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March 29, 2019

Art of Medicine: Borderline Changes for TCMR Painting

The painting above of a kidney transplant biopsy shows mild interstitial inflammation and tubulitis.   If this field is representative, these changes would be consistent with borderline changes suspicious for T cell-mediated rejection (TCMR).   A diagnosis for borderline changes suspicious for TCMR can be made with mild interstitial inflammation (i1; 10-25% of cortex) with any degree of tubulitis (i1t1 with 0-4 lymphocytes/tubular profile, i1t2 with 4-10 lymphocytes per tubular profile, i1t3 with >10 lymphocytes per tubular profile or tubular basement membrane rupture), by moderate interstitial inflammation (25-50% of cortex) with mild tubulitis (i2t1), or with isolated tubulitis without interstitial inflammation (i0t1).

In the Banff 2005 and 2017 updated criteria for kidney allograft pathology (Rousfosse C et al, 2018), interstitial inflammation was removed as a criterion to diagnose borderline changes suspicious for TCMR, which was a required criterion in the previous Banff 1997 guidelines.  This change allowed for isolated, mild tubulitis (i0, t1) to be included in the definition of borderline changes for TCMR.  This criterion has not been uniformly adapted by kidney pathologists, and in a study by the Renal Pathology Society, 67 percent of kidney pathologists require interstitial inflammation for a diagnosis of borderline changes suspicious for TCMR, following the 1997 Banff guidelines (Becker JU et al, 2016).  In a recent study in the American Journal of Transplantation,  transplant biopsies were studied with follow-up and cliniopathologic correlation to determine the cause of isolated tubulitis in patients with this finding on kidney biopsy.   Isolated tubulitis was associated with HLA mismatch, acute tubular injury, prior episodes of T cell mediated rejection, antibody-mediated rejection, pulse corticosteroid treatment, and BK nephritis (Nankivell BJ et al, 2019).   Additionally, allograft function of isolated tubulitis frequently improved and had a graft survival rate of 92% at 5 years (Nankivell BJ et al, 2019).  With the great prognosis and non-specificity of isolated tubulitis, which may not represent an early stage of TCMR but another disease process, there are suggestions to reinstate the Banff 1997 criteria (Racusen LC et al, 1999) and require mild interstitial inflammation for a diagnosis of borderline changes suspicious for TCMR.    

References:

Becker JU, Chang A, Nickeleit V, Randhawa P, Roufosse C.   Banff borderline changes suspicious for acute T cell-mediated rejection: where do we stand?  Am J Transplant 2016 Sept; 16 (9): 2654-2660.

Nankivell BJ, P’Ng CH, Chapman JR.  Does tubulitis without interstitial inflammation represent borderline acute T cell mediated rejection?  Am J Transplant 2019 Jan; 19 (1): 132-144.

Racusen LC, Solez K, Colvin RB, Bonsib SM, Castro MC, Cavallo T, Croker BP, Demetris J, Drachenberg CB, Fogo AB, Furness P, Gaber LW, Gibson IW, Glotz D, Goldberg JC, Grande J, Halloran PF, Hansen HE, Hartley B, Hayrey PJ, Hill CM, Hoffman EO, Hunsicker LG, Lindblad AS, Marcussen N, Mihatsch MJ, Nadasdy T, Nickerson P, Olsen TS, Olsen TS, Papadimitriou JC, Randhawa PS, Rayner DC, Roberts I, Rose S, Rush D, Salinas-Madrigal L, Salomon DR, Sund S, Taskinen E, Trpkov K, Yamaguchi Y.   The Banff 97 working classification of renal allograft pathology.  Kidney International 1999; 55: 713-723.

Rousfosse C, Simmonds N, Clahsen-van Groningen M, Haas M, Henriksen K, Horsfield C, Loupy A, Mengel M, Perkowska-Ptasinska A, Rabant M, Racusen L, Solez K, Becker J.  A 2018 reference guide to the Banff classification of renal allograft pathology.  Transplantation 2018 Nov; 102 (11): 1795-1814.