Metaplastic carcinoma of the breast with squamous differentiation: prognostic factors and multidisciplinary treatment

A 39-year-old female patient presented with a 5-cm nodule in the upper quadrants of the right breast, which had appeared 1 month before, plus inflammatory changes and palpable axillary adenopathy. She had undergone medical examination 6 years before, in a different healthcare center, due to fibrocystic disease. She provided three annual ultrasound studies that showed multiple cystic formations, parenchymal disruption, and ductal ectasia. She also provided the results of a biopsy study showing abundant epithelial and myoepithelial cellularity, fibrosis, cysts with apocrine metaplasia, and sclerosing adenosis. She had not received therapy. As a part of our examination, mammography and ultrasound studies were performed, where a large area of fibrocystic changes could be observed in the upper external quadrant of the right breast, as well as a 37-mm-diameter mass in the right armpit BI-RADS VI (Fig. 1A). Such findings were confirmed in a magnetic resonance study, which showed a 40-mm adenopathy plus metastatic involvement consisting of smaller surrounding adenopathies. Core needle biopsy revealed infiltrating carcinoma, probably of ductal origin, in the breast plus well-differentiated epidermoid carcinoma (p:63 positive) in the armpit, both were triple negative, ki 67: 60%, p:53 negative and ck 19 positive. Distant disease of stage T4N2M0 was ruled out. The tumor board decided that the patient be administered neoadjuvant chemotherapy consisting of four FEC cycles (5-fluorouracil-epirubicin-cyclophosphamide) and four docetaxel cycles. The treatment produced a 50% regression of the disease in the breast but a poor response in the armpit, where the disease actually progressed (Fig. 1B). Eventually, surgical management was scheduled (Fig. 2A).

The patient underwent skin-sparing mastectomy. Wide resection of the tumor was achieved, although an irresectable tumor residue remained, which infiltrated into the axillary vein, latissimus dorsi and right brachial plexus (Fig. 2B). The surgical specimen was collected for subsequent study (Fig. 2C). The defect was covered with a rotation myocutaneous flap of the latissimus dorsi. The donor zone was filled with flaps from the mastectomy (anterior part) and by dissecting the back until the midline and iliac crest (lower posterior part) (Fig. 2D). The surgical procedure was uneventful and the patient was discharged on day 3 postoperative. A histological study of the specimen revealed a high-grade 5-cm metaplastic ductal carcinoma with squamous differentiation, with axillary metastasis. In the breast, ductal predominance was found with associated high-grade intraductal carcinoma and free margins. In the armpit, a 12-cm ulcerated tumor mass was observed with a predominantly squamous pattern and extensive involvement of the deep margin. Adjuvant radiotherapy was initiated. However, 1 month later, ulcerations were observed in the armpit, which were related to the progression of the disease. Palliative chemotherapy was initiated. One month later, the patient reported low back pain and a D2–L1 metastatic lesion was found in bone scintigraphy. Later on, she presented dyspnea, multiple nodular lesions on both lungs and a metastatic lesion in the liver, all of which were managed with medical therapy until she died due to pulmonary embolism 11 months after diagnosis.

A 57-year-old female patient presented with an 8-cm nodule in the upper quadrants plus 2-cm axillary adenopathy. She complained of a 1-month long pain in the right breast. Her medical record showed not events of interest. She underwent a mammography and an ultrasound study, which showed a hypoechoic solid nodule with internal microcalcifications, anfractuous edges, and 33 mm maximum diameter (BI-RADS V) (Fig. 3A). The ipsilateral axilla showed a ganglion with cortical thickening and infiltrative appearance. Core needle biopsy revealed metaplastic infiltrating ductal carcinoma with squamous differentiation, associated with high-grade intraductal carcinoma. Axillary lymph nodes were positive. An immunohistochemical study showed a triple negative, ki 67: 60%, p53 negative and ck 19-positive tumor. In an extension study, computed axial tomography and positron emission tomography showed two lesions indicative of liver metastasis on segments VI and II without signs of significant metabolic activity. The disease was in stage T2N1M1. The tumor board decided to administer neoadjuvant chemotherapy consisting of 4 cycles of anthracyclines and docetaxel. The treatment produced 50% disease regression in the breast (Fig. 3B) and the armpit, although with a poor response in the liver, where the disease progressed. The case was then re-evaluated and surgery was ruled out. The patient was treated with local–regional radiotherapy plus administration of two more lines of chemotherapy, in an attempt to maintain the distance disease under control. However, the response was poor and the patient died 19 months after the diagnosis due to severe liver failure.

Below we analyze the characteristics of our patients plus those reported in the literature (Table 1). The mean age was 52.5 years; 40% of them had pre-existing breast lesions (cases 2 [7], 5 [8], 6 [9], and 9); tumor size was large in all cases and axillary involvement was present in 50% of cases (cases 3 [10], 6, 7 [11], 9, and 10); 70% of patients presented radiological findings of a solid mass, four of them in association with a cystic component (cases 1[12], 5, 6, and 9). Less than a half of patients were diagnosed using core needle biopsy (cases 1, 4, 6, and 10) and three of them underwent an incomplete surgical resection (cases 7, 8[13], and 9). Six patients received chemotherapy: neoadjuvant for half of them (cases 1, 9, and 10) and post-surgery for the rest of them (cases 3, 6, and 7). Radiotherapy was used in half of the patients. As much as 80% of tumors were triple negative, 30% of them progressing to distant metastatic disease (liver, lungs, and brain).