Gastrointest Radiol 16: 62-66 (1991)
Gastrointestinal
Radiology 9 Springer-VerlagNewYorkInc.1991
Microcystic Adenoma of the Pancreas: Report on Four Cases and Review of the Literature B. Padovani, 1 P. Neuveut, 2 S. Chanalet, 1 D. Benchimol, 3 M.C. Saint-Paul, 4 J.F. Michiels, 4 J.P. Arpurt, 2 and J.J. Serres 1 1 Service Central de Radiodiagnostic, 2 Service de Gastro-ent6rologie, 3 Service de Chirurgie Visc6rale et Thoracique, and 4 Service d'Anatomo-pathologie, Centre Hospitalier R6gional de Nice, H6pital Pasteur, Nice, France
Abstract. Four cases of microcystic adenoma of
the pancreas, including ultrasonographic (US) and computed tomographic (CT) data, are described. These tumors generally present as large, well-delimited pancreatic masses whose multicystic nature is readily evidenced on postcontrast CT scans. While the presence of cysts less than 2 cm in diameter and a central, star-like calcification are very specific, the frequency of atypical forms generally justifies exploratory surgery. Key words: Pancreas - Microcystic adenoma -
as were his carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), and CA-19-9 levels. Abdominal US failed to disclose any abnormality. Endoscopic retrograde cholangiopancreatography (ERCP) suggested pancreas divisum. Barium examination of the small intestine demonstrated three smooth strictures at the level of the first jejunal loop which prompted surgical exploration. The first loop was resected using a jejunojejunal anastomosis. At surgery, a 3-cm diameter tumor was palpated at the superior aspect of the pancreatic isthmus. Extemporaneous biopsy gave a diagnosis of microcystic adenoma. Histologic examination confirmed the ischemic origin of the intestinal stenoses and disclosed multiple small cystic cavities (1-2 m m maximum) in the pancreas. The final histologic diagnosis was microcystic adenoma.
Cystadenoma - CT scan - US. Case 2
Formerly termed serous cystadenomas, microcystic pancreatic adenomas are rare cystic tumors of the exocrine pancreas that have a constantly benign prognosis. The development of modern radiologic techniques, such as ultrasonography (US) and computed tomography (CT) currently permits early diagnosis. The four cases reported here prompted us to review the literature on this infrequent pathologic entity.
A 74-year-old male was hospitalized because of a 6 kg weight loss and persistent fever. Physical examination and laboratory tests were unremarkable. U S examination revealed a hypoechoic zone in the tail of the pancreas. CT demonstrated a wellcircumscribed, 4.5-cm tumor occupying the body and tail of the pancreas. On precontrast scans, this tumor was homogeneous and hypodense compared to the remainder of the pancreas. Heterogeneous enhancement was noted on postcontrast scans. The vascular axes were uninvolved. Celiac arteriography revealed tumoral hypervascularity, without arterial or venous invasion. Laparotomy confirmed the presence of a solitary tumor, and the body and tail of the pancreas were resected. Histologic examination revealed the microcystic nature of the tumor, which exhibited a star-like appearance. The final diagnosis was microcystic adenoma, with no adverse prognostic features.
Case Reports Case 3 Case 1 A 74-year-old m a n was hospitalized for tests after a weight loss of 16 kg over 3 months. His recent history included onset of an abdominal syndrome with hyperamylasemia 3 months previously. Physical examination was noncontributory. Biochemical tests revealed anemia, but no inflammatory syndrome. Biochemical liver and pancreatic function tests were normal, Address offprint requests to: Bernard Padovani, M.D., Service Central de Radiodiagnostic, Centre Hospitalier R6gional de Nice, H6pital Pasteur, B.P. No. 69, 06002 Nice Cedex, France
A 65-year-old woman was hospitalized for workup of a cystic tumor in the head of the pancreas. A n episode of acute digestive intolerance had prompted abdominal US which revealed the cysts. Physical examination revealed a firm mass in the right upper quadrant. Biochemical tests disclosed a moderate inflammatory syndrome, with increased amylase and lipase; tumor markers levels were normal. On abdominal US, a 6-cm diameter mass visualized in the head of the pancreas was shown to have a heterogeneous echostructure and several anechoic zones (the largest measured 3 cm). The bile duct was dilated upstream of the tumor (10 mm). CT confirmed the existence of a 6-cm
B. Padovani et al. : Microcystic A d e n o m a of the Pancreas
Fig. 1. A Nonenhanced CT scan shows a multilobular mass in the head of the pancreas. B Postcontrast CT scan shows a multiloculated cyst with opacification of septae. Fig. 2. A Cross section of gross specimen showing numerous cysts varying in size from 0.3-2 cm. B The cysts are lined by a simple cuboidal epithelium composed of cells with clear cyto-
63
plasm and regular round nuclei. Hematoxylin-eosin, original magnification, x 360. Fig. 3. A ERCP demonstrates an arc-like stenosis of the pancreatic duct at the level of the pancreatic body. B Celiac arteriography shows a well-circumscribed hypervascular mass (arrows) in the body of the pancreas.
