Metaplastic breast carcinomas (MBCs) are rare primary breast malignancies characterized histologically by carcinoma of two epithelial types or co-existence of carcinoma with non-epithelial cellular elements. They are aggressive tumours that carry poor prognosis. We reviewed the pathologic features and clinical outcomes of MBCs seen in our institution between the years 2000 to 2007. Out of 471 breast cancer patients, six female patients were histologically-proven to have MBCs giving an incidence rate of 1.3%. The patients comprised four Malays and two Indians and their mean age was 51 years old. Five patients underwent mastectomy (four with axillary clearance and one without) and one had wide local excision with axillary clearance. Axillary lymph node involvement was seen in four patients (three with epithelial only type tumour and one with the biphasic tumour). In all the cases, the tumours were bigger than 5 cm in diameter (T3), grade 3 and estrogen receptor negative. Five patients received chemotherapy while one refused. All of the patients had tumour recurrence with a mean time of recurrence of 9 months. In conclusion, metaplastic breast carcinomas are rare and aggressive tumours usually affect the post menopausal age group. They present as aggressive, large sized, high grade tumours that are estrogen receptor negative. Tumour size and axillary lymph node involvement indicate poor prognosis. Despite treatment with chemotherapy and radiotherapy, these patients have high risk of local recurrence and distant metastases which are potentially fatal

