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Malignant Adenomyoepithelioma of the Breast with Lymph Node Metastasis

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1 Malignant Adenomyoepithelioma of the Breast with Lymph Node Metastasis
Ahlam A. Awamleh * Mihir Gudi, Sami Shousha ^ Department of Histopathology, Charing Cross Hospital, Imperial College Healthcare NHS Trust and Imperial College, Fulham Palace Road, London W6 8RF, UK * King Hussein Medical Center, Amman – Jordan ^ Charing Cross Hospital, London, UK

2 Introduction Breast Adenomyoepithelioma is a benign neoplasm, resembling adenomyoepithelioma of salivary glands. Uncommon, mean age 60 years.  Considered a variant of intraductal papilloma. It usually presents as a palpable mass. Treatment Complete local excision. The average age for developing an adenomyoepithelioma of the breast is about 60 years. Some physicians consider a breast adenomyoepithelioma to be a variant of an intraductal papilloma. It also seems to be closely related to a clear cell hidradenoma of the breast. Most breast cancers arise in the breast ducts, which are primarily made of epithelial cells. Epithelial cells are normally associated with tissues such as skin and membranes, while myoepithelial cells tend to be associated with muscle tissue. One would have to say that for an adenomyoepithelioma of the breast, there is a 'spectrum' of possibly disease behaviours.

3 Histologically, it is characterized by biphasic proliferation of epithelial cell and myoepithelial cell Shown here is the most common microscopic pattern - tubular type of adenomyoepithelioma. Dark staining cytoplasm of the cuboidal epithelial cells lining the tubular and glandular structures creates a stricking contrast with pale or clear cytoplasm of surrounding myoepithelial cells Note the darker cytoplasm of the lining cuboidal epithelial cells and the clear cytoplasm of the outer layer ofmyoepithelial cells in this case of adenomyoepithelioma of breast. Local excision is adequate treatment in most cases. The tendency of the papillary intraductal component to extend outside the confines of the gross tumor may cause recurrences

4 There is potential for local recurrence and, rarely, distant metastasis.
Malignant adenomyoepithelioma of the breast is rare with around 30 cases reported in the literature Malignant change can be either a pure myoepithelial carcinoma or a combined malignant adenomyoepithelioma Adenomyoepithelioma of the breast is related to ductal adenoma and also shares resemblance to mammary pleomorphic adenoma (mixed tumor). Other histologic features that may be seen include sebaceous metaplasia, squamous metaplasia, apocrine metaplasia, central fibrosis and necrosis. The infiltrative appearance (as seen here) may be mistaken for invasive carcinoma in needle core specimens. 1. M. M. Hayes, “Adenomyoepithelioma of the breast: a review stressing its propensity for malignant transformation,” Journal of Clinical Pathology, vol. 64, no. 6, pp. 477–484, 2011. 2. H. Hamperl, “The myothelia (myoepithelial cells). Normal state; regressive changes; hyperplasia; tumors,” Current Topics in Pathology, vol. 53, pp. 161–220, 1970. 

5 Metastases associated with these malignant tumours are usually haematogenous.
Axillary lymph node metastases are thought to be unusual. It has been recently suggested that axillary lymph node dissection is not indicated unless clinically palpable. 

6 CASE A 63-years-old woman presented with a mass in the left breast.
A core biopsy showed intraductal papilloma with atypical hyperplasia (B3). This was removed by wide local excision. Grossly, the biopsy included two small greyish white soft nodules, each measuring 1 cm in diameter.

7 Microscopic examination
showed multiple intraductal papillary lesions. In some areas, the papillae were covered by a single layer of epithelial cells with underlying several layers of myoepithelial cells (positive for SMA, p63, and CD10) Diagnosed as adenomyoepithelioma. 

8 Adenomyoepithelioma of the breast is a benign circumscribed tumor composed of nodular aggregates ofepithelial and myoepithelial elements. Focal papillary growth pattern is often seen. Strands of basement membrane material separates glands and nodular aggregates.

