Clinical, pathologic, and genetic features of massive soft tissue neurofibromas in a Sicilian patient.

Neurofibromatosis type 1 (NF1) is an autosomal dominant condition seen in all ethnic groups affecting approximately one in 4000 individuals. The disease is caused by mutations in the NF1 gene, one of the largest human genes. In this report we present one case of massive soft tissue neurofibromas arising in a Sicilian patient with NF1. The sequence of NF1 gene in this patient revealed a cluster of variants distributed along the whole gene. Among these we identified two heterozygous frameshift mutations in exon 19 (c.2480delA) and a novel mutation in exon 21 (c.2632delC). Ten novel nonsynonymous missense variations were also identified in this patient.

Clinical and immunohistochemical evaluation of the vulvar Langerhans cell histiocytosis.

We present the case of a woman with diabetes insipidus with subsequent genital and multiorgan Langerhans cell histiocytosis (LCH). A monolateral and slightly infiltrated erythematous plaque of the vulva was observed. Hematoxylin and eosin and immunophenotypic studies were performed. The primary antibodies used were monoclonal antibody to S100, CD1a, CD34, HLA-DR, PCNA, CD45Ro, CD40, and langerin. The histology of the infiltrates revealed a granulomatous reaction pattern, with extensive aggregates of histiocyte proliferation. The histiocytes, morphologically characterized by a pale staining of cytoplasm surrounding a grooved reniform nucleus, sometimes contained small distinct nucleoli. Lymphocytes, eosinophils, macrophages, and both plasma cells and giant cells typically infiltrated the lesions. Cells CD1a+ and S100+ infiltrated the epidermic and were dispersed over the infiltrates as well as in clusters, and around the vessels. A considerable number of CD40-expressing cells were restricted to CD1a+ LCH cells. The specimen contained a high percentage of langerin+ cells in both the dermis and the epidermis. The clinical manifestations of LCH affecting the genital area can be diverse, and in most patients take the form of ulcers or erythematous plaques. Histopathologic examination of the lesion evidences a mixture of Langerhans cell histiocytes (CD1a+, S100+, HLADr+, CD207+, CD 40+), lymphocytes (predominantly helper [CD4] CD 45 Ro+), eosinophils, and macrophages. Each of the cell types produces a "cytokine storm." Many of the cytokines favor recruitment of Langerhans cell progenitors and rescue the Langerhans cell histiocytes from apoptosis.

Progressive symmetric erythro-keratosis associated with oligodontia, severe caries, disturbed hair growth and ectopic nail: a new syndrome?

A 7-year-old girl had well-demarcated erythematous plaques covered with white pityriasiform scales which were symmetrically distributed and involved the extensor surfaces of the extremities as well as the abdomen, buttocks and face. Histological examination showed marked hyperkeratosis with parakeratosis, and a thickened granular cell layer, mild acanthosis and slight lymphocytic infiltration surrounding the papillary blood vessels, compatible with a diagnosis of progressive symmetrical erythro-keratosis. Remarkably, a keratotic excrescence similar to a normal nail plate involved the tip of the nose since the age of 6 months. Moreover, occipital hairlessness, oligodontia and severe caries were noted. Progressive symmetric erythro-keratosis has so far been described as a non-syndromic skin disorder, which is why our patient's multisystem birth defect may represent a new entity.

Amelanotic conjunctival melanoma.

Conjunctival melanoma is a rare condition of the eye pigment predominantly affecting white adults. We describe a 32-year-old white man with an amelanotic malignant melanoma of the conjunctiva that is not associated with primary acquired melanosis (PAM) or melanocytic nevus. The patient presented with a 2-year history of nonpigmented vascularized nodules of the right eye. Results of hematoxylin and eosin (H and E) staining of the lesion showed an invasive nodule with vertical spreading, invasion of the substantia propria corneae, and ulceration. S100 protein was expressed in the cells of the invasive nodule. HMB45 protein was highly positive in the melanoma cells. The de novo amelanotic malignant melanoma of the conjunctiva we describe is an extremely uncommon tumor mainly affecting white adults.

[Fabry disease in Italy: first epidemiologic and collaborative study]. / Primo studio epidemiologico e collaborativo italiano sulla malattia di Fabry.

The authors sought to define the prevalence of Fabry disease and to establish the incidence and its natural history in Italy. The aim of this study was to point out the first clinical signs and symptoms to perform an early diagnosis and hence to start a specific therapeutic treatment. Fabry disease is an inborn error of metabolism caused by the deficiency of the lysosomal enzyme alpha-galactosidase A. Fabry disease is a severe X-linked disorder presenting with a higher morbidity between the third and the fourth decade of life. Fabry disease may be confused with other diseases or completely misdiagnosed: its frequency is estimated worldwide to be 1:117000. In Italy, 65 patients have been identified by several specialized institutions; age, sex, onset of first clinical signs and symptoms were analyzed and reported. In conclusion, this is the first Italian collaborative study that allows to delineate and point out the clinical signs of Fabry disease to perform a correct and early diagnosis. Enzyme replacement therapy is now available and its early beginning can prevent renal and cardiac failure, improve the quality of life and life expectancy in these patients.

