Journal of Surgical Oncology 51:211-215 (1992)
Metastatic Breast Carcinoma Presenting as Persistent Diarrhea AMY S. GIFALDI,
MD,
JAMES G . PETROS,
MO, AND
GAIL R.Z. WOLFE,
MD
From the Departments of Surgery (A.S.C, I.C.P.) and Pathology (C.R.Z.W.),St. EIizabeth’s Hospital of Boston, and Tufts University School of Medicine, Boston, Massachusetts
Patients with breast carcinoma metastatic to the colon generally present with multiple symptoms, usually pain, vomiting, nausea, and ascites. We describe a patient who presented only with persistent diarrhea, underwent surgery for colon cancer, and, on pathological evaluation of the surgical specimen, was found to have metastatic breast cancer affecting the colon. Metastatic breast cancer should therefore be suspected in patients with a history of breast cancer and diarrhea of unknown cause that is not accompanied by other symptoms. Evaluating such patients by colonoscopy and biopsy would provide important information relevant to choosing between colon surgery and systemic therapy. 0 1992 WiIey-Liss, Inc. KEYWORDS:colonoscopy, presentation, metastasis, colon
INTRODUCTION Approximately 50% of all patients with breast carcinoma have a relapse within 10 years of their initial diagnosis [ 13. Metastatic breast carcinoma usually involves the lung, bones, liver, or brain, although disseminated disease can also appear anywhere in the alimentary tract [2]. Most patients with metastases to the colon, which occur infrequently, have multiple symptoms, usually including abdominal pain, vomiting, nausea, melena, and ascites. We report a case of breast carcinoma metastatic to the colon in which the only presenting symptom was persistent diarrhea. CASE HISTORY An 86-year-old otherwise healthy, alert, and oriented woman presented with diarrhea of several weeks duration but no other symptoms. She had no cramping or rectal bleeding and no recent history of hospitalization or antibiotic use. An abdominal examination revealed no masses, organomegaly , distention, shifting dullness, or tenderness. A culture evaluation for Clostridiurn difficile was negative, and a microscopical examination showed normal flora with no white blood cells. Ten years earlier, the patient had undergone a modified radical mastectomy of the left breast for Stage 1 lobular carcinoma. A pathological evaluation at that time demonstrated infiltrating lobular carcinoma with positive estrogen and progesterone receptors but no lymph node me0 1992 Wiley-Liss, Inc.
tastases. The patient had an uneventful recovery, with no postoperative adjuvant therapy. Subsequent yearly physical examinations showed no evidence of local or distant recurrence. The patient was admitted to our hospital, where she initially underwent intravenous hydration and electrolyte repletion. Bone scans, mammographic evaluations, and a digital rectal examination yielded normal results. A barium enema, however, demonstrated an apple-core lesion in the proximal transverse colon, indicative of a primary adenocarcinoma, and a second colonic narrowing, with nodular mucosa, several centimeters distal to the first lesion (Fig. 1). Subsequent colonoscopy showed intact but edematous mucosa in the vicinity of the lesions. Biopsy studies yielded normal results. A computed tomographic scan of the abdomen showed thickening of the proximal transverse colon wall, with intact mucosa. Several days later, the patient underwent an exploratory laparotomy . During the operation, the transverse colonic wall was found to be grossly thickened, with moderate adhesions to adjacent stomach, greater omentum, and gallbladder tissue. The adhesions appeared to represent a fibrotic reaction rather than direct extension of the process to contiguous surfaces. The liver, serosal Accepted for publication March 12, 1992. Address reprint requests to Dr. James G . Petros, Department of Surgery, St. Elizabeth’s Hospital, 736 Cambridge Street, Boston, MA 02135.
