• Cause: dominantly inherited missense mutation in FLCN gene.
• Signs: bilateral, multifocal cystic tumors in the kidneys, uterine leiomyomas and nodules in the skin consisting of dense collagen fibers (nodular dermatofibrosis – ND).
• Diagnosis: CT, radiographs, ultrasound, histopathology.
• Treatment: none efficient, palliative surgery when cutaneous lesions are ulcerated, nephrectomy in unilateral cases.
• Prognosis: poor.

• Nodular dermatofibrosis (ND): multiple slowly growing cutaneous collagenous nodules (2 mm to 5 cm) that are non-painful and non-pruritic – nodules predominantly on the limbs but head and trunk may be affected in advanced cases.
• ND preceded systemic illness from primary kidney cancer or metastasis by months to years.
• Lethargy.
• PUPD.
• Vomiting.
• Abdominal pain.
• Weight loss.
• Hematuria.

• Kidney failure Kidney: acute kidney injury (AKI).
• Abdominal pain.
• Dyspnoea (pulmonary metastasis or pleural effusion).
• Ulcerated skin nodules.

• Worldwide.

• Middle aged to older dogs (≥ 6 years).
• Reported in puppies when loss of heterozygosity at the FLCN locus.

• Males may be overrepresented.
• Females have concurrent uterine leiomyoma Leiomyoma of little clinical significance.

• German shepherd German shepherd
• Also, anecdotally reported in Golden retriever Golden retriever, Australian cattle dog Australian cattle dog, Boxer Boxer and Beagle Beagle.

• None.

• CT scan, biopsies.

• Anesthesia: impaired kidney function Anesthesia: in renal insufficiency.

• Dominantly inherited missense mutation in FLCN (tumor suppressor gene coding for the protein folliculin) on chromosome 5, similar to BHD (Birt-Hogg-Dune) syndrome in humans.
• Rare cases of nodular dermatofibrosis with no renal cysts and no mutation in the FLCN gene have been reported.

• German shepherd breed with mutation of the FLCN gene.

• Missense mutation in FLCN gene (→loss of function) →multiple benign cutaneous and subcutaneous fibrous nodules “nodular dermatofibrosis”, which may proceed (by months to years) or be concurrent with renal lesions: cysts, cystadenomas, and/or cystadenocarcinomas.
• Renal lesions are normally bilateral and multiple, but unilateral lesions are reported.
• Neoplastic transformation and growth appears to be a slow process.
• Risk of metastasis from adenocarcinomas: lymph nodes, lungs, serosal surfaces, liver and spleen.
• Concurrent uterine leiomyomas in females.
• Nodular dermatofibrosis not associated with renal lesions has been reported.

• Months to years.

• Consider screening suspected carrier dogs before breeding, using molecular genetics.

Refereed papers

• Gómez-Barris B R, Balazs V, Chaguay Villamar K & Toro-Valdivieso C (2024) First case of nodular dermatofibrosis with cystic renal disease in a beagle: An atypical case without FLCN gene mutation Vet Med Sci 10 (2), e1401 PubMed.
• Ciccarelli S, Di Bello A, Valastro C et al (2019) Unilateral renal cystadenocarcinoma and nodular dermatofibrosis in a mixed-breed dog carrying a FLCN gene mutation Vet Derm 30 (2), 174-e54 PubMed.
• Zanatta M, Bettini G, Scarpa F et al (2013) Nodular Dermatofibrosis in a Dog without a Renal Tumour or a Mutation in the Folliculin Gene J Comp Path 148 (2-3), 248-251 PubMed.
• Bønsdorff T B, Jansen J H, Thomassen R F 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, 315–320 PubMed.
• Gardiner D W, Spraker T R (2008) Generalized Nodular Dermatofibrosis in the Absence of Renal Neoplasia in an Australian Cattle Dog. Vet Path 45 (6), 901-904 PubMed.
• Guaguere E, Hubert T, Muller A et al (2004) Nodular dermatofibrosis in the German shepherd dog: a retrospective study of 11 cases Vet Derm 15 (s1), 59 WileyOnline.
• Lingaas F, Comstock K E, Kirkness E F et al (2003) A mutation in the canine BHD gene is associated with hereditary multifocal renal cystadenocarcinoma and nodular dermatofibrosis in the German Shepherd dog. Hum Mol Gen 12 (23), 3043–3053 PubMed.
• White R, Schultheiss S (1998) Nodular dermatofibrosis and cystic renal disease in three mixed-breed dogs and a Boxer dog Vet Derm 9 (2), 119-126 PubMed.
• Moe L & Lium B (1997) Hereditary multifocal renal cystadeno-carcinomas and nodular dermatofibrosis in 51 German shepherd dogs JSAP 38 (11), 498-505 PubMed.
• Moe L & Lium B (1997) Computed Tomography of Hereditary Multifocal Renal Cystadenocarcinomas in German Shepherd Dogs Vet Rad and ultra 38 (5), 335-343 PubMed
• Marks S L, Farman C A & Peaston A (1993) Nodular Dermatofibrosis and Renal Cystadenomas in a Golden Retriever Vet Derm 4 (3): 133-137 Semantic Scholar.

Other sources of information

• Withrow S J & MacEwen E G (2020) Small Animal Clinical Oncology. 6th edn. W B Saunders.