doi: 10.1182/bloodadvances.2024013696.
Recurrent ETV3::NCOA2 fusions and MAPK pathway mutations in indeterminate dendritic cell histiocytosis
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- PMID: 39361730
- PMCID: PMC11808610
- DOI: 10.1182/bloodadvances.2024013696
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Recurrent ETV3::NCOA2 fusions and MAPK pathway mutations in indeterminate dendritic cell histiocytosis
Blood Adv.
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No abstract available
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Figures
Clinical and pathologic features of IDCH. (A) Photographs of lesions in cases 1, 3, 4, 5, 9, 10, and 12. Shown are congenital purpuric papules in case 1, which spontaneously regressed over several weeks. Case 3 was a 9-month-old child with multiple yellow-brown papules spread over the body and an erythematous, crusted nodule on the right nasal ala. The lesion on the nose was successfully treated with topical steroids, whereas the other lesions regressed spontaneously over several months. Cases 4 and 5 were adults with multiple brown-red or skin-colored, asymptomatic papules on the trunk and extremities, which responded to ultraviolet B phototherapy. Case 9 was an infant with congenital purpuric skin lesions who developed anemia, thrombocytopenia, and splenomegaly in the first month after birth, reminiscent of infants developing high-risk LCH. The child achieved complete remission with vinblastine/prednisone chemotherapy. In contrast, cases 10 and 12, both adults, died from progressive disease despite systemic treatment. Case 10 presented with >100 papules spread over the body and bilateral lung nodules (indicated by white arrows). Case 12 presented with skin lesions on the right cheek but later developed locally invasive disease requiring facial surgery and bilateral breast lesions (not shown). (B) Photomicrographs of tissue slides stained with hematoxylin and eosin (H&E) or stained for specific proteins; the latter are indicated at the bottom of the images. Case numbers are provided in the upper left corners; black bars in the lower left corners indicate 20 μm. Shown are infiltrates of histiocytoid cells with frequent nuclear grooves or indentations, as highlighted in several inlets. Clusters of cells were often located around vessels, as illustrated by H&E images of cases 1 and 10. In case 4, a small intraepithelial focus of abnormal histiocytes was observed in the lesion of the back (right H&E image); this lesion was also notable for more cellular atypia and CD163+ multinucleated cells (inlet). Dense infiltrations of similar, histiocytoid cells were observed in extracutaneous lesions, often accompanied by prominent lymphocytic infiltrates (not shown). As illustrated by multiple photomicrographs of case 4 (with an ETV3::NCOA2 fusion), lesional cells stained positive for CD1a and CD68, and were negative for CD207/Langerin and S100. Yet, CD68 was negative and S100 was positive in other cases (supplemental Table 2). The pattern of CD68 expression was diffuse granular cytoplasmic expression, with occasional Golgi dot-like accentuation (most notable in cases 1 and 7). The pattern of S100 expression was diffuse cytoplasmic and nuclear expression, although nuclear expression was less apparent in case 11 (shown). As illustrated by the photomicrograph of the back lesion of case 4, CD1a staining sometimes revealed a remarkable branching pattern in the deeper dermis, in which histiocytes were often located around vessels and, from there, spread through the dermal collagen. CD163 was generally negative, with rare positive lesional cells, whereas cyclin D1 frequently stained the lesional cells, and PU.1 was diffusely positive. Mutational status of all patients is depicted in Figure 2A. Detailed clinical and pathologic information is provided in supplemental Tables 1 and 2.
Molecular characterization of IDCH and additional myeloid malignancies. (A) Oncoprint depicting clinicopathologic and molecular features of 12 patients with IDCH, 6 patients with potential IDCH, and 1 patient with MH-IDC (depicted on the far right). Every column represents 1 patient; case numbers are provided at the bottom of the plot. Blue squares indicate the presence of a clinicopathologic characteristic, orange squares indicate the presence of a gene fusion, red squares indicate the presence of a SNV or insertion and/or deletion (indel), and purple squares indicate the presence of CNV. (B) Genetic findings in 4 patients of whom 2 separate IDCH lesions were molecularly analyzed, demonstrating identical mutations in paired lesions in all cases. In addition, mutations unique to 1 lesion were sometimes identified. (C) Genetic findings in 4 patients of whom the additional myeloid malignancy was molecularly analyzed. Shared genetic alterations between the IDCH and additional hematologic malignancy were identified in 2 of 4 cases, strongly suggesting a clonal relationship of these hematopoietic neoplasms. Details on detected genetic alterations, including variant allele frequencies, are provided in supplemental Tables 3 and 4. CNV, copy number variation; MH-IDC, malignant histiocytosis with an indeterminate dendritic cell phenotype; SNV, single-nucleotide variant.
References
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