October 2021 – Renal Pathology

A 23-year-old man presented with anasarca with serum albumin of 1.5 g/dL, and urine protein to creatinine ratio of 4.8 g/g. Serologic studies for hepatitis B and C were negative. A renal biopsy was performed that showed the following lesion.

Figure 1: Trichrome stain
Figure 2: EM

What is this lesion?

  • Focal segmental glomerulosclerosis, perihilar variant
  • Focal segmental glomerulosclerosis, tip variant
  • Focal segmental glomerulosclerosis, NOS
  • Focal segmental glomerulosclerosis, cellular variant

The correct answer is ...

Focal segmental glomerulosclerosis, tip variant.

Focal segmental glomerulosclerosis (FSGS) is a pattern of glomerular injury that typically presents with moderate to heavy proteinuria. It can be classified based on etiology or morphology. Based on etiology, FSGS can be idiopathic (primary); genetic (non-syndromic or syndromic); infection-related (e.g., HIV, parvovirus B19); drug-induced (e.g., interferon alpha and beta, lithium); immunologic disease-related (e.g., SLE, Guillain-Barre syndrome); lymphoma/leukemia-related (e.g., Mantle cell lymphoma); vascular-related (e.g., hypertension, sickle cell disease); or adaptive (e.g., obesity, nephron loss). Based on glomerular morphology, Columbia classification defines five variants of FSGS, which are: 1. collapsing variant, 2. tip variant, 3. cellular variant, 4. perihilar variant and 5. FSGS not otherwise specified (NOS).

Tip variant of FSGS is characterized by intracapillary foam cells near the “tip” of the glomerular tuft adjacent to the origin of proximal tubule and an adhesion of the capillary loop to Bowman capsule. The glomerular tuft can herniate into the origin of the proximal tubule. On immunofluorescence, the glomeruli do not show immune complex deposits. There can be IgM and C3 deposition in the segmental scar, which is considered nonspecific trapping. On electron microscopy, the non-sclerosed glomeruli show diffuse (>80%) podocyte foot process effacement.

Patients with tip variant of FSGS are more likely to respond to glucocorticoid therapy compared to other FSGS variants. It has the most favorable prognosis among the variants of FSGS.


  1. 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):1690-1702.

Sarwat Gilani, M.B.B.S.

Fellow, Renal Pathology
Mayo Clinic

Lynn Cornell, M.D.

Consultant, Anatomic and Clinical Pathology
Mayo Clinic

Professor of Laboratory Medicine and Pathology
Mayo Clinic College of Medicine and Science

MCL Education

This post was developed by our Education and Technical Publications Team.