Metastasis of Cancer to Cancer: Report of a Case of Esophageal Carcinoma Metastasizing to Early Gastric Cancer Takashi KOYAMA,Masayuki MATSUMORI,Kazuo NAKAMURAand Takahiro FUjIMORI ABSTRACT: A rare case of esophageal carcinoma metastasizing to early gastric cancer is reported herein. A 66 year old man who had experienced dysphagia for 8 months was preoperatively diagnosed as simultaneously having esophageal and gastric cancers. Thus, a lower esophagectomy and total gastrectomy with paraesophageal and paragastric lymph node dissection were performed. T h e surgical specimen revealed an ulcerative tumor in the lower esophagus and a slightly depressed lesion with a central elevation similar.to that o f early type IIc + IIa 1 gastric cancer in the u p p e r part o f the stomach. Microscopically, the esophageal tumor was revealed to be well differentiated squamous cell carcinom a while the gastric tumor was found to be early gastric cancer with a metastatic focus of esophageal cancer in the center. T h o u g h less t h a n one h u n d r e d cases o f metastasis o f cancer to cancer have previously b e e n reported, metastasis from cancer o f one digestive organ to that o f another digestive organ is very rare. T o our knowledge, this report represents the first case o f an esophageal carcinoma metastasizing to a gastric carcinoma. KEY WORDS: gastric cancer
cancer to cancer metastasis, esophageal cancer, early
INTRODUCTION
CASE REPORT
M e t a s t a s i s o f one neoplasm to a n o t h e r is quite u n c o m m o n despite the relatively high incidence o f multiple neoplasms in the same individual3 In fact, 'less than 100 cases have b e e n reported since the first description by Bernet in 1902. 3 T h e present report describes an additional case and reviews the literature regarding this p h e n o m e n o n .
A 66 year old m a n was admitted to the Second Department o f Surgery, Kobe University Hospital in March, 1987 complaining o f dysphagia which he had experienced for 8 months. Endoscopy revealed a deep ulceration in the E-C junction (Fig. 1A) and a slightly depressed area with a protrusion in the center, in the u p p e r part o f the stomach (Fig. 1B). Histological e x a m i n a t i o n o f a biopsy specimen taken from the esophagus revealed well differentiated squamous cell carcinoma while a biopsy specimen from the stomach revealed moderately differentiated tubular adenocarcinoma. H e was thereby diagnosed as simultaneously having esophageal cancer and early gastric cancer. A
The Second Department of Surgery and the Second Department of Pathology, Kobe University School of Medicine, Kobe,Japan Reprint requests to" Takashi Koyama, MD, The Second Department of Surgery, Kobe University School of Medicine, 7-Kusunoki-cho, Chuo-ku, Kobe 650, Japan
JAPANESEJOURNALOFSURGERY,VOL.21, No. 3 pp. 352-356, 1991
Volume 21 Number 3
Metastasis of cancer to cancer
353
Fig. 1. Endoscopy showing a deep ulceration on the E-Cjunction (A) and a slightly depressed area with a protrusion in the center in the upper part of the Stomach (B).
Fig. 2. Resected specimen showing a Borrmann II type tumor measuring 22 X 22 mm in the lower esophagus, and a depressed and erosive lesion with a protrusion in the center measuring 10 X 8 mm in the upper part of the stomach.
lower esophagectomy and total gastrectomy with periesophageal and perigastric lymph node dissections were performed on March 31, 1987. T h e postoperative course was uneventful and the patient h a d no recurrence 17 months after his operation. SURGICALPATHOLOGY Gross findings A well-defined ulcerated tumor, measuring 22 X 22 mm, was observed just above the E-C junction and a protruding lesion, measuring 10 X 8 mm, was observed in the'upper part o f the stomach, 2'3 mm away from the E-C
Fig. 3. Cut surface showing an ulcerating circumscribed tumor in the esophagus and a slighfly protruding well-defined tumor in the stomach. junction (Fig. 2). The gastric mucosa surr o u n d i n g the protruding lesion was slightly depressive and erosive. Macroscopically, the gastric region was diagnosed as having early type IIc + IIa I gastric cancer. T h e cut surface o f the esophageal tumor revealed a circumscribed whitish area with ulceration while the gastric tumor had a slightly protruding whitish area, extending to the submucosal layer (Fig. 3). Macroscopically, the tumor of the stomach was similar to that o f the esophagus. Histologic findings The tumor o f the esophagus was composed o f squamous cell carcinoma with in-
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Koyama et al.
