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Year : 2015  |  Volume : 58  |  Issue : 2  |  Page : 220-222
Intraosseous primary malignant peripheral nerve sheath tumor of the calcaneus: An unusual case and review of literature

1 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
2 Department of Orthopaedics, All India Institute of Medical Sciences, New Delhi, India
3 Department of Radiodiagnosis, All India Institute of Medical Sciences, New Delhi, India

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Date of Web Publication17-Apr-2015


Malignant peripheral nerve sheath tumors (MPNSTs) are uncommon sarcomas that originate from a peripheral nerve or neurofibroma either spontaneously or in association with neurofibromatosis type 1. MPNSTs account for approximately 5% of all soft tissue malignancies. The tumor is commonly seen in the extremities and trunk. Most of these tumors are high-grade with the potential to recur and metastasize. Common metastatic sites include the lungs, bone, and pleura. Primary intraosseous MPNST is rare, and the diagnosis of intraosseous MPNST, especially in an unusual location is difficult because of its cellular origin, histomorphological similarities with other sarcomas, and bone is the most common site for metastasis. We report an unusual case of MPNST of the calcaneus in a young male.

Keywords: Bone, calcaneus, malignant peripheral nerve sheath tumors, S-100

How to cite this article:
Gahlot GP, Mridha AR, Nath D, Khan SA, Gamanagatti S. Intraosseous primary malignant peripheral nerve sheath tumor of the calcaneus: An unusual case and review of literature. Indian J Pathol Microbiol 2015;58:220-2

How to cite this URL:
Gahlot GP, Mridha AR, Nath D, Khan SA, Gamanagatti S. Intraosseous primary malignant peripheral nerve sheath tumor of the calcaneus: An unusual case and review of literature. Indian J Pathol Microbiol [serial online] 2015 [cited 2023 Sep 30];58:220-2. Available from:

   Introduction Top

Malignant peripheral nerve sheath tumors (MPNSTs) are primarily soft tissue sarcoma usually seen in the extremities, trunk, head and neck regions. [1],[2] The tumor may arise de novo or from a benign nerve sheath tumor; however, they are increasingly found in patients with the hereditary neurofibromatosis type 1 (NF1) and following irradiation. [1] Primary intraosseous MPNSTs are rare. Approximately, 30 cases have been reported in the English literature, and the most common sites of involvement are facial bones, particularly mandible. Long bones such as femur, humerus, and ulna are rarely affected. [3],[4] Tarsal bone involvement is very uncommon. We describe a case of epithelioid MPNST in the calcaneus in a young male without hereditary NF1.

   Case Report Top

A 23-year-old male presented with pain, swelling and redness of right heel for 4 months. There was no history of trauma, tuberculosis, diabetes or hypertension. Past and family history was unremarkable. Physical examination revealed a tender swelling with a small superficial ulcer in the right heel. No peripheral lymph nodes were palpable. X-ray of the right foot showed a geographic lytic destruction of the calcaneus with an intact cortex [Figure 1]a. T 1 -weighted magnetic resonance image revealed iso- and hypointense lesion in the calcaneus [Figure 1]b. It was hyperintense on T 2 -weighted fat suppression images [Figure 1]c. No associated soft tissue component was seen. The radiologic possibilities considered were chondrosarcoma and osteosarcoma. Tru-cut biopsy from the lesion showed spindle cells infiltrating the bony trabeculae and intertrabecular spaces. The cells revealed epithelioid morphology with a moderate amount of eosinophilic cytoplasm, centrally located vesicular nucleus and prominent nucleolus. The mitotic index was 3-4/10 HPF. No osteoid or cartilaginous areas were seen [Figure 2]a and b. The tumor cells were immunopositive with vimentin (1:300) (Thermo Fisher Scientific Inc, US), S-100 (1:800) (Dako, US), and pan-cytokeratin (1:250) (Bio SB, US) [Figure 2]c-e and; negative for epithelial membrane antigen (EMA) (1:400), CD1a (1:100), smooth muscle actin (1:400), HMB-45 (1:100) (Thermo Fisher Scientific Inc, US); osteopontin (1:100) (Spring BioScience, US); langarin (1:200) (Novacastra, UK); leukocyte common antigen (1:250) (Bio SB, US); CD34 (1:200), and Bcl2 (1:75) (Spring BioScience, US). Ki67 labeling index was approximately 5-6% [Figure 2]f. Histological diagnosis of epithelioid MPNST was offered. As primary MPNST of calcaneus is uncommon, repeat biopsy was performed to avoid misdiagnosis due to sampling error. The repeat biopsy also showed similar histomorphology and immunohistochemical profiles. The diagnosis MPNST was given by two independent pathologists. Chest X-ray and contrast enhanced computed tomography of chest and abdomen did not reveal any other lesions. Complete surgical excision was planned; however, the patient was subsequently lost to follow-up.
Figure 1: (a) An axial radiograph of right foot shows geographic lytic destruction of calcaneus with intact cortex. (b) Axial T1-weighted magnetic resonance image reveals hypointense lesion involving calcaneus with intact cortex (c) and T2-weighted with fat suppression image shows hyperintensity of lesion

