Renal cystadenocarcinoma

From Dog
Multiple cystic renal tumors in a dog with renal cystadenocarcinoma[1]

Renal cystadenoma and cystadenocarcinoma are an uncommon autosomal-dominant hereditary renal cancer syndrome in the German Shepherd associated with nodular dermatofibrosis[2] (Birt-Hogg-Dubé syndrome).

The syndrome is characterized by bilateral, multifocal tumors in kidneys and numerous firm nodules, consisting of dense collagen fibers in the skin and subcutis. Most females develop uterine leiomyomas[3].

This condition is caused by a missense mutation in the canine orthologue of the FLCN gene. Second-hit mutations were found in most of the renal tumours and in about a third of the early cystic renal lesions[4]. In affected puppies, the cytokine TGF-β1 is thought to play an important role in the induction of nodular dermatofibrosis associated with renal cystadenocarcinoma[5].

The disease is characterized by small, macroscopically visible cysts on the surface of the both kidneys found in puppies as young as 6 weeks of age. These cystic transformations within the renal epithelial cells seem to grow slowly in young puppies, which indicates that other mutational events are required for the development of tumors in adult dogs[1].

Clinically affected dogs may not be diagnosed until middle-aged (mean age=8.5 years) and some develop secondary lameness associated with dermatofibrosis[6].

Other clinical signs associated with this syndrome include anorexia, weight loss, polydipsia, polyuria, hematuria due to chronic renal disease and dermatitis[7].

Histological examination of affected kidneys have shown numerous small cystic tubular changes in the renal cortices. Hyperplastic change of the epithelial lining of cysts is frequently observed.

A presumptive diagnosis can be established on renal ultrasonic and CT imaging[8] and histological findings, but definitive diagnosis requires DNA testing[9].

A differential diagnosis includes other causes of renal disease such as renal amyloidosis, polycystic kidney disease, renal dysplasia, X-linked hereditary nephropathy and familial juvenile glomerulonephropathy.

There is no known treatment for this condition but some dogs may live many years with subclinical disease[10].

In suspect litters, microscopical examination of renal biopsies as early as 1 year of age, is warranted before the dogs are used for breeding.

References

  1. 1.0 1.1 Moe L & Lium B (1997) Hereditary multifocal renal cystadenocarcinomas and nodular dermatofibrosis in 51 German shepherd dogs. J Small Anim Pract 38(11):498-505
  2. Zanatta M et al (2012) Nodular Dermatofibrosis in a Dog without a Renal Tumour or a Mutation in the Folliculin Gene. J Comp Pathol Aug 4
  3. Jónasdóttir TJ et al (2000) Genetic mapping of a naturally occurring hereditary renal cancer syndrome in dogs. Proc Natl Acad Sci U S A 97(8):4132-4137
  4. Bønsdorff TB et al (2008) Second hits in the FLCN gene in a hereditary renal cancer syndrome in dogs. Mamm Genome 19(2):121-126
  5. Vercelli A et al (2003) Expression of transforming growth factor-beta isoforms in the skin, kidney, pancreas and bladder in a German shepherd dog affected by renal cystadenocarcinoma and nodular dermatofibrosis. J Vet Med A Physiol Pathol Clin Med 50(10):506-510
  6. Cosenza SF & Seely JC (1986) Generalized nodular dermatofibrosis and renal cystadenocarcinomas in a German shepherd dog. J Am Vet Med Assoc 189(12):1587-1590
  7. Lium B & Moe L (1985) Hereditary multifocal renal cystadenocarcinomas and nodular dermatofibrosis in the German shepherd dog: macroscopic and histopathologic changes. Vet Pathol 22(5):447-455
  8. Moe L & Lium B (1997) Computed tomography of hereditary multifocal renal cystadenocarcinomas in German shepherd dogs. Vet Radiol Ultrasound 38(5):335-343
  9. Bønsdorff TB et al (2009) Loss of heterozygosity at the FLCN locus in early renal cystic lesions in dogs with renal cystadenocarcinoma and nodular dermatofibrosis. Mamm Genome 20(5):315-320
  10. Moe L et al (2000) Renal microcystic tubular lesions in two 1Year-old dogs - an early sign of hereditary renal cystadenocarcinoma? J Comp Pathol 123(2-3):218-221