Fig. 4. Histological features of the gastric tumor showing a metastatic focus of the squamous cell carcinoma of the esophagus located mostly in the submucosal layer (hematoxylin and eosin, Xl0).
Fig. 5. Histological features of the gastric mucosa adjacent to the metastatic focus showing adenocarcinoma with a glandular formation (hematoxylin and eosin, Xl00). dividual cell keratinization and many keratin pearls. T h e protruding lesion o f the stomach consisted of squamous cell carcinoma identical to that o f the esophageal carcinoma, but was not covered with gastric mucosa and was mostly located in the submucosal layer (Fig. 4). T h e gastric mucosa adjacent to the protruding lesion consisted of adenocarcinoma with a glandular formation (Fig. 5). In the area where both components were intermingled, these two components were clearly separated (Fig. 6). In conclusion, the squamous cell carcinoma o f the esophagus metastasized to early gastric cancer (Fig. 7).
1991
Fig. 6. Histological features of the border of these two components. These two components were clearly defined (hematoxylin and eosin, X40).
Fig. 7. Illustration of the resected specimen. i~ well differentiated squamous cell carcinoma moderately differentiated tubular adenocarcinoma In the esophagus, the cancer cells had extended to the adventitia and invaded only the lymph vessels. Microscopically, the right paracardial lymphnode was involved in the esophageal squam0us cell carcinoma. DISCUSSION
Recent advances in diagnostic procedures have led to the n u m b e r o f discovered multiple malignancies increasing, with an inci-
Volume 21 Number 3
Metastasis of cancer to cancer
dence ranging from 2.3 to 7.48 per cent of all malignancies? -6 However, metastasis o f o n e neoplasm to a n o t h e r neoplasm within the same individual is very r a r C a n d to o u r knowledge no other case o f esophageal c a r c i n o m a metastasizing to a gastric carcinoma has b e e n published. According to Campbell a n d co-w0rkers, 7 the criteria for metastasis of cancer to cancer are as follows: 1) the existence of m o r e t h a n one primary tumor, 2 ) t h e recipient t u m o r must be a true n e o p l a s m , 3) the foreign malignant neoplasm must be a true metastasis with established growth a n d no a "collision" or mere embolism of t u m o r cells a n d 4) the term should not pertain to tumors which have metastasized through the lymphatic system that are already the site o f generalized lymphatic malignant diseases. T h o u g h the recipient t u m o r can either be b e n i g n or malignant, metastasis to b e n i g n n e o p l a s m s is twice as c o m m o n as that to malignant tumors. 8 Inoshita and Laurain, 9 who reviewed 103 cases of malignant tumors metastasizing to benign tumors, reported the most frequent benign recipient tumors to be m e n i n g i o m a s (31 cases), followed by adrenal cortical a d e n o m a s (25 cases). O f 46 cases o f malignant metastases reviewed in the English literature by Sella a n d Ro, 1~the most f r e q u e n t m a l i g n a n t r e c i p i e n t t u m o r was renal cell carcinoma (33 cases). O t h e r malign a n t recipient tumors included adenocarc i n o m a o f the stomach, colon and pancreas, r h a b d o m y o s a r c o m a a n d glioblastoma. 11 O n the o t h e r hand, regardless o f w h e t h e r the recipient minor is benign or malignant, the most frequent d o n o r tumors are b r o n c h o genic tumors. 7,~2-16 O u r present case Satisfied all the;criteria for metastasis o f cancer to cancer pi'oposed by Campbell and co-workers. 7 T h e histological findings observed in the esophagus a n d submucosal layer of the stomach were exactly the s a m e as well differentiated squamous cell carcinoma. In the mucosal layer o f the stomach~ c)nly a d e n o c a r c i n o m a which did not have a tendency to differentiate to
355
