Therapy-related myeloid sarcoma with an NPM1 mutation (original) (raw)

Leukemia & Lymphoma, 2010

Abstract

A 73-year-old man with a history of a right frontal meningioma treated with resection and 30 fractions of cranial irradiation 6 years earlier presented with hundreds of 1–3 cm raised violaceous papules and nodules on his chest, back, neck, scalp, and abdomen [Figure 1(A)]. There were no lesions below the waist. The nodules were non-tender, non-pruritic, and slightly elevated, and had developed gradually over the previous two and a half months. His other medical problems included hypertension, end-stage renal disease requiring hemodialysis, and diabetes. Skin biopsy of one of the nodules demonstrated a neoplastic population of cells diffusely infiltrating the dermis, with a distinct grenz zone. Immature blastic cells with round to slightly irregular folded nuclei, indistinct nucleoli, and a scant to moderate amount of cytoplasm infiltrated between collagen bundles in sheets and singly, as well as through the fat in a honeycomb pattern [Figure 1(B)]. Immunoperoxidase staining demonstrated that the neoplastic cells were CD347, CD33þ, lysozymeþ, CD68(KP1)þ, weakly CD4þ, CD56þ, weakly MPOþ, and weakly CD123þ, consistent with myeloid lineage. NPM1 expression was positive by immunohistochemistry in the nucleus and cytoplasm of the neoplastic cells, which is characteristic of a mutation in the NPM1 gene, whereas the normal keratinocytes in the epidermis showed only nuclear staining [Figure 1(C)]. His blood counts were normal except for mild thrombocytopenia (126 000/mL). A bone marrow biopsy showed no evidence of acute myeloid leukemia (AML), and the karyotype was normal 46,XY. Molecular analyses on the myeloid sarcoma tissue showed a 4 bp insert in exon 12 of the NPM1 gene; the signal intensity was approximately equal to the wild-type allele. There was no evidence of an internal tandem duplication (ITD) or D835 mutation of the FLT3 gene. The karyotype on the skin biopsy was also normal. The patient was not a candidate for systemic chemotherapy due to his serious comorbidities. He received 5 weeks of electron beam therapy to the head, chest, back, and abdomen, with near complete resolution of the skin lesions. Shortly afterward, Figure 1. (A) Leukemia cutis. Physical exam reveals diffuse nodular and papular rash with lesions ranging from 1 to 3 cm throughout back (pictured), neck, face, and chest. (B) Skin biopsy. A neoplastic population of cells diffusely infiltrating the dermis and distinct grenz zone. (C) Keratinocytes display nucleus-restricted NPM1 positivity. Myeloid sarcoma cells show the expected nuclear localization in addition to aberrant expression in the cytoplasm.

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