Elsevier

Human Pathology

Volume 65, July 2017, Pages 140-146
Human Pathology

Original contribution
Lipoblasts in spindle cell and pleomorphic lipomas: a close scrutiny,☆☆

https://doi.org/10.1016/j.humpath.2017.05.006Get rights and content

Highlights

  • The presence and frequency of lipoblasts were studied in spindle cell/pleomorphic lipomas.

  • Contemporary reports on spindle cell/pleomorphic lipomas often fail to mention this frequent and important feature.

  • With respect to spindle cell lipomas, this feature is clearly underrecognized.

  • Lipoblasts were found in 41% of spindle cell lipomas and 66% of pleomorphic lipomas, in some cases constituting a very prominent component.

Summary

The presence and frequency of lipoblasts (LPB) in spindle cell lipomas (SCL) and pleomorphic lipomas (PL) has never been studied in detail on a histologically, immunohistochemically and molecular genetically validated set of tumors. The authors investigated this feature by reviewing 91 cases of SCL and 38 PL. When more than 3 unequivocal LPB were found, the case was regarded as positive for the presence of LPB. All positive cases were then stained with CD34 and retinoblastoma (Rb) protein antibodies and tested by fluorescence in situ hybridization for MDM2 and CDK4 amplifications and the FUS gene rearrangements. The patients with SCL and PL containing LPB were 14 women and 47 men, the rest were of unknown gender. The cases usually presented as superficial, well-circumscribed soft tissue masses and most commonly occurred in the upper back and neck. CD34 was expressed in all cases, while Rb protein was consistently absent in all. Molecular genetic results, when available, were in concordance with the morphological diagnosis of SCL/PL. LPB were found in 37 (41%) cases of SCL and 25 cases of PL (66%). While in many cases they are inconspicuous, in some others they constitute a very prominent component of the tumor. It is important to be aware of this fact in order to avoid misinterpretation as liposarcoma.

Introduction

Spindle cell lipomas (SCL) and pleomorphic lipomas (PL) are distinctive soft tissue tumors, originally described as 2 separate entities by Enzinger et al [1], [2]. Based on similar clinicopathological, immunohistochemical as well as molecular genetic features, these neoplasms are today considered as opposite ends in a morphological spectrum of one single entity [3]. This is further supported by a frequent occurrence of cases showing characteristic morphological features of both SCL and PL in the same specimen. In their seminal paper by Shmookler and Enzinger in 1981, it was noted that almost one half of PL exhibited lipoblasts (LPB). Two years later, this finding was confirmed by another group [4]. However, contemporary reports often fail to mention this frequent and important feature of PL; and with respect to SCL, this feature is clearly underrecognized. After a review of the literature, including the major soft tissue pathology textbooks, we have found only 3 publications [3], [5], [6] acknowledging the presence of LPB in SCL. This situation is in stark contrast with our own experience. Over the years, we have encountered many cases of both SCL and PL with a prominent admixture of LPB. Since many of these cases were sent to us because of the concern for liposarcoma by the submitting pathologist, we decided to undertake this study on a large series of cases. To our knowledge, this is the first study which attempts to rigorously assess the frequency of LPB on a histologically, immunohistochemically, and molecular genetically validated set of SCL/PL.

Section snippets

Materials and methods

The 129 cases of SCL/PL constituting the subject of this study were retrieved from the routine biopsy archive and the authors' consultation files; they came from the period between years 1993 and 2016. The clinical information was extracted from the medical records, and follow-up data were obtained from the attending clinicians. To identify cases, we searched our consultation registry files for tumors diagnosed as SCL, PL or SCL/PL. This search yielded altogether 151 specimens, which were

Immunohistochemistry

The immunohistochemical analysis was performed using a Ventana BenchMark ULTRA (Ventana Medical System, Inc, Tucson, AZ). The following primary antibodies were used: CD34 (QBEnd/10, 1:200; Dako, Glostrup, Denmark) and Rb protein (G3–245, 1:50; BD Biosciences, Franklin Lakes, NJ). The primary antibodies were visualized employing the enzymes alkaline phosphatase or peroxidase as detecting systems (both purchased from Ventana Medical System, Inc, Tucson, AZ).

