Journal of the Egyptian National Cancer Institute (2015) 27, 243–246
Cairo University
Journal of the Egyptian National Cancer Institute www.elsevier.com/locate/jnci www.sciencedirect.com
Case Report
Vulvar metastasis from carcinoma breast unveiling distant metastasis: Exploring an unusual metastatic pattern Ajeet Kumar Gandhi a,*, Soumyajit Roy a, Asit Ranjan Mridha b, Daya Nand Sharma a a b
Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi 110029, India Department of Pathology, All India Institute of Medical Sciences, New Delhi 110029, India
Received 11 May 2015; accepted 23 May 2015 Available online 6 July 2015
KEYWORDS Vulvar metastasis; Breast; Cancer
Abstract A 76 year old woman with a previous history of infiltrating ductal carcinoma of right breast (diagnosed and treated 14 years back) presented to us with a non-healing ulcer on the left side of the vulva along with two satellite nodules close to the vulvar lesion. Biopsy showed an infiltrating ductal carcinoma of breast with a strong positivity for estrogen/progesterone receptors. Further, 18F-FDG PET–CT (Fluoro-deoxy glucose positron emission tomography computed tomography) showed multiple bilateral lung metastases. She responded well to hormone therapy (Letrozole) with decrease in the size of primary vulvar lesion and disappearance of the satellite nodules. Repeating PET–CT at 6 months showed partial response of the lung lesions. The present case is unique in the way of metastatic presentation of breast cancer to vulva after a long gap of primary diagnosis (longest reported till date) and also in unveiling of further metastatic sites in otherwise asymptomatic case. Patients (particularly elderly) with this unusual and clinically isolated pattern of metastasis might remain misdiagnosed for a long period of time and this case report aims to increase the awareness of clinicians toward the same. Gynecological surveillance remains of paramount importance in the follow up of breast cancer. ª 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of National Cancer Institute, Cairo University. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
Introduction * Corresponding author. Tel.: +91 9013277915; fax: +91 1126589821. E-mail address: [email protected] (A.K. Gandhi). Peer review under responsibility of The National Cancer Institute, Cairo University.
Breast cancer mostly metastasizes to regional lymph nodes, bones, lung, liver, brain etc. An unusual site of metastasis particularly to gynecological sites is rare and mostly involves ovaries or uterus [1]. Vulvar metastasis is a rare occurrence
http://dx.doi.org/10.1016/j.jnci.2015.05.005 1110-0362 ª 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of National Cancer Institute, Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
244
A.K. Gandhi et al.
[2–4]. We report here an interesting and intriguing case of vulvar metastasis from a breast cancer unveiling further distant sites of metastasis occurring 14 years after the initial diagnosis. Case report A 76 year old female presented with a non-healing ulcer in the vulvar region for 1 year to our department in October 2014. She noticed a small elevated, reddish ulcer in the vulvar region, which was progressively increasing over the period of 1 year. She also complained of infrequent episodes of bleeding from the lesion. She visited local gynecologist for the same and had no relief with the course of antibiotics and medicines. She is already a diagnosed case of carcinoma right breast (infiltrating ductal carcinoma; estrogen and progesterone receptor positive) in January 1999. She was treated with right modified radical mastectomy and pathologically was T2N0M0 as per AJCC staging [5] of cancer (tumor size: 3 · 2 · 1.5 cm; 0/10 axillary lymph nodes positive). She also received 6 cycles of chemotherapy (Cyclophosphamide/Methotrexate/5-Fluoro uracil based chemotherapy) followed by 5 years of hormone therapy (tamoxifen) till July 2005. She was on regular follow up till 2010 and then defaulted for follow up owing to personal reasons. On examination at this presentation, a 3 cm · 2 cm ulcer was noted on the left side of mons pubis close to midline (Fig. 1a). The ulcer was non-tender and had a slough covered base with erythematous and indurated margins without any underlying fixity to deeper structures. Two satellite erythematous nodules (approximately 0.5 cm each) were also seen away from the primary lesion as evident in Fig. 1a. Left breast, right chest wall, bilateral axilla and supraclavicular examination revealed no signs of disease as were the systemic examination. Biopsy from the vulvar lesion was suggestive of infiltrating carcinoma of breast with strong positivity of estrogen and progesterone receptors (Fig. 2a–d). Whole body 18F-Fluoro-deoxy glucose PET–CT (positron emission tomography–computed tomography) revealed multiple avid nodules in bilateral lung fields predominantly in the periphery of lung fields (largest in left lung lower lobe measuring 2.5 · 2.8 · 2 cm with speculated margins). Avid subcutaneous nodule was also seen in the left mons pubic region. Rest of the body showed physiological
