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Sarcoid-like reaction in cases treated by checkpoint inhibitors

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Abstract

Sarcoidosis is a multisystem granulomatous disorder characterized by helper T cell inflammation. Sarcoid-like reaction (SLR) is a well-defined entity and may be related with several malignant disorders and/or their therapies. SLR has been reported more than 20 years ago and in recent years in cases treated by checkpoint inhibitors (CPIs). Better outcome has been reported in cases developing granulomatous reaction and/or SLRs during CPI treatments. However, these lesions clinically may be thought as disease progression and may cause to stop treatment or alterations. These therapeutic manipulations may be harmful for the patients. 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 also unnecessary CPI treatment cessations.

Significance Statement

Clinicians should be aware of sarcoid-like reactions in cases treated by checkpoint inhibitors and tissues must be sampled and reviewed by an experienced pathologist to avoid misdiagnosis and CPI treatment stops.

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References

  1. Hunt BM, Valliers E, Buduhan G, Aye R, Louie B. Sarcoidosis as a benign cause of lymphadenopathy in cancer patients. Am J Surg. 2009;197:629–32.

    PubMed  Google Scholar 

  2. Cohen PR, Kurzrock R. Sarcoidosis and malignancy. Clin Dermatol. 2007;25:326–33.

    PubMed  Google Scholar 

  3. Paydas S, Yavuz S, Disel U, Zeren H, Hastürk S, Hanta I, Ergin M, Sahin B. Granulomatous reaction after chemotherapy for Hodgkin’s disease. Leuk Res. 2002;26:967–70.

    CAS  PubMed  Google Scholar 

  4. Suditu N, Negru D. Bacillus Calmette–Guerin therapy-associated granulomatous prostatitis mimicking prostate cancer on MRI: a case report and literature review. Mol Clin Oncol. 2015;3:249–51.

    PubMed  Google Scholar 

  5. Clerigo V, Castro A, Mourato T, Gomes C. A rare case of granulomatous pneumonitis due to intravesical BCG for bladder cancer. Acta Med Port. 2019;32:316–20.

    PubMed  Google Scholar 

  6. Eckert A, Schoeffler A, Dalle S, Phan A, Kiakouama L, Thomas L. Anti-CTLA4 monoclonal antibody induced sarcoidosis in a metastatic melanoma patient. Dermatology. 2009;218:69–70.

    CAS  PubMed  Google Scholar 

  7. Danlos FX, Pages C, Baroudjian B, Vercellino L, Battistella M, Mimoun M, Jebali M, Bagot M, Tazi A, Lebbe C. Nivolumab-induced sarcoid-like granulomatous reaction in a patient with advanced melanoma. Chest. 2016;149:133–6.

    Google Scholar 

  8. Tirumani SH, Ramaiya NH, Keraliya A, Bailey ND, Ott PA, Hodi FS Nishino M. Radiographic profiling of immune-related adverse events in advanced melanoma patients treated with ipilimumab. Cancer Immunol Res. 2015;3:1185–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Facco M, Cabrelle A, Teramo A, Olivieri V, Gnoato M, Teolato S, Ave E, Gattazzo C, Fadini GP, Calabrese F, Semenzato G, Agostini C. Sarcoidosis is a Th1/Th17 multisystem disorder. Thorax. 2011;66:144–50.

    PubMed  Google Scholar 

  10. Ten Berge B, Paats MS, Bergen IM, van den Blink B, Hoogsteden HC, Lambrecht BN, Hendriks RW, Kleinjan A. Increased IL17A expression in granulomas and in circulating memory T cells in sarcoidosis. Rheumatology. 2012;51:37–46.

    PubMed  Google Scholar 

  11. Naccache JM, Antoine M, Wislez M, Fleury-Feith J, Oksenhendler E, Mayaud C, Cadranel J. Sarcoid-like pulmonary disorder in human immunodeficiency virus-infected patients receiving antiretroviral therapy. Am J Respir Crit Care Med. 1999;159:2009–13.

    CAS  PubMed  Google Scholar 

  12. Ishida M, Hodohara K, Furuya A, Okuno H, Yoshii M, Horinouchi A, Yoshida T. Sarcoidal granulomas in the mediastinal lymph nodes after treatment for marginal zone lymphoma of the esophagus: report of a case with review of the concept of the sarcoidosis-lymphoma syndrome. Int J Clin Exp Pathol. 2014;7(7):4428–32.

