Japanese Journal of Clinical Oncology 30:458-462 (2000)
© 2000 Foundation for Promotion of Cancer Research
Myxofibrosarcoma with an Infiltrative Growth Pattern: A Case Report
1Department of Orthopaedic Surgery, Sapporo Medical University, School of Medicine, Sapporo and 2Pathology Division, National Cancer Center Research Institute, Tokyo, Japan
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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Myxofibrosarcoma, also known as a myxoid variant of malignant fibrous histiocytoma, is one of the most common sarcomas in the extremities of elderly people and is characterized by a high frequency of local recurrence. We report a case of myxofibrosarcoma, intermediate grade, involving the thigh along the fascial plane and between the muscles without the formation of an apparent nodular lesion. On microscopic examination, the tumor lacked areas of necrosis and pronounced cellular pleomorphism, but it was highly cellular with proliferation of spindle cells which contained large elongated, hyperchromatic and irregularly shaped nuclei, slightly eosinophilic cytoplasm and indistinct cell margins, arranged in both interlacing fascicles and a storiform pattern. Immunohistochemically, many of the tumor cells showed intense reactivity to vimentin and CD34. More than 20% of the cells were positive for p53 protein and the MIB-1 labeling index was ~30%. Desmin, alpha-smooth muscle actin, muscle-specific actin, S-100 protein, cytokeratin, epithelial membrane antigen, bcl-2 protein and neurofilament were negative. The absence of a discrete mass lesion and diffuse infiltrative nature precluded early recognition of tumor. Seven years after hindquarter amputation, the patient has been alive without evidence of local recurrence or distant metastasis. This case indicates that myxofibrosarcoma can demonstrate a highly infiltrative growth pattern. It is possible that this infiltrative nature is associated with a high rate of local recurrence of the tumor. A careful radiological examination of the extension of the tumor prior to surgery is mandatory considering the infiltrative nature of myxofibrosarcoma.
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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Myxofibrosarcoma, also known as a myxoid variant of malignant fibrous histiocytoma (MFH), is one of the most common sarcomas in the extremities of elderly people and occurs more frequently in the dermal and subcutaneous tissues than deeper soft tissues. Although myxofibrosarcomas have a circumscribed appearance, they sometimes lack a nodular appearance and demonstrate an infiltrative growth pattern (1). However, the extent of tumor infiltration has not been described previously.
We report a case of myxofibrosarcoma infiltrating the entire thigh without creating an appreciable nodular lesion. The absence of a discrete mass lesion and a diffuse infiltrative nature precluded early recognition of tumor. The patient had been diagnosed and treated as probable MFH. Seven years after hindquarter amputation, the patient has been alive without evidence of recurrence or metastasis. Retrospective review of the histology and the good prognosis of the patient led to a final diagnosis of myxofibrosarcoma, intermediate-grade. This is the first report, to our knowledge, of a myxofibrosarcoma that showed such an extreme infiltrative growth pattern.
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CASE REPORT |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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A 65-year-old man visited a local physician because of diffuse swelling in his left thigh in June 1991. Radiological examinations, including magnetic resonance imaging and computed tomographic scans, however, showed no discrete mass in the left lower limb. A definite diagnosis could not be made and the patient was followed. One year later, the patient noted that the swelling had increased and he was referred to our hospital for evaluation of the lesion.
Physical examination revealed diffuse swelling from the proximal thigh to the popliteal region. The circumference of the thigh, measured 10 cm above the patella, was 43.5 cm compared with 40.0 cm on the contralateral side. The range of motion of the knee was 0–100° of flexion. No circumscribed nodular lesion was detected. The findings of a neurovascular examination were normal. Venous dilatation was observed in the lower leg, suggesting congestion of the lower limb. No abnormalities were seen in the laboratory data.
