Carlo Cota

Cutaneous manifestations of blastic plasmacytoid dendritic cell neoplasm-morphologic and phenotypic variability in a series of 33 patients.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a neoplasm derived from precursors of plasmacytoid dendritic cells. Cutaneous involvement represents often the first manifestation of the disease. We studied 45 skin biopsies from 33 patients (M:F=7.25:1; median age: 71 y; age range: 30 to 89) with BPDCN to delineate histopathologic and immunophenotypic features of this disease. Patients presented with generalized (n=18), localized (n=6), or solitary (n=9) macules, plaques, and/or tumors. Staging investigations at presentation were negative in 20 patients. Unusual histologic features included a perivascular/periadnexal pattern (6 biopsies from 4 patients) and the presence of pleomorphism of neoplastic cells with blastoid cells admixed with elongated, twisted, or hyperchromatic cells (observed in 24 specimens). Negativity of 1 among the 4 markers CD4, CD56, CD123, and TCL-1 was seen in 11 biopsies, and of 2 markers in 4 biopsies. Staining for CD68 revealed positivity of the majority of cells in 1 and of scattered cells in 24/37 stained cases. Terminal deoxynucleotidyl transferase was observed in 22/37 stained cases. Staining for Bcl-6, MUM-1 and FOX-P1 revealed positivity of a variable proportion of neoplastic cells in 16/30, 19/29, and 21/23 cases, respectively. Our study shows that cutaneous lesions of BPDCN display a greater variability of morphologic and phenotypic features than recognized earlier. Discrete perivascular infiltrates, pleomorphic morphology of neoplastic cells, and unusual phenotypic profiles may be the source of diagnostic pitfalls. These atypical variants should be recognized to make an early diagnosis and to manage properly patients with this aggressive hematological disorder.

Concordance between in vivo reflectance confocal microscopy and histology in the evaluation of plaque psoriasis.

Background   Psoriasis is a common skin inflammatory disease that affects 2% of the general population. Plaque psoriasis (PP) is its most common variant. In vivo reflectance confocal microscopy (RCM) is a non‐invasive, reproducible imaging technique that has proven to give useful information for morphometric evaluation of several inflammatory skin conditions, such as acute contact dermatitis and discoid lupus.

Analysis of the ORFK1 hypervariable regions reveal distinct HHV-8 clustering in Kaposi’s sarcoma and non-Kaposi’s cases

BackgroundClassical Kaposi’s Sarcoma (cKS) is a rare vascular tumor, which develops in subjects infected with Human Herpesvirus-8 (HHV-8). Beside the host predisposing factors, viral genetic variants might possibly be related to disease development. The aim of this study was to identify HHV-8 variants in patients with cKS or in HHV-8 infected subjects either asymptomatic or with cKS-unrelated cutaneous lymphoproliferative disorders.MethodsThe VR1 and VR2 regions of the ORF K1 sequence were analyzed in samples (peripheral blood and/or lesional tissue) collected between 2000 and 2010 from 27 subjects with HHV-8 infection, established by the presence of anti-HHV-8 antibodies. On the basis of viral genotyping, a phylogenetic analysis and a time-scaled evaluation were performed.ResultsTwo main clades of HHV-8, corresponding to A and C subtypes, were identified. Moreover, for each subtype, two main clusters were found distinctively associated to cKS or non-cKS subjects. Selective pressure analysis showed twelve sites of the K1 coding gene (VR1 and VR2 regions) under positive selective pressure and one site under negative pressure.ConclusionThus, present data suggest that HHV-8 genetic variants may influence the susceptibility to cKS in individuals with HHV-8 infection.

Role of fibroblast-derived growth factors in regulating hyperpigmentation of solar lentigo

Background  Cutaneous pigmentation is regulated by a complex melanogenic network in which both keratinocytes and fibroblasts synthesize growth factors and cytokines. Solar lentigo (SL) is characterized by hyperpigmented lesions occurring on photodamaged skin areas. Despite the association of SL to ultraviolet (UV) exposure, the mechanisms underlying the development of these spots are not completely defined.

Alterations of the Cell-Cycle Inhibitors p27KIP1 and p16INK4a Are Frequent in Blastic Plasmacytoid Dendritic Cell Neoplasms

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, clinically aggressive malignancy with a median survival of 12-14 months. To identify pathogenetic relevant genomic aberrations and molecular targets for therapy, we analyzed skin biopsy samples obtained from 14 patients using high-resolution array-based comparative genomic hybridization and immunostaining. Losses of chromosomes 9, 12, 13, and 15 were detected most frequently. Loss of the CDKN1B locus was the most common finding and was detected in 64% of tumors. In all but one case, the dose-dependent haploinsufficient cell-cycle inhibitor p27(KIP1), encoded by CDKN1B, was weakly expressed in the nuclei of tumor cells. Losses of the CDKN2A-ARF-CDKN2B locus occurred in 50% of patients, and in one case a distinct biallelic loss was identified. The cell-cycle inhibitor p16(INK4a), which is encoded by CDKN2A, was not expressed in tumor cells, suggesting a complete loss of function. Loss of chromosome 13, including the RB1 gene, was observed in 43% of tumors. These results imply that alterations of the cell-cycle checkpoint controlling proteins p27(KIP1), p16(INK4a), and RB1 may exert a profound effect in malignant transformation in BPDCN. The elucidation of the affected pathways may guide the development of new treatments specifically designed for this aggressive disease entity.

