Predictors of germline status for hereditary melanoma: 5 years of multi-gene panel testing within the Italian Melanoma Intergroup.

BACKGROUND: The incidence of cutaneous melanoma is increasing in Italy, in parallel with the implementation of gene panels. Therefore, a revision of national genetic assessment criteria for hereditary melanoma may be needed. The aim of this study was to identify predictors of susceptibility variants in the largest prospective cohort of Italian high-risk melanoma cases studied to date. MATERIALS AND METHODS: From 25 Italian centers, we recruited 1044 family members and germline sequenced 940 cutaneous melanoma index cases through a shared gene panel, which included the following genes: CDKN2A, CDK4, BAP1, POT1, ACD, TERF2IP, MITF and ATM. We assessed detection rate according to familial status, region of origin, number of melanomas and presence and type of non-melanoma tumors. RESULTS: The overall detection rate was 9.47% (5.53% analyzing CDKN2A alone), ranging from 5.14% in sporadic multiple melanoma cases (spoMPM) with two cutaneous melanomas to 13.9% in familial cases with at least three affected members. Three or more cutaneous melanomas in spoMPM cases, pancreatic cancer and region of origin predicted germline status [odds ratio (OR) = 3.23, 3.15, 2.43, P < 0.05]. Conversely, age > 60 years was a negative independent predictor (OR = 0.13, P = 0.008), and was the age category with the lowest detection rate, especially for CDKN2A. Detection rate was 19% when cutaneous melanoma and pancreatic cancer clustered together. CONCLUSIONS: Gene panel doubled the detection rate given by CDKN2A alone. National genetic testing criteria may need a revision, especially regarding age cut-off (60) in the absence of strong family history, pancreatic cancer and/or a high number of cutaneous melanomas.

Ultrasonography in the pathway to an optimal standard of care of hidradenitis suppurativa: the Italian Ultrasound Working Group experience.

BACKGROUND: Ultrasound (US) is a real-time non-invasive technique that has been demonstrated to support an early diagnosis and a more precise assessment of hidradenitis suppurativa (HS). OBJECTIVES: To compare the clinical and US evaluation of a series of HS patients. METHODS: 434 HS patients (259 F, 175 M; mean age 33.82 ±13.31 years) observed across 19 Italian dermatology centres [members of the Italian Ultrasound Working Group (IUWG)] were enrolled in a retrospective study. Clinical staging was obtained by the Hidradenitis Suppurativa Physician's Global Assessment score (HS-PGA), while the ultrasonographic staging was determined by the US HS-PGA, based on the same scores as clinical HS-PGA but performed with the aid of US. RESULTS: At the end of the study, the mean clinical and US HS-PGA scores were 2.70 and 2.92, respectively. Direct comparison of clinical and ultrasonographic assessment revealed that a higher proportion of patients was classified as having moderate and very severe disease by US. In particular, 117 patients (26.96%) had a worse classification by US HS-PGA compared to clinical assessment. CONCLUSION: Our findings confirm that the use of clinical grading only to assess HS severity may underestimate the real disease severity. US examination can be considered an essential non-invasive imaging tool available to dermatologists for a more accurate diagnosis, staging, treatment planning and monitoring of HS and should be included in the pathway to an optimal standard of care of HS.

Sex-related differences of clinical features in hidradenitis suppurativa: analysis of an Italian-based cohort.

The clinical characteristics associated with hidradenitis suppurativa (HS) severity are poorly understood. In this study, 124 patients with HS from 6 Italian dermatology centres participated in this study. Disease severity was assessed using the Hidradenitis Suppurativa Physician's Global Assessment score (HS-PGA) and Hurley score. The impact of clinical characteristics on disease severity was assessed by logistic regression. Clinical characteristics were similar between men (n = 53) and women (n = 71). Disease severity was also similar; 75% of the patients had Hurley stage II or III disease, and > 60% had moderate, severe or very severe HS as judged by HS-PGA. Lesions were more frequent in the gluteal region in men (32.3% in men vs. 8.7% in women, P < 0.001) and more frequent on the breast in women (16.3% in women vs. 4.6% in men, P = 0.02). Obesity was associated with increased disease severity as measured by HS-PGA (OR: 3.28, 95% CI 1.55-6.95, P < 0.01) and Hurley classification (OR: 3.22, 95% CI 1.34-7.31, P < 0.01). Although severity of HS is similar between the sexes, the localization of lesions is different.

