The Frequency and Significance of Small (15 mm) Hepatic Lesions Detected by CT

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1 535 Elizabeth C. Jones1 Judith L. Chezmar Rendon C. Nelson Michael E. Bernardino Received July 22, 1991 ; accepted after revision October 16, Presented atthe annual meeting ofthe American Aoentgen Ray society, Boston, MA, May All authors: Department of Radiology, Emory University School of Medicine, 1364 Clifton Ad., Materials and Methods N.E., Atlanta, GA Address reprint requests to J. L Chezmar X/92/ C American Roentgen Ray Society The Frequency and Significance of Small (15 mm) Hepatic Lesions Detected by CT ,. S : The purpose of our study was to determine the frequency of detection of small hepatic lesions (15 mm) in outpatients who had abdominal CT and to assess the significance of these lesions in the presence or absence of known malignant tumors. Contrastenhanced abdominal CT scans In 1454 patients were reviewed. In 254 patients (17%), hepatic lesions 15 mm or smaller were detected. In 51% of these patients, lesions were judged benign on the basis of other imaging studies, biopsy results, or stability for at least 6 months as shown by CT. Lesions were judged malignant on the basis of progression seen on radiologic studies or biopsy in 22%. The other 27% of the patients had lesions that could not be classifled The majority of patients with small hepatic lesions (82%) were known to have a malignant tumor- in 51% of these patients, lesions were diagnosed as benign. No patient without a known malignant tumor had a small hepatic lesion that was determined to be malignant. Multiple small lesions were more likely to represent malignant disease than were single small lesions. We conclude that small hepatic lesions are common (seen in 17% of our patients), and that there is a high probability that hepatic lesions smaller than 15 mm are benign, even in patients known to have an extrahepatic malignant tumor. AJR 158: , March 1992 Advances in hepatic imaging, including high-resolution CT, CT during arterial portography, and MR imaging, have resulted in increased detection of small (i 5 mm) lesions in the liver [1]. Refinements in CT techniques, including the use of 5- mm collimation, may further increase detection of small lesions. These lesions could be benign entities, such as congenital hepatic cysts (prevalence, %) or hemangiomas ( %) [2-4]. Alternatively, these lesions could be malignant. If the patient has no known malignant neoplasm, these small hepatic lesions usually cause little clinical concern. However, if it is known that the patient has a malignant tumor, further diagnostic studies to determine the nature of these lesions may be necessary, because the presence of hepatic metastases often radically alters prognosis and therapy. The purpose of this study was to determine the frequency of detection of small lesions in an outpatient population having routine CT scanning and to determine the significance of such a finding in the presence or absence of known extrahepatic malignant neoplasm. Although each case requires an individual approach, guidelines as to the frequency with which solitary or multiple small lesions are malignant would be helpful in weighing the risks and benefits of conservative management, histologic confirmation with percutaneous biopsy, or treatment. Contrast-enhanced abdominal CT scans obtained in consecutive outpatients over a 1 -year period (October through September 1 990) were reviewed retrospectively for the presence of small (1 5 mm) hepatic lesions. All patients were imaged on a Philips 60 TX

2 536 JONES ET AL. AJA:158, March 1992 (Philips Medical Systems, Shelton, CT) scanner. All patients received a bolus IV injection of 150 ml of contrast medium (diatrizoate meglumine 60%, Hypaque-60, Winthrop Pharmaceuticals, New York), and dynamic, incremental, contiguous 1 0-mm transaxial sections were scanned. The majority of patients (82%) were referred for abdominal CT screening because of a history of an extrahepatic malignant tumor or previous known hepatic metastatic disease. The types of known malignant tumors were distributed asfollows: breast, 22%; colorectal, I 9%; renal cell, 10%; melanoma, 10%; lung, 9%; gastrointestinal malignancies(excluding colorectal), 9%; lymphoma, 