Are You Confident of the Diagnosis?

Infantile digital fibromatosis presents as a single or multiple asymptomatic nodules that are usually located on the extensor surfaces of the phalanges of the fingers or toes, with notable sparing of the thumb and great toe. Infantile digital fibromas may be either present at birth or arise spontaneously in infancy. There are rare cases of development in older patients.

Characteristic findings on physical examination

Physical examination demonstrates firm, red to pink or skin colored slowly growing nodules, rarely larger than 2 cm. Large nodules may limit joint mobility and cause deformity (Figure 1). The lesions grow slowly in the first month and typically exhibit rapid growth over the next 10 to 14 months. Spontaneous regression occurs over the next 3 months to 5 years.

Figure 1.

Expected results of diagnostic studies

Radiography results are usually normal; however, bone deformities have rarely been reported. Magnetic resonance imaging (MRI) can delineate the depth and extent of the tumor and involvement of the digital neurovascular supply.

Histology shows whorled or interlacing fascicles of spindle cells (myofibroblasts) with pathognomonic round to ovoid, granular eosinophillic cytoplasmic inclusion bodies (Figure 2). The inclusion bodies represent accumulations of actin and vimentin (identified by immunohistochemistry) and may develop from progressive aggregation of contractile proteins in the cytoplasm. They are juxtanuclear in location and can even cause nuclear indentation.

Figure 2.

Proliferating fibroblasts with eosinophilic inclusion bodies located within the cytoplasm of the fibroblasts. (Courtesy of Bryan Anderson, MD)

The number and density of the inclusion bodies appears to decline as the tumor degenerates, however, but the number of inclusion bodies has no relationship to the stage of the tumor. There is a variable amount of lymphocytic inflammation. Masson-trichrome stains the myofibroblast cells red and phosphotungstic acid-hematoxylin stains the cells purple.

Diagnosis confirmation

The differential diagnosis includes keloids and hypertrophic scars, which are easily distinguished by the absence of inclusion bodies; terminal osseus dysplasia, and pigmentary defects (OMIM 300244) which present in females with “punched out” pigmentary defects of the face and scalp, as well as eye anomalies such as coloboma and hypertelorism; and pachydermodactyly, which usually occurs in young male adults and consists of diffuse symmetric swellings of the proximal fingers. Juvenile aponeurotic fibroma, which is an invasive calcifying tumor of palms and soles and infantile desmoid type fibromatosis that is locally aggressive and has no inclusion bodies on histology, should also be ruled out.

Who is at Risk for Developing this Disease?

Infantile digital fibromatosis is a benign, distinctive condition. There is no sexual, racial or ethnic predeliction.

What is the Cause of the Disease?
Etiology
Pathophysiology

The etiology of this disorder is unclear, but is thought to be related to dysregulation of myofibroblast differentiation and proliferation during wound repair. Animal studies have suggested that aberrant BMP (a member of the TGF beta superfamily) signaling could stimulate myofibroblast growth. There are a handful of cases occurring following trauma, with one case of extensive involvement of all four extremities occurring after syndactyly release. A viral cause has been suggested; however, no evidence of human papilloma virus or herpes simplex virus DNA has conclusively benn found.

Systemic Implications and Complications

There are no associated systemic disorders. Large lesions can reduce joint mobility or compress neurovascular bundles. Incomplete surgical excision can result in recurrences and rebound growth.

Treatment Options

Treatment options are summarized in Table I.

Table I.
Medical Treatment Surgical Procedures Physical Modalities
Observation Excision Physical therapy for patients with limitations in joint mobility
Intralesional injection with fluorouracil Mohs micrographic surgery  
Intralesional steroids Amputation  

Optimal Therapeutic Approach for this Disease

Given the benign nature and propensity for regression , expectant observation of these tumors is a first-line, conservative approach. If lesions become so large that they interfere with function or cause deformity, surgical resection may become necessary. The risk:benefit ratio, however, must be weighed, as a high recurrence rate (range 13% to 75%) has been noted following excision, usually between 2 weeks and 6 years following the procedure.

One case of Mohs micrographic surgery in a 9-month-old child did not recur following treatment. Another viable option for small limited tumors is intralesional injection with fluorouracil, which was reported to cause regression in a 7-year-old boy given 5 monthly intralesional injections of 10mg. The method of regression is thought to work by inhibiting transforming growth factor beta-induced type 1 collagen synthesis.

Amputation of the digit is a last resort for tumors that have caused considerable functional impairment and deformity, such that these lesions would not likely be reversible with regression. Intralesional injections of steroids have had mixed results, with aggravation of the tumor in one report.

