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Year : 2013  |  Volume : 9  |  Issue : 1  |  Page : 131-134

Perineurial malignant peripheral nerve sheath tumor in the setting of multiple soft tissue perineuriomas: A rare presentation of an uncommon tumor

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

Date of Web Publication10-Apr-2013

Correspondence Address:
Bharat Rekhi
Department of Pathology, Tata Memorial Hospital, Dr E.B. Road, Parel, Mumbai - 400 012
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0973-1482.110381

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 > Abstract 

Perineurioma is an uncommon soft tissue tumor with characteristic histological and immunohistochemical features. Herein, this tumor is presented within a rare clinical setting, in a 45-year-old gentleman, with multiple soft tissue swellings and a previous history of surgical excision of a thigh mass. Four years back, he developed multiple soft tissue tumor swellings for which he lately underwent multiple wide excisions, elsewhere that were reported as multiple dermatofibrosarcoma protuberans (DFSPs). Histopathological review of the thigh and axillary tumor showed a perineurioma (EMA+, S100-P-ve, CD34-ve, low MIB1), whereas the recurrent leg mass disclosed a high-grade perineurial malignant peripheral nerve sheath tumor (MPNST) (EMA+, CD56+, S100-P-, high MIB1, CD34-ve, p53+ve). Within four months of post-excision, he developed additional swellings, and died of respiratory insufficiency. This case forms the first documented case of perineurial MPNST with multiple, metachronous soft tissue perineuriomas. Available literature review of perineurial MPNSTs and diagnostic implications are discussed herewith

Keywords: Immunohistochemistry of sarcomas, malignant perineurioma, perineurial malignant peripheral nerve sheath tumor, perineurioma, peripheral nerve sheath tumors, uncommon soft tissue tumors

How to cite this article:
Rekhi B. Perineurial malignant peripheral nerve sheath tumor in the setting of multiple soft tissue perineuriomas: A rare presentation of an uncommon tumor. J Can Res Ther 2013;9:131-4

How to cite this URL:
Rekhi B. Perineurial malignant peripheral nerve sheath tumor in the setting of multiple soft tissue perineuriomas: A rare presentation of an uncommon tumor. J Can Res Ther [serial online] 2013 [cited 2021 Jul 25];9:131-4. Available from: https://www.cancerjournal.net/text.asp?2013/9/1/131/110381

 > Introduction Top

Peripheral nerve sheath tumors (PNST) include schwannomas that arise from Schwann cells; neurofibromas comprising schwann cells, fibroblasts and endoneurial cells and perineuriomas that display perineurial differentiation. [1] Lately, PNSTs with mixed components such as hybrid schwannomas/perineuriomas have been described. [2] Immunohistochemnically, schwannomas are diffusely S100-P positive, neurofibromas show variable S100-P and CD34 positivity and perineuriomas are diffusely epithelial membrane antigen (EMA) positive. [1]

Whereas the malignant counterpart, namely malignant peripheral nerve sheath tumors (MPNST) display variable schwannian differentiation, few MPNSTs with perineurial differentiation/perineurial MPNSTs/malignant perineuriomas have been documented, including none in the setting of multiple soft tissue perineuriomas. [3],[4],[5],[6],[7],[8]

 > Case Report Top

A 45-year-old gentleman referred to us with multiple soft tissue swellings over his body; a previous history of a surgical excision of a painless soft tissue mass over his right thigh, 13 years ago. Four years back, he developed multiple soft tissue swellings, including in right knee; right lower leg that recurred; right axillary region; over abdominal wall and in his left biceps, unassociated with numbness or restricted mobility. He underwent radiological investigations and multiple surgical excisions of his right thigh, right leg and chest wall masses, elsewhere that were reported as multiple dermatofibrosarcoma protuberans (DFSPs).

Radiological findings

Preoperative ultrasonogram thigh showed a well-defined, subcutaneous heterogenous lesion measuring 7.9 × 6.1 × 5.7 cm, with an irregular wall and dense internal echoes along the lateral aspect of the middle right thigh. Chest radiograph and computed tomogram scan were normal.

Pathological findings:

As per referring laboratory notes, the thigh mass measured 20x9x5 cm, with a tumor measuring 8 × 7 × 4.5 cm; the leg soft tissue mass measured 10 × 8 × 6.6. cm, including tumor measuring 8 × 7 × 4 cm and the excised axillary soft tissue mass measured 7 × 5.5. × 4 cm, including tumor measuring 6 × 5 × 3.5 cm. Cut surfaces showed firm, grey-white, well-circumscribed tumors. Twenty Hematoxylin and Eosin (H and E) stained slides and 9 paraffin blocks from the tumor areas and cut margins were submitted for histopathological review.

