Introduction

A typically rare benign neoplasm of Schwannian derivation, granular cell tumours occur most commonly in the tongue, head, neck, skin, and subcutaneous tissue.(1) First described by Russian pathologist, Abrikissoff in 1926, almost 12% of GCTs arise in the breast, accounting to only 0.1% of all breast neoplasms.(2) The challenge presented to clinicians and radiologists alike, is its ability to mimic breast malignancies.(3) Only a handful of cases of GCTs in literature have been reported to have undergone malignant transformation.

Here, we report an unusual case of GCT occurring in the breast, mimicking carcinoma on clinical examination and ultrasonography of the breast, for which confirmatory diagnosis was given after histopathological examination of the corresponding specimen.

Case Presentation

A 61-year-old female patient presented with a painless lump in the right breast of 1 year in duration. She had no personal or family history of malignancy and there was no prior history of breast trauma or infection. The physical examination revealed an ill-defined yet firm lump in the right upper outer quadrant measuring 3x2cm. There were no palpable axillary nodes, nipple retraction or skin changes.

Ultrasonography of the breast showed an irregular lesion measuring 3.1x1.9x1.6cm in the upper outer quadrant showing posterior acoustic shadowing suggestive of BI-RADS 4b lesion (Figure 1A). There was no associated calcification or skin thickness. Initial ultrasound guided FNAC showed mature adipocytes, stromal fragments, fat globules against a background of RBCs and inflammatory cells (Figure 2A-C). An initial trucut biopsy done elsewhere revealed only fibrocollagenous tissue, however a repeat trucut biopsy revealed a combination of atypical cells mixed with fibrocollagenous tissue. Given the lesion's BI-RADS 4b classification and its ill-defined, firm nature, the decision was made to proceed with surgical intervention by excising the lump with axillary clearance. The excised specimen was subsequently sent for detailed histopathological examination.

Figure 1: (A) Ultrasonography of the right breast showing an irregular, microlobulated, heteroechoic lesion measuring 3.1x1.9x1.6cm in the upper outer quadrant showing posterior acoustic shadowing with no significant internal vascularity – suggestive of BI-RADS 4b lesion. (B)Ultrasound guided FNAC of lump in the right breast. showing adipose tissue fragments; (C) Background neutrophil and lymphocytes; (D): RBCs and fat globules. No ductal epithelial cells and no evidence of atypia/malignancy noted.

Figure 2: A: Cut surface of histopathology specimen showing a grey-white, ill-defined, infiltrating tumour area measuring 3x2.5x1.7cm. No areas of necrosis or haemorrhage seen. (B): Clusters of large polygonal cells with abundant eosinophilic granular cytoplasm and peripherally pushed nucleus (H&E, 20x); (C): Pustulo-Ovoid bodies of Milian (Arrows), thick collagenisation and chronic inflammatory cell aggregates (H&E, 40x); (D): No mitosis, no pleomorphism (H&E, 40x)

Grossly, the excision specimen (with pectoralis major muscle) measuring 9x9x4.5cm showed, on sectioning, a grey-white, irregular, ill-defined, infiltrating tumour measuring 3x2.5x1.7cm. No areas of necrosis/haemorrhage were seen. The surrounding tissue was fibrofatty. (Figure 2A)

Microscopically, clusters of large polygonal cells with abundant eosinophilic granular cytoplasm and central to peripherally pushed nucleus were seen(Figure2B). Characteristic Pustulo-Ovoid bodies of Milian were noted(Figure 2C). Abundant thick collagenisation and areas of chronic inflammatory cell aggregates were also present( Figure 2C). Infiltration into the surrounding muscle was also noted. However, there were neither mitoses nor pleomorphism amongst the cells(Figure 2D). Interestingly, no ductal epithelial cells were seen either. Specimen margins were clear of tumour cells. All the 20 lymph nodes examined were uninvolved by the tumour. A final histopathological diagnosis of benign granular cell tumour of the axillary tail was made.