squamous cell lineage was seen. Most of the previously reported cases metastasized to distant recipient organs via a hematogeneous route, however, in the esophagus, the submucosal lymphatic channels are well developed and the lymphatic stream of the lower esophagus descends to drain into the gastric and celiac lymph nodes. I n fact, the paracardial lymph nodes o f our case reVealed metastasis o f esophageal squamous cell carcinoma. Saito, 1~who reported 35 cases o f e s o p h a g e a l c a r c i n o m a with s t o m a c h metastasis, suggested that stomach metastasis was induced mainly via the lymphatic route not only because o f the lymph vessel carcinomatosis in the esophageal a n d stomach wall but also because of paracardial lymph node metastasis. Thus, it is thought that in our case, stomach metastasis was mainly via the lymphatic route. It is still u n k n o w n whether neoplasm to n e o p l a s m metastasis is a r a n d o m event or w h e t h e r it occurs u n d e r special c o n d i tions.8,18,1~ order to explain the grounds for which a t u m o r has the ability tO receive metastatic deposits, several hypotheses have b e e n proposed. Dobbinga~ speculated that renal cell carcinoma is usually richly vascular a n d arises in an organ which receives a large proportion o f the circulating emboli shed f r o m the d o n o r t u m o r as it also receives a large proportion o f the cardiac output. I n addition to the rich vascularity, Orttega and co-workers 12 have stated that the kidney has delicate and well-preserved stroma which permits a second expansive growth. Furthermore, the tumor cells of renal cell carcinoma are rich in glycogen and lipids, which provide a suitable site for the acceptance o f metastatic deposits?~Jackson and Symmers 2a who developed the so-called induction theory described a case o f bronchial carc i n o m a that metastasized to colonic carcinoma and speculated that metastases in the intestinal mucosa may stimulate the developm e n t o f cancer. In this case, the gastric cancer was localized in the mucosa, whereas the metastatic
Koyama et al.
356
lesion of the esophageal cancer was mostly located in the submucosa just below the g a s t r i c c a n c e r . So, t h e m e t a s t a t i c l e s i o n which grew in the gastric mucosa might have induced cancerous changes in the adjucent g a s t r i c m u c o s a a c c o r d i n g to J a c k s o n a n d Symmer's induction theory, N a k a y a m a a n d A b o 22 i n d i c a t e d t h a t t h e incidence of synchronous multiple malignancies associated with esophageal cancer w a s 2.1 p e r c e n t . S e v e n t y - f o u r p e r c e n t o f these cases were double cancers of the stomach and esophageal cancer, so therefore more cases of esophageal carcinoma m e t a s t a s i z i n g to g a s t r i c c a n c e r m u s t b e exp e c t e d . I n s o m e c a s e s , it w o u l d b e d i f f i c u l t to p r o v e m e t a s t a s i s b e c a u s e o f t h e p o s s i b i l i t y of histological continuation as in adenoacant h o m a . O u r p r e s e n t c a s e is t h e first r e p o r t e d case able to demonstrate esophageal cancer metastasizing to a recipient gastric cancer. ACKNOWLEDGMENT T h e a u t h o r s w o u l d l i k e to t h a n k Dr. S a k a n Maeda, Professor of the Second Department of Pathology, Kobe University School of Medicine, for comments on the manuscript. ( R e c e i v e d f o r p u b l i c a t i o n o n F e b . 1, 1990) REFERENCES 1. Japanese Research Society for Gastric Cancer. The General Rules for the Gastric Cancer Study. Tokyo: Kanehara Syuppan 1985; 17: 9. (in Japanese) 2. Robson SM, Stier PL, BaumgartnerJC. Metastasis of cancer to cancer.Am J Cl!n Path 1954; 25: 572-579. 3. Bernet W. Seltene metastasenbildung. Zentrable Allg Pathol 1902; 13: 406-410. 4. Moertel CG, Docket~ MB. Multiple primary malignant neoplasms. I. Introduction and presentation of data. Cancer 1961; 14: 221-247. 5. Watanabe S. Pathology of multiple primary cancers. Gann no Rinsyo (JpnJ Cancer Clinics) 1985; 30:
1489-1498. (in Japanese with English Abst.) 6. Nishitoi H, Okamoto T. Clinical study of 60 cases of multiple primary cancers. Gann no Rinsho 1981; 27: 693-697_(in Japanese with English Abst.) 7. Campbell LV, Gilvert E, Chamberlain CR. Watne AL. Metastasis of cancer to cancer. Cancer 1968; 22: 635-643. 8. RichardsonJF. Katayama I. Neoplasm to neoplasm metastasis: An acidophi! adenoma harbouring metastatic carcinoma: A case report. Arch Path 1971: 91: 135-139. 9. Inoshita T. Laurain AR. Tumor-to-tumor metastasis: Malignant melanoma metastatic to parathyroid adenoma. Milli Med 1985; 150: 323-325. 10. Sella A. Ro JY. Renal cell cancer: Best recipient of tumor-to-tumor metastasis. Urology 1987; 30: 35-38. 11. Seitz G. Schuder G. Neoplasm to neoplasm metastasis: Pheochromocytoma harboring a metastasis of breast cancer. Path Res Pract 1987: 182: 228-232. 12. Ortega P Jr, Li IY. Shimkin M. Metastasis of neoplasms to other neoplasms. Ann West Med Surg 1951; 5: 601-609. 13. Lodrini S. Savoiardo M. Metastasis of carcinoma to intracranial meningioma: Report of two cases and review of the literature. Cancer 1981; 48: 26682673. 14. Sharma HM. Old JW. Metastasis of carcinoma to carcinoma. Arch Path 1969: 88: 191-193. 15. Andersen HJ, Hansen LG, Paulsen SM. Metastasis of cancer to cancer: A case report of breast carcinoma metastasizing to a malignant mesothelioma. Thorac Cardiovasc Surgeon 1986~ 34: 258-259. 16. Singh EO. Benson RCJR, Wold LE+ Cancer to cancer metastasis. J Urology 1984: 132: 340-342. 17. Saito T, Iizuka T, Kato H. Esophageal carcinoma metastatic to the stomach: A clinicopathologic study of 35 cases. Cancer 1985; 56: 2235-2241. 18. Majmudar B. Metastasis of cancer to cancer: Report of a case. Medical Intelligence 1976; 7: 117-119. 19. Willis RA. Spread of tumors in the human body. London:J&A, Churchill 1933: 540. 20. Dobbing ByJ. Cancer to cancer. Guys Hosp Rep 1987; 182: 228-232. 21. JacksonJG, Symmers WStC. Coexistence at one site of two neoplasms: One of local origin and one metastatic. BritJ Cancer 1951; 5: 38-44. 22. Nakayama K, Abo S. Concurrent cancer of the esophagus in Japan. Int Adv Surg Oncol 1979; 2: 243-249.
cancer to cancer metastasis, esophageal cancer, early
INTRODUCTION
CASE REPORT
M e t a s t a s i s o f one neoplasm to a n o t h e r is quite u n c o m m o n despite the relatively high incidence o f multiple neoplasms in the same individual3 In fact, 'less than 100 cases have b e e n reported since the first description by Bernet in 1902. 3 T h e present report describes an additional case and reviews the literature regarding this p h e n o m e n o n .
A 66 year old m a n was admitted to the Second Department o f Surgery, Kobe University Hospital in March, 1987 complaining o f dysphagia which he had experienced for 8 months. Endoscopy revealed a deep ulceration in the E-C junction (Fig. 1A) and a slightly depressed area with a protrusion in the center, in the u p p e r part o f the stomach (Fig. 1B). Histological e x a m i n a t i o n o f a biopsy specimen taken from the esophagus revealed well differentiated squamous cell carcinoma while a biopsy specimen from the stomach revealed moderately differentiated tubular adenocarcinoma. H e was thereby diagnosed as simultaneously having esophageal cancer and early gastric cancer. A
The Second Department of Surgery and the Second Department of Pathology, Kobe University School of Medicine, Kobe,Japan Reprint requests to" Takashi Koyama, MD, The Second Department of Surgery, Kobe University School of Medicine, 7-Kusunoki-cho, Chuo-ku, Kobe 650, Japan
JAPANESEJOURNALOFSURGERY,VOL.21, No. 3 pp. 352-356, 1991
Volume 21 Number 3
Metastasis of cancer to cancer
353
Fig. 1. Endoscopy showing a deep ulceration on the E-Cjunction (A) and a slightly depressed area with a protrusion in the center in the upper part of the Stomach (B).
