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Focal nodular hyperplasia contiguous with an echinococcal cyst
THE AMERICAN JOURNAL OF GASTROENTEROLOGY © 2000 by Am. Coll. of Gastroenterology Published by Elsevier Science Inc.
Vol. 95, No. 4, 2000 ISSN 0002-9270/00/$20.00 PII S0002-9270(00)00739-5
Focal Nodular Hyperplasia Contiguous With an Echinococcal Cyst Jeffrey A. Komisarof, M.D., Kimberly Olthoff, M.D., Evan S. Siegelman, M.D., Thomas J. Lawton, M.D., and Emma E. Furth, M.D. Departments of Pathology and Laboratory Medicine, Surgery, Radiology, and Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
ABSTRACT We report the first case of an Echinococcal cyst and focal nodular hyperplasia, two usually isolated hepatic lesions, in direct contiguity. The patient presented with right upper quadrant pain and subsequent imaging studies found a cystic and solid lesion. These studies suggested that this lesion was an hepatic adenoma, which had bled forming a hematoma. Pathological examination of the surgical resection showed Echinococcus multilocularis with contiguous focal nodular hyperplasia. Because focal nodular hyperplasia is a benign hepatic lesion the etiology of which is thought to be abnormal arterial blood flow, we postulate that the parasitic hepatic infection by E. multilocularis may have incited the formation of this contiguous hepatic lesion. (Am J Gastroenterol 2000;95:1078 –1081. © 2000 by Am. Coll. of Gastroenterology)
INTRODUCTION Echinococcal cysts and focal nodular hyperplasia (FNH) are two usually independent and isolated entities that may present as solitary, incidental, liver masses. Echinococcosis is a parasitic disease of humans caused by the cestodes Echinococcus granulosus, E. multilocularis, and E. vogeli. These parasites are found widespread throughout the world. Liver and lung are the organs most commonly affected. Depending on the species involved, hepatic lesions can have different gross and radiological appearances, but generally consist of an isolated cystic lesion. Focal nodular hyperplasia has been defined as a lesion of hyperplastic hepatic parenchyma within and around which there is a large anomalous artery (1). FNH has been shown to be variably associated with vascular and neoplastic lesions, both in the liver and in other organs, such as hepatic hemangioma, portal vein atresia, meningioma, astrocytoma, telangiectasias of the brain, berry aneurysm, and dysplastic systemic arteries (2). Although FNH can rarely be multiple, it is most commonly an isolated lesion. The differential diagnosis of an incidental liver lesion is broad, including infectious, benign, and neoplastic entities. The radiographic appearance of several lesions is often but not invariably characteristic, with Echinococcus multilocu-
laris cysts displaying calcifications among the multiloculated structures, and FNH showing a central scar. However, definitive diagnosis is usually based upon pathological examination. We report the first case in the literature of an Echinococcal cyst that is contiguous with focal nodular hyperplasia, two usually isolated and unassociated hepatic pathologies. The leading diagnosis, based upon the clinical presentation and imaging studies, was a hemorrhagic hepatic adenoma.
CASE REPORT The patient is a 29-yr-old white woman with no significant past medical history who used oral contraceptives for 6 yr and had a distant travel history to Morocco and a more recent travel history to northern Europe. She presented with right sided flank pain approximately 6 months after she was involved in a motor vehicle accident. Urinalysis was negative, and further laboratory workup including liver function tests was unremarkable. Abdominal ultrasound showed an abnormal liver with regions of abnormal increased and decreased echogenicity. A CT of the abdomen revealed a 6.2 ⫻ 4.5 cm mass in the posterior right hepatic lobe with a differential diagnosis of a cavernous hemangioma, a hepatic laceration (most likely from her accident) that had become a hematoma, a complicated hepatic cyst, or a hepatic adenoma. At this point, the patient discontinued her oral contraceptives, and subsequently underwent MRI of the abdomen, which showed a 5 ⫻ 4.8 ⫻ 4.3 cm complex cystic lesion in the posterior right hepatic lobe compatible with a chronic seroma or hematoma. Adjacent to this cystic lesion was a 1.9 ⫻ 0.9 ⫻ 0.9 cm mass that was characterized as a hepatocellular neoplasm and was thought to represent a hepatic adenoma, given the patient’s age, sex, and use of oral contraceptives (Fig. 1). The working hypothesis was that she had a hepatic adenoma that hemorrhaged, creating a large, adjacent cyst. Because the possibility of a malignant neoplasm could not be completely excluded, the lesion was removed by a right hepatic lobectomy.
