Pediatric mycosis fungoides: a study of the human leukocyte antigen system among Israeli Jewish patients

Abstract

Pediatric mycosis fungoides (MF) is a rare disease characterized by over-representation of atypical clinical variants, with a different prognosis from adult MF. Several human leukocyte antigen (HLA) alleles have been associated with MF in certain adult populations, including Israeli Jews. However, HLA data on pediatric MF as a group are lacking. To evaluate the possible association of the HLA system with pediatric MF, 59 Israeli Jewish patients diagnosed with MF at age ≤ 18 years underwent high- and intermediate-resolution genotyping for HLA class I (HLA-A*, HLA-B*) and class II (HLA-DRB1*, DQB1*) loci. The results were compared with data on 4169 umbilical cord blood units retrieved from a public cord blood bank in Jerusalem and samples from 252 healthy, unrelated Israeli Jewish volunteers. No statistically significant associations were found between pediatric MF and any of the alleles examined except HLA-B*73. However, given the extremely low frequency of B*73 in both the control group (0.1%) and the study group (2%), the biological significance of this finding is questionable. Further subgroup analyses by ethnicity (Ashkenazi and non-Ashkenazi) and clinicopathologic variant (follicular and non-follicular) yielded no significant between-group differences. These results suggest that the associations with the HLA system, reported previously in adult MF, do not hold true for pediatric MF. Thus, pediatric MF differs from its adult counterpart not only in clinical manifestations and course, but apparently also in the underlying immuno-pathogenetic mechanism.

HLA Type Determination in Patients Diagnosed with Mycosis Fungoides and Sézary Syndrome

“…16 In a very recent case-control study evaluating the association between paediatric MF and HLA system, HLA class I and class II allele frequencies did not differ. 20 Our study was limited by the small sample size. Larger sample trials with subgroup analyses according to family history, ethnicity and clinicopathologic variant are needed.…”

Mycosis fungoides in pediatric population: comprehensive review on epidemiology, clinical presentation, and management

“…Most of the studies report hypopigmented MF as the predominant variant accounting for almost 55-100% of the cases. 11,15,20,[30][31][32][33] Other common variants reported are the classical MF, which may account for 15-40% of the cases, 4,9,10,34,35 folliculotropic variant (3-36%), 4,9,11,34 and poikilodermatous MF (5-26%). 16,36 There are few uncommon variants which have been reported in children including pityriasis lichenoides chronica-like (PLC) MF, unilesional MF, pigmented purpuric dermatosis-like MF, granulomatous MF, ichthyosiform MF, hyperpigmented and intraoral presentation, inflammatory linear verrucous epidermal nevus-like MF, and pagetoid reticulosis, which may at times be difficult to diagnose at the initial presentation.…”

“…16,36 There are few uncommon variants which have been reported in children including pityriasis lichenoides chronica-like (PLC) MF, unilesional MF, pigmented purpuric dermatosis-like MF, granulomatous MF, ichthyosiform MF, hyperpigmented and intraoral presentation, inflammatory linear verrucous epidermal nevus-like MF, and pagetoid reticulosis, which may at times be difficult to diagnose at the initial presentation. 20,[37][38][39][40][41][42][43][44] Few rare cases of familial MF and MF post organ transplant have also been reported 21,45,46 (Table 1). Mycosis fungoides with largecell transformation in children is extremely rare and hence lacks a standardized therapeutic regimen.…”

“…Several human leukocyte antigen (HLA) alleles have been associated with MF in adult population, namely HLA‐DQB1 and HLA‐DRB1, however, no statistically significant association was found between pediatric MF and any of these HLA alleles except HLA‐B*73, the biological significance of which remains questionable due to its low frequency 20 . Certain rare cases of familial MF have higher frequency of HLA‐DQB1*03 as compared to controls (66.7% vs. 33%, respectively), which may support an association of this allele with the familial form of MF 21 …”

Pediatric Cutaneous Hematologic Disorders: Cutaneous Lymphoma and Leukemia Cutis—Experience of a Tertiary-Care Pediatric Institution and Review of the Literature

“…[19][20][21][23][24][25][26][27][28][29] Pediatric MF may show the classic presentation of erythematous patches and plaques with lymphocyte epidermotropism, yet various atypical clinical variants have been reported, including hypopigmented, psoriasiform, granulomatous slack skin, follicular, poikilodermic and purpuric. 19,[21][22][23]29,30 The hypopigmented variant seems to be overrepresented in childhood MF, 19,22,24,25,[28][29][30][31][32] and this clinical subtype is more often associated with a cytotoxic phenotype with expression of CD8 and TIA-1 reflecting the adequate antitumor immune response, which explains the better prognosis of that variant. 31,33 The association of MF with PLC has already been noted in other studies 33,34 and has been reported in a ratio as high as four out of five patients.…”