ABSTRACT
We demonstrated that dose-densified and dose-intensified ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine; ABVDDD-DI) was safe and effective. Here, we present a post hoc long-term analysis of the 82 patients enrolled in the original study. The median observation time was 175 months (IQR 159-197). At 15 years, progression-free and overall survival rates were 81.2% (95% CI, 69.9%-88.7%) and 92.7% (95% CI, 82.6%-97.0%), respectively. Four patients with multiple cardiovascular risk factors experienced delayed G3 cardiac events. The cumulative incidence of second malignancies at 20 years was 6.1%. Fertility and childbearing potential were unaffected. Data support an ongoing benefit for ABVDDD-DI without uneven late toxicities.
ABSTRACT
Chondrosarcoma (ChS), a malignant cartilage-producing tumor, is the second most frequently diagnosed osseous sarcoma after osteosarcoma. It represents a very heterogeneous group of malignant chemo- and radiation-resistant neoplasms, accounting for approximately 20% of all bone sarcomas. The majority of ChS patients have a good prognosis after a complete surgical resection, as these tumors grow slowly and rarely metastasize. Conversely, patients with inoperable disease, due to the tumor location, size, or metastases, represent a great clinical challenge. Despite several genetic and epigenetic alterations that have been described in distinct ChS subtypes, very few therapeutic options are currently available for ChS patients. Therefore, new prognostic factors for tumor progression as well as new treatment options have to be explored, especially for patients with unresectable or metastatic disease. Recent studies have shown that a correlation between immune infiltrate composition, tumor aggressiveness, and survival does exist in ChS patients. In addition, the intra-tumor microvessel density has been proven to be associated with aggressive clinical behavior and a high metastatic potential in ChS. This review will provide an insight into the ChS microenvironment, since immunotherapy and antiangiogenic agents are emerging as interesting therapeutic options for ChS patients.
Subject(s)
Chondrosarcoma , Tumor Microenvironment , Humans , Chondrosarcoma/pathology , Chondrosarcoma/genetics , Chondrosarcoma/metabolism , Bone Neoplasms/pathology , Bone Neoplasms/therapy , Bone Neoplasms/metabolism , Bone Neoplasms/genetics , Immunotherapy , Angiogenesis Inhibitors/therapeutic use , Angiogenesis Inhibitors/pharmacologyABSTRACT
The cellularity assessment in bone marrow biopsies (BMBs) for the diagnosis of Philadelphia chromosome (Ph)-negative myeloproliferative neoplasms (MPNs) is a key diagnostic feature and is usually performed by the human eyes through an optical microscope with consequent inter-observer and intra-observer variability. Thus, the use of an automated tool may reduce variability, improving the uniformity of the evaluation. The aim of this work is to develop an accurate AI-based tool for the automated quantification of cellularity in BMB histology. A total of 55 BMB histological slides, diagnosed as Ph- MPN between January 2018 and June 2023 from the archives of the Pathology Unit of University "Luigi Vanvitelli" in Naples (Italy), were scanned on Ventana DP200 or Epredia P1000 and exported as whole-slide images (WSIs). Fifteen BMBs were randomly selected to obtain a training set of AI-based tools. An expert pathologist and a trained resident performed annotations of hematopoietic tissue and adipose tissue, and annotations were exported as .tiff images and .png labels with two colors (black for hematopoietic tissue and yellow for adipose tissue). Subsequently, we developed a semantic segmentation model for hematopoietic tissue and adipose tissue. The remaining 40 BMBs were used for model verification. The performance of our model was compared with an evaluation of the cellularity of five expert hematopathologists and three trainees; we obtained an optimal concordance between our model and the expert pathologists' evaluation, with poorer concordance for trainees. There were no significant differences in cellularity assessments between two different scanners.
ABSTRACT
Plexiform fibromyxoma (PF), also referred to as plexiform angiomyxoid myofibroblast tumor, is an exceedingly rare mesenchymal neoplasm primarily affecting the stomach. Herein, we present a case of PF diagnosed in a 71-year-old male with a history of lung cancer, initially suspected to have a gastrointestinal stromal tumor (GIST) of the stomach, who subsequently underwent subtotal gastrectomy. The histopathological and molecular features of the tumor, including mutations in ABL1, CCND1, CSF1R, FGFR4, KDR, and MALAT1-GLI1 fusion, are elucidated and discussed in the context of diagnostic, prognostic, and therapeutic considerations.