AJG – April, 2000
Focal Nodular Hyperplasia and Echinococcal Cyst
1079
Figure 1. Axial T1-weighted gradient echo image obtained after the i.v. administration of gadolinium contrast shows no internal enhancement within the cyst, minimal irregular cyst wall enhancement, and moderate homogeneous enhancement of the hepatocellular neoplasm (arrows).
Figure 3. Gross image of focal nodular hyperplasia (light arrow) contiguous with the wall of the Echinococcus multilocularis cyst (dark arrows). This firm, tan, well-circumscribed lesion is surrounded by the darker normal hepatic parenchyma.
Figure 2. Gross image of an Echinococcus multilocularis cyst. The white fibrous wall of the cyst, and the multiple daughter cysts within, filled with serous fluid, are shown. At the periphery of the image is the darker normal surrounding hepatic parenchyma.
Pathology A portion of liver measuring 15 ⫻ 11.5 ⫻ 7 cm was received and cross sectioning revealed a well-encapsulated cyst measuring 6 ⫻ 4 ⫻ 3 cm. The cyst was filled with multiple daughter cysts ranging in size from 0.2 to 0.5 cm, which contained yellowish serous fluid consistent with Echinococcus multilocularis (Fig. 2). Contiguous with the cyst was a firm, tan, well-circumscribed mass measuring 1.7 ⫻ 0.9 ⫻ 0.6 cm (Fig. 3). The remainder of the hepatic parenchyma appeared unremarkable. On microscopic examination, the larger lesion was composed of a fibrous, walled cyst containing hooklets and intact organisms, consistent with Echinococcus multilocularis. The contiguous, smaller mass was diagnosed as focal nodular hyperplasia (Fig. 4). Specifically, the area of focal nodular hyperplasia contained fibrous bands with bile ducts, bile ductual proliferation, and dysplastic arteries with intervening nodular hepatic parenchyma with variably present central veins. The nodule was well demarcated from the normal surrounding liver by a rim of the aforementioned fibrotic bands. Importantly, the portal tracts with emanating bands of fibrosis blended directly with
1080
Komisarof et al.
AJG – Vol. 95, No. 4, 2000
Figure 4. Histology of focal nodular hyperplasia (A) with contiguous cyst wall (B). (A) The focal nodular hyperplasia shows nodular hepatocellular proliferation with intervening fibrotic septae containing bile ducts (straight arrow) and arteries (curved arrow). (B) The contiguous cyst wall (asterisk) blends with the emanating fibrotic septae (arrowheads) containing abnormal arteries (curved arrow) going into the area of focal nodular hyperplasia (hematoxylin and eosin, A: ⫻25; B: ⫻40).
the echinococcal cyst wall. The lesion did not, however, contain the central scar that is commonly seen in FNH. The patient’s gallbladder was also received and was unremarkable.
