IAR Journal of Medical Case Reports ISSN Print : 2709-3220 | ISSN Online : 2709-3239 Frequency : Bi-Monthly Language : English Origin : Kenya Website : https://www.iarconsortium.org/journal-info/iarjmcr

Case Report

Accessory Breast Cancer Patient: Follow-Up Case Report

Article History Abstract: Accessory breast is a congenital atavism condition.‎ Accessory breast tissue may be arising anywhere along the mammary line because of the failure of‎ Received: 05.09.2020 complete maturation during embryogenesis. The malignancy in accessory breast Accepted: 02.10.2020 tissue is considered as primary‎ breast cancer. Axillary breast cancer is not well Revision: 05. 10.2020 recognized site of primary breast cancer.‎‏ ‏ This case report for a 55 year-old Published: 10.10.2020 premenopausal female who presented with axillary immobile mass in her left axilla that diagnosed after extensive investigations as stage II B, ER, PR positive Author Details and HER neu positive poorly differentiated accessory‎ breast adenocarcinoma. ‎The patient was staged as stage II B and we followed NCCN guidelines 2013 for Iman Moustafa*1 and M Essam Badawy2 breast cancer in management, so our patient was surgically treated, followed by postoperative adjuvant chemotherapy in the form of 4 cycles doxorubicin and Authors Affiliations cyclophosphamide followed by 4 cycles of paclitaxel and 17 cycles trastuzumab. Subsequently radiotherapy was given followed by hormone therapy. We followed 1King Abdulaziz Medical City, AlHasa, Saudi up the patient for 6 years and she is doing well. Accessory breast cancer is a rare Arabia disease and misdiagnosis of these cases is very immense and lead to extensive unnecessary investigations. Physicians have to be aware about these cases. 2Mohammed Dossary Hospital, AL Khobar, Management of accessory breast cancer is according to the same guidelines for Saudi Arabia management of breast cancer. Follow up data should extensively encourage Corresponding Author* determining the prognosis of accessory breast cancer in comparison to usual Iman Moustafa breast cancer. How to Cite the Article: Keywords: "accessory", "ectopic", auxiliary"," breast cancer ". Iman Moustafa and M Essam Badawy (2020) Accessory Breast Cancer Patient: Follow-Up Case Report. IAR J Med Cse Rep . 1(1)1-7. INTRODUCTION Copyright @ 2020: This is an open-access article Accessory breast cancer is a rare disease developed from distributed under the terms of the Creative accessory breast tissue. Accessory breast tissue can be found along any Commons Attribution license which permits point of the mammary lines, including in the thoracic and abdominal unrestricted use, distribution, and reproduction region (67%) and down to the groin. Ectopic breast tissue can also be in any medium for non commercial use found in locations such as the face, back, and thighs, but the predominant (NonCommercial, or CC-BY-NC) provided the original author and source are credited. site is the axilla. The incidence of supernumerary breast and ectopic breast tissue around the world is 1–6% (Rizvi, G. et al., 2012). It affects 2–6% of females and 1–3% of males ‎but there is no definite incidence number for accessory breast malignancy; furthermore, reports for accessory breast cancer only include case reports and case series. Occurrence rates differ extensively according to ethnicity and gender, ranging from as low as 0.6% in Caucasians (relatively common among Asian women) to as high as 5% in Japanese females and Native ‎American ‎populations (Sookar, N. et al., 2018; & Laor, T. et al., 2004). The 1915 Kajava classification system classified accessory breasts as Class I–VIII according to anatomical structure, and is ‎still ‎used today (Table 1) (Famá, F. et al., 2016; & Amaranathan, A. et al., 2013).

Table 1: Kajava classification 1915 Classes Description Glandular ‎tissue Nipple Areola Comment Class I    Complete breast Class II ‎    Class III ‎    Class IV ‎    Class V ‎    Class VI ‎    Class VII ‎    Class VIII ‎    Hair

Accessory breast tissue can be located along the chest wall, vulva, axilla, knee, lateral thigh, buttocks, face, ear, and neck. Changes or symptoms may be noticed during puberty, at different times of the menstrual cycle, or during

Available: https://iarconsortium.org/journal-info/iarjmcr 1

Iman Moustafa and M Essam Badawy; IAR J Med Cse Rep; Vol-1, Iss- 1 (Sep-Oct, 2020): 1-7 pregnancy and breastfeeding in women. Of note, the accessory breast tissue is often not detected until puberty because it is activated by hormones (Jatoi, I., & Rody, A. 2016). CASE REPORT

Figure 1: Histological examination of specimen. Sections Figure 2: The tumour cells in both mucinous and nonmucinous areas show large deposits of carcinoma replacing most of the show a positive staining for oestrogen receptor. lymph node structure.

