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1
Departments of Radiology and Haematology, Hadassah University Hospital, P. O.
Box 12000, Jerusalem 91120, Israel.
2
Department of Radiology, Sheba Medical Center, Ramat-Gan 52621, Israel.
3
Department of Clinical Radiology, St. James University Hospital, Beckett St.,
Leeds, LS9 7TF, United Kingdom.
Received May 9, 2001;
accepted after revision August 3, 2001.
Address correspondence to J. A. Spencer.
Abstract
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MATERIALS AND METHODS. A retrospective review of medical records and CT examinations of patients who received a diagnosis of primary mediastinal B-cell lymphoma between January 1989 and January 2000 was performed. The first-year follow-up comprised examinations at 3-month intervals of the neck, chest, abdomen, and pelvis, with the examination modality alternating between CT and gallium scintigraphy. Patients who achieved complete remission underwent the same CT protocol twice the following year and then once a year during sequential follow-up.
RESULTS. Fifty-three patients with primary mediastinal B-cell lymphoma at presentation—31 females and 22 males, ranging in age from 17 to 61 years (average age at diagnosis, 34 years)—were studied. The follow-up time ranged from 6 to 143 months (average follow-up time, 42.4 months). Although 11 of the patients had only a partial remission, 42 patients (79%) achieved complete remission, with one patient lost to follow-up and thus excluded from study. Recurrence was diagnosed in six of these 42 patients. All six had mediastinal recurrence with additional involvement of the lungs, chest wall, pericardium, and pleura. One patient also had bone marrow involvement at recurrence.
CONCLUSION. Recurrence of primary mediastinal B-cell lymphoma in patients who achieve complete remission appears to be confined to the chest. Consequently, chest CT alone is sufficient for routine follow-up of these patients.
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No consensus on the follow-up protocol for patients with primary mediastinal B-cell lymphoma has been reached, so the protocol varies depending on the institutions conducting the follow-up but may include chest radiography, total body CT (neck, chest, abdomen, and pelvis), or gallium scintigraphy. We assessed the necessity of total body CT examination for detecting the recurrence of disease in patients with primary mediastinal B-cell lymphoma that is in remission.
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During the first year of follow-up, all patients in our study had been examined with contrast-enhanced CT of the neck, chest, abdomen, and pelvic or gallium scintigraphy every 3 months in an alternating fashion. Complete remission was defined as a return to normal of all radiologic findings in the chest. Small remnants of the mediastinal mass (<25% of the original mass) without any clinical signs of active disease and no evidence of activity on the gallium scan were also defined as showing complete remission because such findings are thought to represent scar tissue [3, 4]. Patients achieving complete remission underwent the same CT protocol twice the following year and then once a year during subsequent follow-up.
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All patients had CT evidence of mediastinal disease. Twenty-four patients had only an anterior mediastinal mass; 29 patients had additional CT findings including invasion of the chest wall, lung, pleura, and pericardium. The largest mass was 15 cm in diameter. At diagnosis, the findings of gallium scintigraphy were positive in all 35 patients in whom it was performed. The findings of bone marrow examination were positive in only one patient.
Forty-two patients (79%) achieved complete remission, including patients with stable residual masses as large as 2.5 cm in diameter. Of these, one patient was lost to follow-up after 4 months. Recurrence of the disease was diagnosed in six patients of the 42 who achieved complete remission (15%). The amount of time elapsed between the first diagnosis and recurrence ranged from 6 to 33 months (average time, 21.8 months).
All six patients had recurrence of the disease in the mediastinum (Fig. 1). Other sites of involvement in the chest were the lungs (two patients) and a direct extension of disease into the anterior chest wall (two patients), pericardium (one patient), and pleura (one patient). The lung involvement was via direct extension from mediastinal disease in one patient and multiple nodules in the other patient. Although no patient had been found to have bone marrow involvement at diagnosis, one patient had recurrence of the disease at that site (in addition to the mediastinal recurrence).
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Eleven patients achieved only a partial remission after primary therapy, and of these, 10 have died showing evidence of intrathoracic lymphoma. At 8 months after diagnosis, the remaining patient has persistent chest wall disease and is receiving further chemotherapy.
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Our study included 53 patients, and we found only a slight predominance of the disease in women (58%). The average age at diagnosis was 34 years. As in other studies, complete remission was defined as disappearance of all radiologic findings in the mediastinum or residua of less than 25% of the original tumor with no clinically or biologically detectable signs of active lymphoma [3, 4]; 42 of the 53 patients achieved complete remission.
In a large multicenter study, Cazals-Hatem et al. [3] compared the clinicopathologic features of 141 patients with primary mediastinal large B-cell lymphoma and those of 916 patients with nonmediastinal large B-cell lymphoma. Unlike patients with nonmediastinal lymphoma, patients with primary mediastinal lymphoma had no hematologic dissemination and only rarely had involvement of peripheral lymph nodes or extrathoracic sites. In primary mediastinal lymphoma, the disease seemed to favor confinement to the chest cavity. Involvement of intrathoracic organs (lung, pleura, or pericardium) was shown to be considerably more common than in nonmediastinal lymphoma; such intrathoracic involvement is apparently attributable to direct spread by the disease.
To our knowledge, no formal evaluation has been conducted of the rationale for using CT in the follow-up of patients with primary mediastinal lymphoma who had complete remission. In our study, all six patients who had recurrence of the disease after remission were found to have the recurrence in the mediastinum. In the study by Cazals-Hatem et al. [3], recurrence in all but one patient was confined to the chest. In our study, the sites of recurrence in the chest included the lung, chest wall, pericardium, and pleura. Only one patient was found to have bone marrow involvement in addition to chest disease.
The uncertainty about appropriate follow-up of lymphoma is not limited to patients with primary mediastinal B-cell tumors. The goal of follow-up is to detect recurrence as early as possible, but exposure of patients to the ionizing radiation used in CT confers the risk of second malignancy and genetic damage. Furthermore, the risks associated with individual CT examinations are multiplied in follow-up. There is increasing concern about this risk for patients with potentially curable cancers such as lymphoma [15].
Strategies to reduce the risk include limiting the number of CT scans, limiting the body parts covered, limiting the number of CT slices obtained, or substituting CT with alternative examinations such as MR imaging or sonography. With large-volume abdominal non-Hodgkin's lymphoma, a few CT slices through the abdomen have been shown to be sufficient to assess treatment response [16]. The situation is different for detailed assessment at initial diagnosis or for confirmation of continued remission. Naik et al. [17] compared alternate-slice and contiguous-slice CT techniques for lymphoma staging. In that study, the researchers found that there was a reduction of nearly 50% in the effective radiation dose exposure with no loss of staging accuracy using alternate-slice CT examinations compared with contiguous-slice CT examinations. Gallium scintigraphy offers an alternative to CT for detection of recurrent disease, but it also subjects the patient to repeated doses of ionizing radiation. We were unable to directly compare CT and gallium scintigraphy as methods for early detection of disease recurrence.
In light of our findings, we suggest that CT examinations of the neck, abdomen, and pelvis are not warranted in the follow-up of patients with primary mediastinal B-cell lymphoma in remission. Limiting follow-up CT examinations to the chest will save patients unnecessary exposure to radiation, reduce patient preparation time and discomfort, and considerably lower the duration and cost of routine follow-up. Primary mediastinal B-cell lymphoma in patients with complete remission recurs in the chest (Fig. 1). Consequently, chest CT examination alone is sufficient for routine follow-up of these patients.
Acknowledgments
We thank Sheila Boyes for her hard work in the preparation of this
manuscript.
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