64 diameter multilobular mass (Fig. 1A). Multiple cystic components became visible on postcontrast CT scans (the largest measured 3 era) (Fig. 1B). The mesenteric vessels did not appear invaded. ERCP, including opaciflcation of the duct of Wirsung, demonstrated stenosis with slight upstream dilatation and dilatation upstream of an irregular stricture in the intrapancreatic portion of the main bile duct. Duodenopancreatectomy including the head of the pancreas was performed. Histologic study revealed a well-delimited, multilobulated tumor that was nearly encapsulated (Fig. 2A), except at the level of the bile duct wall. Microscopic examination confirmed the diagnosis of microcystic adenoma (Fig. 2B).
Case 4 A 68-year-old woman was hospitalized for exploration of a pancreatic mass discovered at US. A recent history of melena prompted endoscopic examination, which revealed esophageal varices. She also gave a history of a 5 kg weight loss over 2 months and complained of epigastric pain that subsided with meals. Physical examination demonstrated firm hepatomegaly with collateral abdominal circulation. Biochemical tests revealed anemia and an inflammatory syndrome. The remainder of the laboratory values were normal, except for an elevation in gamma glutamyl-transpeptidase and a slight rise in CA 19-9 (44 U/ml). A repeat sonogram visualized a generally heterogeneous liver and a partially cystic, 6 x 4 cm tumoral mass in the body of the pancreas. CT scans revealed a heterogeneous mass containing zones that enhanced with contrast material and a 3-cm, fluid-density lesion. A crescent-shaped zone of ascites and small retroperitoneal adenopathies were also observed. ERCP revealed a long arc-like stricture in the prevertebral portion of the duct of Wirsung causing minor dilatation upstream (Fig. 3A). Arteriography demonstrated global tumoral hypervascularization (Fig. 3 B). At laparotomy, the liver was found to be cirrhotic, with portal hypertension. Despite resection of the pancreatic tumor, the patient died of postoperative gastrointestinal hemorrhage. Histologic examination of the hepatic specimen demonstrated primary biliary cirrhosis. Histologic sections of the pancreatic tumor contained well-defined multilocular or microcystic lesions corresponding to microcystic adenoma.
Discussion and Review of the Literature Microcystic a d e n o m a s o f the pancreas are rare entities, accounting for only 1% o f all pancreatic tumors in the series o f Chert and Baithun [1] and 9.4% o f the cystic t u m o r s o f the pancreas in the series o f Becket et al. [2]. The respective frequencies o f microcystic a d e n o m a s and m u c i n o u s cystad e n o m a s remain very controversial. T h e classification o f reference, established by C o m p a g n o and Oertel in 1978 [3, 4], distinguishes between glycogen-rich microcystic a d e n o m a s (or cystadenomas), which are always benign, and macrocystic ade n o m a s (or m u c i n o u s cystadenomas), which are susceptible to malignant t r a n s f o r m a t i o n into mucinous cystadenocarcinomas. Histologic e x a m i n a t i o n demonstrates and irregular, multilocular macrocystic t u m o r which often contains a central star-like fibrous scar, which
B. Padovani et al. : Microcystic Adenoma of the Pancreas m a y be calcified, and n u m e r o u s cysts varying in size f r o m 0.1-2 cm. These cysts, which tend to be largest at the periphery, are separated f r o m one a n o t h e r by fibrous septae radiating out f r o m the center [5]. T u m o r size varies greatly, f r o m 1-25 cm (mean 10.8 cm in the series o f C o m p a g n o et al. [3]). Microscopic study shows that these t u m o r s are generally separated f r o m the healthy pancreatic tissue by a thick b a n d o f fibrous tissue. T h e serous cystic fluid m a y contain erythrocytes. Mitotic activity and nuclear atypia are constantly absent. Review o f the clinical features r e p o r t e d for 134 cases published in the literature showed that these t u m o r s remain a s y m p t o m a t i c for long periods and are often fortuitous discoveries (41% o f cases) during radiological examinations, l a p a r o t o m y , or necropsy. Weight loss was r e p o r t e d in only 2 5 % o f the cases, whereas 62% o f the patients c o m p l a i n e d o f an epigastric a b d o m i n a l mass. Jaundice was infrequent (only eight cases). M a i n bile duct obstruction is thus a rare complication, even with t u m o r s in the head o f the pancreas. E R C P o f the papilla will usually show displacem e n t o f the bile duct and the duct o f Wirsung, and such findings suggest a benign process but are nonspecific. On a b d o m i n a l plain films, large tumors m a y image as a r o u n d e d opacity which m a y contain central calcifications [6, 7] that are highly suggestive o f the diagnosis, especially when their radiating p a t t e r n resembles " s u n b e a m s " [8, 9]. Such cap cifications are r e p o r t e d in 1 0 - 3 6 % o f cases [8, 10]. B a r i u m gastrointestinal series provide no specific findings and will