Unusual Changing Calcification Patterns on the Mammogram in a Pure Mucocele-Like Lesion of the Breast: A Case Report

Background

The mucocele-like lesion is a rare breast lesion that is pathologically defined as a mucin-filled cyst with extravasation of mucin into the surrounding stroma [1,2]. Cysts frequently contain microscopic calcifications [1]. Reflecting such pathologic characteristics, the radiologic features of mucocele-like lesion of the breast are mainly coarse heterogeneous microcalcifications on mammography and various cystic lesions on sonography [3,4]. Despite its rarity, increased detection, likely due to a large volume of breast cancer screenings, sometimes poses diagnostic challenges for radiologists. This report described a case of pure mucocele-like lesion that demonstrated a dramatic pattern of changing calcification from indeterminate (coarse heterogeneous) to benign (large bizarre dystrophic) morphology and fluctuating calcification number during a 2-year follow-up period. Specific mammographic presentation of dystrophic calcification has been reported in a previous case of mucocele-like lesion [5]. Furthermore, changes in the calcification morphology and fluctuations in number over a 2-year follow-up period have not been previously reported in mucocele-like lesion cases. Herein, the clinical, mammographic, gray-scale, and color-Doppler sonographic features of this case are presented.

Case Report

A 39-year-old female was referred to our breast clinic due to screening-detected abnormalities in her right breast on mammography. This was her first screening mammography. She did not complain of any breast symptoms and had no relevant medical history, except a surgical history of an atrial septal defect at 9 years of age. Physical examination did not reveal any discernable abnormalities. She had no family history of breast cancer.

The magnification mammogram of her right breast demonstrated multiple aggregated irregular or oval masses, and focal asymmetries with regional coarse heterogeneous calcifications in the inner central area (Figures 1A, 1B, 2A, 2E). Successive ultrasonography showed multiple aggregated cystic lesions corresponding to mammographic abnormalities (Figure 1C–1E). The individual cysts had multiple septa, and complex cystic and solid echoes. Based on an indeterminate morphology of microcalcifications and the complex cystic and solid echo patterns of the cysts, the radiological assessment was Breast Imaging Reporting and Data System (Bi-RADS) 4; therefore, a biopsy was recommended. However, the patient refused the tissue diagnosis and preferred an imaging follow-up. Follow-up magnification mammography and sonography were performed at intervals of 6, 12, and 24 months from the initial image acquisition. There were no significant changes in the imaging features on mammography (Figure 2B, 2C, 2F, 2G) or on sonography, up to 12 months follow-up (not presented). However, at 24 months follow-up, the magnification mammography showed a dramatic change in calcification morphology from a previous coarse heterogeneous pattern into a large bizarre dystrophic calcification, and an increase in calcification number and size (Figure 2D, 2H). Under the sonography guidance, an 8G-vacuum assisted needle biopsy was performed on the mass. Microscopically, the biopsied specimen showed multiple dystrophic calcifications within extravasated mucin and cysts (Figure 3A–3C), which were consistent with a diagnosis of an mucocele-like lesion. The mass was further excised surgically to remove it completely. Final diagnosis did not change, with no upgrade to atypia or malignancy.

Discussion

This was an unusual case of a pure mucocele-like lesion of the breast. On mammography examinations, calcification number fluctuated and eventually increased, and the morphology changed from the initial coarse heterogeneous pattern into the later typically benign dystrophic pattern over a 2-year period. Although the calcification morphologically changed to the benign pattern reported, tissue diagnosis could not be obviated because of the accompanying masses observed on the mammogram and the complex cystic lesions observed on the sonogram.

