The potential utility of single nucleotide polymorphism microarray (SNP array) in low-grade dedifferentiated liposarcomas.

To the Editor, Dedifferentiated liposarcoma (DD-LPS) is as an atypical lipomatous tumour/well differentiated liposarcoma (ALT/WD-LPS) showing progression to high or low-grade sarcoma either in the primary or in the recurrence.1WHO Classification of Tumours Editorial Board. World Health Organization Classification of Tumours. Soft Tissue and Bone Tumours. 5th ed. IARC, Lyon2020: 36-41Google Scholar,2Kilpatrick S.E. Dedifferentiated liposarcoma: a comprehensive historical review with proposed evidence-based guidelines regarding a diagnosis in need of further clarification.Adv Anat Pathol. 2021; 28: 426-438PubMed Google Scholar ALT/WD-LPS and DD-LPS are both characterised by supernumerary ring or giant marker chromosomes, which contain amplified sequences from the 12q14–q15 region with MDM2 being the main driver gene. Other genes within the 12q14–q15 region (i.e., CDK4, HMGA2, SAS, DDIT3, STAT6, etc) are frequently co-amplified which does not imply increased genomic complexity. MDM2 amplification with or without a small number of other numerical or structural abnormalities is seen in WD-LPS, while a complex karyotype is associated with progression to DD-LPS.1WHO Classification of Tumours Editorial Board. World Health Organization Classification of Tumours. Soft Tissue and Bone Tumours. 5th ed. IARC, Lyon2020: 36-41Google Scholar, 2Kilpatrick S.E. Dedifferentiated liposarcoma: a comprehensive historical review with proposed evidence-based guidelines regarding a diagnosis in need of further clarification.Adv Anat Pathol. 2021; 28: 426-438PubMed Google Scholar, 3Sandberg A.A. Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: liposarcoma.Caner Genet Cytogenet. 2004; 155: 1-24Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar Low-grade DD-LPS (LG-DDL) can show phenotypic diversity, but commonly includes fascicles of spindle cells with mild atypia and mild cellularity mimicking a myofibroblastic tumour. The recognition of pure LG-DDL, in the absence of high-grade dedifferentiation, can be extremely challenging as there can be overlapping morphological features with cellular WD-LPS.1WHO Classification of Tumours Editorial Board. World Health Organization Classification of Tumours. Soft Tissue and Bone Tumours. 5th ed. IARC, Lyon2020: 36-41Google Scholar,2Kilpatrick S.E. Dedifferentiated liposarcoma: a comprehensive historical review with proposed evidence-based guidelines regarding a diagnosis in need of further clarification.Adv Anat Pathol. 2021; 28: 426-438PubMed Google Scholar By using a modified scheme of the Federation Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grading system, Jour et al. demonstrated that grade one LG-DDL is rare, representing 6% of all DD-LPS.4Jour G. Gullet A. Liu M. et al.Prognostic relevance of Federation Nationale des Centres de Lutte Contre le Cancer grade and MDM2 amplification levels in dedifferentiated liposarcoma: a study of 50 cases.Mod Pathol. 2015; 28: 37-47Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar Limited data have shown that LG-DDL has a lower risk of local recurrence and improved overall survival when compared with high-grade DD-LPS;2Kilpatrick S.E. Dedifferentiated liposarcoma: a comprehensive historical review with proposed evidence-based guidelines regarding a diagnosis in need of further clarification.Adv Anat Pathol. 2021; 28: 426-438PubMed Google Scholar,4Jour G. Gullet A. Liu M. et al.Prognostic relevance of Federation Nationale des Centres de Lutte Contre le Cancer grade and MDM2 amplification levels in dedifferentiated liposarcoma: a study of 50 cases.Mod Pathol. 2015; 28: 37-47Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar, 5Gronchi A. Collini P. Miceli R. et al.Myogenic differentiation and histologic grading are major prognostic determinants in retroperitoneal liposarcoma.Am J Surg Pathol. 2015; 39: 383-393Crossref PubMed Scopus (82) Google Scholar, 6Dantey K. Schoedel K. Yergiyev O. et al.Correlation of histological grade of dedifferentiation with clinical outcome in 55 patients with dedifferentiated liposarcomas.Hum Pathol. 