8%; gynecologic, 5%; genitounnary (excluding renal cell), 5%; thyroid carcinoma, 1%; sarcomas, 1 %; and miscellaneous, 1%. Indications in the other patients (1 8%) were disease of the hepatobiliary system (20%); inflammatory or other benign disease of the gastrointestinal tract (1 0%), urinary tract (10%), or gynecologic organs (1 5%); to search for occult malignancy (1 0%); abdominal pain (10%); and miscellaneous (25%). Patients in whom one or more small hypodense hepatic lesions were found were selected for study. The presence of larger hepatic lesions, in addition to the small lesion(s), did not exclude a patient from the study. In these patients, all previous and subsequent CT scans were reviewed for the presence, size, and number of small lesions and the presence of additional lesions larger than 15 mm. Baseline size and number of hepatic lesions were determined from the findings on the earliest CT scan on which lesions were detected. All other imaging studies performed in these patients, including MR, sonography, and Tc-labeled RBC single-photon emission cornputed tomography (SPECT), were also reviewed. Study patients were subdivided into three groups according to the number of small lesions detected: one lesion, two to four lesions, and five or more lesions. Lesions were judged to be benign on the basis of histologic findings, confirmatory imaging studies (MR, sonography, or labeled ABC SPECT), or stability for at least 6 months. Lesions were judged to be malignant on the basis of biopsy results or an increase in size and number on follow-up scans. Lesions that did not meet either of these criteria were classified as indeterminate. Patients with multiple lesions were classified as having malignant disease if any one of their lesions fulfilled the criteria for a malignant lesion. TABLE 1: Classification of Hepatic Lesions Lesion Classification With Small Lesions (n = 254) Results Hepatic lesions 1 5 mm or smaller were identified in 254 (1 7%) of the 1454 CT examinations reviewed. Overall, 129 patients (51 %) were determined to have small hepatic lesions that represented benign disease (Table 1). In 16 patients (6%) the lesions were confirmed as benign on the basis of other imaging studies (1 1 hepatic cysts, three hemangiomas) (Fig. 1) or the results of percutaneous biopsy (two hemangiomas). Thirty-three patients (1 3%) had lesions that were stable on follow-up studies for at least 6 but not more than 12 months after the lesions were first detected. In an additional 80 patients (32%), CT follow-up of at least 12 months confirmed the stability of the lesions (Fig. 2). Mean length of follow-up in this group was 28.5 months. Lesions were considered malignant on the basis of histologic proof or progression of disease as shown on follow-up CT in 55 patients (22%) (Fig. 3). In 70 patients (27%), the lesions were classified as indeterminate. Patients with Known Mallgnant Tumors Of the 254 patients with small lesions, 209 (82%) had a history of extrahepatic malignant tumors. In this subgroup, eight patients (4%) had lesions confirmed as benign on the basis of biopsy or additional imaging studies. Ninety-nine patients (47%) had no change in the size of the small lesions on follow-up CT. Of these 99 patients, 29 (1 4%) had hepatic lesions that were stable for at least 6 but less than 1 2 months, and 70 (33%) had lesions that were stable for 12 months or longer as shown on CT. Overall, 51 % of the patients with a history of cancer probably had small hepatic lesions that were benign. Fifty-five patients (26%) had lesions that were determined to be malignant on the basis of histologic findings or progression in lesion size or number or both as shown on follow-up CT. In this subgroup, lesions in 47 patients (23%) were classified as indeterminate. No. of Patients (%) With Known Malignant Neoplasm (n = 209) With No Known Malignant Neoplasm (n = 45) Benign Histologic or imaging findings (MA, 1 6 (6) 8 (4) 8 (18) sonography, Tc-labeled ABC SPECT) Stability on follow-up (mo) (13) 29 (14) 4 (9) (32) 70 (33) 10 (22) Total 129 (51) 107 (51) 22 (49) Malignant Histology or progression as shown 55 (22) 55 (26) 0 on CT Indeterminate No follow-up or follow-up <6 mo 70 (27) 47 (23) 23 (51) Note.-SPECT = single-photon emission computed tomography.