Plain radiographs of the right lower extremity demonstrated no calcification or destructive bone lesion. The findings of magnetic resonance imaging (Fig. 1), which were taken in our hospital, were basically the same as those taken 1 year before. There was an abnormal signal lesion that appeared as low signal intensity on T1-weighted images and high signal intensity on T2-weighted images; the lesion spread along the fascial planes and muscles between the proximal two-thirds of the thigh and the proximal lower leg. The neurovascular bundle was involved in the lesion. Proximally, the lesion extended into the adductor muscles. However, the gluteus maximus muscle seemed to be intact. In spite of these findings, no discrete mass was demonstrated in the right lower extremity. We could not determine whether the lesion was a tumor or a chronic inflammatory process. Therefore, open biopsy was performed to obtain tissue specimens from the anterior, medial and lateral regions of the thigh. If the lesion was malignant, surgical treatment for this patient to achieve a safety margin was hindquater amputation. Histological examination of the three specimens led to probable diagnosis of MFH. The patient was screened for metastases using computed tomography. No lesions were seen on scans of the lung or abdomen. A hindquarter amputation was performed in November 1992. The surgical margin was planned to locate at least 5 cm apart from an abnormal signal lesion on magnetic resonance images. Histological examination revealed that a wide surgical margin had been obtained. Postoperative adjuvant chemotherapy was not performed owing to the advanced age of the patient. The patient has remained well without local recurrence or distant metastasis for 7 years.
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Pathological Findings
Macroscopically, a firm, ill-defined, white mass extended to the deep fascia involving both the adipose and muscle tissues and demonstrated an infiltrate growth pattern. There was no distinctive nodular appearance.
Histological examination of the specimens obtained at surgery showed similar features to those seen in the biopsy specimens. The tumor was characterized by diffuse infiltration of spindle cells among the adipose tissues and muscle fibers (Fig. 2). The tumor lacked areas of necrosis and pronounced cellular pleomorphism, but it was highly cellular with proliferation of spindle cells which contained large elongated, hyperchromatic and irregularly shaped nuclei, slightly eosinophilic cytoplasm and indistinct cell margins, arranged in both interlacing fascicles and a storiform pattern (Fig. 3). The lesion exhibited a focal myxoid matrix in 10% of the tumor area examined and a prominent vascular pattern of curvilinear small capillaries (Fig. 4). The mitotic count ranged from 3 to 5 mitoses/10 high-power fields. Foci of xanthoma cells and lymphocytes were commonly present.
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Immunohistochemically, many of the tumor cells showed intense reactivity to vimentin and CD34 (Fig. 5). Some tumor cells displayed nuclear staining for p53 protein (DO7) and proliferation-associated antigen Ki-67 (MIB-1). More than 20% of the cells were positive for p53 protein and the MIB-1 labeling index was ~30%. Desmin, alpha-smooth muscle actin, muscle-specific actin (HHF35), S-100 protein, cytokeratin (AE1/3), epithelial membrane antigen, bcl-2 protein and neurofilament (150 kDa) were negative. The final diagnosis was myxofibrosarcoma (myxoid MFH), intermediate-grade.
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DISCUSSION |
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TOPABSTRACTINTRODUCTIONCASE REPORTDISCUSSIONREFERENCES |
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In recent years, the concept of MFH has come under discussion (2–4). This tumor is no longer believed to show histiocytic differentiation but rather fibroblastic differentiation. Because of the broad range of histological appearances, MFH is divided into four subtypes; storiform–pleomorphic, myxoid, giant cell and inflammatory (5,6). The myxoid type, also known as a myxofibrosarcoma, is the second most common type (7,8). It is characterized by myxoid change of the stroma and also contains cellular areas indistinguishable from storiform–pleomorphic type. The myxoid type is generally defined as MFH in which at least half (50%) of the entire tumor displays a highly vascularized myxoid stroma (9). It is separated from the storiform–pleomorphic type not only because of its distinctive appearance but also because of its better prognosis.