Subject(s)
Fibroma , Stomach Neoplasms , Humans , Male , Aged , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Stomach Neoplasms/surgery , Stomach Neoplasms/metabolism , Fibroma/genetics , Fibroma/pathology , Fibroma/metabolism , Immunohistochemistry , Mutation , Biomarkers, Tumor/genetics , GastrectomyABSTRACT
BACKGROUND/AIM: Breast angiosarcoma is a rare and aggressive disease with a poor prognosis. Two subtypes have been identified: primary angiosarcoma (PBA) and secondary breast angiosarcoma (SBA). In this retrospective analysis, we describe and compare our institute experience with the data existing in the literature. MATERIALS AND METHODS: We included in our analysis 29 patients who received a diagnosis of PBA or SBA between 2006 and 2019. RESULTS: All patients received surgery as frontline treatment, but only 6 patients underwent to adjuvant treatment. Neoadjuvant chemotherapy was administered 2 patients. The preferred chemotherapeutic regimen was taxanes with or without gemcitabine and associated with anthracyclines. A lower median RFS and OS were reported in patients with PBA compared to those with SBA, but the difference observed was not statistically significant. Patients with PBA had a lower median age at the diagnosis (38 vs. 75). CONCLUSION: In our analysis, we have shown a lower median RFS and OS in patients with PBA compared with those with SBA, and a significantly younger age at diagnosis in patients affected by PBA.
Subject(s)
Breast Neoplasms , Hemangiosarcoma , Humans , Female , Hemangiosarcoma/drug therapy , Retrospective Studies , Breast Neoplasms/drug therapy , Breast Neoplasms/surgery , Antibiotics, AntineoplasticABSTRACT
The major histocompatibility complex (MHC) class I expression in cancer cells has a crucial impact on the outcome of T cell-mediated cancer immunotherapy. We now determined the HLA class I allelic variants and their expression in PD-L1-deficient and positive rare sarcoma tissues. Tumor tissues were HLA-I classified based on HLA-A and -B alleles, and for class II, the HLA-DR-B by Taqman genomic PCRs. The HLA-A24*:10-B73*:01 haplotype was the most common. A general down-regulation or deletion of HLA-B mRNA and HLA-A was observed, compared to HLA-DR-B. HLA-I was almost too low to be detectable by immunohistochemistry and 32% of grade III cases were positive to PD-L1. Functional cytotoxic assays co-culturing patient biopsies with autologous T cells were used to assess their ability to kill matched tumor cells. These results establish that deletion of HLA-I loci together with their down-regulation in individual patient restrict the autologous lymphocyte cytotoxic activity, even in the presence of the immune checkpoint blocking antibody, Nivolumab. Additionally, the proposed cytotoxic test suggests a strategy to assess the sensitivity of tumor cells to T cell-mediated attack at the level of the individual patient.
ABSTRACT
Rare cancers are identified as those with an annual incidence of fewer than 6 per 100,000 persons and includes both epithelial and stromal tumors from different anatomical areas. The advancement of analytical methods has produced an accurate molecular characterization of most human cancers, suggesting a "molecular classification" that has allowed the establishment of increasingly personalized therapeutic strategies. However, the limited availability of rare cancer samples has resulted in very few therapeutic options for these tumors, often leading to poor prognosis. Long non coding RNAs (lncRNAs) are a class of non-coding RNAs mostly involved in tumor progression and drug response. In particular, the lncRNA HOX transcript antisense RNA (HOTAIR) represents an emergent diagnostic, prognostic and predictive biomarker in many human cancers. The aim of this review is to highlight the role of HOTAIR in rare cancers, proposing it as a new biomarker usable in the management of these tumors.