Figure 4:The tumor cells are arrange in solid sheets or lobules without glandular differentiation

Figure 3: Left axillary mass

Figure 5: Sections show large deposits of Figure 6: A large component of mucinous carcinoma is present in carcinoma replacing most of the lymph node one of these lymph node structure.

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Iman Moustafa and M Essam Badawy; IAR J Med Cse Rep; Vol-1, Iss- 1 (Sep-Oct, 2020): 1-7

Figure 7: The tumor cells stain positively for CK7. ER (50%of tumor cells) Figure 8: The tumor cells stain positively for CK7,PR (5% of tumor cells)

Figure 9: The tumor cells in both mucinous and Figure 10: The tumor cells in both mucinous and non mucinous non mucinous areas show a positive staining for ER areas show a positive staining for PR

A 55-year-old is premenopausal female with arranged in solid sheets or lobules without glandular diabetes, a blood pressure of 130/70 mmHg, a weight of differentiation (Figure 1).‎Immunohistochemistry (IHC) 76 kg, and a height of 167 cm and no family history of methodology reported that the breast cancer. She was presented to the general surgery tumour ‎cells ‎stained ‎positively for pan-cytokeratins outpatient department on the 4th of December 2011. The (CK) (AE1/AE3), suggestive of lymph node patient had a history of left axillary immobile mass of micrometastases (Lerwill, M. F. 2004); CK7; epithelial around 3.0 x 2.0 cm (length/width) which had increased membrane antigen; ER, that formed 50% of tumour in size within the prior six months, but had no history of cells; and PR, ‎‎that formed 5% of tumour cells (Figure a lump in the breast or discharge from the nipple. The 2,7,8,9,10 ). patient mentioned that this axillary mass had been present since puberty but had been gradually increasing IHC results were exclusively positive; HER2, in size. The patient had a negative family history of BerEP4 (histologic stain used to aid in the diagnosis of malignancy and ultrasound (USG) breast screening was basal cell carcinoma), mammoglobulin (highly specific performed which showed no mass in the breast. for most breast cancers), CK5/6 (aid to differentiate Multiple lymph nodes were seen, however, in the left between mesothelioma and other forms of cancer), axilla, with the largest lymph node being 4.4 x 3.5 cm thyroid transcription factor-1 (sensitive marker for (Figure 4, 5, 6). pulmonary and thyroid adenocarcinomas), CD10 (sensitive immunohistochemical marker of normal On the 18th of January 2012, tissue biopsy was endometrial stroma), smooth muscle actin (aid in taken from the left axillary mass which measured 4.5 diagnosis of ovarian carcinoma), S100 (common cm in maximum diameter, weighed 30 g, and to which marker of neural tissue/lesions and bio-section showed a greyish-‎‎‎white solid cut surface melanoma), ‎chromogranin (aid in diagnosis of carcinoid with pinkish and yellowish areas (Figure 3). Four tumours), synaptophysin (neuroendocrine marker), blocks ‎representing ‎the ‎whole ‎cross-section of the CK20, P63 (rules out invasion in breast tumours by tumour were embedded in three ‎cassettes.‎‏ determining presence of myoepithelial cells), and P53 Microscopically the sections showed lobules of a all ‎showed ‎ anegative ‎reaction.‎ Therefore, malignant epithelial the ‎possibilities of neuroendocrine, primary lung, tumour ‎involving ‎the ‎subcutaneous ‎adipose ‎tissue, primary renal tumours‎, among ‎others ‎were dermis, and reaching up to the overlying epidermis. ‎It not ‎supported by the IHC results‎‏. Reports showed showed ‎large ‎areas of ‎partial or ‎complete ischaemic moderate to poorly differentiated adenocarcinoma in necrosis, scattered mitotic figures, and tumour cells favour of primary breast cancer (Table 2). 3

Iman Moustafa and M Essam Badawy; IAR J Med Cse Rep; Vol-1, Iss- 1 (Sep-Oct, 2020): 1-7

Table 2: Immunohistochemistry test results Test Reaction Comment CK AE /1/3 ✓ Suggestive of lymph node micrometastases. CK7 ✓ Oestrogen receptor (that formed 50% of tumour cells) and progesterone receptor (‎‎that formed 5% of tumour cells). EMA ✓ Epithelial membrane antigen. HER-‎‎2 ✓ Human epidermal growth factor receptor 2. BerEP4 Negative Histologic stain used to aid in the diagnosis of basal cell carcinoma.