Figure 1
uptake (Fig. 3a and b). Complete blood counts, liver function tests and kidney function tests were all reported to be within normal laboratory limits. She was started on tab Letrozole 2.5 mg once daily. There was significant improvement of the vulvar lesion at 6 months of follow up (Fig. 1b). The satellite lesion has disappeared and the vulvar lesion has shown a decrease in erythema and indurations. A repeat PET–CT (Fig. 3c and d) also revealed decrease in the uptake and size of the lung nodules and significant reduction of the size of left lower lung lobe nodule (now measures 7 mm) and decrease in avidity of the subcutaneous vulvar lesion. The patient is continuing Letrozole tablet and is on follow up now. Discussion Association of vulvar and breast cancer is very intriguing. Mammary gland at an ectopic site (along the primitive milk streak, extending from axilla to the groin) has been found to be a source of benign or malignant lesion of the breast. Associations of various types have been reported. Primary breast cancer of the vulva is extremely rare [6]. Synchronous or metachronous association of infiltrating ductal carcinoma of breast and vulva has also been reported. Metastasis of breast cancer to vulva and vice versa is a very rare association. Vicus et al. reported metastasis of primary carcinoma of vulva to breast in a 49 year old female [7]. Primary carcinoma of breast with vulvar metastasis was first reported in 1964 by Convington et al. [8]. In cases of diagnosis of breast carcinoma of the vulvar tissue, distinction between primary breast carcinoma of vulva and vulvar metastasis from breast cancer needs to be distinguished. A prior history of breast cancer in the patient, identical histological and hormone receptor status of both breast and vulvar lesion and absence of in-situ elements may help in clinching the diagnosis of metastatic lesion [9]. Exact mechanism of this metastatic pattern is not clearly known, although vascular space involvement has been thought to be a probable cause. Altered lymphatic drainage after surgery may also be a cause of this pattern as it was reported by Valenzano et al. [2]. In this report, 49 year old patient developed a rectus abdominis myocutaneous flap metastasis (3 year after surgery)
(a) Vulvar lesion with satellite nodules at presentation. (b) Same lesion after 6 months of hormone therapy.
Vulvar metastasis from carcinoma breast
245
Figure 2 Hematoxylin & eosin (H&E) stained section shows groups of malignant epithelial cells infiltrating into the dermis (A, 100·). Tumor cells are cuboidal with hyperchromatic nuclei and moderate amount of eosinophilic cytoplasm (B, H&E; 400·). Tumor cells are diffusely and strongly immunopositive with estrogen receptor (C, 400·) and progesterone receptor (D, 400·).
Figure 3 (a and b) 18F FDG PET–CT at presentation showing multiple lung metastases and the subcutaneous vulvar lesion. (c and d) 18 F FDG PET–CT after 6 months of hormone therapy showing partial response at both vulva and lung.
246 and a vulvar metastasis later on (11 years after primary surgery). The authors hypothesized that the lymphatic spread through the newly formed lymphatics might have occurred. Julien et al. [4] presented an almost similar case as ours where a 68 year old woman (with a 6 year history of breast cancer) with ulcerated clitoral lesion was found to have a second lesion in labia majora on magnetic resonance imaging. Most of the reported cases have shown duration between primary breast cancer diagnosis and metastatic vulvar lesion to be 1–6 years and the longest till date was by Papaioannou et al. (being 13 years) [3]. Our patient presented after 14 years of primary diagnosis making her the longest till date. Our case is also the first case reported from our country and is unique as a relatively benign looking vulvar lesion led us to unveil the lung metastasis in this patient. Pelvic/gynecological examination is recommended in the follow up of patients with breast cancers. This assumes importance not only in patients on adjuvant hormone therapy (tamoxifen) where iatrogenic endometrial carcinoma is not rare but also otherwise and this is mandated by the recent ASCO (American Society of Clinical Oncology) guidelines [10]. Awareness of this unusual pattern of metastasis would help in early diagnosis and also systemic work up with deciphering of further distant metastasis and early institution of the therapy. Conflicts of interest None. Acknowledgment None.
