Skin Neurofibromas Research Articles

Whole-exome sequencing revealed a likely pathogenic variant in NF1 causing neurofibromatosis type I and Arrhythmogenic Cardiomyopathy

BackgroundNeurofibromatosis type I (NF1) is a genetic disorder characterized by the tumor’s development in nerve tissue. Complications of NF1 can include pigmented lesions, skin neurofibromas, and heart problems such as cardiomyopathy. In this study, we performed whole-exome sequencing (WES) on an Iranian patient with NF1 to identify the genetic cause of the disease.MethodsFollowing clinical assessment, WES was used to identify genetic variants in a family with a son suffering from NF1. No symptomatic manifestations were observed in other family members. In the studied family, in silico and segregation analysis were applied to survey candidate variants.ResultsClinical manifestations were consistent with arrhythmogenic cardiomyopathy (ACM). WES detected a likely pathogenic heterozygous missense variant, c.3277G > A:p.Val1093Met, in the NF1 gene, confirmed by PCR and Sanger sequencing. The patient’s parents and brother had a normal sequence at this locus.ConclusionsAlthough there is no cure for NF1, genetic tests, such as WES, can detect at-risk asymptomatic family members. Furthermore, cardiac evaluation could also help these patients before heart disease development.

A rare case of pulmonary endobronchial spindle cell carcinoma with liver metastasis along with concurrent cutaneous neurofibroma

Spindle cell carcinoma is one of the histological variants of pulmonary sarcomatoid carcinoma. It is a rare, poorly differentiated, highly malignant, and rapidly growing non-small cell carcinoma of the lung. Information about pulmonary spindle carcinoma incidence, clinical features, and immunohistochemical markers are not well known compared to other variants of sarcomatoid carcinoma. Most sarcomatoid carcinoma features mimic non-small cell carcinoma, so it is easily misdiagnosed. Cutaneous neurofibroma with primary lung spindle cell carcinoma has not been reported in any previous literature. Here we report a rare endobronchial sarcoma with liver metastasis and concurrent skin neurofibroma.

A rare case of superficial temporal artery pseudoaneurysm in a patient with neurofibromatosis type 1

Pseudoaneurysm of the superficial temporal artery (STA) is a rare clinical entity that has been linked with traumatic causes. Neurofibromatosis type I (NF-1) is an autosomal dominant disorder with known but uncommon vascular abnormalities that comprise stenoses, occlusions, aneurysms, fistulas and arteriovenous malformations. We presented a 46-year-old man with clinical features of NF-1 (e.g., café au lait spots, skin neurofibromas) coming to hospital because of a progressively enlarging and painful right temporal mass of about ping-pong ball size. He remembered having slapping a mosquito with his hands at the same area four days ago. CT angiography suggested development of a pseudoaneurysm and emergency surgery was performed to dissect the mass. Histopathological examination revealed disruption of arterial wall structures, including interruption of elastic lamina, expansion of smooth muscle layer, focal thrombosis and positive CD31 and smooth muscle actin staining, consistent with diagnosis of pseudoaneurysm. This is the first report of a STA pseudoaneurysm in patient with NF-1. Deficiency of neurofibromin may impact the integrity of vascular wall structures and predispose it to the development of pseudoaneurysm in the event of minor trauma like current case. Reference 1. Saliba E, Goldberg LJ. Superficial temporal artery pseudoaneurysm: report of two cases and review. J Cutan Pathol 2022; 49: 482–486.

Head circumference and anthropometric changes and their relation to plexiform and skin neurofibromas in sporadic and familial neurofibromatosis 1 Brazilian adults: a cross-sectional study