9 Figure 1b: Benign adenomyoepithelioma part of the lesion showing the myoepithelial component (peripheral clear cells)

10 myoepithelial component (SMA)

11 The epithelial cells were ER negative and many were CK5 and 14 positive, indicating that they are basal-like rather than luminal type. Other areas of the lesion consisted of solid proliferation of a mixture of these epithelial and myoepithelial cells and showed abundant mitotic figures marked nuclear pleomorphism evidence of peripheral invasion. 

12 Malignant component - solid area showing
dual-cell population with marked nuclear pleomorphism. Malignant component - invasive edge of the lesion CK5.

13 The features were considered as a malignant adenomyoepithelioma developing in continuity with a benign adenomyoepithelioma of the breast. The lesion reached the excision margins and re-excision was recommended.

14 A mastectomy was carried out with axillary lymph node sampling.
Pathological examination showed: a partly cystic and partly solid tumour measuring 7x4x4.5 cm, With similar features to those seen previously consisted of a mixture of epithelial and myoepithelial cells arranged in a benign adenomyoepithelioma fashion in some areas, which merged with areas showing malignant features as those described above with invasion of adjacent breast tissue. 

15 Lymph Nodes Examination:
One of the two dissected lymph nodes showed a 1.8 mm metastatic focus positive for CK8/18, CK19, AE1/AE3, CK5/6, CK14, SMA, and CD10  indicating the presence of epithelial and myoepithelial elements.

16 Lymph node metastasis - CK5 staining both epithelial and myoepithelial elements

17 CK19 staining epithelial element
SMA staining myoepithelial element

18 Discussion Malignant adenomyoepithelioma of the breast is generally preceded by a long history of a stable breast mass followed by rapid growth phase. Grossly, the tumour is usually nodular and may show cystic changes as well as necrosis and foci of calcification. 3. A. A. Ahmed and D. S. Heller, “Malignant adenomyoepithelioma of the breast with malignant proliferation of epithelial and myoepithelial elements: a case report and review of the literature,”Archives of Pathology and Laboratory Medicine, vol. 124, no. 4, pp. 632–636, 2000. 4. S. Y. Choi, J. S. Kim, S. J. Kim, Y. J. Kim, L. Kim, and U. C. Young, “Malignant adenomyoepithelioma of the breast presenting as a large mass that grew slowly without metastasis,” Journal of Breast Cancer, vol. 12, no. 3, pp. 219–222, 2009.

19 Histological features of malignant transformation include
nuclear atypia increased mitotic activity necrosis, and infiltrative growth pattern. In our case, all these features were present, except for necrosis.

20 Malignant adenomyoepithelioma has the potential for distant metastases usually through hematogenous spread. These typically occur in lesions larger than 2 cm and in those with high-grade malignant component. Distal metastasis were described in upto 32% of cases Mets involved lungs, brain, soft tissues, liver, bone, and thyroid gland.

21 Axillary lymph node involvement in breast malignant adenomyoepithelioma is thought to be unusual.
Therefore, it has been suggested that axillary lymph node dissection is not indicated in these tumours unless there is clinically enlarged nodes. However, metastases to axillary nodes have been reported in 2 previous cases, in addition to the current case where no palpable lymph nodes were present. P. C. Chen, C. K. Chen, A. D. Nicastri, and R. B. Wait, “Myoepithelial carcinoma of the breast with distant metastasis and accompanied by adenomyoepitheliomas,” Histopathology, vol. 24, no. 6, pp. 543–548, 1994. V. S. Suresh Attili, K. Saini, K. C. Lakshmaiah, U. Batra, M. Malathi, and C. Ramachandra, “Malignant adenomyoepithelioma of the breast,” Indian Journal of Surgery, vol. 69, no. 1, pp. 14–16, 2007.

22 Conclusions We presented a case of a 63-years-old woman, who developed a malignant adenomyoepithelioma. She had axillary lymph node metastasis, that included epithelial and myoepithelial elements, in spite of the absence of clinically enlarged nodes. We suggest that histological examination of axillary sentinel nodes or node sampling may be worthwhile in this condition.

23 Thank You Ahlam A. Awamleh, Mihir Gudi, and Sami Shousha, “Malignant Adenomyoepithelioma of the Breast with Lymph Node Metastasis: A Detailed Immunohistochemical Study,” Case Reports in Pathology, vol. 2012, Article ID , 4 pages, doi: /2012/305858

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