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Adult polycystic liver disease with cutaneous involvement: A brief report
CASE REPORT
Adult Polycystic Liver Disease With Cutaneous Involvement: A Brief Report Jerome T. O'ConnellJr, MD, and KlausJ. Lewin, MD, FRCPath This case report documents the largest example of adult polycystic liver disease reported to date. In addition, the patient was found to have numerous subcutaneous cysts, an association with polycystic disease, which, as far as we could determine from the literature, has not previously been reported. Ann Diagn Pathol 2: 121-124, 1998. Copyright © 1998 by W.B. Saunders Company Index Words: Subcutaneous cysts, polycystic kidneys, epithelium
OVERWHELMING majority of adult polycysi tic liver disease cases are associated with polycystic kidney disease and are inherited in an autosomal dominant manner. 1 An isolated form of polycystic liver disease has recently been described? In addition to the polycystic lesions of the liver and kidney, other associations have been described such as colonic diverticula, cardiac valve complications, ovarian cysts, inguinal hernia, and intracranial aneurysms, s Numerous subcutaneous cysts, as far as we could determine from the literature, ihas not been previously reported. Case Report
A 42-year-old white woman with combined adult polycystic liver and kidney disease was admitted to the hospital to undergo orthotopic liver transplantation for symptomatic hepatomegaly and concomitant resection of cellulitis on her anterior abdominal wall. Her symptoms included abdominal distention, early satiety, shortness of breath, fatigue, bilateral 3 + pitting edema of the lower extremities, and abdominal cellulitis. She had chronic renal insufficiency with a creatinine level of 1.6 mmol/L on admission. There was no evidence of hepatic insufficiency. Her disease was diagnosed 13 years previously while undergoing ultrasound examination of her third pregnancy. On admission computed tomography of the abdomen revealed bilateral polycystic kidneys, massive polycystic hepatomegaly with evidence of ventral herniation, bilat-
From the Department of Pathology, UCLA Medical Center, Los Angeles, CA," and Departmenl!of'Pathology, UCLA Medical Center,Los Angeles, CA. Address correspondenceand reprint requests to KlausJ. Lewin, MD, FRCPath~ Department of Pathology, UCLA Medical Center, Los Angeles, CA 90095. Copyright © 1998 by I4~B. Saunders Company 1092-9134/98/0202/0004508.00/0
eral ovarian cysts, and ascites. It was estimated that greater than 90% of her liver was cystic. She underwent successful transplantation and abdominal skin resection. Her postsurgical course was uneventful.
Pathological Findings
The liver measured 41.5 × 40.5 × 17 cm, weighed 10.7 kg and contained approximately 5 L of fluid. It contained innumerable serous-filled clear cysts, which were largely noncommunicating with one another and not communicating with the biliary tree. The skin and subcutaneous tissue of the anterior abdominal wall revealed dense fibrous tissue with cystic cavities. Microscopically most of the cysts in the liver were lined by cuboidal epithelium resembling biliary epithelium. In some of the larger cysts, the epithelium was markedly attenuated. Many of the cysts were associated with yon Meyenburg complexes. The functional residual liver parenchyma constituted less than 1% of the specimen and revealed edematous hepatocytes and mild parenchymal fibrosis, but othmwise minimal histological changes were seen. Sections of skin and subcutaneous tissue from the anterior abdominal wall demonstrated numerous subcutaneous cysts also focally lined by cuboidal epithelium. The cysts ranged from several millimeters to several centimeters in diameter, many of which had no lining epithelia; however, the others revealed a cuboidal epithelial lining. Cysts were intimately surrounded by a lymphoplasmacytic infiltrate that focally extended into adjacent tissue. The surrounding subcutaneous tissue revealed marked edema, granulation tissue, and fibrosis.
