Adenomyoepithelioma (AME) of breast is a low grade malignant biphasic tumour, usually seen in elderly women as a firm, well circumscribed tumour having both glandular and myoepithelial cells. The cells may show atypical features. The tumour may harbour foci of carcinoma which may be epithelial type, myoepithelial type, both or of metaplastic cells. The behaviour is hard to predict as it can be treated by local excision, recurrence is known or it can present with distant metastasis and hence the prognosis.
We present a case of 50-year-old women who presented with right iliac bone lytic lesion diagnosed as metastatic deposits. Past history revealed that patient was diagnosed and treated for AME of right breast seven years back. The metastatic deposits also showed features of adenomyoepithelioma. Hence, a diagnosis of malignant AME deposits in right iliac bone was made.
Case Report
A 50-year-old woman presented with right flank pain since two weeks. X-ray of pelvis showed lytic lesion involving right posterior iliac bone, adjacent sacroiliac joint extending to right sacral ala. PET-CT showed similar features with pathological fracture of right posterior iliac bone and multiple bilateral nodules in lungs suggesting metastatic deposits. History revealed that the patient had undergone lumpectomy of right breast seven years back and six months later quadrantectomy with axillary clearance for recurrence. Histopathological examination of both specimens was diagnosed as AME without lymph node deposits. Family history was insignificant.
Considering the past history and present clinical/radiological features, CT guided fine needle aspiration cytology (FNAC) and needle biopsy was done which showed tumour cells in tubular and lobular pattern. The tubules lined by cuboidal epithelial cells with peripheral myoepithelial cells. At places myoepithelial cells in lobular pattern seen [Table/Fig-1]. At focal areas myoepithelial cells showed atypical features. Sections of needle biopsy was subjected to immunohistochemistry which was positive for vimentin, Pan-CK, CK5/6, S100, SMA, [Table/Fig-2a-d]. EMA and weakly positive for Her 2/neu. ER and PR were negative. Hence, a diagnosis of malignant AME deposits (myoepithelial carcinoma) was made. The slides of primary tumour was reviewed which showed features of AME, areas of fibrocystic disease/adenosis and the margin of tumour showed local infiltration into adjacent stroma [Table/Fig-3]. At focal areas tumour cells had increased N:C ratio, hyperchromatic nucleus, coarse granular chromatin and increased mitotic activity indicating cytological atypia which might have lead to metastatic deposits [Table/Fig-4]. Patient was lost for follow-up. The institutional ethical committee has approved to present as case report.
Microphotograph of aspirate of lytic lesion of bone showing the tumour deposits. H&E x100
Microphotograph of Pancytokeratin marker (a) of epithelial cells and CD 5/6, S100 and SMA markers (b,c,d) of myoepithelial cells showing cytoplasmic positivity in the tumour. Pancytokeratin/ CD 5/6/ S100/ SMA x100
Microphotograph showing infiltrating primary tumour (lower left) along with features of fibrocystic disease. H&E x100
Microphotograph showing cytological atypia in the primary tumour at focal areas. H&E x100
Discussion
AME is a rare tumour with biphasic proliferation of epithelial/myoepithelial cells and considered as benign or low grade malignant tumour [1,2]. Twenty seven cases of AME, thirty cases of malignant AME and four comprehensive series studies are reported. Sporadic malignant AME with distant metastasis is known [1,3–5]. The first fully described case was reported by Hamperl in 1970 [5,6].
The exact aetiology is obscure. Majority of the cases are sporadic with no familial aggregation [2,5]. The histogenesis is unclear. However, it was suggested that the stem cells in terminal duct lobular unit of mammary tissue with an intermediate epithelial/myoepithelial differentiation give rise to tumour. The evolution of the tumour begins as adenosis with or without myoepithelial hyperplasia and then progress to benign AME which transform to malignant tumour as pure myoepithelial carcinoma or AME with malignant component [1,2,7]. AME is also suggested to arise from myoepithelial overgrowth of long standing adenosis, fibroadenoma or other benign lesions [8]. In our case there was no significant family history, co-existent features of fibrocystic disease/adenosis was noted and final diagnosis was malignant AME.
AME is usually seen between 22-92 years of age with mean age of 59 yrs. It is commonly seen in females, rarely in males and presents as a solitary unilateral palpable painless mass at the periphery of the breast or centrally near the areola for several weeks to months [2,3,5,6]. Malignant AME is usually seen after 60 yrs of age with long history of the stable breast mass followed by rapid growth phase. It can also arise de novo [4–6,9]. In our case the patient was a female of 50 yrs of age.