Microscopically, the thigh and axillary tumors were well-circumscribed, unencapsulated, comprising spindly cells in a lamellar, whorling pattern (onion bulb-like), including focal perivascular whorls. The cells were uniform with thin, wavy nuclei and elongated cytoplasmic processes. Interspersed were rare mitotic figures, without any atypical forms. There were no areas showing 'Verocay bodies' or hyalinized vessels or tumor necrosis.

Tumor sections from the leg soft tissue mass, additionally displayed moderate to marked nuclear atypia, focal epithelioid change, moderate to abundant eosinophilic cytoplasm and prominent nucleoli. Mitoses ranged from 5-6/10 hpf, with few tumor giant cells and tumor necrosis.

On IHC, all three tumors were diffusely positive for vimentin and EMA (cytoplasmic and membranous positivity). S100-P was focally positive within two benign tumors and was negative in the malignant tumor. CD56 was positive in benign and malignant tumors. Smooth muscle actin (SMA) was focally positive in the malignant tumor. MIB1 highlighted 5-6% benign tumor nuclei and nearly 50% malignant tumor cell nuclei. P53 was negative in the benign tumors, but highlighted 60-70% malignant tumor nuclei. CD34, glial fibrillary acidic protein (GFAP), desmin and h-caldesmon were negative [Figure 1]a-e, [Figure 2]a-e, [Figure 3]a-f.
Figure 1: Soft tissue perineurioma. (a) Circumscribed tumor comprising spindle shaped cells in whorls and fascicles (H and E, × 100). Inset: Perivascular arrangement of spindle cells with slender nuclei (H and E, × 400). (b) Uniform spindly cells in whorls (onion bulb-like) and lamellar arrangement (H and E, × 200). Inset: Spindle cells with slender, benign nuclei and elongated cytoplasmic processes (H and E, × 400). (c) Diffuse EMA positivity. DAB × 200. Inset: Cytoplasmic and membranous EMA positivity. (DAB × 400). (d) Focal S100-P positivity within scattered polygonal cells. (DAB × 200). (e) Low MIB1. (DAB × 400).

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Figure 2: MPNST with perineurial differentiation. (a) Spindly tumor cells arranged in fascicles and whorls, exhibiting nuclear atypia, mitoses (circle), focal inclusions (thin arrow) and polygonal cells (thick arrow) (H and E, × 200). Inset: Slender tumor nuclei and elongated processes, reminiscent of perineurial differentiation (H and E,× 400). (b) Prominent mitoses (H and E,x400). (c) Focal myxoid degeneration (H and E,× 200). (d) Focal epithelioid differentiation within the tumor adjacent to necrosis (H and E, × 400). Inset: Epithelioid cells (H and E, × 400). (e) Areas of tumor necrosis (H and E, × 200).

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Figure 3: Immunohistochemical (IHC) results. (a) Diffuse vimentin positivity (DABx200). (b) Prominent areas exhibiting EMA positivity (DABx200). Inset: EMA highlighting cytoplasmic membrane and processes of spindly cells (Diaminobenzidine ×1000). (c) CD56 positivity (DABx400). (d) Focal SMA positivity (DABx200). (e) CD34 negativity (DABx400). (f) MIB1 highlighting 50% tumor nuclei (DABx400).

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Diagnosis of a high-grade perineurial MPNST, with free margins, in the setting of multifocal, metachronous soft tissue perineuriomas, was made. Subsequently, the patient developed additional swellings, pleural effusion and within four months died of respiratory failure. Cytological examination of pleural fluid was not done.

 > Discussion Top

Perineurioma is a benign PNST objectively diagnosed by IHC and/ or ultrastructural analysis. [9],[10] Its rarity is compounded with a lower index of suspicion for its diagnosis and unavailability of ancillary techniques in routine settings. Perineuriomas are mainly intraneural and extraneural, the latter include soft tissue, sclerosing and reticular subtypes. [10] In contrast to other PNSTs, perineuriomas are rarely associated with multifocality and neurofibromatosis (NF) status. [11] Malignant perineurioma/MPNST with perineurial differentiation constitutes nearly 4% of MPNSTs. [Table 1]. There have been contrasting views regarding existence of a low-grade perineurial MPNST versus a perineurioma with atypical features. [4],[10] The present case forms the first documentation of a perineurial MPNST in the setting of multifocal soft tissue perineuriomas, elsewhere diagnosed as multiple DFSPs.
Table 1: Literature Review of Cases Diagnosed as Malignant Peripheral Nerve Sheath tumor with perineurial Differentiation/ Malignant Perineurioma with immunohistochemical results

