Journal of Plastic, Reconstructive & Aesthetic Surgery (2014) 67,27e33

REVIEW Bilateral congenital : A case report and systematic review of the literature

Stephanie E. Dreifuss, Zoe M. MacIsaac, Lorelei J. Grunwaldt*

Department of Plastic Surgery, University of Pittsburgh, 3550 Terrace Street, 6B Scaife Hall, Pittsburgh, PA 15261, USA

Received 17 April 2013; accepted 29 June 2013

KEYWORDS Summary Background: Congenital anomalies present challenging management deci- Congenital; sions to the plastic surgeon. One must consider the optimal age of reconstruction as well as the Breast; ideal surgical technique. Amazia, a very rare condition characterised by a complete lack of breast Amazia; tissue in the presence of a areolar complex (NAC), is one such congenital breast anomaly. Reconstruction Methods: A comprehensive systematic review of the literature was performed to examine the various approaches to reconstruction of congenital breast anomalies. From this review, the data compiled included patient demographics and operative details, including type of reconstruction, treatment of the contralateral breast and treatment of the NAC. A case of bilateral amazia is also reported. Results: Of 178 articles, 13 ultimately met the inclusion criteria and 54 individual patient recon- structions were identified from these papers. At the time of reconstruction, the patients were in the range of 13e54 years, with an average age of 27.6 years. Prosthetic and autologous recon- structions were equally represented (19 patients each, 35.2%; Table 2). Autologous reconstruc- tion with prosthesis was slightly less common (15 patients, 27.8%). One patient was reconstructed using autologous lipo-augmentation only. Of the 36 cases in which the approach to the NAC was addressed, most (66.7%) were not recon- structed. Conclusions: Amazia is a very rare congenital anomaly of the breast. This systematic review of the literature highlights the need for better reporting and examination of this type of data to allow for future study and to better advise on decision making regarding the timing of reconstruction, sur- gical technique and the approach to the NAC. ª 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.

* Corresponding author. Division of Pediatric Plastic Surgery, Children’s Hospital of Pittsburgh of UPMC, 4401 Penn Avenue, Floor 3, Pittsburgh, PA 15224, USA. Tel.: þ1 412 692 3433; fax: þ1 412 692 8614. E-mail address: [email protected] (L.J. Grunwaldt).

1748-6815/$ - see front matter ª 2013 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.bjps.2013.06.048 28 S.E. Dreifuss et al.

