Spindle Cell Carcinoma of the Breast in a Patient with Previous History of Rectal Cancer: A Case Report

Cancer has become one of the main causes of morbidity and mortality on a global scale in recent decades, largely due to demographic, economic, and epidemiological transitions^[1].

Among the female population, breast cancer is the most common malignancy in the world (154 out of 185 countries), except in West Africa, where cervical cancer prevails. In 2018, a total of 2.1 million women were diagnosed with breast cancer^[2,3,4].

Breast cancer can be classified according to its histological type. The most common histological type is invasive ductal carcinoma, which represents about 50% to 80% of newly diagnosed breast cancer cases; the rest of the cases are classified as invasive lobular carcinoma^{[1, 5]}.

Invasive ductal carcinomas can be classified as “no specific type” because these tumours do not present sufficient morphological characteristics to be determined as a characteristic histological type. They can also be recognised as a “special type” if they present sufficient distinctive characteristics and particular cellular and molecular behaviours^{[1, 5, 6]}.

The most common special types of breast cancer include: medullary carcinoma, metaplastic carcinoma, apocrine carcinoma, mucinous carcinoma, cribriform carcinoma, tubular carcinoma, neuroendocrine carcinoma, classic lobular carcinoma, and pleomorphic lobular carcinoma^[6].

In general, neoplastic epithelial cells in metaplastic carcinomas differentiate into other phenotypes, such as squamous, spindle cell, or mesenchymal. Although they are less likely to have nodal involvement at the time of diagnosis, relapse rates are high, and spindle cell carcinoma is now classified as a subtype of malignant epithelial tumour. In this relatively rare histological type, rapid proliferation may cause cystic changes because of internal tissue necrosis^[7].

Metaplastic breast cancer is typically a triple-negative breast cancer (TNBC), meaning the tumour lacks the expression of the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 receptor (HER2). Given the heterogeneous composition of these tumours and the fact that metaplastic carcinomas are rare—comprising less than 1% of invasive breast carcinomas––outcome data are limited and may seem contradictory. However, some subtypes seem to have distinct biologic behaviours^[8].

The prognosis of metaplastic breast cancer has not been well delineated. Although some researchers have reported a better prognosis for metaplastic breast cancer than for invasive ductal carcinoma of the breast, others have reported that the prognosis for metaplastic breast cancer is unfavourable compared to invasive ductal carcinoma^[9,10,11].

Metaplastic breast cancer is significantly correlated with worse progression-free survival (PFS) and overall survival (OS) compared with invasive ductal carcinoma. Patients with this subtype of breast cancer are resistant to conventional chemotherapy, and more efficient treatment regimens are required^[12].

In this case report, we discuss a 56-year-old woman with spindle cell carcinoma of the breast and a previous history of treated rectal cancer. Her spindle cell breast cancer was aggressive with rapid progression and a poor response to systemic chemotherapy.

This patient with a previous history of locally advanced rectal cancer was diagnosed when she was 56 years old, received concurrent chemoradiotherapy (CCRT) and achieved a complete radiological response, but she refused surgery and kept up with the follow-up visits. She presented to her surgeon two years after initial diagnosis with a left breast mass. Mammography revealed a dense mass (22*32 mm) at the 2–3 o’clock position, with skin in the anterior region thickened by scattered macrocalcifications and a clear left axilla. Doppler ultrasonography of the left breast revealed an ill-defined hypoechoic vascular mass surrounded by thick edematous tissue measuring 22*32 mm at 2–3 o’clock with clear left axilla. Fine needle aspiration (FNA) under ultrasound guidance was positive for malignancy. A contrast CT scan of the chest and abdomen revealed no distant metastasis, but a well-defined hypoechoic left breast mass measuring 48*45 mm. She had a left modified radical mastectomy with axillary clearance two weeks later; the mass was 7 cm in the outer quadrant and 2 mm from the deep margin, with 17 lymph nodes identified in the specimen. Sections of the mass revealed an invasive high grade malignant tumour composed of bundles and fascicles of atypical spindle cells with a large hyper metabolic nuclei and eosinophilic neoplasm with brisk mitotic activity and necrotic foci. There was no epithelial component, ductal carcinoma in situ, or non-neoplastic component (Figure 1, Figure 2). All 17 lymph nodes were free of malignancy. Immunohistochemical staining was applied to the tumour, which revealed scattered strong positivity for AE1/3 and negative results for desmin, CD34, s100 protein, and SMA. The final histopathological diagnosis was poorly differentiated metaplastic breast cancer of the spindle cell type.

Figure 1:

Figure 2:

The patient did not receive any chemotherapy until five months after the surgery when she presented with a local recurrence of two small masses at the site of mastectomy, as well as multiple bilateral pulmonary metastasis as revealed by a contrast CT scan of the chest and abdomen. A decision was made to start treatment with single agent Adriamycin chemotherapy at 60 mg/m² every 21 days.

