Correspondence

Hepatocellular Carcinoma (Case 2-1996)

N Engl J Med 1996; 334:1478-1479May 30, 1996

Article

To the Editor:

The Case Records in the January 18 issue of the Journal 1 reflects the difficulties in distinguishing focal nodular hyperplasia from the fibrolamellar variant of hepatocellular carcinoma. Polysomies of chromosome 1, detected by conventional cytogenetic methods, may be characteristic of hepatocellular carcinoma.2,3 We used fluorescence in situ hybridization, a simple and rapid method that allows the detection of chromosomal aberrations in interphase nuclei, to investigate the number of copies of chromosome 1 in cytologic preparations of malignant and benign liver tumors. Polysomy 1, mostly trisomy 1, was found only in hepatocellular carcinoma and not in normal liver tissue, liver-cell adenoma, or focal nodular hyperplasia.4 Trisomy 1 was also detected in a fibrolamellar carcinoma, thus helping to distinguish it from a benign lesion. These findings suggest that interphase cytogenetic analysis with fluorescence in situ hybridization may facilitate the preoperative assessment of tumors in primary hepatic lesions.

Anette Nasarek, M.D.
Martin Werner, M.D.
Hannover University Medical Center, D-30623 Hannover, Germany

4 References

1. 1

   Case Records of the Massachusetts General Hospital (Case 2-1996). N Engl J Med 1996;334:176-182
   Full Text | Web of Science | Medline

2. 2

   Simon D, Knowles BB, Weith A. Abnormalities of chromosome 1 and loss of heterozygosity on 1p in primary hepatomas. Oncogene 1991;6:765-770
   Web of Science | Medline

3. 3

   Werner M, Nolte M, Georgii A, Klempnauer J. Chromosome 1 abnormalities in hepatocellular carcinoma. Cancer Genet Cytogenet 1993;66:130-130
   CrossRef | Web of Science | Medline

4. 4

   Nasarek A, Werner M, Nolte M, Klempnauer J, Georgii A. Trisomy 1 and 8 occur frequently in hepatocellular carcinoma but not in liver cell adenoma or focal nodular hyperplasia: a fluorescence in situ hybridization study. Virchows Arch A Pathol Anat Histopathol 1995;427:373-378
   

To the Editor:

The January 18 case Records described a young woman with a mass in the left hepatic lobe. The discussants concluded that the lesion could be either focal nodular hyperplasia or fibrolamellar hepatocellular carcinoma. They stated that removal of the mass was indicated for diagnostic reasons and that resection is the treatment of choice for both focal nodular hyperplasia and fibrolamellar hepatocellular carcinoma. However, it is well accepted that focal nodular hyperplasia can be managed without surgical intervention.1,2 The risk of death associated with partial hepatic resection in patients without cirrhosis is low, but any risk of lethal complications is unacceptable in the management of a benign disease. Furthermore, in our experience, symptoms may persist in the upper abdomen after the lesion has been removed.3 Therefore, we advocate the inclusion of percutaneous needle biopsy guided by ultrasound or computed tomography in the diagnostic workup. Since most of these lesions have diameters of more than 3 cm, sampling errors during the biopsy are negligible. We think that focal nodular hyperplasia should be managed selectively; resection is warranted only when the lesion causes pain or gastric-outlet obstruction or when the histologic diagnosis of an asymptomatic mass cannot be firmly established preoperatively by needle biopsy.

Jan N. IJzermans, M.D., Ph.D.
Rob A. de Man, M.D., Ph.D.
Erasmus University Hospital, 3015 GD Rotterdam, the Netherlands

3 References

1. 1

   Pain JA, Gimson AE, Williams R, Howard ER. Focal nodular hyperplasia of the liver: results of treatment and options in management. Gut 1991;32:524-527
   CrossRef | Web of Science | Medline

2. 2

   Nagorney DM. Benign hepatic tumors: focal nodular hyperplasia and hepatocellular adenoma. World J Surg 1995;19:13-18
   CrossRef | Web of Science | Medline

3. 3

   de Wilt JHW, de Man RA, Lameris JS, IJzermans JNM. Focal nodular hyperplasia of the liver: analysis of diagnosis and management in 31 patients in a 15-year period. Ned Tijdschr Geneeskd 1996;1:18-22
   

Author/Editor Response

The authors reply:

To the Editor: IJzermans and de Man indicate that focal nodular hyperplasia can be managed conservatively without surgery and imply that the patient in the case under discussion may not have needed surgical resection. We agree that this is true if the lesion is less than 6 cm in diameter, is not causing symptoms, and is definitely benign.1 In the present case, the lesion was greater than 6 cm and the patient symptomatic. Clearly, it may be difficult to distinguish between focal nodular hyperplasia and the fibrolamellar variant of hepatocellular carcinoma with the use of preoperative imaging, and rarely, surgical resection of a focal nodular hyperplasia may be fatal. IJzermans and de Man also suggest that biopsy guided by computed tomography or ultrasound will distinguish focal nodular hyperplasia from a fibrolamellar variant of hepatocellular carcinoma and that a biopsy should have been performed first. Percutaneous liver biopsy may not be a benign procedure, since minor complications occur in 0.32 percent of procedures and death in 0.12 percent.2 Peritoneal dissemination of hepatocellular carcinoma because of hemorrhage through a needle track is possible. Complications are related to the type of biopsy needle used and are more common when cutting needles are used to prepare core samples — an approach that may be necessary to differentiate benign from malignant tumors.

Nasarek and Werner suggest that fluorescence in situ hybridization might have been used to distinguish the fibrolamellar variant of hepatocellular carcinoma from focal nodular hyperplasia. Their study3 was based on “touch” preparations of resected specimens and revealed that three of eight hepatocellular carcinomas did not have serious cytogenetic abnormalities on the basis of fluorescence in situ hybridization. Because the samples are often small, percutaneous biopsies may not distinguish focal nodular hyperplasia from well-differentiated hepatocellular carcinoma even with the use of fluorescence in situ hybridization.

We think that the original surgical approach to this patient represented appropriate therapy. Furthermore, if the possible malignant nature of a lesion that resembles focal nodular hyperplasia or a fibrolamellar variant of hepatocellular carcinoma is unclear owing to size, growth, or symptoms, then the lesion should be resected. Recent results4 suggest that resection can be performed with a mortality rate that is similar to that reported for liver biopsy.

J. Milburn Jessup, M.D.
Deaconess Hospital, Boston, MA 02215

F.M. Graeme-Cook, M.D.
Massachusetts General Hospital, Boston, MA 02114

4 References

1. 1

   Cherqui D, Rahmouni A, Charlotte F, et al. Management of focal nodular hyperplasia and hepatocellular adenoma in young women: a series of 41 patients with clinical, radiological, and pathological correlations. Hepatology 1995;22:1674-1681
   CrossRef | Web of Science | Medline

2. 2

   Tobkes AI, Nord HJ. Liver biopsy: review of methodology and complications. Dig Dis 1995;13:267-274
   CrossRef | Web of Science | Medline

3. 3

   Nasarek A, Werner M, Nolte M, Klempnauer J, Georgii A. Trisomy 1 and 8 occur frequently in hepatocellular carcinoma but not in liver cell adenoma and focal nodular hyperplasia: a fluorescence in situ hybridization study. Virchows Arch A Pathol Anat Histopathol 1995;427:373-378
   

4. 4

   Nagorney DM. Benign hepatic tumors: focal nodular hyperplasia and hepatocellular adenoma. World J Surg 1995;19:13-18
   CrossRef | Web of Science | Medline