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Spontaneous Regression Of Aleukemic Leukemia Cutis Harboring A Npm/rara Fusion Gene In An Infant With Cutaneous Mastocytosis

Kanegane et al., 2009Leukemia

Kanegane, H., Nomura, K., Abe, A., Makino, T., Ishizawa, S., Shimizu, T., Naoe, T., & Miyawaki, T. (2009). spontaneous regression of aleukemic leukemia cutis harboring a NPM/RARA fusion gene in an infant with cutaneous mastocytosis. International journal of hematology, 89(1), 86–90. https://doi.org/10.1007/s12185-008-0216-y

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Abstract

Aleukemic leukemia cutis has been rarely reported in infant leukemia. This report describes a 6-month-old boy with aleukemic leukemia cutis, which regressed without any treatments within 6 months. Interestingly, a cytogenetic analysis disclosed a leukemia clone with the karyotype of 46, XY, t(5;17)(q35;q12), which generated nucleophosmin (NPM)-retinoic acid receptor alpha fusion (RARA) fusion transcripts. The patient simultaneously had cutaneous mastocytosis, which also disappeared with the leukemia cutis. He shows no physical or laboratory abnormalities without any treatments after 12 months, although the NPM/RARA transcripts remain faintly in the bone marrow. The present case is partially compatible with systemic mastocytosis with an associated clonal hematologic non-mast cell lineage disorder, proposed by the WHO classification, and it is also suggestive of the initiation or early stage of acute promyelocytic leukemia.

Case Details

Disease Location

Skin

Personal Characteristics

6 months old male born to nonconsanguineous parents was born at 41 weeks and postnatal development had been good with normal height and weight at 1 month old, he had a few dermal macules appearing on the skin

Clinical Characteristics

Presented for an evaluation of cutaneous lesions physical exam found a few brown dermal macules (5-10mm in diameter) on his face and trunk, a number of gray dermal macules (2-4 mm in diameter) were also seen the brown macules were positive for darier's sign two skin biopsies were taken from both macule types at 9 months old. Hematoxylin and eosin-stained specimens of the brown macule demonstrated a diffuse cell infiltrate in the dermis that formed aggregates, the cells had a round to oval nucleus with clumped chromatin and moderately abundant polygonal and spindle-shaped pale cytoplasm giemsa and toluidine blue stains demonstrated the cells had metachromatic granules and were positive for naphtol-asd-chloroacetate esterase ihc showed cells positive for trypatientase and CD117, indicating mast cells brown macules were then diagnosed as mastocytosis atypical cells were medium and large and had a round to oval nucleus with partial convolution and dispersed chromatin, and relatively abundant eosinophilic cytoplasm ihc of atypical cells resulted in strong positive with antibodies to myeloperoxidase and moderate staining with CD68 leukemia cutis with a myeloid phenotype was suspected bone marrow aspirates revealed approx 5% blasts. Ihc of blasts revealed positivity for CD19 and HLA-dr, suggesting they were precursor b lymphoblasts and/or hematogenous marrow karyotype was 46, xy, t(5;27)(q35;q12) [4/20] suggesting a translocation between 5q35 (npm) and 17q12 (rara) fish analysis indicated the patient had a chromosomal abnormality involving rara marrow cells were observed to be morphologically aleukemic but cytogenetically leukemic right-pcr showed 2 split signals of rara in 52.6% of leukemia cutis cells patient was diagnosed fully with cutaneous mastocytosis and aleukemic leukemia cutis harboring a npm/rara fusion gene

Remission Characteristics

Peripheral blood and marrow were continuously examined but showed no abnormalities for more than 1 year both the brown and gray macules completely resolved by the age of 14 months serial marrow samples showed that a faint band of the npm/rara transcripatient was detected at 14 months, but at 19 months it was not detected

Treatment & Mechanisms

Proposed Remission Mechanisms

No major mechanism proposed

Clinical Treatment

None reported

Non-Clinical Treatment

None reported