Melanoma and intellectual disability: do prognostic factors at diagnosis differ from general population?

BACKGROUND: Few melanoma cases are reported in individuals with intellectual disability (ID), and prognostic factors at diagnosis are unknown in this population. This work was designed to investigate whether prognostic factors at diagnostic are different in patients with ID compared with a general population. METHODS: Melanoma cases retrieved from Hérault's Tumour Registry (HTR) from 1995 to 2015 were cross-referenced against a list of adult patients with ID, living in Hérault. Major prognostic factors were compared with those in non-ID melanoma patients included in HTR and in patients followed by Montpellier University Hospital and included in the Réseau pour la Recherche et l'Investigation Clinique sur le Mélanome (RIC-Mel) database. RESULTS: Ten melanoma cases in individuals with ID were identified and compared with 3804 non-ID melanoma cases in HTR and 1024 non-ID melanoma cases included in RIC-Mel. Mean Breslow thickness at diagnosis was 4.6 mm in melanoma cases among those with ID versus 1.89 mm in HTR (P = 0.109) and 2.36 mm in RIC-Mel (P = 0.156). Stage at diagnosis was superior to stage IIB in 42.9% of ID cases versus 11.4% of non-ID cases in HTR (P < 0.05) and 8.5% in RIC-Mel (P < 0.05). CONCLUSIONS: Melanomas in patients with ID had less favourable prognostic factors at diagnosis, including higher Breslow thickness and more advanced stage, than melanomas in non-ID patients. These adverse prognostic factors indicate a later diagnosis in this population, leading to a poorer prognosis. This work underlines the need to improve melanoma screening among individuals with ID.

Cancer diagnoses among older people with intellectual disability compared with the general population: a national register study.

BACKGROUND: Cancer occurrence among older people with intellectual disability (ID) is poorly documented, so we investigated the frequency and distribution of cancer in older people with ID compared with the general population. METHOD: People with ID who were ≥55years old and alive at the end of 2012 (n = 7936; ID cohort) were identified through a national register of people with ID who received social services in Sweden to optimise the individual's opportunity for good living conditions in daily life. An equally large reference cohort from the general population (gPop cohort) was matched by year of birth and sex. Cancer diagnoses registered in inpatient and outpatient specialist care were collected for 2002-2012 from the ID cohort and compared with diagnoses in the gPop cohort. RESULTS: A lower total cancer frequency was observed in the ID cohort, which contained 555 cancers, compared with 877 cancers in the gPop cohort [odds ratio (OR): 0.63; 95% confidence interval (CI): 0.57-0.70]. Women accounted for 60% of cancers in the ID cohort. Breast and gynaecological organ cancers had similar or slightly lower frequencies in the ID cohort than in the general population, with breast OR of 0.95, uterine corpus OR of 1.00 and ovary OR of 0.73. Surprisingly, cancer frequency of the digestive organs (OR: 0.67), including the colon (OR: 0.82), was lower than in the general population. Cancers of the prostate (OR: 0.25), urinary tract (OR: 0.42) and lung were less frequent than in the general population. CONCLUSIONS: Cancer was diagnosed less frequently in the ID cohort than in the gPop cohort. However, cancers of the breast and colon-rectum remain frequent in people with ID and therefore warrant prevention policies, monitoring and screening similar to those of the general population.

Breast cancer and screening in persons with an intellectual disability living in institutions in France.

BACKGROUND: We aimed to describe, among a population of women with intellectual disabilities (ID) living in institutions in France, the characteristics in whom breast cancer (BC) was diagnosed and of those who participated in BC screening. METHODS: Study was performed in 2009 among a random, representative sample of women with ID living in institutions in France. Participants answered a questionnaire either directly by themselves, or with the help of an intermediary. RESULTS: In total, 978 women with ID aged over 18 years were included, and 14 were diagnosed with BC. The incidence observed in this sample of women with ID is similar to that of the general population (standardised incidence ratio, SIR 0.857, 95% confidence interval (CI) 0.42-1.53). Average age at diagnosis was 47.8 years, and the risk of developing BC before the age of 50 was 2.03% (0.4-3.66). This risk was not significantly different from that of the general population (2.4%, 1.0-3.78). Obesity was almost twice as frequent in women who had BC as compared to those without BC (43% vs. 22.5%, P = 0.0196). Among the 310 women aged >50 years and eligible for the national BC screening programme, 238 (77%) had already had at least one mammogram, and 199 had had it within the previous 2 years. Adherence to the screening programme was 64.2% (199/310) in the participating institutions. This rate was slightly higher than the national average of 62% for the same period. CONCLUSIONS: The results of this study show that BC is equally as frequent among women with ID living in institutions as in the general population, and occurs at around the same age. Obesity was significantly more frequent among women in whom BC was diagnosed in our study. Participation in BC screening is slightly higher among women with ID living in institutions than among the general population.

