Sarcoidosis mimicking recurrent lymphoma
Authors: Wei Li, Karen Holdeman, Javier A. Laurini, Philip J. Bierman, Julie M. Vose, Robert Gregory Bociek, James O. Armitage
Journal: American Journal of Hematology (2011)

A 63-year-old woman became tired, unable to carry out all of her usual activities and had the onset of drenching night sweats in January of 2007. While in the woods feeding deer, she became confused and fell down a hill. She was taken to an emergency room where she was found to have hypercalcemia, renal failure, and retroperitoneal lymphadenopathy. A biopsy of the retroperitoneal lymphadenopathy showed diffuse large B-cell lymphoma. Further evaluation revealed no enlarged supradiaphragmatic lymph nodes, a negative bone marrow biopsy, and an elevated LDH. She was treated with fluids, furosemide, and CHOP plus rituximab in the beginning of March 2007. A restaging evaluation after four cycles of chemotherapy showed a creatinine of 1.0 mg/DL, calcium of 8.7 mg/DL, and LDH of 359 IU/L (maximum normal 618 IU/L). An FDG PET/CT scan showed no evidence of residual lymphoma. The patient received her fifth and sixth cycles of CHOP plus rituximab. In March 2008, she was seen in routine follow-up. She was able to carry out her usual activities, did not complain of being tired, and did not have fevers, drenching night sweats, or weight loss. However, at that time, her calcium was 12.1 mg/DL and LDH 280 IU/L (maximum normal 618 IU/L). Except for some swelling of her eyelids, there were no new physical findings. Because of concern about recurrent lymphoma, an FDG PET/CT scan was performed. (Image 1 is a maximum intensity projection PET image showing focal FDG uptake in multiple lymph nodes of the mediastinum, bilateral hila, and porta hepatis with a maximum SUV of 9.1) Although it appeared that the patient had relapsed, a decision was made to not institute therapy without histological proof of recurrent lymphoma. A biopsy of a mediastinal lymph node and of lacrimal glands showed granulomatous infiltration with occasional multinucleated giant cells consistent with sarcoidosis. (Image 2 shows a lacrimal gland with a noncaseating granuloma H&E stain, 200×). Treatment was instituted with prednisone at a dose of 40 mg. daily. The eye swelling resolved and the serum calcium and the FDG PET/CT scan normalized. As of November 2011, the patient has remained in remission from lymphoma for more than 4 years, and her sarcoidosis and hypercalcemia have never recurred.Image 1., Image 2. Maximum Intensity Projection PET image showing focal FDB uptake in multiple lymph nodes of the mediastinum, bilateral hila, and porta hepatis with a maximum SUV of 9.1 in the right hilar lympho node group. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] Lacrimal gland with a noncaseating granuloma (H&E stain, 3200). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] This patient illustrates the danger of initiating therapy for recurrent lymphoma in a patient in initial complete remission based on abnormal imaging studies when no biopsy has been performed. Whether salvage chemotherapy and an autotransplant (i.e., the standard therapy for recurrent diffuse large B-cell lymphoma) might have cured the patient's sarcoidosis is unknown, but it would have been unnecessary and dangerous. It is our policy to never treat a patient who achieves a complete remission without biopsy proof of recurrence. Over the last 30 years, this has led to avoiding further chemotherapy or radiation in patients with follicular hyperplasia, other malignancies, infections, and sarcoidosis. PET scans represent an important advance in evaluating patients with lymphoma. They are more accurate than CT scans in identifying active disease, and a negative PET scan at the completion of therapy is the best evidence of a complete remission [1]. However, although PET scans are quite sensitive, they are not specific for lymphoma [2-6]. Among the conditions that are also often PET avid and might mimic recurrent lymphoma are other malignancies, sarcoidosis, Wegener's granulomatosis, chronic granulomatous disease, and mycobacterial and aspergillus infections. The accumulation of FDG in inflammatory cells including macrophages, lymphocytes, and neutrophils accounts for many of these false-positive findings.