PDGFβ receptor) proteins that contribute to the development and/or progression of IMF.A mutation in one of the two NOTCH3 genes has been reported to occur in a single family with autosomal dominant inheritance of IMF: 9 of this familys members had IMF plus the mutation while 7 of its members did not have IMF or the mutation. Since the mutated NOTCH3 gene in this family produces an overactive neurogenic locus notch homolog protein 3 product that in cell culture studies increases the expression of the PDGFRB genes product, the PDGFβ receptor, this NOTCH3 mutation may promote the development and/or progression of IMF in a manner similar to PDGFRB mutant genes, i.e. by increasing the number and therefore overall activity of the PDGFβ receptor. Further studies are needed to define NOTCH3 gene mutations frequency of occurrence in, and contribution to the development of, IMF. Solitary IMF tumors
Solitary IMF tumors represent 50 to 74% of all IMF cases. These tumors commonly present with a mass that infiltrates the surrounding tissue in the head and neck areas (e.g. in the ethmoid sinus/maxillary sinus, infratemporal fossa, tongue, hard palate, behind an ear, or temporal bone); less commonly in other sites such as the scapula/axilla area, lower back, or soft tissue/bone in the lower leg; and also less commonly in visceral organs such as the pancreas, spleen, lung, or heart. Solitary IMF tumors often (i.e. 25 to 61% of cases in different studies) regress spontaneously.
The ages range from 50 to 80 years with a male predominance and a median age of 67 years. VC may grow large in size, resulting in the destruction of adjacent tissue, such as bone and cartilage. Diagnosis
Surgeons must provide adequate specimens including the full thickness of the tumors and adjacent uninvolved mucosa for correct histopathology diagnosis. Subtypes
Epithelioma cuniculatum (also known as Carcinoma cuniculatum,: 654  and Ackerman tumor) is a subtype of verrucous carcinoma, characterized by well-differentiated epithelial cells which lack cytological atypia, but display a blunt papillary/pebbly surface and keratin-filled crypts extending deep into the connective tissue. These keratin-filled resemble rabbit burrows. It is located almost exclusively on the foot, but at least oral location has also been described. Treatment
Surgery is considered the treatment of choice, but the extent of surgical margin and the adjuvant radiotherapy are still controversial. Surgical excision alone is effective for controlling VC, but elective neck dissection is not necessary even in patients in the advanced stages. Prognosis
Most patients with verrucous carcinoma have a good prognosis. Local recurrence is not uncommon, but metastasis to distant parts of the body is rare. Patients with oral verrucous carcinoma may be at greater risk of a second oral squamous cell carcinoma, for which the prognosis is worse. See also
List of cutaneous conditions
List of verrucous carcinoma subtypes

References
External links
eMedicine.com article