A.K. Gandhi et al. References [1] Sullivan LG, Sullivan JL, Fairey WF. Breast carcinoma metastatic to an endometrial polyp. Gynecol Oncol 1990;39: 96–8. [2] Valenzano Menada M, Papadia A, Lorenzi P, Fulcheri E, Ragni N. Breast cancer metastatic to the vulva after local recurrence occurring on a rectus abdominis myocutaneous flap: a case report and review of the literature. Eur J Gynaecol Oncol 2003;24:577–9. [3] Papaioannou N, Zervoudis S, Grammatikakis I, Peitsidis P, Palvakis K, Youssef TF. Metastatic lobular carcinoma of the breast to the vulva: a case report and review of the literature. J Egypt Natl Canc Inst 2010;22:57–60. [4] Julien V, Labadie M, Gauthier G, Ronger-Savle S. Clitoral metastasis from ductal breast cancer revealing metastases in multiple sites and review of the literature. J Low Genit Tract Dis 2012;16:66–9. [5] Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 2010;17:1471–4. [6] Gorisek B, Zegura B, Kavalar R, But I, Krajnc I. Primary breast cancer of the vulva: a case report and review of the literature. Wien Klin Wochenschr 2000;112:855–8. [7] Vicus D, Korach J, Friedman E, Rizel S, Ben-Baruch G. Vulvar cancer metastatic to the breast. Gynecol Oncol 2006;103:1144–6. [8] Convington EE. Brendle wk: breast carcinoma with vulvar metastasis. Obstet Gynecol 1964;23:910–1. [9] Sheen-Chen SM, Eng HL, Huang CC. Breast cancer metastatic to the vulva. Gynecol Oncol 2004;94:858–60. [10] Khatcheressian JL, Hurley P, Bantug E, Esserman LJ, Grunfeld E, Halberg F, et al. Breast cancer follow-up and management after primary treatment: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2013;31:961–5.
Cairo University
Journal of the Egyptian National Cancer Institute www.elsevier.com/locate/jnci www.sciencedirect.com
Case Report
Vulvar metastasis from carcinoma breast unveiling distant metastasis: Exploring an unusual metastatic pattern Ajeet Kumar Gandhi a,*, Soumyajit Roy a, Asit Ranjan Mridha b, Daya Nand Sharma a a b
Department of Radiation Oncology, All India Institute of Medical Sciences, New Delhi 110029, India Department of Pathology, All India Institute of Medical Sciences, New Delhi 110029, India
Received 11 May 2015; accepted 23 May 2015 Available online 6 July 2015
KEYWORDS Vulvar metastasis; Breast; Cancer
Abstract A 76 year old woman with a previous history of infiltrating ductal carcinoma of right breast (diagnosed and treated 14 years back) presented to us with a non-healing ulcer on the left side of the vulva along with two satellite nodules close to the vulvar lesion. Biopsy showed an infiltrating ductal carcinoma of breast with a strong positivity for estrogen/progesterone receptors. Further, 18F-FDG PET–CT (Fluoro-deoxy glucose positron emission tomography computed tomography) showed multiple bilateral lung metastases. She responded well to hormone therapy (Letrozole) with decrease in the size of primary vulvar lesion and disappearance of the satellite nodules. Repeating PET–CT at 6 months showed partial response of the lung lesions. The present case is unique in the way of metastatic presentation of breast cancer to vulva after a long gap of primary diagnosis (longest reported till date) and also in unveiling of further metastatic sites in otherwise asymptomatic case. Patients (particularly elderly) with this unusual and clinically isolated pattern of metastasis might remain misdiagnosed for a long period of time and this case report aims to increase the awareness of clinicians toward the same. Gynecological surveillance remains of paramount importance in the follow up of breast cancer. ª 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of National Cancer Institute, Cairo University. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).
Introduction * Corresponding author. Tel.: +91 9013277915; fax: +91 1126589821. E-mail address: [email protected] (A.K. Gandhi). Peer review under responsibility of The National Cancer Institute, Cairo University.
