Neurothekeoma Research Articles

Multiple cellular neurothekeomas—a case report and review on the role of immunohistochemistry as a histologic adjunct

Multiple cellular neurothekeomas—a case report and review on the role of immunohistochemistry as a histologic adjunct

Cellular neurothekeoma with melanocytosis

Cellular neurothekeoma (CNT) is a benign dermal tumor mainly affecting the head and neck and the upper extremities. It is characterized histologically by interconnecting fascicles of plump spindle or epithelioid cells with ample cytoplasm infiltrating in the reticular dermis. The histogenesis of CNT has been controversial, although it is generally regarded as an immature counterpart of classic/myxoid neurothekeoma, a tumor with nerve sheath differentiation. Two rare cases of CNT containing melanin-laden cells were described. Immunohistochemical study with NKI/C3, vimentin, epithelial membrane antigen, smooth muscle antigen, CD34, factor XIIIa, collagen type IV, S100 protein and HMB-45 was performed. Both cases showed typical growth pattern of CNT with interconnecting fascicles of epithelioid cells infiltrating in collagenous stroma. One of the nodules contained areas exhibiting atypical cytological features. Melanin-laden epithelioid or dendritic cells were diffusely scattered throughout one nodule, and focally present in the peripheral portion of the other nodule. Both nodules were strongly immunoreactive to NKI/C3 and vimentin, but negative to all the other markers employed. CNT harboring melanin-laden cells may pose diagnostic problems because of their close resemblance to nevomelanocytic lesions and other dermal mesenchymal tumors. These peculiar cases may also provide further clues to the histogenesis of CNT.

An update on plexiform fibrohistiocytic tumor and addition of 66 new cases from the Armed Forces Institute of Pathology, in honor of Franz M. Enzinger, MD

The seminal article of Drs Franz Enzinger and Renyuan Zhang in 1988 defined plexiform fibrohistiocytic tumor (PFHT) as a distinctive entity. They described 65 cases (from 1965 to 1985) in children and young adults, with female and upper extremity predominance. These tumors were morphologically divided into 3 groups: fibroblastic, histiocytic (often with osteoclast-type giant cells), and mixed. Most tumors exhibited a plexiform and infiltrative arrangement of cells at the dermal/subcutaneous junction. Two fibroblastic PFHT had a metaplastic bone formation. Absence of cellular pleomorphism, low mitotic activity, dense hyalinization, hemorrhage, and chronic inflammation were observed. Vascular invasion was present in 1 recurrent, yet nonmetastatic, case. Tumors were negative for S100 protein, desmin, cytokeratin, factor VIIIrag, and lysozyme. Most patients were without disease up to 60 years after excision; 32 (37.5%) cases with follow-up recurred and 2 of those patients had regional lymph node metastasis at 9 and 36 months, respectively, yet there were no systemic metastases. In the interim, there have been additional studies on PFHT. We wanted to update the literature and add 66 new PFHT cases (1986-present) from the Armed Forces Institute of Pathology, since this seminal article, in honor of Dr Franz Enzinger. There were 37 men and 29 women; patient age ranged from 1 to 77 years (median, 20 years; 53% of patients were younger than 20 years). Twenty-eight cases occurred in the upper extremity (mostly forearm), 16 in lower extremity, 11 in trunk, 9 in head and neck, and 2 of unknown site. Although most cases were observed at the dermal/subcutaneous interface, 22 cases were predominantly dermal, and the rest predominantly subcutaneous, with 4 superficially involving skeletal muscle. Except for 12 predominantly dermal cases, most cases had an infiltrative growth pattern. Thirty-four cases were predominantly histiocytic, 16 predominantly fibroblastic, and the remaining 16 mixed. Two fibroblastic cases demonstrated the microfat cells (probably secondary to subcutis infiltration). All cases exhibited a plexiform growth pattern of small- to medium-sized nodules; 41 cases had giant cells, mainly osteoclast type, often the predominantly histiocytic type. The purely fibroblastic often had surrounding inflammation, 2 cases with marked inflammation. Perineural growth was observed in 5 cases, peri-Pacinian corpuscle growth in 2 cases, adnexal trapping in several, and, increased hyalinized collagen in 17 cases. Eight cases demonstrated focal myxoid change. Only 1 case, a histiocytic, had bone formation. Although increased cytologic atypia and mitotic activity were noted in a few cases, an atypical mitosis was only observed in 1 case. No cases demonstrated vascular or lymphatic invasion or necrosis. The tumors were generally positive for CD68 and SMA, occasionally for MSA, and negative for keratin, desmin, HMB45, S100 protein, and CD34. Overall, the findings were very similar to the original observations made by Dr Enzinger and his colleague, with the minor exceptions of roughly equal sex distribution (possibly due to timely referral bias), and additional morphologic features of myxoid change, adnexal sparing, increased inflammation, and microfat similar to recently described lipofibromatosis. The relationship between PFHT and cellular neurothekeoma is also explored.

