A case of unusual histology of infantile lipoblastoma confirmed by PLAG1 rearrangement
© Shinkai et al.; licensee Springer. 2015
Received: 25 February 2015
Accepted: 5 May 2015
Published: 16 May 2015
Lipoblastoma, a relatively rare benign adipose neoplasm, predominantly affects children younger than 3 years of age. We herein report the case of a 7-month-old girl with an unusual myxomatous histology of lipoblastoma. A rapidly growing mass was detected in the subcutaneous area of the left buttock. Histologically, the tumor consisted of abundant myxoid stroma exhibiting cellular atypia and a high mitotic activity. Although the histological findings were unusual, the tumor was diagnosed as a lipoblastoma according to both PLAG1 immunohistochemistry and the presence of PLAG1 rearrangement on fluorescence in situ hybridization.
Lipoblastoma is a specific and benign adipose neoplasm that consists of embryonic adipose tissue with the capacity for differentiation [1–3]. In general, lipoblastoma occurs most often in infancy and early childhood; nearly 90 % of cases are diagnosed before 3 years of age and 40 % are diagnosed in the first year of life [2, 3]. Adipose tumors are less common in children, accounting for only 6 % of pediatric soft tissue lesions. Lipoblastoma is a relatively rare tumor, estimated to comprise less than 19–30 % of all pediatric adipose masses [1, 2]. Lipoblastoma has an excellent prognosis, and complete local resection is required for treatment. Although this tumor is benign, with no potential for metastasis, it has a tendency to exhibit local recurrence [2, 4–6]. Recently, PLAG1 rearrangement was identified to be a characteristic cytogenetic feature of lipoblastoma [7–14].
We experienced the case of a 7-month-old girl with a subcutaneous tumor demonstrating an unusual adipose and myxoid histology. As the tumor was suspected to be a lipoblastoma, we performed PLAG1 immunohistochemical staining (IHC) and an assessment for PLAG1 rearrangement using fluorescence in situ hybridization (FISH) to confirm the diagnosis. Positive results for the tumor led to the exact diagnosis.
Lipoblastoma is a benign lipomatous tumor that is usually detected in infancy. Indeed, approximately 90 % of these tumors are diagnosed in patients 0–3 years of age [1–4]. This lesion is slightly more predominant in males and occurs primarily in the extremities and trunk region, usually detected as a rapidly growing painless mass [1–6]. Although the prognosis of lipoblastoma is excellent due to its benign status with no potential for metastasis, wide and complete surgical resection is required for treatment. The rate of local recurrence varies between 9 % and 25 %, often attributed to incomplete resection, although recurrent tissue can be successfully re-excised [2, 4–6].
The imaging appearance of lipoblastoma depends on the proportion of fat relative to the amount of myxoid tissue. MRI is an important diagnostic tool for detecting lipoblastoma, and the features of this tumor often correspond to the pathological findings [4–6]. In general, MRI features can be summarized as including well-defined lobulated fatty masses with mostly high signal intensity on T1- and T2-weighted images [5, 6, 15, 16]. The fat suppression technique is helpful for confirming the existence of fatty components [5, 15]. The presence of fat is the predominant feature of lipoblastoma in many patients, particularly older children. In contrast, the detection of nonlipomatous myxoid components with only small elements of fat is a characteristic feature in infants [4, 5]. The myxoid components display enhanced contrast on MRI due to their rich capillary networks [4, 6].
Histologically, lipoblastoma is composed of small lobules containing mature and immature adipose tissue separated by connective tissue septa of varying thickness [1–3]. The adipocytes show a wide spectrum of maturation, with primitive stellate or spindled mesenchymal cells, multivacuolated lipoblasts, small signet ring lipoblasts, and mature adipocytes [1–4, 15, 16]. The observation of a myxoid stroma is more prominent in infants. Furthermore, a plexiform pattern of blood vessels is usually seen in the myxoid stroma in association with primitive mesenchymal cells [2, 15], and the tumor cells display the absence of significant nuclear atypia and pleomorphism with an extremely low mitotic rate [2, 3, 15]. Although an important differential diagnosis for lipoblastoma is myxoid liposarcoma, it is difficult to distinguish between these tumors due to the radiological and histological similarities of these lesions [1–4, 15, 16]. Lipoblastoma usually affects children younger than 10 years of age and predominantly those younger than 3 years of age. On the other hand, liposarcoma often occurs in the third through sixth decades of life. Liposarcoma is extraordinarily rare in patients below 10 years of age [2, 4, 6].
