Clin J Gastroenterol (2012) 5:113–118 DOI 10.1007/s12328-011-0281-2
CASE REPORT
Mesenteric panniculitis presenting as liver dysfunction Kazuhiko Morii • Tomoko Hatono • Hiroaki Okushin • Takanori Watanabe • Shiso Sato • Koichi Uesaka • Shiro Yuasa
Received: 14 September 2011 / Accepted: 25 November 2011 / Published online: 20 December 2011 Ó Springer 2011
Abstract Mesenteric panniculitis is a non-specific inflammatory disorder affecting adipose tissues of the mesentery. Mesenteric adipose tissues contain macrophages and other inflammatory cells, which may secrete tumor necrosis factor a, interleukin (IL)-1, and IL-6. These cytokines collect into the portal vein and thereby flow into the liver, possibly influencing hepatic function. Mesenteric panniculitis often occurs with inflammatory reactions such as fever and elevated erythrocyte sedimentation rates. Systemic inflammatory disorders can evoke acute cholestatic liver involvement, which is mediated by proinflammatory cytokines. However, no reports have focused on the association between mesenteric panniculitis and liver involvement. We report a rare case of mesenteric panniculitis presenting as liver dysfunction. Immunohistochemical staining of the liver demonstrated a marked decrease in expression of canalicular transport systems. These findings indicated cholestatic liver dysfunction associated with mesenteric panniculitis. Keywords Mesenteric panniculitis Liver dysfunction Cholestasis Hepatobiliary transporter Introduction Mesenteric panniculitis is a non-specific inflammatory disorder affecting adipose tissues of the mesentery [1, 2]. It has
been classified into 3 conditions according to predominant histological findings [3]. Mesenteric lipodystrophy is an early stage with predominance of fatty degeneration and necrosis. Mesenteric panniculitis (in the narrow sense) is an intermediate stage with chronic inflammation. Retractile mesenteritis is an advanced stage with predominance of fibrosis [4, 5]. Etiologies of mesenteric panniculitis remain unknown. It may occur independently or in association with other diseases including malignancies [6, 7], rheumatic disorders [8], and granulomatous diseases [9, 10]. Mesenteric adipose tissues contain macrophages which have infiltrated into adipose tissues or transdifferentiated from local preadipocytes [11, 12]. Proinflammatory cytokines such as tumor necrosis factor a (TNFa), interleukin (IL)-1, and IL-6, are secreted from mesenteric adipose tissues, and collect into the portal vein. Concentrated proinflammatory cytokines thereby flow into the liver, where they may influence hepatic pathophysiology. It is well known that systemic inflammatory disorders can evoke acute cholestatic liver involvement as a consequence of the host’s immune response [13, 14]. Mesenteric panniculitis often causes inflammatory reactions [8, 15]. However, there are no reports about a relationship between mesenteric panniculitis and liver involvement. Recently, we experienced a rare case of mesenteric panniculitis with liver dysfunction. We investigated the pathogenesis of liver dysfunction, focusing on hepatobiliary transport systems.
Electronic supplementary material The online version of this article (doi:10.1007/s12328-011-0281-2) contains supplementary material, which is available to authorized users.
