[Invasive squamous cell carcinoma: about 2 cases]. / Carcinome épidermoïde conjonctival invasif : à propos de 2 cas.

Conjunctival tumors are common in tropical areas, where exposure to ultraviolet radiation is high and almost permanent. Malignant tumors are quite rare and the most represented is conjunctival squamous cell carcinoma. We report two cases of invasive squamous cell carcinoma of the conjunctiva received in the ophthalmology department of the Sominé Dolo hospital in Mopti, Mali. The patients were 25 and 51 years old, living in a rural desert area exposed to sunlight and dust. They presented with a mass developed in the area of the palpebral fissure, invading the cornea and preventing palpebral occlusion. The mass was raised, multi-lobulated, well circumscribed, pearly white in color and papillomatous in appearance with dilation of the feeder vessels. A wide surgical excision at 4 - 5 mm from the healthy tissue edges was performed with anatomopathological examination of the specimen, which confirmed a mature and invasive differentiated squamous cell carcinoma of the conjunctiva. The extension workup and HIV serology were negative. The evolution was favorable in the medium term without recurrence.

Les tumeurs conjonctivales sont fréquentes dans les zones tropicales,où l'exposition aux rayons ultraviolets est forte et quasi permanente. Les tumeurs malignes sont assez rares et la plus représentée est le carcinome épidermoïde de la conjonctive.Nous rapportons deux cas de carcinome épidermoïde invasif de la conjonctive reçus dans le service d'ophtalmologie de l'hôpital Sominé Dolo de Mopti au Mali. Il s'agissait de deux patientes de 25 et 51 ans, vivant en zone rurale et désertique exposées aux rayons solaires et à la poussière. Elles présentaient une masse développée dans l'aire de la fente palpébrale, envahissant la cornée et empêchant l'occlusion palpébrale. La masse était en relief, multi lobulée, bien circonscrite, de couleur blanc nacré et d'aspect papillomateux avec une dilatation des vaisseaux nourriciers. Une exérèse chirurgicale large à 4 - 5 mm des berges de tissu sain a été réalisée avec examen anatomopathologique de la pièce qui a confirmé un carcinome épidermoïde différencié mature et invasif de la conjonctive. Le bilan d'extension et la sérologie HIV étaient négatifs. L'évolution était favorable à moyen terme sans récidive.

Carcinome épidermoïde conjonctival invasif: à propos de 2 cas / Invasive squamous cell carcinoma: about 2 cases

Les tumeurs conjonctivales sont fréquentes dans les zones tropicales,où l'exposition aux rayons ultraviolets est forte et quasi permanente. Les tumeurs malignes sont assez rares et la plus représentée est le carcinome épidermoïde de la conjonctive.Nous rapportons deux cas de carcinome épidermoïde invasif de la conjonctive reçus dans le service d'ophtalmologie de l'hôpital Sominé Dolo de Mopti au Mali. Il s'agissait de deux patientes de 25 et 51 ans, vivant en zone rurale et désertique exposées aux rayons solaires et à la poussière. Elles présentaient une masse développée dans l'aire de la fente palpébrale, envahissant la cornée et empêchant l'occlusion palpébrale. La masse était en relief, multi lobulée, bien circonscrite, de couleur blanc nacré et d'aspect papillomateux avec une dilatation des vaisseaux nourriciers. Une exérèse chirurgicale large à 4 - 5 mm des berges de tissu sain a été réalisée avec examen anatomopathologique de la pièce qui a confirmé un carcinome épidermoïde différencié mature et invasif de la conjonctive. Le bilan d'extension et la sérologie HIV étaient négatifs. L'évolution était favorable à moyen terme sans récidive

Conjunctival tumors are common in tropical areas, where exposure to ultraviolet radiation is high and almost permanent. Malignant tumors are quite rare and the most represented is conjunctival squamous cell carcinoma. We report two cases of invasive squamous cell carcinoma of the conjunctiva received in the ophthalmology department of the Sominé Dolo hospital in Mopti, Mali. The patients were 25 and 51 years old, living in a rural desert area exposed to sunlight and dust. They presented with a mass developed in the area of the palpebral fissure, invading the cornea and preventing palpebral occlusion. The mass was raised, multi-lobulated, well circumscribed, pearly white in color and papillomatous in appearance with dilation of the feeder vessels. A wide surgical excision at 4 - 5 mm from the healthy tissue edges was performed with anatomopathological examination of the specimen, which confirmed a mature and invasive differentiated squamous cell carcinoma of the conjunctiva. The extension workup and HIV serology were negative. The evolution was favorable in the medium term without recurrence

Fc gamma receptor IIa-H131R polymorphism and malaria susceptibility in sympatric ethnic groups, Fulani and Dogon of Mali.