DISCUSSION We report the first case of an Echinococcal cyst and FNH occurring in direct contiguity. These two entities are rare and usually isolated lesions. This patient had E. multilocularis as shown by the multiple cyst in contrast to the unilocular cysts seen with E. granulosa. Because E. multilocularis is found in subarctic or arctic regions (including the United States, Canada, and northern Europe), this patient may have acquired the disease either in northern Europe or at home in the US. Surgical excision, followed by a course the antiparasitic agent albendazole, was the appropriate therapeutic procedure for this lesion. Focal nodular hyperplasia is a hepatic lesion of disputed and still unknown etiology. How-
ever, recent evidence seems to support a vascular pathogenesis, with various authors contending that increased pressure in portal veins or arteriovenous malformations (3) and increased regional blood flow (1) are responsible. They occur more often in women, as do hepatic adenomas; however, unlike the strong association of hepatic adenomas, they seem to be associated weakly or not at all with the use of oral contraceptives. FNH is usually an asymptomatic lesion (75% of the time), which is often discovered incidentally on imaging studies or laparotomy done for other indications. However, occasionally it can be felt as a nontender mass in the right upper quadrant. There is a slight risk of hemorrhage or necrosis in large lesions, which can be a source of right upper quadrant pain to the patient; the risk seems to be increased with the use of oral contraceptives. However, the occurrence of these complications is far less likely than that seen with hepatic adenomas (4). The finding of two uncommon lesions in contiguity with each other suggests a causative relation. The mechanism by
AJG – April, 2000
which this may have occurred is only speculative, but if we believe the argument of Wanless et al. that increased blood flow to a region of the liver may be pathogenic in FNH, it seems tenable that the hyperemic rim of the Echinococcal cyst (which was faintly rim enhancing on MRI) may have caused the development of an adjacent focus of FNH. What role the patient’s prior use of oral contraceptives may have played in the subsequent development of the FNH is not known, as they have no real role in its de novo development. An alternative hypothesis is that the Echinococcus organisms came to rest next to a pre-existing focus of FNH. However, because the organisms are thought to be carried primarily in the venous system from gut lumen and because the primary vasculature present in FNH are anomalous arteries, this hypothesis is less likely than the former. There have been cases reported in which foci of FNH were found adjacent to cavernous hemangiomas (2, 5) and to sclerotic vascular lesions (2). Other cases have documented FNH or lesions resembling FNH in association with cirrhosis (6), chronic hepatitis (6), glycogen storage disease type I (7), and fibrolamellar carcinoma (8). However, this is the first reported case of focal nodular hyperplasia associated with an Echinococcal cyst.
ACKNOWLEDGMENTS Special thanks are given to Drs. Matt van de Rijn and Cindy McGrath for their help in editing this work and to Ms. Lisa Bostic for the manuscript preparation.
Focal Nodular Hyperplasia and Echinococcal Cyst
1081
Reprint requests and correspondence: Emma E. Furth, M.D., Hospital of the University of Pennsylvania, 6 Founders, 3400 Spruce Street, Philadelphia, PA 19104 – 4283. Received July16, 1998; accepted Jan. 4, 1999.
REFERENCES 1. Wanless IR, Mawdsley C, Adams R. On the pathogenesis of focal nodular hyperplasia of the liver. Hepatology 1985;5: 1194 –2000. 2. Wanless IR, Albrecht S, Bilbao J, et al. Multiple focal nodular hyperplasia of the liver associated with vascular malformations of various organs and neoplasia of the brain: A new syndrome. Modern Pathol 1989;2:456 – 62. 3. Travers H, D’Amato NA. Vascular alterations in focal nodular hyperplasia of the liver. Milit Med 1978;143:96 –101. 4. Zakim D, Boyer TD. Hepatology. A textbook of liver disease, 2nd ed. Philadelphia: WB Saunders, 1990. 5. Ndimbie OK, Goodman ZD, Chase RL, et al. Hemangiomas with localized nodular proliferation of the liver: A suggestion of the pathogenesis of focal nodular hyperplasia. Am J Surg Pathol 1990;14:142–50. 6. Terada T, Kitani S, Ueda K, et al. Adenomatous hyperplasia of the liver resembling focal nodular hyperplasia in patients with chronic liver disease. Virchows Archiv A, Pathological Anatomy & Histopathology 1993;422:247–52. 7. Sakatoku H, Hirokawa Y, Inoue M, et al. Focal nodular hyperplasia in an adolescent with glycogen storage disease type I with mesocaval shunt operation in childhood: A case report and review of the literature. Acta Paediatrica Japonica 1996;38:172–5. 8. Saxena R, Humphreys S, Williams R, et al. Nodular hyuperplasia surrounding fibrolamellar carcinoma. A zone of arterialized liver parenchyma. Histopathology 1994;25:275– 8.
