- Email: [email protected]
Myoepithelioma: Benign or malignant – A diagnostic dilemma
Egyptian Journal of Ear, Nose, Throat and Allied Sciences xxx (2016) xxx–xxx
Contents lists available at ScienceDirect
Egyptian Journal of Ear, Nose, Throat and Allied Sciences journal homepage: www.ejentas.com
Case report
Myoepithelioma: Benign or malignant – A diagnostic dilemma Boon Chye Gan a,b,⇑, Andrew Chin a, Nor Shahida Abd Mutalib a, Hamidah Mamat a, Che Yusfarina Che Yusop a, Hisham Abdul Rahman a a b
Department of Otorhinolaryngology, Hospital Sultan Abdul Halim, Sungai Petani, Kedah, Malaysia Department of Otorhinolaryngology – Head & Neck Surgery, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kota Bharu, Kelantan, Malaysia
a r t i c l e
i n f o
Article history: Received 20 September 2016 Accepted 15 November 2016 Available online xxxx Keywords: Myoepithelioma Myoepithelial tumor Carcinoma Malignant Submandibular gland Neck dissection
a b s t r a c t Malignant myoepithelioma of salivary gland which is also known as myoepithelial carcinoma is a rare disease. It has a relatively poor clarification of its biologic behavior, clinicopathologic features and immunohistochemical profile. Presentation may be the same as other benign salivary gland tumors. A high index of suspicion is required to diagnose this rare but malignant condition early and this is especially imperative when there is a recurrent tumor with histopathological examination report of benign findings. We report a case of malignant myoepithelioma of right submandibular gland that underwent surgical excision with neck dissection and chemoradiotherapy without signs of recurrence after treatment. Ó 2016 Egyptian Society of Ear, Nose, Throat and Allied Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-ncnd/4.0/).
1. Introduction Malignant myoepithelioma of salivary gland is very rare, accounting for only 0.45% of all salivary gland tumors based on a study of 1945 tumor cases involving major salivary gland.1 Among the 10 cases of malignant myoepithelioma, only two arose from the submandibular gland while another seven from parotid gland and one from minor salivary gland of soft palate.1 It is even more rare to find a case of recurrence in low grade tumors such as myoepithelioma, only about 20% recurrence rate was reported.2 Approximately 75% of these tumors arise in the major salivary glands and about 50% originate from precursor lesions such as pleomorphic adenoma or benign myoepithelioma.3 Due to its varied histomorphology and immunohistochemical profile, it is a real diagnostic dilemma to a pathologist.4 In this case report, we share our experience in diagnosing and managing this condition. 2. Case report A 42 year-old woman presented with 3 years history of a painless, progressive right lower neck swelling that started after a fall. Peer review under responsibility of Egyptian Society of Ear, Nose, Throat and Allied Sciences. ⇑ Corresponding author at: Department of Otorhinolaryngology – Head & Neck Surgery, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kota Bharu, Kelantan, Malaysia. E-mail address: [email protected] (B.C. Gan).
