Myoepithelioma (Myoepithelial Carcinoma) of the Breast: Case Reports.
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1 Myoepithelioma (Myoepithelial Carcinoma) of the Breast: Case Reports. 1 Salah Fayaz, 2 Suzanne Samir, 3 Henney Amanguno, 4 Mustafa El-Sherify, 5 Aaron Adesina, 6 Sadeq Abozlouf, 7 Thomas George, 8 Gerges Attia, 9 Heba Eissa, 10 Ahmed Bedair. 1, 2, 4, 6, 7, 8, 9, 10 Radiation Oncology Department, Kuwait Cancer Control Center, Shuwaikh, Kuwait City, Kuwait. 3, 5 Pathology Department, Kuwait Cancer Control Center, Shuwaikh, Kuwait City, Kuwait. Abstract Myoepithelial carcinoma of the breast is a rare condition. Here, are 2 cases of malignant myoepithelial documented. Both were 51 year-old Kuwaiti women, presenting with abnormal breast masses. The first patient underwent mastectomy while the second patient underwent lumpectomy followed by mastectomy for narrow margins. The tumours were clinically, radiologically and macroscopically demarcated. Diagnosis was made based on histological and immunohistochemical studies. Both cases were positive for α-smooth muscle actin, S-100ptn and one case was positive for Vimentin and the other case was positive for Epithelial Membranous Antigen (EMA). From these findings the cases were diagnosed with malignant Myoepithelioma. One case consisted microscopically of tumour cells with clear cytoplasm, possibly making it one of 3 reported cases of clear cell myoepithelial carcinoma. One case locally recurred and metastasized, while the other is still newly diagnosed and under follow-up. Myoepithelial tumours are generally considered benign but do have a spectrum of behaviour with a potential for local recurrence and rarely distant metastses. Introduction Myoepithelial cells are contractile cells which have both myogenous and epithelial features. Myoepithelioma is a rare tumour that consists of or is derived from myoepithelial cells. Although the presence of myoepithelial cells in the Corresponding author: Dr Mustafa El-Sherify, Radiation Oncology Department, Kuwait Cancer Control Center, Shuwaikh, Kuwait. Tel: , mustafashawki@yahoo.com 51
2 Salah Fayaz salivary gland epithelium has been well documented, and most cases of Myoepithelioma have been found at these sites (Crissman et al. 1977, Dardlick et al. 1989), myoepithelial cells have been found to be widely present in the breast where they comprise part of the normal microscopic anatomy of lobules and ducts. (Gusterson BA, et al, 1982). The ductular system is composed of a 2-cell epithelial lining, an inner secretory epithelium and a surrounding outer myoepithelial cell layer. These myoepithelial cells may participate in many benign proliferative processes. However, myoepithelial lesions of the breast are uncommon. Tavassori (1991) recognized 3 main types of myoepithelial lesions in the breast. They included myoepitheliosis, adenomyoepithelioma, and myoepithelial carcinoma (malignant Myoepithelioma). Myoepitheliomas are typically benign tumours and very few cases have reported being metastatic (Loose JH, et al. 1992). We report two cases of malignant Myoepithelioma diagnosed from histological and immunohistochemical features of the tumour. Case Report: Number One The first case was a 51 year old Kuwaiti female who developed an abscess in the left breast in It was surgically drained several times. A year later she did a mammogram which revealed a calcified region. She was placed under follow up by the surgeon in Kuwait until late 2003 when she developed a mass in the same breast. FNAC was done on 23:9:2003 guided by ultrasound revealing a hypocellular, benign breast aspirate. FNAC was repeated in another centre, ultrasound guided, from a clinically palpable mass at the 12 o clock position revealing epithelial hyperplasia or carcinoma in-situ, but histopathology was required for further verification of the lesion. The mass was then excised on 3:12:2003 revealing a hard area 3cm in the largest diameter showing atypical ductal hyperplasia. The patient continued follow up until 2004 when the lump recurred. FNAC was repeated revealing atypical cells. On 17:1:2005 excision of the recurrent lump was done revealing fibrocystic disease with sclerosing ductal lesion. This was repeated once again via ultrasound guidance revealing probable fat necrosis in fibrosed phase however histopathological examination was required to exclude carcinoma. Another surgeon then saw the patient and advised for surgery however the patient traveled to Bangkok in June A mammogram and