Vol. 95, No. 4, 2000 ISSN 0002-9270/00/$20.00 PII S0002-9270(00)00739-5
Focal Nodular Hyperplasia Contiguous With an Echinococcal Cyst Jeffrey A. Komisarof, M.D., Kimberly Olthoff, M.D., Evan S. Siegelman, M.D., Thomas J. Lawton, M.D., and Emma E. Furth, M.D. Departments of Pathology and Laboratory Medicine, Surgery, Radiology, and Medicine, Hospital of the University of Pennsylvania, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
ABSTRACT We report the first case of an Echinococcal cyst and focal nodular hyperplasia, two usually isolated hepatic lesions, in direct contiguity. The patient presented with right upper quadrant pain and subsequent imaging studies found a cystic and solid lesion. These studies suggested that this lesion was an hepatic adenoma, which had bled forming a hematoma. Pathological examination of the surgical resection showed Echinococcus multilocularis with contiguous focal nodular hyperplasia. Because focal nodular hyperplasia is a benign hepatic lesion the etiology of which is thought to be abnormal arterial blood flow, we postulate that the parasitic hepatic infection by E. multilocularis may have incited the formation of this contiguous hepatic lesion. (Am J Gastroenterol 2000;95:1078 –1081. © 2000 by Am. Coll. of Gastroenterology)
INTRODUCTION Echinococcal cysts and focal nodular hyperplasia (FNH) are two usually independent and isolated entities that may present as solitary, incidental, liver masses. Echinococcosis is a parasitic disease of humans caused by the cestodes Echinococcus granulosus, E. multilocularis, and E. vogeli. These parasites are found widespread throughout the world. Liver and lung are the organs most commonly affected. Depending on the species involved, hepatic lesions can have different gross and radiological appearances, but generally consist of an isolated cystic lesion. Focal nodular hyperplasia has been defined as a lesion of hyperplastic hepatic parenchyma within and around which there is a large anomalous artery (1). FNH has been shown to be variably associated with vascular and neoplastic lesions, both in the liver and in other organs, such as hepatic hemangioma, portal vein atresia, meningioma, astrocytoma, telangiectasias of the brain, berry aneurysm, and dysplastic systemic arteries (2). Although FNH can rarely be multiple, it is most commonly an isolated lesion. The differential diagnosis of an incidental liver lesion is broad, including infectious, benign, and neoplastic entities. The radiographic appearance of several lesions is often but not invariably characteristic, with Echinococcus multilocu-
laris cysts displaying calcifications among the multiloculated structures, and FNH showing a central scar. However, definitive diagnosis is usually based upon pathological examination. We report the first case in the literature of an Echinococcal cyst that is contiguous with focal nodular hyperplasia, two usually isolated and unassociated hepatic pathologies. The leading diagnosis, based upon the clinical presentation and imaging studies, was a hemorrhagic hepatic adenoma.
CASE REPORT The patient is a 29-yr-old white woman with no significant past medical history who used oral contraceptives for 6 yr and had a distant travel history to Morocco and a more recent travel history to northern Europe. She presented with right sided flank pain approximately 6 months after she was involved in a motor vehicle accident. Urinalysis was negative, and further laboratory workup including liver function tests was unremarkable. Abdominal ultrasound showed an abnormal liver with regions of abnormal increased and decreased echogenicity. A CT of the abdomen revealed a 6.2 ⫻ 4.5 cm mass in the posterior right hepatic lobe with a differential diagnosis of a cavernous hemangioma, a hepatic laceration (most likely from her accident) that had become a hematoma, a complicated hepatic cyst, or a hepatic adenoma. At this point, the patient discontinued her oral contraceptives, and subsequently underwent MRI of the abdomen, which showed a 5 ⫻ 4.8 ⫻ 4.3 cm complex cystic lesion in the posterior right hepatic lobe compatible with a chronic seroma or hematoma. Adjacent to this cystic lesion was a 1.9 ⫻ 0.9 ⫻ 0.9 cm mass that was characterized as a hepatocellular neoplasm and was thought to represent a hepatic adenoma, given the patient’s age, sex, and use of oral contraceptives (Fig. 1). The working hypothesis was that she had a hepatic adenoma that hemorrhaged, creating a large, adjacent cyst. Because the possibility of a malignant neoplasm could not be completely excluded, the lesion was removed by a right hepatic lobectomy.
