Fine Needle Aspiration Cytology of Neurothekeoma DO NOT DUPLICATE

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1 Fine Needle Aspiration Cytology of Neurothekeoma A Case Report Agustín Vaillo Vinagre, M.D., Antonia Gutiérrez Martín, M.D., Andrés Pérez Barrios, M.D., M.I.A.C., Nuria Alberti Masgrau, M.D., M.I.A.C., Claudio Ballestín Carcavilla, M.D., and Pedro De Agustín De Agustín, M.D., F.I.A.C. BACKGROUND: Neurothekeoma (NT) is a rare, benign neoplasm of soft parts with a distinctive histologic appearance. To our knowledge, the cytologic findings have not been described before. We present a case of NT with the cytologic features on fine needle aspiration cytology (FNAC). CASE: A 54-year-old female presented with a circumscribed nodule in the left breast. The lesion was evaluated by FNAC. The smears showed an abundant, metachromatic, myxoid matrix with fusiform and epithelioid cells, some binucleated or multinucleated, loose or in groups and sometimes forming concentric whorls. The lesion was removed, and the diagnosis of NT was made after histopathologic study. CONCLUSION: NT is an extremely rare neoplasm in the mammary region. Fusiform and epithelioid cells arranged in concentric whorls in a myxoid tumor of soft The presence of fusiform and epithelioid cells in concentric whorls in a myxoid tumor of soft tissue is a characteristic feature and can suggest the possibility of NT. tissue are a distinctive characteristic of this neoplasm and can suggest the diagnosis. (Acta Cytol 2003;47: ) Keywords: neurothekeoma, nerve sheath tumors, soft tissue neoplasms, aspiration biopsy, myxoid tumors. In 1969, Harkin and Reed 9 defined nerve sheath myxoma (NSM) as a rare, multilobulated neoplasm arising in the endoneurium of the peripheral nerves and composed of fusiform or stellate cells within an abundant, mucoid matrix. In 1980, Gallager and Helwig, 7 in a series of 53 cases, introduced the term neurothekeoma (NT) to describe a neoplasm with characteristics similar to those of NSM. Since then, both terms have been used interchangeably in many publications. Recently, Scheithauer et al 19 differentiated both le- From the Cytology Unit, Department of Pathology, University Hospital 12 de Octubre, Madrid, Spain. Drs. Vaillo and Gutierrez are Residents, Department of Pathology. Drs. Pérez Barrios and Alberti are Fellows, Cytology Unit, Department of Pathology. Dr. De Agustín is Head, Cytology Unit, Department of Pathology. Dr. Ballestín is Fellow, Department of Pathology. Address correspondence to: Andrés Pérez Barrios, M.D., M.I.A.C., Department of Pathology, University Hospital 12 de Octubre, Ctra Andalucía Km , Madrid, Spain. Financial Disclosure: The authors have no connection to any companies or products mentioned in this article. Received for publication February 5, Accepted for publication May 23, /03/ /$19.00/0 The International Academy of Cytology 485

2 486 Vinagre et al sions on the basis of the immunohistochemical and ultrastructural findings. They consider NSM a multilobulated spindle cell neoplasm, predominantly myxoid, showing schwann cell differentiation, while the term NT is used for less myxoid and more cellular lesions with numerous epithelioid cells, lacking this phenotype. It is a benign neoplasm. In the two largest series, covering 123 cases, 7,17 only 3 recurrences were noted, presumably from incomplete resection. Metastasis and malignant forms have not been reported. Complete excision is curative. Case Report A 54-year-old female presented with a painless, subcutaneous nodule in the upper region of the left breast. The lesion was well demarcated, measuring 3 cm in greatest dimension. The patient was asymptomatic, and her medical history was noncontributory. Fine needle aspiration cytology was performed, obtaining material with a mucoid appearance. Cytologic Findings Two alcohol-fixed and one air-dried smear were stained by the Papanicolaou and May-Grünwald- Giemsa method, respectively. The smears had mild to moderate cellularity depending on the examined zone, with numerous single cells and clusters embedded in an abundant, mucoid matrix, which showed metachromasia with Giemsa stain (Figure 1). Vascular component was not observed in the background. The cellular morphology was variable. Some cells were fusiform, with elongated, bipolar Figure 2 Spindle cells with round to ovoid nuclei (Papanicolaou stain, 400). cytoplasm and plump nuclei (Figure 2). Other cells were epithelioid, with wide, homogeneous cytoplasm, occasionally vacuolated and with fine cytoplasmic processes. The epithelioid cells had central or eccentric nuclei with smooth nuclear membranes, granular chromatin and inconspicuous nucleoli. Many of these cells were binucleated or multinucleated. Some cells showed hyperchromatic nuclei. Mitoses were not identified. Many of the cellular groups had a distinctive appearance, with fusiform and epithelioid cells arranged in concentric whorls (Figure 3). Occasional lymphocytes and mast cells were also seen. Immunohistochemical study with cytokeratins was negative, and an epithelial phenotype was ruled out. The findings were Figure 1 Aspirate smear showing a mucoid matrix with whorled groups (Papanicolaou stain, 40). Figure 3 Spindle to epithelioid cells arranged in concentric whorls (Papanicolaou stain, 200).

