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Molecular Cancer Apr 2023Mesenchymal gastrointestinal cancers are represented by the gastrointestinal stromal tumors (GISTs) which occur throughout the whole gastrointestinal tract, and affect... (Review)
Review
Mesenchymal gastrointestinal cancers are represented by the gastrointestinal stromal tumors (GISTs) which occur throughout the whole gastrointestinal tract, and affect human health and economy globally. Curative surgical resections and tyrosine kinase inhibitors (TKIs) are the main managements for localized GISTs and recurrent/metastatic GISTs, respectively. Despite multi-lines of TKIs treatments prolonged the survival time of recurrent/metastatic GISTs by delaying the relapse and metastasis of the tumor, drug resistance developed quickly and inevitably, and became the huge obstacle for stopping disease progression. Immunotherapy, which is typically represented by immune checkpoint inhibitors (ICIs), has achieved great success in several solid tumors by reactivating the host immune system, and been proposed as an alternative choice for GIST treatment. Substantial efforts have been devoted to the research of immunology and immunotherapy for GIST, and great achievements have been made. Generally, the intratumoral immune cell level and the immune-related gene expressions are influenced by metastasis status, anatomical locations, driver gene mutations of the tumor, and modulated by imatinib therapy. Systemic inflammatory biomarkers are regarded as prognostic indicators of GIST and closely associated with its clinicopathological features. The efficacy of immunotherapy strategies for GIST has been widely explored in pre-clinical cell and mouse models and clinical experiments in human, and some patients did benefit from ICIs. This review comprehensively summarizes the up-to-date advancements of immunology, immunotherapy and research models for GIST, and provides new insights and perspectives for future studies.
Topics: Animals; Mice; Humans; Gastrointestinal Stromal Tumors; Neoplasm Recurrence, Local; Gastrointestinal Neoplasms; Sarcoma; Immunotherapy; Antineoplastic Agents; Proto-Oncogene Proteins c-kit
PubMed: 37072770
DOI: 10.1186/s12943-023-01770-6 -
Testicular Tumors: A Contemporary Update on Morphologic, Immunohistochemical and Molecular Features.Advances in Anatomic Pathology Jul 2021Testicular tumors are incredibly diverse and one of the most challenging areas in surgical pathology. Because of the rarity and overlapping features with numerous... (Review)
Review
Testicular tumors are incredibly diverse and one of the most challenging areas in surgical pathology. Because of the rarity and overlapping features with numerous entities occurring in the testis and paratestis, these tumors pose a diagnostic challenge even to the most experienced general pathologists. In 2016, the latest "World Health Organization (WHO) classification of testicular tumors" was released, which incorporated several updates to the previous 2004 classification system. These updates involved several entities, including germ cell tumors, sex cord-stromal tumors, tumors containing both germ cells and sex-cord stromal cells, a miscellaneous group of testicular tumors and paratesticular tumors. In addition, significant changes were also introduced in the 2018 AJCC TNM staging (8th edition) regarding testicular tumors. The germ cell tumors are divided into 2 major groups; tumors derived from germ cell neoplasia in situ (GCNIS) and those unrelated to GCNIS. The GCNIS associated tumors include seminomatous and nonseminomatous germ cell tumors, which constitute a heterogeneous group of tumors. Non-GCNIS-associated tumors include prepubertal-type teratoma, prepubertal yolk sac tumor, mixed prepubertal-type teratoma and yolk sac tumor and spermatocytic seminoma. In the sex cord-stromal category, the tumors are classified based on their cells of origin. Most are Leydig cell tumors and Sertoli cell tumors; however, several mixed and diverse entities based on cell types are included in this group. Gonadoblastoma is the only tumor in the mixed germ cell and sex cord-stromal tumor category. Because of recent advances in molecular techniques, abundant new genetic information has emerged which helped classify the tumors based on the molecular alterations and provided insights into the tumor pathogenesis. This review focused on the updates related to testicular germ cell tumors and sex cord-stromal tumors and described the morphologic, immunohistochemical and molecular characteristics with an aim to provide a practical diagnostic approach and an update on relevant recent molecular advances.