The swelling did not increase with mastication or food intake. She denied odynophagia, dysphagia and constitutional symptoms. She is a housewife with no history of tuberculosis contact, smoking, alcohol consumption nor betel nut chewing. On neck examination, a firm, lobulated, well circumscribed swelling size of 9.0 8.0 cm was palpated over the right submandibular region. Swelling was non tender and no skin changes noted. No other palpable cervical lymph nodes. Other ear, nose and throat examination was unremarkable. Fine needle aspiration cytology (FNAC) was carried out and reported as benign submandibular gland myoepithelioma. Computer tomography (CT) scan neck was scheduled next (Fig. 1). CTscan neck showed a large (8.5 6.3 7.8 cm) right submandibular tumor with necrotic center that extends from right angle of mandible to 6th cervical vertebra. Due to poor fat plane with adjacent muscles and right submandibular gland, probable diagnoses at that time include malignancy, metastatic lymph node or tuberculosis. Full blood count, renal profile, liver function test, erythrocyte sedimentation rate were within normal range and tuberculosis workout were also negative. Right submandibular tumor excision was performed. Intraoperatively, we found a multilobulated, well encapsulated right submandibular mass measuring 6.0 12.0 cm and weighing 490 g. Right submandibular gland cannot be identified and was suspected to be involved together with the mass. No other lymph nodes were found around the mass. Microscopically, the specimen was multilobulated and composed of bland spindle-shaped cells arranged in fascicles. There were minimal mitotic activity with no ductal com-
http://dx.doi.org/10.1016/j.ejenta.2016.11.003 2090-0740/Ó 2016 Egyptian Society of Ear, Nose, Throat and Allied Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Please cite this article in press as: Gan B.C., et al. Myoepithelioma: Benign or malignant – A diagnostic dilemma. Egypt J Ear Nose Throat Allied Sci (2016), http://dx.doi.org/10.1016/j.ejenta.2016.11.003
2
B.C. Gan et al. / Egyptian Journal of Ear, Nose, Throat and Allied Sciences xxx (2016) xxx–xxx
Fig. 1. 1st CTscan neck of axial view showing a large right submandibular aggressive tumor.
Fig. 3. 2nd CTscan neck at four months after tumor excision. This axial view showed another right submandibular lesion that exhibit similar appearance as previous right submandibular mass in the 1st CTscan neck.
ponents. There was a central area of hyaline necrosis and myxoid degeneration but no sign of coagulative tumor cell necrosis (Fig. 2). All margins were negative with no lymphovascular invasion. Immunohistochemical profile showed diffuse positive smooth muscle actin and focal positive pan-keratin. Epithelial membrane Ag, S-100 protein and CD34 marker were negative. Histopathology examination (HPE) reported by pathologist was salivary gland myoepithelioma. Patient was discharged and recovered well. At 4 months clinic follow up, she was found to have a mobile 2.0 2.0 cm mass adjacent to the wound, at the same site as the previous swelling. FNAC over the swelling showed tumor recurrence with cellular atypia. A repeat CTscan neck was performed and showed a single 3.0 3.3 cm recurrence at the same location as the previous tumor (Fig. 3). The previous large right submandibular mass was no longer seen.
Excision of the recurrent right submandibular mass was carried out. Histopathology assessment of the tumor by pathologist confirmed that this is indeed a recurrent benign myoepithelioma. Detailed deliberation with pathologist concluded that the lesion was indeed benign. On subsequent follow up five months later, the patient was again found to have developed 2 further lesions, a 1.0 1.0 cm swelling over the right submandibular region and another 3.0 2.0 cm swelling over the submental region. Repeated FNAC showed recurrent myoepithelial tumor. Third CTscan neck (Fig. 4) was performed and this showed multiple round soft tissues masses of various sizes in the right submandibular and submental region, with the largest measuring 3.0 3.2 4.6 cm over the submental region. Radiological features were suggestive of recurrent right salivary myoepithelioma. There were multiple round soft tissues masses of various sizes noted in the right submandibular and submental region, largest measured 3 3.2 4.6 cm over
Fig. 2. Microscopic examination showing area of hyaline necrosis and myxoid degeneration at its center. (Hematoxylin and eosin staining; magnification 40.)
Fig. 4. 3rd CTscan neck at 5 months after 2nd tumor excision. This axial view showed multiple masses of various sizes in the right submandibular and submental region.