Pharmacokinetic evaluation of mycophenolate mofetil for pemphigus.

INTRODUCTION: Pemphigus is an autoimmune blistering disease of the skin and mucous membranes characterized by the development of autoantibodies against the desmosomal proteins, desmoglein-1 and -3. Before the advent of corticosteroids, therapy was almost fatal. The introduction of high-dose corticosteroid therapy has reduced mortality rates to ∼ 10%, but long-term use of steroids can lead to side effects, many of which are severe and associated with significant morbidity. Thus, the major goal of pemphigus therapy has been to reduce the patient's cumulative exposure to systemic corticosteroids. Over the last 2 decades, a range of corticosteroid-sparing immunosuppressive agents have been described, but these therapies are not without potentially serious complications. Despite the range of treatment options, a proportion of patients do not achieve remission, while others show an initial treatment response but remain poorly controlled. The recent availability of mycophenolate mofetil (MMF), originally developed for preventing allograft rejection, appears to be effective in autoimmune blistering diseases in combination with systemic corticosteroid or as a monotherapy. AREAS COVERED: This review aims to provide an extensive overview of the literature on the clinical pharmacokinetics of MMF in pemphigus treatment and a brief summary of current pharmacodynamic information. After completing this learning activity, readers should be able to summarize the pharmacology of MMF as an immunosuppressant; recognize its potential role in the treatment of pemphigus, including general dosing guidelines and laboratory monitoring schedules, use in patient populations and potential adverse effects; and identify future considerations and developing areas of research regarding the use of mycophenolic acid in the treatment of autoimmune blistering diseases. EXPERT OPINION: Current morbidity of pemphigus is largely iatrogenic, caused by side effects of the long-term, high-dose corticosteroid therapy that is necessary to sustain disease control. MMF demonstrates complex pharmacokinetics and displays large between-subject pharmacokinetic variability. Experience with MMF has demonstrated long-term safety and tolerability in the treatment of pemphigus.

Neurofibromatosis of the nipple-areolar area: a case series.

INTRODUCTION: Neurofibromatosis type 1 is an autosomal dominant disorder that occurs across all ethnic groups and affects approximately one in 4000 individuals. One of the most noticeable characteristics of the disease is the development of neurofibromas. CASE PRESENTATION: A total of 258 patients (131 women, 127 men) with neurofibromatosis type 1 were evaluated between 1994 and 2004 in our hospital's dermatology department. Nine patients (3.45%, 95% confidence limits 1.22 to 5.68) had neurofibromas of the breast. One of these nine patients presented with an extensive congenital plexiform neurofibroma in the outer quadrants of her right breast, extending to the nipple-areolar complex. Meanwhile, three patients had more than one neurofibroma on the nipple-areolar complexes. Three patients had a family history of neurofibroma. Over the years 1994 to 2004, the cutaneous lesions were not associated with any malignancies. Presenting symptoms were related to conditions such as increasing size of the mass, and associated loss of function and pain. CONCLUSIONS: This study suggests that the changes are limited to particular subgroups. That neurofibromatosis is more prevalent in women (7 women and 2 men) suggests that being female could be a susceptibility factor for the development of neurofibromas of the nipple-areolar complexes. There are few reports in the literature describing breast carcinomas in association with von Recklinghausen disease. It has been speculated that the presence of multiple neurofibromas of the breast may obscure a breast mass at palpation, leading to a delay in clinical detection. We suggest that patients with neurofibromas of the breast have more rigorous clinical and mammographic screening of the breast during adulthood to determine the presence or absence of malignancies. The finding that both the neurofibromatosis type 1 gene and a breast cancer predisposition gene are located in close proximity on chromosome 17q makes the association of these two conditions intriguing.

Enteric-coated mycophenolate sodium in the treatment of refractory pemphigus.

BACKGROUND: One of the major goals of pemphigus therapy is to reduce the patient's cumulative exposure to systemic corticosteroids. To investigate the efficacy of enteric-coated mycophenolate sodium (EC-MPS), 10 patients with active, refractory pemphigus vulgaris (PV) or foliaceous (PF) were treated with EC-MPS (1440 mg daily) and prednisone (75 mg daily) over 18 months. OBSERVATIONS: Following EC-MPS/prednisone therapy, disease progression was inhibited between days 30 and 45 in 9/10 patients (8 PV; 1 PF). At 18 months, 8/9 PV patients had clinically quiescent disease; EC-MPS therapy was no longer required in two patients as a result of disease remission. The remaining PV patient showed no response to treatment. The PF patient also had clinically quiescent disease but with high levels of anti-desmoglein-1. ECMPS dose was reduced to 720 mg daily in 4/9 patients by month 6. Average daily prednisone requirement decreased to 25 mg at 6 months and to 15 mg at 18 months. Three adverse events were reported: headache (two cases; one mild and one moderate) and significant increase in blood glucose (one case; moderate). CONCLUSIONS: Enteric-coated mycophenolate sodium is effective and safe as an adjuvant therapy in patients with refractory pemphigus and may be effective even in patients whose disease is unresponsive to azathioprine.