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Figure 2: (a) Section shows malignant spindle cells infiltrating bone, intertrabecular spaces (H and E, ×200). (b) The tumor cells have epithelioid morphology, central vesicular nucleus and moderate amount of eosinophilic cytoplasm (H and E, ×400). (c) Tumor cells are immunoreactive with vimentin (×400), (d) S-100 (×400) and (e) Pan-cytokeratin (×400). (f) Ki67 labeling index is approximately 6% (×400)

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   Discussion Top

Malignant peripheral nerve sheath tumors are primarily soft tissue sarcomas which originate from peripheral nerves or the nerve sheath associated cells, such as Schwann cells, perineural cells, or fibroblasts. It accounts for approximately 5% of soft tissue sarcomas and is usually seen in patients aged 20-50 years; however, it can arise in children, especially those with NF1. The most common sites are extremities, followed by the trunk, head and neck region. [1],[2],[5] About 40-50% of MPNSTs arise in the patients with NF1, 10% following irradiation, and the remainder de novo. [1],[6] Primary intraosseous MPNSTs are most commonly seen in the mandible followed by maxilla. Other rare sites are femur, humerus, ulna, sternum, sacrum, palate, and phalanx. [3],[4] Criteria proposed for intraosseous MPNST include (1) the tumor originates from a nerve in a juxtacortical bone; (2) it is a high grade spindle cell sarcoma in a patient with NF1 and shows neural processes with S-100 immunopositivity; (3) it is contiguous with adjacent neurofibroma or neurolemmoma without prior radiation; and (4) it has no bone, osteoid or cartilage formation. [7] MPNST of small bones of the foot is rare. Ayan et al. reported a case of MPNST in the heel which infiltrated calcaneus, plantar aponeurosis, and surrounding skin. The tumor was found to arise from ramus calcanei medialis of tibial nerve. [8] In our case, the patient was a young male who had a primary tumor in the calcaneus without any soft tissue involvement. Radiologically MPNST shows nonspecific destructive lytic lesions, which is usually isointense on T 1 W 1 and hyperintense on T 2 W 2 images. Microscopic features of a typical lesion include spindle cells in a fascicular growth, often with hemangiopericytoma-like vascular pattern, and alternating hyper- and hypo-cellular areas. The cells are pleomorphic, mitotically active, spindle-or serpentine-shaped with hyperchromatic nuclei and pale cytoplasm. Skeletal muscle, bone, cartilage, and angiosarcomatous areas may be present in a minority of cases. Epithelioid MPNST is a rare variant consisting of <5% of cases and composed of plump, epithelioid cells with abundant eosinophilic cytoplasm. This is not associated with NF1. Immunohistochemically MPNSTs are positive with S-100 and negative for HMB45. Epithelioid MPNST in addition shows cytokeratin positivity. The morphological and immunohistochemical features in our case favored epithelioid MPNST. [9]

Differential diagnoses include osteosarcoma, clear cell sarcoma, epithelioid sarcoma, and spindle cell sarcomas, such as synovial sarcoma, fibrosarcoma, leiomyosarcoma, undifferentiated sarcoma, and a metastatic tumor. Osteosarcoma typically shows pleomorphic cells associated with presence of osteoid matrix. The tumor cells are immunopositive with osteopontin. Epithelioid MPNST morphologically may resemble clear cell sarcoma and epithelioid sarcoma. Immunohistochemically clear cell sarcoma is positive for HMB45; while epithelioid sarcoma cytokeratin, EMA, and vimentin. Generally, there is loss of INI1, and S-100 immunonegativity. [9] In our case, there was no osteoid production, and tumor cells were negative for HMB45 and EMA. S-100 immunopositivity in our case favored the diagnosis of MPNST.