As a whole, congenital breast anomalies including hypo- significant psychological disturbance secondary to her defor- plasia, amazia and are common in the paediatric mity. Socially she was isolated and would not participate in population.1,2 Despite the relative frequency with which age-appropriate activities with her peers. After seeing the these conditions are encountered in clinical practice, the patient back several times over a 1-year period, the decision literature is lacking in quantitative reviews of how to was finally made to proceed with reconstruction. Surgical manage these patients. Therefore, a systematic review of options were discussed. This patient wanted a small- to the existing literature was conducted on congenital breast moderate-sized breast mound, and thus a postoperatively anomalies allowing an analysis that provides data summa- adjustable implant was selected for her reconstruction. rising the age of reconstruction, surgical technique and management of the nipple areolar complex (NAC). Addi- Surgical procedure tionally, we present an unusual case of a patient who presented with congenital amazia. The patient was taken to the operating room for placement of bilateral, subpectoral, dual-plane, postoperatively Case presentation adjustable saline implants. These were placed via periar- eolar incisions with a lateral extension. The dissection was extended down to the pectoralis muscle in a subcutaneous A 13-year-old female presented to the paediatric plastic plane. On the right side the subcutaneous dissection was surgery clinic with bilateral, congenital absence of the done for a slightly greater distance superiorly prior to divi- and low-set NACs. Normal pubertal development was noted with Tanner stage V pubic hair and with onset of sion of the pectoralis muscle as the NAC was sitting slightly more inferiorly on this side. The pectoralis was released menses at 11 years of age. At birth, she was found to have bilaterally from the 3 o’clock to the 9 o’clock position and right foot postaxial polydactyly, bilateral syndactyly of the second and third toes, left and amblyopia, frontal the pocket was extended superiorly such that the implant would sit in a dual plane once inflated. The final pockets upsweep of the hairline and low-set, posteriorly rotated measured approximately 11e12 cm in diameter. ears. Chromosome analysis, renal ultrasound and skeletal survey were all normal, and family history was unremark- Postoperatively adjustable saline implants (Mentor Smooth Round Spectrum implants) measuring 10.8 cm in able. The patient was seen by Genetics and a normal diameter were placed. The projection was 3.5 cm and the chromosomal analysis was confirmed; additionally, a syn- maximum fill volume between 225 and 270 ml. A remote drome was not identified. Of note, the patient complained port was placed in a lateral pocket near the midaxillary line of low self-esteem and social isolation due to the complete and attached to the expander in a standard fashion. absence of breasts. She was diagnosed with amazia. In-office expansion was initiated 2 weeks postoperatively Physical examination revealed no palpable breast tissue. The patient’s NACs were positioned on the chest at the and terminated at a fill volume of 270 cc. The patient tolerated these expansions well and her implants remained midhumeral point, which many use as a reference point for symmetrically positioned on the chest wall (Figure 2). normal nipple position. However, in this case, their position relative to other landmarks on the thorax made them appear Approximately 1 year after the placement of the im- plants, the patient returned for repositioning of the NACs. to be sitting too far inferiorly. The NACs were sitting at the The patient was taken to the operating room for bilateral ideal position for the new inframammary fold (Figure 1). The distance from the midsternal notch to the NAC was 23 cm on free nipple grafts. The donor sites were closed primarily. The grafts were secured in place with a Reston foam bolster the right and 22 cm on the left, and the proposed breast such that the were visible. The patient was admitted pocket diameter measured 11e12 cm. Other findings postoperatively and had some superficial slough of the included an accessory nipple on the left abdomen as well as axillary fullness that felt like fatty tissue. Hormone levels and partial loss of the nipple itself. However, she did heal with an aesthetically acceptable result (Figure 3). were normal and a breast ultrasound revealed no hormone- sensitive glandular tissue. Wrist radiographs revealed fused growth plates with a bone age of 15 years. Systematic review The patient was counselled that given her young age and the fact that she was likely still growing, it would be prudent to A systematic review of the literature was performed using wait to do the reconstruction. She was suffering from the PubMed for MEDLINE articles. Search strategies

Figure 1 Patient before reconstruction. Bilateral congenital amazia 29

Figure 2 Patient after placement of implant. included queries for “Mammaplasty” MeSH þ “Breast/ab- 1).3e15 All included articles were identified from the normalities” MeSH “Breast Diseases/Congenital” MeSH; PubMed literature search. Of these, a total of 54 individual “Amazia” [Title/Abstract] and “Amastia” [Title/Abstract] patient reconstructions were identified. Patients were on for the period between 2003 and March 2012. Papers writ- average 27.6 years of age at the time of reconstruction ten in English, French and Spanish were considered. Titles (range of 13e54). For studies which included follow-up, and abstracts were screened by two different reviewers. 14.3 months was the average, although several studies Full articles, consisting of those with insufficient infor- lacked follow-up beyond the immediate postoperative mation to be excluded based on the abstract and title, period.3,5,7,13,15 were then obtained for potential studies of interest. The Prosthetic and autologous reconstructions were equally inclusion criteria consisted of a description of the operation represented (19 patients each, 35.2%; Table 2). Autologous and a discussion of breast reconstruction for congenital tissue reconstruction with prosthesis was slightly less conditions including amazia, amastia and breast hypopla- common (15 patients, 27.8%). One patient was recon- sia. The exclusion criteria included the lack of operative structed using autologous lipo-augmentation only. details, insufficient patient-specific information (such as The majority of cases that detailed prosthetic recon- mention of general surgical procedures without reference struction did not include information regarding the type of to specific patient cases), description of reconstruction for implant or placement. Of those that did include this in- deformities other than those included and languages other formation, silicone and saline prostheses were chosen at a than English, French or Spanish (Figure 4). Reference lists similar frequency (eight and six patients, respectively). of included articles were then reviewed for potential Most implants were placed in a submuscular, rather than additional articles. Data were compiled for average age and subglandular, location (nine patients vs. one patient, range, months of follow-up and number of patients for each respectively; Table 3). For prosthetic reconstruction, paper. Operative details were included for each individual hypomastia was the most frequent condition being case in which the reconstruction had been completed. addressed (15 patients, 78.9%), while amazia and amastia These details included the type of reconstruction, specific were less common (three patients, 15.9% and one patient, surgical approach (choice of flap, type of implant and 5.2%, respectively; Table 4). implant placement), treatment of the contralateral breast Regarding autologous reconstruction, omental flaps and treatment of the NAC. The authors had no conflicts of were the most frequently reported flaps to be implemented interest or sources of support to disclose in this systematic (11 patients, 31.4%; Table 5). Other flaps were reported review. with relatively similar frequencies. Few articles described the management of the NAC Results (Table 6). Of the 36 patients described, the majority was not altered surgically (24 patients, 66.7%). In several cases, Of 178 citations initially identified in this systematic re- the NAC was surgically reconstructed (seven patients, view, 13 articles ultimately met the inclusion criteria (Table 19.4%), while for several patients, the NAC was described