In 1986, Rosen first introduced the diagnosis of mucocele-like lesion of the breast, which exhibited pathologically mucin filled cysts with extravasated mucin in the adjacent stroma [6]. Rosen initially recognized this lesion as entirely benign [6]; however, successive studies further documented that the biology of mucocele-like lesion is determined by the epithelium lining, which includes benign proliferative and non-proliferative changes, atypical ductal hyperplasia, and in situ or invasive carcinoma [1,7–9]. Microscopically, the cysts are lined by flat to cuboidal epithelium in benign mucocele-like lesion; whereas, the epithelium may exhibit proliferative changes ranging from usual ductal hyperplasia to atypical ductal hyperplasia, and neo-plastic proliferations in situ or invasive carcinoma [1]. The later introduced the term, mucocele-like tumor, which is synonymous with the initial term, mucocele-like lesion [4]. The exact pathogenesis of mucocele-like lesion had not yet been revealed; however, Rosen hypothesized that excess production of mucin or a ductal obstruction may contribute to the distension of a duct or cyst, and incidental trauma from daily activity may cause a rupture and extravasation of mucin [6].

The incidence of mucocele-like lesion has been reported to be between 0.24% to 0.6% of the breast screening population who undergo core biopsy [2,10,11], which is relatively rare when compared with other high-risk lesions in the breast [2].

Therefore, despite current international efforts to determine a consensus for the management of an uncertain malignant potential in the breast [12], there is no consensus for the diagnosis of mucocele-like lesion by core needle biopsy [2]. The small case numbers and varying definition of upgrade (including atypical ductal hyperplasia) of each case series means that reported upgrade rates upon surgical excision have varied as widely as 0–43% [1]. Based on a literature review in 2016, Gibreel et al. summarized the overall rate of malignant upgrade to in situ or invasive carcinoma as 17.3% (8% and 9.3% for invasive and in situ disease, respectively) for 75 mucocele-like lesions with atypia, and 2.9% (1.5% and 1.5% to invasive and in situ disease, respectively) for 204 mucocele-like lesions without atypia [13]. In 2017, a large series of 113 women with mucocele-like lesion identified on core biopsy reported a 5% upgrade rate to malignancy, with no upgrade to invasive carcinoma, which was comparable to papillary lesion upgrade rates [2]. Surgical excision is recommended for atypical mucocele-like lesions diagnosed on needle biopsy [1,2]. However, some investigators have advocated close clinical or imaging surveillance, or vacuum-assisted biopsy for pure mucocele-like lesions as a reasonable alternative to surgical excision [14–16].

When cysts rupture, mucus content collects as pools within the stroma [1]. Microscopically, the presence of large, coarse microcalcification within the cysts and in the extravasated mucous secretion is characteristic [8]. Extravasated mucin develops into dystrophic calcification, which enables mammographic detection of mucocele-like lesions [5,17]. Conversely, the presence of calcification on mammogram infers the presence of a mucin pool [4]. Radiologically, the most common reported features of mucocele-like lesions were microcalcifications on mammography [2,3,18]. In the literature, the calcification morphology of mucocele-like lesion on mammogram is predominantly described as coarse [4,5,18–21] or pleomorphic [18,22], which largely fits the range of coarse heterogeneous calcifications of indeterminate concern in the BI-RADS classification [4,5]. The morphologic features of calcifications in are infrequently reported as round [16,18], punctate [16,18,22], amorphous [16], lucent-centered [22], crescentic (tea-cup) [17], and fine pleomorphic [16,18]. The distribution of calcification in mucocele-like lesions on mammogram is predominantly described as grouped [2,5,16,18,22] and less commonly as regional [5], diffuse [2,16,22], linear [11,18], or segmental [3,22]. Previously, shape, number, and distribution of calcifications have been hard to differentiate between benign and malignant [18,20–24]; however, a recent large case series of 72 patients with mucocele-like lesions found that calcifications of indeterminate concern or a higher probability of malignancy, and calcifications of clustered or segmental distribution, were more frequently presented with atypical ductal hyperplasia or malignancy than pure mucocele-like lesions [3]. In addition, in 25 patients with mucocele-like lesions, calcifications extended to a greater area on mammogram in malignant mucocele-like lesions than benign mucocele-like lesions [22]. Further, in 21 patients with pure mucocele-like lesions, the majority (70%) showed a clustered distribution [16]. Microscopically, calcifications are more frequently found in malignant mucocele-like lesions (71%) than benign mucocele-like lesions (46%) [8], which might imply that mammography is more likely to reveal malignant mucocele-like lesions [23]. In the current case, although initially the calcification manifested as an indeterminate shape (coarse heterogeneous) and involved a large area (approximately 8 cm in size), the calcifications eventually changed to an overtly benign morphology, despite the increasing number of calcification. Finally, a diagnosis of a benign mucocele-like-lesion without upgrade to atypia or malignancy was made.

