• PTC
• cancer
• cancer models
• high-throughput screening
• off-label
• personalized medicine
• sarcoma
• tumor microenvironment

• Humans
• Sarcoma/pathology
• Sarcoma/drug therapy
• Precision Medicine/methods
• Antineoplastic Agents/pharmacology
• Antineoplastic Agents/therapeutic use
• Mesenchymal Stem Cells/pathology
• Mesenchymal Stem Cells/drug effects
• Drug Screening Assays, Antitumor/methods
• Cell Proliferation/drug effects
• Female
• Male

• anthracyclines
• chemotherapy
• immunotherapy
• soft tissue sarcoma
• tyrosine kinase inhibitors

• Humans
• Male
• Lipoma/pathology
• Lipoma/diagnosis
• Lipoma/surgery
• Aged, 80 and over
• Eyelid Neoplasms/pathology
• Eyelid Neoplasms/diagnosis
• Eyelid Neoplasms/surgery
• Diagnosis, Differential
• Eyelids/pathology

• Liposarcoma
• Molecular genetics
• Subtypes
• Therapeutics

• Humans
• Liposarcoma/genetics
• Liposarcoma/therapy
• Liposarcoma/pathology
• Liposarcoma/diagnosis
• Liposarcoma/classification

• 332/2021/KSCSTE Kerala State Council for Science, Technology and Environment

• Gene fusion
• Immunohistochemistry
• Molecular pathology
• Mutation
• Rearrangement
• Sarcoma
• Soft tissue neoplasm
• Translocation

• Humans
• Soft Tissue Neoplasms/genetics
• Soft Tissue Neoplasms/diagnosis
• Soft Tissue Neoplasms/pathology
• Immunohistochemistry/economics
• Immunohistochemistry/methods
• Biomarkers, Tumor/analysis
• Biomarkers, Tumor/genetics
• Bone Neoplasms/genetics
• Bone Neoplasms/diagnosis
• Bone Neoplasms/pathology
• Cost-Benefit Analysis
• Predictive Value of Tests
• Molecular Diagnostic Techniques/economics
• Reproducibility of Results

• case report
• lipoblast-like cells
• lipoblastic nerve sheath tumor
• lymph node
• nuclear atypia

Distinguishing between some benign lipomas (BLs), atypical lipomatous tumors (ALTs), and dedifferentiated liposarcomas (DDLs) can be challenging due to overlapping magnetic resonance imaging characteristics, and poorly understood molecular mechanisms underlying the malignant transformation of liposarcomas.

To identify metabolic biomarkers of the lipomatous tumor spectrum by examining human tissue specimens using high-resolution ¹H magnetic resonance spectroscopy (MRS).

In this prospective study, human tissue specimens were obtained from participants who underwent surgical resection for radiologically-indeterminate lipomatous tumors between November 2016 and May 2019. Tissue specimens were obtained from normal subcutaneous fat (n=9), BLs (n=10), ALTs (n=7) and DDLs (n=8). Extracts from specimens were examined with high-resolution MRS at 17.6T. Computational modeling of pattern recognition-based cluster analysis was utilized to identify significant differences in metabolic signatures between the lipomatous tumor types.

Significant differences between BLs and ALTs were observed for multiple metabolites, including leucine, valine, branched chain amino acids, alanine, acetate, glutamine, and formate. DDLs were distinguished from ALTs by increased glucose and lactate, and increased phosphatidylcholine. Multivariate principal component analysis showed clear clustering identifying distinct metabolic signatures of the tissue types.

Metabolic signatures identified in ¹H MR spectra of lipomatous tumors provide new insights into malignant progression and metabolic targeting. The metabolic patterns identified provide the foundation of developing noninvasive MRS or PET imaging biomarkers to distinguish between BLs, ALTs, and DDLs.

