Granular cell tumor of the male breast: a case report and review of the literature

Introduction

Background

Granular cell tumors (GCTs) are rare neoplasms of Schwann cell origin that may arise in any anatomic location, most commonly the skin and subcutaneous soft tissues (1). GCTs of the breast are rare; approximately 5–15% of all GCTs are in the breast and 0.1–0.7% of all breast tumors are GCTs (2). Male patients account for 6.6% of breast GCTs (2).

Rationale and knowledge gap

The histogenesis of GCTs is unknown and presents a diagnostic and therapeutic challenge due to its rarity and similarity on imaging to other breast neoplasms. Prior reported cases of male GCTs presented as symptomatic palpable breast masses. Here, we present a case of a man incidentally diagnosed with breast GCT while undergoing workup for a breast mass on the contralateral side. After breast GCT was diagnosed on core needle biopsy, he underwent excisional biopsy, which showed complete excision of the GCT from core needle biopsy and an associated granuloma. The complete excision from core needle biopsy as well as the association of breast GCT and granuloma has not been described in the literature previously. After one year of follow-up, he has no evidence of recurrence on physical examination, and will continue to follow-up annually.

Objective

This case describes a rare GCT in a male breast, and adds to previously existing knowledge regarding risk factors for development of male breast GCTs, presentation, and treatment options. Additionally, the association with granuloma has not been previously described, and clinical significance remains unknown. We present this article in accordance with the CARE reporting checklist (available at https://amj.amegroups.com/article/view/10.21037/amj-23-171/rc).

Case presentation

The patient is a 56-year-old African American male with past medical history of hypertension on an angiotensin converting enzyme (ACE) inhibitor, alcohol abuse on folic acid and thiamine, atrial fibrillation on Eliquis, heart failure with reduced ejection fraction, poorly controlled insulin-dependent diabetes, and pancreatitis who presented to his primary care physician on 15 July 2022 with a palpable mass of his left breast and breast pain. He did not have any palpable masses in his right breast. He had no personal or family history of breast cancer. He underwent a bilateral diagnostic mammogram on 1 August 2022 which showed a small focal mass at 9:00–9:30 in the right breast mid-depth and global asymmetry on the left consistent with benign gynecomastia (Figure 1). Bilateral breast ultrasound showed a 0.5×0.4×0.5 cm mass in the right breast at 9:00, 1 cm from the nipple with slightly indistinct margins and mild posterior acoustic shadowing that corresponded to the mass seen on mammogram (Figure 1). Due to the findings on the right, the final assessment was Breast Imaging Reporting and Data System (BIRADS)-4, suspicious abnormality, for which a biopsy was recommended. He was referred to the nurse navigator for surgical consultation and a biopsy. There were no financial or cultural diagnostic challenges.

Figure 1 Mammographic and ultrasound images of breast mass. (A) Left breast craniocaudal image showing scattered areas of fibroglandular density without discrete mass. (B) Left breast mediolateral oblique view. (C) Right breast craniocaudal image, arrow pointing to small focal mass. (D) Right breast mediolateral oblique image, arrow pointing to small focal mass. (E) Ultrasonographic images of hypoechoic round right breast mass (arrow) with posterior acoustic shadowing measuring 0.5×0.4×0.5 cm corresponding to mammogram at 9:00, 1 cm from the nipple with slightly indistinct margins.

The patient was then referred to surgical oncology and saw the surgical oncologist in the office on 11 August 2022. An ultrasound-guided fine needle aspiration and core biopsy of the lesion was performed. Core needle biopsy revealed a GCT (Figure 2). The lesional cells were positive for S-100 and CD68, and negative for CD34, desmin, pancytokeratin, estrogen receptor, and progesterone receptor. He then underwent a right breast ultrasound-guided wire localized excisional biopsy of his GCT on 16 September 2022. There were no changes to the planned surgery. The specimen contained a 0.6×0.5×0.4 cm white firm irregular markedly ill-defined possible mass located 0.4 cm from the medial margin, 0.5 cm from the lateral margin, 1.2 cm from the posterior margin, 1.9 cm from the anterior margin, and 1.3 cm from the inferior margin. Anterior to the mass was a 0.5×0.5×0.4 cm well-circumscribed ovoid cystic cavity grossly consistent with a biopsy cavity containing the coiled biopsy clip. Final pathology revealed a palisading granuloma with adjacent histiocytic deposits consistent with the previous biopsy. There was no evidence of malignancy, including at the resection margin. On immunohistochemical staining, CD68 was positive, while S-100 and estrogen receptor were negative. The patient recovered from his operation and was doing well on his postoperative examination on 30 September 2022. His 8-month follow-up visit on 2 May 2023 showed no evidence of recurrence on clinical exam. He will follow-up with surgical oncology in one year. There were no adverse or unanticipated events during his care.

Figure 2 Microscopic views of the granular cell tumor after core needle biopsy. (A) Hematoxylin-eosin stain showing sheets of polygonal cells with round to oval eccentric nuclei, ×40 magnification. (B) GCT cells staining positive for S-100, ×40 magnification. (C) GCT cells staining positive for CD-68, ×40 magnification. GCT, granular cell tumor.

