VOLUME
32
䡠
NUMBER
10
䡠
APRIL
1
2014
JOURNAL OF CLINICAL ONCOLOGY
Breast Cancer Occurring in the Chest Wall: Rare Presentation of Ectopic Milk Line Breast Cancer Case Report An 82-year-old woman presented with a skin change on her chest wall. Her oncologic medical history was remarkable for a diagnosis of resected left cheek malignant melanoma at age 56 and left breast cancer diagnosed at the age of 62 and treated with modified radical mastectomy. Final pathology at that time revealed grade 4 infiltrating ductal adenocarcinoma 1.0 ⫻ 1.0 ⫻ 0.8 cm in size, positive for both progesterone and estrogen receptors. Thirteen lymph nodes were removed, and all were negative. The patient completed 5 years of tamoxifen and was followed up with on a yearly basis with history and physical exam without evidence of recurrence of her cancer. Fifteen years later, the patient presented for her yearly checkup. She reported about 2 weeks of pain associated with a small lump located on the right anterior chest on the lower aspect of her rib cage, 2 cm below her breast. On surgical evaluation it was noted to be 6 to 7 mm in size, slightly mobile lesion most consistent with a sebaceous cyst, fibroma, or lipoma. Local excision was recommended. Pathology evaluation revealed infiltrating ductal carcinoma estrogen strongly positive, progesterone focally positive, and human epidermal growth factor receptor negative, Nottingham grade 2 with associated highgrade ductal carcinoma in situ (present in resected chest wall lesion; Fig 1). Carcinoma extended to the excision margins. The patient was seen by the Medical Oncology Department in follow-up; at that time, she recalled that about 60 years previously, she had a small skin lesion in that area that was excised after it lactated while she was breast feeding.
Fig 1. Journal of Clinical Oncology, Vol 32, No 10 (April 1), 2014: pp e35-e36
D I A G N O S I S
I N
O N C O L O G Y
Given this history and findings of ductal carcinoma in situ on the pathology specimen, wide local excision was recommended, followed by 5 years of treatment with an aromatase inhibitor for second primary infiltrating ductal carcinoma in an extra mammary breast tissue. Final pathology report from the wide local excision revealed focal residual ductal carcinoma in situ and associated biopsy site changes. All surgical margins were negative for tumor with the closest free margin being 0.3 cm to the deep margin. Discussion The exact incidence of polymastia (supernumerary breasts) and polythelia (supernumerary nipples) is uncertain and ranges from 0.22% to 0.6% in Caucasians to 3.5% in African Americans, although there are reports describing it in up to 6% of the population. It is much more common in females.1,2 Kajave additionally classified different presentations of ectopic breast tissue into eight categories ranging from complete breast with nipple, areola, and glandular tissue (polymastia) to only a patch of hair (polythelia pilosis).2 The most common location of ectopic breast tissue is in the axilla with differing frequency reported for other locations along the so-called milk line, including vulva, subclavicular, parasternal, and submammary locations. However, extramammary nipples (so-called mammae erraticae) have been found in other locations outside of the milk line, including buttock, flank, upper arm, shoulders, hip, extremities, face, or neck.1,2 Milk lines develop as two surface thickenings extend from the axillary region to the groin at between 4 and 6 weeks of embryonic development. After forming mammary ridges in 2 to 3 months, they eventually regress completely except for the two areas that form breasts. Ectopic breast tissue responds to hormonal stimulation. Therefore, extramammary breast tissue may become symptomatic during puberty, pregnancy, and lactation. It can also undergo malignant transformation similar to normal anatomic breasts.1,2 Malignancies encountered in ectopic breast tissue include ductal and lobular carcinoma, secretory carcinoma, mucinous adenocarcinoma, apocrine carcinomas, medullary carcinomas, metaplastic carcinoma, and phyllodes tumor.3-5 A large literature review of ectopic breast cancers from 2009 by Nihon-Yanagi3 reports a total of 94 patients described since 1978. Most patients’ tumors were estrogen receptor positive (61%), and 51% had lymph node metastases at the time of diagnosis. Ectopic breast cancer is found most commonly in the