Given the age of our patient, a diagnosis of liposarcoma was unlikely. Furthermore, the histological findings were unusual for lipoblastoma, including the presence of large myxoid components, cellular atypia, and nuclear hyperchromasia with a high mitotic count. Therefore, it was necessary to further examine the tumor using immunohistochemistry and cytogenetic studies. Consequently, the tumor cells were found to be positive for PLAG1 IHC and demonstrated PLAG1 rearrangement on FISH. Based on these results, we finally diagnosed the tumor as a lipoblastoma.
Cytogenetic karyotyping of lipoblastoma is characterized by the rearrangement of 8q11-13. PLAG1 is a proto-oncogene located on chromosome 8q12 [7–14]. Approximately, 70 % of lipoblastomas exhibit PLAG1 rearrangement located at 8q12, which can result in the transcriptional upregulation of this oncogene via promoter swapping [9, 10]. In addition, lipoblastoma demonstrates polysomy for chromosome 8 with or without PLAG1 rearrangement [9, 10, 12, 13]. The detection of PLAG1 rearrangement is used to distinguish lipoblastoma from other lipomatous tumors as well as liposarcoma [2, 3, 7, 8, 10, 13, 14].
Regarding the results of IHC for PLAG1 reported in a previous study , 8 of 10 cases of lipoblastoma were found to involve a positive expression on PLAG1 immunohistochemistry, whereas all 12 cases of liposarcoma displayed a negative PLAG1 expression. PLAG1 immunohistochemistry is also a very simple and useful diagnostic tool for distinguishing lipoblastoma from liposarcoma.
The sensitivity of PLAG1 rearrangement has been reported 77 %, and the specificity of PLAG1 rearrangement is 98 % . Although FISH analysis of PLAG1 rearrangement in lipoblastoma does not show high sensitivity, combined analysis of both IHC and cytogenetic study may increase the diagnostic accuracy of lipoblastoma with unusual histology.
Lipoblastoma is a benign lipomatous tumor with an excellent prognosis. However, in some cases involving an atypical histology, analyses of the PLAG1 expression using both immunohistochemical and cytogenetic studies are needed to obtain an appropriate diagnosis.
Written informed consent was obtained from the patient’s parents for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
The authors would like to express their sincere appreciation to Atsuji Matsuyama M.D., Department of Pathology and Oncology, School of Medicine, University of Occupational and Environmental Health for performing the PLAG1 immunohistochemistry workup.