Annals of Diagnostic Pathology, Vol 2, No 2 (April), 1998: pp 12t-124
121
122
O'Connell and Lewin
Figure 1. Gross picture of skin and subcutaneous tissue from the abdominal wall demonstrating a large cystic cavity and several smaller cysts. Discussion
The overwhelming majority of adult polycystic liver disease cases are associated with polycystic kidney disease and are inherited in an autosomal dominant manner.1 It has been demonstrated that the responsible allele is linked to either the PKD1 locus on the short arm of chromosome 16 or less commonly to the PKD2 locus, a less severe form. 4 The estimated incidence of the PKD1 allele is 1 in 1,000 and a spontaneous mutation rate of less than 10%. An isolated form of
Figure 2, Microscopic picture of the liver parenchyma with multiple cysts associated with a von Meyenburg complex.
polycystic liver disease not associated with kidney disease has been recently described. 2 The disease course of patients with polycystic liver disease is usually asymptomatic in its early stages. Henson et al 5 reported that the average age for admission for hepatic symptoms was 52.8 years with the duration of symptoms being approximately 3 years. The most frequent hepatic symptoms are a gradually enlarging liver, upper abdominal discomfort or pain with or without nausea, and occasionally vomiting and fever.
Polycystic Liver Disease
Figure 3. Microscopic picture of
123
:~
cysts in the subcutaneous tissue.
Hepatomegaly is the most common physical finding. Evidence of biliary obstruction or portal hypertension is rare. Liver function tests are normal in most instances. 3 The major pathologic features of this disease consist of multiple hepatic cysts ranging in size from a few millimeters; to greater than 12 cm. The cysts contain a serous fluid. Melnick's review6 of autopsy cases reported
Figure 4. High-power view of the epithelial lining of the subcutaneous cysts demonstrating their cuboidal architecture.
that approximately 90% of the cysts are lined by cuboidal epithelium. The remaining had attenuated flat cells resulting from hydrostatic pressure or lacked an epithelial lining3 Similar features were present in our case, as was the finding that many of the cysts originated from von Meyenburg complexes. As the cysts increase in size, the liver becomes greatly enlarged, in this case weighing 10.7 kg, 3 kg heavier than the previously reported largest specimen, which weighed 7.7 kg. 7 The most common hepatic complications of adult polycystic disease are from infection of the cysts and cholangiocarcinoma. The incidence of infection ranges from 1% in otherwise healthy individuals to over 3% in patients with renal failure.3 In addition, a number of commonly reported associated conditions have been described such as colonic diverticula, cardiac valve anomalies, ovarian cysts, inguinal hernia, and intracranial aneurysms. These varied and heterogeneous anomalies have led many to speculate there is a systemic abnormality of organic matrix material. ~ An unusual finding in our patient not .previously described was the numerous subcutaneous cysts. This finding may further support the idea of a systemic matrix abnormality. A second potential etiology could be direct extension of cysts from the enlarging, ventrally herniating liver into the overlying subcutaneous tissue. Metastatic seeding of the cysts seems highly unlikely but the cellulitis and associated tissue damage in the subcutis may have provided the cyst epithelial cells with fertile ground for implantation.
124
O'Connell and Lewin References
1. Pirson Y, Grunfeld JP: Autosomal dominant polycystic kidney disease, in CameonJS, Davidson AM, GrunfeldJP, et at (eds). Oxford Textbook of Clinical Nephrology. New York, Oxford University Press, 1992, pp 2171-2188 2. Pirson Y, Lannoy N, Peters D, et ah Isolated polycystic liver disease as a distinct genetic disease, unlinked to polycystic kidney disease 1 and polycystic kidney disease 2. Hepatology 1996;23:249-252 3. Ishak KG, Sharp HL: Developmental abnormalities and liver disease in childhood, in MacSween RNM, Anthony PP, Scheur PJ, et al
