Digestive Diseases and Sciences, Vol. 37, No. 8 (August 1992), pp. 1297-1301
CASE REPORT
Heterotopic Mucinous Cystadenoma of the Pancreas NED Z. CARP, MD, ANTHONY R. PAUL, MD, MICHAEL J. KOWALYSHYN, MD, ROBERT O. PETERSEN, MD, PhD, and JOHN P. HOFFMAN, MD, FACS KEY WORDS: mucinous cystadenoma; heterotopic pancreatic tissue; premalignant.
Although heterotopic pancreatic tissue is usually an incidental finding at laparotomy without clinical significance, it has been implicated as the causative factor of symptoms in a small percentage of cases. Rare progression to benign or malignant tumors in heterotopic pancreas have been previously reported (1). We present a case of mucinous cystadenoma in heterotopic pancreas that produced disabling symptoms that were reversed by surgical resection. CASE REPORT
A 46-year-old woman had experienced increasing watery diarrhea and an involuntary weight loss of 65 lb for approximately 18 months. A C T scan revealed a large mass with a cystic component at or near the tall of the pancreas (Figure 1). Upper gastrointestinal series and barium enema examinations showed displacement of the stomach, proximal small bowel, and transverse colon by the mass. Stool samples sent for culture and ova and parasites were negative. Serum gastrin, histamine, glucose, carcinoembryonic antigen levels, and urinary 5-HIAA were within normal limits. Two CT-directed needle biopsies obtained no malignant cells but occasional fibroblasts and fat cells were noted. At exploratory celiotomy, a 10 • 15-cm mass was noted at the root of the small bowel mesentery superior and lateral to the duodenum at the ligament of Treitz adjacent to the tail of the pancreas (Figure 2). At no time during the dissection was the mass actually found to be connected to the pancreas. Pathologic examination showed a mucinous cystadenoma in heterotopic pancreas (Figure 3). The patient made an uneventful recover. Two weeks postoperatively she noted that her diarrhea had disapManuscript received December 13, 1990; revised manuscript received April 10, 1991; accepted April 11, 1991. From the Departments of Surgical Oncology and Medical Oncology and Pathology, Fox Chase Cancer Center, Sections of Surgical and Medical Oncology, Temple University School of Medicine, Philadelphia, Pennsylvania. Address for reprint requests: Dr. John P. Hoffman, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, Pennsylvania 19111.
peared, and at one year follow-up she still has no diarrhea and has gained 20 lb. She is taking no antidiarrheal medication. DISCUSSION This case is interesting because of the pathology of the neoplasm and the clinical presentation of the patient. Cystic neoplasms of the pancreas in themselves are uncommon and in this case, the tumor apparently arose in heterotopic pancreatic tissue. Pancreatic heterotopia is defined as pancreatic tissue outside its usual location and without anatomic relation to the pancreas either by direct continuity or by feeding vessel (1). No connection between the neoplasm and the normal pancreas was demonstrated in this case, either at the time of surgery or by histologic study. Heterotopic pancreatic tissue is relatively uncommon and is usually of no clinical importance. The frequency in autopsy material has ranged from 0.55% to 13.7%. No particular symptom complex can be attributed to this condition. Up to 90% are located in the stomach, duodenum, or upper jejunum (2). Feldman et al (3) reported a duodenal syndrome resulting from enlargement of the heterotopic pancreas producing stenosis, ulceration, biliary symptoms, obstruction, and intussusception. Other clinical manifestations produced by heterotopic pancreas include pyloric and intestinal obstruction, peptic ulcer disease, pancreatitis, appendicitis, and hypoglycemia (4). Several theories have been proposed as to the pathogenesis of heterotopic pancreas. It can be due to incomplete regression of the left ventral anlage, implantation of embryonic tissue due to adhesions, nodules of pancreatic anlage attaching themselves to adjacent organs, or lateral budding of the rudimentary pancreatic ducts (4).
Digestive Diseases and Sciences, "Col. 37, No. 8 (August 1992)
0163-2116/92/0800-1297506.50/09 1992PlenumPublishingCorporation
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CARP ET AL
Fig 1. CT scan demonstrating cystic mass arising in the area of the tail of the pancreas (CT-directed biopsy).
