Abstract Background Sarcoidosis is a multisystem inflammatory disorder characterized by the presence of non-caseating granulomas. Diagnosis is often challenging due to lack of a “gold standard” test as well as frequent overlap with other inflammatory, neoplastic, and infectious diseases. Here we present a challenging case with very dramatic clinical presentation and overlapping features with Erdheim-Chester disease. Case Presentation A 42-year-old female presented with bilateral periorbital swelling, followed by progressive dyspnea, fatigue, night sweats, and a 100 lb unintentional weight loss which began after moving into a house infested with rats. Chest Computed Tomography Angiography (CTA) showed multiple intraosseous sclerotic lesions as well as extensive mediastinal, hilar, and abdominal adenopathy. Positron Emission Tomography (PET) scan was notable for multiple hypermetabolic lymph nodes throughout her body. Biomarkers of granulomatous inflammation were extremely elevated. An axillary lymph node biopsy revealed non-caseating epithelioid granulomas with negative infectious stains. Given concern for occult hematologic malignancy, she was referred for excisional biopsy of an inguinal lymph node, which demonstrated non-necrotizing granulomas along with extensive infiltration by polyclonal Langerhans cells forming sheets. Genetic panel for Erdheim-Chester disease (ECD) was negative for all common mutations including BRAF. Given the atypical clinical picture and extensive serologic workup, multidisciplinary evaluation from various subspecialities was performed to rule out vasculitis, histiocytic neoplasm, and zoonosis. Ultimately, sarcoidosis was felt to be the most likely diagnosis, and the patient was started on prednisone with good clinical response, then transitioned to mycophenolate mofetil and infliximab. Discussion This case highlights a unique clinical and histological presentation of extensive granulomatous disease with atypical sarcoidosis and Erdheim-Chester overlap. The initial symptoms of periorbital edema can occur in both sarcoidosis and histiocytic neoplasms. The imaging demonstrated significant sclerotic changes which occurs less so in sarcoidosis and more so in Erdheim-Chester. The typical serological markers of sarcoidosis were significantly elevated, suggesting high T-cell and macrophage activity. On lymph node biopsy, sarcoidosis demonstrates non-caseating granulomas. However, there can be a population of Langerhans cells with sarcoidosis as a reactive process. The biopsy specimen showed extensive sheets of polyclonal Langerhans cells surrounding the granulomas. Langerhans Cell Histiocytosis (LCH) is not typically associated with granulomas and is characterized by clonal proliferation of histiocytes, whereas Erdheim-Chester is polyclonal and commonly associated with granulomas. The myeloid mutation panel was negative, which is unusual in histiocytic neoplasms like LHC and Erdheim-Chester. As a result, the patient was treated as an atypical presentation of sarcoidosis. This abstract is funded by: None
Deol et al. (Fri,) studied this question.