    PubMed  PubMed Central  Google Scholar 

  13. Acosta-Rodriguez EV, Rivino L, Geginat J, Jarrossay D, Gattorno M, Lanzavecchia A, Sallusto F, Napolitani G. Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells. Nat Immunol. 2007;8:639–46.

    CAS  PubMed  Google Scholar 

  14. Ramesh R, Kozhaya L, McKevitt K, Djuretic IM, Carlson TJ, Quintero MA, McCauley JL, Abreu MT, Unutmaz D, Sundrud MS. Pro-inflammatory human Th17 cells selectively express P-glycoprotein and are refractory to glucocorticoids. J Exp Med. 2014;211:89–104.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Ramstein J, Broos CE, Simpson LJ, Ansel KM, Sun SA, Ho ME, Woodruff PG, Bhakta NR, Christian L, Nguyen CP, Antalek BJ, Benn BS, Hendriks RW, van den Blink B, Kool M, Koth LL. IFN-gamma-producing T-helper 17.1 cells are increased in sarcoidosis and are more prevalent than T-helper type 1 cells. Am J Respir Crit Care Med. 2016;193:1281–91.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Lomax AJ, Mcguire HM, Mcneil C, Choi CJ, Hersey P, Karikios D, Shannon K, Van Hal S, Carr U, Crotty A, Gupta SK, Hollingsworth J, Kim H, Groth BF, Mcgill N. Immunotherapy-induced sarcoidosis in patients with melanoma treated with PD-1 checkpoint inhibitors: case series and immunophenotypic analysis. Int J Rheum Dis. 2017;20:1277–85.

    CAS  PubMed  Google Scholar 

  17. Braun NA, Celada LJ, Herazo-Maya JD, Abraham S, Shaginurova G, Sevin CM, Grutters J, Culver DA, Dworski R, Sheller J, Massion PP, Polosukhin VV, Johnson JE, Kaminski N, Wilkes DS, Oswald-Richter KA, Drake WP. Blockade of the programmed death-1 pathway restores sarcoidosis CD4(+) T cell proliferative capacity. Am J Respir Care Med. 2014;190:560–71.

    CAS  Google Scholar 

  18. Zou W, Wolchok JD, Chen L. PD-L1 (B7eH1) and PD-1 pathway blockade for cancer therapy: mechanisms, response biomarkers and combinations. Sci Transl Med. 2016;8:328.

    Google Scholar 

  19. Saidha S, Sotirchos ES, Eckstein C. Etiology of sarcoidosis: does infection play a role? Yale J Biol Med. 2012;85:133–41.

    PubMed  PubMed Central  Google Scholar 

  20. Al-dliw M, Megri M, Shahoub I, Sahay G, Limjoco TI, Shweihat Y. Pembrolizumab reactivates pulmonary granulomatosis. Respir Med Case Rep. 2017;22:126–9.

    PubMed  PubMed Central  Google Scholar 

  21. Cotliar J, Querfeld C, Boswell WJ, Raja N, Raz D, Chen R. Pembrolizumab associated sarcoidosis. JAAD Case Rep. 2016;2:290–3.

    PubMed  PubMed Central  Google Scholar 

  22. Burillo-Martinez S, MoralesRaya C, Prieto-Barrios M, Rodriguez-Peralto JL, Ortiz-Romero P-L. Pembrolizumab-induced extensive panniculitis and nevus regression: two novel cutaneous manifestations of the post-immunotherapy granulomatous reactions spectrum. JAMA Dermatol. 2017;153:721–2.

    PubMed  Google Scholar 

  23. Lopez AT, Khana T, Antonov N, Audrey-Bayan C, Geskin L. A review of bullous pemphigoid associated with PD-1 and PD-L1 inhibitors. Int J Dermatol. 2018;57:664–9.

    CAS  PubMed  Google Scholar 

  24. Wu J, Kwong BY, Martires KJ, Rieger KE, Chung WH, Iyer GV, Lacouture ME. Granuloma annulare associated with immune checkpoint inhibitors. J Eur Acad Dermatol Venereol. 2018;32:124–6.

    Google Scholar 

  25. Hiraki T, Hatanaka M, Arimura A, Kawahira H, Kirishimal M, Kitazono I, Horinouchi M, Higashi M, Kanekura T, Tanimoto A. Granulomatous/sarcoid-like reactions in the setting of programmed cell death-1 inhibition: a potential mimic of disease recurrence. J Cutan Pathol. 2020;47:154–60.

