Sartori‐Valinotti, Julio C.

AbstractBackgroundOral lichen planus confers a 1% risk of transformation to oral squamous cell carcinoma. While prior exome sequencing studies have identified multiple genetic mutations in oral squamous cell carcinoma, mutational analyses of lichen planus‐derived OSCC are lacking. We sought to clarify genomic events associated with oral lichen planus transformation.MethodsUsing rigorous diagnostic criteria, we retrospectively identified patients with non‐transforming oral lichen planus (i.e., known to be non‐transforming with 5 years of clinical follow‐up; n = 17), transforming oral lichen planus (tissue marginal to oral squamous cell carcinoma, n = 9), or oral squamous cell carcinoma arising in lichen planus (n = 17). Gene mutational profiles derived from whole‐exome sequencing on fixed mucosal specimens were compared among the groups.ResultsThe four most frequently mutated genes in transforming oral lichen planus and oral squamous cell carcinoma (TP53, CELSR1, CASP8, and KMT2D) identified 12/17 (71%) of oral squamous cell carcinomas and 5/9 (56%) of transforming oral lichen planus but were absent in non‐transforming oral lichen planus. We identified other known oral squamous cell carcinoma mutations (TRRAP, OBSCN, and LRP2) but also previously unreported mutations (TENM3 and ASH1L) in lichen planus‐associated oral squamous cell carcinomas.ConclusionsThese findings suggest alterations in DNA damage response and apoptosis pathways underlie lichen planus‐related oral squamous cell carcinoma transformation and are supported by mutational signatures indicative of DNA damage. This study characterized patterns of mutational events present in oral lichen planus associated with squamous cell carcinoma and in squamous cell carcinoma associated with oral lichen planus but not in non‐transforming oral lichen planus.

Abstract Introduction Histiocytic disorders pose significant diagnostic and management challenges for the clinicians due to diverse clinical manifestations and often non-specific histopathologic findings. Herein, we report the tumor board experience from the first-of-its-kind Histiocytosis Working Group (HWG). Materials and Methods The HWG was established in June 2017 and consists of experts from 10 subspecialties that discuss cases in a multidisciplinary format. We present the outcome of tumor board case discussions during the first 2 years since its inception (June 2017-June 2019). Results Forty cases with a suspected histiocytic disorder were reviewed at HWG during this time period. Average number of subspecialties involved in HWG case discussion was 5 (range, 2-9). Histiocytosis Working Group tumor board recommendations led to significant changes in the care of 24 (60%) patients. These included change in diagnosis (n = 11, 27%) and change in treatment (n = 13, 33%). Conclusion Our report highlights the feasibility of a multidisciplinary tumor board and its impact on outcomes of patients with histiocytic disorders.

Abstract Introduction: VEXAS syndrome (vacuoles, E1 ubiquitin ligase, X-linked, autoinflammatory, somatic) is a newly recognized inflammatory disorder caused by somatic mutations in the UBA1 gene. Bone marrows from these patients reveal a range of morphological changes in hematopoietic precursor cells. In this study, we aim to assess the laboratory indices and morphologic spectrum of bone marrow pathology in VEXAS syndrome. Methods: We identified 16 cases of VEXAS syndrome. All cases had confirmed UBA1 mutation. We reviewed bone marrow biopsies corresponding to the date of diagnosis. This study was approved by the Mayo Clinic Institutional Review Board. Results: All patients were male with a median age of 73 years - associated autoimmune disorders included Sweet syndrome, inflammatory arthritis, relapsing polychondritis and granulomatosis with polyangiitis. 14/16 patients had anemia with median hemoglobin of 10.4 (Range: 6.7- 14.1 g/dL). 15/16 had macrocytosis with median MCV 110.4 (Range: 94.8- 123.1 /fL). 5/16 had thrombocytopenia with median platelet count 174 (Range: 20- 500 x10^9/L). 7/16 had leukopenia with median WBC 3.65 (Range: 2.4- 11.6 x10^9/ L). The ESR and CRP medians were 61.0 mm/hr and 81.5 mg/L, respectively. Karyotype was performed in 12 patients of which 11 were normal and the remaining case showed a complex karyotype. An NGS panel targeting the most frequent myeloid disorder associated gene mutations was negative in 10/15 cases. GS for myeloid mutations revealed pathogenic mutations in 5 patients, involving genes TET2 (2/5), DNMT3A (2/5), and TP53 (1/5). Conclusions: Bone marrow findings in VEXAS syndrome, in this series of 16 patients, are individually non-specific, yet when taken altogether in the overtly abnormal cases, are very suggestive when the clinical index of suspicion is high. In such scenarios, the combined clinical and bone marrow findings should prompt discussion and consideration for UBA1 mutation testing given the significant clinical implications for patient management and prognosis. Disclosures Patnaik: StemLine: Research Funding; Kura Oncology: Research Funding. Warrington: Eli Lilly: Research Funding; Kiniksa: Research Funding.

