Gastrointest Radiol 17:157-160 (1992)
Gastrointestinal
Radiology 9 Springer-VerlagNew York Inc. 1992
Lymphadenopathy in Sclerosing Cholangitis: Pitfall in the Diagnosis of Malignant Biliary Obstruction Eric Outwater, Marshall M. Kaplan, and Mark S. Bankoff Departments of Radiology and Gastroenterology, New England Medical Center, Boston, Massachusetts, USA
Abstract: We retrospectively reviewed abdominal computed tomographic (CT) studies from 20 patients with sclerosing cholangitis and found evidence of abdominal lymphadenopathy in 13 patients. Enlargement occurred primarily in areas draining the liver, such as the gastrohepatic ligament or celiac axis (N = 8), the porta hepatis (N = 7), and the pancreaticoduodenal region (N = 2). One patient had reactive adenopathy and retroperitoneal fibrosis. The presence of benign reactive lymphadenopathy in at least one intraabdominal location was confirmed by pathological examination of excised lymph nodes in seven patients. Malignancy was excluded by surgical exploration or clinical follow-up. We conclude that enlarged lymph nodes are a common finding by CT in patients with sclerosing cholangitis. Enlarged reactive lymph nodes in this condition should not be mistaken for evidence of periportal metastasis or cholangiocarcinoma. Key words: Sclerosing cholangitis, lymphadenopathy--Computed tomography.
Sclerosing cholangitis can clinically and radiologically mimic malignancy, particularly cholangiocarcinoma [1-6]. Even when the diagnosis of sclerosing cholangitis is established, the radiologic evaluation can be problematic. Computed tomographic (CT) scanning easily detects soft tissue masses near the biliary tree and has been used to detect cholangiocarcinoma in patients with sclerosing cholangitis, with mixed success [1, 2]. Recently, the importance of lymphadenopathy on CT scans in diagnosing and Address offprint requests to: Eric Outwater, M.D., Devon MRI Center, Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA
staging cholangiocarcinoma has been stressed, as this finding may be the only CT evidence of the carcinoma [7]. However, we have encountered patients with sclerosing cholangitis who were surgically explored because of the suspicion of malignancy on a CT examination. The surgical discovery of benign reactive lymphadenopathy as a cause of the false-positive CT scans led us to review CT scans in other patients with sclerosing cholangitis to assess the frequency of lymphadenopathy in these patients.
Patients and Methods A search of medical records disclosed 21 patients with sclerosing cholangitis who underwent abdominal CT scanning. CT scans from 20 patients were judged technically adequate in distinguishing varices from lymph nodes; by this criterion, one patient was therefore excluded from this study. The mean age of the patients was 41 years (range 10-75 years). The average duration of the disease prior to the scans was 6.2 years (range 0-18 years). Thirteen patients were male, seven were female. All patients had endoscopic retrograde cholangiopancreatography and liver biopsies consistent with sclerosing cholangitis. Liver transplantation was performed in nine patients a mean of 2.4 months after CT scanning; the hepatectomy specimens disclosed sclerosing cholangitis in each case. Malignancy was excluded by surgical exploration in 12 patients. Of the remaining seven patients, four have been followed for more than 2 years since the CT scan, and two patients for more than 18 months, and lack clinical or radiographic evidence of malignancy. The final patient developed cytologic atypia of the biliary epithelium on liver biopsies, which was not diagnostic for carcinoma in situ. She did not, however, have CT evidence for adenopathy or periportal mass. The medical and surgical histories in two patients suggested that the sclerosing cholangitis was secondary to choledocholithiasis. Thirteen patients had inflammatory bowel disease. Retroperitoneal fibrosis was proven by biopsy in one patient and one patient had thyroid fibrosis; the other three ~patients had no associated disease. Many patients were receiving methrotrexate in a blinded treatment protocol.