An ovarian dysgerminoma in Down syndrome. Hypothesis about the association.

An 11-year-old girl with Down syndrome (DS) was operated for a stage I right ovary dysgerminoma. She is in good health 33 years later. Some data in the literature suggest that ovarian cancers could be slightly overrepresented in DS. Despite the rarity of ovarian dysgerminoma, our case is the fifth reported in DS. This case is the second one associated with a family history suggesting the possibility of a familial predisposition to cancer. A hypothesis explaining the development of dysgerminoma in DS is proposed.

The epidemiology of neonatal tumours. Report of an international working group.

Neonatal tumours occur every 12,500-27,500 live births and comprise 2% of childhood malignancies, but there is little clarity as to their real prevalence, sites of origin and pathological nature as reported series vary. As an entity, neonatal tumours provide a unique window of opportunity to study tumours in which minimal environmental interference has occurred. The majority of tumours present with a mass at birth (e.g., teratomas, neuroblastomas, mesoblastic nephroma, fibromatosis), which are not infrequently identified on antenatal ultrasound. Histologically, teratoma and neuroblastoma remain the two main tumour types encountered with soft tissue sarcoma, renal tumours, CNS tumours and leukaemia being the next most common tumour types identified. Malignant tumours are uncommon in the neonatal period per se and benign tumours may have malignant potential. A particular problem exists in clinical classification, as histological features of malignancy do not always correlate with clinical behaviour. Benign tumours may also be life threatening because of their size and location. Other tumours may demonstrate local invasiveness, but no metastatic potential, and tumours that are clearly malignant may demonstrate unpredictable or uncertain behaviour. Screening programmes have brought more tumours to light, but do not appear to affect the overall prognosis. They may provide clues to the stage at which tumours develop in foetu. The aetiology of cancer in children is multifactorial and includes both genetic and environmental factors. The association between congenital abnormalities and tumours is well established (15% of neonatal tumours). Genetic defects are highly likely in neonatal tumours and include those with a high risk of malignancy (e.g., retinoblastoma), but also genetically determined syndromes with an increased risk of malignancy and complex genetic rearrangements. Tumours are mostly genetically related at a cellular level and factors influencing cellular maturation or apoptosis within the developing foetus may continue to operate in the neonatal period. Cytogenetics of neonatal neoplasms appear to differ from neoplasms in older children, thus possibly explaining some of the observed differences in clinical behaviour. Certain constitutional chromosome anomalies, however, specifically favour tumours occurring in the foetal and neonatal period. In support of this hypothesis, certain cytogenetic anomalies appear to be specific to neonates, and a number of examples are explored. Other environmental associations include ionizing radiation, drugs taken during pregnancy, infections, tumours in the mother and environmental exposure.

Ulcerative terminal ileitis after BCG therapy for bladder carcinoma.

AIM: We evaluated the aetiology of ulcerative ileitis in a 77-year-old patient receiving BCG therapy for recurring bladder carcinoma. METHODS AND RESULTS: Histological examination, laboratory data and the clinical history allowed us to exclude a classical cause such as Crohn's disease, tuberculosis or ischaemia. The important locoregional reaction suggests a BCG ileitis of the terminal ileum. Intestinal BCG ileitis has been exceptionally described after BCG vaccination. CONCLUSION: Our observation of ulcerative ileitis indicates that a digestive tract location is possible as a reaction to BCG therapy.

An infant with Down syndrome and retinoblastoma. A possible non-fortuitous association.

AIM: To evaluate the association between Down syndrome and retinoblastoma. METHOD: Presentation of a case report and review of the literature. RESULTS: A retinoblastoma was observed in a 10-month-old boy with Down syndrome. A review of the literature yielded 14 other cases, suggesting a possible excess of retinoblastoma in Down syndrome, as previously proposed by two epidemiological studies. The possible roles of external physical agents and hyperplastic and dysplastic lesions of the retina in subjects with Down syndrome is discussed. CONCLUSION: A positive association between Down syndrome and retinoblastoma is possible. An epidemiological study on this subject is needed to better ascertain this potential link.

A Pacinian hyperplasia of the foot.

A case of Pacinian hyperplasia of the right great toe is reported. Pacinian hyperplasia is a rare benign and recently recognized painful lesion composed of an excess of well formed or hyperplastic Pacinian corpuscules, normaly involved in sensory innervation. This lesion that is usually observed in the hand, must be distinguished from nerve tumors harboring onion-bulb structure which are not true well formed Pacinian corpuscules and from Morton neuroma. Pacinian hyperplasia is considered a reactive lesion and not a true neoplasm. To our knowledge, this case is the first described in the foot.

