Molecular and immunohistochemical analysis of BRAF gene in primary cutaneous melanoma: Discovery of novel mutations.

BACKGROUND: Determination of BRAF status is mandatory for targeted therapy but it is not currently available in most developing countries. AIM: We aimed to analyze BRAF mutations in a series of cutaneous melanoma of Tunisian patients and to compare BRAF V600E mutation detection by immunohistochemistry to DNA sequencing. PATIENTS AND METHODS: Archival formalin fixed paraffin embedded tissues from 28 patients with primary cutaneous melanoma were evaluated for the BRAF mutations by Sanger sequencing and immunohistochemistry. RESULTS: BRAF mutations were detected in 19/28 (68%) of analyzed tumors. The sensitivity and specificity of immunohistochemistry compared to DNA sequencing for identification of the BRAF V600E mutation were 100%. We found five novel mutations, one of them had deleterious effect. CONCLUSION: The present study shows an intermediate frequency of mutations of the BRAF gene in cutaneous melanoma of Tunisian patients, and supports the use of immunohistochemistry as a screening test for the assessment of the BRAF V600E status in the management of melanoma in clinical practice.

Mycophenolate Mofetil-induced Oral Ulcerations in a Kidney Transplant Recipient.

INTRODUCTION: Mycophenolate Mofetil (MMF) is an immunosuppressive drug usually used in kidney transplants to prevent rejection. It has various adverse effects such as leucopenia, anemia, diarrhea but Mouth ulcers are rarely reported. METHOD: We present a case report of MMF-induced mouth ulcers in an African patient. CASE REPORT: A 41-year-old African-male patient has painful oral ulcers which developed 5 months after kidney transplantation. The immunosuppressive maintenance regimen comprised Steroids, Tacrolimus and MMF. RESULT: These ulcers were firstly related to a fungic or viral infection so the patient was prescribed Fluconazole and Aciclovir without any improvement. Then, Tacrolimus blood level was checked and it was in a therapeutic range. Finally, we decide to stop MMF and the ulcers healed quickly. DISCUSSION: Oral ulcers are frequently seen complications in immunosuppressant patient but are rarely described with MMF. These ulcers can become large and very painful and degrade patient's life quality. So when infections causes are excluded, we have to keep in mind that these ulcers can be a drug adverse effect.

Retronychia Clinical Features and Surgical Treatment.

Retronychia is a newly described condition characterized by the embedding of the nail plate into the proximal nail fold. It mainly affects the great toe unilaterally as a result of mechanical factors. It is rarely reported, and its pathogenesis is not fully understood. Nail plate avulsion represents both a diagnostic and a therapeutic approach. We describe a 34-year-old woman with a medical history of congenital malalignment of the toenails, diagnosed as having retronychia, and emphasize the disease pathogenesis and surgical procedure.

Sclerosing lymphangitis of the penis associated with marked penile oedema and skin erosions.

Sclerosing lymphangitis of the penis is a benign, under-reported condition consisting of a asymptomatic firm cord-like swelling around the coronal sulcus of the penis usually affecting men in the second or third decade of life. Penile oedema and erosions are rarely reported. Clinical signs may be remarkable contrasting with the self-limited character of the disease. We report a new case of sclerosing lymphangitis of the penis occurring in a 59-year-old patient marked by penile swelling and several overlying skin erosions, and discuss the clinical features and the pathogenesis aspects of the disease.

Reversible Facial Hyperpigmentation Associated With Vitamin B12 Deficiency.

Vitamin B12 (cobalamin) deficiency is common in developing countries. Its dermatologic manifestations include hair and nail changes and glossitis. Cases of generalized hyperpigmentation associated with vitamin B12 deficiency have rarely been reported. Localized hyperpigmentation is less frequently described, affecting palms, soles, and flexural areas. We report a rare case of reversible melasma-like cutaneous hyperpigmentation associated with pernicious anemia and discuss the possible mechanisms of this association.

A founder large deletion mutation in Xeroderma pigmentosum-Variant form in Tunisia: implication for molecular diagnosis and therapy.

Xeroderma pigmentosum Variant (XP-V) form is characterized by a late onset of skin symptoms. Our aim is the clinical and genetic investigations of XP-V Tunisian patients in order to develop a simple tool for early diagnosis. We investigated 16 suspected XP patients belonging to ten consanguineous families. Analysis of the POLH gene was performed by linkage analysis, long range PCR, and sequencing. Genetic analysis showed linkage to the POLH gene with a founder haplotype in all affected patients. Long range PCR of exon 9 to exon 11 showed a 3926 bp deletion compared to control individuals. Sequence analysis demonstrates that this deletion has occurred between two Alu-Sq2 repetitive sequences in the same orientation, respectively, in introns 9 and 10. We suggest that this mutation POLH NG_009252.1: g.36847_40771del3925 is caused by an equal crossover event that occurred between two homologous chromosomes at meiosis. These results allowed us to develop a simple test based on a simple PCR in order to screen suspected XP-V patients. In Tunisia, the prevalence of XP-V group seems to be underestimated and clinical diagnosis is usually later. Cascade screening of this founder mutation by PCR in regions with high frequency of XP provides a rapid and cost-effective tool for early diagnosis of XP-V in Tunisia and North Africa.