Poster 079: A Review of 308 Oral Peripheral Nerve Sheath Tumors

Recently we have started the classification of all oral soft tissue tumors that have been accessioned at the Oral Pathology Laboratories, University of Minnesota, School of Dentistry. We reviewed first peripheral nerve sheath tumors (PNST). In general, oral PNSTs are not infrequent and they may be occasionally associated with syndromes such as neurofibromatosis types 1, schwannomatosis, and multiple endocrine neoplasia type 2B. In this study we included neurofibromas, schwannomas, palisading encapsulating neuromas (PEN), and traumatic neuromas. Also we tried to identify unusual types of PNSTs such as myxomas, perineuriomas, neurothekeomas, etc. Granular cell tumors, although they are of apparent neural origin, were not included this time. The archives from 1959 to 2006 included 410 cases of PNSTs. From these cases we have completed the evaluation of 308. Clinicodemographic data were available in all these cases as were histologic preparations. We performed descriptive statistics. Out of 308 cases of PNSTs, 141 (∼45.8%) were neurofibromas, 74 (∼24.0%) were traumatic neuromas, 48 were (∼15.6%) schwannomas, 39 (∼12.6%) were PEN and 2 (∼0.6%) were nerve sheath myxomas. In this first cataloguing we did not include a potential case of perineurioma since the immunohistochemical evaluation is not performed yet. There were no confirmed cases of neurothekeomas. Among the 141 cases of neurofibromas, 85 (∼60.3%) patients were females and 56 (∼39.7%) males. Age ranged from 11-93 years with the mean of 41 years. The location was known for 139 cases. Specifically, 35 (∼25%) occurred in the palate, 28 (∼20%) on the mandibular gingiva, 19 (∼14%) in the tongue, 15 (∼11%) in the buccal mucosa, 12 (∼8.5%) on the maxillary gingiva, 8 (∼5.7%) on the lower lip, 7 (∼5%) in the mandible, 4 (∼3%) in the retromolar mucosa, 3 (2%) in the upper lip, 2 (∼1%) in the floor of the mouth, and 2 (∼1%) in the maxilla. Among traumatic neuromas, 47 (∼63.5%) patients were females and 27 (∼36.5%) males. Age ranged from 5-90 years with a mean of 41 years. The location was known for 72 cases. Specifically, 23 (∼31%) were found in the tongue, 22 (∼30%) in the lower lip, 8 (∼11%) in the buccal mucosa, 6 (∼8%) in the palate, 3 (∼4%) in the mandibular gingiva, 3 (∼4%) in the upper lip, 2 (∼3%) in the maxillary gingiva and 1 (∼1%) on the floor of mouth. Among 48 schwannomas, 19 (∼39.6%) patients were females and 29 (∼60.4%) were males. Age ranged from 9-71 with a mean 31 years. The location was known for all cases. Specifically, 13 (∼27%) found in the tongue, 9 (∼19%) in the mandible, 5 (∼11%) in the mandibular gingiva, 5 (∼11%) in the lower lip, 4 (∼8%) in the upper lip, 4 (∼8%) in the palate, 4 (∼8%) in the buccal mucosa, 3 (∼6%) on the floor of mouth and 1(∼2%) in the maxillary gingiva. Among 39 PEN, 12 (∼30.7%) were females and 27 (∼69.2%) males. Age ranged from 20-71 year with a mean of 47 years. The location was known for 38 cases. Specifically, 22 (∼56%) found in the palate, 5 (∼13%) in the tongue, 4 (∼10%) in the maxillary gingiva, 4 (∼10%) in the upper lip, 2 (∼5%) in the lower lip and 1 (∼3%) in the maxilla. Of the two nerve sheath myxoma cases both patients were female. Also, among these peripheral nerve sheath tumors there were three hyperplastic neuromas that occurred in patients with MEN 2B. Histologically, most neurofibromas were solitary and showed typical histologic characteristics. Seven patients with solitary neurofibromas had neurofibromatosis type 1. Eleven neurofibromas were intraneural and 12 had a plexiform pattern with 3 of the 12 patients having a history of neurofibromatosis. Since plexiform neurofibromas are seen mostly in association with neurofibromatosis we tried to inquire additional patient information. Among schwannomas we identified 6 cases that were classified as plexiform. None of these patients had schwannomatosis. The above study represents the largest series of oral peripheral nerve sheath tumors.