(eds). Pathology of the Liver. New York, Churchill Livingstone, I994, pp 98-103 4. Pirson Y, Lannoy N, Verellen-Dumoulin C. A family with unlinked PKDI and marked liver involvement. Nephrol Dial Transplant 1992;7:975A 5. Henson SWJr, Gray HK, Doekerty MB: Benign tumors of the liver HI. Solitary cysts. Surg Gynecol Obstet 1956;103:607-612 6. Melnick PJ: Polycystieliver. Arch Pathol 1955;59:162 7. Kwok MK, Lewin KJ: Massive hepatomegaly in adult polycystic liver disease. AmJ Surg Pathol 1988;12:321-324
Adult Polycystic Liver Disease With Cutaneous Involvement: A Brief Report Jerome T. O'ConnellJr, MD, and KlausJ. Lewin, MD, FRCPath This case report documents the largest example of adult polycystic liver disease reported to date. In addition, the patient was found to have numerous subcutaneous cysts, an association with polycystic disease, which, as far as we could determine from the literature, has not previously been reported. Ann Diagn Pathol 2: 121-124, 1998. Copyright © 1998 by W.B. Saunders Company Index Words: Subcutaneous cysts, polycystic kidneys, epithelium
OVERWHELMING majority of adult polycysi tic liver disease cases are associated with polycystic kidney disease and are inherited in an autosomal dominant manner. 1 An isolated form of polycystic liver disease has recently been described? In addition to the polycystic lesions of the liver and kidney, other associations have been described such as colonic diverticula, cardiac valve complications, ovarian cysts, inguinal hernia, and intracranial aneurysms, s Numerous subcutaneous cysts, as far as we could determine from the literature, ihas not been previously reported. Case Report
A 42-year-old white woman with combined adult polycystic liver and kidney disease was admitted to the hospital to undergo orthotopic liver transplantation for symptomatic hepatomegaly and concomitant resection of cellulitis on her anterior abdominal wall. Her symptoms included abdominal distention, early satiety, shortness of breath, fatigue, bilateral 3 + pitting edema of the lower extremities, and abdominal cellulitis. She had chronic renal insufficiency with a creatinine level of 1.6 mmol/L on admission. There was no evidence of hepatic insufficiency. Her disease was diagnosed 13 years previously while undergoing ultrasound examination of her third pregnancy. On admission computed tomography of the abdomen revealed bilateral polycystic kidneys, massive polycystic hepatomegaly with evidence of ventral herniation, bilat-
From the Department of Pathology, UCLA Medical Center, Los Angeles, CA," and Departmenl!of'Pathology, UCLA Medical Center,Los Angeles, CA. Address correspondenceand reprint requests to KlausJ. Lewin, MD, FRCPath~ Department of Pathology, UCLA Medical Center, Los Angeles, CA 90095. Copyright © 1998 by I4~B. Saunders Company 1092-9134/98/0202/0004508.00/0
eral ovarian cysts, and ascites. It was estimated that greater than 90% of her liver was cystic. She underwent successful transplantation and abdominal skin resection. Her postsurgical course was uneventful.
Pathological Findings
The liver measured 41.5 × 40.5 × 17 cm, weighed 10.7 kg and contained approximately 5 L of fluid. It contained innumerable serous-filled clear cysts, which were largely noncommunicating with one another and not communicating with the biliary tree. The skin and subcutaneous tissue of the anterior abdominal wall revealed dense fibrous tissue with cystic cavities. Microscopically most of the cysts in the liver were lined by cuboidal epithelium resembling biliary epithelium. In some of the larger cysts, the epithelium was markedly attenuated. Many of the cysts were associated with yon Meyenburg complexes. The functional residual liver parenchyma constituted less than 1% of the specimen and revealed edematous hepatocytes and mild parenchymal fibrosis, but othmwise minimal histological changes were seen. Sections of skin and subcutaneous tissue from the anterior abdominal wall demonstrated numerous subcutaneous cysts also focally lined by cuboidal epithelium. The cysts ranged from several millimeters to several centimeters in diameter, many of which had no lining epithelia; however, the others revealed a cuboidal epithelial lining. Cysts were intimately surrounded by a lymphoplasmacytic infiltrate that focally extended into adjacent tissue. The surrounding subcutaneous tissue revealed marked edema, granulation tissue, and fibrosis.
