Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma With Features Mimicking Spindle Cell Lipoma

Atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL) and spindle cell lipoma are lipomatous tumors with distinct clinical, molecular, and prognostic features. Although histological and immunophenotypic features can overlap between ALT/WDL and spindle cell lipoma, the oncogenesis and clinical behavior are markedly different. In borderline cases, molecular analysis for MDM2 or CDK4 amplification can aid in distinguishing ALT/WDL from spindle cell lipoma. Although dedifferentiated liposarcoma has been reported to harbor both MDM2 amplification and loss of the RB1 region, we are not aware of a reported RB1 loss in well-differentiated ALT/WDL. In this article, we present a 69-year-old woman with a lipomatous tumor in the gluteal region that histologically, immunohistochemically, and molecularly mimicked spindle cell lipoma (with positive immunohistochemical staining for CD34 and loss of the RB1 gene region), yet harbored amplification of MDM2 and CDK4 confirmed by fluorescence in situ hybridization, supporting classification as ALT/WDL. This case strengthens the argument that in atypical clinical contexts, molecular studies for MDM2/CDK4 should be considered in tumors resembling spindle cell lipoma.

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Atypical Spindle Cell Lipomatous Lesion Resected From Patient With History of CLL

The American Surgeon ◽

10.1177/0003134820933601 ◽

2020 ◽

Vol 86 (9) ◽

pp. 1208-1211

Author(s):

Chase J. Wehrle ◽

J. Will Daigle ◽

Asad Ullah ◽

Suash Sharma ◽

Edmond F. Ritter ◽

...

Keyword(s):

Spindle Cell ◽

Lymphocytic Leukemia ◽

Left Shoulder ◽

Spindle Cell Lipoma ◽

Atypical Lipomatous Tumor ◽

Lipomatous Tumor ◽

Adipocytic Tumors ◽

History Of ◽

Pathologic Analysis ◽

Mdm2 Amplification

Atypical spindle cell lipomatous neoplasm, also known as well-differentiated spindle cell liposarcoma, represents a newly discovered entity of adipocytic tumors. Recent research has shown this tumor variant to be more related to spindle cell lipoma, rather than the originally hypothesized atypical lipomatous tumor spectrum. Here we present a case of a 58-year-old man with a history of chronic lymphocytic leukemia with an enlarging mass on the posterior left shoulder, initially hypothesized to be a benign lipoma. However, magnetic resonance imaging showed a large, multiseptated, heterogeneous mass concerning for soft tissue sarcoma. After resection, pathologic analysis showed cells closely resembling spindle cell lipoma, with additional cellular and fascicular zones containing lipoblasts and mitotic figures. Molecular analysis showed no MDM2 amplification. This lack of amplification indicates this tumor is distinctly different from an atypical lipomatous tumor, which characteristically displays MDM2 amplification. However, tumor expression of RB1 was normal. The majority of atypical spindle cell lipomatous neoplasms are associated with RB1 deletions. We conclude that we have a unique example of an atypical spindle cell lipomatous tumor.

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Spindle Cell Lipoma with Ossification Mimicking Atypical Lipomatous Tumor/Well-Differentiated Liposarcoma: A Case Report

International Journal of Surgical Pathology ◽

10.1177/10668969211055798 ◽

2021 ◽

pp. 106689692110557

Author(s):

Jiro Ichikawa ◽

Tomonori Kawasaki ◽

Hiroki Imada ◽

Atsushi Enomoto ◽

Naofumi Taniguchi ◽

...

Keyword(s):

Spindle Cell ◽

Final Diagnosis ◽

Positive Staining ◽

Cyclin Dependent Kinase ◽

Spindle Cell Lipoma ◽

Osteoid Tissue ◽

Well Differentiated ◽

Atypical Lipomatous Tumors ◽

Lipomatous Tumors

Although spindle cell lipoma (SCL) is a subtype of lipoma, the characteristics of SCL are observed in both lipomatous and non-lipomatous tumors. In this article, we present a case of SCL with ossification mimicking atypical lipomatous tumors/well-differentiated liposarcomas (ALTs/WDLs). Considering the findings of magnetic resonance imaging and needle biopsy, which exhibited ALTs/WDLs, marginal resection was performed. Histopathological findings demonstrated mature adipocytes and spindle cells without atypia and no malignant osteoid tissue in the ossified region. In addition, immunohistochemistry (IHC) showed positive staining for CD34, heterogeneous retinoblastoma protein deficiency, and negative staining for mouse double minute 2 homolog (MDM2) and cyclin-dependent kinase. Fluorescence in-situ hybridization showed negative amplification of MDM2. The final diagnosis of the tumor was established using IHC as an extremely rare SCL with ossification.

