© Borgis - Postępy Nauk Medycznych 9/2012, s. 689-693
*Marek Hartleb1, Ewa Nowakowska-Duława1, Magdalena Lesińska1, Anna Koclęga2, Sławomira Kyrcz-Krzemień2, Jacek Pająk3, Jan Baron4
Pierwotna manifestacja wątrobowo-żółciowa choroby Hodgkina – opis przypadku
Primary hepatobiliary involvement in Hodgkin’s disease – a case report
1Department of Gastroenterology and Hepatology, Medical University of Silesia in Katowice
Head of Department: prof. Marek Hartleb, MD, PhD
2Department of Hematology and Bone Marrow Transplantation, Medical University of Silesia in Katowice
Head of Department: prof. Sławomira Kyrcz-Krzemień, MD, PhD
3Department of Pathomorphology, Medical University of Silesia in Katowice
Head of Department: Maciej Kajor, MD, PhD
4Department of Radiology, Medical University of Silesia in Katowice
Head of Department: Jan Baron, MD, PhD
Chłoniak Hodgkina jest zwykle chorobą ograniczoną do węzłów chłonnych. Zajęcie wątroby jest niekorzystnym czynnikiem prognostycznym, ponieważ na ogół występuje dopiero w późnej fazie tej choroby. Przedstawiono przypadek 48-letniego pacjenta, u którego chłoniak Hodgkina rozpoczął się jako gorączkowa choroba cholestatyczna z postępującą niewydolnością wątroby. Przyczyną cholestazy było zarówno ziarniniakowe zapalenie wątroby, jak i zwężenie żółciowego przewodu wątrobowego, naśladującego raka dróg żółciowych. Rozpoznanie choroby Hodgkina opierało się na badaniu histopatologicznym bioptatu wątrobowego, w którym ujawniono obecność nietypowych komórek limfoidalnych. Rozpoznanie to zostało potwierdzone w badaniu histopatologicznym pachowego węzła chłonnego. Mimo zastosowania leczenia endoskopowego i hematologicznego pacjent zmarł z powodu szybkiego postępu chłoniaka i niewydolności wątroby.
Hodgkin’s lymphoma is usually a lymph node-based disease. Liver involvement is an unfavorable prognostic factor, as it generally occurs in late stage of this disease. We present a case of 48-year old patient, in whom Hodgkin’s lymphoma started as cholestatic febrile disease with progressive liver failure. Cholestasis resulted from both the liver granulomatous hepatitis and stenosis of the hepatic biliary duct, imitating extrahepatic cholangiocarcinoma. The diagnosis of Hodgkin’s disease was based on liver histology showing atypical lymphocytic cells and later confirmed by examination of axillary lymph node. Despite specific endoscopic and hematological treatment the patient died due to aggressive course of lymphoma and liver failure.
In general, Hodgkin’s disease is a lymph node-based disease, which usually spreads along the lymphatic chain to contiguous lymph node areas. Liver involvement in Hodgkin’s disease depends on its stage – it is rare in early phase and common in end-stage of this disease. Consequently, less than 4% of patients with newly identified Hodgkin’s disease have significant hepatic symptoms (1). The liver was infiltrated with atypical lymphoid cells in 5-10% of cases in biopsy studies and in up to 50% of cases at autopsies (2, 3). Only occasionally the initial clinical presentation of Hodgkin’s disease comes from the liver. In such cases this hematological disease may imitate the primary liver or biliary tract disease. We present an unusual case of Hodgkin’s disease that started as cholestatic hepatopathy caused by both the granulomatous hepatitis and the stenosis of extrahepatic biliary duct.
A 48-year old man was admitted to local hospital because of cholestasis, loss of weight (20 kg over 6 months), night sweats and fever (March, 2011). He denied any abdominal pain. Four years earlier he underwent surgery due to perforation of small bowel and peritonitis secondary to blunt abdominal trauma. There was no history of viral hepatitis and he was not taking any medication. The patient was a farmer specialized in fruit growing. Each day he was smoking approximately 20 cigarettes and was drinking 3 cups of coffee.
An abdominal ultrasonography showed hepatosplenomegaly (the longitudinal span of the right hepatic lobe was 15 cm and that of spleen 13 cm). In the right hepatic lobe tumor-like lesions with the greatest diameter of 4 cm were visualized.