Atypical cellular neurothekeoma – a diagnosis to be aware of

We present a rare case of atypical cellular neurothekeoma arising in the area of a previous nose piercing on the ala of a 34-year-old female. Neurothekeoma is a benign tumour of probable nerve sheath origin. The cell of origin for neurothekeoma is still unknown but most ultrastructural and immunohistochemical studies have favoured the Schwann cell perineurium or fibroblasts. A similar but distinct, more cellular variant with a less prominent myxoid component, was termed cellular neurothekeoma and, unlike myxoid neurothekeoma, the cellular variety generally lacks immunoreactivity to most neuronal markers. Atypical cellular neurothekeoma is characterised by the following features: large size of up to 6 cm, penetration into subcutaneous fat and or muscle, diffusely infiltrating borders, vascular invasion, a high mitotic rate and marked cytological pleomorphism. In this report we provide a review of the relevant literature and describe the clinical, histological and immunohistochemical features of an atypical cellular neurothekeoma excised from the ala nasi of a 34-year-old female, a hitherto unreported lesion in the plastic surgery literature.

Nerve Sheath Myxoma of the Gingiva: Report of a Rare Case and Review of the Literature

Nerve sheath myxoma (NSM) is an extremely rare benign neoplasm in the oral cavity. This paper describes the first case, to our knowledge, of NSM in the gingival mucosa of an 84-year-old female patient. Intraoral examination revealed a painless and well-defined nodule in the lingual gingival mucosa of the right mandibular lateral incisor, which measured approximately 1.0 cm in diameter. The lesion was fully excised under local anesthesia, without intercurrences. Hematoxylin and eosin staining was performed in 5-microm sections for histopathologic analysis. Immunohistochemical reactions against vimentin and S-100 protein were carried out in 3-microm histologic sections in accordance with manufacturers' instructions. The patient's medical history and an extraoral exam did not reveal other abnormalities. The patient wore a removable partial denture in the affected area. A trauma-induced gingival hyperplasia was the main diagnostic hypothesis. Microscopically, the lesion was composed of an abundant myxoid matrix and stellated and spindle-shaped cells arranged in lobules separated by fine fibrous septa. The cells presented strong positivity for vimentin and S-100 protein. According to the histopathologic and immunohistochemical features, the diagnosis of NSM was established. After 9 months of treatment, no signs or symptoms of recurrences have been observed. Although NSM is an extremely rare oral tumor, it should be considered in the clinical differential diagnosis of gingival nodules.

Neurothekeoma: An Analysis of 178 Tumors With Detailed Immunohistochemical Data and Long-term Patient Follow-up Information