Figure 3 Patient after final reconstruction. 30 S.E. Dreifuss et al.

Figure 4 Schematic of search strategy for systematic review.

preoperatively but not postoperatively (five patients, most common (14 patients, 28.0%), followed by implant 13.9%). Only patients with absent NAC preoperatively or placement (11 patients, 22%) and lastly mastopexy (seven superiorly displaced NAC preoperatively underwent NAC patients, 14.0%). Overall, of those patients with unilateral reconstruction (five of nine patients and two of ten pa- deformity where a definitive statement was made regarding tients, respectively). treatment of the contralateral, unaffected breast, more Many patients with unilateral deformity received surgery than half received surgery on their contralateral breast, in on their contralateral breast (Table 7). Of the 50 unilateral order to match the normal breast with the reconstructed cases, no treatment of the contralateral breast was the breast.

Discussion Table 1 Overview of all cases identified in literature search. Congenital amazia is defined as the absence of glandular Paper Number of Age at Follow-up breast tissue with a normal NAC. Related conditions include patients Reconstruction (mos) congenital where only the NAC is absent, amastia (years) where both the mammary tissue and the NAC are absent, Costa et al., 2010 11 26.8 [18e53] e breast hypoplasia where there is a deficiency of mammary Derman et al., 2004 1 [15e18] 39 tissue and Poland’s syndrome where the pectoralis muscle Freitas et al., 2007 8 23.2 [14e36] e is also absent.16 Garcia et al., 2007 1 31 15 Normally, breast tissue originates from an anlage of Gautam et al., 2007 12 27.2 [16e43] e ectodermal cells along primitive, paired mammary ridges. Hatano et al., 2011 1 54 6 These are present at around the sixth week of gestation and Klinger et al., 2009 1 26 18 extend from the axilla to the groin. Between weeks 7 and Liao et al., 2005 1 52 12 10 of gestation, the upper and lower regions of these milk Lin et al., 2000 1 33 6 lines undergo apoptotic atrophy, while the middle or pec- Nassab et al., 2005 1 16 1.5 toral ridges persist at the level of the fourth intercostal Ozsoy et al., 2007 1 17 e space. This primordial breast tissue penetrates the under- Pinsolle et al., 2008 7 23.0 [13e40] 12 lying mesenchyme between weeks 10 and 14 of gestation, Spear et al., 2004 8 32.1 [18e40] e and the mesenchymal tissue forms the superficial fascial system and suspensory ligaments of the breast. Finally, the Bilateral congenital amazia 31