AJG – April, 2000
Focal Nodular Hyperplasia and Echinococcal Cyst
1079
Figure 1. Axial T1-weighted gradient echo image obtained after the i.v. administration of gadolinium contrast shows no internal enhancement within the cyst, minimal irregular cyst wall enhancement, and moderate homogeneous enhancement of the hepatocellular neoplasm (arrows).
Figure 3. Gross image of focal nodular hyperplasia (light arrow) contiguous with the wall of the Echinococcus multilocularis cyst (dark arrows). This firm, tan, well-circumscribed lesion is surrounded by the darker normal hepatic parenchyma.
Figure 2. Gross image of an Echinococcus multilocularis cyst. The white fibrous wall of the cyst, and the multiple daughter cysts within, filled with serous fluid, are shown. At the periphery of the image is the darker normal surrounding hepatic parenchyma.
Pathology A portion of liver measuring 15 ⫻ 11.5 ⫻ 7 cm was received and cross sectioning revealed a well-encapsulated cyst measuring 6 ⫻ 4 ⫻ 3 cm. The cyst was filled with multiple daughter cysts ranging in size from 0.2 to 0.5 cm, which contained yellowish serous fluid consistent with Echinococcus multilocularis (Fig. 2). Contiguous with the cyst was a firm, tan, well-circumscribed mass measuring 1.7 ⫻ 0.9 ⫻ 0.6 cm (Fig. 3). The remainder of the hepatic parenchyma appeared unremarkable. On microscopic examination, the larger lesion was composed of a fibrous, walled cyst containing hooklets and intact organisms, consistent with Echinococcus multilocularis. The contiguous, smaller mass was diagnosed as focal nodular hyperplasia (Fig. 4). Specifically, the area of focal nodular hyperplasia contained fibrous bands with bile ducts, bile ductual proliferation, and dysplastic arteries with intervening nodular hepatic parenchyma with variably present central veins. The nodule was well demarcated from the normal surrounding liver by a rim of the aforementioned fibrotic bands. Importantly, the portal tracts with emanating bands of fibrosis blended directly with
1080
Komisarof et al.
AJG – Vol. 95, No. 4, 2000
Figure 4. Histology of focal nodular hyperplasia (A) with contiguous cyst wall (B). (A) The focal nodular hyperplasia shows nodular hepatocellular proliferation with intervening fibrotic septae containing bile ducts (straight arrow) and arteries (curved arrow). (B) The contiguous cyst wall (asterisk) blends with the emanating fibrotic septae (arrowheads) containing abnormal arteries (curved arrow) going into the area of focal nodular hyperplasia (hematoxylin and eosin, A: ⫻25; B: ⫻40).
the echinococcal cyst wall. The lesion did not, however, contain the central scar that is commonly seen in FNH. The patient’s gallbladder was also received and was unremarkable.
