Fibrous hamartoma of infancy (FHI) is an infrequent benign soft tissue lesion that was first described as a subdermal fibromatous tumor of infancy in 1956 [1]. Nine years later, the clinicopathological entity was defined as a hamartoma [2]. It is still being debated whether FHI is a malformation, a hamartoma, or a neoplastic process [3]. Several authors have reported cytogenetic aberrations in HFI, but none have yet described recurrent genomic alterations [3], with the exception of Park et al. [4], who found recurrent EGFR exon 20 mutations.

FHI usually develops during the first 2 years of life. One fifth of cases is congenital [5] with FHI rarely appearing in older children [6], [7]. There is a male predominance [8]. FHI is mostly located in the axilla, trunk, and upper extremities [7] but has also been described in other sites [7], [9], [10], [11], [12]. Usually, FHI constitutes solitary lesions [8], but some cases with multiple FHI have been reported in tuberous sclerosis [13] and William syndrome [14]. The lesion presents as a subcutaneous painless mass [7]. Different cutaneous alterations in the overlying skin have been associated with symptoms such as discoloration, hyperpigmentation, oedema, tethering, hyperhidrosis, and hypertrichosis [5], [7], [15]. The recommended treatment is complete local excision [8].

On ultrasound studies, FHI is a poorly defined mass [9] with a typical serpentine pattern of intervening hypoechoic portions in a hyperechoic mass [16], [17] and poor vascularity on doppler examination [16], [17]. In terms of computerized tomography (CT) and magnetic resonance imaging (MRI), it shows strands of adipose or fibrous intensities traversing the lesions [18], [19]. Fibrous tissue trabeculae intermingled with fat in an organized pattern are highly suggestive of FHI [20]. Calcification areas have also been reported [18].

Macroscopically, these tumors appear as poorly circumscribed and heterogeneous masses, with gray-white areas and fat areas in variable proportions [21]. Most FHI measure 3 to 5 cm [21] but giant cases have been documented [22], [23]. Histologically, FHI is characterized by an organoid pattern with a triphasic morphology [21]. It is composed of varying amounts of mature adipose tissue; well-defined trabeculae consisting of bland and spindle fibroblastic/myofibroblastic cells in a fibrous stroma; and an immature component with small, round, or stellate cells in a myxoid matrix [21]. In some cases, giant cell fibroblastoma-like areas with hyalinized zones and a pseudoangiomatous appearance can be seen [21]. Ellington et al. reported one case with a predominant pseudoangiomatous pattern [24]. Keloidal and neuroid patterns, as well as pigmented cells, have also been described [3]. Scanty mitosis and no necrotic foci are usually identified [21]. Two cases of sarcomatous transformation have been reported [21].

Some different changes may be observed in the overlying epidermis, such as eccrine gland hyperplasia [15], duct dilation, primitive mesenchymal cells replacing the normal eccrine gland stroma [25], squamous syringometaplasia, intraluminal papillary formations [26], foci of lymphoid aggregates, and epithelial-folliculosebaceous-eccrine induction [5].

Inmunohistologically, FHI is positive to CD34 in immature cells and giant cell fibroblastoma-like areas [6], [21]. It is also positive to smooth muscle actin in fibroblastic areas, and, occasionally, in primitive areas, it is positive to S100 in adipocytic cells [27]. FHI is diffusely and strongly cytoplasmic positive to WT1 [28], to BCL2 in mesenchymal and pseudoangiomatous areas [3], to EGFR mostly in the primitive cell component [4], to vimentin in all three components [27], [29] and is negative to Factor VIII, cytokeratins [27], and nuclear beta-catenin [7].

In this study, we report twenty-one cases of FHI diagnosed in La Paz University Hospital of Madrid with a correlation of clinical, radiological, and pathological findings of this infrequent mesenchymal lesion.