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Well-differentiated spindle cell liposarcoma (‘atypical spindle cell lipomatous tumor’) does not belong to the spectrum of atypical lipomatous tumor but has a close relationship to spindle cell lipoma: clinicopathologic, immunohistochemical, and molecular analysis of six cases

Modern Pathology ◽

10.1038/modpathol.2010.66 ◽

2010 ◽

Vol 23 (5) ◽

pp. 729-736 ◽

Cited By ~ 62

Author(s):

Thomas Mentzel ◽

Gabriele Palmedo ◽

Cornelius Kuhnen

Keyword(s):

Molecular Analysis ◽

Spindle Cell ◽

Spindle Cell Lipoma ◽

Atypical Lipomatous Tumor ◽

Lipomatous Tumor ◽

Close Relationship ◽

Well Differentiated

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FluorescenceIn SituHybridization forMDM2Amplification as a Routine Ancillary Diagnostic Tool for Suspected Well-Differentiated and Dedifferentiated Liposarcomas: Experience at a Tertiary Center

Sarcoma ◽

10.1155/2015/812089 ◽

2015 ◽

Vol 2015 ◽

pp. 1-10 ◽

Cited By ~ 38

Author(s):

Khin Thway ◽

Jayson Wang ◽

John Swansbury ◽

Toon Min ◽

Cyril Fisher

Keyword(s):

Gene Amplification ◽

Diagnostic Tool ◽

Spindle Cell ◽

Significant Group ◽

Lipomatous Tumor ◽

Tertiary Center ◽

Benign Histology ◽

Well Differentiated ◽

Correlation Rate

Background. The assessment ofMDM2gene amplification by fluorescencein situhybridization (FISH) has become a routine ancillary tool for diagnosing atypical lipomatous tumor (ALT)/well-differentiated liposarcoma and dedifferentiated liposarcoma (WDL/DDL) in specialist sarcoma units. We describe our experience of its utility at our tertiary institute.Methods. All routine histology samples in whichMDM2amplification was assessed with FISH over a 2-year period were included, and FISH results were correlated with clinical and histologic findings.Results. 365 samples from 347 patients had FISH forMDM2gene amplification. 170 were positive (i.e., showedMDM2gene amplification), 192 were negative, and 3 were technically unsatisfactory. There were 122 histologically benign cases showing a histology:FISH concordance rate of 92.6%, 142 WDL/DDL (concordance 96.5%), and 34 cases histologically equivocal for WDL (concordance 50%). Of 64 spindle cell/pleomorphic neoplasms (in which DDL was a differential diagnosis), 21.9% showedMDM2amplification. Of the cases with discrepant histology and FISH, all but 3 had diagnoses amended following FISH results. For discrepancies of benign histology but positive FISH, lesions were on average larger, more frequently in “classical” (intra-abdominal or inguinal) sites for WDL/DDL and more frequently core biopsies. Discrepancies of malignant histology but negative FISH were smaller, less frequently in “classical” sites but again more frequently core biopsies.Conclusions. FISH has a high correlation rate with histology for cases with firm histologic diagnoses of lipoma or WDL/DDL. It is a useful ancillary diagnostic tool in histologically equivocal cases, particularly in WDL lacking significant histologic atypia or DDL without corresponding WDL component, especially in larger tumors, those from intra-abdominal or inguinal sites or core biopsies. There is a significant group of well-differentiated adipocytic neoplasms which are difficult to diagnose on morphology alone, in which FISH forMDM2amplification is diagnostically contributory.