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E. Outwater et al.: Adenopathy in Sclerosing Cholangitis
Fig. 1. Contrast-enhanced CT scan through the porta hepatis below the celiac axis. Enlarged low attenuation lymph nodes lie in the gastrohepatic ligament and portacaval space (black arrows) in this patient with ascites, cirrhosis, splenomegaly, and falciform ligament collaterals (white arrow). Lymphadenopathy was proven at the time of liver transplantation. Dilated bile ducts can be seen in the right hepatic lobe. Fig. 2. Contrast-enhanced CT scan at the level of the celiac artery. Adenopathy is present in the porta hepatis. Lymphadenopathy was confirmed during liver transplantation. Splenomegaly is seen. Fig. 3. CT scan demonstrates enlarged lymph nodes just anterior to a replaced right hepatic artery.
CT was performed on a whole body scanner (Somatom 2 or DR3: Siemens Medical Systems. lselim NJ, USA) during intravenous bolus and rapid drip administration of contrast material. Contiguous 8-mm thick sections were obtained through the abdomen in all patients. CT scans were retrospectively analyzed. Evidence of lymphadenopathy on CT scans was defined as lymph nodes at least I cm in diameter in the gastrohepatic ligament 18]: lymph nodes at least 1.3 mm in the anteroposterior diameter, regardless of transverse diameter, in the portacaval space (node of the foramen of Winslow): and lymph nodes of at least 15 ram, or groups of four or more lymph nodes, in other locations. Peripancreatic lymphadenopathy was considered to be present only if nodes were clearly separable from the pancreas by fat planes or attenuation difference [101. Cirrhosis (inferred from small liver, relative enlargement of the caudate and left hepatic lobe, nodular contour, and fissural enlargement), hepatosplenomegaly, varices, and ascites were noted when present. The pathology files of the 19 patients were reviewed for surgical specimens of enlarged lymph nodes. Seven patients had intraabdominal lymph nodes removed during liver transplantation or other surgeries. The presence of adenopathy in the other seven patients with CT evidence of lymphadenopathy, therefore, could not be proven.
Results C T e v i d e n c e o f a b d o m i n a l l y m p h a d e n o p a t h y app e a r e d in 13 of 20 p a t i e n t s (65%). Eight p a t i e n t s had
l y m p h a d e n o p a t h y in the g a s t r o h e p a t i c ligament or a r o u n d the celiac axis (Fig. 1), s e v e n in the p o r t a hepatis or p o r t a c a v a l space (Figs. 2 a n d 3), five in the p a r a c a v a l or periaortic c h a i n s , two in the panc r e a t i c o d u o d e n a l n o d e s , a n d two in the m e s e n t e r i c l y m p h n o d e s . H e n c e , l y m p h a d e n o p a t h y t e n d e d to be most p r e v a l e n t in those g r o u p s d r a i n i n g into the liver a n d p o r t a hepatis. L y m p h n o d e s were h o m o g e n e o u s , of l o w e r a t t e n u a t i o n t h a n e n h a n c e d liver, a n d h y p o d e n s e or i s o d e n s e to the p a n c r e a s . N o l y m p h n o d e s d e m o n s t r a t e d low a t t e n u a t i o n c e n t e r s . O t h e r findings o n C T i n c l u d e d s e g m e n t a l i n t r a h e p a t i c bile duct dilatation (N = 16 p a t i e n t s ) , s p l e n o m e g a l y (N = 10), v a r i c e s (N = 8), e v i d e n c e of cirrhosis (N = 6), h e p a t o m e g a l y (N = 5), ascites (N = 4), a n d i n t r a h e p a t i c calculi (N -- 1). T h e i m p r e s s i o n o f a d e n o p a t h y o n C T scan could be c o r r e l a t e d with p a t h o l o g y findings in s e v e n patients. F o u r p a t i e n t s had l y m p h n o d e s r e m o v e d with the h e p a t e c t o m y s p e c i m e n d u r i n g liver t r a n s p l a n t a tion a n d five had a b d o m i n a l l y m p h n o d e s e x c i s e d d u r i n g a v a r i e t y o f surgeries (two of the s e v e n had both at separate times). T h e l y m p h n o d e s in all patients s h o w e d r e a c t i v e h y p e r p l a s i a e x c e p t one, which had s i n u s h i s t i o c y t o s i s .
