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.

A lack of neuroblastoma in Down syndrome: a study from 11 European countries.

An epidemiological investigation in 11 European countries comprising a total childhood population of 54.1 million children and using 8 separate data sources was conducted to evaluate the occurrence of neuroblastoma in Down syndrome (DS). No cases of DS were detected among 6724 infants and children with neuroblastoma, although more than five were expected. This highly significant result (P = 0.0045 according to the Poisson test) is consistent with data in the literature, which contains only two poorly detailed cases in epidemiological studies and one ganglioneuroma in a DS mosaic patient. Like other tumors, such as leukemias, testicular germ cell tumors and lymphomas are in excess in DS patients; the lack of neuroblastomas does not reflect a general decreased incidence of cancer but rather a specific underrepresentation of this precise tumor. S-100 b protein, the gene for which maps to the long arm of chromosome 21, (a) is overproduced in DS patients, (b) produces growth inhibition and differentiation of neural cells in vitro, (c) is abundant in good-prognosis neuroblastomas, and (d) has been shown to induce growth inhibition and differentiation and cell death in several human and murine neuroblastoma cell lines and could be responsible for this variation. Additional epidemiological and experimental studies are warranted to confirm our interpretation of these data.

A tumor profile in Down syndrome.

We conducted a review of cancers in Down syndrome (DS), because solid tumors are poorly understood in DS. Cancers are in excess in this condition because of the 20-fold excess of leukemias, whereas malignant solid tumors seem to be globally underrepresented as compared with those in the general population. However, among these tumors, some tumors are in excess: lymphomas, gonadal and extragonadal germ cell tumors, and possibly retinoblastomas and pancreatic and bone tumors. Neoplasms in excess are seen earlier, sometimes in fetal life (leukemias and testicular germ cell tumors) or neonatally (leukemias and lymphoma) and affect mainly male subjects. There seems to exist an excess of rare karyotypes. Other tumors are underrepresented, particularly neuroblastomas and nephroblastomas, in young children, and perhaps common epithelial tumors in adults. These observations suggest that DS has a particular tumor profile, with some tissues more affected by malignant diseases (hematopoietic tissue and germ cells) and others that seem to be protected (central and peripheral nervous system, renal tissue, and epithelial tissues). The mechanism is mainly genetic, but differences in exposure to exogenous agents compared with the general population must be kept in mind. These findings are of interest for the management of these patients and early detection of cancers. Better knowledge of this tumor profile could help us to understand the mechanisms of carcinogenesis and should be compared to the current knowledge of genes on chromosome 21.

Aspects of the neoplasms observed in patients with constitutional autosomal trisomy.

A review of the literature reveals numerous clinical case reports, systematic histologic analyses, epidemiologic studies, and large series of tumors showing that subjects with trisomy 8, 9, 13, 18, and 21 have an excess of hematologic and various solid tumors compared to the general population. These tumors more frequently affect particular organs for a given type of trisomy. A large proportion of tumors are observed during fetal and neonatal life, are incompletely developed, and subsequently regress. In older children or even adults, tumors are less frequent, are often found on the same organs as earlier in life, are more aggressive, and do not involute. The mechanism responsible for the development of these neoplasms could be similar to that which generates the malformations in these children and may result from cooperation of the chromosomal abnormality with physiologic growth phenomena, which are particularly active early in life. Trisomic subjects must be carefully followed in order to detect tumors as early as possible and to allow treatment under optimal conditions.

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.

Antenatal exposure to atenolol and retroperitoneal fibromatosis.

We present a case of retroperitoneal fibromatosis in a fetus whose mother took atenolol during pregnancy. A 25-year-old obese woman was treated for hypertension with 100 mg atenolol daily from the second month until the end of pregnancy. At 29 weeks, echography disclosed a retroperitoneal mass and at 37 weeks, a boy was delivered. A biopsy of the tumor showed a fibromatosis with medullary compression, treated by antimitotics until 3 months of age. At the age of 4, the mass had disappeared but severe scoliosis was present. This in utero exposure to atenolol drew our attention because the retroperitoneal localization of the tumor is similar to that of fibroses reported in adults after exposure to atenolol and for other reasons: transplacental carcinogenesis has been demonstrated in humans, at least for diethylstilboestrol, atenolol crosses the placental barrier, the drug was taken during nearly the whole pregnancy, and retroperitoneal fibromatosis is exceptional as a neonatal tumour.

