Fibromatosis-like metaplastic carcinoma of the breast: A rare case report

Dear Editor,

Fibromatosis-like metaplastic carcinoma (FLMC) of the breast is an infrequent and inadequately elucidated variant of spindle cell carcinoma, a type of metaplastic breast carcinoma (MBC) comprising approximately 0.5-5% of all breast malignancies.^[1] This rare epithelial breast cancer, reported only 68 times in two decades, often mimics benign fibromatous changes or reactive spindle cells post-biopsy, leading to a high risk of misdiagnosis. Despite its indolent histopathological appearance, its clinical behaviour can be aggressive, emphasizing the need for careful evaluation and advanced diagnostic methods.^[2] We present the case of a 63-year-old woman with a mass in the left breast, emphasizing the clinical presentation, diagnostic challenges, histopathological features, and treatment approaches. This case highlights the importance of recognizing this rare subtype within the spectrum of breast malignancies.

A 63-year-old postmenopausal woman presented with a gradually enlarging left breast lump for 6 to 7 months. On examination, a nodule was felt to be located in the upper inner quadrant of the left breast at the 11 o’clock position. An ultrasonography (USG) mammography revealed a BIRADS IV A, 1.6 x 1.7 cm lesion, which was further biopsied, and histopathological examination (HPE) revealed predominantly sclerotic stroma with focal areas containing plump stellate to spindle cells embedded within collagen fibres, along with occasional tubules, and the nuclei appeared hyperchromatic without significant pleomorphism or mitotic activity [Figure 1].

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Figure 1: Histopathological findings of fibromatosis-like metaplastic carcinoma of breast. (a) Areas of spindle cells with collagenous stroma, (b) Areas of plump stellate spindle cells, (c) Spindle cells with areas of peripheral clearing. No significant nuclear atypia, (d) Focus of invasive carcinoma with squamous metaplasia. Haematoxylin and eosin, 10x.

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These findings suggested a low-grade fibromatosis-like malignancy.

Immunohistochemistry revealed positivity for Pancytokeratin (Pan-CK) and p63 in the spindle cells and some tubules, with oestrogen receptor (ER), progesterone receptor (PR), and HER2 being negative (HER2 score 0) [Figure 2a-e].

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Figure 2: Immunohistochemical findings in fibromatosis-like metaplastic carcinoma of the breast. (a) CK AE1 AE3- positive in neo-plastic spindle cells, (b) P63- positive in neoplastic spindle cells, (c) ER-negative, (d) PR- negative, (e) Her2Neu- negative, The stains used include CK, P63, ER and PR, HER2, 10x. CK: Cytokeratin, ER: Estrogen receptor, PR: Progesterone receptor, HER2: Human epidermal growth factor receptor 2.

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A routine staging PET-CT scan revealed a single, FDG-avid, lobulated soft tissue lesion in the left breast. Based on the radiological and pathological findings, which did not indicate an infiltrative malignancy, the multidisciplinary team recommended a complete local excision of the tumour. The patient initially underwent a left breast lumpectomy; however, after confirmation of invasive component on intraoperative frozen section, a left modified radical mastectomy with axillary lymph node clearance was performed.

The final histopathology exhibited an infiltrative grade A. A routine staging PET-CT scan revealed a single, FDG-avid, lobulated soft tissue lesion in the left breast. Based on the radiological and pathological findings, which did not suggest infiltrative malignancy, the multidisciplinary team recommended a complete local excision of the tumour. The patient initially underwent a left breast lumpectomy; however, after confirmation of an invasive component on intraoperative frozen section, a left modified radical mastectomy with axillary lymph node clearance was performed—growth pattern with significant fibrosis, spindle and ovoid cells, peripheral clearing, and minimal mitotic activity. A small 1-2 mm focus of invasive carcinoma with squamoid differentiation was identified without evidence of ductal carcinoma in situ (DCIS). IHC analysis confirmed positivity for Pan-CK and p63.The resection margins were all tumour-free with no evidence of lymphovascular or perineural invasion. Additionally, focal areas of intermediate-grade comedo-type intraductal carcinoma were identified with a Ki-67 proliferation index of 15%.The final diagnosis was low-grade fibromatosis-like metaplastic carcinoma with focal squamous differentiation, classified as pathological stage pT2N0.

Given the negative resection margins, absence of lymph node involvement, and the favourable prognosis associated with this entity, no adjuvant therapy was administered, in accordance with the National Comprehensive Cancer Network (NCCN) guidelines. The patient was enrolled in a surveillance program consisting of quarterly follow-ups, including clinical examinations, diagnostic imaging, thoracic X-rays, and abdominal and breast ultrasounds. Over 12 months of follow-up, there has been no evidence of recurrent or refractory disease. The patient remains disease-free and continues to be monitored closely.

