662 @ 1992 The Japanese Society of Pathology
Polyarteritis Nodosa with Atrophy of the Left Hepatic Lobe
Koh Nakazawa'y2, Nobuo Itoh', Hui-Jun Duan', Yuichi Komiyama', and Hidekazu Shigematsd A 73-year-old Japanese man with a history of partial gastrectomy due to gastric cancer 4 years previously was admitted because of intermittent fever. The patient developed abdominal pain, erythema, and myalgia in addition to the fever during the final clinical course, and died of acute heart failure. Autopsy disclosed atrophy of the left lobe of the liver and acute myocardial infarction. Neither metastasis nor recurrence of the cancer was observed. Smalland medium-sized arteries of the visceral organs showed various stages of necrotizing vasculitis with narrowing of the lumina. The vasculitis was most prominent in the left lobe of the liver and in the heart. Narrowing of the portal vein due to portal tract inflammation in addition to vasculitis of the hepatic arteries may have induced ischemia and infarction, which had resulted in atrophy of the left hepatic lobe. Acta Pathol Jpn 42 : 662-666, 1992. Key words : Polyarteritis nodosa, Hepatic lobar atrophy, Gastric cancer
Polyarteritis nodosa (PN), a fo rm of systemic necrotizing vasculitis, has various manifestations including cutaneous, renal, cardiovascular, neurologic and gastrointestinal involvement due to ischemia and/or hemorrhage. Infarction of the entire hepatic lobe is uncommon, because of the abundant collateral circulation and dual blood supply via the hepatic artery and portal vein. We describe an unusual case of PN characterized by marked atrophy of the lateral segment of the liver due to vascular invo Ivement.
Received February 17, 1992. Accepted for publication June 15, 1992. 'First Department of Pathology, Shinshu University School of Medicine, Matsurnoto. ZDepartment of Pathology, Nagano Red Cross Hospital, Nagano. Mailing address: Koh Nakazawa, First Department of Pathology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390, Japan. This case was presented at the 81st Annual Meeting of the Japanese Society of Pathology in Sendai on May 16, 1992.
CASEREPORT A 73-year-old Japanese man was admitted to Shinshu University Hospital on March 1, 1988. He had undergone partial gastrectomy for gastric cancer 4 years before. He had received Picibanil therapy thereafter until March 1987, when intermittent fever developed and persisted without any documented infection. During hospitalization elsewhere from November 1 9 8 7 to February 1988, relevant laboratory data were as follows: white blood cell count 16,200/mm3 with 91% neutrophils (10% stab, 81% seg, 9% lymph), erythrocyte sedimentation rate 6 2 mm/h, CRP 1 8 . 2 mg/dl, rheumatoid factor 2+, RAHA positive ( x 1,280). Tests for anti-nuclear antibodies, lupus erythematosus cell, and hepatitis B surface antigen gave negative results. Urinalysis showed no proteinuria and 1 hematuria. The urinary sediment contained 7 red blood cells per high-power field. Administration of prednisolone (30 mg/day) resolved the fever, and CRP decreased from18.2 to 2.6 mg/dl. However, after reduction of the
+
Figure 1. CT scan obtained on admission, showing absence of the left lobe of the liver.
663
Acta Pathologica Japonica 42 (9): 1992
Figure 2. The liver shows marked atrophy of the left lobe (arrow). notable change.
The right lobe shows no
Figure 3. a : Low-power view of the left lobe of the liver, showing widespread vasculitis in the hepatic arteries (arrows) and loss of hepatocytes. The capsules are coarsely wrinkled. b : The internal elastic lamina of the hepatic artery is partially disrupted with intirnal cellular proliferation and luminal narrowing. Elastica van Gieson stain.
664
PN with Hepatic Lobar Atrophy (Nakazawa et a/.)