Discussion

Originally hypothesised to be of muscular origin in 1926 by the Russian pathologist, Abrikossoff, granular cell tumours are now proven to be neuroectodermal in origin, probably Schwannian derived.(4) Recently, two recurrent pathognomonic mutations have been identified as responsible for granular cell tumours - ATP6AP1 and ATP6AP2 inactivating somatic mutations.(5)

GCTs occur over wide range of ages, most commonly arising in the 4^th to 6^th decade with a male to female ratio of 1:1.8-2.4.(6) Although hormone independent, these tumours are seen to be associated with premenopausal women. A rare tumour known to involve majorly the cutis and subcutaneous tissues, 12% of all GCTs can present in the breasts, followed by respiratory tract and GI tract. (7)

Granular cell tumours of the breasts are commonly found in the upper inner quadrant, although they can occur in any location including the axilla and nipple.(2) These tumours are said to arise from the interlobular stroma, along the course of the supraclavicular nerve.(3) As in our case, the presentation of GCT is of a painless, slowly growing, palpable lump around 3cm which may be mobile or fixed to the underlying pectoralis or overlying skin.(8) Some patients have reported pain, pruritis, skin retraction, thickening or dimpling, and reactive lymphadenopathy, thereby clinically mimicking a malignant lesion.(2)

Diagnostic imaging of the breasts with GCTs show variable presentations on mammography and ultrasound, making it impossible to distinguish it from malignancy. Mammographically, a well-circumscribed lesion less than 3cm is usually seen. Non-specific ultrasound findings of a heterogeneous, solid, poorly defined mass with posterior shadowing and high depth to width ratio with or without vascularisation are most common.(9) Some studies suggest that the presence of an internal hyperechoic halo or component could be used to differentiate lesion from carcinomas, suggesting that this could be related to the infiltrative growth pattern and also reflect their Schwannian origin. MRI demonstrates intermediate signal in T1-weighter sequences and peripheral enhancement in T2-weighted images with iso-intensity to muscle.(2)

Given that this lesion is a challenge clinically and radiologically to distinguish from carcinomas, an accurate histopathologic analysis becomes mandatory. Granular cell tumours are non-encapsulated characterized by infiltrative nests, cords, or sheets of polygonal cells with abundant eosinophilic, finely granular cytoplasm and peripherally pushed nucleus, separated by fibrous tissue. Pustulo-ovoid bodies of Milian, which are large granules with clear halos are also seen. These lysosomal granules are PAS positive and diastase resistant. Fanberg-Smith categorises GCTs into benign, atypical, and malignant based on the presence of six criteria – necrosis, spindling, vesicular nuclei with large nucleoli, increased mitotic activity (>2/10 HPF at 200x magnification), high N:C ratio and pleomorphism. Three or more of these criteria is a must to call it a malignant GCT.(10) If the lesion is location deep to the skin or mucosal surface, features of pseudoepitheliomatous hyperplasia, which mimics squamous cell carcinoma, can be seen. Occasionally, benign lesions can also show vascular and perineural invasion. The differentials include alveolar soft parts sarcoma, rhabdomyoma, hibernoma, reactive histiocytic lesions.

Immunohistochemically, S-100, CD68, NSE, CD57, inhibin, calretinin, TFE3, SOX10, CD56 and vimentin are expressed. Ki-67 is a good predictor of atypical histology.

The treatment of choice is local excision with wide margins and is curative. However, because of its infiltrative pattern, recurrence is possible if excision is incomplete. This validates the need for close clinical and radiological follow-up of patients with granular cell tumour of the breast. The prognosis of benign GCT is excellent.(4)

Conclusion

A rare tumor such as granular cell tumor that has a diverse clinical presentation, poses many challenges. This entity should always be borne in mind as a differential owing to its ability to mimic malignancy. A holistic approach encompassing clinical, radiological, and histopathological assessments is paramount for accurate diagnosis and optimal management of this unique breast neoplasm. Follow up is mandatory to monitor recurrence.

References

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