Metaplastic Carcinoma of the Breast Dr. Gary Tse

Clinical History A 49 year old woman with a history of thyrotoxicosis for two years, presented with an incidental finding of a left axillary mass. Palpation showed a large axillary mass about 5 cm, and in the left breast, a firm to hard nodule is present in the 6 o'clock position. Mammography showed a 3 cm mass with partially lobulated margin. No calcification was noted. Sonography showed two enlarged lymph nodes in the axilla, measuring about 4 cm each. Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Biopsy, and subsequent mastectomy with axillary dissection was done. 17 of 17 lymph nodes showed metastases. Clinical History A 74 year old Chinese woman with a hard right breast lump. Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Metaplastic carcinoma of the breast Metaplastic carcinoma of the breast denotes a heterogeneous group of uncommon malignant entities. This term is used by many to denote tumours with mixed epithelial and sarcomatoid components, as well as primary squamous or mixed adenocarcinoma and squamous carcinoma. In those cases with a sarcomatoid component, they can be classified into monophasic, composed of spindle cells only; or biphasic, being admixed witha carcinomatous (either ductal carcinoma or squamous cell carcinoma) component. [1] Other authors have systematically grouped the tumours into various diagnostic labels, based on the presence of heterologous elements or osteoclastic giant cells, or whether the tumour cells are monophasic, biphasic or squamoid. [2, 3, 4, 5, 6] Metaplastic carcinoma is generally considered high grade, and the clinical features are similar to infiltrating duct carcinoma, although it may rarely present as inflammatory carcinoma. [7] Recently a low grade variant, the fibromatosis like group, has been reported, with a better outcome with mostly local recurrences but not distant metastases. [8, 9, 10] Biphasic metaplastic carcinoma can be defined as an intraduct or infiltrating carcinoma being contiguous or subtly merged with a highly cellular, mitotically active pleomorphic spindle cell stroma, which appears sarcomatous, and accounts for a significant proportion of the tumour. [4] Within the tumour, the carcinomatous component can either be invasive only or invasive and in situ, each constituting about 40-45% of the cases. In about 20% of the cases, squamous differentiation or squamous cell carcinoma is noted in the carcinomatous component. In the sarcomatous component, most of the cases show polymorphous tumour cells or spindle cells, and are usually of high cellularity and highly pleomorphic with giant cells. In about 17% of the cases, heterologous components including bone or cartilage or both can be seen. Monophasic metaplastic carcinomas are composed predominately of spindle cells or a sarcomatoid tumour cell component. They can have a variable range of nuclear features, from high grade to low grade, where the latter is reminiscent of fibromatosis. [8] Most of the monophasic metaplastic carcinomas are high grade, and a significant proportion shows lymph node [11] or extranodal [12] metastasis at the time of presentation. The fibromatosis like metaplastic carcinoma is a low grade variant that behaves in a much less aggressive manner, characterised by local recurrence but not metastasis. [8] Differential diagnoses for this group of tumours include phyllodes tumours, especially in cases with prominent stromal overgrowth, and other breast sarcomas. Immunohistochemistry is helpful in the diagnosis of metaplastic carcinoma. In biphasic tumours, the carcinomatous component will be positive for cytokeratins, and for the sarcomatous component, most of the tumour cells express vimentin, and with variable degree of positivity for actin, cytokeratin and embryonal membrane antigen (EMA). p63 has also been