A Rare Case Report of Malignant Peripheral Nerve Sheath Tumor Involving Both the Small Bowel and Large Bowel

Abstract

Malignant peripheral nerve sheath tumor (MPNST) contains properties and histologic markers of both neural crest cells and mesenchymal cells. It is a rare diagnosis, with an incidence of 1:100,000/year or 4%–10% of soft-tissue sarcomas. There are very few cases reported and studied. Therefore, establishing a proper diagnosis and treatment of MPNST provides a challenge. We present this unique and rare case of metastatic MPNST of the small and large bowel with bone, pulmonary, liver, and splenic metastases. The patient subsequently developed hemorrhagic brain metastases and died 6 months after THE initial diagnosis.

INTRODUCTION

Often debated in its definition, malignant peripheral nerve sheath tumor (MPNST) contains properties and histological markers of both neural crest cells and mesenchymal cells.[1,2,3] MPNST is defined as a tumor of, or differentiating from, peripheral nerves; therefore, historically it had been referred to as malignant schwannoma, malignant neurilemmoma, and neuro fibrosarcoma. MPNST yields few results in literature review with the majority of cases reported in association with neurofibromatosis 1 (NF1). Search results reflect the epidemiology of this malignancy; MPNST is a rare diagnosis, with an incidence of 1:100,000/year or 4%–10% of soft-tissue sarcomas.[2,3,4,5] To the best of our knowledge, this is the first case of an initial presentation of extensive metastatic MPNST involving both the small and large bowel.

CASE REPORT

We present the case of a 71-year-old Portuguese male with a past medical history of hypertension, hyperlipidemia, and gout with no significant family history. He presented with 8-week history of persistent right lower quadrant pain, anorexia with 20 pound weight loss. Vital signs were stable and normal.

On physical examination, a firm, tender, fixed abdominal mass in the right lower quadrant was palpable. Computed tomography (CT) scan of the abdomen showed evidence of multiple masses in the peritoneum and mesentery. A necrotic mass on the right side of the abdomen measured 10 cm with communication to the small bowel and a suggestion of a walled-off perforation. The patient underwent CT-guided biopsy of the abdominal mass. Pathology revealed a tumor consisting mixed spindle and pleomorphic cells with focal rhabdoid features, high-grade nuclear features, and brisk mitotic activity. Ki67 expression was up to 70% [Figure 1]. Initially, a differential diagnosis of poorly differentiated synovial sarcoma of the colon was considered, but fluorescence in situ hybridization (FISH) studies for Ewing sarcoma and synovial sarcoma were negative.

Figure 1.

Histopathology of computed tomography guided biopsy revealed mixed spindle and pleomorphic cells with focal rhabdoid features, high grade nuclear features and brisk mitotic activity. Ki67 expression was up to 70%

A week later, the patient presented with symptoms of small bowel obstruction. In addition to the previous masses, the CT scan at this time showed a left-sided abdominal mass measuring 8 cm with communication to the small bowel with dilation of the jejunum suggesting a new partial obstruction [Figure 2a]. Three lesions were also identified on the liver [Figure 2b] at this time measuring 7 mm, 11 mm, and 1.3 cm as well as a 2.6 cm low-density mass in the spleen. The patient (at this time-delete) underwent an exploratory laparotomy with palliative debulking of the tumor. Multiple large obstructive masses were found in the Ligament of Treitz, proximal jejunum, significant portion of the small bowel, right colon, left ascending colon, and omentum. For palliation purposes, these masses were resected and primary anastomosis was performed. In addition, 300 cc of bloody ascites was encountered. Gross examination [Figure 3a and b] of the surgical specimens revealed grayish-tan cystic masses filled with brownish tan hemorrhagic material.

Figure 2.

(a) Computed tomography scan showed a left sided abdominal mass measuring 8 cm with communication to the small bowel with dilation of the jejunum suggesting a new partial obstruction. (b) Liver and spleen metastases detected on computed tomography scan

Figure 3.

