Surg Today DOI 10.1007/s00595-014-0991-4
Case Report
Umbilical metastasis derived from breast cancer: report of a case Hajime Abe · Keiichi Yamazaki · Tsuyoshi Mori · Yuki Kawai · Yoshihiro Kubota · Tomoko Umeda · Mitsuaki Ishida · Tohru Tani
Received: 27 December 2013 / Accepted: 1 April 2014 © Springer Japan 2014
Abstract Umbilical metastases mainly arise from malignancies of the digestive and gynecological systems, but rarely from breast cancer. A 64-year-old woman with a history of breast cancer was referred to us for investigation of a painful lesion in the umbilicus. Immunohistochemical staining of a specimen obtained by biopsy from the nodule showed umbilical metastasis of breast cancer. After a work up, she was successfully treated with a combination of surgery and endocrine therapy. We report this case to reinforce that not all periumbilical tumoral deposits are consistent.
metastases from gastrointestinal or gynecological cancers [1–3], and known as “Sister Mary Joseph nodules” [4]. Sporadic cases of umbilical metastases originating from hematological malignancies or thoracic cancers have also been described. While breast cancers can spread to various parts of the body, umbilical metastasis from breast cancer is highly unusual. We report a rare case of umbilical metastasis from breast cancer.
Case report Keywords Umbilical metastasis · Breast cancer · Immunohistochemical staining
Introduction The most common benign umbilical mass is endometriosis, whereas malignant umbilical tumors are likely to be
H. Abe (*) · K. Yamazaki Breast Center, Bell Land General Hospital, 500‑3 Higashiyama, Naka‑ku, Sakai, Osaka 599‑8247, Japan e-mail: [email protected]‑med.ac.jp H. Abe · T. Mori · Y. Kawai · Y. Kubota · T. Umeda Division of Breast and General Surgery, Shiga University of Medical Science Hospital, Ōtsu, Japan M. Ishida Department of Clinical Laboratory Medicine and Division of Diagnostic Pathology, Shiga University of Medical Science, Ōtsu, Japan T. Tani Department of Surgery, Shiga University of Medical Science, Ōtsu, Japan
A 64-year-old woman with hypothyroidism was referred to our hospital for investigation of umbilical pain. The patient had been aware of slow-growing umbilical erosion for about a year. She had a history of estrogen receptor (ER)positive breast cancer, invasive ductal carcinoma without lymph-nodal metastasis (T1N0M0) 20 years earlier, for which she had received 2 years adjuvant endocrine therapy with tamoxifen. On physical examination, we noted a cutaneous nodule, approximately 3 × 2 cm in diameter, on the umbilicus (Fig. 1). The lesion was seen as a firm indurated nodule with erosion and the mobility in the subcutaneous tissue was poor. Laboratory test results revealed a slightly elevated level of the tumor marker CEA to 9.5 ng/ml (normal: 5.0 ng/ml), but all other results were within the normal ranges. Chest and abdominal computed tomography (CT) showed only the umbilical nodule (Fig. 2). Tissue biopsy of the umbilical nodule demonstrated adenocarcinoma arranged in foamy or tubular formation. These tumor cells had large oval nuclei and slightly eosinophilic cytoplasm. The tumor had invaded the surrounding fatty tissue and skin (Fig. 3). Immunohistochemical tissue staining was positive for cytokeratin 7 (CK7), gross cystic disease fluid protein-15 (GCDFP-15), ER and progesterone receptor
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Surg Today
of neoplastic cells. Positron emission tomography (PET) revealed increased 18F-fluorodeoxyglucose (FDG) uptake in the umbilicus that had late maximum standardized uptake value (SUVmax) 1.9 (Fig. 4). Thus, we diagnosed late recurrence of breast cancer localized to the umbilicus. The patient underwent wide excision of the lesion with clearance margins containing the umbilicus, followed by endocrine therapy of anastrazole (1 mg/day). She is remains well after 8 months of follow-up.