Pathologically, heterotopic pancreatic tissue is subject to all disease processes found in normally located pancreas including acute pancreatitis, chronic interstitial pancreatitis, cystic fibrosis, cyst formation, and neoplastic change (both benign and malignant) (4). Barbosa et al (1) feel that malignant change is more likely to occur in heterotopic pancreas, although there are no data to support this. There have been several reports of neoplastic changes occurring in heterotopic pancreatic tissue. White and Gilden (5) report an adenoma of heterotopic pancreatic tissue producing symptoms of hypoglycemia. Holman et al (6) report a case of hyperinsulinism and hypoglycemia secondary to two islet cell tumors. Removal of an intrapancreatic adenoma failed to relieve symptoms, but removal of an adenoma found in the gastrosplenic ligament resulted in cure. Duff et al (7) report a case of carcinoma of the infraampullary portion of the duodenum originating from heterotopic pancreatic tissue. Cystic neoplasms of the pancreas are believed to originate from the epithelium of the larger pancre-
1298
atic ducts. They are classified morphologically into two types: (1) mucinous cystadenoma, large mucinous cystic tumors lined by tall columnar cells that often form papillae and can be of variable malignant potential depending on the presence or absence of stromal invasion of (2) microcystic cystadenoma, composed of cuboidal cells rich in glycogen, with little or no mucin and having no malignant potential (4, 8). Three cases of cystadenoma occurring in heterotopic pancreatic tissue have been reported previously. Tocchi et al (9) reported heterotopic mucinous cystadenoma located caudal to the head of the pancreas causing epigastric pain in a 38-year-old female. Fresnel et al (10) reported heterotopic cystadenoma of the pancreas arising within the stomach causing epigastric distress in a 7-year-old child. Stahlschmidt et al (11) reported one case of heterotopic cystadenoma of the pancreas in a large retropancreatic tumor that was found incidentally after an abnormal intravenous pyelogram. Although pain was a common denominator in these three cases of heterotopic pancreatic cystadenoma, none had the Digestive Diseases and Sciences, Vol. 37, No. 8 (August 1992)
PANCREATIC MUCINOUS CYSTADENOMA
Fig 2a. Illustrations demonstrating relationship between heterotopic mucinous cystadenoma of the pancreas and the duodenum and pancreas. Heterotopic of pancreatic mass is identing the fourth portion of the duodenum and displacing the pancreas anteriorly.
debilitating diarrhea and weight loss as in our patient. Only Tocchi et al (9) reported a mucinous cystadenoma while the subtype of the other two cases was not described.
Clinically the patient's severe diarrhea and marked weight loss resolved after resection and were probably secondary to intestinal lymphatic drainage. There was no endocrinologic basis for her symptoms as her urinary 5-HIAA, serum gastrin, and histamine levels were all within normal limits. Unfortunately, VIP levels were not done, but the pathology did not support the diagnosis of islet cell tumor. Soloway (12) reported two patients with pancreatic cystadenomas presenting with diarrhea as well as 12 patients presenting with weight loss. There was a high incidence of associated benign and malignant tumors and premature menopause, as well as sterility, obesity, thyroid dysfunction, and diabetes mellitus (12). Our patient, however, did not have the clinical features of this syndrome. There are no reports of malignant degeneration in a heterotopic mucinous cystadenoma of the pancreas. However, one suspects that the potential of malignant degeneration would be the same as mucinous cystadenomas arising within the pancreas, and it is the rarity of the ectopic lesion that accounts for the absence of reported cancer development.
