|Ahead of print publication
Malignant peripheral nerve sheath tumor of mesocolon: A rare case
Sakshi Rana1, Divya Khosla1, Kannan Periasamy1, Rakesh Kapoor2
1 Department of Radiotherapy and Oncology, PGIMER, Punjab, Chandigarh, India
2 Department of Radiotherapy and Oncology, HBCH AND RC Sangrur / Mullanpur, Punjab, Chandigarh, India
|Date of Submission||02-Feb-2021|
|Date of Acceptance||07-Mar-2021|
|Date of Web Publication||20-Jul-2021|
Department of Radiotherapy and Oncology, PGIMER, Punjab, Chandigarh
Source of Support: None, Conflict of Interest: None
Malignant peripheral nerve sheath tumor (MPNST) is a soft-tissue sarcoma arising from or differentiating toward peripheral nerve sheath cells. It accounts for 5%–10% of soft-tissue sarcomas. The most common sites of origin are proximal portion of upper, lower limbs and trunk. MPNST arising from the nerve plexus of gastrointestinal tract is extremely rare, and only very few cases have been reported in literature. In this report, we are describing a case of MPNST from mesocolon. An 82-year-old male presented to hospital with complaint of pain abdomen and feeling of lump on the left side of lower abdomen for the past 2 months. On contrast-enhanced computed tomography (CECT) of chest and abdomen, there was 15 cm × 10 cm mass palpable in left lumbar region without ascites and multiple random subpleural nodules in bilateral lung. Intraoperatively, there was 15 cm × 10 cm hard irregular mass in left paracolic gutter infiltrating mesentry of descending colon. Left hemicolectomy was performed with end-to-end anastomosis. Histopathological examination revealed malignant peripheral nerve sheath tumor, and on immunohistochemistry, tumor cells were positive for S-100 and negative for C-kit and Smooth Muscle Actin (SMA). The patient was started on tamoxifen in view of old age and lung metastasis. The patient is on follow-up from 2 years with stable disease. In this report, we highlight the possibility of clinical differential diagnosis of MPNST arising from mesocolon should be kept while dealing with mesenchymal tumors of colon. Radical surgery with negative margins is required for achieving palliation, and adjuvant tamoxifen could offer advantage in patient who cannot tolerate chemotherapy.
Keywords: Chemotherapy, colon, malignant peripheral nerve sheath tumor
| Introduction|| |
Malignant peripheral nerve sheath tumor (MPNST) is a soft-tissue sarcoma arising from or differentiating toward peripheral nerve sheath cells. It accounts for 5%–10% of soft-tissue sarcomas. In 1993, the WHO has coined the term “MPNST” and replaced the previous terminology on tumors of neurogenic origin with similar biological behavior such as malignant schwannoma, malignant neurilemmoma, and neurofibrosarcoma. It can arise as a sporadic form with incidence of 0.0001% in general population or can be associated with neurofibromatosis-1 (NF-1) with incidence of 2%–5%. These tumors can arise from any part of the body and high predilection for previously irradiated regions. The most common sites of origin are proximal portion of upper, lower limbs and trunk. The diagnostic criteria include the presence of Schwann cells, origin from a nerve, the presence of neurofibromata, nuclear palisading on microscopy, and immunohistochemistry (IHC) positivity for S-100. MPNST arising from the nerve plexus of gastrointestinal tract is extremely rare and only very few cases have been reported in literature. In this report, we are describing a case of MPNST from mesocolon.
