Ga-67 Citrate Imaging of Abdominal Visceral Lymphoma

Richard C. Hom, M.D., Ph.D.

Annick Van den Abbeele, M.D.

Milos Janicek, M.D., Ph.D.

September 20, 1994

Case Presentation:

A 42 year old man presented with fevers, cervical lymphadenopathy, and a mediastinal mass on the chest X-ray. Biopsy of the cervical node demonstrated follicular non-Hodgkin's lymphoma.

Findings:

Gallium SPECT images of the chest (50k bytes) demonstrates an prominent retrosternal lesion (arrow, 50k bytes). The liver appears to be inhomogeneous. SPECT images of the abdomen (transverse, 54k bytes; and coronal, 68k bytes) confirming the inhomogeneous distribution within the liver parenchyma with focal areas of increased uptake in the liver (arrow: transverse, 54k bytes) and the kidney (coronal, 68k bytes). A CT scan confirmed the presence of metastatic lesions in the liver. The CT scan (41k bytes) also showed metastatic renal involvement (arrows, 41k bytes). A SPECT Ga scan was performed 2 months later after 2 cycles of intensive chemotherapy and demonstrated a minimal decrease in the chest, liver, and renal lesions.

Imaging Technique

Ga-67 SPECT images were acquired using a Siemen's MS-2 MultiSpect dual head camera with medium energy collimators for 64 views (2 x 32), 180o, 50 sec/image with a matrix size of 64 x 64. A Butterworth filter was used in the reconstruction of the raw data using a cut-off of 0.6 and an order of 7.

Discussion:

Extralymphatic organ involvement (such as the liver) by lymphoma with or without lymph node involvement is Stage IV by the Ann Arbor staging system with a low cure rate and discouraging prognosis. Liver biopsies of non-Hodgkin's lymphoma (NHL) patients have demonstrated liver involvement in as many as 58% of patients. Similarly, 23% of untreated patients in Hodgkin's disease (HD) may have liver involvement. In both Hodgkin's disease and non-Hodgkin's lymphoma, when there is hepatic involvement, the liver is often enlarged. In addition, when the spleen is enlarged in Hodgkin's disease, the risk of liver involvement may be as high as 28%. The involvement may be focal or diffuse. When it is focal, it tends to involve the portal tracts, often resulting in jaundice. Hepatomegaly in non-Hodgkin's lymphoma tends to suggest lymphomatous involvement more than in Hodgkin's disease. Frequently, there is a rise in nucleotidase and alkaline phosphatase.

Noninvasive Diagnosis of Extralymphatic Lymphoma

Noninvasive diagnosis of hepatic involvement by lymphoma may be difficult to make. Diffuse lymphomatous involvement is particularly difficult to image as plain radiographs may demonstrate only nonspecific hepatomegaly. Radiographic techniques may be better for the more focal lesions. Angiography may demonstrate hypovascular or avascular masses with vascular displacement while ultrasound may identify lymphoma as hypoechoic masses. CT scan at present is considered the preferred imaging modality for hepatic lymphoma with one series reporting a sensitivity of 57% and a specificity of 88% (Zornoza). Tc-99m sulfur colloid imaging has not been used extensively in staging lymphoma or in assessing hepatic involvement by lymphoma because of its low sensitivity and specificity.

Gallium Scintigraphy in Hepatic Lymphoma

Gallium is normally taken up by both the liver and the spleen and has not been used routinely to diagnose hepatic lymphoma. Even with the widespread use of SPECT imaging, little has been published on the use of the technique in the diagnosis of solid organ involvement by lymphoma. No sensitivity or specificity data are consequently available for the use of Ga-67 SPECT imaging for the diagnosis of hepatic involvement by lymphoma. While its role has not been established, it is at the very least an adjunct to other imaging modalities such as the CT scan to exclude benign abnormalities.

