Infantile digital fibromatosis: Inclusions and exclusions

By Warren R. Heymann, MD, FAAD
Aug. 3, 2022
Vol. 4, No. 31

In 1965, Reye described 18 small, fibrous tumors from 12 children submitted to his laboratory for histological examination, that he had accumulated over two decades. Initially, these lesions were tentatively classified as well-differentiated fibrosarcomas. His seminal observation was: “The feature which sets these tumors apart from all other fibrous tumors at the histological level is the presence, within the cell cytoplasm, of inclusion bodies.” He titled his manuscript “Recurring digital fibrous tumors of childhood.” (1)

Now known as infantile digital fibromatosis (IDF), the disorder is also known as a Reye tumor, recurring digital fibrous tumor of childhood, and inclusion body fibromatosis. (2) IDF is a rare, benign, spontaneously regressing, fibrous tissue tumor of infancy and childhood that characteristically appears in the first year of life; it is congenital in one-third of cases. IDF tends to be locally recurrent without bony invasion or metastasis. Single or multiple, firm reddish-pink slowly growing nodules, about 2 cm in size are present on the extensor aspects of the phalanges of the last four fingers or toes, sparing the thumb and great toe. (3) (Why thumb and great toes are spared still defies explanation.) The natural history of IDF is characterized by slow growth in the lesions’ first month, followed by rapid growth in the ensuing 10 to 14 months, before the lesions steadily regress. Should lesions be extensive or cross joints, they may result in limited joint mobility and digital deformity. (4)

Although considered a pediatric disorder, identical cases of IDF have been reported in adults. (2) Additionally, extradigital cases have been observed in adults. Viale et al detailed two such cases: a nodule of the right leg in a 32-year-old woman and a nodule of the right arm of a 42-year-old man. (5) Technically IDF is, of course, an incorrect name in these circumstances, with digital fibromatosis appropriate for the former and inclusion body fibromatosis or IDF-like tumor of adulthood for the latter (or both).

Histologically, IDF appears as spindled cells (myofibroblasts) containing round or ovoid, eosinophilic 3- to 10-μm cytoplasmic inclusion bodies (an accumulation of actin and vimentin filaments), representing the histologic hallmark of this disorder, as first recognized by Reye. The cells stain red with the Masson trichrome stain and purple with phosphotungstic acid–hematoxylin (PTAH). (3)

I had always considered IDF inclusions to be pathognomonic, and they are — in the right context. Inclusions, however, are not exclusive to IDF. Kishibe et al found that such inclusions were observed to some degree in 25 of 30 angioleiomyomas compared to none in piloleiomyomas. Inclusions have also been observed in leiomyomas of other organs such as the bladder and uterus. (6) Hiraoka et al reported the case of a 42-year-old Japanese woman with a benign phyllodes tumor of the breast with stromal myofibroblasts demonstrating inclusions identical those observed in IDF. (7)

The cornerstone of managing IDF is observation for spontaneous regression in asymptomatic lesions. Variable success has been reported with imiquimod, steroids (topical or intralesional), tacrolimus, and 5-fluorouracil. Because of the potential for recurrence, surgery (excisional or Mohs) should be reserved for those patients demonstrating functional impairment. (8,9,10)

In conclusion, although IDF usually presents as Reye originally described the lesions, dermatologists should be cognizant of atypical presentations — lesions may not be infantile (being adult-onset) or digital (appearing on the extremities). Dermatopathogists must also recognize that actin-vimentin inclusions are not unique to IDF. Until further research defines the pathogenesis of IDF, if possible, watchful waiting for regression, while avoiding surgery, remains first-line therapy.

Point to Remember: Infantile digital fibromatosis may present atypically. Therapy must be tailored to the patient to determine if the standard “watch and wait” approach is most appropriate.

Our expert’s viewpoint

Andrew C. Krakowski, MD, FAAD
Network Chair of Dermatology
Program Director for the Residency in Dermatology
St. Luke’s University Health Network
Bethlehem, Pennsylvania

I always need an extra hand when it comes to the differential diagnosis and management for a digital lesion in a kid. I cannot put my finger on it, but sometimes I just need to be pointed in the right direction. Of course, polydactyly is a snap, but consider the acquired digital fibrokeratoma (ADF). As a rule of thumb, this lesion may present at any age as an asymptomatic, flesh-colored growth circumscribed by a collarette of scale. On the other hand, supernumerary digits can look similar to ADFs but they are reliably present at birth. These lesions represent a duplication of a digit with a tissue core of bone, cartilage, and/or nerve, so it really pains me when they are not managed correctly. Periungal fibromas (Koenen’s tumor) are hyperkeratotic papules that tend to develop in late childhood and increase in number with age. Their presence can really help you nail the diagnosis of tuberous sclerosis. Pyogenic granulomas are rapidly growing vascular tumors that can occur anywhere and often affect the hands. Like ADF, they tend to have a collarette of scale. Because they are composed of friable tissue, they also tend to bleed easily with friction, which really rubs me the wrong way.

