Rapidly progressive malignant glomus tumor of the breast: a case report and review of the literature

Abstract

The glomus tumor is a rare neoplasm that is typically found subungually in the extremities and functions as a specialized neurovascular organ. An extremely rare site for glomus tumors is the breast, with only a few reported cases. Breast glomus tumors present with three typical clinical signs: dull pain, focal tenderness, and cold sensitivity. Less than 10% of all glomus tumors are malignant. We herein present a case of a malignant glomus tumor originating in the breast. Distant metastasis was ruled out, and the tumor was completely resected. However, the patient unexpectedly developed rapid systemic metastasis, detected 5 weeks after tumor removal. Despite the administration of analgesics and targeted therapy, the patient died 1 month later. When treating patients with undiagnosed breast tumors, clinicians should pay attention to unexplained and repeatedly reported symptoms and consider the possibility of a rare disease. Our literature search revealed no cases of malignant glomus tumors originating in the breast, making this case the first of its kind.

Introduction

Glomus tumors are uncommon benign mesenchymal neoplasms that result from hyperplasia of the glomus body and account for ≤2% of soft tissue tumors. ¹ These tumors often occur in the extremities, usually in the subungual regions of the digits or the deep dermis of the extremities. However, several case reports have described glomus tumors occurring in almost all organs. ² Malignant glomus tumors are even rarer than their benign counterparts. ³ An extensive literature search revealed that although several cases of glomus tumors originating from the breast have been reported, no case of a malignant glomus tumor arising from the breast followed by systemic metastases, as observed in the present case, has been reported. We herein present an extremely rare case of malignant glomus tumor of the breast and share our experience with its management.

Case report

A 57-year-old woman presented to the hospital with a 1-year history of a mass in the left breast accompanied by mild local tenderness. The mass had gradually increased in size over the past 6 months, along with an increase in pain. Mammography revealed a cystic-solid mass measuring 62 × 38 × 46 mm in the upper outer quadrant of the left breast (Figure 1). Ultrasonography showed the mass to be mixed echoic, hypervascular, and irregularly shaped with unclear borders.

Figure 1.

Mammography. (a) Mediolateral oblique view and (b) craniocaudal view show a high-density mass in the upper outer quadrant of the left breast (green arrows), measuring 62 × 38 × 46 mm. Preoperative computed tomography scans of the (c) head and (e) chest show no metastatic lesions. Postoperative (d) contrast-enhanced T1 magnetic resonance imaging of the head and (f) thoracoabdominal computed tomography show multiple metastatic lesions (green arrows).

An ultrasound-guided core needle biopsy suggested that the lesion was a mesenchymal tumor. To ensure an accurate pathological diagnosis for further treatment planning, the entire mass was completely resected. Considering the possibility of malignancy, all resection margins were ensured to be at least 1 cm from the tumor. Intraoperative frozen biopsy of the sample showed hemorrhage and necrosis within the mass, and all margins were tumor-free; however, the specific pathological nature of the tumor remained unclear.

The final pathological report, obtained 5 weeks later, described the tumor as having varied colors and densities, with areas of low density appearing gray-red and areas of high density appearing gray-white. In addition, the tumor had abundant vessels. All pathological findings regarding the shape, size, density, and vascular characteristics of the tumor were consistent with the radiologic findings. Immunohistochemical staining indicated that the tumor was negative for desmin, cytokeratin, and S100 but positive for smooth muscle actin and fluorescence in situ hybridization. No gene translocation in EWSR1, SS18, BCOR, or CIC was noted. Based on these results, the diagnosis was a malignant glomus tumor of the breast (Figure 2) and the optimal treatment was determined to be total mastectomy.

Figure 2.

Histological and immunohistochemical images of the tumor. (a) Neoplastic cells with small round cell morphology surrounding the tumor blood vessels (hematoxylin and eosin, ×100). (b) Tumor cells showing cellular atypia with prominent nuclear division (hematoxylin and eosin, ×200) and (c, d) tumor cells positive for smooth muscle actin (c, ×100; d, ×200).