Please cite this article in press as: Gan B.C., et al. Myoepithelioma: Benign or malignant – A diagnostic dilemma. Egypt J Ear Nose Throat Allied Sci (2016), http://dx.doi.org/10.1016/j.ejenta.2016.11.003
B.C. Gan et al. / Egyptian Journal of Ear, Nose, Throat and Allied Sciences xxx (2016) xxx–xxx
3
the submental region. Radiological features were suggestive of recurrent right salivary myoepithelioma. Right type II modified radical neck dissection with right segmental mandibulectomy and left supraomohyoid neck dissection was performed (see Fig. 5). Multiple large lymph nodes were found over the level IB and level II which were adherent to the sternocleidomastoid muscle. The right submental tumor measured 5.0 5.0 cm, extending across to the left side and eroding the right body of mandible. No reconstruction was done as no expertise was available in our center. The affected bone was removed for adequate oncological clearance. Histopathology of the resected specimen showed similar features to the previously resected tumors (Fig. 6) but with high mitotic activity. There was no involvement of level I–V lymph nodes. This specimen was reported as a malignant myoepithelioma. Patient underwent post operative adjuvant chemoradiotherapy and at 1 year follow up, she was found to be well and free of recurrence. We also noticed that functional outcome including chewing and speech was acceptable even without reconstruction.
3. Discussion Malignant myoepithelioma is a rare salivary gland tumor that has diverse clinical, pathological and immunohistochemical presentation.1 Most patients with malignant myoepithelioma present with a painless swelling, occasionally with a recent rapid increase in size. The symptoms vary depending on the location.5 A neck presentation may just be a painless swelling like in this case.5 Other sites such as laryngeal location may manifest as hoarseness, paranasal sinus location may be associated with epistaxis, nasal blockage or facial pain while parotid swelling may present with facial nerve paralysis.6–8 Due to the varying presentations, the average duration for diagnosis can be from 3 months to 3 years from the onset of symptoms.9 A good history taking, routine clinical examination, CTscan and FNAC may not be adequate to diagnose malignant myoepithelioma. This condition may be missed in FNAC because the cytological features of the disease are diverse and may lack overt feature of malignancy.10 False negative results have been reported mainly due to errors made in underdiagnosis because low grade tumors usually demonstrate bland cytologic features.11 In this case report,
Fig. 5. Right segmental mandibulectomy was performed because there were intraoperative signs of mandibular invasion over the right body of mandible including thinning and erosion of the bone.
Fig. 6. Microscopic examination showed spindled tumor cells arranged in intersecting fascicles with minimal nuclear pleomorphism but high mitotic activity. (Hematoxylin and eosin staining; magnification 200.)
we had a dilemma in both diagnosing and treating this condition. Despite having a clinical and radiological features that suggest malignancy, extensive surgery and adjuvant chemoradiotherapy cannot be proposed to the patient when both of the 1st and 2nd operative specimens were concluded as benign. However, we still proceeded with an extensive resection and deep cervical nodes clearance at the 3rd operation without histopathological report. This decision was made solely based on clinical suspicion of malignancy following the recurrent and aggressive nature of the tumor. To diagnose malignant myoepithelioma, the most notable criteria in microscopy is tumor infiltration into adjacent tissues and high cell proliferative activity (>7 mitoses per 10 high-power fields or a Ki-67 labeling index of >10%).5 Myoepithelial markers such as muscle actins, cytokeratin 14, vimentin, calponin and S-100 protein are highly expressed.1 Prognosis is deemed poorer when there is presence of marked cellular pleomorphism, p53 expression and high cell proliferative activity.1 In terms of treatment, extensive excision is the most favorable choice for malignant myoepithelioma.12 When the submandibular gland is involved, supraomohyoid lymph