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Cytopathology of Metastatic Breast Cancer
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breast cancer Cytopathology of Metastatic Breast Cancer Harvey Cramer Abstract
A 52-year-old woman developed an infiltrating ductal carcinoma of the breast 16 years after being treated for comedocarcinoma of the left breast. Although the tumor was high grade with lymphatic space invasion and incompletely excised, the patient declined adjunctive therapy. Within 2 years, she developed metastasis to supraclavicular lymph nodes, which was diagnosed by fine-needle aspiration cytology. Clinical Breast Cancer, Vol. 1, No. 3, 243-244, 2000 Key words: Breast cancer, Metastasis, Fine needle aspiration
Patient History and Pathologic Findings Approximately 16 years ago, a 52-year-old woman developed comedocarcinoma of the left breast. She was treated with a left modified radical mastectomy and an axillary lymph node dissection. There was no evidence of metastatic adenocarcinoma in any of the 13 lymph nodes removed. Bilateral breast reconstruction with insertion of silicone implants was performed. As recommended by her physician, she underwent annual follow-up mammography. Two years ago, a mammogram disclosed the presence of a 1.8 cm mass involving the upper inner quadrant of the right breast. A core needle biopsy was performed and disclosed an infiltrating ductal carcinoma. Immunohistochemical analysis performed on the core biopsy indicated that the carcinoma was negative for both estrogen receptor (ER) and progesterone receptor (PR) proteins. She underwent a sentinel lymph node biopsy followed by a right modified radical mastectomy and immediate bilateral breast reconstruction with replacement of the previous silicone implants with saline implants. Two sentinel lymph nodes were sampled and both were free of tumor. In the mastectomy specimen, the tumor measured a maximum of 1.6 cm and was poorly differentiated (Figure 1). Lymphatic invasion was present (Figure 2), and coexistent high-grade ductal carcinoma in situ was also noted. Both infiltrating and intraductal carcinomas were identified at the inked superficial margin and within 0.55 mm of the deep margin. The patient was offered a standard 4-cycle regimen of cytotoxic chemotherapy consisting of doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2). Due
to perceived toxicities occurring during the first course of chemotherapy, the patient decided to discontinue
Figure 1
High-Grade Infiltrating Duct Carcinoma
A section of the tumor in the mastectomy specimen disclosed a highgrade infiltrating duct carcinoma. There was a marked degree of nuclear pleomorphism and the mitotic count was high (hematoxylin and eosin, x 400).
Figure 2
Lymphatic Spaces Containing Malignant Tumor Cells
Wishard Memorial Hospital, Indianapolis, IN Submitted: July 28, 2000; Revised: Oct. 5, 2000; Accepted: Oct. 6, 2000 Address for correspondence: Harvey Cramer, MD, Wishard Memorial Hospital, LL Myers Building, 1001 West Tenth Street, Indianapolis, IN 46202-2879 Fax: 317-630-7913; e-mail: [email protected]
In one section, lymphatic spaces containing malignant tumor cells were identified. Lymphatic invasion is a poor prognostic sign (hematoxylin and eosin, x 400).1
Clinical Breast Cancer October 2000 • 243
Metastatic Breast Cancer Figure 3
Cytology of Lymph Node Aspirate
The aspirate contained numerous groups of malignant epithelial groupings. In the smear background, scattered reactive lymphoid cells could also be identified, indicating that the metastasis was arising within a lymph node (Papanicolaou stain, x 400).
further treatment against the advice of her oncologist. She also declined adjunctive radiation therapy. The patient did well until approximately 2 months ago, when she noticed an enlarged left supraclavicular lymph node. After examining her, the patient’s surgeon contacted the cytopathologist and requested that a fine-needle aspiration (FNA) of this supraclavicular lymph node be performed. The enlarged lymph node was very firm and measured approximately 2 cm in maximum diameter. After administering local anesthesia, FNA was performed using a 25-gauge needle. The aspirate contained obvious metastatic adenocarcinoma (Figures 3 and 4). At the time of the FNA, both the patient and her daughter, who accompanied her during the procedure, requested the results of the rapid-assessment diagnosis. The patient and her daughter were informed of the diagnosis. The patient’s surgeon was contacted and returned to the examining room. Soon afterwards, the patient met with her oncologist to discuss her prognosis and remaining therapeutic options. Although HER2/neu analysis by either immunohistochemistry or fluorescence in situ hybridization (FISH) could have been performed on the abundant cytologic material that had been collected, the oncologist requested that the FISH analysis be performed on tumor from the mastectomy specimen. This study showed no evidence of HER2/neu amplification.
