PEDIATRICS Vol. 105 No. 1 January 2000, pp. 123-128

EXPERIENCE AND REASON:
Forehead Lipoblastoma Mimicking a Hemangioma

	ABSTRACT

Top Abstract Introduction Discussion Conclusion References

A case of forehead lipoblastoma simulating a hemangioma in a male infant is reported, to alert pediatricians to this rare tumor and to increase the index of suspicion in atypical hemangiomas.

A 2-month-old male infant developed a protruding forehead mass with increased vascularity. It demonstrated progressive and accelerated growth over the subsequent 6 months, unresponsive to steroid therapy. A magnetic resonance imaging scan supported the diagnosis of hemangioma because of the hypervascular nature of the lesion. Surgical excision was performed because of visual obstruction. Pathologic examination of the specimen was consistent with a very primitive lipoblastoma.

This tumor is a rare, benign lesion of immature fat cells that is found almost exclusively in the pediatric population. Lipoblastomas are more common in males than females and frequently present as asymptomatic, rapidly enlarging, soft lobular masses on the extremities. Complete surgical excision is the definitive treatment. In the vast majority of reported cases, however, the preoperative diagnosis was incorrect, underscoring the diagnostic dilemma presented by these rare tumors.

Although hemangiomas are by far the most common benign tumors of infancy, other tumors will infrequently occur and must be included in the differential diagnosis.

	CASE REPORT

A 7-month-old white boy was referred to the Children's Hospital of Philadelphia for evaluation of a rapidly enlarging forehead mass (Fig 1). His history was notable for having been born 6 weeks prematurely, requiring a 10-day stay in the neonatal intensive care unit and apnea monitoring for 5 months. His parents first noticed a flat red spot on the child's forehead at 2 months of age. Over the next several months, the spot progressively enlarged (Fig 2). The lesion evolved into a tense lobule with a purple hue and prominent cutaneous vessels.

View larger version (111K): [in this window] [in a new window]   Fig. 1.   The patient presented to our institution at 7 months of age with an enlarging soft tissue mass with potential obstruction of his right eye.

View larger version (112K): [in this window] [in a new window]   Fig. 2.   Appearance at 5 months of age with small protruding forehead mass, entirely consistent with a subcutaneous hemangioma.

Although hemangioma was felt to be the most likely diagnosis, the rather firm nature of the lesion and relative lack of increased warmth normally associated with hypervascular tissue prompted a magnetic resonance imaging (MRI) study. The study was consistent with a large hemangioma measuring 3 × 4.5 × 5.5 cm overlying the right frontal bone without intracranial extension (Fig 3A and B). Initial ophthalmologic examination did not reveal any evidence of amblyopia, but oral steroid therapy was begun (3 mg/kg/d) because of the risk of impending visual obstruction.

View larger version (116K): [in this window] [in a new window]   Fig. 3.   A, MRI scan at 7 months reveals a well circumscribed soft tissue mass with flow voids consistent with hemangioma with draining veins. B, the mass shows marked uniform enhancement after the intravenous administration of gadolinium, consistent with the highly vascular nature of a hemangioma. In retrospect, a true hemangioma might have demonstrated a more lobular architectural pattern.

The mass continued to enlarge over the subsequent month, unresponsive to steroid therapy. A repeat ophthalmologic evaluation revealed a diffuse amblyopia, attributed to the obstruction of the visual field by the expanding lesion, and a daily patching regimen was begun.

At 8 months of age, the mass measured 7 cm in maximum dimension (Fig 4), and the decision was made to proceed with surgical excision because it continued to expand despite maximum medical treatment, it was causing significant visual obstruction and potentially irreversible disuse amblyopia, and surgical resection of the redundant skin would be necessary even with spontaneous regression. His insurance carrier mandated a second opinion regarding the need for surgery, and evaluation by multiple physicians at another institution again confirmed the lesion to be a hemangioma requiring surgical excision because of visual obstruction.

View larger version (106K): [in this window] [in a new window]   Fig. 4.   Appearance at 8.5 months at the time of surgical excision. A prominent cutaneous vascular pattern is evident, hemangioma remains the preoperative diagnosis.