E. Outwater et al.: Adenopathy in Sclerosing Cholangitis
One patient's CT initially showed gastrohepatic ligament adenopathy and subsequently developed typical CT findings of retroperitoneal fibrosis l year later. Two exploratory laparotomies were performed in this patient because of the suspicion of cholangiocarcinoma. The second revealed fibrosis extending from the porta hepatis along the anterior retroperitoneum into the pelvis. Liver, retroperitoneal, and lymph node biopsies revealed sclerosing cholangitis, fibrosis, and reactive hyperplasia, respectively. A question of malignancy in or near the porta hepatis causing lymphadenopathy was raised in the original CT readings or by CT reports from referring hospitals in six cases. Two patients underwent exploratory laparotomy for suspicion of tumor obstructing the bile duct.
Discussion
Lymphadenopathy has not been noted in studies describing the CT manifestations of sclerosing cholangitis, possibly because they have concentrated on findings related to the biliary tree [1, l 1, 12]. Benign enlarged lymph nodes are noted, however, as a frequent surgical finding. Thompson et al. [13], often found enlarged gastrohepatic ligament nodes in their surgically explored primary sclerosing cholangitis patients. Warren et ai. [5], discovered benign lymphadenopathy at surgery in eight of 12 patients with sclerosing cholangitis associated with ulcerative colitis, six of 11 patients with sclerosing cholangitis only, and two of 19 patients with sclerosing cholangitis secondary to choledocholithiasis, surgery, or other local inflammatory conditions. In addition, iymphadenopathy has been mentioned as an incidental surgical finding in case reports of patients with sclerosing cholangitis [14-16]. In all of these studies, pathologic examination of the nodes revealed reactive hyperplasia or sinus histiocytosis. A single case of periportal, peripancreatic, and periaortic reactive lymphadenopathy discovered on CT scan in association with sclerosing cholangitis has been described [16]. Thus, although such extensive adenopathy as occurred in this latter case is uncommon, the surgical literature yields ample evidence that enlarged lymph nodes are indeed common in sclerosing cholangitis, despite the lack of its description in radiologic studies. Sclerosing cholangitis has been associated with diseases which cause lymphadenopathy, including histiocytosis X [13, 17], angioimmunoblastic lymphadenopathy [18], and acquired immune deficiency syndrome [19]. None of our patients had evidence of these diseases. Sclerosing cholangitis can also occur
159
with other benign masses, such as inflammatory fibrosing pancreatic "pseudotumors" [14, 20], and retroperitoneal fibrosis [15]. Whether these cause a secondary sclerosing cholangitis or represent an epiphenomenon of primary sclerosing cholangitis is unclear. Enlarged lymph nodes lying in or near the porta hepatis are often cited as a feature distinguishing malignant from benign biliary obstruction [4]. Of course, neoplasms of diverse origin may have periportal lymphatic metastases as the sole or as a secondary finding on CT scan, and duct obstruction can ensue from such metastases or from an inapparent biliary, pancreatic, or gastrointestinal tract tumor. In contrast, benign lymphadenopathy causing biliary obstruction is rare, and common benign causes of biliary obstruction, such as choledocholithiasis, chronic pancreatitis, and iatrogenic stricture, are not reported to be ssociated with adenopathy. Our results show that upper abdominal lymphadenopathy is a common CT finding in sclerosing cholangitis. Therefore, the possibility of benign reactive lymph nodes should be taken into account when attempting to distinguish benign from malignant biliary obstruction and when evaluating patients with sclerosing cholangitis for possible cholangiocarcinoma. Reiman et al. [4] found benign causes of suprapancreatic biliary obstruction in 17 of 44 cases; four of 29 patients with a portal mass or