Monitoring minimal residual disease (MRD) is an important predictor of outcome in acute lymphoblastic leukemia (ALL) and is used in risk stratification, prognosis determination, and therapy guidance. Several laboratory techniques have proven utility for characterizing leukemic cells and following MRD through diagnosis, remission and possible recurrence. Methods for determining MRD are based on the detection of leukemia-specific aberrant immunophenotypes by mulitparameter flow cytometry or the evaluation of leukemia-specific rearranged immunoglobulin or T-cell receptor sequences by quantitative real-time PCR. Next-generation sequencing (NGS) is emerging as a new flexible and sensitive tool to detect MRD, which allows identification of clonal composition and scalable sensitivity depending on sequence coverage. As NGS becomes more accessible and affordable, guidelines should be established for its application to MRD surveillance.

Cutaneous eruptions associated with hemophagocytic lymphohistiocytosis (HLH) have been reported in 6%-63% of patients. Clinical findings of these skin lesions vary widely and include maculopapular rashes, ulcers, and violaceous nodules. Corresponding histologic findings are also variable and are considered nonspecific. We report the case of a 4-year-old boy who initially developed a widespread popular-pustular rash 2 weeks after his 12month measles, mumps, and rubella vaccinations. These resolved with scarring then recurred following his 24-month vaccinations. Multiple skin biopsies were negative for infectious organisms and showed a granulomatous infiltrate with perforation and necrobiosis. The differential diagnosis included perforating granuloma annulare, infection, or rheumatoid nodules. At the age of 4, he developed fever, hepatosplenomegaly, pancytopenia and other laboratory abnormalities, requiring hospitalization. A number of studies were performed including biopsies of bone marrow and liver. Molecular testing revealed 2 mutations in UNC13D known to be associated with familial HLH. His prior cutaneous lesions were likely caused by immune dysregulation exacerbated by immunizations because of underlying familial HLH. This case illustrates the importance of recognizing an unusual cutaneous manifestation of a rare disease to arrive at an earlier diagnosis in a pediatric patient. Although cutaneous eruptions usually develop concurrently with other systemic symptoms of HLH, preceding unusual skin lesions may be the first indication of this rare disease.

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