Original Report. Mucocele-Like Tumors of the Breast: Mammographic and Sonographic Appearances. Katrina Glazebrook 1 Carol Reynolds 2

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1 Katrina Glazebrook 1 Carol Reynolds 2 Received January 2, 2002; accepted after revision August 28, Department of Radiology, Mayo Clinic, 200 First St. S.W., Rochester, MN Address correspondence to K. Glazebrook. 2 Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, MN AJR 2003;180: X/03/ American Roentgen Ray Society Original Report Mucocele-Like Tumors of the Breast: Mammographic and Sonographic Appearances OBJECTIVE. The purpose of our study was to describe the mammographic and sonographic appearances of the mucocele-like tumor of the breast. CONCLUSION. The mucocele-like tumor is a rare lesion of the breast, the benign form of which has a nonspecific mammographic appearance. The tumor can present as indeterminate microcalcifications or as a nodule, often containing calcifications. The sonographic findings are of multiple well-defined hypoechoic oval or tubular structures with low-level internal echoes resembling complex cysts. Mucocele-like tumors of the breast can be associated with atypical hyperplasia or carcinoma. If a mucocele-like tumor is diagnosed at core needle biopsy, complete surgical excision is recommended, with careful evaluation of the entire specimen to exclude the presence of atypia or carcinoma. T he mucocele-like tumor of the breast is a rare lesion analogous to a mucocele of the minor salivary glands [1]. The terminology used in the literature is confusing. The terms mucocelelike tumors and mucocele-like lesions are synonymous, and these entities are classified as benign or malignant, depending on their association with carcinoma [2]. The use of the term mucocele of the breast is confined to the benign form of the tumor. The mucocele-like tumor of the breast was first described by Rosen [1] in 1986 as a benign lesion consisting of multiple cysts of mucinous material that have ruptured and discharged their contents into the surrounding stroma. Subsequent studies reported in the pathology literature that the mucocele-like tumor of the breast may be associated with atypical ductal hyperplasia or carcinoma [2 6]. Cribriform and micropapillary ductal carcinoma in situ and invasive carcinoma, usually of the mucinous type, have been reported. Several studies have reported the pathologic and clinical findings in the mucocele-like tumor of the breast [1 5, 7], but findings on imaging have not been well documented [8, 9]. The purpose of our study was to describe the mammographic and sonographic appearances of the mucocele-like tumor of the breast. Materials and Methods Records of all breast lesions coded as mucocele or mucocele-like tumor from 1992 through 2001 were retrieved from the surgical pathology database files at our institution. Five patients with mucocelelike tumors of the breast were identified from the approximately 10,000 breast biopsies performed during that period. The ages of the five patients ranged from 29 to 73 years (mean age, 48 years). Four lesions were clinically occult and were identified on screening mammography, and one lesion presented as a palpable mass. In two of the women with a screening-detected lesion, a prior malignancy had been diagnosed in the contralateral breast. All five patients had undergone mammography, and three had also undergone sonography; these studies were all available for review. Three patients had imaging-guided large-core needle biopsies, and in all five patients, the lesion was surgically excised. We retrospectively analyzed the mammographic and sonographic findings. AJR:180, April

2 Glazebrook and Reynolds Results Mammograms obtained in the five patients with a mucocele-like tumor of the breast were reviewed (Table 1). Circumscribed masses were shown in three patients, ranging in size from 6 mm to 1.5 cm (mean, 13 mm). One patient had a well-defined mass identified on her initial screening mammogram. In two patients who had undergone prior mastectomies for invasive ductal carcinoma, a nodule was identified on the screening mammogram of the contralateral breast. In both patients, the size of the nodule had increased over 1 2 years. One patient had developed indeterminate calcifications in the mass (Fig. 1A). Two patients presented with calcifications as the only mammographic finding. One patient was found to have a cluster of pleomorphic calcifications in the background of dense breast tissue (Fig. 2). Because of the density of the breast tissue, any associated mass could have been obscured. The second patient, a 29-year-old woman who presented with a palpable mass in the upper outer quadrant of the left breast, was found to have pleomorphic calcifications in the upper outer quadrants of both breasts (Fig. 3). The microcalcifications extended over an area ranging from 3 3 to 5 5 cm. Sonography was performed on three patients, two with mammographically detected TABLE 1 Patient Age (yr) Note. Not all patients underwent sonography or core biopsy. NA = not