(a) Large obstructive mass was found in the Ligament of Treitz and proximal jejunum. (b) Large obstructive mass was found in the Ligament of Treitz and proximal jejunum

Histology of the masses showed spindle cell neoplasm with brisk mitotic activity and associated necrosis [Figure 4a]. There were multifocal areas showing myoid to edematous stroma imparting the characteristic marble-like appearance with alternating light and dark areas. In addition, there were areas of high-grade epithelioid morphology imparting a rhabdoid or plasmacytoid appearance. There were also areas of focal chondroid differentiation. On immunohistochemistry, tumor cells showed patchy weak S100 [Figure 4b] immunoreactivity. Melan A [Figure 4c] and CD34 stains [Figure 4d] were positive. HMB45, chromogranin, synaptophysin, and myogenin were negative. Ki-67 proliferation index was 70%. Finally, FISH testing of the surgical masses was negative for EWSR1 and SS18 (SYT) genes, decreasing the likelihood of Ewing sarcoma and synovial sarcoma as etiologies of the malignancy. The diagnosis of MPNST was established. One of twelve lymph nodes resected was positive for metastatic disease.

Figure 4.

(a) Histology of the mass showed spindle cell neoplasm with brisk mitotic activity and associated necrosis (×100). (b) S100 stain on pathology specimen was positive. (c) MelA stain on pathology specimen was positive. (d) CD34 stain on pathology specimen was positive

The patient however had a rapidly downhill course. He developed lytic sternal bone metastasis causing significant chest pain. He also developed multiple pulmonary, liver, and splenic metastases. This was followed by, within A couple of weeks, by the development of multiple brain metastases causing facial droop, slurred speech, and focal weakness. He received palliative radiation to the sternum and whole-brain radiation as well. He was also started on palliative chemotherapy with single-agent doxorubicin. However, he could only receive one cycle as he developed new hemorrhagic brain metastases causing him to be unable to ambulate and restricted to his bed. He died under hospice care within 6 months of his initial presentation.

DISCUSSION

MPNST is a highly aggressive soft tissue sarcoma. Sporadic cases (0.001% cases) are rare and it occurs more in association with NF1 (8%–13%).[3,4,5,6,7,8] When associated with NF1, the tumor arises after the transformation of a plexiform neurofibroma or as sequelae to radiation exposure. In a retrospective study of 120 cases of MPNST, the tumor manifested at an earlier age in patients with NF1 (mean age 28.7 years) in comparison to patients who developed the tumor without NF1 (mean age 35.3 years).[8,9] Our patient did not have a history of either NF1 or radiation exposure and remarkably, developed the condition at 71 years of age, within 2 years of diagnosis.

The tumor typically originates from the nerve sheaths of the major nerves in the extremities (40%), trunk/retroperitoneal (38%), and head and neck region (21%).[10]

However, recent case reports have also documented MPNST of the liver, thyroid gland, skin, eighth cranial nerve, greater omentum as seen in our patient, without a history of radiation or NF1.[4,5,6,7] Patients with MPNST of the GI tract clinically present with weight loss, fatigue, vomiting or palpable mass, and as a result, can be diagnosed late in its course.[3,4,5,6,7]

Morphologically, MPNST is usually composed of monomorphic elongated cells in a hypocellular stroma with gaping vascular spaces often with geographic necrosis and frequent mitotic figures.[11,12] Rhabdomyoblastic, metaplastic cartilage, or bone features may be present[1,2,3,13] and support a malignant diagnosis. Spindle cell is the most commonly encountered histologic subtype (71.8%), followed by Triton (17.7%) followed by epithelioid MPNSTs (<5%) were identified.[11,13] Immunohistochemistry helps in further delineation. MPNSTs express the neural marker S-100 in 50%–60% of cases. Other neural markers like CD99, Neuron-specific enolase, FLI-1, CD 56, Myelin basic protein, Leu-7, protein gene product 9.5 may be positive.[14] Among mesenchymal markers vimentin is usually positive. Although MPNSTs generally do not express actin and desmin, the rare Triton tumor with rhabdomyoblastic elements may express desmin.[12] Epithelial markers like cytokeratins, CEA are negative except in the rare epitheloid variant which may express epithelial membrane antigen.[12] A weak S-100 staining in MPNST is also associated with undifferentiated tumors and a five-fold higher risk of distant metastasis.[15]