axilla and comprises 91% of ectopic breast cancers.3 It needs to be differentiated from the tumor originating from cutaneous adnexal glands and from metastatic breast cancer. Diagnosis may be clear if there is underlying normal breast parenchyma detectable; however, absence of normal breast tissue does not rule out ectopic breast cancer.6 Immunohistochemical markers are useful but may not be enough to distinguish the tissue of origin, and so location of the neoplasm within the axilla and the composition of surrounding tissue may be essential for diagnosis.7 Finding of concurrent lesion in the breast tissue nearly always proves © 2014 by American Society of Clinical Oncology
Information downloaded from jco.ascopubs.org and provided by at Northeastern University on October 4, 2014 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 155.33.16.124
e35
Wysokinska and Keeney
that axillary changes are metastatic; however, there are reports of proliferative changes in breast and axilla occurring independently of each other.8 In the largest review to date, by Visconti et al,9 of ectopic breast cancer presenting in the axilla, summarizing 170 patients described in the literature since 1861, the median age at diagnosis was 51 with mean delay to diagnosis of 40.5 months. The most frequent histology was invasive ductal carcinoma (72%), followed by invasive lobular and medullary carcinoma (12%). Authors speculate that poorer prognosis in patients may result from diagnostic delay related to low clinical suspicion. The second most common location for ectopic breast cancer is in the vulva, with the first case reported by Greene10 in 1935. On the basis of a 1998 review,11 the mean age of onset is 62 years, unlike a median of age 72 years for primary vulvar cancer. Determining whether vulvar lesions are actually derived from ectopic breast cancer tissue or from transformation of anogenital glands may be challenging. Some of the criteria include presence of an in situ component, morphologic pattern consistent with breast cancer, presence of estrogen and progesterone receptors, and/or positivity for common breast cancer markers.11-13 Primary ectopic breast cancer in the vulvar location may also occur simultaneously with malignant breast changes.14 The anterior chest wall is a rare location of ectopic breast cancer. In a review article, Da Silva15 describes 12 cases reported in the literature between 1966 and 2007. To our knowledge, ours would be a 16th case described in the literature since 1966.15,16 The treatment for ectopic breast cancer is the same as for similar-stage cancer located in the breast and includes surgery with or without lymph node dissection, radiation, chemotherapy, and hormonal therapy.3,9,13 What makes our case especially interesting is the patient’s prior history of a contralateral hormone receptor–positive breast cancer. The patient would have been diagnosed with recurrent, metastatic breast cancer had there not been ductal carcinoma in situ on histopathology. To our knowledge, this is the only case describing a new ectopic breast cancer occurring in a patient with prior history of breast cancer. In conclusion, ectopic breast tissue is found in up to 6% of the female population and may undergo malignant transformation. Ectopic breast cancer needs to be considered in cases when malignant breast tissue is found in the axilla, vulva, or a chest wall lesion. The possibility of a second primary ectopic breast cancer also needs to be kept in mind in patients with prior history of orthotopic breast cancer when a new malignant lesion is found in the milk line distribution.
Ewa M. Wysokinska and Gary Keeney Mayo Clinic, Rochester, MN
ACKNOWLEDGMENT
We thank Harry Long, MD, for substantial contributions to this article. Long died unexpectedly on January 20, 2013. He was the primary oncologist involved in this case, and without his mentorship, encouragement, and support, this article could not have been written/created. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest. REFERENCES 1. Grossl NA: Supernumerary breast tissue: Historical perspectives and clinical features. South Med J 93:29-32, 2000 2. Velanovich V: Ectopic breast tissue, supernumerary breasts and supernumerary nipples. South Med J 88:903-906, 1995 3. Nihon-Yanagi Y, Ueda T, Kameda N, et al: A case of ectopic breast cancer with a literature review. Surg Oncol 20:35-42, 2011 4. van Herwaarden-Lindeboom MY, van Hillegersberg R, van Diest PJ: Ectopic lobular breast cancer on the anterior chest wall: A rare entity. J Clin Pathol 60:940-941, 2007 5. Caceres M, Shih J, Eckert M, et al: Metaplastic carcinoma in an ectopic breast. South Med J 95:462-466, 2002 6. Toman N, Buschmann A, Muehlberger T: Ectopic breast cancer without breast parenchyma. Breast 17:3-4, 2008 7. Brandt SM, Swistel AJ, Rosen PP: Secretory carcinoma in the axilla: Probable origin from axillary skin appendage glands in a young girl. Am J Surg Pathol 33:950-953, 2009 8. Dzodic R, Stanojevic B, Saenko V, et al: Intraductal papilloma of ectopic breast tissue in axillary lymph node of a patient with a previous intraductal papilloma of ipsilateral breast: A case report and review of the literature. Diagn Pathol 5:17, 2010 9. Visconti G, Eltahir Y, Van Ginkel RJ, et al: Approach and management of primary ectopic breast carcinoma in the axilla: Where are we? A comprehensive historical literature review. J Plast Reconstr Aesthet Surg 64:e1-e11, 2011 10. Greene HJ: Adenocarcinoma of supernumerary breasts of the labia majora in a case of epidermoid carcinoma of the vulva. Am J Obstet Gynecol 31:660-663, 1935 11. Irvin WP, Cathro HP, Grosh WW, et al: Primary breast carcinoma of the vulva: Case report and review of literature. Gynecol Oncol 73:155-159, 1999 12. Ohira S, Itoh K, Osada K: Vulvar Paget’s disease with underlying adenocarcinoma simulating breast carcinoma: Case report and review of the literature. Int J Gynecol Cancer 14:1012-1017, 2004 13. Fracchioli S, Puopolo M, de la Lograis IA, et al: Primary “breast-like” cancer of the vulva: A case report and critical review of the literature. Int J Gynecol Cancer 16:423-428, 2006 (suppl 1) 14. Intra M, Maggioni A, Sonzogni A, et al: A rare association of synchronous intraductal carcinoma of the breast and invasive carcinoma of ectopic breast tissue of the vulva: Case report and literature review. Int J Gynecol Cancer 16:428-433, 2006 (suppl 1) 15. da Silva BB, dos Santos AR, Pires CG, et al: Ectopic breast cancer in the anterior chest wall: A case report and literature review. Eur J Gynaecol Oncol 29:653-655, 2008 16. Ogino T, Ishitobi M, Komoike Y, et al: Ectopic breast cancer located in the anterior chest wall. Breast 16:320-321, 2010
DOI: 10.1200/JCO.2012.47.8958; published online ahead of print at www.jco.org on January 21, 2014 ■ ■ ■
e36
© 2014 by American Society of Clinical Oncology
JOURNAL OF CLINICAL ONCOLOGY
Information downloaded from jco.ascopubs.org and provided by at Northeastern University on October 4, 2014 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 155.33.16.124
32
䡠
NUMBER
10
䡠
APRIL
1
2014
JOURNAL OF CLINICAL ONCOLOGY
Breast Cancer Occurring in the Chest Wall: Rare Presentation of Ectopic Milk Line Breast Cancer Case Report An 82-year-old woman presented with a skin change on her chest wall. Her oncologic medical history was remarkable for a diagnosis of resected left cheek malignant melanoma at age 56 and left breast cancer diagnosed at the age of 62 and treated with modified radical mastectomy. Final pathology at that time revealed grade 4 infiltrating ductal adenocarcinoma 1.0 ⫻ 1.0 ⫻ 0.8 cm in size, positive for both progesterone and estrogen receptors. Thirteen lymph nodes were removed, and all were negative. The patient completed 5 years of tamoxifen and was followed up with on a yearly basis with history and physical exam without evidence of recurrence of her cancer. Fifteen years later, the patient presented for her yearly checkup. She reported about 2 weeks of pain associated with a small lump located on the right anterior chest on the lower aspect of her rib cage, 2 cm below her breast. On surgical evaluation it was noted to be 6 to 7 mm in size, slightly mobile lesion most consistent with a sebaceous cyst, fibroma, or lipoma. Local excision was recommended. Pathology evaluation revealed infiltrating ductal carcinoma estrogen strongly positive, progesterone focally positive, and human epidermal growth factor receptor negative, Nottingham grade 2 with associated highgrade ductal carcinoma in situ (present in resected chest wall lesion; Fig 1). Carcinoma extended to the excision margins. The patient was seen by the Medical Oncology Department in follow-up; at that time, she recalled that about 60 years previously, she had a small skin lesion in that area that was excised after it lactated while she was breast feeding.