On clinical examination after three cycles of chemotherapy, the size of the two masses had decreased. She was put on single agent Adriamycin for another three cycles and had new CT scans of her chest and abdomen with contrast to see how she was responding to the treatment. The new CT scan revealed three new suspicious lesions in the liver. During her preparation for an ultrasound guided biopsy of the liver, she developed a severe headache and a disturbed level of consciousness. A contrast CT scan of the brain revealed multiple enhancing scattered nodules in the supra- and infratentorial compartments, with the largest one (24 mm) seen in the right parietal lobe. There was evidence of a 9 mm pontine nodule associated with brain oedema. The patient refused palliative radiotherapy to the brain and remained on supportive treatment until she passed away due to complicated aspiration pneumonia.

Spindle cell carcinoma of the breast is a rare histological carcinoma, accounting for approximately 0.08% of all breast cancers^[13]. Because metaplastic carcinoma of the breast with spindle cell variation is a rare disease, most of the information about this cancer type is based on case reports.

Tumours are commonly large, well-circumscribed, cyst-containing lesions that are most frequently located in the upper outer quadrant of the breast^[14]. At the time of initial diagnosis, numerous spindle cell carcinomas tend to be large and localised, with histopathological examination often showing well-defined margins or a partially nodular appearance^[15].

Treating patients with metaplastic breast cancer is difficult and challenging due to the rarity of this type of tumour, the poor response of this type of malignancy to treatment, the lack of data to support any type of chemotherapy, and the nature of these tumours, which are indicative of an aggressive and rapidly progressive disease. A study carried out by Song et al. ^[9] found that patients with metaplastic breast cancer presented with a larger tumour size, fewer lymph node metastases, a higher percentage of triple-negative (estrogen receptor-negative, progesterone receptor-negative, and HER2-negative) cases, higher proliferation rates, and high expression of Ki-67 compared to those with invasive ductal carcinomas.

Immunohistochemistry is the key examination that allows for a more accurate diagnosis. Specific markers have high sensitivity and specificity for spindle cells and are useful for the diagnosis of spindle cell carcinoma. Findings of focal positivity for cytokeratin (AE1/AE3, CK5/6, CK7, and CK14) and the presence of S100 protein are in favour of this lesion. There may be a positive reaction for muscle markers such as calponin (86%) and smooth muscle actin (36%) (16–18). In this case, our patient's breast tumour IHC was negative for estrogen (Figure 3), progesterone (Figure 4), and HER2 (Figure 5), desmin, S100, SMA, and CD34, and strongly positive for AE1/3.

Figure 3:

Figure 4:

Figure 5:

Spindle cell carcinoma of the breast has the propensity for both local and distant metastasis. The risk factors for recurrence are not well known; however, in a study conducted by Bauer et al.^[19], they found that tumour size (greater than 2 cm) is a very significant risk factor for recurrence. Another risk factor reported by a study conducted by Zhang et al.^[20] was P53 and P63 mutational accumulation. In this presented case, the size of the tumour was 7 cm by macroscopic examination, so the tumour size was a great risk factor for recurrence.

Due to the rarity of this type of tumour, little is known about its biological behaviour and systemic treatment. The treatment is very difficult, and there is no standard course of treatment. Mastectomy could be considered in patients with a significant tumour size, and partial mastectomy can be performed in patients with a smaller tumour size. However, some studies concluded that there was no significant difference in survival between patients who underwent partial mastectomy and those who underwent total mastectomy ^[21]. Though, generally, the outcome of a radical mastectomy was better than that of a partial mastectomy. In this case report, our patient underwent a modified radical mastectomy with axillary clearance, but nevertheless, she had a local recurrence within five months of the diagnosis, which gives us an idea about the aggressiveness of her tumour.

Chemotherapy treatment is not well established; however, chemotherapy has been used in adjuvant and metastatic settings. These tumours have short PFS and OS times. In a study carried out by Khan et al.^[22], they concluded that the median disease-free interval was seven months. Our patient developed multiple metastatic lesions within a short period of time. The first disease progression occurred within five months of the surgery, and the second progression occurred within five months of the first progression with a poor response to the chemotherapy.

In this study, we discussed a case of aggressive spindle cell cancer of the breast in a 56-year-old women who unfortunately had rapid progression despite having undergone surgery in the form of a modified radical mastectomy with axillary clearance. It is worth noting that there was a delay of about five months between surgery and the start of chemotherapy, so this delay in treatment, in addition to the aggressive nature of the disease could be a contributing factor to her rapid progression which occurred in the form of both local recurrence and bilateral pulmonary metastasis only five months after surgery. Although she remained stable for four months on single agent Adriamycin, she deteriorated at the appearance of liver and brain metastases, and one month later, she died of aspiration pneumonia as she and her relatives refused any further treatment (Figure 6).

Figure 6:

To our knowledge, this is the first case in our institution to be diagnosed with spindle cell carcinoma, and unfortunately, she died of the disease's progression and the associated complications. She had an aggressive disease that progressed rapidly with a poor response to treatment.

Spindle cell cancer of the breast is a subtype of metaplastic breast cancer which has a poor prognosis. It is a very rare type of breast cancer and due to its rarity, little and conflicting data is available regarding its management and the treatment approach which remains underexplored. More clinical trials are required for optimal treatment and better outcome.