Breast cancer mostly metastasizes to regional lymph nodes, bones, lung, liver, brain etc. An unusual site of metastasis particularly to gynecological sites is rare and mostly involves ovaries or uterus [1]. Vulvar metastasis is a rare occurrence
http://dx.doi.org/10.1016/j.jnci.2015.05.005 1110-0362 ª 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of National Cancer Institute, Cairo University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
244
A.K. Gandhi et al.
[2–4]. We report here an interesting and intriguing case of vulvar metastasis from a breast cancer unveiling further distant sites of metastasis occurring 14 years after the initial diagnosis. Case report A 76 year old female presented with a non-healing ulcer in the vulvar region for 1 year to our department in October 2014. She noticed a small elevated, reddish ulcer in the vulvar region, which was progressively increasing over the period of 1 year. She also complained of infrequent episodes of bleeding from the lesion. She visited local gynecologist for the same and had no relief with the course of antibiotics and medicines. She is already a diagnosed case of carcinoma right breast (infiltrating ductal carcinoma; estrogen and progesterone receptor positive) in January 1999. She was treated with right modified radical mastectomy and pathologically was T2N0M0 as per AJCC staging [5] of cancer (tumor size: 3 · 2 · 1.5 cm; 0/10 axillary lymph nodes positive). She also received 6 cycles of chemotherapy (Cyclophosphamide/Methotrexate/5-Fluoro uracil based chemotherapy) followed by 5 years of hormone therapy (tamoxifen) till July 2005. She was on regular follow up till 2010 and then defaulted for follow up owing to personal reasons. On examination at this presentation, a 3 cm · 2 cm ulcer was noted on the left side of mons pubis close to midline (Fig. 1a). The ulcer was non-tender and had a slough covered base with erythematous and indurated margins without any underlying fixity to deeper structures. Two satellite erythematous nodules (approximately 0.5 cm each) were also seen away from the primary lesion as evident in Fig. 1a. Left breast, right chest wall, bilateral axilla and supraclavicular examination revealed no signs of disease as were the systemic examination. Biopsy from the vulvar lesion was suggestive of infiltrating carcinoma of breast with strong positivity of estrogen and progesterone receptors (Fig. 2a–d). Whole body 18F-Fluoro-deoxy glucose PET–CT (positron emission tomography–computed tomography) revealed multiple avid nodules in bilateral lung fields predominantly in the periphery of lung fields (largest in left lung lower lobe measuring 2.5 · 2.8 · 2 cm with speculated margins). Avid subcutaneous nodule was also seen in the left mons pubic region. Rest of the body showed physiological
Figure 1
uptake (Fig. 3a and b). Complete blood counts, liver function tests and kidney function tests were all reported to be within normal laboratory limits. She was started on tab Letrozole 2.5 mg once daily. There was significant improvement of the vulvar lesion at 6 months of follow up (Fig. 1b). The satellite lesion has disappeared and the vulvar lesion has shown a decrease in erythema and indurations. A repeat PET–CT (Fig. 3c and d) also revealed decrease in the uptake and size of the lung nodules and significant reduction of the size of left lower lung lobe nodule (now measures 7 mm) and decrease in avidity of the subcutaneous vulvar lesion. The patient is continuing Letrozole tablet and is on follow up now. Discussion Association of vulvar and breast cancer is very intriguing. Mammary gland at an ectopic site (along the primitive milk streak, extending from axilla to the groin) has been found to be a source of benign or malignant lesion of the breast. Associations of various types have been reported. Primary breast cancer of the vulva is extremely rare [6]. Synchronous or metachronous association of infiltrating ductal carcinoma of breast and vulva has also been reported. Metastasis of breast cancer to vulva and vice versa is a very rare association. Vicus et al. reported metastasis of primary carcinoma of vulva to breast in a 49 year old female [7]. Primary carcinoma of breast with vulvar metastasis was first reported in 1964 by Convington et al. [8]. In cases of diagnosis of breast carcinoma of the vulvar tissue, distinction between primary breast carcinoma of vulva and vulvar metastasis from breast cancer needs to be distinguished. A prior history of breast cancer in the patient, identical histological and hormone receptor status of both breast and vulvar lesion and absence of in-situ elements may help in clinching the diagnosis of metastatic lesion [9]. Exact mechanism of this metastatic pattern is not clearly known, although vascular space involvement has been thought to be a probable cause. Altered lymphatic drainage after surgery may also be a cause of this pattern as it was reported by Valenzano et al. [2]. In this report, 49 year old patient developed a rectus abdominis myocutaneous flap metastasis (3 year after surgery)
(a) Vulvar lesion with satellite nodules at presentation. (b) Same lesion after 6 months of hormone therapy.