ultrasound was done on 11:6:2005 revealing several masses of mixed echo, cystic and solid components. The sizes ranged from 3.5 x 3.9cm in UIQ, 1.5x2cm, 1.8 x 2.1cm and a 2.7 x 4.6cm mass in the central region. This central mass was suspicious for malignancy and advised for further investigation. A ductogram was done on the same day which showed findings in favor of an inflammatory process, but a malignant mass could not be excluded. An ultrasound guided biopsy was done revealing the mass to be a malignant epitheliomatous lesion. Revision was done in Kuwait on 20:6:2006 revealing a malignant lesion with spindle and pleomorphic features and the suggested possibilities were Malignant epithelioma, metastatic carcinoma, malignant phyloides and histopathology was recommended. Final diagnosis was made with Malignant Epithelioma. On 5:7:2005, there was a combined surgical, medical and radiation oncology meeting in the Kuwait Cancer Control Centre to discuss the case and the consensus was for mastectomy. This was done on the 10:7:2005 with Sentinel lymph node biopsy and histopathology report confirmed Malignant Myoepithelioma with no lymph node metastases. Post operative period was uneventful. The patient continued a regular follow up until 20:2:2006 when she presented complaining of left chest wall pain. Examination revealed no abnormality and patient was told to continue follow up. Analgesics were prescribed. Then in early March 2006 the patient noticed a 2cm nodule on the left chest wall at the site of mastectomy. It was found to be rapidly increasing in size. Bone scan was done on 14:3:2006 and a suspicious lesion was found in the left 3 rd rib anteriorly. Ultrasound on the left chest wall was done on 15:3:2006 and an irregular heterogenous focal lesion of approximately 3.3 x 1.8cm was found in the left anterior infraclavicular region. Ill demarcated diffuse heterogenous areas were found adjacent to the nodule. Further evaluation of the thorax was requested via CT scan; however the patient traveled to Bangkok once again. There the patient did a CT scan revealing a large mediastinal mass (7 x 7.5 x 6.8cm) with partial extension to the chest wall and left lung, with multiple pulmonary metastases. The patient was started on CAPP chemotherapy regimen (Cyclophosphamide, Liposomal Doxorubicin, Cisplatin, and Prednisolone). 52
3 Myoepithelioma (Myoepithelial Carcinoma) of the Breast:... Follow up CT scan reported that the huge lobulated mass at the anterior and superior mediastinum, although less bulging, there was no significant change in size, and the rest of the scan revealed stable disease. The patient returned to the Kuwait on 19:4:2006 and the consensus was to continue the chemotherapy regimen received in Bangkok. She received the third cycle on 24:4:2006 with G-CSF support and tolerated the treatment well. She was then sent for follow up with the pain clinic until the next chemotherapy appointment. The patient then traveled to the USA. She received four cycles of chemotherapy (with no documentation). The last cycle received was on 14:9:2006. The patient then underwent a complete workup including a final CT Chest. It revealed progression in the form of a large heterogenous mass almost completely replacing the right lower lobe. The mediastinal window revealed a stationary mass in the left anterior chest wall measuring 8.1 x 5.7cm with extension through the wall and into the pectoralis musculature. There was also small pericardial effusion. The consensus was for no further active management, and only supportive treatment. She then returned to Kuwait. She was admitted as an inpatient on 14:10:2006 complaining of increasing dyspnea for seven days duration and an intermittent fever for about one month duration with generalized weakness. She was put on supportive measures but her condition continued to deteriorate rapidly leading to death from respiratory failure on 16:10:2006. Case Report : Number Two On examination, the mass was felt in the UOQ, 2 x 2cm, mobile, firm with no skin changes. The left axilla also presented with a mobile 1.5 x 1.5cm lymph node. The rest of the examination was unremarkable. Metastatic work up including chest x-ray, abdominal ultrasound and bone scan was negative and tumour markers CEA and CA15.3 were within normal levels. Therefore, clinically staging the patient ct1 N1 M0. The patient then underwent wide local excision and axillary clearance at the KCCC on 1:8:2007, histopathology revealed malignant Myoepithelioma with a final