It has been previously shown that there are some interethnic differences in susceptibility to malaria between two sympatric ethnic groups of Mali, the Fulani and the Dogon. The lower susceptibility to Plasmodium falciparum malaria seen in the Fulani has not been fully explained by genetic polymorphisms previously known to be associated with malaria resistance, including haemoglobin S (HbS), haemoglobin C (HbC), alpha-thalassaemia and glucose-6-phosphate dehydrogenase (G6PD) deficiency. Given the observed differences in the distribution of FcγRIIa allotypes among different ethnic groups and with malaria susceptibility that have been reported, we analysed the rs1801274-R131H polymorphism in the FcγRIIa gene in a study of Dogon and Fulani in Mali (n = 939). We confirm that the Fulani have less parasite densities, less parasite prevalence, more spleen enlargement and higher levels of total IgG antibodies (anti-CSP, anti-AMA1, anti-MSP1 and anti-MSP2) and more total IgE (P < 0.05) compared with the Dogon ethnic group. Furthermore, the Fulani exhibit higher frequencies of the blood group O (56.5%) compared with the Dogon (43.5%) (P < 0.001). With regard to the FcγRIIa polymorphism and allele frequency, the Fulani group have a higher frequency of the H allele (Fulani 0.474, Dogon 0.341, P < 0.0001), which was associated with greater total IgE production (P = 0.004). Our findings show that the FcγRIIa polymorphism might have an implication in the relative protection seen in the Fulani tribe, with confirmatory studies required in other malaria endemic settings.

BHD mutations, clinical and molecular genetic investigations of Birt-Hogg-Dubé syndrome: a new series of 50 families and a review of published reports.

BACKGROUND: Birt-Hogg-Dubé syndrome (BHDS) (MIM 135150) is an autosomal dominant predisposition to the development of follicular hamartomas (fibrofolliculomas), lung cysts, spontaneous pneumothorax, and kidney neoplasms. Germline mutations in BHD are associated with the susceptibility for BHDS. We previously described 51 BHDS families with BHD germline mutations. OBJECTIVE: To characterise the BHD mutation spectrum, novel mutations and new clinical features of one previously reported and 50 new families with BHDS. METHODS: Direct bidirectional DNA sequencing was used to screen for mutations in the BHD gene, and insertion and deletion mutations were confirmed by subcloning. We analysed evolutionary conservation of folliculin by comparing human against the orthologous sequences. RESULTS: The BHD mutation detection rate was 88% (51/58). Of the 23 different germline mutations identified, 13 were novel consisting of: four splice site, three deletions, two insertions, two nonsense, one deletion/insertion, and one missense mutation. We report the first germline missense mutation in BHD c.1978A>G (K508R) in a patient who presented with bilateral multifocal renal oncocytomas. This mutation occurs in a highly conserved amino acid in folliculin. 10% (5/51) of the families had individuals without histologically confirmed fibrofolliculomas. Of 44 families ascertained on the basis of skin lesions, 18 (41%) had kidney tumours. Patients with a germline BHD mutation and family history of kidney cancer had a statistically significantly increased probability of developing renal tumours compared to patients without a positive family history (p = 0.0032). Similarly, patients with a BHD germline mutation and family history of spontaneous pneumothorax had a significantly increased greater probability of having spontaneous pneumothorax than BHDS patients without a family history of spontaneous pneumothorax (p = 0.011). A comprehensive review of published reports of cases with BHD germline mutation is discussed. CONCLUSION: BHDS is characterised by a spectrum of mutations, and clinical heterogeneity both among and within families.

[Spatial cluster detection without point source specification: the use of five methods and comparison of their results]. / Détection de clusters spatiaux sans point source prédéfini: utilisation de cinq méthodes et comparaison de leurs résultats.

BACKGROUND: Various statistical methods have been developed to describe spatial heterogeneity, in terms of high risk zones. If no source can be determined, this heterogeneity can be globally or locally described. Global methods test a statistic estimated over the whole studied geographical area, whereas local methods estimate a statistic on each spatial unit (or regrouping unit). This paper aimed to present, and to compare results of an epidemiological application, of five methods of spatial cluster detection. METHODS: The two global detection methods were: 1) Moran's coefficient, a classically used autocorrelation coefficient; 2) Tango's statistic, a spatial generalization of the Chi(2) statistic. The three local methods were: 1) the local application of Moran's coefficient, proposed by Anselin; 2) the scan statistic, which searches for grouping of spatial units; 3) the oblique regression tree, which splits the studied zone into sub-zones of different risks. These five methods were applied to the description of the spatial heterogeneity of the malaria risk over a hyperendemic village, in Mali. RESULTS: All the methods highlighted a significant spatial heterogeneity. Both global methods (Moran's coefficient and Tango's statistic) showed weak spatial correlations. Local Moran's coefficient (with Bonferronis' adjustment) highlighted five spatial units. The scan statistic identified a single high risk cluster. The regression oblique tree split the study area into six sub-zones; the sub-zone with the higher risk was consistent with the cluster identified by the scan statistic. CONCLUSION: These presented methods do not require any previous knowledge of a source. They allow evaluating spatial risk heterogeneity over the entire geographical area under study. It is noteworthy that shape, size, and spatial heterogeneity characteristics (either global or local) of the study area, as well as the definition of the proximity, significantly influence the spatial risk analysis' outcome. Although their results should be cautiously interpreted, these methods are useful for preliminary field studies or epidemiological surveys.