Discussion
Fig. 1 Umbilical nodule with erosion
Fig. 2 Computed tomography of the abdomen showed enhancement of the umbilical nodule
(PgR), and negative for cytokeratin 20 (CK20) and human epidermal growth factor receptor-2 (HER2). Based on these results, the pathology of the umbilical lesion was considered the same as that of the primary breast cancer. Staining for Ki67 showed a low proliferative index of 5–7 %
Fig. 3 Histological examination of the umbilical nodule revealed large oval nuclei and slightly eosinophilic cytoplasm tumor cells invading the surrounding fatty tissue and skin (a H&E, ×40, b H&E, ×200)
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This report describes a rare case of umbilical metastasis from breast cancer. According to our search of the literature, only 7 (1.7 %) of 407 umbilical metastases [3] were derived from breast cancer. Breast cancer is considered a chronic disease that can spread to various parts of body. The intrinsic sub-types triple-negative and HER2-positive, which reflect higher proliferation, predict early recurrence, whereas the luminal/HER2-negative subtype is considered a factor that predicts late recurrence, with the recurrence rate over 10 years reported as 5.8 % [5, 6]. The umbilical metastasis of any malignancy is an uncommon phenomenon, accounting for only 10 % of all secondary tumors that have spread to the skin [1]. The evaluation of an umbilical mass should be directed by suspicion of its being a metastatic deposit, keeping in mind its potential to be either a primary malignant umbilical lesion or a benign lesion. Malignant tumors can be primary or metastatic. Primary malignant umbilical tumors are rare and comprise mainly melanomas and squamous or basal cell carcinomas. The Sister Mary Joseph nodule is described as a malignant umbilical tumor usually associated with the advanced metastasizing of intra-abdominal cancer and generally indicates a poor prognosis [4]. These umbilical nodules usually present as a painful lump with irregular margins and a hard fibrous consistency. The surface may be ulcerated and necrotic, with either blood, serous, purulent, or mucinous discharge. Spread of metastatic carcinoma
Surg Today
analysis, GCDFP-15 is a marker for breast carcinoma [12, 13]. In fact, 55-72 % of breast carcinomas studied stained positively for GCDFP-15. The combination of CK7 and CK20 immunoprofiling has been helpful in identifying adenocarcinomas derived from different sites. CK7 is expressed in a wide variety of epithelial neoplasms, including the lung, salivary gland, endometrium, and breast, while CK20 is distributed predominantly in carcinomas of the colon and pancreas and in Merkel cell tumor of the skin. Breast carcinoma is known to be CK7-positive and CK20-negative [14]. In general, umbilical metastasis is associated with a poor prognosis consistent with advanced neoplastic disease, usually manifesting 2–11 months from the time of initial diagnosis [2]. Therapeutic prognosis in recent years has made possible the long-term survival of patients with certain types of cancer. The primary treatment for metastatic breast cancer is systemic therapy, with consideration of surgery for the palliation of symptoms after systemic treatment, although such surgery should be undertaken only if complete local clearance of tumor is obtained as in the present case [15]. We recommend that physicians be cognizant of changes to the umbilicus in patients with a history of breast cancer. Conflict of interest We declare no conflicts of interest.
References
Fig. 4 Positron emission tomography image revealed increased 18 F-fluorodeoxyglucose uptake in the umbilicus (arrows)