This report describes the clinicopathologic findings in 176 patients who presented with 178 tumors currently referred to as neurothekeomas. Our study group included 64 males and 112 females, ranging from 20 months to 85 years old at the time of their first surgical procedure (median age: 17 y). Twenty-four percent of patients were <or=10 years of age and only 20% of patients were >or=30 years of age at initial diagnosis. The patients typically presented with a solitary, superficial, slow-growing, and relatively asymptomatic mass in the 0.3 to 2.0 cm size range. One patient had multiple tumors. More than 75% of the lesions involved the head (n=63), upper extremities (n=44), and shoulder girdle (n=27) regions. The tumors were evident a few weeks to 4 years (median duration: approximately 7 mo) before surgical resection was sought. Histologically, the lesions involved the dermis and/or subcutis, and they formed multinodular masses with varying amounts of myxoid matrix and peripheral fibrosis. On the basis of the amount of myxoid matrix, the tumors were subclassified as cellular (n=63), mixed (n=67), or myxoid (n=48). All cases had spindled and epithelioid mononuclear neoplastic cells with relatively abundant cytoplasm and indistinct cell borders. The majority of cases also had occasional multinucleated tumor cells. The lesional cells had a strong tendency for whorled growth, and oftentimes, focal fascicular growth was also present. Nuclear atypia was minimal in 62 cases, mild in 73 cases, at least focally moderate in 41 cases, and focally marked in 2 cases. Mitotic activity ranged from 0 to 124 mitotic figures/25 wide-field high power fields (WHPFs) (median mitotic count: 4 mitotic figures/25WHPFs). Twenty-five lesions had >10 mitotic figures/25WHPFs. A total of 16 cases (9%) had atypical mitotic figures. Osteoclastlike giant cells were detected in 39% of cases. Immunoreactivity was typically present for vimentin, NKI/C3, CD10, microphthalmia transcription factor, and PGP9.5, and focal reactivity was sometimes noted for smooth muscle actin and CD68. All tumors tested were negative for S100 protein, glial fibrillary acidic protein, and Melan A. The overwhelming majority of cases had involvement of the tissue margins. A complete follow-up record is available for 71 patients (40.3%) with follow-up intervals ranging from 3 years 2 months to 34 years 9 months (median: 17 y 9 mo). Limited or incomplete follow-up information is also available for an additional 14 patients with follow-up intervals ranging from weeks to approximately 10 years (median: 5 mo). Regrowth of tumor after biopsy or local excision was reported in 13 patients, one of whom had 2 recurrences. However, because of the nature of our consultation practice and a tendency for clinicians to specifically send us cases with a complex clinical course, this is believed an overestimation of the true recurrence rate. Neurothekeomas are morphologically and immunohistochemically distinct from true nerve sheath myxomas. An origin from fibroblastic cells with the ability to differentiate into myofibroblasts and a tendency to recruit histiocytic cells is postulated.

Unusual Benign Myxoid Nerve Sheath Lesion: Myxoid Palisaded Encapsulated Neuroma (PEN) or Nerve Sheath Myxoma With PEN/PEN-like Features?

A 38-year-old woman had a polypoid nodule on her scalp. The lesion histopathologically demonstrated an extensive myxoid lobular lesion associated with a nonmyxoid and cellular area in the peripheral area of the lesion. The features of the peripheral cellular area resembled those of palisaded encapsulated neuroma (PEN). Most of the lesion was myxoid, with a large lobule in which several thin fibrous septa were present, dividing it into smaller lobules. The myxomatous area was composed of spindle cells or stellate cells with elongated cytoplasmic processes. There was a loose cellular network with a reticular and netlike network pattern or a lamellar pattern. From the immunohistochemical findings, as well as the histopathologic features, the whole lesion was thus considered to be a PEN, whereas the main, myxoid, lobular lesion was thought to have been caused by myxoid changes within a PEN, namely, myxoid PEN. It cannot be completely ruled out, however, that this case could be that of a nerve sheath myxoma with a PEN/PEN-like lesion. Thus, the present case may suggest that PEN can show extensive myxoid change or may demonstrate a relationship between PEN and nerve sheath myxoma.