Figure 4. a : Section of the left lobe showing various stages of arteritis (arrows). The hepatocytes have been lost and portal veins are obscure. B D ; bile duct, HV; hepatic vein. b : Portal tract showing fibrinoid necrosis of the hepatic artery (HA) and dense infiltration of lymphocytes, plasma cells, eosinophils, and neutrophils. Branches of the portal vein (PV) are narrowed in the inflamed portal tract (arrows). HE. c : A small number of remaining hepatocytes show degenerative changes in the atrophic left lobe (large arrows). Remnant interlobular bile ducts (small arrows) are also present. HE.
665
Acta Pathologica Japonica 42 (9) : 1992
pred-nisolone dose, the fever and inflammation recurred, and the patient was referred to Shinshu University Hospital. On admission, his blood pressure was 140/90 mmHg. Chest X-ray showed old tuberculous lesions in the apical field of the right lung. The hemoglobin level was 13.6 g/dl, white blood cell count 15,300/mm3, erythrocyte sedimentation rate 70 mm/h, and CRP 13.9 mg/dl. Levels of serum transaminase, creatinine and urea nitrogen were within normal limits. The stools were negative for occult blood. A CT scan carried out on March 11 (Fig. 1) failed to reveal the left lobe of the liver. After admission, prednisolone was discontinued, and antibiotics and tuberculostatics were prescribed. Two weeks later, severe intermittent pain appeared in the right upper abdominal quadrant and lower abdomen, and transient elevation of sGOT (455 U/l), sGPT (195 U/l), and bilirubin (total; 2.2, direct; 1.6 mg/dl) was observed. On March 27, erythema and myalgia developed on the bilateral lower extremities. Severe abdominal pain appeared on April 3 and the patient died of acute heart failure on the following day.
AUTOPSY FINDINGS Postmortem examination revealed no evidence of recurrence or metastasis of the gastric cancer, but generalized PN at various stages was evident. The liver weighed 1,130 g. The left lobe was markedly atrophic (Fig. 2), but the right lobe had a smooth surface without atrophy or infarction. Histological sections revealed a massive loss of hepatocytes and various stages of necrotizing arteritis in small and- mediumsized hepatic arterial branches (Fig. 3). The portal tracts around the arteries were infiltrated by lymphocytes, plasma cells, eosinophils, and polymorphonuclear leukocytes (Figs. 4a, b). The portal veins were obscure, and branches of the portal vein were narrowed in the inflamed portal tracts. Interlobular bile ducts and a small number of hepatocytes remained in the fibrotic left lobe (Fig. 4c). No obvious thrombus was found in the portal vein. In the right lobe of the liver, there was no significant fibrosis except for mild vasculitis of the hepatic arteries. There was no cholelithiasis or obstruction of the bile duct. A wide area of the left ventricle of the heart showed acute myocardial necrosis. The coronary arteries showed necrotizing arteritis with narrowing of the lumina and thrombotic occlusion. Vasculitis was also observed in the arteries of the kidneys, urinary bladder, gastrointestinal tract, pancreas, gallbladder and adrenal glands, as well as in the liver and heart. There were no ischemic necrotic lesions in organs
other than the liver and heart.