show only signs o f displacement and the absence o f parietal invasion. US demonstrates the pancreatic mass in m o s t cases. In all 21 literature cases o f microcystic pancreatic a d e n o m a investigated by US, the pancreatic site o f the t u m o r was confirmed. However, in o u r first case the t u m o r was not visible. T h e sonographic findings r e p o r t e d included: a mass u n d e r 2 cm in diameter (three cases); a solid h y p o e c h o i c mass (five cases); a t u m o r containing cystic zones over 2 cm (four cases); anechoic images (two cases); and calcifications (five cases). T u m o r s composed solely o f cysts less t h a n 2 m m in diameter a p p e a r e d hyperechoic and well delimited with respect to the remainder o f the pancreas. Peripheral cystic f o r m a t i o n s typically image as thin-walled anechoic lesions with posterior reinforcement [8]. T h e central fibrous scar is occasionally d e m o n s t r a t e d as a hyperechoic zone f r o m which echoic septae radiate o u t w a r d [7]. Atypical forms containing large cysts m a y not contain any identifiable septae. Along with evaluating possible involvement o f the
B. Padovani et al. : Microcystic Adenoma of the Pancreas
bile ducts or contiguous vessels, US can confirm the absence of hepatic or nodal metastases. CT must be performed both before and after intravenous iodinated contrast medium injection. CT features depend on the size of the cysts making up the tumor. In the literature, 24 CT studies are described. Three of our patients were also explored by CT. In 11 cases, the diagnosis was suggested by a well-circumscribed, homogeneous mass that appeared hypodense compared to the healthy pancreas on precontrast scans [7, 11, 12], then heterogeneous, with opacification of the intercystic septurn, after contrast medium injection. A heterogeneous mass containing visible cystic formations was reported in 11 cases; in five cases, a hypodense mass was described. Central calcifications were described in 17 patients (63%). Overall, tumors containing very small cysts exhibit diffuse enhancement on postcontrast scans. With larger cysts, only zones of tissue involvement are typically opacified after contrast medium injection; intravenous bolus injection permits better visualization of the radiating intercystic septae which converge toward the central fibrous zone creating a " h o n e y c o m b " pattern [7, 11-14]. The hyperdense peripheral rim visualized on rare occasion corresponds to opacification of the large peritumoral veins [5]. CT scans can also confirm the absence of invasion of contiguous structures and the absence of hepatic or nodal metastases. Thus, the combined use of US and CT scans play an essential role in the preoperative workup of these tumors, owing to the complementary nature of these two imaging techniques. For Stovall [15], detection of cysts under 2 cm in a cystic pancreatic tumor is highly suggestive of the diagnosis, which is confirmed when accompanied by a central star-like calcification. For other authors [7], positive diagnosis requires the presence of a mass in the head of the pancreas with cysts less than 2 cm in diameter, as well as central calcifications. To our knowledge, no magnetic resonance imaging studies of microcystic pancreatic adenoma have been published to date. Fine-needle percutaneous biopsy under US or CT guidance is advocated by numerous authors [5, 9, 16-19] to differentiate microcystic adenoma from mucinous cystadenoma or cystadenocarcinoma when radiologic data are nondiagnostic [14, 20]. Other investigators [11, 14, 20] have emphasized the potential risk of intraperitoneal hemorrhage after puncture of a hypervascularized tumor. Finally, certain authors [14, 21] feel that this technique does not permit differentiation of these tumor types. In fact, analysis and comparison of
65
published series is difficult because few studies have been reported and the number of cases covered is usually small. Cytology or examination of the intracystic fluid is required to affirm the malignant nature of cystic pancreatic tumors with atypical sonographic and/or CT features [22]. Differential diagnosis from the many other cystic tumors of the pancreas, for which the diagnostic approach is usually conditioned by clinical and biochemical data, lies outside the scope of this article. Differentiation from mucinous cystadenomas is more challenging because these entities cannot be distinguished from microcystic adenomas on the basis of clinical or biochemical parameters. Along with a marked sex predominance (80% of cases occur in women) [23], mucinous cystadenomas are most prevalent in the body and tail of the pancreas [4, 13, 24]. Peripheral calcifications are inconstant (15% of cases), but suggest the diagnosis. US and CT are also suggestive when they demonstrate a well-encapsulated mass containing one or more cystic components, but these lesions often contain few cavities. The presence of parietal nodules or an intracystic growth are also suggestive of the diagnosis. In fact, aside from several typical appearances, positive diagnosis is difficult prior to surgery. There are no radiologic features that can be used to differentiate mucinous cystadenocarcinomas from mucinous cystadenomas, other than discovery of visceral metastases. The natural history of microcystic adenomas corresponds to a slow-growing tumor which can nevertheless provoke life-threatening complications [3]. The course of these tumors was long controversial, but most authors currently consider them benign [3, 7, 18, 25-27]. However, a case that had a malignant course was recently reported