Now, we come to the topic at hand: Infantile digital fibromatosis. One indisputable truth I had locked away while studying for my pediatric dermatology boards was that IDF inclusions and infantile digital fibromatosis always go hand in hand. Indexing my brain, I could not come up with another condition in which these inclusions were associated. So, imagine my initial reaction after reading Dr. Heymann’s update and review of the literature around this topic. It was like thumbing my nose to everything I once held dear and true. I admit I was so riled up that I wanted to give someone a knuckle sandwich!

While this paradigm shift seemed a bit underhanded at first, I was eventually able to calm down enough to realize that this does not really change much for me as a clinician. IDFs are pretty distinct morphologically from the other lesions in my aforementioned handy differential diagnosis. So, I will likely not have to lift a finger in order to accommodate the fact that inclusions can be seen in at least several other conditions. Instead, this responsibility will fall into the hands of our dermatopathology colleagues, and for that they deserve a great, big thumbs-up.

1. Reye RD. Recurring digital fibrous tumors of childhood. Arch Pathol. 1965 Sep;80:228-31. PMID: 14322942.

2. Heymann WR. Infantile digital fibromatosis. J Am Acad Dermatol. 2008 Jul;59(1):122-3. doi: 10.1016/j.jaad.2007.11.025. PMID: 18571599.

3. Kanwar AJ, Kaur S, Thami GP, Mohan H. Congenital infantile digital fibromatosis. Pediatr Dermatol. 2002 Jul-Aug;19(4):370-1. doi: 10.1046/j.1525-1470.2002.00109.x. PMID: 12220294.

4. Han XF, Liang Y, Ma L. Disabled fingers due to infantile digital fibromatosis: A report of two cases with residual functional joint deformity. Dermatol Ther. 2020 Sep 25:e14335. doi: 10.1111/dth.14335. Epub ahead of print. PMID: 32975351.

5. Viale G, Doglioni C, Iuzzolino P, Bontempini L, Colombi R, Coggi G, Dell'Orto P. Infantile digital fibromatosis-like tumour (inclusion body fibromatosis) of adulthood: report of two cases with ultrastructural and immunocytochemical findings. Histopathology. 1988 Apr;12(4):415-24. doi: 10.1111/j.1365-2559.1988.tb01956.x. PMID: 2836293.

6. Kishibe M, Igawa S, Kanno K, Matsuo R, Ishida-Yamamoto A. Inclusion bodies are not uncommon in angioleiomyoma. J Cutan Pathol. 2021 Feb;48(2):269-273. doi: 10.1111/cup.13891. Epub 2020 Oct 21. PMID: 33034917.

7. Hiraoka N, Mukai M, Hosoda Y, Hata J. Phyllodes tumor of the breast containing the intracytoplasmic inclusion bodies identical with infantile digital fibromatosis. Am J Surg Pathol. 1994 May;18(5):506-11. doi: 10.1097/00000478-199405000-00011. PMID: 8172324.

8. Eypper EH, Lee JC, Tarasen AJ, Weinberg MH, Adetayo OA. An Algorithmic Approach to the Management of Infantile Digital Fibromatosis: Review of Literature and a Case Report. Eplasty. 2018 May 7;18:e19. PMID: 29780440; PMCID: PMC5950536.

9. Karadağ AS, Koska MC, Cebeci Kahraman F, Bilgiç B, Bostan AB, Özkan K. Infantile digital fibromatosis successfully treated with topical imiquimod 5% combined with methylprednisolone aceponate 0.1. Dermatol Ther. 2020 Nov;33(6):e14012. doi: 10.1111/dth.14012. Epub 2020 Aug 6. PMID: 32657516.

10. Karadağ AS, Koska MC, Cebeci Kahraman F, Bilgiç B, Bostan AB, Özkan K. Infantile digital fibromatosis successfully treated with topical imiquimod 5% combined with methylprednisolone aceponate 0.1. Dermatol Ther. 2020 Nov;33(6):e14012. doi: 10.1111/dth.14012. Epub 2020 Aug 6. PMID: 32657516.

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