DISCUSSION PN is a primary disease of the vascular system and shows various clinical manifestations (1, 2). The disease involves chiefly the small elastic arteries in a segmental manner, causing hemorrhage and infarction of the organs. The pathological changes in the liver are similar to those found in other organs (3,4). These changes include aneurysm formation and rupture of the hepatic arteries, infarction, disruption of the lobular architecture, inflammatory infiltration by leukocytes, lymphocytes and plasma cells into the periportal tissue adjacent to the involved arteries, bile duct proliferation, and atrophy and degeneration of the liver parenchyma. Massive infarction of the liver is uncommon, unlike the situation in other organs (5-8), since the liver has abundant collateral arterial circulation and a dual blood supply via the hepatic artery and the portal vein (3-8). Haratake et a/. (8) presented a case of massive hepatic infarction, 1 2 x 1 0 x 7 cm in size, associated with PN showing fresh coagulative necrosis including both the .parenchyma and portal areas. Parker (6) stated that many of the dead cells in the areas of parenchymal necrosis were removed by the eighth day and that the lobular stroma tended to collapse. In the present case, there remained no evidence of fresh parenchymal necrosis. The left lobe was atrophic and consisted of stromal tissue. Although several attacks of abdominal pain and transient mild hepatic dysfunction were observed 3 weeks prior to death, the atrophy of the left hepatic lobe was already evident by CT scan on admission. It is uncertain whet her the infarction occurred without clinica I manif estation or whether chronic ischemia induced the disappearance of parenchymal cells, leaving the fibrotic stroma. Congenital absence of the left lobe of the liver is a rare condition (9). In this case, unfortunately, CT scan was not performed at the time of surgery for gastric cancer, and there were no details of hepatic lesions in the case record. However, coarse wrinkling of the capsule of the left lobe, indicative of atrophy after organ formation, and the fact that interlobular bile ducts were not atrophic and hepatocytes remained in small clusters in the fibrotic left lobe along with some degenerative changes make such a condition unlikely. Moreover, there was no evidence of cholelithiasis, bile duct obstruction or other vascular diseases. It seems that PN would involve the hepatic arteries and that an inflammatory reaction in the portal tracts could also involve the portal veins, which run close t o the main artery, inducing marked atrophy of the left lobe(10, 11). The malignancies associated with vasculitis reported in
666
PN with Hepatic Lobar Atrophy (Nakazawa et a/.)
the literature are hairy cell leukemia, lymphoma, multiple myeloma, and some carcinomas (12-14). instances of vasculitis have been reported to occur both before and after the onset of malignancy, and several explanations have been advanced for the possible relationship between them. Paraneoplastic v a s c u l i ti s u s u a l l y shows cutaneous or subcutaneous involvement, whereas visceral organ involvement or systemic vasculitis is rare (14). The present case showed marked systemic manifestations of vasculitis without recurrence of the cancer, and the clinical course was not consistent with drugs or Picibanil therapy. Therefore this case seems to have been not a secondary but a primary fo rm of PN, manifested as marked atrophy of the left hepatic lobe.
REFERENCES Arkin A. A clinical and pathological study of periarteritis nodosa. A report of five cases, one histologically healed. Am J Pathol 6: 401-431,1930. Nagasawa T. Polyarteritis nodosa. Byori to Rinsho 8: 1336-1340, 1 990 (in Japanese). Mowrey FH and Lundberg EA. The clinical rnanifestations of essential polyangiitis (periarteritis nodosa), with emphasis on the hepatic manifestations. Ann Intern Med 40: 1145-1164,1954. Nakanurna Y, Ohta G, and Sasaki K. Nodular regener.
ative hyperplasia of the liver associated with polyarteritis nodosa. Arch Pathol Lab Med 108: 133-135,
1984. 5. Carroll R. Infarction of the human liver. J Clin Pathol 16: 133-136,1963. 6. Parker RGF. Arterial infarction of the liver in man. J Pathol Bacteriol 70: 521-528,1955. 7. Seeley TT, Blumenfeld CM, lkeda R, Knapp W, and Ruebner BH. Hepatic infarction. Hum Pathol 3: 265-276,1972. 8. Haratake J, Horie A, Furuta A, and Yamato H. Massive hepatic infarction associated with polyarteritis nodosa. Acta Pathol Jpn 38: 89-93,1988. 9. Merrill GG. Complete absence of the left lobe of the liver. Arch Pathol 42: 232-233,1946. 10. Benz EJ, Baggenstoss AH, and Wollaeger EE. Atrophy of the left lobe of the liver. Arch Path0153 : 315-
330,1952. 11. Ham JM. Partial and complete atrophy affecting hepatic segments and lobes. Br J Surg 66: 333-337, 1979. 12. Elkon KB, Hughes GRV, and Catovsky D. Hairy-cell leukemia with polyarteritis nodosa. Lancet 2 : 280282, 1979. 13. Goedert JJ, Neefe JR, Smith FS, et a/. Polyarteritis nodosa, hairy cell leukemia and splenosis. Am J Med
71 : 323-326,1981. 14. Greer JM, Longley S, Edwards NL, Elfenbein GJ, and Panush RS. Vasculitis associated with malignancy : Experience with 13 patients and literature review. Medicine 67 : 220-230,1988.
