Low-grade Osteosarcomatous Dedifferentiation of an Atypical Lipomatous Tumor in a Pediatric Patient

Atypical and malignant lipomatous tumors are infrequent in the pediatric population. Within this uncommon cohort, the morphologically and genetically related spectrum of atypical lipomatous tumor/well-differentiated liposarcoma/dedifferentiated liposarcoma (ALT/WDL/DDLS) is markedly rare. Their shared characteristic molecular aberration is a genomic amplicon of a region of chromosome 12q, including the oncogenes MDM2 and CDK4. We present an unusual case of a pediatric patient with an ALT, with recurrence after 2 years in the form of a bone-forming mass, radiologically and pathologically mimicking parosteal osteosarcoma, a tumor also molecularly characterized by amplification of MDM2 and CDK4. However, with ample histologic sampling, a single focus of lipogenic differentiation was identified, thus representing the first near complete low-grade osteosarcomatous dedififferentation reported within ALT/WDL/DDLS and the first ever in pediatric patient. The case serves a reminder of a diagnosis differential and pitfalls within MDM2-amplified tumors.

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“Fat-Rich” (Spindle Cell-Poor) Variant of Atypical Spindle Cell/Pleomorphic Lipomatous Tumor: Striking Mimic of “Classical” Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma

International Journal of Surgical Pathology ◽

10.1177/1066896919846561 ◽

2019 ◽

Vol 27 (8) ◽

pp. 868-871 ◽

Cited By ~ 4

Author(s):

David Creytens ◽

Thomas Mentzel ◽

Liesbeth Ferdinande ◽

Joost van Gorp ◽

Jo Van Dorpe ◽

...

Keyword(s):

Spindle Cell ◽

Molecular Genetic ◽

Low Grade ◽

Tissue Mass ◽

Atypical Lipomatous Tumor ◽

Lipomatous Tumor ◽

Multinucleated Cells ◽

Pericytic Mimicry ◽

Well Differentiated ◽

The Right

We report the case of a “fat-rich” (spindle cell-poor) variant of an atypical spindle cell/pleomorphic lipomatous tumor in a 63-year-old female patient presenting with a firm, painless soft tissue mass on the right hip. Atypical spindle cell/pleomorphic lipomatous tumor is a very recently described low-grade adipocytic neoplasm, which occurs predominantly in adults with a predilection for the limbs and limb girdles. In the present case, the diagnosis of an atypical spindle cell/pleomorphic lipomatous tumor was challenging because the tumor was almost exclusively composed of an atypical adipocytic component (resembling “classical” atypical lipomatous tumor/well-differentiated tumor) with only very focal presence of the diagnostic atypical morphologic features (atypical spindle-shaped cells, floret-like multinucleated cells, and “bizarre” pleomorphic [multinucleated] cells). The possibility of a “classical” atypical lipomatous tumor/well-differentiated liposarcoma was ruled out by immunohistochemistry (lack of MDM2 expression and loss of Rb expression) and molecular genetic testing (no amplification of MDM2 and presence of monoallelic deletion of RB1). Another interesting morphologic observation in this case was the striking perivascular location of the atypical spindle/pleomorphic cells in some areas (so-called “pericytic mimicry”). To our knowledge, pericytic mimicry has not been reported in the setting of an atypical spindle cell/pleomorphic lipomatous tumor.

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MDM2 Amplified Sarcomas: A Literature Review

Diagnostics ◽

10.3390/diagnostics11030496 ◽

2021 ◽

Vol 11 (3) ◽

pp. 496

Author(s):

Raf Sciot

Keyword(s):

Suppressor Gene ◽

Negative Regulator ◽

Low Grade ◽

P53 Mutations ◽

Lipomatous Tumor ◽

Double Minute ◽

Genetic Features ◽

Murine Double Minute ◽

Well Differentiated ◽

Mdm2 Amplification

Murine Double Minute Clone 2, located at 12q15, is an oncogene that codes for an oncoprotein of which the association with p53 was discovered 30 years ago. The most important function of MDM2 is to control p53 activity; it is in fact the best documented negative regulator of p53. Mutations of the tumor suppressor gene p53 represent the most frequent genetic change in human cancers. By overexpressing MDM2, cancer cells have another means to block p53. The sarcomas in which MDM2 amplification is a hallmark are well-differentiated liposarcoma/atypical lipomatous tumor, dedifferentiated liposarcoma, intimal sarcoma, and low-grade osteosarcoma. The purpose of this review is to summarize the typical clinical, histopathological, immunohistochemical, and genetic features of these tumors.

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LGG-28. NOVEL BRAF INTRAGENIC DELETION IN A GLIOMA: A CASE REPORT OF A PEDIATRIC PATIENT

Neuro-Oncology ◽

10.1093/neuonc/noaa222.410 ◽

2020 ◽

Vol 22 (Supplement_3) ◽

pp. iii371-iii372

Author(s):

Valerie Cruz Flores ◽

Maxine Sutcliffe ◽

Thomas Geller ◽

Ignacio Gonzalez Gomez ◽

Stephanie Smith ◽

...

