Rossana Tiberio

A Mycobacterium ulcerans toxin, mycolactone, induces apoptosis in primary human keratinocytes and in HaCaT cells.

The pathogenicity of Mycobacterium ulcerans (Buruli ulcer) depends on cytotoxic effect of its exotoxin mycolactone. Since epidermis represents a barrier against infectious agents and balanced apoptosis is essential in epidermal homeostasis, we explored if mycolactone A/B induces apoptosis on two human keratinocyte populations, stem cells (KSC) and transit amplifying cells (TAC), and on human keratinocyte line, HaCaT. Treatment of TAC with 1 and 10 ng/ml mycolactone-induced 60 and 90% apoptosis. KSC were more resistant than TAC: 50 and 75% of cells underwent apoptosis after 10 and 100 ng/ml toxin-treatment. Higher doses (1000 ng/ml) induced about 30% apoptosis on HaCaT. In contrast, mycolactone A/B was devoid of toxicity neither on human hepatoma HuH7 nor on human embryonic kidney HEK 293 T cell lines. In conclusion, mycolactone induces apoptosis in human keratinocytes, thus contributing to Buruli ulcer lesions development.

Knuckle pads, in an epidermal palmoplantar keratoderma patient with Keratin 9 R163W transgrediens expression

Epidermolytic PalmoPlantar keratoderma (EPPK) Vörner-type is an autosomal dominantly inherited skin disease, characterized by severe thickening of the palms and soles, caused by mutations in the keratin K9 (KRT9) gene. To date, a number of KRT9 mutations have been detected, most of which affect the highly conserved 1A region of the central alpha-helical domain, important for keratin heterodimerization. The most common mutation is the substitution of the arginine in position 163 with a tryptophan (R163W), which has been reported in North American, European, and Japanese populations. In a small number of cases, EPPK is associated with knuckle pad keratosis, but no correlation between this additional phenotype and a specific mutation has been found. Moreover, K9 is not normally expressed in knuckle skin, raising the question of the pathogenic mechanism leading to this additional phenotype. Here we show that in a family affected by EPPK and knuckle pad keratosis, carrying the R163W substitution, wild type (wt) and mutated K9 are strongly expressed in knuckle pads. These results suggest that the knuckle pad phenotype is due to ectopical expression of K9.

Activation of caspase-8 triggers anoikis in human neuroblastoma cells

Cells require appropriate interaction with extracellular matrix proteins mediated by integrins to grow, differentiate and survive. Many cell types including nervous cells undergo anoikis, a substrate-dependent apoptosis, when adhesion is impaired. Resistance of tumors to cytotoxic drugs is probably due to disturbed apoptosis programs. The proteolytic enzymes caspases are the main executioners of apoptosis. It was reported that caspase-8 expression is deficient in some neuroblastoma cells. We demonstrated that human neuroblastoma cell line SK-B-BE, differentiated with retinoic acid, expressed caspases 3, 8 and 9. Caspases 8 and 3, but not caspase-9 were activated in SK-N-BE cells cultured in suspension or on aspecific adhesive substrate. Cell positive to caspase-8 were classified into four stages, by morphometric and densitometric parameters. The use of the specific caspase-8 inhibitor Z-IETD-FMK dramatically reduced apoptosis, demonstrating that caspase-8 is the upstream initiator caspase during SK-N-BE cells anoikis. Among matrix proteins, type I collagen is the most effective and fibronectin the least in delaying anoikis. The activation of caspases 8 and 3 by unligated integrins was dependent on the state of neuronal differentiation, since the most differentiated cell was the most vulnerable to anoikis. These data show that activation of caspase-8 is specifically required to promote anoikis in SK-N-BE neuroblastoma cells.

Dermatofibrosarcome de Darier-Ferrand : traitement par la technique chirurgicale de Tübingen (31 cas)

Resume Introduction Le dermatofibrosarcome protuberans est un sarcome cutane rare a evolution lente. Il a une agressivite locale prononcee, mais metastase rarement. Sa croissance asymetrique et imprevisible, et la frequence des recidives, sont a la source de difficultes therapeutiques. Son traitement est principalement chirurgical. Malades et methode Nous rapportons 31 cas de dermatofibrosarcome protuberans operes a la Clinique dermatologique de Novara entre 1997 et 2004 avec la technique de Tubingen. Une etude immunohistochimique a ete realisee et la presence d’une eventuelle invasion musculaire de la neoplasie a ete evaluee. Resultats Une atteinte musculaire a ete trouvee dans quatre cas. Il n’y a pas eu de recidive apres une periode mediane de suivi de 3 ans. Aucun malade n’a ete perdu de vue. Discussion La technique de Mohs est la technique chirurgicale de reference. Elle permet d’eradiquer la tumeur en epargnant du tissu sain. La methode de Tubingen represente une alternative therapeutique permettant de reduire le nombre de coupes histologiques. Le resultat therapeutique dans notre serie a ete bon avec une absence de recidive avec un delai median de 3 ans.BACKGROUND Dermatofibrosarcoma protuberans is a rare cutaneous sarcoma that progresses slowly. Although it exhibits pronounced local aggressiveness, it rarely metastasises. The condition is difficult to treat on account of asymmetric and unpredictable growth as well as the frequency of relapse. Treatment is primarily surgical. PATIENTS AND METHODS We report 31 cases of dermatofibrosarcoma protuberans operated at the Dermatology Clinic of Novara between 1997 and 2004 using the Tübingen technique. An immunohistochimical study was performed and screening was carried out for possible extension of the neoplasm into muscle. RESULTS Muscular involvement was seen in 4 cases. No relapses were seen over a median survival period of 3 years and no patients were lost to follow-up. DISCUSSION The Mohs technique is the surgical method of reference and allows tumour eradication with sparing of healthy tissue. The Tübingen method constitutes an alternative approach requiring fewer histological sections. The results obtained in our series were good and no relapses were seen over a median survival period of 3 years.