Localized morphea after breast implant for breast cancer: A case report.

PURPOSE: Early breast cancer follow-up guidelines for patients who underwent surgery suggest a regular and accurate clinical examination of the breast area, for an early identification of cutaneous or subcutaneous breast cancer relapse. Nonetheless, breast skin lesions arising in patients treated with mastectomy for breast cancer can be caused by several diseases. A series of diagnostic hypotheses should be considered, not only focusing on cutaneous metastasis, but also on dermatologic and systemic diseases. CASE REPORT: In February 2015, a 37-year-old patient underwent a right subcutaneous mastectomy for stage IIA breast cancer. Five months after beginning adjuvant chemotherapy, she noted hyperpigmentation and thickening of the skin on the right breast. Differential diagnosis included local relapse, skin infection, lymphoma, or primary cutaneous disease, and a skin biopsy was performed. The histopathologic specimen showed full-thickness sclerosis, with features of localized morphea. Therapy with clobetasol was prescribed, with progressive resolution of the thickness. The collaboration between many professionals in a multidisciplinary team (oncologist, dermatologist, plastic surgeon, and pathologist) was crucial to achieving the diagnosis. CONCLUSION: In the literature, some articles describe correlation between connective tissue diseases and silicone breast implants, but the pathogenetic mechanisms are unknown. We report a rare case of breast morphea after positioning a silicone implant in a patient who had undergone mastectomy. This clinical report represents an interesting model of multidisciplinary management of a patient with breast cancer who developed an uncommon dermatologic disease. Further studies are needed to clarify the association between silicone implants and breast morphea.

Mechanisms behind inter-individual differences in lung diffusing capacity.

We measured diffusing capacity (DLCO), alveolar membrane properties (D (m)), capillary lung volume (V (c)), and alveolar volume (V (A) ) in 20 healthy subjects (12 males; age 32.4 +/- 13 (SD); BMI 21.7 +/- 3; non smokers) at total lung capacity (TLC) and at approximately 80, 60, and 40% TLC. In all subjects, D (m) increased with lung volume, the increase being significantly greater for higher values of D (m)(TLC): the inter-individual differences can be interpreted by a greater number of alveolar units coupled to a lower thickness of the air-blood barrier (thus a higher alveolar surface to thickness ratio S (A)/tau). On the average, the volume-dependent increase of D (m) from approximately 40 to 100% TLC is less than expected based on geometrical increase of S (A) /tau. In fact, up to approximately 80% TLC, the increase in D (m) closely reflects only the increase of S (A), suggesting "unfolding" of the septa with no appreciable decrease in tau. Conversely, above 80% TLC, the decrease in tau due to parenchymal stretching becomes the main factor affecting D (m). In all subjects, V (c) decreased with increasing lung volume, in line with an increase in parenchymal stretching; the decrease was significantly larger for higher values of V (c) (40% TLC). Possibly reflecting differences in alveolar capillary density. No correlation was found between D (m)(TLC) and V (c)(40%TLC). The individual specificity in the lung volume dependence of V (c) and D (m) can be reasonably described by evaluating the V (c)/D (m) ratio at TLC and at approximately 40%TLC.

Indeterminate cell histiocytosis in association with later occurrence of acute myeloblastic leukaemia.

Indeterminate cell histiocytosis (ICH) is a proliferation of indeterminate CD1a+, CD68+, S100+ and CD207- dermal dendritic cells. We describe a 39-year-old man who developed diffuse ICH and, 6 years later, acute myeloblastic leukaemia (AML). He was treated with cyclophosphamide, etoposide and vinblastine until 2003. In August 2004, he presented dyspnoea, hyperpyrexia and infiltration of the lung parenchyma, compatible with an AML invasion, and died after a course of induction chemotherapy. Cytomorphology and immunophenotype analyses suggested an ICH clonal evolution. The leukaemogenic role of etoposide is discussed. ICH has previously been reported in association with B-cell malignancy, but only one case has shown systemic progression.