Fig 1. Journal of Clinical Oncology, Vol 32, No 10 (April 1), 2014: pp e35-e36
D I A G N O S I S
I N
O N C O L O G Y
Given this history and findings of ductal carcinoma in situ on the pathology specimen, wide local excision was recommended, followed by 5 years of treatment with an aromatase inhibitor for second primary infiltrating ductal carcinoma in an extra mammary breast tissue. Final pathology report from the wide local excision revealed focal residual ductal carcinoma in situ and associated biopsy site changes. All surgical margins were negative for tumor with the closest free margin being 0.3 cm to the deep margin. Discussion The exact incidence of polymastia (supernumerary breasts) and polythelia (supernumerary nipples) is uncertain and ranges from 0.22% to 0.6% in Caucasians to 3.5% in African Americans, although there are reports describing it in up to 6% of the population. It is much more common in females.1,2 Kajave additionally classified different presentations of ectopic breast tissue into eight categories ranging from complete breast with nipple, areola, and glandular tissue (polymastia) to only a patch of hair (polythelia pilosis).2 The most common location of ectopic breast tissue is in the axilla with differing frequency reported for other locations along the so-called milk line, including vulva, subclavicular, parasternal, and submammary locations. However, extramammary nipples (so-called mammae erraticae) have been found in other locations outside of the milk line, including buttock, flank, upper arm, shoulders, hip, extremities, face, or neck.1,2 Milk lines develop as two surface thickenings extend from the axillary region to the groin at between 4 and 6 weeks of embryonic development. After forming mammary ridges in 2 to 3 months, they eventually regress completely except for the two areas that form breasts. Ectopic breast tissue responds to hormonal stimulation. Therefore, extramammary breast tissue may become symptomatic during puberty, pregnancy, and lactation. It can also undergo malignant transformation similar to normal anatomic breasts.1,2 Malignancies encountered in ectopic breast tissue include ductal and lobular carcinoma, secretory carcinoma, mucinous adenocarcinoma, apocrine carcinomas, medullary carcinomas, metaplastic carcinoma, and phyllodes tumor.3-5 A large literature review of ectopic breast cancers from 2009 by Nihon-Yanagi3 reports a total of 94 patients described since 1978. Most patients’ tumors were estrogen receptor positive (61%), and 51% had lymph node metastases at the time of diagnosis. Ectopic breast cancer is found most commonly in the axilla and comprises 91% of ectopic breast cancers.3 It needs to be differentiated from the tumor originating from cutaneous adnexal glands and from metastatic breast cancer. Diagnosis may be clear if there is underlying normal breast parenchyma detectable; however, absence of normal breast tissue does not rule out ectopic breast cancer.6 Immunohistochemical markers are useful but may not be enough to distinguish the tissue of origin, and so location of the neoplasm within the axilla and the composition of surrounding tissue may be essential for diagnosis.7 Finding of concurrent lesion in the breast tissue nearly always proves © 2014 by American Society of Clinical Oncology
Information downloaded from jco.ascopubs.org and provided by at Northeastern University on October 4, 2014 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 155.33.16.124
e35
Wysokinska and Keeney
that axillary changes are metastatic; however, there are reports of proliferative changes in breast and axilla occurring independently of each other.8 In the largest review to date, by Visconti et al,9 of ectopic breast cancer presenting in the axilla, summarizing 170 patients described in the literature since 1861, the median age at diagnosis was 51 with mean delay to diagnosis of 40.5 months. The most frequent histology was invasive ductal carcinoma (72%), followed by invasive lobular and medullary carcinoma (12%). Authors speculate that poorer prognosis in patients may result from diagnostic delay related to low clinical suspicion. The second most common location for ectopic breast cancer is in the vulva, with the first case reported by Greene10 in 1935. On the basis of a 1998 review,11 the mean age of onset is 62 years, unlike a median of age 72 years for primary vulvar cancer. Determining whether vulvar lesions are actually derived from ectopic breast cancer tissue or from transformation of anogenital glands may be challenging. Some of the criteria include presence of an in situ component, morphologic pattern consistent with breast cancer, presence of estrogen and progesterone receptors, and/or positivity for common breast cancer markers.11-13 Primary ectopic breast cancer in the vulvar location may also occur simultaneously with malignant breast changes.14 The anterior chest wall is a rare location of ectopic breast cancer. In a review article, Da Silva15 describes 12 cases reported in the literature between 1966 and 2007. To our knowledge, ours would be a 16th case described in the literature since 1966.15,16 The treatment for ectopic breast cancer is the same as for similar-stage cancer located in the breast and includes surgery with or without lymph node dissection, radiation, chemotherapy, and hormonal therapy.3,9,13 What makes our case especially interesting is the patient’s prior history of a contralateral hormone receptor–positive breast cancer. The patient would have been diagnosed with recurrent, metastatic breast cancer had there not been ductal carcinoma in situ on histopathology. To our knowledge, this is the only case describing a new ectopic breast cancer occurring in a patient with prior history of breast cancer. In conclusion, ectopic breast tissue is found in up to 6% of the female population and may undergo malignant transformation. Ectopic breast cancer needs to be considered in cases when malignant breast tissue is found in the axilla, vulva, or a chest wall lesion. The possibility of a second primary ectopic breast cancer also needs to be kept in mind in patients with prior history of orthotopic breast cancer when a new malignant lesion is found in the milk line distribution.