Case report K. Morii (&) T. Hatono H. Okushin T. Watanabe S. Sato K. Uesaka S. Yuasa Department of Hepatology, Japanese Red Cross Society Himeji Hospital, 1-12-1 Shimoteno, Himeji, Hyogo 670-8540, Japan e-mail: [email protected]
A 63-year-old man was admitted to our hospital because of liver dysfunction and a high fever. He was in his usual health until 1 week earlier, when the high fever developed. He also
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had diminished appetite and epigastric discomfort without abdominal pain. His family physician diagnosed a common cold and prescribed non-steroidal anti-inflammatory drugs. During the next 5 days, he had remained febrile despite taking the medication. Two days before evaluation at our hospital, laboratory data showed liver dysfunction and significant inflammatory reactions. Serum total bilirubin was 2.4 mg/dl, direct bilirubin 1.4 mg/dl, aspartate aminotransferase 393 IU/l, alanine aminotransferase (ALT) 338 IU/l, alkaline phosphatase (ALP) 1,047 IU/l (reference range 115–359), gamma-glutamyltranspeptidase (cGT) 370 IU/l, and lactate dehydrogenase 363 IU/l (reference range 119–229). The erythrocyte sedimentation rate was 50 mm/h, C-reactive protein was 18.9 mg/dl (reference range 0–0.3), and the white blood cell count was 10,400/ll with a leftward shift. He was referred to our hospital for further evaluation. His past medical history was unremarkable except for a benign gastric polyp. He drank a glass of beer every weekend and did not smoke or use illicit drugs. He took neither prescriptions nor herbal remedies on a regular basis. On physical examination, no skin rash or superficial lymphadenopathy was present. The abdomen was soft without hepatosplenomegaly. Serological examination revealed significant elevation of inflammatory reactions. Serum ferritin was 2,241 ng/ml (reference range 13–301) and soluble interleukin-2 receptor (sIL-2R) was 3,710 U/ml (reference range 145–519). Blood coagulation tests showed moderate abnormalities with prothrombin time 64%, activated partial thromboplastin time 50.1 s (reference range 23–40), and fibrinogen 795 mg/dl (reference range 170–400). Extensive testing for viral hepatitis was negative. A serum interferongamma release assay was negative for Mycobacterium tuberculosis. Serum endotoxin was within reference range. Autoantibodies were also negative including antinuclear antibody, antimitochondrial antibody, and antismoothmuscle antibody. Immunoglobulin (Ig)G was 1,111 mg/dl, IgA 280 mg/dl, and IgM 104 mg/dl. Tumor markers of a-fetoprotein, carcinoembryonic antigen, and carbohydrate antigen19-9 were all within reference ranges. Abdominal computed tomography (CT) revealed a highly attenuated heterogeneous mass in the gastrocolic ligament (Fig. 1). There were discrete low density nodules in the mass, delineated by hyperdense stripes without vascular involvement. Multiple knotty thickenings within the mesenterium in this case were characteristic findings of the subtype of mesenteric lipodystrophy [3, 12]. There was no hepatobiliary obstruction. No hepatosplenomegaly, lymphadenopathy, or ascitic fluid was detected. Fiberoptic endoscopy of the upper and lower intestines showed no evidence of malignant disorders or inflammatory bowel disease. Further radiological examination revealed no pulmonary or urological abnormalities. No abnormal high uptakes were
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Fig. 1 CT scan of the abdomen obtained with contrast material administration shows the highly attenuated heterogeneous mass in the gastrocolic ligament (arrows). There are discrete low density nodules (small arrows) in the mass, delineated by hyperdense stripes without vascular involvement
observed in whole body inspection with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)–CT scan. Bone marrow aspiration from the posterior iliac crest revealed normocellular marrow without evidence of hematologic malignancies. Malignant lymphoma must be ruled out due to high serum sIL-2R, even though no abnormal high uptakes of FDG were observed in PET–CT [6]; it is warranted to histologically exclude malignant involvement of the mesentery [16]. Upon receiving informed consent, we conducted exploratory laparoscopy followed by partial resection of the mesenteric nodules. During laparoscopic examination, nodules were found to be firmly attached to the cologastric mesentery. The liver appeared smooth with normal consistency. Liver biopsy was also performed with an 18-gauge Tru-cut biopsy needle. Histological examination of the mesenteric nodules showed infiltration of mixed inflammatory cells and macrophages, as well as extensive fat necrosis (Fig. 2a). ‘Foamy cells’ of lipid-laden macrophages were also present (Fig. 2b). The mesenteric artery was occluded by thrombus (Fig. 1 in online appendices). No fibrosis or mitotic figures were seen. These findings confirmed the diagnosis of mesenteric panniculitis, especially mesenteric lipodystrophy. Hepatic histology showed only mild portal inflammation without interface hepatitis. No necrosis or drop-out of hepatocytes, and no hypertrophy of Kupffer cells was observed. There was no architectural derangement or fibrosis (Fig. 3a). A periodic acid–Schiff (PAS) stain with diastase digestion showed only scant PASpositive macrophages. Under high magnification, brownish granular deposits were apparent in hepatocytes mainly around bile canalicular sites (Fig. 3b).
