Fibrous hamartoma of infancy with a rare pseudoangiomatous pattern: A case report

Abstract

Fibrous hamartoma of infancy (FHI) is a rare benign mesenchymal tumor typically presenting with a triphasic histologic pattern. We report an unusual case of FHI presenting as a breast mass in a 6-month-old infant, characterized by a predominant pseudoangiomatous pattern. Diagnosis was confirmed through clinical, radiologic, and histopathologic correlation, supported by the identification of a specific epidermal growth factor receptor exon 20 mutation. This case highlights the importance of molecular analysis in distinguishing atypical FHI variants from other pediatric tumors.

Introduction

Fibrous hamartoma of infancy (FHI) is a benign mesenchymal proliferation that typically manifests within the first 2 years of life. While it most commonly arises in the axilla, trunk, or upper extremities, atypical localizations can pose significant diagnostic challenges. Histologically, FHI is defined by a characteristic triphasic morphology consisting of mature fibrous tissue, mature adipose tissue, and immature mesenchymal cells. However, variations in these patterns can lead to confusion with other benign or malignant pediatric tumors. We present a case of FHI with a rare pseudoangiomatous histologic pattern occurring in the breast of a male infant.

Case report

A healthy 6-month-old boy was referred for a firm, painless, and progressively enlarging subcutaneous purplish mass of the left breast, first noted at 3 months of age. Clinical examination revealed a solid mass without palpable axillary lymphadenopathy (Figure 1). Doppler ultrasound identified a poorly vascularized, solid, hypoechoic lesion measuring 3.9 × 1.7 × 1.2 cm.

Figure 1.

(a) Clinical image: Front view of the left purplish breast mass (b) Clinical image: Lateral view of the left purplish breast mass.

Initial echo-guided needle biopsies showed a pseudoangiomatous fibroblastic stroma characterized by anastomosing slit-like spaces lined with bland spindle cells, lacking cytonuclear atypia. Immunohistochemical staining revealed that the lining cells were positive for CD34, alpha-smooth muscle actin, and WT1, consistent with a myofibroblastic phenotype. Stains for desmin, GLUT-1, and cytokeratin were negative. Furthermore, molecular testing for the COL1A1/PDGFB fusion gene was negative, excluding giant cell fibroblastoma (GCL).

Given the non diagnostic findings and a growing mass, a complete surgical excision was performed. The final histopathologic analysis not only revealed identical pseudoangiomatous findings but also identified a small, focal area of mature adipose and fibroblastic tissue, suggestive of FHI (Figure 2). To confirm the diagnosis, molecular analysis was performed and detected a tandem duplication mutation in exon 20 of the Epidermal Growth Factor Receptor (EGFR), confirming the diagnosis of a fibrous hamartoma of infancy. At 16 months of age, the patient remains healthy with no evidence of recurrence.

Figure 2.

(a) Hematoxylin-eosin, original magnification × 100.

Discussion

FHI, first described by Reye in 1956, ¹ is a rare benign mesenchymal proliferation that typically arises in the axilla or chest wall of infants under age of two. Breast localization is uncommon. ² Histologically, FHI is characterized by a triphasic composition of mature fibrous tissue, mature adipose tissue, and immature mesenchymal cells in variable quantity.^{1 –3} These patterns may not be uniformly distributed, making the diagnosis challenging in small biopsy specimens or when one component predominates.^4,5 In our case, the initial needle biopsies failed to reveal the triphasic components, instead demonstrating a pseudoangiomatous pattern of slit-like spaces within a fibrous stroma. The differential diagnosis for such a pattern includes pseudoangiomatous stromal hyperplasia (PASH), GCL, and deep infantile hemangioma. PASH, while histologically similar, is exceptionally rare in the pediatric population and lacks the EGFR mutation.^6,7 GCL was ruled out by the absence of the COL1A1–PDGFB gene fusion,^4,8 and deep infantile hemangioma was excluded by the negative GLUT-1 staining and low vascularity on ultrasound. ⁹

The detection of a tandem duplication mutation in EGFR exon 20 was pivotal in our case. Recent literature suggests that this specific mutation characterizes most FHI cases,^5,8,10 making it a highly useful molecular marker for confirming the diagnosis in atypical or monophasic presentations.

Conclusion

This case emphasizes the diagnostic complexity of FHI when it presents with atypical histologic patterns or in unusual anatomical sites. Clinicians and pathologists should maintain a high index of suspicion for FHI in pediatric mesenchymal tumors and consider molecular confirmation via EGFR mutation analysis to ensure an accurate diagnosis.