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Automated Bright-Field Dual-Color In Situ Hybridization for MDM2: Interobserver Reproducibility and Correlation With Fluorescence In Situ Hybridization in a Series of Soft Tissue Consults

Archives of Pathology & Laboratory Medicine ◽

10.5858/arpa.2015-0249-oa ◽

2016 ◽

Vol 140 (10) ◽

pp. 1111-1115 ◽

Cited By ~ 6

Author(s):

Gloria Zhang ◽

Christopher P. Lanigan ◽

John R. Goldblum ◽

Raymond R. Tubbs ◽

Erinn Downs-Kelly

Keyword(s):

In Situ Hybridization ◽

Fluorescence In Situ Hybridization ◽

Chromosome 12 ◽

Interobserver Reproducibility ◽

Bright Field ◽

Well Differentiated ◽

Atypical Lipomatous Tumors ◽

Mdm2 Amplification ◽

Lipomatous Tumors

Context.—Atypical lipomatous tumors/well-differentiated liposarcomas contain alterations in the 12q13-15 region resulting in amplification of MDM2 and nearby genes. Identifying MDM2 amplification is a useful ancillary test, as the histologic mimics of atypical lipomatous tumors/well-differentiated liposarcomas have consistently shown a lack of MDM2 amplification. Objective.—To assess the interobserver reproducibility of a bright-field assay for MDM2 amplification (dual-color, dual-hapten in situ hybridization [DDISH]) among reviewers with varying degrees of experience with the assay and to assess the concordance of MDM2 DDISH with MDM2 fluorescence in situ hybridization (FISH). Design.—In total, 102 cases were assessed in parallel for MDM2 by FISH and DDISH. MDM2 amplification was defined as an MDM2 to chromosome 12 ratio of 2.0 or greater, whereas an MDM2 to chromosome 12 ratio of less than 2 was nonamplified. Fluorescence in situ hybridization was scored in the routine clinical laboratory and DDISH was evaluated by 3 different pathologists blinded to the final diagnosis and FISH results. Results.—Fluorescence in situ hybridization categorized 27 cases (26%) as MDM2 amplified and 75 cases (74%) as nonamplified; the consensus DDISH diagnosis was 98% concordant with FISH. Agreement between MDM2 DDISH by each reviewer and MDM2 FISH was highly concordant (99%, 98%, and 98%, respectively, for reviewers 1, 2 and 3). The κ agreement of the 3 reviewers scoring DDISH was excellent (κ = 0.949, 0.95, and 0.95, respectively, for reviewers 1, 2, and 3). Conclusions.—This study highlights excellent concordance between DDISH and FISH in MDM2 copy number assessment. Moreover, excellent interobserver reproducibility of the DDISH assay was found among reviewers with varying levels of experience evaluating bright-field assays.

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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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Spindle Cell Lipoma of the Parapharyngeal Space: First Report of a Case

Ear Nose & Throat Journal ◽

10.1177/014556130108000414 ◽

2001 ◽

Vol 80 (4) ◽

pp. 244-250 ◽

Cited By ~ 4

Author(s):

Ingo Baumann ◽

Florian Dammann ◽

Hans Peter Horny ◽

Peter Karl Plinkert

Keyword(s):

Spindle Cell ◽

Parapharyngeal Space ◽

Subcutaneous Tissue ◽

Resonance Imaging ◽

Spindle Cell Lipoma ◽

Lipomatous Tumor ◽

Pharyngeal Muscles ◽

Parapharyngeal Tumor ◽

The Right ◽

Total Parotidectomy

Spindle cell lipomas are usually located in the subcutaneous tissue of the back, shoulders, and neck. To our knowledge, the presence of such a tumor in the parapharyngeal space has not yet been described. We evaluated a 45-year-old man with a tender swelling of the right parotid area that had reached the submandibular area. Clinical examination and magnetic resonance imaging revealed the presence of a tumor that coated the parotid area laterally and extended into the center of the parapharyngeal space, thus causing a dislocation of the pharyngeal muscles and mucosa. We performed a total parotidectomy and submandibulectomy on the right side and extirpated the parapharyngeal tumor. We were able to spare the facial nerve, and no facial paralysis occurred. Histologic examination revealed an atypical lipomatous tumor with a remarkably large portion of spindles.

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