Evaluation of plexiform neurofibroma in neurofibromatosis type 1 in 18 family members of 3 generations: ultrasonography and magnetic resonance imaging a diagnostic supplement

Plexiform neurofibroma in neurofibromatosis type 1, an autosomal-dominant genetic disorder, is characterized by a combination of interlacing components or a network. The prominent enlargement of a nerve with tumor nodules results in the gross pathologic appearance termed "bag of worms." Plexiform neurofibroma was found in two of seven family members with neurofibromatosis type 1 in three generations. Ultrasonography/color doppler and magnetic resonance imaging, in addition to microscopic pathology, were used as diagnostic tools, and their indications for future use in the diagnosis of plexiform neurofibroma are highlighted.     

A Case of Isolated Plexiform Neurofibroma in a Patient with Myasthenia Gravis

We report a case of an isolated plexiform neurofibroma occurring in a patient with myasthenia gravis. A 48-year-old man presented with asymptomatic skin-colored nodules on the tip of his 4th finger. Microscopically, a plexiform neurofibroma was identified located in the dermis that appeared to originate from small superficial nerves. He had a 20-year history of treated myasthenia gravis; otherwise, his personal and family histories were unremarkable. Given that myasthenia gravis is a disorder of the peripheral nerves, plexiform neurofibromas could be associated with myasthenia gravis. However, the development of an isolated plexiform neurofibroma in a case of myasthenia gravis has not yet been reported. The occurrence of a neurofibromas in a patient with myasthenia gravis suggests a link in the pathogenesis of these two diseases.     

Cutaneous Plexiform Schwannoma of the Finger Not Associated with Neurofibromatosis

Plexiform schwannoma is a rare, benign, peripheral nerve sheath tumor that occurs as an uncommon nodular variant of schwannoma. It is important to recognize this tumor because it can be misdiagnosed as plexiform neurofibroma. In contrast to the latter, however, plexiform schwannoma is not associated with neurofibromatosis (von Recklinghausen disease). We report a case of plexiform schwannoma located on the index finger of a 20-year-old male patient with no signs of neurofibromatosis.     

Hair Whorl as an Indicator of a Mediastinal Plexiform Neurofibroma

Abstract: We report a boy with neurofibromatosis type 1 (NF-1) who had nonspecific respiratoi symptoms and a mediastinal mass. In addition to multiple cafe au lait macules and subcutaneous neurofibromas, he had a hair whorl over the spine at the level of a deep mediastinal mass demonstrated by CT scan and MR examination. Thoracoscopy and biopsy of the mass revealed a plexiform neurofibroma. The clinical sign of a hair whorl may assist the clinician in early recognition of a paraspinal plexiform neurofibroma.     

Vacuolated cells in neurofibroma: an immunohistochemical study

BACKGROUND: Vacuolated cells could be encountered in neurofibroma. OBJECTIVES: Frequency and immunohistochemical feature of vacuolated cells in neurofibroma. METHODS: Sixty-two lesions of neurofibroma including five plexiform neurofibromas were re-evaluated for the search of vacuolated cells. Immunohistochemical analysis was performed for cases with vacuolated cells. RESULTS: In five cases of plexiform neurofibroma and four cases of sporadic neurofibroma with endoneurial component, presence of vacuolated cells in the endoneurial mucoid area was noted. They were immunoreactive both with S-100 protein and CD34, mostly negative for factor XIIIa and negative for epithelial membrane antigen. Vacuolated cells were found neither in the diffuse portion of plexiform neurofibroma nor in sporadic diffuse neurofibroma. CONCLUSION: Presence of vacuolated cells is a highly characteristic feature of endoneurial portion of neurofibroma. Considering immunoreactivity both with S-100 protein and CD34 in the majority of vacuolated cells, they could be regarded as to represent endoneurial precursor cells in a certain stage of differentiation to Schwann cells.     

A Case of Diffuse Neurofibroma of the Scalp

A neurofibroma is a benign tumor of the peripheral nerve sheath characterized by proliferation of Schwann cells, perineural cells, and endoneurial fibroblasts. Different types of neurofibromas can be identified, including localized, plexiform, and diffuse types. Neurofibromas can involve any site on the body skin. The diffuse variant is rare and occurs primarily in children and young adults. It involves the skin and subcutaneous tissue in a plaque-like fashion on the head and neck regions. We present a case of a 10-year-old boy who had a diffuse neurofibroma on the scalp.     