Table 2 Reconstruction of congenital amazia, amastia Table 4 Prosthetic reconstruction by implant type and and hypomastia. breast condition. Reconstruction n of Cases (%) n of Cases (%) Breast condition (%) All 54 (100) Amastia Amazia Hypomastia Prosthesis 19 (35.2) All 19 (100) 1 (5.2)a 3 (15.9) 15 (78.9)a Autologous flap 19 (35.2) Silicone 8 1 1 6 þ Autologous flap Prosthesis 15 (27.8) Saline 6 0 1 5 Fat grafting only 1 (1.8) Unknown 5 0a 14 a 10 of the 100 cases were not specified as either amastia or hypoplasia. areola develops at a pectoral position along the milk line at approximately the 20th week of gestation, while the nipple 1,16 appears after birth. accompanied by bilateral choanal atresia and midface hy- It is hypothesised that in this particular case the pa- poplasia, respectively. As in our case, these patients had tient’s breast deformity may have resulted from atrophy of unremarkable family histories and no known chromosomal the entire between weeks 7 and 10 of abnormalities.13,19 gestation. Subsequently there was no development of a Though our systematic review made a distinction be- breast or NAC in the normal position; the primordial breast tween amastia, amazia and breast hypoplasia, many of the tissue did not penetrate the underlying mesenchyme at the articles used only a clinical diagnosis to verify the presence location of the patient’s areola that formed at 20 weeks. or absence of breast tissue. In order to definitively diagnose Her inferiorly positioned NACs may actually have been an one of these conditions, complementary testing such as accessory nipple or NACs along the milk line that did not ultrasound or mammography should be used as a supple- properly regress. ment to the physical exam. Thus, some of the articles While few other cases of bilateral amazia have been featured in our systematic review might be inaccurately reported, other authors have detailed congenital conditions reporting hypoplasia or amazia. The latter underscores the that affect breast and nipple development. Poland’s syn- important role of supplemental imaging in arriving at a drome has a one in 100,000 incidence, affecting males 3 correct diagnosis in patients with congenital hypoplastic times more frequently than females. The condition is most breast abnormalities. often unilateral, but may sometimes present bilaterally. As would be expected for such rare conditions, there is The absence of the sternocostal head of the pectoralis paucity in the literature regarding the surgical approach to major muscle is pathognomonic for this condition, while it reconstructing hypomastia, amazia and amastia; only 13 may be accompanied by malformations of the ipsilateral articles described reconstruction, including 54 individual 17 torso and upper extremity or absence of the NAC. patients. The lack of peer-reviewed articles on amazia is in Congenital ectodermal defects are associated with sharp contrast to the number of articles on the subject of amastia and affect male and female patients equally. breast hypoplasia. If an unlimited-time MEDLINE search is Because it is a sex-linked trait, males present with more conducted, a search for ‘amazia’ returns only four articles, severe malformations. The typical patient presentation while a search for ‘breast hypoplasia’ returns 5219. includes bilateral amastia with associated abnormalities of Among decisions pertinent to breast reconstruction in the skin, skin appendages (hair, eccrine glands and seba- this patient population are age at reconstruction and type 2,11,18 ceous glands), teeth and nails. Bilateral amastia has of reconstruction (autologous vs. prosthetic reconstruc- been described as an isolated finding or with other associ- tion). Timing is crucial: while breast abnormalities have less ated anomalies. Examples of these accompanying findings functional impact, psychological sequelae resulting from from reported cases include scant axillary and pubic hair, embarrassment and social isolation are important consid- cleft or high-arched palate, absence of a finger or lobster erations in the adolescent patient.20 claw deformity and others.11,18 In addition to the case described here, two cases of bilateral amazia had been reported, demonstrating the Table 5 Autologous reconstruction. rarity of this condition.18 These two cases of amazia were n of Cases (%) All 34 (100) Table 3 Prosthetic reconstruction by implant type and Omentum 11 (31.4) position. DIEP 5 (14.3) n of Placement LD 5 (14.3) Cases (%) SGAP 4 (11.5) Submuscular Subglandular Unknown TRAM 3 (8.6) All 19 (100) 9 (47.4) 1 (5.2) 9 (47.4) SIEA 3 (8.6) Silicone 8 3 1 4 IGAP 2 (5.7) Saline 6 6 0 0 Lipo-augmentation 1 (2.8) Unknown 5 0 0 5 Unknown 1 (2.8) 32 S.E. Dreifuss et al.

