Neurothekeoma Research Articles

Atypical cellular neurothekeoma: a case report with a novel NF1 mutation

Atypical cellular neurothekeoma is a rare benign soft-tissue tumour that usually arises in the head and neck region, shoulder girdles, and proximal extremities, predominantly in young women. This dermal neoplasm is under-reported in the literature and is not uncommonly misdiagnosed as a malignant tumour due to its worrisome histologic characteristics. Currently, the diagnosis of cellular neurothekeoma relies on a panel of non-specific immunohistochemical markers and its etiopathogenesis is unknown.Herein, we present the case of an atypical cellular neurothekeoma in the arm of a 49-year-old woman, describing its microscopic features and immunohistochemical profile. Additionally, we present a novel heterozygous predicted inactivating NF1 mutation, not previously reported, which was identified using high-throughput molecular techniques. Such finding might provide insights into the pathogenesis of neurothekeoma, potentially contributing to future refinements in diagnosis, which would enable more precise identification of this neoplasm.

Ectomesenchymal chondromyxoid tumor: A rare case report

Abstract Ectomesenchymal chondromyxoid tumor is a very rare tumor, which mostly occurs in the tongue. Here, we are presenting a case of a 55-year-old man with a swelling in the anterior dorsum of his tongue. The mass was excised and subsequent histopathological examination revealed a subepithelial well-circumscribed mass comprising oval to fusiform tumor cells, arranged in sheets, whorls, and reticular pattern within a prominent chondromyxoid stroma. The tumor cells were positive for glial fibrillary acidic protein, S100, and vimentin, whereas negative for epithelial membrane antigen and p63 on immunohistochemistry. These tumors have to be differentiated from other myxoid lesions, such as oral focal mucinosis, nerve sheath myxoma, soft tissue myxoma, glial choristoma, and ossifying fibromyxoid tumor of soft parts.

Cellular neurothekeoma of the eyelid: A rare tumor with a common clinical presentation

We report a case of cellular neurothekeoma (NTK) in a 4-year-old male boy, which presented as a painless, progressive, left upper lid mass of 6 months’ duration. The left upper lid mass was solitary and dome shaped, causing mechanical ptosis. A magnetic resonance imaging (MRI) was performed followed by surgical excision of the mass in two stages, which, after histopathology and immunohistochemistry, was confirmed to be cellular NTK with no recurrence reported so far. To our knowledge, cellular NTK (a variant of NTK), an uncommon benign skin neoplasm involving the ocular adnexa (eyelid), is extremely rare. It is important to differentiate it from other malignant lesions, so that aggressive treatment can be avoided. The treatment of choice in cellular NTK is complete excision with clear margins.

Nerve sheath myxoma masqueraded as intramuscular myxoma: an extremely rare tumor with unusual location - a case report and literature review.

The authors present the first reported case of NSM in the anterior tibialis muscle in a 39-year-old man presented as deep swelling in the left leg. NSM is difficult to diagnose clinically or using standard imaging techniques; MRI and ultrasonography cannot differentiate it from other anomalies. Histopathology alone is not enough to distinguish NSM from neurothekeomas, which were considered synonymous in the past. They can be distinguished by using immunohistochemical markers. Soft tissue tumors in lower extremity muscles are somewhat difficult to diagnose. Excision of the tumor by a specialized orthopedic surgeon and histopathological/immunohistochemical analysis were the only avenues to correctly diagnose the NSM.

Spinal Nerve Sheath Myxoma

Nerve sheath myxoma (NSM) is a rare myxoid form of schwannoma, which is a benign tumor that usually grows in the same place. They usually arise from small cutaneous nerves in the head, neck, and extremities, but exceptionally, they have also been reported to develop in the spinal canal. Here we describe a case of spinal NSM. The patient was a 4-month-old male who presented with incomplete tetra paresis. Spine magnetic resonance imaging showed a well-demarcated small intradural extramedullary mass at the T10-L1 level. The tumor has typical histological features of myxoid type NSM with myxoid lobules that are separated by fibrous septa or bands of more compact cellular area. Nerve sheath myxomas should be included in the differential diagnosis of spinal canal tumors. Ultrastructural observation of tumor cefis with perineurial, fibroblast-like, and Schwann differentiation suggests an origin from nerve sheath precursor cefis.

Resection of Orbital Myxoma With Magnetic Resonance Imaging Evidence of Ethmoid Sinus Origin: Case Report and Review of 20 Patients in the Literature.

