Deep Venous Thrombosis in a 21-Year-Old Woman With a Retroperitoneal Mass.

A 21-year-old white woman presented with complaints of left groin and hip pain for 3 days. Physical examination revealed thoracic scoliosis, erythema, and tenderness in the left anterior hip and groin area, with reduced range of motion and hip flexion. Examination with venous Doppler ultrasound showed a large thrombus in the inferior vena cava at the level of the liver and also thrombi in the entire venous system of the left lower extremity. Computed tomography showed a clot within the left femoral and saphenous veins and a large mass (arrow) displacing the inferior vena cava at the level of the porta hepatis (Figure 1). Subsequently, an exploratory laparos-copy was performed. A retroperitoneal mass was identified and resected.

[Figure 1 ILLUSTRATION OMITTED]

Grossly, the mass was well circumscribed and measured 5.5 x 1.74 x 1.5 cm. The cut surface was yellow-tan and showed an area of necrosis, hemorrhage, and thrombosis (Figure 2). Histopathologic examination revealed a neoplasm with hypocellular areas of fairly bland-appearing spindle cells intermixed with areas of hypercellularity (Figure 3). Neoplastic cells displayed nuclear atypia and mitotic activity (Figure 4). An area of vascular necrosis is seen.

[Figures 2-4 ILLUSTRATION OMITTED]

What is your diagnosis?

Pathologic Diagnosis: Malignant Peripheral Nerve Sheath Tumor 

Malignant peripheral nerve sheath tumor (MPNST) is currently the preferred term for the neoplasm also known as malignant schwannoma. This preference is related to the fact that such tumors can recapitulate the appearance of any cell of the nerve sheath, including the Schwann cell, perineural fibroblast, or fibroblast.

About 10% of all soft tissue sarcomas are MPNSTs. Half of these tumors arise de novo, and the other half derive from nerves involved by neurofibroma as part of von Recklinghausen disease (neurofibromatosis type 1). Some cases have occurred in areas of previous irradiation,[1] and a few have originated from the Schwann cell-line (satellite cell) component of ganglioneuroma.[2] The development of MPNST in von Recklinghausen disease has been found to be associated with chromosome 17p deletions and p53 gene mutation.[3] Malignant peripheral nerve sheath tumor is typically a disease of adult life; most tumors occur in patients between 20 and 50 years of age.[4] Patients with neurofibromatosis type 1 develop these tumors at an earlier age. However, the average reported age at the time of diagnosis for patients with neurofibromatosis type 1 was 29 and 36 years in the Mayo Clinic[5] and Memorial Sloan-Kettering[6] studies, respectively, compared with 40 and 44 years for patients without the disease. Four percent of patients with neurofibromatosis type 1 develop MPNST. The sex ratio of patients with MPNSTs varies, depending on patient selection. Men predominate in studies having a high percentage of patients with neurofibromatosis type 1, as a result of the bias toward men in this disease.[4,7] In studies of sporadic cases of MPNST, the sex ratio is roughly equal or slightly biased toward women.

Like other sarcomas, lesions present as enlarging masses that are usually noted several months before diagnosis. Malignant peripheral nerve tumors that arise from major nerves typically give rise to a striking constellation of sensory and motor symptoms, including projected pain, paresthesias, and weakness. Pain is variable, but seems to be more prevalent in patients with neurofibromatosis type 1. In fact, pain or sudden enlargement of a pre-existing mass in this setting should lead to immediate biopsy to exclude the possibility of malignant transformation of a neurofibroma.

Most MPNSTs arise in association with major nerve trunks, including the sciatic nerve, brachial plexus, and sacral plexus. Consequently, the most common anatomical sites include the proximal portions of the upper and lower extremities and trunk. Comparatively few MPNSTs arise in the head and neck, a feature that contrasts with the distribution of neurofibromas. Malignant peripheral nerve sheath tumors can occur almost anywhere, including the retroperitoneum, but a more peripheral location on the extremities is more common in the solitary (non-von Recklinghausen disease) form, whereas central lesions on the trunk or head and neck predominate in neurofibromatosis.