Intraoperative dissection revealed numerous enlarged peripheral veins, a well encapsulated mass, markedly attenuated frontalis muscle, and a single enlarged feeding artery from the frontal branch of the right superficial temporal artery. Redundant skin was used to achieve complete skin closure. In subsequent follow-up he demonstrated uneventful healing with good symmetry (Fig 5).

View larger version (115K): [in this window] [in a new window]   Fig. 5.   Appearance at 2 months after excision reveals good eyebrow symmetry and satisfactory soft tissue coverage.

Pathologic examination documented an ovoid mass measuring 8.5 × 7.0 × 6.0 cm and weighing 236 g. Multiple thin-walled vessels were noted to be traversing the surface of the specimen. Additionally, the mass was lined by a thin fibrous capsule. Cut surface revealed a tan-red, fleshy, vaguely lobulated surface without necrosis or identifiable normal tissue.

Histologically, the lesion was composed of spindle cells containing little cytoplasm set in a myxoid stroma containing a prominent vascular network (Fig 6). Some cells had vacuolated cytoplasm. The cells were primitive but not markedly atypical. The stroma in some areas was slightly cystic. Mitotic figures were present but did not exceed 3 per 10 high-power fields. There was not a definite lobular architecture. Necrosis was not present. The cells stained diffusely with antibodies to S 100 protein and muscle actin. The differential diagnosis included lipoblastoma, peripheral nerve sheath tumor, and a rhabdomyosarcoma. The absence of staining with antidesmin was inconsistent with rhabdomyosarcoma. Staining with S 100 was consistent with either a nerve sheath tumor or a tumor arising from adipose tissue. The histology and the clinical setting were most consistent with an atypical primitive lipoblastoma.

View larger version (149K): [in this window] [in a new window]   Fig. 6.   Microscopic examination (400×, S 100 protein immunohistochemical stain): primitive spindle cells are set in a myxoid stroma. Some cells show cytoplasmic vacuoles and the stroma contains microcysts in some areas.

	DISCUSSION

Top Abstract Introduction Discussion Conclusion References

Hemangiomas are by far the most common benign tumor of infancy, occurring in 10% of full-term, and as high as 25% of premature infants weighing <1 kg. This case report underscores the need to remember that other rare tumors can occur and must be considered in the differential diagnosis.

Despite the numerous case reports of lipoblastomas clinically simulating other lesions in their presentation,^1-5 to our knowledge this is the first report of a lipoblastoma mimicking a hemangioma. The early clinical history was entirely consistent with the appearance and growth of a hemangioma. Hemangiomas are rarely present at birth, but many appear as a small red dot during the first few weeks of life as dermal endothelial cells proliferate. The lesions demonstrate disproportionate growth over the next 6 to 18 months. Subcutaneous hemangiomas do not demonstrate the bright strawberry red pigmentation of cutaneous hemangiomas, their deeper location imparting a blue or purple hue. They may protrude and cause distortion and expansion of the overlying skin. Hemangiomas involve the head and neck area in about 60% of cases.⁶

Although the lesion was not noticed until 2 months of age, it was still consistent with a slowly growing subcutaneous forehead hemangioma. Clinical features that made it atypical on presentation to our institution at 7 months of age included its firm nature, its relative lack of warmth despite its hypervascular appearance, and its progressive growth that appeared to be accelerating rather than slowing down. Although none of these features by themselves ruled out a hemangioma, their collective presence raised enough suspicion to obtain a diagnostic scan to rule out other congenital neoplasms. For example, congenital fibrosarcoma has been reported to masquerade clinically as a hemangioma, but on computed tomography (CT)/MRI scan has mixed cystic/solid architecture, a heterogeneous density, and inhomogeneous enhancement that distinguishes it.⁷ On MRI, this lipoblastoma manifested flow voids and homogeneous gadolinium enhancement consistent with the hypervascularity of hemangiomas, although in retrospect it lacked the classic lobular architecture of hemangiomas. Reassured by the scan results, continued observation and systemic steroid therapy were appropriate management options. Its failure to respond to steroid therapy was also unusual, as the vast majority of hemangiomas will demonstrate detectable regression within the first week of therapy. Although interferon therapy was briefly considered, the accelerated growth and visual obstruction left surgical excision as his best option. Despite a preoperative and postoperative diagnosis of hemangioma, pathologic analysis was most consistent with a primitive lipoblastoma.

