A RARE CASE OF PULMONARY NON-LANGERHANS CELL HISTIOCYTOSIS

Abstract

SESSION TITLE: Medical Student/Resident Lung Pathology SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Histiocytic neoplasms are a rare group of heterogeneous disorders which may involve the lung. The most common, Langerhans cell histiocytosis (LCH), is often associated with smoking. Less common are the Non-Langerhans cell histiocytosis, Erdheim-Chester disease (ECD) and Rosai-Dorman disease (RDD). Diagnosis and treatment are often delayed due to lack of proper interpretation of clinical, radiological and histological findings. The following case poses as a diagnostic challenge as the patient is elderly, with no smoking history, and thus falls into an unsuspecting population vulnerable to prolonged invasive workup and missed diagnoses. CASE PRESENTATION: A 75-year-old male, non-smoker, was admitted for evaluation of persistent dyspnea and cough for several weeks despite outpatient treatment with antibiotics. Presented afebrile, and hypoxic requiring 4L/min via nasal cannula. History revealed recurrent pneumonias for several months and persistent infiltrates on CXR. Chest CT showed emphysematous changes with intralobular septae thickening, and bilateral pleural effusions. Thoracentesis was attempted but was unsuccessful due to the thick nature of the aspirate. Following an unyielding bronchoscopy, a subsequent right upper lobe wedge biopsy showed histological features diagnostic of pulmonary histiocytosis. Pleomorphic inflammatory infiltrates were seen with variably abundant pale staining cytoplasm and focal emperipolesis. There was fibrosis distributed in a lymphangitic pattern with diffuse involvement, and focal necrosis without granuloma formation. Immunohistochemical stains of the histiocytes were positive for CD163 and Factor XIIIa with focal staining of S100 and negative for cytokeratins (AE1/AEE3 and CAM5.2), calretinin, WT-1 and BRAF V600E. As a result, patient was not a candidate for targeted therapy; yet, improved with a course of tapered steroids. Planned for further genetic workup involving the MAPK signaling pathway in the future. DISCUSSION: This case illustrates the significant histological similarities seen in ECD and RDD including lymphangitic distribution, S100-positive histiocytes and emperipolesis. A positive BRAF V600E mutation can be seen in about 50% of ECD cases but not in RDD, giving both diagnostic and therapeutic value. Unfortunately for this patient, the mutation was negative and a definitive subclassification could not be made. However, given the patient’s lack of multisystem involvement including the classic long bone osteosclerosis, a diagnosis of RDD could be favored. CONCLUSIONS: Histiocytic lung disorders vary in clinical manifestations, making it difficult to establish a timely diagnosis. A disparity in identification and targeted treatment still exists, as illustrated in this case. It is prudent to raise awareness of these disorders and highlight the key clinical and histopathologic features which discern them for accurate diagnosis and medical therapy. Reference #1: Haroche J, Abla O; Uncommon histiocytic disorders: Rosai–Dorfman, juvenile xanthogranuloma, and Erdheim–Chester disease. Hematology Am Soc Hematol Educ Program 2015; 2015 (1): 571–578. doi: https://doi.org/10.1182/asheducation.V2015.1.571.3916289 Reference #2: DeMartino E et al. Langerhans Cell Histiocytosis and Other Histiocytic Diseases of the Lung. Clinics in Chest Medicine, Volume 37, Issue 3, 421 - 430 Reference #3: Goyal G, Young JR, Koster MJ, et al. The Mayo Clinic Histiocytosis Working Group Consensus Statement for the Diagnosis and Evaluation of Adult Patients With Histiocytic Neoplasms: Erdheim-Chester Disease, Langerhans Cell Histiocytosis, and Rosai-Dorfman Disease. Mayo Clin Proc. 2019;94(10):2054-2071. doi:10.1016/j.mayocp.2019.02.023 DISCLOSURES: No relevant relationships by Victoria Gonzalez, source=Web Response No relevant relationships by Kristen Hughes, source=Web Response No relevant relationships by Bernadette Schmidt, source=Web Response No relevant relationships by Emad Shehada, source=Web Response