Mentzel et al. (1) analyzed clinicopathological features of 75 cases of myxofibrosarcoma which had myxoid areas at least 10% of the whole tumor. These lesions varied in appearance from a hypocellular, mainly myxoid and purely low-grade spindle cell to high-grade, pleomorphic (MFH-like) neoplasms with multinucleated giant cells, high mitotic activity and areas of necrosis. Thirty-three of 60 (54%) cases recurred locally between 2 and 72 months after surgery. Thirteen patients developed metastases and 13 tumor-related deaths occurred. The rate of local recurrence was found to be independent of histological grade. The low-grade tumor did not develop metastases and most metastasizing lesions were high-grade.
According to Enzinger and Weiss (6), MFH often spreads for a considerable distance along fascial planes or between muscle fibers microscopically instead of its gross circumscribed appearance. Mentzel et al. (1) classified myxofibrosarcoma (myxoid type of MFH) into two groups: superficial (dermal/subcutaneous) and deep (intramuscular/mainly subfascial). The first group tends to infiltrate although the second group tends to form a single discrete mass. The first group is characterized by lesions composed of gelatinous or firmer nodules that often spread extensively in a longitudinal manner. Sometimes these tumors extend to the deep fascia, losing their nodular appearance and demonstrating a more infiltrative growth pattern. However, none of the authors described the extent of infiltrative growth of this tumor or presented an actual case.
If Enzinger and Weiss’s criteria are applied to this case, the tumor would be viewed as the storiform–pleomorphic type. However, the present tumor lacked pronounced cellular pleomorphism, as is seen in ordinary MFH, but was highly cellular with proliferation of atypical spindle cells with focal myxoid matrix and moderately increased mitotic figures. Immunohistochemical examinations revealed intense reactivity for vimentin and CD34, suggesting the primitive fibroblastic nature of the tumor cells. Thus, this tumor is best classified as myxofibrosarcoma (myxoid variant of MFH), intermediate-grade, based on Mentzel’s criteria.
As radiological and histopathological differential diagnoses of the present tumor, small round cell tumors such as extraskeletal primitive neuroectodermal tumor/Ewing’s sarcoma and malignant lymphoma may show such an infiltrative pattern, while benign intramuscular hemangioma also may reveal an infiltrative growth. However, these tumors can be distinguished from our case easily in the light of obvious morphological differences. Several myxoid mesenchymal tumors, such as low-grade fibromyxoid sarcoma, also show an infiltrative nature (10). Low-grade fibromyxoid sarcoma is characterized by a swirling, whorled growth pattern and bland, deceptively benign-appearing fibroblastic spindle cells. Our case is considerably more cellular than this tumor and has much more malignant cytological features, that is, greater nuclear hyperchromatism and pleomorphism.
The strong CD34 positivity in the present tumor may raise a suspicion of other CD34-positive spindle cell tumors, such as solitary fibrous tumor and dermatofibrosarcoma protuberans. Solitary fibrous tumor is a grossly circumscribed or pedunculated lesion and usually shows a classical morphological appearance, characterized by a haphazard, storiform arrangement of more bland spindle cells with prominent vascularity often in a hemangiopericytoma-like pattern and a fibrocollagenous stroma (11). CD34-positive malignant solitary fibrous tumor may be listed in the differential diagnosis, but malignant solitary fibrous tumor retains at least in part the above-described histological patterns with cellular atypia and increased mitotic activity (>4/10 HPF). Dermatofibrosarcoma protuberans is a nodular or multinodular infiltrating tumor of skin and, often, subcutis composed of more slender, uniform spindle cells arranged in a cartwheel or short storiform pattern. In addition, MFH, even myxoid type, as seen in our case, contains many more inflammatory cells than dermatofibrosarcoma protuberans. Reactivity for CD34 has been reported in five of 37 cases (13.5%) of MFH, although the histological subtype has not been given (12). Likewise, we have seen substantial CD34 positivity in eight of 21 cases (38%) of myxofibrosarcoma (myxoid MFH) (T. Hasegawa, unpublished data).