reported to be positive for the sarcomatous tumour cells, [13, 14] and this is reputed to be quite specific, being negative in phyllodes tumours and other sarcomas of the breast. For the monophasic tumour, the malignant cells are positive to a variable extent for cytokeratins with PanK (MNF116) and CK14 being more commonly positive than others like AE1/3, CAM5.2 or EMA. p63 positivity ranges from 57 to 100%. [12, 14] The histogenesis of metaplastic remains elusive. It is now accepted that despite the variable histology of the different components, they are clonal [15, 16] in origin. The observation that many metaplastic carcinomas tend to be negative for HER2/neu and positive for EGFR may have important treatment implications. [17, 18, 19] References Elston CW, Ellis IO. The Breast. Systemic Pathology, Vol 13, 3rd Edition, pp323-331. Churchill Livingstone, Edinburgh. Wargotz ES, Norris HJ. Metaplastic carcinomas of the breast. I. Matrix-producing carcinoma. Hum Pathol 1989; 20: 628-635. Wargotz ES, Deos PH, Norris HJ. Metaplastic carcinomas of the breast. II. Spindle cell carcinoma. Hum Pathol 1989; 20: 732-740. Wargotz ES, Norris HJ. Metaplastic carcinomas of the breast. III. Carcinosarcoma. Cancer 1989; 64: 1490-1499. Wargotz ES, Norris HJ. Metaplastic carcinomas of the breast. IV. Squamous cell carcinoma of ductal origin. Cancer 1990; 65: 272-276. Wargotz ES, Norris HJ. Metaplastic carcinomas of the breast. V. Metaplastic carcinoma with osteoclastic giant cells. Hum Pathol 1990; 21: 1142-1150. Kuo SH, Chen CL, Huang CS et al. Metaplastic carcinoma of the breast: analysis of eight Asian patients with special emphasis on two unusual cases presenting with inflammatory-type breast cancer. Anticancer Res 2000; 20: 2219-2222. Gobbi H, Simpson JF, Borowsky A et al. Metaplastic breast tumours with a dominant fibromatosis-like phenotype have a high risk of local recurrence. Cancer 1999; 85: 2170-2182. Sneige N, Yaziji H, Mandavilli SR et al. Low-grade (fibromatosis-like) spindle cell carcinoma of the breast. Am J Surg Pathol 2001; 25: 1009-1016. Al-Bozom IA, Abrams J. Spindle cell carcinoma of the breast, a mimicker of benign lesions: case report and review of the literature. Arch Pathol Lab Med 1996; 120: 1066-1068. Tse GM, Tan PH, Putti TC et al. Metaplastic carcinoma of the breast: a clinico-pathological review. J Clin Pathol 2006 Feb 7; [Epub]. Carter MR, Hornick JL, Lester S, Fletcher CD. Spindle cell (sarcomatoid) carcinoma of the breast: a clinicopathologic and immunohistochemical analysis of 29 cases. Am J Surg Pathol 2006; 30: 300-309. Tse GM, Tan PH, Chaiwun B et al. p63 is useful in the diagnosis of mammary metaplastic carcinomas. Pathol 2006; 38: 16-20. Koker MM, Kleer CG. p63 expression in breast cancer: a highly sensitive and specific marker of metaplastic carcinoma. Am J Surg Pathol 2004; 28: 1506-1512. Zhuang Z, Lininger RA, Man YG et al. Identical clonality of both components of mammary carcinosarcoma with differential loss of heterozygosity. Mod Pathol 1997; 10: 354-362. Kung FY, Tse GM, Lo KW et al. Metachronous bilateral mammary metaplastic and infiltrating duct carcinomas: a molecular study for clonality. Hum Pathol 2002; 33: 677-679. Barnes PJ, Boutilier R, Chiasson D, Rayson D. Metaplastic breast carcinoma: clinical-pathologic characteristics and HER2/neu expression. Br Cancer Res Treat 2005; 91: 173-178. Leibl S, Moinfar F. Metaplastic breast carcinomas are negative for Her-2 but frequently express EGFR (Her-1): potential relevance to adjuvant treatment with EGFR tyrosine kinase inhibitors? J Clin Pathol 2005; 58: 700-704. Reis-Filho JS, Milanezi F, Carvalho S et al. Metaplastic breast carcinomas exhibit EGFR, but not HER2, gene amplification and overexpression: immunohistochemical and chromogenic in situ hybridisation analysis. Br Cancer Res 2005; 7(6): R1028-1035. Epub 2005 Oct 25.