CD38 Expression by Circulating and Skin-Infiltrating Lymphocytes from Sezary Syndrome Patients: A Flow Cytometry and Immunohistochemistry Study.

Background: Reports on the expression of CD38 in Sézary syndrome (SS), erythrodermic primary cutaneous T cell lymphoma with leukemic involvement, are limited. The aim of the present study is the analysis of the expression of CD38 by skin-infiltrating mononuclear cells and circulating T lymphocytes in a cohort of SS patients.

Methods: SS patients diagnosed since 1985 in our clinic were retrospectively analyzed for CD38 expression in biopsy and blood samples by immunohistochemistry and flow cytometry, respectively.

Phenotypical Markers, Molecular Mutations, and Immune Microenvironment as Targets for New Treatments in Patients with Mycosis Fungoides and/or Sézary Syndrome.

Primary cutaneous lymphomas encompass a wide spectrum of rare lymphoproliferative disorders originating in the skin, among which, mycosis fungoides (MF) is the most common subtype. The treatment of this disease is based on skin-directed therapies eventually in association with biologic response modifiers in the early phases, whereas in patients with the advanced stages, several therapeutic strategies can be used including mono and/or polychemotherapy and bone marrow transplantation. In recent years, the identification of specific markers (phenotypical, immunological, and molecular) has led to the development of several studies (including two randomized phase III trials).

Isolation of extracellular vesicles improves the detection of mutant DNA from plasma of metastatic melanoma patients.

Detection of BRAF within cell free tumor DNA (ctDNA) is emerging as a promising means to improve patients' stratification or enable BRAF inhibitor (BRAFi) therapeutic monitoring in a minimally invasive manner. Here, we investigated whether extracellular vesicle-(EV)-associated-DNA (EV-DNA) has value as an alternative source of circulating BRAF. To do so, we identified a clinical practice-compatible protocol for the isolation of EV-DNA and assessed BRAF gene status on plasma samples from metastatic melanoma patients at the beginning and during BRAFi therapy.

HERV-E expression in peripheral mononuclear cells of patients with psoriasis.

Background: Psoriasis is a common inflammatory skin disease characterized by uncontrolled proliferation of keratinocytes and recruitment of T lymphocytes into the skin. Possible triggers for psoriasis have been attributed to drugs or pathogens such as bacteria and possibly virus. Human endogenous retroviruses (HERVs) might play a role in triggering these antiviral immune responses, since the role of HERVs in the pathogenesis of autoimmune diseases has generated considerable interest.

DNA from Human Polyomaviruses, MWPyV, HPyV6, HPyV7, HPyV9 and HPyV12 in Cutaneous T-cell Lymphomas.

Background/aim: The etiopathogenesis of mycosis fungoides and Sézary syndrome remains obscure. Different viruses have been proposed to have a role in the etiopathogenesis of cutaneous T-cell lymphomas (CTCL). In the present study, the presence of five recently discovered human polyomaviruses 6 (HPyV6), human polyomaviruses 7 (HPyV7), human polyomaviruses 9 (HPyV9), human polyomaviruses 12 (HPyV12), and Malawi polyomavirus (MWPyV), have been analyzed in 55 CTCL in order to confirm the skin tropism and the possible pathological association of these new polyomaviruses.

BRAF and MEK Inhibitors Increase PD-1-Positive Melanoma Cells Leading to a Potential Lymphocyte-Independent Synergism with Anti-PD-1 Antibody.

BRAF and MEK inhibitors (BRAF/MEKi) favor melanoma-infiltrating lymphocytes, providing the rationale for current combinatorial trials with anti-PD-1 antibody. A portion of melanoma cells may express PD-1, and anti-PD-1 antibody could have a direct antitumor effect. Here, we explore whether BRAF/MEKi modulate rates of PD-1 melanoma cells, supporting an additional-lymphocyte-independent-basis for their therapeutic combination with anti-PD-1 antibody.

Is HERV-K and HERV-W expression regulated by mir-155 in Sézary Syndrome?

Background: According to the latest update, 2578 unique mature miRNAs are currently annotated in the human genome and participate in the regulation of multiple events, such as cellular proliferation or apoptosis. A previous study analyzing global miRNA expression patterns in GH cells (high HERV-K versus low) showed that two miRNAs (miR-663 and miR-638) are differentially regulated and exhibit expression parallel to that of HERV-K. The aim of this study was to evaluate HERV-K and -W pol gene and mir-155 expression in SS patients and possible relationship between them.