A 41-year-old woman showed a palpable mass at the superonasal orbital edge on the right side. Magnetic resonance imaging demonstrated a lobulated fluid-containing tubular mass which extended anteriorly to posteriorly along the medial orbital wall, nasal to the eyeball. She was followed once a year for 8 years until the age of 49 years when she decided to undergo surgical resection because of the enlarged mass. The lobulated large mass was resected and the pathology showed sparsely distributed spindle cells, positive for CD34, in alcian blue-positive mucous substances, indicative of myxoma. Postoperative magnetic resonance imaging showed residual lobulated tubular mass along the optic nerve on the medial side and superior to the eyeball. The residual orbital mass showed stable structure with more evident connection with the ethmoid sinus lesion, suggestive of the ethmoid origin, in 12 years until the age of 61 years. In the review of 20 patients with orbital myxomas in the literature, in addition to this case, roughly classified locations in the orbit were retrobulbar in 8 patients, on the lateral side of the orbit in 4, on the superior side in 6, on the medial side in 1 (this patient), and in the orbit with no specific description in 2. In pathological examinations, immunohistochemistry was not done in 8 patients, done but all negative in 2, and positive in 11 patients: nerve sheath myxoma was diagnosed in 3 patients based on positive S100 staining. Orbital myxoma is rare but considered in differential diagnosis of orbital masses.

32748 A case series of pediatric cellular neurothekeomas and a review of the histologic spectrum

Neurothekeomas are rare, benign neoplasms of unknown histogenesis. These neoplasms are a frequent source of diagnostic challenge due to their incompletely defined clinical and morphologic spectrum. Clinically, they may present as a solitary, slow-growing papule or nodule on the head, neck, or extremities of younger individuals, with a slight female predominance. They have traditionally been classified into 3 histologic variants: classical (myxoid), cellular, and mixed, depending on immunohistochemical (IHC) staining and the amount of myxoid matrix. Although the classical variant is believed to be derived from neural sheath cells due to positive S-100 staining, the cellular variant is presumably derived from perineural or dermal lineage. IHC findings for cellular neurothekeomas are typically positive for NKI/C3, smooth muscle actin (SMA) and neuron-specific enolase (NSE), while negative for epithelial membrane antigen (EMA) and S-100. There have been few reports of a rare myxoid cellular neurothekeoma entity that presents with histologic features of the myxoid variant combined with IHC findings of the cellular variant. We herein report a case series of 3 pediatric patients diagnosed with cellular neurothekeoma, particularly highlighting 2 unusual case of a myxoid cellular neurothekeoma with atypical IHC that was negative for NKI/C3, SMA, and NSE as well as negative for S-100. In addition to reporting on our institutional experience with 3 clinical cases of cellular neurothekeomas in a pediatric population, we will explore the histologic spectrum and discuss the current understanding of cellular neurothekeomas.

Histopathological and Immunohistochemical Evaluation of Canine Nerve Sheath Tumors and Proposal for an Updated Classification.

Nerve sheath tumors are a group of tumors originating from Schwann cells, fibroblasts, and perineurial cells. In veterinary pathology, the terminology for nerve sheath tumors remains inconsistent, and many pathologists follow the human classification of such tumors in practice. Immunohistochemistry plays an important role in the diagnosis of nerve sheath tumors, but specific immunohistochemical and molecular biomarkers are lacking. In our study, we histopathologically reevaluated 79 canine nerve sheath tumors and assessed their reactivity for the immunohistochemical markers Sox10, claudin-1, GFAP, CNPase, and Ki-67. Based on the results, we classified the tumors according to the most recent human classification. Twelve cases were diagnosed as benign nerve sheath tumors, including six neurofibromas, three nerve sheath myxomas, two hybrid nerve sheath tumors (perineurioma/neurofibroma and perineurioma/schwannoma), and one schwannoma. Sixty-seven tumors were malignant nerve sheath tumors, including fifty-six conventional, four perineural, one epithelioid malignant nerve sheath tumor, and six malignant nerve sheath tumors with divergent differentiation. We believe that with the application of the proposed panel, an updated classification of canine nerve sheath tumors could largely follow the recent human WHO classification of tumors of the cranial and paraspinal nerves, but prospective studies would be needed to assess its prognostic value.