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Fig. 2 a Histological examination of the resected mesenteric nodules shows infiltration of mixed inflammatory cells and extensive fat necrosis. Scale bar 500 lm; H&E stain. b Foamy cells of lipid-laden macrophages are present. Scale bar 100 lm. H&E stain
Fig. 3 a Histological examination of the liver shows mild portal inflammation without an interface hepatitis (arrow). There is neither necrosis nor drop-out of hepatocytes. There is no architectural derangement or fibrosis. Scale bar 200 lm; H&E stain. b There are
only scant PAS-positive macrophages. Under high magnification (inset), scattered brownish granular deposits are apparent in hepatocytes. The deposits are mainly around bile canalicular sites (arrows). Scale bar 100 lm (50 lm in inset); PAS stain with diastase digestion
We administered corticosteroids (oral prednisolone at a daily dose of 20 mg) which promptly alleviated the fever. Both liver function and the inflammatory reactions improved with subsequent normalization. The patient was discharged on the 16th day with a prescription for corticosteroids, which were tapered and finally discontinued. At 6 months after the initial presentation, a follow-up CT showed complete resolution of the mesenteric mass. To date, the patient remains afebrile and symptom-free.
[1, 9]. The prevalence of this disease was estimated to be 1.26% during a lifetime in autopsy cases [3]. Daskalogiannaki et al. described a mesenteric panniculitis prevalence of 0.6% (49 of 7,620 consecutive patients who underwent abdominal CT). Among the 49 patients, 34 (69.4%) had coexistent malignant diseases, 11 (22.4%) benign diseases, and the remaining 4 (8.2%) no abnormalities other than mesenteric panniculitis. Non-Hodgkin’s lymphoma, breast, lung, and colorectal cancers were the main coexistent neoplastic disorders. Abdominal aortic aneurysms and pulmonary sarcoidosis were predominant in benign diseases [2, 9]. Some patients with mesenteric panniculitis reportedly develop malignant lymphoma during follow-up [3]. Zissen et al. reported a negative PET with typical CT features of mesenteric panniculitis to have high diagnostic accuracy
Discussion Mesenteric panniculitis is a non-specific inflammatory disorder with a propensity for jejunal mesentery involvement
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Fig. 4 a Immunohistochemical staining for the bile salt export pump (BSEP), major transport system for bile salts. BSEP-positive canaliculi are overall reduced in the patient’s liver (P left side). Normal canalicular staining pattern of BSEP is observed in control liver (C right side). Control liver sample was obtained from unaffected area from surgical liver resection of hepatic metastases, which displayed no histological evidence of underlying liver diseases. Scale bar 50 lm. b Immunohistochemical staining for the multidrug export pump isoform (MDR3), a phospholipid translocase. MDR3-positive canaliculi are reduced in the patient’s liver (P left side), as compared
with the control liver (C right side). Scale bar 50 lm. c Immunohistochemical staining for the familial intrahepatic cholestasis-1 protein (FIC1), a P-type adenosine triphosphatase. FIC1-positive canaliculi are reduced in the patient’s liver (P left side), as compared with the control liver (C right side). Scale bar 50 lm. d Immunohistochemical staining for the multidrug resistance-related protein isoform (MRP2). MRP2-positive canaliculi are preserved or even enhanced in the patient’s liver (P left side), as compared with the control liver (C right side). Scale bar 50 lm
for excluding tumoral mesenteric involvement [17, 18]. On the other hand, Ehrenpreis et al. [6] recommended biopsy of mesenteric masses, becauase PET–CT alone might miss the presence of mesenteric lymphoma. Etiologies of mesenteric panniculitis remain unknown, but several hypotheses have been presented. Soumerai et al. [19] indicated that mesenteric thrombosis might influence the mesenteric blood supply and the occurrence of mesenteric panniculitis. We observed thrombotic arterial occlusion in the resected specimen (Fig. 1 in online appendices). The thrombus was composed of new and old
structures, suggesting the thrombus to not merely be a result of mesenteric panniculitis, but to possibly cause or promote the development of the disease. Characteristic CT findings of mesenteric panniculitis are reportedly a solitary well-defined mass composed of inhomogeneous fatty tissue with attenuation values higher than those of the retroperitoneal fat at the root of the small bowel mesentery, engulfment of superior mesenteric vessels without vascular involvement, and no evidence of invasion of the adjacent small-bowel loops even if they are displaced [9]. These features are useful for distinguishing
