Myoepithelial carcinoma of the nasopharynx: Rare case report with clinicopathologic and immunohistochemical features review of literature

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1 Received: 25 September 2017 Revised: 20 November 2017 Accepted: 5 February 2018 DOI: /hed CASE REPORT Myoepithelial carcinoma of the nasopharynx: Rare case report with clinicopathologic and immunohistochemical features review of literature Linyan Chen MD 1 Yiyun Fu MD 2 Haiyang Wang MD 3 Fuyao Yang MD 1 Jun Liu MD 3 Fan Xia MD 1 Xuelei Ma MD 1 1 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University and Collaborative Innovation Center, Chengdu, People s Republic of China 2 Department of Pathology, West China Hospital, Sichuan University, Chengdu, People s Republic of China 3 Department of Otolaryngology, Head and Neck Surgery, West China Hospital, Sichuan University, Chengdu, People s Republic of China Correspondence Xuelei Ma, Department of Pathology, West China Hospital, Sichuan University, No. 37, Guoxue Alley, Chengdu , People s Republic of China. drmaxuelei@gmail.com Abstract Background: Myoepithelial carcinoma is a rare salivary carcinoma, which most often arises from the major salivary glands. Only a few cases of myoepithelial carcinoma of the nasopharynx have been reported, thus, the treatment guideline and prognosis remain undefined. Methods: We reported a case of nasopharyngeal myoepithelial carcinoma in a 31- year-old man. The tumor cells showed specific cell types and arrangements histologically, which were immunoreactive with myoepithelial markers. The patient received surgical excision with transpalatal approach. A literature review of previous cases was also presented. Results: The patient reflected residual tumor 4 weeks later. After concurrent chemoradiotherapy (CRT), the tumor reduced and remained stable without signs of progression. Conclusion: The nasopharyngeal mass with spindled, plasmacytoid, epithelioid, and clear cell types, was suggested to raise the suspicion of myoepithelial carcinoma in order to diagnose and treat early. The wide surgical excision followed by optimal adjuvant therapy might offer a mode of treatment with better survival results. KEYWORDS case report, immunohistochemistry, myoepithelial carcinoma, nasopharynx, surgical treatments 1 INTRODUCTION Myoepithelial carcinoma, also referred to as malignant myoepithelioma, is a rare salivary carcinoma occupying approximately 10% of the myoepithelioma. Compared to myoepithelioma, the main characteristics of myoepithelial carcinoma included variable degrees of cellular atypia and infiltrative growth of malignant cells. 1 Myoepithelial carcinomas were mainly found in major salivary glands, such as the parotid gland (48%-75%) and less often occurred in minor Linyan Chen and Xuelei Ma contributed equally to this work. salivary glands sites. 2 According to the reported cases, a few myoepithelial carcinomas developed in unusual locations, for instance, the lung, maxillary sinus, breast, and nasal cavity. 3 The existence of minor salivary glands in nasopharyngeal mucosa may provide a possibility for the occurrence of myoepithelial carcinoma. For all we know, myoepithelial carcinoma rarely happened in the nasopharynx, accounting for 0.3%-0.5% of nasopharyngeal cancer, and only 6 cases in English have previously been reported to date. 4 9 Therefore, we reported a case of a 31-year-old man with nasopharyngeal myoepithelial carcinoma and performed a literature review of previous cases. E62 VC 2018 Wiley Periodicals, Inc. wileyonlinelibrary.com/journal/hed Head & Neck. 2018;40:E62 E67.

