Cytogenetic Analysis of a Pseudoangiomatous Pleomorphic/Spindle Cell Lipoma

Case Report

Ethics statement. The study was approved by the Regional Committee for Medical and Health Research Ethics, South-East Norway (Regional komité for medisinsk forskningsetikk Sor-Ost, Norge, http://helseforskning.etikkom.no, REC no S-07474a). All patient information has been de-identified.

Patient. A 35-year-old man noticed a tumor of his left elbow after a trauma. It seemed to grow over 2 years, when a magnetic resonance imaging investigation measured it at 6 cm in diameter. The subcutaneous tumor contained fatty and myxoid tissues and was surgically removed by marginal excision.

Macroscopically, the encapsulated tumor's yellow cut surface was partly myxoid, partly fleshy. Microscopically, the appearance was mixed, with mature fat cells intermingled with bands of fibrous, partly myxoid tissue, bundles of ‘ropey’ collagen and small, spindled cells that mostly lacked atypia (Figure 1A-C). In some areas, however, atypically-appearing cells and scattered floret-like giant cells were seen (Figure 1B-C). Centrally, the tumor had a pseudoangiomatous appearance, with papillary formations surrounding the vascular spaces (Figure 1A). There was no necrosis and the mitotic activity was low (Ki67 index <5%).

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Figure 1.

Histological examination of the pseudoangiomatous pleomorphic/spindle cell lipoma. A: Pseudoangiomatous cavity [×4 hematoxylin and eosin stain (HE)]. B: Lipoma transition to spindle cell lipoma (×4 HE). C: Pleomorphic/spindle cell lipoma with floret cells (×10 HE). D: Immunohistochemical analysis showing positivity for CD34 (×10). E: Immunohistochemical analysis demonstrating focal CD31-positive cells along the cavities (×20).

Immunohistochemical analysis showed extensive positivity for CD34 in the fibrous tissue (Figure 1D). The fat cells were S100-positive (Figure 1E). The angiomatous areas were partly CD31-positive, but negative for podoplanin (using D2-40). MDM2 proto-oncogene (MDM2) staining was negative.

The combination of ‘ropey’ collagen, fibrous tissue with no atypia, and floret-like giant cells fits very well with a spindle cell or pleomorphic lipoma. The rare pseudoangiomatous growth led to the final diagnosis of pseudoangiomatous pleomorphic/spindle cell lipoma.

G-Banding and karyotyping. As part of our diagnostic service, fresh tissue from a representative area of the tumor was received and analyzed cytogenetically after short-term culturing as described elsewhere (11). The karyotype was described according to the International System for Human Cytogenetic Nomenclature 2016 guidelines (12).

FISH analysis. The following three probes were used for FISH analysis. I: Vysis LSI FOXO1 (13q14) Dual Color Break Apart Rearrangement Probe (Abbott Laboratories, Abbott Park, IL, USA). This probe hybridizes to a 1.5 Mbp sequence on 13q14.11 which contains the FOXO1 gene. II: RB transcriptional corepressor 1 (RB1) deletion probe, purchased from Cytocell (Cytocell, Cambridge, UK), was used to detect deletion of the RB1 locus in 13q14.2. It consists of a 318-kb red probe spanning RB1 and a 13qter green probe acting as a control for chromosome 13. III: The 13q14.3 deletion probe from Cytocell. This probe is normally used for detection of 13q14 deletion in B-cell chronic lymphocytic leukemia. It spans the tripartite motif containing 13 (TRIM13) gene, two non-coding RNA genes, deleted in lymphocytic leukemia 1 (DLEU1) and deleted in lymphocytic leukemia 2 (DLEU2), and the genetic marker D13S319. It also contains a 13qter subtelomere specific probe (clone 163C9), labeled in green, which allows for identification of chromosome 13 and acts as a control.

Fluorescent signals were captured and analyzed using the CytoVision system from Leica Biosystems (http://www.leicabiosystems.com/pathology-imaging/cytogenetics/).

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Figure 2.

G-Banding analysis of the pseudoangiomatous pleomorphic/spindle cell lipoma. Karyotype showing the chromosomal aberrations of tumor cells: 45,XY,del(1)(p32),add(3)(p13),ins(6;?)(p21;?),-13,der(17;22)(q10;q10),-17,-22,+der(?)t(3;?)(p13;?),+mar1,+mar2[14]. Arrows indicate breakpoints.

Findings. G-Banding analysis of short-term cultured cells from the pseudoangiomatous pleomorphic/spindle cell lipoma yielded the karyotype 45,XY,del(1)(p32),add(3)(p13),ins(6;?) (p21;?),-13,der(17;22)(q10;q10),-17,-22,+der(?)t(3;?) (p13;?),+mar1,+mar2[14] (Figure 2).

Interphase FISH was performed, using commercially available probes, for the FOXO1, RB1, and TRIM13 genes, the two DLEU1 and DLEU2 non-coding RNA genes, and the genetic markers RH44686 and D13S25 (Figure 3A). All of them are mapped on chromosome band 13q14 to different sub-bands (Figure 3A).

No loss of the FOXO1 probe (sub-band 13q14.11) was seen in the 115 nuclei examined (Figure 3B). However, FISH showed heterozygous loss of the RB1 probe (sub-band 13q14.2). In 102 out of 112 (91%) nuclei examined, one red signal (probe spanning RB1) and two green signals (13qter probe) were seen (Figure 3C). Similarly, heterozygous loss of the region spanning TRIM13, DLEU1, DLEU2, and the genetic markers RH44686 and D13S25 was found (sub-bands 13q14.2-q14.3). In 92 out of 98 (94%) interphase nuclei, one red signal (probe spans TRIM13, DLEU1, DLEU2, RH44686, and D13S25) and two green (13qter subtelomere specific probe) signals were observed (Figure 3D).