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Breast biopsy in young women
LETTERS TO THE EDITOR
METASTATIC CARCINOMA IN THE CIRRHOTIC LIVER To the Editor:
In a recent article in the Journal, Uetsuji et al [I] showed that colorectal cancer metastasized to the normal liver, but not the injured liver, especially the cirrhotic liver. In terms of preventive treatment of liver metastases, these findings might be extremely valuable, as contrasted with the recurrence pattern of hepatocellular carcinoma (HCC). In Japan, approximately 80% of patients with H C C have associated liver cirrhosis [2]. H C C tends to spread intrahepatically from the portal vein system, because the portal vein is a draining vessel of H C C [3]. We have confirmed that intrahepatic recurrences were the most common type [4]. Why does colorectal cancer metastasize with difficulty to the cirrhotic liver, whereas H C C can do so easily? In fact, the rarity of the occurrence of metastatic malignancy in hepatic cirrhosis has been noted by several observers, especially pathologists, for more than a half century, and the explanation is still an open question. In 1942, Lisa et al [5] offered the opinion that the cirrhotic liver is not a favorable soil for the transplanted tumor cells. Lieber [6] suggested that the fibrosis and subsequent distortion of the small vessels in the liver constitute a mechanical impediment to the spread of the cancerous tissue. Uetsuji et al [1] noted that epidemiologic findings show that liver cirrhosis caused by viral infection is more frequent in Japan than in Western countries. However,; there is an excellent article by Gall [7] on the relationship between the rarity of metastatic carcinoma in the cirrhotic liver and the etiology of cirrhosis. He found 5 patients with such combined lesions (2.3%) among 217 with posthepatitic cirrhosis and only 1 patient (0.6%) among 161 with nutritional (alcoholic, fatty) cirrhosis. Thus, the rarity of co-existing hepatic metastases and cirrhosis is observed not only in the patients with liver cirrhosis produced by viral hepatitis but also in those with nutritional cirrhosis. Uetsuji et al [1] suggest-
776
ma does so easily. It is possible that each cancer cell has organ specificity because of the different generating ground. In regard to their statement, "The rarity of co-existing hepatic metastasis and cirrhosis is observed not only in patients with liver cirrhosis produced by viral hepatitis but also in those with nutritional cirrhosis," it is possible that metastasis might arise from differences in the histologic grade of liver cirrhosis. As to their statement, "The rarity of metastatic malignancy in hepatic cirrhosis may be attributed to anatomic-mechanical factors and/or Tohru Utsunorniya, Me other factors," since fibronectin [1,2] Takashi Matsumata, MD as a factor in cell adhesion is known, Kyushu University it is possible that hepatic metastasis Fukuoka, Japan might occur from the interaction be1. Uetsuij S, Yamamura M, Yamamichi K, tween fibronectin receptors on hepatOkuda Y, Takada H, Hioki K. Absence of ic cells and fibronectin cancer cells. colorectal cancer metastasis to the cirrhotic Perhaps there are fibronectin recepliver. Am J Surg 1992; 164: 176-7, tors on the intact hepatic cells, but 2. The Liver Cancer Study Group of Japan. few of them on the hepatic cells in the Primary liver cancer in Japan. Ann Surg cirrhotic liver. I am investigating the 1990; 211: 277-87. mechanism of hepatic metastasis 3. Matsumata T, Kanematsu T, Takenaka K, Sugimachi K. Lack of intrahepatic recur- with respect to fibronectin.
ed that a decrease in the blood flow in cirrhotic livers may be another probable cause. We believe that this rarity results, at least in part, from intrahepatic and extrahepatic portosystemic shunt in cirrhotic patients. Unfortunately, Uetsuji and coworkers failed to mention the incidence of systemic metastases. Because it is very important to know whether this rarity is attributed to anatomic-mechanical factors and/or other reasons (for example, organ specificity of cancer cells [8]) in order to conduct better preventive treatment of liver metastases, we consider this to be a serious omission.
rence of hepatocellular carcinoma by temporary portal venous embolization with starch microspheres. Surgery 1989; 105: 188-91. 4. Kanematsu T, Matsumata T, Takenaka K, Yoshida Y, Higashi H, Sugimachi K, Clinical management of recurrent hepatocellular carcinoma after primary resection. Br J Surg 1988; 75: 203-6. 5. Lisa JR, Solomon C, Gordon EJ. Secondary carcinoma in cirrhosis of the liver. Am j Pathol 1942; 18: 13%40. 6. Lieber MM. The rare occurrence of metastatic carcinoma in the cirrhotic liver. Am J Med Sci 1957; 233: 145-52. 7. Gall EA. Primary and metastatic carcinoma of the liver. Arch Pathol 1960; 70: 226-32. 8. Utsunomiya T, Matsumata T, Nishizaki T, Adachi E, Kanematsu T, Sugimachi K. VX2 carcinoma has a higher affinity in lungs than liver of rabbits after intravenous administration via different routes. Dig Surg 1992; 9: 35-7.