Topics: Endodermal Sinus Tumor; Humans; Male; Neoplasm Staging; Neoplasms, Germ Cell and Embryonal; Seminoma; Teratoma; Testicular Neoplasms
PubMed: 33871428
DOI: 10.1097/PAP.0000000000000302 -
Molecular Cell Jul 2019Bulk genomic analyses and expression profiling of clinical specimens have shaped much of our understanding of cancer in patients. However, human tumors are intricate... (Review)
Review
Bulk genomic analyses and expression profiling of clinical specimens have shaped much of our understanding of cancer in patients. However, human tumors are intricate ecosystems composed of diverse cells, including malignant, immune, and stromal subsets, whose precise characterization is masked by bulk genomic methods. Single-cell genomic techniques have emerged as powerful approaches to dissect human tumors at the resolution of individual cells, providing a compelling approach to deciphering cancer biology. Here, we discuss some of the common themes emerging from initial studies of single-cell RNA sequencing in cancer and then highlight challenges in cancer biology for which emerging single-cell genomics methods may provide a compelling approach.
Topics: Antineoplastic Agents; Cell Communication; Cell Line, Tumor; Cell Lineage; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; High-Throughput Nucleotide Sequencing; Humans; Neoplasms; Neoplastic Cells, Circulating; RNA, Neoplasm; Single-Cell Analysis
PubMed: 31299208
DOI: 10.1016/j.molcel.2019.05.003 -
Annals of Surgical Oncology Oct 2020Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Complete resection is the only potentially curative... (Review)
Review
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract. Complete resection is the only potentially curative treatment, although recurrence is common, occurring in approximately 40-50% of patients. The introduction of effective molecularly targeted therapies for GISTs has dramatically changed the clinical management paradigms for, and prognosis of, patients with intermediate- and high-risk GISTs, as well as those with locally advanced and metastatic disease. In this article, we review landmark studies that evaluated the use and efficacy of the tyrosine kinase inhibitors imatinib and sunitinib in the adjuvant and neoadjuvant settings for resectable primary and limited resectable metastatic GISTs.
Topics: Antineoplastic Agents; Chemotherapy, Adjuvant; Gastrointestinal Neoplasms; Gastrointestinal Stromal Tumors; Humans; Imatinib Mesylate; Molecular Targeted Therapy; Neoadjuvant Therapy; Neoplasm Recurrence, Local
PubMed: 32734368
DOI: 10.1245/s10434-020-08869-w -
American Society of Clinical Oncology... Apr 2022Gastrointestinal stromal tumor (GIST) is the most common malignant neoplasm of mesenchymal origin and a compelling clinical and biologic model for the rational... (Review)
Review
Gastrointestinal stromal tumor (GIST) is the most common malignant neoplasm of mesenchymal origin and a compelling clinical and biologic model for the rational development of molecularly targeted agents. This is because the majority of GISTs are driven by gain-of-function mutations in KIT or PDGFRA receptor tyrosine kinases. Specific GIST mutations circumscribe well-defined molecular subgroups that must be determined during the diagnostic work-up to guide clinical management, including therapeutic decisions. Surgery is the cornerstone treatment in localized disease and can also be clinically relevant in the metastatic setting. The correct combination and sequence of targeted agents and surgical procedures improves outcomes for patients with GIST and should be discussed individually within multidisciplinary expert teams. All currently approved agents for the treatment of GIST are based on orally available tyrosine kinase inhibitors targeting KIT and PDGFRA oncogenic activation. Although first-line imatinib achieves remarkable prolonged disease control, the benefit of subsequent lines of treatment is more modest. Novel therapeutic strategies focus on overcoming the heterogeneity of KIT or PDGFRA secondary mutations and providing more potent inhibition of specific challenging mutations. This article reviews the current understanding and treatment of GIST, with an emphasis on recent advances.
Topics: Antineoplastic Agents; Drug Resistance, Neoplasm; Gastrointestinal Neoplasms; Gastrointestinal Stromal Tumors; Humans; Imatinib Mesylate; Mutation; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-kit
PubMed: 35522913
DOI: 10.1200/EDBK_351231 -
International Journal of Surgery... Nov 2022Phyllodes tumor is rare but has a high recurrence rate. Treatment modalities and clinicopathological prognostic factors for recurrence remain unclear. The synthesis of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Phyllodes tumor is rare but has a high recurrence rate. Treatment modalities and clinicopathological prognostic factors for recurrence remain unclear. The synthesis of real-world data can enable the integration of sufficient evidence on optimal treatment for this population.
