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In many centers, Stage I-II melanoma patients are considered "cured" after 10 years of disease-free survival and follow-up visits are interrupted. However, melanoma may relapse also later. We retrospectively analyzed a cohort of 1,372 Stage I-II melanoma patients who were disease-free 10 years after diagnosis. The aim of this study was to characterize patients who experienced a late recurrence and to compare them to those who remained disease-free to identify possible predictive factors. Multivariate Cox proportional-hazards regression analyses were carried out to evaluate the influence of different factors on the risk of recurrence. Seventy-seven patients out of 1,372 (5.6%) relapsed, 52 in regional sites and 25 in distant ones. The majority of patients (31 out of 52) experienced late recurrence in regional lymph nodes. Brain and lung were the most common site of single distant recurrence (24% each). Patients with multiple distant metastases showed a brain and lung involvement in, respectively, 40 and 48% of cases. A Cox proportional-hazards regression model analysis showed the independent role of age under 40 years, Breslow thickness2 mm, and Clark Level IV/V in increasing the risk of Late Recurrence. These patients should be followed-up for longer than 10 years. The pattern of recurrence suggests that melanoma cells can be dormant preferentially in lymph nodes, brain and lung. A particular attention should be reserved to these anatomic sites during the follow-up after 10 years of disease-free.

Melanocytic nevi in the genital, acral, and flexural sites often display clinical and histologic features that may simulate melanoma. We verified whether this is the case also for nevi of the breast.Eleven dermatopathologists, from nine Italian Institutions, collected the specimens of melanocytic lesions from the breast and other body sites, excluding the acral, genital, and flexural areas, as controls. Cases and controls were matched for sex and age. All nevi were observed 'blindly' and simultaneously by all participants. For each lesion, 10 histological parameters were analyzed: asymmetry, absence of lateral demarcation of melanocytes, lentiginous proliferation, nested and dyshesive pattern, intraepidermal melanocytes above the basal layer, involvement of the hair follicle, absence of maturation of dermal melanocytes, melanocytic atypia, fibroplasia of the papillary dermis, and lymphocytic dermal infiltrate. Each parameter was scored 2 when present and 1 when absent or not valuable. A total score was calculated for each lesion. Results were statistically analyzed by the chi-square test and the Mann-Whitney U-test.One hundred and one nevi came from the breast area and 97 from elsewhere. Breast nevi exhibited significantly more atypical features than nevi from other sites. In particular, breast nevi with intraepidermal melanocytes, melanocytic atypia, and dermal fibroplasia were significantly more numerous. We did not find any sexual difference.To avoid undue concerns, dermatopathologists should be aware that melanocytic nevi of the breast may show a high degree of atypical features.

Several factors hamper the clinical and histologic diagnosis of panniculitis. Clinically the patients tend to present with erythematous subcutaneous nodules with quite a monotonous appearance, without additional symptoms. Histopathologically, as the subcutaneous fat responds to a variety of insults in a limited number of forms, there are sometimes subtle pathologic differences among the conditions. Although the biopsy plays a critical role in the diagnostic process of a panniculitis, a series of prerequisites must be met in order to obtain as much information as possible from this procedure. If the biopsy is inadequate, i.e., does not include sufficient subcutaneous fat or the site of sampling site/biopsy timing is wrong, histopathologic assessment is limited and the correct diagnosis may be delayed and further sampling may be required. This article introduces the reader to the field of panniculitides under the histopathologic perspective through a brief description of the normal histology of subcutaneous fat. I also includes the definition of the types of fat necrosis, role of biopsy of panniculitis and its rules and pitfalls, up to a microscopic approach of a slide.

Aim of this work was to define the histopathological features of post-surgical panniculitis. Dermal and hypodermal changes will be analyzed in detail, to understand the cascade of events that characterize the tissue response to surgical trauma. Cutaneous re-excision specimens of cases of basal cell carcinoma, squamous cell carcinoma, and melanoma consecutively seen from January 1, 2011 to June 30, 2011 at the Department of Dermatology, University of Pavia, were included in this study. Only the cases in which the first surgical procedure included the subcutaneous fat, were considered. In addition, the time elapsed from the first surgical procedure and the re-excision had to be included in a period of time from one to three months. All the specimens were stained with hematoxylin and eosin. Thirty cutaneous re-excision specimens were studied. Histopathologic examination revealed changes of epidermis, ranging from slight atrophy to moderate hyperplasia. In two cases focal ulceration was seen, with transfollicular elimination of foreign body material. The main dermal changes observed were the: 1) scar with well defined vertical orientation along the dermal suture line; 2) rounded cicatricial areas with radial branching septa of scarring tissue; 3) foreign body granuloma formation; 4) alignment of hystiocytes at the dermo-hypodermal border; 5) traumatic neuromas. The subcutaneous fat changes included: 1) lobular panniculitis with consistent presence of foam cells; 2) striking anisocytosis with pseudocystic degeneration and necrosis of adipocytes; 3) eritrocyte extravasation, mainly at the dermo-hypodermal border; 4) deep seated phlebitis. Post-surgical panniculitis is a lobular foam cell panniculitis characterized by simultaneous dermal and hypodermal changes, expression of the multi-faceted tissue response to a surgical trauma. This type of peculiar lipophagic response puts post-surgical panniculitis into the wider chapter of lipophage tissue response seen in atherosclerosis, glomerulosclerosis and some infectious models such as Mycobacterium tuberculosis and Chlamydia pneumoniae infections. Furthermore it may be seen as a reliable and convenient model for laboratory investigation on foam cell tissue response.

The synthesis of conformationally constrained amino acids is an important tool for the preparation of oligomers that assume a well defined secondary structure. We have recently described the synthesis of oligomers of L-Oxd and L-pGlu and we have demonstrated that these molecules fold in ordered structures characterized by a semi-extended helical conformation. As a part of this project, we report here a straightforward synthesis of 4(S)-oxazolidineacetic acid, 2-oxo benzyl ester (H-Oxac-OBzl), a beta-amino acid derivative, the preparation of its homo-oligomers up to the tetramer level by solution methods and their conformational analysis in structure supporting solvents.

By a chemo-enzymatic approach we performed a large-scale, stereoselective synthesis of the C-alpha-methylated alpha-hydroxy acid L-(alpha-Me)Hyv. We also prepared model depsipeptides based on this sterically demanding residue in combination with the alpha-amino acids L-Ala, L-Val, and Aib. From solution (FT-IR absorption and NMR) and crystal-state (X-ray diffraction) conformational analyses we found that L-(alpha-Me)Hyv forces depsipeptides to fold into right-handed beta-turn/helical structures.