Radical surgical excision of the tumor is the mainstay of therapy. Preoperative radiation therapy in soft tissue MPNST improves overall survival rates and success of limb salvage surgery. High-dose radiation therapy with or without chemotherapy may be recommended in an inoperable case and in patients with incomplete surgical resection. Local recurrence rate, as well as distant metastasis, is about 40-65%. The common metastatic sites are the lungs, bone, and pleura. [1],[4] Longer survival has been associated with complete surgical excision, small tumor size (<5 cm) and low-grade morphology. 5 and 10 years survival in patients with MPNST are approximately 51% and 41% respectively. [9],[10] Though the patient was lost to follow-up; localized tumor, small size, low histologic grade and low proliferation index in our case suggest a favorable prognosis. Diagnosis of intraosseous MPNST is often challenging due to its nonspecific radiological features, morphological similarities with other sarcomas, and unusual location. Immunohistochemistry in such a case is helpful for the diagnosis, and proper management of the patient.

   References Top

Ducatman BS, Scheithauer BW, Piepgras DG, Reiman HM, Ilstrup DM. Malignant peripheral nerve sheath tumors. A clinicopathologic study of 120 cases. Cancer 1986;57:2006-21.  Back to cited text no. 1
Stucky CC, Johnson KN, Gray RJ, Pockaj BA, Ocal IT, Rose PS, et al. Malignant peripheral nerve sheath tumors (MPNST): The Mayo Clinic experience. Ann Surg Oncol 2012;19:878-85.  Back to cited text no. 2
Tamgadge S, Modak N, Tamgadge AP, Bhalerao S. Intraosseous malignant peripheral nerve sheath tumor of maxilla: A case report with review of the literature. Dent Res J (Isfahan) 2014;11:405-10.  Back to cited text no. 3
Kendi TK, Erakar A, Yildiz HY, Saglik Y, Erekul S. Intraosseous malignant peripheral nerve sheath tumor with local recurrence, lung metastases and death. Skeletal Radiol 2004;33:223-5.  Back to cited text no. 4
Lewis JJ, Brennan MF. Soft tissue sarcomas. Curr Probl Surg 1996;33:817-72.  Back to cited text no. 5
Lau D, Moon DH, Park P, Hervey-Jumper S, McKeever PE, Orringer DA. Radiation-induced intradural malignant peripheral nerve sheath tumor of the cauda equina with diffuse leptomeningeal metastasis. J Neurosurg Spine 2014;21:719-26.  Back to cited text no. 6
Mirra JM. Bone Tumors: Clinical, Radiologic and Pathologic Correlations. Beckenham Kent, Philadelphia: Lea and Febiger; 1989. p. 855-67.  Back to cited text no. 7
Ayan I, Çolak M, Karabacak T. An unusual localization of malignant peripheral nerve sheath tumor: Case report. Am J Curr Immunol 2007;1:118-21.  Back to cited text no. 8
Goldblum JR, Weiss SW, Folpe AL, editors. Malignant peripheral nerve sheath tumors. In: Enzinger and Weiss's Soft Tissue Tumors. 6 th ed. Philadelphia: Saunders-Elsevier; 2013. p. 855-79.  Back to cited text no. 9
Wong WW, Hirose T, Scheithauer BW, Schild SE, Gunderson LL. Malignant peripheral nerve sheath tumor: Analysis of treatment outcome. Int J Radiat Oncol Biol Phys 1998;42:351-60.  Back to cited text no. 10

Correspondence Address:
Dr. Asit Ranjan Mridha
Department of Pathology, All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110 029
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0377-4929.155321

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