Ewa M. Wysokinska and Gary Keeney Mayo Clinic, Rochester, MN
ACKNOWLEDGMENT
We thank Harry Long, MD, for substantial contributions to this article. Long died unexpectedly on January 20, 2013. He was the primary oncologist involved in this case, and without his mentorship, encouragement, and support, this article could not have been written/created. AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST
The author(s) indicated no potential conflicts of interest. REFERENCES 1. Grossl NA: Supernumerary breast tissue: Historical perspectives and clinical features. South Med J 93:29-32, 2000 2. Velanovich V: Ectopic breast tissue, supernumerary breasts and supernumerary nipples. South Med J 88:903-906, 1995 3. Nihon-Yanagi Y, Ueda T, Kameda N, et al: A case of ectopic breast cancer with a literature review. Surg Oncol 20:35-42, 2011 4. van Herwaarden-Lindeboom MY, van Hillegersberg R, van Diest PJ: Ectopic lobular breast cancer on the anterior chest wall: A rare entity. J Clin Pathol 60:940-941, 2007 5. Caceres M, Shih J, Eckert M, et al: Metaplastic carcinoma in an ectopic breast. South Med J 95:462-466, 2002 6. Toman N, Buschmann A, Muehlberger T: Ectopic breast cancer without breast parenchyma. Breast 17:3-4, 2008 7. Brandt SM, Swistel AJ, Rosen PP: Secretory carcinoma in the axilla: Probable origin from axillary skin appendage glands in a young girl. Am J Surg Pathol 33:950-953, 2009 8. Dzodic R, Stanojevic B, Saenko V, et al: Intraductal papilloma of ectopic breast tissue in axillary lymph node of a patient with a previous intraductal papilloma of ipsilateral breast: A case report and review of the literature. Diagn Pathol 5:17, 2010 9. Visconti G, Eltahir Y, Van Ginkel RJ, et al: Approach and management of primary ectopic breast carcinoma in the axilla: Where are we? A comprehensive historical literature review. J Plast Reconstr Aesthet Surg 64:e1-e11, 2011 10. Greene HJ: Adenocarcinoma of supernumerary breasts of the labia majora in a case of epidermoid carcinoma of the vulva. Am J Obstet Gynecol 31:660-663, 1935 11. Irvin WP, Cathro HP, Grosh WW, et al: Primary breast carcinoma of the vulva: Case report and review of literature. Gynecol Oncol 73:155-159, 1999 12. Ohira S, Itoh K, Osada K: Vulvar Paget’s disease with underlying adenocarcinoma simulating breast carcinoma: Case report and review of the literature. Int J Gynecol Cancer 14:1012-1017, 2004 13. Fracchioli S, Puopolo M, de la Lograis IA, et al: Primary “breast-like” cancer of the vulva: A case report and critical review of the literature. Int J Gynecol Cancer 16:423-428, 2006 (suppl 1) 14. Intra M, Maggioni A, Sonzogni A, et al: A rare association of synchronous intraductal carcinoma of the breast and invasive carcinoma of ectopic breast tissue of the vulva: Case report and literature review. Int J Gynecol Cancer 16:428-433, 2006 (suppl 1) 15. da Silva BB, dos Santos AR, Pires CG, et al: Ectopic breast cancer in the anterior chest wall: A case report and literature review. Eur J Gynaecol Oncol 29:653-655, 2008 16. Ogino T, Ishitobi M, Komoike Y, et al: Ectopic breast cancer located in the anterior chest wall. Breast 16:320-321, 2010
DOI: 10.1200/JCO.2012.47.8958; published online ahead of print at www.jco.org on January 21, 2014 ■ ■ ■
e36
© 2014 by American Society of Clinical Oncology
JOURNAL OF CLINICAL ONCOLOGY
Information downloaded from jco.ascopubs.org and provided by at Northeastern University on October 4, 2014 from Copyright © 2014 American Society of Clinical Oncology. All rights reserved. 155.33.16.124
