Diagnostic Radiology
•
Angiographic Findings in Multiple Bile-Duct Hamartomas of the Liver 1
•
material and bile casts. Medium-sized arteries and veins were present in some of the lesions (Fig. 3). The appearance was typical of bile-duct hamartomas.
Michael J. McLoughlin, M. B., and M. James Phillips, M.D.
DISCUSSION
The angiographic appearance in a patient with multiple bile-duct hamartomas of the liver is described. The lesions showed abnormal vascularity, consisting of grapelike clusters of small rings, which could be confused with other benign and malignant conditions demonstrable by angiography; however, it may ultimately prove to be characteristic of this uncommon lesion. The angiographic differential diagnosis is discussed. INDEX TERMS:
Bile-duct hamartomas have a very characteristic pathology. It is generally accepted that they represent developmental anomalies rather than true neoplasms, and their relationship to congenital cystic disease of the liver and congenital hepatic fibrosis is well known (1). They have been described under a number of terms, including cholangioadenoma (4), multiple bile-duct adenomas (16), fibroadenomatosis (13), Meyenburg complexes (9), von Meyenburg plexuses (16), and multiple microhamartomatosis (15). Bile-duct hamartomas should not be confused with other hamartomas of the liver (14). Bile-duct hamartomas are uncommon; Chung found them in only 6 of 875 autopsies (0.69%) (1). They are usually small (0.1-0.5 em in diameter) and multiple and are usually encountered as incidenfal findings at surgery or autopsy. Their primary clinical significance is the fact that they are easily confused with metastatic foci of carcinoma on gross examination; however, the microscopic findings are characteristic. One pathological feature which has not received much attention is the fact that bile-duct hamartomas often contain medium-sized arteries and veins, which presumably accounts for their increased vascularity on angiography. Hamartomas also tend to surround small areas of normal hepatic parenchyma, which may explain the ring pattern formed by some lesions on angiography. The angiographic differential diagnosis in our patient included hepatoma, focal nodular hyperplasia, liver-cell adenoma, cavernous hemangioma, and vascular metastases. The appearance suggested multiple small lesions or possibly a tumor of multicentric origin. The absence of large feeding arteries, bizarre' tumor vessels, irregular laking, or arteriovenous shunting made multicentric hepatoma unlikely. Focal nodular hyperplasia and liver-cell adenomas range from 1 to 20 em in diameter (2, 3, 6, 7, 12, 14), compared to bile-duct hamartomas, which usually range from 0.1 to 0.5 em in diameter and rarely reach 1.5 em (4). Both focal nodular hyperplasia and liver-cell adenomas are usually solitary; when they are multipie, only a few masses are present. Larger lesions show irregular tumor vessels; in addition, adenomas also have circumferential arterial branches which may represent capsular arteries (6, 7). Cavernous hemangiomas vary in size from a few millimeters to massive lesions and can be numerous; however, the abnormal vascularity seen in these lesions is due to puddling of contrast material in vascular spaces, which appear as coarse, blob-like opacities on the angiogram and have a strong tendency to form ring-like and C-shaped arrangements 0.5 em or more in diameter (5). The most difficult differential diagnosis in our patient was from multiple small, highly vascular metastases. However, the appearance of clusters of small rings 2-3 mm in diameter, much smaller and different in appearance from those formed in cavernous hemangiomas, is unique in our experience. We attribute this to a tendency of hamartomas to surround and isolate areas of normal liver parenchyma. It will be of interest
Bile Ducts, neoplasms • Hamartoma • Liver Neoplasms, angi-
ography Radiology 116:41-43, July 1975
•
•
S
EVERAL tumors and tumor-like conditions of the liver
show abnormal vascularity on angiography, including primary malignant tumors (17), metastases (11), cavernous hemangiomas (5), hemangioendotheliomas (10), liver-cell adenomas (3, 7, 12), and focal nodular hyperplasia (3, 6, 8). We recently encountered a patient with multiple bile-duct hamartomas having an angiographic appearance which we do not believe has been described previously. This condition should be added to this list of benign and malignant lesions of the liver which may show abnormal vascularity on angiography.