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mesenteric panniculitis from more common malignant conditions of the mesentery, including lymphoma, carcinomatous dissemination, and liposarcoma [20]. In systemic inflammation-associated liver dysfunction, cholestasis is typical [13, 14]. Recently, our understanding has progressed substantially about the mechanisms of inflammation or sepsis-induced cholestasis [21, 22]. Whiting et al. [23] postulated that an important mediator of the cholestasis in sepsis is TNFa, which impacts hepatic organic anion transport. TNFa and IL-1b modulate gene expressions of transporters at the canalicular membrane at both transcriptional and post-transcriptional levels, thereby impairing hepatocyte transport function [14, 21, 24]. Zollner et al. [25] demonstrated coordinated reductions of basolateral and canalicular transport systems in acquired cholestatic liver diseases by determining hepatic mRNA levels using human liver biopsy tissues. Therefore, the liver dysfunction associated with systemic inflammation is functional [26]. Our patient had a distinct clinical course with liver dysfunction and substantial acute inflammatory reactions. The liver dysfunction was consistent with acute cholestasis as defined by serum ALP level higher than 2.5 times the upper limit of normal (ULN), cGT level higher than 3 times the ULN, ALT/ALP ratio fewer than 2 times the ULN, and conjugated hyperbilirubinemia [27]. However, histological examination of the liver revealed no typical features observed in cholestatic liver diseases (e.g., bilirubin stasis in bile canaliculi, hepatocytes, Kupffer cells, and feathery degeneration of hepatocytes). We investigated canalicular hepatobiliary transporter expression and distribution by immunohistochemical staining. Staining for bile salt export pump (BSEP), multidrug export pump (MDR3), and familial intrahepatic cholestasis-1 protein (FIC1) were all reduced in the patient’s liver, as compared with the control (Fig. 4a–c). Interestingly, staining for multidrug resistance-related protein (MRP2) appeared to be relatively preserved or even enhanced in some canaliculi (Fig. 4d). MRP2 might serve as a compensatory protective overflow system against potentially toxic biliary constituents under cholestatic conditions [25, 28]. These findings strongly suggest that coordinated alterations in canalicular transport systems may be relevant for liver dysfunction in this patient. Diastase-resistant PASpositive granular deposits were observed in hepatocytes (Fig. 3b). Except for cases with a1-antitrypsin deficiency [29], almost no specific reports have been published about liver dysfunction and diastase-resistant PAS-positive deposits within the hepatocytes. It is intriguing to speculate that the distribution of the deposits along the canalicular sites may suggest decreased excretion into bile canaliculi. Inflammation-induced cholestasis is functional and reversible with control of inflammation [21]. Active febrile mesenteric panniculitis with histological predominance of
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inflammation and minimal fibrosis is likely to respond favorably to steroid treatment [30]. Moreover, mesenteric lipodystrophy can regress spontaneously [3]. These tendencies are consistent with the good therapeutic response of our patient. Liver dysfunction associated with mesenteric lipodystrophy might occur more frequently than previously thought. Since symptoms of mesenteric lipodystrophy are relatively subtle or even absent [3], they may not be recognized by patients or clinicians. Patients with refractory mesenteritis can, however, have obvious abdominal symptoms despite low inflammatory activity; this context may reflect the rarity of liver dysfunction associated with mesenteric panniculitis. In conclusion, we have described a case of mesenteric panniculitis with liver involvement. Histological examination excluded malignant involvement of the mesentery, especially malignant lymphoma. Immunohistochemical analysis suggested that altered hepatobiliary transport systems could play an important role in the pathogenesis of liver dysfunction. The patient was successfully treated with corticosteroid administration. Acknowledgments The authors acknowledge Masayoshi Kage, M.D., Ph.D., Department of Pathology, Kurume University Hospital, Kurume, Japan, who performed the immunohistochemical staining in liver biopsy specimens with specific primary antibodies against BSEP, MDR3, FIC1, and MRP2. Conflict of interest of interest.