node dissection is recommended.12 Postoperative radiotherapy have questionable result in terms of prognosis but chemotherapy may be helpful.13 In ideal setting, where reconstruction is possible with available expertise, reconstruction with osteomyocutaneous graft like free fibular graft would have provided an excellent outcome. However, due to limited resources being a third world developing country and lack of plastic surgeons and free flap expertise, a patient would also achieve relatively good functional outcome with adequate oncological clearance with what was done in this case. In conclusion, diagnosis may be difficult for pathologist as this disease is very rare and it may present in different stages of myoepithelial differentiation.1 In our case, the diagnosis cannot be concluded until the 3rd histopathologic examination as immunohistochemical profile was not suggestive in the earlier 2 samples. Rare type of salivary gland tumors, especially those arising from unusual locations with unfamiliar histomorphologies can cause diagnostic difficulties to pathologist.4 Therefore, awareness of the disease and its pathologic features with diligent use of immunohistochemistry are crucial for the accurate diagnosis of malignant myoepithelioma.4,12 A high index of suspicion is required to diagnose despite microscopical examination that may
Please cite this article in press as: Gan B.C., et al. Myoepithelioma: Benign or malignant – A diagnostic dilemma. Egypt J Ear Nose Throat Allied Sci (2016), http://dx.doi.org/10.1016/j.ejenta.2016.11.003
4
B.C. Gan et al. / Egyptian Journal of Ear, Nose, Throat and Allied Sciences xxx (2016) xxx–xxx
reveal only benign findings. In this case, despite two adequate excisions, patient still presented back to the clinic with recurrent swelling after several months of operation. Clinical presentation like this should prompt clinicians on the possibility of malignant myoepithelioma. References 1. Nagao T, Sugano I, Ishida Y, et al.. Salivary gland malignant myoepithelioma: a clinicopathologic and immunohistochemical study of ten cases. Cancer. 1998;83:1292–1299. 2. Hornick JL, Fletcher CD. Myoepithelial tumors of soft tissue: a clinicopathologic and immunohistochemical study of 101 cases with evaluation of prognostic parameters. Am J Surg Pathol. 2003;27:1183–1196. 3. Hayashi A, Yokoyama J, Sato R, et al.. Massive myoepithelial carcinoma originating from the submandibular gland that was successfully treated with surgical excision, using a part of the lengthened skin as a local flap. Plastic Reconstr Surg Global Open. 2015;3:e329. 4. Gore Charusheela R, Panicker NK, Chandanwale SS, Singh Bikash K. Myoepithelioma of minor salivary glands – a diagnostic challenge: report of three cases with varied histomorphology. J Oral Maxillofac Pathol. 2013;17 :257–260
5. 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;24:761–774. 6. Yu G, Qu G, Kong L, Pan X, Wang W, Lv J. Primary myoepithelial carcinoma of the larynx: case report and review of the literature. Pathol Res Pract. 2011;207:127–130. 7. Yamanegi K, Uwa N, Hirokawa M, et al.. Epithelial-myoepithelial carcinoma arising in the nasal cavity. Auris Nasus Larynx. 2008;35:408–413. 8. Saliba Issam, El Khatib Nazir, Nehme Antoine, Nasser Selim, Moukarzel Nabil. Metastatic parotid myoepithelial carcinoma in a 7-year-old boy. Case Rep Pediatr. 2012;2012:212746. 9. Sasaguri T, Tanimoto A, Arima N, Hamada T, Hashimoto H, Sasaguri Y. Myoepithelioma of soft tissue. Pathol Int. 1999;49:571–576. 10. Sehgal Shelly, Goyal Prashant, Singh Sompal, Kumar Awanindra. Fine-needle aspiration cytology of myoepithelial carcinoma of salivary gland: diagnostic challenge to cytopathologist. J Cytol. 2013;30(3):207–210. 11. Fernandes Hilda, D’souza Clement RS, Khosla Charu, George Lovely, Katte Namitha Hegde. Role of FNAC in the preoperative diagnosis of salivary gland lesions. J Clin Diagn Res. 2014;8(9):FC01–FC03. 12. Wang C, Zhang Z, Ge Y, et al.. Myoepithelial carcinoma of the salivary glands: a clinicopathologic study of 29 patients. J Oral Maxillofac Surg. 2015;1. 13. Xua Tao, Liao Zhiwei, Tang Jun, et al.. Myoepithelial carcinoma of the head and neck: a report of 23 cases and literature review. Cancer Treatment Commun. 2014;2:24–29.