Comments This patient developed a metachronous, contralateral invasive carcinoma 16 years after a diagnosis of comedocarcinoma was established. This phenomenon occurs in 10% to 12.5% of patients with intraductal carcinoma.2 Although treatment of the comedocarcinoma involving her left breast cancer was successful, the second invasive carcinoma arising in the right breast was high grade and demonstrated evidence of
244 • Clinical Breast Cancer October 2000
Figure 4
Histology of Lymph Node Aspirate
A portion of the aspirate was instilled into CytoRich-fixative and a paraffin-embedded cell block was prepared. The histologic sections cut from this cell block demonstrated obvious malignant glandular epithelium, which was almost identical in appearance to the histologic sections of the breast tumor obtained from the mastectomy specimen (hematoxylin and eosin, x 400). Lymphocytes from the uninvolved portion of the lymph node were not seen in this preparation.
lymphatic invasion, features that are known to be associated with a high risk of occult metastases. For this reason, she was offered cytotoxic chemotherapy. The identification of metastatic adenocarcinoma in a supraclavicular lymph node provides pathologic evidence of stage IV disease. Documenting the presence of metastatic adenocarcinoma in lymph nodes is most effectively accomplished by FNA cytology. Usually, as was true in this case, the diagnosis of metastatic adenocarcinoma is straightforward and can be reliably made by the assessment of the cytomorphologic features alone. Ancillary studies such as immunocytochemistry for ER, PR, or HER2/neu can be performed on cytologic material obtained by FNA.3,4 The importance to the patient and the physician of a cytologic diagnosis of metastatic adenocarcinoma is obvious. Pathologic proof of metastasis is necessary before discussing the prognostic and therapeutic implications with the patient or initiating treatment. Alternatives to the FNA diagnosis of metastatic disease, including either core or excisional biopsy of the lymph node, are much more invasive and costly procedures with higher complication rates. For these reasons, FNA is the diagnostic technique of first choice for the documentation of suspected metastases.
References 01. Rosen PP. Rosen’s Breast Pathology. New York: Lippincott-Raven, 1996: 283-285. 02. Rosen PP. Rosen’s Breast Pathology. New York: Lippincott-Raven, 1996: 230-232. 03. Troncone G, Panico L, Vetrani A, et al. c-erbB-2 expression in FNAB smears and matched surgical specimens of breast cancer. Diagn Cytopathol 1996; 14:135-139. 04. Marrazzo A, Taormina P, Leonardi P, et al. Immunocytochemical determination of estrogen and progesterone receptors on 219 fine-needle aspirates of breast cancer. A prospective study. Anticancer Res 1995; 15:521526.
breast cancer Cytopathology of Metastatic Breast Cancer Harvey Cramer Abstract
A 52-year-old woman developed an infiltrating ductal carcinoma of the breast 16 years after being treated for comedocarcinoma of the left breast. Although the tumor was high grade with lymphatic space invasion and incompletely excised, the patient declined adjunctive therapy. Within 2 years, she developed metastasis to supraclavicular lymph nodes, which was diagnosed by fine-needle aspiration cytology. Clinical Breast Cancer, Vol. 1, No. 3, 243-244, 2000 Key words: Breast cancer, Metastasis, Fine needle aspiration
Patient History and Pathologic Findings Approximately 16 years ago, a 52-year-old woman developed comedocarcinoma of the left breast. She was treated with a left modified radical mastectomy and an axillary lymph node dissection. There was no evidence of metastatic adenocarcinoma in any of the 13 lymph nodes removed. Bilateral breast reconstruction with insertion of silicone implants was performed. As recommended by her physician, she underwent annual follow-up mammography. Two years ago, a mammogram disclosed the presence of a 1.8 cm mass involving the upper inner quadrant of the right breast. A core needle biopsy was performed and disclosed an infiltrating ductal carcinoma. Immunohistochemical analysis performed on the core biopsy indicated that the carcinoma was negative for both estrogen receptor (ER) and progesterone receptor (PR) proteins. She underwent a sentinel lymph node biopsy followed by a right modified radical mastectomy and immediate bilateral breast reconstruction with replacement of the previous silicone implants with saline implants. Two sentinel lymph nodes were sampled and both were free of tumor. In the mastectomy specimen, the tumor measured a maximum of 1.6 cm and was poorly differentiated (Figure 1). Lymphatic invasion was present (Figure 2), and coexistent high-grade ductal carcinoma in situ was also noted. Both infiltrating and intraductal carcinomas were identified at the inked superficial margin and within 0.55 mm of the deep margin. The patient was offered a standard 4-cycle regimen of cytotoxic chemotherapy consisting of doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2). Due
to perceived toxicities occurring during the first course of chemotherapy, the patient decided to discontinue
Figure 1
High-Grade Infiltrating Duct Carcinoma
A section of the tumor in the mastectomy specimen disclosed a highgrade infiltrating duct carcinoma. There was a marked degree of nuclear pleomorphism and the mitotic count was high (hematoxylin and eosin, x 400).
