Expression of TFE3 in Cellular and Myxoid Type of Neurothekeoma: Four Cases in Young Children and Adolescents.

Introduction: Cellular neurothekeoma is a benign tumor that mainly occurs in young children and adolescents. The aberrant expression of transcription factor E3 (TFE3) has not been reported in cellular neurothekeoma previously. Case report: We report four cellular neurothekeoma with aberrant immunohistochemical expression of TFE3 protein. The fluorescence in situ hybridization (FISH) showed no TFE3 gene rearrangement or amplification. Discussion/Conclusion: TEF3 protein expression may not be related to TFE3 gene translocation in cellular neurothekeoma. TFE3 may be a potential pitfall in diagnosis, for several malignant tumors in children also express TFE3. The aberrant expression of TFE3 may offer insights into cellular neurothekeoma etiology, and associated molecular mechanisms.

Neurothekeoma With PI3K w552*, ALK P1469S, SMO G461S, and ERBB3 L77M Genetic Alterations.

ABSTRACT: Neurothekeoma, a lesion of possible fibrohistiocytic origin, is a rare, benign, superficial soft tissue tumor, histologically subclassified in 3 types: myxoid, cellular, or mixed. It clinically presents as a solitary, pink to brown nodule, ranging from 0.3 to 2.0 cm. Four point mutations (PI3K w552*, ALK P1469S, SMO G461S, and ERBB3 L77M) were identified by next-generation sequencing of a neurothekeoma presenting in the left inner thigh of a 53-year-old man. We highlight novel genetic alterations (SMO G461S and ERBB3 L77M) and previously known mutations (PI3KCA w552* and ALK P1469S) that play a role in other pathogenic pathways, but to the best of our knowledge, these have not yet been reported in neurothekeoma.

Cellular neurothekeoma occurring at the site of radiation therapy in a child with medulloblastoma.

Cellular neurothekeoma is a rare, benign cutaneous neoplasm. We report a case of cellular neurothekeoma arising on the mid-back of a 10-year-old boy within the previous radiation therapy field for medulloblastoma. Clinical features of cellular neurothekeoma in children are similar to those in adults, except that there have been no reports of local recurrence in children following surgical excision, and the presence of atypical histological features does not predict clinical behavior. Recognition of this entity in children is important to avoid misdiagnosis and overly aggressive treatments.

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

BACKGROUND: 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. MATERIALS: 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. RESULTS: 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. CONCLUSIONS: 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.

Neurothekeoma: Another differential in the diagnosis of a subungual swelling.

CASE: Lesions, which commonly grow and protrude beneath the distal end of a toe nail and present to the podiatrist or foot and ankle surgeon, include subungual exostosis or enchondroma and a Nora lesion. Neurothekeoma is a benign dermal tumour of the peripheral nerve sheath that usually affects the skin of the head, neck, shoulders and arms. It occurs less commonly in the lower limbs and has only been reported twice in a subungual location. A case of subungual neurothekeoma that recurred twice due to inadequate margins of resection is presented. CONCLUSION: Although rare, neurothekeoma should be included in the differential diagnosis of a subungual lesion. Histopathological diagnosis is reached by differential immunostaining. Adequate clear margins of resection are recommended to prevent recurrence.

Multiple myxoid cellular neurothekeomas in a patient with systemic lupus erythematosus.

Cellular neurothekeoma is a cutaneous tumor with a distinctive histopathologic appearance characterized by a dermal-based multinodular proliferation of epithelioid to spindled cells. Although the tumor may show varying amounts of myxoid stroma, extensive myxoid change is uncommon. The tumor typically presents as a solitary nodule with a predilection for the head and neck and upper limbs; examples of multiple cellular neurothekeomas are decidedly rare. The present report describes a unique case of multiple myxoid cellular neurothekeomas arising in a 60-year-old female with systemic lupus erythematosus. Two papular lesions were identified involving the skin inferior to the umbilicus and the left inguinal crease. Both lesions were histopathologically similar, forming a nodular mass composed of epithelioid cells in a prominent myxoid stroma. By immunohistochemistry the lesional cells expressed NKI/C3, microphthalmia transcription factor (MiTF), and CD68, with focal staining for PGP9.5, factor XIIIa, and CD10 also observed. The tumors were negative for S-100, SOX-10, epithelial membrane antigen, desmin, smooth muscle actin, glial fibrillary acid protein, and CD34. The present case confirms that cellular neurothekeoma can present clinically as multiple lesions and can have a predominantly myxoid appearance, potentially mimicking other cutaneous myxoid lesions.