[281. References 1. Chen J, Baithun SI: Morphological study of 391 cases of exocrine pancreatic tumors with special reference to the classification of exocrine pancreatic carcinoma. J Pathol 146:17-29, 1985 2. Becker WF, Welsh RA, Pratt HS : Cystadenoma and cystadenocarcinoma of the pancreas. Ann Surg 161:845-860, 1965 3. Compagno J, Oertel JE : Microscystic adenomas of the pancreas (glycogen-rich cystadenomas). Am J Clin Pathol 69:289-298, 1978 4. Compagno J, Oertel JE: Mucinous cystic neoplasms of the pancreas with overt and latent malignancy (cystadenocarcinoma and cystadenoma). A clinicopathologic study of 41 cases. Am J Clin Patho169:573-580, 1978 5. Leborgne J, Albisetti J, Heloury Y, Joubert B, Legoff M, Charles JF, Le N e d JC, Lenne Y, Malvy P: Les cystad+n-
66 omes microkystiques et mucineux du pancr6as. Rbflexions partir de 15 observations. Chirurgie 11:244-251, 1985 6. Haukhol RS, Melamed A: Cystadenoma of the pancreas: A report of two cases showing calcifications. A JR 63.'234-245, 1950 7. Vilgrain V, Menu Y, Lorphelin JM, Nahum H: Cystad~nomes pancr6atiques. Pi6ges et limites du diagnostic radiologique. J Radiol 68:455-463, 1987 8. Freeny P, Lawson TL: Cystic neoplasms of the pancreas. In Radiology of the Pancreas. New York, Heidelberg, Berlin: Springer-Verlag, 1982, pp 514-538 9. Zamora JL, Gunn LC, Manaligod JR: Microcystic adenoma of the pancreas: A newly recognized benign lesion. Curr Surg 41.'448-452, 1984 10. Friedman AC, Lichtenstein JE, Dachman AH: Cystic neoplasms of the pancreas. Radiological pathological correlation. Radiology 149.'45-50, 1983 1I. Algard M, Ponsot P, Hautefeuille M, Menu Y, Fekete F, Paolaggi JA: Cystadbnomes pancr6atiques : Int~r6t diagnostique de l'~chographie et de la tomodensitom6trie. Gastroenterol Clin Biol 10.'23-28, 1986 12. Zirinsky K, Abiri M, Baer JW: Computed tomography demonstration of pancreatic microcystic adenoma. Am J Gastroenterol 79:139-142, 1984 23. Itai Y, Moss AA, Ohtomo K: Computed tomography of cystadenoma and cystadenocarcinoma of the pancreas. Radiology 145: 419-425, 1982 14. Leborgne J: Les cystad6nomes pancr6atiques. Gastroentdrologie 2:35-38, 1988 15. Stovall JM: Microcystic adenoma: The specificity of computerized tomography in making the distinction. JAMA 78:1119-1121, 1986 16. Jones EC, Suen KC, Grant DR, Chan NH: Fine-needle aspiration cytology of neoplastic of the pancreas. Diagn Cytopathol 3:238-243, 1987 17. Pinto MM, Kaye AD, Brogan DA, Criscuolo EH: Diagnosis of cystic lesions of the pancreas: A biochemical and cytologic analysis of material obtained utilizing radiograph-
B. Padovani et al. : Microcystic Adenoma of the Pancreas ic or intraoperative technique. Diagn Cytopathol 2.'40-45, 1986 18. Torres-Barrera G, Fernandez-Del Castillo C, Reyes E, Robles-Diaz G, Campuzano M: Microcystic adenoma of the pancreas. Dig Dis Sci 32.'454-458, 1987 19. Warshaw AL, Rutledge PL: Cystic tumors mistaken for pancreatic pseudocysts. Ann Surg 205: 393-398, 1987 20. Hodgkinson D J, Remine WH, Weiland LH : Pancreatic cystadenoma. A clinicopathologic study of 45 cases. Arch Surg 113.512-519, 1978 21. Von Segesser L, Rohner A: Pancreatic cystadenoma and cystadenocarcinoma. Br J Surg 71 : 449-451, 1984 22. Neuveut Ph: Les ad6nomes microkystiques du pancr6as. Apropos de 4 observations. ThOse M4decine Nice 1988 23. De Saint-Julien J, Pedinielli L, Martin J, Gandon A: Les kystes mucineux du pancr6as. Apropos de 8 cas. Chirurgie 111 : 252-257, 1985 24. Bogomoletz WV, Adnet JJ, Widgren S, Stavrou M, Mc Lauglin JE: Cystadenoma of the pancreas: A histological, histochemical and ultrastrnctural study of seven cases. Histopathology 4: 309-320, 1980 25. Alpert LC, Truong LD, Bossart MI, Spjut H J: Microcystic adenoma (serous cystadenoma) of the pancreas. A study of 14 cases with immunohistochemical and electron-microscopic correlation. Am J Surg Pathol 12:251-263, 1988 26. Rosai J: Cystadenoma and cystadenocarcinoma. In Ackerman's Surgical Pathology, Vol. 2. St Louis, CV Mosby, 1981, pp 687-688 27, Shorten SD, Hart WR, Petras RE: Microcystic adenomas (serous cystadenoma) of pancreas. A clinicopathologic investigation of eight cases with immunohistochemical and ultrastructural studies. Am J Surg Pathol 10:365-372, 1986 28. George D, Murphy F, Michalski R, Ulmer B: Serous eystadenocarcinoma of the pancreas: A new entity? Am J Surg Pathol 13: 61-66, 1989 Received. January 23, 1990; accepted: February 24, 1990
Gastrointestinal
Radiology 9 Springer-VerlagNewYorkInc.1991
