Isolated Myeloid Sarcoma with Testicular and Cutaneous Involvement Harboring NPM1 and FLT3-TKD Mutations without Bone Marrow Disease
Myeloid sarcoma (MS) is a rare extramedullary tumor composed of immature myeloid cells that may occur concurrently with acute myeloid leukemia (AML) or, less commonly, as an isolated presentation without bone marrow involvement. Isolated MS with simultaneous testicular and cutaneous involvement is exceptionally uncommon and represents a diagnostic and therapeutic challenge.
Materials and Methods/Case Presentation/Objective:
Case Presentation
A 41-year-old man underwent left orchiectomy in August 2025 for a testicular mass initially suspected to be a primary testicular neoplasm. Subsequently, he developed progressive multiple subcutaneous nodules involving the trunk and extremities without constitutional symptoms. PET/CT demonstrated hypermetabolic retroperitoneal lymphadenopathy suspicious for neoplastic infiltration.
Histopathological examination of a cutaneous lesion revealed diffuse infiltration by a monocytic-lineage hematologic neoplasm expressing CD15, CD56, CD68, CD4, BCL2, and vimentin. Flow cytometry confirmed a monocytic immature population compatible with monocytic myeloid sarcoma. Molecular analysis performed on extramedullary tissue identified NPM1 and FLT3-TKD D835E mutations, whereas FLT3-ITD, IDH1, and IDH2 mutations were negative.
Comprehensive bone marrow evaluation, including morphology, flow cytometry, cytogenetics, FISH, and molecular studies, showed no evidence of leukemic involvement. Karyotype was normal (46,XY), and FISH analysis was negative for MECOM, KMT2A, and NUP98 rearrangements as well as TP53 deletion. Cerebrospinal fluid studies excluded central nervous system involvement.
The patient received AML-like induction chemotherapy with idarubicin and cytarabine (7+3 regimen), combined with midostaurin because of the FLT3-TKD mutation. Triple intrathecal chemotherapy was administered prophylactically. During aplasia, he developed febrile neutropenia and severe gastrointestinal mucositis requiring broad-spectrum antibiotics, transfusional support, and total parenteral nutrition. Midostaurin was discontinued because of gastrointestinal toxicity. After hematologic recovery, complete clinical resolution of cutaneous lesions was achieved.
Given the multifocal extramedullary presentation and molecular profile, consolidation with allogeneic hematopoietic stem cell transplantation from an HLA-identical sibling donor was performed in December 2025 using myeloablative total body irradiation-based conditioning. The patient currently remains in complete remission.
Results/Description/Main Outcome Measure(s):
Conclusion(s).: Conclusions
This case highlights a rare presentation of isolated multifocal MS without bone marrow involvement. Molecular profiling of extramedullary tissue identified therapeutically relevant mutations and supported intensive AML-directed treatment followed by allogeneic transplantation, achieving sustained remission.
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