to the umbilical region has been hypothesized to occur by either contiguous spread of peritoneal cancer, hematogenous spread through arterial and venous systems, or lymphatic spread with extension along ligaments of embryonic origin, such as round ligament of liver, urachus, vitello intestinal duct remnant, and obliterated vitelline artery [7, 8]. It is the extensive vascular and lymphatic communications of the umbilicus, including axillary and thoracic sites, which allow the migration of tumor cells to the umbilicus from the breast [9]. Ultrasonography and CT scan of the tumor are invaluable in the diagnosis of umbilical tumors and help to exclude a primary benign neoplasm. Fine needle aspiration cytology is adequate to establish an easy diagnosis [10], and early biopsy is appropriate to evaluate the neoplasmatic nature of these lesions. Histology of the metastatic umbilical tumor usually reveals adenocarcinoma [11]. In immunohistochemical
1. Shetty MR. Metastatic tumors of the umbilicus: a review 19801989. J Surg Oncol. 1990;45:212. 2. Gabriele R, Conte M, Egidi F, Borghese M. Umbilical metastases: current viewpoint. World J Surg Oncol. 2005;3:13. 3. Galvan VG. Sister Mary Jopseph’s nodule. Ann Intern Med. 1998;128:410. 4. Bailey H. Demonstrations of physical signs in clinical surgery. 11th ed. Baltimore: Williams & Wilkins; 1949. p. 227. 5. Esserman LJ, Moore DH, Tsing PJ, Chu PW, Yau C, Ozanne E, et al. Biologic markers determine the risk and the timing of recurrence in breast cancer. Breast Cancer Res Treat. 2011;129:607–16. 6. Nishimura R, Osako T, Nishiyama Y, Tashima R, Nakano M, Fujisue M, et al. Evaluation of factors related to late recurrencelater than 10 years after the initial treatment-in primary breast cancer. Oncology. 2013;85:100–10. 7. Srinivasan R, Ray R, Nijhawan R. Metastatic cutaneous and subcutaneous deposits from internal carcinoma. An analysis of cases diagnosed by fine needle aspiration. Acta Cytol. 1993;37:894–8. 8. Powell FC, Cooper AJ, Massa MC, Goellner JR, Su WP. Sister Mary Joseph’s nodule: a clinical and histologic study. J Am Acad Dermatol. 1984;10:610–5. 9. Ching AS, Lai CW. Sonography of umbilical metastasis (Sister Mary Joseph’s nodule) from embryology to imaging. Abdom Imaging. 2002;27:746–9. 10. Schneider V, Smyczek B. Sister Mary joseph’s nodule. Diagnosis of umbilical metastases by fine needle aspiration. Acta Cytol. 1990;34:555–8. 11. Majmudar B, Wiskind AK, Croft BN, Dudley AG. The Sister (Mary) Joseph nodule: its significance in gynecology. Gynecol Oncol. 1991;40:152–9.
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12. Wick MR, Lillemoe TJ, Copland GT, Swanson PE, Manivel JC, Kiang DT. Gross cystic disease fluid protein-15 as a marker for breast cancer immunohistochemical analysis of 690 kuman neoplasms and comparison with alpha-lactalbumin. Hum Pathol. 1989;20:281–7. 13. Mazoujian G, Bodian C, Haagensen DE Jr, Haagensen CD. Expression of GCDFP-15 in breast carcinoma; relationship to pathologic and clinical factors. Cancer. 1989;63:2156–61.
13
Surg Today 14. Chu P, Wu E, Weiss LM. Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: a survey of 435 cases. Mod Pathol. 2000;13:962–72. 15. NCCN clinical Practice Guidelines in oncology. ver. 3, 2013. Breast Cancer. http://www.nccn.org/professionals/physisician_gl s/pdf/breast.pdf
Case Report
Umbilical metastasis derived from breast cancer: report of a case Hajime Abe · Keiichi Yamazaki · Tsuyoshi Mori · Yuki Kawai · Yoshihiro Kubota · Tomoko Umeda · Mitsuaki Ishida · Tohru Tani
Received: 27 December 2013 / Accepted: 1 April 2014 © Springer Japan 2014
Abstract Umbilical metastases mainly arise from malignancies of the digestive and gynecological systems, but rarely from breast cancer. A 64-year-old woman with a history of breast cancer was referred to us for investigation of a painful lesion in the umbilicus. Immunohistochemical staining of a specimen obtained by biopsy from the nodule showed umbilical metastasis of breast cancer. After a work up, she was successfully treated with a combination of surgery and endocrine therapy. We report this case to reinforce that not all periumbilical tumoral deposits are consistent.
metastases from gastrointestinal or gynecological cancers [1–3], and known as “Sister Mary Joseph nodules” [4]. Sporadic cases of umbilical metastases originating from hematological malignancies or thoracic cancers have also been described. While breast cancers can spread to various parts of the body, umbilical metastasis from breast cancer is highly unusual. We report a rare case of umbilical metastasis from breast cancer.