Subject(s)
Neoplasms/metabolism , RNA, Long Noncoding/metabolism , Animals , Gene Expression Regulation, Neoplastic , Humans , Neoplasms/genetics , RNA, Long Noncoding/geneticsABSTRACT
The tumor microenvironment modulates cancer growth. Extracellular vesicles (EVs) have been identified as key mediators of intercellular communication, but their role in tumor growth is largely unexplored. Here, we demonstrate that EVs from sarcoma patients promote neoangiogenesis via a purinergic X receptor 4 (P2XR4) -dependent mechanism in vitro and in vivo. Using a proteomic approach, we analyzed the protein content of plasma EVs and identified critical activated pathways in human umbilical vein endothelial cells (HUVECs) and human progenitor hematopoietic cells (CD34+). We then showed that vessel formation was due to rapid mitochondrial activation, intracellular Ca2+ mobilization, increased extracellular ATP, and trafficking of the lysosomal P2XR4 to the cell membrane, which is required for cell motility and formation of stable branching vascular networks. Cell membrane translocation of P2XR4 was induced by proteins and chemokines contained in EVs (e.g. Del-1 and SDF-1). Del-1 was found expressed in many EVs from sarcoma tumors and several tumor types. P2XR4 blockade reduced EVs-induced vessels in angioreactors, as well as intratumor vascularization in mouse xenografts. Together, these findings identify P2XR4 as a key mediator of EVs-induced tumor angiogenesis via a signaling mediated by mitochondria-lysosome-sensing response in endothelial cells, and indicate a novel target for therapeutic interventions.
Subject(s)
Cell-Derived Microparticles/metabolism , Lysosomes/metabolism , Neovascularization, Pathologic/metabolism , Receptors, Purinergic P2X4/metabolism , Sarcoma/blood supply , Sarcoma/pathology , Animals , Calcium/metabolism , Cell Movement , Cytosol/metabolism , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Mice , Mitochondria/metabolism , Retina/pathology , Sarcoma/blood , Signal Transduction , ViscosityABSTRACT
Myxoid liposarcoma (MLPS) is the second most common subtype of liposarcoma and has tendency to metastasize to soft tissues. To date, the mechanisms of invasion and metastasis of MLPS remain unclear, and new therapeutic strategies that improve patients' outcomes are expected. In this study, we analyzed by immunohistochemistry the immune cellular components and microvessel density in tumor tissues from patients affected by MLPS. In order to evaluate the effects of primary human MLPS cells on macrophage polarization and, in turn, the ability of macrophages to influence invasiveness of MLPS cells, non-contact and 3D organotypic co-cultures were set up. High grade MLPS tissues were found heavily vascularized, exhibited a CD3, CD4, and CD8 positive T lymphocyte-poor phenotype and were massively infiltrated by CD163 positive M2-like macrophages. Conversely, low grade MLPS tissues were infiltrated by a discrete amount of CD3, CD4, and CD8 positive T lymphocytes and a scarce amount of CD163 positive macrophages. Kaplan-Meier analysis revealed a shorter Progression Free Survival in MLPS patients whose tumor tissues were highly vascularized and heavily infiltrated by CD163 positive macrophages, indicating a clear-cut link between M2-like macrophage abundance and poor prognosis in patients. Moreover, we documented that, in co-culture, soluble factors produced by primary human MLPS cells induce macrophage polarization toward an M2-like phenotype which, in turn, increases MLPS cell capability to spread into extracellular matrix and to cross endothelial monolayers. The identification of M2-like polarization factors secreted by MLPS cells may allow to develop novel targeted therapies counteracting MLPS progression.