Pigmented plexiform neurofibroma: Distinction from a large congenital melanocytic nevus

The substantial clinical and histologic overlap between neurotized congenital melanocytic nevi and the subset of plexiform neurofibromas with hyperpigmentation and hypertrichosis of the overlying skin (pigmented neurofibroma) has led to considerable confusion in the literature. A dark-brown, hypertrichotic plaque covered much of the right lower aspect of the trunk of a 1-year-old girl with a diffuse and plexiform neurofibroma in the same area, numerous café-au-lait macules, and intertriginous freckling. The latter findings were diagnostic of neurofibromatosis-1, which was further supported by the presence of unidentified bright objects on magnetic resonance imaging of the brain. Histologic examination of the hyperpigmented plaque revealed melanocytic hyperplasia at the dermoepidermal junction and a proliferation of rounded, pigmented melanocytes dispersed individually and in occasional small nests in the papillary dermis and scattered within underlying neurofibromatous tissue. Immunohistochemical staining with A103 (Melan-A/MART-1) and PNL2 confirmed the melanocytic differentiation of the pigmented cells, whereas glial fibrillary acidic protein and Leu-7 were detected only within plexiform areas and slender neuroid spindle cells. This case draws attention to the pigmented neurofibroma as a distinct clinicopathologic entity resulting from proliferation of melanocytes and neurosustentacular cells in the setting of neurofibromatosis-1.     

Solitary plexiform neurofibroma

A 35-year-old man with a solitary subcutaneous cord running on the abdomen wall is reported. Histologic examination of the lesion permitted a diagnosis of plexiform neurofibroma. In this patient and in his family no other signs of von Recklinghausen's disease were found. The plexiform neurofibroma considered as pathognomonic of neurofibromatosis may occur in a solitary form.     

Primary cutaneous meningioma associated with von Recklinghausen's disease

Cutaneous meningeal tumors are rare and can pose a diagnostic problem. We present a case of a 12-year-old girl with a family history of von Recklinghausen's disease. The patient was asymptomatic until the age of 11, when she developed two lesions on the head, both diagnosed as plexiform neurofibroma. Subsequently, she presented with a subcutaneous nodule on the left posterior occipital scalp which was excised. On histology, the tumor was composed of spindle-shaped cells with diffuse and nested patterns. A whorled configuration of the cells, with occasional giant cells and psammoma bodies, was present. There was no evidence of connection between the tumor and the underlying tissues. Immunohistochemical studies were positive for epithelial membrane antigen, vimentin, and weakly for neuron-specific enolase. Cytokeratin, S-100 protein, and muscle markers were negative. Based on these features, the diagnosis of cutaneous meningioma was made. An MRI examination failed to detect any communication between the tumor site and the meninges; however, asymptomatic bilateral acoustic neuromas were identified. This case, besides being of interest as a primary cutaneous meningioma, also documents a unique combination of findings, i.e., plexiform neurofibroma, meningioma, and cerebellopontine acoustic neuromas, which should alert the clinician to a forme fruste presentation of von Recklinghausen's disease.
Argenyi ZB, Thieberg MD, Hayes CM, Whitaker DC. Primary cutaneous meningioma associated with von Recklinghausen's disease.     

Treatment of MEK inhibitor-induced paronychia with doxycycline

A 12-year-old girl with neurofibromatosis type 1 and a large facial plexiform neurofibroma had been participating in a selumetinib clinical trial for the past 5 years. Despite decreased tumor size, she developed recalcitrant selumetinib-induced paronychia. Various antibiotics, topical medications, and surgeries were only minimally effective. Full-dose doxycycline resolved the paronychia, and sub-antimicrobial dosing has prevented recurrences for several months, permitting her to continue her selumetinib course.     

