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Year : 2012  |  Volume : 55  |  Issue : 4  |  Page : 598-600
Perineurial soft tissue tumors: A tale of three cases exemplifying underdiagnoses of these "uncommon" tumors

Department of Pathology, Tata Memorial Hospital, Parel, Mumbai, Maharashtra, India

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Date of Web Publication4-Mar-2013

How to cite this article:
Rekhi B. Perineurial soft tissue tumors: A tale of three cases exemplifying underdiagnoses of these "uncommon" tumors. Indian J Pathol Microbiol 2012;55:598-600

How to cite this URL:
Rekhi B. Perineurial soft tissue tumors: A tale of three cases exemplifying underdiagnoses of these "uncommon" tumors. Indian J Pathol Microbiol [serial online] 2012 [cited 2022 May 19];55:598-600. Available from: https://www.ijpmonline.org/text.asp?2012/55/4/598/107847


Peripheral nerve sheath tumors (PNSTs) include schwannomas that arise from schwann cells; neurofibromas that are composed of an admixture of schwann cells, fibroblasts, and endoneurial cells, and perineuriomas that display perineurial differentiation. [1] On immunohistochemistry (IHC), schwannomas are diffusely S-100P positive, neurofibromas show variable S-100P and CD34 positivity, and perineuriomas are diffusely epithelial membrane antigen (EMA) positive. [1] PNSTs with two components, including hybrid schwannoma/perineuriomas, have also been objectively identified with IHC and ultrastructure. [1],[2] Recently, malignant peripheral nerve sheath tumor MPNST in the setting of hybrid perineurioma/schwannoma has been documented. [3]

Herein, three unusual soft tissue tumors displaying perineurial differentiation are described, including IHC results. Various antibodies utilized have been enlisted in [Table 1].
Table 1: List of various antibody markers utilized in the present cases

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A 50-year-old gentleman referred with a soft tissue mass in his left thigh. Four paraffin blocks and hematoxylin and eosin (H and E) stained slides from the resected mass were reviewed.

Microscopy showed a circumscribed, non-encapsulated tumor comprising spindle-shaped cells with wavy, elongate nuclei and cytoplasmic processes, arranged in fascicles and whorls, embedded in a dense collagenous stroma with focal myxoid areas. There were no mitotic figures, thrombosed/hyalinized vessels, nerve structures, Antoni A areas, or coagulative tumor necrosis. Immunohistochemically, tumor cells were diffusely positive for EMA, vimentin, focally for CD34, while negative for S-100P, smooth muscle actin (SMA), desmin, h-caldesmon, and β-catenin. Diagnosis of sclerosing perineurioma was offered.

A 22-year-old lady referred with a paraspinal mass. Her preoperative imaging revealed a heterogeneously enhancing mass measuring 8.4 × 7.3 × 9.5 cm in the suprarenal region, in close proximity to the superior part of left psoas and abutted the spleen and left kidney, displacing it and pancreas, and was seen abutting the aorta medially, reaching the pre- and paravertebral region. She underwent an excision elsewhere and five paraffin blocks were submitted to us for with a diagnosis of neurofibroma versus low-grade MPNST. As per referral notes, grossly a well-circumscribed, encapsulated, lobulated pale white mass was received weighing 329.4 g and measuring 11 × 6 × 5 cm. Cut surface was pale white with mucoid areas. Adrenal gland weighed 227 g and measured 5.5 × 3 × 0.2 cm, and spleen weighed 227 g and measured 12 × 10 × 5 cm.

Microscopy showed a circumscribed, unencapsulated tumor with oval to spindly, slender nuclei and cytoplasmic processes, arranged in fascicles, whorls and neuroid/"onion-bulb-like" arrangements. There were no mitotic figures, thrombosed vessels, Antony A areas, or coagulative necrosis. Immunohistochemically, tumor cells showed alternate EMA positivity, especially in the spindly cells, and intranuclear S-100P positivity in oval cells. Diagnosis of hybrid schwannoma/perineurioma was offered. Sections from spleen showed congestion.

A 22-year-old lady referred with a thigh lesion. Two representative paraffin blocks from the resection that she underwent at another hospital were submitted.

Microscopy showed a focally circumscribed, unencapsulated spindle cell tumor composed of cells with slender nuclei arranged in fascicles and whorls. There were no significant mitotic figures, thrombosed blood vessels, neural structures, Antony A areas, or foci of coagulative necrosis.