Cellular Neurothekeoma: Detailed Characterization in a Series of 133 Cases

Cellular neurothekeomas are distinctive benign cutaneous tumors of uncertain histogenesis. As relatively few cases have been reported, their clinical features and morphologic spectrum remain incompletely defined, and the significance of atypical histologic features is uncertain. This study examined the clinicopathologic and immunohistochemical features of 133 cellular neurothekeomas received between 1987 and 2003. There was a 1.8:1 female predominance, with a mean age of 25 years (84% <40 y). Mean tumor size was 1.1 cm (range: 0.3 to 6 cm; 90% <2 cm). The tumors arose most often on the upper limb (35%) or head and neck (33%). Fifty-two percent of the tumors were limited to the dermis, and 48% also involved superficial subcutaneous tissue. In 30% of cases, neurothekeoma was suggested by the referring pathologist; the most common other diagnoses offered were plexiform fibrohistiocytic tumor, benign fibrous histiocytoma, and a low-grade sarcoma. Histologically, most cases were poorly marginated; 33 (25%) infiltrated fat, and 10 (8%) entrapped skeletal muscle (all but 1 situated on the face). Nearly all tumors had a lobulated or micronodular architecture and were composed of nests and bundles of epithelioid to spindled cells with palely eosinophilic cytoplasm, often separated by dense hyaline collagen; 17 (13%) showed focally sheetlike areas, and 5 (4%) were notably plexiform. Myxoid stroma was observed in 38 (29%) tumors; 11 (8%) were predominantly myxoid. Five (4%) showed marked stromal hyalinization. Osteoclastic giant cells were seen in 20 (15%) cases. The mean mitotic rate was 3 per 10 high power fields; 28 (21%) had > or =5 per 10 high power fields. Most tumors showed mild cytologic atypia in the form of nuclear variability and small nucleoli; 33 (25%) contained notably pleomorphic cells. All tumors were reactive for NKI-C3, 110/123 (89%) expressed neuron-specific enolase, 73/127 (57%) showed at least focal staining for smooth muscle actin, and only 1 was focally desmin positive. All tumors were negative for S-100 protein. Follow-up ranged from 5 to 146 months (mean 44 mo). Ten tumors recurred locally (7 situated on the face), after a mean of 18 months; tumor had been marginally excised or had involved excision margins in all cases with available information. No other clinical or pathologic features correlated with recurrence. Cellular neurothekeomas have a predilection for the upper limbs and head and neck of pediatric and young adult females and rarely recur following incomplete excision. There is no good evidence that these lesions show nerve sheath differentiation and the nomenclature will likely change when the tumor cell lineage is better defined. Atypical histologic features (including pleomorphism, infiltration of subcutis, and a high mitotic rate) seem to have no clinical significance.

Cellular Neurothekeoma Treated with Mohs Micrographic Surgery

Cellular Neurothekeoma Treated with Mohs Micrographic Surgery

Cellular Neurothekeoma Treated with Mohs Micrographic Surgery

*Departments of Dermatology and Mohs Surgery, Bend Memorial Clinic, Bend, Oregon †Departments of Billings Clinic, Billings, Montana Address correspondence and reprint requests to: Gerald E. Peters Jr., MD, Departments of Dermatology and Mohs Surgery, Bend Memorial Clinic, Bend, OR 97701, or e-mail: [email protected]. Gerald E. Peters Jr., MD, and Michael Wentzell, MD, have indicated no significant interest with commercial supporters.

Neurothekeoma of the sciatic nerve

Neurothekeoma, also known as nerve sheath myxoma, perineural myxoma and plexiform myxoma, is a rare benign neoplasm of presumed nerve sheath origin. This tumour typically presents as a slowly enlarging painless cutaneous swelling most commonly in female adolescents in the head and neck region or upper limb. Nerves in the dermis are more frequently involved than those in the subcutaneous tissue. It rarely affects subfascial peripheral nerves or the central nervous system. Of the 150 cases published since its first description in 1969, three cases involved deep peripheral nerves in the hand. To the best of our knowledge a neurothekeoma affecting a deep peripheral nerve of the lower limb has not been reported. We present such a case involving the sciatic nerve with significantly larger size compared with previously described cases.

Chromosomal imbalances and NF2 mutational analysis in a series of 10 spinal nerve sheath myxomas

To report the demographic, clinical and molecular profile of a series of intraspinal nerve sheath myxomas. Nerve sheath myxomas are diagnostically challenging, mainly cutaneous spindle cell neoplasms exhibiting Schwann cell differentiation. They are frequently mistaken for neurothekeomas and their genetic features are essentially unknown. Ten spinal nerve sheath myxomas with a preferential location in the lumbar spine (70%) were investigated. Presenting symptoms consisted of sciatic pain (100%), muscle weakness and paraesthesia (60% each). Intraoperatively, all tumours were attached to a spinal nerve. Chromosomal imbalances by comparative genomic hybridization were found in 8/10 cases, consisting of -22q (80%) and -19 (30%). Polymerase chain reaction analysis of the NF2 gene (exons 1-16) revealed two tumours with mutations in exon 8 and 14, respectively. Although these 10 nerve sheath myxomas exhibited Schwann cell differentiation and frequently showed loss of chromosome 22q typically encountered in peripheral nerve tumours, only two cases demonstrated mutations of the NF2 gene. This may indicate involvement of other tumour suppressor genes on 22q in nerve sheath myxomas and shows that they are more closely related at the molecular level to sporadic schwannomas, underscoring the presumption that they are true nerve sheath tumours.

