Four weeks after the initial visit, she visited our hospital again complaining of markedly enlarged lower eyelid mass (Fig. 1B). A magnetic resonance imaging (MRI) scan revealed the lobulated medial lesion had increased to 3 × 2.2 × 2.3 cm and a new 2 × 2 × 2 cm round enhancing mass was observed in the lateral area of the left lower eyelid (Fig. 2B). After assessing the cardiac risk preoperatively and discontinuing antiplatelet therapy, the patient underwent complete surgical excision followed by reconstruction with a free flap of latissimus dorsi myocutaneous graft under general anesthesia. This was 6 weeks after the initial presentation and at that time the 2 masses had merged and grown up to 8 × 5 × 5 cm (Fig. 1C). Macroscopically, the tumor was originated from lower eyelid and did not invade adjacent periosteum or bony structure. The natures of the excised tumor were reddish, hard, dense, and hemorrhagic without evidence of external necrosis (Fig. 1D). Six frozen sections were examined to achieve complete surgical resection of the tumor and were found to have negative intraoperative margins. The patient and her son refused adjuvant radiation therapy. The survival of the graft was excellent at 6 weeks of follow-up (Fig. 1E).
Histological findings with immunomarkers led to a definitive diagnosis of undifferentiated pleomorphic sarcoma of the lower eyelid. The tumor was composed of fascicular and haphazard arrangement of spindle and pleomorphic cells with eosinophilic cytoplasm and many typical and atypical mitoses. Frequent multinucleated giant cells were present (Fig. 3A). The tumor also showed hemorrhage and focal necrosis. A prominent inflammatory infiltrate, fibrosis, or myxoid change were not found. By immunohistochemistry, some tumor cells were weakly positive for epithelial membrane antigen (EMA), but they were negative for cytokeratin (Fig. 3B), smooth muscle actin (SMA) (Fig. 3C), desmin (Fig. 3D), S-100, Melan-A, and CD34. The tumor did not show a reproducible immunohistochemical profile. The tumor was graded by the French Federation of Cancer Centers Sarcoma Group method and classified as high grade.
No metastatic lesions were detected on a positron emission tomography/CT scan. The patient and her son refused further radiation therapy. Two months after the operation, the lesion was stable without evidence of a local recurrence; however, she died from sepsis caused by pneumonia.
This study was approved by the Institutional Review Board of Chonnam National University Hospital. It was in accordance with the principle of the Helsinki Declaration II. Because she died, the written informed consent was obtained from legal guardian.
The 2002 WHO soft tissue sarcoma classification regarded the alternative name of old nomenclature MFH to undifferentiated pleomorphic sarcoma because it provided a more accurate description of the origin of the tumor cells. According to up to date available immunohistochemical techniques, many previously diagnosed MFH tumors have been reanalyzed and only one-tenth of the cases have been rediagnosed as MFH. Furthermore, the category of MFH was completely deleted from the 2013 WHO classification of soft tissue sarcoma. In the head and neck, undifferentiated pleomorphic sarcoma is extremely rare and accounts for only about 3% of all undifferentiated pleomorphic sarcomas. After the 2002 WHO classification, there has been few articles published about a primary undifferentiated pleomorphic sarcoma of the eyelid.[1–3] Hence, our report represents an extremely rare case of a rapidly progressing primary undifferentiated pleomorphic sarcoma of the eyelid after 2002 and 2013 WHO classification.
Our case involved a 67-year-old woman who initially presented to our hospital with a 2 cm3 volumed yellow nodule on the lower eyelid. Four weeks after initial visit, she visited again complaining of a marked increase in the size of the previous mass and the appearance of a new round lower eyelid mass. The tumor's volume increased approximately 12 times over just 4 weeks. Furthermore, 6 weeks after the initial visit, 2 masses had emerged and grown to 100 times larger than at the initial visit. Therefore, this is the first report specifically describing the very aggressive nature of undifferentiated pleomorphic sarcoma of the eyelid according to the time passes. The patient underwent complete surgical excision and reconstruction with a free flap of latissimus dorsi myocutaneous graft; however, she died from sepsis caused by pneumonia even though the lesion was stable without evidence of local recurrence.
The primary management of undifferentiated pleomorphic sarcomas in the head and neck is complete surgical resection. The type of surgical resection can be decided by various aspects, which consist of tumor location, size, depth, invasion of adjacent structures, requirement for reconstruction, and the patient's general condition. The excision contains the skin, subcutaneous tissue, and soft tissue or bone adhere to the mass. Positive resection margin is an important predictor of local recurrence and disease-related mortality.[8,9] Neoadjuvant chemoradiation treatment have been investigated at the extremity and retroperitoneal tissue sarcomas during the past 2 decades, however, similar approaches for head and neck sarcomas have been investigated less. Adjuvant radiotherapy is advised for undifferentiated pleomorphic sarcoma. This is based on the findings of previous randomized trials that surgery plus adjuvant radiotherapy reduces the local recurrence rate compared with surgery-only group.[10,11] However, previous studies have shown that adjuvant radiation therapy does not increase overall survival. Chemotherapy is usually reserved for metastatic cases. The most commonly used anticancer drugs are cyclophosphamide, vincristine, and adriamycin. Trials evaluating the advantages of chemotherapy did not help to detect differences in overall survival. In addition, trials often enrolled patients with tumors of various sizes, grades, histologic subtypes, and location, and used different chemotherapy regimens. Therefore, the role of chemotherapy in undifferentiated pleomorphic sarcoma is very limited. In our case, negative intraoperative margins were obtained; therefore, the lesion was stable until she died 2 months after the operation.
