A 60-year-old man employed as a sanitation worker presented to his primary physician with several weeks of a dry cough. His past medical history was significant for chronic sinusitis. A chest X-ray revealed mediastinal fullness, and further imaging studies included a positron emission tomography and computed tomography scan that was notable for hypermetabolic cervical and mediastinal lymph nodes.
Biopsy was consistent with classical Hodgkins lymphoma. A complete staging workup revealed normal pulmonary and cardiac function, and the patient completed six cycles of chemotherapy with adriamycin, bleomycin, vinblastine and dacarbazine without complications. He then underwent involved field radiation. Follow-up PET/CT confirmed a complete response. Six months later a restaging PET/CT revealed new linear, band-like metabolic activity in the anterior mediastinum to the right of the midline, adjacent to the location of the initial lymphoma.
Figure 1. An axial image through the chest from the staging PET/CT examination.
Figure 2. An axial image through the chest from the staging PET/CT examination, slightly caudal to figure 1.
Figure 3. Axial CT, PET and fusion images through the chest. Three rows of images depict baseline examination (1st row), one-year follow-up (2nd row) and 18-month follow-up (3rd row).
Figure 4. Another set of baseline, and two follow-up examinations emphasizing the findings discussed in the legend of the figure 3.
Source: M Ghesani
This case illustrates a phenomenon called thymic rebound (also called benign thymic hyperplasia), which is defined as thymic regrowth 50% greater than baseline volume. Benign thymic hyperplasia occurs mainly after treatment with chemotherapy, but infrequent case reports describe its occurrence after periods of stress in cancer patients off chemotherapy as well. Chemotherapy causes thymic atrophy and a decrease in average volume of 33%, and regrowth occurs after treatment completion.
Benign thymic hyperplasia was initially described in children recovering from thermal burns, and later recognized as thymic rebound in children following chemotherapy. It has been associated with various types of pediatric cancers, including lymphomas, leukemias, testicular cancer, sarcomas and in the stem cell transplant setting.
The literature in adults is scarce, but it may occur in about 25% of adult chemotherapy patients. Benign thymic hyperplasia in adults has been documented in early stage breast cancer, lymphoma and uterine leiomyosarcoma. It usually occurs within the first year after chemotherapy, but it can present as many as five years later. In one case series, 31 of 134 PET scans (23.1%) for lymphoma showing focal flurodeoxyglucose uptake were diagnosed as nontumoral radiotracer uptake. Five of the 31 false-positive PET scans were related to thymic hyperplasia.
Benign thymic hyperplasia may result in diagnostic inaccuracies in PET scan interpretation with potential implications on patient management. However, an experienced interpreter of PET/CT scans can readily recognize its pattern on both PET and CT imaging, and temporally correlate it with a history of chemotherapy to avoid misinterpretation. If there remains a high suspicion of malignancy despite consideration of thymic rebound, tissue confirmation should be obtained to avoid the morbidity of unnecessary treatment.
Benign thymic hyperplasia, or thymic rebound, should be included in the differential diagnosis of a soft tissue mass appearing in the anterior mediastinum on follow-up imaging, particularly following chemotherapeutic treatment for malignancy. In our case, since the region of presumed thymic rebound was not primarily involved with Hodgkins disease but appeared only on the follow-up scans, we have chosen not to subject the patient for biopsy, but instead perform a close-interval follow-up for assessment of stability and resolution.
Munir Ghesani, MD, is Associate Clinical Professor of Radiology at Columbia University College of Physicians and Surgeons.
Frank Colella, MD, is a private practice hematologist/oncologist.
Carrie Wasserman, MD, is second year Hematology Oncology Fellow at St. Lukes Roosevelt Hospital Center.
For more information:
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- Flieder DB, Vora SK, Sanders A, Gelbman B. Benign thymic hyperplasia as a cause of anterior mediastinal mass after chemotherapy. Chest. 2004;126:929S.
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- Castellucci P, Nanni C, Forsad M, et al. Potential pitfalls of 18F-FDG PET in a large series of patients treated for malignant lymphoma: prevalence and scan interpretation. Nucl Med Commun. 2005;26:689-694.
- Yarom N, Zissin R, Apter S, et al. Rebound thymic enlargement on CT in adults. Int J Clin Pract. 2007;61:562-568.