The authors declare that they have no conflict
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CASE REPORT
Mesenteric panniculitis presenting as liver dysfunction Kazuhiko Morii • Tomoko Hatono • Hiroaki Okushin • Takanori Watanabe • Shiso Sato • Koichi Uesaka • Shiro Yuasa
Received: 14 September 2011 / Accepted: 25 November 2011 / Published online: 20 December 2011 Ó Springer 2011
Abstract Mesenteric panniculitis is a non-specific inflammatory disorder affecting adipose tissues of the mesentery. Mesenteric adipose tissues contain macrophages and other inflammatory cells, which may secrete tumor necrosis factor a, interleukin (IL)-1, and IL-6. These cytokines collect into the portal vein and thereby flow into the liver, possibly influencing hepatic function. Mesenteric panniculitis often occurs with inflammatory reactions such as fever and elevated erythrocyte sedimentation rates. Systemic inflammatory disorders can evoke acute cholestatic liver involvement, which is mediated by proinflammatory cytokines. However, no reports have focused on the association between mesenteric panniculitis and liver involvement. We report a rare case of mesenteric panniculitis presenting as liver dysfunction. Immunohistochemical staining of the liver demonstrated a marked decrease in expression of canalicular transport systems. These findings indicated cholestatic liver dysfunction associated with mesenteric panniculitis. Keywords Mesenteric panniculitis Liver dysfunction Cholestasis Hepatobiliary transporter Introduction Mesenteric panniculitis is a non-specific inflammatory disorder affecting adipose tissues of the mesentery [1, 2]. It has
been classified into 3 conditions according to predominant histological findings [3]. Mesenteric lipodystrophy is an early stage with predominance of fatty degeneration and necrosis. Mesenteric panniculitis (in the narrow sense) is an intermediate stage with chronic inflammation. Retractile mesenteritis is an advanced stage with predominance of fibrosis [4, 5]. Etiologies of mesenteric panniculitis remain unknown. It may occur independently or in association with other diseases including malignancies [6, 7], rheumatic disorders [8], and granulomatous diseases [9, 10]. Mesenteric adipose tissues contain macrophages which have infiltrated into adipose tissues or transdifferentiated from local preadipocytes [11, 12]. Proinflammatory cytokines such as tumor necrosis factor a (TNFa), interleukin (IL)-1, and IL-6, are secreted from mesenteric adipose tissues, and collect into the portal vein. Concentrated proinflammatory cytokines thereby flow into the liver, where they may influence hepatic pathophysiology. It is well known that systemic inflammatory disorders can evoke acute cholestatic liver involvement as a consequence of the host’s immune response [13, 14]. Mesenteric panniculitis often causes inflammatory reactions [8, 15]. However, there are no reports about a relationship between mesenteric panniculitis and liver involvement. Recently, we experienced a rare case of mesenteric panniculitis with liver dysfunction. We investigated the pathogenesis of liver dysfunction, focusing on hepatobiliary transport systems.
Electronic supplementary material The online version of this article (doi:10.1007/s12328-011-0281-2) contains supplementary material, which is available to authorized users.