BackgroundNeurofibromatosis 1 (NF1) is a common autosomal dominant syndrome with complete penetrance and highly variable expressivity. The cutaneous neurofibroma (Cnf) and plexiform neurofibroma (Pnf), café-au-lait spots, and freckle-like lesions are common in NF1, but many other manifestations can occur. We aimed to evaluate head circumference, height, weight, body mass index (BMI), head circumference-to-height ratio (HCHR) and waist–hip ratio (WHR) in adult NF1 Brazilian individuals versus a paired control group and investigate their correlation with the presence of clinically visible Pnfs, and number of “skin neurofibromas” (Snf), which include both cutaneous and subcutaneous neurofibromas.MethodsA case–control study was conducted with 168 individuals, 84 with NF1 and 84 without NF1, paired by sex and age. Head circumference and anthropometric measurements, Snf quantification, evaluation of clinically visible Pnf and familial inheritance were accessed.ResultsPrevalence of macrocephaly was significantly higher in NF1 women. Height and weight were significantly lower in both males and females with NF1. HCHR was higher in the NF1 group than in the control group for both sexes. BMI was significantly lower in men with NF1. Waist and hip circumferences were significantly reduced in NF compared with the controls, but the mean WHR was significantly lower only in NF1 women. No correlation was found between the Snf and head circumference and anthropometric measurements, sex or family history. The presence and larger size of clinically visible plexiform neurofibromas were associated with normal stature (p = 0.037 and p = 0.003, respectively).ConclusionsNF1 individuals have increased prevalence of macrocephaly, short stature, low BMI, and reduced abdominal fat. There is no relation between head circumference and anthropometric data with family history, or neurofibromas.

A case of appendiceal ganglioneuroma in neurofibromatosis type 1

BackgroundNeurofibromatosis type 1 is an autosomal dominant inherited disease associated with multiple skin neurofibromas or other neurogenic tumors, such as nodular plexiform neurinoma or cerebrospinal tumor. Gastrointestinal stromal tumors are often complicated in patients with neurofibromatosis type 1, although involvement of the appendix is rare, and there have been few reports of appendiceal ganglioneuroma.Case presentationThe patient was a 29-year-old man diagnosed with neurofibromatosis type 1 based on physical findings and his family history. During the follow-up of neurofibromatosis, computed tomography was performed to detect neurological tumors, such as neurofibromas in the brain, spinal cord, and gastrointestinal tract. Computed tomography showed a markedly thickened appendix wall, and an appendiceal tumor was suspected. Laparoscopic appendectomy was performed, and a 50 × 35 mm appendiceal submucosal tumor was resected with a negative resection margin. At histopathological examination, the tumor was diagnosed as ganglioneuroma; it showed short spindle-shaped cells and ganglion cells diffusely infiltrated into the proper muscle layer and fibrous tissue that grew around nerve cells. The patient was discharged on the 5th postoperative day without postoperative complications and was doing well at 13 months following the operation.ConclusionsGastrointestinal stromal tumor and neurofibroma are the most common gastrointestinal tumors associated with neurofibromatosis type 1, but ganglioneuroma of the appendix is rare. Appendiceal neurogenic tumors should be considered in patients with neurofibromatosis type 1, and surgical resection is necessary because of the risk of malignancy.

Targeted Deep Sequencing Reveals Unrecognized KIT Mutation Coexistent with NF1 Deficiency in GISTs.

PurposeNF1-deficient GISTs account for about 1% of gastrointestinal stromal tumors (GISTs) and are usually considered as a subtype of KIT/PDGFRA wild-type GISTs that have no detectable KIT and PDGFRA mutations. Some KIT/PDGFRA wild-type GISTs actually have cryptic KIT mutations (mKIT). So we investigate whether concurrent mKIT existed in NF1-associated GISTs.Patients and MethodsThree independent cohorts were retrospectively analyzed. KIT/PDGFRA wild-type GISTs in Xiangya Hospital between May 2017 and Oct 2019 were investigated by next-generation sequencing (NGS) approach targeted 1021 cancer-related genes regions. GISTs cases in Gene+ dataset from May 2017 to May 2020 were collected from the platform of this company. The genotypes of GISTs in MSKCC cohort were downloaded from cBioPortal.ResultsA total of 290 cases including 23 KIT/PDGFRA wild-type GISTs in Xiangya Hospital, 136 GISTs in Gene+ database, and 131 GISTs in MSKCC were enrolled. Twenty-six cases have NF1 mutations (mNF1), and 48% (12/26) of NF1-mutated GISTs have concurrent mKIT. Compared with MSKCC (2/10, 20%), a higher ratio of mKIT in NF1-associated GISTs was detected in Xiangya Hospital (3/5, 60%) and Gene+ (7/11, 64%) (p<0.05). No mutation hotspot existed in mNF1. Most of mKIT centered within exon 11 (7/12, 58%) and others including exon 17 (3/12, 25%), exon 9(1/12, 8%), exon 13 (1/12, 8%) and exon 21 (1/12, 8%). No differences in age, gender, and location were detected between NF1-related GISTs with mKIT and those without mKIT. Three GIST cases of type I neurofibromatosis, skin neurofibromas and micro-GISTs (≤1 cm) were devoid of mKIT, but all the mini-GISTs (1~2 cm) and clinic GIST lesions (>2 cm) in two cases harbored mKIT.ConclusionmKIT was not unusual in NF1-associated GISTs, especially in Chinese populations. The gain-of-function mKIT possibly facilitated the progression of NF1-deficient lesions to clinic GISTs, however, the underlying mechanism warrants further studies.