2 E63 FIGURE 1 A, Nasoscopic image and B, preoperative MRI scans with axial, C, coronal, and D, sagittal plane of a huge mass (arrows) in the nasopharyngeal space 2 CASE REPORT A 31-year-old man with complaints of neoplasms in the nasopharyngeal site was referred to the Department of Head and Neck Oncology, Cancer Center of West China Hospital. He had symptoms of recurrent nasal obstruction for 1 year, and felt a foreign body sensation and dysphagia for 4 weeks duration. A week before this medical consultation, the patient was diagnosed with chronic tonsillitis in another hospital, and was treated by tonsillectomy of the right side while under general anesthesia. The tonsillectomy of the left side was terminated due to the neoplasms located in the parapharyngeal space posterior to the left tonsils. Hence, the patient was admitted to West China Hospital for further diagnosis and treatment. During nasoscopic examination, we found a large mass in the nasopharynx, and no active bleeding had occurred (Figure 1A). There were no palpably enlarged lymph nodes in the neck, and a chest radiograph did not reveal any abnormal changes of distant metastases. An MRI scan of the nasopharynx showed the huge soft tissue mass with maximum cross-section area of cm and blurred boundary (Figure 1B-D). The mass was apparently enhanced on contrast MRI, and had a downward extension involving the upper part of the oropharynx. The destruction of bone of clivus and the anterior arch of atlas was detected. The MRI also showed bilateral lymphadenopathy of the carotid sheath and increased submandibular lymph nodes. In general, there was no conclusive evidence of regional or distant metastases preoperatively. 2.1 Treatment and outcome Then, 2 days later, the excisional biopsy and surgical resection were performed with the patient under general anesthesia. With transpalatal approach, the surgeons longitudinally incised the soft palate and posterior pharyngeal wall to fully expose the mass. The nasopharyngeal tumor was well encapsulated, about cm, had an upward extension of the skull base, and a downward extension of the upper part of the oropharynx. The tumor was adjacent to the left internal carotid artery, but it did not cover the artery. The intraoperative frozen section biopsy found mitotic figures in tumor cells; however, it was still difficult in differentiating if it was a benign or malignant tumor. Therefore, the surgeons continued to peel off the capsule and remove the mass, then anastomosed the incision, and conducted tracheal intubation. After surgery, the patient refused to drink and eat for 3 days; therefore, he was fed by a nasogastric tube. One week after surgery, the tracheal intubation was extracted, and the patient was discharged from the hospital the next day. The patient came back to the hospital about 4 weeks after the operation, the new MRI scans of the nasopharynx showed a soft tissue mass with maximum cross-section area of cm and obvious enhancement. The tumor recurred rapidly with remarkable size, and we suggested that it was more likely to be a residual tumor than the local relapse (Figure 2A-C). Furthermore, the contrast CT of the chest and upper abdomen found patchy shadows in the lingula of left lung and a small nodule of 0.3 cm in the right lobe of the liver. Considering the risk of progression, the patient received concurrent chemoradiotherapy (CRT) for 4 months. The 3 cycles of chemotherapy were based on the docetaxel 1 cisplatin 1 Xeloda regimen, and 2 cycles of radiotherapy were performed on volumetric-modulated arc therapy with a dose of Gy in 43 fractions. During the period of concurrent CRT, the size of the tumor remained stable, and the patchy shadow of the left lung due to infection had been absorbed. Three months after termination of concurrent CRT, the MRI scans revealed the reduced tumor of cm, and the nodule of the right lobe of the liver tended to be a cyst rather than metastasis. According to the latest MRI at 6 months after concurrent CRT, the tumor still was cm (Figure 3A-C). The second cervical vertebra reflected an abnormal signal, which indicated the possibility of invasion but brain metastases were not founded. In short, there were no signs of progression in the latest follow-up. 2.2 Histopathological findings Histologically, myoepithelial carcinoma revealed varied cell types, including spindle-shaped cells and polygonal epithelioid cells with nuclear pleomorphism and distinct nucleoli, which

