Increasing Size of Cholesterol Granuloma of the Breast in the Vicinity of a Previous Breast Biopsy: Imaging Features and Review of the Literature

Background

Cholesterol granuloma is a benign condition that can occur in the breast following trauma, breast biopsy, or surgical procedures. Cholesterol granuloma can mimic breast cancer on imaging studies. Currently, there have been 21 cases of cholesterol granuloma of the breast reported in the English literature [1–16]. The breast ultrasound or mammographic features of cholesterol granuloma have described in 15 of these reports [1–3,5–14], while 11 of the reports also showed imaging findings [1–3,6–14]. The mammographic features of cholesterol granuloma have described in 16 of these previous publications [1–3,6,8–15], and ten published reports also provided mammographic images [1–3,6,8–14].

This report is of a case of an enlarging breast mass due to a repeat needle biopsy in the vicinity of a previous biopsy that resulted in a cholesterol granuloma that appeared to increase in size on ultrasound imaging. The mammographic and high-resolution sonographic imaging features of cholesterol granuloma of the breast are described, with a review of the literature of published cases of cholesterol granuloma of the breast diagnosed on imaging.

Case Report

A 52-year-old woman with a history of multiple breast nodules had undergone multiple rounds of mammography, performed with a Philips iU22 5-MHz to 12-MHz linear transducer (Philips Medical Systems, Bothell, WA, USA). The patient had no family history of breast cancer or chest wall trauma.

At the initial breast ultrasound scan, a circumscribed, round, hypoechoic mass, measuring 0.6 cm in diameter was identified in the right breast. The breast mass was without a posterior acoustic feature and was located at the 12 o’clock position of the right breast (Figure 1). The mass had no internal vascularity on color Doppler ultrasound (Figure 1). Ultrasound imaging was not able to distinguish between a solid mass lesion or a complicated cyst with homogeneous internal echo-genicity. The mass was classified as Breast Imaging-Reporting and Data System (BI-RADS) category III, or BI-RADS III (probably benign, short-interval follow-up recommended). Multiple cystic or hypoechoic nodular lesions with similar features were present in both breasts.

At six-month follow-up mammography, the mass at the 12 o’clock position of the right breast had not changed in size. However, a new focal non-mass lesion was detected at the 11 o’clock position in the right breast (Figure 2) and was classified as BI-RADS IVa (low level of suspicion for malignancy). Therefore a 14-gauge core needle biopsy was performed for the non-mass lesion. Histopathology confirmed a diagnosis of benign fibrocystic change.

At 18-month follow-up mammography, after the breast biopsy, the round mass at the 12 o’clock position of the right breast had slightly increased in size, from 0.6 cm to 0.7 cm, and had changed into an oval shape on longitudinal breast imaging (Figure 3). Mammography at that time revealed no corresponding abnormality in the mass at the 12 o’clock position in the right breast. The mass was again assessed as BI-RADS category 3 and follow-up breast ultrasound was recommended.

At the 25-month follow-up breast ultrasound after the biopsy, the mass at the 12 o’clock position of the right breast had further increased in size, from 0.7 cm to 0.9 cm, and had changed into a more elongated shape, in the longitudinal scan (Figure 3), and had no internal vascularity on color Doppler ultrasound (Figure 3). Mammography at that time also revealed no corresponding abnormality in the mass at the 12 o’clock position of the right breast. Although the mass was still assessed as BI-RADS III (probably benign, short-interval follow-up recommended), because the mass appeared to be increasing in size. Therefore, a further 14-gauge core needle biopsy of the breast was performed. Histopathology confirmed the diagnosis of a benign cholesterol granuloma (Figure 4).

Throughout the follow-up period, the patient did not present with a palpable breast mass or symptoms of breast disease.

Discussion

Cholesterol granuloma is a benign non-neoplastic condition that has features of chronic inflammation [5]. The histological hallmark of cholesterol granuloma is fibrous granulation tissue, with abundant cholesterol crystals deposited centrally, surrounded by foreign-body giant cells [14]. Cholesterol granuloma is commonly described in the mastoid region and in the middle ear cavity, and is related to cholesteatoma, and has also been reported in other sites, including the parotid gland, lymph node, thyroglossal duct, kidneys, testis, liver, spleen, gall bladder, and peritoneum [2,3,9,14]. However, cholesterol granuloma is less common in the breast [7].

Cholesterol granuloma is a rare manifestation of mammary duct ectasia and duct rupture [7,14,15]. Some reports have suggested that mammary duct ectasia and subsequent periductal inflammation may result in rupture of a dilated duct [7]. The release of the lipid-rich content of the duct results in the formation of cholesterol crystals, leading to a foreign-body inflammatory reaction [7]. Other reports have suggested that periductal inflammation is the initial step, which causes damage to the elastic lamina of the duct wall, which is then followed by dilatation of the duct [7].