In Response:
I wholeheartedly agree with the comments of Drs. Utsunomiya and Matsumata regarding the absence of colorectal metastasis to the cirrhotic liver. It is difficult for colorectal cancer to metastasize to the cirrhotic liver, whereas hepatocellular carcino-
THE AMERICAN JOURNAL OF SURGERY
Shofi Uetsufi, MD Kansai Medical University Osaka, Japan 1. Szendr6i M, Lapis K. Fibronectin in differential diagnosis of primary hepatomas and carcinoma metastases in the liver. Aeta Morphol Hungarica 1985; 33: 101-9. 2. Lance A. Tumor invasion and metastasis: role of the basement membrane. Am J Pathol 1984; 117: 339-48.
BREAST BIOPSY IN YOUNG WOMEN To the Editor:
Drs. Palmer and Tsangaris must be commended on their recent comprehensive study of breast biopsy in women under age 30 years [I]. After finding an incidence of 2.5% for breast cancer in this age group, the authors advocate biopsy of solid masses that persist beyond an observation period of 2 or 3 months. In their discussion, the authors suggest that this strategy will prevent misdiagnosis, thereby decreasing negli-
VOLUME 166 DECEMBER 1993
LETTERS TO THE EDITOR
gence litigation. In support of their reasoning, the authors cite a medical news summary of the Physician Insurers Association Breast Cancer Study (1990), documenting 69% of 273 negligence claims involved women under age 50 years. More to the point, a review of the primary document itself shows that 9% of women were aged 20 t o 29 years, and 40% were 39 years of age or younger [2]. From another insurance payment survey, the authors noted the average indemnity paid for negligence claims was $100,000 [3]. In the Physician Insurers Survey, 12% of the total indemnity paid was for women under age 30 years, averaging $286,000 per claim [2]. My own medicolegal analysis of the delayed diagnosis of breast cancer, published in 1992, underscores both the youthfulness of women with misdiagnosed breast cancer and the expense of court actions [4]. In a review of 45 cases of misdiagnosed breast cancer tried in the U.S. civil court system between 1971 and 1990, I noted that 19% of patients involved in such cases were aged 20 to 29 years, 39% were 30 to 39 years of age, and 30% were 40 to 49 years of age. Overall, the mean age of patients was 40 years. The average liability payment for the 22 known cases was $675,532; for general surgeons alone, the average liability payment was $885,528. The highest award of $3 million resulted from a 6-month diagnostic delay in a 30year-old pregnant woman, who died of metastatic disease within several years. Although I support the major conclusions of Palmer and Tsangaris, I believe that caution is warranted when acting upon several of the authors' recommendations. First, I must warn of the consequences of accepting the results of fine-needle biopsy as diagnostic in breast masses. In my study of 45 malpractice cases, the 1 patient who underwent needle biopsy had a false-negative result.
