A Case Report of a Rare ER+, PR- Pure Metaplastic Breast Squamous Cell Carcinoma with HER2 Overexpression

Abstract

BACKGROUND Breast squamous cell carcinoma (SCC) is a subtype of metaplastic breast carcinoma (MBC), which is a rare malignancy and accounts for 0.1% of all invasive breast carcinomas. Guidelines on definitive management and treatment of breast SCC are not well established, given its rarity and diverse immunohistochemistry (IHC) profile, and lack of clinical data. Most cases of breast SCC are triple-negative breast cancer - negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). This case report outlines the clinicopathological profile of a pure breast SCC case with a rare IHC profile; HER2 and ER positive. CASE REPORT A 41-year-old woman presented with a right breast mass that had been growing for 2 months. Biopsy confirmed breast SCC, a rare malignancy with IHC profile as follows: HER2 overexpression, ER positive, and PR negative. She underwent neoadjuvant chemotherapy for 3 months followed by right mastectomy with axillary clearance, adjuvant radiotherapy, and oral tamoxifen therapy. Unfortunately, she did not receive anti-HER2 therapy. She developed early locoregional recurrence at 2 months postoperatively, which was treated with excision of the right chest wall and transverse rectus abdominis musculocutaneous (TRAM) flap. She developed liver and lung metastasis and succumbed to her disease at 15 months post-diagnosis. CONCLUSIONS Breast SCC is a rare and aggressive tumor with heterogeneous clinicopathological features. Available guidelines do not outline the definitive treatment for breast SCC, given its rarity and heterogenous IHC profile, leading to a general lack of clinical data. Hence, due to the challenges in managing this rare condition, treatment modalities need to be individualized.

Figure 1.

(A, B) Histopathological slides from cyst wall curettage. The image shows multiple fragments of fibro-collagenous tissue infiltrated by malignant squamous cells arranged in trabeculae, nests, and singly distributed surrounded by desmoplastic stroma. The malignant cells are enlarged, polygonal, and moderately to markedly pleomorphic, displaying hyperchromatic nuclei, some with prominent nucleoli and ample eosinophilic cytoplasm. Mitosis is frequently seen. Dyskeratotic cells and focal intercellular bridges are present. No keratin pearl formation was noted. No lymphovascular invasion was seen. The background shows blood and some foamy macrophages. Hematoxylin & Eosin (H&E): 200× and 400× magnification. (C, D) The malignant cells are positive for squamous markers: (C) strong membrane/cytoplasmic staining for CK5/6, and (D) mild to moderate nuclear staining for the p63 tumor protein (400X magnification).

Figure 2.

(A, B) Immunohistochemistry (IHC) of the cyst wall curettage. (A) IHC shows that malignant cells are positive for estrogen receptors with 40% positivity of moderate to strong intensity. (B) IHC shows strong expression (3+) for erythroblastic oncogene B-2 (c-erb-B2). (400× magnification) Progesterone receptor: negative.

Figure 3.

(A) Right breast mammogram. (B) Ultrasound of the right breast. (C) Ultrasound of the right axillary lymph node. (A) Right breast mammogram showing heterogenous fibro glandular density. The Breast imaging reporting and data system (BIRADS) level was C, showing a large mass at the right upper quadrant. Multiple smaller high-density lesions in the right upper quadrant of the breast are visible. An area of hyperdensity over the right breast, upper quadrant, is visible. The red arrows show a dense, microlobulated cystic mass (these are typical mammography findings prompting suspicion of breast cancer). There is an associated right breast diffuse opacity due to edema. No suspicious grouped microcalcifications were seen. (B) Large thick-walled lobulated cystic mass with septations occupying the right upper quadrant, measuring 2.7×3.4×3.4 cm. There was a linear hypoechogenicity across the anterior aspect of the lesion in keeping with the previous wound. Several ill-defined hypoechoic lesions at the medial aspect of the above-mentioned lesions were visible. They were increased in size and number compared with recent sonograms, at the 12 o’clock and 1 o’clock positions; ranging from 0.7 cm to 2.3 cm. The overlying skin appeared to be thickened. (C) Enlarged right axillary node with cystic area measuring 1.2 cm in short axis diameter.