-
Archives of Pathology & Laboratory... Mar 2016Müllerian adenosarcoma is an uncommon biphasic tumor composed of malignant stromal and benign epithelial components. Morphologically, adenosarcoma is characterized by a...
Müllerian adenosarcoma is an uncommon biphasic tumor composed of malignant stromal and benign epithelial components. Morphologically, adenosarcoma is characterized by a broad leaflike architecture, reminiscent of phyllodes tumors of the breast. Periglandular cuffing of the stromal cells around the compressed or cystically dilated glands is characteristic. The mesenchymal component is typically a low-grade spindle cell sarcoma, whereas the epithelial counterpart is commonly endometrioid with frequent squamous or mucinous metaplasia and may, in some circumstances, show mild to moderate atypia. In all cases, it is important to assess for the presence of sarcomatous overgrowth and myometrial invasion, which are the prognostic factors. In this brief review, we present the clinical, histopathologic, and immunohistochemical features of adenosarcoma, as well as updates on the molecular biology of this neoplasm.
Topics: Adenosarcoma; DNA Helicases; Diagnosis, Differential; Female; Gene Amplification; Humans; Immunohistochemistry; Mixed Tumor, Mullerian; Molecular Diagnostic Techniques; Mutation; Neoplasm Invasiveness; Neoplasm Proteins; Neoplasm Staging; Nuclear Proteins; Practice Guidelines as Topic; Prognosis; Proto-Oncogene Proteins; Stromal Cells; Trans-Activators; Uterine Neoplasms; Uterus; X-linked Nuclear Protein
PubMed: 26927725
DOI: 10.5858/arpa.2014-0523-RS -
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 -
Gastric Cancer : Official Journal of... May 2023Gastrointestinal stromal tumours (GISTs) are soft-tissue sarcomas of the gastrointestinal tract. Surgery is the standard treatment for localised disease, but the risk of... (Review)
Review
Gastrointestinal stromal tumours (GISTs) are soft-tissue sarcomas of the gastrointestinal tract. Surgery is the standard treatment for localised disease, but the risk of relapse and progression to more advanced disease is substantial. Following the discovery of the molecular mechanisms underlying GISTs, targeted therapies for advanced GIST were developed, with the first being the tyrosine kinase inhibitor (TKI) imatinib. Imatinib is recommended in international guidelines as first-line therapy to reduce the risk of GIST relapse in high-risk patients, and for locally advanced, inoperable and metastatic disease. Unfortunately, imatinib resistance frequently occurs and, therefore, second-line (sunitinib) and third-line (regorafenib) TKIs have been developed. Treatment options are limited for patients with GIST that has progressed despite these therapies. A number of other TKIs for advanced/metastatic GIST have been approved in some countries. Ripretinib is approved as fourth-line treatment of GIST and avapritinib is approved for GIST harbouring specific genetic mutations, while larotrectinib and entrectinib are approved for solid tumours (including GIST) with specific genetic mutations. In Japan, pimitespib, a heat shock protein 90 (HSP90) inhibitor, is now available as a fourth-line therapy for GIST. Clinical studies of pimitespib have indicated that it has good efficacy and tolerability, importantly not displaying the ocular toxicity of previously developed HSP90 inhibitors. Additional approaches for advanced GIST have been investigated, including alternative uses of currently available TKIs (such as combination therapy), novel TKIs, antibody-drug conjugates, and immunotherapies. Given the poor prognosis of advanced GIST, the development of new therapies remains an important goal.
Topics: Humans; Gastrointestinal Stromal Tumors; Imatinib Mesylate; Gastrointestinal Neoplasms; Stomach Neoplasms; Neoplasm Recurrence, Local; Antineoplastic Agents; Protein Kinase Inhibitors
PubMed: 36913072
DOI: 10.1007/s10120-023-01381-6 -
Molecular and Cellular Biochemistry Jun 2021The regulation of aromatase, an enzyme involved in the biosynthesis of estrogen in normal and cancer cells, has been associated with growth factor signaling and immune... (Review)
Review
The regulation of aromatase, an enzyme involved in the biosynthesis of estrogen in normal and cancer cells, has been associated with growth factor signaling and immune response modulation. The tissue-specific regulatory roles of these factors are of particular importance as local aromatase expression is strongly linked to cancer development/progression and disease outcomes in patients. Therefore, aromatase has become a chemotherapeutic target and aromatase inhibitors (AIs) are used in the clinic for treating hormone-dependent cancers. Although AIs have shown promising results in the treatment of cancers, the emerging increase in AI-resistance necessitates the development of new and improved targeted therapies. This review discusses the role of tumor and stromal-derived growth factors and immune cell modulators in regulating aromatase. Current single-agent and combination therapies with or without AIs targeting growth factors and immune checkpoints are also discussed. This review highlights recent studies that show new connections between growth factors, mediators of immune response, and aromatase regulation.
Topics: Animals; Aromatase; Aromatase Inhibitors; Humans; Neoplasm Proteins; Neoplasms
PubMed: 33599895
DOI: 10.1007/s11010-021-04099-0 -
Histology and Histopathology Aug 2023Phyllodes tumor (PT) is a relatively rare breast tumor, accounting for <1% of all breast tumors. (Review)
Review
BACKGROUND
Phyllodes tumor (PT) is a relatively rare breast tumor, accounting for <1% of all breast tumors.
