{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T06:50:36Z","timestamp":1765695036866,"version":"3.48.0"},"reference-count":34,"publisher":"BMJ","issue":"11","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Clin Pathol"],"published-print":{"date-parts":[[1989,11]]},"abstract":"<jats:p>To determine whether portal lymphadenopathy in primary biliary cirrhosis is caused by deposition of lipofuscin pigment in sinus histiocytes and to compare primary biliary cirrhosis with other liver diseases a retrospective study on a consecutive series of 169 livers obtained at transplantation was carried out. There were grouped into eight diagnostic categories: primary biliary cirrhosis (n = 51), primary sclerosing cholangitis (n = 10), extrahepatic biliary atresia (n = 6), chronic rejection (n = 9), cirrhosis (other causes) (n = 38), primary liver neoplasia (n = 21), acute liver disease (n = 20), and retransplantation (other) (n = 14). Lymph nodes were present in 66 specimens. Fifty of these contained granules of lipofuscin pigment. The highest incidence of lymph node enlargement and the largest amounts of pigment were present in cases of primary biliary cirrhosis. A similar pattern of lymph node enlargement was also commonly observed in other chronic cholestatic conditions (primary sclerosing cholangitis, biliary atresia, chronic rejection). Much less pigment was seen in nodes draining livers with non-cholestatic cirrhosis or primary tumours. Nodes were not found in acute liver disease. It is concluded that portal lymphadenopathy associated with lipofuscin is a common finding in various chronic cholestatic liver diseases. The pathogenesis of this lesion is uncertain. Most cases are asymptomatic with enlarged nodes which may be detected only at laperotomy or necropsy and may be wrongly attributed to neoplastic disease. Diagnostically, the finding of large amounts of lipofuscin in enlarged portal lymph nodes is a good indicator of underlying chronic cholestatic liver disease.<\/jats:p>","DOI":"10.1136\/jcp.42.11.1160","type":"journal-article","created":{"date-parts":[[2007,6,9]],"date-time":"2007-06-09T00:50:46Z","timestamp":1181350246000},"page":"1160-1165","source":"Crossref","is-referenced-by-count":13,"title":["Portal lymphadenopathy associated with lipofuscin in chronic cholestatic liver disease."],"prefix":"10.1136","volume":"42","author":[{"given":"S G","family":"H\u00fcbscher","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R F","family":"Harrison","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1989,11,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1016\/S0016-5085(19)35377-6","article-title":"Primary biliary cirrhosis (chronic intrahepatic obstructive jaundice)","volume":"37","author":"Sherlock, S.","year":"1959","unstructured":"Sherlock S. Primary biliary cirrhosis (chronic intrahepatic obstructive jaundice). Gastroenterology 1959;37:574-86.","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1111\/j.1365-2559.1987.tb01903.x","article-title":"Chromolipid induced portal lymphadenopathy in primary biliary cirrhosis","volume":"11","author":"Benbow, E.W.; McMahon, R.F.T.","year":"1987","unstructured":"Benbow EW, McMahon RFT. Chromolipid induced portal lymphadenopathy in primary biliary cirrhosis. Histopathology 1987;11:971-7.","journal-title":"Histopathology"},{"key":"ref_3","first-page":"385","article-title":"Pathology ofliver transplantation","volume-title":"Liver transplanation: the Cambridge\/Kings College experience","author":"Wight, D.G.D.","year":"1987","unstructured":"Wight DGD. Pathology ofliver transplantation. In: Calne RY, ed. Liver transplanation: the Cambridge\/Kings College experience. 2nd edition. London: Grune and Stratton, 1987:385-435.","edition":"2nd edition"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1136\/jcp.38.12.1366","article-title":"Biopsy findings in cases of rejection of liver allograft","volume":"38","author":"Hubscher, S.G.; Clements, D.; Elias, E.; McMaster, P.","year":"1985","unstructured":"Hubscher SG, Clements D, Elias E, McMaster P. Biopsy findings in cases of rejection of liver allograft. J Clin Pathol 1985;38:1366-73.","journal-title":"J Clin Pathol"},{"issue":"4","key":"ref_5","first-page":"128","article-title":"Chronic rejection in liver transplants. A histopathologic analysis of failed grafts and antecedent serial biopsies","volume-title":"Transplant Proc 1986","volume":"18","author":"Grond, J.; Gouw, A.S.H.; Poppema, S.; SlooffMJH, Gips; G.H.","unstructured":"Grond J, Gouw ASH, Poppema S, SlooffMJH, Gips GH. Chronic rejection in liver transplants. A histopathologic analysis of failed grafts and antecedent serial biopsies. Transplant Proc 1986;18 (Suppl 4):128-35."