staging of pt1 N0 M0. On 6:9:2007, the case was discussed within the KCCC s multidisciplinary meeting and a final consensus was not easily reached. Due to the rarity of the condition, the literature was reviewed and it was decided that the 1cm margin was inadequate. The patient was offered wider excision followed by radiation therapy to the breast or mastectomy. She agreed for the latter and it was performed on the 3:10:2007. The histopathology reported foreign body giant cell reaction with no residual tumour. And she was placed under follow-up. Materials and Methods All breast tumours in the department of histopathology at Kuwait Cancer Control Centre are routinely formalin fixed. Paraffin embedded and 4um thick sections are cut and stained with haematoxylin and eosin. Sections from the two cases were examined immunohistochemically by using avidin-biotin peroxidase complex (ABC) technique. The following commercially available antibodies were used. The second case is another diabetic and hypertensive 51-year-old Kuwaiti female. She complained of a left breast mass of 25 days duration. She sought medical advice in Mubarak Hospital in Kuwait and mammography and breast ultrasound (1:7:2007) showed a highly suspicious left breast mass (1.7 x 1.2cm) of BIRAD s 4 score with a 1.4 x 1.4cm lymph node in the left axillary tail. Ultrasound showed the mass to be oval in shape, and hypoechoic with some lobulated echogenic margins at the 1 o clock position of the breast. FNAC was inconclusive so a core biopsy was taken on 4:7:2007 revealing invasive ductal carcinoma, grade III, both estrogen and progesterone receptor status were found negative and HER2 neu was found to have a positive score of 3+. She then presented to the KCCC for further management. 53
4 Salah Fayaz Results Case One (A) The mastectomy specimen meas ured 22 x 18 x 18cm, overlying skin measured 25 x 18cm, areola measured 6 x 6cm, nipple measured 1 x 1cm, overlying skin showed peau d range changes, serial sections show multilobulated tumour mass measuring 15 x 7 x 7cm. The tumour mass has areas of necrosis and cystic areas. The mass is 1cm to the deep margin, medial and lateral margins are 5.5cm away respectively, while upper and lower resection margins are 4.5cm away respectively. Sections taken from multiple representative areas of the breast tumour showed essentially similar histological changes. There is a solid spindle cell tumour growth infiltrating breast adipose tissue and surrounding remnant of ductal structures. The tumour cells have oval elongated vesicular nucleoli with small nucleate and numerous mitotic figures. Tumour cytoplasm is predominantly clear however several tumour areas show eosinophilic to basophilic cytoplasm. There is variable cellularity with areas partly hyalinised and acellular to areas that are densely cellular. The neoplasm shows marked cellular pleomorphism including giant cell formation. There is no area of this tumour suggesting a growth pattern of phylloides tumour and no part show any clear cut epithelial differentiation. Surgical margins are free with no evidence of lymphovascular tumour permeation, and the axillary node submitted is free of tumour extension. The final diagnosis was Malignant Myoepithelioma (Myoepithelial carcinoma). Immunohistochemical staining done showing the following: Case Two (B) The tumour mass was found 2 x 1.6 x 1.6cm and the mass was surrounded by the following margins: 1cm superiorly, 1.5cm inferiorly, 3.5cm deeply, 3.5cm medially, and 3cm from the skin. It was a well demarcated malignant tumour growth with extensive central necrosis, marked pleomorphism, high mitotic index, moderate lymphocytic infiltration at the periphery, peculiar myxoid stroma in the background of the lesion. There were occasional foci of ductal cancerization, and no evidence of lymphovascular permeation. All margins and all eleven axillary lymph nodes were free. The final pathological diagnosis was a high grade malignant tumour of the breast with evidence of epithelial and myoepithelial differentiation, therefore called Myoepithelial carcinoma. Immunohistochemical staining done showed the following: Discussion Adenomyoepithelioma of the breast is an unusual and rare benign tumour composed of biphasic proliferation of epithelial and myoepithelial cellular constituents. One or more constituents may undergo malignant change, Malignant Myoepithelioma (Myoepithelial carcinoma). These tumours have found to be very rare, only documented to occur in women, and the age group affected ranges from 26 to 76 years. They are found to be generally non- aggressive in behaviour. It may present as a rapidly enlarging mass, may be tender, and usually laterally placed in the breast. They rarely metastasize, and only do in tumours 2cm in diameter or larger. Metastasis is hematogenous rather than lymphatic and most commonly to the lungs. The likelihood of local recurrence is predicted by narrow or incomplete excision margins. These characteristics have been achieved by comparing reported cases in textbooks (Page and Anderson 1987, Young and Clement 1988, Rosen 1997) and many other previously reported cases consisting of spindle cells 54