CASE REPORT A 42-year-old white man had had peptic ulceration and recurrent pancreatitis with cyst formation for eight years. In April 1972, he underwent drainage of a pancreatic cyst, and in July he had a vagotomy and pyloroplasty. In January 1973 further exploratory laparotomy was undertaken for suspected biliary obstruction. At each of these operations the liver was noted to be riddled with small white nodules. Open biopsies at both the first and last operations revealed multiple bile-duct hamartomas. In October 197;3, aortography and selective celiac and superior mesenteric angiography revealed that the left lobe of the liver was supplied by the celiac artery and the right lobe by the superior mesenteric artery. The branches of the hepatic artery were unremarkable. Multiple areas of abnormal vascularity approximately 1 em in diameter were scattered throughout both lobes of the liver and persisted into the venous phase (Fig. 1). In several areas they took the form of grape-like clusters of small rings 2-3 mm in diameter (Fig. 2). Tumor vessels, laking, and arteriovenous shunting were not observed. Liver biopsy revealed multiple well-defined lesions 0.1-0.5 em in diameter, surrounded by normal liver parenchyma and composed of dilated bile channels lined by flattened and cuboidal epithelial cells embedded in fibrous tissue which showed areas of hyalinization (Figs. 3 and 4). The biliary channels were tortuous and branching and contained pinkish-brown
1 From the Departments of Radiology (M.J.M.) and Pathology (M.J.P.), Toronto General Hospital, Toronto, Ontario, Canada. Accepted for publication in February 1975. sjh
41
42
MICHAEL J. MCLOUGHLIN AND
M. JAMES
PHILLIPS
July 1975
.1
Fig. 1. Selective superior mesenteric angiogram shows the right hepatle artery arising from the superior mesenteric artery. Multiple small areas of abnormal vascularity are scattered throughout the right lobe of the liver. In several areas they appear to be composed of grape-like clusters of small rings (arrows). Fig. 2. Magnified view of Figure 1, showing the ring-like appearance of the bile-duct hamartomas (arrows).
Fig. 3. Low-power view of a bile-duct hamartoma in the liver. The lesion is well-delineated but not encapsulated. Note the epithelium-lined channels embedded in fibrous tissue and the medium-sized arteries and veins on the left side of the hamartoma. Fig. 4. Higher magnification of' bile-duct hamartoma. Many of the biliary channels are widely dilated. Tortuosity and branching of the biliary channels are evident. The stroma on the upper right is hyalinized.
to see whether this proves to be a characteristic angiographic appearance of this uncommon condition. ADDENDUM: Since this article was submitted for publication, Plishkin has described the angiographic appearance in a case of peliosis
hepatis (Radiology 114: 29-30, Jan 1975) involving multiple abnormal accumulations of contrast material up to 1.0 em in diameter seen on the parenchymal phase of the angiogram. This condition should also be included in the differential diagnosis of lesions causing abnormal vascularity in the liver at angiography.