Mammoglobulin Negative Highly specific for most breast cancers.

CK5/6 Negative Cytokeratin 5/6: help to differentiate between mesothelioma and other forms of cancer.

TTF-‎‎1 Negative Thyroid transcription factor-1: sensitive marker for pulmonary and thyroid adenocarcinomas. CD10 Negative Sensitive immunohistochemically marker of normal endometrial stroma. Negative Smooth Muscle Actin aid in diagnosis of ovarian carcinoma. SMA S100 Negative Common marker of neural tissue/lesions and melanoma. CgA Negative Chromogranin help diagnose carcinoid tumours. Synaptophysin ‎Negative ‎ Common neuroendocrine marker.

CK20 ‎Negative ‎ Cytokeratin 20.

p63 ‎Negative (Rule out invasion in breast tumours by determining presence of myoepithelial cells).

p53 ‎ ‎eNiaageN Tumour marker in early stages of lung, skin, head and neck, and oesophageal cancer. (CA 15-3) High Tumour marker for breast cancer. 7.101 CA 125 Normal Tumour marker for breast cancer.

‎ On the first ‏March‎1023, the patient was well. The patient then underwent radiotherapy and referred to medical oncologists for further management hormonal therapy (tamoxifen 20 mg oral daily). She and ‏workup. Chest, abdomen, and pelvis CT scans were underwent follow-up ‎every 6 months until present. To performed to rule out any primary sites, which all came assess the prognosis for the case, the Nottingham back negative, and only the left axillary lymph node prognostic index for breast cancer was used. It gave an was seen to be involved. Bone scan results, as well as index value of 4.6, placing it in the moderate group, upper gastrointestinal endoscopy and colonoscopy with 5 year survival (Todd, J. H. et al., 1987). The NHS results investigating for primary tumours, were also Predict tool was applied as well for prognostic negative, and there were no signs of any malignancy.‏ assessment, including hormonal status, and showed a MRI of the breast revealed no pathology apart from result of 10 years survival (NHS. 2019). In 2020, after 7 multiple axillary lymph nodes.‏‏ Tumour markers; cancer years of starting the treatment, the patient is doing well, antigen-breast (CA 15-3) was high at 7.101 and ‏CA 125 free from any ‎signs of malignancy, recurrence, or was normal (Table 2). complications. The mammography (MMG) results were negative. In April ‏‎2013‎‏, ‏she ‎underwent left axillary clearance and the histopathology report confirmed DISCUSSION primary breast adenocarcinoma. Accessory breast is a congenital condition ‎‎On the ‎‏19th of ‎May ‎‏2013, the patient received when accessory normal breast tissue is present aa‎ chemotherapy; AC protocol ‏doxorubicin 60 mg/m2 ‎and aanormal sites (Patel, P. P. et al., 2012). ‎Accessory cyclophosphamide 600 mg/m2 every 21 days for 4 breast is also known as polymastia, supernumerary cycles, followed by 4 ‎cycles of ‎paclitaxel 175 mg/m2 breasts, auxiliary breast, ectopic breast, adnexal, or and 17 cycles of Trastuzumab(first cycle 8mg /kg as mammae erraticae. These types of breasts sometimes loading dose then 6mg/kg for subsequent doses) . appear to have/lack nipples or areolae, making them Every cycle was 21 days and the patient tolerated it ambiguous (Zhang, R. R. et al., 2012). 4

Iman Moustafa and M Essam Badawy; IAR J Med Cse Rep; Vol-1, Iss- 1 (Sep-Oct, 2020): 1-7