Microcystic Adenoma of the Pancreas: Report on Four Cases and Review of the Literature B. Padovani, 1 P. Neuveut, 2 S. Chanalet, 1 D. Benchimol, 3 M.C. Saint-Paul, 4 J.F. Michiels, 4 J.P. Arpurt, 2 and J.J. Serres 1 1 Service Central de Radiodiagnostic, 2 Service de Gastro-ent6rologie, 3 Service de Chirurgie Visc6rale et Thoracique, and 4 Service d'Anatomo-pathologie, Centre Hospitalier R6gional de Nice, H6pital Pasteur, Nice, France
Abstract. Four cases of microcystic adenoma of
the pancreas, including ultrasonographic (US) and computed tomographic (CT) data, are described. These tumors generally present as large, well-delimited pancreatic masses whose multicystic nature is readily evidenced on postcontrast CT scans. While the presence of cysts less than 2 cm in diameter and a central, star-like calcification are very specific, the frequency of atypical forms generally justifies exploratory surgery. Key words: Pancreas - Microcystic adenoma -
as were his carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), and CA-19-9 levels. Abdominal US failed to disclose any abnormality. Endoscopic retrograde cholangiopancreatography (ERCP) suggested pancreas divisum. Barium examination of the small intestine demonstrated three smooth strictures at the level of the first jejunal loop which prompted surgical exploration. The first loop was resected using a jejunojejunal anastomosis. At surgery, a 3-cm diameter tumor was palpated at the superior aspect of the pancreatic isthmus. Extemporaneous biopsy gave a diagnosis of microcystic adenoma. Histologic examination confirmed the ischemic origin of the intestinal stenoses and disclosed multiple small cystic cavities (1-2 m m maximum) in the pancreas. The final histologic diagnosis was microcystic adenoma.
Cystadenoma - CT scan - US. Case 2
Formerly termed serous cystadenomas, microcystic pancreatic adenomas are rare cystic tumors of the exocrine pancreas that have a constantly benign prognosis. The development of modern radiologic techniques, such as ultrasonography (US) and computed tomography (CT) currently permits early diagnosis. The four cases reported here prompted us to review the literature on this infrequent pathologic entity.
A 74-year-old male was hospitalized because of a 6 kg weight loss and persistent fever. Physical examination and laboratory tests were unremarkable. U S examination revealed a hypoechoic zone in the tail of the pancreas. CT demonstrated a wellcircumscribed, 4.5-cm tumor occupying the body and tail of the pancreas. On precontrast scans, this tumor was homogeneous and hypodense compared to the remainder of the pancreas. Heterogeneous enhancement was noted on postcontrast scans. The vascular axes were uninvolved. Celiac arteriography revealed tumoral hypervascularity, without arterial or venous invasion. Laparotomy confirmed the presence of a solitary tumor, and the body and tail of the pancreas were resected. Histologic examination revealed the microcystic nature of the tumor, which exhibited a star-like appearance. The final diagnosis was microcystic adenoma, with no adverse prognostic features.
Case Reports Case 3 Case 1 A 74-year-old m a n was hospitalized for tests after a weight loss of 16 kg over 3 months. His recent history included onset of an abdominal syndrome with hyperamylasemia 3 months previously. Physical examination was noncontributory. Biochemical tests revealed anemia, but no inflammatory syndrome. Biochemical liver and pancreatic function tests were normal, Address offprint requests to: Bernard Padovani, M.D., Service Central de Radiodiagnostic, Centre Hospitalier R6gional de Nice, H6pital Pasteur, B.P. No. 69, 06002 Nice Cedex, France
A 65-year-old woman was hospitalized for workup of a cystic tumor in the head of the pancreas. A n episode of acute digestive intolerance had prompted abdominal US which revealed the cysts. Physical examination revealed a firm mass in the right upper quadrant. Biochemical tests disclosed a moderate inflammatory syndrome, with increased amylase and lipase; tumor markers levels were normal. On abdominal US, a 6-cm diameter mass visualized in the head of the pancreas was shown to have a heterogeneous echostructure and several anechoic zones (the largest measured 3 cm). The bile duct was dilated upstream of the tumor (10 mm). CT confirmed the existence of a 6-cm
B. Padovani et al. : Microcystic A d e n o m a of the Pancreas
Fig. 1. A Nonenhanced CT scan shows a multilobular mass in the head of the pancreas. B Postcontrast CT scan shows a multiloculated cyst with opacification of septae. Fig. 2. A Cross section of gross specimen showing numerous cysts varying in size from 0.3-2 cm. B The cysts are lined by a simple cuboidal epithelium composed of cells with clear cyto-
63
plasm and regular round nuclei. Hematoxylin-eosin, original magnification, x 360. Fig. 3. A ERCP demonstrates an arc-like stenosis of the pancreatic duct at the level of the pancreatic body. B Celiac arteriography shows a well-circumscribed hypervascular mass (arrows) in the body of the pancreas.
