“Cup-like” blasts in acute myeloid leukemia with FLT3 and NPM1 mutations

Abstract

A 61-year-old man presented with left-side neck pain and swelling, dizziness, night sweats, and significant weight loss. His laboratory investigations showed pancytopenia with hemoglobin of 8.6 g/dL, leukocyte count of 600 per mL, and platelet count of 15 000 per mL. Bone marrow aspiration and biopsy revealed 90% blasts (panel A) with a peculiar "cup-shaped" nuclear morphology (panel B). Molecular diagnostics revealed the presence of cooccurring mutations of the nucleophosmin (NPM1) and Fms-like tyrosine kinase (FLT3) genes. Cytogenetic studies did not show any abnormalities. The patient was started on induction chemotherapy with cytarabine and idarubicin and demonstrated good response.

Blasts with folded nuclei: A histopathologic finding in myeloid leukemia cutis with NPM1 and FLT3 mutations

“…16 It is worth mentioning that the folded or indented nuclei observed in cutaneous tissue sections of leukemia cutis may represent the equivalent "cup-like" structures previously described in bone marrow specimens. 4 Table 1 provides a comprehensive summary of the clinical, morphological, immunophenotypic, cytogenetic, and molecular characteristics observed in previously reported cases of myeloid leukemia cutis with FLT3 and NPM1 mutations.…”

“…Prior reports of acute myeloid leukemia (AML) have revealed a strong association between the cup‐like nuclear morphology observed in bone marrow specimens and concurrent mutations of NPM1 and FLT3‐ITD or TKD 4–9 . In cutaneous tissue sections of leukemia cutis, folded or indented nuclei may represent the “cup‐like” counterpart previously described in bone marrow specimens.…”

Acute myeloid leukemia with cup-like blasts and FLT3-ITD and NPM1 mutations mimics features of acute promyelocytic leukemia: a case of durable remission after sorafenib and low-dose cytarabine

“…However, methods to effectively treat the AML subtype with cup-like blasts in patients with mutations of both FLT3 and NPM1 or one of them remain unknown. Two previous studies suggested that cytarabine-based intensive chemotherapy might be effective in such patients [ 1 , 5 ]. Moreover, there are few therapeutic options in elderly patients due to their age, performance status and complications, which make them inappropriate for intensive chemotherapy and stem cell transplantation.…”

“…Acute myeloid leukemia (AML) is a molecularly and cytogenetically heterogeneous hematological malignancy. Previous studies have indicated a potential AML subtype characterized by a distinct cup-like blast phenotype with mutations of both FLT3 and NPM1 or one of them [1–5]. However, the clinical features, treatment and prognosis of this subtype remain to be depicted.…”

Explainable AI identifies diagnostic cells of genetic AML subtypes

“…Genetic subtype discrimination of AML derived blood smears is an ideal use case for explainable AI for two reasons: First, morpho-genetic correlations between the appearance of atypical cells and the PML::RARA fusion are established for APL and allow validation of the model. For other subtypes, morpho-genetic correlations are discussed, as in the case of a NPM1 mutation that is assumed to correlate with the appearance of blasts with a cup-like nuclear shape [18]. Second, the AML genetic subtype is included in the patient information, providing annotated training data without any label noise.…”