Case 49
Diagnosis and discussion
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Diagnosis: Tip lesion variant of focal and segmental glomerulosclerosis

The two segmental lesiones identified in two glomeruli were localized at the tubular extreme of the tuft: the "tip domain". This lesion has been called from several decades ago as "tip lesion" and it is acepted by most authors as the "focal segmental glomerulosclerosis (FSGS) tip variant", which is defined, according to the Columbia classification of FSGS as: "the presence of at least 1 segmental lesion involving the tip domain (ie, the outer 25% of the tuft next to the origin of the proximal tubule) with either adhesion between the tuft and Bowman’s capsule at the tubular lumen or neck, or confluence of podocytes with parietal or tubular epithelial cells at the tubular lumen or neck". The proximal tubular pole must be identified in the defining glomerulus. This category requires that the collapsing variant be excluded, and the presence of segmental lesions in a perihilar location in any glomerulus rules out the tip variant of FSGS.

In the present case, the tubular lumen was only identified in serial sections of the biopsy, so in some cases the tip lesion is identified after many histologic sections:

This is the Figure 5. Green arrow indicates the proximal tubule, and blue arrow the tip lesion.

Several reports in nephrotic patients with glomerular tip lesion (GTL) suggest an excellent response to steroids and favourable course similar to that of minimal-change disease rather than FSGS; but other authors have reported that the response and course are similar to that of patients with FSGS and question the clinical significance of this feature. In our center we had found that near to 28% of the patients with GTL developed chronic kidney disease and 16% end-stage renal disease, at a median follow-up of 48 months (manuscript in preparation).

In the present case previous episodes of malaria have not relation (at least known) with the glomerulopathy.

See the chapter Focal and Segmental Glomerulosclerosis of our Tutorial.

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  • Howie AJ, Agarwal A, Sebire NJ, Trompeter RS. Glomerular tip changes in childhood minimal change nephropathy. Pediatr Nephrol. 2008;23(8):1281-6. [PubMed link]
  • Haas M. The glomerular tip lesion: what does it really mean? Kidney Int. 2005;67(3):1188-9. [PubMed link]
  • Howie AJ, Pankhurst T, Sarioglu S, Turhan N, Adu D. Evolution of nephrotic-associated focal segmental glomerulosclerosis and relation to the glomerular tip lesion. Kidney Int. 2005;67(3):987-1001. [PubMed link]
  • Stokes MB, Markowitz GS, Lin J, Valeri AM, D'Agati VD. Glomerular tip lesion: a distinct entity within the minimal change disease/focal segmental glomerulosclerosis spectrum. Kidney Int. 2004;65(5):1690-702. [PubMed link]
  • D’Agati VD, Fogo AB, Bruijin JA, Jennette JC. Pathologic Classification of Focal Segmental Glomerulosclerosis: A Working Proposal. Am J Kidney Dis 2004; 43: 368-382 [PubMed link]
  • Haas M, Yousefzadeh N. Glomerular tip lesion in minimal change nephropathy: a study of autopsies before 1950. Am J Kidney Dis. 2002;39(6):1168-75. [PubMed link]


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