD in an HIV-negative patient and only the third case of isolated intestinal KS in the setting of CD. A review of the literature suggests that attenuation of immunosuppressive therapy may be adequate management of iatrogenic KS in the absence of a systemic HHV-8 infection.