A 2-month-old male infant presented with a subcutaneous mass on the left middle finger; the mass had been present since birth. This was treated with local excision, and there has been no recurrence. Histology revealed the typical features of a fibrous hamartoma. Cytogenetic studies revealed a reciprocal translocation, t(2;3)(q31;q21), as the sole abnormality. To our knowledge, this is the first report of the cytogenetic findings in fibrous hamartoma, and it suggests that this lesion represents a benign neoplasm.
(Arch Pathol Lab Med. 2005;129:520-522)
A rare and unique tumor of infants, fibrous hamartoma was first described by Reye1 in 1956 as a subdermal fibromatous tumor of infancy. Reye described 6 cases that occurred in children within the first 2 years of life. Two of these tumors were present at birth. The term fibrous hamartoma of infancy was later coined by Enzinger2 in 1965. We report a case of congenital fibrous hamartoma in an infant, discuss the histologie findings, and review the cytogenetic findings.
REPORT OF A CASE
A male infant first presented when he was 2 months of age with a painless mass lesion in the left middle finger. The soft tissue lesion had been present since birth and extended from the metacarpophalangeal joint to the proximal interphalangeal joint; the lesion measured 3 × 3 cm. Radiographically, there was no evidence of bony involvement. The infant was developing appropriately and achieving normal milestones. Local excision of the lesion was performed. Follow-up to date has revealed no recurrence.
MATERIALS AND METHODS
Tumor tissue was minced and digested overnight with collagenase and was set up as an in situ culture in standard culture media with gentamicin for 7 days. The cells were harvested with colcemid and hypotonie potassium chloride solution and fixed in methanol acetic acid. Metaphase chromosome preparations were G-banded using the standard trypsin-Giemsa method.1 At least 20 metaphases were analyzed. A clonal abnormality was defined as 2 or more metaphases with the same additional chromosome or structural rearrangement, or 3 or more cells with the same missing chromosome. The karyotype was described according to the 1995 guidelines of the International System for Human Cytogenetic Nomenclature.4
Grossly, the lesion was a single nodule, 3.5 × 3.5 cm, covered by normal intact skin. sections revealed a glistening gray-white fibrotic appearance with focal yellow areas resembling fat. Microscopically, the small short spindleshaped to polygonal cells formed nests and whorls in the superficial and deep dermis. These primitive mesenchymal cells were admixed in some areas with mature adipose tissue islands (Figure 1). Collagen bands and haphazard bundles of fibrous tissue dissected through the lesion. The lesion involved much of the superficial dermis without encapsulation.
Immunohistochemistry of the primitive mesenchymal cells revealed positive staining with vimentin. The myofibroblastic cells were negative for human muscle actin and desmin. S100 protein was positive in adipose tissue.
Evaluable metaphases were obtained from the tumor tissue with a banding resolution of at least 425 bands. The karyotype showed a modal number of 46 chromosomes with a simple reciprocal translocation, t(2;3)(q31;q21), as the sole abnormality in 12 metaphases (Figure 2). The remaining 8 metaphases showed a normal male chromosomal complement and likely represent the constitutional karyotype of the surrounding normal tissue.
