The authors describe a case of nodular regenerative hyperplasia of the liver and its findings on liver SPECT with Tc-99m radiocolloid and Tc-99m neoglycoalbumin. A 22-year-old woman with systemic lupus erythematosus was hospitalized for intractable thrombocytopenia. A diagnostic work-up including CT revealed multiple liver nodules and portal hypertension with splenomegaly, suggesting hypersplenism as a cause of the thrombocytopenia. Liver SPECT with Kupffer cell–oriented Tc-99m stannous colloid and hepatocyte-oriented Tc-99m neoglycoalbumin showed increased uptake in the liver nodules, indicating the presence of Kupffer cells and hepatocytes. The patient underwent splenectomy and wedge liver biopsy. Pathologic analysis of the liver specimen revealed many hyperplastic nodules and sinusoidal congestion without cirrhosis. Based on these histopathologic features, the diagnosis of nodular regenerative hyperplasia of the liver was made. FIGURE 1Fig. 1: (A) CT shows no appreciable liver nodules. Contrast-enhanced liver nodules are demonstrated in (B) the arterial-dominant and (C) the portal-dominant phases of the sequential contrast-enhanced liver CT. (D) CT during arterioportography shows many contrast-enhanced liver nodules. The largest nodule is seen in the left medial segment. These findings indicate that these nodules had arterial and portal blood supplies. Although most nodules were described to be hypodense as seen on plain CT (1), all nodules in this case are isodense.FIGURE 2Fig. 2: Planar (A) anterior and (B) posterior images with Tc-99m stannous colloid show a heterogeneous distribution and focal increased uptake. Splenomegaly with increased splenic uptake is also noted. According to previous reports, patchy liver uptake, focal photopenic areas with focal patchy uptake within the nodule, and photon-deficient defects were described as the findings of nodular regenerative hyperplasia on radiocolloid liver scintigraphy (2,3).FIGURE 3Fig. 3: Transaxial SPECT images with Tc-99m stannous colloid show focal increased uptake in the liver. The obvious focal uptake (arrow) corresponds to the nodule seen in the left medial segment on the contrast-enhanced CT. Because Smith (3) has raised the possibility of this finding, the focal increased uptake could be related to hyperplasia of Kupffer cells and to possible heterogeneous blood flow (4).FIGURE 4Fig. 4: Transaxial SPECT images with Tc-99m neoglycoalbumin, which is a specific ligand for the asialoglycoprotein (galactose-terminated glycoprotein) receptor on the surface of the hepatocyte (5), show focal increased uptake in the same areas as in the Tc-99m stannous colloid SPECT. The obvious focal uptake (arrow) corresponds to the nodule seen in the left medial segment on Tc-99m stannous colloid SPECT. Because the presence of both Kupffer cells and virtually normal hepatocytes in the nodules were shown, these SPECT findings suggested that the hepatic nodules could have a benign character, although it was difficult to recognize small nodules and confluent nodules on the SPECT images. Multiple benign liver nodules associated with systemic lupus erythematosus and portal hypertension raised the possibility of nodular regenerative hyperplasia of the liver. The patient underwent splenectomy to treat the thrombocytopenia, and a wedge liver biopsy was performed. Histopathologic examination of the liver specimen revealed many noncirrhotic hyperplastic liver nodules without perinodular fibrosis, the sizes of which ranged from 1 mm to 2 cm in diameter. Microscopic examination showed that the the nodules consisted of hyperplastic normal hepatocytes. Perivascular fibrosis was also seen. However, fibrous septa or infiltration of the inflammatory cells, which were suggestive of cirrhosis, were not seen. The diagnosis of nodular regenerative hyperplasia of the liver was made based on these histopathologic findings (4).