2017; 66: 86-92Crossref PubMed Scopus (17) Google Scholar nonetheless, universal defining criteria for LG-DDL are applied variably across different series.1WHO Classification of Tumours Editorial Board. World Health Organization Classification of Tumours. Soft Tissue and Bone Tumours. 5th ed. IARC, Lyon2020: 36-41Google Scholar,2Kilpatrick S.E. Dedifferentiated liposarcoma: a comprehensive historical review with proposed evidence-based guidelines regarding a diagnosis in need of further clarification.Adv Anat Pathol. 2021; 28: 426-438PubMed Google Scholar Microarray testing by either single nucleotide polymorphism array (SNP array) or array comparative genomic hybridisation (aCGH) allows genome-wide screening for copy number variants (CNVs)7Theisen A. Microarray-based comparative genomic hybridization (aCGH).Nat Educ. 2008; 1: 45Google Scholar and has been widely utilised to characterise the genomic imbalances of ALT/WD-LPS and DD-LPS.1WHO Classification of Tumours Editorial Board. World Health Organization Classification of Tumours. Soft Tissue and Bone Tumours. 5th ed. IARC, Lyon2020: 36-41Google Scholar,8Horvai A.E. DeVries S. Roy R. et al.Similarity in genetic alterations between paired well-differentiated and dedifferentiated components of dedifferentiated liposarcoma.Mod Pathol. 2009; 22: 1477-1488Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar, 9Tap W.D. Eilber F.C. Ginther C. et al.Evaluation of well-differentiated/de-differentiated liposarcomas by high-resolution oligonucleotide array-based comparative genomic hybridization.Genes Chromosomes Cancer. 2011; 50: 95-112Crossref PubMed Scopus (80) Google Scholar, 10Crago A.M. Socci N.D. DeCarolis P. et al.Copy number losses define subgroups of dedifferentiated liposarcoma with poor prognosis and genomic instability.Clin Cancer Res. 2012; 18: 1334-1340Crossref PubMed Scopus (59) Google Scholar However, there are only very limited data8Horvai A.E. DeVries S. Roy R. et al.Similarity in genetic alterations between paired well-differentiated and dedifferentiated components of dedifferentiated liposarcoma.Mod Pathol. 2009; 22: 1477-1488Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar addressing the degree of genomic complexity of LG-DDL. In this report we utilised SNP array to assess the degree of CNVs in five cases with either definitive or suspicious features of pure LG-DDL. This study was approved by our local research ethics committee (NSLHD HREC Ref. 1312-417M). Five cases with confirmed MDM2 amplification by fluorescent in situ hybridisation (FISH) were selected for this study. FISH was performed as previously reported.11Vargas A.C. Joy C. Cheah A.L. et al.Lessons learnt from MDM2 fluorescence in-situ hybridisation analysis of 439 mature lipomatous lesions with an emphasis on atypical lipomatous tumour/well-differentiated liposarcoma lacking cytological atypia.Histopathology. 2022; 80: 369-380Crossref PubMed Scopus (4) Google Scholar Three cases (Cases 1–3) were reported as DD-LPS with dedifferentiation consistent with low-grade (referred to as LG-DDL for this study). The following criteria were used to define low-grade dedifferentiation: lack of lipogenic differentiation across >10% of the tumour in at least a low-power (×10 objective) field and presenting as a well-defined area of sharp interface, absence of marked cytological atypia and necrosis, and <5 mitoses/10 high power fields (HPFs).2Kilpatrick S.E. Dedifferentiated liposarcoma: a comprehensive historical review with proposed evidence-based guidelines regarding a diagnosis in need of further clarification.Adv Anat Pathol. 2021; 28: 426-438PubMed Google Scholar,4Jour G. Gullet A. Liu M. et al.Prognostic relevance of Federation Nationale des Centres de Lutte Contre le Cancer grade and MDM2 amplification levels in dedifferentiated liposarcoma: a study of 50 cases.Mod Pathol. 2015; 28: 37-47Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar, 5Gronchi A. Collini P. Miceli R. et al.Myogenic differentiation and histologic grading are major prognostic determinants in retroperitoneal liposarcoma.Am J Surg Pathol. 