Type 2 NF1 deletions are highly unusual by virtue of the absence of nonallelic homologous recombination hotspots and an apparent preference for female mitotic recombination.

Approximately 5% of patients with neurofibromatosis type 1 (NF1) exhibit gross deletions that encompass the NF1 gene and its flanking regions. The breakpoints of the common 1.4-Mb (type 1) deletions are located within low-copy repeats (NF1-REPs) and cluster within a 3.4-kb hotspot of nonallelic homologous recombination (NAHR). Here, we present the first comprehensive breakpoint analysis of type 2 deletions, which are a second type of recurring NF1 gene deletion. Type 2 deletions span 1.2 Mb and are characterized by breakpoints located within the SUZ12 gene and its pseudogene, which closely flank the NF1-REPs. Breakpoint analysis of 13 independent type 2 deletions did not reveal any obvious hotspots of NAHR. However, an overrepresentation of polypyrimidine/polypurine tracts and triplex-forming sequences was noted in the breakpoint regions that could have facilitated NAHR. Intriguingly, all 13 type 2 deletions identified so far are characterized by somatic mosaicism, which indicates a positional preference for mitotic NAHR within the NF1 gene region. Indeed, whereas interchromosomal meiotic NAHR occurs between the NF1-REPs giving rise to type 1 deletions, NAHR during mitosis appears to occur intrachromosomally between the SUZ12 gene and its pseudogene, thereby generating type 2 deletions. Such a clear distinction between the preferred sites of mitotic versus meiotic NAHR is unprecedented in any other genomic disorder induced by the local genomic architecture. Additionally, 12 of the 13 mosaic type 2 deletions were found in females. The marked female preponderance among mosaic type 2 deletions contrasts with the equal sex distribution noted for type 1 and/or atypical NF1 deletions. Although an influence of chromatin structure was strongly suspected, no sex-specific differences in the methylation pattern exhibited by the SUZ12 gene were apparent that could explain the higher rate of mitotic recombination in females.

Epidermal growth factor receptor gene numerical aberrations are frequent events in actinic keratoses and invasive cutaneous squamous cell carcinomas.

Epidermal growth factor receptor (EGFR) gene amplification and protein overexpression are common in several cancers. EGFR status has seldom been studied in cutaneous squamous carcinomas (SCCs), or their precursors, actinic keratoses (AKs). We evaluated the presence of EGFR genomic aberrations and EGFR protein overexpression in 25 AKs and 35 invasive SCCs by means of fluorescence in situ hybridization (FISH) and immunohistochemistry. EGFR numerical aberrations were detected in 52% of AKs and 77.1% of SCCs (P = 0.042). EGFR amplification was identified in 12% of AKs and 20% of SCCs. No differences regarding EGFR numerical aberrations were observed when AKs with high-grade dysplasia were compared with SCCs. A good correlation was observed between EGFR numerical aberrations and EGFR overexpression. Our results suggest that EGFR numerical aberrations occur in the early stages of epithelial carcinogenesis in skin, not playing a role in the progression from low-grade SCCs into more aggressive phenotypes.

Childhood bullous pemphigoid: clinical and immunological findings in a series of 4 cases.

BACKGROUND: Bullous pemphigoid (BP) is an autoimmune blistering disease that is rare in childhood. As in adult BP, antibodies against the 180-kDa antigen (BP180) seem to be involved in the pathogenesis of the disease, but, to date, only a small number of children with the disease have been examined immunologically. OBSERVATIONS: We report the cases of 4 infants with BP aged 5 to 12 months. All of them had involvement of the hands and feet, and they all achieved a complete remission in less than 6 months when treated with oral prednisolone stearoyl glycolate. Three patients could be examined using antigen characterization techniques. Autoantibodies against the NC16A domain of BP180 were found by immunoblot assay in all 3 and by enzyme-linked immunosorbent assay in 2 of them. Interestingly, although IgA autoantibodies were detected in only 1 of them by indirect immunofluorescence, all of them had IgA autoantibodies, and 2 of the 3 had IgG autoantibodies against NC16A as detected by immunoblot assay. One patient also had IgG autoantibodies against the carboxyterminal domain of BP180. CONCLUSIONS: IgA-specific antibodies against BP180 were detected in all our patients. These findings further raise the question about the relationship between BP and linear IgA bullous dermatosis, the most common autoimmune blistering disorder in children.

Cranial fasciitis in an 8-year-old boy: clinical and histopathologic features.

Cranial fasciitis is an uncommon benign disorder characterized by a fibroblast-like cell proliferation, observed almost exclusively in children. Clinically, it manifests as a rapidly growing, solitary nodule in the head or neck area. Underlying bone involvement (cranial cortical erosion) is frequently detected. Histopathologic analysis allows differentiation between cranial fasciitis and fibrohistiocytic or even sarcomatous lesions observed in children. Cranial fasciitis is considered to be a reactive, non-neoplastic disorder and is usually cured by a simple excision. An increased awareness of the clinical and histopathologic characteristics of this entity seems important to establish the diagnosis, to adopt an adequate, conservative treatment and to avoid unnecessarily aggressive procedures.

Acanthosis nigricans as an adverse effect of highly active antiretroviral therapy in an adolescent girl with human immunodeficiency virus infection.