Naqiyah I,

Nurismah MI,

Rohaizak M,

Shahrun NS,

English

UKM Journal Article Repository

Med & Health 2009; 4(2): 127-132   CASE REPORT Metaplastic Breast Carcinomas: A Report of Six Cases   Shahrun NS1, Rohaizak M1, Naqiyah I1, Nurismah MI2  Department of 1Surgery and 2Pathology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur   ABSTRAK  `Metaplastic breast carcinoma’ (MBC) adalah jenis kanser payu dara yang amat jarang ditemui yang dari segi histologinya, bercirikan karsinoma yang terdiri daripada dua jenis epitelia atau kehadiran karsinoma bersama-sama dengan elemen ‘bukan-epitelial’. Ianya adalah agresif dan mempunyai ciri prognosis yang buruk. Ciri-ciri  patologikal dan klinikal kanser ini dikalangan pesakit kanser payu dara di Pusat Perubatan Universiti Kebangsaan Malaysia (PPUKM) telah dikaji dari tahun 2000 sehingga 2007. Daripada 471 pesakit kanser payu dara di PPUKM terdapat enam  pesakit wanita dikenal pasti melalui diagnosis histologi mengidap MBC yang mana ianya melibatkan 1.3% dari keseluruhan kes kanser payu dara. Empat daripada mereka adalah dari etnik Melayu manakala dua adalah India dan min umur mereka adalah 51 tahun. Di dalam kesemua kes, kanser ini adalah besar, bersaiz lebih dari 5 sm, gred 3 dan bereseptor estrogen negatif. Lima pesakit menjalani mastectomi (empat bersama ‘axillary clearance’ manakala satu tanpa ‘axillary clearance’). Penglibatan kelenjar limfa aksilari didapati pada empat pesakit (tiga pesakit mempunyai tumor jenis epithelia sahaja dan satu tumor dwifasa). Lima pesakit menerima kemoterapi, seorang lagi enggan dirawat secara kemoterapi. Kesemua pesakit mengalami rekuren tumor dengan min masa rekuren selama 9 bulan. Kesimpulannya, MBC  jarang berlaku, agresif dan biasanya melibatkan golongan wanita yang sudah menopos. Mereka selalunya bersaiz besar, mempunyai gred histopatologi tinggi dan bereseptor estrogen negatif. Saiz tumor yang besar serta perebakan tumor ke kelenjar limfa menjangkakan prognosis buruk. Walaupun dengan rawatan kemoterapi dan radioterapi, pesakit-pesakit ini mempunyai risiko yang tinggi untuk mendapat kanser berulang atau merebak ke organ lain.  Kata kunci:  kanser metaplastik payu dara, ciri-ciri patologikal, kesan klinikal   ABSTRACT   Metaplastic breast carcinomas (MBCs) are rare primary breast malignancies characterized histologically by carcinoma of two epithelial types or co-existence of carcinoma with non-epithelial cellular elements. They are aggressive tumours that carry poor prognosis. We reviewed the pathologic features and clinical outcomes of MBCs seen in our institution between the years 2000 to 2007. Out of 471 breastAddress for correspondence and reprint requests:  Prof Dr Rohaizak Muhammad, Department of Surgery, Faculty of Medicine, Universiti Kebangsaan Malaysia, Jalan Yaacob Latif, Bandar Tun Razak, 56000 Cheras, Kuala Lumpur. Tel: 603-91455002. Fax: 603-91737831. Email: rohaizak@ppukm.ukm.my 127  Med & Health 2009; 4(2): 127-132  Shahrun N.S. et al  cancer patients, six female patients were histologically-proven to have MBCs giving an incidence rate of 1.3%. The patients comprised four Malays and two Indians and their mean age was 51 years old.  Five patients underwent mastectomy (four with axillary clearance and one without) and one had wide local excision with axillary clearance. Axillary lymph node involvement was seen in four patients (three with epithelial only type tumour and one with the biphasic tumour). In all the cases, the tumours were bigger than 5 cm in diameter (T3), grade 3 and estrogen receptor negative. Five patients received chemotherapy while one refused. All of the patients had tumour recurrence with a mean time of recurrence of 9 months. In conclusion, metaplastic breast carcinomas are rare and aggressive tumours usually affect the post menopausal age group. They present as aggressive, large sized, high grade tumours that are estrogen receptor negative. Tumour size and axillary lymph node involvement indicate poor prognosis. Despite treatment with chemotherapy and radiotherapy, these patients have high risk of local recurrence and distant metastases which are potentially fatal.  