2015; 39: 383-393Crossref PubMed Scopus (82) Google Scholar, 6Dantey K. Schoedel K. Yergiyev O. et al.Correlation of histological grade of dedifferentiation with clinical outcome in 55 patients with dedifferentiated liposarcomas.Hum Pathol. 2017; 66: 86-92Crossref PubMed Scopus (17) Google Scholar These cases were equivalent to grade 1 of the modified FNCLCC grading system.4Jour G. Gullet A. Liu M. et al.Prognostic relevance of Federation Nationale des Centres de Lutte Contre le Cancer grade and MDM2 amplification levels in dedifferentiated liposarcoma: a study of 50 cases.Mod Pathol. 2015; 28: 37-47Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar DNA was extracted from 4 μm unstained formalin-fixed, paraffin-embedded (FFPE) tissue sections using the QIAgen GeneRead FFPE DNA Kit (Qiagen, Australia). DNA was concentrated using the Zymo DNA Clean & Concentrator-25 kit (ThermoFisher, Australia) and quantified using Qubit and the dsDNA Quantitation, Broad Range kit (ThermoFisher Scientific). Genome-wide SNP array using Illumina Infinium GSAMD v3.0 Psych v1.1 (Illumina, USA) was performed at a resolution of 10 Mb for copy number abnormalities and regions of copy-neutral loss of heterozygosity. Analytical limit of detection for MDM2 amplification was 5 copies in a diploid sample with 20% neoplastic cell content. This was analysed by NxClinical software v6.0 (Bionano, USA; genome build GRCh37/hg19). Three cases (Cases 1–3) of LG-DDL and two cases of ALT suspicious but not definitive for LG-DDL (Cases 4 and 5) were subjected to SNP array (Fig. 1, Fig. 2, Table 1). Morphologically, Case 1 (primary DD-LPS) displayed a well circumscribed discrete myxoid nodule with ‘chicken-wire’ vasculature resembling myxoid liposarcoma (ML) in a background of WD-LPS. This case harboured DDIT3 co-amplification by FISH. Case 2, presenting as pulmonary metastasis in a patient with history of abdominal DD-LPS, displayed prominent myxoid morphology and homologous dedifferentiation. Occasional scattered pleomorphic cells were present, and although this may represent a high-grade dedifferentiated component, pleomorphic cells were not confluent, representing the minority of the cell population, and were absent in the block submitted for molecular analysis. Case 3 (primary DD-LPS) was a paratesticular mass almost entirely (>70%) comprised of whorls of spindle cells and palisade formation. Cases 4 and 5 were recurrent ALTs, as located in the extremities, with features suspicious but insufficient for LG-DDL. Case 4 showed ML-like areas and DDIT3 co-amplification but lacked circumscription of the myxoid areas, which intermingled with the lipomatous component. Case 5 displayed numerous hyperchromatic atypical stromal cells in cellular fibroconnective septae. On CT scan, this case was highly suspicious for DD-LPS. Myoid differentiation (based on IHC expression of SMA and desmin) was not identified in any of the cases.Fig. 2Low-grade dedifferentiated liposarcoma (LG-DDL), Case 3, and atypical lipomatous tumour (ALT), Cases 4 and 5. Case 3 (A,B) was comprised of whorls of spindle cells of myofibroblastic appearance and palisade formation. Case 4 (D) and Case 5 (E) showed ALTs with confluent myxoid areas alternating with a lipomatous component (D) or numerous hyperchromatic atypical stromal cells in cellular fibroconnective septae (E). SNP microarray of Case 1 (C) and Case 4 (F) demonstrated 12q14–q15 amplification in a background of a simple karyotype. Case 4 (F) also showed 18q gain.View Large Image Figure ViewerDownload Hi-res image Download (PPT)Table 1Summary of five cases with findings of array comparative genomic hybridisationCase IDDxGender, age, siteSizeCNVs other than MDM2 amplificationFollow-upCase 1 DD-LPSM 75, paratesticular mass50 mmHigh gain (>4 copies) of 2q34q36; high gain (>4 copies) of 6q21 and 6q22; loss of 7q11.23q36.1; gains of 4q28 and 13q331 year, developed lung adenocarcinomaCase 2 DD-LPSM 77, lung metastasis (primary abdominal)20 mm and 10 mm nodulesLoss 1p31.3–p12; gain of 1q21.3–q42.2; trisomy 8; whole arm loss of 