3 E64 FIGURE 2 Postoperative MRI images with A, axial, B, coronal, and C, sagittal plane of a residual mass (arrows) in the nasopharyngeal space formed the sheet-like and irregularly reticular collections without glandular or ductal differentiation (Figure 4A,B). In the immunohistochemistry tests, there existed wide and intense positive expression of pan-cytokeratin (pan-ck; Figure 4C), calponin (Figure 4D), as well as epithelial membrane antigen (EMA). The tumor cells were focally positive for P63 (Figure 4E) and CK5/6, and weakly positive for P40, calrenin, and S-100 protein (Figure 4F). The Ki-67 (proliferation index) was approximately 10%. 3 DISCUSSION As the malignant variant of myoepithelioma, myoepithelial carcinoma showed similar cytological and architectural appearance to myoepithelioma. Myoepithelial carcinoma usually consists of polymorphic cells, such as spindleshaped, plasmacytoid, epithelioid, and clear cells, which can form nesting, sheet-like, reticular, or cord-like arrangements. 1 Moreover, myoepithelial carcinoma was characterized by marked nuclear pleomorphism, mitotic activity, cellular atypia, and capability of metastasis, probably with lymphovascular or perineural invasion. 10 Based on a review of 70 cases, the median age at diagnosis was patients in their 60s with a wide range of 14 to 86 years. There existed no significant sex predominance. 11 The characteristics of previous 6 cases are summarized in Table Through CT and MRI scans, the definite heterogeneous lesions with smooth edges and mild enhancement can be found. Compared with the low specificity of CT and MRI, the immunohistochemistry test was useful in distinguishing myoepithelial carcinoma via the discrimination of characteristic myoepithelial phenotype. 12 On immunohistochemical staining, the primary or entire myoepithelial tissues were positive for myoepithelial markers. Therefore, probable positive expressions of cytokeratin, EMA, S-100 protein, glial fibrillary acidic protein (GFAP), calponin, smooth muscle actin (SMA), and nuclear staining of p63, as well as rare expression of desmin were reflected in the tumor cells. 1,11 Based on the review of nasopharyngeal myoepithelial carcinoma, all cases demonstrated positive epithelial and myogenic markers (cytokeratin, S-100 protein, SMA, and calponin), however, 2 case did not express GFAP or EMA. 8,9 Recommended as the probably best myoepithelial marker, P63 was not significantly expressed in a previous case. 8 In the current case, P63 and calponin were positive, however, it should be taken into account that calponin can also be expressed in smooth muscle and myofibroblastic tumors. Although there were few available clinical cases, patients with myoepithelial carcinoma showed an increased risk of local recurrence, metastasis, and cancer-specific mortality. Considering the risk of relapse, the radical surgery was advised to operate with enough normal range. The lymph node metastasis rate usually was not significant, thus it is better to perform elective neck dissection rather than radical neck dissection. However, the wide range of tumors, especially in the parotid and submandibular glands, could be treated with appropriate radical neck dissection. 10 In FIGURE 3 space The latest MRI after chemoradiotherapy with A, axial, B, coronal, and C, sagittal plane of a reduced mass (arrows) in the nasopharyngeal