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Fig. I . Barium enema film obtained in 1990, showing annular lesion in the proximal transverse colon (arrow) and narrowing, with nodular mucoba, in the distal transverse colon (arrowhead).
surfaces, and pelvis were grossly free of metastases. Because primary colon cancer was not suspected, neither en bloc resection nor frozen-section assessment was performed. Instead, the patient underwent an extended right hemicolectomy with an ileotransverse colostomy. Postoperative pathological studies revealed metastatic carcinoma affecting the colon and contiguous serosal surfaces. The colonic wall was markedly thickened at both stricture sites, but the mucosa was intact with a slight cobblestone appearance. Microscopy showed that tumor cells had invaded the serosa, muscularis propria, and submucosa, but spared the mucosa (Fig. 2). The cells were histologically and cytologically identical to those in the lobular breast carcinoma specimen resected 10 years earlier (Fig. 3) in that they were arranged in rows (“Indian files”) and showed focal signet-ring cell differentiation (Fig. 4). The metastatic tumor, like the primary lesion, was positive for estrogen and progesterone receptors. The patient recovered uneventfully from colon surgery and was scheduled to receive tamoxifen therapy postoperatively.
DISCUSSION Carcinoma of the breast is the most common source of hematogenous metastases to the colon [3], although colon metastasis is not as well documented as gastric and small-bowel dissemination [4]. In an autopsy study of 337 patients with breast carcinoma, Asch et al. [5] observed metastases to the colon in 4.5%. Breast carcinoma metastatic to the gastrointestinal tract appears to spread embolically to the submucosa, with subsequent infiltra-
tion through to the muscularis propria and deeper layers [6]. As in our patient, the metastases are often derived from lobular carcinomas [7-91. Symptoms of metastasis to the colon usually mimic those of colorectal carcinoma [4,8] or inflammatory colitis [ 101. They are not specific, however, and may resemble the symptoms of radiation enteritis, chemotherapy toxicity, hypercalcemia, gastritis, and peptic ulcer disease [ 1I]. A study of 35 patients with breast carcinoma in whom gastrointestinal metastases developed found that the most prominent symptoms were abdominal pain ( 3 1 % of patients), vomiting (31%), nausea (25%),hematemesis ( 1 9%), dysphagia ( 1 5 % ) , melena ( 1 5 % ) , weight loss (12%), and anorexia (6%) [ 121. A palpable abdominal mass is present in 15% of patients [ 131. Although Meyers mentioned that chronic diarrhea may be a presenting symptom 131, he did not cite any particular instances in which this had occurred and we found no previous reports of a case in which it was the only symptom. The lack of specific symptoms explains why the diagnosis of gastrointestinal metastases is established antemortem in only 8% of cases [ 141. Radiological diagnosis of early colonic metastases may be difficult because of the initial absence of substantial changes in the colon. As the disease progresses, however, barium studies characteristically show mucosal thickening and nodularity , multiple strictures, loss of the haustral pattern, and involvement of the terminal ileum [3,8,11]. These findings may be diffuse, limited to the right colon, or rarely, confined to the rectum [3]. Mucosal ulcerations and intraluminal defects, which are common in primary colorectal carcinoma, are unusual [8,111. Frequently, the diagnosis of gastrointestinal metastases from breast carcinoma depends on examining tissue obtained either endoscopically or surgically [3]. Microscopical evaluation shows carcinoma cells infiltrating from the serosa into the muscularis propria and submucosa. The cells are usually arranged in rows, or “Indian files,” which is characteristic of lobular breast carcinoma. The surrounding tissues often show an intense desmoplastic reaction IS]. Gastrointestinal symptoms resulting from disseminated breast carcinoma may appear many years after the initial diagnosis of breast cancer [ 1 I I. Our patient, who had undergone regular physical examinations after her mastectomy, had no such symptoms for more than 10 years, and her only symptom on presentation was persis-
Fig. 2. Surgical specimen obtained in 1990, showing tumor cells invading the entire thickness of the colonic wall. Hematoxylin-eosin stain. X I O . Fig. 3. Mastectomy specimen obtained in 1980, showing infiltrating lobular carcinoma. Hematoxylin-eosin stain. X 10.
Metastatic Breast Carcinoma
Figs. 2 and 3 . Legends appear on page 212
213
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Gifaldi et al.