},{"key":"ref_6","series-title":"Proceedings of the Vlth International Meeting","first-page":"561","article-title":"Sporadic non-A non-B hepatitis as a cause ofacute liver failure. In: Viral hepatitis and liver disease","author":"Vickers, C.R.; Hiibscher, S.G.; Skidmore, S.J.; McMaster, P.; Elias, E.","year":"1988","unstructured":"Vickers CR, Hiibscher SG, Skidmore SJ, McMaster P, Elias E. Sporadic non-A non-B hepatitis as a cause ofacute liver failure. In: Viral hepatitis and liver disease. Proceedings of the Vlth International Meeting. New York: AR Liss, 1988:561-3."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1136\/jcp.42.4.360","article-title":"Massive haemorrhagic necrosis of the liver following liver transplantation","volume":"42","author":"Huibscher, S.G.; Adams, D.H.; Buckels, J.A.C.; McMaster, P.; Neuberger, J.; Elias, E.","year":"1989","unstructured":"Huibscher SG, Adams DH, Buckels JAC, McMaster P, Neuberger J, Elias E. Massive haemorrhagic necrosis of the liver following liver transplantation. J Clin Pathol 1989;42:360-70.","journal-title":"J Clin Pathol"},{"key":"ref_8","first-page":"267","article-title":"Ultrastructural and histochemical investigations of spindle-shaped corpuscles in phagocytic cells of lymph nodes","volume":"161","author":"Roggendorf, W.; Gross, U.","year":"1977","unstructured":"Roggendorf W, Gross U. Ultrastructural and histochemical investigations of spindle-shaped corpuscles in phagocytic cells of lymph nodes. Beitageftir Pathologie 1977;161:267-82.","journal-title":"Beitageftir Pathologie"},{"issue":"301","key":"ref_9","first-page":"490","article-title":"Ueber ein neues, siurefeste Substanz fiuhrendes Spindelkorperchen der menschlicher Lymphdruisen","volume":"1938","author":"Hamazaki, Y.","unstructured":"Hamazaki Y. Ueber ein neues, siurefeste Substanz fiuhrendes Spindelkorperchen der menschlicher Lymphdruisen. Virchows Arch (Cell Pathol) 1938;301:490-522.","journal-title":"Virchows Arch (Cell Pathol)"},{"key":"ref_10","first-page":"347","article-title":"Pathology of the orthotopic homograft and heterograft","volume":"1","author":"Porter, K.A.","year":"1969","unstructured":"Porter KA. Pathology of the orthotopic homograft and heterograft. In: Starzl TE, ed: Experience in hepatic transplantation. Philadelphia: WB Saunders, 1969:422-68. 1 1 Demetris AJ, Jaffe R, Starzl TE. A review of adult and paediatric post-transplant liver pathology. Pathol Annu 1987;Part 2: 347-86.","journal-title":"Pathol Annu; Experience in hepatic transplantation"},{"key":"ref_11","first-page":"152","article-title":"Differential diagnosis of cholestasis","volume-title":"liver allografts. Transplant Proc 1986; 18(Suppl 4)","author":"Wight, D.G.D.","unstructured":"Wight DGD. Differential diagnosis of cholestasis in liver allografts. Transplant Proc 1986;18(Suppl 4):152-6."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/0002-9610(86)90013-9","article-title":"Cholestatic jaundice after hepatic transplantation. A non-immunologically mediated event","volume":"151","author":"Williams, J.W.; Vera, S.; Peters, T.G.","year":"1986","unstructured":"Williams JW, Vera S, Peters TG, et al. Cholestatic jaundice after hepatic transplantation. A non-immunologically mediated event. Am J Surg 1986;151:65-70.","journal-title":"Am J Surg"},{"key":"ref_13","first-page":"874","article-title":"Pigments and pigment precursors","volume-title":"Histochemistry, theoretical and applied. Vol 2","author":"Pearse, A.G.E.","year":"1985","unstructured":"Pearse AGE. Pigments and pigment precursors. In: Histochemistry, theoretical and applied. Vol 2, 4th Edition. Edinburgh: Churchill Livingstone, 1985:874-928.","edition":"4th Edition"},{"key":"ref_14","first-page":"122","article-title":"Atlas ofliver biopsies","author":"Poulsen, H.; Christofferson, P.","year":"1979","unstructured":"Poulsen H, Christofferson P. Atlas ofliver biopsies. Munksgaard: JB Lippincott Co, 1979:122."},{"key":"ref_15","first-page":"19","article-title":"Liver biopsy interpretation","author":"Scheuer, P.J.","year":"1978","unstructured":"Scheuer PJ. Liver biopsy interpretation. 