    PubMed  Google Scholar 

  26. Mitchell MA, Hogan K, Amjadi K. Atezolizumab-induced sarcoid-like granulomatous reaction in a patient with urothelial cell carcinoma. Immunotherapy. 2018;10:1189–92.

    CAS  PubMed  Google Scholar 

  27. Lafon M, Blaye C, Kind M, Bechade D, Chassaigne F, Italiano A, Grellety T. Sarcoidosis-like reaction in metastatic triple negative breast cancer treated by anti-PD-L1. Breast J. 2019;25:971–3.

    CAS  PubMed  Google Scholar 

  28. Balestra R, Benzaquen S, Wang J. Sarcoidosis-like granulomatous lung reaction associated with anti-programmed death receptor-1 ligand therapy. Ann Am Thorac Soc. 2017;14:296–9.

    PubMed  Google Scholar 

  29. Garcıa-Manso IG, del Mar Garda Rodenas M, Barroso Medel ME, Illân Gambın FJ. Sarcoidosis-like granulomatous reaction associated with pembrolizumab immunotherapy. Sci Lett/Arch Bronconeumol. 2018;54:592–3.

    Google Scholar 

  30. Cervantes J, Rosen A, Dehesa L, Dickinson G, Alonso-Llamazares J. Granulomatous reaction in a patient with metastatic melanoma treated with ipilimumab: first case reported with isolated cutaneous findings. Actas Dermosifiliogr. 2019;110(1):43–9.

    CAS  PubMed  Google Scholar 

  31. Honigman AD, Lai F, Elakis J, Prall O, Goh M, McCormack C. Pembrolizumab-induced sarcoid granulomatous panniculitis and bullous pemphigoid in a single patient. Clin Case Rep. 2019;7:773–5.

    PubMed  PubMed Central  Google Scholar 

  32. Cousin S, Toulmonde M, Kind M, Cazeau AL, Bechade D, Coindre JM, Italiano A. Pulmonary sarcoidosis induced by the anti-PD1 monoclonal antibody pembrolizumab. Ann Oncol. 2016;27:1178–9.

    CAS  PubMed  Google Scholar 

  33. Firwana B, Ravilla R, Raval M, Hutchins L, Mahmoud F. Sarcoidosis-like syndrome and lymphadenopathy due to checkpoint inhibitors. J Oncol Pharm Pract. 2017;23:620–4.

    CAS  PubMed  Google Scholar 

  34. Reuss JE, Kunk PR, Stowman AM, Gru AA, Slingluff CL, Gaughan EM. Sarcoidosis in the setting of combination ipilimumab and nivolumab immunotherapy: a case report and review of the literature. J Immunother Cancer. 2016;4:94.

    PubMed  PubMed Central  Google Scholar 

  35. Wigenhof S, Mortion V, Seghers AC. Du four S, Wanderlinden E, Hanon S, Sarcoidosis in a patient with metastatic melanoma sequentially treated with anti-CTLA-4 monoclonal antibody and selective BRAF inhibitör. Anticancer Res. 2012;32:1355–9.

    Google Scholar 

  36. Izzedine H, Mateus C, Boutros C, Robert C, Rouvier P, Amoura Z, Mathian A. Renal effects of immune checkpoint inhibitors. Nephrol Dial Transplant. 2017;32:936–42.

    CAS  PubMed  Google Scholar 

  37. Andersen R, Norgaard P, Al-Jailawi MK, Svane IM. Late development of splenic sarcoidosis-like lesions in a patient with metastatic melanoma and long-lasting clinical response to ipilimumab. Oncoimmunology. 2014;3:954506.

    Google Scholar 

  38. van Baar MLM, Guminski AD, Ferguson PM, Martin LK. Pembrolizumab for cutaneous squamous cell carcinoma: report of a case of inoperable squamous cell carcinoma with complete response to pembrolizumab complicated by granulomatous inflammation. JAAD Case Rep. 2019;5:491–4.

    PubMed  PubMed Central  Google Scholar 

  39. Koelzer VH, Rothschild SI, Zihler D, Wicki A, Willi B, Willi N, Voegeli M, Cathomas G, Zippelius A, Mertz KD. Systemic inflammation in a melanoma patient treated with immune checkpoint inhibitors—an autopsy study. J Immunother Cancer. 2016;4:1–8.

    Google Scholar 

  40. Cornejo CM, Haun P, English J, Rosenbach M. Immune checkpoint inhibitors and the development of granulomatous reactions. J Am Acad Dermatol. 2018. https://doi.org/10.1016/j.jaad.2018.07.051.

