Management and outcome of metastatic melanoma during pregnancy.

BACKGROUND: Although metastatic melanoma occurrence during pregnancy challenges the physician in several ways, only a few studies have been published. OBJECTIVES: Our aim was to investigate therapeutic management together with maternal and fetal outcomes in pregnant women with advanced melanoma. METHODS: A French national retrospective study was conducted in 34 departments of Dermatology or Oncology. All patients with American Joint Committee on Cancer (AJCC) stage III/IV melanoma diagnosed during pregnancy were included. Data regarding melanoma history, pregnancy, treatment, delivery, maternal and infant outcomes were collected. RESULTS: Twenty-two women were included: 10 AJCC stage III and 12 stage IV. Abortion was performed in three patients. Therapeutic abstention during pregnancy was observed in three cases, 14 patients underwent surgery, four patients received chemotherapy and one patient was treated with brain radiotherapy alone. The median gestational age was 36 weeks amenorrhoea. Neither neonatal metastases nor deformities were observed. Placenta metastases were found in one case. Among 18 newborns, 17 are currently alive (median follow up, 17 months); one died of sudden infant death. The 2-year maternal survival rates were 56% (stage III) and 17% (stage IV). CONCLUSIONS: Faced with metastatic melanoma, a majority of women chose to continue with pregnancy, giving birth, based on our samples, to healthy, frequently premature infants. Except during the first trimester of pregnancy, conventional melanoma treatment was applied. No serious side effect was reported, except one case of miscarriage after surgery. Mortality rates do not suggest a worsened prognosis due to pregnancy but larger prospective controlled studies are necessary to assess this specific point.

[Tumour regression is not predictive for higher risk of sentinel node involvement in thin melanomas (Breslow thickness < or = 1 mm)]. / La régression tumorale n'est pas un facteur de risque d'atteinte du ganglion sentinelle dans les mélanomes fins (indice de Breslow < or = 1 mm).

BACKGROUND: Thin melanomas (Breslow thickness < or = 1 mm) are considered highly curable. The aim of this study was to evaluate the correlation between histological tumour regression and sentinel lymph node (SLN) involvement in thin melanomas. PATIENTS AND METHODS: This was a retrospective single-centre study of 34 patients with thin melanomas undergoing SLN biopsy between April 1998 and January 2005. RESULTS: The study included 14 women and 20 men of mean age 56.3 years. Melanomas were located on the neck (n=3), soles (n=4), trunk (n=13) and extremities (n=14). Pathological examination showed 25 SSM, four acral lentiginous melanomas, three in situ melanomas, one nodular melanoma and one unclassified melanoma with a mean Breslow thickness of 0.57 mm. Histological tumour regression was observed in 26 over 34 cases and ulceration was found in one case. Clark levels were as follows: I (n=3), II (n=20), III (n=9), IV (n=2). Growth phase was available in 15 cases (seven radial and eight vertical). Mitotic rates, available in 24 cases, were: 0 (n=9), 1 (n=11), 2 (n=2), 3 (n=1), 6 (n=1). One patient with histological tumour regression (2.9% of cases and 3.8% of cases with regressing tumours) had a metastatic SLN. One patient negative for SLN had a lung relapse and died of the disease. Mean follow-up was 26.2 months. CONCLUSION: The results of the present study and the analysis of the literature show that histological regression of the primary tumour does not seem predictive of higher risk of SLN involvement in thin melanomas. This suggests that screening for SLN is not indicated in thin melanomas, even those with histological regression.

[Melanoma in HIV patients: 14 cases]. / Mélanomes chez des patients séropositifs pour le VIH : 14 cas.

BACKGROUND: a clinical study of 14 patients presenting both malignant melanoma and HIV infection, and analysis of the literature to determine the frequency and specific features of this association. PATIENTS AND METHODS: ten men and four women of median age 43 years were included. In 50% of cases, the primary melanoma consisted of spreading superficial melanoma with a mean Breslow thickness of 2.83 mm. In two cases, regional lymph node metastasis was discovered but with no primary melanoma being identified. HIV infection was already documented on diagnosis of melanoma in 11 cases, and it was discovered in three cases at the time of surgery for melanoma (treatment of the primary melanoma in two cases, and in one case, regional lymph node dissection two years after the initial diagnosis). Eight patients died within a mean period of 39 months, with melanoma being the cause of death in six cases. Following relapse of melanoma, the course of the disease was severe, with mean stage IV survival of 3.6 months. No response to chemotherapy was observed where such treatment was feasible. DISCUSSION: the presence of HIV appears to be an aggravating factor for the outcome of metastatic melanoma. CONCLUSION: our study suggests the importance of clinical examination of pigmented lesions in HIV patients in order to ensure early identification of melanoma.