Mosaic Neurofibromatosis Type 1 With Multiple Cutaneous Diffuse and Plexiform Neurofibromas of the Lower Leg

Neurofibromatosis type 1 (NF1) is an autosomal dominant hereditary disease with complete penetrance and a very variable phenotype. Recent research has shown that postzygotic NF1 gene mutations occur to a far greater extent than previously thought. The phenotype of affected individuals reflects the time of somatic mutation and the phenotype is correspondingly diverse. This report describes histological and genetic findings in a case of mosaic NF1, the clinical control of which documents almost stationary skin findings over a period of 9 years. The 55-year-old female first presented for advice on a strip of nodular skin tumours of the calf skin. She had no hallmarks of NF1. It was only 9 years later that she had the skin tumours removed, all of which were partially diffuse and partially plexiform neurofibroma. The genetic examination showed an atypical large deletion of the NF1 gene in the skin tumours, but not in overlying skin or blood. Segmental NF1 is a distinct type of mosaic/somatic NF1 mutation. The phenotype of diffuse and plexiform skin neurofibromas can resemble cutaneous neurofibroma. Surgical therapy for segmental neurofibromatosis does not differ from the concepts for treating nerve sheath tumours in NF1 patients with a germline NF1 mutation.

Satisfaction from surgical treatment and its’ influence on comfort of feeling in patients with Recklinghausen disease

&lt;b&gt;Background:&lt;/b&gt; Neurofibromatosis type 1 (NF-1) is one of the most common autosomal dominant disorders. Multiple benign dermal neurofibromas, café au lait spots, axillary and inguinal freckling are the hallmarks of NF-1. &lt;br&gt;&lt;b&gt;Aim:&lt;/b&gt; The aim of this paper is to verify if surgical treatment performed in patients with NF-1 is satisfactory to them and to describe demographic factors characteristic for patients with Recklinghausen disease. &lt;br&gt;&lt;b&gt;Methods: &lt;/b&gt;A special questionnaire was prepared for the study, which contained 45 questions. Seventeen patients with neurofibromatosis type 1 agreed to fill in the questionnaire aged from 22 to 61 years. &lt;br&gt;&lt;b&gt;Results:&lt;/b&gt; Surgical treatment in patients was started between 6 and 45 years of age. All patients declared their will to continue surgical treatment. After treatment patients felt more comfortable, more self-confident and sociable. The first symptoms of neurofibromatosis were seen at about 13 years of life in most patients. All women who gave birth noticed progression of the disease during pregnancy. &lt;br&gt;&lt;b&gt;Conclusions: &lt;/b&gt;Performed surgical treatment raises life comfort and increases self-confidence in patients with neurofibromatosis type 1. Due to visible skin changes in neurofibromas it is worth referring patients to Plastic Surgery Departments. Doctors dealing with patients with NF-1 should inform them about the potential heredity of the disease and that puberty and pregnancy intensify the process of skin neurofibroma development.

Giant dumbbell C2C3 neurofibroma invading prebulbar cistern: Case report and literature review

Background:Neurofibromatosis 1 (NF1) has a broad spectrum of clinical manifestations, most typically involving café-au-lait spots and skin neurofibromas. Only 2% of patients with NF1 have symptomatic spinal tumors.Case Description:A patient with a previous diagnosis of NF1 presented with cervicalgia, dysphagia/mild dysphonia, gait alteration, and progressive hypoesthesia involving all four limbs. The magnetic resonance documented a giant dumbbell neurofibroma arising between the C2 and C3 levels which extended toward the foramen magnum, causing medullary and bulbar compression. The major challenge of surgical management was the enormous size and location this C2–C3 (5 cm × 4 cm × 5.1 cm) lesion.Conclusions:Compression of the foramen magnum attributed to a dumbbell giant spinal neurofibroma at the C2C3 level resulting in prebulbar cisterns should be among the differential diagnostic considerations for patients presenting with tetraparesis and underlying NF1.

