SNPs at miR-155 binding sites of TYRP1 explain discrepancy between mRNA and protein and refine TYRP1 prognostic value in melanoma.

BACKGROUND: We previously demonstrated an inverse correlation between tyrosinase-related protein 1 (TYRP1) mRNA expression in melanoma metastases and patient survival. However, TYRP1 protein was not detected in half of tissues expressing mRNA and did not correlate with survival. Based on a study reporting that 3' untranslated region (UTR) of TYRP1 mRNA contains two miR-155-5p (named miR-155) binding sites exhibiting single-nucleotide polymorphisms (SNPs) that promote (matched miRNA-mRNA interaction) mRNA decay or not (mismatched), we aimed to investigate the role of miR-155 in the regulation of TYRP1 mRNA expression and protein translation accounting for these SNPs. METHODS: The effect of miR-155 on TYRP1 mRNA/protein expression was evaluated in two melanoma cell lines harbouring matched or mismatched miR-155-TYRP1 mRNA interaction after transfection with pre-miR-155. In parallel, 192 skin and lymph node melanoma metastases were examined for TYRP1 mRNA/protein, miR-155 and SNPs and correlated with patient survival. TYRP1 mRNA, SNPs at its 3'UTR and miR-155 were analysed by RT-qPCR, whereas TYRP1 protein was evaluated by western blot in cell lines and by immunohistochemistry in metastatic tissues. RESULTS: The miR-155 induced a dose-dependent TYRP1 mRNA decay and hampered its translation into protein in the line with the 'match' genotype. In melanoma metastases, TYRP1 mRNA inversely correlated with miR-155 expression but not with TYRP1 protein in the 'match' group, whereas it positively correlated with protein but not with miR-155 in the 'mismatch' group. Consequently, in the latter group, TYRP1 protein inversely correlated with survival. CONCLUSION: Polymorphisms in 3'UTR of TYRP1 mRNA can affect TYRP1 mRNA regulation by miR-155 and its subsequent translation into protein. These SNPs can render TYRP1 mRNA and protein expression nonsusceptible to miR-155 activity and disclose a prognostic value for TYRP1 protein in a subgroup of melanoma patients. These data support the interest in the prognostic value of melanogenic markers and propose TYRP1 to refine prognosis in patients with advanced disease.

[Superficial acral fibromyxoma in a sub-matricial location: An unusual variant]. / Fibromyxome acral superficiel de localisation sous-matricielle : une forme clinique inhabituelle.

BACKGROUND: Superficial acral fibromyxoma (SAFM) is a benign soft tissue tumor located in the acral areas, particularly the peri- and sub-ungueal areas. Sub-matricial localisations have not been reported to date. PATIENTS AND METHODS: We report herein the clinical and pathological presentation of three cases of SAFM located solely under the matrix. The patients presented with pseudo-clubbing, onychogryphosis or triangular macrolunula. The histopathological appearance was characteristic. DISCUSSION: SAFM is a slow-growing, skin-colored, firm nodule, located chiefly on the digits or the toes, and especially in the nail area. It may or may not be painful. Microscopically, it presents as a relatively well-circumscribed but unencapsulated dermal tumor, composed of spindle shaped cells integrated in a myxocollagenic matrix, sometimes invading the subcutis. Tumor cells diffusely express CD34. A conservative surgical approach is recommended. Both clinicians and pathologists should be aware of this entity in order to avoid misdiagnosis, which can lead to unwarranted mutilating surgery. CONCLUSION: Sub-matricial localisation of SAFM is extremely rare and may present as pseudo-clubbing, isolated onychogryphosis or a triangular macrolunula. A conservative surgical approach should be recommended.

Management of in situ melanoma of the nail apparatus with functional surgery: report of 11 cases and review of the literature.

BACKGROUND: Nail apparatus melanoma (NAM) is a rare melanocytic neoplasm with pejorative prognosis often related to late diagnosis. Early diagnosis at in situ stage (NAMis) is difficult, but essential to improve prognosis. NAMis management is not well established yet. Removal of the whole nail unit has been advocated in several small series as a potential treatment for NAMis. OBJECTIVE: To report and assess 'functional' or 'conservative' surgery for NAMis and evaluate its long-term oncologic safety. METHODS: Retrospective study of cases diagnosed in the University Hospital Saint-Pierre collected over a 13 year period and compared with the published data. RESULTS: Eleven cases of NAMis were identified: 73% concerned females. Thumb and first toe were the most affected digits (63% of total). Monodactylic longitudinal melanonychia (LM) was the most frequent presentation (92%). Mean diagnosis delay was 5 years. Diagnosis was suspected on the basis of clinical and dermatoscopic signs and was confirmed by pathological examination. All patients underwent complete nail unit removal with 6 mm security margins around the anatomic boundaries of the nail. Two late local recurrences were observed at 7 and 11 years follow-up. CONCLUSIONS: Our series, the largest up to now, demonstrates that 'functional surgery' is a rational approach for NAMis with an excellent oncologic safety at 5 years. However, this study suggests that a very long-term follow-up is mandatory, as recurrences may appear late.