• National Institutes of Health

Mammary-type myofibroblastoma (MTMF) is a rare benign extramammary soft tissue tumor with myofibroblastic differentiation. Although 160 cases of MTMF have been reported in the literature since 2001, no cases of infarction or atypical mitosis have been reported so far. Herein, we report an unusual case of MTMF in the pelvic cavity, which mimicked some malignant features, including infarction, atypical mitosis, infiltrative growth, and prominent cytologic atypia, making it difficult to ascertain whether the tumor was benign.

A 49-year-old man complained of pain and discomfort in the right buttock for more than 4 mo and did not receive any treatment. Nuclear magnetic resonance imaging (MRI) showed a 13-cm-sized mass in his right pelvic cavity. Histologically significant differences were atypical mitosis figures and multiple necrotic foci in the tumor. In addition, smooth muscle and skeletal muscle were invaded within and at the edge of the tumor. These morphologic features are often reminiscent of malignant tumors and therefore pose a diagnostic challenge to pathologists. The tumor cells were strongly positive for both cluster of differentiation 34 and desmin, and the loss of retinoblastoma 1 shown by immunohistochemical and fluorescence in situ hybridization results confirmed the pathological diagnosis of MTMF. Currently, the patient is alive and in good condition without tumor recurrence or metastasis after 2.5 years of follow-up by telephone and MRI.

The two pseudo-malignant characteristics of infarction and atypical mitosis broaden the morphological lineage of MTMF, a rare mesenchymal tumor.

• Mammary-type myofibroblastoma
• Infarction
• Atypical mitosis
• Infiltrative growth
• Cytologic atypia
• Case report

• Head and neck pathology
• Immunohistochemistry
• Molecular genetics
• Sarcoma
• Soft tissue

• Head and Neck Neoplasms
• Humans
• Soft Tissue Neoplasms/pathology
• World Health Organization

Dedifferentiated liposarcoma (DDLPS) is an extremely rare neoplasm that exhibits various morphologies. The tumor is characterized by immunoreactivity to MDM2 and CDK4 and can be confirmed by detecting MDM2 amplification via fluorescence in situ hybridization (FISH). Herein, we report an unusual case of DDLPS arising from the duodenum.

A 64-year-old man presented with repeated abdominal pain and weight loss. Radiologic studies revealed a mass of the duodenum involving the pancreas. The patient was treated with pylorus-preserving pancreaticoduodenectomy. Histologically, the tumor showed a high-grade sarcoma. Immunohistochemistry demonstrated that the tumor cells were positive for MDM2 and CDK4 expression. MDM2 amplification was detected via FISH, leading to the final diagnosis of DDLPS. Following surgery, the patient was treated in the intensive care unit due to peritonitis, and died 60 d after surgery.

To the best of the authors’ knowledge, this is the first case of primary duodenal DDLPS in Korea and the third case in the English-language literature. Care must be taken not to misdiagnose DDLPS as another high-grade tumor. Liposarcoma should be in the differential diagnosis list.

• Liposarcoma
• Primary
• Small bowel
• Duodenum
• Immunohistochemistry
• Case report

• Atypical lipomatous tumor
• Lipoma
• Liposarcoma
• MRI
• Neoplasm

• Animals
• Carcinogenesis/genetics
• Carcinogenesis/metabolism
• Carcinogenesis/pathology
• Epithelial-Mesenchymal Transition/genetics
• Humans
• Mesenchymal Stem Cells/metabolism
• Mesenchymal Stem Cells/pathology
• Neoplasms, Experimental/genetics
• Neoplasms, Experimental/metabolism
• Neoplasms, Experimental/pathology
• Neoplasms, Experimental/therapy
• Sarcoma/genetics
• Sarcoma/metabolism
• Sarcoma/pathology
• Sarcoma/therapy