ABSTRACT
Patients with non-hodgkin lymphomas (NHL) represent a population of special interest during the current Coronavirus disease-19 (COVID-19) pandemics. NHLs are associated with disease- and treatment-related immunodeficiencies which may generate unusual COVID-19 dynamics and pose unique management challenges. We report the unusual clinical course of COVID-19 in a patient with mantle cell lymphoma (MCL) exposed to nine doses of Rituximab shortly before infection with severe acute respiratory syndrome corona virus 2 (SARS-CoV-2). He had a prolonged asymptomatic phase, with negative molecular and antibody testing for SARS-CoV-2, followed by a rapidly progressive evolution to severe COVID-19. Despite detection of viral RNA overlapped with first symptoms occurrence, anti-SARS-CoV-2 antibodies displayed an asynchronous pattern, with IgG first appearing 2 days after RNA positivity and IgM never being detected throughout the entire clinical course. While disease-associated immune derangements and/or previous treatments involving anti-CD20 antibodies might have contributed to COVID-19 dynamics in our patient, data suggests that antibody testings, without concurrent molecular assessment for SARS-CoV-2, may turn inadequate for monitoring of MCL patients, and in general NHL patients heavily exposed to anti-CD20 antibodies, during the current pandemics. We suggest that repeated molecular testing of nasopharyngeal swab should be implemented in these subjects despite a negative serology and absence of symptoms of SARS-CoV-2 infection. For the same reasons, a customized strategy needs to be developed for patients exposed to anti-CD20 antibodies, based on different features and mechanism of action of available SARS-CoV-2 vaccines and novel vaccinomics developments.
ABSTRACT
Sarcomas are rare, ubiquitous and heterogeneous tumors usually treated with surgery, chemotherapy, target therapy, and radiotherapy. However, 25-50% of patients experience local relapses and/or distant metastases after chemotherapy with an overall survival about 12-18 months. Recently, immuno-therapy has revolutionized the cancer treatments with initial indications for non-small cell lung cancer (NSCLC) and melanoma (immune-checkpoint inhibitors).Here, we provide a narrative review on the topic as well as a critical description of the currently available trials on immunotherapy treatments in patients with sarcoma. Given the promising results obtained with anti-PD-1 monoclonal antibodies (pembrolizumab and nivolumab) and CAR-T cells, we strongly believe that these new immunotherapeutic approaches, along with an innovative characterization of tumor genetics, will provide an exciting opportunity to ameliorate the therapeutic management of sarcomas.
Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Sarcoma , Humans , Immunotherapy , Neoplasm Recurrence, Local , Sarcoma/therapyABSTRACT
Angiosarcomas are ubiquitous neoplasms involving both cutaneous and soft tissue and visceral locations. Accumulating biomolecular evidences suggest that cutaneous angiosarcomas are distinctive entities with molecular, clinical and pathological peculiarities. Despite several ongoing clinical trials with promising therapeutic agents, the prognosis of cutaneous angiosarcomas is dismal and survival still rely on early diagnosis and surgery. An accurate diagnosis and the knowledge of the underlying molecular landscape are therefore essential to improve the prognosis. We detail the molecular, clinical, dermoscopic, morphological and prognostic features of cutaneous angiosarcoma. Although the molecular landscape of cutaneous angiosarcoma is not completely understood, accumulating evidences suggest that there are characteristic molecular alterations including dysregulation of angiogenesis and several complex molecular pathways. Secondary cutaneous angiosarcomas, arising in correlation with chronic lymphedema and ionizing radiation, have different molecular hallmarks, which are also leading to the first diagnostic applications. The diagnosis of cutaneous angiosarcoma may be challenging, as well-differentiated forms can be hard to distinguish from benign and low-grade vascular neoplasms, while poorly differentiated forms can be easily confounded with other non-vascular high-grade neoplasms. An accurate and early diagnosis, which is mandatory to ensure the best survival for the patients, is mainly based on morphological hallmarks.