Facial neurothekeoma in a 10-year-old child

Facial neurothekeoma in a 10-year-old child

Nerve Sheath Myxoma: A Clinicopathologic and Immunohistochemical Analysis of 57 Morphologically Distinctive, S-100 Protein- and GFAP-Positive, Myxoid Peripheral Nerve Sheath Tumors With a Predilection for the Extremities and a High Local Recurrence Rate

Nerve Sheath Myxoma: A Clinicopathologic and Immunohistochemical Analysis of 57 Morphologically Distinctive, S-100 Protein- and GFAP-Positive, Myxoid Peripheral Nerve Sheath Tumors With a Predilection for the Extremities and a High Local Recurrence Rate

Benign nerve sheath myxoma (myxoid neurothekeoma) in the leg

Myxoid neurothekeoma is a rare benign cutaneous neoplasm of nerve sheath origin and is also called as benign nerve sheath myxoma. This entity is seen in head, neck and upper extremity and seldom on the lower limb. A myxoid neurothekeoma in the lower leg of a 33-year-old woman is described.

Dermal Nerve Sheath Myxoma

We report a rare case of a dermal nerve sheath myxoma of the left intranasal skin occurring in a 33-year-old female. A brief review of nerve sheath myxoma and a similar tumor, neurothekeoma, is presented.

Atypical neurothekeoma: a new case and review of the literature

Neurothekeoma is a rare neoplasm ascribed into the broad category of benign peripheral nerve sheath tumors. The atypical cellular variant of this neoplasm, showing a peculiar histological pattern, has been very rarely reported in literature. The clinical, histopathological and immunohistochemical profile of a new case of atypical cellular neurothekeoma in a 32-year-old woman is reported. The described neoplasm showed the histological features of atypical variant of cellular neurothekeoma with high-rate mitotic activity and deep penetration into subcutaneous fat. Because only few cases of atypical neurothekeoma have been reported in literature, clinical and morphological available data on this neoplasm are very few, and its prognosis remains uncertain; anyway, dermatologists should be aware of histological features of this neoplasm for which a complete surgical excision is recommended.

Cellular neurothekeoma with a plexiform morphology: a case report with a discussion of the plexiform lesions of the skin

Neurothekeoma is a rare benign dermal lesion that is commonly seen in children and teenagers. Despite its name, the true nature of this lesion is uncertain and controversial, particularly after the emergence of the cellular (spindle/epithelioid) variant. We describe the histological and immunohistochemical findings of a right thigh skin lesion in an 11-year-old girl. It consists of a dermal ill-defined plexiform mass composed of nests and fascicles of spindle cells with pale eosinophilic cytoplasm that lie within a sclerotic stroma. The immunohistochemistry shows diffuse reactivity to CD68, matrix metalloproteinase-II, CD10 and PGP9.5 with focal reactivity to CD57 and CD34. The lesion is negative for S100, factor XIIIa, smooth muscle markers and melanocytic markers. The features are compatible with a cellular variant of neurothekeoma with plexiform pattern that also exhibits an unusual pattern of fibrohistiocytic phenotype. Although such a lesion is benign, it has a wide but important differential diagnoses that are reviewed briefly together with a brief discussion about the origin of this rare entity.

Frequent Positive Staining With NKI/C3 in Normal and Neoplastic Tissues Limits Its Usefulness in the Diagnosis of Cellular Neurothekeoma

NKI/C3 originally was described as a marker for melanoma. Recently, it resurfaced as a marker to separate cellular neurothekeoma from other dermal tumors in the differential diagnosis. To determine the sensitivity and specificity of NKI/C3, we evaluated its staining pattern in 709 normal and neoplastic tissues, including 92 dermal tumors, using tissue microarrays and conventional sections. We found that although NKI/C3 is positive in only a few normal tissues, it stains a broad spectrum of neoplastic tissues. NKI/C3 is also positive in many dermal tumors of possible histiocytic origin, including juvenile xanthogranuloma (6/10), atypical fibroxanthoma (4/12), cellular fibrous histiocytoma (5/10), reticulohistiocytoma (3/6), and xanthoma (8/10). However, it is negative in epithelioid cell histiocytomas (0/7) and Langerhans cell histiocytosis (0/9). Given the wide spectrum of positive staining in morphologic mimics of cellular neurothekeomas, pathologists should be cautious when making this diagnosis based solely on positive staining with NKI/C3.