Idiopathic acquired leukonychia in a 34-year-old patient.

We present a rare case of a 34-year-old patient with persistent, progressive, acquired leukonychia totalis and partialis. Idiopathic acquired leukonychia is a rare chromatic disorder of the nail not associated with other abnormalities and discernible etiology. Our case report did not link the inheritance of leukonychia with diverse clinical syndromes. To our knowledge, only five cases of idiopathic, acquired, true total leukonychia were found in literature. This case was the sixth patient with asymptomatic idiopathic, white fingernails, and toenails without a hereditary cause.

Unusual clinical variants of cutaneous leishmaniasis in Sicily.

BACKGROUND: The term "leishmaniasis" defines a group of vector-borne diseases caused by species of the genus Leishmania and characterized by a spectrum of clinical manifestations. Parasite properties (infectivity, pathogenicity, virulence), host factors, and host responses regulate heterogeneous disease expression. Sicily is one of the major islands of the Mediterranean Basin and is considered to be a hypo-endemic area for cutaneous leishmaniasis. Leishmania infantum is the most common species on the island. METHODS: Fifty patients (both sexes and different ages) with lesions clinically suggestive of cutaneous leishmaniasis were recorded over a 1-year period. The diagnosis was based on positive slit-skin smear and histopathologic studies when needed. Polymerase chain reaction (PCR) was performed as test confirmation. RESULTS: Twenty-five patients had typical solitary lesions of cutaneous leishmaniasis. Multiple lesions were present in five patients. In 20 patients, the lesions were very unusual, including erysipeloid, zosteriform, and lupoid leishmaniasis. The results of Leishmania isoenzyme characterization identified Leishmania infantum as the species responsible for the 20 atypical cases. CONCLUSION: The global number of cases of cutaneous leishmaniasis in Sicily has increased in recent years, and such increases can be explained, in part, by the fact that, in this region, sandflies are present during a large part of the year. This is a result of the climatic variation in recent years (increasing temperature and humidity). There has also been an increase in the number of new and rare variants of cutaneous leishmaniasis. A knowledge of the unusual clinical variants of cutaneous leishmaniasis, as well as classical forms, allows early detection.

Novel terphenyls and 3,5-diaryl isoxazole derivatives endowed with growth supporting and antiapoptotic properties.

A new study on terphenyl and diaryl-isoxazole and -isoxazoline derivatives, maintaining a common 3-adamantyl-4-hydroxyphenyl moiety, has been conducted to find compounds with growth supporting and antiapoptotic properties. Unexpectedly, diphenyisoxazole derivatives bearing a nitro group replacing the carboxylic function have been found with the highest cell protective activity within the series, in complete and in serum-free conditions. Inhibition of apoptosis induced by daunorubicin has also been observed for the most active compound.

Exogenous ochronosis and striae atrophicae following the use of bleaching creams.

Exogenous ochronosis is a paradoxical hyper-pigmentation of the skin caused by the long-term use of hydroquinone-containing bleaching creams. Ochronosis is an uncommon condition characterized by yellow-brown pigmented deposits in the dermis. We report two cases of exogenous ochronosis in two female patients of the sub-Saharan African population. The lesions were characterized by an asymptomatic hyper-pigmentation of the face with gradually progressive blue-black macular patches, and in case no. 2, in addition to dyschromic lesions, striae atrophicae were present. This phenomenon is the outcome of the use of skin care products containing high concentrations of hydroquinone- and glucocorticoid-based products, and, in addition, certain modalities in the use of bleaching products are likely to facilitate complications.

Primary malignant melanoma of the oral cavity: case report.

An 80-year-old-female patient had a pigmented lesion on: the hard palate, the soft palate, the alveolar mucosa and the vestibular mucosa of the maxillary gingiva. Pigmented macules and patches had been persistent and asymptomatic for many years (Fig. 1). The lesion exhibited irregularities of pigmentation, border and surface contour. About 1 year later the patient had noticed an extension of the pigmented macules and plaques; there was also the appearance of nodules of the maxillary gingiva accompanied by swelling. Loosening of teeth as a result of extensive destruction of bone was further noted (Fig. 2). The histological examination showed a downward streaming in the dermis of the tumor cells and a disintegration and ulceration of the epidermis (Fig. 3). An increased number of large round or polygonal cells resembling atypical epithelioid cells were found on the submucosa. The atypical cells had enlarged, pleomorphic nuclei with prominent and sometimes multiple nucleoli. Mitoses were observed at various tissue levels (Fig. 4). Abundant pigmented melanin was present in the tumor cells (Fig. 5). Many cells had fine, dusty melanin particles. The tumor cells showed great variations in size. Immunohistochemical staining, with S100 protein and HMB45 antibodies, stained many of the spindleshaped cells, indicating that they were melanocytic cells. An inflammatory infiltrate of lymphocytes was seen in a band beneath the invading tumor cells.