Pineal germinoma in a child with interferon-γ receptor 1 deficiency. case report and literature review.

Interferon-γ receptor 1 (IFN-γR1) deficiency is one of the primary immunodeficiencies conferring Mendelian Susceptibility to Mycobacterial Disease (MSMD). Some cases of neoplasms have been recently reported in patients with MSMD, underlying the already known link between immunodeficiency and carcinogenesis. We report the first case of intracranial tumour, i.e. pineal germinoma, in a 11-year-old patient with complete IFN-γR1 deficiency. The first clinical presentation of the genetic immunodeficiency dates back to when the child was aged 2 y and 10 mo, when he presented a multi-focal osteomyelitis caused by Mycobacterium scrofulaceum. The diagnosis of IFN-γR1 deficiency (523delT/523delT in IFNGR1 gene) was subsequently made. The child responded to antibiotic therapy and remained in stable clinical condition until the age of 11 years, when he started complaining of frontal, chronic headache. MRI revealed a solid pineal region mass lesion measuring 20 × 29 × 36 mm. Histological findings revealed a diagnosis of pineal germinoma. The patient received chemotherapy followed by local whole ventricular irradiation with boost on pineal site, experiencing complete remission, and to date he is tumor-free at four years follow-up. Four other cases of tumors have been reported in patients affected by MSMD in our knowledge: a case of Kaposi sarcoma, a case of B-cell lymphoma, a case of cutaneous squamous cell carcinoma and a case of oesophageal squamous cell carcinoma. In conclusion, in patients with MSMD, not only the surveillance of infectious diseases, but also that of tumors is important.

Caffeine consumption among eating disorder patients: epidemiology, motivations, and potential of abuse.

OBJECTIVE: Aim of the study was to investigate caffeine use in different types of eating disorders (ED) patients either using a categorical approach [Diagnostic and Statistical Manual of Mental Disorders - Fourth Edition - Text Revision (DSM-IV-TR) diagnostic criteria] or a dimensional perspective. METHOD: Fifty-eight ED female patients [anorexia nervosa (AN), restricting and binge-eating/purging type, N=15; bulimia nervosa (BN) purging type/nonpurging type, N=26; binge eating disorder (BED), N=17] referred to an Eating Disorder Unit and 15 non-clinical controls were administered the Eating Disorder Inventory-2 (EDI-2), the Clinical Global Impression (CGI) and the Caffeine Use Test, an interview specifically developed to investigate caffeine intake. Statistical analyses were then repeated clustering patients according to the presence/absence of purging behaviors (purgers, N=22; non-purgers, N=19; BED, N=17). RESULTS: Current and lifetime caffeine use, measured as mg/day, were similar comparing controls and ED patients as a whole. BN patients showed a significantly higher maximum lifetime caffeine intake (817.4+/-528,9 vs 325.0+/-294.6 mg/die, F=3.246, p<0.05); the same for purgers vs controls (p<0.05). Caffeine abuse was significantly more represented among patients vs controls (p<0.01), but similar among different patients' groups. As for diagnoses according to DSM-IV-TR Substance Use modified for caffeine, no significant difference was found among the different groups, for either Dependence, Intoxication or Withdrawal. Most of patients and controls reported pleasure as the main motivation for caffeine use, followed by increased vigilance and attention and appetite suppression in AN and BN patients. Note that a shift in diagnosis in the course of the ED from non-purging to purging type was associated with an increase in caffeine current, lifetime and maximum lifetime intake (F=1.667 p<0.05), except for BED patients. Severity of the ED measured as CGI score or comorbidity did not affect caffeine intake in patients as a whole, but in the purging subgroup current caffeine use was increased in presence of an anxiety disorder (p<0.05), and decreased in presence of a mood disorder (p<0.01). CONCLUSIONS: Data from the present study are in agreement with previous evidence in literature that a high percentage of ED patients ordinarily use caffeine with an average intake similar to that of the general population, however with a kind of binge attitude. Among heavy drinkers, daily caffeine intake and alcohol/cigarettes use are associated supporting the link with the dimension of impulse disregulation. The substantial number of subjects from our sample satisfying research criteria for Dependence, together with increasing reports of caffeine intoxication, suggests the growing relevance of these issues that deserve further investigation.

Human cutaneous nevi transplanted onto nude mice: a model for the study of the lesional steps in tumor progression.

Normal human cutaneous nevi were transplanted to the skin of nude mice and some of the grafts were treated topically with 7,12-dimethylbenz[a]anthracene (DMBA, 1.6 mumol weekly). Histologically proven human skin was present in 22 grafts. In the 9 untreated control grafts, the tendency of nevic cells to form nests and the number of nevomelanocytes decreased with time; the melanocytic cells showed no signs of hypertrophy or atypia. In most of the 14 specimens treated with DMBA, the nevomelanocytes showed distinct signs of hypertrophy. The cells were enlarged and often dendritic and were filled with melanin granules for which the transfer to keratinocytes appeared to be blocked. The nevomelanocytes of 4 of the 9 specimens treated with DMBA for greater than or equal to 82 days (9-16 DMBA applications), showed atypical enlarged nuclei with mitotic figures. Since atypia is one criterion for identifying precursors of transformed cells, the model of human nevi grafted onto nude mouse skin may be useful for studying the various steps involved in the progression of benign melanocytic nevi to malignant melanoma.