DISCUSSION We report the first case of an Echinococcal cyst and FNH occurring in direct contiguity. These two entities are rare and usually isolated lesions. This patient had E. multilocularis as shown by the multiple cyst in contrast to the unilocular cysts seen with E. granulosa. Because E. multilocularis is found in subarctic or arctic regions (including the United States, Canada, and northern Europe), this patient may have acquired the disease either in northern Europe or at home in the US. Surgical excision, followed by a course the antiparasitic agent albendazole, was the appropriate therapeutic procedure for this lesion. Focal nodular hyperplasia is a hepatic lesion of disputed and still unknown etiology. How-
ever, recent evidence seems to support a vascular pathogenesis, with various authors contending that increased pressure in portal veins or arteriovenous malformations (3) and increased regional blood flow (1) are responsible. They occur more often in women, as do hepatic adenomas; however, unlike the strong association of hepatic adenomas, they seem to be associated weakly or not at all with the use of oral contraceptives. FNH is usually an asymptomatic lesion (75% of the time), which is often discovered incidentally on imaging studies or laparotomy done for other indications. However, occasionally it can be felt as a nontender mass in the right upper quadrant. There is a slight risk of hemorrhage or necrosis in large lesions, which can be a source of right upper quadrant pain to the patient; the risk seems to be increased with the use of oral contraceptives. However, the occurrence of these complications is far less likely than that seen with hepatic adenomas (4). The finding of two uncommon lesions in contiguity with each other suggests a causative relation. The mechanism by
AJG – April, 2000
which this may have occurred is only speculative, but if we believe the argument of Wanless et al. that increased blood flow to a region of the liver may be pathogenic in FNH, it seems tenable that the hyperemic rim of the Echinococcal cyst (which was faintly rim enhancing on MRI) may have caused the development of an adjacent focus of FNH. What role the patient’s prior use of oral contraceptives may have played in the subsequent development of the FNH is not known, as they have no real role in its de novo development. An alternative hypothesis is that the Echinococcus organisms came to rest next to a pre-existing focus of FNH. However, because the organisms are thought to be carried primarily in the venous system from gut lumen and because the primary vasculature present in FNH are anomalous arteries, this hypothesis is less likely than the former. There have been cases reported in which foci of FNH were found adjacent to cavernous hemangiomas (2, 5) and to sclerotic vascular lesions (2). Other cases have documented FNH or lesions resembling FNH in association with cirrhosis (6), chronic hepatitis (6), glycogen storage disease type I (7), and fibrolamellar carcinoma (8). However, this is the first reported case of focal nodular hyperplasia associated with an Echinococcal cyst.
ACKNOWLEDGMENTS Special thanks are given to Drs. Matt van de Rijn and Cindy McGrath for their help in editing this work and to Ms. Lisa Bostic for the manuscript preparation.
Focal Nodular Hyperplasia and Echinococcal Cyst
1081
Reprint requests and correspondence: Emma E. Furth, M.D., Hospital of the University of Pennsylvania, 6 Founders, 3400 Spruce Street, Philadelphia, PA 19104 – 4283. Received July16, 1998; accepted Jan. 4, 1999.
REFERENCES 1. Wanless IR, Mawdsley C, Adams R. On the pathogenesis of focal nodular hyperplasia of the liver. Hepatology 1985;5: 1194 –2000. 2. Wanless IR, Albrecht S, Bilbao J, et al. Multiple focal nodular hyperplasia of the liver associated with vascular malformations of various organs and neoplasia of the brain: A new syndrome. Modern Pathol 1989;2:456 – 62. 3. Travers H, D’Amato NA. Vascular alterations in focal nodular hyperplasia of the liver. Milit Med 1978;143:96 –101. 4. Zakim D, Boyer TD. Hepatology. A textbook of liver disease, 2nd ed. Philadelphia: WB Saunders, 1990. 5. Ndimbie OK, Goodman ZD, Chase RL, et al. Hemangiomas with localized nodular proliferation of the liver: A suggestion of the pathogenesis of focal nodular hyperplasia. Am J Surg Pathol 1990;14:142–50. 6. Terada T, Kitani S, Ueda K, et al. Adenomatous hyperplasia of the liver resembling focal nodular hyperplasia in patients with chronic liver disease. Virchows Archiv A, Pathological Anatomy & Histopathology 1993;422:247–52. 7. Sakatoku H, Hirokawa Y, Inoue M, et al. Focal nodular hyperplasia in an adolescent with glycogen storage disease type I with mesocaval shunt operation in childhood: A case report and review of the literature. Acta Paediatrica Japonica 1996;38:172–5. 8. Saxena R, Humphreys S, Williams R, et al. Nodular hyuperplasia surrounding fibrolamellar carcinoma. A zone of arterialized liver parenchyma. Histopathology 1994;25:275– 8.