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Journal of Clinical Oncology, Vol 23, No 34 (December 1), 2005: pp. 8906-8907 © 2005 American Society of Clinical Oncology. DOI: 10.1200/JCO.2004.00.4606
Positive Positron Emission Tomography Scan in Sarcoidosis and Two Challenging Cases of Metastatic CancerCASE 1. Mediastinal Sarcoidosis in a Melanoma Patient Treated With InterferonUniversity Medical Center Nijmegen, Departments of Nuclear Medicine, Medical Oncology, Surgery, and Pathology, Nijmegen, the Netherlands A 51-year-old white woman had a Clark I Breslow 2.5 mm melanoma on her left ankle diagnosed in September 2000. Two months later she underwent a re-excision with radioguided sentinel lymph node biopsy and subsequently underwent dissection of the lymph nodes in the left groin, because of sentinel lymph node involvement. Because one of seven lymph nodes was positive for melanoma, she was entered onto a phase III study and was randomly assigned to receive adjuvant therapy with peginterferon alpha-2b (Pegintron; Schering-Plough, Kenilworth, NJ) in January 2001 for a period of 5 years. The initial dose was 6 µg/kg/wk for 8 weeks, followed by an initial dose 3 µg/kg/wk, which was lowered to 2 µg/kg/wk, because of poor condition. In July 2003, she developed multiple in-transit metastases on her left leg, for which she was treated with liquid nitrogen. Because she had no signs of distant metastases, peginterferon alpha-2b was continued. In March 2004, enlargement of the mediastinum was observed on a routine chest x-ray. Computed tomography (CT) of the chest showed multiple enlarged lymph nodes, mainly in the hilar region of the left lung and below the bifurcation of the trachea (Fig 1). Subsequently, whole-body fluorodeoxyglucose positron emission tomography (FDG-PET) indicated multiple FDG-positive hilar and mediastinal lymph nodes (Fig 2). Because the patient had no histologically proven distant metastases, it was decided that biopsies would be taken by a mediastinoscopy. Histologic examination with routinely processed hematoxylin-eosin sections showed surprisingly that the follicular architecture of the removed lymph nodes was completely effaced by numerous well-formed non-necrotizing granulomas (Fig 3A). The granulomas consisted of epitheloid cells and scattered small-multinucleated giant cells, similar to Langerhans' cells (Fig 3B). Additional histologic stains were negative for microorganisms; particularly Ziehl-Neelsen stain for tubercle bacilli and Grocott and periodic acid Schiff tests (PAS) for fungi. Immunohistochemical staining with MART1 for melanoma cells was also negative. The final diagnosis was a non-necrotizing granulomatous inflammation, compatible with sarcoidosis. There was no evidence of metastastic melanoma. The diagnosis of sarcoidosis was further supported by the lung function test, which indicated mild diffusion abnormalities. Because abnormalities were limited, it was decided to continue peginterferon alpha-2b for local treatment of in-transit metastases and to refrain from treatment with corticosteroids. The patient did not develop distant metastases in the next year of follow-up.
Sarcoidosis is rarely associated with interferon alfa treatment. Most cases have been described in patients treated with interferon alfa for chronic hepatitis.3,7 In this condition, sarcoidosis may be underdiagnosed, because these patients do not undergo frequent routine examinations that detect sarcoidosis that is highly sensitive. However, in patients with malignant diseases such as melanoma and renal cell carcinoma, restaging during interferon-alfa treatment may eludicidate abnormalities due to sarcoidosis, mimicking metastatic disease. CT of the chest may show enlarged mediastinal lymph nodes, but does not discriminate between sarcoidosis and metastases.6 The same result holds true for FDG-PET testing; metastases showed no statistically significant difference in Standardized Uptake Value (SUV) as compared with sarcoidosis.1 Since FDG-PET is an extremely sensitive (94.2%) and very specific (83.3%) tool to detect metastatic melanoma,5 it is becoming more commonly used during follow-up of patients with stage III and IV melanoma.2,9 However, accumulation of FDG merely indicates enhanced cellular metabolism, irrespective of the nature of the cells. Thus, areas of activated macrophages, as well as melanoma lesions, are FDG positive. This is a well-known phenomenon in patients staged with FDG-PET for non–small-cell lung cancer (NSCLC).8 Thus, the limited specificity of FDG-PET for ruling out malignancy in FDG-PET–positive lymph nodes requires histologic assessment of these nodes to avoid incorrect staging and unjustified cancellation of NSCLC resection. In contrast, it has been shown that the absence of FDG-accumulation in enlarged lymph nodes detected by CT, is highly predictive for the absence of metastases,4 indicating that FDG-PET could serve as an instrument to rule out metastases in enlarged mediastinal lymph nodes. However, when unaware of interferon alfa–induced sarcoidosis, a positive CT and FDG-PET may result in an unjustified diagnosis of recurrence in oncological patients. In conclusion, before advanced metastatic melanoma can be established in patients treated with interferon alfa, mediastinoscopy is mandatory to obtain histologic verification, especially when only mediastinal abnormalities are observed on CT and FDG-PET. Authors' Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest.
REFERENCES 1. Aoki J, Watanabe H, Shinozaki T, et al: FDG-PET for preoperative differential diagnosis between benign and malignant soft tissue masses. Skeletal Radiol 32:133-138, 2003[Medline] 2. Boni R, Boni RA, Steinert H, et al: Staging of metastatic melanoma by whole-body positron emission tomography using 2-fluorine-18-fluoro-2-deoxy-D-glucose. Br J Dermatol 132:556-562, 1995[Medline] 3. Gotto J, Dusheiko GM: Hepatitis C and treatment with pegylated interferon and ribavirin. Int J Biochem Cell Biol 36:1874-1877, 2004[CrossRef][Medline]
4. Gould MK, Kuschner WG, Rydzak CE, et al: Test performance of positron emission tomography and computed tomography for mediastinal staging in patients with non-small-cell lung cancer: A meta-analysis. Ann Intern Med 139:879-892, 2003 5. Holder WD Jr, White RL Jr, Zuger JH, et al: Effectiveness of positron emission tomography for the detection of melanoma metastases. Ann Surg 227:764-769, 1998[CrossRef][Medline]
6. Hunsaker AR, Munden RF, Pugatch RD, et al: Sarcoidlike reaction in patients with malignancy. Radiology 200:255-261, 1996 7. Kryczka W, Zarebska-Michaluk D, Chrapek M: Assessment of selected clinical factors as predictors of response to combined interferon-alpha plus ribavirin therapy among patients with chronic hepatitis C. Med Sci Monit 9:32-35, 2003 (suppl 3)
8. Pieterman RM, van Putten JWG, Meuzelaar JJ, et al: Preoperative staging of non-small-cell lung cancer with positron-emission tomography. N Engl J Med 343:254-261, 2000 9. Stas M, Stroobants S, Dupont P, et al: 18-FDG PET scan in the staging of recurrent melanoma: Additional value and therapeutic impact. Melanoma Res 12:479-490, 2002[CrossRef][Medline]
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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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