periportal lymphadenopathy had benign causes of biliary obstruction. As examples, enlarged lymph nodes may occur in cholangitis associated with the acquired immunodeficiency syndrome [19], and in tuberculous periportal adenitis, which can cause biliary obstruction [21]. Several authors have outlined strict criteria for the diagnosis of primary sclerosing cholangitis [5, 6, 17, 22]. The typical liver and bile duct histology in conjunction with the expected cholangiographic appearance should be present. In addition, these criteria require the exclusion of (a) previous biliary tree surgery which may have caused stricture, (b) choledocholithiasis, (c) primary biliary cirrhosis, (d) congenital biliary abnormality (e.g., Caroli's disease), and (e) cholangiocarcinoma. Cholangiocarcinoma, in particular, may be difficult to exclude in many patients, short of laparotomy. This is because the progression of bile duct inflammation may simulate tumor by cholangiography, and because the incidence of cholangiocarcinoma is increased in patients with sclerosing cholangitis [3]. The CT and cholangiographic findings in sclerosing cholangitis will not, in most cases, simulate malignant biliary obstruction. Instead of the usual single focal obstruction due to malignancy, CT can usually identify the typical widespread focal intrahe-
160
patic segmental biliary dilatations of sclerosing cholangitis [1, 11, 12]. Cholangiocarcinoma, however, particularly when it occurs in association with sclerosing cholangitis, can be difficult to detect on CT [1, 2]. Infiltrating tumor may have no primary mass which can be distinguished from the thickened bile ducts. Enlarged lymph nodes seen on CT have been asserted to be a distinguishing sign of malignancy [1, 2, 4] since lymphatic metastases frequently occur from cholangiocarcinoma and may be the only CT evidence of the tumor [7]. Engels et al. [7] found periportal nodal metastases in 34 of 56 patients with biliary carcinoma. CT predicted nodal metastases with only one false-positive and one false-negative case, based on a 1.5-cm size criteria. Our results suggest that mildly enlarged lymph nodes are a nonspecific finding in sclerosing cholangitis and not necessarily indicative of malignancy.
References 1. Teefey SA, Baron RL, Rohrman CA, Shuman WP, Freeny PC. Sclerosing cholangitis: CT findings. Radiology 1988; 169:635-639 2. Nesbit GM, Johnson CD, James EM, MacCarty RL, Nagorney DM, Bender CE. Cholangiocarcinoma: diagnosis and evaluation of resectability by CT and sonography as procedures complementary to cholangiography. A JR 1988:151:933938 3. MacCarty RL, LaRussao NF, May GR, Bender CE, Wiesner RH, King JE, Coffey RJ. Cholangiocarcinoma complicating primary sclerosing cholangitis: cholangiographic appearances. Radiology 1985;156:43--46 4. Reiman TH, Balfe DM, Weyman PJ. Suprapancreatic biliary obstruction: CT evaluation. Radiology 1987;163:49-56 5. Warren KW, Athanassiades S, Monge JI. Primary sclerosing cholangitis: a study of forty-two cases. Am J Sarg 1966; 111:23-38 6. Longmire WP. When is cholangitis sclerosing? Am J Surg 1978;135:312-320 7. Engels JR, Balfe DM. Lee JKT. Biliary carcinoma: CT evaluation of extrahepatic spread. Radiology 1989:172:35-40
E. Outwater et al.: Adenopathy in Sclerosing Cholangitis 8. Balfe DM, Mauro MA, Koehler RE, et al. Gastrohepatic ligament: normal and pathologic CT anatomy. Radiology 1984:150:485-490 9. Zirinsky K, Auh YH, Rubenstein WA, Kneeland JBK, Whalen JP, Kazam E. The portacaval space: CT with MR correlation. Radiology 1985;156:453-460 10. Zeman RK, Schiebler M, Clark LR, et al, The clinical and imaging spectrum of pancreaticoduodenal lymph node enlargement. A JR 1985;144:1223-1227 11. Rahn NH, Koehler RE, Weyman PJ, Truss CD, Sagel SS, Stanely RJ. CT appearance of sclerosing cholangitis. A JR 1983:141:549-552 12. Ament AE, Haaga JR, Wiedenmann SD, Barkmeier JD, Morrison SC. Primary sclerosing cholangitis: CT findings. J" Comput Assist Tomo[4r 1983;7:795-800 13. Thompson HH, Pitt