3 AJR:158, March 1992 CT OF SMALL HEPATIC LESIONS 537 Fig. 1.-Small hepatic hemangioma. A, CT scan shows single hypodense lesion (arrow) in lateral segment of left hepatic lobe. B, 72-weighted spin-echo MR image (2000/150 [TRITE]) shows well-circumscribed, homogeneous, high-signal-intensity lesion consistent with hepatic hemangioma. Fig. 2.-A and B, CT scans obtained initially (A) and 1 year later (B) show stability of single lesion (arrows) in lateral segment of left hepatic lobe. Fig. 3.-A, Initial CT scan shows single small lesion (arrow). B, Follow-up CT scan obtained 1 year after A shows progression in size and number of lesions, consistent with progression of metastatic disease.

4 538 JONES ET AL. AJA:158, March 1992 Patients with Known Malignant Tumors and a Single Small Hepatic Lesion Of particular interest were the 86 patients with known malignancy and only one small lesion. In six of these patients, lesions were confirmed as benign on the basis of biopsy results or other imaging studies. Thirty-four patients had small lesions that were stable for more than 12 months, and 16 had lesions that were stable for more than 6 but less than 12 months. If these groups are combined, 65% of the patients with known malignant tumor and only one small lesion probably had benign hepatic lesions. These single small lesions were diagnosed as malignant on the basis of histologic findings or progression as shown on CT in only four patients (5%). Lesions were judged indeterminate in 26 patients (30%) in this group (Fig. 3). Patients with Known Malignant Tumors and Two to Four Small Hepatic Lesions In the 74 patients with a known malignant neoplasm and two to four small lesions, two (3%) had lesions that were benign on imaging studies. Ten patients (1 4%) had lesions that were stable for at least 6 months as shown on CT, and 32 (43%) had lesions that were stable for at least 1 2 months as shown by CT. If these groups are combined, 44 (59%) of these patients probably had benign lesions. Fourteen (19%) of these 74 patients probably had malignant lesions, as mdicated by progression in lesion size. Lesions were classified as indeterminate in the remaining 1 6 patients (22%). Patients with Known Malignant Tumors and Five or More Small Hepatic Lesions Conversely, of the 49 patients with a known malignant neoplasm and five or more small lesions, only seven patients (1 4%) had lesions that were stable for at least 6 months as shown on CT, five patients (1 0%) had no follow-up, and the remaining 37 (76%) had progression of disease (Fig. 4). Patients with Concomitant Large Lesion(s) In general, the presence of one or more large lesions increased the probability of any small lesion or lesions being malignant. However, most of the cases in which small lesions proved malignant were in the group of patients with five or more small lesions, or to a lesser extent in the group with two to four small lesions. The presence of a larger lesion had little effect on outcome in the patients who had only one small lesion. Eleven of the 86 patients with only one small lesion had one or more associated large lesions, but none of these patients showed progression in the size of the small lesion. In the group with two to four small lesions, the presence of large lesions was associated with an increased probability of the small lesions being malignant. Eleven of the 74 patients in this group had concomitant large lesions, and, of these, seven had small lesions that showed progression on CT. In the group of 49 patients with five or more small lesions, Number of small hepatic lesions Fig. 4.-Graph shows percentage of patients with benign, malignant, or unknown small hepatic lesions, categorized according to number of small hepatic lesions detected. patients (65%) had one or more large lesions as well; all of these patients had progression in one or more of their small lesions, consistent with a malignant tumor. Of the 17 patients in the group with five or more small lesions that did not have an associated large lesion, seven patients had lesions that were stable on follow-up, five had lesions that progressed, and five had lesions that were classified as indeterminate. Patients Without Known Malignant Tumors and Hepatic Lesions Of the 45 patients with small hepatic lesions and no history of malignancy, eight (1 8%) had benign lesions as shown by other imaging studies and 1 4 (31 %) had stable lesions as shown by follow-up CT. In no patient in this group was a lesion diagnosed as malignant, regardless of the number of lesions present. No patient in this group had percutaneous biopsy, however, and the remaining 23 patients (51 %) in this group had either no follow-up or less than 6 months of follow-up. Discussion Recent advances in imaging techniques have led to the detection of an increasing number of small hepatic lesions [5-7}. The detection of lesions of this size is a problem for both clinicians and radiologists because the significance of these lesions is unknown. Many questions arise after their detection. Are they malignant or benign? Should biopsy be attempted? In some cases, the lesions can be diagnosed as benign by other imaging studies, such as MR imaging, Tc-Iabeled RBC SPECT, or sonography. Unfortunately, our current imaging techniques do not always permit characterization of very small lesions. Similarly, biopsy to obtain histologic proof may be technically difficult owing to the small size and multiplicity of lesions. Our results indicate that a significant proportion of these lesions are benign, even in patients with a known extrahepatic malignant neoplasm. Single small lesions were benign in 65% of patients in our study, and, even when two to four small lesions were present, the lesions were benign in 59% of

