Sarcoid like reaction (SLR) is a well defined entity and SLR has been reported in cases treated by checkpoint inhibitors (CPIs) (1). So far the majority of the cases reported associated with CPIs are melanoma; here we reported a case with malignant mesothelioma (MM) tretaed by nivolumab and developing granulomatous reaction mimicking progressive disease. Case report 53 year old woman admitted with pleural MM epitheloid type. After surgery, pemetrexate-cisplatinum and bevacizumab had been given for 6 cycles and bevacizumab maintenance for 10 cycles. Vinorelbine was given for 4 cycles for progressive disease; there was partial response however at the end of 8 cycles PET/CT showed considerable progression and carboplatin-gemcitabine combination was given and at the end there was metabolic nodules at left lung, pleural thickening and soft tissue masses at PET/CT (Figure 1). Due to active tumor and severe pains nivolumab was given as 6 cycles, her general condition was excellent and she did not require analgesics. However PET/CT showed considerable progression (Figure 2). Her condition was very well and post-immunotherapy granulomatous inflammation was thought clinically. Biopsy was done from a pelvic lymph node and was reported as MM metastasis. She had no other treatment choice and salvage surgery was done: omentectomy, paraaortic and coeliac lymphadenectomy, right (6/11) and left pelvic lymphadenectomy, diaphragma resection, pulmonary parencyhmal resection, pleurectomy, pericardiectomy were performed. All of the tissue samples except 6 of 17 right pelvic lymph nodes and paraaortic lymph nodes were reported as granulomatous reaction. Figures 3 and 4 show granulomas Discussion CPIs have various adverse events but SLR is relatively little known reaction in cases treated by CPIs. SLRs may mimic disease progression and may cause to discontinuation of the useful therapies (1, 2). It is well known that CPI related adverse effects are generally associated with favorable clinical outcome and lastly it has been suggested, at least in some reports, that SLR is associated with better outcome. Also sarcoid like reaction associated with CPIs have been found as better response to therapy (3). There is no specific recommendation for patients developing SLR during CPI treatment: asymptomatic patients do not reqire treatment and symptomatic cases respond to steroid. If there is no response to steroid, other immunosuppressives may be used (3, 4). In our case there was clear evidence of progression at PET/CT but her clinical condition was excellent. At this point granulomatous reaction was thought but biopsy showed MM and brutal surgery was done. However the majority of the surgical specimens showed granuolmatous reaction while only paraaortic and one third of right pelvic lymph nodes showed tumor. Clinicians should be aware of SLRs in cases treated by CPIs and tissues must be sampled and reviewed by an experienced pathologist to avoid misdiagnosis and drug stops while responding to tumor (1). In clinical practice FDG PET/CT is the most frequently used imaging to measure the response to CPIs but is not sensitive enough to predict atypical immune related adverse events including pseudoprogression and SLR. Newer imaging modalities including 18F-fluorothymidine (FLT) PET imaging may be useful. It is known that FLT is a substrate for thymidine kinase which is transported into the cell during DNA synthesis and trapped, but not incorporated into the DNA, it has been hypothesized that FLT PET is an important tool to show the proliferative activity of the tumor and has advantage to detect to differentiate tumor progression from pseudoprogression associated with tumor infiltrating immune cells which are low proliferative capacity than tumor cells (5). By analogy it can be proposed that FLT/PET may be used in cases with good clinical outcome in spite of progression detected by FDG/PET. The clinical outcome of this patient is very interesting: 1-A case with malignant mesothelioma responded CPI treatment at fourth line setting, 2-PET CT imaging showed progressive findings due to granulomatous reaction, 3-It can be said that SLR is not a rare event in cases treated with CPIs and awareness of these reactions will save the patients from unnecessary procedures and allows the patients to continue useful treatment. Newer PET/CT imaging modalities may be useful to differentiate SLR from progressive disease.