| Case Report|| |
An 82-year-old male presented to hospital with a complaint of pain abdomen and feeling of lump on the left side of lower abdomen for the past 2 months. He denied having any history of fever, jaundice, altered bowel habits, vomiting, bleeding per rectum, and urinary symptoms. The patient was a known case of hypertension and diabetes mellitus and on medication for the past 10 years. He had a history of surgery for hernia repair. He was nonsmoker and nonalcoholic. He has no family history of malignancy and NF type-1. General physical examination revealed that moderately nourished, moderately built, and had ECOG-2 status with no pallor, icterus, pedal edema, and palpable lymphadenopathy. On per-abdominal examination, there was 15 cm × 10 cm mass palpable in left lumbar region without ascites. Ultrasound abdomen was done which showed hypoechoic lesion measuring 8.2 cm × 5.1 cm with echogenic strands in left lumbar region, and abdominal contrast-enhanced computed tomography showed a heterogenous mass seen in the left lower flank (from lower border of L3 to S1) measuring 10.3 cm × 6.8 cm × 8.2 cm causing displacement of left ureter medially and fat planes with gut were maintained [Figure 1]. CECT chest showed bilateral random multiple subpleural nodules. In lower gastrointestinal endoscopy, mucosa was seen till caecum, and it was normal. Tumor markers (carcinoembryonic antigen, CA19.9, and prostate-specific antigen) were within normal limits.
|Figure 1: Contrast-enhanced computed tomography axial section; soft-tissue mass showing heterogeneous contrast enhancement seen in left hemipelvis|
Click here to view
The patient was taken up for surgery with clinical differential diagnosis of gastrointestinal stromal tumor (GIST) or mesenchymal tumor. Exploratory laparotomy was done. Intraoperatively, there was 15 cm × 10 cm hard irregular mass in left paracolic gutter infiltrating mesentry of descending colon. Left hemicolectomy was performed with end-to-end anastomosis. Gross examination revealed tumor arising from mesentry of descending and sigmoid colon with the size of 15 cm × 13 cm × 10 cm. Cut surface of tumor was grayish white, fleshy with areas of myxoid degeneration, and calcification. Histologically, tumor cells were arranged in fascicles in fibrous and edematous background. The tumor cells were predominantly spindle shaped and have round to elongated hyperchromatic nucleoli. Tapering ends were noticed at the periphery of lesion. Mitotic figures are 4–6/10 hpf. Tumor cells infilterated surrounding adipose tissue but not the colonic segment. Resection limits of colon are free of tumor. On IHC, tumor cells were positive for S-100 and negative for C-kit and SMA [Figure 2]. Overall, morphological and IHC features were suggestive of MPNST.
|Figure 2: (a) Tumor infiltrating the adjacent fat (H and E, ×100). (b) Tumor cells are arranged in fascicles in a fibrous stroma with elongated nuclei having tapering ends (H and E, ×200). (c and d) Immunohistochemistry showing positive S-100 and negative C-Kit respectively|
Click here to view
Patient's postoperative period was uneventful. Postoperative CECT chest and abdomen showed no abnormal soft-tissue thickening in the region of descending colon to indicate residual/recurrent lesion. There were multiple random nodules in subpleural location in both the lungs suggestive of metastasis. The patient was started on tamoxifen in view of old age and lung metastasis. The patient is alive under follow-up with stable disease on tamoxifen for 24 months.
| Discussion|| |
MPNST is a high-grade sarcoma arising from nerve sheath of major or minor peripheral nerves., MPNST occurs most commonly in age group between 20 and 50 years with a median age of 35 years. The most common sites of MPNSTs are located along major nerve trunks commonly arising on the body trunk, extremities, head, neck, and paravertebral regions. MPNSTs arising from nerves of the mesentry of colon are extremely rare. There are two hypotheses about their origin within abdomen. First, they can arise from retroperitoneal nerves as silent painless gradually progressive mass lesions then involving the surrounding structures, second they can arise from submucosal Auerbach plexus, can grow intramurally or exophytically. To the best of our knowledge, there are total of seven cases of MPNST of small and large intestine reported in literature [Table 1].