Fig. 2. Resected specimen showing a Borrmann II type tumor measuring 22 X 22 mm in the lower esophagus, and a depressed and erosive lesion with a protrusion in the center measuring 10 X 8 mm in the upper part of the stomach.
lower esophagectomy and total gastrectomy with periesophageal and perigastric lymph node dissections were performed on March 31, 1987. T h e postoperative course was uneventful and the patient h a d no recurrence 17 months after his operation. SURGICALPATHOLOGY Gross findings A well-defined ulcerated tumor, measuring 22 X 22 mm, was observed just above the E-C junction and a protruding lesion, measuring 10 X 8 mm, was observed in the'upper part o f the stomach, 2'3 mm away from the E-C
Fig. 3. Cut surface showing an ulcerating circumscribed tumor in the esophagus and a slighfly protruding well-defined tumor in the stomach. junction (Fig. 2). The gastric mucosa surr o u n d i n g the protruding lesion was slightly depressive and erosive. Macroscopically, the gastric region was diagnosed as having early type IIc + IIa I gastric cancer. T h e cut surface o f the esophageal tumor revealed a circumscribed whitish area with ulceration while the gastric tumor had a slightly protruding whitish area, extending to the submucosal layer (Fig. 3). Macroscopically, the tumor of the stomach was similar to that o f the esophagus. Histologic findings The tumor o f the esophagus was composed o f squamous cell carcinoma with in-
354
Koyama et al.
Fig. 4. Histological features of the gastric tumor showing a metastatic focus of the squamous cell carcinoma of the esophagus located mostly in the submucosal layer (hematoxylin and eosin, Xl0).
Fig. 5. Histological features of the gastric mucosa adjacent to the metastatic focus showing adenocarcinoma with a glandular formation (hematoxylin and eosin, Xl00). dividual cell keratinization and many keratin pearls. T h e protruding lesion o f the stomach consisted of squamous cell carcinoma identical to that o f the esophageal carcinoma, but was not covered with gastric mucosa and was mostly located in the submucosal layer (Fig. 4). T h e gastric mucosa adjacent to the protruding lesion consisted of adenocarcinoma with a glandular formation (Fig. 5). In the area where both components were intermingled, these two components were clearly separated (Fig. 6). In conclusion, the squamous cell carcinoma o f the esophagus metastasized to early gastric cancer (Fig. 7).
1991
Fig. 6. Histological features of the border of these two components. These two components were clearly defined (hematoxylin and eosin, X40).
Fig. 7. Illustration of the resected specimen. i~ well differentiated squamous cell carcinoma moderately differentiated tubular adenocarcinoma In the esophagus, the cancer cells had extended to the adventitia and invaded only the lymph vessels. Microscopically, the right paracardial lymphnode was involved in the esophageal squam0us cell carcinoma. DISCUSSION
Recent advances in diagnostic procedures have led to the n u m b e r o f discovered multiple malignancies increasing, with an inci-
Volume 21 Number 3
Metastasis of cancer to cancer
dence ranging from 2.3 to 7.48 per cent of all malignancies? -6 However, metastasis o f o n e neoplasm to a n o t h e r neoplasm within the same individual is very r a r C a n d to o u r knowledge no other case o f esophageal c a r c i n o m a metastasizing to a gastric carcinoma has b e e n published. According to Campbell a n d co-w0rkers, 7 the criteria for metastasis of cancer to cancer are as follows: 1) the existence of m o r e t h a n one primary tumor, 2 ) t h e recipient t u m o r must be a true n e o p l a s m , 3) the foreign malignant neoplasm must be a true metastasis with established growth a n d no a "collision" or mere embolism of t u m o r cells a n d 4) the term should not pertain to tumors which have metastasized through the lymphatic system that are already the site o f generalized lymphatic malignant diseases. T h o u g h the recipient t u m o r can either be b e n i g n or malignant, metastasis to b e n i g n n e o p l a s m s is twice as c o m m o n as that to malignant tumors. 