Thalidomide treatment for hypertrophic cutaneous lupus erythematosus.

INTRODUCTION: In recent years numerous reports have been published regarding satisfactory thalidomide therapy for refractory chronic cutaneous lesions of lupus erythematosus (CCLE); to date, in the literature, there is just one report describing two patients affected by hyperkeratotic CCLE successfully treated with thalidomide. METHODS: Six patients affected by a hypertrophic/verrucous variant of CCLE were treated with thalidomide during the period October 1999 to December 2002 and their medical records were retrospectively reviewed. The initial dose of thalidomide was 100 mg/die by mouth for all the cases, while the duration of therapy was variable among the patients. RESULTS: All six patients responded to treatment: two had partial resolution of the lesions and four achieved almost complete clearing of cutaneous disease. Response to treatment was seen in the first month of therapy in all the patients. Follow-up nerve conduction studies were negative but a patient had to discontinue the drug because of neurological problems. DISCUSSION/CONCLUSION: Our case series confirms the efficacy of a 'low-dose' thalidomide regimen in verrucous/hyperkeratotic CCLE, which is normally unresponsive to conventional treatment; in this setting, thalidomide should be kept in mind as an extremely valid therapeutic option despite the lack of prospective, randomized, double-blind, placebo-controlled studies.

Neurologic abnormalities in two patients with facial hemiatrophy and sclerosis coexisting with morphea.

Progressive facial hemiatrophy or Parry-Romberg syndrome is a rare entity characterized by unilateral atrophy of the skin, subcutaneous tissue, and the underlying bony structures. This syndrome has many features of linear scleroderma en coup de sabre but is distinguished by more extensive involvement of the lower face and by only slight cutaneous sclerosis. We describe two unusual children with both atrophic and sclerotic changes of half of the face coexisting with multiple plaques of typical morphea. Both children developed neurologic disturbances with cranial magnetic resonance imaging (MRI) abnormalities 2 years and 15 years, respectively, after the onset of cutaneous lesions. Thus considering that it may not be possible to correlate impairment in neurologic function and cutaneous disease, as illustrated by our patients, we emphasize the importance of an accurate follow-up.

[The Sceptor system: relation of results from antibiograms in diffusion agar to MIC]. / Sistema Sceptor: confronto dei risultati degli antibiogrammi in agar diffusione rispetto alla MIC.

The Sceptor system and the susceptibility of Gram-positive cocci and Gram-negative rods to several antibiotics were presented. The accuracy of methicillin and gentamicin MIC of Staphylococcus aureus was determined. The MIC of methicillin-resistant strain was less than 8 mg/l. Finally the MIC accuracy to 29 Pseudomonas aeruginosa strains was compared with the results obtained by the standard disk diffusion method.

New pharmacological aspects of the bronchodilating activity of procaterol.

The selectivity of procaterol for beta 2-adrenoceptors vs beta 1-adrenoceptors in animals has been already described. In these studies the ability of procaterol to protect guinea-pig against bronchoconstriction induced by various spasmogens such as histamine, LTC4 and acetylcholine is demonstrated. The results obtained both in anaesthetized animals and in perfused lungs clearly show that procaterol antagonizes not only the direct effect of the bronchoconstrictors quoted above but also their ability to activate arachidonic acid metabolism and to augment the generation of TXA2. Procaterol (0, 3-3 micrograms/Kg i.v.) is more potent than salbutamol in protecting passively sensitized guinea-pig from massive bronchoconstriction following antigen challenge: a phenomenon which is paralleled by an increment of the circulating TXA2. The possibility that the adenylate-cyclase-stimulating properties of procaterol may explain its antiasthmatic activity is discussed.