Subject(s)
Early Detection of Cancer/standards , Hemangiosarcoma/diagnosis , Skin Neoplasms/blood supply , Skin Neoplasms/pathology , Aged , Chronic Disease , Dermoscopy/methods , Early Detection of Cancer/statistics & numerical data , Female , Hemangiosarcoma/etiology , Hemangiosarcoma/metabolism , Hemangiosarcoma/pathology , Humans , Lymphedema/complications , Middle Aged , Neoplasms, Radiation-Induced/pathology , Neovascularization, Pathologic/metabolism , Neovascularization, Pathologic/pathology , Pathology, Clinical/methods , Prognosis , Progression-Free Survival , Radiation, Ionizing , Skin Neoplasms/mortalityABSTRACT
Pleomorphic rhabdomyosarcoma (PRMS) is a rare but highly aggressive soft tissue tumor, accounting for 3% of soft tissue sarcomas. PRMS is the most frequent subtype of RMS in adulthood and it is mainly located in the large muscles of the extremities, particularly the lower limbs and the trunk, more rarely in other locations especially in the bladder. At our knowledge, only six cases of adult pleomorphic rhabdomyosarcoma of the bladder have been reported in the literature. In this study, we report a case of PRMS of bladder with a very poor prognosis. In fact, the patient died a month after surgery. The tumor was characterized by poorly differentiated, medium-sized sometimes rhabdoid cells, mixed with large-sized and pleomorphic elements with evident anisonucleosis, and with large areas of necrosis. We used an extensive immunohistochemical panel to exclude other tumors much more frequently reported at this site. The positivity for myogenic markers such as actin, desmin, myogenin and MyoD1 allowed the correct diagnosis. Furthermore, since preliminary studies highlighted a series of specific molecular alterations in PMRS cell lines, we analyzed a panel of specific mutations and gene rearrangements by RT-PCR and FISH methods. We showed a copy gains of CCND1 and MALT genes in our samples, suggesting an accurate molecular characterization of PRMS to establish a better management of patients and new therapeutic opportunities.
Subject(s)
Rhabdomyosarcoma/genetics , Rhabdomyosarcoma/pathology , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/pathology , Biomarkers, Tumor/analysis , Cyclin D1/genetics , DNA Mutational Analysis , Fatal Outcome , Humans , Male , Middle Aged , Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein/geneticsABSTRACT
Chondrosarcomas (CHS) are malignant cartilaginous neoplasms with diverse morphological features, characterized by resistance to chemo- and radiation therapies. In this study, we investigated the role of tumor-associated macrophages (TAM)s in tumor tissues from CHS patients by immunohistochemistry. Three-dimensional organotypic co-cultures were set up in order to evaluate the contribution of primary human CHS cells in driving an M2-like phenotype in monocyte-derived primary macrophages, and the capability of macrophages to promote growth and/or invasiveness of CHS cells. Finally, with an in vivo model of primary CHS cells engrafted in nude mice, we tested the ability of a potent peptide inhibitor of cell migration (Ac-d-Tyr-d-Arg-Aib-d-Arg-NH2, denoted RI-3) to reduce recruitment and infiltration of monocytes into CHS neoplastic lesions. We found a significant correlation between alternatively activated M2 macrophages and intratumor microvessel density in both conventional and dedifferentiated CHS human tissues, suggesting a link between TAM abundance and vascularization in CHS. In 3D and non-contact cu-culture models, soluble factors produced by CHS induced a M2-like phenotype in macrophages that, in turn, increased motility, invasion and matrix spreading of CHS cells. Finally, we present evidence that RI-3 successfully prevent both recruitment and infiltration of monocytes into CHS tissues, in nude mice.
Subject(s)
Chondrosarcoma/pathology , Monocytes/pathology , Tumor-Associated Macrophages/pathology , Adult , Aged , Animals , Antigens, CD/metabolism , Collagen/pharmacology , Female , Fibroblasts/drug effects , Fibroblasts/metabolism , Fibroblasts/pathology , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Immunophenotyping , Male , Mice, Nude , Microvessels/pathology , Middle Aged , Monocytes/drug effects , Phenotype , Spheroids, Cellular/drug effects , Spheroids, Cellular/pathology , THP-1 Cells , Time Factors , Tumor-Associated Macrophages/drug effectsABSTRACT
Neoplastic transformation is a rare but serious complication of Paget's disease of bone (PDB), occurring in fewer than 1% of individuals with polyostotic disease. Their prognosis is poor, with less than 50% surviving 5 years. In 2016, the genetic alteration of giant cell tumor (GCT) complicating PDB was identified as a founder germline mutation (P937R) in the ZNF687 gene. However, the study population was exclusively of Italian descent, and patients of different ethnic origins were not studied. To fill this gap, herein we performed mutation analysis of ZNF687 in a GCT in the pelvis of a 45-year-old black American woman with polyostotic PDB. The P937R mutation in ZNF687 was found in her tumor but, as expected, the ancestral haplotype that characterizes the Italian GCT/PDB patients was not found. Furthermore, we identified two additional Italian GCT/PDB patients with this ZNF687 mutation, now constituting a cohort of 18 GCT/PDB cases, all harboring the identical mutation. We also searched for ZNF687 mutations in a unique collection of tumor tissues derived from Italian PDB patients, including 28 osteosarcomas (OS/PDB), 8 undifferentiated sarcomas (SRC/PDB), 1 fibrosarcoma (FS/PDB), and 1 chondrosarcoma (CS/PDB). We identified the P937R mutation in one SRC/PDB and a different ZNF687 mutation (R331W) in 1 of 28 pagetic osteosarcomas. Thus, whereas GCT/PDB pathogenesis globally seems to involve the P937R mutation in ZNF687, other neoplasms associated with PDB seem to be less related to mutations in this gene. Finally, we identified the G34W mutation in the H3F3A gene in the maxillary tumor masses of two PDB patients, defining them as conventional GCT rather than GCT/PDB. Thus, combined molecular analysis of H3F3A and ZNF687 is essential to clarify the origin and diagnosis of tumors in PDB. © 2020 American Society for Bone and Mineral Research.