While focal hepatic abnormalities suggest recurrent disease following treatment of lymphoma, other entities may cause focal abnormalities. One is focal hepatic candidiasis. This disease is most often manifested as the bone marrow is recovering following prolonged fever and neutropenia with multiple courses of antibiotics. Often it is difficult to diagnose but is suggestive with rising liver function tests (especially the alkaline phosphatase) and fever. Cultures including those obtained from biopsies often demonstrate no growth. The role of Ga-67 citrate imaging has not been well established for the diagnosis. Early studies were done with Tc-99m sulfur colloid and had variable results (Tashjian). SPECT imaging for this disease has not been reported in the literature. Whether Ga-67 citrate SPECT imaging, while unable to distinguish recurrent lymphoma from focal hepatic candidiasis, might be helpful when used in conjunction with other studies remains to be established.

Gallium Scintigraphy in Other Viscera

Other solid abdominal viscera that can be involved in both Hodgkin's disease and non-Hodgkin's lymphoma are the spleen and pancreas. Lymphoma is the most common malignant splenic tumor and is frequently microscopic. Tc-99m sulfur colloid imaging has a 54% sensitivity and 64% specificity while CT scanning has an 89% sensitivity and a 94% specificity. Like hepatic lymphoma, the role of gallium scanning has not been well defined and no data is available regarding it's sensitivity or specificity in the diagnosis of lymphomatous involvement. Pancreatic involvement by lymphoma is rare in Hodgkin's disease based on clinical findings but the incidence is much higher on autopsies and is frequently under appreciated. The disease may be related to peripancreatic lymph node involvement. No data is available for the best diagnostic modality.

Gallium Scintigraphy in Lymphoma

While data are not available for the sensitivity and specificity of gallium scanning in hepatic lymphoma, much has been published on the use of gallium scanning in the detection of lymphoma involvement above and below the diaphragm before and after treatment as well as a predictor of clinical outcome during or following therapy. An early study by Tumeh and colleagues demonstrated that SPECT imaging obtained following injection of 10 mCi of Ga-67 citrate can be quite useful in the diagnosis of disease above and below the diaphragm (Kostakoglu et al had similar data, also using 10 mCi of Ga-67). For the detection of disease at any site in 54 studies with 40 patients, planar imaging had a sensitivity of 66% and a specificity of 66%. SPECT was 96% sensitive and 100% specific. For the abdomen, the authors found planar imaging had a sensitivity and specificity of 69% and 85%, respectively, while SPECT was 87% and 100%, respectively.

In a larger study using only 5-7 mCi of Ga-67, Front and colleagues found in 77 patients with lymphoma (38 Hodgkin's disease + 39 non-Hodgkin's lymphoma) at 240 sites, the sensitivity and specificity in patients before treatment was 78% and 97%, respectively, for planar imaging and 85% and 96%, respectively for SPECT imaging. After treatment, the planar study had a sensitivity of 84% with 96% specificity. SPECT had 92% and 99%, respectively.

Gallium-67 imaging has also been used as a predictor of survival from Hodgkin's disease or non-Hodgkin's lymphoma after treatment, by Front and colleagues. When compared with CT (which cannot distinguish between active/residual tumor from necrotic or fibrotic tumor), Ga-67 imaging has been more useful. The positive predictive value for survival for Hodgkin's disease was 0.80 and 0.29 for CT in 43 patients while the negative predictive values were 0.84 and 0.88 respectively. In non-Hodgkin's lymphoma, for 56 patients, the positive predictive values for Ga-67 and CT were 0.73 and 0.35 while the negative predictive values were 0.84 and 0.80, respectively.

Conclusions:

While data are not available for the sensitivity and specificity of gallium scanning in hepatic lymphoma or the lymphomatous involvement of other intra-abdominal solid organs, awareness that Ga-67 imaging can image solid visceral lymphoma is helpful in the evaluation of patients particularly for staging, during and after therapy and may have an impact in determining their subsequent therapies and prognoses.

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J. Anthony Parker, MD PhD, Tony_Parker@bih.harvard.edu