TYRP1 mRNA expression in melanoma metastases correlates with clinical outcome.

BACKGROUND: Clinical outcome of patients with high-risk melanoma cannot be reliably predicted on the basis of classical histopathological examination. Our study aimed to determine in melanoma metastases a gene expression profile associated with patient survival, and to identify and validate marker(s) of poor clinical outcome. METHODS: Skin and lymph node metastases from melanoma patients (training population) were used to identify candidate prognostic marker(s) based on DNA microarray analysis. Additional skin metastases (validation population) were used to assess the prognostic value of the first ranked gene by real-time PCR. RESULTS: We performed microarray analysis in the training population and generated a list of 278 probe sets associated with a shorter survival. We used the first ranked gene, tyrosinase-related protein 1 (TYRP1), further measured its expression in the validation population by real-time PCR and found it to be significantly correlated with distant metastasis-free survival (DMFS), overall survival (OS) and Breslow thickness. We also found that it was fairly well conserved in the course of the disease regardless of the delay to metastasis occurrence. Finally, although Tyrp1 protein (immunohistochemistry (IHC)) was only detected in about half of the samples, we showed that its expression also correlated with Breslow thickness. CONCLUSION: Our data indicate that TYRP1 mRNA expression level, at least in skin metastases, is a prognostic marker for melanoma, and is particularly useful when prognostic pathology parameters at the primary lesion are lacking. Its conserved expression further supports its use as a target for therapy.

[Granulomatous skin disease in an immunocompromised child]. / Granulomatose cutanée chez un enfant immunodéficient.

BACKGROUND: The development of systemic and/or cutaneous granulomas associated with immunodeficiency is well established, particularly with common variable immunodeficiency (CVID). We report the case of an immunocompromised child presenting with cutaneous granulomas, predominantly on the face. PATIENTS AND METHODS: A boy aged 6 years and 9 months presenting complex and incompletely defined immunodeficiency presented with gradually worsening cutaneous lesions of granulomatous aspect on his face and right foot. Extensive laboratory tests showed no infectious or neoplastic processes. Biopsies of the lesions confirmed the presence of granulomas. Systemic corticosteroids produced no satisfying improvement and were changed to anti-TNFα. The lesions had completely disappeared after 6 months. Treatment was continued for 6 months, with no relapse 6 months after discontinuation. CONCLUSION: The originality of our case lies in the presentation of cutaneous granulomas, appearing in the context of an undefined immunodeficiency other than CVID, as well as in the therapeutic aspect, with the successful use of biotherapies in such a clinical setting.

Left paraduodenal hernia: a case report.

Congenital internal hernias often remain unrecognized since they are infrequent and produce nonspecific abdominal symptoms. Abdominal imaging during a symptomatic episode leads to the diagnosis. Surgical treatment is essential regarding the risks of incarceration. We report a case of left paraduodenal hernia misdiagnosed for over thirty years despite extensive imaging and surgical exploration.

Intra-abdominal lymphatic malformation.

Intra-abdominal lymphangioma is a rare congenital lymphatic vascular malformation. It is found, most commonly, in adult patients who present with abdominal pain, and whom medical imaging (ultrasound, endoscopy and tomography) reveals a cystic intra-abdominal mass. Such masses may be on the mesentery, in contact with abdominal viscera or may be part of the visceral wall. Diagnosis of intra-abdominal lymphangioma is difficult because of its rarity, and because other pathologies may have the same radiological signs. The diagnosis is confirmed by anatomopathological examination with immunohistochemistry. The treatment is complete surgical excision, in order to prevent recurrence.

Assessment of the amount of body water in the Red Knot (Calidris canutus): an evaluation of the principle of isotope dilution with 2H, (17)O, and (18)O as measured with laser spectrometry and isotope ratio mass spectrometry.

We have used the isotope dilution technique to study changes in the body composition of a migratory shorebird species (Red Knot, Calidris canutus) through an assessment of the amount of body water in it. Birds were quantitatively injected with a dose of water with elevated concentrations of 2H, (17)O, and (18)O. Thereafter, blood samples were taken and distilled. The resulting water samples were analysed using an isotope ratio mass spectrometry (for 2H and (18)O only) and a stable isotope ratio infrared laser spectrometry (2H, (17)O, and (18)O) to yield estimates of the amount of body water in the birds, which in turn could be correlated to the amount of body fat. Here, we validate laser spectrometry against mass spectrometry and show that all three isotopes may be used for body water determinations. This opens the way to the extension of the doubly labelled water method, used for the determination of energy expenditure, to a triply labelled water method, incorporating an evaporative water loss correction on a subject-by-subject basis or, alternatively, the reduction of the analytical errors by statistically combining the (17)O and (18)O measurements.

Clear cell 'sugar' tumor (PEComa) of the skin: a case report.

