Myeloid sarcoma (MS) is a rare extramedullary tumor composed of immature myeloid blasts that may occur in association with acute myeloid leukemia or during blast-phase transformation of chronic myeloid leukemia (CML). Cutaneous involvement is uncommon and frequently mimics chronic infections, inflammatory dermatoses, and cutaneous malignancies, often resulting in delayed diagnosis. We report a patient with longstanding CML who developed an ulcerated cutaneous myeloid sarcoma as the initial manifestation of extramedullary relapse, highlighting the importance of integrating clinicopathologic, immunophenotypic, and molecular findings for timely diagnosis.

A 73-year-old man with a 20-year history of CML, diagnosed in 2005, was treated initially and maintained on imatinib for 16 years before transitioning to nilotinib for 4 years. Serial molecular monitoring demonstrated molecular stability, and nilotinib was subsequently discontinued. He remained off tyrosine kinase inhibitor therapy for 11 months before presenting with a progressively enlarging, darkly erythematous, ulcerated, exophytic, painful, and recurrently bleeding mass over the left lower leg. Initial differential diagnoses included pyoderma gangrenosum, squamous cell carcinoma, ulcerated melanoma, cutaneous lymphoma, deep fungal infection, atypical mycobacterial infection, and myeloid sarcoma.

Laboratory evaluation demonstrated severe normocytic anemia (hemoglobin 4.7 g/dL) from blood loss with relatively preserved leukocyte and platelet counts. Given the chronic ulcerative lesion, an extensive infectious work-up was performed. Wound fungal culture, fungal smear (KOH), mycobacterial culture, acid-fast bacilli smear, and MTB PCR were all negative, effectively excluding deep fungal and mycobacterial infections as the primary etiology. As the lesion continued to enlarge despite antimicrobial therapy, an incision biopsy was performed. Histopathologic examination demonstrated a malignant round cell tumor with diffuse dermal infiltration and effacement of normal tissue architecture. Initial immunohistochemistry showed positivity for CD45 and negativity for CD3, CD20, pancytokeratin, and p40, excluding lymphoma and poorly differentiated carcinoma. Additional immunohistochemistry demonstrated positivity for CD34 and CD117, confirming cutaneous myeloid sarcoma. Bone marrow biopsy demonstrated a markedly hypercellular marrow (80-90%) with panhyperplasia, consistent with chronic-phase CML. Serial molecular monitoring demonstrated loss of molecular response, with BCR::ABL1 increasing to 42.57% IS (MR0.37) at presentation. In conjunction with the biopsy-confirmed cutaneous myeloid sarcoma, these findings were consistent with extramedullary relapse of CML.

Following the diagnosis of extramedullary relapse of CML, treatment was escalated to a newer-generation tyrosine kinase inhibitor. Although asciminib was initially considered, ponatinib was selected because of ease of access. Therapy was well tolerated and resulted in progressive regression of the cutaneous tumor, cessation of bleeding, marked reduction in lesion size, and near-complete epithelialization with healthy granulation tissue. Follow-up molecular monitoring demonstrated a decline in BCR::ABL1 transcript levels from 42.57% IS (MR0.37) at diagnosis to 0.03% IS (MR3.43), consistent with restoration of major molecular response.

Cutaneous myeloid sarcoma may be the initial manifestation of extramedullary relapse in patients with CML, even in the absence of overt marrow blast transformation. This case highlights the importance of integrating histopathology, comprehensive immunophenotyping, bone marrow evaluation, and serial BCR::ABL1 molecular monitoring to establish the diagnosis and promptly initiate appropriate leukemia-directed therapy. Early recognition may prevent unnecessary surgical intervention, avoid delays in definitive treatment, and improve clinical outcomes.