applicable. circumscribed nodules and one with the palpable abnormality, which corresponded to the 5- cm area of microcalcification. On sonography, the three lesions showed hypoechoic round or tubular masses with minimal diffuse internal echoes, suggestive of complex cysts (Figs. 1B and 3C). In one patient, the mass appeared to have a thick septation in it (Fig. 4). The three patients with circumscribed nodules underwent sonographically guided large-core needle biopsy. Histologic examination revealed that the three lesions were mucocele-like tumors of the breast with associated atypia. The pathologist believed that the possibility of mucinous carcinoma could not be excluded, and surgical excision was recommended for all three patients. At open biopsy, none of these patients had atypical ductal hyperplasia or carcinoma. Only annual mammographic and close clinical follow-up was recommended. The remaining two patients, who each had mammographically detected calcifications, underwent surgical excision for diagnosis. The 29-year-old woman with the palpable lesion corresponding to the suspicious calcifications underwent a surgical biopsy of this area. Microscopically, the entire specimen was involved by a mucocele-like tumor with focal areas of atypical ductal hyperplasia. Reexcision of the left breast plus biopsy of the right breast was offered to the patient; however, she refused any further surgical treatment, medical care, or imaging follow-up. Because the calcifications in both upper outer quadrants had similar morphology, it seems likely that the right breast calcifications were due to the same pathologic process. However, this supposition was not proven histopathologically. The fifth patient also had surgical excision of the screening-detected calcifications, which at histology were also found to be a mucocele-like tumor with atypical hyperplasia. Follow-up was recommended to the patient, but she elected to have a mastectomy. No atypia or malignancy was found in the mastectomy specimen. The three women who underwent local excisions are all well and remain disease-free months after resection. The patient who underwent mastectomy is well, with no evidence of disease in the contralateral breast after 10 years of follow-up. The young woman with presumed bilateral mucocele-like tumors of the breast (tumor in one breast had associated atypia) has been lost to follow-up. Discussion The mucocele-like tumor of the breast was first described by Rosen [1] in 1986 as a benign lesion consisting of cysts of mucinous material that have ruptured, discharging secretions and epithelium into the surrounding tis- Mammographic, Sonographic, and Histopathologic Findings in Five Women with Mucocele-Like Tumors of the Breast Mammographic Findings Sonographic Findings 48 Well-defined 1.5-cm nodule Well-defined hypoechoic mass with central septation 73 Irregularly marginated 6-mm NA nodule showing increased size over 12 months 52 Well-defined 1.5-cm nodule showing increased size as well as development of new calcifications over 24 months 41 Cluster of indeterminate calcifications in dense breast tissue 29 Both breasts: pleomorphic calcifications in upper outer quadrants; dense breast tissue Cluster of complex cysts; calcification identified within mass Core Biopsy Results atypia atypia ductal hyperplasia atypia; mucinous carcinoma could not be excluded Histopathologic Findings Excisional Surgical Results mild hyperplasia without atypia florid hyperplasia without atypia Mucocele-like tumor without atypia NA NA atypical hyperplasia Left breast: palpable lesion as well as tubular hypoechoic structures with low-level internal echoes Right breast: not imaged NA Excision of only palpable lesion, which was mucocele-like tumor involving all tissue with atypical ductal hyperplasia Follow-Up Findings No recurrence for 12 months No recurrence for 18 months No recurrence for 12 months Mastectomy; no malignancy; no recurrence for 10 yr Patient refused any further medical, surgical, or imaging followup 950 AJR:180, April 2003

3 Mammography and Sonography of Breast Tumors Fig year-old woman with mucocele-like tumor of breast. A, Screening mammogram shows well-defined nodule that increased in size since previous mammogram 2 years earlier. New pleomorphic calcifications (arrow) have also developed during interval. B, Sonogram of nodule shows multiple cysts without increased acoustic through-transmission. Calcifications (not shown) were evident within mass. sues. Mucocele-like tumors probably result from excess production of mucinous secretions or ductal obstruction, which may lead to ductal distention and enlargement and to subsequent rupture and extravasation of mucin into the surrounding stroma. This occurrence is depicted in the histopathologic sections from the surgical excision specimen of the 29-year-old woman (Fig. 3D and 3E). Calcifications are often found within the mucin-containing cysts, surrounding stroma, or ductal epithelium lining the cysts, as shown in this patient (Fig. 3F). Subsequent reports [2 5] found mucocelelike tumors associated with