Download diffuse lipoblastomatosis - California Tumor Tissue Registry

“A three month-old boy with multiple masses”
California Tumor Tissue Registry
Case of the Month
September, 2004
A three month-old boy presented with multiple, rapidly
enlarging subcutaneous masses ranging from 1 to 6 cm. The nodules were palpable in the
superficial tissues of the scalp, neck, chest, breast, back, lumbar, inguinal, and scrotal regions as
well as on the upper and lower extremities. Initial biopsy of a thigh mass was felt to be
lipomatous. The patient developed coryza, progressing to respiratory distress. He became
hypoxic and was put on a respirator. Pseudomonas was cultured from the lungs, and despite
multiple antibiotics, O2, and bronchodilators, he progressed to sepsis, and death.
The nodules were generally solid, firm, and white to yellow tan and freely-moveable (Figs. 1-4).
In additional to the palpable tumors, an autopsy showed systemic involvement of the cerebellum
(Fig. 5), heart (Fig.6), liver, mesentry, and kidneys.
Microscopic sections from all masses were similar, showing a hypercellular proliferation of
mature and immature fat cells with prominent vacuolization (Fig. 7). Occasional lipoblasts were
present (not illustrated). The supporting stroma was mildly myxoid and exhibited a striking fine
plexiform vascular network (Fig. 8). Although the tumors were hypercellular, cellular
pleomorphism and mitotic activity were absent.
DIAGNOSIS
Multicentric Diffuse Lipoblastomatosis
Sajjad P Syed, MD*, Myrna G Duldualo-Milan, MD, Donald R Chase, MD*
*Loma Linda University Medical Center, California, U.S.A.
Manila Sanitarium and Hospital, Pasay City, Philippines.
Lipoblastoma/lipoblastomatosis is a relatively rare benign disorder that recapitulates the early
developmental stages of white fat. It has been described almost exclusively in infants and
children, ranging from 5 days to 6 years. A slight female predominance has been observed 1.
Maturing lipoblastomas are sometimes encountered in older children, and, less often, in
teenagers 2-8 and may assume the appearance of fibrolipoma. The tumors are usually painless,
and involve the upper and lower extremities, however the trunk, head, neck, retroperitoneum,
mesentery, inguinal canal, peritoneal cavity, and the lung can be involved 1-4, 9-13. The tumors
may arise in the subcutis or deep soft tissue, and range from 3 to 5 cm, however some cases have
been reported to be as large as 21cm 2.
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September, 2004
The disease exists in two forms: the more common being the solitary subcutaneous and
circumscribed lipoblastoma, sometimes designated as embryonal or fetal lipoma. It also occurs
as the multicentric, deep-seated and ill-defined, diffuse “lipoblastomatosis” which arises in
skeletal muscle, retroperitoneum, or mesentry 14. The diffuse form can be difficult to excise
completely, contributing to the average local recurrence rate of 14% 2,15. Lipoblastomatosis may
occur in association with hemangiomas, other soft tissue lesions, intestinal neuronal dysplasia
and/or macrodactyly 2,15,16. Grossly, the tumor is lobulated, soft, and encapsulated, and it has a
yellow or creamy white cut surface, paler than an ordinary lipoma, with mottled gray myxoid
areas.
The characteristic microscopic pattern is of multiple, well defined, paucicellular lobules formed
by small signet ring adipocytes and uniform stellate and spindled cells with scant cytoplasm.
Occasionally, the cells are sufficiently multivacuolated to resemble brown fat cells. The cells lie
in a stroma which is often myxoid with a rich delicate plexiform vascular network. The amount
of myxoid matrix is generally inversely proportional to the degree of fatty maturation. Mature
adipose tissue may predominate in the center of the lobule, with less mature foci at the periphery.
Mitotic figures are sometimes apparent but never atypical. The lobules are separated by
connective tissue septa that are usually narrow but may be quite wide. The nonsubcutaneous,
more diffuse form has identical morphologic features except for a less well-defined lobular
pattern. Sometimes the lobular pattern may be lost altogether. Deeply-seated lesions frequently
contain entrapped muscle fibers. Hypertrophy of subjacent bone has been reported 17. Electron
microscopic examination has demonstrated a mixed population of cells with features of white fat
closely associated with a plexiform vascular network 13,18. Recently, lipoblastomas have been
reported to exhibit karyotypic abnormalities involving chromosome 8, while lacking the
translocation associated with myxoid liposarcoma 19-24.
The major differential diagnosis is myxoid liposarcoma, especially for those lipoblastomas with
cellular and vascular myxoid areas. Although the diagnosis of myxoid liposarcoma in infants and
children in some reports must be questioned, there are some myxoid fatty tumors which
legitimately raise the question of myxoid or other liposarcomas 25. The low cellularity, lobular
arrangement, encapsulation and lack of invasion (with the exception of the diffuse form), and the
younger age group with predominant subcutaneous location support a diagnosis of lipoblastoma.
However, in some cases, the histologic distinction may be problematic in the absence of
lobulation, fibrous septa, and the central pattern of maturation. Molecular studies may be
indicated to differentiate between the two entities. Microcystic spaces can be found in both
tumors 3.
Maturing lipoblastoma is phenotypically similar to fibrolipoma, but myxoid foci and lipoblasts
are usually seen in a lipoblastoma, and not in a fibrolipoma.
When recurrent, lipoblastoma/lipoblastomatosis may have undergone maturation, and appear
almost entirely to be of adult fat cells.
Complete surgical excision is the preferred therapy, and because recurrences are not uncommon,
followup of at least two years is suggested. Recurrent lesions are best imaged with magnetic
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resonance imaging to assess extent and to plan reconstruction if necessary 26. Metastasis of this
tumor has not been observed.
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