Dermatofibrosis

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A large renal cysts associated with dermatofibrosis[1]

Dermatofibrosis is an autosomal-dominant congenital disease of dogs characterized by multifocal tumors in the kidneys, uterine leiomyomas and nodules in the skin consisting of dense collagen fibers[2].

Although the German Shepherd is predisposed, this disease has been reported in other breeds[3], usually diagnosed in middle-aged and older dogs[4].

Similar to the human disease Birt-Hogg-Dubé syndrome, this disease is caused by a missense mutation in the gene encoding folliculin (FLCN), which is located on chromosome 5[5][6].

The genetic mutation results in cutaneous cytokine-induced expression of transforming growth factor[7], which leads to collagen metaplasia, similar to what is reported in humans[8].

The syndrome in dogs is characterized by bilateral, multifocal renal cystadenocarcinoma and cystadenoma with numerous firm nodules, consisting of dense collagen fibers in the skin and subcutis. Most females develop uterine leiomyomas[9].

Clinically affected heterozygous dogs develop numerous firm cutaneous nodules up to 4 cm in diameter over the entire body surface, with concurrent prolonged oestrus in bitches due to ovarian adenomas and symptoms associated with chronic renal disease[10].

Subcutaneous paraneoplastic nodules may also occur throughout tissues of the axial and appendicular skeleton, epimysium of skeletal muscles and lining the parietal peritoneum.

Fine-needle aspiration and cytologic evaluation are often unrewarding, but histopathology usually confirm dermatofibrosis.

In severely affected dogs, bilateral renal medullary (papillary) necrosis lead to interstitial nephritis, subsequent chronic renal disease and eventual death[11].

Renal disease is common, with renal nonneoplastic epithelial cysts, hyperplastic and dysplastic nodules, adenomas and cystadenomas[12].

Ultrasonography, imaging and biopsy of the kidneys usually reveals bilateral multiple cysts and tumor masses of various sizes.

Histologically, skin nodules consist of dense, coarse collagen fibers arranged in irregular bundles, displaying a very low cellularity involving the entire dermal thickness[1].

A differential diagnosis would include other cutaneous paraneoplastic syndromes such as feminization syndrome associated with testicular tumours, superficial necrolytic dermatitis, Malasezzia dermatitis, sebaceous adenitis, solar-induced dermatitis, acrodermatitis and paraneoplastic pemphigus[13].

There is no specific treatment for this condition and in diagnosed cases, some homoxygous dogs develop renal failure and eventually die within 6 months of diagnosis.

Regular renal ultrasonography is recommended since neoplasia is a distinct complication of this syndrome.

Determination of suspected carriers by microscopical examination of renal biopsies as early as 1 year of age should be considered to minimize transmission of this hereditary condition[14].

References

  1. 1.0 1.1 Vilafranca M et al (1994) Chromophilic-eosinophilic (oncocyte-like) renal cell carcinoma in a dog with nodular dermatofibrosis. Vet Pathol 31(6):713-716
  2. Lingaas F et al (2003) A mutation in the canine BHD gen is associated with hereditary multifocal renal cystadenocarcinoma and nodular dermatofi brosis in the German Shepherd dog. Hum Mol Genet 12:3043–3053
  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. 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
  5. Comstock KE et al (2005) A high-resolution comparative map of canine Chromosome 5q14.3-q33 constructed utilizing the 1.5x canine genome sequence. Mamm Genome 15(7):544-551
  6. Bønsdorff TB et al (2008) Second hits in the FLCN gene in a hereditary renal cancer syndrome in dogs. Mamm Genome 19:121–126
  7. 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
  8. van Steensel MA et al (2007) Novel mutations in the BHD gene and absence of loss of heterozygosity in fibrofolliculomas of Birt-Hogg-Dubé patients. J Invest Dermatol 127:588–593
  9. 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
  10. 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
  11. Gardiner DW & Spraker TR (2008) Generalized nodular dermatofibrosis in the absence of renal neoplasia in an Australian Cattle Dog. Vet Pathol 45(6):901-904
  12. Mutz ML et al (2011) What is your diagnosis? Nodular dermatofibrosis. J Am Vet Med Assoc 239(4):431-432
  13. Turek MM (2003) Cutaneous paraneoplastic syndromes in dogs and cats: a review of the literature. Vet Dermatol 14(6):279-296
  14. 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