HA, Lewin K J, Longmire WP. Sclerosing cholangitis and histiocytosis X. Gut 1984:25:526-530 14. Jafri SZH, Bree RL, Agha EP, Schwab RE. Inflammatory pseudotumor from sclerosing cholangitis. J Comput Assist Tomogr 1983;7:902-904 15. Bartholonew LG, Cain JC, Woolner LB, Utz DC, Ferris DO. Sclerosing cholangitis: its possible association with Riedel's struma and fibrous retroperitonitis--report of two cases. N Engl J Med 1963;269:8-12 16. Alberti-Flor J J, Kalemeris G, Dunn GD, Avant GR. Primary sclerosing cholangitis associated with massive intra-abdominal lymphadenopathy. Am J Gastroenterol 1986;81:55-60 17. Thompson HH, Pitt HA, Tompkins RK, Longmire WP. Primary sclerosing cholangitis: a heterogenous disease. Ann Surg 1982;196:127-136 18. Bass NM, Chapman RW, O'Rielly A, Sherlock S. Sclerosing cholangitis associated with angioimmunoblastic lymphadenopathy. Gastroenterology 1983;85:420-424 19. Dolmatch BL, Laing FC, Federle MP, Jeffrey RB, Cello J. AIDS-related cholangitis: radiographic findings in nine patients. Radiology 1987; 163:313-316 20. Clark A, Zeman RK, Choyke PL, White EM, Burrell MI, Grant EF, Jaffe MH. Pancreatic pseudotumors associated with multifocal idiopathic fibrosclerosis. Gastrointest Radiol 1988:13:30-32 21. Matieu D, Ladeb MF, Guigui B, Rousseau M. Vasile N. Periportal tuberculous adenitis: CT features. Radiology 1986;161:713-715 22. Whelton MJ. Sclerosing cholangitis. Clin Gastroenterol 1973; 2:163-173 Received: August 5, 1991; accepted." September 19. 1991
Gastrointestinal
Radiology 9 Springer-VerlagNew York Inc. 1992
Lymphadenopathy in Sclerosing Cholangitis: Pitfall in the Diagnosis of Malignant Biliary Obstruction Eric Outwater, Marshall M. Kaplan, and Mark S. Bankoff Departments of Radiology and Gastroenterology, New England Medical Center, Boston, Massachusetts, USA
Abstract: We retrospectively reviewed abdominal computed tomographic (CT) studies from 20 patients with sclerosing cholangitis and found evidence of abdominal lymphadenopathy in 13 patients. Enlargement occurred primarily in areas draining the liver, such as the gastrohepatic ligament or celiac axis (N = 8), the porta hepatis (N = 7), and the pancreaticoduodenal region (N = 2). One patient had reactive adenopathy and retroperitoneal fibrosis. The presence of benign reactive lymphadenopathy in at least one intraabdominal location was confirmed by pathological examination of excised lymph nodes in seven patients. Malignancy was excluded by surgical exploration or clinical follow-up. We conclude that enlarged lymph nodes are a common finding by CT in patients with sclerosing cholangitis. Enlarged reactive lymph nodes in this condition should not be mistaken for evidence of periportal metastasis or cholangiocarcinoma. Key words: Sclerosing cholangitis, lymphadenopathy--Computed tomography.
Sclerosing cholangitis can clinically and radiologically mimic malignancy, particularly cholangiocarcinoma [1-6]. Even when the diagnosis of sclerosing cholangitis is established, the radiologic evaluation can be problematic. Computed tomographic (CT) scanning easily detects soft tissue masses near the biliary tree and has been used to detect cholangiocarcinoma in patients with sclerosing cholangitis, with mixed success [1, 2]. Recently, the importance of lymphadenopathy on CT scans in diagnosing and Address offprint requests to: Eric Outwater, M.D., Devon MRI Center, Department of Radiology, Hospital of the University of Pennsylvania, 3400 Spruce Street, Philadelphia, PA 19104, USA
staging cholangiocarcinoma has been stressed, as this finding may be the only CT evidence of the carcinoma [7]. However, we have encountered patients with sclerosing cholangitis who were surgically explored because of the suspicion of malignancy on a CT examination. The surgical discovery of benign reactive lymphadenopathy as a cause of the false-positive CT scans led us to review CT scans in other patients with sclerosing cholangitis to assess the frequency of lymphadenopathy in these patients.