The differential diagnosis of undifferentiated pleomorphic sarcoma includes sarcomatoid carcinoma, melanoma, anaplastic large cell lymphoma, and other high grade pleomorphic sarcomas such as leiomyosarcoma, liposarcoma, and rhabdomyosarcoma. The appropriate immunohistochemical cocktail usually resolves any diagnostic dilemmas in the distinction from carcinoma, melanoma, and lymphoma. Sarcomatoid carcinoma can be distinguished from undifferentiated pleomorphic sarcoma by the positive staining result for cytokeratin. Positive results for S-100 and Melan-A stainings can be valuable clues with regard to the differential diagnosis of this tumor from melanoma. In addition, CD30 or CD45 staining by immunohistochemistry provides helpful clues to differentiate undifferentiated pleomorphic sarcoma from lymphoma. Judicious use of additional immunohistochemistry can facilitate the identification of the origin of tumors to rule out pleomorphic leiomyosarcoma (SMA, desmin, and h-caldesmon), pleomorphic rhabdomyosarcoma (desmin), pleomorphic liposarcoma (S-100, SMA).[9,12,15] In our case, some tumor cells were weakly positive for EMA, however, they were negative for cytokeratin, smooth muscle actin, desmin, S-100, melan-A, CD34, etc. Therefore, we could exclude such entities and finally diagnosed as undifferentiated pleomorphic sarcoma. These are summarized in Table 1, including our case.
According to the literature, the 5-year overall survival rate for head and neck undifferentiated pleomorphic sarcoma was known as 50% to 60%. On the other hand, trunk and extremity tumors were 73%, which indicated better prognosis than head and neck undifferentiated pleomorphic sarcoma. This result could be explained by higher grade tumors and difficulties to obtain negative tumor margins due to adjacent important structures in the cases of head and neck cancer. At initial presentation, size larger than 5 cm, high histologic grade, presence of metastases were related to a poor prognosis.[18–21] In our patient, the tumor was greater than 5 cm and high histologic grade, however, since she died at 2 months after operation due to sepsis originated from pneumonia, there are limitations for analyzing prognostic factors.
In our case, periocular undifferentiated pleomorphic sarcoma was small, nodular, and located superficially at initial presentation similar to the previous reports. The tumor was located at the medial aspect of lower eyelid. Previously reported eyelid MFH did not show a tendency of location at the eyelid (upper eyelid, medial, and lateral canthus).[2,3] In the previous case report series, all cases underwent local excision as initial treatment and additional wide resection with adjuvant radiotherapy were used for subsequent local recurrence. While all of these cases were high grade and had local recurrence, it is notable that no patient has died as a result of the tumor until several years after operation. This could also be a result of the anatomic location of periocular undifferentiated pleomorphic sarcoma, which leads to earlier presentation, as compared with undifferentiated pleomorphic sarcoma arising in deeper soft tissue.
Our case is important for several reasons. First, this is an extremely rare case of primary undifferentiated pleomorphic sarcoma of the eyelid that was progressing very rapidly as we presented with time passes. Second, this case highlights the necessity of a prompt diagnosis and immediate surgical intervention if clinically suspected. Therefore, it is necessary to keep the possibility of rapid progression in mind for plastic surgeon and ophthalmologists in the cases of clinically suspected as undifferentiated pleomorphic sarcoma.
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. Yang JC, Chang AE, Baker AR, et al. Randomized prospective study of the benefit of adjuvant radiation therapy in the treatment of soft tissue sarcomas of the extremity. J Clin Oncol 1998;16:197–203.
. Matsumoto S, Ahmed AR, Kawaguchi N, et al. Results of surgery for malignant fibrous histiocytomas of soft tissue. Int J Clin Oncol 2003;8:104–9.
. Antman K, Ryan L, Borden E. Salmon SE, et al. Pooled results from three randomized adjuvant studies of doxorubicin versus observation in soft tissue sarcomas: 10 year result and review of the literature. Adjuvant Therapy of Cancer. Philadelphia: W.B. Saunders; 1990. 529.
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. Hornick JL, Bosenberg MW, Mentzel T, et al. Pleomorphic liposarcoma: clinicopathologic analysis of 57 cases. Am J Surg Pathol 2004;28:1257–67.
. Sabesan T, Xuexi W, Yongfa Q, et al. Malignant fibrous histiocytoma: outcome of tumours in the head and neck compared with those in the trunk and extremities. Br J Oral Maxillofac Surg 2006;44:209–12.
. Furlong MA, Mentzel T, Fanburg-Smith JC. Pleomorphic rhabdomyosarcoma in adults: a clinicopathologic study of 38 cases with emphasis on morphologic variants and recent skeletal muscle-specific markers. Mod Pathol 2001;14:595–603.
. Gibbs JF, Huang PP, Lee RJ, et al. Malignant fibrous histiocytoma: an institutional review. Cancer Invest 2001;19:23–7.
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Keywords:Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.
eyelid; rapid progression; undifferentiated pleomorphic sarcoma