Nerve Sheath Myxoma in the Lower Extremity: A Rare Case with Description of Magnetic Resonance Imaging and Sonographic Findings.

BACKGROUND This report is of a nerve sheath myxoma presenting as a slow-growing mass in the back of the left ankle of a 36-year-old man that was investigated by ultrasound and magnetic resonance imaging (MRI) before the diagnosis was confirmed by histopathology. CASE REPORT We report a nerve sheath myxoma of the ankle in a 36-year-old man. The palpable abnormality was falsely assumed to be a ganglion cyst prior to advanced imaging. Magnetic resonance imaging demonstrated a lobular mass with high T2 and intermediate T1 signal as well as moderate enhancement. T2 sequences also demonstrated distinctive internal septae. These internal septae were also noted on sonographic evaluation prior to biopsy. The patient was treated with surgical excision, and pathologic analysis showed myxoid nodules with loose arrangements of spindled cells separated by fibrous septae. S-100 protein and glial fibrillary acidic protein positivity by immunohistochemistry staining was demonstrated. Follow-up imaging at 12 months showed no evidence of tumor recurrence. CONCLUSIONS This case highlights that while nerve sheath myxomas are rare tumors, they should be considered in cases of cutaneous soft-tissue masses with myxoid imaging features. Ultrasound and magnetic resonance imaging features of thin internal septae may be present and correspond well with the unique histopathological characteristics of these lesions. This report shows the importance of imaging of peripheral soft-tissue masses, including ultrasound and MRI, which can identify localized and benign features and the solid, cystic, and myxoid areas, which were characteristic in this case of benign nerve sheath myxoma.

Nerve Sheath Myxoma Involving the Medial Rectus Muscle: A Case Report.

A 63-year-old man reported a 2-year history of painless OS proptosis. The first MRI, performed in the institution of origin, resulted in a diagnosis of hemangioma versus orbital pseudotumor. Examination revealed proptosis and mild chemosis. Ancillary tests were normal, and oral prednisone was initiated without remarkable changes. Later, an incisional biopsy identified the lesion as an intramuscular myxoma of the left rectus, and a new MRI was ordered. It described a fusiform thickening of the medial rectus with and exophytic growth below the inferior rectus and upward toward the superior oblique. Due to the localization of the lesion, a combined transcaruncular and swinging eyelid approach with a lateral orbitotomy was performed. Histopathological examination revealed a proliferation of stromal origin composed of myxoid matrix with fusocellular and stellate-shaped cells. Cells were S-100, CD34, and CD56 positive and negative for epithelial membrane antigen, CD68, CD10, actin, and desmin. Results were consistent with a left medial rectus nerve sheath myxoma.

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

BACKGROUND: 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. MATERIALS AND METHODS: 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. RESULTS: 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%). CONCLUSION: CNT and DF share demographic, histopathologic, and immunohistochemical features, including shared expression of MITF and NKI/C3, especially cellular DF.

Neurothekeoma in the Axilla Causing Persistent Shoulder Pain: Case Report / Neurotecoma na axila causando dor persistente no ombro: Relato de caso

Abstract Neurothekeomas, also known as neural sheath myxomas, are rare benign tumors of the neural sheath affecting most commonly the head, arms and shoulder of women in their 2nd and 3rd decades of life. Due to the low prevalence and undefined clinical picture, they are hardly considered in the initial differential diagnosis of skin tumors. We report the case of a 24 year-old woman who was seen in 2016 reporting > 1 year of moderate pain and limited mobility of her left shoulder. Clinical evaluation revealed restricted mobility of the affected shoulder and nuclear magnetic resonance imaging showed a T2-weighted contrast-enhanced multilobular mass in the quadrilateral area apparently invading the adjacent humeral cortical region. Histopathology of a needle sample material revealed loose fibroconnective tissue with no signs of invasion, mitosis or atypical figures. Successful surgical excision was performed and the diagnosis of neurothekeoma was confirmed after detailed histopathology, including immunohistochemistry. The patient was asymptomatic at 18 months of follow-up, with full recovery of shoulder movement and no signs of relapse.