Case report K. Morii (&) T. Hatono H. Okushin T. Watanabe S. Sato K. Uesaka S. Yuasa Department of Hepatology, Japanese Red Cross Society Himeji Hospital, 1-12-1 Shimoteno, Himeji, Hyogo 670-8540, Japan e-mail: [email protected]
A 63-year-old man was admitted to our hospital because of liver dysfunction and a high fever. He was in his usual health until 1 week earlier, when the high fever developed. He also
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had diminished appetite and epigastric discomfort without abdominal pain. His family physician diagnosed a common cold and prescribed non-steroidal anti-inflammatory drugs. During the next 5 days, he had remained febrile despite taking the medication. Two days before evaluation at our hospital, laboratory data showed liver dysfunction and significant inflammatory reactions. Serum total bilirubin was 2.4 mg/dl, direct bilirubin 1.4 mg/dl, aspartate aminotransferase 393 IU/l, alanine aminotransferase (ALT) 338 IU/l, alkaline phosphatase (ALP) 1,047 IU/l (reference range 115–359), gamma-glutamyltranspeptidase (cGT) 370 IU/l, and lactate dehydrogenase 363 IU/l (reference range 119–229). The erythrocyte sedimentation rate was 50 mm/h, C-reactive protein was 18.9 mg/dl (reference range 0–0.3), and the white blood cell count was 10,400/ll with a leftward shift. He was referred to our hospital for further evaluation. His past medical history was unremarkable except for a benign gastric polyp. He drank a glass of beer every weekend and did not smoke or use illicit drugs. He took neither prescriptions nor herbal remedies on a regular basis. On physical examination, no skin rash or superficial lymphadenopathy was present. The abdomen was soft without hepatosplenomegaly. Serological examination revealed significant elevation of inflammatory reactions. Serum ferritin was 2,241 ng/ml (reference range 13–301) and soluble interleukin-2 receptor (sIL-2R) was 3,710 U/ml (reference range 145–519). Blood coagulation tests showed moderate abnormalities with prothrombin time 64%, activated partial thromboplastin time 50.1 s (reference range 23–40), and fibrinogen 795 mg/dl (reference range 170–400). Extensive testing for viral hepatitis was negative. A serum interferongamma release assay was negative for Mycobacterium tuberculosis. Serum endotoxin was within reference range. Autoantibodies were also negative including antinuclear antibody, antimitochondrial antibody, and antismoothmuscle antibody. Immunoglobulin (Ig)G was 1,111 mg/dl, IgA 280 mg/dl, and IgM 104 mg/dl. Tumor markers of a-fetoprotein, carcinoembryonic antigen, and carbohydrate antigen19-9 were all within reference ranges. Abdominal computed tomography (CT) revealed a highly attenuated heterogeneous mass in the gastrocolic ligament (Fig. 1). There were discrete low density nodules in the mass, delineated by hyperdense stripes without vascular involvement. Multiple knotty thickenings within the mesenterium in this case were characteristic findings of the subtype of mesenteric lipodystrophy [3, 12]. There was no hepatobiliary obstruction. No hepatosplenomegaly, lymphadenopathy, or ascitic fluid was detected. Fiberoptic endoscopy of the upper and lower intestines showed no evidence of malignant disorders or inflammatory bowel disease. Further radiological examination revealed no pulmonary or urological abnormalities. No abnormal high uptakes were
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Fig. 1 CT scan of the abdomen obtained with contrast material administration shows the highly attenuated heterogeneous mass in the gastrocolic ligament (arrows). There are discrete low density nodules (small arrows) in the mass, delineated by hyperdense stripes without vascular involvement
observed in whole body inspection with 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET)–CT scan. Bone marrow aspiration from the posterior iliac crest revealed normocellular marrow without evidence of hematologic malignancies. Malignant lymphoma must be ruled out due to high serum sIL-2R, even though no abnormal high uptakes of FDG were observed in PET–CT [6]; it is warranted to histologically exclude malignant involvement of the mesentery [16]. Upon receiving informed consent, we conducted exploratory laparoscopy followed by partial resection of the mesenteric nodules. During laparoscopic examination, nodules were found to be firmly attached to the cologastric mesentery. The liver appeared smooth with normal consistency. Liver biopsy was also performed with an 18-gauge Tru-cut biopsy needle. Histological examination of the mesenteric nodules showed infiltration of mixed inflammatory cells and macrophages, as well as extensive fat necrosis (Fig. 2a). ‘Foamy cells’ of lipid-laden macrophages were also present (Fig. 2b). The mesenteric artery was occluded by thrombus (Fig. 1 in online appendices). No fibrosis or mitotic figures were seen. These findings confirmed the diagnosis of mesenteric panniculitis, especially mesenteric lipodystrophy. Hepatic histology showed only mild portal inflammation without interface hepatitis. No necrosis or drop-out of hepatocytes, and no hypertrophy of Kupffer cells was observed. There was no architectural derangement or fibrosis (Fig. 3a). A periodic acid–Schiff (PAS) stain with diastase digestion showed only scant PASpositive macrophages. Under high magnification, brownish granular deposits were apparent in hepatocytes mainly around bile canalicular sites (Fig. 3b).