An abdominal computed tomography (CT) scan demonstrated enlarged and heterogenous liver with disseminated hypovascular focal lesions located in the segments 2, 5, 6 and 8. The spleen was enlarged and contained solid focal lesions suggestive of metastases (fig. 1). Besides, CT demonstrated multiple retroperitoneal and hepatic perihilar lymph nodes 10-13 mm in size. The pancreas was of normal size without focal lesions. An endoscopic retrograde cholangiopancreatography (ERCP) showed stenosis of the hepatic biliary duct at the level of the cystic duct. The intrahepatic biliary ducts were moderately dilated. The plastic stent 10 F 12 cm was inserted through the stenosis. It resulted in a decrease of serum bilirubin level from 4.5 to 0.8 mg/dl.
Fig. 1. Abdominal CT in portal venous phase shows hepatosplenomegaly with markedly heterogenous perfusion of the liver and large focal lesion within the spleen.
The liver biopsy showed features of granulomatous hepatitis with no evidence of malignant disease (April, 2011). The patient was referred to our department with strong suspicion of cholangiocarcinoma (July, 2011). The physical examination confirmed hepatosplenomegaly and disclosed mild bilateral enlargement of axillary (size 1-1.5 cm) and inguinal (size 1 cm) lymph nodes. The patient was febrile and used antipyretics. The administration of corticosteroids (prednisone 40 mg) justified by hepatic histology stopped the fever immediately. Relevant laboratory findings included: total bilirubin 3.2 mg/dl, alkaline phosphatase; ALP 622 IU/l (upper reference value 120 IU/l), gama-glutamyltranspetidase; GGTP 646 IU/l (upper reference value 55 IU/l), alanine aminotransferases; ALT 118 IU/l (upper reference value 45 IU/l), aspartate aminotransferases; AST 86 IU/l (upper reference value 35 IU/l) and C-reactive protein; CRP 74.6 mg/l (upper reference value 5 mg/l). Serological examinations for hepatitis A virus, hepatitis B virus, hepatitis C virus, human immunodeficiency virus and Epstein?Barr virus were negative. Tests for HCV RNA, antinuclear antibodies, antimitochondrial antibodies and anti-smooth muscle antibodies were also negative. The serum level of CA19-9 was 71.8 IU/l (upper reference value 39 IU/l). The Quantiferon test was negative.
During hospital follow-up the left-side anisocoria has occurred. For this reason the computed tomography of the brain and the chest radiography were performed. These examinations did not reveal any significant pathology.
Subsequently, the patient underwent second percutaneous liver biopsy that was examined by pathomorphologist experienced in diagnostics of lymphomas. The core including 12 portal areas was available for histological examination. The lobular architecture was preserved. The hepatocytes were swollen and showed features of canalicular and cytoplasmic cholestasis. Most of the portal tracts contained a mixed inflammatory infiltrate predominantly composed of lymphocytes. The infiltrate was mostly composed of T cells (CD3+, CD2+), although focally B cells (CD20+, CD79a+) were also seen. No eosinophils were identified. Several granulomas were found within the hepatic lobules. The granulomas were composed of histiocytic cells showing no signs of necrosis or polinuclearity and large lymphocytes showing ‘atypical’ nuclear features, such as angulated and enlarged nuclei and detectable small nucleoli. Immunohistochemical studies showed following immunophenotype of the atypical cells: CD30 (+), PAX5 (+), CD3 (-), CD2 (-), Alk-1 (-), CD20 (-), EMA (-), CD79a inconclusive and CD15 (-). Despite absence of classical Reed-Sternberg cells the diagnosis of Hodgkin’s disease has been proposed (fig. 2 A and B).
Fig. 2. Histology from the liver biopsy, stain H-E, 400x. Liver granuloma composed of large, atypical mononuclear cells of Hodgkin’s type (A). These cells stain positive for CD30 (B).
Consequently, the patient was transferred to hematological department for further diagnosis and specific treatment (August, 2011). On admission the hemoglobin level was 13.3 g/dl, the white blood cells count was 9.76 G/l and platelets count was 223 G/l. Among liver function tests the serum level of ALT was 107 IU/l, AST was 67 IU/l, ALP was 497 IU/l, GGTP was 459 IU/l and LDH was 285 IU/l (upper reference value 180 IU/l). The serum albumin level was 2.9 g/dl (reference range 3.5-5.0 g/dl) and serum IgG level was 4.2 g/l (reference range 7-16 g/l).
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