Sarcoid Like Reactýon Mimicking Disease Progression Associated With Nivolumab in A Case Wýth Malignant Mesothelýoma: Is There a Solution For This Dilemma
Semra Paydas1, Ilhan Tuncer2, Ahmet Baris Guzel3, Cem Kaan Parsak4, Isa Burak Guney51Departments of Medical Oncology, Faculty of Medicine, Cukurova University, Adana, Turkey, 2Departments of Pathology, Faculty of Medicine, Cukurova University, Adana, Turkey, 3Departments of Gynecologic Oncology, Faculty of Medicine, Cukurova University, Adana, Turkey, 4Departments of Surgical Oncology, Faculty of Medicine, Cukurova University, Adana, Turkey, 5Departments of Nuclear Medicine, Faculty of Medicine, Cukurova University, Adana, Turkey,
Sarcoid like reaction (SLR) is a well defined entity and SLR has been reported in cases treated by checkpoint inhibitors (CPIs) (1). So far the majority of the cases reported associated with CPIs are melanoma; here we reported a case with malignant mesothelioma (MM) tretaed by nivolumab and developing granulomatous reaction mimicking progressive disease. Case report 53 year old woman admitted with pleural MM epitheloid type. After surgery, pemetrexate-cisplatinum and bevacizumab had been given for 6 cycles and bevacizumab maintenance for 10 cycles. Vinorelbine was given for 4 cycles for progressive disease; there was partial response however at the end of 8 cycles PET/CT showed considerable progression and carboplatin-gemcitabine combination was given and at the end there was metabolic nodules at left lung, pleural thickening and soft tissue masses at PET/CT (Figure 1). Due to active tumor and severe pains nivolumab was given as 6 cycles, her general condition was excellent and she did not require analgesics. However PET/CT showed considerable progression (Figure 2). Her condition was very well and post-immunotherapy granulomatous inflammation was thought clinically. Biopsy was done from a pelvic lymph node and was reported as MM metastasis. She had no other treatment choice and salvage surgery was done: omentectomy, paraaortic and coeliac lymphadenectomy, right (6/11) and left pelvic lymphadenectomy, diaphragma resection, pulmonary parencyhmal resection, pleurectomy, pericardiectomy were performed. All of the tissue samples except 6 of 17 right pelvic lymph nodes and paraaortic lymph nodes were reported as granulomatous reaction. Figures 3 and 4 show granulomas Discussion: CPIs have various adverse events but SLR is relatively little known reaction in cases treated by CPIs. SLRs may mimic disease progression and may cause to discontinuation of the useful therapies (1, 2). It is well known that CPI related adverse effects are generally associated with favorable clinical outcome and lastly it has been suggested, at least in some reports, that SLR is associated with better outcome. Also sarcoid like reaction associated with CPIs have been found as better response to therapy (3). There is no specific recommendation for patients developing SLR during CPI treatment: asymptomatic patients do not reqire treatment and symptomatic cases respond to steroid. If there is no response to steroid, other immunosuppressives may be used (3, 4). In our case there was clear evidence of progression at PET/CT but her clinical condition was excellent. At this point granulomatous reaction was thought but biopsy showed MM and brutal surgery was done. However the majority of the surgical specimens showed granuolmatous reaction while only paraaortic and one third of right pelvic lymph nodes showed tumor. Clinicians should be aware of SLRs in cases treated by CPIs and tissues must be sampled and reviewed by an experienced pathologist to avoid misdiagnosis and drug stops while responding to tumor (1). In clinical practice FDG PET/CT is the most frequently used imaging to measure the response to CPIs but is not sensitive enough to predict atypical immune related adverse events including pseudoprogression and SLR. Newer imaging modalities including 18F-fluorothymidine (FLT) PET imaging may be useful. It is known that FLT is a substrate for thymidine kinase which is transported into the cell during DNA synthesis and trapped, but not incorporated into the DNA, it has been hypothesized that FLT PET is an important tool to show the proliferative activity of the tumor and has advantage to detect to differentiate tumor progression from pseudoprogression associated with tumor infiltrating immune cells which are low proliferative capacity than tumor cells (5). By analogy it can be proposed that FLT/PET may be used in cases with good clinical outcome in spite of progression detected by FDG/PET. The clinical outcome of this patient is very interesting: 1-A case with malignant mesothelioma responded CPI treatment at fourth line setting, 2-PET CT imaging showed progressive findings due to granulomatous reaction, 3-It can be said that SLR is not a rare event in cases treated with CPIs and awareness of these reactions will save the patients from unnecessary procedures and allows the patients to continue useful treatment. Newer PET/CT imaging modalities may be useful to differentiate SLR from progressive disease.
Cite This Article
Paydas S, Tuncer I, Guzel A, Parsak C, Guney I. Sarcoid Like Reactýon Mimicking Disease Progression Associated With Nivolumab in A Case Wýth Malignant Mesothelýoma: Is There a Solution For This Dilemma. EJMO. 2022; 6(1): 89-91
Corresponding Author: Semra Paydas