Please cite this article in press as: Gan B.C., et al. Myoepithelioma: Benign or malignant – A diagnostic dilemma. Egypt J Ear Nose Throat Allied Sci (2016), http://dx.doi.org/10.1016/j.ejenta.2016.11.003
Contents lists available at ScienceDirect
Egyptian Journal of Ear, Nose, Throat and Allied Sciences journal homepage: www.ejentas.com
Case report
Myoepithelioma: Benign or malignant – A diagnostic dilemma Boon Chye Gan a,b,⇑, Andrew Chin a, Nor Shahida Abd Mutalib a, Hamidah Mamat a, Che Yusfarina Che Yusop a, Hisham Abdul Rahman a a b
Department of Otorhinolaryngology, Hospital Sultan Abdul Halim, Sungai Petani, Kedah, Malaysia Department of Otorhinolaryngology – Head & Neck Surgery, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kota Bharu, Kelantan, Malaysia
a r t i c l e
i n f o
Article history: Received 20 September 2016 Accepted 15 November 2016 Available online xxxx Keywords: Myoepithelioma Myoepithelial tumor Carcinoma Malignant Submandibular gland Neck dissection
a b s t r a c t Malignant myoepithelioma of salivary gland which is also known as myoepithelial carcinoma is a rare disease. It has a relatively poor clarification of its biologic behavior, clinicopathologic features and immunohistochemical profile. Presentation may be the same as other benign salivary gland tumors. A high index of suspicion is required to diagnose this rare but malignant condition early and this is especially imperative when there is a recurrent tumor with histopathological examination report of benign findings. We report a case of malignant myoepithelioma of right submandibular gland that underwent surgical excision with neck dissection and chemoradiotherapy without signs of recurrence after treatment. Ó 2016 Egyptian Society of Ear, Nose, Throat and Allied Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-ncnd/4.0/).
1. Introduction Malignant myoepithelioma of salivary gland is very rare, accounting for only 0.45% of all salivary gland tumors based on a study of 1945 tumor cases involving major salivary gland.1 Among the 10 cases of malignant myoepithelioma, only two arose from the submandibular gland while another seven from parotid gland and one from minor salivary gland of soft palate.1 It is even more rare to find a case of recurrence in low grade tumors such as myoepithelioma, only about 20% recurrence rate was reported.2 Approximately 75% of these tumors arise in the major salivary glands and about 50% originate from precursor lesions such as pleomorphic adenoma or benign myoepithelioma.3 Due to its varied histomorphology and immunohistochemical profile, it is a real diagnostic dilemma to a pathologist.4 In this case report, we share our experience in diagnosing and managing this condition. 2. Case report A 42 year-old woman presented with 3 years history of a painless, progressive right lower neck swelling that started after a fall. Peer review under responsibility of Egyptian Society of Ear, Nose, Throat and Allied Sciences. ⇑ Corresponding author at: Department of Otorhinolaryngology – Head & Neck Surgery, School of Medical Sciences, Universiti Sains Malaysia, Health Campus, 16150 Kota Bharu, Kelantan, Malaysia. E-mail address: [email protected] (B.C. Gan).