A history of previous breast biopsy or trauma can cause rupture of an ectatic breast duct [14,15]. Fat necrosis can also be associated with the formation of cholesterol granuloma [12,16]. Although a history of previous biopsy or trauma has been described as a possible underlying mechanism, only one case of cholesterol granuloma with this association has been identified by this author [12]. In this previously reported case, an excisional biopsy had been performed 40 years before the diagnosis of cholesterol granuloma, which developed adjacent to a surgical scar [12]. Duct ectasia was not found to be associated with cholesterol granuloma in this previously reported case [12].

To this author’s knowledge, there have been no previous reports that have described the association between the development of cholesterol granuloma of the breast and a history of needle biopsy leading to the increase in the size of a preexisting cholesterol granuloma also due to a previous needle biopsy of the breast. In the present case, the close spatial apposition and chronological context supported the relationship between the performance of the biopsy and the development of the cholesterol granuloma and enlargement of a pre-existing cholesterol granuloma.

In this case, the ultrasound features of the initial mass, prior to biopsy, raised the possibility of both a solid mass and a complicated cyst. Complicated cysts of the breast are sometimes difficult to differentiate from a solid mass [17]. Cysts are fluid-filled round or oval structures with an epithelial lining and usually arise from an obstructed duct [17]. Therefore, it is possible to deduce that the previous needle biopsy might have damaged a pre-existing complicated cyst.

The previously reported mammographic and ultrasound features of cholesterol granuloma have mainly emphasized the similarity with malignant breast lesions (Table 1). Reported suspicious mammographic features of cholesterol granuloma of the breast include a non-circumscribed margin [3,14], irregular shape [12], increased density [3,7,10,11], and calcifications [1,7,9,12,15]. Unusual annular calcifications we reported in one case [9]. Reported suspicious sonographic features included a non-circumscribed margin that was angular, ill-defined, and microlobulated [2,3,5,8,9,11], an irregular or lobulated shape [1,2,9–12,14], and complex cystic and solid echogenicity [7,13]. Complex cystic and solid echogenicity on ultrasound had been reported in two cases, in which corresponding features on the mammography were a circumscribed, oval, or round mass [7,13]. In two cases, breast carcinoma was present in close association with cholesterol granuloma, with the mass consisting of two components, the cholesterol granuloma and the breast cancer, which had contrasting imaging features on both ultrasound and magnetic resonance imaging (MRI) [1,10]. On ultrasound, part of the cholesterol granuloma was oval-shaped [1], or had hyperechoic internal echogenicity with increased posterior echogenicity [10], whereas the breast cancer component showed an irregular shape, internal micro-calcifications [1], or hypoechoic internal echogenicity with decreased posterior echogenicity [10]. On MRI, the cholesterol granuloma had an oval shape with mild progressive enhancement, whereas the breast cancer component showed an irregular shape with rapid enhancement [1]. In the case of breast cancer associated with cholesterol granuloma, shear wave elastography showed marked stiffness of the overall mass [1].

Rarely, cholesterol granulomas have been detected incidentally using a fluorodeoxyglucose (FDG) positron-emission tomography/computed tomography (PET/CT) scan, which demonstrated a nodule with mild FDG-avidity [4]. Rarely, cholesterol granuloma has been detected incidentally on abdominal CT, with an oval, ill-defined, heterogeneously enhancing mass with progressive delayed enhancement [3]. On physical examination, cholesterol granuloma is frequently palpable and is usually firm, mobile, and nontender [5,7,9–15]. The frequency of a palpable mass on presentation was found in 12 of the 21 reported cases [5,7,9–15].

A longstanding palpable mass that does not increase in size can distinguish between cholesterol granuloma and breast cancer [7]. However, unlike previously published reports, this case of cholesterol granuloma retained benign radiological features on successive ultrasound examinations, but it increased in size. It is likely that the majority of cholesterol granulomas may be undetected due to their benign radiological features, and only some cases of cholesterol granuloma that have unusual and suspicious radiological features have been highlighted.

Conclusions

This case has shown that cholesterol granuloma can develop following core biopsy of the breast and that biopsy can enlarge a pre-existing cholesterol granuloma. Despite the increasing size of cholesterol granuloma, ultrasound imaging may confirm the benign features. Cholesterol granuloma can be considered as a rare differential diagnosis when a mass develops or increases in size after a breast biopsy and is in the vicinity of the biopsy site, especially in cases of suspected injury to pre-existing duct ectasia or cysts of the breast.