Fumarate hydratase enzyme activity in lymphoblastoid cells and fibroblasts of individuals in families with hereditary leiomyomatosis and renal cell cancer.

BACKGROUND: Hereditary leiomyomatosis and renal cell cancer (HLRCC) is the autosomal dominant heritable syndrome with predisposition to development of renal cell carcinoma and smooth muscle tumours of the skin and uterus. OBJECTIVE: To measure the fumarate hydratase (FH) enzyme activity in lymphoblastoid cell lines and fibroblast cell lines of individuals with HLRCC and other familial renal cancer syndromes. METHODS: FH enzyme activity was determined in the whole cell, cytosolic, and mitochondrial fractions in 50 lymphoblastoid and 16 fibroblast cell lines including cell lines from individuals with HLRCC with 16 different mutations. RESULTS: Lymphoblastoid cell lines (n = 20) and fibroblast cell lines (n = 11) from individuals with HLRCC had lower FH enzyme activity than cells from normal controls (p<0.05). The enzyme activity in lymphoblastoid cell lines from three individuals with mutations in R190 was not significantly different from individuals with other missense mutations. The cytosolic and mitochondrial FH activity of cell lines from individuals with HLRCC was reduced compared with those from control cell lines (p<0.05). There was no significant difference in enzyme activity between control cell lines (n = 4) and cell lines from affected individuals with other hereditary renal cancer syndromes (n = 22). CONCLUSIONS: FH enzyme activity testing provides a useful diagnostic method for confirmation of clinical diagnosis and screening of at-risk family members.

Novel mutations in FH and expansion of the spectrum of phenotypes expressed in families with hereditary leiomyomatosis and renal cell cancer.

BACKGROUND: Hereditary leiomyomatosis and renal cell cancer (HLRCC; OMIM 605839) is the predisposition to develop smooth muscle tumours of the skin and uterus and/or renal cancer and is associated with mutations in the fumarate hydratase gene (FH). Here we characterise the clinical and genetic features of 21 new families and present the first report of two African-American families with HLRCC. METHODS: Using direct sequencing analysis we identified FH germline mutations in 100% (21/21) of new families with HLRCC. RESULTS: We identified 14 germline FH mutations (10 missense, one insertion, two nonsense, and one splice site) located along the entire length of the coding region. Nine of these were novel, with six missense (L89S, R117G, R190C, A342D, S376P, Q396P), one nonsense (S102X), one insertion (111insA), and one splice site (138+1G>C) mutation. Four unrelated families had the R58X mutation and five unrelated families the R190H mutation. Of families with HLRCC, 62% (13/21) had renal cancer and 76% (16/21) cutaneous leiomyomas. Of women FH mutation carriers from 16 families, 100% (22/22) had uterine fibroids. Our study shows that expression of cutaneous manifestations in HLRCC ranges from absent to mild to severe cutaneous leiomyomas. FH mutations were associated with a spectrum of renal tumours. No genotype-phenotype correlations were identified. CONCLUSIONS: In combination with our previous report, we identify 31 different germline FH mutations in 56 families with HLRCC (20 missense, eight frameshifts, two nonsense, and one splice site). Our FH mutation detection rate is 93% (52/56) in families suspected of HLRCC.

[Trypanosomiasis and trypanocidal treatments in Ndama calves in a glossina infected area (the ranch of Madina-Diassa in Mali)]. / Trypanosomose et traitements trypanocides chez le veau Ndama en milieu fortement infesté de glossines (ranch de Madina-Diassa au Mali).

This work aims at contributing to the knowledge of trypanosomiasis epidemiology in calves of trypanotolerant breeds and at defining an appropriate treatment to improve the survival of such calves in a tsetse infested area. The first study was a parasitological survey of 100 calves from the day of birth to the age of one year. According to the results of this survey, the period from birth to three months is a "critical" moment in the life of the calves, due to a high infection rate and mortality related to trypanosomiasis. The purpose of the second study was to investigate the possible interference of early trypanocidal treatments with the further expression of trypanotolerance. For this purpose three groups of over one-year old animals were established. The groups had different trypanosomiasis history due to the different treatments they had undergone during their first year of life. All the animals had been exposed to trypanosomiasis without treatment and followed up parasitologically and clinically during the second year. The results showed no interference of early trypanocidal treatments (including preventive ones) with the expression of resistance in potentially trypanotolerant animals.