Introduction Dermatologic complaints are a common reason for emergency department visits. Methods Retrospective chart review from 1 January 2015 to 31 December 2019. Patients in the Mayo Clinic Emergency Department receiving dermatology consultation were included. Results Dermatitis (24.7%, n = 113), infection (20.4%, n = 93), and drug reaction (10.3%, n = 47) accounted for the majority of diagnoses. Emergency department providers often provide no diagnosis (38%) or a differential diagnosis (22%), and dermatology consultation frequently alters diagnosis (46%) and treatment (83%). Patients receiving in-person consultations are admitted more frequently than those receiving teledermatology consultations (40% vs. 16%, p < 0.001). Primary diagnostic concordance with subsequent dermatology evaluation is high for in-person (94%) and teledermatology (88%) consultations. Discussion This is the largest study of emergency department dermatology consultations in the United States and the first to compare in-person and teledermatology emergency department consultation utilization in clinical practice. These modalities are utilized in a complementary fashion at our institution, with severe dermatologic diagnoses seen in-person. The valuable role of emergency department dermatologists is highlighted by frequent changes to diagnosis and treatment plans that result from dermatology consultation. Furthermore, our data suggest that teledermatology is an effective modality with the potential to expand access to dermatologic expertise in the emergency department setting.

AbstractBackgroundHospitalized patients with hematologic malignancies are medically complex and commonly affected by dermatologic conditions.MethodsRetrospective chart review from January 1, 2014, to December 31, 2018, at Rochester Methodist Hospital (Rochester, Minnesota, USA). Patients hospitalized on hematology and BMT services receiving dermatology consultation were included.ResultsIn all, 578 consultations (63% male, median age 61 years) were reviewed. Drug reactions (22%), infection (17%), and malignant neoplasm (10%) accounted for nearly half of diagnoses. Exanthematous drug reaction (10%), graft‐versus‐host disease (7%), and lymphoma or leukemia cutis (6%) were the commonest individual diagnoses. There were significantly more drug reactions in severe neutropenia (33.2% vs. 15.0%), neutrophilic dermatoses in myeloid neoplasm (5.2% vs. 0.3%), and viral infection in lymphoid neoplasm (8.3% vs. 1.2%). Consultation frequently altered treatment (68%), diagnostic workup (63%), and the primary service’s initial diagnostic impression (53%). Biopsies were performed in 52% of consultations and helped secure a diagnosis 73% of the time. A total of 16.4% of consultations did not receive a definitive final diagnosis, and 18.5% were resolved in one visit.ConclusionThis is the largest study to date of hospital dermatology consultation in hematology patients. Biopsies are utilized frequently and are diagnostically useful. The complexity of this patient population is evidenced by the fact that a final diagnosis remains elusive in a number of cases despite the multiple visits required for the vast majority of consultations. Nevertheless, dermatology consultation alters diagnosis and treatment in the majority of patients, highlighting the critical role dermatologists have in the care of these patients.