• programmed cell death 1 receptor
• sarcoma

• Aminopyridines/administration & dosage
• Aminopyridines/pharmacology
• Animals
• Antineoplastic Combined Chemotherapy Protocols/administration & dosage
• Antineoplastic Combined Chemotherapy Protocols/pharmacology
• B7-H1 Antigen/metabolism
• Benzamides/administration & dosage
• Benzamides/pharmacology
• Cell Line, Tumor
• Gene Amplification
• Gene Expression Profiling
• Gene Expression Regulation, Neoplastic/drug effects
• Histone Deacetylase 1/genetics
• Histone Deacetylase 2/genetics
• Histone Deacetylases/genetics
• Humans
• Immune Checkpoint Inhibitors/administration & dosage
• Immune Checkpoint Inhibitors/pharmacology
• Liposarcoma/drug therapy
• Liposarcoma/genetics
• Liposarcoma/metabolism
• Mice
• Programmed Cell Death 1 Receptor/antagonists & inhibitors
• Sequence Analysis, RNA
• Exome Sequencing
• Xenograft Model Antitumor Assays

• National Scientific Foundation of China
• National Key Research and Dvelopment Program of China

• Adipose tissue
• Lipoma
• Magnetic resonance imaging
• Murine double minute 2 (MDM2)
• Neoplasms

• atypical lipomatous tumor
• diagnosis
• liposarcoma
• surgical therapy
• well-differentiated/dedifferentiated

• Aged
• Biopsy
• Diagnosis, Differential
• Humans
• Liposarcoma/diagnosis
• Lower Extremity
• Magnetic Resonance Imaging/methods
• Male
• Soft Tissue Neoplasms/diagnosis
• Tomography, X-Ray Computed/methods

Pancreatic liposarcoma is a rare tumor. According to a literature review, the patient described in this study is the seventh case of pancreatic liposarcoma reported in the English literature and the third case of dedifferentiated liposarcoma. Furthermore, this case had the largest primary tumor volume, and a primary pancreatic liposarcoma was diagnosed based on sufficient evidence.

We here report a rare case of a 28-year-old female with a huge dedifferentiated liposarcoma in the pancreatic tail. In June 2015, the patient underwent distal pancreatectomy with splenectomy. During the operation, a huge liposarcoma of approximately 28.0 cm × 19.0 cm × 8.0 cm was found, which had a yellow and white fish-like incisal surface. Based on both pathology and MDM2 gene amplification, the tumor was diagnosed as a dedifferentiated liposarcoma. The patient was treated with surgery but declined postoperative chemotherapy. She was well at the 26-mo follow-up, and no relapse was observed.

Pancreatic liposarcoma has a low incidence. Chemotherapy should be included in the treatment regimens. Complete resection is the only effective treatment.

• Pancreatic liposarcoma
• Huge tumor
• Distal pancreatectomy and splenectomy
• Chemotherapy
• Case report

• Collagen scaffolds
• Near-patient models
• Primary cultures
• Zebrafish

• adipocytic sarcoma
• eribulin
• microtubule inhibitors
• primary culture

• Antineoplastic Agents/pharmacology
• Cell Transformation, Neoplastic
• Drug Screening Assays, Antitumor
• Furans/pharmacology
• Humans
• Ketones/pharmacology
• Liposarcoma/drug therapy
• Liposarcoma/pathology
• Middle Aged
• Primary Cell Culture
• Tubulin Modulators/pharmacology
• Tumor Cells, Cultured