It should be noted that the patient developed unexplained rapid-onset body pain during the interval between hospitalizations. Contrast-enhanced brain magnetic resonance imaging and thoracoabdominal computed tomography revealed systemic metastases to the brain, lungs, liver, pancreas, spleen, left adrenal gland, kidneys, left gluteus medius, and para-aortic lymph nodes (Figure 1). The extensive spread indicated complete loss of the surgical opportunity. Despite the administration of analgesics and targeted therapy, the patient died 1 month later. The reporting of this study conforms to the CARE guidelines. ⁴

Discussion

Glomus tumors are rare mesenchymal neoplasms that usually occur as subungual tumors in the extremities, functioning as specialized neurovascular organs. They have been reported in various organs, including the breast, ⁵ gastrointestinal tract,^6,7 lungs,^8,9 kidneys, ¹⁰ bones,^11,12 heart,^13,14 muscle, ¹⁵ and other sites. ¹⁶

Histopathologically, glomus bodies are mainly composed of glomus cells, vasculature, and smooth muscle cells. Based on the type of component that undergoes hyperplasia, glomus tumors can be categorized as solid tumors (75%), glomangiomas (20%), or glomangiomyomas (5%). ¹⁷ Typically, a glomus tumor is a small solitary mass with an irregular, blue-red surface. ¹⁸ Generally, glomus tumors are benign and measure <1 cm in diameter. Clinically, glomus tumors typically present with dull pain, focal tenderness, and cold sensitivity. ¹⁹ These signs are reliable diagnostic tools; 90% of patients with glomus tumors exhibit these symptoms. Two tests, Hildreth’s sign and Love’s test, have been proposed for the diagnosis of glomus tumors, but neither is useful for breast glomus tumors. ²⁰ Compared with glomus tumors, glomangiomas are usually asymptomatic and often multifocal, occurring in childhood and adolescence. Histologically, glomangiomas contain more dilated venous channels and are less likely to be encapsulated, more closely resembling venous malformations. ²¹ Glomangiomyomas resemble solid glomus tumors and glomangiomas but they are composed of cell types that transition from glomus cells to elongated mature smooth muscle cells. ²² Malignant glomus tumors reportedly account for <10% of all glomus tumors. ³ Based on a study of 57 patients with malignant glomus tumors, diagnostic features include deep location, a size of >2 cm, the presence of atypical mitotic figures, moderate-to-high nuclear grades, and mitotic activity of more than five mitoses per 50 high-power fields. ²³

Mammography and ultrasonography are the first-choice techniques for diagnosing a breast mass. On mammography, breast glomus tumors appear as round or oval superficial masses that are well-marginated and without microcalcifications. ¹⁹ On ultrasonography, they appear as solid hypoechoic masses with turbulent intratumoral flow.^1,19 Thus, breast glomus tumors lack specific diagnostic features in these modalities, necessitating histopathologic examination of the completely excised tumor for confirmation. Immunohistochemical staining of glomus tumors yields positive results for vimentin and smooth muscle actin and negative results for desmin, cytokeratin, and S100. ²³

Surgical resection is the only effective therapy for glomus tumors of the breast, with >90% of patients achieving a clinical cure. In a previous report, seven of eight patients with breast glomus tumors experienced complete resolution of symptoms after total excision of the lesion; the remaining patient, who had avoided surgery, remained symptom-free for 2 years of follow-up. ⁵ Recurrences due to inadequate excision have been reported in 1% to 2% of glomus tumors in other organs but not for breast glomus tumors.^5,23

Malignant glomus tumors are usually aggressive, with metastasis to other organs from the primary lesion. ² Once metastasis to multiple organs occurs, there is no effective treatment. Malignant glomus tumors originating from breast tissue have not been reported previously.

This case highlights the importance of recognizing rare forms of common diseases with atypical symptoms, which may be easily overlooked in routine practice. Clinicians encountering patients with repeatedly reported symptoms should consider rarer diseases if conventional investigation results are negative. Attributing symptoms to psychological factors could lead to incorrect diagnoses.

Conclusion

Breast glomus tumors are rare and generally benign lesions that can be cured by complete surgical resection with excellent outcomes. Our patient had a malignant breast glomus tumor, an even rarer entity. Currently, there are no effective treatment options for this type of tumor, and despite our efforts, the patient developed rapid systemic metastasis and eventually died. More reports of similar cases are needed to gain further insight into the clinical features and treatment of malignant breast glomus tumors.