An umbilical cord teratoma in a 17-week-old fetus.

A therapeutic abortion was conducted on a 17-week-old male fetus with a large umbilical cord teratoma associated with an exomphalos. A review of the literature revealed ten other cases of umbilical cord teratoma and shows that these tumors have a very polymorphic presentation. Four fetuses and infants died from various causes indicating that there is a need for close follow-up of pregnancies with umbilical cord teratoma.

Aspects of intracranial and spinal tumors in patients with Down syndrome and report of a rapidly progressing Grade 2 astrocytoma.

BACKGROUND: Brain tumors in patients with Down syndrome (DS) rarely are reported, and their behavior is not well known. METHODS: The authors report on a male patient age 19 years who had DS with diffuse astrocytoma (World Health Organization Grade 2) that recurred twice despite treatment, leading to a glioblastoma and, finally, to death in just over 2 years. The literature on brain tumors in patients with DS is reviewed. RESULTS: Although brain neoplasms were suspected to be in excess in patients with DS, the authors found only 36 patients with brain neoplasms and 2 spinal tumors. An unusual distribution of histologic tumor types, with an over-representation of germ cell and mesenchymal tumors and a lack of embryonal tumors, was observed, in agreement with what is known currently about the tumor profile of patients with DS. CONCLUSIONS: Cerebral tumors in patients with DS have a specific distribution and may behave differently compared with the general population. These features may be related to the gene dosage effect of oncogenes, antioncogenes, and genes involved in cerebral development due to the supernumerary chromosome 21.

[Breast cancer in women with trisomy 21]. / Les cancers mammaires des femmes trisomiques 21.

The population with Down's syndrome has a different cancer profile compared to the general population, even after taking into account issues of survival and ageing. Several solid tumours are unusually rare, whereas in contrast leukaemias are increased. In addition, few studies are available on this topic. We therefore decided to conduct a mortality study based on the INSERM national mortality statistics in France comparing over a 24 year period deaths from female breast cancer in the general French population with the cancer deaths in women with Down's syndrome. Only 5 deaths with Down's syndrome could be found compared to 68.98 expected based on national statistics. This clear reduction in risk agrees with other studies available in Down's syndrome patients. This observation could be partly explained by over expression of genes linked to gene dosage effects on chromosome 21, playing a role in cell growth, differentiation, survival and death. An additional protective effect could come from the marked and continued decreased exposure to oestrogens, starting in utero for women with trisomy 21 and lasting all over life.

[Fatal mesenteric ischemic accident caused by mesenteric inflammatory veno-occlusive disease]. / Accident ischémique mésentérique fatal par maladie inflammatoire veino-occlusive du mésentère.

A 72-year-old woman in good general health presented a massive intestinal and colonic ischemia with rapid post-operative death, due to mesenteric inflammatory veno-occlusive disease. Mesenteric inflammatory veno-occlusive disease, first described in 1994, is a vasculitis of unknown etiology limited to the mesenteric area, affecting exclusively veins and venules and sparing arteries. Histologically, there are acute lesions of lymphocytic and/or necrotizing, sometimes granulomatous phlebitis and chronic lesions of myointimal hyperplasia reducing the lumen of the veins. In this case, polymorphonuclear eosinophils were particularly numerous.

Identification of novel L1CAM mutations using fluorescence-assisted mismatch analysis.

The L1CAM gene, which is located in Xq28 and codes for a neuronal cell adhesion molecule, is involved in three distinct conditions: HSAS (hydrocephalus-stenosis of the aqueduct of Sylvius), MASA (mental retardation, aphasia, shuffling gait, adductus thumbs), and SPG1 (spastic paraplegia). Molecular analysis of the L1CAM gene is labor-intensive because of the size of the coding region, which is fragmented in numerous exons, and because of the great allelic heterogeneity and distribution of the mutations. The FAMA (fluorescent assisted mismatch analysis) method combines the excellent sensitivity of the chemical cleavage method for scanning PCR fragments larger than 1 kb and the power of automated DNA sequencers. In order to optimize this method for L1CAM, we divided the gene into nine genomic fragments, each including three to four exons. These fragments were PCR-amplified using nine sets of primers containing additional rare universal sequences. A second-stage PCR, per formed with the two dye-labeled universal primers, allowed us to generate 1-kb-labeled fragments, which were then submitted to the chemical cleavage analysis. Among 12 French families with HSAS and/or MASA, we identified nine distinct L1CAM mutations, seven of which were novel, and an intronic variation. This study demonstrates that FAMA allows rapid and reliable detection of mutations in the L1CAM gene and thus represents one of the most appropriate methods to provide diagnosis for accurate genetic counseling in families with HSAS, MASA, or SPG1.