Table 6 Management of the NAC. NAC n of Cases (%) NAC Reconstruction Yes (%) No (%) Unknown (%) All 36 (100) 7 (19.4) 24 (66.7) 5 (13.9) Absent 9 (25.0) 5 2 2 Superior displacement 10 (27.8) 2 8 0 Hypoplasia 4 (11.1) 0 4 0 Superior Displacement þ Hypoplasia 9 (25.0) 0 9 0 No abnormality 4 (11.1) 0 1 3

The age at reconstruction from our literature search deformities, in order to allow them to make the best de- ranged from 13 to 54, possibly due in part to lack of access cision regarding reconstructive treatment. and education regarding reconstructive options. One pa- In our systemic review of breast reconstruction in the tient visited a plastic surgeon at 18 years of age and was setting of amazia, we found several reports, although too informed that there were no options; her reconstruction few to perform an objective analysis or to guide our was not performed until 54 years of age when she again operative decisions. Both prosthetic and autologous op- consulted a plastic surgeon.8 While it may be ideal to cor- tions have been described with reasonable follow-up and rect congenital breast anomalies during the late teens so as few reported morbidities. In the hopes of determining to limit the degree to which growth will impact the optimal approach, it is important that these cases continue reconstruction, earlier reconstruction at 11e12 years to be reported. As with other operations, the optimal should be considered given psychological concerns.16,20 reconstruction technique depends on patient-specific fac- Ideally, reconstruction should be performed when the pa- tors, the surgeon’s skills and patient and surgeon tient’s peers are developing breasts as this process impacts preferences. adolescent females’ psychosocial growth and self-esteem.1 In the case presented here, given the patient’s age, Our patient’s primary concern was low self-esteem and postoperatively adjustable implants/expanders were social isolation, leading us to reconstruct her breasts at 13 selected in order to maintain an appropriate size for her years of age. This patient was suffering psychological con- stage of growth and development. These expanders have a sequences from not having breasts. While some surgeons size range in which they can be filled allowing the plastic would elect to wait to reconstruct the breasts given the surgeon to add fluid and thus increase the size of the breast limited number of options available in a 13-year-old, here as the patient grows. Also, if the patient is ultimately happy we chose to proceed with an implant-based reconstruction with a saline implant, the remote port can be easily using a postoperatively adjustable saline implant with a removed in an outpatient procedure and the implant can remote port. function as the final reconstruction for several years. In a In one study, the mean age of patients receiving surgery 13-year-old female, one could certainly entertain autolo- for hypoplastic breast abnormalities was 16.7 years, with gous reconstruction options. In her case, given the com- patients undergoing an average of 1.5 surgeries.2 Given this plete lack of breast tissue, one would have to reconstruct patient’s young age and so as to ascertain whether the the breast mound with a deep inferior epigastric perforator patient’s skeletal growth was complete, a wrist X-ray was (DIEP) flap or a transverse rectus abdominis myocutaneous obtained to look at skeletal age. It showed growth-plate (TRAM) flap. She did not have enough excess abdominal fusion indicating skeletal maturity. This finding allowed tissue to allow this. Also, doing an implant-based recon- for proper positioning of the reconstructed breasts on the struction does not prevent the surgeon from doing autolo- chest wall given the very low-set NACs. Ultimately, the gous reconstruction in the future. The patient wished to breast mound was positioned relative to the sternal notch have a small breast mound and did not want a drastic and the chest width. It is important that patients and their change in her appearance. The reconstruction chosen met families, in conjunction with their primary-care physician, her current desires, although further reconstructive surgery be presented the surgical options when discussing breast may be needed in the future.

