Acute Leukemias of Ambiguous Lineage presenting in Extramedullary Location – Unusual and Challenging Diagnoses: A Report of Two Cases

Abstract

Abstract Introduction/Objective Acute leukemias of ambiguous lineage are uncommon, accounting for <1% of all leukemias, and extramedullary presentations of these leukemias are rare. Methods/Case Report We report two cases of acute leukemia of ambiguous lineage presenting in extramedullary sites. Case 1 is a 41-year-old female who presented with right cervical lymphadenopathy and fatigue. Laboratory and imaging studies showed leukopenia, anemia, and abnormal cervical, supraclavicular, axillary, mediastinal, and abdominal pelvic lymphadenopathy. Biopsy of the axillary lymph node revealed sheets of morphologic blasts. Flow cytometry showed the blasts were of mixed phenotype, with T-cell differentiation supported by CD3 and TdT, and myeloid subpopulation supported by myeloperoxidase and lysozyme. Both these populations were negative for CD10, CD20, CD4, CD8, CD34, CD138, CD1a, CD79a. The morphology and immunophenote establish the diagnosis of T/myeloid mixed-phenotype acute leukemia, not otherwise specified. Case 2 is a 65-year-old female who presented with bilateral lower extremity weakness. Multiple lytic lesions involving the thoracic and cervical spine were detected by imaging. Biopsy of a T12 vertebral lesion revealed sheets of large malignant cells. Extensive immunohistochemical workup revealed positivity for CD45 (weak), CD4, and CD43, supporting a diagnosis of hematopoietic neoplasm of likely hematopoietic origin. Subsequent evaluation eventually led to discovery of chronic myeloid leukemia in blast phase with undifferentiated blasts, BCR-ABL1 positive, originally presenting as extramedullary acute leukemia with undifferentiated blasts. Results (if a Case Study enter NA) NA. Conclusion These cases highlight the challenges of diagnosing peripheral solid tumors of unknown origin. Extramedullary presentation of acute leukemia of ambiguous lineage are particularly challenging and, although rare, include phenotypes ranging from mixed phenotype to undifferentiated types.