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Fig. 2 a Histological examination of the resected mesenteric nodules shows infiltration of mixed inflammatory cells and extensive fat necrosis. Scale bar 500 lm; H&E stain. b Foamy cells of lipid-laden macrophages are present. Scale bar 100 lm. H&E stain
Fig. 3 a Histological examination of the liver shows mild portal inflammation without an interface hepatitis (arrow). There is neither necrosis nor drop-out of hepatocytes. There is no architectural derangement or fibrosis. Scale bar 200 lm; H&E stain. b There are
only scant PAS-positive macrophages. Under high magnification (inset), scattered brownish granular deposits are apparent in hepatocytes. The deposits are mainly around bile canalicular sites (arrows). Scale bar 100 lm (50 lm in inset); PAS stain with diastase digestion
We administered corticosteroids (oral prednisolone at a daily dose of 20 mg) which promptly alleviated the fever. Both liver function and the inflammatory reactions improved with subsequent normalization. The patient was discharged on the 16th day with a prescription for corticosteroids, which were tapered and finally discontinued. At 6 months after the initial presentation, a follow-up CT showed complete resolution of the mesenteric mass. To date, the patient remains afebrile and symptom-free.
[1, 9]. The prevalence of this disease was estimated to be 1.26% during a lifetime in autopsy cases [3]. Daskalogiannaki et al. described a mesenteric panniculitis prevalence of 0.6% (49 of 7,620 consecutive patients who underwent abdominal CT). Among the 49 patients, 34 (69.4%) had coexistent malignant diseases, 11 (22.4%) benign diseases, and the remaining 4 (8.2%) no abnormalities other than mesenteric panniculitis. Non-Hodgkin’s lymphoma, breast, lung, and colorectal cancers were the main coexistent neoplastic disorders. Abdominal aortic aneurysms and pulmonary sarcoidosis were predominant in benign diseases [2, 9]. Some patients with mesenteric panniculitis reportedly develop malignant lymphoma during follow-up [3]. Zissen et al. reported a negative PET with typical CT features of mesenteric panniculitis to have high diagnostic accuracy
Discussion Mesenteric panniculitis is a non-specific inflammatory disorder with a propensity for jejunal mesentery involvement
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Fig. 4 a Immunohistochemical staining for the bile salt export pump (BSEP), major transport system for bile salts. BSEP-positive canaliculi are overall reduced in the patient’s liver (P left side). Normal canalicular staining pattern of BSEP is observed in control liver (C right side). Control liver sample was obtained from unaffected area from surgical liver resection of hepatic metastases, which displayed no histological evidence of underlying liver diseases. Scale bar 50 lm. b Immunohistochemical staining for the multidrug export pump isoform (MDR3), a phospholipid translocase. MDR3-positive canaliculi are reduced in the patient’s liver (P left side), as compared
with the control liver (C right side). Scale bar 50 lm. c Immunohistochemical staining for the familial intrahepatic cholestasis-1 protein (FIC1), a P-type adenosine triphosphatase. FIC1-positive canaliculi are reduced in the patient’s liver (P left side), as compared with the control liver (C right side). Scale bar 50 lm. d Immunohistochemical staining for the multidrug resistance-related protein isoform (MRP2). MRP2-positive canaliculi are preserved or even enhanced in the patient’s liver (P left side), as compared with the control liver (C right side). Scale bar 50 lm
for excluding tumoral mesenteric involvement [17, 18]. On the other hand, Ehrenpreis et al. [6] recommended biopsy of mesenteric masses, becauase PET–CT alone might miss the presence of mesenteric lymphoma. Etiologies of mesenteric panniculitis remain unknown, but several hypotheses have been presented. Soumerai et al. [19] indicated that mesenteric thrombosis might influence the mesenteric blood supply and the occurrence of mesenteric panniculitis. We observed thrombotic arterial occlusion in the resected specimen (Fig. 1 in online appendices). The thrombus was composed of new and old
structures, suggesting the thrombus to not merely be a result of mesenteric panniculitis, but to possibly cause or promote the development of the disease. Characteristic CT findings of mesenteric panniculitis are reportedly a solitary well-defined mass composed of inhomogeneous fatty tissue with attenuation values higher than those of the retroperitoneal fat at the root of the small bowel mesentery, engulfment of superior mesenteric vessels without vascular involvement, and no evidence of invasion of the adjacent small-bowel loops even if they are displaced [9]. These features are useful for distinguishing