typical or atypical ductal hyperplasia or with carcinoma. For example, Hamele-Bena et al. [2] studied 53 mucocele-like tumors from 49 patients; 25 were benign and 28 were malignant. Fourteen of the malignant mucocele-like tumors were associated with cribriform or micropapillary ductal carcinoma in situ, and 14 were associated with an invasive carcinoma, predominantly mucinous carcinoma. These studies support the concept of a spectrum of mucocele-like lesions of the breast ranging from an entirely benign cystic lesion to low-grade mucinous carcinoma. Hamele-Bena et al. recommended that a diagnosis of benign mucocele-like tumor be rendered only after careful histopathologic examination and exclusion of atypical ductal hyperplasia, intraductal carcinoma, and invasive mucinous carcinoma. Carcinoma associated with a mucocele-like tumor has never been documented at our institution, perhaps because the malignant features of the lesion took precedence over the associated mucocele-like component in the final diagnostic coding for the database. However, mucocele-like tumors of the breast are extremely rare, and it is possible that such a tumor associated with malignancy has not been encountered at our institution. To our knowledge, the imaging findings of benign mucocele-like tumors have not been well documented. Kirk et al. [9] reported two patients with benign mucocele-like tumors presenting as suspicious clustered microcalcifications. In each patient, a stereotactic fine-needle aspiration yielded calcific debris in mucinous material and a few benign epithelial cells; and in each patient, an excisional biopsy showed a mucocele-like tumor and fibrocystic changes. In a series of 27 cases of mucocele-like tumors reported by Chinyama and Davies [5], 12 such tumors were detected mammographically as suspicious microcalcifications. In the study by Hamele-Bena et al. [2] cited earlier, 19 of 53 lesions studied were mammographically detected. In that series, mammography revealed 50% of the benign lesions and 82% of Fig year-old woman with mucocele-like tumor of breast. Specimen radiograph obtained during wire localization of calcifications (which were originally found on screening mammography) shows calcifications have pleomorphic appearance. Histopathologic examination showed atypical ductal hyperplasia associated with mucocele-like tumor. A the malignant lesions. One striking microscopic finding was the presence of large, coarse microcalcifications in the cysts and in the extravasated mucinous secretions. These calcifications were found in 46% of the benign and 71% of the malignant tumors. The authors commented that mammography was more likely to reveal mucocele-like tumors associated with carcinoma because these lesions had more prominent calcifications. Seven of the 11 benign mucocele-like tumors with these calcifications were associated with atypical ductal hyperplasia. In our study, calcifications were present in three of five tumors, one of which was associated with a well-defined mass (Figs. 1 3). Two patients had associated atypical ductal hyperplasia. This finding suggests that the histopathologic specimen should be carefully B AJR:180, April

4 Glazebrook and Reynolds evaluated for atypia or malignancy if calcifications are present and if a mucocele-like tumor is histologically identified, especially at core needle biopsy. The sonographic features of the mucocelelike tumor have not been previously described, to our knowledge. Rosen [1], in his original report on this lesion, described six cases, five presenting as a mass and one presenting as an incidental finding. He noted that macroscopically the lesion seen in the six patients was either multicystic or multiloculated. This observation correlates with the sonographic findings in our series. We found tubular or oval hypoechoic structures with low-level internal echoes resembling complex cysts and no flow on color Doppler sonography within these cystic masses. Our sonographic findings overlap with the findings of A pure mucinous carcinomas ( 90% mucin). In a study by Chopra et al. [10] of pure mucinous carcinomas, 86% showed a heterogeneous but hypoechoic echogenicity, and 71% showed distal acoustic enhancement, whereas none showed distal acoustic shadowing. On mammography, most lesions in that study appeared as poorly defined (86%), lobulated (71%) masses. Fourteen percent contained calcifications. These features again overlap with our mammographic findings of mucocele-like tumors. With the decreasing percentage of mucin in the tumor, the mammographic appearance of the tumor changes and becomes more suspicious, with spiculated, infiltrating margins [11]. This change in appearance is reflected in more malignant-looking findings on sonography, with microlobulated or spiculated margins and posterior shadowing. B D Histologically, multiple cysts are characteristic of mucocele-like tumors of the breast. The epithelium that lines the cysts ranges from flat to cuboidal to columnar, with a tendency to exhibit focal papillary hyperplasia. At fine-needle aspiration biopsy, the