Fig 2b. Intraoperative photograph demonstrating mass lying in the root of the small bowel mesentery. Digestive Diseases and Sciences, Vol. 37, No. 8 (August 1992)
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Fig 3. Photomicrograph of mucinous cystadenoma of heterotopic pancreas revealing typical mucinous epithelium. (A) low power (hematoxylin and eosin, 40• and (B) high power (hematoxylin and eosin, 400 • 1300
Digestive Diseases and Sciences, Vol. 37, No. 8 (August 1992)
P A N C R E A T I C M U C I N O U S CYSTADENOMA
Therefore, we would advise total rather than partial removal of such a lesion. Although heterotopic pancreas does occur in a small percentage of the normal population, severe debilitating symptomatology is extremely unusual. Mucinous cystadenoma, a potential premalignant neoplasm, has been reported once before in heterotopic pancreas. Total removal of the lesion reversed the symptoms in this patient as well as removed the potential malignant degeneration of this lesion. SUMMARY
A 46-year-old female who had been experiencing severe diarrhea and marked weight loss underwent exploratory laparotomy because of a mass near the tail of the pancreas noted on CT scan. Pathologic examination revealed a mucinous cystadenoma of the pancreas occurring in heterotopic pancreatic tissue. This is the second reported case of mucinous cystadenoma occurring in heterotopic pancreatic tissue. REFERENCES 1. Barbosa JD, Dockerty MB, Waugh JM: Pancreatic heterotopia--review of the literature and report of 41 authenticated surgical cases, of which 25 were clinically significant. Surg Gynecol Obstet 82:527-542, 1946
Digestive Diseases and Sciences, Vol. 37, No. 8 (August 1992)
2. Dolan RV, Remine WH, Dockorty MB: The fate of heterotopic pancreatic tissue. Arch Surg 109:762-765, 1974 3. Feldman M, Weinberg T: Aberrant pancreas: A case of duodenal syndrome. JAMA 148:893-898, 1952 4. Pearson S: Aberrant pancreas. Review of the literature and report of three cases, one of which produced pancreated duct obstruction. Arch Surg 63:168-184, 1951 5. White BV, Gilden EF: Adenoma of the pancreas and hyperinsulinism. N Engl J Med 217:307-313, 1937 6. Holman CE, Wood DA, Stockton AB: Unusual cases of hyperinsulinism and hypoglycemia. Arch Surg 47:165-177, 1943 7. Duff GL, Foster HL, Bryan WW: Primary carcinoma of the infra-ampullary portion of the duodenum with example of probable origin of aberrant pancreatic tissue. Arch Surg 46:494-503, 1943 8. Compugno J, Oertel JE: Mucinous cystic neoplasms of the pancreas with overt and latent malignancy (cystsadenocarcinoma and cystadenoma). Am J Clin Pathol 69:573-580, 1978 9. Tocchi A, Puma F, Cerroni M, DiGeorgio A, Daddi G: Mucinous cystadenoma occurring in heterotopic pancreatic tissue. Ital J Surg Sci 4:355-357, 1987 10. Fresnel P, Sidilly A, Fouchor G, Fresnel PL: Cystadenoma Pancreatique ectopique intragastrique. Presse Med 79:2496, 1971 11. Stahlschmidt M, Schafer A, Schmidt-Koppler A, Hohle E: Zystadenoa I1 Heterotopen Pankreasgewebe. Leber Magen Darh 4:247-250, 1974 12. Soloway HB: Constitutional abnormalities associated with pancreatic cystadenomas. Cancer 18:1297-1300, 1965P
1301
CASE REPORT
Heterotopic Mucinous Cystadenoma of the Pancreas NED Z. CARP, MD, ANTHONY R. PAUL, MD, MICHAEL J. KOWALYSHYN, MD, ROBERT O. PETERSEN, MD, PhD, and JOHN P. HOFFMAN, MD, FACS KEY WORDS: mucinous cystadenoma; heterotopic pancreatic tissue; premalignant.
Although heterotopic pancreatic tissue is usually an incidental finding at laparotomy without clinical significance, it has been implicated as the causative factor of symptoms in a small percentage of cases. Rare progression to benign or malignant tumors in heterotopic pancreas have been previously reported (1). We present a case of mucinous cystadenoma in heterotopic pancreas that produced disabling symptoms that were reversed by surgical resection. CASE REPORT
A 46-year-old woman had experienced increasing watery diarrhea and an involuntary weight loss of 65 lb for approximately 18 months. A C T scan revealed a large mass with a cystic component at or near the tall of the pancreas (Figure 1). Upper gastrointestinal series and barium enema examinations showed displacement of the stomach, proximal small bowel, and transverse colon by the mass. Stool samples sent for culture and ova and parasites were negative. Serum gastrin, histamine, glucose, carcinoembryonic antigen levels, and urinary 5-HIAA were within normal limits. Two CT-directed needle biopsies obtained no malignant cells but occasional fibroblasts and fat cells were noted. At exploratory celiotomy, a 10 • 15-cm mass was noted at the root of the small bowel mesentery superior and lateral to the duodenum at the ligament of Treitz adjacent to the tail of the pancreas (Figure 2). At no time during the dissection was the mass actually found to be connected to the pancreas. Pathologic examination showed a mucinous cystadenoma in heterotopic pancreas (Figure 3). The patient made an uneventful recover. Two weeks postoperatively she noted that her diarrhea had disapManuscript received December 13, 1990; revised manuscript received April 10, 1991; accepted April 11, 1991. From the Departments of Surgical Oncology and Medical Oncology and Pathology, Fox Chase Cancer Center, Sections of Surgical and Medical Oncology, Temple University School of Medicine, Philadelphia, Pennsylvania. Address for reprint requests: Dr. John P. Hoffman, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, Pennsylvania 19111.
