Title:  Bone Marrow Involvement in Sarcoidosis: A Case Report of Granulomatous and Hematologic ComplicationsAbstract: Bone marrow involvement in sarcoidosis is rare and poorly understood. This case highlights the hematologic complexity of sarcoidosis, including its association with aplastic anemia and T-cell large granular lymphocytic leukemia (T-LGLL). We report a 70-year-old male with longstanding sarcoidosis who developed multiple hematologic complications, including bone marrow granulomatous infiltration, aplastic anemia, and T-LGLL.Key Words: sarcoidosis, granulomatous inflammation, bone marrow, aplastic anemia, T-LGLL, hematologyIntroduction:  Bone marrow involvement in sarcoidosis is a rare manifestation with an incidence of <5%1. Clinical indications for obtaining a bone marrow biopsy in sarcoidosis remain poorly defined2. We report a case of a patient who experienced multiple hematologic complications, including aplastic anemia, T-cell large granular lymphocytic leukemia (T-LGLL), and granulomatous bone marrow involvement.Case Presentation : A 70-year-old male with a known history of sarcoidosis presented with progressive anemia. The patient was initially diagnosed with sarcoidosis twenty years prior in the setting of parotid gland swelling with biopsy revealing non-caseating granulomas. At that time, he was found to be pancytopenic; bone marrow biopsy showed hypocellularity consistent with aplastic anemia and increased CD8+ T-cells and a clonal peak by TCRB PCR indicative of T-LGLL, but no granulomas. He was treated with anti-thymocyte globulin (ATG) and long-term cyclosporine with good response. Five years later, the patient developed dyspnea and chest CT imaging showed a micronodular pattern with mediastinal adenopathy. He was therefore started on steroid treatment with improvement in both his respiratory symptoms and radiographic findings. Over the following decade, attempts to taper steroids below five milligrams daily, as well as his cyclosporine, resulted in recurrent anemia and thrombocytopenia. A repeat bone marrow biopsy, 10 years after initial diagnosis, revealed persistence of T-LGLL (with a similar TCRB PCR clone, increased CD7(dim)+CD26-CD16+CD8+ T-cells and abnormal TCR-Vb spectratyping by flow cytometry with no STAT3 or STAT5 mutation detected), but no evidence of granulomas. Attempts to taper steroids again resulted in recurrent anemia and another bone marrow biopsy, now 20 years after his initial diagnosis, identified persistent low-level T-LGLL and notably scattered non-caseating sarcoid granulomas in the bone marrow (Image 1). Reintroduction of low dose prednisone has resulted in improvement in his anemia.Discussion: Sarcoidosis can involve bone marrow leading to hematologic abnormalities such as anemia, leukopenia, and thrombocytopenia. Hematologic abnormalities can be due to direct granulomatous infiltration of the bone marrow, spleen, lymph nodes, or related to immune dysfunction.2 The association between sarcoidosis and hematologic manifestations such as aplastic anemia and T-LGLL have been rarely reported, although T-LGLL is known to have a high concordance with autoimmune disease, at over 30%3. There has been one previously reported case of aplastic anemia as a presenting feature of sarcoidosis4. This case described a young female who presented with pancytopenia and interstitial lung disease without mediastinal adenopathy. A bone marrow biopsy revealed aplastic anemia, and the patient responded to ATG and cyclosporine. After bone marrow recovery a transbronchial biopsy was performed which revealed noncaseating granulomas. Additionally, rare case reports describe pure red cell aplasia in patients with sarcoidosis, though these were attributed to infection or medication5,6. The mechanism of involvement related to aplastic anemia in sarcoidosis is unclear, but potential explanations include immune mediated destruction of hematopoietic cells, T cell dysregulation leading to bone marrow suppression and granulomatous involvement leading to pancytopenia7. Despite its rarity, aplastic anemia should be considered among the range of hematologic manifestations of sarcoidosis.The association between sarcoidosis and T-cell Large Granular Lymphocytic (T-LGL) leukemia is exceedingly rare. A small study by Karakantza et al. highlighted the association between sarcoidosis and lymphoid malignancies which included the first documented case of T-LGLL in a patient with sarcoidosis8. A population-based cohort study by Patt et al. found a significant association between sarcoidosis and hematologic malignancies, with an increased odds ratio for lymphoma9. The study included 24,000 patients with sarcoidosis and found sarcoidosis patients had a significantly higher prevalence of malignancies compared to controls. The association remained significant for both hematologic and solid organ malignancies. The strongest association was observed with lymphoma, particularly within the first year of sarcoidosis diagnosis. This supports the notion that sarcoidosis patients are at a higher risk for developing lymphoproliferative disorders, likely including T-LGLL. The pathogenesis linking sarcoidosis to lymphoproliferative disorders, including T-LGLL, likely involves chronic inflammation and immune dysregulation, which may promote malignant transformation of lymphocytes10. This highlights the importance of vigilant monitoring for hematologic malignancies in patients with sarcoidosis. Bone marrow biopsy and flow cytometry are crucial to distinguish between sarcoid-related marrow infiltration and T-LGLL.Conclusion : This case highlights the complex relationship between sarcoidosis and hematologic complications, emphasizing the potential for granulomatous involvement of the bone marrow and its association with conditions like aplastic anemia and T-LGLL. Corticosteroids remain the primary treatment option, while immunosuppressive agents may be effective in refractory cases. Additionally, while T-LGLL has long been associated with autoimmune diseases, with up 37% of T-LGLL patients having a concomitant autoimmune disease3, it is rarely reported to be associated with sarcoidosis. Long-term monitoring and a multidisciplinary approach are crucial to optimizing outcomes in patients with sarcoidosis and hematologic involvement.