cytologic features of mucocele-like tumors of the breast can be difficult and challenging to identify because typically they are indistinguishable from mucinous carcinoma [7]. Core needle biopsies of mammary mucocele-like tumors can also be diagnostically challenging. Mucinous extravasation can be seen in benign lesions as well as in intraductal carcinoma and mucinous carcinoma. The mucinous content in the cysts of benign mucocelelike tumors is similar to that found in mucinous carcinomas of the breast [3]. Deschryver et al. [8] had three patients with mammary mucocele-like lesions in their series C E F Fig year-old woman presenting with palpable mass in upper outer quadrant of left breast. A, Mediolateral oblique view of right breast shows pleomorphic calcifications (arrows) in upper quadrant extending over large area. B, Mediolateral oblique view of left breast shows pleomorphic calcifications (arrows) in upper quadrant in region of palpable abnormality. C, Sonogram of palpable area shows tubular cystic-appearing structures containing calcifications (arrows). D F, Photomicrographs of histopathologic specimen reveal multiple cysts containing mucinous material and lined by cuboidal to columnar epithelium (D, H and E, 25) and extravasation of mucin (arrows, E) within adjacent stroma (E, H and E, 50). Microcalcifications (arrows, F) are present in mucin and are in association with ductal epithelium-lined cyst (F, H and E, 100). 952 AJR:180, April 2003

5 Mammography and Sonography of Breast Tumors Fig year-old woman with mucocele-like tumor of breast. Sonogram shows well-defined mass originally identified on screening mammography. Mass is visualized as well-circumscribed hypoechoic mass with slightly increased acoustic through-transmission, suggestive of complex cyst, and thick central septation (arrow). of 217 large-core stereotactic biopsies for nonpalpable breast lesions. All three patients underwent surgical biopsy to exclude the possibility of in situ or infiltrating carcinoma with mucinous differentiation. All these lesions proved to be benign at open biopsy. In our study, three of the five patients underwent core needle biopsy. Histopathologic examination showed a mucocele-like lesion with atypical epithelium, and mucinous carcinoma could not be excluded in any of the three patients. One patient treated at our institution, a 61- year-old woman, underwent a sonographically guided 18-gauge core biopsy of a newly discovered palpable 1.8-cm solid mass, which was assessed as Breast Imaging Reporting and Data System (BI-RADS) [12] category 5 on the basis of imaging features. The initial pathologic study showed extravasation of mucin and florid ductal hyperplasia without atypia (Fig. 5A). This mass did not fulfill our criteria for a mucocele-like tumor because no mucus-filled cysts were seen; therefore, we did not include it in our study group. Excisional biopsy was recommended in view of the discordance between the clinical and radiologic impression and the histopathologic findings in the core biopsy specimen. Final histopathologic examination of the surgically excised specimen found a low-grade mucinous carcinoma (Fig. 5B). Using larger core needle biopsy or vacuum-assisted biopsy for these lesions may reduce the rates of false-negative findings for in situ or invasive carcinoma with mucinous features. Surgical excision is recommended at our institution if a mucocele-like tumor or extravasated mucin alone is found at core biopsy, especially if there is a possibility of atypia, because a well-differentiated paucicellular mucinous carcinoma and a mucocele-like tumor associated with malignancy can show similar histologic features at core needle biopsy. This possibility also reinforces the need for sampling and careful examination to exclude the presence of atypical hyperplasia or carcinoma before making a diagnosis of benign mucocele-like tumor of the breast. In our five patients, no malignancy was revealed at surgical excision of the mucocele-like tumors of the breast. Ours is a small series, however, and in view of the significant association reported in the literature of mucocele-like tumors with malignancy [2, 3], we believe that surgical excision of these lesions is warranted, even in the absence of atypia. The age of the patient can also be helpful in discriminating between a mucinous carcinoma A and a mucocele-like tumor: mucinous carcinoma is uncommon in young premenopausal women, especially in those younger than 40 years, whereas a mucocele-like tumor of the breast can occur in young women the youngest woman in our series was 29 years old. Recurrences of mucocele-like tumor are rare but have been noted in the literature [2, 5, 6]. A mucocele-like tumor with atypia, ductal carcinoma in situ, or focal invasion is the more likely tumor to recur [2]. Fisher and Millis [6] reported a case of a mucocele-like tumor with atypia excised from a 31-year-old woman. One year later, three masses with histologic features of pure mucinous carcinoma with associated papillary carcinoma in situ were removed from the same