Plexiform spitz nevus: an intradermal spitz nevus with plexiform growth pattern

Two cases of a distinctive variant of Spitz (spindle and epithelioid cell) nevus are described. One lesion developed on the lower leg of a 17-year-old boy and the other lesion on the back of a 52-year-old man. The microscopic appearance was characterized by a plexiform arrangement of bundles and lobules of enlarged spindle to epithelioid melanocytes throughout the superficial and deep dermis. Intraepidermal melanocytic proliferation was unappreciated. Some lobules were circumscribed by a thin rim of compressed fibrous tissue. In both cases a myxoid stroma was present. The cells had abundant eosinophilic cytoplasm with well-defined borders. The nuclei were enlarged, consistently ovoid and vesicular, with small nucleoli. Both cases contained scattered multinucleate giant cells similar to those observed in classical form of Spitz nevi. No melanin pigment was detectable by light microscopy. No mitoses were observed in one case and a rare mitosis was present in the other. Tumor cells were strongly immunoreactive for S-100, but not for HMB-45, desmin, and actin. The differential diagnosis of this distinctive tumor includes desmoplastic/neurotropic melanoma, plexiform spindle cell nevus, cellular blue nevus, plexiform neurofibroma, and cellular neurothekeoma. The designation of "plexiform Spitz nevus" is chosen to emphasize its distinctive plexiform growth pattern.     

Giant Plexiform Neurofibroma of the Perineum and Pelvic Cavity Manifesting as Segmental Neurofibromatosis

Segmental neurofibromatosis (SN) is rare form of neurofibromatosis characterized that cutaneous or neural changes are limited to one region of the body. SN present neurofibroma and less frequently, café au lait macules (CALMs) on usually unilateral or rarely bilateral of the body region. SN seems to have fewer systemic complications than neurofibromatosis type I or II, except patients with plexiform neurofibromas (PNFs). PNFs are rare benign peripheral nerve sheath tumors which arise from single or multiple nerves. PNFs can easily become aggressive growth particularly during puberty or pregnancy and leading to disfigurement and functional impairment. Also, PNFs can transform to malignant peripheral nerve sheath tumor, higher rate than classic neurofibroma. So, it is important to decide appropriate treatment modalities and time to intervention.     

Tactile corpuscle-like structures in a case of plexiform neurofibromatosis

Summary Tactile corpuscle-like structures were identified in a plexiform neurofibroma, which was localized on the right cranial hemisphere of a 16-year-old boy and had necessitated repeated surgery. These structures were studied by light and electron microscopy. The origin of their component cells is, however, still controversial. We believe to have accumulated sufficient evidence for a Schwann cell origin of these cells.Chairman: Prof. Dr. F. Seitelberger     

Large hairy pigmented spots in neurofibromatosis type 1: an atypical form of neurofibromas]

INTRODUCTION: Large hairy pigmented spots have been observed in patients with neurofibromatosis type 1. In this study we tried to determine the nature and the frequency of these hairy pigmented spots in neurofibromatosis type 1. PATIENTS AND METHODS: In patients with neurofibromatosis type 1, hairy pigmented spots with a diameter more than 3 cm were systematically notified. Realisation of the biopsy of the spot was proposed to the patient. RESULTS: Among 614 patients with neurofibromatosis type 1, seven (1.1 p. 100) had a large hairy pigmented spot. Biopsy was realized in six cases. In five cases, diagnosis was superficial and plexiform neurofibroma, the 6(th) case was a Becker's nevus. CONCLUSION: Large hairy pigmented spot is a rare aspect of superficial and plexiform neurofibroma during neurofibromatosis type 1. A biopsy may be useful if it is necessary for the disorder diagnosis.     

Histopathologically dysplastic neurofibromas in neurofibromatosis 1: diagnostic criteria, prevalence and clinical significance

BACKGROUND: Malignant peripheral nerve sheath tumours (MPNSTs) correspond to the most frequent and aggressive neoplasic complications associated with poor prognosis in neurofibromatosis 1. OBJECTIVES: To define the dysplastic neurofibroma potentially at risk of transformation and evaluate its prevalence and incidence. METHODS: According to our database, we retrospectively included, between 1 March 2000 and 31 August 2004, all patients who had subcutaneous and/or plexiform neurofibromas removed surgically. Tumour specimens were systematically reviewed; dysplastic neurofibroma was defined by the association of high cellularity and the presence of atypical cells. Clinically atypical and histopathologically dysplastic neurofibromas were analysed using Fisher's exact test. In addition, three high-grade MPNSTs were analysed retrospectively for the presence of associated histopathologically dysplastic neurofibroma. RESULTS: Among the 89 plexiform and/or subcutaneous neurofibromas surgically removed, high cellularity and cytonuclear atypia were observed in 19% and 17% of cases, respectively. Both criteria were associated in 8.9% of cases (n=8); Mib-1 immunostaining was negative in all cases (n=7). In univariate analysis, only neurological symptoms were significantly associated with dysplasia (P=0.02). Interestingly, dysplastic neurofibroma areas could be identified within or at the periphery of two MPNSTs. CONCLUSIONS: The association of hypercellularity and cytonuclear atypia could be considered as a potential histological prognostic factor of transformation leading to increased surveillance.     