A case report of Down syndrome and centroblastic lymphoma.

We describe a case of left cervical stage I centroblastic lymphoma in a 29-year old male patient with Down's syndrome due to a (14; 21) Robertsonian translocation. The disease presented as extensive lymph node necrosis leaving rare areas of tumor cells, accounting for the diagnostic difficulties. According to our review of the literature, lymphoma is one of the most common neoplasms in DS patients and may represent the second most common malignancy in this condition, far behind leukemia.

A decreased incidence of neuroblastomas in Down's syndrome and overproduction of S-100 b protein.

Neuroblastoma, one of the most frequent solid tumors found in childhood, is very rare in Down's syndrome subjects. This lack could possibly be due to overproduction of S-100 b protein for the following reasons: 1) the gene coding for S-100 b protein is situated on chromosome 21, and the protein is overproduced via a gene dosage effect; 2) S-100 b protein is found in glial cells and Schwann cells of the central and peripheral nervous system and has been shown to have a differentiating effect on normal neural cells; 3) neuroblastomas with a stroma rich in S-100 protein have a good prognosis. Preliminary studies demonstrated an inhibition of growth of two human neuroblastoma cell lines in the presence of S-100 b protein compared to controls. It is postulated that S-100 b protein may inhibit the development of neuroblastomas in Down's syndrome either antenatally, or after birth and may be a therapeutic agent against neuroblastoma.

Endometrial müllerian carcinosarcoma after cessation of tamoxifen therapy for breast cancer.

The aim of this report is to draw the attention of clinicians to the possible occurrence of endometrial cancers of rare histological type among women currently undergoing or having in the past undergone tamoxifen therapy, in particular for breast cancer. We report a case of heterologous mixed malignant müller tumor occurring in an 80-year-old woman. At 69, she had been diagnosed with breast cancer and received tamoxifen for a total of 55 months over a 6-year period. In the 5th year after cessation of tamoxifen therapy, an endometrial carcinosarcoma was diagnosed. Although the association between tamoxifen use and endometrial cancer is recognized, only a few reports of occurrence long after cessation of therapy exist. We believe ours is the second for this particular histological type. Tamoxifen may have played a role in the occurrence of this tumor although it is also known that this type of tumor may arise de novo in elderly women. The etiologic hypothesis obtained from this case description will now be tested in a formal epidemiological investigation which hopefully will provide more definitive evidence.

[Neonatal carcinoma. Review of the literature apropos of a case]. / Les carcinomes néonatals. Revue de la litterature a propos d'un cas.

A cortical adrenal carcinoma arising during the neonatal period and associated with virilization recurred after an initial excision and is in complete remission after a follow-up period of 10 years. The authors have performed a review of the medical literature which has yielded 56 neonatal carcinomas including this one. More than half of these cases concerned the thyroid gland (15 cases) and the adrenal cortex (14 cases). These were followed by malignant melanomas (12 cases), carcinomas of the parotid gland (6 cases), oropharyngeal region (3 cases), adrenal medulla (2 cases) and stomach, liver, breast and cutaneous sweat gland (one case each). Six tumors were associated with congenital malformations which included Beckwith-Wiedeman's syndrome; 4 tumors arose from preexisting tissue lesions; in one case, oral contraceptives were taken during pregnancy. The main treatment of neonatal carcinomas is surgery. Local recurrences (7 cases) do not markedly affect the outcome, whereas metastases (12 cases) have a very unfavorable prognosis. Superficial tumors are diagnosed earlier and more frequently cured. Out of 44 cases for which the outcome is known, only 18 children survived.

[Cardiac rhabdomyoma and apoptosis: are regression controlled by the body?]. / Rhabdomyomes cardiaques et apoptose: les régressions sont-elles contrôlées par l'organisme?

