Hydroa-Vacciniforme like Lymphoproliferative Disorder
Hydroa vacciniforme (HV)-like lymphoproliferative disorder (HV-like LPD) is a chronic EBV-positive cutaneous T-cell lymphoproliferative disorder of childhood, associated with the risk of developing systemic lymphoma. HV-like LPD is a polyclonal or (most often) monoclonal disorder of T-cells and/or NK cells, regardless of the presence or absence of systemic symptoms and the severity of the skin lesions. Classic HV, severe HV, and HV-like cutaneous T-cell lymphoma constitute a continuous spectrum of EBV-associated HV-like LPD (Quintanilla-Martinezz et al. 2013, 2017).
HV-like LPD is rare and occurs mainly in children and adolescents from Latin America and East Asia. It is rare in adults. There is a seasonal increased occurrence during the summer (Quintanilla-Martinezz et al. 2013).
The median age of the time of diagnosis is 8 years (range: 1–15 years) (Quintanilla-Martinezz et al. 2013.
The male to female ratio is slightly elevated (2.3,1) (Quintanilla-Martinezz et al. 2013).
Although lesions most commonly involved face, dorsal surface of the hands, and earlobes, skin lesions are not exclusively limited to sun-exposed areas. Half of the patients presented with disseminated dermatosis and systemic symptoms, such as fever, wasting, lymphadenopathy, and hepatosplenomegaly. Twenty percent of the patients also have hypersensitivity to mosquito bite, which usually associates with a proliferation of EBV-infected NK cells (Quintanilla-Martinezz et al. 2013).
Currently, no standard treatment has been established. Chemotherapy and/or radiotherapy have been shown to be of little or no benefit. Immunomodulating therapies, such as predonisolone, cyclosporine A, interferon alfa, chloroquine, and thalidomide, have been shown to result in temporary remission or improvement of symptoms (Barrionuevo et al. 2002; Kimura et al. 2012; Beltran et al. 2014). In indolent cases, a conservative treatment is recommended, whereas hematopoietic stem cell transplantation has been introduced as a curative therapy in more advanced cases (Kimura et al. 2012).
The clinical course is variable, and some patients are alive with recurrent skin lesions for 9–13 years, while less than 50% of patients died of organ failure or systemic lymphoma including a nasal-type NK/T-cell lymphoma and a peripheral T-cell lymphoma, NOS (Quintanilla-Martinezz et al. 2013). Some patients present with a very indolent course, with localized skin lesions in sun-exposed areas and no systemic symptoms (classic HV)(Iwatsuki et al. 2006). EBV-infected lymphocyte subsets, anti-EBV antibody titres, EBV DNA load, T-cell clonality, the amount of EBV-positive cells, and/or the density of the infiltrate do not predict the outcome. Late onset (onset age > 9 years) and EBV reactivation are both related to more severe phenotypes of the disease (Quintanilla-Martinezz et al. 2013; Miyake et al. 2015).
In situ hybridization for EBV-encoded small RNA (EBER) is positive; however, the amount of EBER-positive cells represents only a subpopulation of the CD3-positive infiltrating cells. EBER-positive cells concentrated mainly around the blood vessels and adnexa in the dermis, in the subcutaneous tissue, and in the basal epithelial layer in cases with intraepidermal vesicles. Most cases with T-cell phenotype have clonal rearrangements of the TCR genes, while NK-cell phenotype cases show a polyclonal rearrangement of the TCR genes. EBV is monoclonal by terminal repeat analysis (Iwatsuki et al. 2006; Kimura et al. 2012; Quintanilla-Martinezz et al. 2013).
Morphologically, HV-like LPD can mimic subcutaneous panniculitis-like T-cell lymphoma (SPTCL), primary cutaneous γδ T-cell lymphoma, or cutaneous involvement by an extranodal NK/T-cell lymphoma of the nasal type. Without clinical information, the differential diagnoses with the latter might be impossible because the morphology and phenotype of the neoplastic cells are indistinguishable.
References and Further Reading
- Quintanilla-Martinezz L, Ko Y-H, Kimura H, et al (2017) Hydroa vacciniforme-like lymphoproliferative disorder. In S. H. Swerdlow, E. Campo, N. L. Harris, et al. (Eds.), WHO classification of Tumours of Haematopoietic and lymphoid tissues (revised 4th ed., pp. 360–362). Lyon: IARC.Google Scholar