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Updated: Jun 13, 2025
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Investigation of NPM1 mutation frequency in cutaneous blastic plasmacytoid dendritic cell neoplasms
Hanan Hamdan1, Alexa Siddon2, Maximiliano Ramia de Cap3
1University of Texas Southwestern Medical Center, UTSW, 2230 Inwood Rd, Dallas, TX, 75235, USA.
Background:
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) and acute myeloid leukemia (AML) show overlapping clinicopathological presentations, which makes it challenging to differentiate on a small skin biopsy. NPM1 mutations are the most common genetic lesions in AML, accounting for one third of cases and cause an aberrant cytoplasmic delocalization of NPM1 mutants, which can be detected by an immunohistochemical stain. Frequency of NPM1 mutations in BPDCN remains controversial. We aimed to investigate NPM1 mutations in cutaneous BPDCN cases and compare them with cutaneous NPM1 positive leukemia cutis cases.
Methods:
From a multi-institutional search, we identified and analyzed 13 cases of cutaneous BPDCN and 19 cases of cutaneous myeloid sarcoma (7 of which were primary leukemia cutis) with NPM1 mutations. We compared the clinical and pathological findings of these patients and identified distinguishing features between these groups.
Results:
BPDCN patients presented at an older age, with lower white blood cell count, higher hemoglobin level, and elevated platelets counts as compared to cutaneous myeloid sarcoma patients (p < 0.05). The bone marrow of patients in both groups was similarly involved at the time of diagnosis with no significant difference in rate; however, the percentage of involvement was significantly different among the two groups. Complex karyotype was more frequently seen in BPDCN patients (37.5 %) as compared with 15.7 % of cutaneous myeloid sarcoma patients (p < 0.05). Mutational profile differed among the two groups with absence of NPM1 mutations in BPDCN cases. Comparison of co-mutations detected in both groups revealed that BPDCN cases were significantly enriched in IDH2, NRAS, and SRSF2 mutations.
Conclusion:
We find that BPDCN patients present in a similar way to cutaneous AML patients but appear to uniformly lack NPM1 mutations. Our study suggests that NPM1 can be used as a surrogate immunohistochemical stain to differentiate this rare disease from myeloid sarcoma in a rapid and cost-effective method.