Patients and Methods A search of medical records disclosed 21 patients with sclerosing cholangitis who underwent abdominal CT scanning. CT scans from 20 patients were judged technically adequate in distinguishing varices from lymph nodes; by this criterion, one patient was therefore excluded from this study. The mean age of the patients was 41 years (range 10-75 years). The average duration of the disease prior to the scans was 6.2 years (range 0-18 years). Thirteen patients were male, seven were female. All patients had endoscopic retrograde cholangiopancreatography and liver biopsies consistent with sclerosing cholangitis. Liver transplantation was performed in nine patients a mean of 2.4 months after CT scanning; the hepatectomy specimens disclosed sclerosing cholangitis in each case. Malignancy was excluded by surgical exploration in 12 patients. Of the remaining seven patients, four have been followed for more than 2 years since the CT scan, and two patients for more than 18 months, and lack clinical or radiographic evidence of malignancy. The final patient developed cytologic atypia of the biliary epithelium on liver biopsies, which was not diagnostic for carcinoma in situ. She did not, however, have CT evidence for adenopathy or periportal mass. The medical and surgical histories in two patients suggested that the sclerosing cholangitis was secondary to choledocholithiasis. Thirteen patients had inflammatory bowel disease. Retroperitoneal fibrosis was proven by biopsy in one patient and one patient had thyroid fibrosis; the other three ~patients had no associated disease. Many patients were receiving methrotrexate in a blinded treatment protocol.
158
E. Outwater et al.: Adenopathy in Sclerosing Cholangitis
Fig. 1. Contrast-enhanced CT scan through the porta hepatis below the celiac axis. Enlarged low attenuation lymph nodes lie in the gastrohepatic ligament and portacaval space (black arrows) in this patient with ascites, cirrhosis, splenomegaly, and falciform ligament collaterals (white arrow). Lymphadenopathy was proven at the time of liver transplantation. Dilated bile ducts can be seen in the right hepatic lobe. Fig. 2. Contrast-enhanced CT scan at the level of the celiac artery. Adenopathy is present in the porta hepatis. Lymphadenopathy was confirmed during liver transplantation. Splenomegaly is seen. Fig. 3. CT scan demonstrates enlarged lymph nodes just anterior to a replaced right hepatic artery.
CT was performed on a whole body scanner (Somatom 2 or DR3: Siemens Medical Systems. lselim NJ, USA) during intravenous bolus and rapid drip administration of contrast material. Contiguous 8-mm thick sections were obtained through the abdomen in all patients. CT scans were retrospectively analyzed. Evidence of lymphadenopathy on CT scans was defined as lymph nodes at least I cm in diameter in the gastrohepatic ligament 18]: lymph nodes at least 1.3 mm in the anteroposterior diameter, regardless of transverse diameter, in the portacaval space (node of the foramen of Winslow): and lymph nodes of at least 15 ram, or groups of four or more lymph nodes, in other locations. Peripancreatic lymphadenopathy was considered to be present only if nodes were clearly separable from the pancreas by fat planes or attenuation difference [101. Cirrhosis (inferred from small liver, relative enlargement of the caudate and left hepatic lobe, nodular contour, and fissural enlargement), hepatosplenomegaly, varices, and ascites were noted when present. The pathology files of the 19 patients were reviewed for surgical specimens of enlarged lymph nodes. Seven patients had intraabdominal lymph nodes removed during liver transplantation or other surgeries. The presence of adenopathy in the other seven patients with CT evidence of lymphadenopathy, therefore, could not be proven.