More recently, a jury trial in New York resulted in a $1.5 million verdict against a surgeon, pathologist, and internist for failure to diagnose breast cancer, based upon an erroneous fine-needle biopsy result. In this instance, a 37-year-old homemaker with a breast mass underwent a fineneedle biopsy, which was interpreted incorrectly by a pathologist as benign. Because of this false-negative report, the mass was not excised. Sixteen months later, the mass grew larger, and excisional biopsy revealed invasive breast cancer. Despite mastectomy and chemotherapy, the patient died 33 months after initial misdiagnosis [Smith v. Dutkewych, No. 88-1980 (Madison Cty. Sup. Ct. N.Y. June 8, 1992)]. Second, applying mammography as part of the authors' proposed "diagnostic triplet" is unlikely to improve the accuracy of diagnosis in women under age 30 years. In my study (in which the average age was 40 years), 80% of mammograms were interpreted as normal, despite the presence of a documented, palpable breast cancer. In another study, mammography failed to yield images of 74% of masses in women 30 years of age or younger [5]. Finally, when breast cancer is diagnosed in young women, a delay in obtaining a biopsy specimen in order to observe a mass for 2 or 3 months may serve as grounds for medicolegal action. The risks and benefits of delay should be explained carefully to the patient, and the decision to delay biopsy should be mutual. In my recent review of historical trends in breast cancer litigation [6], I cited a malpractice trial from New Mexico in 1978, in which a delay in breast biopsy of only 28 days led to a jury verdict against a surgeon. In this case, the surgeon decided to determine the need for excisional biopsy by re-evaluating a breast mass after the patient completed one menstrual cycle. After 28 days, the mass persisted, and excisional biopsy proved
THE AMERICAN JOURNAL OF SURGERY
malignant. The patient sued the surgeon and won her case; she claimed recommendations from the National Cancer Institute in 1977 called for immediate biopsy of suspicious breast masses. Because of the unusually short diagnostic delay, the jury's decision against the surgeon was appealed, but the verdict was upheld by the New Mexico Court of Appeals. In its judicial decision, the Court unequivocally supported the jury's verdict that waiting 1 month was a deviation from the standard of care for breast diagnosis [Henning v. Parsons, N.M. App., 623 P. 2d 574 (1978)]. Given these medicolegal actions, I, like Palmer and Tsangaris, support the excision of isolated, solid breast masses in women under age 30 years. If another option is selected, such as observation, mammography, or needle biopsy, I believe a clear explanation to the patient is mandatory about the potential for diagnostic error. In litigation surrounding the three aforementioned cases, the patients stated that they were not warned about the potential for a delayed diagnosis of breast cancer. Kenneth A. Kern, MD University of Connecticut School of Medicine Hartford, CT 1. Palmer ML, Tsangaris TN. Breast biopsy in women 30 years old or less. Am J Surg 1993; 165: 708-12. 2. Physician Insurers Association of America. Breast Cancer Study. Lawrenceville, N J: Physician Insurers Association of America; 1990. 3. Spratt JS, Spratt SW. Medical and legal implications of screening and follow-up procedures for breast cancer. Cancer 1990; 66: 1351-62. 4. Kern KA. Causes of breast cancer malpractice litigation. A 20-year civil court review. Arch Surg 1992; 127: 542-7. 5. Brenner RJ. Medicolegal aspects of breast imaging: variable standards of care relating to different types of practice. A JR Am J Roentgenol 1991; 156: 719-23. 6. Kern KA. Historical trends in breast cancer litigation: a clinician's perspective. Surg Oncol Clin North Am. In press.
VOLUME 166 DECEMBER 1993
777
METASTATIC CARCINOMA IN THE CIRRHOTIC LIVER To the Editor:
In a recent article in the Journal, Uetsuji et al [I] showed that colorectal cancer metastasized to the normal liver, but not the injured liver, especially the cirrhotic liver. In terms of preventive treatment of liver metastases, these findings might be extremely valuable, as contrasted with the recurrence pattern of hepatocellular carcinoma (HCC). In Japan, approximately 80% of patients with H C C have associated liver cirrhosis [2]. H C C tends to spread intrahepatically from the portal vein system, because the portal vein is a draining vessel of H C C [3]. We have confirmed that intrahepatic recurrences were the most common type [4]. Why does colorectal cancer metastasize with difficulty to the cirrhotic liver, whereas H C C can do so easily? In fact, the rarity of the occurrence of metastatic malignancy in hepatic cirrhosis has been noted by several observers, especially pathologists, for more than a half century, and the explanation is still an open question. In 1942, Lisa et al [5] offered the opinion that the cirrhotic liver is not a favorable soil for the transplanted tumor cells. Lieber [6] suggested that the fibrosis and subsequent distortion of the small vessels in the liver constitute a mechanical impediment to the spread of the cancerous tissue. Uetsuji et al [1] noted that epidemiologic findings show that liver cirrhosis caused by viral infection is more frequent in Japan than in Western countries. However,; there is an excellent article by Gall [7] on the relationship between the rarity of metastatic carcinoma in the cirrhotic liver and the etiology of cirrhosis. He found 5 patients with such combined lesions (2.3%) among 217 with posthepatitic cirrhosis and only 1 patient (0.6%) among 161 with nutritional (alcoholic, fatty) cirrhosis. Thus, the rarity of co-existing hepatic metastases and cirrhosis is observed not only in the patients with liver cirrhosis produced by viral hepatitis but also in those with nutritional cirrhosis. Uetsuji et al [1] suggest-
776
ma does so easily. It is possible that each cancer cell has organ specificity because of the different generating ground. In regard to their statement, "The rarity of co-existing hepatic metastasis and cirrhosis is observed not only in patients with liver cirrhosis produced by viral hepatitis but also in those with nutritional cirrhosis," it is possible that metastasis might arise from differences in the histologic grade of liver cirrhosis. As to their statement, "The rarity of metastatic malignancy in hepatic cirrhosis may be attributed to anatomic-mechanical factors and/or Tohru Utsunorniya, Me other factors," since fibronectin [1,2] Takashi Matsumata, MD as a factor in cell adhesion is known, Kyushu University it is possible that hepatic metastasis Fukuoka, Japan might occur from the interaction be1. Uetsuij S, Yamamura M, Yamamichi K, tween fibronectin receptors on hepatOkuda Y, Takada H, Hioki K. Absence of ic cells and fibronectin cancer cells. colorectal cancer metastasis to the cirrhotic Perhaps there are fibronectin recepliver. Am J Surg 1992; 164: 176-7, tors on the intact hepatic cells, but 2. The Liver Cancer Study Group of Japan. few of them on the hepatic cells in the Primary liver cancer in Japan. Ann Surg cirrhotic liver. I am investigating the 1990; 211: 277-87. mechanism of hepatic metastasis 3. Matsumata T, Kanematsu T, Takenaka K, Sugimachi K. Lack of intrahepatic recur- with respect to fibronectin.