10p; whole arm loss of 11p; high gain at 11q14; loss at 11q14.1–q25; loss 15q11.2–q21.3; Y loss1 year, developed further metastatic disease to distant soft tissueCase 3 DD-LPSM 84, left paratesticular mass35 mmNil3 year (current), no recurrence/metastasisCase 4 ALTF 59, recurrent left arm75 mmHigh gain (>4 copies) of 18q12.3q22.13 year (current), no recurrence/metastasisCase 5 ALTM 69, recurrent right thigh mass125 mmAmplification of 1q23-q24N/A (recent case)ALT, atypical lipomatous tumour; CNV, copy number variation; DD-LPS, dedifferentiated liposarcoma; Dx, diagnosis; F, female; M, male; N/A, not available. Open table in a new tab ALT, atypical lipomatous tumour; CNV, copy number variation; DD-LPS, dedifferentiated liposarcoma; Dx, diagnosis; F, female; M, male; N/A, not available. SNP array demonstrated that both cases of ALT with histological features suspicious but not definitive for LG-DDL (Cases 4 and 5) and one LG-DDL case (Case 3) displayed, apart from MDM2 amplification, a simple karyotype with 18q12 gain and 1q23–q24 co-amplification, presenting each in an individual sample (Table 1). None of these three cases developed recurrence or metastasis on follow-up, reflecting the genomic changes underlying typical ALT/WD-LPS. On the other hand, the two remaining LG-DDLs (Cases 1 and 2) harboured a complex karyotype associated with gains of 2q34q36, 6q21–22, 4q28 and 13q33, and loss of 7q11.23 (Case 1) or gains of 1q21.3–q42.2 and 11q14 and loss of 1p31.3–p12, 11q14.1–q25, 15q11.2–q21, whole arm of 10 p and 11 p and trisomy 8 (Case 2; Table 1). Horvai et al.8Horvai A.E. DeVries S. Roy R. et al.Similarity in genetic alterations between paired well-differentiated and dedifferentiated components of dedifferentiated liposarcoma.Mod Pathol. 2009; 22: 1477-1488Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar and others1WHO Classification of Tumours Editorial Board. World Health Organization Classification of Tumours. Soft Tissue and Bone Tumours. 5th ed. IARC, Lyon2020: 36-41Google Scholar, 2Kilpatrick S.E. Dedifferentiated liposarcoma: a comprehensive historical review with proposed evidence-based guidelines regarding a diagnosis in need of further clarification.Adv Anat Pathol. 2021; 28: 426-438PubMed Google Scholar, 3Sandberg A.A. Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: liposarcoma.Caner Genet Cytogenet. 2004; 155: 1-24Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar,9Tap W.D. Eilber F.C. Ginther C. et al.Evaluation of well-differentiated/de-differentiated liposarcomas by high-resolution oligonucleotide array-based comparative genomic hybridization.Genes Chromosomes Cancer. 2011; 50: 95-112Crossref PubMed Scopus (80) Google Scholar,10Crago A.M. Socci N.D. DeCarolis P. et al.Copy number losses define subgroups of dedifferentiated liposarcoma with poor prognosis and genomic instability.Clin Cancer Res. 2012; 18: 1334-1340Crossref PubMed Scopus (59) Google Scholar,12Beird H.C. Wu C.C. Ingram D.R. et al.Genomic profiling of dedifferentiated liposarcoma compared to matched well-differentiated liposarcoma reveals higher genomic complexity and a common origin.Cold Spring Harb Mol Case Stud. 2018; 4: a002386Crossref PubMed Scopus (45) Google Scholar have demonstrated that no genetic changes uniformly distinguish well differentiated and dedifferentiated components of DD-LPS within the same tumour and that individual genetic abnormalities are non-repetitive. Reported CNVs of DD-LPS include amplifications in 1p31–32, 1q21–24, 3q13.2–q25, 6q23–24, 12q13.3 and 12q24; gains at 6q14.1, 6q23.2, 10q21.1, 12q14.1–14, 14q, 17q21, 19q13.2 and 20q11; and losses at 3p14–21, 6p, 6q, 9p22–24, 10p15, 11q23–24, 11p, 13q, 17p11 and 19q13.1WHO Classification of Tumours Editorial Board. World Health Organization Classification of Tumours. Soft Tissue and Bone Tumours. 5th ed. IARC, Lyon2020: 36-41Google Scholar, 2Kilpatrick S.E. Dedifferentiated liposarcoma: a comprehensive historical review with proposed evidence-based guidelines regarding a diagnosis in need of further clarification.Adv Anat Pathol. 2021; 28: 426-438PubMed Google Scholar, 3Sandberg A.A. Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: liposarcoma.Caner Genet Cytogenet. 2004; 155: 1-24Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar,8Horvai A.E. DeVries S. Roy R. et al.Similarity in genetic alterations between paired well-differentiated and dedifferentiated components of dedifferentiated liposarcoma.Mod Pathol. 2009; 22: 1477-1488Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar, 9Tap W.D. Eilber F.C. Ginther C. et al.Evaluation of well-differentiated/de-differentiated liposarcomas by high-resolution oligonucleotide array-based comparative genomic hybridization.Genes Chromosomes Cancer. 2011; 50: 95-112Crossref PubMed Scopus (80) Google Scholar, 10Crago A.M. Socci N.D. DeCarolis P. et al.Copy number losses define subgroups of dedifferentiated liposarcoma with poor prognosis and genomic instability.Clin Cancer Res. 2012; 18: 1334-1340Crossref PubMed Scopus (59) Google Scholar,12Beird H.C. Wu C.C. Ingram D.R. et al.Genomic profiling of dedifferentiated liposarcoma compared to matched well-differentiated liposarcoma reveals higher genomic complexity and a common origin.Cold Spring Harb Mol Case Stud. 2018; 4: a002386Crossref PubMed Scopus (45) Google Scholar Although we identified some of the chromosomal aberrations previously reported (amp 1q23–24; gain at 6q21–22; and losses at 10p, 11p and 11q14.1–q25), additional CNVs were present in our cases: gains at 1q21.3–q42.2, 2q34–36, 4q28, 11q14, 13q33 and 18q12; loss of 1p31.3–p12, 7q11; whole arm loss of 10p, 15q11.2–q21.3 and trisomy 8. Although Horvai et al.8Horvai A.E. DeVries S. Roy R. et al.Similarity in genetic alterations between paired well-differentiated and dedifferentiated components of dedifferentiated liposarcoma.Mod Pathol. 2009; 22: 1477-1488Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar analysed LG-DDL by using aCGH as part of a larger series of cases, comparative analysis of genomic alterations presenting in low-versus high-grade DD-LPS was not documented in that study. This limited analysis has demonstrated that there is a high concordance between the findings of microarray testing and the morphological features of ALT/DD-LPS. For two cases of ALT with suspicious but not definitive features of DD-LPS, SNP array showed absence of a complex karyotype as expected in conventional type WD-LPS/ALT. Only a few additional genomic alterations were identified in these cases including DDIT3 co-amplification, which on its own it is not indicative of underlying complex karyotype. Concordantly, SNP array identified a complex genome in two of three samples with unequivocal dedifferentiation. Altogether, SNP array was predictive of the morphological features of ALT/WD-LPS with or without dedifferentiation in four of five cases (80%) with only one case of DD-LPS (Case 3) demonstrating absence of CNVs by the assay utilised, reflecting the genome of conventional ALT/WD-LPS. That case showed mild cytological atypia, absence of necrosis and low numbers of mitoses (1 per 10 HPFs), in the absence of a lipogenic component across the entire lesion (Fig. 2A,B). Therefore, it is possible that there is a subset of true LG-DDL with a genomic signature similar to conventional ALT/WD-LPS. An important observation of our study is that chromosomal imbalances identified in two of three LG-DDL (Cases 1 and 2) were those of a complex karyotype sarcoma, and although these are non-recurrent predictive alterations, they are within the spectrum of CNVs expected in high-grade DD-LPS.1WHO Classification of Tumours Editorial Board. World Health Organization Classification of Tumours. Soft Tissue and Bone Tumours. 5th ed. IARC, Lyon2020: 36-41Google Scholar, 2Kilpatrick S.E. Dedifferentiated liposarcoma: a comprehensive historical review with proposed evidence-based guidelines regarding a diagnosis in need of further clarification.Adv Anat Pathol. 2021; 28: 426-438PubMed Google Scholar, 3Sandberg A.A. Updates on the cytogenetics and molecular genetics of bone and soft tissue tumors: liposarcoma.Caner Genet Cytogenet. 