The swelling did not increase with mastication or food intake. She denied odynophagia, dysphagia and constitutional symptoms. She is a housewife with no history of tuberculosis contact, smoking, alcohol consumption nor betel nut chewing. On neck examination, a firm, lobulated, well circumscribed swelling size of 9.0 8.0 cm was palpated over the right submandibular region. Swelling was non tender and no skin changes noted. No other palpable cervical lymph nodes. Other ear, nose and throat examination was unremarkable. Fine needle aspiration cytology (FNAC) was carried out and reported as benign submandibular gland myoepithelioma. Computer tomography (CT) scan neck was scheduled next (Fig. 1). CTscan neck showed a large (8.5 6.3 7.8 cm) right submandibular tumor with necrotic center that extends from right angle of mandible to 6th cervical vertebra. Due to poor fat plane with adjacent muscles and right submandibular gland, probable diagnoses at that time include malignancy, metastatic lymph node or tuberculosis. Full blood count, renal profile, liver function test, erythrocyte sedimentation rate were within normal range and tuberculosis workout were also negative. Right submandibular tumor excision was performed. Intraoperatively, we found a multilobulated, well encapsulated right submandibular mass measuring 6.0 12.0 cm and weighing 490 g. Right submandibular gland cannot be identified and was suspected to be involved together with the mass. No other lymph nodes were found around the mass. Microscopically, the specimen was multilobulated and composed of bland spindle-shaped cells arranged in fascicles. There were minimal mitotic activity with no ductal com-
http://dx.doi.org/10.1016/j.ejenta.2016.11.003 2090-0740/Ó 2016 Egyptian Society of Ear, Nose, Throat and Allied Sciences. Production and hosting by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Please cite this article in press as: Gan B.C., et al. Myoepithelioma: Benign or malignant – A diagnostic dilemma. Egypt J Ear Nose Throat Allied Sci (2016), http://dx.doi.org/10.1016/j.ejenta.2016.11.003
2
B.C. Gan et al. / Egyptian Journal of Ear, Nose, Throat and Allied Sciences xxx (2016) xxx–xxx
Fig. 1. 1st CTscan neck of axial view showing a large right submandibular aggressive tumor.
Fig. 3. 2nd CTscan neck at four months after tumor excision. This axial view showed another right submandibular lesion that exhibit similar appearance as previous right submandibular mass in the 1st CTscan neck.
ponents. There was a central area of hyaline necrosis and myxoid degeneration but no sign of coagulative tumor cell necrosis (Fig. 2). All margins were negative with no lymphovascular invasion. Immunohistochemical profile showed diffuse positive smooth muscle actin and focal positive pan-keratin. Epithelial membrane Ag, S-100 protein and CD34 marker were negative. Histopathology examination (HPE) reported by pathologist was salivary gland myoepithelioma. Patient was discharged and recovered well. At 4 months clinic follow up, she was found to have a mobile 2.0 2.0 cm mass adjacent to the wound, at the same site as the previous swelling. FNAC over the swelling showed tumor recurrence with cellular atypia. A repeat CTscan neck was performed and showed a single 3.0 3.3 cm recurrence at the same location as the previous tumor (Fig. 3). The previous large right submandibular mass was no longer seen.
Excision of the recurrent right submandibular mass was carried out. Histopathology assessment of the tumor by pathologist confirmed that this is indeed a recurrent benign myoepithelioma. Detailed deliberation with pathologist concluded that the lesion was indeed benign. On subsequent follow up five months later, the patient was again found to have developed 2 further lesions, a 1.0 1.0 cm swelling over the right submandibular region and another 3.0 2.0 cm swelling over the submental region. Repeated FNAC showed recurrent myoepithelial tumor. Third CTscan neck (Fig. 4) was performed and this showed multiple round soft tissues masses of various sizes in the right submandibular and submental region, with the largest measuring 3.0 3.2 4.6 cm over the submental region. Radiological features were suggestive of recurrent right salivary myoepithelioma. There were multiple round soft tissues masses of various sizes noted in the right submandibular and submental region, largest measured 3 3.2 4.6 cm over
Fig. 2. Microscopic examination showing area of hyaline necrosis and myxoid degeneration at its center. (Hematoxylin and eosin staining; magnification 40.)
Fig. 4. 3rd CTscan neck at 5 months after 2nd tumor excision. This axial view showed multiple masses of various sizes in the right submandibular and submental region.