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Discussion

First described by Abrikossoff in 1926, GCTs are rare tumors arising from Schwann cells arising in varied anatomic locations (3). They occur more commonly in premenopausal women and in African American patients (4). GCTs of the breast in men are rare; there have been approximately thirty case reports of GCTs in males in the literature (summarized in Table 1) (4-10). This was a case of an African American male who had an incidentally found asymptomatic benign GCT that was associated with a granuloma.

GCTs of the breast have a variable presentation; usually a painless, solid, firm, poorly circumscribed mass (4). They may cause skin retraction or adhesion to the pectoralis due to their infiltrating growth pattern, leading clinicians to be concerned for breast cancer (4). In prior cases, most GCTs in the male breast were palpable masses measuring 1 to 3 cm (Table 1). However, in this case, the GCT was incidentally found during workup for a palpable mass on the contralateral breast. This led to diagnosis of a smaller GCT than previously reported, measuring 0.5 cm and was subsequently found to be completely excised during core needle biopsy.

During workup for GCTs, imaging patterns on mammography or ultrasound may also be variable. Imaging findings may include heterogenous echo texture, indistinct or spiculated margins, increased blood flow, and posterior acoustic shadowing, which may mimic breast carcinoma (8). In our case, a mass with slightly indistinct margins and mild acoustic shadowing was seen, which was indeterminate for malignancy. Although GCTs may have features that mimic carcinoma on imaging, tissue diagnosis is required to differentiate between these two entities.

On pathologic examination, GCT cells show granular cytoplasm and strong cytoplasmic and nuclear staining for S-100 (4). They also stain positive for neuron specific enolase, CD68, and CKI-C3. They typically stain negative for estrogen receptor and progesterone receptor (4). In this case, the GCT stained positive for S-100 and CD68 on core needle biopsy. After the GCT was excised, there was no residual GCT in the specimen, as demonstrated by negative staining for S-100, indicating complete excision from the core needle biopsy. The mass seen on ultrasound and mammogram likely correlated with the granuloma, not the GCT, indicating that the GCT was radiographically occult. Additionally, this GCT was found to be associated with a granuloma upon final pathology review after excisional biopsy. Granulomas in male breasts are also rare entities and may occur as a result of cancer, sutures, sarcoidosis, tuberculosis, or cholesterol (11-13). The cause and clinical significance of the granuloma in this patient is unclear, though it may have been a response to the adjacent GCT. There have been several case reports of male idiopathic granulomatous mastitis in association with gynecomastia (14). Our patient was diagnosed with gynecomastia which may have been a risk factor for the development of his GCT and granuloma. He had multiple risk factors for development of gynecomastia, such as alcohol abuse and ACE inhibitor usage, which may place him at higher risk for development of benign and malignant breast conditions.

Treatment of benign GCT of the breast consists of surgical excision. Benign GCTs have a recurrence rate of 2–8% when resection margins are free of tumor and 20% if margins are positive for tumor (15). Annual follow-up is advised. In less than 1% of cases, breast GCTs are malignant. Malignant GCTs are aggressive, and recurrence rates are as high as 32% with a 39% 3-year mortality rate (15). Metastases are also common in malignant GCTs (50%), and most common sites are lung, liver, bone, and axillary lymph nodes (15). It is important to consider the malignant and aggressive potential when encountering GCTs in men, and to ensure patients are followed closely. At postoperative visit and 6-month follow-up the patient reported relief that his GCT was excised and understood the necessity to continue to undergo additional annual surveillance.

The identification of several potential risk factors in the development of rare breast pathologies in males is a strength of this study. One weakness of this study is the short period of follow-up for this patient, less than a year since diagnosis. The GCT was found to be completely excised during his core needle biopsy, and it is unclear what the margins from the GCT were. His GCT was likely radiographically occult, but completely excised. He will need longer term follow-up to determine if he will have a recurrence. It is also not clear what the clinical significance or etiology of his granuloma is, and more cases and studies will have to be performed to determine if there is any association between granulomas and GCTs. It is also likely that a subset of the population is also harboring radiographically occult GCTs that are not excised, and potentially not require excision, despite a small chance of malignancy.

Conclusions

This case contributes to the limited existing literature regarding male breast GCTs and male breast granulomas. It highlights a rare case of an asymptomatic GCT in association with a granuloma in a patient with gynecomastia due to multiple factors such as alcohol abuse and ACE inhibitor usage. Additionally, upon pathology review after his excisional biopsy, his GCT was found to be completely excised, likely during his core needle biopsy. The patient will require long term follow-up to determine if he has any recurrence. He additionally had a granuloma that was found on excisional biopsy for his GCT, the etiology and clinical implications of which is unknown.

Acknowledgments

Funding: None.

Footnote

Reporting Checklist: The authors have completed the CARE reporting checklist. Available at https://amj.amegroups.com/article/view/10.21037/amj-23-171/rc

Peer Review File: Available at https://amj.amegroups.com/article/view/10.21037/amj-23-171/prf

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://amj.amegroups.com/article/view/10.21037/amj-23-171/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Helsinki Declaration (as revised in 2013). Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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