In Caucasians the incidence of ectopic breast Cancer of ectopic breasts is depicted as a tissue is 1–4%, while it is more frequent in the Far East, typical malignant mass with the same characteristics of especially Japan, among both genders. Its incidence rate those of metastatic axillary lymph nodes associated was evaluated as 5.19% in Japanese women, and as with malignant tumour. No specific findings for 1.68% in Japanese men with hereditary factor (Önel, S. accessory breast cancer are detected (Adler, D. D. et al., et al., 2013). These abnormal tissues are most 1987). Using MRI, the signal intensity of ectopic breast frequently seen in the axilla, followed by the area just tissue is similar to that of the adjacent breast tissue, but lower and in half of the cases this abnormality is shown with variability of the amount of interspersed fat. on both sides(Önel, S. et al., 2013). In rare cases it was Pathological confirmation through fine needle reported in some other areas including the acromial or aspiration cytology or Tru-cut® biopsy of the mass scapular region, vulva, and in the midline of the thorax should be performed to harvest suspect cells or tissue. and abdomen (Chung-Park, M. et al., 2002). Ectopic Invasive ductal carcinoma, like in traditional breast breasts enlarge during pregnancy and lactation and may cancer, is the most common histological type with 79% lactate if they have a working ductal system. of all accessory breast cancer (Francone, E. et al., Breastfeeding from ectopic breasts was reported (Önel, 2013). S. et al., 2013). Disorders of breast tissue such as adenofibroma, cysts, and carcinomas have also been Lobular, mucinous, medullary, apocrine, and reported in ectopic breasts similar to normal breast papillary carcinomas are detected in these cases and tissue and carcinomas are rare (Avilés Izquierdo, J. et cystosarcoma phyllodes are also described. In 2009, al., 2005; Shin, S. J. et al., 2001; & Pardo, M. et al., Nihon-Yanagi et al., (2011) found that medullary, 2001). The types of carcinoma seen within the ectopic mucinous, and apocrine carcinomas were more breast tissue include ductal, lobular, mucinous, common among accessory breast cancer for unknown medullary, papillary, and invasive secretory (juvenile) reasons. carcinomas (Chung-Park, M. et al., 2002; Shin, S. J. et al., 2001; & Pardo, M. et al., 2001). Regarding the management, surgical interference of accessory breast cancer combines wide Ectopic breast tissue develops embryologically resection of the tumour with surrounding tissue, skin, because of failed resolution of the mammary ridge or and axillary lymph nodes dissection.18 Ipsilateral milk line. An ectodermal tissue extends from the axilla mastectomy has no additional benefit regarding survival to the inguinal folds and shows in the 6th week of considering that MMG and USG of the anatomic breast gestation. The axilla is the most frequent site followed are normal, as was in the present case, but should be by the area inferior to the normal breast and may appear performed when differential diagnosis is challenging in anywhere along the milk line (Cherrabi, F. et al., 2018). some situations.18

Hormonal influences affect ectopic breast In 2015, Zhang, S. et al., (2015) recommended tissue, just as they would in a healthy breast, and can mastectomy if the accessory breast is closely connected develop similar types of benign and malignant to normal breast tissue, otherwise it is unnecessary. disorders. Fibroadenomas, cysts, duct hyperplasia, and infrequently carcinoma can arise (Zhang, S. et al., 2015; The same regimens and protocols for & Abisowo, O. Y. et al., 2017). The incidence of postoperative treatment are used for anatomic breast accessory breast cancer as per reports is between 0.3% carcinoma. Radiotherapy of the tumour site is and 0.6% of all breast cancers (Abisowo, O. Y. et al., recommended to control local spread, and radiation of 2017). the ipsilateral anatomic breast is not usually performed. Adjuvant therapy is mostly required because lymph Ectopic primary breast cancer in the axilla node disease is usually also present. The prognosis of comprises 60–70% of all cases reported (Nihon-Yanagi, accessory breast cancer is difficult to assess due to Y. et al., 2011). Differential diagnosis of the accessory limited follow-up and staging data as well as small breast cancer includes many disorders. In the axillary sample size. Some authors have reported worse area, it can be confused with lipoma, lymphoma, outcomes of accessory breast cancer than other lymphadenitis, metastatic lymphadenopathy, sebaceous anatomic breast cancer as the tumour is near the axillary cyst, and hidradenitis suppurativa. MMG and USG of lymph nodes and is therefore exposed to early the breast can aid the exclusion of other breast metastasis to these nodes (Zhang, S. et al., 2015). pathologies. USG can also detect ectopic breast tissue 94 Japanese cases were reviewed in a report in as an echogenic area resembling normal glandular 2009 and indicated that accessory breast cancer has a tissue, as well as detect characteristics of the mass. higher risk of lymph node metastasis than usual breast MMG cannot capture ectopic breasts because of their cancer (Nihon-Yanagi, Y. et al., 2011). peculiar location, but it can be visualised in the axilla by oblique and exaggerated craniocaudal views (Adler, Accessory breast tissue is more disposed to D. D. et al., 1987). malignant change than normal breast tissue. No definite

