Duchenne's muscular dystrophy involves a defective transsulfuration pathway activity.

Duchenne muscular dystrophy (DMD) is the most frequent X chromosome-linked disease caused by mutations in the gene encoding for dystrophin, leading to progressive and unstoppable degeneration of skeletal muscle tissues. Despite recent advances in the understanding of the molecular processes involved in the pathogenesis of DMD, there is still no cure. In this study, we aim at investigating the potential involvement of the transsulfuration pathway (TSP), and its by-end product namely hydrogen sulfide (H2S), in primary human myoblasts isolated from DMD donors and skeletal muscles of dystrophic (mdx) mice. In myoblasts of DMD donors, we demonstrate that the expression of key genes regulating the H2S production and TSP activity, including cystathionine γ lyase (CSE), cystathionine beta-synthase (CBS), 3 mercaptopyruvate sulfurtransferase (3-MST), cysteine dioxygenase (CDO), cysteine sulfonic acid decarboxylase (CSAD), glutathione synthase (GS) and γ -glutamylcysteine synthetase (γ-GCS) is reduced. Starting from these findings, using Nuclear Magnetic Resonance (NMR) and quantitative Polymerase Chain Reaction (qPCR) we show that the levels of TSP-related metabolites such as methionine, glycine, glutathione, glutamate and taurine, as well as the expression levels of the aforementioned TSP related genes, are significantly reduced in skeletal muscles of mdx mice compared to healthy controls, at both an early (7 weeks) and overt (17 weeks) stage of the disease. Importantly, the treatment with sodium hydrosulfide (NaHS), a commonly used H2S donor, fully recovers the impaired locomotor activity in both 7 and 17 old mdx mice. This is an effect attributable to the reduced expression of pro-inflammatory markers and restoration of autophagy in skeletal muscle tissues. In conclusion, our study uncovers a defective TSP pathway activity in DMD and highlights the role of H2S-donors for novel and safe adjuvant therapy to treat symptoms of DMD.

[Splenic hamartoma]. / Amartoma splenico.

The Authors present a case of Splenic Hamartoma. This is a rare unique complex vascular lesion of the spleen. This is also a recently reinterpreted lesion with some persistent confusion regarding its definition, histogenesis and classification. The patient is a young woman who following a check up with a raised erythrocyte sedimentation rate underwent abdominal sonography demonstrating an incidental slightly hypoechoic nodular splenic lesion. The pathologic study of the splenectomy specimen showed a large (10 cm) sharply demarcated mass. Histologically the lesion presented a remarkably angiomatoid lobular-nodular configuration with abundant fibrosclerotic stroma with areas of calcification. The immunohistochemical study revealed within the angiomatoid tissue different types of blood vessels: a) capillaries CD31+, CD34+, CD8-; b) structures consistent with splenic venous sinuses CD31+, CD34+/- , CD8-/+; c) small veins CD31+, CD34+, CD8-. The Authors judge this complex picture as indicative of a Splenic Hamartoma with a peculiar lobular-nodular pattern that seems to coincide with the recently described SANT: Sclerosing Angiomatoid Nodular Transformation of the spleen. In this report the Authors discuss the pathology of the lesion and the problems concerning its vasular profile. It is also emphasized the Hamartoma's great variety of morphologic patterns derived from the preponderant growth of one or another of several histologic components. This is the cause of the presence in literature of some different pathologic entities which today are fairly recognized as part of a large pathologic spectrum of the same lesion. The Authors discuss the differential diagnosis of Splenic Hamartoma with other lesions as haemangiomas and inflammatory pseudotumor.

[Solid pseudopapillary tumour of the pancreas. Report of a case]. / Il tumore solido pseudopapillare del pancreas. Presentazione di un caso clinico.

Solid pseudopapillary pancreatic tumour is an uncommon disease including 2.7% of exocrine malignancies of the pancreas. Its low incidence is associated with an uncertain prognosis and with difficult diagnostic and therapeutic problems, despite routine use of ultrasonography, TC and RMN. A case of solid pseudopapillary pancreatic tumour in a young woman is reported: the clinicopathologic features, diagnostic imaging and surgical treatment are discussed. Surgery is the primary option. Prognosis is however not fully known. From a review of the literature it is suggested that these tumours should be regarded as potentially malignant.

[Hypertrophic and polypoid gastropathy associated with juvenile adenomatous polyposis coli]. / Gastropatia ipertrofica e polipoide associata a poliposi del colon di tipo giovanile ed adenomatoso.

Juvenile Polyposis is a syndrome with gastrointestinal polyps and increased cancer risk. The commonest form of this syndrome is inherited as autosomal dominant trait and presents as Familial Juvenile Polyposis Coli. Another variant involves mainly the stomach and another is generalized throughout the gastrointestinal tract. We present the case of two brothers with polyposis coli complicated by colonic cancer. The polyps were of juvenile, adenomatous and mixed types. The two patients after a decade of colonic endoscopic polypectomies presented gastric involvement by polyps and needed multiple endoscopic gastric resections. One brother underwent total gastrectomy. This stomach showed diffuse polyposis of hyperplastic and fundic gland types within an unexpected background of foveolar and glandular hypertrophic gastropathy. The patients at present are followed up with endoscopic procedures.

Epithelioid hemangioendothelioma of the larynx.

Epithelioid hemangioendothelioma is an uncommon vascular tumor of the soft tissues. Several reports have described this tumor in visceral locations such as liver, lung, and brain. To the best of our knowledge this is the first report of an immunohistochemical and ultrastructural study of a primary epithelioid hemangioendothelioma occurring in the larynx. Difficulties concerning the differential diagnosis and clinical problems arising from surgical therapy in the laryngeal area are also discussed.

