DIFFUSE LIPOBLASTOMATOSIS - California Tumor Tissue …：加利福尼亚肿瘤组织弥漫性脂肪母细胞瘤病…

DIFFUSE LIPOBLASTOMATOSIS - California Tumor Tissue …：加利福尼亚肿瘤组织弥漫性脂肪母细胞瘤病… “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 1children, ranging from 5 days to 6 years. A slight female predominance has been observed . Maturing lipoblastomas are sometimes encountered in older children, and, less often, in 2-8teenagers 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, 1-4, 9-13mesentery, inguinal canal, peritoneal cavity, and the lung can be involved . The tumors may arise in the subcutis or deep soft tissue, and range from 3 to 5 cm, however some cases have 2been reported to be as large as 21cm . 1 CTTR’s Case of the Month 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 14skeletal muscle, retroperitoneum, or mesentry . The diffuse form can be difficult to excise 2,15completely, contributing to the average local recurrence rate of 14% . Lipoblastomatosis may occur in association with hemangiomas, other soft tissue lesions, intestinal neuronal dysplasia 2,15,16and/or macrodactyly . 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 reas. a 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. casionally, the cells are sufficiently multivacuolated to resemble brown fat cells. The cells lie Oc 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 17contain entrapped muscle fibers. Hypertrophy of subjacent bone has been reported . Electron microscopic examination has demonstrated a mixed population of cells with features of white fat 13,18closely associated with a plexiform vascular network . Recently, lipoblastomas have been reported to exhibit karyotypic abnormalities involving chromosome 8, while lacking the 19-24translocation associated with myxoid liposarcoma . 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 25legitimately raise the question of myxoid or other liposarcomas . 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 3tumors . 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 2 CTTR’s Case of the Month September, 2004 26resonance imaging to assess extent and to plan reconstruction if necessary . Metastasis of this tumor has not been observed. References: 1. Hicks J, Dilley A, Patel D, et al. Lipoblastoma and lipoblastomatosis in infancy and childhood: histopathologic, ultrastructure, and cytogenetic features. Ultrastruct Patho. 2001, 25(4):321-333. 2. Collins MH, Chatten J. Lipoblastoma/lipoblastomatosis: a clinicopathologic study of 25 tumors. Am J Surg Pathol 1997, 21:1131-1137. 3. Mentzel T, Calonje E, Fletcher CD. Lipoblastoma and lipoblastomatosis. A clinicopathologic study of 14 cases. Histopathology 1993, 23:527-533. 4. Chung EB, Enzinger FM. Benign lipoblastomatosis: an analysis of 35 cases. Cancer 1973;32:482-492. 5. Coffin CM. Lipoblastoma: an embryonal tumor of soft tissue related to organogenesis. Semin Diagn Pathol 1994;11:98-103. 6. Rubin BP, Dal Cin P. The genetics of lipomatous tumors. Semin Diagn Pathol 2001, 18:286-293. 7. Stringel G, Shandling B, Mancer K, Ein SH. Lipoblastoma in infants and children. J Pediatr Surg 1982;17:277- 280. 8. Vellios F, Baez MF, Schumacher HB. Lipoblastomatosis. A tumor of fetal fat different from hibernoma. Am J Pathol 1958,34:1149-1155. 9. Zanetti G. Benign lipoblastoma: first case report of a mesentric origin. Tumori. 1998 Aug31;74(4):495-498. 10. Arda IS, et al. A case of benign intrascrotal lipoblastoma clinically mimicking testicular torsion and review of the literature. J Pediatr Surg 1993;28(2):259-261. 11. Schulman H, et al. Case report: mesenteric lipoblastoma. Clin Radiol 1992;46:57-58. 12. Hoehn JG, et al. Benign lipoblastomatosis: report of a case involving the face and neck. Plast Reconstr Surg 1984;73:455-458. 13. Greco MA, Garcia RL, Vuletin JC. Benign lipoblastomatosis: ultrastructure and histiogenesis. Cancer 1980;45:511-515. 14. Merton DA, et al. Lipoblastoma: diagnosis with computer tomography, and color Doppler imaging. J Ultrasound Med 1992;11:549-552. 15. Huang CC, Ko SF, Chuang JH, et al. Lipoblastomatosis combined with intestinal neuronal dysplasia. Arch Pathol Lab Med 1998;122:191-193. 16. Colot G et al. Macrodactyly associated with benign lipoblastomatosis. Ann Chir Main. 1984;3(3):262-265. 17. De Rosa et al. Congenital infiltrating lipomatosis of the face: report of cases and review of the literature. J Oral Maxillofac Surg. 1998 Oct;45(10):879-883. 18. Bolen JW, Thorning D. Benign lipoblastoma and myxoid liposarcoma: a comparative light- and electron- microscopic study. Am J Surg Pathol 1980;4:163-174. 19. Miller GG, Yancher NL, Magee JF, et al. Lipoblastoma and liposarcoma in children: an analysis of 9 cases and a review of the literature. Can J Surg 1998;41:455-458. 20. Miller GG, Yancher NL, Magee JF, et al. Tumor karyotype differentiates lipoblastoma from liposarcoma. J Pediatr Surg 1997;32:1771-1772. 21. Posey Y, Valdivia E, Persons DL, et al. Lipoblastoma presenting as a mesenteric mass in an infant. J Pediatr Hematol Oncol 1998;20:580-582. 22. Fletcher CD, et al. Correlation between clinicopathologic features and karyotype in lipomatous tumors. Am J Pathol 1996;148:623-630. 23. Fletcher JA, Kozakewich HP, Schoenberg ML, Morton CC. Cytogenetic findings in pediatric adipose tumors: consistent rearrangement of chromosome 8 in lipoblastoma. 24. Ohjimi Y, et al. A case of lipoblastoma with t(3;8)(q12;q11.2). Cancer Gent Cytogenet 1992;62:103-105. 25. Castleberry RP, et al. Childhood liposarcoma. Report of a case and review of the literature. Cancer 1984;54:579-584. 26. Dilley A, et al. Lipoblastoma: pathophysiology and surgical management. J Pediatr Surg. 2001 Jan;36(1):229- 231. 3 CTTR’s Case of the Month September, 2004