Polyarteritis Nodosa with Atrophy of the Left Hepatic Lobe
Koh Nakazawa'y2, Nobuo Itoh', Hui-Jun Duan', Yuichi Komiyama', and Hidekazu Shigematsd A 73-year-old Japanese man with a history of partial gastrectomy due to gastric cancer 4 years previously was admitted because of intermittent fever. The patient developed abdominal pain, erythema, and myalgia in addition to the fever during the final clinical course, and died of acute heart failure. Autopsy disclosed atrophy of the left lobe of the liver and acute myocardial infarction. Neither metastasis nor recurrence of the cancer was observed. Smalland medium-sized arteries of the visceral organs showed various stages of necrotizing vasculitis with narrowing of the lumina. The vasculitis was most prominent in the left lobe of the liver and in the heart. Narrowing of the portal vein due to portal tract inflammation in addition to vasculitis of the hepatic arteries may have induced ischemia and infarction, which had resulted in atrophy of the left hepatic lobe. Acta Pathol Jpn 42 : 662-666, 1992. Key words : Polyarteritis nodosa, Hepatic lobar atrophy, Gastric cancer
Polyarteritis nodosa (PN), a fo rm of systemic necrotizing vasculitis, has various manifestations including cutaneous, renal, cardiovascular, neurologic and gastrointestinal involvement due to ischemia and/or hemorrhage. Infarction of the entire hepatic lobe is uncommon, because of the abundant collateral circulation and dual blood supply via the hepatic artery and portal vein. We describe an unusual case of PN characterized by marked atrophy of the lateral segment of the liver due to vascular invo Ivement.
Received February 17, 1992. Accepted for publication June 15, 1992. 'First Department of Pathology, Shinshu University School of Medicine, Matsurnoto. ZDepartment of Pathology, Nagano Red Cross Hospital, Nagano. Mailing address: Koh Nakazawa, First Department of Pathology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto 390, Japan. This case was presented at the 81st Annual Meeting of the Japanese Society of Pathology in Sendai on May 16, 1992.
CASEREPORT A 73-year-old Japanese man was admitted to Shinshu University Hospital on March 1, 1988. He had undergone partial gastrectomy for gastric cancer 4 years before. He had received Picibanil therapy thereafter until March 1987, when intermittent fever developed and persisted without any documented infection. During hospitalization elsewhere from November 1 9 8 7 to February 1988, relevant laboratory data were as follows: white blood cell count 16,200/mm3 with 91% neutrophils (10% stab, 81% seg, 9% lymph), erythrocyte sedimentation rate 6 2 mm/h, CRP 1 8 . 2 mg/dl, rheumatoid factor 2+, RAHA positive ( x 1,280). Tests for anti-nuclear antibodies, lupus erythematosus cell, and hepatitis B surface antigen gave negative results. Urinalysis showed no proteinuria and 1 hematuria. The urinary sediment contained 7 red blood cells per high-power field. Administration of prednisolone (30 mg/day) resolved the fever, and CRP decreased from18.2 to 2.6 mg/dl. However, after reduction of the
+
Figure 1. CT scan obtained on admission, showing absence of the left lobe of the liver.
663
Acta Pathologica Japonica 42 (9): 1992
Figure 2. The liver shows marked atrophy of the left lobe (arrow). notable change.
The right lobe shows no
Figure 3. a : Low-power view of the left lobe of the liver, showing widespread vasculitis in the hepatic arteries (arrows) and loss of hepatocytes. The capsules are coarsely wrinkled. b : The internal elastic lamina of the hepatic artery is partially disrupted with intirnal cellular proliferation and luminal narrowing. Elastica van Gieson stain.
664
PN with Hepatic Lobar Atrophy (Nakazawa et a/.)
Figure 4. a : Section of the left lobe showing various stages of arteritis (arrows). The hepatocytes have been lost and portal veins are obscure. B D ; bile duct, HV; hepatic vein. b : Portal tract showing fibrinoid necrosis of the hepatic artery (HA) and dense infiltration of lymphocytes, plasma cells, eosinophils, and neutrophils. Branches of the portal vein (PV) are narrowed in the inflamed portal tract (arrows). HE. c : A small number of remaining hepatocytes show degenerative changes in the atrophic left lobe (large arrows). Remnant interlobular bile ducts (small arrows) are also present. HE.
