COLLECTIVE REVIEWS Areola-Sparing Mastectomy: Defining the Risks Alan J Stolier, MD, FACS, Baiba J Grube, MD, FACS The recent development and popularity of skin-sparing to actual risk of cancer arising in the areola and is pertinent mastectomy (SSM) is a likely byproduct of high-quality to any application of ASM in prophylactic operations. autogenous tissue breast reconstruction. Numerous non- 7. Based on clinical studies, what are the outcomes when randomized series suggest that SSM does not add to the risk some degree of nipple-areola complex (NAC) is preserved of local recurrence.1–3 Although there is still some skepti- as part of the surgical treatment? cism,4 SSM has become a standard part of the surgical ar- mamentarium when dealing with small or in situ breast ANATOMY OF THE AREOLA cancers requiring mastectomy and in prophylactic mastec- In 1719, Morgagni first observed that there were mam- tomy in high-risk patients. Some have suggested that SSM mary ducts present within the areola. In 1837, William also compares favorably with standard mastectomy for Fetherstone Montgomery (1797–1859) described the 6 more advanced local breast cancer.2 Recently, areola- tubercles that would bare his name. In a series of schol- sparing mastectomy (ASM) has been recommended for a arly articles from 1970 to 1974, William Montagna and similar subset of patients in whom potential involvement colleagues described in great detail the histologic anat- 7,8 by cancer of the nipple-areola complex is thought to be low omy of the nipple and areola. He noted that there was or in patients undergoing prophylactic mastectomy.5 For “confusion about the structure of the glands of Mont- ASM, the assumption is that the areola does not contain gomery being referred to as accessory mammary glands glandular tissue and can be treated the same as other breast or as intermediates between mammary and sweat 9 skin. Because no large series exists to define the risks of glands.” He found that the glands of Montgomery were preserving the areola, it seems appropriate to critically re- true mammary glands, the ducts and parenchyma of view our knowledge of the areola and thereby attempt to which were no different from the mammary glands and define those patients in whom ASM might be appropriate. ducts that opened into the tip of the nipple. Some topics thought to be relevant to ASM are: Perhaps the most enlightening work on the anatomic structure of the areola came from Smith and col- 1. What is the histologic anatomy of the areola? leagues.10 Serial sections of the areola were performed 2. Does the areola contain ductal tissue or breast lobules? If from 12 patients who had undergone modified radical not, it would seem appropriate to apply the same rules to mastectomy for invasive ductal carcinoma. Thirty-six the areola as one applies to removal of breast skin. areola tubercles were sampled in the 12 patients. In 4 of 3. What is the risk of occult involvement of the areola in the 12 patients, pathologic abnormalities were identified patients with established breast cancer? in the areola tubercle, including 2 patients showing fea- 4. Based on histopathologic data, what are the risk factors tures consistent with fibrocystic disease, 1 showing in- that can favor areola involvement? traductal hyperplasia, and 1 showing both hyperplasia 5. What is the incidence of cancer involvement of nonareola skin? and ductal carcinoma in situ. They noted that the “ducts 6. What is the incidence of Paget’s disease of the breast in- volving the areola in the absence of nipple involvement? coursed from the underlying mammary lobules, through This is an important question to answer because it speaks the SC tissues and into the region of the sebaceous ap- paratus.” The ducts terminate by joining the sebaceous gland ducts or through a separate opening in the epider- 9 Received October 14, 2004; Revised February 3, 2005; Accepted February 3, mis nearby (Fig. 1). These findings were in agreement 2005. with Montagna and colleagues, who also found that the From the Department of Surgery, Tulane University and Tulane University Cancer Center, New Orleans, LA (Stolier); and the Department of Surgery, ducts extending from the breast lobules can at times University of Texas Medical Branch, Galveston, TX (Grube). empty directly into the secretory ducts of the sebaceous Correspondence address: Alan J Stolier, MD, FACS, Tulane University 9 Health Sciences Center, Department of Surgery; 1430 Tulane Ave, New Or- glands or directly into the epidermis. leans, LA 70112. In an attempt to address ASM, which was termed © 2005 by the American College of Surgeons ISSN 1072-7515/05/$30.00 Published by Elsevier Inc. 118 doi:10.1016/j.jamcollsurg.2005.02.013 Vol. 201, No. 1, July 2005 Stolier and Grube Areola-Sparing Mastectomy 119 Abbreviations and Acronyms ASM ϭ areola-sparing mastectomy LR ϭ local recurrence NAC ϭ nipple-areola complex