Alexander Maley

Discordance of histopathologic parameters in cutaneous melanoma: Clinical implications

BACKGROUND Histopathologic analysis remains the gold standard for the diagnosis of melanoma, however previous studies have shown a substantial rate of interobserver variability in the evaluation of melanocytic lesions. OBJECTIVE We sought to evaluate discordance in the histopathological diagnosis and microstaging parameters of melanoma and subsequent impact on clinical management. METHODS This was a retrospective review of 588 cases of cutaneous melanoma and melanoma in situ from January 2009 to December 2014 that were referred to Emory University Hospital, Atlanta, GA, for treatment. Per institutional policy, all outside melanoma biopsy specimens were reviewed internally. Outside and institutional reports were compared. RESULTS Disagreement between outside and internal reports resulted in a change in American Joint Committee on Cancer pathologic stage in 114/588 (19%) cases, resulting in a change in management based on National Comprehensive Cancer Network guidelines in 105/588 (18%) cases. LIMITATIONS Given the retrospective nature of data collection and the bias of a tertiary care referral center, cases in this study may not be representative of all melanoma diagnoses. CONCLUSION These findings confirm consistent subjectivity in the histopathologic interpretation of melanoma. This study emphasizes that a review of the primary biopsy specimen may lead to significant changes in tumor classification, resulting in meaningful changes in clinical management.

Rituximab combined with conventional therapy versus conventional therapy alone for the treatment of mucous membrane pemphigoid (MMP)

BACKGROUND The use of rituximab for refractory autoimmune blistering diseases is increasing. Data related to rituximab for the treatment of mucous membrane pemphigoid (MMP) are limited. OBJECTIVE We sought to compare the efficacy of adding rituximab with traditional immunosuppressive therapies in the treatment of MMP. The primary outcome was achievement and time to disease control. METHODS Patients with a diagnosis of MMP from August 2001 to June 2015 who had greater than 6 months of follow-up after the initiation of therapy were reviewed. RESULTS In all, 24 patients were treated with rituximab and 25 were treated with conventional immunosuppression. Of patients, 100% in the rituximab group achieved disease control compared with 40% in the conventional group (P < .01), with a mean time to disease control of 10.17 months and 37.7 months (P = .02). Adverse events were seen in 33% of patients after rituximab, compared with 48% of patients in the conventional group (P = .2). LIMITATIONS Rituximab dosing was not uniform and the 2 groups were not matched in terms of disease severity, nor were they randomized. CONCLUSIONS Our study indicates that the addition of rituximab to conventional therapy in patients with MMP results in more rapid and sustained disease control with potentially fewer adverse events.

Noma: A disease of poverty presenting at an urban hospital in the United States

Noma, also known as cancrum oris or the face of poverty, is a rapidly progressive polymicrobial opportunistic infection resulting in orofacial gangrene and eventually death if untreated. The etiopathogenesis of the disease has been attributed to extreme malnutrition, dehydration, and inadequate oral hygiene.1, 2 Noma is primarily observed among children younger than 6 years in countries with a low human development index, with the highest incidence occurring in the noma belt, which extends from sub-Saharan West Africa to central Sudan.3 Cases in adults and citizens of high income countries are exceedingly rare and have been limited to those with immunodysfunction.4, 5, 6 We report a case of noma in an immunocompetent man who presented to an urban hospital in the United States.

More than keratitis, ichthyosis, and deafness: multisystem effects of lethal GJB2 mutations

Background: Infant death in keratitis‐ichthyosis‐deafness (KID) syndrome is recognized; its association with specific genotypes and pathophysiology is inadequately understood. Objective: We sought to discover characteristics that account for poor outcomes in lethal KID syndrome. Methods: We collected 4 new cases and 9 previously reported, genotyped cases of lethal KID syndrome. We performed new molecular modeling of the lethal mutants GJB2 p.A88V and GJB2 p.G45E. Results: Infant death occurred in all patients with GJB2 p.G45E and p.A88V; it is unusual with other GJB2 mutations. Early death with those 2 “lethal” mutations is likely multifactorial: during life all had ≥1 serious infection; most had poor weight gain and severe respiratory difficulties; many had additional anatomic abnormalities. Structural modeling of GJB2 p.G45E identified no impact on the salt bridge previously predicted to account for abnormal central carbon dioxide sensing of GJB2 p.A88V. Limitations: This clinical review was retrospective. Conclusion: GJB2 p.G45E and p.A88V are the only KID syndrome mutations associated with uniform early lethality. Those electrophysiologically severe mutations in GJB2 reveal abnormalities in many organs in lethal KID syndrome. All patients with KID syndrome may have subtle abnormalities beyond the eyes, ears, and skin. Early genotyping of KID syndrome births will inform prognostic discussion.

Compliance with the College of American Pathologists Protocol for Melanoma in Synoptic and Non-Synoptic reports: A cross-sectional study

fees from AbbVie and Eli Lilly and reimbursement for attending symposia from Janssen, Pfizer, and AbbVie. E.M.G.J. de Jong has received research grants for the independent research fund of the Department of Dermatology of the University Medical Center St Radboud, Nijmegen, The Netherlands, from AbbVie, Pfizer, and Janssen, and has acted as a consultant and/or paid speaker for and/or participated in research sponsored by companies that manufacture drugs used for the treatment of psoriasis, including AbbVie, Janssen, Pfizer, and Merck, Sharp & Dohme.