Next-generation sequencing is a straightforward tool for the identification of disease genes in extended genomic regions. Autozygosity mapping was performed on a five-generation inbred Italian family with three siblings affected with Clericuzio-type poikiloderma with neutropenia (PN [MIM %604173]), a rare autosomal-recessive genodermatosis characterised by poikiloderma, pachyonychia, and chronic neutropenia. The siblings were initially diagnosed as affected with Rothmund-Thomson syndrome (RTS [MIM #268400]), with which PN shows phenotypic overlap. Linkage analysis on all living subjects of the family identified a large 16q region inherited identically by descent (IBD) in all affected family members. Deep sequencing of this 3.4 Mb region previously enriched with array capture revealed a homozygous c.504-2 A>C mismatch in all affected siblings. The mutation destroys the invariant AG acceptor site of intron 4 of the evolutionarily conserved C16orf57 gene. Two distinct deleterious mutations (c.502A>G and c.666_676+1del12) identified in an unrelated PN patient confirmed that the C16orf57 gene is responsible for PN. The function of the predicted C16orf57 gene is unknown, but its product has been shown to be interconnected to RECQL4 protein via SMAD4 proteins. The unravelled clinical and genetic identity of PN allows patients to undergo genetic testing and follow-up.

MNH is an aggressive tumour and should be diagnosed and excised as early as possible. Histological parameters are paramount, but correct diagnosis also calls for attention to clinical presentation and any history of recurrence or recent enlargement of long-standing lesions. In our experience, radiotherapy and chemotherapy do not seem to prolong survival.

Noninvasive diagnostic methods such as dermoscopy or epiluminescence light microscopy have been developed in an attempt to improve diagnostic accuracy of pigmented skin lesions. The evaluation of the many morphologic characteristics of pigmented skin lesions observable by epiluminescence light microscopy, however, is often extremely complex and subjective. With the aim of obviating these problems of qualitative interpretation, methods based on mathematical analysis of pigmented skin lesions have recently been designed. These methods are based on computerized analysis of digital images obtained by epiluminescence light microscopy. In this study we used a digital dermoscopy analyzer with 147 clinically atypical pigmented skin lesions (90 nevi and 57 melanomas) to determine its discriminating power with respect to histologic diagnosis. The system evaluated 48 objective parameters used to train an artificial neural network. Using the artificial neural network with 10 variables selected by a stepwise procedure, we obtained a maximum accuracy in distinguishing melanoma from benign lesions of about 93%. Comparing this result with those of the many studies using classical epiluminescence light microscopy, it emerges that the method proposed is equal or even superior in diagnostic accuracy and has the advantage of not depending on the expertise of the clinician who examines the lesion.

SUMMARYExtracorporeal photochemotherapy ( ECP) has been shown to be a potent activator of peripheral blood macrophages because it causes a marked release of macrophage-dependent proinflammatory cytokines, and it is therefore currently considered to be a safe and non-toxic immunomodulatory treatment. On this basis we studied the function of peripheral blood mononuclear cells (PBMC ) in eight patients with early stage (Ib) cutaneous T-cell lymphoma (CTCL), before and 1 year after ECP, together with their clinical and histological responses. In particular we evaluated in vitro phytohaemagglutinin (PHA)-stimulated proliferation and production of interleukin-4 (IL-4) and interferon-c (IFN-c) as well as lipopolysaccharide (LPS)-induced production of IL-12. Before treatment we observed that PBMC of patients produced significantly higher levels of IL-4 and lower levels of IFN-c and IL-12 than those of healthy control subjects. After 1 year of ECP, IL-4, IFN-c and IL-12 production no longer differed from that of control subjects. Moreover, we observed a good clinical result matched by histological response. Our data confirm that earlystage CTCL patients show a predominantly type-2 immune response that might be responsible for several immunological abnormalities found in this disease. We have demonstrated that ECP reverses the T-helper type 1/T-helper type 2 (Th1/Th2) imbalance and may therefore be considered an efficient biological response modifier.

BACKGROUND: Mycosis fungoides (MF) is an indolent primary cutaneous T‐cell lymphoma. To the authors' knowledge, no data currently are available regarding the evolution over time of the risk of developing specific pathways of disease progression. METHODS: This retrospective study analyzed 1422 patients with MF who were diagnosed and followed from 1975 through 2010 in 27 Italian Study Group for Cutaneous Lymphoma centers. The primary objectives were to ascertain the time course, pathways, and hazards risk trends of cutaneous/extracutaneous disease progression; to evaluate whether different tumor‐lymph node‐metastasis‐blood (TNMB) stages have different pathways of disease progression; and to analyze differences between tumor‐stage and erythrodermic MF with regard to clinical onset, disease evolution, and prognosis. The secondary objective was to provide a further validation for the revised International Society for Cutaneous Lymphomas and the Cutaneous Lymphoma Task Force of the European Organization of Research and Treatment of Cancer (ISCL/EORTC) classification. RESULTS: The median follow‐up was 14.5 years; stage progression occurred in 29.7% of patients and blood involvement was the most frequent extracutaneous site of disease progression. Patients with stage IA to stage IB disease demonstrated a steady low annual incidence of disease progression to tumor‐stage (1%‐2%); patients with stage IIA disease had a higher risk within the first years (up to 9.4%). Erythroderma evolved with a significantly higher frequency from patches/plaques (13.9%/28.2%) than tumors (P = .028 and P = .013, respectively). Hazards rates of extracutaneous involvement were low (< 1%). The T‐score was found to be associated with extracutaneous involvement site, tumor‐stage disease with lymph node/visceral lesions, and erythroderma with blood involvement. TNMB classification and stage progression resulted as independent prognostic variables being detected on multivariate analysis; the type of extracutaneous involvement was found to affect survival . CONCLUSIONS: The data from the current study support the need for a stage‐tailored follow‐up, suggest that the classification of tumor‐stage disease at a stage below erythroderma could be modified, and offer a further validation for the revised TNMB classification. Cancer 2012. © 2012 American Cancer Society.