Unusual presentation of metastatic ovarian carcinoma as an enlarged intramammary lymph node Callan Mason, MD, Kendall Yokubaitis, MD, Raynal Hamilton, MD, Umesh Oza, MD, Zeeshan Shah, MD, Joseph Spigel, MD, and Jean Wang, MD
Metastasis to the breast most commonly arises from a contralateral primary breast malignancy; however, metastatic disease can also result from extramammary malignancies by hematogenous or lymphatic dissemination. This case report reviews an unusual presentation of primary ovarian carcinoma with metastasis to an intramammary lymph node.
P
rimary breast cancer is one of the most frequently occurring malignancies in women, but metastatic disease to the breast is relatively uncommon. Although malignancies metastatic to the breast parenchyma have no characteristic radiographic presentation, they can present as a rounded or oval mass at the fat-parenchymal interface. Enlarged nonfatty axillary lymph nodes with spiculated or illdefined margins have a strong association with an underlying malignancy. This case report reviews an unusual presentation of primary ovarian carcinoma with metastasis to an intramammary lymph node. Breast or axillary lymph node involvement from a primary ovarian carcinoma is rare, and ovarian carcinoma metastatic to the breast is associated with a poor prognosis, as it is usually related to widespread systemic disease. CASE REPORT An asymptomatic 58-year-old woman with no significant past medical or family history presented for a routine screening mammogram, which revealed a 1.0 cm mass in the upper outer quadrant of the left breast, favored to reflect an enlarging intramammary lymph node (Figure 1a). An additional enlarged lymph node was noted in the right axilla. Further evaluation with bilateral breast ultrasound confirmed a mass in the upper outer quadrant of the left breast, again favored to represent an enlarged intramammary lymph node (Figure 1b), as well as at least two enlarged right axillary lymph nodes. An ultrasound-guided core biopsy of the left intramammary lymph node as well as an additional core biopsy of a right axillary lymph node were performed. Immunohistochemical stains were positive for paired-box gene 8 (PAX8) and Wilm’s tumor gene (WT1), with a final pathologic diagnosis of high-grade serous ovarian carcinoma. Given the unexpected diagnosis of metastatic ovarian carcinoma, further evaluation and staging workup were initiated with 18F-fluoro-2-deoxy-D-glucose positron emission tomog386
raphy/computed tomography (18F-FDG PET-CT). The PETCT confirmed a hypermetabolic mass in the left hemipelvis in close association with the left ovary (Figure 2), corresponding to the pathologic diagnosis of ovarian carcinoma. Multifocal FDG-avid hepatic metastases were also identified, as well as extensive serosal, peritoneal, mesenteric, and omental carcinomatosis (Figure 2b). Intra-abdominal FDG-avid lymphadenopathy, to include portocaval and bilateral common iliac chain lymph nodes, as well as bilateral inguinal lymphadenopathy, was demonstrated and was compatible with additional nodal metastatic disease. PET-CT evaluation of the thorax demonstrated a hypermetabolic mass in the upper outer quadrant of the left breast, corresponding to the biopsy-proven malignancy (Figure 2d), as well as hypermetabolic right axillary lymphadenopathy. The patient’s laboratory values revealed an elevated CA-125 of 900 units/mL. These collective findings were compatible with stage IV metastatic ovarian carcinoma. The patient is currently receiving carboplatin and paclitaxel chemotherapy. DISCUSSION While primary breast cancer is one of the most common malignancies in women, metastatic disease to the breast is relatively rare, accounting for approximately 0.5% to 2.0% of all breast cancer cases (1). Metastatic disease to the breast most often arises from a contralateral primary breast malignancy; however, hematogenous or lymphatic metastasis from extramammary malignancies may also occur. The most common extramammary malignancies known to metastasize to the breast include lymphoma, melanoma, lung, and gynecological primary cancers (1). Studies reveal that axillary nodal metastases also most commonly occur from primary breast cancer, followed by lymphoma, and infrequently from a nonbreast primary site or an unknown primary site (2). Ovarian carcinoma usually presents with intraperitoneal metastases by direct seeding into the peritoneal cavity, and distant metastasis most commonly involves the lung or pleura (3).