Annals of Diagnostic Pathology, Vol 2, No 2 (April), 1998: pp 12t-124
121
122
O'Connell and Lewin
Figure 1. Gross picture of skin and subcutaneous tissue from the abdominal wall demonstrating a large cystic cavity and several smaller cysts. Discussion
The overwhelming majority of adult polycystic liver disease cases are associated with polycystic kidney disease and are inherited in an autosomal dominant manner.1 It has been demonstrated that the responsible allele is linked to either the PKD1 locus on the short arm of chromosome 16 or less commonly to the PKD2 locus, a less severe form. 4 The estimated incidence of the PKD1 allele is 1 in 1,000 and a spontaneous mutation rate of less than 10%. An isolated form of
Figure 2, Microscopic picture of the liver parenchyma with multiple cysts associated with a von Meyenburg complex.
polycystic liver disease not associated with kidney disease has been recently described. 2 The disease course of patients with polycystic liver disease is usually asymptomatic in its early stages. Henson et al 5 reported that the average age for admission for hepatic symptoms was 52.8 years with the duration of symptoms being approximately 3 years. The most frequent hepatic symptoms are a gradually enlarging liver, upper abdominal discomfort or pain with or without nausea, and occasionally vomiting and fever.
Polycystic Liver Disease
Figure 3. Microscopic picture of
123
:~
cysts in the subcutaneous tissue.
Hepatomegaly is the most common physical finding. Evidence of biliary obstruction or portal hypertension is rare. Liver function tests are normal in most instances. 3 The major pathologic features of this disease consist of multiple hepatic cysts ranging in size from a few millimeters; to greater than 12 cm. The cysts contain a serous fluid. Melnick's review6 of autopsy cases reported
Figure 4. High-power view of the epithelial lining of the subcutaneous cysts demonstrating their cuboidal architecture.
that approximately 90% of the cysts are lined by cuboidal epithelium. The remaining had attenuated flat cells resulting from hydrostatic pressure or lacked an epithelial lining3 Similar features were present in our case, as was the finding that many of the cysts originated from von Meyenburg complexes. As the cysts increase in size, the liver becomes greatly enlarged, in this case weighing 10.7 kg, 3 kg heavier than the previously reported largest specimen, which weighed 7.7 kg. 7 The most common hepatic complications of adult polycystic disease are from infection of the cysts and cholangiocarcinoma. The incidence of infection ranges from 1% in otherwise healthy individuals to over 3% in patients with renal failure.3 In addition, a number of commonly reported associated conditions have been described such as colonic diverticula, cardiac valve anomalies, ovarian cysts, inguinal hernia, and intracranial aneurysms. These varied and heterogeneous anomalies have led many to speculate there is a systemic abnormality of organic matrix material. ~ An unusual finding in our patient not .previously described was the numerous subcutaneous cysts. This finding may further support the idea of a systemic matrix abnormality. A second potential etiology could be direct extension of cysts from the enlarging, ventrally herniating liver into the overlying subcutaneous tissue. Metastatic seeding of the cysts seems highly unlikely but the cellulitis and associated tissue damage in the subcutis may have provided the cyst epithelial cells with fertile ground for implantation.
124
O'Connell and Lewin References
1. Pirson Y, Grunfeld JP: Autosomal dominant polycystic kidney disease, in CameonJS, Davidson AM, GrunfeldJP, et at (eds). Oxford Textbook of Clinical Nephrology. New York, Oxford University Press, 1992, pp 2171-2188 2. Pirson Y, Lannoy N, Peters D, et ah Isolated polycystic liver disease as a distinct genetic disease, unlinked to polycystic kidney disease 1 and polycystic kidney disease 2. Hepatology 1996;23:249-252 3. Ishak KG, Sharp HL: Developmental abnormalities and liver disease in childhood, in MacSween RNM, Anthony PP, Scheur PJ, et al
(eds). Pathology of the Liver. New York, Churchill Livingstone, I994, pp 98-103 4. Pirson Y, Lannoy N, Verellen-Dumoulin C. A family with unlinked PKDI and marked liver involvement. Nephrol Dial Transplant 1992;7:975A 5. Henson SWJr, Gray HK, Doekerty MB: Benign tumors of the liver HI. Solitary cysts. Surg Gynecol Obstet 1956;103:607-612 6. Melnick PJ: Polycystieliver. Arch Pathol 1955;59:162 7. Kwok MK, Lewin KJ: Massive hepatomegaly in adult polycystic liver disease. AmJ Surg Pathol 1988;12:321-324