Head and Neck Neurothekeoma of Lower Lip with Aggressive Reconstruction using Bengt-Johanson’s Step Technique: Case Presentation and Systematic Review of Literature

Aim: Neurothekeoma is a benign lesion of superficial tissue mainly localized in the head-neck area. The aim of the article is to provide a systematic literature review on the tumor’s main characteristics and its correct surgical treatment. We support our theory with the report of an aggressive case of the lower lip region which required a large excision and reconstruction with local flaps. Materials and Methods: The literature review is based on the scientific materials produced from December 1980 to March 2020 on the head and neck neurothekeomas. In total, 76 papers were included in the study. We presented a classic neurothekeoma S-100 protein positive case that required wide local excision with healthy margins and reconstruction with Bengt-Johanson’s step technique. Results: Most of the papers were case reports (47,4 %) and reviews (19,7 %) with 721 evaluated neurothekeomas. The male to female ratio was 1:1,8 with a mean age of 26,4 years. The most frequent site of lesions was the head (36,1%), and the three subtypes were divided in cellular (65,7%) mixed (17,5%) and classic (16,8%). The classic neurothekeoma resulted more immunoreactive for S-100 Protein while cellular neurothekeomas for NKI/C3. Our case was successful without recurrence at 1 year follow-up. Conclusion: Our review highlights that neurothekeoma mainly occurs in young women in the superficial planes of the head and neck. The most frequent type is the cellular one, but the most aggressive is the classic type due to a high local recurrence of protein S-100. A local excision is sufficient for the cellular neurothekeoma, while for the classic type a wide local excision with healthy tissue margins is necessary. The treatment of our case demonstrates that by following this guide, relapse can be avoided.

Atypical cellular neurothekeoma: Report of a case.

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PRAME expression in cellular neurothekeoma: A study of 11 cases.

Preferentially expressed antigen in melanoma (PRAME) has been widely investigated in the skin, mainly in melanocytic tumors, and constitutes an aid in differentiating benign from malignant lesions. Very few studies have been performed on non-melanocytic tumors. We investigated the immunohistochemical expression of PRAME on a series of 11 neurothekeomas (NTKs), together with 3 cases of nerve sheath myxoma (NSM) and 1 case of plexiform fibrohistiocytic tumor (PFT), in order to evaluate the presence and usefulness of this marker in their differential diagnosis. PRAME was variably expressed in all cases of NTK, with moderate intensity in three cases and faint in the remaining cases; on the contrary, cases of NSM and PFT were negative. This study expands the entities of cutaneous non-melanocytic tumors expressing PRAME, and confirms that this marker is not restricted to malignant tumors. Expression of PRAME in NTK does not seem to be related to distinctive histopathologic features.

NERVE SHEATH MYXOMA OF THE ORAL CAVITY

<h3>Introduction</h3> Nerve sheath myxomas are rare, benign neoplasms of nerve sheath origin. They are often found arising from the dermis and subcutaneous tissues at the head and neck region. However, presentation in the oral cavity is rather unusual. <h3>Case Summary</h3> We report a case of a 33-year-old woman who presented with a 12-month history of an extensively large, firm swelling in the left buccal space extending to the retromolar area, resulting in a slight facial asymmetry. A well-defined radiopaque mass was seen on magnetic resonance imaging studies. The diagnosis of oral nerve sheath myxoma was established, adding to the literature its incidence and subsequently improving understanding of its clinicopathologic features, histogenesis, and distinct entity relative to other oral lesions that can mimic its presentation.

Positive MITF and NKI/C3 Expression in Cellular Neurothekeoma and Dermatofibroma.

Cellular neurothekeoma (CNT) is a benign mesenchymal tumor with uncertain cellular differentiation. Studies have found evidence of myofibroblastic differentiation and possible relation to dermatofibromas (DFs). As microphthalmia transcription factor (MITF) and NKI/C3 stains are routinely positive in CNT, we compared expression patterns of both markers in CNT and DF to assess their relationship. We assessed cases of CNT (n=25) and DFs (n=35) for histopathologic characteristics and MITF and NKI/C3 expression. Immunostaining results were classified as negative, focally positive (<50%), and diffusely positive (>50%). At least 1 additional melanocytic marker was assessed in each case of CNT. Both DFs and CNTs showed a female predilection and a wide age range. Immunostaining in CNTs for MITF was positive in the vast majority (focal 68%, diffuse 24%), as was NKI/C3 (focal 72%, diffuse 24%). All DFs were MITF positive (diffuse 74%, focal 26%), and most DFs were NKI/C3 positive (focal 57%, diffuse 3%). CNT and DF share demographic, histopathologic, and immunohistochemical features, including shared expression of MITF and NKI/C3, especially cellular DF.

Peripheral Nerve Sheath Tumors of Head and Neck: Imaging-Based Review of World Health Organization Classification.