Fig. 4. Mastectomy specimen obtained in 1980, showing signet-ring cell formation among lobular carcinoma cells. Hematoxylin-eosin stain. x 25.
tent diarrhea. Gross examination of the colon during surgery revealed no evidence of colonic or small-bowel dilatation proximal to the colonic lesions. In addition, there was no stercoraceous stasis, and gas and fluid could easily be passed manually through the lesions. Therefore, the diarrhea in our patient was not due to obstruction. Instead, it could have been caused by involvement of the terminal ileum, which occurs often with colonic metastasis [13], or by colonic wall thickening and mucosal edema, which, as in inflammatory or Crohn’s colitis, can lead to diarrhea [3]. This case demonstrates that diarrhea may be the sole symptom of metastatic breast cancer. Clearly, all patients with a history of breast cancer and diarrhea do not require a full work-up for metastatic disease. However, breast cancer metastatic to the gastrointestinal tract should be suspected in patients with a history of breast cancer and diarrhea of unknown origin that is unaccompanied by other symptoms. Colonoscopic and biopsy evaluations of such patients will provide information indicating whether colon surgery or systemic therapy would be the most appropriate treatment.
ACKNOWLEDGMENT We thank Renee J. Robillard for editing the manuscript. REFERENCES 1. Valagussa P, Bonadonna G, Veronesi U: Patterns of relapse and survival following radical mastectomy: Analysis of 7 16 consecutive patients. Cancer 41:1170-1178, 1978. 2. Haubrich WS: Adenocarcinoma of the breast metastatic to the rectum [letter]. Gastrointest Endosc 31:403404, 1985. 3. Meyers MA: Intraperitoneal spread of malignancies and its effect on the bowel. Clin Radio1 32:129-146, 1981. 4. Rabau MY, Alon RJ, Webrin N, Yossipov Y: Colonic metastases from lobular carcinoma of the breast. Dis Col Rectum 31:401402, 1988. 5 . Asch MJ, Wiedel PD, Habif DV: Gastrointestinal metastases from carcinoma of the breast: Autopsy study and 18 cases requiring operative intervention. Arch Surg 96:840-843, 1968. 6. Graham WP 111, Goldman L: Gastrointestinal metastases from carcinoma of the breast. Ann Surg 159:477-480, 1964. 7. Merino MJ, Livolsi VA: Signet ring carcinoma of the female breast. A clinicopathologic analysis of 24 cases. Cancer 48: 18301837, 1981. 8. Fayemi AO, Ali M, Braun EV: Metastatic carcinoma simulating linitis plastica of the colon. Am J Gastroenterol 71:311-314, 1979. 9. Harris M, Howell A, Chrissohou M, Swindell RIC, Hudson M,
Metastatic Breast Carcinoma
10.
11. 12. 13.
14.
Sellwood RA: A comparison of the metastatic pattern of infiltrating lobular carcinoma and infiltrating duct carcinoma of the breast. Br J Cancer 50:23-30, 1984. Weisberg A: Metastatic adenocarcinoma of the breast masquerading as Crohn’s disease of the colon. Am J Proctol Gastroenterol Colon Rectal Surg 33:1&15, 22, 1982. Chang SF, Burrell MI, Brand MH, Garsten JJ: The protean gastrointestinal manifestations of metastatic breast carcinoma. Radiology 126:611-617, 1978. Marshall ME: Gastrointestinal metastases from carcinoma of the breast. JKyMedAssoc81:154-157, 1983. Caramella E, Bruneton JN, Roux P, Aubanel D, Lecomte P: Metastases of the digestive tract: Report of 77 cases and review of the literature. Eur J Radio1 3:331-338, 1983. Hagemeister FB Jr, Buzdar AU, Luna MA, Blumenschein GR: Causes of death in breast cancer. A clinicopathologic study. Cancer 46:162-167, 1980.