Phenotypic characteristics of cells derived from precursors of human melanoma.

Of 66 specimens from benign melanocytic nevi, including common acquired and congenital nevi, Spitz tumors (epithelioid cell nevi), and melanocytic nevi with dysplasia, 57 could be grown in tissue culture. The cultured cells were identified as melanocytes by the presence of premelanosomes and melanosomes. Cells from 28 of 32 nevus cultures grew in an anchorage-independent way in soft agar with a colony-forming efficiency between 0.001 and 1%. Clones derived from single cells and soft agar-selected colonies showed marked phenotypic heterogeneity, but all had a limited life span and did not undergo transformation in culture. These cells were nontumorigenic in nude mice. Cultured nevus cells expressed antigens present on melanoma but absent on normal fibroblasts and/or melanocytes as tested with monoclonal anti-melanoma antibodies. The anti-melanoma antibodies bound equally well to dysplastic, congenital, and common acquired nevi. Antigens are released by nevus cells similar to melanoma cells.

Specific immunoreactivity of hybridoma-secreted monoclonal anti-melanoma antibodies to cultured cells and freshly derived human cells.

The specificities of monoclonal antibodies against melanoma cells were analyzed using radioimmunoassay, mixed-hemadsorption assay, and quantitative absorption on a variety of malignant and nonmalignant cells. Three of the six hybridoma-secreted antibodies bound to the majority of melanoma cell lines, melanoma tumors, and astrocytoma cell lines as well as to all normal and Epstein-Barr virus-transformed lymphocytes tested. The binding pattern coincides with the presence or absence of the DR antigen on human cells. Conversely, two other antibodies, 19-19 and Nu4B, detected two different antigens common to melanoma and astrocytoma cells only. Cloning of melanoma cells resulted in establishment of DR-positive and DR-negative clones, with the binding of Nu4B antibody retained in all.

Characteristics of cultured human melanocytes isolated from different stages of tumor progression.

Normal melanocytes and melanocytes of normal nevi, primary melanoma in the radial (RGP) and vertical (VGP) growth phases, and metastatic melanoma exhibited and maintained phenotypic differences when grown in tissue culture or in experimental animals. Only metastatic and VGP primary melanoma cells were tumorigenic in athymic nude mice and had nonrandom chromosomal abnormalities involving chromosomes 1, 6, and 7. The colony-forming efficiency in soft agar was also highest in these two cell types. A cell line of RGP primary melanoma had characteristics of both benign and malignant cells: nevus-like morphology; nontumorigenicity in nude mice; but karyotypic abnormality of chromosome 6. It also had a ganglioside pattern similar to that of normal melanocytes but not melanomas, i.e., a high GM3 ganglioside content compared to the amounts of GM2, GD2, and GD3 gangliosides. Binding of monoclonal antibodies secreted by hybridomas generated by immunization of mice with VGP primary and metastatic melanoma was highest with cells and supernatants of cultures from advanced melanoma and least with nevus cells. There was no binding to normal melanocytes except with the monoclonal antibodies specific for nerve growth factor receptor or 9-O-acetyl-GD3 ganglioside. On the other hand, monoclonal anti-nevus antibodies bound to melanocytes, nevus cells, and RGP primary melanoma cells but not to VGP primary or metastatic melanoma cells. Cultured human melanocytic cells appear to be a unique model for the study of tumor progression.

Varicella and its complications as cause of hospitalization.

Varicella is an acute contagious disease that most commonly occurs in childhood. Although normally benign, varicella can occasionally develop into a more serious illness. Moreover, the infection can lead to serious complications, such as Staphylococcus aureus infections, otitis media, endocarditis, pneumonia, and rare central nervous system (CNS) events like cerebellar ataxia and encephalitis. This study was conducted to analyze the hospitalization rate due to varicella or its complications in a tertiary care hospital in Italy, where varicella vaccination has not yet been implemented. The review was carried out on cases of children with varicella identified by ICD9 and ICD9-CM diagnostic codes and admitted to the Giannina Gaslini Children's Research Hospital of Genoa, Italy, from January 1st, 1995 to December 31st, 2004. For each case reporting complications, the clinical report form was extracted and the events recorded. Varicella was recorded in 346 (0,16%) out of 212,647 total hospital discharges. Chickenpox with detailed complications and cerebrovascular diseases accounted for 56 discharges (12.14%), for a total of 728 days. Fifteen patients needed more than one hospitalization because of severe sequelae as result of CNS involvement. We reported three particular cases of invasive infections and four children affected with cerebrovascular diseases following varicella. Our retrospective data regarding a single tertiary care pediatric hospital shows that hospitalization due to varicella or its sequelae may present an important medical and indirect economic problem.

A rare malposition of the central venous catheter.

The left pericardiacophrenic vein was accidentally cannulated during an attempt to establish central venous catheterization through the left internal jugular vein. Chest roentgenograms and intravenous contrast material confirmed the position of the catheter. Although our patient developed no problems during a five-day cannulation, based on published information, it is advisable to reposition the catheter to avoid perforation of the pericardiacophrenic vein and possible cardiac tamponade.