Selective release of cytokines, chemokines, and growth factors by minced skin in vitro supports the effectiveness of autologous minced micrografts technique for chronic ulcer repair.

A new effective surgical procedure to repair chronic ulcers called minced micrografts technique has been recently reported. The technique consists in spreading a finely minced skin sample upon the wound bed. In this study, we investigate the in vitro release of cytokines (interleukin‐6, tumor necrosis factor‐α, interleukin‐1α, and granulocyte‐colony stimulating factor), chemokines (monocyte chemoattractant protein‐1 and growth‐related oncogene‐α), and growth factors (platelet‐derived growth factor, basic fibroblast growth factor, vascular endothelial growth factor, hepatocyte growth factor, and nerve growth factor) by minced (referred to as the minced sample) vs. not minced (referred to as the whole sample) human skin biopsy samples from the same donor. Factor release in the culture medium at different time points was detected using a multiplexed protein assay. The minced sample, which could behave like the skin fragments used in vivo in the autologous minced micrografts technique, expressed higher levels of tumor necrosis factor‐α, interleukin‐1α, platelet‐derived growth factor, and basic fibroblast growth factor, and lower levels of interleukin‐6, monocyte chemoattractant protein‐1, growth related oncogene‐α, and vascular endothelial growth factor compared with the whole sample. In conclusion, mincing of healthy skin may allow appropriate regulation of the inflammatory phase of wound healing and could induce overexpression of some growth factors, which facilitates the proliferative phase of healing.

Human dirofilariasis: 10 new cases in Piedmont, Italy

Dirofilariases are zoonoses caused by nematodes. Cats, dogs, and wild animals are the common intermediate hosts. In Europe, there are two species of Dirofilaria . D. immitis (adult male: length, 12–17 cm; width, 0.7–0.9 mm; adult female: length, 25–30 cm; width, 1–1.3 mm) is a pathogenic parasite of the dog (intermediate and definitive host). The preferred anatomic localization in the animal is the right side of the heart or the pulmonary arteries and their branches. The clinical manifestations, especially of a number of helminths, are very serious and often fatal. 1 D. repens (adult male: length, 5–7 cm; width, 0.3–0.35 mm; adult female: length, 14–17 cm; width, 0.42–0.6 mm) is a parasite of both dogs and humans, and mainly causes nodular dermal and hypodermal lesions only. It is difficult to demonstrate D. repens microfilariae in the blood of an infected patient, although the possibility of migration from the inoculation site to other sites in the body is very great. 2,3

Basal Cell Carcinoma of the Nipple in a Male Patient: A Particular Case Report.

Basal cell carcinoma (BCC) is a common skin cancer worldwide. However, BCC of the nipple and areola complex is rare. Men are more affected than women. Most of the cases were treated with simple excision. We report a case of BCC of the right nipple–areola complex in a 75‐year‐old man, treated with Mohs surgery and simple mastectomy.

Extension cutanée d’un chordome

Resume Introduction Les chordomes sont des tumeurs osseuses extradurales rares, qui derivent des residus de la notochorde, une structure embryonnaire formant l’axe originel de la colonne vertebrale. Ils representent 0,1 p. 100 de toutes les tumeurs intracrâniennes. Le chordome est un cancer a malignite locale, avec une tendance a l’envahissement des tissus environnants. La localisation cutanee est exceptionnelle. Observation Chez un homme âge de 56 ans, apparaissait une lesion nodulaire vegetante du sillon nasogenien gauche de la taille d’une noisette. Cette lesion survenait quelques mois apres une intervention chirurgicale pour une recidive fronto-glabellaire d’un chordome qui s’etait manifeste 6 ans auparavant a la base du crâne. Discussion Nous rapportons ce cas en raison de la rarete des localisations cutanees et des conditions particulieres de survenue de cette localisation faciale. Celle-ci pourrait etre due a un ensemencement tumoral per operatoire lors des interventions chirurgicales anterieures.

Stewart–Treves Syndrome of the Breast after Quadrantectomy for Breast Carcinoma

multiple nodules. Also, some case reports have demonstrated an association of a breast mass and lung nodules at the time of diagnosis as in the present case. The radiological appearance has been described by some authors as an ill-defined irregular mass or focal asymmetric density on a mammogram that is suspicious for carcinoma and as an irregular hypoechoic nodular mass or mass with parenchymal mixed echogenicity, consistent with mastitis or abscess on ultrasound examination. However, none of these cases was associated with a tumor mass and included pleomorphic microcalcifications. This is the first case in the published literature in which microcalcifications are present within a suspect breast mass on mammography. Wegener’s granulomatosis of the breast needs to be reconsidered in the differential diagnosis of a single breast mass associated with microcalcifications and multiple associated lung nodules, especially in patients in which the clinical history is unknown or in patients diagnosed by using a small tissue fragment from a core biopsy, as in this case. Several inflammatory entities need to be excluded before making the diagnosis of Wegener’s granulomatosis of the breast, but especially, in cases of a breast mass associated with microcalcifications on mammography, an invasive and/or in situ carcinoma has to be excluded through microscopic examination. This emphasizes the importance of clinical features and clinic-pathologic correlations in establishing the diagnosis.

Absence of filaggrin mutation in a patient affected by pachyonychia congenita and mild atopic dermatitis

Abstract