8 Inoshita and Laurain, 9 who reviewed 103 cases of malignant tumors metastasizing to benign tumors, reported the most frequent benign recipient tumors to be m e n i n g i o m a s (31 cases), followed by adrenal cortical a d e n o m a s (25 cases). O f 46 cases o f malignant metastases reviewed in the English literature by Sella a n d Ro, 1~the most f r e q u e n t m a l i g n a n t r e c i p i e n t t u m o r was renal cell carcinoma (33 cases). O t h e r malign a n t recipient tumors included adenocarc i n o m a o f the stomach, colon and pancreas, r h a b d o m y o s a r c o m a a n d glioblastoma. 11 O n the o t h e r hand, regardless o f w h e t h e r the recipient minor is benign or malignant, the most frequent d o n o r tumors are b r o n c h o genic tumors. 7,~2-16 O u r present case Satisfied all the;criteria for metastasis o f cancer to cancer pi'oposed by Campbell and co-workers. 7 T h e histological findings observed in the esophagus a n d submucosal layer of the stomach were exactly the s a m e as well differentiated squamous cell carcinoma. In the mucosal layer o f the stomach~ c)nly a d e n o c a r c i n o m a which did not have a tendency to differentiate to
355
squamous cell lineage was seen. Most of the previously reported cases metastasized to distant recipient organs via a hematogeneous route, however, in the esophagus, the submucosal lymphatic channels are well developed and the lymphatic stream of the lower esophagus descends to drain into the gastric and celiac lymph nodes. I n fact, the paracardial lymph nodes o f our case reVealed metastasis o f esophageal squamous cell carcinoma. Saito, 1~who reported 35 cases o f e s o p h a g e a l c a r c i n o m a with s t o m a c h metastasis, suggested that stomach metastasis was induced mainly via the lymphatic route not only because o f the lymph vessel carcinomatosis in the esophageal a n d stomach wall but also because of paracardial lymph node metastasis. Thus, it is thought that in our case, stomach metastasis was mainly via the lymphatic route. It is still u n k n o w n whether neoplasm to n e o p l a s m metastasis is a r a n d o m event or w h e t h e r it occurs u n d e r special c o n d i tions.8,18,1~ order to explain the grounds for which a t u m o r has the ability tO receive metastatic deposits, several hypotheses have b e e n proposed. Dobbinga~ speculated that renal cell carcinoma is usually richly vascular a n d arises in an organ which receives a large proportion o f the circulating emboli shed f r o m the d o n o r t u m o r as it also receives a large proportion o f the cardiac output. I n addition to the rich vascularity, Orttega and co-workers 12 have stated that the kidney has delicate and well-preserved stroma which permits a second expansive growth. Furthermore, the tumor cells of renal cell carcinoma are rich in glycogen and lipids, which provide a suitable site for the acceptance o f metastatic deposits?~Jackson and Symmers 2a who developed the so-called induction theory described a case o f bronchial carc i n o m a that metastasized to colonic carcinoma and speculated that metastases in the intestinal mucosa may stimulate the developm e n t o f cancer. In this case, the gastric cancer was localized in the mucosa, whereas the metastatic
Koyama et al.