3 Volume 47, Number 3/May June FNAC of Neurothekeoma in accordance with a mesenchymal tumor of indeterminate aggressiveness, and removal of the lesion was recommended. Histopathologic Findings On gross examination the mass was well demarcated, measuring 4 2, 6 2 and 4 cm in greatest dimensions. The cut surface had a lobulated appearance and was gray-white, with a mucoid appearance in wide zones. The lesion occupied the reticular dermis and extended with a pushing margin into subcutaneous tissue. There was a grenz zone of dermis sparing between the epidermis and tumor. The neoplasm was well circumscribed and composed of various-sized lobules surrounded by a narrow rim of collagen (Figure 4). Some lobules contained spindle and plump, stellate cells within an abundant, myxoid stroma. Other lobules showed great cellularity, containing fusiform and epithelioid cells, sometimes in whorls (Figure 5). The epithelioid cells had wide, eosinophilic cytoplasm, occasionally vacuolated. Some of these cells were binucleated or multinucleated, and occasionally they had hyperchromatic nuclei. Mitoses were not observed. Lymphoid cells were present in the vascular fibrous septa. Occasional mast cells were noted within the lobules as well as in the fibrous septa. With immunohistochemistry the cells showed positivity for vimentin and were negative for S-100 protein, Leu-7, actin and desmin. Epithelial membrane antigen was negative in the septa as well as neoplastic cells. Figure 4 NT. Well-circumscribed and lobulated neoplasm occupying the thickness of the dermis (hematoxylin and eosin, 40). Figure 5 Characteristic whorled nests with spindle and epithelioid cells (hematoxylin and eosin, 200). Discussion NSM and NT have been described under a variety of terms, including pacinian neurofibroma, 13 myxomatous perineurioma, 22 bizarre cutaneous neurofibroma, 12 plexiform myxoma, 1 cutaneous lobular neuromyxoma 10 and perineurial myxoma. 17 These tumors involve the skin of the hands, 2,5,10,22 arms, 6 back, 2,8 shoulder, 7 face and neck. 6,8 Less frequently they affect the skin of the trunk and breast. 19 They also have been found in extracutaneous locations, such as intraspinal space, 15 intracranial space, 16 external auditory canal 24 and oral mucosa. 11,14,18,20,21,23 Scheithauer et al 19 differentiated between NSM and NT on the basis of the histopathologic, immunohistochemical and ultrastructural findings. They consider NSM a multilobulated, myxoid neoplasm composed of fusiform and stellate cells. Immunohistochemically, the tumor cells are S-100 positive, 2,4-6,11,15,21,23 and ultrastructural study shows interdigitating processes and continuous or discontinuous external lamina. 2,3,5,15,21,22 Some use the term NT for less myxoid and more cellular lesions, formed by fusiform and epithelioid cells that, in contrast to NSM, are negative for S-100 and ultrastructurally do not exhibit Schwann cell differentiation, showing fibroblast and undifferentiated polygonal cells. 3,4 To our knowledge, the cytologic findings of NT have not been described before. Our case showed a mesenchymal proliferation with moderate cellularity; abundant, metachromatic myxoid matrix;