Erythema multiforme-like lesions in primary cutaneous aggressive cytotoxic epidermotropic CD8+ T-cell lymphoma: A diagnostic and therapeutic challenge.

Primary cutaneous aggressive cytotoxic epidermotropic CD8+ T-cell lymphoma is an extremely rare, rapidly progressing, cutaneous lymphoma, with frequent systemic involvement and poor prognosis, that still represents a diagnostic and therapeutic challenge, especially in the early stage. Herein, we report a case of an elderly woman with a fulminant course, who at onset presented with clinical and pathological features mimicking erythema multiforme (EM) and treated with cyclosporine that led to rapid deterioration with fatal outcome 6 months after disease onset. Histopathology showed a lichenoid, epidermotropic and nodular, angiocentric, dermal and subcutaneous infiltrate of sF1, CD8+, CD45RA+ small to medium-sized atypical lymphoid cells, which strongly expressed cytotoxic markers.

PCR Real time Mismatch Amplification Mutation Assay (MAMA Real Time PCR) for evaluation of TNF-α promoter gene polymorphism -308 G/A in patients with psoriasis.

Background: Psoriasis is a common chronic inflammatory disease, the plaques are infiltrated by leukocytes producing high levels of proinflammatory cytokines and TNF-α. Single-nucleotide polymorphisms within the gene promoters have been shown to affect gene expression. The -308 G/A polymorphism could affect TNF synthesis at transcriptional level.

Human Endogenous Retrovirus Expression in Primary Cutaneous T-Cell Lymphomas.

Background: Mycosis fungoides (MF) and Sézary syndrome (SS) are the most frequent cutaneous T-cell lymphomas (CTCL). Human endogenous retroviruses (HERVs) were reverse transcribed and integrated into primate chromosomal DNA, becoming noninfectious, although various stimuli may reactivate them. HERV expression seems to be impaired in several human diseases but limited data regarding CTCL are available.

Improved Anti-Tumoral Therapeutic Efficacy of 4-Hydroxynonenal Incorporated in Novel Lipid Nanocapsules in 2D and 3D Models.

4-hydroxynonenal (HNE), a lipid peroxidation product, is a promising anti-neoplastic drug due to its remarkable anti-cancer activities. However, this possibility has not been explored, because the delivery of HNE is very challenging as a result of its low solubility and its poor stability. This study intentionally designed a new type of lipid nanocapsules specifically for HNE delivery.

Melanoma of the lower extremities: foot site is an independent risk factor for clinical outcome.

Background: Despite the better prognosis of melanomas localized on lower extremities, some studies have suggested that melanomas on the foot are related to a poorer survival and should be considered separately.

Objective: To review our case series of cutaneous melanomas on the lower extremities and to analyze the clinicopathological association, time course, types of progression, and survival differences.

Methods: We included 1671 patients (stage 0-II) with a cutaneous melanoma on the lower extremities (subungual melanomas were excluded).

Blood flow cytometry in Sézary syndrome: new insights on prognostic relevance and immunophenotypic changes during follow-up.

Objectives: Sézary syndrome (SS) is characterized by erythroderma, generalized lymphadenopathy, and the presence of circulating atypical lymphocytes, which are difficult to identify by morphologic data.

Methods: We revised our series of 107 patients in an attempt to better define the phenotypic aberrancies in blood at diagnosis and the immunophenotypic stability over time detected by flow cytometry. Polymerase chain reaction assay was also used to study CD26/dipeptidyl peptidase IV (DPPIV) gene methylation.

Regulatory T cells as well as IL-10 are reduced in the skin of patients with dermatitis herpetiformis.

Background: Dermatitis herpetiformis (DH) and celiac disease (CD) are considered as autoimmune diseases that share a defined trigger (gluten) and a common genetic background (HLA-DQ2/DQ8). However, the pathogenesis of DH is not fully understood and no data are available about the immune regulation in such a disease.

Objective: The aim of this study was to assess if alterations in the pattern of the immune response and, in particular, impairments of regulatory T (Tregs) cells may contribute to the phenotypic differences between DH and CD.

Spiky follicular mycosis fungoides: a clinicopathologic study of 8 cases.

Background: The early stages of follicular mycosis fungoides (FMF) have not been described previously in the literature.