We aim to review the imaging appearance of peripheral nerve sheath tumors (PNSTs) of head and neck according to updated fourth edition of World Health Organization classification. Peripheral nerve sheath tumor can be sporadic or associated with neurofibromatosis type 1, neurofibromatosis type 2, and schwannomatosis. Schwannoma is the most common benign PNST that can be intracranial or extracranial and appears heterogeneous reflecting its histologic composition. Melanotic schwannoma is a different entity with high prediction of malignancy; it shows hypointense signal on T2-weighted image. Neurofibroma can present by localized, plexiform, or diffuse lesion. It usually appears homogeneous or shows a characteristic target sign. Perineurioma can be intraneural seen with the nerve fiber or extraneural appearing as a mass. Solitary circumscribed neuroma and neurothekeoma commonly present as dermal lesions. Nerve sheath myxoma may exhibit high signal on T1 weighted image. Benign triton tumors can be central, aggressive lesion, or peripheral nonaggressive lesion. Granular cell tumor shows hypointense signal on T2 weighted image. Neuroglial heterotopia most commonly occurs in the nasal cavity. Ectopic meningioma arises from ectopic arachnoid cells in the neck. In hybrid PNST, combined histological features of benign PNST occur in the same lesion. Malignant PNSTs are rare with an aggressive pattern. Computed tomography and magnetic resonance imaging are complementary studies to determine the location and extent of the tumor. Advanced magnetic resonance sequences, namely, diffusion-weighted imaging and dynamic contrast enhancement, can help in differentiation of benign from malignant PNST.

Pediatric cellular neurothekeoma: Seven cases and systematic review of the literature.

Neurothekeoma is a rare, benign, cutaneous neoplasm consisting of Schwann cells and perineural cells in myxoid stroma. Cellular neurothekeoma (CNT) was previously thought to represent a morphologic variant of neurothekeoma, but recent studies have shown that CNTs are unrelated to neurothekeomas and are more likely of histiocytic lineage. Herein, we describe seven cases of CNT in pediatric patients. A comprehensive search of PubMed was performed, and 71 cases of cellular neurothekeoma in pediatric patients were reviewed. The clinical differential diagnosis for these lesions included Spitz nevi, keloid, juvenile xanthogranuloma, cutaneous lymphoid hyperplasia, and lymphomatoid papulosis. All cases were treated by excision or excisional biopsy. Histopathologically, all demonstrated multilobular, primarily intradermal neoplasms composed of plump spindled or epithelioid mononuclear cells with abundant eosinophilic pale-staining cytoplasm. Immunophenotypic findings included CD68 and NKI/C3 positivity, and negative staining with cytokeratin, S-100, Melan-A, and SOX-10. Cellular neurothekeoma is distinguished from conventional neurothekeoma by increased cellularity, a lack of myxoid stroma, and a lack of neural expression with immunohistochemical stains. These uncommon neoplasms should be included in the differential diagnosis of dermal nodules in children. Accurate diagnosis of these lesions is essential, as they can be mistaken for malignancy leading to unnecessary treatment.

Neurothekeoma of the scalp in a child: A rare case

Neurothekeoma (NT) is a rare, benign tumor that is derived from peripheral nerve sheath cells. There are less than 300 cases reported in the literature to date. Historically, this tumor has been subclassified as myxoid (classic), mixed, or the cellular type, depending on the amount of myxoid stroma and cellularity. Here, we present a case of NT (mixed type) of the scalp in a 3-year-old female child. The tumor was completely excised. No recurrence was detected in the past 3 months after the local excision.

”Myxoma of the Jaws”: Report of an atypical presentation and review of literature

Oral lesions of myxomatous origin are relatively rare and include nerve sheath myxomas, soft tissue myxomas, oral focal mucinosis, and odontogenic myxomas. These lesions have a common histologic appearance of abundant myxoid ground substance. A 61-year-old edentulous female presented with nasal stuffiness since the past 4 months. Clinical examination revealed an asymptomatic intraoral swelling in the edentulous maxillary ridge which had ulcerated. Plain film radiography and CT showed an expansile osteolytic lesion involving the right maxillary sinus. A partial maxillectomy was performed and direct microscopy showed a predominant embryonic mesenchymal stroma with fibroblasts and calcifications suggestive of a myxoma. The central myxoma is hypothesized to originate from the odontogenic apparatus due to its almost exclusivity to the jaw bones. However, when a central myxoma occurs in an edentulous jaw at an age when the odontogenic apparatus is apparently nonfunctional, explaining the genesis of this unique tumor based on present understanding becomes difficult. We present one such case while reviewing the existing literature on the present concepts of pathogenesis.