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mesenteric panniculitis from more common malignant conditions of the mesentery, including lymphoma, carcinomatous dissemination, and liposarcoma [20]. In systemic inflammation-associated liver dysfunction, cholestasis is typical [13, 14]. Recently, our understanding has progressed substantially about the mechanisms of inflammation or sepsis-induced cholestasis [21, 22]. Whiting et al. [23] postulated that an important mediator of the cholestasis in sepsis is TNFa, which impacts hepatic organic anion transport. TNFa and IL-1b modulate gene expressions of transporters at the canalicular membrane at both transcriptional and post-transcriptional levels, thereby impairing hepatocyte transport function [14, 21, 24]. Zollner et al. [25] demonstrated coordinated reductions of basolateral and canalicular transport systems in acquired cholestatic liver diseases by determining hepatic mRNA levels using human liver biopsy tissues. Therefore, the liver dysfunction associated with systemic inflammation is functional [26]. Our patient had a distinct clinical course with liver dysfunction and substantial acute inflammatory reactions. The liver dysfunction was consistent with acute cholestasis as defined by serum ALP level higher than 2.5 times the upper limit of normal (ULN), cGT level higher than 3 times the ULN, ALT/ALP ratio fewer than 2 times the ULN, and conjugated hyperbilirubinemia [27]. However, histological examination of the liver revealed no typical features observed in cholestatic liver diseases (e.g., bilirubin stasis in bile canaliculi, hepatocytes, Kupffer cells, and feathery degeneration of hepatocytes). We investigated canalicular hepatobiliary transporter expression and distribution by immunohistochemical staining. Staining for bile salt export pump (BSEP), multidrug export pump (MDR3), and familial intrahepatic cholestasis-1 protein (FIC1) were all reduced in the patient’s liver, as compared with the control (Fig. 4a–c). Interestingly, staining for multidrug resistance-related protein (MRP2) appeared to be relatively preserved or even enhanced in some canaliculi (Fig. 4d). MRP2 might serve as a compensatory protective overflow system against potentially toxic biliary constituents under cholestatic conditions [25, 28]. These findings strongly suggest that coordinated alterations in canalicular transport systems may be relevant for liver dysfunction in this patient. Diastase-resistant PASpositive granular deposits were observed in hepatocytes (Fig. 3b). Except for cases with a1-antitrypsin deficiency [29], almost no specific reports have been published about liver dysfunction and diastase-resistant PAS-positive deposits within the hepatocytes. It is intriguing to speculate that the distribution of the deposits along the canalicular sites may suggest decreased excretion into bile canaliculi. Inflammation-induced cholestasis is functional and reversible with control of inflammation [21]. Active febrile mesenteric panniculitis with histological predominance of
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inflammation and minimal fibrosis is likely to respond favorably to steroid treatment [30]. Moreover, mesenteric lipodystrophy can regress spontaneously [3]. These tendencies are consistent with the good therapeutic response of our patient. Liver dysfunction associated with mesenteric lipodystrophy might occur more frequently than previously thought. Since symptoms of mesenteric lipodystrophy are relatively subtle or even absent [3], they may not be recognized by patients or clinicians. Patients with refractory mesenteritis can, however, have obvious abdominal symptoms despite low inflammatory activity; this context may reflect the rarity of liver dysfunction associated with mesenteric panniculitis. In conclusion, we have described a case of mesenteric panniculitis with liver involvement. Histological examination excluded malignant involvement of the mesentery, especially malignant lymphoma. Immunohistochemical analysis suggested that altered hepatobiliary transport systems could play an important role in the pathogenesis of liver dysfunction. The patient was successfully treated with corticosteroid administration. Acknowledgments The authors acknowledge Masayoshi Kage, M.D., Ph.D., Department of Pathology, Kurume University Hospital, Kurume, Japan, who performed the immunohistochemical staining in liver biopsy specimens with specific primary antibodies against BSEP, MDR3, FIC1, and MRP2. Conflict of interest of interest.
The authors declare that they have no conflict
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