Please cite this article in press as: Gan B.C., et al. Myoepithelioma: Benign or malignant – A diagnostic dilemma. Egypt J Ear Nose Throat Allied Sci (2016), http://dx.doi.org/10.1016/j.ejenta.2016.11.003
B.C. Gan et al. / Egyptian Journal of Ear, Nose, Throat and Allied Sciences xxx (2016) xxx–xxx
3
the submental region. Radiological features were suggestive of recurrent right salivary myoepithelioma. Right type II modified radical neck dissection with right segmental mandibulectomy and left supraomohyoid neck dissection was performed (see Fig. 5). Multiple large lymph nodes were found over the level IB and level II which were adherent to the sternocleidomastoid muscle. The right submental tumor measured 5.0 5.0 cm, extending across to the left side and eroding the right body of mandible. No reconstruction was done as no expertise was available in our center. The affected bone was removed for adequate oncological clearance. Histopathology of the resected specimen showed similar features to the previously resected tumors (Fig. 6) but with high mitotic activity. There was no involvement of level I–V lymph nodes. This specimen was reported as a malignant myoepithelioma. Patient underwent post operative adjuvant chemoradiotherapy and at 1 year follow up, she was found to be well and free of recurrence. We also noticed that functional outcome including chewing and speech was acceptable even without reconstruction.
3. Discussion Malignant myoepithelioma is a rare salivary gland tumor that has diverse clinical, pathological and immunohistochemical presentation.1 Most patients with malignant myoepithelioma present with a painless swelling, occasionally with a recent rapid increase in size. The symptoms vary depending on the location.5 A neck presentation may just be a painless swelling like in this case.5 Other sites such as laryngeal location may manifest as hoarseness, paranasal sinus location may be associated with epistaxis, nasal blockage or facial pain while parotid swelling may present with facial nerve paralysis.6–8 Due to the varying presentations, the average duration for diagnosis can be from 3 months to 3 years from the onset of symptoms.9 A good history taking, routine clinical examination, CTscan and FNAC may not be adequate to diagnose malignant myoepithelioma. This condition may be missed in FNAC because the cytological features of the disease are diverse and may lack overt feature of malignancy.10 False negative results have been reported mainly due to errors made in underdiagnosis because low grade tumors usually demonstrate bland cytologic features.11 In this case report,
Fig. 5. Right segmental mandibulectomy was performed because there were intraoperative signs of mandibular invasion over the right body of mandible including thinning and erosion of the bone.
Fig. 6. Microscopic examination showed spindled tumor cells arranged in intersecting fascicles with minimal nuclear pleomorphism but high mitotic activity. (Hematoxylin and eosin staining; magnification 200.)
we had a dilemma in both diagnosing and treating this condition. Despite having a clinical and radiological features that suggest malignancy, extensive surgery and adjuvant chemoradiotherapy cannot be proposed to the patient when both of the 1st and 2nd operative specimens were concluded as benign. However, we still proceeded with an extensive resection and deep cervical nodes clearance at the 3rd operation without histopathological report. This decision was made solely based on clinical suspicion of malignancy following the recurrent and aggressive nature of the tumor. To diagnose malignant myoepithelioma, the most notable criteria in microscopy is tumor infiltration into adjacent tissues and high cell proliferative activity (>7 mitoses per 10 high-power fields or a Ki-67 labeling index of >10%).5 Myoepithelial markers such as muscle actins, cytokeratin 14, vimentin, calponin and S-100 protein are highly expressed.1 Prognosis is deemed poorer when there is presence of marked cellular pleomorphism, p53 expression and high cell proliferative activity.1 In terms of treatment, extensive excision is the most favorable choice for malignant myoepithelioma.12 When the submandibular gland is involved, supraomohyoid lymph node dissection is recommended.12 Postoperative radiotherapy have questionable result in terms of