CORRESPONDENCE

Positron Emission Tomography for Lymphoma Staging: Tissue Remains the Issue

Ramaprasad Srinivasan, Armando Filie, James Reynolds, Richard Chang, Catherine Chow, David S. Schrump, Yoshiyuki Takahashi, Anthony F. Suffredini, Richard W. Childs

Affiliations of authors: Hematology Branch, National Heart, Lung and Blood Institute (RS, YT, RWC); Urologic Oncology Branch, National Cancer Institute (RS); Laboratory of Pathology, National Cancer Institute (AF), Warren Magnusson Grant Clinical Center, National Institutes of Health (JR, RC, CC, A FS); and Surgery Branch, National Cancer Institute (DSS), Bethesda, MD

Correspondence to: Richard W. Childs, MD, Hematology Branch, National Heart, Lung and Blood Institute, 10 Center Dr., Bldg. 10/CRC-3–5330, Bethesda, MD 20892 (e-mail: childsr{at}nhlbi.nih.gov).

Positron emission tomography (PET) has gained favor as an imaging modality to assess tumor extent and response to chemotherapy and to predict the risk of disease relapse in patients with Hodgkin disease and non-Hodgkin lymphoma (15). Although PET is highly sensitive for diagnosing relapsed lymphomas, the following case from our institution demonstrates that PET positivity does not always imply disease recurrence. A 14-year-old girl with stage III-B diffuse large B-cell lymphoma achieved a complete remission after being treated with cyclophosphamide, doxorubicin, etoposide, prednisone, cytarabine, bleomycin, vincristine, methotrexate, and leucovorin (ProMACE-CytaBOM) chemotherapy. A computed tomography (CT) scan 3 months after the patient completed chemotherapy revealed recurrent mediastinal adenopathy and new lung nodules; lymphoma relapse was confirmed by thoracoscopic lung biopsy. The thoracoscopy was complicated by a pneumothorax and a recurrent left-sided pleural effusion, both of which resolved after the patient underwent talc pleurodesis. The patient received salvage chemotherapy, and follow-up staging studies (CT scans and whole-body gallium and PET scans) revealed that she had achieved a second complete response. She then received an investigational allogeneic hematopoietic cell transplant (HCT) from her human leukocyte antigen–identical brother after reduced intensity conditioning with cyclophosphamide and fludarabine. She was subsequently discharged from the hospital and remained in complete response 100 days after the transplant.

The patient returned to our facility 31/2 years after her transplant for routine restaging studies. She denied having any B symptoms, and her physical examination, bone marrow biopsy, and blood analyses were normal. CT scans revealed no evidence of recurrent lymphadenopathy; multiple left-sided pleural-based masses remained unchanged compared with those detected by CT scans performed after pleurodesis and immediately before HCT (Fig.1, a). However, a PET scan (Fig. 1, b) now showed intense metabolic activity in the pleural-based nodules that was suggestive of lymphoma relapse. A subsequent CT-guided fine-needle aspiration biopsy of a left pleural mass revealed no histopathologic evidence of lymphoma; instead, a granulomatous background with numerous polarizable foreign bodies in multinucleated giant cells (Fig. 1, c) established a diagnosis of talc granulomas. The patient remains well and in complete remission more than 41/2 years after transplantation.



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Fig. 1. Computed tomography (CT), positron emission tomography (PET), and histopathologic features of talc-induced pleural granulomas. a) Three CT scans of the chest obtained 43 months after transplant reveal multiple pleural-based masses (arrows). b) A whole-body PET scan using [2-18F]fluoro-2-deoxy-D-glucose obtained 43 months after transplant shows markedly increased metabolic activity in multiple left pleural–based nodules (arrows). Top panel: Axial view. Bottom panel: Coronal view. c) Biopsy of a left apical pleural–based mass revealed talc granulomas. Top panel: A multinucleated histiocyte containing two plate-like foreign bodies (black arrows) in the cytoplasm (Papanicolaou stain, x400). Middle panel: Two birefringent plate-like foreign bodies (green arrows) consistent with talc crystals (polarized light, x400). Bottom panel: A single foreign body (red arrow) is present in the cytoplasm of a multinucleated histiocyte. Background shows red blood cells and a few polymorphonuclear leukocytes (Diff-Quik stain, x400).

 
PET scan positivity depends on the presence of tissue that has more metabolic activity than normal tissue; however, tissue that is positive on a PET scan is not necessarily neoplastic. Diseases associated with chronic tissue inflammation (i.e., rheumatologic diseases), exposure of bone marrow to granulocyte colony-stimulating factor, and sarcoidosis are examples of non-neoplastic conditions that can result in a false-positive PET scan (6). Talc granulomas are metabolically hyperactive and show increased activity on PET imaging (7). False-positive PET scans are relatively rare, particularly if uptake of [18F]fluorodeoxyglucose is markedly elevated. However, because this imaging modality is not 100% specific for tumor, carefully interpretation of PET scans in the context of the clinical scenario is important.

This case report highlights the importance of considering the possibility that patients who have undergone talc pleurodesis may develop talc granulomas that produce a false-positive PET scan. Histologic or cytologic examination of pleural abnormalities remains the only method to determine whether a positive PET scan is the consequence of malignancy versus a benign inflammatory process, such as a talc-induced granuloma. The time interval required for talc-induced pleural granulomas to resolve is unclear. This case, as well as one reported previously (7), demonstrates that metabolically active granulomas that mimic a tumor relapse on PET scans may persist for years after talc pleurodesis. Therefore, it is important for oncologists to be aware that talc pleurodesis might result in metabolically active pleural granulomas that would diminish the specificity of PET scans obtained for tumor restaging.

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