64 diameter multilobular mass (Fig. 1A). Multiple cystic components became visible on postcontrast CT scans (the largest measured 3 era) (Fig. 1B). The mesenteric vessels did not appear invaded. ERCP, including opaciflcation of the duct of Wirsung, demonstrated stenosis with slight upstream dilatation and dilatation upstream of an irregular stricture in the intrapancreatic portion of the main bile duct. Duodenopancreatectomy including the head of the pancreas was performed. Histologic study revealed a well-delimited, multilobulated tumor that was nearly encapsulated (Fig. 2A), except at the level of the bile duct wall. Microscopic examination confirmed the diagnosis of microcystic adenoma (Fig. 2B).
Case 4 A 68-year-old woman was hospitalized for exploration of a pancreatic mass discovered at US. A recent history of melena prompted endoscopic examination, which revealed esophageal varices. She also gave a history of a 5 kg weight loss over 2 months and complained of epigastric pain that subsided with meals. Physical examination demonstrated firm hepatomegaly with collateral abdominal circulation. Biochemical tests revealed anemia and an inflammatory syndrome. The remainder of the laboratory values were normal, except for an elevation in gamma glutamyl-transpeptidase and a slight rise in CA 19-9 (44 U/ml). A repeat sonogram visualized a generally heterogeneous liver and a partially cystic, 6 x 4 cm tumoral mass in the body of the pancreas. CT scans revealed a heterogeneous mass containing zones that enhanced with contrast material and a 3-cm, fluid-density lesion. A crescent-shaped zone of ascites and small retroperitoneal adenopathies were also observed. ERCP revealed a long arc-like stricture in the prevertebral portion of the duct of Wirsung causing minor dilatation upstream (Fig. 3A). Arteriography demonstrated global tumoral hypervascularization (Fig. 3 B). At laparotomy, the liver was found to be cirrhotic, with portal hypertension. Despite resection of the pancreatic tumor, the patient died of postoperative gastrointestinal hemorrhage. Histologic examination of the hepatic specimen demonstrated primary biliary cirrhosis. Histologic sections of the pancreatic tumor contained well-defined multilocular or microcystic lesions corresponding to microcystic adenoma.
Discussion and Review of the Literature Microcystic a d e n o m a s o f the pancreas are rare entities, accounting for only 1% o f all pancreatic tumors in the series o f Chert and Baithun [1] and 9.4% o f the cystic t u m o r s o f the pancreas in the series o f Becket et al. [2]. The respective frequencies o f microcystic a d e n o m a s and m u c i n o u s cystad e n o m a s remain very controversial. T h e classification o f reference, established by C o m p a g n o and Oertel in 1978 [3, 4], distinguishes between glycogen-rich microcystic a d e n o m a s (or cystadenomas), which are always benign, and macrocystic ade n o m a s (or m u c i n o u s cystadenomas), which are susceptible to malignant t r a n s f o r m a t i o n into mucinous cystadenocarcinomas. Histologic e x a m i n a t i o n demonstrates and irregular, multilocular macrocystic t u m o r which often contains a central star-like fibrous scar, which
B. Padovani et al. : Microcystic Adenoma of the Pancreas m a y be calcified, and n u m e r o u s cysts varying in size f r o m 0.1-2 cm. These cysts, which tend to be largest at the periphery, are separated f r o m one a n o t h e r by fibrous septae radiating out f r o m the center [5]. T u m o r size varies greatly, f r o m 1-25 cm (mean 10.8 cm in the series o f C o m p a g n o et al. [3]). Microscopic study shows that these t u m o r s are generally separated f r o m the healthy pancreatic tissue by a thick b a n d o f fibrous tissue. T h e serous cystic fluid m a y contain erythrocytes. Mitotic activity and nuclear atypia are constantly absent. Review o f the clinical features r e p o r t e d for 134 cases published in the literature showed that these t u m o r s remain a s y m p t o m a t i c for long periods and are often fortuitous discoveries (41% o f cases) during radiological examinations, l a p a r o t o m y , or necropsy. Weight loss was r e p o r t e d in only 2 5 % o f the cases, whereas 62% o f the patients c o m p l a i n e d o f an epigastric a b d o m i n a l mass. Jaundice was infrequent (only eight cases). M a i n bile duct obstruction is thus a rare complication, even with t u m o r s in the head o f the pancreas. E R C P o f the papilla will usually show displacem e n t o f the bile duct and the duct o f Wirsung, and such findings suggest a benign process but are nonspecific. On a b d o m i n a l plain films, large tumors m a y image as a r o u n d e d opacity which m a y contain central calcifications [6, 7] that are highly suggestive o f the diagnosis, especially when their radiating p a t t e r n resembles " s u n b e a m s " [8, 9]. Such cap cifications are r e p o r t e d in 1 0 - 3 6 % o f cases [8, 10]. B a r i u m gastrointestinal series provide no specific