4 E65 FIGURE 4 Histopathological findings. A, Whole view of the biopsy fragments (hematoxylin-eosin stain; original magnification 310). B, Spindleshaped and epithelioid cells with nuclear pleomorphism and distinct nucleoli in sheet-like and irregular reticular arrangement (hematoxylin-eosin stain; original magnification 340). C and D, Wide and intense positive expression of pan-cytokeratin (original magnification 310) and calponin (original magnification 310). E, Focal positive expression of P63 (original magnification 340). F, Weak positive expression of S-100 protein (original magnification 320) addition, myoepithelial carcinoma showed high ability of hematogenous metastasis, which probably occurred in the postoperative period, often with the recurrence of primary lesions. Thus, the patients should undergo the routine examinations of the lung and other organs, such as chest radiography. Postoperative chemotherapy was considered as an effective prevention of hematogenous metastasis. 13 Postoperative radiotherapy was widely used and showed effectiveness for high-grade myoepithelial carcinoma with recurrence or extension; however, articles also suggested that myoepithelial carcinoma might not be sensitive to radiotherapy. 10 Therefore, further researches were required to assess the efficacy of surgery, chemotherapy, and radiotherapy for patients with myoepithelial carcinoma. In addition, we summarized 86 patients with myoepithelial carcinoma in other sites according to several studies. 2,12,14 Among 44 patients with adequate follow-up, 24 patients developed tumor recurrence, mostly multiple, and 11 patients developed lymph node or distant metastases, mainly in the lungs. In addition, 9 patients died of disease. It seems that myoepithelial carcinoma led to a poor prognosis due to the ability of aggressiveness and recurrence despite the application of surgery and adjuvant therapies. Meanwhile, according to the previous 6 cases about nasopharyngeal myoepithelial carcinoma, the patient of 1 case was treated by the midfacial degloving approach with postoperative CRT, but developed intracranial and pulmonary metastases 15 months later and died 4 weeks later. 9 Three cases applied the infratemporal fossa approach type C, lateronasal approach, or transpalatal approach with mandibulotomy to enable adequate resection, and the patients lived without recurrence and metastasis during follow-up. 4 6 In another case, the patient was free of progression at 5 months

5 E66 TABLE 1 Clinical and immunohistological characteristics of previously reported cases of myoepithelial carcinoma of the nasopharynx Immunohistochemistry Author and publication year Age, years Sex Size cm Follow-up, months Histopathology Epithelial markers Myogenic markers Other markers Treatments Survival outcome Tuncel et al Female Clear cells arranged in reticular pattern CK(1), EMA(-), GFAP(-) SMA(1) S-100(1) Midfacial degloving approach with a LeFort 1 osteotomy, RT, CT Reflected metastases 15 mo later. Died of disease 4 wk later. Magliulo et al Female NA 60 Clear cells arranged in lumps separated by fibrous layers CK(1) SMA(1) S-100(1) Infratemporal fossa approach type C No signs of recurrence Gaio et al Female Clear cells arranged in nesting pattern CK5/6(1) SMA(1), calponin(1), P63(1) S-100(1) Transfacial excision with lateronasal approach No signs of recurrence Dhawan et al Female Spindled and epithelioid cells arranged in sheetlike and cord-like patterns CK(1) SMA(1) S-100(1) Paramedian mandibulotomy with transpalatal approach, RT No signs of recurrence and metastasis Soon et al Male Spindled and epithelioid cells arranged in islandslike and nesting pattern CK5/6(1), EMA(1), GFAP(-) SMA(1), P63(-) S-100(6) CT, RT Residual tumor without signs of progression Lu et al Male NA 8 Polymorphous cells arranged in sheet-like and reticular patterns CK(1), EMA(1), GFAP(1) SMA(1), calponin(1), P63(1) S-100(1) CT, RT Died of disease 8 mo after the diagnosis Present case 31 Male Spindled and epithelioid cells arranged in sheetlike and reticular patterns Pan-CK(1), CK5/6(1), EMA(1) Calponin(1), P63(1) S-100(6) Transpalatal approach, CT, RT Residual tumor without signs of progression Abbreviations: CK, cytokeratin; CT, chemotherapy; EMA, epithelial membrane antigen; GFAP, glial fibrillary acidic protein; NA, not available; PCK, pan-cytokeratin; RT, radiotherapy; SMA, smooth muscle actin.