Microscopically, a wide range of histologic findings can be encountered. Patterns reminiscent of fibrosarcoma or malignant fibrous histiocytoma may be found. In other areas, the tumor cells resemble Schwann cells, with elongated nuclei and prominent bipolar processes. Fascicle formation may be present. Mitoses, necrosis, and extreme nuclear anaplasia are common. Mitoses are important; they are not identified in benign lesions, and any significant mitotic rate ([is greater than] 1 mitosis per 20 high-power fields) can be construed as evidence of potential malignant behavior In addition to the basic appearance of these tumors, a wide variety of "divergent" histologic patterns may be admixed, including epithelial structures, rhabdomyoblastic differentiation (called Triton tumors), cartilage, and even bones. The term epithelioid malignant schwannoma has been applied to cases in which aggressive tumors are derived from nerve sheaths and contain tumor cells having visible cell borders, epithelial-type nests, and immunoreactivity for S100 protein, but not for keratin. The purely epithelioid type is one of the most difficult variants to diagnose. It accounts for approximately 5% of all MPNSTs and may easily cause confusion with carcinoma or melanoma. This type grows in a nodular pattern and practically always exhibits necrosis. The epithelioid cells are closely packed and grow in sheets. However, small foci of spindling with more classic schwannian histology are practically always found in areas of hypocellularity.

The morphologic features, which if present in combination help confirm the diagnosis of MPNST, include (a) alternating hypocellular-hypercellular regions; (b) appearance of a thin wavy or comma-shaped nucleus, particularly in hypocellular areas; (c) presence of nuclear palisading; (d) presence of nervelike whorls or tactoid bodies resembling Wagner-Meissner corpuscles; (e) prominent thick-walled vasculature; and (f) the presence of heterologous elements.

Malignant peripheral nerve sheath tumors exhibit the same immunohistochemical profile as benign peripheral nerve sheath tumors. In about 50% to 80% of the tumors, reactivity for S100 protein is demonstrated; however, the staining tends to be focal and limited to small proportions of tumor cells. A similar pattern is seen for Leu-7 and myelin basic protein, with focal positivity occurring in about 50% of the cases. It may be that epithelial membrane antigen is focally positive, a finding in agreement with the presence of perineurial cell component in the tumors.

Electron microscopic findings of the MPNSTs are also characterized by many of the same features as benign nerve sheath tumors. In well-differentiated MPNSTs, the cells and branched cytoplasmic processes are coated with basal lamina, and occasional wisps of cytoplasm curl around themselves. In less well-differentiated MPNSTs, the basal laminae are poorly developed or incomplete.[8]

Despite the relatively slow growth rate of some cases, MPNSTs demonstrate the clinical evolution of a highly malignant neoplasm.[9] Local recurrence (often in the cut nerve ends) and distant metastases are frequent.[10] In general, there is little correlation between microscopic grading and prognosis. However, a plexiform variant of MPNST occurring in a superficial location in children has been associated with a better prognosis.

References

[1.] Newbould MJ, Wilkinson N, Mene A. Post-radiation malignant peripheral nerve sheath tumor: a report of two cases. Histopathology. 1990;17:263-265.

[2.] Ghali VS, Gold JE, Vincent RA, Cosgrove JM. Malignant peripheral nerve sheath tumor arising spontaneously from retroperitoneal ganglioneuroma: a case report, review of the literature, and immunohistochemical study. Hum Pathol. 1992;23:72-75.

[3.] Menon AG, Anderson KM, Riccardi VM, et al. Chromosome 17p deletions and p53 gene mutations associated with the formation of malignant neurofibrosarcomas in von Recklinghausen neurofibromatosis. Proc Natl Acad Sci U S A. 1990;87:5435-5439.

[4.] D'Agostino AN, Soule EN, Miller RH. Sarcomas of the peripheral nerves and somatic soft tissues associated with multiple neurofibromatosis (von Recklinghausen's disease). Cancer. 1963;16:1015.

[5.] Ducatman BS, Scheithauer BW, Piepgras DG. Malignant peripheral nerve sheath tumors: a clinicopathologic study of 120 cases. Cancer. 1986;57:2006-2021.

[6.] Hruban RH, Shiu MH, Senie RT, et al. Malignant peripheral nerve sheath tumors of the buttock and lower extremity. Cancer. 1990;66:1253-1265.

[7.] Guccion JG, Enzinger FM. Malignant schwannoma associated with von Recklinghausen's neurofibromatosis. Virchows Arch Virchows Arch A Pathol Anat Histol. 1979;383:43-57.

[8.] Erlandson RA, Woodruff JM. Peripheral nerve sheath tumors: an electron microscopic study of 43 cases. Cancer. 1982;49:273-287.

[9.] Bojsen-Moller M, Myhre-Jensen O. A consecutive series of 30 malignant schwannomas: survival in relation to clinical-pathological parameters and treatment. Acta Pathol Microbiol Immunol Scand [A]. 1984;92:147-155.

[10.] Wanebo JE, Malic JM, Vanden Berg SR, Wanebo HJ. Malignant peripheral nerve sheath tumors: a clinicopathologic study of 28 cases. Cancer. 1993;71: 1247-1253.

Accepted for publication December 3, 1999.

From the Department of Pathology, Medical College of Ohio, School of Medicine, Toledo, Ohio.

Reprints not available from the author.