findings and will show only signs o f displacement and the absence o f parietal invasion. US demonstrates the pancreatic mass in m o s t cases. In all 21 literature cases o f microcystic pancreatic a d e n o m a investigated by US, the pancreatic site o f the t u m o r was confirmed. However, in o u r first case the t u m o r was not visible. T h e sonographic findings r e p o r t e d included: a mass u n d e r 2 cm in diameter (three cases); a solid h y p o e c h o i c mass (five cases); a t u m o r containing cystic zones over 2 cm (four cases); anechoic images (two cases); and calcifications (five cases). T u m o r s composed solely o f cysts less t h a n 2 m m in diameter a p p e a r e d hyperechoic and well delimited with respect to the remainder o f the pancreas. Peripheral cystic f o r m a t i o n s typically image as thin-walled anechoic lesions with posterior reinforcement [8]. T h e central fibrous scar is occasionally d e m o n s t r a t e d as a hyperechoic zone f r o m which echoic septae radiate o u t w a r d [7]. Atypical forms containing large cysts m a y not contain any identifiable septae. Along with evaluating possible involvement o f the
B. Padovani et al. : Microcystic Adenoma of the Pancreas
bile ducts or contiguous vessels, US can confirm the absence of hepatic or nodal metastases. CT must be performed both before and after intravenous iodinated contrast medium injection. CT features depend on the size of the cysts making up the tumor. In the literature, 24 CT studies are described. Three of our patients were also explored by CT. In 11 cases, the diagnosis was suggested by a well-circumscribed, homogeneous mass that appeared hypodense compared to the healthy pancreas on precontrast scans [7, 11, 12], then heterogeneous, with opacification of the intercystic septurn, after contrast medium injection. A heterogeneous mass containing visible cystic formations was reported in 11 cases; in five cases, a hypodense mass was described. Central calcifications were described in 17 patients (63%). Overall, tumors containing very small cysts exhibit diffuse enhancement on postcontrast scans. With larger cysts, only zones of tissue involvement are typically opacified after contrast medium injection; intravenous bolus injection permits better visualization of the radiating intercystic septae which converge toward the central fibrous zone creating a " h o n e y c o m b " pattern [7, 11-14]. The hyperdense peripheral rim visualized on rare occasion corresponds to opacification of the large peritumoral veins [5]. CT scans can also confirm the absence of invasion of contiguous structures and the absence of hepatic or nodal metastases. Thus, the combined use of US and CT scans play an essential role in the preoperative workup of these tumors, owing to the complementary nature of these two imaging techniques. For Stovall [15], detection of cysts under 2 cm in a cystic pancreatic tumor is highly suggestive of the diagnosis, which is confirmed when accompanied by a central star-like calcification. For other authors [7], positive diagnosis requires the presence of a mass in the head of the pancreas with cysts less than 2 cm in diameter, as well as central calcifications. To our knowledge, no magnetic resonance imaging studies of microcystic pancreatic adenoma have been published to date. Fine-needle percutaneous biopsy under US or CT guidance is advocated by numerous authors [5, 9, 16-19] to differentiate microcystic adenoma from mucinous cystadenoma or cystadenocarcinoma when radiologic data are nondiagnostic [14, 20]. Other investigators [11, 14, 20] have emphasized the potential risk of intraperitoneal hemorrhage after puncture of a hypervascularized tumor. Finally, certain authors [14, 21] feel that this technique does not permit differentiation of these tumor types. In fact, analysis and comparison of
65
published series is difficult because few studies have been reported and the number of cases covered is usually small. Cytology or examination of the intracystic fluid is required to affirm the malignant nature of cystic pancreatic tumors with atypical sonographic and/or CT features [22]. Differential diagnosis from the many other cystic tumors of the pancreas, for which the diagnostic approach is usually conditioned by clinical and biochemical data, lies outside the scope of this article. Differentiation from mucinous cystadenomas is more challenging because these entities cannot be distinguished from microcystic adenomas on the basis of clinical or biochemical parameters. Along with a marked sex predominance (80% of cases occur in women) [23], mucinous cystadenomas are most prevalent in the body and tail of the pancreas [4, 13, 24]. Peripheral calcifications are inconstant (15% of cases), but suggest the diagnosis. US and CT are also suggestive when they demonstrate a well-encapsulated mass containing one or more cystic components, but these lesions often contain few cavities. The presence of parietal nodules or an intracystic growth are also suggestive of the diagnosis. In fact, aside from several typical appearances, positive diagnosis is difficult prior to surgery. There are no radiologic features that can be used to differentiate mucinous cystadenocarcinomas from mucinous cystadenomas, other than discovery of visceral metastases. The natural history of microcystic adenomas corresponds to a slow-growing tumor which can nevertheless provoke life-threatening complications [3]. The course of these tumors was long controversial, but most authors currently consider them benign [3, 7, 18, 25-27]. However, a case that had a malignant course was recently reported
