Karin Soares Gonçalves Cunha

Neurofibromatosis type I with periodontal manifestation. A case report and literature review

The term neurofibromatosis (NF) is used for a group of genetic disorders that primarily affect the cell growth of neural tissues. Neurofibromatosis type 1 (NF1), also known as von Recklinghausens disease, is the most common type of NF and accounts for about 90% of all cases. It is one of the most frequent human genetic diseases, with a prevalence of one case in 3,000 births. The expressivity of NF1 is extremely variable, with manifestations ranging from mild lesions to several complications and functional impairment. Oral manifestations can be found in almost 72% of NF1 patients. A case of a NF1 patient with a gingival neurofibroma in the attached gingiva of the lingual aspect of the lower central incisors is presented. The lesion was nodular, with sessile base, non-ulcerated, non-painful, with normal colour and measured 1 cm in diameter. An excisional biopsy of the oral lesion was performed. Histopathological and immunohistochemical analysis confirmed the clinical hypothesis of neurofibroma. Because NF1 is one of the most common genetic diseases and oral manifestations are very common, dentists should be aware of the characteristics of this disease.

Identification of growth hormone receptor in localised neurofibromas of patients with neurofibromatosis type 1

Background: The hallmark of neurofibromatosis type 1 (NF1) is the development of multiple neurofibromas. Solitary neurofibroma may occur in an individual who does not have NF1, but multiple neurofibromas tend to develop only in those with NF1. It has been suggested that hormones may influence the neurofibromas of patients with NF1. The evidence that hormones may influence the growth of neurofibromas comes mainly from the observation that localised neurofibromas of patients with NF1 commonly grow during puberty and pregnancy. Because growth hormone (GH) concentrations increase during puberty, it is possible that GH influences the growth of these tumours. Aims: To investigate the presence of GH receptors (GHRs) in neurofibromas. Methods: By means of immunohistochemistry, the presence of GHRs was investigated in two groups of patients: 16 patients without NF1 with solitary neurofibromas (group A) and 10 patients with NF1 with localised neurofibromas (group B). Results: Six of the 16 patients in group A had neurofibromas that were immunopositive for GHR, whereas nine of the 10 patients in group B were immunopositive. Conclusions: Most patients with NF1 have localised neurofibromas that express GHR. This suggests that GH may play some role in the development of localised neurofibromas in patients with NF1.

Identification of growth hormone receptor in plexiform neurofibromas of patients with neurofibromatosis type 1

OBJECTIVE The aim of this study was to investigate the presence of growth hormone receptor in plexiform neurofibromas of neurofibromatosis type 1 patients. INTRODUCTION The development of multiple neurofibromas is one of the major features of neurofibromatosis type 1. Since neurofibromas commonly grow during periods of hormonal change, especially during puberty and pregnancy, it has been suggested that hormones may influence neurofibromatosis type 1 neurofibromas. A recent study showed that the majority of localized neurofibromas from neurofibromatosis type 1 patients have growth hormone receptor. METHODS Growth hormone receptor expression was investigated in 5 plexiform neurofibromas using immunohistochemistry. RESULTS Four of the 5 plexiform neurofibromas were immunopositive for growth hormone receptor. CONCLUSION This study suggests that growth hormone may influence the development of plexiform neurofibromas in patients with neurofibromatosis type 1.

Neurofibromatoses: part 1 ? diagnosis and differential diagnosis

Neurofibromatoses (NF) are a group of genetic multiple tumor growing predisposition diseases: neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2) and schwannomatosis (SCH), which have in common the neural origin of tumors and cutaneous signs. They affect nearly 80 thousand of Brazilians. In recent years, the increased scientific knowledge on NF has allowed better clinical management and reduced complication morbidity, resulting in higher quality of life for NF patients. In most cases, neurology, psychiatry, dermatology, clinical geneticists, oncology and internal medicine specialists are able to make the differential diagnosis between NF and other diseases and to identify major NF complications. Nevertheless, due to its great variability in phenotype expression, progressive course, multiple organs involvement and unpredictable natural evolution, NF often requires the support of neurofibromatoses specialists for proper treatment and genetic counseling. This Part 1 offers step-by-step guidelines for NF differential diagnosis. Part 2 will present the NF clinical management.

Progesterone and Estrogen Receptors in Neurofibromas of Patients with NF1

Neurofibromatosis type 1 (NF1) or von Recklinghausen disease is a genetic disorder affecting the growth of cells in nervous system. One of the most remarkable characteristics of this disease is the development of benign tumors of the nervous system (neurofibromas). The purpose of this study was to test tissue samples taken from neurofibromas and plexiform neurofibromas of NF1 patients for the presence of estrogen and progesterone receptors. We used previously collected samples from patients registered in the database of the Centro Nacional de Neurofibromatose (CNNF-Brazil). Samples from twenty-five patients in the database presenting plexiform neurofibromas (N1 group) and 25 samples from the same database from patients presenting neurofibromas (N2 group) were tested. We observed positive staining for progesterone receptors in 13 of the neurofibroma samples and 19 of the plexiform neurofibroma samples. Among the neurofibroma samples, we observed one sample with positive estrogen receptor staining, but none of the plexiform neurofibroma samples showed positive staining. We suggest further studies to investigate in greater depth possible hormonal influences on the development and growth of neurofibromas and plexiform neurofibromas in NF1.