|Table 1: Literature review of malignant peripheral nerve sheath tumor from small intestine and large intestine|
Click here to view
There are no characteristic clinical symptoms of MPNST of mesocolon. Patients of MPNST fromb expansion : gastrointestinal tract (GIT)experience abdominal pain (63%), weight loss (44%), intestinal obstruction (23%), obstruction, mass, intussusception, fatigue, emesis, neurological deficits, and bone erosion. Our patient presented with lump and pain abdomen. The diagnosis is often delayed because of the presence of vague symptoms. Preoperative definite diagnosis of MPNST is difficult because radiological features are similar to other mesenchymal neoplasms and benign tumors of nervous tissue. Endoscopy-based biopsy is not possible because the mucosal abnormalities will be very minimal. Histopathology and IHC are the only definitive diagnostic techniques.
MPNST tumors are well-described with morphological heterogeneity, and staining reveals highly cellular spindle cell tumor in fascicles. S-100 protein is the most widely used antigen for documenting nerve sheath differentiation. CD34 is antigen for perineural differentiation and is seen in some MPNSTs. Our patient was also S-100 positive. Differential diagnosis of MPNST includes malignant fibrous histiocytoma (MFH), pleomorphic liposarcoma, and synovial sarcoma. MFH is generally S-100 negative, and pleomorphic liposarcoma is well circumscribed, nonencapsulated tumor with infiltrative borders and pleomorphic cells. MPNST can be differentiated from synovial sarcoma by IHC as in synovial sarcoma CK7 and CK19 are positive. Desmin and SMA exclude tumors of smooth muscle origin. GISTs were excluded by IHC positivity of CD117(C-Kit) and CD34.
Optimal management is complete surgical resection with negative surgical margins. The poor prognostic factors include tumor location in the trunk and close proximity of the vital structures, residual disease, tumor size >5 cm, positive margins, and the presence of NF1. Among all sarcomas, MPNST has the highest recurrence rate, and appropriate initial management gives the best survival results. Adjuvant radiotherapy in MPNST has been used in patients with tumor size >5 cm, positive margin, residual disease, and close proximity to vital structure but has very little effect on survival. Adjuvant chemotherapy is given in MPNST after surgical treatment, however, there are no trials which evaluate the role of chemotherapy in unresectable and metastatic tumors. Doxorubicin-Ifosfamide-based chemotherapy has compared with placebo and found to be having better outcomes.
Tamoxifen has shown some benefit in MPNSTs. An active metabolite, 4-hydroxy-tamoxifen, of the selective estrogen receptor modulator, inhibits the proliferation and survival of neoplastic schwann cells derived from NF1-associated and sporadic MPNSTs., Hence, in view of old age and metastatic lung nodules, the patient was started on tamoxifen. The patient is still under follow-up with stable disease on tablet tamoxifen for 1½ years.
| Conclusion|| |
In this report, we highlight the possibility of clinical differential diagnosis of MPNST arising from mesocolon should be kept while dealing with mesenchymal tumors of colon. Diagnosis is confirmed by histopathology, IHC, and there is no definite radiological investigation to differentiate MPNST from other tumors of mesenchymal origin. Radical surgery with negative margins is the option for achieving palliation. On the basis of poor prognostic factors, adjuvant radiotherapy can be given. Tamoxifen can be added as an adjuvant treatment as there has been an evidence of benefit in MPNSTs.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Enzinger FM, Weiss SW. Malignant Tumors of the Peripheral Nerves. 3rd
ed. St. Louis, MO: Mosby; 1995. p. 7.
Lewis JJ, Brennan MF. Soft tissue sarcomas. Curr Probl Surg 1996;33:817-80.
Wanebo JE, Malik JM, VandenBerg SR, Wanebo HJ, Driesen N, Persing JA. Malignant peripheral nerve sheath tumors. A clinicopathologic study of 28 cases. Cancer 1993;71:1247-53.
Marwah S, Gurawalia JP, Sheoran KD, Marwah N, Gupta S, Ranga H.