Results

The clinical features are summarized in Tables 1 (SCL) and 2 (PL). The patients were 14 women and 47 men; and in one case, the gender was unknown. The age of the patients at the time of diagnosis ranged from 27 to 90 years (mean, 60.1 years). Twenty-two cases were retrieved from the routine biopsy archive, and the remaining 40 cases were sent to us for a second opinion. When provided, the referral diagnoses of the consult cases are summarized in Tables 1 and 2. Overall, the most common

Immunohistochemical findings

All tested cases (n = 55) reacted with the CD34 antibody (Fig. 3A), albeit in 5 cases of SCL the expression was fairly weak. Conversely, all tested cases (n = 54) consistently showed Rb protein deficiency.

Molecular genetic findings

The molecular genetic findings are summarized in Tables 1 and 2. One case was excluded based on the presence of MDM2 and CDK4 amplification. Seventeen cases were not analyzable due to the poor quality of the archival tissue. For the same reason, not all three assays were analyzable in the subsequent 10 cases. The rest of the cases showed neither MDM2 or CKD4 amplification nor a break of the FUS gene.

Discussion

Since Stout described liposarcoma as a malignant tumor of lipoblasts (LPB), their identification has been overemphasized by pathologists as an indispensable criterion of malignancy. The morphologic definition of LPB may vary, but in a narrow sense, LPB are cells having hyperchromatic nuclei that are indented or sharply scalloped due to lipid-rich mono- or multivacuolated cytoplasmic droplets [6], [10]. Although the histologic background on which the LPB are encountered is far more important for

References (16)

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    The ratio of mature adipocytes to spindle cells can markedly differ, making an accurate diagnosis challenging, particularly when the SC/PL has little to no fat present.11 Lipoblasts were once assumed to be an indispensable criterion for diagnosis of liposarcoma,54 but are now known to occasionally appear in benign tumors such as SC/PL.52,55,56 Lipoblasts are an immature-appearing form of adipocytes with an indented hyperchromatic nucleus in a lipid-rich mono- and multivacuolated cytoplasm believed to have the potential to recapitulate adipogenesis similar to preadipocytes.55,56

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    Pleomorphic lipomas, on the other end of the histologic spectrum, contain variable numbers of floret-like multinucleated giant cells in addition to components of conventional spindle cell lipoma (Fig. 1(c)).3,5 Lipoblasts may be observed in both spindle cell lipomas and pleomorphic lipomas; however, infiltrative growth, necrosis, atypical spindle cells, bizarre pleomorphic cells, pleomorphic lipoblasts and significant mitotic activity are generally not found.9 The spindled and multinucleated floret-like cells show a consistent CD34-positive/S100-negative immunoprofile (Fig. 1(d)), while the mature adipocytes may stain for S100.

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    Given overlapping histologic and molecular features, ASLT (including atypical spindle cell lipoma) and APLT may be part of the same spectrum (atypical spindle cell/pleomorphic lipomatous tumor)25,26 and can be difficult to distinguish from SCPL. Distal extremity location, spindle cell atypia, marked variation in adipocyte size, infiltrative growth, and lack of ropey collagen favor ASLT21; however, criteria for separating SCPL from ASLT/APLT are evolving.27–29 Other Rb loss family tumors, especially MTMFB, can also mimic ASLT (see Table 2).

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Competing interests: The authors have no conflict of interest to disclose. Neither ethics approval nor informed consent was required for our study.

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Funding/Support: This study was supported by the National Sustainability Program I (NPU I) Nr. LO1503 provided by the Ministry of Education Youth and Sports of the Czech Republic.

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