Three rhabdomyomas detected in utero regressed after birth. These personal observations and others in medical literature show that regressions are more frequent than it was formerly believed, and are almost always observed during the first two years of life. The same clinical features of these involutions, histological appearances of apoptosis (programmed cell death), and the absence of inflammation suggest that spontaneous regressions may be controlled by the body. Regression of rhabdomyomas may be compared with other observations of benign and malignant tumours which show spontaneous involution in early life. Medical treatment is advisable even in the absence of life-threatening symptoms.

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.

[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.

[Association of a pheochromocytoma and a homolateral clear cell renal carcinoma]. / Association d'un phéochromocytome à un carcinome rénal à cellules claires homolatéral.

A 61 years old man had a clear cell type carcinoma of the right kidney and a small asymptomatic homolateral adrenal pheochromocytoma. A von Hippel-Lindau disease suggested by this association was not confirmed in this case. However the measurement of plasma and urinary catecholamines, VMA and Iodine 131 MIBG (meta-iodo-benzyl-guanidine) scans are usefull in case of clinical doubt in patients with renal adenocarcinoma. This observation and others in medical literature demonstrate the interest of resection of adrenal glands during a nephrectomy for adenocarcinoma.

[Valvular cyst and atrioventricular canal in a child with trisomy 21]. / Kyste valvulaire et canal atrioventriculaire chez un enfant trisomique 21.

A child with Down's syndrome with an atrioventricular canal of ostium primum type had also a blood cyst of the mitral valve. Aside more frequent complex heterotopic cysts due to migration anomalies, simple cysts are rare with only 27 cases described in medical literature. They are often symptomatic and are cured by surgical removal. Our hypothesis, in accord with recent embryologic observations, is that simple cysts situated close to the valves and fibrous ring of the heart may result from heteroplastic change of tissue coming from primitive pericardial mesothelium. This primitive mesothelium participates to the formation of the fibrous skeleton of the heart.

[Histologic study of 100 pregnant fallopian tubes]. / Etude histologique de 100 trompes gravides.

The 100 fallopian tubes had been obtained from women whose mean age was 30 and whose mean period of amenorrhea was 38 days. Each fallopian tube gave rise to at least sixteen samples and was sectioned if necessary several times. There had been tubal rupture in 25 cases, and in at least 7 cases the rupture involved the ovum and its implantation site. The location of the implantation site could be determined in only 30 cases: 10 in the mesosalpin; x 10 in the antimesosalpinx; 8 lateral and 2 circumferential. The anatomic site of the implantation was isthmic in 7 cases; ampullary in 85 cases, of which 6 were near to the isthmus; infundibular in 7 cases and fimbrial in 1 case. Tubal lesions were found in 22% of the cases, but associated were also found frequently: tubal adenomyosis (17 cases); adherent tubal fimbriae (14 cases); peritoneal adhesions (11 cases) and decidual changes in 12 cases. The 74 remaining fallopian tubes were considered to have been previously normal and to have been affected only by changes linked to the pregnant state (edema, congestion, lymphocytic infiltration) or to complications or this state (a smoothing out of the tubal mucosa; a peritoneal granuloma surrounding blood products; a localized infarct of the fimbriae or wall; and haemorrhage involved in thromboses, ovum detachment or necrosis). The ovum and implantation appeared to be normal in 26 cases and to have had development prematurely stopped because of extensive haemorrhage in 41 cases. In 22 cases there was hypoplasia, and difficulty in determining the cause in 11 cases. From a morphological point of view preserving at least one third of gravid fallopian tubes is justifiable, because the chronic lesions are often discrete and the changes of pregnancy generally appear to be reversible. The persisting pathogenic factors are not necessarily tubal, as can be seen by the role of delays in transport of the ova.

[Sacrococcygeal teratoma in 2 fetuses at 5 and 6 months]. / Tératome sacro-coccygien chez deux foetus de 5 et 6 mois.

The two large mature sacro-coccygeal teratomas reported seem to be responsible for the death of fetuses in the fifth and sixth months of pregnancy. A review of the literature shows that teratomas are exceptionally rare during this period. Their outcome depends upon the degree of maturity of the tumor, its size, whether its location is pelvic or not, the presence of any associated malformations and upon prematurity.