The pattern of benign dystrophic calcification as a mammographic feature of mucocele-like lesions has been reported in only 1 case, in which a single large dystrophic calcification was contained centrally within circumscribed, oval, isodense mass on mammogram, corresponding to a complex cystic and solid mass on sonogram [5]. In another study, a different benign morphologic pattern of calcification was described as large coarse eggshell-shaped calcifications accompanying pleomorphic calcifications [22]. Furthermore, this case described a characteristic distribution of multiple calcific clusters connected like a rosary [22]. The differences in size of calcifications on sonogram has been reported previously; macrocalcifications were present in 29.2% of pure mucocele-like lesions, 16.7% of mucocele-like lesions with atypical ductal hyperplasia, and 4.2% of mucocele-like lesions with malignancy [3].

Changing patterns of microcalcifications relating to the number or extent in mucocele-like lesions on mammogram have described [22,25]. Glazebrook et al. reported the development of new calcifications accompanied by increasing size of the nodule over 24-months follow-up in benign mucocele-like lesion [23]. Kim et al. reported interval increases in the numbers of calcifications in 5 cases of benign mucocele-like lesions [22]. In addition, Farshid et al. reported that in 53.8% of cases, microcalcifications were new or had grown since the previous mammogram [25]. In line with this, Carkaci et al. reported that in 63% of cases, calcifications had developed since the patient’s most recent mammogram [18]. However, these previous studies did not address the focal disappearance of calcification in mucocele-like lesions on mammogram. Furthermore, changing morphologic calcification patterns have not been reported in mucocele-like lesions; and generally, in breast imaging, changing microcalcification patterns on mammography have been insufficiently discussed. However, one recent study has shown that the appearance or increased extent of micro-calcification on screening mammography can more accurately predict breast cancer than shape or changes in the number microcalcifications without extension [26]. In our current case of benign mucocele-like lesion, calcifications increased in terms of number rather than their extent.

Mammographic findings in cases of mucocele-like lesions also can include a mass with microcalcification [11,25], a mass without calcification [5,11,16,25], asymmetry [16], and architectural distortion [25]. On sonography, mucocele-like lesions exhibit as various cystic lesions, which reflects the pathologic characteristics of mucin filled cysts in mucocele-like lesions [3,5,11,16,18,22,23,25]. Cysts show various internal echo patterns, ranging from anechoic, clustered microcystic, complicated, and complex cystic and solid. Mucocele-like lesions with atypia or malignancy tend to present with clustered cysts, cysts with thick septations, or complex masses [3]. Less common sonographic features include solid mass [3,5,11,18,22,25], tubular structure with low-level internal echoes [25], calcification only [22], and slight architectural distortion [25].

Conclusions

In this case report, we described a rare case of mucocele-like lesion exhibiting dramatic changing patterns of calcification morphology, from coarse heterogeneous to large bizarre dystrophic calcifications, and fluctuations in the number of calcification over a 2-year period. In this case, the presence of morphologic changes in calcification into a typical benign dystrophic pattern did not preclude the possibility of an indeterminate breast lesion. Awareness of this unusual pattern might aid in the provision of a differential diagnosis when faced with cystic breast lesion accompanying calcifications.