Trabecular Bone Score (TBS) and Bone Metabolism in Patients Affected with Type 1 Neurofibromatosis (NF1)

In patients with neurofibromatosis type 1 (NF1), decreased bone mineral density (BMD) and low levels of 25-hydroxy vitamin D3 (25OHD) have been reported. Recently, the trabecular bone score (TBS) measurement has been proposed as index of bone microarchitecture and fracture risk. In 74 NF1 patients (48 females, 26 males, age 41 ± 12), we measured TBS and investigated clinical stage, lifestyle, vitamin D, serum bone turnover markers, vertebral and femoral BMD. A homogenous cohort of 61 healthy subjects was used as control group. TBS was lower in NF1 patients (1.266 ± 0.113 vs. 1.346 ± 0.105) without differences between sexes. No correlations with 25OHD, low exercise, low calcium intake, reduced sun exposure, and number of skin neurofibromas were observed. As expected, hypovitaminosis D was common (98.6%), as well as BMD reduction in hip and spine sites: In NF1 patients, bone texture evaluated by TBS was low in both sexes without any correlation with clinical or metabolic parameters, suggesting a direct role of the fibromin mutation.

Rectal carcinoma and multiple gastrointestinal stromal tumors (GIST) of the small intestine in a patient with neurofibromatosis type 1: a case report

BackgroundNeurofibromatosis type 1 (NF1) is an autosomally dominant inherited disorder characterized by multiple pigmented skin spots (café-au-lait spots) and neurofibroma. NF1 is associated with a wide variety of benign or malignant tumors. We report a NF1 patient who received surgical treatment for rectal carcinoma and multifocal small intestinal gastrointestinal stromal tumors (GISTs).Case presentationA 70-year-old female patient with NF1 was referred to our hospital after a positive fecal occult blood test. Locally advanced rectal carcinoma was detected in the upper rectum using colonoscopy. A submucosal tumor 20 mm in diameter was detected in the duodenal bulb during the upper gastrointestinal endoscopy. The biopsy specimen from the duodenum was GIST with positive immunostaining of KIT and CD34 microscopically. Laparoscopic low anterior resection for rectal carcinoma and local excision of the duodenal GIST were performed successfully. During the operation, five white small nodules were found on the serosa of the jejunum. One nodule was excised for histological examination. The resected rectal tumor was a well-differentiated adenocarcinoma with multiple lymph nodes metastases according to the histology. The duodenal tumor was found to be low-risk GIST. Moreover, the nodule from the jejunum was very low risk GIST. An excised skin wart was neurofibroma according to the histology.ConclusionsGIST or carcinomas have been reported to occasionally occur in the digestive tract of the patients with NF1. We present a rare case of a NF1 patient with GISTs and colorectal carcinoma.

The case of malignant peripheral nerve sheath tumor of the cheek

Abstract Introduction Malignant peripheral nerve sheath tumor (MPNST), formerly known as neurogenic sarcoma or malignant neuroblastoma, rarely occurs in the head and neck area and can mimic benign proliferative lesions. The tumor develops from the peripheral nerve cells and can occur on the surface of the skin neurofibromas in von Recklinghausen disease or de Novo. Aim The aim of this paper was to present the case of the 86-year-old female patient with MPNST in the soft tissues of the right cheek. Case study 86-year-old female patient was admitted due to the right cheek tumor growing for about a month of the size 5 × 5 cm that caused significant asymmetry of the face. Results and discussion The patient was diagnosed on the basis of the history, craniofacial visualization, histopathological examination of the tumor sample and referred for surgical treatment and possible adjuvant radiotherapy. Extensive resection of the tumor was followed by a reconstruction of buccal defect with regional lobes. The postoperative course was uneventful. Adjuvant radiotherapy was not performed due to a number of aggravating systemic illness and old age of the patient. She is the subject of constant surgical–oncological follow-up medical care. No local recurrence or distant metastases were observed during follow-up. Conclusions MPNST rarely occurs in the head and neck region. This kind of sarcoma can cause problems in the process of diagnosis and therapy. Resection is the primary treatment in case of MPNST. Due to high incidence of local recurrence and distant metastases, the patients treated for MPNST require continuous outpatient follow-up after the treatment.