    Article  PubMed  Google Scholar 

  41. Trinidad C, Nelson KC, Glitza Oliva IC, Torres-Cabala CA, Nagarajan P, Tetzlaff MT, Ivan D, Hwu WJ, Prieto VG, Curry JL, Aung PP. Dermatologic toxicity from immune checkpoint blockade therapy with an interstitial granulomatous pattern. J Cutan Pathol. 2018;45:504–7.

    PubMed  Google Scholar 

  42. Berthol G, Lazor R, Letonovic I, Romano E, Noirez L, Stalder JM, Speiser DE, Peters S, Michielin O. Pulmonary sarcoid-like granulomatosis induced by ipilimumab. J Clin Oncol. 2012;30:156–9.

    Google Scholar 

  43. Montaudie H, Pradelli J, Passeron T, Lacour JP, Leroy S. Pulmonary sarcoid-like granulomatosis induced by nivolumab. Br J Dermatol. 2017;176:1060–3.

    CAS  PubMed  Google Scholar 

  44. Murphy KP, Kennedy MP, Barry JE, O’Regan KN, Power DG. New-onset mediastinal and central nervous system sarcoidosis in a patient with metastatic melanoma undergoing CTLA4 monoclonal antibody treatment. Oncol Res Treat. 2014;37:351–3.

    CAS  PubMed  Google Scholar 

  45. Tetzlaff MT, Nelson KC, Diab A, Staerkel GA, Nagarajan P, Torres-Cabala CA, Chasen BA, Wargo JA, Prieto VG, Amaria RN, Curry JL. Granulomatous/sarcoid-like lesions associated with checkpoint inhibitors: a marker of therapy response in a subset of melanoma patients. J Immunother Cancer. 2018;6(1):14.

    PubMed  PubMed Central  Google Scholar 

  46. Zhang Y, Liu Z, Tian M, Hu X, Wang L, Ji J, Liao A. The altered PD-1/PD-L1 pathway delivers the ‘one-two punch’ effects to promote the Treg/Th17 imbalance in pre-eclampsia. Cell Mol Immunol. 2018;15:710–23.

    CAS  PubMed  Google Scholar 

  47. Woodbeck R, Metelitsa AI, Naert KA. Granulomatous tumoral melanosis associated with pembrolizumab therapy: a mimicker of disease progression in metastatic melanoma. Am J Dermatopathol. 2018;40:523–6.

    PubMed  Google Scholar 

  48. O’Kane GM, Labre C, Doherty MK, Young K, Albalâ H, Leigbl NB. Monitoring and management of immune-related adverse events associated with programmed cell death protein-1 axis inhibitors in lung cancer. Oncologist. 2017;22:70–80.

    PubMed  Google Scholar 

  49. Weber JS, Postow M, Lao CD, Schadendorf D. Management of adverse events following treatment with anti-programmed death-1 agents. Oncologist. 2016;21:1230–40.

    PubMed  PubMed Central  Google Scholar 

  50. Crandall JP, Tahari AK, Juergens RA, Brahmer JR, Rudin CM, Esposito G, Subramaniam DS, Knopp MV, Hall NC, Gajwani P, Leal JP, Lodge MA, Joo HO, Gabrielson EW, Shankar LK, Wahl RL. A comparison of FLT to FDGPET/CT in the early assessment of chemotherapy response in stages IB–IIIA resectable NSCLC. EJNMMI Res. 2017;7:8.

    PubMed  PubMed Central  Google Scholar 

  51. Yeh R, Trager MH, Rizk ME, Finkel GG, Barker LW, Carvajal RD, Geskin LJ, Schwartz GK. FLT-PET at 6 weeks predicts response assessed by CT at 12 weeks in melanoma patients treated with pembrolizumab. Clin Nucl Med. 2020;45:267–77.

    PubMed  Google Scholar 

  52. Li Z, Graf N, Herrmann K, Jünger A, Aichler M, Feuchtinger A, Baumgart A, Walch A, Peschel C, Schwaiger M, Buck A, Keller U, Dechow T. FLT-PET is superior to FDG-PET for very early response prediction in NPM-ALK-positive lymphoma treated with targeted therapy. Cancer Res. 2012;72:5014–24.

    CAS  PubMed  Google Scholar 

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  1. Çukurova University Faculty of Medicine Department of Medical Oncology, Adana, Turkey

    Semra Paydas

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Paydas, S. Sarcoid-like reaction in cases treated by checkpoint inhibitors. Med Oncol 38, 29 (2021). https://doi.org/10.1007/s12032-021-01477-y

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