Resumo Neurotecomas, também conhecidos como mixomas da bainha neural, são tumores benignos raros da bainha neural afetando mais comumente a cabeça, braços e ombros de mulheres entre 20 e 40 anos de idade. Devido à baixa prevalência e quadro clínico mal definido, essas lesões são raramente consideradas no diagnóstico diferencial de tumores cutâneos. Relatamos o caso de uma mulher de 24 anos de idade que procurou atendimento em 2016 relatando dor moderada por mais de um ano e limitação dos movimentos do ombro esquerdo. Ao exame, foi constatada restrição da mobilidade dessa articulação e uma ressonância magnética revelou imagem multilobular com aumento de sinal em T2 na região quadrilateral, aparentando invasão da região cortical do úmero subjacente. A histopatologia de uma biópsia incisional mostrou lesão composta por tecido conjuntivo frouxo, sem sinais de invasão, figuras de mitose ou atipias. Foi realizada excisão completa da lesão e o diagnóstico de neurotecoma foi confirmado após análise histopatológica que incluiu painel imunohistoquímico. À revisão de 18 meses, a paciente estava assintomática com recuperação completa do movimento e sem evidência de recidiva da lesão.

Intraosseous Neurothekeoma of the Hand in a 16-year-old Boy / Neurotequeoma intraósseo da mão de um jovem de 16 anos

Abstract Soft-tissue tumors are rare in the pediatric population. First described in 1969 as myxoma of the nerve sheath, the neurothekeoma is a benign tumor lesion with presumable origin in the nerve sheath. It occurs mainly in female children and presents as a mass of slow, subcutaneous growth, asymptomatic and without alteration of the local pigmentation. It is predominantly located in the head, neck, and extremities of the upper limbs. This report presents the case of a 16-year-old male with a tumor mass originating from the nerve sheath in the 4th left metacarpal, intraosseous, and relapsed after previous surgical resection 2 years before this observation. A marginal resection of the tumor mass was performed on the distal region of the fourth metacarpal, followed by curettage of the proximal phalanx and filling with structural autologous bone graft. The patient maintained a favorable postoperative clinical evolution, without local pain or range of motion limitation in his fingers. Radiologically, a progressive trabecular filling of the proximal phalanx of the fourth metacarpal was observed. At 17 months of follow-up, the patient is asymptomatic and shows no signs of relapse. The description of this case serves to increase the familiarity with this rare pathology, and aid its diagnosis and treatment.

Resumo Os tumores dos tecidos moles são raros em idade pediátrica. Descrito pela primeira vez 1969 como um mixoma da bainha nervosa, o neurotequeoma é uma lesão tumoral benigna com presumível origem na bainha nervosa. Ocorre maioritariamente em crianças do sexo feminino e apresenta-se como uma massa de crescimento lento, subcutânea, assintomática e sem alteração da pigmentação local. Localiza-se predominantemente na cabeça, no pescoço, e nas extremidades dos membros superiores. Os autores apresentam um caso clínico de um jovem de 16 anos do sexo masculino com massa tumoral com origem na bainha nervosa no 4º metacarpo esquerdo, intraóssea e recidivada após ressecção cirúrgica 2 anos antes do estudo. Foi feita ressecção marginal da massa tumoral localizada sobre a região distal do quarto metacarpo e curetagem da falange proximal e preenchimento com enxerto ósseo autólogo corticoesponjoso. O paciente apresentou uma evolução clínica pós-operatória favorável, sem queixas álgicas e sem limitações da mobilidade dos dedos da mão. Radiologicamente, foi observado preenchimento trabecular progressivo da falange proximal do quarto metacarpo. Aos 17 meses de seguimento, o paciente se encontra assintomático e não apresenta quaisquer sinais de recidiva. Com a descrição deste caso, os autores pretendem aumentar a familiaridade com essa rara patologia, seu diagnóstico e tratamento.

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

BACKGROUND/OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.