Diffuse Mesangial Sclerosis



Diffuse Mesangial Sclerosis


Helen Liapis, MD

Joseph Gaut, MD, PhD





Key Facts


Terminology



  • Diffuse mesangial sclerosis


Etiology/Pathogenesis



  • WT1 mutations (Denys-Drash or Frasier syndromes)


  • Laminin β2 mutations (Pierson syndrome)


  • Idiopathic


Clinical Issues



  • Progression to ESRD in 3 years


  • Presents early in life, usually under 2 years of age


  • Slower progression to ESRD if no mutation is identified


Microscopic Pathology



  • Early glomerular changes resemble fetal glomeruli


  • Late glomerular changes consist of replacement of mesangium by fibrillar matrix and mesangial consolidation


  • Pseudocrescents


  • Tubules dilated with hyaline casts


Ancillary Tests



  • Gene sequencing of WT1, PLCE1, and LAMB2 genes


  • Karyotyping to rule out male pseudohermaphroditism (Frasier syndrome)


Top Differential Diagnoses



  • Denys-Drash syndrome


  • Frasier syndrome


  • Pierson syndrome







Classic late diffuse mesangial sclerosis (DMS) shows replacement of the mesangium with matrix image and podocyte proliferation forming a pseudocrescent image.






In DMS, the trichrome stain highlights mesangial collagen deposition and reveals the absence of capillary loops.


TERMINOLOGY


Abbreviations



  • Diffuse mesangial sclerosis (DMS)


Definitions



  • Glomerular disease early in life with characteristic mesangial accumulation of extracellular matrix and podocyte proliferation



    • Although most cases are idiopathic, a subset are caused by a variety of genetic and other factors


ETIOLOGY/PATHOGENESIS


Genetic Factors



  • WT1



    • Encodes Wilms tumor-1



      • Zinc finger transcription factor involved in regulating cellular proliferation and gonad and podocyte differentiation


    • Maps to chromosome 11p13


    • Mutations in exons 8 and 9 are occasionally associated with sporadic DMS


    • Exon 9 mutations typical of Denys-Drash syndrome



      • Hotspot in exon 9 R394W/Q/L


    • Intron 9 mutations typical of Frasier syndrome


  • PLCE-1



    • Encodes phospholipase C enzyme (PLC∈1) on chromosome 10q


    • Truncating mutations are associated with DMS


    • Nontruncating missense mutations are associated with FSGS


    • Inherited in autosomal recessive pattern


  • Gallaway-Mowat syndrome


  • Type 1 carbohydrate-deficient glycoprotein syndrome


  • Laminin-β2 mutations (Pierson syndrome)


Infectious Agents



  • Cytomegalovirus



    • DMS associated with cytomegalic inclusion bodies described in newborn with congenital nephrotic syndrome


CLINICAL ISSUES


Presentation



  • Nephrotic syndrome



    • Steroid resistant


    • < 2 years of age but may be as late as 4 years

Tags:
Jul 7, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Diffuse Mesangial Sclerosis

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