Sarcomas are a heterogeneous group of mesenchymal tumors arising from soft tissue or bone, with an uncertain etiology and difficult classification. Soft tissue sarcomas (STSs) account for around 1% of all adult cancers. Till date, more than 50 histologic subtypes have been identified. Adipocyte sarcoma or liposarcoma (LPS) is one of the most common STS subtypes, accounting for 15% of all sarcomas, with an incidence of 24% of all extremity STSs and 45% of all retroperitoneal STSs. The new World Health Organization classification system has divided LPS into four different subgroups: atypical lipomatous tumor/well-differentiated LPS, dedifferentiated LPS, myxoid LPS, and pleomorphic LPS. These lesions can develop at any location and exhibit different aggressive potentials reflecting their morphologic diversity and clinical behavior. Patients affected by LPS should be managed in specialized multidisciplinary cancer centers. Whereas surgical resection is the mainstay of treatment for localized disease, the benefits of adjuvant and neoadjuvant chemotherapy are still unclear. Systemic treatment, particularly chemotherapy, is still limited in metastatic disease. Despite the efforts toward a better understanding of the biology of LPS, the outcome of advanced and metastatic patients remains poor. The advent of targeted therapies may lead to an improvement of treatment options and clinical outcomes. A larger patient enrollment into translational and clinical studies will help increase the knowledge of the biological behavior of LPSs, test new drugs, and introduce new methodological studies, that is, on treatment response.

• adipocytic sarcomas
• classification
• liposarcomas
• management

• Uterine tumors
• diagnosis
• endometrial stromal sarcomas
• genetic classification
• hyperhaploidy
• leiomyosarcomas
• monosomy 14
• monosomy 22
• retinoblastoma gene
• uterine sarcomas

Spindle cell tumors are clinically heterogeneous but morphologically similar neoplasms that can occur anywhere, mostly in adult patients. They are treated primarily with surgery to which is often added adjuvant or neoadjuvant radiation. Sub-classification of spindle cell sarcomas requires integration of histology, clinicopathological parameters, immunohistochemistry, cytogenetics (including fluorescence in situ hybridization) and/or molecular genetics. Some of the tumor subtypes are characterized by the presence of distinct chromosomal translocations and fusion genes. When no signs of differentiation are seen, the diagnosis by exclusion becomes undifferentiated spindle cell sarcoma. Cytogenetic, RNA sequencing and RT-PCR analyses were performed on a case of spindle cell sarcoma. The karyotype of the primary tumor was 46,X,del(X)(p?11p?22), der(12)(12pter→12q?22::12q?15→ q?22::16p11→16pter),-16,+r(12). MDM2 was found amplified in both the primary tumor and a metastasis. RNA-Seq of the primary tumor identified four fusion genes, PTGES3-PTPRB, HMGA2-DYRK2, TMBIM4-MSRB3 and USP15-CNTN1, in which all the partner genes map to the q arm of chromosome 12. In material from the metastasis, RT-PCR detected the PTGES3-PTPRB, HMGA2-DYRK2 and TMBIM4-MSRB3 whereas no USP15-CNTN1 fusion transcript was found. Because MDM2 amplification and the fusion transcripts PTGES3-PTPRB, HMGA2-DYRK2 and TMBIM4-MSRB3 were found both in the primary tumor and in the metastasis, they are components of the same clone and may be involved both in initiation and progression of the tumor. Which of them is pathogenetically primary remains unknown.

Diagnosing adipocytic tumors can be challenging because it is often difficult to morphologically distinguish between benign, intermediate and malignant adipocytic tumors, and other sarcomas that are histologically similar. Recently, a number of tumor-specific chromosome translocations and associated fusion genes have been identified in adipocytic tumors and atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDL), which have a supernumerary ring and/or giant chromosome marker with amplified sequences of the MDM2 and CDK4 genes. The purpose of this study was to investigate whether quantitative real-time polymerase chain reaction (PCR) could be used to amplify MDM2 and CDK4 from total RNA samples obtained from core-needle biopsy sections for the diagnosis of ALT/WDL.

A series of lipoma (n = 124) and ALT/WDL (n = 44) cases were analyzed for cytogenetic analysis and lipoma fusion genes, as well as for MDM2 and CDK4 expression by real-time PCR. Moreover, the expression of MDM2 and CDK4 in whole tissue sections was compared with that in core-needle biopsy sections of the same tumor in order to determine whether real-time PCR could be used to distinguish ALT/WDL from lipoma at the preoperative stage.