Case report Keywords Umbilical metastasis · Breast cancer · Immunohistochemical staining
Introduction The most common benign umbilical mass is endometriosis, whereas malignant umbilical tumors are likely to be
H. Abe (*) · K. Yamazaki Breast Center, Bell Land General Hospital, 500‑3 Higashiyama, Naka‑ku, Sakai, Osaka 599‑8247, Japan e-mail: [email protected]‑med.ac.jp H. Abe · T. Mori · Y. Kawai · Y. Kubota · T. Umeda Division of Breast and General Surgery, Shiga University of Medical Science Hospital, Ōtsu, Japan M. Ishida Department of Clinical Laboratory Medicine and Division of Diagnostic Pathology, Shiga University of Medical Science, Ōtsu, Japan T. Tani Department of Surgery, Shiga University of Medical Science, Ōtsu, Japan
A 64-year-old woman with hypothyroidism was referred to our hospital for investigation of umbilical pain. The patient had been aware of slow-growing umbilical erosion for about a year. She had a history of estrogen receptor (ER)positive breast cancer, invasive ductal carcinoma without lymph-nodal metastasis (T1N0M0) 20 years earlier, for which she had received 2 years adjuvant endocrine therapy with tamoxifen. On physical examination, we noted a cutaneous nodule, approximately 3 × 2 cm in diameter, on the umbilicus (Fig. 1). The lesion was seen as a firm indurated nodule with erosion and the mobility in the subcutaneous tissue was poor. Laboratory test results revealed a slightly elevated level of the tumor marker CEA to 9.5 ng/ml (normal: 5.0 ng/ml), but all other results were within the normal ranges. Chest and abdominal computed tomography (CT) showed only the umbilical nodule (Fig. 2). Tissue biopsy of the umbilical nodule demonstrated adenocarcinoma arranged in foamy or tubular formation. These tumor cells had large oval nuclei and slightly eosinophilic cytoplasm. The tumor had invaded the surrounding fatty tissue and skin (Fig. 3). Immunohistochemical tissue staining was positive for cytokeratin 7 (CK7), gross cystic disease fluid protein-15 (GCDFP-15), ER and progesterone receptor
13
Surg Today
of neoplastic cells. Positron emission tomography (PET) revealed increased 18F-fluorodeoxyglucose (FDG) uptake in the umbilicus that had late maximum standardized uptake value (SUVmax) 1.9 (Fig. 4). Thus, we diagnosed late recurrence of breast cancer localized to the umbilicus. The patient underwent wide excision of the lesion with clearance margins containing the umbilicus, followed by endocrine therapy of anastrazole (1 mg/day). She is remains well after 8 months of follow-up.
Discussion
Fig. 1 Umbilical nodule with erosion
Fig. 2 Computed tomography of the abdomen showed enhancement of the umbilical nodule
(PgR), and negative for cytokeratin 20 (CK20) and human epidermal growth factor receptor-2 (HER2). Based on these results, the pathology of the umbilical lesion was considered the same as that of the primary breast cancer. Staining for Ki67 showed a low proliferative index of 5–7 %
Fig. 3 Histological examination of the umbilical nodule revealed large oval nuclei and slightly eosinophilic cytoplasm tumor cells invading the surrounding fatty tissue and skin (a H&E, ×40, b H&E, ×200)
13
This report describes a rare case of umbilical metastasis from breast cancer. According to our search of the literature, only 7 (1.7 %) of 407 umbilical metastases [3] were derived from breast cancer. Breast cancer is considered a chronic disease that can spread to various parts of body. The intrinsic sub-types triple-negative and HER2-positive, which reflect higher proliferation, predict early recurrence, whereas the luminal/HER2-negative subtype is considered a factor that predicts late recurrence, with the recurrence rate over 10 years reported as 5.8 % [5, 6]. The umbilical metastasis of any malignancy is an uncommon phenomenon, accounting for only 10 % of all secondary tumors that have spread to the skin [1]. The evaluation of an umbilical mass should be directed by suspicion of its being a metastatic deposit, keeping in mind its potential to be either a primary malignant umbilical lesion or a benign lesion. Malignant tumors can be primary or metastatic. Primary malignant umbilical tumors are rare and comprise mainly melanomas and squamous or basal cell carcinomas. The Sister Mary Joseph nodule is described as a malignant umbilical tumor usually associated with the advanced metastasizing of intra-abdominal cancer and generally indicates a poor prognosis [4]. These umbilical nodules usually present as a painful lump with irregular margins and a hard fibrous consistency. The surface may be ulcerated and necrotic, with either blood, serous, purulent, or mucinous discharge. Spread of metastatic carcinoma
Surg Today
analysis, GCDFP-15 is a marker for breast carcinoma [12, 13]. In fact, 55-72 % of breast carcinomas studied stained positively for GCDFP-15. The combination of CK7 and CK20 immunoprofiling has been helpful in identifying adenocarcinomas derived from different sites. CK7 is expressed in a wide variety of epithelial neoplasms, including the lung, salivary gland, endometrium, and breast, while CK20 is distributed predominantly in carcinomas of the colon and pancreas and in Merkel cell tumor of the skin. Breast carcinoma is known to be CK7-positive and CK20-negative [14]. In general, umbilical metastasis is associated with a poor prognosis consistent with advanced neoplastic disease, usually manifesting 2–11 months from the time of initial diagnosis [2]. Therapeutic prognosis in recent years has made possible the long-term survival of patients with certain types of cancer. The primary treatment for metastatic breast cancer is systemic therapy, with consideration of surgery for the palliation of symptoms after systemic treatment, although such surgery should be undertaken only if complete local clearance of tumor is obtained as in the present case [15]. We recommend that physicians be cognizant of changes to the umbilicus in patients with a history of breast cancer. Conflict of interest We declare no conflicts of interest.