[281. References 1. Chen J, Baithun SI: Morphological study of 391 cases of exocrine pancreatic tumors with special reference to the classification of exocrine pancreatic carcinoma. J Pathol 146:17-29, 1985 2. Becker WF, Welsh RA, Pratt HS : Cystadenoma and cystadenocarcinoma of the pancreas. Ann Surg 161:845-860, 1965 3. Compagno J, Oertel JE : Microscystic adenomas of the pancreas (glycogen-rich cystadenomas). Am J Clin Pathol 69:289-298, 1978 4. Compagno J, Oertel JE: Mucinous cystic neoplasms of the pancreas with overt and latent malignancy (cystadenocarcinoma and cystadenoma). A clinicopathologic study of 41 cases. Am J Clin Patho169:573-580, 1978 5. Leborgne J, Albisetti J, Heloury Y, Joubert B, Legoff M, Charles JF, Le N e d JC, Lenne Y, Malvy P: Les cystad+n-
66 omes microkystiques et mucineux du pancr6as. Rbflexions partir de 15 observations. Chirurgie 11:244-251, 1985 6. Haukhol RS, Melamed A: Cystadenoma of the pancreas: A report of two cases showing calcifications. A JR 63.'234-245, 1950 7. Vilgrain V, Menu Y, Lorphelin JM, Nahum H: Cystad~nomes pancr6atiques. Pi6ges et limites du diagnostic radiologique. J Radiol 68:455-463, 1987 8. Freeny P, Lawson TL: Cystic neoplasms of the pancreas. In Radiology of the Pancreas. New York, Heidelberg, Berlin: Springer-Verlag, 1982, pp 514-538 9. Zamora JL, Gunn LC, Manaligod JR: Microcystic adenoma of the pancreas: A newly recognized benign lesion. Curr Surg 41.'448-452, 1984 10. Friedman AC, Lichtenstein JE, Dachman AH: Cystic neoplasms of the pancreas. Radiological pathological correlation. Radiology 149.'45-50, 1983 1I. Algard M, Ponsot P, Hautefeuille M, Menu Y, Fekete F, Paolaggi JA: Cystadbnomes pancr6atiques : Int~r6t diagnostique de l'~chographie et de la tomodensitom6trie. Gastroenterol Clin Biol 10.'23-28, 1986 12. Zirinsky K, Abiri M, Baer JW: Computed tomography demonstration of pancreatic microcystic adenoma. Am J Gastroenterol 79:139-142, 1984 23. Itai Y, Moss AA, Ohtomo K: Computed tomography of cystadenoma and cystadenocarcinoma of the pancreas. Radiology 145: 419-425, 1982 14. Leborgne J: Les cystad6nomes pancr6atiques. Gastroentdrologie 2:35-38, 1988 15. Stovall JM: Microcystic adenoma: The specificity of computerized tomography in making the distinction. JAMA 78:1119-1121, 1986 16. Jones EC, Suen KC, Grant DR, Chan NH: Fine-needle aspiration cytology of neoplastic of the pancreas. Diagn Cytopathol 3:238-243, 1987 17. Pinto MM, Kaye AD, Brogan DA, Criscuolo EH: Diagnosis of cystic lesions of the pancreas: A biochemical and cytologic analysis of material obtained utilizing radiograph-
B. Padovani et al. : Microcystic Adenoma of the Pancreas ic or intraoperative technique. Diagn Cytopathol 2.'40-45, 1986 18. Torres-Barrera G, Fernandez-Del Castillo C, Reyes E, Robles-Diaz G, Campuzano M: Microcystic adenoma of the pancreas. Dig Dis Sci 32.'454-458, 1987 19. Warshaw AL, Rutledge PL: Cystic tumors mistaken for pancreatic pseudocysts. Ann Surg 205: 393-398, 1987 20. Hodgkinson D J, Remine WH, Weiland LH : Pancreatic cystadenoma. A clinicopathologic study of 45 cases. Arch Surg 113.512-519, 1978 21. Von Segesser L, Rohner A: Pancreatic cystadenoma and cystadenocarcinoma. Br J Surg 71 : 449-451, 1984 22. Neuveut Ph: Les ad6nomes microkystiques du pancr6as. Apropos de 4 observations. ThOse M4decine Nice 1988 23. De Saint-Julien J, Pedinielli L, Martin J, Gandon A: Les kystes mucineux du pancr6as. Apropos de 8 cas. Chirurgie 111 : 252-257, 1985 24. Bogomoletz WV, Adnet JJ, Widgren S, Stavrou M, Mc Lauglin JE: Cystadenoma of the pancreas: A histological, histochemical and ultrastrnctural study of seven cases. Histopathology 4: 309-320, 1980 25. Alpert LC, Truong LD, Bossart MI, Spjut H J: Microcystic adenoma (serous cystadenoma) of the pancreas. A study of 14 cases with immunohistochemical and electron-microscopic correlation. Am J Surg Pathol 12:251-263, 1988 26. Rosai J: Cystadenoma and cystadenocarcinoma. In Ackerman's Surgical Pathology, Vol. 2. St Louis, CV Mosby, 1981, pp 687-688 27, Shorten SD, Hart WR, Petras RE: Microcystic adenomas (serous cystadenoma) of pancreas. A clinicopathologic investigation of eight cases with immunohistochemical and ultrastructural studies. Am J Surg Pathol 10:365-372, 1986 28. George D, Murphy F, Michalski R, Ulmer B: Serous eystadenocarcinoma of the pancreas: A new entity? Am J Surg Pathol 13: 61-66, 1989 Received. January 23, 1990; accepted: February 24, 1990