The contribution of large genomic deletions at the CDKN2A locus to the burden of familial melanoma.

Mutations in two genes encoding cell cycle regulatory proteins have been shown to cause familial cutaneous malignant melanoma (CMM). About 20% of melanoma-prone families bear a point mutation in the CDKN2A locus at 9p21, which encodes two unrelated proteins, p16(INK4a) and p14(ARF). Rare mutations in CDK4 have also been linked to the disease. Although the CDKN2A gene has been shown to be the major melanoma predisposing gene, there remains a significant proportion of melanoma kindreds linked to 9p21 in which germline mutations of CDKN2A have not been identified through direct exon sequencing. The purpose of this study was to assess the contribution of large rearrangements in CDKN2A to the disease in melanoma-prone families using multiplex ligation-dependent probe amplification. We examined 214 patients from independent pedigrees with at least two CMM cases. All had been tested for CDKN2A and CDK4 point mutation, and 47 were found positive. Among the remaining 167 negative patients, one carried a novel genomic deletion of CDKN2A exon 2. Overall, genomic deletions represented 2.1% of total mutations in this series (1 of 48), confirming that they explain a very small proportion of CMM susceptibility. In addition, we excluded a new gene on 9p21, KLHL9, as being a major CMM gene.

[Non-bacterial thrombotic endocarditis complicating metastatic melanoma]. / Endocardite thrombotique non bactérienne compliquant un mélanome métastasé.

INTRODUCTION: Non-bacterial thrombotic endocarditis is defined by the presence of cardiac aseptic valvular vegetations made of fibrin and platelets. We report a case diagnosed ante mortem that occurred in a patient with metastatic melanoma. CASE REPORT: M. S., presented with a metastatic melanoma associated with an acute neurological deficit. Cerebral computerized tomographies and nuclear magnetic resonance showed occipital ischaemic lesions in the territory of the posterior cerebral artery. Cardiac echography showed large vegetations of the mitral valve. Bacterial endocarditis was eliminated. The diagnosis of non-bacterial thrombotic endocarditis was made, confirmed by post mortem examination. DISCUSSION: Non-bacterial thrombotic endocarditis is the second cause of neurological manifestations in patients with cancer. The presentation of our case was unusual because of an audible heart murmur and vegetations visible on echography.

[Double-blind study versus excipient of 0.75% metronidazole gel in the treatment of rosacea]. / Etude en double insu contre excipient du métronidazole gel à 0.75 p. 100 dans le traitement de la rosacée.

INTRODUCTION: The proven value of tetracyclines and metronidazole administered orally in the treatment of the chronic and recurrent disease that is rosacea is tempered by the important undesirable effects observed in long-term therapy. The purpose of this study was to test the effectiveness of an 0.75 p. 100 metronidazole gel in the treatment of rosacea. PATIENTS AND METHODS: The study involved two groups of patients: one received the metronidazole gel and the other the vehicle of the gel used as placebo. The multicentre randomized trial was conducted in the double-blind fashion by 18 private dermatologists working in the Paris region. Fifty one patients who, since more than 3 months, had been presenting with rosacea, defined as at least 4 papulopustules associated with erythema and/or telangiectasia, entered the trial. Topical treatments and systemic treatments which had shown some activity against rosacea had been interrupted for 15 days or 2 months respectively. The product (or the placebo) was applied a.m. and p.m. on the whole dry face. The patients were seen on days 0, 21 and 42. The evaluation was purely clinical, and the principal criterion of judgement was a change in the number of papulopustules between days 0 and 42. RESULTS: The metronidazole gel reduced the number of papulopustules between day 0 and day 42, and this reduction was significantly greater than that observed with the excipient alone. The active product began to be effective during the third week and remained so during the next three weeks. Both the metronidazole gel and its excipient seemed to be poorly tolerated, with frequent complaints of dry skin, but in 5 women of the metronidazole group this dryness was alleviated by application of moisturizers. CONCLUSION: This study has demonstrated that the 0.75 p. 100 metronidazole gel is effective in the treatment of the papulopustular component of rosacea.