Vol. 116
MULTIPLE BILE-DuCT HAMARTOMAS OF THE LIVER
ACKNOWLEDGMENTS: We are grateful to Guelda Farr for her secretarial assistance and to the Department of Photography of Toronto General Hospital. Department of Radiology Toronto General Hospital 101 College St. Toronto, Ontario, Canada
REFERENCES 1. Chung EB: Multiple bile-duct harmartomas. Cancer 26: 287-296, Aug 1970 2. Edmondson HA: Tumors of the liver and intrahepatic bile ducts. Atlas of Tumor.Pathology, Sect VII, Fasc 25. Washington DC, AFIP, 1958, pp 202-205 3. Goldstein HM, Neiman HL, Mena E, et al: Angiographic findings in benign liver cell tumors. Radiology 110:339-343, Feb 1974 4.· Henson SW Jr, Gray HK; Dockerty MB: Benign tumors of the liver. I. Adenomas. Surg Gynecol Obstet 103:23-30, Jul1956 5. McLoughlin MJ: Angiography in cavernous hemangioma of the liver. Am J RoentgenoI113:50-55, Sep 1971 6. McLoughlin MJ, Colapinto RF, GildayDL, et al: Focal nodular hyperplasia of the liver. Angiography and radioisotope scanning. Radiology 107:257-263, May 1973
43
Diagnostic Radiology
7. McLoughlin MJ, Gilday DL: Angiography and colloid scanning of benign mass lesions of the liver. Clin Radiol 23:377-391, Jul 1972 8. McMullen CT, Montgomery JL: Arteriographic findings of focal nodular hyperplasia of the liver and review of the literature. Am J RoentgenoI117:380-387, Feb 1973 9. Melnick PJ: Polycystic liver. Analysis of seventy cases. Arch PathoI59:162-172, Feb 1955 10. Moss AA, Clark RE, Palubinskas AJ, et al: Angiographic appearance of benign and m~lignant hepatic tumors in infants and children. Am J RoentgenoI113:61-69, Sep 1971 11. Nebesar RA, Pollard JJ, Stone DL: Angiographic diagnosis of malignant disease of the liver. Radiology86:284-291, Feb 1966 12. Palubinskas AJ, Baldwin J, McCormack KR: Liver-cell adenoma. Angiographic findings and report of a case. Radiology 89: 444-447, Sep 1967 13. Parker RGF: Fibrosis of the liver as a congenital anomaly. J Pathol BacterioI71:359-368, Apr 1956 14. Phillips MJ, Langer B, Stone R, et al: Benign liver cell tumors. Classification and ultrastructural pathology. Cancer 32:463470, Aug 1973 . 15. Popper H, Schaffner F: Liver: Structure and Function. New York, McGraw-Hill, 1957, pp 587-589 16. Schiff L, ed: Diseases of the Liver. Philadelphia, Lippincott, 3d Ed, 1969, P 846 17. YU C: Primary carcinoma of the liver (hepatoma). Its diagnosis by selective celiac arteriography. Am J Roentgenol 99:142-149, Jan 1967
•
Angiographic Findings in Multiple Bile-Duct Hamartomas of the Liver 1
•
material and bile casts. Medium-sized arteries and veins were present in some of the lesions (Fig. 3). The appearance was typical of bile-duct hamartomas.
Michael J. McLoughlin, M. B., and M. James Phillips, M.D.
DISCUSSION
The angiographic appearance in a patient with multiple bile-duct hamartomas of the liver is described. The lesions showed abnormal vascularity, consisting of grapelike clusters of small rings, which could be confused with other benign and malignant conditions demonstrable by angiography; however, it may ultimately prove to be characteristic of this uncommon lesion. The angiographic differential diagnosis is discussed. INDEX TERMS:
Bile-duct hamartomas have a very characteristic pathology. It is generally accepted that they represent developmental anomalies rather than true neoplasms, and their relationship to congenital cystic disease of the liver and congenital hepatic fibrosis is well known (1). They have been described under a number of terms, including cholangioadenoma (4), multiple bile-duct adenomas (16), fibroadenomatosis (13), Meyenburg complexes (9), von Meyenburg plexuses (16), and multiple microhamartomatosis (15). Bile-duct hamartomas should not be confused with other hamartomas of the liver (14). Bile-duct hamartomas are uncommon; Chung found them in only 6 of 875 autopsies (0.69%) (1). They are usually small (0.1-0.5 em in diameter) and multiple and are usually encountered as incidenfal findings at surgery or autopsy. Their primary clinical significance is the fact that they are easily confused with metastatic foci of carcinoma on gross examination; however, the microscopic findings are characteristic. One pathological feature which has not received much attention is the fact that bile-duct hamartomas often contain medium-sized arteries and veins, which presumably accounts for their increased vascularity on angiography. Hamartomas also tend to surround small areas of normal hepatic parenchyma, which may explain the ring pattern formed by some lesions