Cutaneous neuroblastoma‐like schwannoma: a report of two cases,one with a plexiform pattern,and a review of the literature

Cutaneous schwannomas in their classical form are readily identified histologically. A number of variants, including ancient, cellular, epithelioid, plexiform, microcystic and neuroblastoma‐like, may cause diagnostic difficulty and rarely be confused with malignancy. Neuroblastoma‐like schwannoma was first described by Goldblum et al. in 1994, and very few cases have since been reported. It is a benign sporadic neoplasm with no reported association with neurofibromatosis, and is characterized histologically by small round lesional cells surrounding collagenous cores forming rosette‐like structures. The differential diagnosis includes other lesions with the formation of rosettes including neuroblastoma, low‐grade fibromyxoid sarcoma and dendritic cell neurofibroma, as well as primitive neuroectodermal tumors and rare malignant transformation in a schwannoma. We describe two further cases of this rare entity and review the literature on the subject. Our first case additionally has a plexiform multinodular pattern, a feature described in only one previous report. Suchak R, Luzar B, Bacchi CE, Maguire B, Calonje E. Cutaneous neuroblastoma‐like schwannoma: a report of two cases, one with a plexiform pattern, and a review of the literature.     

Halolike Phenomenon Around a Café au Lait Spot Superimposed on a Mongolian Spot

An 8‐month‐old Caucasian infant with neurofibromatosis type 1 presented with a congenital plexiform neurofibroma and multiple café au lait spots. A pale area surrounded one of the café au lait spots located on the left gluteus in the area of dermal melanocytosis. This halolike phenomenon results from the disappearance of the Mongolian spot around the café au lait spots, revealing normal pigmented skin. This sign has been described rarely in the literature and the pathogenic mechanism is unclear.     

Pigmented neurofibroma

Pigmented neurofibroma is a rare tumour of the dermis. The clinical features and histology of a lesion occurring in a female of 69 years are described in this report. This entity was first described by Willis in 1959 in three patients with pigmented dermal tumours which showed a plexiform structure and the presence of pseudo-Meissnerian bodies.     

Cutaneous epithelioid melanocytic neurofibroma arising in a patient with neurofibromatosis‐1

Tumors expressing both melanocytic and neural features can pose a diagnostic challenge to the dermatopathologist and provoke questions regarding their lineage. We report a case of a tumor arising on the right cheek of a 9‐year‐old boy with neurofibromatosis type 1 (NF‐1). This neoplasm featured nests of non‐pigmented epithelioid cells arising within a neurofibroma. The entire tumor stained strongly with S100, whereas the epithelioid population stained with MART‐1, HMB‐45 and MiTF. The neoplasm shows only scattered Ki‐67 positivity. This tumor represents a neurofibroma with portions that have undergone melanocytic differentiation (melanocytic neurofibroma). This exceedingly rare tumor represents a distinct entity from neurotized melanocytic nevi, combined melanocytic nevi or pigmented neurofibromas and provides further evidence that melanocytes arise indirectly from ventromedial neural crest‐derived Schwann cell precursors.     

Solitary subungual neurofibroma: a previously unreported finding in a male patient

A neurofibroma is a hamartomatous proliferation of neuromesenchymal origin. It may be found in combination with neurofibromatosis or in the form of a solitary tumor. Clinical presentation as a solitary subungual tumor is very rare. Neurofibroma is more common in females and surgery is the treatment of choice. The present paper reports the case of a male patient with a subungual tumor on his toe. Biopsy and immunohistochemistry findings were compatible with a neurofibroma. To date, fewer than ten cases of subungual neurofibromas unassociated with von Recklinghausen's disease have been documented, this being the first case to be reported in Brazil and the only report worldwide to have described this condition in a male patient.