Neurofibromatosis Type 1 (NF1): Case Report and Review of literature

Neurofibromatosis type 1 (NF1) or Von Recklinghausen's disease is a rare genetic disorder characterized by the development of multiple noncancerous (benign) tumors of nerves and skin (neurofibromas) and areas of abnormally decreased or increased coloration of the skin. We present a case of 11-year-old boy with NF-1. The disease started in childhood with the appearance of multiple hyper pigmented skin macules. The boy presents excruciating lower back pain and lumbar scoliosis. The diagnosis NF-1 was made according to the presence of two or more diagnostic criteria of the National Institute of Health Consensus Development Conference. NF1 is a multisystem disorder requiring management by multiple disciplines, often coordinated through a primary care physician or a geneticist and dermatologist.

Bimodal Treatment of a Huge Hypervascular Neurofibroma on the Groin.

Bimodal Treatment of a Huge Hypervascular Neurofibroma on the Groin.

Molecular Characterization of NF1 and Neurofibromatosis Type 1 Genotype-Phenotype Correlations in a Chinese Population

Neurofibromatosis type 1 (NF1) is an autosomal dominant hereditary disease that is primarily characterized by multiple café au-lait spots (CALs) and skin neurofibromas, which are attributed to defects in the tumor suppressor NF1. Because of the age-dependent presentation of NF1, it is often difficult to make an early clinical diagnosis. Moreover, identifying genetic alterations in NF1 patients represents a complex challenge. Currently, there are no effective detective methods, and no comprehensive NF1 mutation data are available for mainland China. We screened 109 Chinese patients from 100 families with NF1-like phenotypes (e.g., CALs, neurofibromas, etc.) using Sanger sequencing, multiplex ligation-dependent probe amplification and cDNA sequencing. NF1 mutations were identified in 97 individuals, among which 34 intragenic mutations have not previously been reported. Our exhaustive mutational analysis detected mutations in 89% (89/100) of the NF1-like probands and 93% (70/75) of subjects fulfilling the National Institutes of Health (NIH) criteria. Our findings indicate that individuals who exclusively present with multiple CALs exhibit a high possibility (76%) of having NF1 and show a significantly lower mutation rate (p = 0.042) compared with subjects who fulfill the NIH criteria, providing clinicians with the information that subjects only with multiple CALs harbor a considerable possibility (24%) of being attributed to other comparable diseases.

Association between Neurofibromatosis Type I and Central Giant Cell Lesion: Case Report

Neurofibromatosis type I (NF1), or Von Recklinghausen disease, is characterized by cafe-au-lait spots and neurofibromas of the skin, bone defects, iris hamartomas (Lisch nodules) and tumors in the central nervous system. The central giant cell lesion (CGCL) is a non-neoplastic entity, intra-osseous, radiolucent, uni or multilocular, well-defined edges, and it can change the position of the teeth, but rarely causes resorption of them. The association between CGCL and NF1 has been described in the literature. Patient C.R.P, 42 years old, female, who has NF1 attended the service presenting asymptomatic swelling in the anterior maxilla and discrete painless intraoral bulge in the anterior mandible with approximate evolution of one year. Incisional biopsy was performed, and the result was CGCL. The patient didn’t have hyperparathyroidism. Treatment consisted of curettage of the lesion and bone regularization performed three years ago, without signs of recurrence. The occurrence of CGCL in multiple locations is uncommon and it is usually associated with hyperparathyroidism, cherubism, and can be also found in syndromes such as: Ramon Jaffe Campanacci, Noonan-like and NF1. The patient presented four features of NF1 (multiple skin neurofibromas, cafeau- lait spots, Lisch nodules and freckles in the armpits) and CGCL in two locations, which corroborate the existence of this association in the literature. The apparent relationship between NF1 and an increased incidence of CGCL s in the jaws could represent a coincidental association, genetic relationship, or susceptibility to developing CGCL in abnormal bone quality. In cases of multiple CGCL, the presence of hyperparathyroidism, cherubism and syndromes such as NF1, should be considered. One realizes the importance of investigation of systemic factors and clinical signs for performing differential diagnosis. The differentiation of these lesions in aggressive and nonaggressive should be done to improve individual treatment plan. Surgical curettage is acceptable for the treatment of non-aggressive CGCL.

