Emergence of Two Rare Malignancies, Langerhans Cell Sarcoma and Myeloid Sarcoma, After Targeted Therapy for Chronic Lymphocytic Leukaemia: A Case Report

Chronic lymphocytic leukaemia (CLL), Langerhans cell sarcoma (LCS), and myeloid sarcoma are distinct haematological malignancies. While CLL is a common mature B-cell lymphoproliferative disorder, LCS and isolated myeloid sarcoma are rare entities that can present significant diagnostic and therapeutic challenges. We report the case of a patient with established CLL whose clinical condition deteriorated rapidly during treatment. Computed tomography (CT) imaging demonstrated the development of new masses that were initially suspicious for Richter's transformation. However, tissue biopsy confirmed the unexpected diagnosis of LCS. Chemotherapy for the LCS was commenced, initially demonstrating a favourable response. Three months later, the patient re-presented with pyrexia and new masses identified on repeat CT imaging. A further biopsy unexpectedly revealed myeloid sarcoma. Despite further investigation and management, the patient's condition continued to deteriorate, and they subsequently died from progressive disease. The sequential development of two exceptionally rare malignancies in a patient with CLL raises important questions regarding disease pathogenesis, clonal evolution, tumour surveillance, and the potential influence of novel targeted therapies. No BRAF mutation was detected in either the CLL or LCS biopsy specimens, making it difficult to establish a mutational link between the malignancies. To our knowledge, the occurrence of LCS followed by myeloid sarcoma in a patient with CLL has not previously been reported. This case highlights the importance of repeat tissue biopsy when disease progression does not follow the anticipated clinical course.