METHODS
We searched PubMed, Embase, and Cochrane Library databases for studies focusing on the management of phyllodes tumor including the surgical margin, different clinicopathological prognostic factors, and postoperative adjuvant radiotherapy versus no radiotherapy.
RESULTS
Fifty-two studies were retrieved. The pooled estimated recurrence rates of benign, borderline, and malignant tumors were 7.1%, 16.7%, and 25.1%, respectively. Surgical margins of 1 mm (odds ratio [OR]: 0.4, 95% confidence interval [CI]: 0.27-0.61) and 1 cm (OR: 0.45, 95% CI: 0.15-0.85) resulted in significantly higher recurrence rates. Postoperative adjuvant radiotherapy significantly reduced the recurrence rate of malignant tumors relative to no radiotherapy (P = 0.034) but did not significantly reduce the recurrence rates of overall and borderline tumors. Regarding clinicopathological features, moderate or severe stromal atypia and hypercellularity, stromal overgrowth, mitotic number of 5, tumor necrosis, tumor border, and margin status were determined as independent prognostic factors for recurrence, except a tumor size of 5 cm.
CONCLUSION
The ideal surgical margin for phyllodes tumor incision should be at least 1 cm in width. Adjuvant radiotherapy reduced the recurrence of malignant tumor. By identifying patients with poor clinicopathological risk factors, surgeons may reduce the recurrence rate of phyllodes tumor.
Topics: Humans; Female; Phyllodes Tumor; Margins of Excision; Neoplasm Recurrence, Local; Radiotherapy, Adjuvant; Adjuvants, Immunologic; Breast Neoplasms; Prognosis; Retrospective Studies
PubMed: 36328344
DOI: 10.1016/j.ijsu.2022.106969 -
Nature Communications Aug 2019The tumor milieu consists of numerous cell types each existing in a different environment. However, a characterization of metabolic heterogeneity at single-cell...
The tumor milieu consists of numerous cell types each existing in a different environment. However, a characterization of metabolic heterogeneity at single-cell resolution is not established. Here, we develop a computational pipeline to study metabolic programs in single cells. In two representative human cancers, melanoma and head and neck, we apply this algorithm to define the intratumor metabolic landscape. We report an overall discordance between analyses of single cells and those of bulk tumors with higher metabolic activity in malignant cells than previously appreciated. Variation in mitochondrial programs is found to be the major contributor to metabolic heterogeneity. Surprisingly, the expression of both glycolytic and mitochondrial programs strongly correlates with hypoxia in all cell types. Immune and stromal cells could also be distinguished by their metabolic features. Taken together this analysis establishes a computational framework for characterizing metabolism using single cell expression data and defines principles of the tumor microenvironment.
Topics: Algorithms; Cell Line, Tumor; Cellular Reprogramming; Gene Expression Regulation, Neoplastic; Genes, Neoplasm; Glycolysis; Humans; Melanoma; Mitochondria; Neoplasms; Stromal Cells; Transcriptome; Tumor Microenvironment
PubMed: 31434891
DOI: 10.1038/s41467-019-11738-0 -
Surgical Pathology Clinics Sep 2023Mesenchymal neoplasms of the liver can be diagnostically challenging, particularly on core needle biopsies. Here, I discuss recent updates in neoplasms that are specific... (Review)
Review
Mesenchymal neoplasms of the liver can be diagnostically challenging, particularly on core needle biopsies. Here, I discuss recent updates in neoplasms that are specific to the liver (mesenchymal hamartoma, undifferentiated embryonal sarcoma, calcifying nested stromal-epithelial tumor), vascular tumors of the liver (anastomosing hemangioma, hepatic small vessel neoplasm, epithelioid hemangioendothelioma, angiosarcoma), and other tumor types that can occur primarily in the liver (PEComa/angiomyolipoma, inflammatory pseudotumor-like follicular dendritic cell sarcoma, EBV-associated smooth muscle tumor, inflammatory myofibroblastic tumor, malignant rhabdoid tumor). Lastly, I discuss metastatic sarcomas to the liver, as well as pitfalls presented by metastatic melanoma and sarcomatoid carcinoma.