Key words:  metaplastic breast carcinomas, pathologic features, outcome    INTRODUCTION   Metaplastic breast carcinomas (MBCs) encompass a heterogeneous group  of breast cancers characterised histologi-cally by intimate admixture of adenocar-cinoma with dominant areas of spindle cell, squamous, and/or mesenchymal differentiation (Devilee & Tavasoli 2003). The tumour may present in pure form of metaplastic spindle cell or squamous cell component without recognizable adeno-carcinoma. It can be categorised into purely epithelial (when it is composed of squamous cell carcinoma only or adeno-carcinoma and squamous cell) or mixed epithelial and mesenchymal e.g. carcino-sarcoma. These tumours are rare, ac-counting for less than 1% of all breast cancer cases with mean age of presen-tation at 55 years old (Devilee &Tavasoli  2003). Between 1984 to 2005, there were only 16 published reports of 505 cases discussing the clinical and pathological characteristics of this tumour (Beatty et al. 2006). Due to its rarity, data on the current understanding and management of metaplastic breast carcinomas are scanty. We report our experience in managing six cases of metaplastic breast carcinomas encountered at our centre over an 8-year study period. The histo-pathological features and clinical out-comes from these patients are reviewed.   MATERIALS AND METHODS  Cases were retrieved from the Breast Cancer Database at The Breast and En-docrine Unit, Universiti Kebangsaan Ma-laysia Medical Center (UKMMC). Infor-mation on the demographics, diagnosis, tumour grade, oestrogen (ER) and progesterone (PR) receptors status, HER2 expression, clinical staging, treat-ment, recurrence status and patient sur-vival was recorded. Information on the patients’ survival details were obtained from the medical records and through telephone conversations with their family members. The patients were grouped according to tumour types; epithelial and biphasic histological subtypes. Disease free survival was defined as the time from diagnosis to distant recurrence (or death from cancer in the absence of re- 128 Metaplastic Breast Carcinoma  Med & Health 2009; 4(2): 127-132 currence) or last follow-up. Overall sur-vival was defined as the time from diag-nosis to the time of death from the cancer or date of last contact for patients who are still alive or who had died from other causes.  RESULTS  A total of 471 breast cancer patients were operated between 2000 and 2007 at our institution, of which six female pa-tients were histologically confirmed to have MBCs, giving an incidence rate of 1.3%. Ethnically, the patients comprised four Malays and two Indians. The mean age of our patients was 51 years with the epithelial only group being slightly younger age (42 years) than the biphasic group (55 years). The mean tumour size was 9.5cm with the epithelial only group presenting with slightly bigger tumor size (13cm) compared to the biphasic group (8 cm). Histologicaly, three of the six pa-tients had epithelial only tumours com-posed of both adenocarcinoma and squamous cell carcinoma while the other three patients were diagnosed with tu-mours of the biphasic type expressing both carcinoma and sarcomatoid compo-nents. All patients had grade 3 tumours and all tumours were ER and PR negative. Only four patients had the HER2 status tested, all of which were negative. Axillary nodal involvement was found in all epithelial only group and one in the biphasic group.  Four patients underwent mastectomy with axillary clearance, one patient had mastectomy only and one had wide local excision with axillary clearance. Two patients received neoadjuvant chemotherapy while another three had adjuvant chemotherapy. One patient refused chemotherapy. All of the patients had tumour recurrence with mean time of recurrence of 9 months. Five of them died two to three months after tumour recurrence. Table 1 summa-rises the relevant clinicopathological findings.   Table 1 :  Summary of metaplastic breast cancer cases  Patient No. Tumour grade ER PR No of lymph nodes involved Operation date Type of operation Chemo- therapy Recurrence date & site Death 1 3 negative negative 12/28 15.01.05 Mastectomy +AC Yes 12.09.05 local 07.10.05 2 3 negative negative 1/31 15.10.02 Mastectomy +AC No 07.05.03 brain 17.06.03 3 3 negative negative 1/8 28.03.03 Mastectomy +AC Yes May - 2004 bone still alive  4 3 negative negative 0/7 26.02.05 WLE + AC Yes 30.09.05 liver 31.10.05 5 3 negative negative - 15.06.02 Mastectomy Yes Aug – 2002 bone 09.10.02 6 3 negative negative 0/12 06.08.02 Mastectomy + AC Yes July – 2004 lung, liver 05.08.04 ER: estrogen receptor; PR: progesterone receptor; AC: axillary clearance; WLE : wide local excision    129 Med & Health 2009; 4(2): 127-132  Shahrun N.S. et