ed that a decrease in the blood flow in cirrhotic livers may be another probable cause. We believe that this rarity results, at least in part, from intrahepatic and extrahepatic portosystemic shunt in cirrhotic patients. Unfortunately, Uetsuji and coworkers failed to mention the incidence of systemic metastases. Because it is very important to know whether this rarity is attributed to anatomic-mechanical factors and/or other reasons (for example, organ specificity of cancer cells [8]) in order to conduct better preventive treatment of liver metastases, we consider this to be a serious omission.
rence of hepatocellular carcinoma by temporary portal venous embolization with starch microspheres. Surgery 1989; 105: 188-91. 4. Kanematsu T, Matsumata T, Takenaka K, Yoshida Y, Higashi H, Sugimachi K, Clinical management of recurrent hepatocellular carcinoma after primary resection. Br J Surg 1988; 75: 203-6. 5. Lisa JR, Solomon C, Gordon EJ. Secondary carcinoma in cirrhosis of the liver. Am j Pathol 1942; 18: 13%40. 6. Lieber MM. The rare occurrence of metastatic carcinoma in the cirrhotic liver. Am J Med Sci 1957; 233: 145-52. 7. Gall EA. Primary and metastatic carcinoma of the liver. Arch Pathol 1960; 70: 226-32. 8. Utsunomiya T, Matsumata T, Nishizaki T, Adachi E, Kanematsu T, Sugimachi K. VX2 carcinoma has a higher affinity in lungs than liver of rabbits after intravenous administration via different routes. Dig Surg 1992; 9: 35-7.
In Response:
I wholeheartedly agree with the comments of Drs. Utsunomiya and Matsumata regarding the absence of colorectal metastasis to the cirrhotic liver. It is difficult for colorectal cancer to metastasize to the cirrhotic liver, whereas hepatocellular carcino-
THE AMERICAN JOURNAL OF SURGERY
Shofi Uetsufi, MD Kansai Medical University Osaka, Japan 1. Szendr6i M, Lapis K. Fibronectin in differential diagnosis of primary hepatomas and carcinoma metastases in the liver. Aeta Morphol Hungarica 1985; 33: 101-9. 2. Lance A. Tumor invasion and metastasis: role of the basement membrane. Am J Pathol 1984; 117: 339-48.
BREAST BIOPSY IN YOUNG WOMEN To the Editor:
Drs. Palmer and Tsangaris must be commended on their recent comprehensive study of breast biopsy in women under age 30 years [I]. After finding an incidence of 2.5% for breast cancer in this age group, the authors advocate biopsy of solid masses that persist beyond an observation period of 2 or 3 months. In their discussion, the authors suggest that this strategy will prevent misdiagnosis, thereby decreasing negli-
VOLUME 166 DECEMBER 1993
LETTERS TO THE EDITOR
gence litigation. In support of their reasoning, the authors cite a medical news summary of the Physician Insurers Association Breast Cancer Study (1990), documenting 69% of 273 negligence claims involved women under age 50 years. More to the point, a review of the primary document itself shows that 9% of women were aged 20 t o 29 years, and 40% were 39 years of age or younger [2]. From another insurance payment survey, the authors noted the average indemnity paid for negligence claims was $100,000 [3]. In the Physician Insurers Survey, 12% of the total indemnity paid was for women under age 30 years, averaging $286,000 per claim [2]. My own medicolegal analysis of the delayed diagnosis of breast cancer, published in 1992, underscores both the youthfulness of women with misdiagnosed breast cancer and the expense of court actions [4]. In a review of 45 cases of misdiagnosed breast cancer tried in the U.S. civil court system between 1971 and 1990, I noted that 19% of patients involved in such cases were aged 20 to 29 years, 39% were 30 to 39 years of age, and 30% were 40 to 49 years of age. Overall, the mean age of patients was 40 years. The average liability payment for the 22 known cases was $675,532; for general surgeons alone, the average liability payment was $885,528. The highest award of $3 million resulted from a 6-month diagnostic delay in a 30year-old pregnant woman, who died of metastatic disease within several years. Although I support the major conclusions of Palmer and Tsangaris, I believe that caution is warranted when acting upon several of the authors' recommendations. First, I must warn of the consequences of accepting the results of fine-needle biopsy as diagnostic in breast masses. In my study of 45 malpractice cases, the 1 patient who underwent needle biopsy had a false-negative result.