5 Myoepithelioma (Myoepithelial Carcinoma) of the Breast:... 55
6 Salah Fayaz (Erlandson and Rosen 1982, Kiaer et al 1984, Schurch et al 1985, Bigotti and DiGiorgeo 1986, Weider and Levine 1988, Lakhani et al 1995, Loose JH et al 1992, and Kdous M et al 2004) and only two cases of clear cell malignant Myoepithelioma (Cartegena et al 1988, Miura Y et al 2003). Malignant myopepitheliomas have high mitotic rates (11 14 / 10 HPF) diffusely through the tumour with foci of cytologically malignant cells. It was found that the myoepitheliomas that metastasized had infiltrative growth patterns that increased with successive local recurrences. Electron microscopic examination of malignant myoepitheliomas that metastasized also confirmed dual epithelial / myoepithelial cell populations in local recurrences as well as metastases. Therefore confirming that malignant myoepitheliomas have a spectrum of biological behaviour with a potential for local recurrence and rarely distant metastases. Surgical management is similar to other breast malignancies, namely wide local excision or modified radical mastectomy, with axillary clearance. If, following wide local excision, the excision margin is narrow or incomplete, re-excision is advised to gain adequate margins. The response to chemotherapy and radiotherapy is so far unknown. References 1. Crissman JD, Wirman JA, and Harris A. (1977) Malignant Myoepithelioma of the parotid gland. Cancer, 40, Dardlick I, Thomas MJ, and Van Nostrand AWP, (1989) New concepts of histology and classification: A light and electron microscopic study. Ultrastructural Pathol., 13, Gusterson BA, Warburton MJ, Mitchell D, et al. Distribution of myoepithelial cells and basement membrane proteins in the normal breast and in benign and malignant breast diseases. Cancer Res 1982; 42: Tavassoli FA (1991) Myoepithelial lesions of the breast. Myoepitheliosis, adenomyoepithioma, and myoepithelial carcinoma. Am. J. Surg. Pathol., Loose JH, Patchefsky AS, Hollander IJ, et al. (1992) Adenomyoepithelioma of the breast. A spectrum of biologic behavior. Am. J. Surg. Pathol., 16(9) Page DL, and Anderson TJ (1987) Diagnostic Histopathology of the Breast. Churchill Livingstone, Young RH and Clement PB (1988) Adenomyoepithelioma of the breast: A report of three cases and review of the literature. Am. J. Surg. Pathol., Rosen PP (1997) Breast Pathology. Lippincott-Raven, , , Erlandson RA and Rosen PP (1982) Infiltrating Myoepithelioma of the breast. Am. J. Surg. Pathol., Kiaer H, Nielson B, Paulsen S, Sorensen IM, Dyreborg U, and Mogens BT (1984) Adenomyoepithelial adenosis and low-grade malignant adenomyoepithelioma of the breast. Virchows Arch. (A), 405, Schurch W, Potvin C, and Seemayer TA (1985) Malignant Myoepithelioma (myoepithelial carcinoma) of the breast: An ultrastructural and immunohistochemical study. Ultrastructural Pathol., 8, Bigotti G and DiGiorgeo G (1986) Myoepithelioma of the breast: Histologic, immunologic, and electromicroscopic appearance. J. Surg. Oncol., 32, Weider N and Levine JD (1988) Spindle-cell adenomyoepithelioma of the breast: A microscopic, ultrastructural, and immunocytochemical study. Cancer, 62, Lakhani SR, O Hare MJ, Monaghan P, Winehouse J, Gazet JC, and Sloane JP (1995) Malignant Myoepithelioma (myoepithelial carcinoma) of the breast: A detailed cytokeratin study. J. Clin. Pathol., 48, Kdous M, Hachicha R, Gamoudi A, Rahal K (2004) Breast Myoepithelioma. Diagnostic and therapeutic difficulties. A case report. Gynecol Obstet Fertil., 32, Cartegena N, Carberro-Inchausti B, Willis I, and Poppiti R (1988) Clear cell myoepithelial neoplasm of the breast. Hum. Pathol., 19, Miura Y, Kurose A, Kondo M, Maruyama A, Shibata Y, Kanno H, and Sawai T (2003)Clear Cell Myoepithelial Carcinoma of the Breast.Tohoku J. Exp. Med., 200(2),
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