Objective: Our goal was to better categorize the clinicopathologic features of early stages of FMF.

Methods: The clinical notes of patients with a diagnosis of FMF seen during the previous 5 years were reviewed to identify any cases that at presentation had only hyperkeratotic follicular lesions.

Eruptive dermal clear cell desmo-plastic mesenchymal tumors with perivascular myoid differentiation in a young boy. A clinical, histopathologic, immunohistochemical and electron microscopy study of 17 lesions.

Clear cell tumors of the skin are observed in a wide variety of benign and malignant conditions with different histogenesis, sharing the presence of cells with abundant clear cytoplasm. Herein, we report the clinicopathologic features of a healthy young patient affected by asymptomatic, eruptive and disseminated, benign clear cell dermal tumors since early infancy. Neither family history nor genetic testing and counseling provided further useful information.

The inclusion complex of 4-hydroxynonenal with a polymeric derivative of β-cyclodextrin enhances the antitumoral efficacy of the aldehyde in several tumor cell lines and in a three-dimensional human melanoma model.

4-Hydroxynonenal (HNE) is the most studied end product of the lipoperoxidation process, by virtue of its relevant biological activity. The antiproliferative and proapoptotic effects of HNE have been widely demonstrated in a great variety of tumor cell types in vitro. Thus, it might represent a promising new molecule in anticancer therapy strategies.

Functional and phenotypical impairment of polymorphonuclear cells in atopic dermatitis: an additional cause for the known susceptibility to infections?

Background: Atopic dermatitis (AD) patients present an high susceptibility to infections. The phagocytic activity of polymorphonuclear granulocytes (PMNs) is mediated by the interactions between Toll-like receptors (TLRs) and pathogen-associated molecular patterns.

Objective: To investigate functional activity and phenotype of PMNs in AD patients.

Functional and phenotypical alterations of polymorphonuclear cells in Sézary syndrome patients.

Sézary syndrome (SS), the leukemic variant of cutaneous T-cell lymphoma (CTCL), has a poor prognosis and infections represent the most frequent cause of death. Polymorphonucleate granulocytes (PMNs) constitute an essential part of the innate immune system: their phagocytic and killing activity against pathogens is mediated by the interactions between Toll-like receptors (TLRs) and the Pathogen-associated molecular patterns (PAMPs). The aim of this study was to investigate PMN functional activity and phenotype in SS patients and their correlation with the onset of infectious complications.

Therapeutic hotline. A rare vandetanib-induced photo-allergic drug eruption.

Vandetanib is an inhibitor of the vascular endothelial growth factor receptor 2 tyrosine kinase and the epidermal growth factor receptor tyrosine kinase, recently used in the treatment of different tumors. We describe a case of a photo-allergic reaction to vandetanib in an 80-year-old Caucasian woman affected by metastatic non-small cell lung cancer. Phototoxic reactions to vandetanib have been rarely reported in the literature.

TCRgamma-chain gene rearrangement by GeneScan: incidence and significance of clonal heterogeneity in Sézary syndrome.

GeneScan (GS) analysis is a highly sensitive method for the early detection of cutaneous T-cell lymphoma (CTCL) and allows the identification of clonal heterogeneity, defined as the coexistence of two or more different T-cell clones in multiple samples from the same patient. We analyzed by GS the incidence and the significance of long-lived oligoclonal expansions in multiple skin and blood samples from 24 Sézary syndrome (SS) patients, and tried to correlate them with the clinical outcome. A skin clonal heterogeneity with additional reproducible TCRgamma-gene rearrangements (TCRgamma-GRs) was detected at diagnosis in 19/24 patients, 13 of whom had a constant prevalence of pathological TCRgamma-GRs in both skin and blood (dominant clonal pattern).

Long-term evolution of an untreated primary cutaneous follicle center lymphoma of the scalp.

Among primary cutaneous B-cell lymphomas, follicle center lymphomas represent, according to the World Health Organization-European Organisation For Research and Treatment of Cancer classification, a subgroup with a favorable prognosis. We describe the case of a 45-year-old man who presented with large infiltrated tumors and nodules coalescing into a wide ulcerated plaque of the scalp, extending from the frontal to the occipital region. At the vertex, 2 large ulcerations were present, reaching the subcutaneous tissues and the underlying bone structures with osseus infiltration and erosion and consequent meningeal exposure.