Patient Management

Patients should be monitored regularly for both signs of progression or regression. Parents should be informed that regression may take several years. If signs of pain or reduced joint movement develop, imaging studies and surgical consultation are warranted.

Patients should also be closely monitored following, as both a high local rate of recurrence as well as development of new tumors at distant sites following surgery have been reported. Flurouracil injection should only be used in small and limited tumors, as there is no data on the systemic absorption of this medication following injection of these tumors. The risks associated with injection include pain, purpura, ulceration, burning sensation, and dyschromia.

Unusual Clinical Scenarios to Consider in Patient Management

As these lesions have been reported to regress up to 5 years after diagnosis, patients and parents should not be discouraged by the length of time often needed for complete regression.

What is the Evidence?

Grenier, N, Liang, C, Capaldi, L, Ney, A, Lapidus, C, Schappell, D, Katarincic, J, Robinson-Bostom, L. “A range of histologic findings in infantile digital fibromatosis”. Pediatric Dermatology. vol. 25. 2008. pp. 72-5. (This report of three patients highlights the histologic variability observed in digital fibromatosis; from few to many cytoplasmic perinuclear inclusions, well organized to haphazzardly arranged spindle cells and variable amounts of lymphocytic infiltration.)

Oh, CK, Son, HS, Kwon, YW, Jang, HS, Kwon, KS. “Intralesional fluorouracil injection in infantile digital fibromatosis”. Pedatr Dermatol. vol. 141. 2005. pp. 549-50. (Five monthly injections of 50mg/dl 5-florouracil produced complete photographically documented regression of a digital tumor in a 7-year-old child that had reported histologic features (though not shown) of an infantile digital fibroma.

Niamba, P, Le’aute-Labreze, C, Boralevi, F, Lepreux, S, Chamaillard, M, Vergnes, P. “Further documentation of spontaneous regression of Infantile digital fibromatosis”. Pediatr Dermatol. vol. 24. 2007. pp. 280-4. (Four cases are reported with follow-up to regression of 1 to 9 years. One patient had multiple surgeries during that time.)

Kanwar, SK, Kaur, S, Thami, G, Mohan, H. “Congenital infantile digital fibromatosis”. Pediatr Dermatol. vol. 19. 2002. pp. 370-1. (This is a single case of a 6-month-old Indian boy with no follow-up. There is no ethnic or racial predelection.)

Keltz, M, DiCostanzo, D, Desai, P, Cohen, SR. “Infantile (Desmoid-Type) fibromatosis”. Pediatr Dermatol. vol. 12. 1995. pp. 149-51. (This is a case report of the potentially agressive form of fibromatois, which should be distinguished histologically from an infantile digital fibroma. The latter has intracytoplasmic inclusions whilst the former does not. The authors emphasize that excision/amputation is necessary for desmoid fibromatosis.)

Rimareix, F, Bardot, J, Andrac, L, Vasse, D, Galinier, P, Magalon, G. “Infantile digital fibroma: report on eleven cases”. Eur J Pediatr Surg. vol. 7. 1997. pp. 345-48. (Treatment of 11 cases with surgery resulted in a nearly 40% recurrence rate, the longest follow up being 14 years.)

Zhu, WY, Xia, MY, Huang, YF, Leonardi, C, Penneys, NS. “Infantile digital fIbromatosis: Ultrastructural human papillomavirus and Herpes simplex virus DNA observation”. Pediatr Dermatol. vol. 8. 1991. pp. 137-9. (Neither human papilloma virus DNA nor herpes simplex DNA was found in one case of infantile digital fibromatosis.)

Taylor, HB, Gellis, SE, Schmidt, BAR, Upton, J, Rogers, GF. “Infantile digital fibromatosis”. Ann Plast Surg. vol. 61. 2008. pp. 472-76. (This unusual case occured on digits of all four extremities during the postsurgical period of syndactyly release in one case. A preoperative biopsy was not included.)

Talbot, C, Tahir, K, Smith, M. “Infantile digital fibromatosis”. J Pediatr Orthop. vol. 16. 2007. pp. 110-12. (Four cases on the toes were surgically excised. No recurrences were reported. These authors recommend surgery, unlike most other authors.)

Heymann, WR. “Infantile digital fibromatosis”. J Am Acad Dermatol. vol. 59. 2008. pp. 122-3. (This Dr. Heymann’s commentary based on a discussion in “Dialogues in Dermatology” between pediatric dermatologists Victoria Barrio and Stuart Brown about this benign tumor.)

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