Mammography of the AME shows round, lobulated, dense, circum–scribed and rarely as indistinct mass. Ultrasound shows the lesion as solid or solid and cystic appearance [3,6]. AME is reported in salivary gland, skin, breast and lung [5,8]. Grossly the size of tumour varies from 0.3 to 7 cms with an average of 2.5 cms, usually round/lobulated, well circumscribed and firm. Cut section is pink white to grey tan. The recurrent tumour usually is 2-6cms in size with irregular border [3,5–7]. Malignant AME is usually >2cm in size ranging from 1-15cm and is nodular with cystic change, necrosis and calcification [4,9]. In our case, the radiological/gross findings of primary tumour was not available.
WHO in 2012 has classified AME into benign and malignant [1]. AME has spectrum of histologic patterns which is seen even in different areas of the same tumour challenging the diagnosis in core biopsy. The tumour has both epithelial and myopepithelial cells, cytologically bland, has minimal pleomorphism and low mitotic count generally <2 per 10 HPF. Histologically, AME is classified into tubular, lobulated, spindled and carcinoma arising in AME. Tubular type is common. Tubular and some lobular type with high mitotic activity are prone to local recurrence [1]. In tubular type the epithelial cells are columnar or cuboidal arranged in tubular pattern surrounded by myoepithelial cells which are plasmacytoid/polygonal cells with clear cytoplasm or spindle cells. In lobular pattern nests of myoepithelial cells are seen around compressed tubules. The fibrous connective tissue surrounds both cells forming septa of varying thickness. In spindle cell type, the spindle myoepithelial cells predominate with a few columnar epithelial cells in tubules. Papillary component is also described. Focal areas of apocrine/squamous/sebaceous/mucinous/chondroid and osseous metaplasia is described [3,5,6,8,9]. Co-existent areas of fibroadenoma or phylloides tumour is described suggesting its origin [6,8]. Atypical features like pronounced nuclear pleomorphism, increased mitotic activity (>3 per 10 HPF), prominent nucleoli, hyperchromatic nucleus, necrosis, invasive growth and overgrowth of one of the two components are seen in recurrent and malignant tumour [3,6,9]. The differential diagnosis of AME in breast are benign and malignant solid lesions [1–3,5,6]. In our case the tumour had both tubular and lobular pattern. Coexistent areas of fibrocytic disease/adenosis, focal areas of cytologic atypia and local infiltration at tumour margin were seen in primary tumour.
The markers of myoepithelial cells are glycogen, keratin, p63, SMA-high molecular weight (SMMH), calponin, high molecular weight CK 5/6, CK 14, S100, GFAP, CD10, vimentin and EMA. Myoepithelial cells are negative for desmin, low molecular weight CK 8/18. S100 is positive in myopepithelial cells and luminal epithelial cells. Neoplastic epithelial cells display cross reactivity and show variable protein expression compared to normal myoepithelial cells. Hence, panel of two or more markers has to be used. The markers of epithelial cells are CK AE1/AE3, CAM 5.2, CK 7 and CEA which are cytoplasmic markers. The luminal surface epithelial cell marker is EMA. ER is negative or weakly positive (patchy). PR and Her 2/neu are usually negative. Ki67 marker is seen in both epithelial and myopepithelial cells [2,3,5,6,8,9]. In our case the needle biopsy of metastatic deposit showed positive for vimentin, Pan-CK, CK5/6, S100, SMA, EMA and weakly positive for Her 2/neu. ER and PR were negative.
The local recurrence usually occurs eight months to five years after initial excision and is related to multinodular growth, intraductal extension giving rise to satellite nodules away from main tumour mass or incomplete excision [5,6,8]. Recurrent tumour shows increased mitotic activity (8 per 10 HPF) [3]. Malignant change in AME is rare and can occur in either epithelial, myoepithelial or both components which can be either diffuse or focal [1,2,4,8,9]. AME spread by hematogenous route than lymphatic especially in primary tumour of >1.6 cm in size [1,4]. Distant metastasis are seen in lung, liver, brain, soft tissue, bone, thyroid gland and mediastinal lymph nodes [1,3,4,6,8,9]. Deposits in axillary lymph node is unusual and is reported in two cases in malignant AME [4,6]. 40% of malignant AME presents with metastasis [5]. In our case local recurrence occurred six months after excision of primary tumour, HPE showed cytologic atypia and infiltrative peripheral borders, malignant change was seen in myoepithelial component with metastatic deposits in bone and lung.
Conclusion
AME is rare. The diagnosis, treatment and outcome are difficult to predict and is challenging. Proper diagnosis should be done by its biphasic cellular pattern and IHC marker studies so that patient will receive appropriate treatment.
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