Cellular neurothekeoma of the vulva, an unusual location

ARTICLE

Auteur(s) : Dina EL DEMELLAWY¹, Ahmed NASR², Ilan WEINRED³, Meagan KENNEDY⁴, Salem ALOWAMI⁵

¹Northern Ontario School of Medicine, William Osler health center, Department of Pathology and Laboratory Medicine, Brampton, Ontario, Canada
²Department of Pediatric Surgery, Toronto, Canada
³Pathology Department, University of Toronto, University Health Network, Toronto, Canada
⁴Pathology and Laboratory Medicine, Thunder Bay, Canada
⁵Pathology and Molecular Medicine, Hamilton, Canada

Cellular neurothekeoma (CN) is a rare benign cutaneous neoplasm of uncertain histogenesis. Nerve sheath, smooth muscle, and myofibroblastic origins have been suggested. CN usually presents as a single lump or swelling and is most commonly found in the upper body, particularly in young female adults. We report an unusual case. Knowing the vulva as a potential rare location of CN may avoid misdiagnosis and therefore guarantee the best management.

A two-year-old female infant presented with a single persistent lesion in the left labium majus with a stationary course. No other significant findings were noted. Simple excision of the lesion was performed.

Pathological examination of the lesion showed a well-defined subepidermal nodule measuring 1.3 × 1.0 cm with a firm homogenous grey-white cut surface. Microscopically, the lesion was well circumscribed, but non-encapsulated and formed of plexiform spindle cell proliferation involving the papillary, reticular dermis and subcutis (figure 1A). The proliferating cells showed uniform elongated and normochromic nuclei with tapered ends and pale cytoplasm (figure 1B). The surrounding stroma was collagenized (figure 1C). The epidermis was intact and papillomatous. Necrosis, atypia, pleomorphism, and mitosis were absent. Immunohistochemistry showed the lesional cells diffusely and strongly expressed collagen type IV (figure 1C) and Protein Gene Product (PGP 9.5) (figure 1D). They were negative for S100, Epithelial Membrane Antigen (EMA), Smooth Muscle Actin, Desmin, Smooth Muscle Myosin Heavy Chain, Cam 5.2, AE1/AE3, CD68, NSE, Melan A, CD34, Factor XIIIa, GFAP, and Neurofilament. The lesion was diagnosed as CN. The patient had a non-complicated recovery with no evidence of recurrence during the two-year follow-up.

In 1969, Harkin and Reed described an unusual myxoid tumor and named it myxoma of nerve sheath [1]. Gallagher and Helwig reported identical lesions as neurothekeomas [2]. Later, Barnhill and Mihm described CN [3]. Neurothekeomas are rare soft tissue tumors, initially thought to have three types: myxoid, cellular, and mixed. Myxoid neurothekeomas are considered to be of nerve sheath origin, as they show neural differentiation and S100 expression. CN lacks S100 expression and evidence of neural differentiation. CN is negative to all markers with the exception of Vimentin, PGP 9.5, and collagen type IV; hence, the consensus was that its histogenesis is uncertain [4]. Most ultrastructural and immunohistochemical studies have favored the Schwann cell perineurium or fibroblast to be the cell of origin of CN5. Some authors suggested that CN should be included under the “fibrohistiocytic” category [5].

The largest series in the literature described CN as showing female predominance, mean age of 25 years and more than 65% occurring in the upper limb or head and neck region. Most neurothekeoma cases follow a benign course, even in the presence of atypical findings. In our case, atypical findings were absent and though the lesion involved the surgical margins of excision, the patient was asymptomatic during the follow-up period. Generally, CN must be distinguished from certain benign and low-grade sarcomas, particularly those showing a plexiform pattern. Common soft tissue tumors of the vulva must also be excluded.

Histological and immunohistochemical features, with negativity for S-100 protein and HMB-45, allow differentiating CN from myxoid neurothekeoma, granular cell tumor and melanocytic tumors. Negativity for CD34 excludes cellular angiofibroma, angiomyofibroblastoma and dermatofibrosarcoma protuberans, which, in contrast to neurothekeoma, are CD34 positive. Aggressive angiomyxoma is actin- and desmin- positive and dermatofibroma is factor XIIIa-positive. The plexiform pattern and the spindling of the tumor cells, the collagenized stroma with absence of inflammatory cells, and the immuno-profile of the cells (CD68 negative and PGP9.5 positive) were diagnostic of CN.

Though plexiform fibrohistiocytic tumor and fibrous hamartoma of infancy show different immuno-profiles from CN, they represent the major differential diagnosis of the current case. Plexiform fibrohistiocytic tumor frequent occurs in children, adolescents, and young adults with a strong female predilection. It involves, preferentially, the upper extremity. Like neurothekeoma, plexiform fibrohistiocytic tumor has never been described in the vulva. Histologically, both tumors show a plexiform proliferation but, in contrast to neurothekeoma, plexiform fibrohistiocytic tumors show mononuclear histiocytic-like cells, multinucleated osteoclastic-like cells, and spindle fibroblast-like cells in variable proportions. The tumor cells express CD68 and smooth muscle actin. Fibrous hamartoma of infancy is a unique lesion of the subcutis and lower dermis. Most cases occur within the first year of life but, unlike cellular neurothekeoma, showing predilection for boys. The most common locations are the axillary region, upper arm, upper trunk, inguinal region, and external genital area. Histologically, the lesion shows well-defined bundles of dense and uniform fibrous connective tissue projecting into the fat, admixed with primitive mesenchyme. The latter is arranged in nests, concentric whorls or bands. Immunohistochemistry of the lesion shows positive staining with Vimentin and Actin.

We report a very rare case of neonatal vulvar CN. Awareness of the potential occurrence of CN in the vulva of a neonate is crucial to avoid misdiagnosis with other common and well-recognized lesions and tumors in this location. Correct diagnosis is important for proper management.

Acknowledgements

References

2 Gallagher RL, Helwig EB. Neurothekeoma: a benign cutaneous tumor of neural origin. Am J Clin Pathol 1980; 74: 759-65.

3 Barnhill RL, Mihm MC. Cellular neurothekeoma. Am J Surg Pathol 1990; 14: 113-20.

4 Laskin WB, Fetsch JF, Miettinen M. The “neurothekeoma”: immunohistochemical analysis distinguishes the true nerve sheath myxoma from its mimics. Hum Pathol 2000; 31: 1230-41.

5 Mahalingam M, Alter JN, Bhawan J. Multiple in head and neck. Multiple cellular neurothekeomas--a case report and review on the role of immunohistochemistry as a histologic adjunct. J Cutan Pathol 2006; 33: 51-6.