Lipoblastoma is a rare, benign tumor of lipoblasts found almost exclusively in the pediatric population. In 1926, Jaffe⁸ provided the first English language literature description of a lipoblastoma when he used the term to describe an atypical lipomatous tumor of the groin. The lipoblastoma consisted of cells resembling embryonic fat cells. He further noted that lipoblastomas do not recur or metastasize. Thirty-two years later, Vellios⁹ proposed the term lipoblastomatosis for a tumor histologically resembling myxoid liposarcoma but remaining circumscribed without invasion into surrounding tissue. He speculated that the tumor developed from postnatal proliferation of lipoblasts. Chung and Enzinger¹⁰ published the largest case series to date in 1973. In their analysis, they suggested designating the discrete, circumscribed form of the tumor lipoblastoma, and the diffuse form lipoblastomatosis. In 1997, Collins and Chatten¹¹ offered a 2-part definition for lipoblastoma that distinguishes it from other adipose tissue tumors. First, septae divide the tumor into lobules. Second, the lobules contain a variable concentration of immature fat cells.

Lipoblastomas are a rare pediatric tumor. Various previous reviews of the literature report fewer than 100 case reports of lipoblastoma in the English language literature.^1,2,12,13 However, 1 review of 18 677 benign soft tissue lesions identified 114 lipoblastomas (.6%).¹⁴

The tumor is found predominantly in the younger pediatric population. Eighty-eight percent of tumors in 1 case series presented in children <3 years of age.¹⁰ Other case series have found up to 55% of tumors occurring in children <1 year of age.^2,13,15 Some reports note the presence of lipoblastomas at birth.^3,10,16 The oldest patients with lipoblastomas reported in English literature case series have been 5, 6, 7, and 18 years old.^10,11,16,17 Based on their personal files, Stout and Lattes¹⁸ referred to 6 cases of lipoblastoma occurring in adults.¹⁸ Additionally, in 1964 Carcassonne¹⁹ reported a lipoblastoma of the mesentery in a 63-year-old man.

Lipoblastomas are more commonly found in males than females, and may occur more often in the extremities. The reported incidence ratio ranges from being 1.3 to 3.8 times more common in males than females.^10,11,13,14 Case series focusing on lipoblastomas reveal a predilection for the tumor to present on the extremities in up to 72% of the cases^10,11,13. However, the largest reported group of lipoblastomas showed extremity involvement in only 46 of 114 cases (40%).¹⁴ Additionally, Collins and Chatten¹¹ note a predilection for the tumor to develop on the left side of the body (13 of 18 samples). This increased incidence of left-sided lesions may suggest a genetic association with genes determining asymmetry.

The classic presentation of lipoblastoma is a rapidly enlarging, asymptomatic growth of a soft, nontender mass^{4,10,11,13,15.} Less frequently, lipoblastomas located in the retroperitoneum may present with emesis or diarrhea.^2,11 The literature includes a report of an intrascrotal lipoblastoma mimicking testicular torsion.¹ The lesions may display prominent blood vessels regularly distributed.^2,3,4,11

Accurate preoperative diagnosis of lipoblastoma is rare, and the alternative diagnoses are numerous and varied. Incorrect preoperative diagnoses have included sarcoma, Wilms' tumor, neuroblastoma, germ cell tumor, lymphoma, epidermal inclusion cyst, lymphangioma, lipoma, and Baker's cyst.^3,11,12 Only 1 published English language case reports accurate preoperative diagnosis of a lipoblastoma. The lesion was accurately diagnosed based on fine-needle aspiration cytology and consideration of the patient's young age.²⁰

Various imaging modalities have been used to improve the accuracy of preoperative diagnosis of lipoblastomas. These modalities include MRI, CT, and ultrasound^4,21-24. Ha et al²² report that the tumor is bright on both T1 and T2 scans, consistent with fat, but the lesion is hypointense on T1 relative to subcutaneous fat. The increased cellularity of lipoblastomas probably accounts for this difference, as well as the presence of immature fat cells in lipoblastomas in contrast to mature fat cells in subcutaneous tissue. Furthermore, this difference may aid in distinguishing lipoblastomas from other lipomatous lesions such as lipomas. Our patient had a very primitive lipoblastoma with a paucity of lipoblasts and a prominent network of vessels, which explains its misleading appearance on MRI scan. It was distinctly different in appearance from subcutaneous fat, and its enhancement with gadolinium injection suggested a vascular, not a lipomatous tumor. Its lack of a lobular architecture was not typical of hemangiomas, but neither was it typical of lipoblastomas, which also tend to be lobular. Our experience underscores the fact that CT and MRI studies cannot provide a tissue diagnosis and can only suggest likely diagnoses.