Malignant peripheral nerve sheath tumor of the colon in a patient with von Recklinghausen's disease: Report of a case. Clin J Gastroenterol 2013;6:429-33.
Lee YJ, Moon H, Park ST, Ha WS, Choi SG, Hong SC, et al.
Malignant peripheral nerve sheath tumor arising from the colon in a newborn: Report of a case and review of the literatures. J Pediatr Surg 2006;41:e19-22.
D'Agostino AN, Soule EH, Miller RH. Sarcoma of the peripheral nerves and somatic soft tissues associated with multiple neurofibromatosis (Von Recklinghausen's disease). Cancer 1963;16:1015-27.
Cashen DV, Parisien RC, Raskin K, Hornicek FJ, Gebhardt MC, 54 Mankin HJ. Survival data for patients with malignant schwannoma. Clin Orthop Relat Res 2004:69-73.
Zou C, Smith KD, Liu J, Lahat G, Myers S, Wang WL, et al.
Clinical, pathological, and molecular variables predictive of malignant peripheral nerve sheath tumor outcome. Ann Surg 2009;249:1014-22.
Anghileri M, Miceli R, Fiore M, Mariani L, Ferrari A, Mussi C, et al.
Malignant peripheral nerve sheath tumors: Prognostic factors and survival in a series of patients treated at a single institution. Cancer 2006;107:1065-74.
Yilmaz F, Uzunlar AK, Bükte Y. Recurrent malignant schwannoma of the small bowel. Acta Med Austriaca 2004;31:58-60.
Górecki T, Ostrowska M, Kaszuba B, Nowicki P, Dudzik T, Wojnowski S. Malignant peripheral nerve sheath tumor originating in neurofibroma of the mesentery. Case report. Pol J Pathol 2005;56:145-7.
Goyal V, Thomas S, Pathania OP, Agarwal S. Malignant nerve sheath tumor of the mesentery. Indian J Cancer 2010;47:233-4.
] [Full text]
Pandey D, Verma A, Akhtar A, Arsia A, Singh N. Malignant peripheral nerve sheath tumour of small intestine presenting as ileo-ileal intussusception-A rare tumour with unusual complication. J Clin Diagn Res 2015;9:XD03-4.
Zhu LB, Li PF, Xiao WH, Zhang PB, Li JQ, Sun MF. A distal ileum malignant peripheral nerve sheath tumor causing intussusception in a patient in China: A case report. World J Surg Oncol 2017;15:29.
Kumar K, Sekhar G, Srinivasan C, Parthasarathy J. Malignant peripheral nerve sheath tumor arising from plexiform neurofibroma of the mesentery in a patient with neurofibromatosis 1. Oncology, Gastroenterology and Hepatology Reports. 2015;4:58..
Mohtaram A, Mesmoudi S, M'rabti H, Rami A, Latib R, Bernoussi Z, et al.
Malignant peripheral nerve sheath tumor of the small bowel: An unusual presentation with fatal outcome. Case Rep Oncol Med 2013;2013:423867.
Telem DA, Pertsemlidis D. Malignant peripheral nerve sheath tumor: An unusual cause of intussusception. J Gastrointest Surg 2008;12:1609-11.
James AW, Shurell E, Singh A, Dry SM, Eilber FC. Malignant peripheral nerve sheath tumor. Surg Oncol Clin N Am 2016;25:789-802.
Kahn J, Gillespie A, Tsokos M, Ondos J, Dombi E, Camphausen K, et al.
Radiation therapy in management of sporadic and neurofibromatosis type 1-associated malignant peripheral nerve sheath tumors. Front Oncol 2014;4:324.
Byer SJ, Eckert JM, Brossier NM, Clodfelder-Miller BJ, Turk AN, Carroll AJ, et al.
Tamoxifen inhibits malignant peripheral nerve sheath tumor growth in an estrogen receptor-independent manner. Neuro Oncol 2011;13:28-41.
[Figure 1], [Figure 2]