peared, and at one year follow-up she still has no diarrhea and has gained 20 lb. She is taking no antidiarrheal medication. DISCUSSION This case is interesting because of the pathology of the neoplasm and the clinical presentation of the patient. Cystic neoplasms of the pancreas in themselves are uncommon and in this case, the tumor apparently arose in heterotopic pancreatic tissue. Pancreatic heterotopia is defined as pancreatic tissue outside its usual location and without anatomic relation to the pancreas either by direct continuity or by feeding vessel (1). No connection between the neoplasm and the normal pancreas was demonstrated in this case, either at the time of surgery or by histologic study. Heterotopic pancreatic tissue is relatively uncommon and is usually of no clinical importance. The frequency in autopsy material has ranged from 0.55% to 13.7%. No particular symptom complex can be attributed to this condition. Up to 90% are located in the stomach, duodenum, or upper jejunum (2). Feldman et al (3) reported a duodenal syndrome resulting from enlargement of the heterotopic pancreas producing stenosis, ulceration, biliary symptoms, obstruction, and intussusception. Other clinical manifestations produced by heterotopic pancreas include pyloric and intestinal obstruction, peptic ulcer disease, pancreatitis, appendicitis, and hypoglycemia (4). Several theories have been proposed as to the pathogenesis of heterotopic pancreas. It can be due to incomplete regression of the left ventral anlage, implantation of embryonic tissue due to adhesions, nodules of pancreatic anlage attaching themselves to adjacent organs, or lateral budding of the rudimentary pancreatic ducts (4).
Digestive Diseases and Sciences, "Col. 37, No. 8 (August 1992)
0163-2116/92/0800-1297506.50/09 1992PlenumPublishingCorporation
1297
CARP ET AL
Fig 1. CT scan demonstrating cystic mass arising in the area of the tail of the pancreas (CT-directed biopsy).
Pathologically, heterotopic pancreatic tissue is subject to all disease processes found in normally located pancreas including acute pancreatitis, chronic interstitial pancreatitis, cystic fibrosis, cyst formation, and neoplastic change (both benign and malignant) (4). Barbosa et al (1) feel that malignant change is more likely to occur in heterotopic pancreas, although there are no data to support this. There have been several reports of neoplastic changes occurring in heterotopic pancreatic tissue. White and Gilden (5) report an adenoma of heterotopic pancreatic tissue producing symptoms of hypoglycemia. Holman et al (6) report a case of hyperinsulinism and hypoglycemia secondary to two islet cell tumors. Removal of an intrapancreatic adenoma failed to relieve symptoms, but removal of an adenoma found in the gastrosplenic ligament resulted in cure. Duff et al (7) report a case of carcinoma of the infraampullary portion of the duodenum originating from heterotopic pancreatic tissue. Cystic neoplasms of the pancreas are believed to originate from the epithelium of the larger pancre-
1298
atic ducts. They are classified morphologically into two types: (1) mucinous cystadenoma, large mucinous cystic tumors lined by tall columnar cells that often form papillae and can be of variable malignant potential depending on the presence or absence of stromal invasion of (2) microcystic cystadenoma, composed of cuboidal cells rich in glycogen, with little or no mucin and having no malignant potential (4, 8). Three cases of cystadenoma occurring in heterotopic pancreatic tissue have been reported previously. Tocchi et al (9) reported heterotopic mucinous cystadenoma located caudal to the head of the pancreas causing epigastric pain in a 38-year-old female. Fresnel et al (10) reported heterotopic cystadenoma of the pancreas arising within the stomach causing epigastric distress in a 7-year-old child. Stahlschmidt et al (11) reported one case of heterotopic cystadenoma of the pancreas in a large retropancreatic tumor that was found incidentally after an abnormal intravenous pyelogram. Although pain was a common denominator in these three cases of heterotopic pancreatic cystadenoma, none had the Digestive Diseases and Sciences, Vol. 37, No. 8 (August 1992)
PANCREATIC MUCINOUS CYSTADENOMA
Fig 2a. Illustrations demonstrating relationship between heterotopic mucinous cystadenoma of the pancreas and the duodenum and pancreas. Heterotopic of pancreatic mass is identing the fourth portion of the duodenum and displacing the pancreas anteriorly.
debilitating diarrhea and weight loss as in our patient. Only Tocchi et al (9) reported a mucinous cystadenoma while the subtype of the other two cases was not described.