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Iman Moustafa and M Essam Badawy; IAR J Med Cse Rep; Vol-1, Iss- 1 (Sep-Oct, 2020): 1-7 number is reported for the incidence of accessory breast endoscopy, but all results were negative for the cancer among population (Gilmore, H. T. et al., 1996). detection of unknown primary tumours. Accessory breast cancer patients experience clinical presentations as swelling, thickening, tenderness, A Tumour board committee was held to irritation, and sometimes limited motion of shoulder. discuss this case and it was agreed that it is a primary These symptoms are commonly exacerbated at the accessory breast tumour because no original tumour onset of puberty and pregnancy (Lesavoy, M. A. et al., could be detected in the breast, adnexa, colon, or lung. 1995). Accessory breast cancer is a rare entity and has a The histopathology was in favour of primary breast substantial chance for misdiagnosis especially when since CA 15-3 high and ER and PR were positive as there is an absence of anatomical breast structure such well as previous case reports and literature review for as the nipple and areola (Loukas, M. et al., 2007). The similar cases. accessory breast may also not show up; therefore, MRI can be used to differentiate it from the normal breast The patient was staged as Stage IIB, ER/PR tissue (Laor, T. et al., 2004). positive and HER2/neu negative poorly differentiated adenocarcinoma. The diagnosis as well as symptoms of accessory breast carcinoma are the same as for‎asNara The patient was treated with common breast carcinoma (Pardo, M. et al., 2001), except for some carcinoma methods following NCCN guideline 2012 differences including excess axillary fat, lymphadenitis, (National Comprehensive Cancer Network. 2012) by lymphoma, ‎metastatic carcinoma, and hidradenitis surgery followed by chemotherapy. This included four suppurativa (Jatoi, I., & Rody, A. 2016). Accessory cycles of AC and 4 cycles of docetaxel followed by a breast cancer is ‎diagnosed as breast carcinoma using 50 g radiotherapy and tamoxifen for 5 years, and cancer MMG and ‎USG, followed by pathologic diagnosis by antigen (CA 15-3) showed a significant decline after fine needle aspiration cytology or core biopsy (Roorda, treatment (Figure 1). A. K. et al., 2002). The mammogram is an effective tool for the Prognosis of accessory breast cancer is assessment of breast carcinoma but not for accessory difficult to institute because of the absence or limited breast cancer assessment. Core tissue biopsy especially follow-up data as well as the small sample size (Evans, when accompanied by IHC is a very effective tool for D. M., & Guyton, D. P. 1995), in our follow-up case the early diagnosis and treatment of accessory breast patient is stable with very good performance status for 7 carcinoma (Sookar, N. et al., 2018). years and without any complications.

The presented case was very perplexing CONCLUSION because it was a rare condition for primary axillary breast cancer. The lack of areola and nipple (according Accessory breast cancer is an uncommon type to Kajava classification 1915‎‏ this case classified as of cancer and the incidence of it has no definite number. class IV) made the clinical diagnosis very difficult, The diagnosis of these cases is challenging, and confounded by the IHC results not being conclusive. misdiagnosis will lead to extensive and unnecessary This lead to extensive and unnecessary lab tests and investigations. Despite the fact that carcinoma arising in investigations. The possibility of the normal breast axilla as a primary site is a rare condition, still the being the primary site was not supported by negative possibility of accessory breast cancer should still be staining of mammoglobulin, gross cystic disease fluid considered. ‎Management of accessory breast cancer protein. Furthermore, IHC did not support the should follow the same guidelines for breast cancer. It possibilities of a neuroendocrine tumour or the lung, is important to encourage follow up data for these cases and the kidney as the primary sites. to establish the prognosis of accessory breast cancer comparing breast carcinoma. In the beginning the case was suspected to be a metastatic adenocarcinoma with small components of Funding and Conflict of Interest mucinous carcinoma; however, the lymph nodes were No potential conflicts of interest positive (13/15) with large deposits of carcinoma replacing most of the lymph node structure favouring REFERENCES primary breast including the possibility of axillary 1. Abisowo, O. Y., Oyinyechi, A. J., Olusegun, F. A., (accessory) primary breast. The possibilities included Oyedokun, O. Y., Motunrayo, A. F., & Abimbola, breast, and to a lesser extent, primary adnexal tumour. O. T. (2017). Feto-maternal outcome of induced Oncologists were not satisfied about histopathology versus spontaneous labour in a Nigerian Tertiary results, and so all thoughts were redirected towards it Maternity Unit. Tropical Journal of Obstetrics and being a secondary tumour from the breast or other sites. Gynaecology, 34(1), 21-27. As such, more investigations were requested including 2. Adler, D. D., Rebner, M., & Pennes, D. R. (1987). CT, MRI, CA 125, and upper gastrointestinal Accessory breast tissue in the axilla:

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