The protean spectrum of non-Hodgkin lymphomas with prominent involvement of subcutaneous fat

Background:  Subcutaneous T‐cell lymphoma (STCL) represents a controversial entity and a confused concept in the field of cutaneous T‐cell lymphomas (CTCLs). Recently, α/β+/CD8+ STCL has been recognized by the new World Health Organization (WHO)–European Organization for Research and Treatment of Cancer (EORTC) classification of primary cutaneous lymphomas as a distinct entity in the group of CTCLs.

Vitiligo: A Possible Model of Degenerative Diseases

Vitiligo is characterized by the progressive disappearance of pigment cells from skin and hair follicle. Several in vitro and in vivo studies show evidence of an altered redox status, suggesting that loss of cellular redox equilibrium might be the pathogenic mechanism in vitiligo. However, despite the numerous data supporting a pathogenic role of oxidative stress, there is still no consensus explanation underlying the oxidative stress-driven disappear of melanocytes from the epidermis. In this study, in vitro characterization of melanocytes cultures from non-lesional vitiligo skin revealed at the cellular level aberrant function of signal transduction pathways common with neurodegenerative diseases including modification of lipid metabolism, hyperactivation of mitogen-activated protein kinase (MAPK) and cAMP response element-binding protein (CREB), constitutive p53-dependent stress signal transduction cascades, and enhanced sensibility to pro-apoptotic stimuli. Notably, these long-term effects of subcytotoxic oxidative stress are also biomarkers of pre-senescent cellular phenotype. Consistent with this, vitiligo cells showed a significant increase in p16 that did not correlate with the chronological age of the donor. Moreover, vitiligo melanocytes produced many biologically active proteins among the senescence-associated secretory phenotype (SAPS), such as interleukin-6 (IL-6), matrix metallo proteinase-3 (MMP3), cyclooxygenase-2 (Cox-2), insulin-like growth factor-binding protein-3 and 7 (IGFBP3, IGFBP7). Together, these data argue for a complicated pathophysiologic puzzle underlying melanocytes degeneration resembling, from the biological point of view, neurodegenerative diseases. Our results suggest new possible targets for intervention that in combination with current therapies could correct melanocytes intrinsic defects.

Erosive Pustular Dermatosis of the Scalp: A Case Report and Review of the Literature

Erosive pustular dermatosis of the scalp (EPDS) is a rare entity characterized by pustular, erosive and crusted lesions of the scalp with progressive scarring alopecia. The aetiology is unknown, but predisposing factors have been reported such as trauma, skin grafting, prolonged exposure to UV light of a bald scalp as well as co-existence of auto-immune diseases. Laboratory data, bacteriological and mycological investigations and histopathology are generally not diagnostic. A 45-year-old Caucasian man with 1-year-old pustular, erosive and crusted lesions on his bald scalp was seen. Laboratory data, including auto-immunity, bacteriological and mycological investigations were negative. Histopathology was not diagnostic showing a diffuse polymorphous infiltrate involving the dermis. A diagnosis of EPDS was made. The patient was treated with topical and systemic antibiotics and steroids as well as oral nimesulide with no or partial response. Consequently, isotretinoin (0.75 mg/kg/day) was started obtaining complete resolution in few months. No relapse after 1 year of follow-up was seen. EPDS represents a distinct disease with a history of relapsing and unsatisfactory response to common treatments. Systemic retinoids may be considered as a potentially resolutive choice.

Confocal microscopy of recurrent naevi and recurrent melanomas: a retrospective morphological study.

Background  Repigmentation within a scar after different procedures (shave biopsy, partial excision, cryotherapy, laser) is a challenging diagnostic situation.

Confocal microscopic features of scarring alopecia: preliminary report.

Background  Lichen planopilaris (LPP) and discoid lupus erythematosus (DLE) are the most common causes of lymphocytic primary cicatricial alopecia. The management of scarring alopecia can be difficult. The combination of clinical, dermoscopy and reflectance confocal microscopy (RCM), a noninvasive, high‐resolution imaging technique, examinations have already been demonstrated to be useful for choosing the correct biopsy site in patients with inflammatory skin disease and obtaining microscopic diagnostic criteria.