5 AJR:158, March 1992 CT OF SMALL HEPATIC LESIONS 539 patients. As the number of lesions increased, or in the presence of an additional large lesion, the chance of malignancy increased. In no patient with a large lesion and single small lesion was progression of the small lesion seen on CT. We suggest that in patients with hepatic metastases being considered for hepatic resection in whom a lesion smaller than 1 5 mm is present, the nature ofthe small lesion be determined if it is in a location that would exclude the patient as a candidate for resection. The study has several limitations, the foremost being the lack of pathologic proof in the majority of patients. Results of imaging studies or stability with time as shown by CT was the basis for confirming a lesion as benign. Most of the patients did not have biopsy, as the risks and technical limitations were judged to outweigh the potential benefits. In only three patients could biopsies be done of all the small lesions present. In patients who had biopsy of one small lesion only, the nature of all small lesions present was not proved. Similarly, in those patients with multiple lesions, progression of a single lesion placed the lesion in the malignant category, but the nature of the additional lesions could not always be determined. We acknowledge that some of the patients with known cancer whose hepatic lesions were stable as shown by CT follow-up at 6 months may have stable or slow-growing metastases. Six (21 %) of the 29 patients with a known malignant tumor and stability for more than 6 but less than 1 2 months had had interval chemotherapeutic or immunotherapeutic treatment, which may have contributed to apparent stability. This may result in overestimation of the number of benign lesions. However, even if all patients with less than 1 2 months of follow-up are excluded from the benign group, 38% of all patients and 37% of patients with a known malignant tumor would still be classified as having benign disease. The study is also somewhat limited by technical variations between scans. The entrance studies were selected to include only patients who had been given a bolus of IV contrast material. However, because of clinical circumstances, it could not be guaranteed that identical doses, volumes, rates, or contrast agents were used on previous or subsequent studies in each patient. These differences could result in less sensitive comparison CT study. The subgroup affected by this limitation comprises those who were classified as having stable disease but may actually have had undetected new lesions or those in whom an increase in lesion size was not detected. However, in patients with cancer in whom lesions were classified as stable on the basis of CT, significant technical variations between studies were found for only eight of 99 patients. Other technical limitations that may account for missed lesions include volume averaging or slight differences in slice location or respiratory excursion. When adequate technique was used and small lesions were not repeatedly visualized, they could probably be considered stable; they definitely had not enlarged. We did not attempt to characterize the lesions by margin or density, as these methods are plagued by partial-volume effects in lesions of this small size [8]. In conclusion, we have shown that the presence of small hepatic lesions in patients with a known malignant tumor does not necessarily imply metastatic disease. On the contrary, hepatic lesions 1 5 mm and smaller were benign in approximately half the patients with cancer in our study population. Our finding that a single small lesion in the presence of a second larger lesion was likely to represent benign disease should also be considered before excluding a patient from hepatic resection on this basis. In addition, patients with small hepatic lesions and no known extrahepatic malignant neoplasm were unlikely to have occult malignant hepatic disease. Although this group was small, our results suggest these patients should probably have follow-up with CT or other confirmatory imaging studies rather than invasive diagnostic procedures. ACKNOWLEDGMENTS We thank Shirley C. Wray and Patti Frizzell for assistance in manuscript REFERENCES preparation. 1. Ferrucci JT. Liver tumor imaging: current concepts. AJR 1990; 155: Gaines PA, Sampson MA. The prevalence and characterization of simple hepatic cysts by ultrasound examination. Br J Radio! 1989;62: Ishak KB, Rabin L. Benign tumors of the liver. Med Clin North Am 1975; 59: Karhunen PJ. 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