Validity and interexaminer reliability of a new method to quantify skin neurofibromas of neurofibromatosis 1 using paper frames.

BackgroundSkin neurofibromas represent one of the main clinical manifestations of neurofibromatosis 1, and their number varies greatly between individuals. Quantifying their number is an important step in the methodology of many clinical studies, but counting neurofibromas one by one in individuals with thousands of tumors is arduous, time-consuming, and subject to intra and interexaminer variability. We aimed to evaluate the efficacy of a new methodology for skin neurofibromas quantification using paper frames.MethodsThe sample comprised 92 individuals with NF1. Paper frames, with a central square measuring 100 cm2, were placed on the back, abdomen and thigh. Images were taken, transferred to a computer and two independent examiners counted the neurofibromas. The average number of neurofibromas/100 cm2 of skin was obtained from the mean of the three values. The differences in the quantity of neurofibromas counted by two examiners were evaluated with Intraclass correlation coefficient (ICC), paired t-test, Bland-Altman and survival-agreement plots. To evaluate the predictive value of the method in obtaining the total number of neurofibromas, 49 participants also had their tumors counted one by one. Reproducibility was assessed with Pearson’s correlation coefficients and simple linear regression model.ResultsThere was excellent agreement between examiners (ICC range 0.992-0.997) and the total number of skin neurofibromas could be predicted by the adhesive frames technique using a specific formula (P < 0.0001).ConclusionsIn this article we describe a reliable, easy and rapid technique using paper frames to quantify skin neurofibromas that accurately predicts the total number of these tumors in patients with NF1. This method may be a useful tool in clinical practice and clinical research to help achieve an accurate quantitative phenotype of NF1.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-014-0202-9) contains supplementary material, which is available to authorized users.

Melanocytic Differentiation Is Present in a Significant Proportion of Nonpigmented Diffuse Neurofibromas

Whereas the pigmented (melanotic) variant of diffuse neurofibroma (DNF) with positivity for melanocytic markers is well recognized, expression of melanocytic markers in nonpigmented DNF has not been systematically studied. We analyzed 28 unselected consecutive DNFs for expression of melanocytic markers, including melan A, microphthalmia transcription factor (MITF), and HMB-45 antigen. For comparison, we also analyzed 40 localized skin neurofibromas and 7 intraneural neurofibromas. One case of nonpigmented DNF was analyzed by electron microscopy. Of the 28 DNFs studied by immunohistochemistry, 3 were pigmented and 25 nonpigmented. The 3 pigmented DNFs and 9 of 25 (36%) nonpigmented DNFs expressed melan A, MITF, and HMB-45 antigen. These markers were expressed either focally or more diffusely, typically in a minority of the lesional cells, and usually both in the dermal and subcutaneous portion of the DNF. Melan A was expressed in the largest number of the lesional cells (up to 50%), whereas only a small fraction of the melan A-positive cells (from 5% to 10% in most cases) also expressed HMB-45 antigen. None of the 47 non-DNFs expressed these markers. Ultrastructurally, melanosomes were present in some cells in nonpigmented DNF that expressed the melanocytic markers. Twenty-three of 28 (82%) DNFs, including 10 of 12 (83%) DNFs with melanocytic differentiation, were associated with neurofibromatosis type 1. Expression of melanocytic markers, including melan A, HMB-45 antigen, and MITF in DNF is a potential pitfall in differential diagnosis with melanocytic lesions that may clinically or histopathologically resemble DNF, in particular congenital melanocytic nevus with neurotization and neurofibroma-like melanoma.

Bilateral Internal Auditory Canal Melanoma

Bilateral Internal Auditory Canal Melanoma

Von Recklinghausen Hastalığı Olan Bir Olguda Diffüz Çekal Ganglionöromatozis

A 41-year-old female with 'cafe au lait' and multiple skin neurofibromas was admit - ted with a complaint of constipation, abdominal pain and distention. The colonoscopic investiga - tion was normal, however computed tomography revealed a mass in the cecal wall. Thereon, right hemicolectomy was performed to the patient. Histopathologic examination revealed ganglioneu - romatosis of the cecum. There was not any recurrence after three years of follow-up. An intestinal manifestation of von Recklinghausen's disease should be kept in mind in a patient who has multi - ple neurofibromas and 'cafe au lait' spots with intractable constipation and intestinal obstruction. a