Hepatobiliary Malignancies in Wilson Disease
Hepatobiliary Malignancies in Wilson Disease
A total of 1186 patients with a confirmed diagnosis of WD were analysed. Fourteen cases (1.2%) of histologically confirmed hepatobiliary malignancies were detected (for details see Data S1 http://onlinelibrary.wiley.com/store/10.1111/liv.12727/asset/supinfo/liv12727-sup-0001-DataS1.docx?v=1&s=3b22f2c72de075aa9d6b1e66c3341e62fadf8e29).
Nine patients were male and five patients were female. The median age at time of initial diagnosis of WD was 29 (range 20–49) years. Five patients presented with hepatic manifestations only at the time of WD diagnosis, three patients presented with neurological manifestations and six patients had combined hepatic and neurological symptoms at the time of diagnosis. KFR were present in ten cases. Liver cirrhosis was evident in eleven cases at the time of WD diagnosis. Treatment of WD consisted of DPA in eight cases, zinc in one case and trientine in two cases. Three patients who initially were on DPA were switched to trientine due to intolerance to penicillamine.
Two patients (patient 1 and 5) reported daily alcohol consumption of 2–3 units/day. No patient presented with concomitant liver diseases.
The median age at time of cancer diagnosis was 53 (range 33–72) years. The median time between diagnosis of WD and tumour diagnosis was 20.5 (range 2–41) years. In eight patients histopathology revealed HCC, while ICC was diagnosed in six patients (see Table 1).
The incidence of hepatobiliary malignancies in this cohort was 0.28 per 1000 person years (see Table 2).
The histological analysis of tumour tissue of patients 1, 2, 3 and 13 revealed moderately differentiated ICC. Liver cirrhosis was present in the tumour adjacent tissue in all cases. Rhodanine staining of tumour samples showed no significant copper accumulation, in contrast to the surrounding liver tissue. In patient 5, histological analysis showed macrotrabecular poorly differentiated HCC with cirrhosis in the surrounding tissue. Rhodanine staining showed no abnormal copper accumulation of tumour tissue in contrast to tumour adjacent tissue (see Fig. 1).
(Enlarge Image)
Figure 1.
(A and B) Pathology specimen from patient 1 (moderately differentiated ICC). (C and D) Pathology specimen from patient 5 (poorly differentiated HCC). Left: Haematoxylin staining. Right: Rhodanine staining. Arrows: Tumour, NL: Normal liver tissue
Results
Patient Characteristics
A total of 1186 patients with a confirmed diagnosis of WD were analysed. Fourteen cases (1.2%) of histologically confirmed hepatobiliary malignancies were detected (for details see Data S1 http://onlinelibrary.wiley.com/store/10.1111/liv.12727/asset/supinfo/liv12727-sup-0001-DataS1.docx?v=1&s=3b22f2c72de075aa9d6b1e66c3341e62fadf8e29).
Nine patients were male and five patients were female. The median age at time of initial diagnosis of WD was 29 (range 20–49) years. Five patients presented with hepatic manifestations only at the time of WD diagnosis, three patients presented with neurological manifestations and six patients had combined hepatic and neurological symptoms at the time of diagnosis. KFR were present in ten cases. Liver cirrhosis was evident in eleven cases at the time of WD diagnosis. Treatment of WD consisted of DPA in eight cases, zinc in one case and trientine in two cases. Three patients who initially were on DPA were switched to trientine due to intolerance to penicillamine.
Two patients (patient 1 and 5) reported daily alcohol consumption of 2–3 units/day. No patient presented with concomitant liver diseases.
The median age at time of cancer diagnosis was 53 (range 33–72) years. The median time between diagnosis of WD and tumour diagnosis was 20.5 (range 2–41) years. In eight patients histopathology revealed HCC, while ICC was diagnosed in six patients (see Table 1).
The incidence of hepatobiliary malignancies in this cohort was 0.28 per 1000 person years (see Table 2).
Histopathology
The histological analysis of tumour tissue of patients 1, 2, 3 and 13 revealed moderately differentiated ICC. Liver cirrhosis was present in the tumour adjacent tissue in all cases. Rhodanine staining of tumour samples showed no significant copper accumulation, in contrast to the surrounding liver tissue. In patient 5, histological analysis showed macrotrabecular poorly differentiated HCC with cirrhosis in the surrounding tissue. Rhodanine staining showed no abnormal copper accumulation of tumour tissue in contrast to tumour adjacent tissue (see Fig. 1).
(Enlarge Image)
Figure 1.
(A and B) Pathology specimen from patient 1 (moderately differentiated ICC). (C and D) Pathology specimen from patient 5 (poorly differentiated HCC). Left: Haematoxylin staining. Right: Rhodanine staining. Arrows: Tumour, NL: Normal liver tissue