Meningioma-like Tumor of the Skin Revisited: A Distinct CD34+ Dermal Tumor With an Expanded Histologic Spectrum.

The term meningioma-like tumor of the skin (MLTS) was coined in 1993 to designate a particular whorled spindle cell superficial cutaneous tumor. No additional confirmed cases of this entity have been reported to date. Some authors have speculated that these cases might be cellular neurothekeomas. In order to delineate the histologic spectrum and the immunophenotype of this unusual tumor, we studied 5 cases, 2 previously unreported and the 3 original cases. The immunohistochemical findings of case 5, however, were limited to those from the original study. Clinically, the tumor presented as a reddish papule, plaque, or nodule, located in the extremities or trunk. The patient often referred to a recent growth of a longstanding lesion. Histologically, the characteristic whorled spindle and stellate dendritic cell population, commonly in a perivascular arrangement, and variable myxoid component, were consistently found in all cases. A prominent microvasculature was also a constant finding. The presence of large deciduoid cells was conspicuous in one case. A reticular pattern of multivacuolated cells giving a chordoma-like appearance was evident in another case. Tumor cells were diffusely positive for CD34 in all 4 cases studied, and negative for S-100, EMA, NKI-C3, CD68, and smooth muscle markers. No complete loss of retinoblastoma protein was found. No brachyury immunostaining was found in the case with chordoid features. No EWSR1 or NAB2-STAT6 gene fusions were found. From these findings, we demonstrate that MLTS is a distinct CD34 spindle cell benign dermal tumor, unrelated to cellular neurothekeoma, and exhibiting myxoid, deciduoid, or chordoma-like features.

Oral neural tumors: Clinicopathologic analysis of 157 cases and review of the literature.

BackgroundOral neural tumors (ONTs) are rare lesions and represent reactive or neoplastic proliferations of nerve sheath cells. The purpose of the present study is to report the clinical, demographic and histopathologic features of 157 ONTs diagnosed in a single Oral Pathology Department and review the pertinent literature.Material and Methods157 cases of ONTs diagnosed during a 44-year period were retrospectively collected and the diagnosis was reconfirmed by studying representative haematoxylin and eosin stained tissue sections. The patients’ gender and age, as well as the main clinical features of the lesions, were retrieved from the biopsy submission forms.ResultsThe 157 ONTs represented approximately 0.4% of 35,590 biopsies accessioned during the study period. They affected 71 male and 86 female patients with a mean age of 38.4±18.8 years. They mainly appeared as asymptomatic nodules of normal or white colour on the tongue, lip mucosa and hard palate. The most common ONT was granular cell tumour (38.9%) followed by neurofibroma (19.7%), schwannoma (15.9%), traumatic neuroma (15.9%), palisaded encapsulated neuroma (8.3%) and nerve sheath myxoma (1.3%).ConclusionsThis study confirmed the rarity of ONTs. Their clinical characteristics mimic other oral lesions; thus, microscopic examination is the only mean to arrive at a definitive diagnosis. Key words:Oral neural tumors; oral neural neoplasms; neurofibroma; oral neurofibroma; schwannoma; oral schwannoma; neurilemmoma; oral neurilemmoma; granular cell tumor; oral granular cell tumor; traumatic neuroma; oral traumatic neuroma; palisaded encapsulated neuroma; oral palisaded encapsulated neuroma.

Multiple cellular neurothekeomas in a middle-aged woman including the lower extremity: A case report and review of the current literature

Cellular neurothekeoma is a benign cutaneous neoplasm that typically occurs on the head, neck, and upper body of young adults with a slight female predominance. It is a rare lesion to diagnose and multiple neurothekeomas in one patient are even more uncommon finding. We present a case of multiple neurothekeomas in a middle-aged woman with lower extremity involvement and summarize the current literature on multiple neurothekeoma patients. A 46-year-old female presented with nearly one dozen skin-colored papules on the head, upper limb, and lower limb. The lesions were clinically diagnosed as dermatofibromas and a nevus. Eight lesions were biopsied and confirmed to be cellular neurothekeomas, with one initially misinterpreted on histology as a dermatofibroma. Awareness of cellular neurothekeoma as a diagnostic entity and the possibility of atypical presentations as seen in our case (eg, in multiple numbers, in older adults, and on the lower extremity) are important in allowing for accurate clinical and histological diagnosis of these lesions. The possibility of a syndromic association with multiple cellular neurothekeomas should be explored further.