From the Department of Radiology, Baylor University Medical Center at Dallas. Corresponding author: Callan Mason, MD, Department of Radiology, Baylor University Medical Center, 3500 Gaston Avenue, Dallas, TX 75246 (e-mail: callan. [email protected]). Proc (Bayl Univ Med Cent) 2015;28(3):386–388
a
b
Figure 1. (a) Annual screening mammogram of the left breast shows a well-circumscribed dense intramammary lymph node in the upper outer quadrant. (b) Targeted ultrasound of the upper outer quadrant of the left breast demonstrates an enlarged intramammary lymph node with loss of normal fatty hilum.
The most frequent sites of lymphatic involvement in ovarian carcinoma are abdominal (47%), para-aortic (38%), mediastinal (29%), and pelvic (17%) lymph nodes (4). Serous ovarian carcinoma is the most common ovarian malignancy to metastasize to the breast, and metastases to the breast parenchyma or axillary lymph nodes are rare and are typically seen in patients with advanced disease (5). Our case is particularly unusual in that an enlarged intramammary lymph node was the patient’s initial presentation of ovarian carcinoma, despite the disease being widespread. Mammographically, metastatic tumors to the breast parenchyma classically present as a rounded or oval noncalcified mass found in the subcutaneous breast tissue at the fat-parenchymal interface. They generally lack the features of primary breast malignancy such as microcalcifications, spiculation, or architectural distortion. Intramammary or axillary lymph node enlargement can also occur, and ill-defined or spiculated nodal margins show a significant association with malignancy (2).
a
b
c
d
Figure 2. (a) PET-CT image at the level of the pelvis shows moderately intense FDG uptake within a metastatic implant involving the left adnexa (arrow). (b) Multiple regions of hepatic metastatic disease are identified at the level of the upper abdomen, with the most intense lesion in the caudate lobe (arrow). (c) At the level of the iliac crests, there is uptake within the omentum along the anterior abdominal wall extending into an umbilical hernia (arrow). (d) At the level of the mid thorax there is mildly increased FDG uptake in the upper outer quadrant of the left breast (arrow), corresponding to the intramammary lymph node seen on comparison mammogram and ultrasound. July 2015
Unusual presentation of metastatic ovarian carcinoma as an enlarged intramammary lymph node
387
Specifically, ovarian cancer metastatic to the breast parenchyma can present as a focal mass without definite characteristic radiographic features (6); however, a few studies reveal that serous ovarian carcinoma metastatic to axillary lymph nodes can occasionally demonstrate a peripheral amorphous lymph node calcification pattern on a mammogram (7), which is related to psammoma body formation. This calcification pattern could potentially be used to differentiate from metastatic breast carcinoma, which typically demonstrates pleomorphic lymph node calcifications. This case also highlights the utility of PET-CT in detecting suspected metastatic disease such as ovarian carcinoma. PET-CT can be particularly useful for site-specific treatment planning such as biopsy, surgery, or radiotherapy (8). Breast and ovarian tumors can be difficult to pathologically distinguish due to overlapping morphology (9), and immunohistochemistry may be required to distinguish the two. Estrogen and progesterone receptor expression are inadequate markers, as these can be seen in both breast and ovarian neoplasms. PAX8 has been shown to be an excellent distinguishing marker between ovarian and breast carcinoma, as it is positive in nearly all ovarian carcinoma stains and is negative in breast cancer stains (10, 11). WT1 can also be a sensitive marker for serous ovarian carcinoma since it is rarely positive for breast cancer samples but is immunoreactive in up to 85% of ovarian samples (10, 11). Ovarian carcinoma metastatic to the breast is associated with a poor prognosis, largely because it is associated with widespread systemic dissemination of disease (3). On average, ovarian carcinoma metastatic to the breast is diagnosed 2 years following the initial diagnosis of ovarian cancer (12). Several studies have demonstrated survival rates ranging from 13 days to 3.5 years following detection of metastatic disease in the breast (12), and the 1-year survival rate has been reported at 40% (13). With the unanticipated diagnosis of metastatic ovarian carcinoma, this case not only highlights the significance of imaging workup at
388
diagnosis, but also the value of multidisciplinary communication between the radiologist, pathologist, and clinician. 1. 2.
3. 4.
5.
6. 7.
8.
9.
10.
11.
12.
13.