Among radiological modalities, CT and magnetic resonance imaging (MRI) help in the initial diagnosis and characterization of the tumor. Some pointers towards MPNST include a larger size (>5 cm), infiltrative ill-defined margins, peritumoral edema, intratumoral lobulation, bone destruction, and peripheral enhancement with noncystic appearance or heterogeneous enhancement on MRI.[13]

Wide resection of the primary tumor with negative margins is the treatment of choice in localized disease with adjuvant radiation therapy reserved for cases with positive margins or recurrent disease or bulky disease (>5 cm). In terms of adjuvant chemotherapy for localized disease, there's a lack of randomized control trials, although some meta-analyses have shown marginal improvements in local and overall recurrences and hence may be considered in high-risk groups.[16] Neoadjuvant chemotherapy or radiation may be considered in locally advanced or unresectable MPNST to make the disease more amenable to local treatment. This is based on mainly retrospective analyses and a Phase II SARC 006 study.[17,18,19] Doxorubicin forms the backbone of many chemotherapy options. In a retrospective analysis, Kroep et al. identified a doxorubicin-ifosfamide regimen superior to doxorubicin or ifosfamide alone in the treatment of MPNST.[10,12,15,20] The outcomes in the metastatic setting are poor with response rates of around 21%.[10] As the combination of doxorubicin and ifosfamide are quite toxic, risk versus? Benefits of therapy should be strongly considered. In this regard, Judson et al. determined there was no major change in THE overall survival between the two groups (Doxorubicin and Ifosfamide vs. Doxorubicin alone), and combination treatment was most effective for tumor shrinkage. With an increasing understanding of the signaling pathways activated in MPNSTs, sorafenib, which targets the mitogen-activated protein kinase pathway, has been tested in single cases and in a histology-specific clinical trial.[21,22,23] Radiation also has a role in the palliation of symptoms such as bone pain, bleeding, and brain metastasis.

MPNST is a tumor associated with aggressive behavior and its prognosis is poor with death occurring in 63%, usually with 2-year of diagnosis.[14] The prognosis for abdominal MPNST remains unclear. The presence of NF1 syndrome, female sex, deep location, positive margins, lack of adjuvant chemotherapy, lack of adjuvant radiation therapy, and high-grade tumors were all associated with adverse disease-free survival in a recent review.[11] Tumors with the recurrent presentation, large size, and location in the trunk, head and neck had a poorer prognosis than those that manifested as primary tumors with smaller size and located on extremities.[9,10,20] In the case of this patient, gross findings of >5 cm and ill-defined margins suggested a poor prognosis.

CONCLUSION

True to its name, MPNST manifested rapidly and aggressively in this case of a 71-year-old Portuguese male with right lower quadrant abdominal pain. Following an extensive pathology analysis, treatment for the patient included surgical resection with adjunct Doxorubicin treatment. Faster surgical resection and combination chemotherapy with radiation may potentially affect prognosis. Therein lies the objective of this paper: To shed light on the unique morphological findings of MPNST and highlight its aggressive course to emphasize the need to diligently and quickly act should similar findings present in other patients. Future direction should aim to continue the development of the multimodal and less toxic targeted treatment approach.

Declaration of patient consent

The authors certify that they have obtained allappropriate 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

Nil.

Conflicts of interest

There are no conflicts of interest.