Subject(s)
Bone Neoplasms , DNA-Binding Proteins/genetics , Osteitis Deformans , Bone Neoplasms/genetics , Female , Humans , Italy , Middle Aged , Mutation , Osteitis Deformans/geneticsABSTRACT
Selection of cancer patients for treatment with immune checkpoint inhibitors remains a challenge due to tumour heterogeneity and variable biomarker detection. PD-L1 expression in 24 surgical chordoma specimen was determined immunohistochemically with antibodies 28-8 and E1L3N. The ability of patient-derived organoids to detect treatment effects of nivolumab was explored by quantitative and qualitative immunofluorescence and FACS analysis. The more sensitive antibody, E1L3N (ROC = 0.896, p = 0.001), was associated with greater tumour diameters (p = 0.014) and detected both tumour cells and infiltrating lymphocytes in 54% of patients, but only 1-15% of their cells. Organoids generated from PD-L1-positive patients contained both tumour cells and PD-1/CD8-positive lymphocytes and responded to nivolumab treatment with marked dose-dependent diameter reductions of up to 50% and increased cell death in both PD-L1-positive and negative organoids. Patient-derived organoids may be valuable to predict individual responses to immunotherapy even in patients with low or no immunohistochemical PD-L1 expression.
Subject(s)
B7-H1 Antigen/antagonists & inhibitors , Chordoma/metabolism , Drug Discovery/methods , Immunotherapy/methods , Nivolumab/pharmacology , Organoids/drug effects , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Aged , Aged, 80 and over , Apoptosis/drug effects , B7-H1 Antigen/immunology , B7-H1 Antigen/metabolism , CD8-Positive T-Lymphocytes/drug effects , Chordoma/pathology , Chordoma/surgery , Female , Humans , Immunohistochemistry/methods , Lymphocytes, Tumor-Infiltrating/immunology , Male , Middle Aged , Models, Biological , Programmed Cell Death 1 Receptor/metabolismABSTRACT
Solitary fibrous tumor (SFT) is a mesenchymal neoplasm that was originally described to be localized in the pleura, but thereafter, this has been reported in several anatomic sites. Although the etiology of the neoplasm remains largely unknown, the pathogenesis seems to be related to an NAB2-STAT6 fusion gene due to paracentric inversion on chromosome 12q13. The diagnosis of extrapleural SFT is challenging, owing to its rarity, and requires an integrated approach that includes specific clinical, histological, immunohistochemical, and even molecular findings. Histologically, extrapleural SFT shares morphological features same as those of the pleural SFT because it is characterized by a patternless distribution of both oval- and spindle-shaped cells in a variable collagen stroma. In addition, morphological variants of mixoid, fat-forming, and giant cell-rich tumors are described. A correct diagnosis is mandatory for a proper therapy and management of the patients with extrapleural SFT, as extrapleural SFT is usually more aggressive than pleural form, particularly cases occurring in the mediastinum, retroperitoneum, pelvis, and meninges. Although SFT is usually considered as a clinically indolent neoplasm, the prognosis is substantially unpredictable and only partially related to morphological features. In this context, cellularity, neoplastic borders, cellular atypias, and mitotic activity can show a wide range of variability. We review extrapleural SFT by discussing diagnostic clues, differential diagnosis, recent molecular findings, and prognostic factors.