on angiography. The angiographic differential diagnosis in our patient included hepatoma, focal nodular hyperplasia, liver-cell adenoma, cavernous hemangioma, and vascular metastases. The appearance suggested multiple small lesions or possibly a tumor of multicentric origin. The absence of large feeding arteries, bizarre' tumor vessels, irregular laking, or arteriovenous shunting made multicentric hepatoma unlikely. Focal nodular hyperplasia and liver-cell adenomas range from 1 to 20 em in diameter (2, 3, 6, 7, 12, 14), compared to bile-duct hamartomas, which usually range from 0.1 to 0.5 em in diameter and rarely reach 1.5 em (4). Both focal nodular hyperplasia and liver-cell adenomas are usually solitary; when they are multipie, only a few masses are present. Larger lesions show irregular tumor vessels; in addition, adenomas also have circumferential arterial branches which may represent capsular arteries (6, 7). Cavernous hemangiomas vary in size from a few millimeters to massive lesions and can be numerous; however, the abnormal vascularity seen in these lesions is due to puddling of contrast material in vascular spaces, which appear as coarse, blob-like opacities on the angiogram and have a strong tendency to form ring-like and C-shaped arrangements 0.5 em or more in diameter (5). The most difficult differential diagnosis in our patient was from multiple small, highly vascular metastases. However, the appearance of clusters of small rings 2-3 mm in diameter, much smaller and different in appearance from those formed in cavernous hemangiomas, is unique in our experience. We attribute this to a tendency of hamartomas to surround and isolate areas of normal liver parenchyma. It will be of interest
Bile Ducts, neoplasms • Hamartoma • Liver Neoplasms, angi-
ography Radiology 116:41-43, July 1975
•
•
S
EVERAL tumors and tumor-like conditions of the liver
show abnormal vascularity on angiography, including primary malignant tumors (17), metastases (11), cavernous hemangiomas (5), hemangioendotheliomas (10), liver-cell adenomas (3, 7, 12), and focal nodular hyperplasia (3, 6, 8). We recently encountered a patient with multiple bile-duct hamartomas having an angiographic appearance which we do not believe has been described previously. This condition should be added to this list of benign and malignant lesions of the liver which may show abnormal vascularity on angiography.
CASE REPORT A 42-year-old white man had had peptic ulceration and recurrent pancreatitis with cyst formation for eight years. In April 1972, he underwent drainage of a pancreatic cyst, and in July he had a vagotomy and pyloroplasty. In January 1973 further exploratory laparotomy was undertaken for suspected biliary obstruction. At each of these operations the liver was noted to be riddled with small white nodules. Open biopsies at both the first and last operations revealed multiple bile-duct hamartomas. In October 197;3, aortography and selective celiac and superior mesenteric angiography revealed that the left lobe of the liver was supplied by the celiac artery and the right lobe by the superior mesenteric artery. The branches of the hepatic artery were unremarkable. Multiple areas of abnormal vascularity approximately 1 em in diameter were scattered throughout both lobes of the liver and persisted into the venous phase (Fig. 1). In several areas they took the form of grape-like clusters of small rings 2-3 mm in diameter (Fig. 2). Tumor vessels, laking, and arteriovenous shunting were not observed. Liver biopsy revealed multiple well-defined lesions 0.1-0.5 em in diameter, surrounded by normal liver parenchyma and composed of dilated bile channels lined by flattened and cuboidal epithelial cells embedded in fibrous tissue which showed areas of hyalinization (Figs. 3 and 4). The biliary channels were tortuous and branching and contained pinkish-brown
1 From the Departments of Radiology (M.J.M.) and Pathology (M.J.P.), Toronto General Hospital, Toronto, Ontario, Canada. Accepted for publication in February 1975. sjh
41
42
MICHAEL J. MCLOUGHLIN AND
M. JAMES
PHILLIPS
July 1975
.1
Fig. 1. Selective superior mesenteric angiogram shows the right hepatle artery arising from the superior mesenteric artery. Multiple small areas of abnormal vascularity are scattered throughout the right lobe of the liver. In several areas they appear to be composed of grape-like clusters of small rings (arrows). Fig. 2. Magnified view of Figure 1, showing the ring-like appearance of the bile-duct hamartomas (arrows).