In whole tissue sections, the medians for MDM2 and CDK4 expression in ALT/WDL were higher than those in the lipomas (P < 0.05). Moreover, karyotype subdivisions with rings and/or giant chromosomes had higher MDM2 and CDK4 expression levels compared to karyotypes with 12q13-15 rearrangements, other abnormal karyotypes, and normal karyotypes (P < 0.05). On the other hand, MDM2 and CDK4 expression levels in core-needle biopsy sections were similar to those in whole-tissue sections (MDM2: P = 0.6, CDK4: P = 0.8, Wilcoxon signed-rank test).

Quantitative real-time PCR of total RNA can be used to evaluate the MDM2 and CDK4 expression levels in core-needle biopsies and may be useful for distinguishing ALT/WDL from adipocytic tumors. Thus, total RNA from core-needle biopsy sections may have potential as a routine diagnostic tool for other tumors where gene overexpression is a feature of the tumor.

• diagnosis
• genetics
• liposarcoma

• Biomarkers, Tumor/metabolism
• Chromosomes, Human, Pair 12/genetics
• Comparative Genomic Hybridization
• Diagnosis, Differential
• Esophageal Neoplasms/diagnosis
• Esophageal Neoplasms/genetics
• Humans
• In Situ Hybridization, Fluorescence
• Liposarcoma/diagnosis
• Liposarcoma/genetics
• Male
• Middle Aged
• Neoplasms, Multiple Primary/diagnosis
• Neoplasms, Multiple Primary/genetics
• Prognosis
• Proto-Oncogene Proteins c-mdm2/genetics

• Amelanotic melanoma
• Liposarcoma

Background. Spindle cell lipoma (SCL) is a benign lipomatous tumour, typically occurring in the posterior neck, shoulder or upper back of elderly males. They compose of fat, CD34 positive spindle cells, and ropey collagen on a myxoid matrix. This case highlights a rare presentation of SCL and the need for pre-operative diagnosis. Case Report. A 63-year-old gentleman presented with a pre-existing left supraclavicular mass that had recently increased in size. FNA and CT Scans were performed and results discussed in the mutidisciplinary team meeting. Excisional biopsy was recommended. Radiology. CT neck showed a left supraclavicular mass of fatty density with fine internal septations. A low-grade liposarcoma could not be excluded. Histopathology. FNA was indeterminate. Histology of specimen showed bland spindle cells with no evidence of malignancy. Immuno-histochemistry showed SCL with CD34 positivity and negative staining on CDK4 and p16. Management. Excision biopsy of the mass was performed which was technically difficult as the mass invaginated around the brachial plexus. The patient recovered well post-operatively with no neurological deficits. Conclusion. Spindle cell lipoma is a rare benign tumour and a pre-operative diagnosis based on the clinical context, imaging and immuno-histochemistry is crucial to management.

Treatment decisions and prognosis assessment for liposarcoma is based on a classification that depends on morphological and genetic features. Revisions by experienced referral pathologists are often advocated.

The process of histopathological classification in referring hospitals and subsequently in a referral center in relation to molecular biological information is evaluated. A total of 331 consecutive liposarcoma patients were evaluated for the added value of histological review at time of referral. Subsequently, cases were reclassified with implementation of present-day molecular information. For all patients, complete data on staging, treatment, and follow-up were available.

Upon histological revision, 15/54 (28%) diagnoses were reclassified in the first decade, 14/65 (22%) in the second, and 14/53 (26%) in the last decade. Molecular biological analysis enabled well-differentiated liposarcoma with or without dedifferentiated component to be better recognized as such and distinguished from myxoid liposarcoma and pleomorphic liposarcoma. Inclusion of cytogenetic information resulted in reclassification after revision in 4/18 (22%) cases in the first decade, 10/38 (26%) cases in the second decade, and 19/75 (25%) cases in the last decade.

This study indicates that liposarcomas are heterogeneous tumors. Expert assessment and implementation of molecular biological analysis are valuable for adequate classification as a basis for treatment decisions.