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Original Article Metaplastic Breast Carcinoma: a Clinical Analysis of 26 Cases

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Original Article Metaplastic Breast Carcinoma: a Clinical Analysis of 26 Cases Int J Clin Exp Pathol 2018;11(4):2112-2117 www.ijcep.com /ISSN:1936-2625/IJCEP0072589 Original Article Metaplastic breast carcinoma: a clinical analysis of 26 cases Xin Jin1, Dajun Yu1, Chenxu Guo1, Xiaomeng Gong2, Nan Li2, Yan Zhao2 Departments of 1Surgical Oncology, 2Pathology, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui, P. R. China Received January 11, 2018; Accepted February 21, 2018; Epub April 1, 2018; Published April 15, 2018 Abstract: Metaplastic breast carcinoma (MBC) is a rare and aggressive neoplasm. Morphologically, it is character- ized by the presence of multiple cellular differentiation and heterologous elements (squamous cells, spindle cells, cartilage or bone, etc). The clinical significance, prognostic risk factors and optimal treatment modalities of MBC are limited. This study collected clinical and pathological data of 26 MBC cases in the First Affiliated Hospital of Bengbu Medical College from July 2002 to July 2012 and investigated the clinicopathological features and the prognosis data. All patients were females aged 34-76 years old. Median tumor size was 3.5 cm and 88.5% patients were triple-negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2). MBC is associated with a poor prognosis compared with conventional invasive ductal carcinoma (IDC). In our study, 5-year Overall Survival (OS) rate and 5-year Disease-Free Survival (DFS) rate were 61.5% and 53.8% re- spectively. Most patients in this series had high-grade, triple-negative tumors and were treated with optimal therapy. Keywords: Breast, metaplastic breast carcinoma, clinicopathologic features, prognosis Introduction unknown and the potential predictors of treat- ment efficacy need to be explored. We reviewed Invasive breast carcinoma is the most leading the clinicopathologic features, treatment strat- cause of cancer mortality in women. MBC com- egies, and clinical outcomes of 26 MBC patients prise 0.2-1% of all invasive breast carcinomas treated in our hospital over a 10-year period to [1]. They consist of a heterogeneous group of further investigate the behavior of these neo- invasive carcinomas characterized by an admix- plasms and to provide more factual evidence. ture of adenocarcinoma with dominant areas of spindle cell, squamous and/or mesenchymal Materials and methods differentiation [2]. The current WHO classifica- tion distinguishes five subtypes: low-grade Among 8973 patients who underwent surgery adenosquamous carcinoma, fibromatosis-like for breast cancer at the First Affiliated Hospital metaplastic carcinoma, squamous cell carci- of Bengbu Medical College from July 2002 to noma, spindle cell carcinoma, and carcinoma July 2012, 26 (0.29%) patients were identified with mesenchymal differentiation (chondroid as MBC. We performed retrospective analysis differentiation, osseous differentiation, and of the clinical information, pathologic charac- other types of mesenchymal differentiation) teristics, treatment regimen, and follow-up [3]. Because the incidence rate of MBC is low details of these 26 patients. Specimens were and the pathological character is variable, the double-blind pathological review by two pathol- clinical characteristics, prognosis information ogists. According to the 2012 WHO Classification and treatment modalities are unclear and of Tumours of Breast and Female Reproductive controversial. Until now only a few large res- System: Pathology and Genetics, all patients earch and literature on MBC have been pub- were diagnosed as MBC and clinical staging lished. In clinical therapy, MBC is usually fol- were based on the TNM staging of breast can- lows the treatment paradigm for conventional cer developed by the American Joint Committee IDC. The ideal treatment guideline for MBC is on Cancer (AJCC, 7th edition) (17). All patients Twenty-six cases of metaplastic breast carcinoma Table 1. Sources of the antibodies used in months intervals for the first two year, and then the immunohistochemistry analysis at 6 months intervals for the following 2 years Source Antibody and then annually thereafter. All patients were followed up until mortality or the cut-off date CK Monoclonal AE1/AE3 of July 2012. All patients were followed by CKH (34βE12) Monoclonal, clone34βE12 phone or outpatient visit. Follow-up includes Ki-67 Monoclonal, cloneSP6 patient survival, postoperative adjuvant treat- ER Monoclonal, clone SP1 ment, tumor recurrence and metastasis. No PR Monoclonal, clone1A6 lost cases. HER-2 Monoclonal, cloneCB11 p63 Monoclonal, clone 4A4 Statistical analysis Vimentin Monoclonal, cloneSP20 All statistical analyses were carried out using All antibodies were obtained from Maixin Biotech, Inc. (Fuzhou, China), and were ready to use. SPSS 17.0 (SPSS, Inc., Chicago, IL, USA) for Windows. The Kaplan-Meier method was used to calculate the survival rate and draw the sur- were females and their ages ranged from 34 to vival curve. 