The Gallium Avidity of Untreated Hodgkin's and Non-Hodgkin's Lymphoma

Laurent Dinh M.D.

Milos Janicek M.D. Ph.D.

May 10, 1994

Case Presentation:

A 31 year-old male presented with a node in his left lower neck region. A biopsy of the node revealed Hodgkin's lymphoma, nodular sclerosis type. Subsequently a mediastinal mass was found. Prior to Gallium scintigraphy he was initially staged as IIA.

Findings:

The baseline 67-Ga scan (68k bytes) showed much more extensive disease. Ga avid tumors were present in the left supraclavicular, left upper cervical regions, right axilla, mediastinum, both hila, right infraclavicular region, left para aortic region, and a small focus in the splenic hilar region (arrows, 68k bytes). Activity in the cecum cleared on delayed images.

Course:

He underwent 6 cycles of chemotherapy. The first 67-Ga scan (63k bytes) after chemotherapy demonstrated response to therapy even in the presence of a residual mass in the mediastinum on CT. (Incidental throat infection is seen on the Gallium scan arrow (63k bytes).) However the follow-up scan (68k bytes) 6 months after chemotherapy demonstrated the presence of residual disease in the left mediastinum, the right axilla, and the right lower lung field (arrows, 68k bytes). These finding correlates with the disease progression noted on CT. He went on to receive a second chemotherapy and radiation. On the follow-up scan the disease was still active. Unfortunately, the patient decided to try an alternate medicine.

Discussion:

67-Ga scintigraphy has been used for more than 20 years in the detection of malignancies. Its exact role in malignant lymphoma has been disputed, mainly because of the high false-negative rate reported in the earlier studies. However numerous reports have been published and have highlighted its major contributions in malignant lymphoma:

1. To stage the disease.

Gallium scintigraphy has shown to have an impact on the management by altering staging. It obviates the need for the staging laparotomy. It can alter the radiation therapy planning. Furthermore, the Gallium avidity of the patient's disease should be determine at the time of diagnosis, as this will act as a positive control for follow-up.

2. To detect relapse during follow-up.

Gallium scintigraphy has demonstrated its superiority to detect early relapse, as CT cannot differentiate fibrotic tissue from active disease.

3. To predict response to therapy.

Patients with a positive Gallium scan prior to therapy who fail to normalize their Gallium scan during therapy have a poor prognosis. It is a important indicator to the clinician to institute an alternative therapy.

4. To predict outcome and prognosis (future trends).

Failure to convert to a normal Gallium scan during therapy is a sign of less favorable prognosis in non-Hodgkin's lymphoma (DLCL).

The role of 67-Ga scintigraphy in lymphoma relies on its ability to detect viable residual disease with or without residual radiographic abnormalities and conversely to identify patients with no viable disease whose radiographic studies are still abnormal. Such an application may depend on a high 67-Ga avidity in untreated tumors. The delectability of malignant lymphoma by 67-Ga scintigraphy appears to be related to the histologic type, and also to imaging parameters such as the anatomic location and the size of the lesion. The role of the histologic type in the 67-Ga uptake was expressed in the Cooperative Group studies, and is displayed as follow:

Untreated Malignant Lymphoma 
Histologic type      Positive (%)  Negative (%)  Equivocal (%)
Lymphocytic well diff     59          35            6
Lymphocytic poorly diff   73          21            6
Histiocytic               89          11            0
Mixed cell                70          28            2
Undifferentiated          50          25           25
Burkitt's                100           0            0
total                     76          21            3

Hodgkin's Disease 
Histologic type   Positive (%)  Negative (%)  Equivocal (%)
Nodular sclerosis     89           6             6
Mixed cellularity     90           8             1
Lymphocyte depletion  90          10             0
Lymphocyte predom.    79           9            12
total                 88           7             5

These results rely however on data from the `70 using older 67-Ga imaging techniques: rectilinear scanners, one acquisition window, low dose of 67-Ga, and no additional delayed views. In addition, relatively insensitive methods of detecting disease were used. In Dr. Bekerman's review in 1985, a sensitivity of 70% is reported for Hodgkin's and histiocytic non-Hodgkin's lymphomas and 50% for the lymphocytic or mixed lymphocytic-histiocytic lymphomas. In Dr. Anderson's study, a more optimal imaging technique was used, sensitivity and specificity are reported as 97% and 100% for Hodgkin's and 92% and 100% for non-Hodgkin's lymphoma. More recently, Dr. Tumeh demonstrated that using SPECT the sensitivity and specificity values for Hodgkin's and non-Hodgkin's lymphoma combined were 96% and 100% for the chest, and 85% and 100% for the abdomen.

The mechanism of 67-Ga uptake in tumor remains uncertain. Experimental studies have linked the degree of Gallium uptake to the metabolic activity. In an in vitro study with regenerating liver, the Gallium uptake was associated to the G2 phase of the protein synthesis phase of the cell cycle. Others have shown that the Gallium uptake was related to the proliferation of the ribosomal protein synthesis structures. The tumor perfusion is also an integral part of the Gallium uptake. Tumor perfusion is often increased as compared to normal surrounding tissue, and capillary permeability is also increased. Transferrin receptors at the cell surface have been postulated as responsible for uptake in tumor. The increase of the extracellular fluid coupled with the increased capillary permeability in tumor might also favor diffusion in the tumor.

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