The so-called perivascular epithelioid cell neoplasm (PEComa) family includes angiomyolipoma, clear cell 'sugar' tumor (CCST), lymphangioleiomyomatosis, and clear cell myomelanocytic tumor (CCMMT). These rare tumors are characterized by the co-expression of melanocytic and muscle markers. They have been recognized in an increasing number of sites but currently only one case of PEComa, of the CCMMT subtype, has been reported in the skin in abstract form. We provide the clinicopathologic description of a case of extrapulmonary CCST located in the dermis and superficial subcutis of the thigh of a 60-year-old female. The lesion was composed of nests of epithelioid and spindle cells with abundant clear to granular cytoplasm and distinct cell borders. The tumor showed strong and diffuse immunoreactivity with HMB-45. Scattered cells expressed desmin and h-caldesmon. Antibodies to S-100 protein, melan-A, cytokeratins, and smooth muscle actin were negative. This first case of cutaneous PEComa of the CCST type expands the differential diagnosis of clear cell/granular cell tumors of the skin.

Multiple HPV-positive basal cell carcinomas on the abdomen in a young pregnant woman.

Basal cell carcinoma (BCC) is the most common malignant skin tumour. In the last few years, the incidence of multiple BCC has also increased in young patients. We describe the clinical case of a young 29-year-old woman who developed 7 BCC on her abdomen during her first pregnancy and 4 other similar tumours 2 years later during her second pregnancy, all located on the abdomen. Polymerase chain reaction revealed the presence of numerous human papillomavirus DNA sequences. To our knowledge, such a clinical presentation has not been previously reported. Different physiopathological considerations are discussed.

A case of subungual reactive eccrine syringofibroadenoma.

Eccrine syringofibroadenoma (ESFA) is a rare eccrine tumor. We report the case of a 70-year-old woman who had presented a pincer nail deformity on the toes for 55 years and a left painless subungual tumor for 2 years. Histologic examination revealed branching anastomosing strands of epithelial cells with ductal structures in a fibrovascular stroma. The luminal cells showed positive staining for carcinoembryonic antigen, as in acrosyringeal cells and cells of dermal ducts. To our knowledge, our case is the first with a subungual location. In the context of chronic trauma due to a pincer nail, it may be classified in the reactive subtype recently described.

Localized pigmented villonodular synovitis of the knee with bone involvement mimicking a benign bone tumor: CT and MR findings.

The localized form of pigmented villonodular synovitis is characterized by a limited involvement of synovium. Although the knee is the joint that is commonly affected, bone changes in this location are not usual. We report the case of a histologically proven localized form of this entity in the knee, which mimicked a benign bone tumor on the basis of an MR pattern, CT findings, and scintigraphic results. Bone changes which may cause a pitfall in the diagnosis of the disorder are discussed.

Epithelioid sarcoma: a puzzling soft tissue neoplasm in a child.

Epithelioid sarcoma (ES) is a rare soft tissue neoplasm that usually occurs on the upper extremity of adolescents and young adults. It rarely occurs during childhood. ES is a slowly growing tumor with a high propensity for recurrences and metastases. This neoplasm is likely to be confused with a variety of benign and malignant conditions. Recognition of ES is important. The treatment consists of wide excision. Misdiagnosis can lead to inappropriate treatment and local recurrences or metastases. We report the case of a 5-year-old girl with an ES on the right forefinger.

Evaluation of the role of genital human papillomavirus in the pathogenesis of ungual squamous cell carcinoma.

Human papillomaviruses (HPV), and particularly HPV 16, have been associated with ungual squamous cell carcinoma (USCC). But their role in tumor development remains unclear. In genital carcinoma, where the oncogenic role of HPV is well established, integration of HPV DNA into the host cell genome seems to be important for malignant transformation. To clarify the issue, we have studied the physical state of HPV 16 in 3 cases of in situ USCC by the polymerase chain reaction and by in situ hybridization. HPV DNA was integrated into the human genome in 2 cases and episomal in 1 case. This particular physical state of HPV 16 in USCC, similar to those encountered in anogenital SCC, confirms the probable role of this kind of virus in the pathogenesis of USCC.

[Value of puncture-lavage in abdominal closed trauma. Comparison with the laparoscopy and symptomatology (author's transl)]. / Intérêt de la ponction-lavage dans les traumatismes abdominaux fermés. Confrontation avec la laparoscopie et la symptomatologie abdominale

In a series of 120 closed abdominal trauma the authors compare the reliability of the abdominal symptomatology (60%), of puncture-lavage with an Intracath (92.5%) or with a Diacath (98%) and of laparoscopy (100%). Laparoscopy and puncture-lavage with a Diacath have the same advantages: rapid execution, safeness, reliability. However the preference of the authors goes to the catheter and peritoneal dialysis because of its simplicity and feasability by the surgeon himself. This technique discloses visceral lesions: if positive it allows an earlier diagnosis and operation; if negative it avoids unnecessary laparotomies especially in cases of multiple trauma.