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False‐positive FDG–PET findings due to bone metastasis from prostate cancer in staging of non‐Hodgkin’s lymphoma

To the Editor: The routine use of FDG–PET in the initial staging of lymphoma increases the probability of incidentally detecting occult cancer other than lymphoma, which is a common cause of false-positive PET findings (1, 2). The misinterpretation of such findings may lead to incorrect clinical management. Here, as a new pitfall in interpreting PET scans, we describe a patient with non-Hodgkin’s lymphoma, in whom increased FDG uptake was detected only in a metastatic bone lesion and not in a primary lesion of a concurrent cancer. A 71-yr-old man presented with left axillary lymphadenopathy. Computed tomography (CT) scans of the chest showed a swelling in two left axillary lymph nodes (Fig. 1A) and an expanded lesion in the posterior arch of the left eighth rib (Fig. 1B). A biopsy of the larger lymph node revealed diffuse proliferation of lymphoma cells (Fig. 1C). These cells expressed CD20, but not CD3, and showed immunoglobulin lambda light chain restriction by flow cytometry. A bone marrow biopsy revealed no evidence of lymphoma involvement. Gallium-67 scans showed abnormal tracer accumulation only in the left axillary region (Fig. 1D), whereas FDGPET scans showed that in both the lesions (Fig. 1E). The patient had no history of traumatic fracture in the rib. FDG–PET scans showed no increased uptake in any other extraskeletal lesions, such as lung or prostate cancer, which have the propensity to metastasize to bones. An open biopsy of the rib under general anesthesia was not performed because of its invasiveness. Although benign hyperplasia could not be completely excluded as a cause of the bone lesion, he was tentatively diagnosed with stage IIE diffuse large B-cell lymphoma. After three cycles of CHOP chemotherapy in combination with rituximab, restaging PET ⁄CT fusion scans showed the disappearance of the lymph node but continued to manifest an increased FDG uptake solely in the bone lesion. Because of the differences in treatment response, we questioned whether the bone lesion was a primary or metastatic bone tumor. Moreover, we observed that the serum prostate-specific antigen (PSA) level was elevated at 31.73 ng ⁄ml (normal value, <3.53 ng ⁄ml), along with an abnormal digital rectal examination of the prostate. A transrectal needle biopsy of the prostate revealed poorly differentiated adenocarcinoma (Fig. 1F). Furthermore, an open biopsy of the rib suggested metastasis of prostate cancer (Fig. 1G), because the tumor cells were positive for PSA by immunohistochemistry (Fig. 1H). We retrospectively confirmed no focal FDG uptake in the prostate bed on restaging PET ⁄CT fusion scans (Fig. 1I). His lymphoma staging was eventually corrected to stage I, and the left axillary area was subjected to involved-field radiotherapy. For prostate cancer, non-steroidal antiandrogen bicalutamide was used in combination with orchiectomy as androgen deprivation therapy. FDG–PET was quite helpful for revealing bone metastasis of prostate cancer in our patient, which otherwise might have gone undetected. In contrast to the better visualization of distant bone metastases, FDG–PET is generally less sensitive for detecting primary prostate cancer because of the relatively slow growth in most prostate cancer cells, with a consequently low glucose metabolism, and the interference of physiologic tracer excretion in the bladder (3). On the other hand, FDG– PET has been reported to have a high sensitivity for detecting that in some advanced-stage patients (4). Despite a higher PSA level, bone metastasis, and higher Gleason score, FDG–PET showed false negative detection of the primary lesion in our patient, suggesting that prostate cancer cells have diversity in metabolic activity. In conclusion, pathological examinations of bone lesions become important when different treatment responses are obtained at each lesion after initial chemotherapy in patients with lymphoma and suspected bone involvement. However, in a study of 18 patients with lymphoma and FDG-avid bone lesions, all direct bone biopsies have proved the presence of lymphoma involvement (5). In elderly male patients, a digital rectal examination and PSA measurement is a less invasive and suitable test for excluding bone metastases of prostate cancer.