Immunohistochemically, tumor cells alternately expressed S-100P, especially in plump cells, and EMA in slender cells with cytoplasmic processes. CD34 was focally positive. MIB1 highlighted 5-6% nuclei. Diagnosis of hybrid neurofibroma/perineurioma was offered [Figure 1]a-g.
Figure 1: Case 1 (a) Sclerosing perineurioma. Benign spindly cells in fascicles (H and E, ×400). (b) Sclerotic stroma (H and E, ×400). (c) Diffuse EMA positivity (also in inset) (DAB, ×400). (d) Case 2. Hybrid schwannoma/perineurioma. Spindly cells in whorls and fascicles. Inset: Perineurial cells. (H and E, ×200). Case 3: (e-g) Hybrid neurofibroma/perineurioma. Bland spindly cells in fascicles and whorls (H and E, ×200). Inset: Focal MIB1 positivity (DAB, ×200). (f) EMA positivity with alternate negativity (schwannian cells) (arrow heads) (DAB, ×200). (g) S-100P positivity (schwannian) (DAB, ×400)

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Rarity of perineurial tumors is compounded with a lower index of suspicion for diagnosis and lack of ancillary techniques in routine settings. [4] Perineurioma is a benign PNST, objectively diagnosed by IHC and/or ultrastructural analysis. [1],[5] Perineuriomas are intraneural and extraneural; the latter include soft tissue, sclerosing, and reticular subtypes. [6] The presented cases exemplify under-recognition of perineurial tumors. All three cases were referred as spindle cell tumors, including diagnosis of a PNST.

Microscopically, various differential diagnoses considered were fibromatosis and solitary fibrous tumor, especially in the first case; and neurofibroma, a low-grade fibromyxoid sarcoma, and dermatofibosarcoma (DFSP), especially in the third case, as previously reported. [6] Presence of slender nuclei with cytoplasmic processes was indicative of perineurial differentiation in all three tumors. IHC stains, including diffuse EMA positivity, reinforced perineurial differentiation. β-catenin negativity in the first case ruled out fibromatosis. CD34 has been found to be positive in some perineuriomas wherein lays a need to include additional stains and/or ultrastructural analysis for an objective diagnosis. Other IHC stains for diagnosing a perineurioma include claudin-1 Glut1, collagen Type 4, and CD56, in different studies. [6],[7] Hornick et al.[6] observed claudin-1 positivity in 21% perineuriomas, attributed to differences in techniques for antigen retrieval, in contrast to findings of Folpe et al. [7] EMA positivity has been noted in synovial sarcomas and some low-grade fibromyxoid sarcomas (LGFMS). The aforementioned histopathologic features ruled out these entities. Therapeutically, all cases underwent surgical excision.

To conclude, perineurial tumors display a histopathologic spectrum. Careful attention toward characteristic histopathologic features, with application of EMA, CD34, S-100P is vital for accurate diagnosis of PNSTs, especially those with suspected perineurial differentiation. Perineuriomas need to be distinguished from their mimics that include sarcomas such as LGFMS and DFSP.

   References Top

1.Scheithauer BW, Louis DN, Hunter S, Woodruff JM, Antonescu CR. Neurofibroma. In: Louis DN, Ohgaki H, Wiestler OD, Cavenee WK. editors. WHO Classification of Tumours of the Central Nervous System. Lyon, France: International Agency for Research on Cancer; 2007. p. 156-7.  Back to cited text no. 1
2.Hornick JL, Bundock EA, Fletcher CD. Hybrid schwannoma/perineurioma: Clinicopathologic analysis of 42 distinctive benign nerve sheath tumors. Am J Surg Pathol 2009;33:1554-61.  Back to cited text no. 2
3.Rekhi B, Jambhekar NA. Malignant transformation in a hybrid schwannoma/perineurioma: Addition to the spectrum of a malignant peripheral nerve sheath tumor. Indian J Pathol Microbiol 2011;54:825-8.  Back to cited text no. 3
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4.Macarenco RS, Ellinger F, Oliveira AM. Perineurioma: A distinctive and under recognized peripheral nervesheath neoplasm. Arch Pathol Lab Med 2007;131:625-36.  Back to cited text no. 4
5.Lazarus SS, Trombetta LD. Ultrastructural identification of a benign perineurial cell tumor. Cancer 1978;41:1823-9.  Back to cited text no. 5
6.Hornick JL, Fletcher CD. Soft tissue perineurioma: Clinicopathologic analysis of 81 cases including those with atypical histologic features. Am J Surg Pathol 2005;29:845-58.  Back to cited text no. 6
7.Folpe AL, Billings SD, McKenney JK, Walsh SV, Nusrat A, Weiss SW. Expression of claudin-1, a recently described tight junction-associated protein, distinguishes soft tissue perineurioma from potential mimics. Am J Surg Pathol 2002;26:1620-6.  Back to cited text no. 7

Correspondence Address:
Bharat Rekhi
Department of Pathology, Tata Memorial Hospital, Dr. E. B. Road, Parel, Mumbai
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.107847

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