3rd Edition. London: Balliere Tindall, 1978:19-22, 245-9.","edition":"3"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1002\/1097-0142(197508)36:2<528::AID-CNCR2820360232>3.0.CO;2-U","article-title":"Survival with mammary cancer related to interaction of germinal centre hyperplasia and sinus histocytosis in axillary and internal mammary lymph nodes","volume":"36","author":"Hunter, R.; Ferguson, D.; Coppleson, L.","year":"1975","unstructured":"Hunter R, Ferguson D, Coppleson L. Survival with mammary cancer related to interaction of germinal centre hyperplasia and sinus histocytosis in axillary and internal mammary lymph nodes. Cancer 1975;36:528-39.","journal-title":"Cancer"},{"key":"ref_17","first-page":"550","article-title":"The lymphoreticular system. In: Systemic pathology","author":"C, Symmers W.St","year":"1978","unstructured":"Symmers W St C. The lymphoreticular system. In: Systemic pathology. 2nd Edition. Edinburgh: Churchill Livingstone, 1978:550-71.","edition":"2"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1002\/1097-0142(19800815)46:4+<908::AID-CNCR2820461310>3.0.CO;2-5","article-title":"Pathologic findings from the National Surgical Adjuvant Breast Project","volume":"46","author":"Fisher, E.; Redmond, C.; Fisher, B.","year":"1980","unstructured":"Fisher E, Redmond C, Fisher B. Pathologic findings from the National Surgical Adjuvant Breast Project. Cancer 1980;46:908-18.","journal-title":"Cancer"},{"key":"ref_19","first-page":"222","article-title":"Types of tumour lymphoid response and sinus histiocytosis","volume":"107","author":"Fisher, E.; Kotwal, N.; Herman, C.; Fisher, B.","year":"1983","unstructured":"Fisher E, Kotwal N, Herman C, Fisher B. Types of tumour lymphoid response and sinus histiocytosis. Arch Pathol Lab Med 1983;107:222-7.","journal-title":"Arch Pathol Lab Med"},{"key":"ref_20","first-page":"146","article-title":"Cholestasis","volume-title":"advances in histopathology. No 12","author":"Desmet, V.J.","year":"1984","unstructured":"Desmet VJ. Cholestasis. In: Anthony PP, MacSween RNM, eds. Recent advances in histopathology. No 12. Edinburgh: Churchill Livingstone, 1984:146-57."},{"key":"ref_21","article-title":"Pathologic basis ofdisease","volume":"23","author":"Robbins, S.L.; Cotran, R.; Kumar, V.","year":"1984","unstructured":"Robbins SL, Cotran R, Kumar V. Pathologic basis ofdisease. 3rd Edition, Philadelphia: WB Saunders, 1984:23.","edition":"3"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/BF02532441","article-title":"Studies on chemical composition of lipofuscin (age pigment) from normal human brain","volume":"10","author":"Tombald, R.D.","year":"1975","unstructured":"Tombald RD. Studies on chemical composition of lipofuscin (age pigment) from normal human brain. Lipids 1975;10:383-90.","journal-title":"Lipids"},{"key":"ref_23","first-page":"250","article-title":"The lipofuscins. In: Theory andpractice of histological techniques","author":"Bancroft, J.D.; Stevens, A.","year":"1982","unstructured":"Bancroft JD, Stevens A. The lipofuscins. In: Theory andpractice of histological techniques. 2nd Edition. Edinburgh: Churchill Livingstone, 1982:250-2.","edition":"2"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1177\/3.6.479","article-title":"Histochemistry of human esterases","volume":"3","author":"Gomori, G.","year":"1955","unstructured":"Gomori G. Histochemistry of human esterases. J Histochem Cytochem 1955;3:479-84.","journal-title":"J Histochem Cytochem"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1177\/14.9.641","article-title":"The demonstration of acid hydrolase, thermostable reduced diphosphopyridine nucleotide tetrazolium reductase and peroxidase activities in human lipofuscin pigment granules","volume":"14","author":"Goldfischer, S.; Villarverde, H.; Forschirm, R.","year":"1956","unstructured":"Goldfischer S, Villarverde H, Forschirm R. The demonstration of acid hydrolase, thermostable reduced diphosphopyridine nucleotide tetrazolium reductase and peroxidase activities in human lipofuscin pigment granules. J Histochem Cytochem 1956;14:641-52.","journal-title":"J Histochem Cytochem"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1136\/gut.17.10.787","article-title":"Demonstration of an intracellular copper-binding protein by orcein staining in longstanding cholestatic liver diseases","volume":"17","author":"Salaspuro, M.; Sipponen, P.","year":"1976","unstructured":"Salaspuro M, Sipponen P. Demonstration of an intracellular copper-binding protein by orcein staining in longstanding cholestatic liver diseases. Gut 