Table 7 Management of the contralateral breast (unilateral cases only). n Cases (%) Reduction (%) Implant (%) Mastopexy (%) None (%) Unknown (%) All 50 (100) 2 (4.0) 11 (22.0) 7 (14.0) 14 (28.0) 16 (32.0) Amastia 6 0 0 1 2 3 Amazia 11 0 1 2 2 6 Hypomastia 22 1 8 1 5 7 Unknown 11 1 2 3 5 0 Bilateral congenital amazia 33

Conclusion 5. Freitas R-S, Tolazzi A-R, Martins V-D, et al. Poland’s syndrome: different clinical presentations and surgical reconstructions in 18 cases. Aesthetic Plast Surg 2007;31:140e6. This unique presentation of the management of bilateral 6. Garcia Jr O. Reconstruction of total absence of the breast. Ann congenital absence of the breasts accompanied by inferi- Plast Surg 2007;58:12e7. orly displaced NACs merits discussion as it presents a unique 7. Gautum A-K, Allen R-J, LoTempio M-M, et al. Congenital breast challenge to the plastic surgeon. The timing of surgery, deformity reconstruction using perforator flaps. Ann Plast Surg procedure selection and approach to the NAC are chal- 2007;58:353e8. lenging and require consideration given the significant 8. Hatano A, Nagasao T, Sotome K, et al. A case of congenital impact on a patient’s psychosocial development and quality unilateral amastia. J Plast Reconstr Aesthet Surg 2012;65: of life. Discussions of this problem and related conditions in 671e4. the literature are primarily limited to case reports and case 9. Klinger M, Caviggioli F, Banzatti B, et al. series. To further add to the body of literature, a summary with amastia: a case of one-step reconstruction. Case Rep Med 2009. of the existing data was done via a systematic review of the 10. Liao H-T, Cheng M-H, Ulusal B-G, et al. Deep inferior epigastric literature. Although there are numerous publications in the perforator flap for successful simultaneous breast reconstruc- literature about congenital breast anomalies, the data are tion in a Poland anomaly patient. Ann Plast Surg 2005;55: rarely complete, thus making it difficult to come to a 422e6. consensus about the best practice. Further studies that 11. Lin K-Y, Nguyen D-B, Williams R-M. Complete breast absence include larger volumes and more systematic evaluation and revisited. Plast Reconstr Surg 2000;106:98e101. management schemes are needed to help the plastic sur- 12. Nassab R, Lahiri A, Iqbal A, et al. Breast reconstruction using geon best understand how to manage this complex patient deep inferior epigastric perforator flaps in EEC syndrome. e population. J Plast Reconstr Aesthet Surg 2006;59:600 3. 13. Ozsoy Z, Gozu A, Ozyigit M-T, et al. Amazia with midface anomaly: case report. Aesthetic Plast Surg 2007;31:392e4. Conflict of interest/funding statement 14. Pinsolle V, Chichery A, Grolleau J-L, et al. Autologous fat in- jection in Poland’s syndrome. J Plast Reconstr Aesthet Surg None. 2008;61:784e91. 15. Spear S-L, Pelletiere C-V, Lee E-S, et al. Anterior thoracic hy- poplasia: a separate entity from . Plast References Reconstr Surg 2004;113:69e77. 16. Van Aalst J-A, Phillips J-D, Sadove A-M. Pediatric chest wall and 1. Pryor L-S, Lehman J-A, Workman M-C. Disorders of the female breast deformities. Plast Reconstr Surg 2009;124:38ee49e. breast in the pediatric age group. Plast Reconstr Surg 2009; 17. Araco A, Gravante G, Araco F, et al. Breast asymmetries: a 124:50ee60e. brief review and our experience. Aesthetic Plast Surg 2006;30: 2. Sadove A-M, Van Aalst J-A. Congenital and acquired pediatric 309e19. breast anomalies: a review of 20 years’ experience. Plast 18. Trier W-C. Complete breast absence: case report and review of Reconstr Surg 2005;115:1039e50. the literature. Plast Reconstr Surg 1965;36:430e9. 3. Costa S-S, Blotta R-M, Mariano M-B, et al. Laparoscopic treat- 19. Papadimitriou A, Karapanou O, Papadolpoulou A, et al. ment of Poland’s syndrome using the omentum flap technique. Congenital bilateral amazia associated with bilateral choanal Clinics (Sao Paulo) 2010;65:401e6. atresia. Am J Med Genet A 2009;149A:1529e31. 4. Derman O, Gold M-A. Poland’s syndrome and premature 20. Kulkarni K, Dixon J-M. Congenital abnormalities of the breast. ovarian failure. J Pediatr Adolesc Gynecol 2004;17:389e92. Women Health 2012;8(1):75e88.