Results C T e v i d e n c e o f a b d o m i n a l l y m p h a d e n o p a t h y app e a r e d in 13 of 20 p a t i e n t s (65%). Eight p a t i e n t s had
l y m p h a d e n o p a t h y in the g a s t r o h e p a t i c ligament or a r o u n d the celiac axis (Fig. 1), s e v e n in the p o r t a hepatis or p o r t a c a v a l space (Figs. 2 a n d 3), five in the p a r a c a v a l or periaortic c h a i n s , two in the panc r e a t i c o d u o d e n a l n o d e s , a n d two in the m e s e n t e r i c l y m p h n o d e s . H e n c e , l y m p h a d e n o p a t h y t e n d e d to be most p r e v a l e n t in those g r o u p s d r a i n i n g into the liver a n d p o r t a hepatis. L y m p h n o d e s were h o m o g e n e o u s , of l o w e r a t t e n u a t i o n t h a n e n h a n c e d liver, a n d h y p o d e n s e or i s o d e n s e to the p a n c r e a s . N o l y m p h n o d e s d e m o n s t r a t e d low a t t e n u a t i o n c e n t e r s . O t h e r findings o n C T i n c l u d e d s e g m e n t a l i n t r a h e p a t i c bile duct dilatation (N = 16 p a t i e n t s ) , s p l e n o m e g a l y (N = 10), v a r i c e s (N = 8), e v i d e n c e of cirrhosis (N = 6), h e p a t o m e g a l y (N = 5), ascites (N = 4), a n d i n t r a h e p a t i c calculi (N -- 1). T h e i m p r e s s i o n o f a d e n o p a t h y o n C T scan could be c o r r e l a t e d with p a t h o l o g y findings in s e v e n patients. F o u r p a t i e n t s had l y m p h n o d e s r e m o v e d with the h e p a t e c t o m y s p e c i m e n d u r i n g liver t r a n s p l a n t a tion a n d five had a b d o m i n a l l y m p h n o d e s e x c i s e d d u r i n g a v a r i e t y o f surgeries (two of the s e v e n had both at separate times). T h e l y m p h n o d e s in all patients s h o w e d r e a c t i v e h y p e r p l a s i a e x c e p t one, which had s i n u s h i s t i o c y t o s i s .
E. Outwater et al.: Adenopathy in Sclerosing Cholangitis
One patient's CT initially showed gastrohepatic ligament adenopathy and subsequently developed typical CT findings of retroperitoneal fibrosis l year later. Two exploratory laparotomies were performed in this patient because of the suspicion of cholangiocarcinoma. The second revealed fibrosis extending from the porta hepatis along the anterior retroperitoneum into the pelvis. Liver, retroperitoneal, and lymph node biopsies revealed sclerosing cholangitis, fibrosis, and reactive hyperplasia, respectively. A question of malignancy in or near the porta hepatis causing lymphadenopathy was raised in the original CT readings or by CT reports from referring hospitals in six cases. Two patients underwent exploratory laparotomy for suspicion of tumor obstructing the bile duct.