215
EDITORIAL COMMENTS It is generally accepted that breast carcinoma can metastasize anywhere, but this example of metastasis only to the large bowel after 10 years is unusual. It is not clear how future cases can be handled any other way from what was done. This case may raise the index of suspicion but the clinical impression would have to be confirmed. Edward F. Scanlon, MD Department of Surgery Evanston Hospital Northwestern University Medical School Northbrook, Illinois 60062
Metastatic Breast Carcinoma Presenting as Persistent Diarrhea AMY S. GIFALDI,
MD,
JAMES G . PETROS,
MO, AND
GAIL R.Z. WOLFE,
MD
From the Departments of Surgery (A.S.C, I.C.P.) and Pathology (C.R.Z.W.),St. EIizabeth’s Hospital of Boston, and Tufts University School of Medicine, Boston, Massachusetts
Patients with breast carcinoma metastatic to the colon generally present with multiple symptoms, usually pain, vomiting, nausea, and ascites. We describe a patient who presented only with persistent diarrhea, underwent surgery for colon cancer, and, on pathological evaluation of the surgical specimen, was found to have metastatic breast cancer affecting the colon. Metastatic breast cancer should therefore be suspected in patients with a history of breast cancer and diarrhea of unknown cause that is not accompanied by other symptoms. Evaluating such patients by colonoscopy and biopsy would provide important information relevant to choosing between colon surgery and systemic therapy. 0 1992 WiIey-Liss, Inc. KEYWORDS:colonoscopy, presentation, metastasis, colon
INTRODUCTION Approximately 50% of all patients with breast carcinoma have a relapse within 10 years of their initial diagnosis [ 13. Metastatic breast carcinoma usually involves the lung, bones, liver, or brain, although disseminated disease can also appear anywhere in the alimentary tract [2]. Most patients with metastases to the colon, which occur infrequently, have multiple symptoms, usually including abdominal pain, vomiting, nausea, melena, and ascites. We report a case of breast carcinoma metastatic to the colon in which the only presenting symptom was persistent diarrhea. CASE HISTORY An 86-year-old otherwise healthy, alert, and oriented woman presented with diarrhea of several weeks duration but no other symptoms. She had no cramping or rectal bleeding and no recent history of hospitalization or antibiotic use. An abdominal examination revealed no masses, organomegaly , distention, shifting dullness, or tenderness. A culture evaluation for Clostridiurn difficile was negative, and a microscopical examination showed normal flora with no white blood cells. Ten years earlier, the patient had undergone a modified radical mastectomy of the left breast for Stage 1 lobular carcinoma. A pathological evaluation at that time demonstrated infiltrating lobular carcinoma with positive estrogen and progesterone receptors but no lymph node me0 1992 Wiley-Liss, Inc.
tastases. The patient had an uneventful recovery, with no postoperative adjuvant therapy. Subsequent yearly physical examinations showed no evidence of local or distant recurrence. The patient was admitted to our hospital, where she initially underwent intravenous hydration and electrolyte repletion. Bone scans, mammographic evaluations, and a digital rectal examination yielded normal results. A barium enema, however, demonstrated an apple-core lesion in the proximal transverse colon, indicative of a primary adenocarcinoma, and a second colonic narrowing, with nodular mucosa, several centimeters distal to the first lesion (Fig. 1). Subsequent colonoscopy showed intact but edematous mucosa in the vicinity of the lesions. Biopsy studies yielded normal results. A computed tomographic scan of the abdomen showed thickening of the proximal transverse colon wall, with intact mucosa. Several days later, the patient underwent an exploratory laparotomy . During the operation, the transverse colonic wall was found to be grossly thickened, with moderate adhesions to adjacent stomach, greater omentum, and gallbladder tissue. The adhesions appeared to represent a fibrotic reaction rather than direct extension of the process to contiguous surfaces. The liver, serosal Accepted for publication March 12, 1992. Address reprint requests to Dr. James G . Petros, Department of Surgery, St. Elizabeth’s Hospital, 736 Cambridge Street, Boston, MA 02135.
212
Gifaldi et al.