On gross pathology, most tumors were lobular, encapsulated, and soft. Cut surface revealed tumor colors described as light yellow, tan, white, pink, and red. Fibrous connective septae divide the lipoblastoma into numerous lobules.^10,11 Microscopically, the tumors contain predominantly adipocytes in various stages of differentiation. Mature adipocytes are more prevalent in the center of the tumor lobule. No atypical mitotic figures are present.^10,11 Immunohistochemical and ultrastructural study suggest that lipoblastoma is most closely related to developing white fat.^426-28 Again, our patient was atypical in that there was an absence of lobular architecture, no mature fat cells, and a paucity of lipoblasts, consistent with the very primitive nature of the tumor.

Karyotypic abnormalities characteristic of lipoblastomas have been identified. The genetic anomalies involve the long arm of chromosome 8 (8q)^29-33. In at least 1 case report, the region involved included known oncogene loci for MYC and MOS.³¹ These chromosomal abnormalities appear to be specific for lipoblastomas and differ from previously identified chromosomal abnormalities associated with lipomas and liposarcomas.^29,30,31,34 Cytogenetic study in the future may help distinguish lipoblastomas from liposarcomas, which is an otherwise difficult histologic distinction.^{9,11,16,29,35} Additionally, these chromosomal findings suggest cytological clonality and a neoplastic cause for lipoblastomas.³⁰

Definitive therapy is complete surgical excision of the lipoblastoma. Recurrence rates have been reported to range from 9% to 22%.^10,11,16 One recurrence is reported to have appeared as long as 10 years after the initial tumor was resected.¹⁶ Most authors attribute any recurrences to incomplete initial excision of the tumor.^15,16 No metastasis have ever been reported.

	CONCLUSION

Top Abstract Introduction Discussion Conclusion References

In summary, lipoblastoma is a benign tumor of immature fat cells found almost exclusively in the pediatric population. Lipoblastomas are more common in males and children <5 years old. Clinically, the tumor may mimic numerous other lesions. The tumor most commonly presents as an asymptomatic, rapidly enlarging, soft, lobular mass located on the upper or lower extremities. Preoperative diagnosis with imaging studies is difficult, and in this case the highly vascular nature of the lesion was felt to be consistent with a hemangioma. In retrospect, the highly uniform nature of the lipoblastoma did not demonstrate the usual lobular architecture of a hemangioma. Fine-needle aspiration may provide cytological material for definitive diagnosis, and if inadequate, a formal biopsy may be necessary. Complete surgical excision is the definitive treatment for lipoblastoma.

	ACKNOWLEDGMENT

We thank Cheryl M. Coffin, MD, Department of Pathology, Primary Children's Medical Center, Salt Lake City, Utah, for her review of the pathology and for her helpful suggestions.

Clifford S. Perlis^*, Margaret H. Collins, MD, Paul J. Honig, MD^§, and David W. Low, MD^¶
* University of Pennsylvania School of Medicine
 Department of Pathology
^§ Division of General Pediatrics-Dermatology Section
^¶ Division of Plastic Surgery
Children's Hospital of Philadelphia
Philadelphia, PA 19104

	FOOTNOTES

Received for publication Feb 8, 1999; accepted Jun 8, 1999.

Address correspondence to David W. Low, MD, Division of Plastic Surgery, Children's Hospital of Philadelphia, 34th and Civic Center Blvd, Philadelphia, PA 19104. E-mail: low{at}mail.med.upenn.edu

	ABBREVIATIONS

MRI, magnetic resonance imaging; CT, computed tomography.

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Top Abstract Introduction Discussion Conclusion References

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