2004; 155: 1-24Abstract Full Text Full Text PDF PubMed Scopus (138) Google Scholar,8Horvai A.E. DeVries S. Roy R. et al.Similarity in genetic alterations between paired well-differentiated and dedifferentiated components of dedifferentiated liposarcoma.Mod Pathol. 2009; 22: 1477-1488Abstract Full Text Full Text PDF PubMed Scopus (53) Google Scholar, 9Tap W.D. Eilber F.C. Ginther C. et al.Evaluation of well-differentiated/de-differentiated liposarcomas by high-resolution oligonucleotide array-based comparative genomic hybridization.Genes Chromosomes Cancer. 2011; 50: 95-112Crossref PubMed Scopus (80) Google Scholar, 10Crago A.M. Socci N.D. DeCarolis P. et al.Copy number losses define subgroups of dedifferentiated liposarcoma with poor prognosis and genomic instability.Clin Cancer Res. 2012; 18: 1334-1340Crossref PubMed Scopus (59) Google Scholar,12Beird H.C. Wu C.C. Ingram D.R. et al.Genomic profiling of dedifferentiated liposarcoma compared to matched well-differentiated liposarcoma reveals higher genomic complexity and a common origin.Cold Spring Harb Mol Case Stud. 2018; 4: a002386Crossref PubMed Scopus (45) Google Scholar These findings are in line with previous observations that genetic abnormalities associated with dedifferentiation/progression may precede phenotypic changes, which would support a biology of LG-DDL similar to that of high-grade DD-LPS. Nonetheless, a similar degree of underlying genomic complexity would not explain the reported superior outcome of LG-DDL when compared with its high-grade counterpart.4Jour G. Gullet A. Liu M. et al.Prognostic relevance of Federation Nationale des Centres de Lutte Contre le Cancer grade and MDM2 amplification levels in dedifferentiated liposarcoma: a study of 50 cases.Mod Pathol. 2015; 28: 37-47Abstract Full Text Full Text PDF PubMed Scopus (38) Google Scholar, 5Gronchi A. Collini P. Miceli R. et al.Myogenic differentiation and histologic grading are major prognostic determinants in retroperitoneal liposarcoma.Am J Surg Pathol. 2015; 39: 383-393Crossref PubMed Scopus (82) Google Scholar, 6Dantey K. Schoedel K. Yergiyev O. et al.Correlation of histological grade of dedifferentiation with clinical outcome in 55 patients with dedifferentiated liposarcomas.Hum Pathol. 2017; 66: 86-92Crossref PubMed Scopus (17) Google Scholar It is important to emphasise that diagnostic criteria for LG-DDL have been applied variably and homogeneous cohorts with detailed follow-up and combined molecular data are lacking.2Kilpatrick S.E. Dedifferentiated liposarcoma: a comprehensive historical review with proposed evidence-based guidelines regarding a diagnosis in need of further clarification.Adv Anat Pathol. 2021; 28: 426-438PubMed Google Scholar In a recent comprehensive review, Kilpatrick2Kilpatrick S.E. Dedifferentiated liposarcoma: a comprehensive historical review with proposed evidence-based guidelines regarding a diagnosis in need of further clarification.Adv Anat Pathol. 2021; 28: 426-438PubMed Google Scholar identified that the reported survival and prognostic data of pure LG-DDL are inconsistent, partly due to the fact that most cases have displayed admixed high-grade component and their recurrent/metastatic deposits have been unavailable for further review. In summary, microarray testing can be helpful to assess the genomic diversity of LG-DDL, which is a very challenging diagnosis that subspecialised soft tissue pathologists often struggle with, and with resultant inter-variability discordance. Our limited study showed that assessment of genomic complexity using SNP microarray in ALT/WD-LPS can act as a complementary ancillary tool in the classification of cases with equivocal areas for low-grade dedifferentiation. Knowledge of the underlying karyotype of difficult cases may potentially impact immediate clinical management and long-term surveillance. Absence of CNV by microarray can potentially be utilised to support the diagnosis of ALT/WD-LPS without dedifferentiation in cases with equivocal morphology, but it can also be suggestive of a clinical behaviour more similar to ALT/WD-LPS in cases with unequivocal de-differentiation. The authors state that there are no conflicts of interest to disclose.