Fig. I . Barium enema film obtained in 1990, showing annular lesion in the proximal transverse colon (arrow) and narrowing, with nodular mucoba, in the distal transverse colon (arrowhead).
surfaces, and pelvis were grossly free of metastases. Because primary colon cancer was not suspected, neither en bloc resection nor frozen-section assessment was performed. Instead, the patient underwent an extended right hemicolectomy with an ileotransverse colostomy. Postoperative pathological studies revealed metastatic carcinoma affecting the colon and contiguous serosal surfaces. The colonic wall was markedly thickened at both stricture sites, but the mucosa was intact with a slight cobblestone appearance. Microscopy showed that tumor cells had invaded the serosa, muscularis propria, and submucosa, but spared the mucosa (Fig. 2). The cells were histologically and cytologically identical to those in the lobular breast carcinoma specimen resected 10 years earlier (Fig. 3) in that they were arranged in rows (“Indian files”) and showed focal signet-ring cell differentiation (Fig. 4). The metastatic tumor, like the primary lesion, was positive for estrogen and progesterone receptors. The patient recovered uneventfully from colon surgery and was scheduled to receive tamoxifen therapy postoperatively.
DISCUSSION Carcinoma of the breast is the most common source of hematogenous metastases to the colon [3], although colon metastasis is not as well documented as gastric and small-bowel dissemination [4]. In an autopsy study of 337 patients with breast carcinoma, Asch et al. [5] observed metastases to the colon in 4.5%. Breast carcinoma metastatic to the gastrointestinal tract appears to spread embolically to the submucosa, with subsequent infiltra-
tion through to the muscularis propria and deeper layers [6]. As in our patient, the metastases are often derived from lobular carcinomas [7-91. Symptoms of metastasis to the colon usually mimic those of colorectal carcinoma [4,8] or inflammatory colitis [ 101. They are not specific, however, and may resemble the symptoms of radiation enteritis, chemotherapy toxicity, hypercalcemia, gastritis, and peptic ulcer disease [ 1I]. A study of 35 patients with breast carcinoma in whom gastrointestinal metastases developed found that the most prominent symptoms were abdominal pain ( 3 1 % of patients), vomiting (31%), nausea (25%),hematemesis ( 1 9%), dysphagia ( 1 5 % ) , melena ( 1 5 % ) , weight loss (12%), and anorexia (6%) [ 121. A palpable abdominal mass is present in 15% of patients [ 131. Although Meyers mentioned that chronic diarrhea may be a presenting symptom 131, he did not cite any particular instances in which this had occurred and we found no previous reports of a case in which it was the only symptom. The lack of specific symptoms explains why the diagnosis of gastrointestinal metastases is established antemortem in only 8% of cases [ 141. Radiological diagnosis of early colonic metastases may be difficult because of the initial absence of substantial changes in the colon. As the disease progresses, however, barium studies characteristically show mucosal thickening and nodularity , multiple strictures, loss of the haustral pattern, and involvement of the terminal ileum [3,8,11]. These findings may be diffuse, limited to the right colon, or rarely, confined to the rectum [3]. Mucosal ulcerations and intraluminal defects, which are common in primary colorectal carcinoma, are unusual [8,111. Frequently, the diagnosis of gastrointestinal metastases from breast carcinoma depends on examining tissue obtained either endoscopically or surgically [3]. Microscopical evaluation shows carcinoma cells infiltrating from the serosa into the muscularis propria and submucosa. The cells are usually arranged in rows, or “Indian files,” which is characteristic of lobular breast carcinoma. The surrounding tissues often show an intense desmoplastic reaction IS]. Gastrointestinal symptoms resulting from disseminated breast carcinoma may appear many years after the initial diagnosis of breast cancer [ 1 I I. Our patient, who had undergone regular physical examinations after her mastectomy, had no such symptoms for more than 10 years, and her only symptom on presentation was persis-
Fig. 2. Surgical specimen obtained in 1990, showing tumor cells invading the entire thickness of the colonic wall. Hematoxylin-eosin stain. X I O . Fig. 3. Mastectomy specimen obtained in 1980, showing infiltrating lobular carcinoma. Hematoxylin-eosin stain. X 10.
Metastatic Breast Carcinoma
Figs. 2 and 3 . Legends appear on page 212
213
214
Gifaldi et al.