665
Acta Pathologica Japonica 42 (9) : 1992
pred-nisolone dose, the fever and inflammation recurred, and the patient was referred to Shinshu University Hospital. On admission, his blood pressure was 140/90 mmHg. Chest X-ray showed old tuberculous lesions in the apical field of the right lung. The hemoglobin level was 13.6 g/dl, white blood cell count 15,300/mm3, erythrocyte sedimentation rate 70 mm/h, and CRP 13.9 mg/dl. Levels of serum transaminase, creatinine and urea nitrogen were within normal limits. The stools were negative for occult blood. A CT scan carried out on March 11 (Fig. 1) failed to reveal the left lobe of the liver. After admission, prednisolone was discontinued, and antibiotics and tuberculostatics were prescribed. Two weeks later, severe intermittent pain appeared in the right upper abdominal quadrant and lower abdomen, and transient elevation of sGOT (455 U/l), sGPT (195 U/l), and bilirubin (total; 2.2, direct; 1.6 mg/dl) was observed. On March 27, erythema and myalgia developed on the bilateral lower extremities. Severe abdominal pain appeared on April 3 and the patient died of acute heart failure on the following day.
AUTOPSY FINDINGS Postmortem examination revealed no evidence of recurrence or metastasis of the gastric cancer, but generalized PN at various stages was evident. The liver weighed 1,130 g. The left lobe was markedly atrophic (Fig. 2), but the right lobe had a smooth surface without atrophy or infarction. Histological sections revealed a massive loss of hepatocytes and various stages of necrotizing arteritis in small and- mediumsized hepatic arterial branches (Fig. 3). The portal tracts around the arteries were infiltrated by lymphocytes, plasma cells, eosinophils, and polymorphonuclear leukocytes (Figs. 4a, b). The portal veins were obscure, and branches of the portal vein were narrowed in the inflamed portal tracts. Interlobular bile ducts and a small number of hepatocytes remained in the fibrotic left lobe (Fig. 4c). No obvious thrombus was found in the portal vein. In the right lobe of the liver, there was no significant fibrosis except for mild vasculitis of the hepatic arteries. There was no cholelithiasis or obstruction of the bile duct. A wide area of the left ventricle of the heart showed acute myocardial necrosis. The coronary arteries showed necrotizing arteritis with narrowing of the lumina and thrombotic occlusion. Vasculitis was also observed in the arteries of the kidneys, urinary bladder, gastrointestinal tract, pancreas, gallbladder and adrenal glands, as well as in the liver and heart. There were no ischemic necrotic lesions in organs
other than the liver and heart.
DISCUSSION PN is a primary disease of the vascular system and shows various clinical manifestations (1, 2). The disease involves chiefly the small elastic arteries in a segmental manner, causing hemorrhage and infarction of the organs. The pathological changes in the liver are similar to those found in other organs (3,4). These changes include aneurysm formation and rupture of the hepatic arteries, infarction, disruption of the lobular architecture, inflammatory infiltration by leukocytes, lymphocytes and plasma cells into the periportal tissue adjacent to the involved arteries, bile duct proliferation, and atrophy and degeneration of the liver parenchyma. Massive infarction of the liver is uncommon, unlike the situation in other organs (5-8), since the liver has abundant collateral arterial circulation and a dual blood supply via the hepatic artery and the portal vein (3-8). Haratake et a/. (8) presented a case of massive hepatic infarction, 1 2 x 1 0 x 7 cm in size, associated with PN showing fresh coagulative necrosis including both the .parenchyma and portal areas. Parker (6) stated that many of the dead cells in the areas of parenchymal necrosis were removed by the eighth day and that the lobular stroma tended to collapse. In the present case, there remained no evidence of fresh parenchymal necrosis. The left lobe was atrophic and consisted of stromal tissue. Although several attacks of abdominal pain and transient mild hepatic dysfunction were observed 3 weeks prior to death, the atrophy of the left hepatic lobe was already evident by CT scan on admission. It is uncertain whet her the infarction occurred without clinica I manif estation or whether chronic ischemia induced the disappearance of parenchymal cells, leaving the fibrotic stroma. Congenital absence of the left lobe of the liver is a rare condition (9). In this case, unfortunately, CT scan was not performed at the time of surgery for gastric cancer, and there were no details of hepatic lesions in the case record. However, coarse wrinkling of the capsule of the left lobe, indicative of atrophy after organ formation, and the fact that interlobular bile ducts were not atrophic and hepatocytes remained in small clusters in the fibrotic left lobe along with some degenerative changes make such a condition unlikely. Moreover, there was no evidence of cholelithiasis, bile duct obstruction or other vascular diseases. It seems that PN would involve the hepatic arteries and that an inflammatory reaction in the portal tracts could also involve the portal veins, which run close t o the main artery, inducing marked atrophy of the left lobe(10, 11). The malignancies associated with vasculitis reported in
666
PN with Hepatic Lobar Atrophy (Nakazawa et a/.)