4 488 Vinagre et al fusiform and epithelioid cells in variable proportions; binucleated and multinucleated cells; hyperchromatic nuclei; and numerous cells loose or in groups, occasionally forming characteristic concentric whorls. With the above cytologic features, a number of differential diagnoses have to be considered in cytology of the breast, such as colloid carcinoma, metaplastic carcinoma and phyllodes tumor. Colloid carcinoma presents numerous capillaries embedded in abundant, mucoid material and small, cohesive groups of uniform, malignant epithelial cells. Metaplastic carcinoma can have a mesenchymal chondrosarcomatous component or wide myxoid zones in the aspirates. However, it contains epithelial cells with marked nuclear atypia. In doubful cases or those with a scarce epithelial component, positivity for epithelial markers on immunohistochemistry can guide one to the correct diagnosis. Phyllodes tumor can have an abundant mesenchymal component with variable cytologic atypia, depending on the malignant grade of the tumor, but the presence of benign ductal cells or bipolar, naked nuclei in the smears suggest the diagnosis. Other myxoid tumors of soft tissue should be considered in the cytologic differential diagnosis, particularly intramuscular myxoma, myxoid neurofibroma and malignant fibrous histiocytoma (MFH). Their cytologic features have been documented in several papers. Intramuscular myxoma possesses hypocellular smears with plump, fusiform and stellate cells as well as poor vascularity. Myxoid neurofibroma is characterized by groups of bland, fusiform cells and scattered mast cells embbeded in myxoid material, which can show metachromasia. MFH has moderate cellularity, showing fibroblastlike and histiocytelike cells, typical curved vessels and variable pleomorphism, depending on the grade. However, in none of these tumors is the presence of fusiform and epithelioid cells arranged in whorls a feature. Another, extremely rare entity that should be included in the differential diagnosis is extracranial meningioma because the cells may also present a whorl formation. In contrast to NT, the cells have round to oval, uniform nuclei and can have psammoma bodies and nuclear pseudoinclusions. An abundant, metachromatic, myxoid matrix is not characteristic. NT should be considered among the differential diagnoses of myxoid tumors of soft tissue. Although experience with the cytologic findings is still limited, fine needle aspiration cytology can make a valuable contribution to the diagnosis. The presence of fusiform and epithelioid cells in concentric whorls in a myxoid tumor of soft tissue is a characteristic feature and can suggest the possibility of NT. This cytologic feature is distinctive and correlate with histology. References 1. Allen PW: Myxoid tumors of soft tissue. Pathol Annu 1980; 15: Angervall L, Kindblom LG, Haglid K: Dermal nerve sheath myxoma: A light and electron microscopic, histochemical and immunohistochemical study. Cancer 1984;53: Argenyi ZB, Kutzner H, Seaba MM: Ultrastructural spectrum of cutaneous nerve sheath myxoma/cellular neurothekeoma. J Cutan Pathol 1995;22: Argenyi ZB, LeBoit PE, Santa Cruz D, Swanson PE, Kutzner H: Nerve sheath myxoma (neurothekeoma) of the skin: Light microscopic and inmunohistochemical reappraisal of the cellular variant. J Cutan Pathol 1993;20: Blumberg AK, Kay S, Adelaar RS: Nerve sheath myxoma of digital nerve. Cancer 1989;63: Fletcher CD, Chan JK, McKee PH: Dermal nerve sheath myxoma: A study of three cases. Histopathology 1986;10: Gallager RL, Helwig EB: Neurothekeoma: A benign cutaneous tumor of neural origin. Am J Clin Pathol 1980;74: Goldstein J, Lifshitz T: Myxoma of the nerve sheath: Report of three cases, observations by light and electron microscopy and histochemical analysis. Am J Dermatopathol 1985;7: Harkin JC, Reed RJ: Myxoma of the nerve sheath. In Tumors of the Peripheral Nervous System: Atlas of Tumor Pathology. Second series, fascicle 3. Washington, DC, Armed Forces Institute of Pathology, 1969, pp Holden CA, Wilson-Jones E, MacDonald DM: Cutaneous lobular neuromyxoma. Br J Dermatol 1982;106: Katsourakis M, Kapranos N, Papanicolaou SI, Patrikion A: Nerve sheath myxoma (neurothekeoma) of the oral cavity: A case report and review of the literature. J Oral Maxillofac Surg 1996;54: King DT, Barr RJ: Bizarre cutaneous neurofibroma. J Cutan Pathol 1980;7: MacDonald DM, Wilson-Jones E: Pacinian neurofibroma. Histopathology 1977;1: Mincer HH, Spears KD: Nerve sheath myxoma in the tongue. Oral Surg Oral Med Oral Pathol 1974;37: Paulus W, Jellinger K, Perneczky G: Intraspinal neurothekeoma (nerve sheath myxoma): A report of two cases. Am J Clin Pathol 1991;95: Paulus W, Warmuth-Metz M, Sorensen N: Intracranial neurothekeoma (nerve sheath myxoma): Case report. J Neurosurg 1993;79: Pulitzer DR, Reed RJ: Nerve-sheath myxoma (perineurial myxoma). Am J Dermatopathol 1985;7:

5 Volume 47, Number 3/May June FNAC of Neurothekeoma 18. Rodriguez-Peralto JL, El Naggar AK: Neurothekeoma of the oral cavity: Case report and review of the literature. J Oral Maxillofac Surg 1992;50: Scheithauer BW, Woodruff JM, Erlandson RA: Nerve sheath myxoma and neurothekeoma. In Tumors of the Peripheral Nervous System: Atlas of Tumor Pathology. Third series, fascicle 24. Washington, DC, Armed Forces Institute of Pathology, 1999, pp Sist TC, Green GW: Benign nerve sheath myxoma: Light and electron microscopic features of two cases. Oral Surg Oral Med Oral Pathol 1979;47: Tiffe JC, Pulitzer DR: Nerve sheath myxoma of the oral cavity: Case report and review. Oral Surg Oral Med Oral Pathol 1996;82: Webb JN: The histogenesis of nerve sheath myxoma: Report of a case with electron microscopy. J Pathol 1979;127: Yamamoto H, Kawana T: Oral nerve sheath myxoma: Report of a case with findings of ultrastructural and immunohistochemical studies. Acta Pathol Jpn 1988;38: Youngs R, Kwok P, Hawke M, Hyams VJ: Neurothekeoma (peripheral nerve sheath myxoma) of the external auditory canal. J Otolaryngol 1989;18:90 93