- Coffin CM, Dehner LP. The soft tissues. In: Stocker JT, Dehner LP, editors. Pediatric pathology. 2nd ed. Philadelphia: Lippincott Williams & Wilkins; 2001. p. 1163–93.Google Scholar
- Coffin CM, Alaggio R. Adipose and myxoid tumor of childhood and adolescence. Pediatr Dev Pathol. 2012;15:239–54. doi:10.2350/10-05-0836-PB.1.View ArticlePubMedGoogle Scholar
- Coffin CM, Lowichik A, Putnam A. Lipoblastoma (LPB): a clinicopathologic and immunohistochemical analysis of 59 cases. Am J Surg Pathol. 2009;33:1705–12.View ArticlePubMedGoogle Scholar
- Murphey MD, Carroll JF, Flemming DJ, Pope TL, Gannon FH, Kransdorf MJ. From the archive from AFIP: benign musculoskeletal lipomatous lesions. Radiographics. 2004;24:1433–66. doi:10.1148/rg.245045120.View ArticlePubMedGoogle Scholar
- Navarro OM, Laffan EE, Ngan BY. Pediatric soft-tissue tumors and pseudotumors: MR imaging features with pathologic correlation. Radiographics. 2009;29:887–906. doi:10.1148/rg.293085168.View ArticlePubMedGoogle Scholar
- Bruyeer E, Lemmerling M, Poorten VV, Sciot R, Hermans R. Pediatric lipoblastoma in the head and neck: three cases and review of literature. Cancer Imaging. 2012;12:484–7. doi:10.1102/1470-7330.2012.0037.View ArticlePubMed CentralPubMedGoogle Scholar
- Hibbard MK, Kozakewich HP, Cin PD, Sciot R, Tan X, Xiao S, et al. PLAG1 fusion oncogenes in lipoblastoma. Cancer Res. 2000;60:4869–72.PubMedGoogle Scholar
- Brandal P, Bjerkehagen B, Heim S. Rearrangement of chromosomal region 8q11-13 in lipomatous tumours: correlation with lipoblastoma morphology. J Pathol. 2006;208:388–94. doi:10.1002/path.1879.View ArticlePubMedGoogle Scholar
- Gisselsson D, Hibbard MK, Cin PD, Sciot R, Hsi BL, Kozakewich HP, et al. PLAG1 alterations in lipoblastoma. Am J Pathol. 2001;159:955–62. doi:10.1016/S0002-9440(10)61771-3.Google Scholar
- Somerhausen NSA, Coindre JM, Debiec-Rychter M, Delplace J, Sciot R. Lipoblastoma in adolescents and young adults: report of six cases with FISH analysis. Histopathology. 2008;52:294–8. doi:10.1111/j.1365-2559.2007.02954.x.View ArticleGoogle Scholar
- Bartuma H, Domanski HA, Von Steyern FV, Kullendorff CM, Mandahl N, Mertens F. Cytogenetic and molecular cytogenetic findings in lipoblastoma. Cancer Genet Cytogenet. 2008;183:60–3. doi:10.1016/j.cancergencyto.2008.01.017.View ArticlePubMedGoogle Scholar
- Amra NK, Amr SS. Mediastinal lipoblastomatosis: report of a case with complex karyotype and review of the literature. Pediatr Dev Pathol. 2009;12:469–74. doi:10.2350/08-09-0525.1.View ArticlePubMedGoogle Scholar
- Choi J, Dal Soglio DB, Fortier A, Fetni R, Mathonnet G, Laillier M, et al. Diagnostic utility of molecular and cytogenetic analysis in lipoblastoma: a study of two cases and review of the literature. Histopathology. 2014;64:731–40. doi:10.1111/his.12317.View ArticlePubMedGoogle Scholar
- Brandal P, Bjerkehagen B, Heim S. Rearrangement of chromosomal region 8q11-13 in lipomatous tumors: correlation with lipoblastoma morphology. J Pathol. 2006; 388–394. doi:10.1002/psth.1879.Google Scholar
- Moholkar S, Sebire NJ, Roebuck DJ. Radiological-pathological correlation in lipoblastoma and lipoblastomatosis. Pediatr Radiol. 2006;36:851–6. doi:10.1007/s00247-006-0175-5.View ArticlePubMedGoogle Scholar
- Nagano A, Ohno T, Nishimoto Y, Hirose Y, Miyake S, Shimizu K. Lipoblastoma mimicking myxoid liposarcoma: a case report and literature review. Tohoku J Exp Med. 2011;223:75–8. doi:10.1620/tjem.223.75.View ArticlePubMedGoogle Scholar
- Matsuyama A, Hisaoka M, Hashimoto H. PLAG1 expression in mesenchymal tumors: an immunohistochemical study with special emphasis on the pathogenetical distinction between soft tissue myoepithelioma and pleomorphic adenoma of the salivary gland. Pathol Int. 2012;62:1–7. doi:10.1111/j1440-1827.2011.02740.x.View ArticlePubMedGoogle Scholar
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.