Clinically the patient's severe diarrhea and marked weight loss resolved after resection and were probably secondary to intestinal lymphatic drainage. There was no endocrinologic basis for her symptoms as her urinary 5-HIAA, serum gastrin, and histamine levels were all within normal limits. Unfortunately, VIP levels were not done, but the pathology did not support the diagnosis of islet cell tumor. Soloway (12) reported two patients with pancreatic cystadenomas presenting with diarrhea as well as 12 patients presenting with weight loss. There was a high incidence of associated benign and malignant tumors and premature menopause, as well as sterility, obesity, thyroid dysfunction, and diabetes mellitus (12). Our patient, however, did not have the clinical features of this syndrome. There are no reports of malignant degeneration in a heterotopic mucinous cystadenoma of the pancreas. However, one suspects that the potential of malignant degeneration would be the same as mucinous cystadenomas arising within the pancreas, and it is the rarity of the ectopic lesion that accounts for the absence of reported cancer development.
Fig 2b. Intraoperative photograph demonstrating mass lying in the root of the small bowel mesentery. Digestive Diseases and Sciences, Vol. 37, No. 8 (August 1992)
1299
C A R P E T AL
i
Fig 3. Photomicrograph of mucinous cystadenoma of heterotopic pancreas revealing typical mucinous epithelium. (A) low power (hematoxylin and eosin, 40• and (B) high power (hematoxylin and eosin, 400 • 1300
Digestive Diseases and Sciences, Vol. 37, No. 8 (August 1992)
P A N C R E A T I C M U C I N O U S CYSTADENOMA
Therefore, we would advise total rather than partial removal of such a lesion. Although heterotopic pancreas does occur in a small percentage of the normal population, severe debilitating symptomatology is extremely unusual. Mucinous cystadenoma, a potential premalignant neoplasm, has been reported once before in heterotopic pancreas. Total removal of the lesion reversed the symptoms in this patient as well as removed the potential malignant degeneration of this lesion. SUMMARY
A 46-year-old female who had been experiencing severe diarrhea and marked weight loss underwent exploratory laparotomy because of a mass near the tail of the pancreas noted on CT scan. Pathologic examination revealed a mucinous cystadenoma of the pancreas occurring in heterotopic pancreatic tissue. This is the second reported case of mucinous cystadenoma occurring in heterotopic pancreatic tissue. REFERENCES 1. Barbosa JD, Dockerty MB, Waugh JM: Pancreatic heterotopia--review of the literature and report of 41 authenticated surgical cases, of which 25 were clinically significant. Surg Gynecol Obstet 82:527-542, 1946
Digestive Diseases and Sciences, Vol. 37, No. 8 (August 1992)
2. Dolan RV, Remine WH, Dockorty MB: The fate of heterotopic pancreatic tissue. Arch Surg 109:762-765, 1974 3. Feldman M, Weinberg T: Aberrant pancreas: A case of duodenal syndrome. JAMA 148:893-898, 1952 4. Pearson S: Aberrant pancreas. Review of the literature and report of three cases, one of which produced pancreated duct obstruction. Arch Surg 63:168-184, 1951 5. White BV, Gilden EF: Adenoma of the pancreas and hyperinsulinism. N Engl J Med 217:307-313, 1937 6. Holman CE, Wood DA, Stockton AB: Unusual cases of hyperinsulinism and hypoglycemia. Arch Surg 47:165-177, 1943 7. Duff GL, Foster HL, Bryan WW: Primary carcinoma of the infra-ampullary portion of the duodenum with example of probable origin of aberrant pancreatic tissue. Arch Surg 46:494-503, 1943 8. Compugno J, Oertel JE: Mucinous cystic neoplasms of the pancreas with overt and latent malignancy (cystsadenocarcinoma and cystadenoma). Am J Clin Pathol 69:573-580, 1978 9. Tocchi A, Puma F, Cerroni M, DiGeorgio A, Daddi G: Mucinous cystadenoma occurring in heterotopic pancreatic tissue. Ital J Surg Sci 4:355-357, 1987 10. Fresnel P, Sidilly A, Fouchor G, Fresnel PL: Cystadenoma Pancreatique ectopique intragastrique. Presse Med 79:2496, 1971 11. Stahlschmidt M, Schafer A, Schmidt-Koppler A, Hohle E: Zystadenoa I1 Heterotopen Pankreasgewebe. Leber Magen Darh 4:247-250, 1974 12. Soloway HB: Constitutional abnormalities associated with pancreatic cystadenomas. Cancer 18:1297-1300, 1965P
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