Subject(s)
Biomarkers, Tumor/genetics , Gene Rearrangement , Hemangiopericytoma/diagnosis , Soft Tissue Neoplasms/diagnosis , Solitary Fibrous Tumor, Pleural/diagnosis , Solitary Fibrous Tumors/diagnosis , Biomarkers, Tumor/metabolism , Cell Dedifferentiation , Diagnosis, Differential , Hemangiopericytoma/genetics , Hemangiopericytoma/pathology , Humans , Oncogene Proteins, Fusion/genetics , Oncogene Proteins, Fusion/metabolism , Prognosis , Repressor Proteins/genetics , Repressor Proteins/metabolism , STAT6 Transcription Factor/genetics , STAT6 Transcription Factor/metabolism , Soft Tissue Neoplasms/genetics , Soft Tissue Neoplasms/pathology , Solitary Fibrous Tumor, Pleural/genetics , Solitary Fibrous Tumor, Pleural/pathology , Solitary Fibrous Tumors/genetics , Solitary Fibrous Tumors/pathologyABSTRACT
Cancer treatment is rapidly evolving toward personalized medicine, which takes into account the individual molecular and genetic variability of tumors. Sophisticated new in vitro disease models, such as three-dimensional cell cultures, may provide a tool for genetic, epigenetic, biomedical, and pharmacological research, and help determine the most promising individual treatment. Sarcomas, malignant neoplasms originating from mesenchymal cells, may have a multitude of genomic aberrations that give rise to more than 70 different histopathological subtypes. Their low incidence and high level of histopathological heterogeneity have greatly limited progress in their treatment, and trials of clinical sarcoma are less frequent than trials of other carcinomas. The main advantage of 3D cultures from tumor cells or biopsy is that they provide patient-speciï¬c models of solid tumors, and they overcome some limitations of traditional 2D monolayer cultures by reflecting cell heterogeneity, native histologic architectures, and cell-extracellular matrix interactions. Recent advances promise that these models can help bridge the gap between preclinical and clinical research by providing a relevant in vitro model of human cancer useful for drug testing and studying metastatic and dormancy mechanisms. However, additional improvements of 3D models are expected in the future, specifically the inclusion of tumor vasculature and the immune system, to enhance their full ability to capture the biological features of native tumors in high-throughput screening. Here, we summarize recent advances and future perspectives of spheroid and organoid in vitro models of rare sarcomas that can be used to investigate individual molecular biology and predict clinical responses. We also highlight how spheroid and organoid culture models could facilitate the personalization of sarcoma treatment, provide specific clinical scenarios, and discuss the relative strengths and limitations of these models.
Subject(s)
Precision Medicine , Sarcoma/pathology , Spheroids, Cellular/pathology , Animals , Humans , Models, Biological , Tumor Cells, Cultured , Tumor MicroenvironmentSubject(s)
Breast Neoplasms/pathology , Hemangiosarcoma/pathology , Adult , Breast Neoplasms/diagnosis , Breast Neoplasms/etiology , Breast Neoplasms/surgery , Environmental Exposure/adverse effects , Fatal Outcome , Female , Hazardous Waste Sites , Hemangiosarcoma/diagnosis , Hemangiosarcoma/etiology , Hemangiosarcoma/surgery , Humans , Italy , Mastectomy , Risk Factors , Young AdultABSTRACT
Intestinal perineuriomas without crypt serration are mainly polypoid lesions characterized by a proliferation of stromal cells expressing perineurial markers. These lesions morphologically differ from those with serrated crypts because of the serrated/hyperplastic architecture in addition to the disorganization of the crypts. These tumors, despite both expression of perineurial cell markers (epithelial membrane antigen, claudin-1, GLUT-1, and collagen type IV), show well-characterized molecular differences such as BRAFV600E mutation, suggesting that they might represent two distinct variants of a single lesion. In this report, we describe a polypoid intestinal perineurioma without crypt serration of the transverse colon, showing an unusual large size compared with other reported polypoid lesions ranging from 0.2 to 0.6 cm in size.