Fig. 4. Mastectomy specimen obtained in 1980, showing signet-ring cell formation among lobular carcinoma cells. Hematoxylin-eosin stain. x 25.
tent diarrhea. Gross examination of the colon during surgery revealed no evidence of colonic or small-bowel dilatation proximal to the colonic lesions. In addition, there was no stercoraceous stasis, and gas and fluid could easily be passed manually through the lesions. Therefore, the diarrhea in our patient was not due to obstruction. Instead, it could have been caused by involvement of the terminal ileum, which occurs often with colonic metastasis [13], or by colonic wall thickening and mucosal edema, which, as in inflammatory or Crohn’s colitis, can lead to diarrhea [3]. This case demonstrates that diarrhea may be the sole symptom of metastatic breast cancer. Clearly, all patients with a history of breast cancer and diarrhea do not require a full work-up for metastatic disease. However, breast cancer metastatic to the gastrointestinal tract should be suspected in patients with a history of breast cancer and diarrhea of unknown origin that is unaccompanied by other symptoms. Colonoscopic and biopsy evaluations of such patients will provide information indicating whether colon surgery or systemic therapy would be the most appropriate treatment.
ACKNOWLEDGMENT We thank Renee J. Robillard for editing the manuscript. REFERENCES 1. Valagussa P, Bonadonna G, Veronesi U: Patterns of relapse and survival following radical mastectomy: Analysis of 7 16 consecutive patients. Cancer 41:1170-1178, 1978. 2. Haubrich WS: Adenocarcinoma of the breast metastatic to the rectum [letter]. Gastrointest Endosc 31:403404, 1985. 3. Meyers MA: Intraperitoneal spread of malignancies and its effect on the bowel. Clin Radio1 32:129-146, 1981. 4. Rabau MY, Alon RJ, Webrin N, Yossipov Y: Colonic metastases from lobular carcinoma of the breast. Dis Col Rectum 31:401402, 1988. 5 . Asch MJ, Wiedel PD, Habif DV: Gastrointestinal metastases from carcinoma of the breast: Autopsy study and 18 cases requiring operative intervention. Arch Surg 96:840-843, 1968. 6. Graham WP 111, Goldman L: Gastrointestinal metastases from carcinoma of the breast. Ann Surg 159:477-480, 1964. 7. Merino MJ, Livolsi VA: Signet ring carcinoma of the female breast. A clinicopathologic analysis of 24 cases. Cancer 48: 18301837, 1981. 8. Fayemi AO, Ali M, Braun EV: Metastatic carcinoma simulating linitis plastica of the colon. Am J Gastroenterol 71:311-314, 1979. 9. Harris M, Howell A, Chrissohou M, Swindell RIC, Hudson M,
Metastatic Breast Carcinoma
10.
11. 12. 13.
14.
Sellwood RA: A comparison of the metastatic pattern of infiltrating lobular carcinoma and infiltrating duct carcinoma of the breast. Br J Cancer 50:23-30, 1984. Weisberg A: Metastatic adenocarcinoma of the breast masquerading as Crohn’s disease of the colon. Am J Proctol Gastroenterol Colon Rectal Surg 33:1&15, 22, 1982. Chang SF, Burrell MI, Brand MH, Garsten JJ: The protean gastrointestinal manifestations of metastatic breast carcinoma. Radiology 126:611-617, 1978. Marshall ME: Gastrointestinal metastases from carcinoma of the breast. JKyMedAssoc81:154-157, 1983. Caramella E, Bruneton JN, Roux P, Aubanel D, Lecomte P: Metastases of the digestive tract: Report of 77 cases and review of the literature. Eur J Radio1 3:331-338, 1983. Hagemeister FB Jr, Buzdar AU, Luna MA, Blumenschein GR: Causes of death in breast cancer. A clinicopathologic study. Cancer 46:162-167, 1980.
215
EDITORIAL COMMENTS It is generally accepted that breast carcinoma can metastasize anywhere, but this example of metastasis only to the large bowel after 10 years is unusual. It is not clear how future cases can be handled any other way from what was done. This case may raise the index of suspicion but the clinical impression would have to be confirmed. Edward F. Scanlon, MD Department of Surgery Evanston Hospital Northwestern University Medical School Northbrook, Illinois 60062