More recently, a jury trial in New York resulted in a $1.5 million verdict against a surgeon, pathologist, and internist for failure to diagnose breast cancer, based upon an erroneous fine-needle biopsy result. In this instance, a 37-year-old homemaker with a breast mass underwent a fineneedle biopsy, which was interpreted incorrectly by a pathologist as benign. Because of this false-negative report, the mass was not excised. Sixteen months later, the mass grew larger, and excisional biopsy revealed invasive breast cancer. Despite mastectomy and chemotherapy, the patient died 33 months after initial misdiagnosis [Smith v. Dutkewych, No. 88-1980 (Madison Cty. Sup. Ct. N.Y. June 8, 1992)]. Second, applying mammography as part of the authors' proposed "diagnostic triplet" is unlikely to improve the accuracy of diagnosis in women under age 30 years. In my study (in which the average age was 40 years), 80% of mammograms were interpreted as normal, despite the presence of a documented, palpable breast cancer. In another study, mammography failed to yield images of 74% of masses in women 30 years of age or younger [5]. Finally, when breast cancer is diagnosed in young women, a delay in obtaining a biopsy specimen in order to observe a mass for 2 or 3 months may serve as grounds for medicolegal action. The risks and benefits of delay should be explained carefully to the patient, and the decision to delay biopsy should be mutual. In my recent review of historical trends in breast cancer litigation [6], I cited a malpractice trial from New Mexico in 1978, in which a delay in breast biopsy of only 28 days led to a jury verdict against a surgeon. In this case, the surgeon decided to determine the need for excisional biopsy by re-evaluating a breast mass after the patient completed one menstrual cycle. After 28 days, the mass persisted, and excisional biopsy proved
THE AMERICAN JOURNAL OF SURGERY
malignant. The patient sued the surgeon and won her case; she claimed recommendations from the National Cancer Institute in 1977 called for immediate biopsy of suspicious breast masses. Because of the unusually short diagnostic delay, the jury's decision against the surgeon was appealed, but the verdict was upheld by the New Mexico Court of Appeals. In its judicial decision, the Court unequivocally supported the jury's verdict that waiting 1 month was a deviation from the standard of care for breast diagnosis [Henning v. Parsons, N.M. App., 623 P. 2d 574 (1978)]. Given these medicolegal actions, I, like Palmer and Tsangaris, support the excision of isolated, solid breast masses in women under age 30 years. If another option is selected, such as observation, mammography, or needle biopsy, I believe a clear explanation to the patient is mandatory about the potential for diagnostic error. In litigation surrounding the three aforementioned cases, the patients stated that they were not warned about the potential for a delayed diagnosis of breast cancer. Kenneth A. Kern, MD University of Connecticut School of Medicine Hartford, CT 1. Palmer ML, Tsangaris TN. Breast biopsy in women 30 years old or less. Am J Surg 1993; 165: 708-12. 2. Physician Insurers Association of America. Breast Cancer Study. Lawrenceville, N J: Physician Insurers Association of America; 1990. 3. Spratt JS, Spratt SW. Medical and legal implications of screening and follow-up procedures for breast cancer. Cancer 1990; 66: 1351-62. 4. Kern KA. Causes of breast cancer malpractice litigation. A 20-year civil court review. Arch Surg 1992; 127: 542-7. 5. Brenner RJ. Medicolegal aspects of breast imaging: variable standards of care relating to different types of practice. A JR Am J Roentgenol 1991; 156: 719-23. 6. Kern KA. Historical trends in breast cancer litigation: a clinician's perspective. Surg Oncol Clin North Am. In press.
VOLUME 166 DECEMBER 1993
777