Neonatal and Early Infantile Cutaneous Langerhans Cell Histiocytosis

Abstract

To describe clinical and immunohistochemical findings in patients with cutaneous Langerhans cell histiocytosis (LCH) beginning in the first 3 months of life and to define predictors of disease evolution.

Langerhans cell histiocytosis in children – a disease with many faces. Recent advances in pathogenesis, diagnostic examinations and treatment

“…Skin lesions are the second most-common clinical manifestation of LCH (30–60%) [ 17 , 33 ], which is particularly frequent in infants [ 17 ] and the most common presentation of “non-self-regressive” cutaneous LCH in neonates and young infants [ 45 ]. However, an isolated cutaneous form of the disease is rare (the number of described cases does not exceed 12% of all patients with LCH), typically concerns only male infants and has a good prognosis [ 12 , 46 ].…”

“…However, both patients born with skin-only LCH and patients who develop skin-only LCH during infancy can have a “self-healing” disease with spontaneous regression or may progress to MS-LCH with a worse prognosis [ 47 ]. The special form of congenital cutaneous LCH in neonates is uncommon Hashimoto-Pritzker disease characterized by self-regressive red-brown cutaneous nodules [ 45 , 47 ]. The skin disease in patients older than 18 months of age at diagnosis is associated with the presence of MS-LCH [ 48 ].…”

Apparent Lack of BRAFV600E Derived HLA Class I Presented Neoantigens Hampers Neoplastic Cell Targeting by CD8+ T Cells in Langerhans Cell Histiocytosis

“…This dissimilarity between LCH and other neoplastic disorders may be due to their vast differences in mutational load and, correspondingly, the number of T cell activating neoantigens that can arise from this mutational burden. Furthermore, the immune suppressive microenvironment in LCH-lesions (5,14,15,18,(78)(79)(80)(81) may hamper CD8 + T cell infiltration (non-mutated), antigen recognition and cytolytic function .…”

“…Thus, the reported increased PD-L1 expression by BRAF V600E positive LCH-cells (19,80) could explain the decreased LCH-lesional CD8 + T cell density in BRAF V600E mutated patients from our study. In addition, the immune suppressive microenvironment in LCH-lesions (5,14,15,18,(78)(79)(80)(81) may clarify why the rare CD8 + T cells that did make it into these lesions had no significant clinical impact. This is supported by our own observation of low numbers of HLA-DR pos LCH-lesional CD8 + T cells (Figure 1), low numbers of "licensed-to-kill" CD8 + T cells co-expressing the cytolytic enzymes Perforin and Granzyme B (85) (Figure S12), and rare presence of Caspase 3 expressing LCH-cells (data not shown).…”

Histiocitose De Células De Langerhans Autolimitada E De Início Tardio: Relato De Uma Entidade Raríssima

“…However, there are no definitive clinical or histopathologic findings that reliably predict the long-term behavior of skin-only LCH in neonates; therefore, it is recommended that all patients be monitored at regular intervals throughout childhood with noninvasive monitoring 10 21 In neonates and young infants, cutaneous involvement is also the most common presentation of non-self regressive Langerhans cell histiocytosis (NSRLCH) 22 . Patients with systemic involvement may have a mortality rate as high as 20%.…”