NSM ϭ nipple-sparing mastectomy SCM ϭ subcutaneous mastectomy SSM ϭ skin-sparing mastectomy nipple-coring in 1991, Schnitt and colleagues11 pub- lished data on histology of the areola in 8 patients who underwent mastectomy for cancer. They noted that the ducts present in the areola dermis consisted of two cell layers, including a cuboidal to columnar layer and a layer of myoepithelial cells. They noted that in some instances the ducts were seen to arise from the underlying breast tissue.They also noted that “the histologic appearance of these ducts was identical to that of extralobular ducts ѧ within the breast parenchyma .” Figure 1. Tubercle of Montgomery. (Reprinted from Smith DM Jr, Peters DG, Donegan WL. Montgomery’s areolar tubercle. Arch RISK OF OCCULT INVOLVEMENT OF THE Pathol Lab Med 1982;106:60–63, with permission. © 1982 Amer- AREOLA IN PATIENTS WITH ESTABLISHED ican Medical Association.) BREAST CANCER Nipple-areola complex involvement NAC involvement.14 Occult tumor in the NAC was de- Innumerable studies have been published looking at the tected in 5.6%. In this instance, tumor size, nuclear incidence of occult nipple-areola complex (NAC) in- grade, and histologic subtype did not impact risk. Loca- volvement with an established breast cancer (Table 1). tion of the tumor in the subareola region, multicentric- Unfortunately, most have not specifically looked at are- ity, and axillary nodal involvement did adversely impact ola involvement and tend to focus on nipple involve- risk of NAC involvement. ment. Lagios and colleagues12 examined 149 consecutive Morimoto and colleagues15 published data from a mastectomy specimens for frequency of nipple involve- study of 141 mastectomy specimens. Forty-four (31%) ment. Using serial subgross and correlated radiographic demonstrated neoplastic involvement of the NAC.15 examination they found carcinoma in the nipple in They also measured the distance from the tumor to the 30.2% of cases. Poor differentiation, tumor size Ͼ20 nipple and found that there were no cases of NAC in- mm, and axillary metastases were found to be risk factors volvement with a distance of Ն4cm. for occult NAC involvement. The largest study of NAC involvement is by Santini In examining pathologic specimens from the NSABP and colleagues,16 from Bologna, Italy. They studied B-04 study (radical mastectomy versus total mastectomy 1,291 consecutive mastectomy specimens with primary Ϯ radiation) occult nipple involvement was noted in invasive carcinoma. Overall, 12% were found to have 107 of 967 cases (11.1%). Fisher and colleagues13 NAC involvement with 8% of the total being unsus- noted that when cancer had invaded the skin, there pected clinically. They found that occult NAC involve- was greater likelihood that the tumor was beneath the ment was directly related to tumor size, but not to type nipple-areola region. It was also more likely that the of, or presence of, an extensive intraductal component. tumor was Ն4.1 cm, had an extensive intraductal Again, the data did not allow one to distinguish between component, and had lymphovascular or perineural nipple and areola involvement. invasion. Several smaller studies have been published with the A series of 286 mastectomy specimens was reviewed at aim of examining incidence of occult NAC involve- MD Anderson Cancer Center for presence of occult ment, presumably to determine feasibility of retaining 120 Stolier and Grube Areola-Sparing Mastectomy J Am Coll Surg Table 1. Studies Examining Occult Involvement of the Nipple-Areola Complex NAC Study Cases involvement (%) Risk factors Lagios et al12 149 30.2 Ͼ2 cm, poor differentiation, positive axillary nodes NSABP B-0413 967 11.1 Ն4.1 cm, beneath nipple, Ն4 positive axillary nodes, EIC Laronga et al14 286 5.6 Subareola location, multicentricity, positive axillary nodes Morimoto et al15 141 31 Ͻ4 cm from NAC Santini et al16 1,291 12 Tumor size EIC, extensive intraductal component; NAC, nipple-areola complex. the NAC during skin-sparing mastectomy.17–22 All fail to who examined skin flaps in 1,000 mastectomy speci- distinguish between cancerous involvement of the nip- mens to determine frequency of neoplastic involvement. ple and areola, making it difficult to determine the true They found skin involvement away from the nipple are- risk of areola involvement in patients with established ola complex in 12.7% of evaluable cases, most of which breast cancer. were by direct infiltration and approximately a third of which were clinically occult. In 1.3% of patients, tumor Occult involvement of the areola emboli were noted in clinically uninvolved skin and over Aside from the study by Smith and colleagues10 describ- half involved more than one quadrant. Again, there was ing a single case of ductal carcinoma in situ involving the noted to be a correlation between tumor size and skin areola, only the study by Simmons and associates5 spe- involvement.