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On review, the thigh and axillary masses revealed perineuriomas, while the leg mass disclosed a high-grade perineurial MPNST. The differential diagnoses were DFSP, neurofibroma, a low-grade fibromyxoid sarcoma (LGFMS), a MPNST and a solitary fibrous tumor. [5] Tumor circumscription within all the nodules and distinct cytomorphological features, despite conspicuous whorling favored a perineurioma over a DFSP. Whereas the present tumors were spindly, along with focal epithelioid change in the malignant tumor mass, Fukunaga [6] identified round cell component. IHC stains reinforced perineurial differentiation. CD34 has been found to be positive in some perineuriomas that necessitates additional stains like claudin-1 Glut1, collagen Type 4 and CD56 and/or ultrastructural analysis for an objective diagnosis, over a DFSP [8],[10] CD56 was also positive in the present tumors. Hornick, et al,[10] observed claudin-1 positivity in 21% perineuriomas. CD34 negativity ruled out a DFSP. Clinically, multiple soft tissue swellings suggested a PNST, although, rarely, multiple recurrent DFSPs have been documented. [12] Hirose et al,[3] documented seven perineurial MPNSTs with EMA positivity that showed perineurial differentiation on ultrastructure. [10] EMA positivity has been noted in some LGFMSs. The aforementioned features ruled out a LGFMS and also a synovial sarcoma.

Therapeutically, all tumor masses in our case were widely excised. Further, the patient was followed-up. Within four months, he died of respiratory insufficiency. Whereas Hirose et al, [3] observed tumor recurrences and metastasis within seven perineurial MPNSTs; Fukunga [6] documented death in a single case. Karaki et al,[5] documented recurrence and metastasis after 10 years in another low-grade perineurial MPNST. Hirose et al,[3] indicated a relatively favorable prognosis of a perineurial MPNST, as compared to a conventional MPNST. However, most cases were of low-grade.

 > Conclusion Top

This case report is a rare documentation of high-grade perineurial MPNST in the setting of multifocal perineuriomas, forming the first such documented case. An index of suspicion, clinical features, and IHC stains are useful in substantiating this diagnosis. It would be worthwhile to document more perineurial MPNSTs, with grade and clinical outcomes.

 > References Top

1.Scheithauer BW, Louis DN, Hunter S. Neurofibroma. In: Louis DN, Ohgaki H, Wiestler OD, editors. WHO Classification of Tumors 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.Hirose T, Scheithauer BW, Sano T. Perineurial malignant peripheral nerve sheath tumor (MPNST): A clinicopathologic, immunohistochemical, and ultrastructural study of seven cases. Am J Surg Pathol 1998;22:1368-78.  Back to cited text no. 3
4.Zámecník M, Michal M. Malignant peripheral nerve sheath tumor with perineurial cell differentiation (malignant perineurioma) Pathol Int 1999;49:69-73.  Back to cited text no. 4
5.Karaki S, Mochida J, Lee YH, Nishimura K, Tsutsumi Y. Low-grade malignant perineurioma of the paravertebral column, transforming into a high-grade malignancy. Pathol Int 1999;49:820-5.  Back to cited text no. 5
6.Fukunaga M. Unusual malignant perineurioma of soft tissue. Virchows Arch 2001;439:212-4.  Back to cited text no. 6
7.Rosenberg AS, Langee CL, Stevens GL, Morgan MB. Malignant peripheral nerve sheath tumor with perineurial differentiation: "malignant perineurioma". J Cutan Pathol 2002;29:362-7.  Back to cited text no. 7
8.Sato K, Ueda Y, Miwa S, Yokogawa A, Ozaki M, Katsuda S. Low-grade malignant soft-tissue perineurioma: Interphase fluorescence in situ hybridization. Pathol Int 2008;58:718-22.  Back to cited text no. 8
9.Lazarus SS, Trombetta LD. Ultrastructural identification of a benign perineurial cell tumor. Cancer 1978;41:1823-9.  Back to cited text no. 9
10.Hornick JL, Fletcher CD. Soft tissue perineurioma: Clinicopathologic analysis of 81 cases including those with atypical histologic features. Am J Surg Pathol 2005;29:845-8.  Back to cited text no. 10
11.Rubin AI, Yassaee M, Johnson W, Rosalie E, Joseph Z Jr, John TS. Multiple cutaneous sclerosing perineuriomas: An extensive presentation with involvement of the bilateral upper extremities. J Cutan Pathol 2009;36:60-5.  Back to cited text no. 11
12.Demiri EC, Dionyssiou DD, Kirkos JM, Panayotopoulou C, Papadimitriou DK. Multiple recurrent dermatofibrosarcoma protuberans of the hand. J Plast Reconstr Aesthet Surg 2008;61:842-5.  Back to cited text no. 12


  [Figure 1], [Figure 2], [Figure 3]

  [Table 1]


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