prognosis but chemotherapy may be helpful.13 In ideal setting, where reconstruction is possible with available expertise, reconstruction with osteomyocutaneous graft like free fibular graft would have provided an excellent outcome. However, due to limited resources being a third world developing country and lack of plastic surgeons and free flap expertise, a patient would also achieve relatively good functional outcome with adequate oncological clearance with what was done in this case. In conclusion, diagnosis may be difficult for pathologist as this disease is very rare and it may present in different stages of myoepithelial differentiation.1 In our case, the diagnosis cannot be concluded until the 3rd histopathologic examination as immunohistochemical profile was not suggestive in the earlier 2 samples. Rare type of salivary gland tumors, especially those arising from unusual locations with unfamiliar histomorphologies can cause diagnostic difficulties to pathologist.4 Therefore, awareness of the disease and its pathologic features with diligent use of immunohistochemistry are crucial for the accurate diagnosis of malignant myoepithelioma.4,12 A high index of suspicion is required to diagnose despite microscopical examination that may
Please cite this article in press as: Gan B.C., et al. Myoepithelioma: Benign or malignant – A diagnostic dilemma. Egypt J Ear Nose Throat Allied Sci (2016), http://dx.doi.org/10.1016/j.ejenta.2016.11.003
4
B.C. Gan et al. / Egyptian Journal of Ear, Nose, Throat and Allied Sciences xxx (2016) xxx–xxx
reveal only benign findings. In this case, despite two adequate excisions, patient still presented back to the clinic with recurrent swelling after several months of operation. Clinical presentation like this should prompt clinicians on the possibility of malignant myoepithelioma. References 1. Nagao T, Sugano I, Ishida Y, et al.. Salivary gland malignant myoepithelioma: a clinicopathologic and immunohistochemical study of ten cases. Cancer. 1998;83:1292–1299. 2. Hornick JL, Fletcher CD. Myoepithelial tumors of soft tissue: a clinicopathologic and immunohistochemical study of 101 cases with evaluation of prognostic parameters. Am J Surg Pathol. 2003;27:1183–1196. 3. Hayashi A, Yokoyama J, Sato R, et al.. Massive myoepithelial carcinoma originating from the submandibular gland that was successfully treated with surgical excision, using a part of the lengthened skin as a local flap. Plastic Reconstr Surg Global Open. 2015;3:e329. 4. Gore Charusheela R, Panicker NK, Chandanwale SS, Singh Bikash K. Myoepithelioma of minor salivary glands – a diagnostic challenge: report of three cases with varied histomorphology. J Oral Maxillofac Pathol. 2013;17 :257–260
5. 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;24:761–774. 6. Yu G, Qu G, Kong L, Pan X, Wang W, Lv J. Primary myoepithelial carcinoma of the larynx: case report and review of the literature. Pathol Res Pract. 2011;207:127–130. 7. Yamanegi K, Uwa N, Hirokawa M, et al.. Epithelial-myoepithelial carcinoma arising in the nasal cavity. Auris Nasus Larynx. 2008;35:408–413. 8. Saliba Issam, El Khatib Nazir, Nehme Antoine, Nasser Selim, Moukarzel Nabil. Metastatic parotid myoepithelial carcinoma in a 7-year-old boy. Case Rep Pediatr. 2012;2012:212746. 9. Sasaguri T, Tanimoto A, Arima N, Hamada T, Hashimoto H, Sasaguri Y. Myoepithelioma of soft tissue. Pathol Int. 1999;49:571–576. 10. Sehgal Shelly, Goyal Prashant, Singh Sompal, Kumar Awanindra. Fine-needle aspiration cytology of myoepithelial carcinoma of salivary gland: diagnostic challenge to cytopathologist. J Cytol. 2013;30(3):207–210. 11. Fernandes Hilda, D’souza Clement RS, Khosla Charu, George Lovely, Katte Namitha Hegde. Role of FNAC in the preoperative diagnosis of salivary gland lesions. J Clin Diagn Res. 2014;8(9):FC01–FC03. 12. Wang C, Zhang Z, Ge Y, et al.. Myoepithelial carcinoma of the salivary glands: a clinicopathologic study of 29 patients. J Oral Maxillofac Surg. 2015;1. 13. Xua Tao, Liao Zhiwei, Tang Jun, et al.. Myoepithelial carcinoma of the head and neck: a report of 23 cases and literature review. Cancer Treatment Commun. 2014;2:24–29.
Please cite this article in press as: Gan B.C., et al. Myoepithelioma: Benign or malignant – A diagnostic dilemma. Egypt J Ear Nose Throat Allied Sci (2016), http://dx.doi.org/10.1016/j.ejenta.2016.11.003