Concordance between cytopathology and incisional biopsy in the diagnosis of oral squamous cell carcinoma

Oral cytopathology is a simple, non-invasive technique that could be used for early detection of oral premalignant and malignant lesions, but the effectiveness of this diagnostic approach remains controversial. The aim of this study was to evaluate the sensitivity, specificity, positive and negative predictive values, and accuracy of cytopathology for diagnosing oral squamous cell carcinoma (OSCC) and the diagnostic concordance between cytopathological and histopathological diagnoses. The study enrolled 172 patients at outpatient clinics who presented with oral lesions suspicious of malignancy. All patients underwent oral cytological scrapes followed by an incisional biopsy. Of 148 cases that were histopathologically diagnosed with OSCC, the cytopathological method diagnosed 123 positive cases and resulted in a suspicion of OSCC in 16 patients. Based on these data, the sensitivity was 83.1%, the specificity was 100.0%, the positive predictive value was 100.0%, the negative predictive value was 49.0%, and the accuracy was 85.5%. The diagnostic concordance between histopathological and cytopathological examinations was 83.1% for OSCC and 85.7% for non-neoplastic lesions. The results indicate that cytopathological diagnosis had good concordance with histopathological diagnosis and showed high sensitivity, specificity, positive predictive value, and accuracy. We conclude that the sensitivity of oral cytopathology is sufficient to justify its use as a diagnostic screening test and to confirm the malignant nature of epithelial cells, mainly for the classification of OSCC. Therefore, cytopathology may be a reliable method for referring patients who require diagnosis of suspected oral cancer for starting treatment.

Intraoral nerve sheath myxoma: Case report and systematic review of the literature

Oral nerve sheath myxoma (NSM) is an uncommon benign neoplasm with Schwann‐cell origin, which is frequently mistaken for neurothekeoma. We report a case of NSM on the buccal mucosa in a 42‐year‐old woman. This case is compared with previously reported cases and a systematic review is performed.

Breast cancer and neurofibromatosis type 1: a diagnostic challenge in patients with a high number of neurofibromas

BackgroundNeurofibromatosis 1 is one of the most common genetic diseases in humans, presenting with multiple neurofibromas and an increased risk of various benign and malignant tumors, including breast cancer.Case presentationIn this paper we report a case of a woman with neurofibromatosis 1 and the challenge associated with detecting an advanced breast cancer because of numerous skin neurofibromas, which were responsible for a substantial delay in cancer diagnosis. Literature concerning the association of neurofibromatosis 1 and breast cancer is reviewed and discussed.ConclusionsBest practice guidelines for breast cancer detection are not sufficient for the screening of neurofibromatosis 1 carriers. A more intensive clinical and imaging approach should be used if the same early detection rate as in non-neurofibromatosis 1 women is to be achieved.

Hybridization Capture-Based Next-Generation Sequencing to Evaluate Coding Sequence and Deep Intronic Mutations in the NF1 Gene

Neurofibromatosis 1 (NF1) is one of the most common genetic disorders and is caused by mutations in the NF1 gene. NF1 gene mutational analysis presents a considerable challenge because of its large size, existence of highly homologous pseudogenes located throughout the human genome, absence of mutational hotspots, and diversity of mutations types, including deep intronic splicing mutations. We aimed to evaluate the use of hybridization capture-based next-generation sequencing to screen coding and noncoding NF1 regions. Hybridization capture-based next-generation sequencing, with genomic DNA as starting material, was used to sequence the whole NF1 gene (exons and introns) from 11 unrelated individuals and 1 relative, who all had NF1. All of them met the NF1 clinical diagnostic criteria. We showed a mutation detection rate of 91% (10 out of 11). We identified eight recurrent and two novel mutations, which were all confirmed by Sanger methodology. In the Sanger sequencing confirmation, we also included another three relatives with NF1. Splicing alterations accounted for 50% of the mutations. One of them was caused by a deep intronic mutation (c.1260 + 1604A > G). Frameshift truncation and missense mutations corresponded to 30% and 20% of the pathogenic variants, respectively. In conclusion, we show the use of a simple and fast approach to screen, at once, the entire NF1 gene (exons and introns) for different types of pathogenic variations, including the deep intronic splicing mutations.

High prevalence of hyposalivation in individuals with neurofibromatosis 1: a case-control study.

BackgroundNeurofibromatosis type 1 (NF1) is one of the most common genetic diseases in humans and has widely variable expressivity. Oral manifestations are common, but there are no studies that investigated functional alterations in salivary glands in NF1. Our aim was to evaluate the salivary flow rate in NF1 individuals, comparing to a control group, and to investigate the possible causes and some consequences of salivary gland alteration.MethodsThis is a case–control study that evaluated the salivary flow rate of NF1 individuals (n = 49) and compared to an age and sex-matched control group. We have also investigated the possible causes and consequences of hyposalivation in NF1 individuals through anamnesis, a specific questionnaire, physical examination, tongue coating evaluation and cytopathological exam to assess the prevalence of oral candidiasis.ResultsHyposalivation at rest was present in 59% (29/49) of NF1 individuals in contrast to 22% (11/49) in the control group, being statistically significant (P <0.0001; Wilcoxon rank-sum test). The analysis of the adjusted residual showed that the prevalence of hyposalivation in NF1 individuals (46.9%) was 4-fold higher than in controls (10.2%). None of the possible causes of hyposalivation (medications, low liquid intake, caffeinated or stimulant drink use, mouth breathers, alcohol, smoke and plexiform neurofibroma close to or involving major salivary glands areas) had important impact on the salivary flow rate in NF1 individuals.ConclusionsHyposalivation may be a consequence of NF1, as occurs in other genetic diseases. More studies are necessary to understand if there is and what is the relationship between NF1 and hyposalivation.