Vulvar metastasis from carcinoma breast
245
Figure 2 Hematoxylin & eosin (H&E) stained section shows groups of malignant epithelial cells infiltrating into the dermis (A, 100·). Tumor cells are cuboidal with hyperchromatic nuclei and moderate amount of eosinophilic cytoplasm (B, H&E; 400·). Tumor cells are diffusely and strongly immunopositive with estrogen receptor (C, 400·) and progesterone receptor (D, 400·).
Figure 3 (a and b) 18F FDG PET–CT at presentation showing multiple lung metastases and the subcutaneous vulvar lesion. (c and d) 18 F FDG PET–CT after 6 months of hormone therapy showing partial response at both vulva and lung.
246 and a vulvar metastasis later on (11 years after primary surgery). The authors hypothesized that the lymphatic spread through the newly formed lymphatics might have occurred. Julien et al. [4] presented an almost similar case as ours where a 68 year old woman (with a 6 year history of breast cancer) with ulcerated clitoral lesion was found to have a second lesion in labia majora on magnetic resonance imaging. Most of the reported cases have shown duration between primary breast cancer diagnosis and metastatic vulvar lesion to be 1–6 years and the longest till date was by Papaioannou et al. (being 13 years) [3]. Our patient presented after 14 years of primary diagnosis making her the longest till date. Our case is also the first case reported from our country and is unique as a relatively benign looking vulvar lesion led us to unveil the lung metastasis in this patient. Pelvic/gynecological examination is recommended in the follow up of patients with breast cancers. This assumes importance not only in patients on adjuvant hormone therapy (tamoxifen) where iatrogenic endometrial carcinoma is not rare but also otherwise and this is mandated by the recent ASCO (American Society of Clinical Oncology) guidelines [10]. Awareness of this unusual pattern of metastasis would help in early diagnosis and also systemic work up with deciphering of further distant metastasis and early institution of the therapy. Conflicts of interest None. Acknowledgment None.
A.K. Gandhi et al. References [1] Sullivan LG, Sullivan JL, Fairey WF. Breast carcinoma metastatic to an endometrial polyp. Gynecol Oncol 1990;39: 96–8. [2] Valenzano Menada M, Papadia A, Lorenzi P, Fulcheri E, Ragni N. Breast cancer metastatic to the vulva after local recurrence occurring on a rectus abdominis myocutaneous flap: a case report and review of the literature. Eur J Gynaecol Oncol 2003;24:577–9. [3] Papaioannou N, Zervoudis S, Grammatikakis I, Peitsidis P, Palvakis K, Youssef TF. Metastatic lobular carcinoma of the breast to the vulva: a case report and review of the literature. J Egypt Natl Canc Inst 2010;22:57–60. [4] Julien V, Labadie M, Gauthier G, Ronger-Savle S. Clitoral metastasis from ductal breast cancer revealing metastases in multiple sites and review of the literature. J Low Genit Tract Dis 2012;16:66–9. [5] Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol 2010;17:1471–4. [6] Gorisek B, Zegura B, Kavalar R, But I, Krajnc I. Primary breast cancer of the vulva: a case report and review of the literature. Wien Klin Wochenschr 2000;112:855–8. [7] Vicus D, Korach J, Friedman E, Rizel S, Ben-Baruch G. Vulvar cancer metastatic to the breast. Gynecol Oncol 2006;103:1144–6. [8] Convington EE. Brendle wk: breast carcinoma with vulvar metastasis. Obstet Gynecol 1964;23:910–1. [9] Sheen-Chen SM, Eng HL, Huang CC. Breast cancer metastatic to the vulva. Gynecol Oncol 2004;94:858–60. [10] Khatcheressian JL, Hurley P, Bantug E, Esserman LJ, Grunfeld E, Halberg F, et al. Breast cancer follow-up and management after primary treatment: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2013;31:961–5.
