Granular cell tumour of the breast: A rare mimic of breast carcinoma

Background

Granular cell tumours (GCTs) of the breast are usually benign, with approximately only 1% exhibiting malignant properties; ¹ however, they frequently display malignant features on imaging and can cause diagnostic and management dilemmas. In this case, we present a patient with a final diagnosis of breast GCT and discuss the investigation and management of these rare tumours.

Case presentation

A 43-year-old female presented to the breast clinic for further investigation of a lesion in her left breast, which was incidentally detected on a thoracic computed tomography (CT) scan performed in primary care. She had no relevant previous medical history of note.

Clinical examination of the breasts and axillae where unremarkable, and she was referred for breast imaging as part of her triple assessment. Mammography confirmed a poorly defined area of increased density in the left outer lower quadrant (Figure 1). Ultrasound of the left breast demonstrated a poorly defined avascular hypoechoic lesion with distal acoustic shadowing, perilesional oedema and loss of adjacent fat planes, corresponding with the CT/mammographic lesion (Figure 2). There were no concerning axillary nodes.

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Figure 1.

(a) Mediolateral oblique (MLO). (b) Craniocaudal (CC) mammograms. Arrow points to an asymmetrical poorly defined density in the outer lower quadrant of the left breast.

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Figure 2.

Longitudinal Sonogram highlighting an irregular hypoechoic lesion in the lateral aspect of the left breast (callipers). Note the surrounding oedematous halo and distal acoustic shadowing.

The breast imaging findings were considered highly suspicious for malignancy, and the patient proceeded to ultrasound-guided percutaneous core biopsy. Samples were obtained using a 16G needle following local anaesthetic administration and sent to histology. While a 14G needle is often used in screening due to its increased diagnostic yield, in our practice needle gauge varies according to the patient, lesion type, and depth. Histological analysis revealed an ill-defined lesion composed of cohesive sheets of large cells with abundant, eosinophilic and finely granular cytoplasm infiltrating into the adjacent tissue. The tumour cells showed strong and diffuse positive staining for S100 (Figure 3).

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Figure 3.

(a) Hematoxylin and eosin immunostaining, with 10 times magnification. (b) Hematoxylin and eosin immunostaining, with 20 times magnification. (c) S100 immunostaining, with times 20 magnification.

Although there was a core biopsy diagnosis of GCT, the biopsy was categorised as B3 (uncertain malignant potential, requires further investigation) and surgical excision was recommended. Current local practice would normally indicate vacuum assisted biopsy for B3 lesions. However, following MDT (multidisciplinary team) discussion, due to the malignant features on imaging, the lesion was widely excised using ultrasound-guided wire localisation. Final histological analysis of the resected specimen confirmed a completely excised GCT measuring 20 mm at its largest dimension, with no malignant features.

Following further MDT discussion, the patient was reassured of the lesion’s benign nature. Due to this being a rare case with no national consensus on follow-up, the MDT opted for annual clinical examination and surveillance mammography for the next 5 years as a precautionary measure (Figure 1).

Discussion

In 1926, Abrikossoff was the first author to classify GCTs. ² GCTs can occur throughout the body, with approximately 5% found in the breast. ² Almost all GCTs are benign, with only 1% of cases showing malignant features, and most commonly affect women aged 30 to 50. About 0.1% of breast neoplasms are thought to be GCTs, making them extremely rare at this site. ³

The genetic aetiology and pathophysiology of GCTs remain poorly understood. Initially believed to be myogenic in origin, the prevailing theory currently suggests that breast GCTs arise from peripheral nerve Schwann cells in lobular breast tissue. ³ This neural origin may explain their more frequent occurrence in the upper inner quadrant of the breast, aligning with the dermatomal distribution of the supraclavicular nerve. ² Although no single genetic cause has been identified, multiple GCTs occurring at different sites in the body have been associated with syndromes such as Noonan syndrome, typically presenting as metachronous lesions. ⁴

Nearly all breast GCTs are benign; however, malignant transformation is a possibility. A study in 2012 reported a very rare case of malignant granular cell tumour (MGCT) transforming from benign GCT with breast metastasis after two local recurrences. Malignant features are only seen in 1% of cases; however, this demonstrates the need for adequate follow-up. ⁵

Clinically, GCTs can be challenging to differentiate from breast carcinoma. Their presentation varies but usually includes painless, firm, and well-circumscribed solitary masses, which may cause skin or nipple retraction. Reactive lymphadenopathy is also described. While solitary masses are more common, GCTs can be multicentric and can even coexist with breast carcinoma. ⁶ With the expansion of breast screening and other imaging which includes the breast (such as CT an increasing number of asymptomatic cases of GCT are being detected.

GCTs can also be difficult to distinguish from breast malignancy on imaging. Ultrasound findings range from well-circumscribed solid nodules to heterogenous poorly defined lesions with irregular margins. Malignant-like features such as a raised depth-to-width ratio and variable posterior acoustic shadowing are also described. ⁷ The extent of posterior attenuation is thought to correlate with the degree of reactive fibrosis within GCTs. GCTs are often visualised in the upper inner aspects of the breast and may appear vascularised or non-vascularised. ³ In addition, as seen in our case, surrounding perilesional oedomatous halo is a common feature.

Mammographic findings range from irregular, dense masses to well-circumscribed lesions, with associated calcification an uncommon finding. ⁸ A distinguishing feature proposed to differentiate GCTs from breast carcinoma is their tendency to occur in a subcutaneous location; however, other malignant lesions may also present superficially. GCT scan also be found at varying depths, including within the pectoralis major muscle. ³

The magnetic resonance imaging (MRI) findings in GCT are not well described. GCTs on T1 W are known to display low to intermediate signal intensity. They are not as readily visualised on T2-WI. GCTs show enhancement with gadolinium contrast. ⁹

CT appearances are not well documented in the literature. In this case, the GCT appeared as a non-specific soft tissue density nodule.

There is no definitive imaging feature that reliably differentiates a GCT from breast carcinoma. Consequently, histopathological evaluation remains crucial, with adequate tissue sampling key. Fine needle aspiration (FNA) is felt to be inferior to (ultrasound-guided) core biopsy which gathers material that can be sent for immunohistochemistry, with improved tumour typing and grading. ⁷ The hallmark histological findings for GCTs are granular eosinophilic cytoplasm. Immunohistochemistry, particularly S-100 protein positivity, confirms the Schwann cell origin. ³

There is no consensus on how best to manage benign GCTs. Excision is recommended for definitive diagnosis and wide local excision with complete resection of the margins is considered the standard approach. ⁴ The mainstay of treatment is surgery, with no current evidence for additional adjuvant therapy. ⁷ There is also no consensus on after treatment care. For benign lesions, some decide to discharge while others, as was the MDT suggestion in this case, choose imaging surveillance with 6 monthly mammograms initially with annual mammograms for 5 years thereafter.

Conclusion

This case report highlights the diagnostic challenge of breast GCT, a rare entity that mimics breast carcinoma and underscores the importance of considering GCTs in the differential diagnosis of malignant-appearing breast lesions. Accurate identification and prompt investigation with biopsy is critical, as the prognosis and management strategies differ significantly from breast malignancy.