Case10
Infantile digital fibromatosis

History
1 1/2- year-old girl with recent growth of a cutaneous lesion on the second toe of the left foot.

Pathology
A representative slide of a skin specimen measuring 3 x 2.5 x 0.5 cm is submitted.
The surface was pigmented showing patchy whitish foci. The cut surface was pale and
relatively firm.

Discussion
Synonyms: Digital fibrous tumour of Reye, inclusion body fibromatosis, digital fibrous
swelling, recurrent digital fibrous tumour of childhood.
First reported by Reye in 1965, IDF occupies a unique position among the fibrous
proliferative disorders because of the presence of characteristic intracytoplasmic inclusions. IDF is a recurring lesion of the digits of infants. Extradigital locations and rare examples arising in adults have been described (tongue, breast, arm and leg). This relatively rare lesion, representing 0,1% of childhood fibrous tumours, is present at birth in 1/3 of the cases. Most are diagnosed within the first year of life and nearly all in children usually younger than 3 years. There is neither sex prevalence nor evidence of familial tendency.

IDF is a rapidly growing indolent pink nodular tumour, usually less than 2 cm in diameter, arising on the lateral and dorsal surfaces of fingers and toes. Strangely, thumbs and great toes are usually spared. Tumour may be single; 1/3 of IDF are multiple or multifocal.

Macroscopically, IDF is a firm, white, poorly circumscribed dermal or subcutaneous nodule, covered by intact skin, often less than 1cm in diameter.
Microscopically, the tumour, which replaces most of the dermis, consists of moderately cellular whorls and interdigitating sheets of uniform (myo-)fibroblasts, surrounded by avariably, often dense, collagenous stroma. There are usually no myxoid changes. Occasional mitosis is seen. The overlying epidermis may show hyperkeratosis, acanthosis and flattening of the rete ridges. Adnexal structures and fat may be entrapped in the fibrous proliferation which exceptionnally may extend to the periosteum and erodes it, with no invasion of bone.

The typical sine qua non diagnostic features are distinctive eosinophilic bright cytoplasmic inclusions. They are small (2-13 mm), round, eosinophilic, frequently adjacent to the nucleus, sometimes surrounded with a clear halo. They differ from red blood cells varying in size and lacking birefringence.They stain in bright red with Masson’s trichrome and Lendrum’s phloxin tartrazine or haematoxylin-phloxin safran, in deep purple with PTAH and in yellow with elastin-van Gieson. They do not stain with PAS, Alcian blue, Colloidal iron, Feulgen and Methyl green pyronin stains. Maturation of the lesion may result in a decreased number of inclusions.

With immunohistochemistry, IDF tumour cells are keratin, vimentin, desmin and actin positive; they are S-100 protein and GFAP negative. CD57 may be positive in some cases. IDF cells’actin composition is confirmed by electron microscopy. Tumour cells are active fibroblasts and myofibroblasts with endoplasmic reticulum, prominent Golgi and condensed microfilaments. Bundles of axially oriented cytoplasmic filaments run toward the cell membranes and form whorled bodies which correlate with the inclusions. These actin inclusions are rarely encountered in other myofibroblastic or smooth muscle component in other lesions.

Differential diagnosis is relatively easy because the location, age and cytoplasmic inclusions of IDF are unique among childhood fibrous tumours. Fibrosarcomas and peripheral nerve sheat tumours are more cellular and more polymorphic than IDF, usually associated with necrosis.
Fibrous histiocytoma, dermatofibroma-type, has a more storiform pattern than IDF. IDF is more cellular than keloid. Inclusion bodies can extremely rarely be seen in myofibroblastomas and benign leiomyomas.

The nature of the cytoplasmic inclusions of IDF has been the subject of considerable research and debate. The demonstration of actin in the inclusions and heavy meromyosin binding in cultured cells has led to the hypothesis that the inclusions represent defective regulation of cellular filaments organization in neoplastic myofibroblasts. A viral etiology has never been confirmed, even in cultures of tumour cells together with human embryonic lung cells. There is no history of trauma or prior infection, and no family history. Karyotypes on cultured IDF cells are always diploid, 46 XX. This tumour may undergo a decrease in the number of inclusions with maturation and regress spontaneously, becoming fibrotic with time. Nevertheless, there is a high recurrence rate (up to 60%) in digital locations in children. The same tumour in extradigital locations of adults does not seem to recur after excision. There is no single feature clearly identified to predict the risk of recurrence even if some clinical and/or pathological features, such as presentation at greater than 5 years of age, incomplete surgical or histological resection, mitotic index of 5 or more/10HPF and areas of necrosis and inflammation within the tumor, can be suggestive of recurrence. IDF never metastasizes. Local complete excision is the recommended treatment, rather than immediate aggressive surgical treatment.

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