References
Fig. 4 Positron emission tomography image revealed increased 18 F-fluorodeoxyglucose uptake in the umbilicus (arrows)
to the umbilical region has been hypothesized to occur by either contiguous spread of peritoneal cancer, hematogenous spread through arterial and venous systems, or lymphatic spread with extension along ligaments of embryonic origin, such as round ligament of liver, urachus, vitello intestinal duct remnant, and obliterated vitelline artery [7, 8]. It is the extensive vascular and lymphatic communications of the umbilicus, including axillary and thoracic sites, which allow the migration of tumor cells to the umbilicus from the breast [9]. Ultrasonography and CT scan of the tumor are invaluable in the diagnosis of umbilical tumors and help to exclude a primary benign neoplasm. Fine needle aspiration cytology is adequate to establish an easy diagnosis [10], and early biopsy is appropriate to evaluate the neoplasmatic nature of these lesions. Histology of the metastatic umbilical tumor usually reveals adenocarcinoma [11]. In immunohistochemical
1. Shetty MR. Metastatic tumors of the umbilicus: a review 19801989. J Surg Oncol. 1990;45:212. 2. Gabriele R, Conte M, Egidi F, Borghese M. Umbilical metastases: current viewpoint. World J Surg Oncol. 2005;3:13. 3. Galvan VG. Sister Mary Jopseph’s nodule. Ann Intern Med. 1998;128:410. 4. Bailey H. Demonstrations of physical signs in clinical surgery. 11th ed. Baltimore: Williams & Wilkins; 1949. p. 227. 5. Esserman LJ, Moore DH, Tsing PJ, Chu PW, Yau C, Ozanne E, et al. Biologic markers determine the risk and the timing of recurrence in breast cancer. Breast Cancer Res Treat. 2011;129:607–16. 6. Nishimura R, Osako T, Nishiyama Y, Tashima R, Nakano M, Fujisue M, et al. Evaluation of factors related to late recurrencelater than 10 years after the initial treatment-in primary breast cancer. Oncology. 2013;85:100–10. 7. Srinivasan R, Ray R, Nijhawan R. Metastatic cutaneous and subcutaneous deposits from internal carcinoma. An analysis of cases diagnosed by fine needle aspiration. Acta Cytol. 1993;37:894–8. 8. Powell FC, Cooper AJ, Massa MC, Goellner JR, Su WP. Sister Mary Joseph’s nodule: a clinical and histologic study. J Am Acad Dermatol. 1984;10:610–5. 9. Ching AS, Lai CW. Sonography of umbilical metastasis (Sister Mary Joseph’s nodule) from embryology to imaging. Abdom Imaging. 2002;27:746–9. 10. Schneider V, Smyczek B. Sister Mary joseph’s nodule. Diagnosis of umbilical metastases by fine needle aspiration. Acta Cytol. 1990;34:555–8. 11. Majmudar B, Wiskind AK, Croft BN, Dudley AG. The Sister (Mary) Joseph nodule: its significance in gynecology. Gynecol Oncol. 1991;40:152–9.
13
12. Wick MR, Lillemoe TJ, Copland GT, Swanson PE, Manivel JC, Kiang DT. Gross cystic disease fluid protein-15 as a marker for breast cancer immunohistochemical analysis of 690 kuman neoplasms and comparison with alpha-lactalbumin. Hum Pathol. 1989;20:281–7. 13. Mazoujian G, Bodian C, Haagensen DE Jr, Haagensen CD. Expression of GCDFP-15 in breast carcinoma; relationship to pathologic and clinical factors. Cancer. 1989;63:2156–61.
13
Surg Today 14. Chu P, Wu E, Weiss LM. Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: a survey of 435 cases. Mod Pathol. 2000;13:962–72. 15. NCCN clinical Practice Guidelines in oncology. ver. 3, 2013. Breast Cancer. http://www.nccn.org/professionals/physisician_gl s/pdf/breast.pdf
