Fibrous hamartoma of infancy (FHI) is a rare, typically painless, benign tumor that develops in the subcutaneous tissues of the axilla (i.e. armpit), arms, external genitalia, or, less commonly, various other areas. It is diagnosed in children who are usually less than 2 years old or, in up to 20% of cases, develops in utero and is diagnosed in an infant at birth.
The cells involved in FHI include bland fibroblasts/myofibroblasts, mature fat cells, and primitive-appearing spindle-shaped and/or star-shaped cells. The tumor was first described by R.D. Reye in 1956 who termed the disorder "subdermal fibromatous tumor of infancy" and regarded it as a reactive lesion. In a 1964 study of 30 patients, F.M. Enzinger renamed the tumor hamartoma of infancy; he regarded it to be a hamartoma (i.e. a local malformation of various normal cell types due to a systemic genetic condition) rather than a reactive lesion. However, subsequent studies have found gene mutations in FHI tumor cells and conclude that it is a true neoplasm, i.e. a growth of cells which is uncoordinated with that of the normal surrounding tissue and persists in growing abnormally even if the original trigger is removed. In 2020, the World Health Organization classified FHI in the category of benign fibroblastic and myofibroblastic tumors.
Fibrous hamartoma of infancy is generally a benign tumor but may be locally aggressive, locally infiltration, and in uncommon cases produce symptoms such as tenderness. Surgical excision is the treatment of choice for FHI tumors.
Presentation
The largest study to date examined 197 cases of FHI. In this study, most individuals presented with a slowly growing, symptomless, subcutaneous mass although rarely these masses were rapidly growing, and/or were tender, painful, warm, and/or were accompanied by skin changes, pigmentation, sweat gland enlargement, and/or increased hair overlaying the tumor. Sixty-eight percent of these cases were diagnosed in the first year of life, 23% were diagnoses at birth, and 9% were diagnosed in children 2–5 years old. The male-to female ratio was 2.4. The tumors were most common in the axilla (23% of cases), upper arm (12.5%), lower arm (10.5%), external genitalia area (9.5%), and inguinal region (7.5%); less common or rare sites for these tumors were the buttocks, back of the head, back of the neck, back of the torso, lower arm, leg, foot, chest, and anal area. Most cases presented as solitary masses but 3 cases presenting with 2 tumors and 1 case presenting with 5 tumors. Overall, the size of these tumors varied between 0.5 and 4.0 cm but in rare cases were as large as 20 cm. Two subsequent studies of 145 and 60 individuals agreed with all of these results but also did diagnose FHI in individuals as old as 8 and 14 years, respectively.
Pathology
On gross pathological examination, FHI tumors are soft, poorly demarcated, fibro-fatty masses located in subcutaneous tissues. These tumor masses tend to blend with the surrounding fat tissues, may be lobulated, and in rare cases, especially when large, extend into nearby muscles, nerves, and/or fibrous/connective tissue structures. Microscopic histopathological analyses of hematoxylin and eosin stained FHI tumor tissues consistently reveal three very different component zones in virtually all cases: 1) haphazardly arranged, intersecting bundles of bland fibroblast-like/myofibroblast-like cells; 2) mature adipose (i.e. fat) tissue; and 3) highly vascular, myxoid (i.e. connective tissue appearing more blue or purple than normal connective) nodules of primitive-appearing spindled-shaped to star-shaped cells. Chronic inflammatory cell (e.g. lymphocytes, macrophages, and plasma cells) aggregates are commonly present in these lesion. The relative proportion of fibroblast/myofibroblast, adipose tissue, and myxoid zones commonly vary from case to case.