al  DISCUSSION  Metaplastic breast carcinomas (MBCs) are rare types of breast cancer which are difficult to diagnose clinically as they do not have specific imaging patterns. They are also challenging to the pathologists as the tumours have a wide range of histopathological features and the metaplastic area may dominate the whole tumour or occupy a very small area within the lesion. In this report, we identified six metaplastic breast carcinomas and evaluated their clinicopathological parameters. We record an incidence rate of 1.3% which concurs with the reported incidence of 1-2% elsewhere (Roses 2005). Interes-tingly, the six patients in our series were comprised of four Malay and two Indian ethnicity with no MBC diagnosed among Chinese patients. Similar ethnic differ-ences in risks for MBCs was reported in an earlier study which reported a higher percentage of MBCs among African Americans or Hispanics (Pezzi et al. 2007). The reason for this observation is unclear but probably suggests that racial or genetic factors may underlie the in-creased risk for MBCs.  MBCs were thought to have either ori-ginated as a single entity or clone that originates in the myoepithelial cells or its precursor, or those arising from pre-ex-isting lesions such as papillomas, com-plex sclerosing lesions and nipple ade-noma (Denley et al. 2000; Gobbi et al. 2003; Popnikolov et al. 2003; Reis-Filho et al. 2003). This has been further sup-ported by the fact that these neoplastic cells express vimentin, smooth muscle actin, muscle specific actin and p63 that are commonly associated with myoepi-thelial cells (Schnitt & Collins 2008). Cytokeratin positivity is seen in the epi-thelial and mesenchymal component of this tumour and it is thought that it is the metaplasia of the epithelial elements of a carcinoma that could have given rise to the sarcomatous changes (Saxena et al. 2004). In most literatures, MBCs are ER and PR negative, as was the case in all pa-tients reported here (Kuo et al. 2000; Khan et al. 2003; Luini et al. 2007; Pezzi et al. 2007). Similarly, most of the MBCs in our series did not express HER2 which is in keeping with a previous study (Barnes et al. 2005). The reported inci-dences of lymph node involvement in these tumors were between 8%-56% (Kurian & Al-Nafussi 2002; Khan et al. 2003). In this series of cases, axillary nodal involvement was found in the entire epithelial only group and only one of the patients in the biphasic group had nodal metastases. The distinctive lymph node negativity was observed in the presence of spindle cell component which may be due to the nature of sarcoma that tends to metastasize haematogenously rather than through lymphatic channels (Sneige et al. 2001; Gobbi et al. 2003). Despite the lower incidence of axillary lymph node involvement, these tumours had high metastatic potential either locally, to distant organs or both, in more than 50% of cases (Wargotz et al. 1989; Wargotz & Norris 1989a; Rayson et al. 1999). Most distant metastases involve lung or bone (Wargotz et al. 1989; Wargotz & Norris 1989b; Kurian & Al-Nafussi 2002). In our series, we had five patients with distant metastases and one local recurrence (Table 1). The average size of the tumours in this series was 9.5cm which was bigger than the usual size of infiltrating ductal carci-nomas. This is most likely due to the ag-gressive nature of the tumours with rapid growth rates. Most of these patients had poorly differentiated or undifferentiated tumours (compared to infiltrating ductal carcinoma) which will further lead to rapid growth rates (Pezzi et al. 2007). We were unable to do a statistical analysis on whether the epithelial only group tumours were larger than the biphasic group due  130 Metaplastic Breast Carcinoma  Med & Health 2009; 4(2): 127-132 to the limited number of cases. However, in this series the mean tumour size for the epithelial group was greater than the biphasic group. Five of our patients had mastectomy due to the large size of the tumours. Five of the patients had systemic therapy (one refused) and most of them died within a year after surgery. In our series, the mean time of recurrence was 9 months and survival after recurrence was short. This concurs with other studies that showed that MBCs are less responsive to therapy with the conventional regimes that are usually used for infiltrating ductal carcinoma (Wargotz & Norris 1989a; Rayson et al. 1999). There is no survival advantage either with chemotherapy or radiotherapy for distant metastases (Wargotz & Norris 1989a). The median survival after metastases is 8 months after systemic treatment (Rayson et al. 1999). This means that the optimal systemic therapy for metaplastic breast carcinoma still needs further defining.   