The present patient may be an extreme case even as a myxofibrosarcoma which shows an infiltrative growth pattern. There was no discrete nodular appearance in the entire lesion. The physical and radiological examinations could not determine whether the lesion was a tumor or a chronic inflammatory process. The high rate of local recurrence in myxofibrosarcoma is possibly associated with its infiltrative nature.
It has been reported that myxofibrosarcoma tends to become progressively higher grade in recurrences. The higher-grade neoplasms may then metastasize. After myxofibrosarcoma is diagnosed in biopsy specimens, a careful radiological examination to determine the tumor extension prior to surgical resection is mandatory considering the infiltrative growth nature. An adequate wide surgical margin should be recommended even for a low-grade or intermediate-grade myxofibrosarcoma to prevent a local recurrence.
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Acknowledgement |
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This work was supported by Grants-in-Aid from the Ministry of Education, Science, and Culture, and from the Ministry of Health and Welfare of Japan.
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FOOTNOTES |
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+ For reprints and all correspondence: Takuro Wada, Department of Orthopaedic Surgery, Sapporo Medical University, School of Medicine, S-1, W-16, Sapporo, 060-8543, Japan. E-mail: twada@sapmed.ac.jp
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REFERENCES |
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1 Mentzel T, Calonje E, Wadden C, Camplejohn RS, Beham A, Smith MA, et al. Myxofibrosarcoma: clinicopathological analysis of 75 cases with emphasis on the low-grade variant. Am J Surg Pathol 1996;20:391–405.[Web of Science][Medline]
2 Dehner LP. Malignant fibrous histiocytoma. Nonspecific morphologic pattern, specific pathologic entity or both? Arch Pathol Lab Med 1988;112:236–7.[Medline]
3 Fletcher CDM. Pleomorphic malignant fibrous histiocytomas: fact or fiction? A critical reappraisal based on 159 tumors diagnosed as pleomorphic sarcoma. Am J Surg Pathol 1992;16:213–28.[Web of Science][Medline]
4 Hollowood K, Fletcher CDM. Malignant fibrous histocytoma: morphologic pattern or pathologic entity? Semin Diagn Pathol 1995;12:210–20.[Medline]
5 Enjoji M, Hashimoto H, Tsuneyoshi M, Iwasaki H. Malignant fibrous histiocytoma: a clinicopathologic study of 130 cases. Acta Pathol Jpn 1980;30:727–41.[Medline]
6 Enzinger FM, Weiss SW. Soft Tissue Tumors. St. Louis: Mosby Year Book 1995;351–80.
7 Weiss SW, Enzinger FM. Myxoid variant of malignant fibrous histiocytoma. Cancer 1977;39:1672–85.[Web of Science][Medline]
8 Wood GS, Beckstead JH, Turner PR. Malignant fibrous histiocytoma tumor cells resemble fibroblasts. Am J Surg Pathol 1986;10:323–35.[Medline]
9 Weiss SW. Histological typing of soft tissue tumours. Berlin: Springer 1994;22.
10 Evans HL. Low-grade fibromyxoid sarcoma: a report of 12 cases. Am J Surg Pathol 1993;17:595–600.[Web of Science][Medline]
11 Hasegawa T, Matsuno Y, Shimoda T, Hasegawa F, Sano T, Hirohashi S. Extrathoracic solitary fibrous tumors: their histological variability and potentially aggressive behavior. Hum Pathol 1999;30:1464–73.[Web of Science][Medline]
12 Miettinen M, Lindenmayer AE, Chaubal A. Endothelial cell markers CD31, CD34 and BNH9 antibody to H- and Y-antigens: evaluation of their specificity and sensitivity in the diagnosis of vascular tumors and comparison with von Willebrand factor. Mod Pathol 1994;7:82–90. [Web of Science][Medline]
Received May 10, 2000; accepted July 27, 2000.
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