We report an 11-year-old girl with acanthosis nigricans that appeared after 4 years of treatment with didanosine, stavudine and amprenavir. Laboratory studies showed hyperglycemia, hyperinsulinemia and hypertriglyceridemia. Withdrawal of amprenavir resulted in disappearance of acanthosis nigricans and improvement of metabolic abnormalities.

Cutaneous alternariosis in transplant recipients: clinicopathologic review of 9 cases.

OBJECTIVES: We sought to evaluate and review the clinical and histopathologic features of cutaneous infections caused by the environmental opportunistic fungus Alternaria observed in transplant recipients. METHODS: We conducted a retrospective study of cases of cutaneous alternariosis in transplant recipients given a diagnosis in 3 hospitals in Catalonia, Spain, between 1991 and 2001. The clinical and evolution features were reviewed. A panel of histopathologic features was evaluated by two independent observers in all cutaneous biopsy specimens. RESULTS: In all, 9 transplant recipients (8 men and 1 woman) presenting opportunistic cutaneous alternariosis were studied. The patients were 4 renal, 2 cardiac, 1 liver, and 2 lung transplant recipients. All patients were treated with different immunosuppressive therapeutic regimes. The lesions were solitary (3 patients) or multiple grouped (6 patients): papules (4 patients), plaques (5 patients), inflammatory nodules (2 patients), and recurrent cellulitis with secondary ulceration (1 patient), mainly located on the lower extremities. No extracutaneous involvement was detected. A previous traumatic event was recorded in two patients. A total of 12 cutaneous biopsy specimens were reviewed. Biopsy specimens from early lesions (<3 months evolution) were often characterized by the presence of epidermal changes (3/6 pseudoepitheliomatous hyperplasia; 50%), a diffuse dermal mixed inflammatory infiltrate of lymphocytes, plasma cells, histiocytes, neutrophils, and giant cells, and rare and focal granuloma formation. Dermal abscess or necrotizing folliculitis was occasionally noted. In biopsy specimens from more advanced lesions (>3 months evolution), the presence of a granulomatous inflammatory infiltrate was a constant feature. Suppurative granulomas (2/6; 33%) and sarcoidlike granulomas (2/6; 33%) were noted. In all biopsy specimens, fungal structures with a typical round-to-oval, thick refractile wall were identified. CONCLUSION: Different clinical and histopathologic patterns can be noted in cutaneous alternariosis. Clinically the lesions manifest as solitary or grouped papules, plaques, or nodules mainly involving the lower extremities. Histologically, a relationship between the evolution of the cutaneous lesions and granuloma formation is detected. An increased awareness regarding the clinical and histopathologic features of cutaneous alternariosis in transplant recipients is important to achieve early detection and treatment.

Treatment of localized persistent plaque psoriasis with incoherent narrowband ultraviolet B phototherapy.

PURPOSE: This study evaluated the efficacy of targeted UVB phototherapy treatment of chronic persistent psoratic plaques with localized incoherent UVB phototherapy. METHODS: Sixteen subjects were enrolled. The final group was composed of eight men and seven women, each having one to seven chronic, stable psoriatic plaques. Each plaque was treated with fluences ranging from 3 to 7 MED using a fibre-coupled incoherent phototherapy device twice weekly for a maximum of 13 sessions. Assessments with a combination of three scores, each on a scale from 0 to 4, for scaling, erythema and induration (SEI score) were performed. RESULTS: The patients received from 6 to 13 sessions (mean 9.6). The SEI score decreased by 3.3 (p = 0.01). This reduction was equally detected in all subscores. In a few patients, blistering and burning sensation after some sessions were noted. CONCLUSION: Localized UVB phototherapy is an effective treatment option for persistent plaques of psoriasis. Compared with conventional UVB, localized phototherapy has the added safety benefit of virtually eliminating unwanted exposure of the healthy tissue to UVB.

Ultrastructural features of highly active antiretroviral therapy-associated partial lipodystrophy.

Chronic treatment with highly active antiretroviral therapy (HAART) results in a novel variety of partial lipodystrophy, combining lipoatrophic and hypertrophic areas. We have previously reported the histopathological features of this disease and have also shown that adipocyte apoptosis is involved in its origin. With the aim of further elucidating the mechanisms underlying this peculiar disorder, we performed an ultrastructural study of the adipocytes of ten HIV-1-infected patients treated with HAART for 20-42 months. In all ten cases, two main sets of ultrastructural changes were identified. Some adipocytes showed disruption of cell membranes, fragmented cytoplasmic rims, irregular cell outlines, and eventually fat droplets laying free in the connective tissue, with a histiocytic reaction around them. In addition, many adipocytes showed variable compartmentalization of fat droplets with decrease in cell size and abundant, mitochondria-rich cytoplasm. Often, a dual "white and brown" fat appearance was observed with a large unilocular vacuole surrounded by a rim of multilocular cytoplasm containing smaller isometric fat droplets and numerous mitochondria. These findings suggest that HAART-associated partial lipodystrophy is probably the result of a remodeling process of fat cells involving variable combinations of apoptosis, defective lipogenesis, and increased metabolic activity in different adipose areas of the body.

Acute generalized exanthematous pustulosis induced by terbinafine.

Terbinafine is an allylamine fungicidal agent that is widely used for the treatment of onychomycoses and other fungal infections. Adverse effects may occur in more than 10% of patients receiving oral terbinafine, with cutaneous reactions in 2.7%. We describe the development of acute generalized exanthematous pustulosis in a 36-year-old woman who took oral terbinafine.