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Journal of Clinical Oncology, Vol 23, No 31 (November 1), 2005: pp. 8113-8116 © 2005 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.08.107
Variable Problems in LymphomasCASE 2. Sarcoidosis Mimicking Progressive LymphomaGreenwich Hospital, Yale New Haven Health System, Greenwich, CT
Memorial Sloan-Kettering Cancer Center, New York, NY A 56-year-old woman presented with postmenopausal bleeding. A pelvic mass was palpable. Computed tomography (CT) scan demonstrated a uterine mass, right iliac adenopathy, and bilateral hydronephrosis. Surgical exploration demonstrated a large uterine mass, infiltration of the round ligaments bilaterally, bilateral ureteral dilation, and dense adherence of the bladder to the lower uterine segment and cervix. The patient underwent a supracervical hysterectomy, bilateral salpingo-oophorectomy, and bilateral ureterolysis. Pathology showed diffuse large B-cell lymphoma (Fig 1) extensively infiltrating the pelvic peritoneum, uterus, and both fallopian tubes. Postoperative CT staging showed bilateral hydronephrosis, debulking of the pelvic mass, and postoperative changes. Chest CT showed 1- to 2-cm right paratracheal nodes and a 1.5-cm left aortopulmonic window node. There was no hilar adenopathy. An [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) scan (Fig 2) demonstrated mutiple foci of abnormal tracer activity in both hilar and the right paratracheal area. Tracer activity in the pelvis was mild and felt consistent with the postoperative state. There was no definite nodal positivity in the retroperitoneum. Hydronephrosis was again evident. Serum creatinine and lactate dehydrogenase were within normal limits. Bone marrow and spinal fluid examinations were negative. The patient was treated with four cycles of rituximab, cyclophosphamide, vincristine, doxirubicin, and prednisone, and intrathecal methotrexate with G-CSF support on a 2-week cycle. After the fourth cycle, follow-up CT scans demonstrated that the mediastinal adenopathy was slightly smaller, although persistent. The residual soft tissue mass in the pelvis had diminished, and the hydronephrosis had resolved. A follow-up FDG-PET scan (Fig 3) revealed interval increased activity in the mediastinum. The maximum standard uptake value of these lesions had approximately doubled. Also noted was increased bone marrow activity felt to be a result of chemotherapy. There was no abnormal activity below the diaphragm. The patient completed two additional cycles of treatment without difficulty. A third PET scan (not shown) obtained 4 weeks after cycle 6 showed the same findings as the second scan. Mediastinoscopy was performed for tissue diagnosis. The pathology (Fig 4) showed noncaseating granuloma consistent with sarcoidosis. Fungal and mycobacterial cultures were negative. Serum angiotensin-converting enzyme level was 3 (range, 9 to 67 U/L). The patient remains in clinical complete remission after chemotherapy. She has had no symptoms related to her sarcoidosis and has required no treatment for it.
The association of sarcoidosis and malignant lymphoma was described in 1979.1 In two cases, the lymphoma preceded the diagnosis of sarcoidosis.2 In 1996, a patient was described whose preexisting sarcoidosis was exacerbated by chemotherapy for non-Hodgkin's lymphoma.3 Two additional patients reported to have non-Hodgkin's lymphoma developed active sarcoidosis during or immediately after combination chemotherapy.4 Our patient is another example. In all of these cases, treatment of the lymphoma appears to have exacerbated pre-existing, occult sarcoidosis. This is particularly unexpected because sarcoidosis itself is treated with similar immunosuppressive therapies, including corticosteroids and, in refractory cases, chemotherapy itself.5 Sarcoidosis has also been described after treatment for solid tumors, including radiation and chemotherapy for testicular cancer,6 chemotherapy for osteosarcoma,7 and interferon for renal cell cancer.8 FDG-PET scanning is being used more commonly in the management of patients with malignant lymphoma.9 Similar to lymphoma, sarcoidosis can cause increased FDG uptake in mediastinal lymph nodes.10-12 Abnormal uptake of FDG caused by sarcoidosis is indistinguishable from that caused by lymphoma. Therefore, the possibility that abnormal PET scans of lymphoma patients could be due to sarcoidosis and not malignancy must be considered. In cases of apparent progressive lymphoma during or subsequent to combination chemotherapy, biopsy confirmation should be considered. Tissue confirmation of sarcoidosis was critical for the further management of our case. Authors' Disclosures of Potential Conflicts of Interest Although all authors completed the disclosure declaration, the following authors or their immediate family members indicated a financial interest. No conflict exists for drugs or devices used in a study if they are not being evaluated as part of the investigation. For a detailed description of the disclosure categories, or for more information about ASCO's conflict of interest policy, please refer to the Author Disclosure Declaration and the Disclosures of Potential Conflicts of Interest section in Information for Contributors.
Dollar Amount Codes (A) < $10,000 (B) $10,000-99,999 (C)
REFERENCES 1. Brincker H: The incidence of malignant tumors in patients with respiratory sarcoidosis. Br J Cancer 29:247-251, 1979 2. Brincker H: The sarcoidosis-lymphoma syndrome. Br J Cancer 54:467-473, 1986[Medline] 3. Keohane GSG, Savin JA, Tidman MJ, et al: The sarcoidosis-lymphoma syndrome: Acceleration of the cutaneous sarcoidosis during chemotherapy of lymphoma. Acta Derm Venereol 76:251-253, 1996[Medline] 4. Kornacker M, Kraemer A, Leo E, et al: Occurrence of sarcoidosis subsequent to chemotherapy for non-Hodgkin's lymphoma: Report of two cases. Ann Hematol 81:103-105, 2002[CrossRef][Medline] 5. Baughman RP, Ohmichi M, Lower EE: Combination therapy for sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 18:133-137, 2001[Medline]
6. Trum DL, Ettinger DS, Feldman MJ, et al: Sarcoidosis and sarcoid-like lesions: Their occurrence after cytotoxic and radiation therapy of testis cancer. Arch Intern Med 141:37-38, 1981
7. Sybert A, Butler TP: Sarcoidosis following adjuvant high-dose methotrexate therapy for osteosarcoma. Arch Intern Med 138:488-489, 1978 8. Abdi EA, Nguyen G, Ludwig RN, et al: Pulmonary sarcoidosis following interferon therapy for advanced renal cell carcinoma. Cancer 59:896-900, 1987[CrossRef][Medline]
9. Elstrom R, Guan L, Baker G, et al: Utility of FDG-PET scanning in lymphoma by WHO classification. Blood 101:3875-3876, 2003
10. Lewis PJ, Salama A: Uptake of fluorine-18-flurodeoxyglucose in sarcoidosis. J Nucl Med 35:1647-1649, 1994 11. Yasuda S, Shohisu A, Ide M, et al: High fluorine-18 labeled deoxyglucose uptake in sarcoidosis. Clin Nucl Med 21:983-984, 1996[CrossRef][Medline]
12. Yamada Y, Uchida Y, Tatsumi K, et al: Flurine-18-flurodeoxygenase and carbon-11-methionine evaluation of lymphadenopathy in sarcoidosis. J Nucl Med 39:1160-1166, 1998
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Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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