Sarcoidosis mimicking lymphoma on positron emission tomography-computed tomography in two patients treated for lymphoma: two case reports

Abstract:

Introduction:
Sarcoidosis is a granulomatous disease that mostly involves the lungs. Its association with malignancies has been well documented. Several mechanisms have been proposed that may underlie this concurrence including triggering tumour antigens and defective cellular immunity.

Case presentations:
We briefly review the literature on malignancy associated sarcoidosis and report two female lymphoma patients of 49 and 56 years of age who, during their course of disease, developed sarcoidosis that was misinterpreted as a lymphoma relapse on positron emission omography-computed tomography.

Conclusion:
We hypothesise that T cell dysfunction and exposure to tumour associated antigens might be the underlying mechanisms of development of sarcoidosis in patients with lymphoma. Positron emission tomography-positive lesions do not always indicate malignancy and therefore a tissue biopsy is always mandatory to confirm the diagnosis.

Introduction
Sarcoidosis is an uncommon granulomatous disease primarily manifesting itself with pulmonary involvement. Any organ, including the eye, central nervous system, and even gonads can be involved. Systemic sarcoidosis, in particular localised sarcoidal reaction, is well documented in association with malignancies. We report two patients who developed sarcoidal reactions in association with lymphoma.

Case 1
A 56-year-old woman presented with enlarged right cervical lymph nodes (LN) that failed to regress following appropriate treatment with antibiotics. The largest LN Page 1 of 4 (page number not for citation purposes) measured 3.8 cm in diameter. A fine needle aspiration of the LN was highly suspicious for Hodgkin’s lymphoma (HL). The excisional biopsy of the LN revealed complete architectural effacement with scattered Reed-Sternberg (RS) cells, histiocytes and eosinophils (Figure 1). RS cells were CD20-, CD45- and CD30+. Fascin, which is not specific for HL, but its negativity would make a diagnosis of HL doubtful, stained most of the RS cells. A diagnosis was made of “HL, classical type, mixed cellularity subtype”. Positron emission tomography-computed tomography (PET-CT) revealed additional LNs in the cervical and supraclavicular region. Bone marrow biopsy was negative for lymphoma. Serologic tests for hepatitis B, C and HIV were negative. The patient was, thus, staged as stage I, non-bulky HL, unfavourable, due to her age being over 50. Combined therapy with four cycles of doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy followed by involved field irradiation was scheduled. During chemotherapy, our patient experienced respiratory difficulties which was not associated with infection. Two control PET–CTs taken at the end of four cycles of ABVD and at the end of 30.6 Gy/17 fractionated radiotherapy to the right neck and supraclavicular region showed complete remission. However, a routine third PET-CT performed 3 months following completion of chemoradiotherapy, revealed several fluorodeoxyglucose(FDG) enhancing mediastinal LNs (Figure 2). There was also FDG-enhancing thickening of the pleura in the left lung laterobasal segment and an ill-defined increase in parenchymal density. The findings were interpreted asstrongly likely to be recurrent lymphoma and the possibility of high-dose chemotherapy with autologous stem cell transplantation was discussed with the patient. To confirm the diagnosis, a mediastinoscopic LN biopsy was performed. The LN architecture was completely effaced by tightly packed non-caseating granulomas, indicating sarcoidosis (Figure 3). There was no histological evidence of HL. The patient was then referred to a chest physician for consultation. A tuberculin test was negative. Carbon dioxide diffusion was slightly reduced. Based on the clinical and radiological findings, the patient was diagnosed with sarcoidosis and steroid therapy was initiated.

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