Fibrous hamartomas of infancy are usually diagnosed within the first 2 years of life, and nearly 25% may occur congenitally.1,5 The male-to-female ratio is 2:1, and there is no apparent familial or syndromic association. The common sites of involvement are the axillary regions, upper arms, upper trunk, inguinal region, and external genital areas.2,5 Occurrence in the extremities, as was seen in this case, is rare. Fibrous hamartomas of infancy usually present as solitary subcutaneous masses ranging from 0.5 cm to 4 cm in diameter.3 They are poorly demarcated and unencapsulated and are contiguous with the surrounding fat. Routine hematoxylin-eosin-stained sections are generally sufficient for a diagnosis, but immunochemistry may be useful. The primitive mesenchymal cells are vimentin positive, the fibroblastic component is actin positive, and the adipocytes are Sl00 protein positive.5
The differential diagnoses to be considered are infantile digital fibromatosis, myofibroma, lipofibromatosis, and calcifying aponeurotic fibroma.6 Infantile digital fibromatosis occurs almost exclusively in the fingers and toes. These tumor cells are characterized by intracytoplasmic perinuclear eosinophilic inclusions. Myofibromas are commonly found in the head and neck region and trunk. Histologically, they appear biphasic, with alternating lightand dark-staining areas. The dark-staining areas are composed of bundles of myofibroblasts exhibiting a hemangiopericytoma-like pattern. A characteristic histologie pattern called zouation7 has been described in calcifying aponeurotic fibroma, where calcific areas are surrounded by hyalinized collagenous foci, which in turn are palisaded by plump fibroblasts. Calcifying aponeurotic fibroma may not exhibit foci of calcification in its earliest phase and often infiltrates fat in infants and young children. The absence of immature mesenchyme and trabecular arrangement of fibroblasts distinguishes this from fibrous hamartoma of infancy.
Pediatric soft tissue tumors composed of adipose tissue and fibroblastic elements have been recently classified as lipofibromatosis by Fetsch et al.s Histologically, these tumors have abundant adipose tissue traversed by bundles of fibroblast-like cells. Nests of immature cells in a myxoid matrix are typically lacking in these tumors as compared to fibrous hamartoma of infancy.
Benign tumors almost always display simple karyotypic rearrangements. Reciprocal translocations are the most common finding and occur as the sole abnormality. Malignant solid tumors are characterized by a triploid or near-tetraploid modal chromosome number with multiple numeric and unbalanced structural abnormalities.9
A similar breakpoint, involving chromosome 2 (q31) as a t(2;ll)(q31-32;ql2), has been reported in a tendon sheath fibroma and a desmoplastic fibroblastoma.10,11 Chromosome 3q21 is a recurrent breakpoint in nodular fasciitis.12
Abnormalities of 2q and 3q seem to be recurrent aberrations in benign fibrous tumors. Fibromas and other fibrous growths have rarely been reported with karyotypic information. The finding of a simple karyotypic aberration can provide confirmation of a benign process and distinguish it from a malignant tumor. With more data, recurring abnormalities may become apparent.
A possible gene on chromosome 2q31 may be related to the development of fibrous hamartoma of infancy. The vitronectin receptor-α subunit gene belongs to the integrin family. Integrins serve as the major receptors for extracellular matrix-mediated cell adhesion and cellular proliferation, apoptosis, and differentiation.13 Additional studies are needed to determine if this cytogenetic abnormality is recurring in fibrous hamartomas and to investigate the molecular mechanisms of this benign fibrous tumor.
We thank Ms Sandra Hatcher, MS, and Ms Helen Jenks, BS, for their technical assistance in the cytogenetic analysis.
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13. Fernandez-Ruiz E, Pardo-Manuael de Villena F, Rodriguez de Cordolia S, Sanchez-Madrid F. Regional localization of the human vitronectin receptor alpha subunit gene (VNRA) to chromosome 2q31-[arrow right]q32. Cytogenet Cell Genet. 1993; 62:26-81.
Renuka Lakshminarayanan, MD; Thomas Konia, MD; jeanna Welborn, MD
Accepted for publication October 13, 2004.
From the Departments of Pathology and Laboratory Medicine (Drs Lakshminarayanan, Konia, and Welborn) and Hematology and Oncology (Dr Welborn), University of California Davis Medical Center, Sacramento.
The authors have no relevant financial interest in the products or companies described in this article.
Corresponding author: Thomas Konia, MD, Department of Pathology and Laboratory Medicine, University of California Davis Medical Center, 4400 V St, Sacramento, CA 95817 (e-mail: Thomas.Konia@ ucdmc.ucdavis.edu).
Reprints not available from the authors.
Copyright College of American Pathologists Apr 2005
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