Topics: Humans; Liver Neoplasms; Hemangiosarcoma; Hemangioma; Sarcoma; Soft Tissue Neoplasms; Hamartoma
PubMed: 37536892
DOI: 10.1016/j.path.2023.04.013 -
Acta Obstetricia Et Gynecologica... Oct 2021Ovarian granulosa cell tumor (GCT) is a rare, low-grade malignant tumor that accounts for 70% of the sex cord-stromal tumors. It has two histopathologic types with...
Ovarian granulosa cell tumor (GCT) is a rare, low-grade malignant tumor that accounts for 70% of the sex cord-stromal tumors. It has two histopathologic types with different clinical and biologic features: adult GCT and juvenile GCT. Most women diagnosed with the adult GCT have a favorable prognosis, with a 5-year survival rate of 97%-98%, but adult GCT has a feature of late relapse; the recurrence time could be more than 20 years after diagnosis. Juvenile GCT has a survival rate of 97% in stage I and a 5-year survival rate of 0%-22% in advanced stage with earlier recurrence than adult GCT. Consequently, the scenario emphasizes the need for early diagnosis, standardized treatment protocols, and long-term follow up. However, there is a lack of consensus regarding accurate diagnosis of GCT and adjuvant treatment. Furthermore, GCT tends to occur in young women, which emphasizes the viability of fertility-sparing surgery. The current review performed a systematic literature review of 60 articles to summarize the latest advances in GCT, with an emphasis on the molecular pathogenesis and survival after fertility-sparing surgery. We found that young women with fertility-sparing surgery had a desirable reproductive and survival outcome compared with those undergoing radical surgery.
Topics: Female; Fertility Preservation; Granulosa Cell Tumor; Humans; Neoplasm Recurrence, Local; Ovarian Neoplasms; Survival Analysis
PubMed: 34027996
DOI: 10.1111/aogs.14189 -
Gynecologic Oncology Nov 2022The landscape of uterine sarcomas is becoming increasingly complex with the description of new entities associated with recurrent molecular alterations. Uterine... (Review)
Review
The landscape of uterine sarcomas is becoming increasingly complex with the description of new entities associated with recurrent molecular alterations. Uterine sarcomas, as well as soft tissue sarcomas, can be distinguished into complex genomic sarcomas and simple genomic sarcomas. Leiomyosarcoma and pleomorphic type undifferentiated uterine sarcoma belong to the first group. Low-grade and high-grade endometrial stromal sarcomas, NTRK, COL1A1::PDGFB, ALK, RET, ROS1 associated sarcomas, and SMARCA4 deficient uterine sarcoma belong to the second group. Leiomyosarcoma is the most common uterine sarcoma followed by endometrial stromal sarcomas. Three different histologic subtypes of leiomyosarcomas are recognized with distinct diagnostic criteria and different clinical outcomes, the myxoid and epithelioid leiomyosarcomas being even more aggressive than the fusiform type. The distinction between low-grade and high-grade endometrial stromal sarcoma is based first on morphology and immunohistochemistry. The detection of fusion transcripts helps in the diagnosis. Definitely recognized as a separate entity, uterine PEComa is a rare tumor whose diagnostic criteria are being recently defined. Uterine PEComa has a specific algorithm stratifying the tumors into uncertain malignant potential and malignant tumors. Embryonal rhabdomyosarcomas of the uterine cervix are not restricted to children but can also be observed in adult women and are almost always DICER1 mutated, unlike embryonal rhabdomyosarcoma of the vagina which are DICER1wild-type, and adenosarcoma which can be DICER1 mutated but with less frequency. As sarcomas associated with fusion transcripts involving the NTRK, ALK, COL1A1::PDGFB genes can benefit from targeted therapy, systematic detection are now relevant especially for patients with high risk of relapse or in recurrent setting. The integration of molecular data with dedicated expert pathology review for histology and clinical data allows better identification of uterine sarcomas in order to better treat them.
Topics: Adult; Child; Female; Humans; Leiomyosarcoma; Genital Neoplasms, Female; Sarcoma, Endometrial Stromal; Protein-Tyrosine Kinases; Proto-Oncogene Proteins; Neoplasm Recurrence, Local; Uterine Neoplasms; Pelvic Neoplasms; Rhabdomyosarcoma, Embryonal; Endometrial Neoplasms; Perivascular Epithelioid Cell Neoplasms; Receptor Protein-Tyrosine Kinases; DNA Helicases; Nuclear Proteins
PubMed: 36114030
DOI: 10.1016/j.ygyno.2022.07.031