TOPIC: Lung Cancer TYPE: Medical Student/Resident Case Reports INTRODUCTION: Hypertrophic Osteoarthropathy (HOA) is a condition characterized by abnormal proliferation of skin and osseous structures of extremities. Periostitis is the imaging hallmark of HOA and most commonly manifests symmetrically along the shaft of tubular bones. Incidence of HOA in patients with intrathoracic malignancy is 5-10%. CASE PRESENTATION: A 49-year-old male presented to his primary care physician for bilateral knee pain with associated swelling. After failing conservative management, bilateral knee x-rays were performed which revealed a thin periosteal reaction in both femoral shafts, prepatellar soft tissue swelling and small bilateral joint effusions.The radiologist recommended a chest x-ray for further evaluation, which showed subtle soft tissue fullness at the right lung base. Chest CT was then performed revealing a 4.2 x 2.2 x 4.7 cm spiculated soft tissue lung mass of the right lower lobe with extension into the mediastinum and right hilar, paratracheal and subcarinal lymph nodes.The patient underwent bronchoscopy with FNA of the right lower lobe mass and station 7 and 11 lymph nodes. Highly atypical cells suspicious for malignancy were noted, but analysis was limited by scant material. IR guided biopsy was subsequently performed revealing patchy proliferation of epithelioid cells with ample eosinophilic cytoplasm, occasional cytoplasmic vacuoles and necrosis. Immunohistochemically, the tumor cells stained positive for ERG, CD31, and CD24. The cytomorphologic and immunohistochemical features support the diagnosis of epithelioid hemangioendothelioma (EHE). DISCUSSION: This case illustrates EHE's heterogeneous presentations. The primary lesion of EHE has been documented in numerous locations throughout the body, but most commonly arises in the liver, lungs, and bones. HOA as the presenting sign in pulmonary EHE is not well documented in the literature and periosteal reaction is considered rare. Digital clubbing was not present in this case and the only known location of periosteal reaction was the femoral shafts. While the mechanism of EHE is not well understood, it is believed that angiogenic stimulators, such as vascular endothelial growth factor (VEGF), may act as promoters of endothelial cell proliferation.The proposed pathogenesis of HOA has been linked to hypersecretion of vasoactive agents such as VEGF, platelet derived growth factor (PDGF), and prostaglandin E2 (PGE2). The proposed pathogenesis of secondary HOA has been linked to hypersecretion of vasoactive agents such as VEGF, PDGF, and PGE2. These agents are released both systemically in response to hypoxemia and by the tumor itself. CONCLUSIONS: Pulmonary Epithelioid Hemangioendothelioma can also present with Hypertrophic Osteoarthropathy.Bone X- ray can lead to the diagnosis of Hypertrophic Osteoarthropathy if careful evaluation is done. Periostitis is frequently a sign of pulmonary and systemic pathology. REFERENCE #1: Chakraborty, Rebanta K. "Secondary Hypertrophic Osteoarthropathy." StatPearls [Internet]., U.S. National Library of Medicine, 1 Mar. 2021, www.ncbi.nlm.nih.gov/books/NBK513342/. REFERENCE #2: Sardaro, Angela, et al. "Epithelioid Hemangioendothelioma: an Overview and Update on a Rare Vascular Tumor." Oncology Reviews, PAGEPress Publications, Pavia, Italy, 13 Oct. 2014, www.ncbi.nlm.nih.gov/pmc/articles/PMC4419652/. REFERENCE #3: Silveira LH;Martínez-Lavín M;Pineda C;Fonseca MC;Navarro C;Nava A; "Vascular Endothelial Growth Factor and Hypertrophic Osteoarthropathy." Clinical and Experimental Rheumatology, U.S. National Library of Medicine, pubmed.ncbi.nlm.nih.gov/10728444/. DISCLOSURES: No relevant relationships by Julia Lawinger, source=Web Response No relevant relationships by Raul Mendoza-Ayala, source=Web Response