[A double-blind placebo-controlled study of a 2 percent foaming lotion of ketoconazole in a single application in the treatment of pityriasis versicolor]. / Etude en double insu contre excipient du kétoconazole lotion moussante à 2 p. 100 en application unique dans le traitement du pityriasis versicolor.

A double-blind, placebo-controlled therapeutic trial of ketoconazole presented as a foam and applied only once was carried out on 61 patients by a group of 15 private dermatologists practising in the Paris region. All patients had tinea versicolor clinically diagnosed, then confirmed by a positive patch test, as assessed by a single mycologist. The main criterion of therapeutic effectiveness was negativation of the patch test 30 days after a single topical application of the ketoconazole foam. On day 30, the test was negative in 22 of the 28 patients in the ketoconazole group and in 5 of the 29 patients in the placebo (i.e. excipient) group (p less than 10(-5). Clinical and mycological cure was observed in only 11 of the 28 patients treated with the active substance, but among the 11 patients who still showed skin lesions despite a negative mycological examination 10 had achromic lesions which could be regarded as residual. This clearly indicates that the only criterion that can be used in a therapeutic trial on tinea versicolor is the mycological result. The active substance and the excipient were well tolerated; two patients in the ketoconazole group reported tingling of the skin at the site of application. We conclude that a single application of ketoconazole foam in effective and well tolerated in tinea versicolor. The single application technique unquestionably has advantages over repeated applications and should result in better patient's compliance and greater effectiveness in the long term.

Late occurrence of Histoplasma duboisii cutaneous and pulmonary infection 18 years after exposure.

We report an imported case of Histoplasma capsulatum var. duboisii (H. duboisii) infection in a white French woman revealed by cutaneous lesions of the scalp, 18 years after her last stay in West and Central Africa. Asymptomatic bilateral pulmonary infiltrates were discovered on thoracic computed tomography. Skin biopsy allowed the positive diagnosis showing the typical yeasts; culture of biopsy specimens was positive for H. capsulatum. In the absence of criteria of severity, the patient was treated for one year with oral itraconazole 400mg/day. The outcome was favourable, skin and pulmonary lesions resolved slowly. The follow up is 5 years without relapse after the end of treatment. This case illustrates the possibility of late occurrence of H. duboisii infection, many years after exposure and the major importance of asking any patient for travelling or residency in tropical countries.

Photon extrabunching in ultrabright twin beams measured by two-photon counting in a semiconductor.

For many years twin beams originating from parametric down-converted light beams have aroused great interest and attention in the photonics community. One particular aspect of the twin beams is their peculiar intensity correlation functions, which are related to the coincidence rate of photon pairs. Here we take advantage of the huge bandwidth offered by two-photon absorption in a semiconductor to quantitatively determine correlation functions of twin beams generated by spontaneous parametric down-conversion. Compared with classical incoherent sources, photon extrabunching is unambiguously and precisely measured, originating from exact coincidence between down-converted pairs of photons, travelling in unison. These results strongly establish that two-photon counting in semiconductors is a powerful tool for the absolute measurement of light beam photon correlations at ultrashort timescales.

Microcystic adnexal carcinoma: report of seven cases including one with lung metastasis.

BACKGROUND: Microcystic adnexal carcinoma (MAC) is a rare cutaneous neoplasm, with a high rate of local recurrences. OBJECTIVE: A series of MAC was analyzed and compared to previously published cases. METHODS: Seven cases of MAC were identified in the register of the institution. Medical and pathological records were reviewed. RESULTS: The primary MAC were located on the face in all patients, and 85% were initially misdiagnosed. The mean follow-up duration was 108 months. The recurrence rate was high: 4 patients developed recurrences. In 3 patients, the course of the disease was severe: one of them developed pathologically proven lung metastasis. CONCLUSION: The present study and review of the literature confirm the clinically aggressive evolution of MAC and its rare ability to give rise to metastasis. Long-term clinical follow-ups with imaging investigations are mandatory.