Toombs BD, Klisher L. Metastatic disease to the breast: clinical, pathologic and radiologic features. Am J Roentgenol 1977;129(4):673–676. Walsh R, Kornguth PJ, Soo MS, Bentley R, DeLong DM. Axillary lymph nodes: mammographic, pathologic, and clinical correlation. Am J Roentgenol 1997;168(1):33–38. Goyal H, Mattoo V, Singla U. Isolated axillary lymph node metastasis from serous ovarian cancer. Case Rep Oncol Med 2012:307567. Skagias L, Ntinis A, Vasou O, Kondi-Pafiti A, and Politi E. Ovarian carcinoma presenting with axillary lymph node metastasis: a case documented by fine-needle aspiration and brief review of the literature. Diagn Cytopathol 2008;36(12):891–893. Recine M, Deavers M, Middleton, L, Silva E, Malpica A. Serous carcinoma of the ovary and peritoneum with metastases to the breast and axillary lymph nodes: a potential pitfall. Am J Surg Pathol 2004;28(12):1646– 1651. Moore D, Wilson D, Hurteau J, Look K, Stehman F, Sutton G. Gynecologic cancers metastatic to the breast. J Am Coll Surg 1998;187:178–181. Singer C, Blankstein E, Koenigsberg T, Mercado C, Pile-Spellman E, Smith S. Mammographic appearance of axillary lymph node calcification in patients with metastatic ovarian carcinoma. Am J Roentgenol 2001;176(6):1437–1440. Viswanathan C, Bhosale PR, Shah SN, Vikram R. Positron emission tomography-computed tomography imaging for malignancies in women. Radiol Clin N Am 2013;51(6):1111–1125. Yamasaki H, Saw D, Zdanowitz J, Faltz L. Ovarian carcinoma metastasis to the breast: a case report and review of the literature. Am J Surg Pathol 1993;17(2):193–197. Xiang L, Kong B. PAX8 is a novel marker for differentiating between various types of tumor, particularly ovarian epithelial carcinomas. Oncol Lett 2013;5(3):735–738. DeLair DF, Corben AD, Catalano JP, Vallejo CE, Brogi E, Tan LK. Nonmammary metastases to the breast and axilla: a study of 85 cases. Mod Pathol 2013;26(3):343–349. Ozguroglu M, Ersavasti G, Ilvan S, Hatemi G, Demir G, Demirelli F. Bilateral inflammatory breast metastases of epithelial ovarian cancer. Am J Clin Oncol 1999;22(4):408–410. Loredo D, Powell J, Reed W, Rosenbaum J. Ovarian carcinoma metastatic to breast: a case report and review of the literature. Gynecol Oncol 1990;37(3):432–436.
Baylor University Medical Center Proceedings
Volume 28, Number 3
Metastasis to the breast most commonly arises from a contralateral primary breast malignancy; however, metastatic disease can also result from extramammary malignancies by hematogenous or lymphatic dissemination. This case report reviews an unusual presentation of primary ovarian carcinoma with metastasis to an intramammary lymph node.
P
rimary breast cancer is one of the most frequently occurring malignancies in women, but metastatic disease to the breast is relatively uncommon. Although malignancies metastatic to the breast parenchyma have no characteristic radiographic presentation, they can present as a rounded or oval mass at the fat-parenchymal interface. Enlarged nonfatty axillary lymph nodes with spiculated or illdefined margins have a strong association with an underlying malignancy. This case report reviews an unusual presentation of primary ovarian carcinoma with metastasis to an intramammary lymph node. Breast or axillary lymph node involvement from a primary ovarian carcinoma is rare, and ovarian carcinoma metastatic to the breast is associated with a poor prognosis, as it is usually related to widespread systemic disease. CASE REPORT An asymptomatic 58-year-old woman with no significant past medical or family history presented for a routine screening mammogram, which revealed a 1.0 cm mass in the upper outer quadrant of the left breast, favored to reflect an enlarging intramammary lymph node (Figure 1a). An additional enlarged lymph node was noted in the right axilla. Further evaluation with bilateral breast ultrasound confirmed a mass in the upper outer quadrant of the left breast, again favored to represent an enlarged intramammary lymph node (Figure 1b), as well as at least two enlarged right axillary lymph nodes. An ultrasound-guided core biopsy of the left intramammary lymph node as well as an additional core biopsy of a right axillary lymph node were performed. Immunohistochemical stains were positive for paired-box gene 8 (PAX8) and Wilm’s tumor gene (WT1), with a final pathologic diagnosis of high-grade serous ovarian carcinoma. Given the unexpected diagnosis of metastatic ovarian carcinoma, further evaluation and staging workup were initiated with 18F-fluoro-2-deoxy-D-glucose positron emission tomog386