Fig. 3. Low-power view of a bile-duct hamartoma in the liver. The lesion is well-delineated but not encapsulated. Note the epithelium-lined channels embedded in fibrous tissue and the medium-sized arteries and veins on the left side of the hamartoma. Fig. 4. Higher magnification of' bile-duct hamartoma. Many of the biliary channels are widely dilated. Tortuosity and branching of the biliary channels are evident. The stroma on the upper right is hyalinized.
to see whether this proves to be a characteristic angiographic appearance of this uncommon condition. ADDENDUM: Since this article was submitted for publication, Plishkin has described the angiographic appearance in a case of peliosis
hepatis (Radiology 114: 29-30, Jan 1975) involving multiple abnormal accumulations of contrast material up to 1.0 em in diameter seen on the parenchymal phase of the angiogram. This condition should also be included in the differential diagnosis of lesions causing abnormal vascularity in the liver at angiography.
Vol. 116
MULTIPLE BILE-DuCT HAMARTOMAS OF THE LIVER
ACKNOWLEDGMENTS: We are grateful to Guelda Farr for her secretarial assistance and to the Department of Photography of Toronto General Hospital. Department of Radiology Toronto General Hospital 101 College St. Toronto, Ontario, Canada
REFERENCES 1. Chung EB: Multiple bile-duct harmartomas. Cancer 26: 287-296, Aug 1970 2. Edmondson HA: Tumors of the liver and intrahepatic bile ducts. Atlas of Tumor.Pathology, Sect VII, Fasc 25. Washington DC, AFIP, 1958, pp 202-205 3. Goldstein HM, Neiman HL, Mena E, et al: Angiographic findings in benign liver cell tumors. Radiology 110:339-343, Feb 1974 4.· Henson SW Jr, Gray HK; Dockerty MB: Benign tumors of the liver. I. Adenomas. Surg Gynecol Obstet 103:23-30, Jul1956 5. McLoughlin MJ: Angiography in cavernous hemangioma of the liver. Am J RoentgenoI113:50-55, Sep 1971 6. McLoughlin MJ, Colapinto RF, GildayDL, et al: Focal nodular hyperplasia of the liver. Angiography and radioisotope scanning. Radiology 107:257-263, May 1973
43
Diagnostic Radiology
7. McLoughlin MJ, Gilday DL: Angiography and colloid scanning of benign mass lesions of the liver. Clin Radiol 23:377-391, Jul 1972 8. McMullen CT, Montgomery JL: Arteriographic findings of focal nodular hyperplasia of the liver and review of the literature. Am J RoentgenoI117:380-387, Feb 1973 9. Melnick PJ: Polycystic liver. Analysis of seventy cases. Arch PathoI59:162-172, Feb 1955 10. Moss AA, Clark RE, Palubinskas AJ, et al: Angiographic appearance of benign and m~lignant hepatic tumors in infants and children. Am J RoentgenoI113:61-69, Sep 1971 11. Nebesar RA, Pollard JJ, Stone DL: Angiographic diagnosis of malignant disease of the liver. Radiology86:284-291, Feb 1966 12. Palubinskas AJ, Baldwin J, McCormack KR: Liver-cell adenoma. Angiographic findings and report of a case. Radiology 89: 444-447, Sep 1967 13. Parker RGF: Fibrosis of the liver as a congenital anomaly. J Pathol BacterioI71:359-368, Apr 1956 14. Phillips MJ, Langer B, Stone R, et al: Benign liver cell tumors. Classification and ultrastructural pathology. Cancer 32:463470, Aug 1973 . 15. Popper H, Schaffner F: Liver: Structure and Function. New York, McGraw-Hill, 1957, pp 587-589 16. Schiff L, ed: Diseases of the Liver. Philadelphia, Lippincott, 3d Ed, 1969, P 846 17. YU C: Primary carcinoma of the liver (hepatoma). Its diagnosis by selective celiac arteriography. Am J Roentgenol 99:142-149, Jan 1967