The fibromatosis-like metaplastic carcinoma (FLMC) of the breast, a rare subtype of breast tumours, was newly recognized in the 4th edition of the World Health Organization's classification of breast tumours, published in 2012.^[3] The FLMC variant, characterized by its low-grade histological appearance resembling pure fibromatosis, has a high propensity for local recurrence but a favourable prognosis, leading some authors to prefer the term 'fibromatosis-like tumour' to avoid the 'carcinoma' label.^[4] Diagnosing FLMC is often challenging, particularly on core needle biopsy, as the morphologic features are similar to other low-grade spindle cell lesions of the breast. Immunohistochemical testing aids in the definitive diagnosis by identifying epithelial foci through antibodies specific for epithelial and myoepithelial differentiation.^[3,4]

This present case had a similar conundrum, where the initial biopsy was inconclusive, indicating a low-grade fibromatosis-like malignancy, and immunohistochemistry played a crucial role in establishing the definitive diagnosis.

FLMC can pose considerable diagnostic problems to pathologists and can be underdiagnosed as a benign tumour.^[5] These neoplasms are diagnosed during initial presentation or upon recurrence, especially in cases where an incompletely excised FLMC was originally misdiagnosed as a benign lesion, and pathologists often differentiate FLMC from fibromatosis using IHC markers.^[6] The literature suggests that the risk of local recurrence is partly related to inadequate local resection.^[7] Currently, there are no established evidence-based treatment guidelines for FLMC, but wide local excision has been shown to prevent local recurrence effectively. This stands in stark contrast to the management of other triple-negative breast cancer (TNBC) variants, where adjuvant radiotherapy or chemotherapy is integral to treatment protocols. In most TNBC cases, these therapies significantly reduce the risk of recurrence and distant metastasis due to the aggressive nature of the disease and its tendency to spread. Conversely, in FLMC, existing data indicate that adjuvant radiotherapy or chemotherapy offers little to no benefit in mitigating recurrence or metastasis. This highlights the distinct clinical behaviour of FLMC and underscores the need for specialized, tailored treatment approaches that differ from standard TNBC protocols.^[8] However, some authors recommend adjuvant radiotherapy for larger, bulky lesions, while other authors argue against axillary lymph node dissection in pure FLMC, particularly in the management of small tumours.^[6] This concurs with what was done in the present case.

The key factor in preventing local recurrence, aside from adjuvant radiotherapy, is achieving clear microscopic margins during lumpectomy. Surgeons performed intraoperative frozen-section analysis while performing lumpectomy to obtain a clear resection margin and prevent reoperation. The primary advantage of intraoperative frozen section margin assessment is the reduction in reoperation rates, which confers psychological, physical, and financial burdens on patients and potentially delays subsequent treatment.^[9] Immunohistochemically, the tumour cells consistently expressed p63 and cytokeratin (CK), while lacking expression of oestrogen receptors (ER), progesterone receptors (PR), and HER2 receptors.^[10] Similar findings have been reported by Nozoe et al.^[11], Rekhi et al.^[12], Rito et al.^[13], and others, demonstrating that FLMC exhibits a triple-negative immunohistochemical profile.

This case highlights the critical importance of accurately diagnosing FLMC, despite its rarity. Recognizing spindle cell breast lesions requires a thorough differential diagnosis that integrates clinical, radiological, pathological, and immunohistochemical data to avoid misdiagnosis. The strengths of this study lie in its detailed evaluation across these domains, coupled with the comprehensive use of immunohistochemistry, which not only ensured diagnostic precision but also informed a practical and well-guided surgical approach. The discussion also provides valuable insight into decision-making processes and follow-up protocols. However, the study is limited by being a single case report, which constrains its generalizability. Additionally, the follow-up period is restricted to 12 months, which may not capture long-term recurrence rates.

The findings may not reflect the full spectrum of fibromatosis-like metaplastic carcinoma (FLMC) across diverse patient populations. To enhance the understanding of clinical variability, refine diagnostic criteria, and optimize treatment approaches, larger, multi-center studies are essential. Future research should focus on exploring the molecular and genetic characteristics of FLMC, assessing the potential role of adjuvant therapy, and establishing standardized management protocols to improve patient outcomes and prognostic accuracy.

FLMC of the breast is a rare and challenging diagnosis, frequently mimicking benign lesions. This case highlights the importance of a multidisciplinary approach for accurate diagnosis and surgical management. FLMC exhibits TNBC phenotype; however, they are not as aggressive and have a low-grade histology. They can recur locally, making complete excision with clear margins essential. Further research is needed to establish optimal treatment strategies and long-term outcomes for FLMC.