CONCLUSION  Metaplastic breast carcinomas are rare types of breast cancers usually affecting the post menopausal age group. These tumours have aggressive clinical beha-viour, present with locally advanced dis-ease, are large in size, high grade tu-mours and triple negative. Despite treat-ment with chemotherapy and radiothe-rapy, the patients have a high risk of local recurrence and distant metastases which are potentially fatal.  REFERENCES   Barnes, P.J. Boutilier, R., Chiasson, D. 2005. Metaplastic breast carcinoma: clinical-pathologic characteristics and HER2/neu expression. Breast Cancer Research and Treatment 91:173-178. Beatty, J. D., Atwood, M., Tickman, R. & Reiner, M. 2006. Metaplastic breast cancer: clinical significance. Am J Surg 191:657-664. Denley, H., Pinder, S.E., Tan, P.H., Sim, C.S., Brown, R., Barker, T., Gearty, J., Elston C.W. & Ellis, I.O. 2000. Metaplastic carcinoma of the breast arising within complex sclerosing lesions: a report of five cases. Histopathology 36: 203-209. Devilee, P. & Tavasoli, F.A. 2003. World Health Organisation Classification of Tumours. Pathology and Genetics of Tumours of the Breast and Female Genital Organs. Lyon, IARC Press. Gobbi, H., Simpson, J.F., Jensen, R.A., Olson S.J. and Page, D.L. 2003. Metaplastic breast tumours arising within papillomas, complex sclerosing lesions and nipple adenomas. Mod Pathol 16: 893-901. Luini, A., Aguilar, M. & Gatti, G. 2007. Metaplastic carcinoma of the breast, an unusual disease with worse prognosis: the experience of the European Institute of Oncology and review of the literature. Breast Cancer Res Treat. 101:349-353. Khan, H. N., Wyld, L., Dunne, B., Lee, A. H. S., Pinder, S. E., Evans, A. J. & Robertson, J. F. R.. 2003. Spindle cell carcinoma of the breast: a case series of a rare histological subtypes. Eur J Surg Oncol 29: 600-603. Kuo, S. H. Chen, C. L. Huang C. S. & Cheng, A. L. 2000. 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 20: 2219-2222. Kurian, K.M. & Al-Nafussi, A. 2002. Sarcomatoid/ metaplastic carcinoma of the breast: a clinicopathological study of 12 cases. Histopathology 40:58-64. Pezzi, C.M., Patel-Parekh, L., Cole, K., Franko, J., Klimberg, V.S. & Bland, K. 2006. Characteristics and treatment of metaplastic breast cancer: Analysis of 892 cases from National Cancer Data Base. Annals of Surgical Oncology. 14(1):166-173. Popnikolov, N.K., Ayala, A.G., Graves, K. & Gatalica, Z. 2003. Benign myoepithelial tumours of the breast have immunophenotypic characteristics similar to metaplastic matrix-producing and spindle cell carcinomas. Am J Clin Pathol 120(2):161-167. Rayson, D., Adjei, A.A., Suman, V.J., Wold, L.E.  & Ingle, J.N. 1999.  Metaplastic breast carcinoma cancer: prognosis and response to systemic therapy. Ann Oncol 10: 413-419. Reis-Filho, J.S., Milanezi, F., Paredes, J., Silva, P., Pereira, E.M., Maeda, S.A., de Carvalho, L.V., Schmitt, F.C. 2003. Novel and classic myoepithelial/ stem cell markers in metaplastic  131 Med & Health 2009; 4(2): 127-132  Shahrun N.S. et al   132 carcinomas of the breast. Appl Immunohistochem Mol Morphol 11:1-8. Roses, D.F. 2005. Breast Cancer: 2nd Edition. Churchill Livingstone; 117-119. Saxena, S., Bansal, A., Mohil, R.S. & Bhatnagar, D. 2004. Metaplastic carcinoma of the breast – a rare breast tumour. Indian J Pathol Microbiol 47: 217-220.  Schnitt, S.J. & Collins, L. 2008. Biopsy Interpretation of the Breast: 1st Edition. Lippincott Williams and Wilkins; 327. Sneige, N., Yaziji, H., Mandavilli, S.R., Perez, E.R., Ordonez, N.G., Gown, A.M., Ayala, A. 2001. Low grade (fibromatous-like) spindle cell carcinoma of the breast. Am J Surg Pathol 25:1009-16. Wargotz, E.S., Deos, P.H. & Norris, H.J. 1989. Metaplastic carcinoma of the breast: II. Spindle cell carcinoma. Human Pathol 20(8): 732-740 Wargotz, E.S. & Norris, H.J. 1989a. Metaplastic carcinoma of the breast: I. Matrix producing carcinoma. Human Pathol 20(7): 628-635. Wargotz, E.S. & Norris, H.J. 1989b. Metaplastic carcinomas of the breast: III. Carcinosarcoma. Cancer 64(7):1490-1499. 

Metaplastic breast carcinomas: a report of six cases

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