raphy/computed tomography (18F-FDG PET-CT). The PETCT confirmed a hypermetabolic mass in the left hemipelvis in close association with the left ovary (Figure 2), corresponding to the pathologic diagnosis of ovarian carcinoma. Multifocal FDG-avid hepatic metastases were also identified, as well as extensive serosal, peritoneal, mesenteric, and omental carcinomatosis (Figure 2b). Intra-abdominal FDG-avid lymphadenopathy, to include portocaval and bilateral common iliac chain lymph nodes, as well as bilateral inguinal lymphadenopathy, was demonstrated and was compatible with additional nodal metastatic disease. PET-CT evaluation of the thorax demonstrated a hypermetabolic mass in the upper outer quadrant of the left breast, corresponding to the biopsy-proven malignancy (Figure 2d), as well as hypermetabolic right axillary lymphadenopathy. The patient’s laboratory values revealed an elevated CA-125 of 900 units/mL. These collective findings were compatible with stage IV metastatic ovarian carcinoma. The patient is currently receiving carboplatin and paclitaxel chemotherapy. DISCUSSION While primary breast cancer is one of the most common malignancies in women, metastatic disease to the breast is relatively rare, accounting for approximately 0.5% to 2.0% of all breast cancer cases (1). Metastatic disease to the breast most often arises from a contralateral primary breast malignancy; however, hematogenous or lymphatic metastasis from extramammary malignancies may also occur. The most common extramammary malignancies known to metastasize to the breast include lymphoma, melanoma, lung, and gynecological primary cancers (1). Studies reveal that axillary nodal metastases also most commonly occur from primary breast cancer, followed by lymphoma, and infrequently from a nonbreast primary site or an unknown primary site (2). Ovarian carcinoma usually presents with intraperitoneal metastases by direct seeding into the peritoneal cavity, and distant metastasis most commonly involves the lung or pleura (3).
From the Department of Radiology, Baylor University Medical Center at Dallas. Corresponding author: Callan Mason, MD, Department of Radiology, Baylor University Medical Center, 3500 Gaston Avenue, Dallas, TX 75246 (e-mail: callan. [email protected]). Proc (Bayl Univ Med Cent) 2015;28(3):386–388
a
b
Figure 1. (a) Annual screening mammogram of the left breast shows a well-circumscribed dense intramammary lymph node in the upper outer quadrant. (b) Targeted ultrasound of the upper outer quadrant of the left breast demonstrates an enlarged intramammary lymph node with loss of normal fatty hilum.
The most frequent sites of lymphatic involvement in ovarian carcinoma are abdominal (47%), para-aortic (38%), mediastinal (29%), and pelvic (17%) lymph nodes (4). Serous ovarian carcinoma is the most common ovarian malignancy to metastasize to the breast, and metastases to the breast parenchyma or axillary lymph nodes are rare and are typically seen in patients with advanced disease (5). Our case is particularly unusual in that an enlarged intramammary lymph node was the patient’s initial presentation of ovarian carcinoma, despite the disease being widespread. Mammographically, metastatic tumors to the breast parenchyma classically present as a rounded or oval noncalcified mass found in the subcutaneous breast tissue at the fat-parenchymal interface. They generally lack the features of primary breast malignancy such as microcalcifications, spiculation, or architectural distortion. Intramammary or axillary lymph node enlargement can also occur, and ill-defined or spiculated nodal margins show a significant association with malignancy (2).