Discussion
Lymphadenopathy has not been noted in studies describing the CT manifestations of sclerosing cholangitis, possibly because they have concentrated on findings related to the biliary tree [1, l 1, 12]. Benign enlarged lymph nodes are noted, however, as a frequent surgical finding. Thompson et al. [13], often found enlarged gastrohepatic ligament nodes in their surgically explored primary sclerosing cholangitis patients. Warren et ai. [5], discovered benign lymphadenopathy at surgery in eight of 12 patients with sclerosing cholangitis associated with ulcerative colitis, six of 11 patients with sclerosing cholangitis only, and two of 19 patients with sclerosing cholangitis secondary to choledocholithiasis, surgery, or other local inflammatory conditions. In addition, iymphadenopathy has been mentioned as an incidental surgical finding in case reports of patients with sclerosing cholangitis [14-16]. In all of these studies, pathologic examination of the nodes revealed reactive hyperplasia or sinus histiocytosis. A single case of periportal, peripancreatic, and periaortic reactive lymphadenopathy discovered on CT scan in association with sclerosing cholangitis has been described [16]. Thus, although such extensive adenopathy as occurred in this latter case is uncommon, the surgical literature yields ample evidence that enlarged lymph nodes are indeed common in sclerosing cholangitis, despite the lack of its description in radiologic studies. Sclerosing cholangitis has been associated with diseases which cause lymphadenopathy, including histiocytosis X [13, 17], angioimmunoblastic lymphadenopathy [18], and acquired immune deficiency syndrome [19]. None of our patients had evidence of these diseases. Sclerosing cholangitis can also occur
159
with other benign masses, such as inflammatory fibrosing pancreatic "pseudotumors" [14, 20], and retroperitoneal fibrosis [15]. Whether these cause a secondary sclerosing cholangitis or represent an epiphenomenon of primary sclerosing cholangitis is unclear. Enlarged lymph nodes lying in or near the porta hepatis are often cited as a feature distinguishing malignant from benign biliary obstruction [4]. Of course, neoplasms of diverse origin may have periportal lymphatic metastases as the sole or as a secondary finding on CT scan, and duct obstruction can ensue from such metastases or from an inapparent biliary, pancreatic, or gastrointestinal tract tumor. In contrast, benign lymphadenopathy causing biliary obstruction is rare, and common benign causes of biliary obstruction, such as choledocholithiasis, chronic pancreatitis, and iatrogenic stricture, are not reported to be ssociated with adenopathy. Our results show that upper abdominal lymphadenopathy is a common CT finding in sclerosing cholangitis. Therefore, the possibility of benign reactive lymph nodes should be taken into account when attempting to distinguish benign from malignant biliary obstruction and when evaluating patients with sclerosing cholangitis for possible cholangiocarcinoma. Reiman et al. [4] found benign causes of suprapancreatic biliary obstruction in 17 of 44 cases; four of 29 patients with a portal mass or periportal lymphadenopathy had benign causes of biliary obstruction. As examples, enlarged lymph nodes may occur in cholangitis associated with the acquired immunodeficiency syndrome [19], and in tuberculous periportal adenitis, which can cause biliary obstruction [21]. Several authors have outlined strict criteria for the diagnosis of primary sclerosing cholangitis [5, 6, 17, 22]. The typical liver and bile duct histology in conjunction with the expected cholangiographic appearance should be present. In addition, these criteria require the exclusion of (a) previous biliary tree surgery which may have caused stricture, (b) choledocholithiasis, (c) primary biliary cirrhosis, (d) congenital biliary abnormality (e.g., Caroli's disease), and (e) cholangiocarcinoma. Cholangiocarcinoma, in particular, may be difficult to exclude in many patients, short of laparotomy. This is because the progression of bile duct inflammation may simulate tumor by cholangiography, and because the incidence of cholangiocarcinoma is increased in patients with sclerosing cholangitis [3]. The CT and cholangiographic findings in sclerosing cholangitis will not, in most cases, simulate malignant biliary obstruction. Instead of the usual single focal obstruction due to malignancy, CT can usually identify the typical widespread focal intrahe-
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patic segmental biliary dilatations of sclerosing cholangitis [1, 11, 12]. Cholangiocarcinoma, however, particularly when it occurs in association with sclerosing cholangitis, can be difficult to detect on CT [1, 2]. Infiltrating tumor may have no primary mass which can be distinguished from the thickened bile ducts. Enlarged lymph nodes seen on CT have been asserted to be a distinguishing sign of malignancy [1, 2, 4] since lymphatic metastases frequently occur from cholangiocarcinoma and may be the only CT evidence of the tumor [7]. Engels et al. [7] found periportal nodal metastases in 34 of 56 patients with biliary carcinoma. CT predicted nodal metastases with only one false-positive and one false-negative case, based on a 1.5-cm size criteria. Our results suggest that mildly enlarged lymph nodes are a nonspecific finding in sclerosing cholangitis and not necessarily indicative of malignancy.
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