1976;17:787-90.","journal-title":"Gut"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1136\/jcp.31.8.784","article-title":"Histological demonstration of copper and copper-associated protein in chronic liver diseases","volume":"31","author":"Jain, S.; Scheuer, P.J.; Archer, B.; Newman, S.P.; Sherlock, S.","year":"1978","unstructured":"Jain S, Scheuer PJ, Archer B, Newman SP, Sherlock S. Histological demonstration of copper and copper-associated protein in chronic liver diseases. J Clin Pathol 1978;31:784-90.","journal-title":"J Clin Pathol"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1007\/BF01102738","article-title":"Orcein positive granules in the hepatocytes in chronic intrahepatic cholestasis","volume":"382","author":"Nakamura, Y.; Karino, T.; Ohta, G.","year":"1979","unstructured":"Nakamura Y, Karino T, Ohta G. Orcein positive granules in the hepatocytes in chronic intrahepatic cholestasis. Virchows Arch (Pathol Anat) 1979;382:21-30.","journal-title":"Virchows Arch (Pathol Anat)"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1136\/jcp.36.1.18","article-title":"Value of copper-associated protein in diagnostic assessment of liver biopsy","volume":"36","author":"Guarascio, P.; Yentis, F.; Cevikbas, U.; Portmann, B.; Williams, R.","year":"1983","unstructured":"Guarascio P, Yentis F, Cevikbas U, Portmann B, Williams R. Value of copper-associated protein in diagnostic assessment of liver biopsy. J Clin Pathol 1983;36:18-23.","journal-title":"J Clin Pathol"},{"key":"ref_30","first-page":"51","article-title":"Liver cell lysosomes in Wilson's disease: acid phosphatase activity by light and electron microscopy","volume":"43","author":"Goldfischer, S.","year":"1963","unstructured":"Goldfischer S. Liver cell lysosomes in Wilson's disease: acid phosphatase activity by light and electron microscopy. Am J Pathol 1963;43:51 1-25.","journal-title":"Am J Pathol"},{"key":"ref_31","first-page":"305","article-title":"Electron probe micro analysis of liver in Wilson's disease","volume":"48","author":"Goldfischer, S.; Moskal, J.","year":"1966","unstructured":"Goldfischer S, Moskal J. Electron probe micro analysis of liver in Wilson's disease. Am J Pathol 1966;48:305-15.","journal-title":"Am J Pathol"},{"key":"ref_32","first-page":"883","article-title":"Changes in the distribution of hepatic copper in relation to the progression of Wilson's disease (hepatolenticular degeneration)","volume":"53","author":"Goldfischer, S.; Sternlieb, I.","year":"1968","unstructured":"Goldfischer S, Sternlieb I. Changes in the distribution of hepatic copper in relation to the progression of Wilson's disease (hepatolenticular degeneration). Am J Pathol 1968;53:883-907.","journal-title":"Am J Pathol"},{"key":"ref_33","first-page":"715","article-title":"Tne significance ofvariations in the distribution of copper in liver disease","volume":"99","author":"Goldfischer, S.; Popper, H.; Sternlieb, I.","year":"1980","unstructured":"Goldfischer S, Popper H, Sternlieb I. Tne significance ofvariations in the distribution of copper in liver disease. Am J Pathol 1980;99:715-30.","journal-title":"Am J Pathol"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"240","DOI":"10.1016\/S0016-5085(76)80016-9","article-title":"The biliary system in primary biliary cirrhosis. A study by endoscopic retrograde cholangiopancreatography","volume":"70","author":"Summerfield, J.A.; Elias, E.; Hungerford, G.D.; Nikapota, V.L.B.; Dick, R.; Sherlock, S.","year":"1976","unstructured":"Summerfield JA, Elias E, Hungerford GD, Nikapota VLB, Dick R, Sherlock S. The biliary system in primary biliary cirrhosis. A study by endoscopic retrograde cholangiopancreatography. Gastroenterology 1976;70:240-3.","journal-title":"Gastroenterology"}],"container-title":["Journal of Clinical Pathology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jcp.42.11.1160","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T06:48:35Z","timestamp":1765694915000},"score":1,"resource":{"primary":{"URL":"https:\/\/jcp.bmj.com\/lookup\/doi\/10.1136\/jcp.42.11.1160"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1989,11]]},"references-count":34,"journal-issue":{"issue":"11","published-online":{"date-parts":[[1989,11,1]]},"published-print":{"date-parts":[[1989,11]]}},"alternative-id":["10.1136\/jcp.42.11.1160"],"URL":"https:\/\/doi.org\/10.1136\/jcp.42.11.1160","relation":{},"ISSN":["0021-9746","1472-4146"],"issn-type":[{"type":"print","value":"0021-9746"},{"type":"electronic","value":"1472-4146"}],"subject":[],"published":{"date-parts":[[1989,11]]}}}