a
b
c
d
Figure 2. (a) PET-CT image at the level of the pelvis shows moderately intense FDG uptake within a metastatic implant involving the left adnexa (arrow). (b) Multiple regions of hepatic metastatic disease are identified at the level of the upper abdomen, with the most intense lesion in the caudate lobe (arrow). (c) At the level of the iliac crests, there is uptake within the omentum along the anterior abdominal wall extending into an umbilical hernia (arrow). (d) At the level of the mid thorax there is mildly increased FDG uptake in the upper outer quadrant of the left breast (arrow), corresponding to the intramammary lymph node seen on comparison mammogram and ultrasound. July 2015
Unusual presentation of metastatic ovarian carcinoma as an enlarged intramammary lymph node
387
Specifically, ovarian cancer metastatic to the breast parenchyma can present as a focal mass without definite characteristic radiographic features (6); however, a few studies reveal that serous ovarian carcinoma metastatic to axillary lymph nodes can occasionally demonstrate a peripheral amorphous lymph node calcification pattern on a mammogram (7), which is related to psammoma body formation. This calcification pattern could potentially be used to differentiate from metastatic breast carcinoma, which typically demonstrates pleomorphic lymph node calcifications. This case also highlights the utility of PET-CT in detecting suspected metastatic disease such as ovarian carcinoma. PET-CT can be particularly useful for site-specific treatment planning such as biopsy, surgery, or radiotherapy (8). Breast and ovarian tumors can be difficult to pathologically distinguish due to overlapping morphology (9), and immunohistochemistry may be required to distinguish the two. Estrogen and progesterone receptor expression are inadequate markers, as these can be seen in both breast and ovarian neoplasms. PAX8 has been shown to be an excellent distinguishing marker between ovarian and breast carcinoma, as it is positive in nearly all ovarian carcinoma stains and is negative in breast cancer stains (10, 11). WT1 can also be a sensitive marker for serous ovarian carcinoma since it is rarely positive for breast cancer samples but is immunoreactive in up to 85% of ovarian samples (10, 11). Ovarian carcinoma metastatic to the breast is associated with a poor prognosis, largely because it is associated with widespread systemic dissemination of disease (3). On average, ovarian carcinoma metastatic to the breast is diagnosed 2 years following the initial diagnosis of ovarian cancer (12). Several studies have demonstrated survival rates ranging from 13 days to 3.5 years following detection of metastatic disease in the breast (12), and the 1-year survival rate has been reported at 40% (13). With the unanticipated diagnosis of metastatic ovarian carcinoma, this case not only highlights the significance of imaging workup at
388
diagnosis, but also the value of multidisciplinary communication between the radiologist, pathologist, and clinician. 1. 2.
3. 4.
5.
6. 7.
8.
9.
10.
11.
12.
13.
Toombs BD, Klisher L. Metastatic disease to the breast: clinical, pathologic and radiologic features. Am J Roentgenol 1977;129(4):673–676. Walsh R, Kornguth PJ, Soo MS, Bentley R, DeLong DM. Axillary lymph nodes: mammographic, pathologic, and clinical correlation. Am J Roentgenol 1997;168(1):33–38. Goyal H, Mattoo V, Singla U. Isolated axillary lymph node metastasis from serous ovarian cancer. Case Rep Oncol Med 2012:307567. Skagias L, Ntinis A, Vasou O, Kondi-Pafiti A, and Politi E. Ovarian carcinoma presenting with axillary lymph node metastasis: a case documented by fine-needle aspiration and brief review of the literature. Diagn Cytopathol 2008;36(12):891–893. Recine M, Deavers M, Middleton, L, Silva E, Malpica A. Serous carcinoma of the ovary and peritoneum with metastases to the breast and axillary lymph nodes: a potential pitfall. Am J Surg Pathol 2004;28(12):1646– 1651. Moore D, Wilson D, Hurteau J, Look K, Stehman F, Sutton G. Gynecologic cancers metastatic to the breast. J Am Coll Surg 1998;187:178–181. Singer C, Blankstein E, Koenigsberg T, Mercado C, Pile-Spellman E, Smith S. Mammographic appearance of axillary lymph node calcification in patients with metastatic ovarian carcinoma. Am J Roentgenol 2001;176(6):1437–1440. Viswanathan C, Bhosale PR, Shah SN, Vikram R. Positron emission tomography-computed tomography imaging for malignancies in women. Radiol Clin N Am 2013;51(6):1111–1125. Yamasaki H, Saw D, Zdanowitz J, Faltz L. Ovarian carcinoma metastasis to the breast: a case report and review of the literature. Am J Surg Pathol 1993;17(2):193–197. Xiang L, Kong B. PAX8 is a novel marker for differentiating between various types of tumor, particularly ovarian epithelial carcinomas. Oncol Lett 2013;5(3):735–738. DeLair DF, Corben AD, Catalano JP, Vallejo CE, Brogi E, Tan LK. Nonmammary metastases to the breast and axilla: a study of 85 cases. Mod Pathol 2013;26(3):343–349. Ozguroglu M, Ersavasti G, Ilvan S, Hatemi G, Demir G, Demirelli F. Bilateral inflammatory breast metastases of epithelial ovarian cancer. Am J Clin Oncol 1999;22(4):408–410. Loredo D, Powell J, Reed W, Rosenbaum J. Ovarian carcinoma metastatic to breast: a case report and review of the literature. Gynecol Oncol 1990;37(3):432–436.
Baylor University Medical Center Proceedings
Volume 28, Number 3