Granular cell basal cell carcinoma of the skin. Report of a case with immunocytochemical positivity for lysozyme.

Granular cell tumors have been described in many sites throughout the body. To our knowledge, few cases have been described in the literature. We report here the sixth case, in which positivity for lysozyme was also observed for the first time. The problems of the histogenesis and differential diagnosis of this rare variant of basal cell carcinoma are also discussed.

Fibroadenoma of the vulva. Report of a case.

A case of fibroadenoma occurring in the vulva of a 24 year old woman is presented. This rare benign tumor appears as dermal or subcutaneous well circumscribed nodule. Histologically the fibroadenoma is characterized by epithelial and stromal proliferation. Two different concepts concerning histogenesis are cited; the authors believe that this tumor arises in ectopic mammary tissue.

The prognostic significance of tumor angiogenesis in nonaggressive and aggressive basal cell carcinoma of the human skin.

Basal cell carcinoma (BCC) is currently the most common cutaneous cancer found in humans. Although it generally shows a relatively benign course (BCC1), some cases of BCCs show "aggressive" behavior, rapidly infiltrating deeper structures, or metastasizing (BCC2). Until now, the traditional histological diagnostic criteria have failed to discriminate unequivocally between BCC1 and BCC2. Therefore, there is still a need to find reliable prognostic indicators that correlate with outcome and may detect patients at high risk for BCC recurrence, or metastasis and death. Recent studies have suggested that there is a significant correlation between tumor angiogenesis, expressed as the microvessel density within and toward a tumor, tumor aggressiveness, and the overall survival of patients with solid tumors. In this study, the authors examined the angiogenic rate in human cutaneous BCCs, to establish if it correlates with their biological behavior. Vessels were highlighted by immunocytochemical staining for FVIII-related antigen in formalin-fixed, paraffin-embedded tissues. All BCC2 samples of this series showed a significantly higher microvessel count than did BCC1. The existence of a significant discrepancy between the neovascularization in BCC1 and BCC2 suggests that the angiogenetic process may be an important step in the acquisition of the aggressive (malignant) phenotype in human. BCCs. The findings of the present study seem to establish a correlation between tumor vascularization and clinicobiological parameters of aggressiveness in BCC. Considering the emerging studies on the possible clinical use of substances interfering with the angiogenetic process, it is possible that the local therapy for BCCs could become less destructive, with consequent improvement in the quality of life of these patients, apart from the prolongation of the overall survival. From this view-point, the assay of microvessel density might be helpful in selecting patients with cutaneous BCCs at high risk for recurrence or metastasis, who could benefit ab initio from additional therapies and closer follow-up.

Peripheral ameloblastoma: report of a case with malignant aspect.

Peripheral ameloblastoma is a very rare tumour with histological characteristics similar to those of the centrally located ameloblastoma. It appears in the gum and in the alveolar process of the jaws. We report a case of tumour of the left maxillary region, near the canine area. Histologically it presented itself with follicles and nests of cells with a trabecular architectural pattern. High mitotic index and clear images of perineural infiltration were present. The diagnosis was peripheral ameloblastoma with malignant aspects. At 12-month follow-up no local recurrence was noted.

Histiocytosis X of the thyroid gland.

Histiocytosis X rarely involves the thyroid gland and occurs as one of the unusual manifestations of systemic diseases. Diagnosis is based on the identification of the Langerhans' cells in an appropriate background. We report a case of histiocytosis X confined to the thyroid gland that represents the primary manifestation of the disease. A careful histological, immunohistochemical and ultrastructural study has been performed and problems of differential diagnosis are discussed.

Symplastic leiomyoma of the scrotum. A case report.

Mesenchimal tumors of the scrotum are rare lesions. Here, we describe a case of symplastic leiomyoma of the scrotum, in a 49-year old man. This is the third case reported in the world literature. Grossly, the lesion is a white-gray nodule, with fasciculated pattern, on sectioning. Histologically, the neoplasm is formed by whorling bundles of fusiform cells, which have atypical nuclei, with occasional cytoplasmatic inclusions. Mitoses are absent. The muscolar nature of the lesion is demonstrated by positivity for Masson-trichrome stain and for actin and desmine antigens.

Cutaneous metastases from gastric adenocarcinoma. Report of two cases and review of the literature.

The skin is rarely involved by metastatic tumors. Breast and pulmonary carcinoma are the most frequent primary lesions that may spread to the skin. Head and neck, chest and abdominal wall are the commonest sites of cutaneous metastases. The authors report two cases of cutaneous metastases from gastric adenocarcinoma, one of which is particularly interesting as it developed on the extremities, a very rare site for skin metastasis. The authors also stress the differential diagnosis with primary cutaneous adenocarcinomas.

Primary malignant melanoma of the ovary.

Primary malignant melanoma of the ovary is an exceedingly rare pathologic event: only eight cases have been reported in literature and in every case they arised in a cystic mature teratoma. The differential diagnosis of primary malignant melanoma is a challenge for pathologist: in fact it must be differentiated by metastatic melanoma and by numerous primary ovarian tumours. We report a rare case of primary malignant melanoma of the ovary with immunohistochemical and ultrastructural study and with a review of the literature.

Primary mucinous carcinoma of the skin. Report of case.

The authors report a case of a primary mucinous carcinoma of the skin. This is a rare adnexial tumor arising from the eccrine secretory coils. The histologic characteristic finding of this lesion is the heap of abundant mucinous material (sialomucin) in the dermis in which rare epithelial islands are free-floating. In this study we also value the importance of a correct diagnosis for an appropriate therapy.