site. Hamele-Bena et al. [2] noted a patient in whom a mucocele-like tumor with focal invasion (this term was not further defined in their article) was followed 5 Fig year-old woman with 1.8-cm palpable mass that did not meet criteria for mucocele and thus was not included in our study. A, Photomicrograph of histopathologic specimen obtained during 18-gauge core needle biopsy reveals that several core fragments of fibrous breast stroma show extracellular mucin without associated epithelium (arrow). Surgical excision was recommended because pathologic findings were not concordant with mammographic impression of Breast Imaging Reporting and Data System [12] category 5 lesion. Presence of mucinous carcinoma could not be excluded. (H and E, 50) B, Photomicrograph of surgical specimen reveals small clusters of malignant cells (arrows) floating in extracellular mucin, diagnostic of mucinous carcinoma. (H and E, 200) B AJR:180, April

6 Glazebrook and Reynolds years later by a mucocele-like tumor with focal invasion in the same breast. This patient also had a contralateral mucocele-like tumor with ductal carcinoma in situ. Bilateral mucocele-like tumors are rare; only four cases have been reported [2, 6]. Weaver et al. [4] postulated that there is a spectrum of mucinous lesions of the breast that may represent a pathologic continuum. Mucocele-like tumors may be precursors of mucinous carcinoma either in the pure form or as part of invasive ductal carcinoma of no particular type. It is the presence of atypical ductal hyperplasia that puts the patient at high risk for subsequent malignant transformation. Patients with mucocele-like tumors especially those associated with atypical ductal hyperplasia warrant close 6-month clinical follow-up with annual screening mammography. In summary, the mucocele-like tumor, a rare lesion of the breast, can be an asymptomatic lesion detected on a screening mammogram as a nodule or as microcalcifications, or it may present as a palpable mass. Sonographically, it can appear as a cluster of apparently complex cysts or hypoechoic tubular structures with no flow visualized on color Doppler evaluation. Calcifications may be seen in the mass. Although the lesion was originally described as a benign entity, subsequent reports have shown an association with atypical hyperplasia and malignancy. Microcalcifications are more commonly seen in mucocele-like tumors that are associated with atypical hyperplasia or carcinoma. Differentiating a mucocele-like tumor from a mucinous carcinoma can be difficult with fine-needle aspiration or large-core needle biopsy, although the rate of false-negative biopsy findings may be reduced with the use of vacuum-assisted devices. Because mucinous carcinoma is uncommon in women younger than 40 years, a mucocele-like tumor should be considered as a possible diagnosis if a biopsy in a young woman reveals extravasation of mucin into the adjacent stroma. However, surgical excision is recommended for women of all age groups to exclude the possibility of mucinous carcinoma or a mucocele-like tumor associated with atypia or carcinoma, and examination of the entire pathologic specimen is necessary to exclude a more worrisome lesion. Patients receiving the diagnosis of a mucocele-like tumor warrant close follow-up because of the association of this lesion with atypical ductal hyperplasia and malignancy. References 1. Rosen PP. Mucocele-like tumors of the breast. Am J Surg Pathol 1986;10: Hamele-Bena D, Cranor ML, Rosen PP. Mammary mucocele-like lesions: benign and malignant. Am J Surg Pathol 1996;20: Ro JY, Sneige N, Sahin AA, Silva EG, del Junco GW, Ayala AG. Mucocele-like tumor of the breast associated with atypical ductal hyperplasia or mucinous carcinoma: a clinicopathologic study of seven cases. Arch Pathol Lab Med 1991;115: Weaver MG, Abdul-Karim FW, al-kaisi N. Mucinous lesions of the breast: a pathological continuum. Pathol Res Pract 1993;189: Chinyama CN, Davies JD. Mammary mucinous lesions: congeners, prevalence and important pathological associations. Histopathology 1996; 29: Fisher CJ, Millis RR. A mucocoele-like tumour of the breast associated with both atypical ductal hyperplasia and mucoid carcinoma. Histopathology 1992;21: Bhargava V, Miller TR, Cohen MB. Mucocelelike tumors of the breast: cytologic findings in two cases. Am J Clin Pathol 1991;95: Deschryver K, Radford DM, Schuh ME. Pathology of large-caliber stereotactic biopsies in nonpalpable breast lesions. Semin Diagn Pathol 1999;16: Kirk IR, Schultz DS, Katz RL, Libshitz HI. Mucocele of the breast. AJR 1991;156: Chopra S, Evans AJ, Pinder SE, et al. Pure mucinous breast cancer: mammographic and ultrasound findings. Clin Radiol 1996;51: Conant EF, Dillon RL, Palazzo J, Ehrlich SM, Feig SA. Imaging findings in mucin-containing carcinomas of the breast: correlation with pathologic features. AJR 1994;163: American College of Radiology. Breast imaging reporting and data system (BI-RADS), 3rd. Reston, VA: American College of Radiology, AJR:180, April 2003

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