Keyword(s):

Pediatric Patient ◽

Pilocytic Astrocytoma ◽

Pediatric Population ◽

Binding Pocket ◽

Genetic Alterations ◽

Low Grade ◽

Braf Gene ◽

Intragenic Deletion ◽

Whole Genome Microarray ◽

Intragenic Deletions

Abstract BACKGROUND Numerous variant BRAF genetic alterations have been associated with malignancies. BRAF activating fusions/mutations are frequently present in low grade gliomas. BRAF intragenic deletions have been reported in melanoma, but have not previously been reported in gliomas. OBJECTIVE To report a BRAF intragenic deletion in a pediatric patient with recurrent low-grade glioma. RESULTS A 3-year-old female underwent a complete resection of a posterior fossa pilocytic astrocytoma. She had recurrences at age 4, and then at age 9; pathology was consistent with pilocytic astrocytoma. Microarray analysis on sample from the first recurrence showed one region of loss encompassing 86 Kbp within the BRAF gene. The deletion breakpoints are within intron 1 and 9, resulting in loss of exons 2 through 9, inclusive. This has been previously described melanoma, but appears to be a novel finding in glioma. It is hypothesized that, since the loss retains the kinase and ATP binding pocket domains but deletes the N-terminal conserved region 1 and 2 (CR1, CR2) of the BRAF gene, it is likely functionally similar to the loss and activation resulting from the more usually described KIAA1549 and BRAF gene fusion. CONCLUSION This is the first BRAF intragenic deletion involving exons 2–9 reported in a glioma. Although 86kbp is small using whole genome microarray technology, it is large using sequencing strategies, and a targeted sequencing approach to investigate the BRAF gene would not readily identify this deletion. It is speculated that the deletion may be under ascertained in the pediatric population.

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Orbital Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma Masquerading as Pleomorphic Lipoma

Ophthalmic Plastic and Reconstructive Surgery ◽

10.1097/iop.0000000000001378 ◽

2019 ◽

Vol 35 (3) ◽

pp. e76-e80 ◽

Cited By ~ 1

Author(s):

Kyle McKey ◽

Paul J. L. Zhang ◽

Carol L. Shields ◽

Sara E. Lally ◽

Ralph C. Eagle ◽

...

Keyword(s):

Atypical Lipomatous Tumor ◽

Lipomatous Tumor ◽

Pleomorphic Lipoma ◽

Well Differentiated

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Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma of the Gingiva: A Case Report and Review of Literature

Journal of Oral and Maxillofacial Surgery ◽

10.1016/j.joms.2013.06.222 ◽

2014 ◽

Vol 72 (2) ◽

pp. 431-439 ◽

Cited By ~ 12

Author(s):

Young Bin Kim ◽

Dae Ho Leem ◽

Jin A. Baek ◽

Seung O. Ko

Keyword(s):

Case Report ◽

Review Of Literature ◽

Atypical Lipomatous Tumor ◽

Lipomatous Tumor ◽

Well Differentiated

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A Retrospective Study of Superficial Type Atypical Lipomatous Tumor

Frontiers in Medicine ◽

10.3389/fmed.2020.609515 ◽

2020 ◽

Vol 7 ◽

Author(s):

Emi Mashima ◽

Yu Sawada ◽

Natsuko Saito-Sasaki ◽

Kayo Yamamoto ◽

Shun Ohmori ◽

...

Keyword(s):

Surgical Resection ◽

Tumor Size ◽

Clinical Characteristics ◽

Clinical Manifestations ◽

Tumor Location ◽

Atypical Lipomatous Tumor ◽

Lipomatous Tumor ◽

Physical Examinations ◽

Superficial Type ◽

Well Differentiated

Atypical lipomatous tumor (ALT) has been defined as a well-differentiated liposarcoma exhibiting a higher frequency of a local recurrence after surgical resection. ALT is mainly classified into deep type and superficial type. Compared with deep type ALT, superficial type ALT is rarely observed. One of the most important issues is that little has been known about superficial type ALT and it is not easy to predict the presence of superficial type ALT before surgical resection. To clarify the clinical manifestations of superficial type ALT, we examined 15 cases with superficial type ALT and 118 cases with benign lipoma, and analyzed their differences in clinical characteristics and the findings of MRI test. In clinical characteristics, the tumor size of superficial type ALT was significantly greater than that of benign lipoma, and superficial type ALT showed a significantly higher frequency of the tumor size of more than 4 cm. Superficial type ALT exhibited poor tumor mobility and hardness with elastic soft. In addition, a significantly higher frequency of tumor location of superficial type ALT was observed in extremities. Among tumor sites at the trunk, buttocks, and shoulder were high frequent location in superficial type ALT. In an MRI examination, superficial type ALT exhibited a significantly higher frequency of the septal structures compared with benign lipoma. The combinations of clinical characteristics, including physical examinations, MRI, and histological examinations, are helpful for the diagnosis of superficial type ALT.

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