the literature are hairy cell leukemia, lymphoma, multiple myeloma, and some carcinomas (12-14). instances of vasculitis have been reported to occur both before and after the onset of malignancy, and several explanations have been advanced for the possible relationship between them. Paraneoplastic v a s c u l i ti s u s u a l l y shows cutaneous or subcutaneous involvement, whereas visceral organ involvement or systemic vasculitis is rare (14). The present case showed marked systemic manifestations of vasculitis without recurrence of the cancer, and the clinical course was not consistent with drugs or Picibanil therapy. Therefore this case seems to have been not a secondary but a primary fo rm of PN, manifested as marked atrophy of the left hepatic lobe.
REFERENCES Arkin A. A clinical and pathological study of periarteritis nodosa. A report of five cases, one histologically healed. Am J Pathol 6: 401-431,1930. Nagasawa T. Polyarteritis nodosa. Byori to Rinsho 8: 1336-1340, 1 990 (in Japanese). Mowrey FH and Lundberg EA. The clinical rnanifestations of essential polyangiitis (periarteritis nodosa), with emphasis on the hepatic manifestations. Ann Intern Med 40: 1145-1164,1954. Nakanurna Y, Ohta G, and Sasaki K. Nodular regener.
ative hyperplasia of the liver associated with polyarteritis nodosa. Arch Pathol Lab Med 108: 133-135,
1984. 5. Carroll R. Infarction of the human liver. J Clin Pathol 16: 133-136,1963. 6. Parker RGF. Arterial infarction of the liver in man. J Pathol Bacteriol 70: 521-528,1955. 7. Seeley TT, Blumenfeld CM, lkeda R, Knapp W, and Ruebner BH. Hepatic infarction. Hum Pathol 3: 265-276,1972. 8. Haratake J, Horie A, Furuta A, and Yamato H. Massive hepatic infarction associated with polyarteritis nodosa. Acta Pathol Jpn 38: 89-93,1988. 9. Merrill GG. Complete absence of the left lobe of the liver. Arch Pathol 42: 232-233,1946. 10. Benz EJ, Baggenstoss AH, and Wollaeger EE. Atrophy of the left lobe of the liver. Arch Path0153 : 315-
330,1952. 11. Ham JM. Partial and complete atrophy affecting hepatic segments and lobes. Br J Surg 66: 333-337, 1979. 12. Elkon KB, Hughes GRV, and Catovsky D. Hairy-cell leukemia with polyarteritis nodosa. Lancet 2 : 280282, 1979. 13. Goedert JJ, Neefe JR, Smith FS, et a/. Polyarteritis nodosa, hairy cell leukemia and splenosis. Am J Med
71 : 323-326,1981. 14. Greer JM, Longley S, Edwards NL, Elfenbein GJ, and Panush RS. Vasculitis associated with malignancy : Experience with 13 patients and literature review. Medicine 67 : 220-230,1988.