76 years old, with a median age of 57 years. Clinical demographics and follow-up data were Results obtained from medical records and referring physicians. Clinicopathological characteristics This study was approved by the Ethics The clinicopathological characteristics of 26 Committees of the First Affiliated Hospital of MBC patients are summarized in Table 2. The Bengbu Medical College and was conducted in patient median age was 57 years. All patients accordance with the ethical guidelines of the were presented with a palpable, painless lump Declaration of Helsinki. in the breast, in which 3 patients had a history of blood nipple discharge. The tumor was locat- Immunohistochemistry (IHC) ed in the left breast in 15 cases and in the right breast in 11 cases. Tumor sizes were deter- Formalin-fixed paraffin embedded tissue sec- mined by gross pathological examination and tions were employed in each case using a ranged from 2.2-6.5 cm, the median tumor size standard protocol. HE-stained sections (4 µm was 3.5 cm. Most patients (20/26, 76.9%) had thickness) were re-examined to evaluate the T2 disease (tumor size 2-5 cm) and positive tumor’s histological features and immunohisto- lymph node metastases was reported in 34.6% chemistry were performed with Elivision tech- (9/26) of the 26 MBC patients. ER was negative nique. Antibody details are given in Table 1. The in 24 (92.3%) patients and PR negative in 26 threshold used for positive ER and PR expres- (100.0%) patients. HER-2 was negative in 23 sion was any nuclear labeling 1% or higher. (88.5%) patients. Most tumors were triple neg- HER-2 immunoreactivity was evaluated on a ative. Ki-67 was low expression in 6 cases, high standardized scale from 0-3 based on the expression in 17 cases, in the critical state in 3 intensity of staining of the cell membrane and cases. the proportion of invasive tumor cells stained. Strong complete staining of the membrane in The histologic subtypes of the metaplastic >10% of tumor cells (score, 3+) was considered components varied from a single metaplastic positive. Intensity patterns with scores 0-1+ component to mixed components, consisting of were considered negative, and samples scored any degree of squamous, chondroid, spindled, as 2+ were further assessed by FISH test. and sarcomatoid elements. (Figure 1) Among Fluorescence in situ hybridization ratio of 2.0 or all the patients, spindle cell carcinoma was the more was considered positive for HER-2 gene most common histological subtype (13/26, amplification. 50%), followed by metaplastic carcinoma with Follow-up squamous cell component (8/26, 30.8%), the third was fibromatosis-like metaplastic carci- For all patients, follow-up started from the date noma (3/26, 11.5%), and the fourth was carci- of operation. The patients were followed up at 3 noma with chondroid mesenchymal differentia- 2113 Int J Clin Exp Pathol 2018;11(4):2112-2117 Twenty-six cases of metaplastic breast carcinoma Table 2. Clinicopathological features of patients with 1 patient in 3 cases with HER-2 positive MBC expression had received targeted treat- Clinicopathologic Parameter Number (%) ment. Age, years Outcome, recurrence and prognosis <50 11 (42.3%) ≥50 15 (57.7%) Up to the cut-off date, 14 patients were Tumor size, cm still alive without recurrence. Twelve <2 2 (7.7%) patients experienced locoregional recur- 2-5 20 (76.9%) rence, distant metastasis, in which 10 >5 4 (15.4%) patients died due to disease progres- Nodal status sion. Among the 12 cases with local Positive 9 (34.6%) recurrence and distant metastasis, 4 cases of local chest wall recurrence; 2 Negative 17 (65.4%) cases of contralateral breast metastasis. Histologic subtype The most common organs involved were Low-grade adenosquamous carcinoma 0 (0.00%) the lung (n=5), liver (n=2), bone (n=1), Fibromatosis-like metaplastic carcinoma 3 (11.5%) supraclavicular LNs (n=1) and brain Squamous cell carcinoma 8 (30.8%) (n=1). The 5-year overall survival rate and Spindle cell carcinoma 13 (50.0%) 5-year disease-free survival rate were Carcinoma with mesenchymal differentiation 2 (7.7%) 61.5% and 53.8% respectively (Figure 2). ER status Negative 24 (92.3%) Discussion Positive 2 (7.7%) MBC was first described in 1973 by PR status Huvos et al. and was defined as a mam- Negative 26 (100.0%) mary carcinoma with mixed epithelial Positive 0 (0.0%) and sarcomatoid components [4]. The HER-2 status histologic classification of MBC was pri- Negative 23 (88.5%) marily based on the morphologic findings Positive 3 (11.5%) of tumor cell types: purely epithelial Ki-67 (squamous, adenosquamous and spin- <30% 6 (23.1%) dle cell carcinomas) or mixed epithelial 15%-30% 3 (11.5%) and mesenchymal (carcinoma with chon- >30% 17 (65.4%) droid/osseous metaplasia and carcino- sarcoma) components [5]. It may arise with or without an accompanying conven- tion (2/26, 7.7%). There was no low-grade ade- tional in situ or invasive mammary carcinoma. nosquamous carcinoma in our group. Most Pathological assessment remains the gold patients (17/26, 65.4%) had an associated con- standard for diagnosing MBC.
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