Clinical differentiation of adult-onset cavernous angioma from nodular malignant melanoma.

Asymptomatic nodules, suspected of being nodular melanomas, were subjected to 30 s of direct pressure. All the biopsy-proven nodular melanomas remained unchanged by this procedure. The nodules later proven by biopsy to be angiomas were found to collapse slowly in response to pressure. This test can be used to identify angiomas. It should be employed in the routine clinical examination of lesions suspected of being nodular melanomas.

Target blue nevus.

In two cases of target blue nevi of the foot, both lesions displayed a distinctive concentric pigmentary variation. This correlated histologically with a peripheral alteration of dermal collagen accompanied by a focal regression or differentiation of blue nevus cells. The resulting distinctive target blue nevus can be clinically differentiated from a malignant melanoma.

Malignant angioendotheliomatosis proliferans treated with doxorubicin.

An 84-year-old man was examined for progressive pain, edema, and infiltrating skin lesions on his lower extremities. A skin biopsy specimen confirmed the suspected diagnosis of angioendotheliomatosis proliferans. The clinical course and histologic changes suggested the malignant form of this disease. Treatment with intravenous doxorubicin hydrochloride caused a complete clinical remission.

Topical chemotherapy of dysplastic melanocytic nevi with 5% fluorouracil.

A therapeutic response to topical fluorouracil in a patient with the large atypical nevus syndrome is presented. Six of the patients' dysplastic melanocytic nevi were treated with topical fluorouracil. Four common acquired melanocytic nevi from normal individuals were also treated. All six dysplastic nevi responded with inflammation, ulceration, and subsequent disappearance of the lesion, while the four control melanocytic nevi remained unchanged. Although we do not presently advocate the therapeutic use of fluorouracil for large atypical nevi until its safety and efficacy have been established, the response reported herein may herald an important advance in the therapy of these troublesome lesions that are known to be histogenetic precursors of malignant melanoma.

Lack of association between intraocular melanoma and cutaneous dysplastic nevi.

The occurrence of uveal and cutaneous malignant melanoma and the dysplastic nevus syndrome in the same individual suggests an etiologic relationship among these diseases. Thus, the dysplastic nevus syndrome could be viewed as marking an increased risk of both cutaneous and ocular melanoma. We postulated that if such a relationship exists, patients with both forms of melanoma should have a high prevalence of dysplastic nevi. We examined 44 patients (31 women and 13 men ranging in age from 20 to 80 years) with uveal melanoma for evidence of cutaneous melanoma and dysplastic nevi. We also examined photographs of 46 patients (24 men and 22 women ranging in age from 19 to 67 years) with nonfamilial cutaneous melanoma to determine the prevalence of dysplastic nevi. We found a 4.5% prevalence of dysplastic nevi in patients with uveal melanoma, significantly lower than the 41% prevalence in patients with cutaneous melanoma (two of 44 patients vs 19 of 46 patients). This study indicates that uveal and cutaneous melanoma are not etiologically linked through dysplastic nevi and suggests that patients with uveal melanoma are no more likely to have cutaneous dysplastic nevi than the general population.

Local antimicrobial therapy of oral mucositis in paediatric patients undergoing bone marrow transplantation.

The present investigation has examined the clinical benefits of tobramycin, polymyxin E and amphotericin therapy in the management of oral mucositis in children undergoing chemotherapy prior to bone marrow transplantation. Tobramycin, polymyxin E, and amphotericin reduced the degree of oral mucositis more than conventional therapy of diphenhydramine, Maalox, and local analgesic. While there was a statistically significant fall in the severity of the mucositis with tobramycin, polymyxin E and amphotericin, this was unlikely to be of practical benefit.

Ulcerated necrobiosis lipoidica diabeticorum in a patient with a history of generalized granuloma annulare.

Granuloma annulare and necrobiosis lipoidica diabeticorum have rarely been reported in the same patient. We describe the unusual case of a woman with diabetes and a history of generalized granuloma annulare who noted leg ulcers that clinically represented ulcerated necrobiosis lipoidica diabeticorum and had histologic features of necrobiosis lipoidica diabeticorum and granuloma annulare. Her condition responded to treatment with antiplatelet agents.

Scleromyxedema: successful treatment of cutaneous and neurologic symptoms.

Scleromyxedema is a rare systemic disorder characterized by cutaneous sclerosis and papulosis, accompanied by deposition of mucin in the skin and other organs. We describe a case of scleromyxedema in a 62-year-old man. The cutaneous symptoms of the disorder were preceded by episodes of acute central nervous system dysfunction that included mental confusion, hemiparesis, tremor, and migraine. As the cutaneous symptoms progressed, the patient experienced persistent confusion and difficulty concentrating. Therapy with melphalan and plasmapheresis led to complete resolution of the cutaneous symptoms as well as near-resolution of the neurologic symptoms. This is the first report to describe the successful treatment of the cutaneous symptoms of scleromyxedema accompanied by reversal of chronic neurologic dysfunction.