COLLAPSING GLOMERULOPATHY- MICROSCOPY ON AUTOPSY TISSUE AN ENRICHING EXPERIENCE

Introduction:

Collapsing glomerulopathy is defined on diagnostic renal biopsies of patients presenting with heavy protienuria. These descriptions generally refer to collapse with active podocytic changes, but it is obvious these active podocytic changes will not remain in such state f and should evolve to chronic phase. We had experience of evaluating kidneys of 4 patients with collapsing glomerulopathy at autopsy. Evolution of renal changes could be better understood on these sections which were equivalent to thousands of biopsies. 

Methods:

Kidney sections from medical autopsies done on patients with collapsing glomerulopathy (n-4) were analyzed. Sections were stained with H&E, PAS, Masson’s trichrome, EVG and silver methenamine jones. Immunohistochemistry to establish de-differentiation (Ki67, Podocin, WT-1, PAX2 and CK7) was done. 

Results:

Early or active glomerular changes were characterized by segmental or global glomerular collapse (Figure 1 a-d). Sometimes collapse was so subtle and segmental that it may not be seen in first cut and sometimes podocyte hyperplasia was so exuberant it appeared as collections of freely floating podocytes in bowman’s space with barely visible tuft (Figure 2 a-d). However, podocyte were hypertrophied with moderate to abundant cytoplasm which may have protein absorption droplets or vacuolations. Activated podocytes had occasional mitosis (Figure 3a), bi nucleation (Figure 3d), or multinucleation and vesicular nuclie with prominent nucleoli (Figure 3b-c). These nuclear features are suggestive of dedifferentiation of podocytes to primitive stages of podocyte differentiation. These dedifferentiated nuclei showed Ki67 positivity which should not be seen in terminally differentiated mature normal podocyte. Cytokeratin 7(CK7) and PAX 2 which are not seen in mature differentiated podocytes and are present in early stages of podocyte differentiation become positive in these hyperplastic podocytes. Similarly, podocin and WT1 which are normally present in mature podocytes were lost in these activated podocytes. Podocin was lost during early stages whereas WT1 was lost during relatively later stage. (Figure 4a-f) After this active phase, podocytes become cuboidal and arrange as linear crown over collapsed tuft. A layer of collagenized basement membrane which is poor in elastic tissue formed over this collapsed tuft (Figure 5-6). These podocyte now do not have protein absorption droplets or vacuolations. Mitosis was not seen in this phase and Ki 67 was no longer positive. After this, collagenization between collapsed capillaries occurs which later replaced collapsed capillaries (Best seen in Jone’s) (Figure 5-6). There may be focal synechiae formation with subsequent sclerosis. No intraglomerular fibrosis along Bowman ’s capsule was seen. Collagenized collapsed tuft merged with interstitium. (Figure 5-6). WT 1 was lost along with podocin and Pax2 and CK 7 were acquired (positive) (Figure 7 a-f). Tubules showed marked tubulocystic dilatation, PAS negative casts and protein absorption droplets. Interstitial fibrosis was seen in later stages. No thyroidization of tubules was seen 

Conclusions:

Collapsing glomerulopathy in active stage shows morphologic and immunohistochemical feature of de-differentiation. These tufts gradually become acellular balls, merge with interstitium without intraglomerular fibroses.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.