356
lesion of the esophageal cancer was mostly located in the submucosa just below the g a s t r i c c a n c e r . So, t h e m e t a s t a t i c l e s i o n which grew in the gastric mucosa might have induced cancerous changes in the adjucent g a s t r i c m u c o s a a c c o r d i n g to J a c k s o n a n d Symmer's induction theory, N a k a y a m a a n d A b o 22 i n d i c a t e d t h a t t h e incidence of synchronous multiple malignancies associated with esophageal cancer w a s 2.1 p e r c e n t . S e v e n t y - f o u r p e r c e n t o f these cases were double cancers of the stomach and esophageal cancer, so therefore more cases of esophageal carcinoma m e t a s t a s i z i n g to g a s t r i c c a n c e r m u s t b e exp e c t e d . I n s o m e c a s e s , it w o u l d b e d i f f i c u l t to p r o v e m e t a s t a s i s b e c a u s e o f t h e p o s s i b i l i t y of histological continuation as in adenoacant h o m a . O u r p r e s e n t c a s e is t h e first r e p o r t e d case able to demonstrate esophageal cancer metastasizing to a recipient gastric cancer. ACKNOWLEDGMENT T h e a u t h o r s w o u l d l i k e to t h a n k Dr. S a k a n Maeda, Professor of the Second Department of Pathology, Kobe University School of Medicine, for comments on the manuscript. ( R e c e i v e d f o r p u b l i c a t i o n o n F e b . 1, 1990) REFERENCES 1. Japanese Research Society for Gastric Cancer. The General Rules for the Gastric Cancer Study. Tokyo: Kanehara Syuppan 1985; 17: 9. (in Japanese) 2. Robson SM, Stier PL, BaumgartnerJC. Metastasis of cancer to cancer.Am J Cl!n Path 1954; 25: 572-579. 3. Bernet W. Seltene metastasenbildung. Zentrable Allg Pathol 1902; 13: 406-410. 4. Moertel CG, Docket~ MB. Multiple primary malignant neoplasms. I. Introduction and presentation of data. Cancer 1961; 14: 221-247. 5. Watanabe S. Pathology of multiple primary cancers. Gann no Rinsyo (JpnJ Cancer Clinics) 1985; 30:
1489-1498. (in Japanese with English Abst.) 6. Nishitoi H, Okamoto T. Clinical study of 60 cases of multiple primary cancers. Gann no Rinsho 1981; 27: 693-697_(in Japanese with English Abst.) 7. Campbell LV, Gilvert E, Chamberlain CR. Watne AL. Metastasis of cancer to cancer. Cancer 1968; 22: 635-643. 8. RichardsonJF. Katayama I. Neoplasm to neoplasm metastasis: An acidophi! adenoma harbouring metastatic carcinoma: A case report. Arch Path 1971: 91: 135-139. 9. Inoshita T. Laurain AR. Tumor-to-tumor metastasis: Malignant melanoma metastatic to parathyroid adenoma. Milli Med 1985; 150: 323-325. 10. Sella A. Ro JY. Renal cell cancer: Best recipient of tumor-to-tumor metastasis. Urology 1987; 30: 35-38. 11. Seitz G. Schuder G. Neoplasm to neoplasm metastasis: Pheochromocytoma harboring a metastasis of breast cancer. Path Res Pract 1987: 182: 228-232. 12. Ortega P Jr, Li IY. Shimkin M. Metastasis of neoplasms to other neoplasms. Ann West Med Surg 1951; 5: 601-609. 13. Lodrini S. Savoiardo M. Metastasis of carcinoma to intracranial meningioma: Report of two cases and review of the literature. Cancer 1981; 48: 26682673. 14. Sharma HM. Old JW. Metastasis of carcinoma to carcinoma. Arch Path 1969: 88: 191-193. 15. Andersen HJ, Hansen LG, Paulsen SM. Metastasis of cancer to cancer: A case report of breast carcinoma metastasizing to a malignant mesothelioma. Thorac Cardiovasc Surgeon 1986~ 34: 258-259. 16. Singh EO. Benson RCJR, Wold LE+ Cancer to cancer metastasis. J Urology 1984: 132: 340-342. 17. Saito T, Iizuka T, Kato H. Esophageal carcinoma metastatic to the stomach: A clinicopathologic study of 35 cases. Cancer 1985; 56: 2235-2241. 18. Majmudar B. Metastasis of cancer to cancer: Report of a case. Medical Intelligence 1976; 7: 117-119. 19. Willis RA. Spread of tumors in the human body. London:J&A, Churchill 1933: 540. 20. Dobbing ByJ. Cancer to cancer. Guys Hosp Rep 1987; 182: 228-232. 21. JacksonJG, Symmers WStC. Coexistence at one site of two neoplasms: One of local origin and one metastatic. BritJ Cancer 1951; 5: 38-44. 22. Nakayama K, Abo S. Concurrent cancer of the esophagus in Japan. Int Adv Surg Oncol 1979; 2: 243-249.