Figure 2
Lymphatic Spaces Containing Malignant Tumor Cells
Wishard Memorial Hospital, Indianapolis, IN Submitted: July 28, 2000; Revised: Oct. 5, 2000; Accepted: Oct. 6, 2000 Address for correspondence: Harvey Cramer, MD, Wishard Memorial Hospital, LL Myers Building, 1001 West Tenth Street, Indianapolis, IN 46202-2879 Fax: 317-630-7913; e-mail: [email protected]
In one section, lymphatic spaces containing malignant tumor cells were identified. Lymphatic invasion is a poor prognostic sign (hematoxylin and eosin, x 400).1
Clinical Breast Cancer October 2000 • 243
Metastatic Breast Cancer Figure 3
Cytology of Lymph Node Aspirate
The aspirate contained numerous groups of malignant epithelial groupings. In the smear background, scattered reactive lymphoid cells could also be identified, indicating that the metastasis was arising within a lymph node (Papanicolaou stain, x 400).
further treatment against the advice of her oncologist. She also declined adjunctive radiation therapy. The patient did well until approximately 2 months ago, when she noticed an enlarged left supraclavicular lymph node. After examining her, the patient’s surgeon contacted the cytopathologist and requested that a fine-needle aspiration (FNA) of this supraclavicular lymph node be performed. The enlarged lymph node was very firm and measured approximately 2 cm in maximum diameter. After administering local anesthesia, FNA was performed using a 25-gauge needle. The aspirate contained obvious metastatic adenocarcinoma (Figures 3 and 4). At the time of the FNA, both the patient and her daughter, who accompanied her during the procedure, requested the results of the rapid-assessment diagnosis. The patient and her daughter were informed of the diagnosis. The patient’s surgeon was contacted and returned to the examining room. Soon afterwards, the patient met with her oncologist to discuss her prognosis and remaining therapeutic options. Although HER2/neu analysis by either immunohistochemistry or fluorescence in situ hybridization (FISH) could have been performed on the abundant cytologic material that had been collected, the oncologist requested that the FISH analysis be performed on tumor from the mastectomy specimen. This study showed no evidence of HER2/neu amplification.
Comments This patient developed a metachronous, contralateral invasive carcinoma 16 years after a diagnosis of comedocarcinoma was established. This phenomenon occurs in 10% to 12.5% of patients with intraductal carcinoma.2 Although treatment of the comedocarcinoma involving her left breast cancer was successful, the second invasive carcinoma arising in the right breast was high grade and demonstrated evidence of
244 • Clinical Breast Cancer October 2000
Figure 4
Histology of Lymph Node Aspirate
A portion of the aspirate was instilled into CytoRich-fixative and a paraffin-embedded cell block was prepared. The histologic sections cut from this cell block demonstrated obvious malignant glandular epithelium, which was almost identical in appearance to the histologic sections of the breast tumor obtained from the mastectomy specimen (hematoxylin and eosin, x 400). Lymphocytes from the uninvolved portion of the lymph node were not seen in this preparation.
lymphatic invasion, features that are known to be associated with a high risk of occult metastases. For this reason, she was offered cytotoxic chemotherapy. The identification of metastatic adenocarcinoma in a supraclavicular lymph node provides pathologic evidence of stage IV disease. Documenting the presence of metastatic adenocarcinoma in lymph nodes is most effectively accomplished by FNA cytology. Usually, as was true in this case, the diagnosis of metastatic adenocarcinoma is straightforward and can be reliably made by the assessment of the cytomorphologic features alone. Ancillary studies such as immunocytochemistry for ER, PR, or HER2/neu can be performed on cytologic material obtained by FNA.3,4 The importance to the patient and the physician of a cytologic diagnosis of metastatic adenocarcinoma is obvious. Pathologic proof of metastasis is necessary before discussing the prognostic and therapeutic implications with the patient or initiating treatment. Alternatives to the FNA diagnosis of metastatic disease, including either core or excisional biopsy of the lymph node, are much more invasive and costly procedures with higher complication rates. For these reasons, FNA is the diagnostic technique of first choice for the documentation of suspected metastases.
References 01. Rosen PP. Rosen’s Breast Pathology. New York: Lippincott-Raven, 1996: 283-285. 02. Rosen PP. Rosen’s Breast Pathology. New York: Lippincott-Raven, 1996: 230-232. 03. Troncone G, Panico L, Vetrani A, et al. c-erbB-2 expression in FNAB smears and matched surgical specimens of breast cancer. Diagn Cytopathol 1996; 14:135-139. 04. Marrazzo A, Taormina P, Leonardi P, et al. Immunocytochemical determination of estrogen and progesterone receptors on 219 fine-needle aspirates of breast cancer. A prospective study. Anticancer Res 1995; 15:521526.