6 E67 follow-up after CRT without surgery. 8 Of the most recent case, the patient also received CRT because of poor performance status but showed poor response and intolerance to chemotherapy, and eventually died 8 months later. 7 Although without specific treatment guidelines, the radical surgery with widely clear margins was the mainstay and refers to the previous treatments for myoepithelial carcinoma in relatively common sites, such as the parotid gland. 12,14 In the present case, based on the combined situation (tumor size, anatomic location, histopathological condition, and physical state) of our patient, surgical incision with the transpalatal approach may be convenient and safe. However, the residual tumor was detected 4 weeks later. Therefore, the postoperative CRT was used with a view to the residual tumor and risk of metastasis. Then, the size of the persistent tumor reduced 7 months later and remained stable without signs of progression in the latest follow-up. The effectiveness and strategy of treatments for nasopharyngeal myoepithelial carcinoma were uncertain. Therefore, more relevant cases are needed for the clinical treatment guidance. 4 CONCLUSION In conclusion, regarding the high aggressive behavior, a nasopharyngeal mass with 4 major cell types (spindled, plasmacytoid, epithelioid, and clear cell) were suggested to raise the suspicion of myoepithelial carcinoma in order to diagnose and treat the disease early. Although the recommended treatment strategy remained undefined, wide surgical excision followed by optimal adjuvant therapy might offer a mode of treatment with better survival results for patients with myoepithelial carcinoma of the nasopharynx. ORCID Xuelei Ma MD REFERENCES [1] El-Mofty SK, Oleary TR, Swanson PE. Malignant myoepithelioma of salivary glands: clinocopathologic and immunophenotypic features: review of literature and report of two cases. Int J Surg Pathol. 1994;2(2): [2] Nagao T, Sugano I, Ishida Y, et al. Salivary gland malignant myoepithelioma: a clinicopathologic and immunohistochemical study of ten cases. Cancer. 1998;83(7): [3] Wei J, Yuan X, Yao Y, Sun L, Yao X, Sun A. Primary myoepithelial carcinoma of the lung: a case report and review of literature. Int J Clin Exp Pathol. 2015;8(2): [4] Magliulo G, Pulice G, Fusconi M, Cuiuli G. Malignant myoepithelioma of the rhinopharynx: case report. Skull Base. 2005;15 (2): ; discussion 117. [5] Dhawan A, Shenoy A, Sriprakash D. Myoepithelial carcinoma of the nasopharynx: case report of a rare entity. Natl J Maxillofac Surg. 2011;2(2): [6] Gaio E, Perasole A, Bagatella F. Bilateral myoepithelioma of the nasopharynx: a case report. Auris Nasus Larynx. 2009;36(4): [7] Lu CS, Peng YJ, Kao HW, Chen HC, Ho CL, Chang PY. Nasopharyngeal myoepithelial carcinoma mimicking nasopharyngeal carcinoma. J Cancer Res Pract. 2015;2(4): [8] Soon G, Petersson F. Myoepithelial carcinoma of the nasopharynx: report of a rare case and a review of the literature. Head Neck Pathol. 2015;9(4): [9] Tuncel U, Ergul G, Ozlugedik S, Unal A. Myoepithelial carcinoma in the nasopharynx: an unusual localization. Yonsei Med J. 2004;45(1): [10] Yu G, Ma D, Sun K, Li T, Zhang Y. Myoepithelial carcinoma of the salivary glands: behavior and management. Chin Med J (Engl). 2003;116(2): [11] Gnepp DR, Henley JD, Simpson RHW, Eveson J. Chapter 6 Salivary Gland (Major and Minor) and Lacrimal Gland. Diagnostic Surgical Pathology of the Head and Neck, 2nd Edition. New York, NY, Elsevier, 2009: [12] Savera AT, Sloman A, Huvos AG, Klimstra DS. Myoepithelial carcinoma of the salivary glands: a clinicopathologic study of 25 patients. Am J Surg Pathol. 2000;24(6): [13] Shigeishi H, Mizuta K, Higashikawa K, Yoneda S, Ono S, Kamata N. Correlation of CENP-F gene expression with tumorproliferating activity in human salivary gland tumors. Oral Oncol. 2005;41(7): [14] Kane SV, Bagwan IN. Myoepithelial carcinoma of the salivary glands: a clinicopathologic study of 51 cases in a tertiary cancer center. Arch Otolaryngol Head Neck Surg. 2010;136(7): How to cite this article: Chen L, Fu Y, Wang H, et al. Myoepithelial carcinoma of the nasopharynx: Rare case report with clinicopathologic and immunohistochemical features review of literature. Head & Neck. 2018;40:E62 E67.