MAIN BODY
Adjuvant therapy with chemotherapy or radiation therapy, other than surgical excision, has not been established yet. PT, similar to other breast tumors, is classified as benign, borderline, and malignant according to the World Health Organization classification system, depending on stromal cellularity, stromal atypia, mitotic activity, stromal overgrowth, and tumor border. However, this histological grading system cannot effectively or fully reflect the clinical prognosis of PT. Several studies have investigated prognostic factors for PT as some PTs recur or metastasize to distant sites, and thus, prediction of prognosis is clinically imperative.
CONCLUSION
This review discusses clinicopathological factors, immunohistochemical markers, and molecular factors that have been investigated in previous studies to have an impact on the clinical prognosis of PT.
Topics: Humans; Female; Phyllodes Tumor; Prognosis; Neoplasm Recurrence, Local; Stromal Cells; Breast Neoplasms; Retrospective Studies
PubMed: 36866915
DOI: 10.14670/HH-18-600 -
Advances in Experimental Medicine and... 2021Phyllodes tumors of breast (PTB) have been known to an uncommon and particular disease to handle owing to diagnostic ambiguity and unpredictable clinical outcome....
Phyllodes tumors of breast (PTB) have been known to an uncommon and particular disease to handle owing to diagnostic ambiguity and unpredictable clinical outcome. Malignant phyllodes tumors (MPT) are diagnosed when there are marked stromal hypercellularity, atypia, increased mitoses of ≥10/10 HPFs, permeative tumor borders, and stromal overgrowth. The presence of a malignant heterologous element (MHE) places the tumor into the malignant category regardless of other histological features. Excision with negative margins should be achieved for recurrent and malignant phyllodes tumor. An ideal margin width remains to be determined, and may need to be considered in relation to factors such as tumor size and cosmesis. Without the convincing evidence of survival benefit, adjuvant RT has revealed more favorable local control rate compared with observation group. Stromal expression of Twist and Foxc2, epithelial-mesenchymal transition marker, was associated with high tumor grade and poor prognosis. Tumor-associated macrophage drives myoblast differentiation and malignant progression of PTB through a CCL18-driven signaling cascade amenable to antibody disruption. Recent targeted sequencing on PTBs provided insights into the molecular pathogenesis and genetic characterization with potential clinical implications.
Topics: Breast Neoplasms; Cell Differentiation; Epithelial-Mesenchymal Transition; Humans; Neoplasm Recurrence, Local; Phyllodes Tumor
PubMed: 33983602
DOI: 10.1007/978-981-32-9620-6_32 -
Cancer Research Oct 2022Epithelial transformation and carcinogenesis are characterized by profound alterations in cell mechanics that significantly affect multiple steps of the metastatic...
Epithelial transformation and carcinogenesis are characterized by profound alterations in cell mechanics that significantly affect multiple steps of the metastatic cascade. The ability of cancer cells to grow in the primary tumor, to locally invade through the confining extracellular matrix, to survive in circulation, and to extravasate into distant vital organs all depend on specific mechanical characteristics. Importantly, recent studies have shown that the mechanical properties of cancer cells also influence their interactions with immune and stromal cells. Here, we discuss the mechanical changes that cancer cells undergo during metastasis, how these changes affect immune and stromal responses, and the implications of these new insights for therapeutic intervention.
Topics: Extracellular Matrix; Humans; Neoplasm Metastasis; Neoplasms; Stromal Cells
PubMed: 35877197
DOI: 10.1158/0008-5472.CAN-22-0419 -
Trends in Cancer Jun 2016Hypoxia is a potent microenvironmental factor that promotes tumor metastasis. Recent studies have revealed mechanisms by which hypoxia and activation of hypoxia... (Review)
Review
Hypoxia is a potent microenvironmental factor that promotes tumor metastasis. Recent studies have revealed mechanisms by which hypoxia and activation of hypoxia inducible factor (HIF)-dependent signaling promotes metastasis through the regulation of metabolic reprogramming, the stem cell phenotype, invasion, angiogenesis, immune suppression, the premetastatic niche, intravasation and/or extravasation, and resistance to apoptosis. These discoveries suggest novel paradigms in tumor metastasis and identify new opportunities for therapeutic intervention in the prevention and treatment of metastatic disease. Here, we review the impact of hypoxia and hypoxic signaling pathways in tumor and stromal cells on each step of the metastatic cascade.
Topics: Animals; Cell Hypoxia; Humans; Neoplasm Metastasis; Neoplasms; Signal Transduction; Stromal Cells; Tumor Microenvironment
PubMed: 28741527
DOI: 10.1016/j.trecan.2016.05.006 -
Genes & Development Apr 2016Primary tumors are known to constantly shed a large number of cancer cells into systemic dissemination, yet only a tiny fraction of these cells is capable of forming... (Review)
Review
Primary tumors are known to constantly shed a large number of cancer cells into systemic dissemination, yet only a tiny fraction of these cells is capable of forming overt metastases. The tremendous rate of attrition during the process of metastasis implicates the existence of a rare and unique population of metastasis-initiating cells (MICs). MICs possess advantageous traits that may originate in the primary tumor but continue to evolve during dissemination and colonization, including cellular plasticity, metabolic reprogramming, the ability to enter and exit dormancy, resistance to apoptosis, immune evasion, and co-option of other tumor and stromal cells. Better understanding of the molecular and cellular hallmarks of MICs will facilitate the development and deployment of novel therapeutic strategies.
Topics: Animals; Anoikis; Drug Resistance, Neoplasm; Epithelial-Mesenchymal Transition; Humans; Neoplasm Metastasis; Neoplasms; Neoplastic Stem Cells
PubMed: 27083997
DOI: 10.1101/gad.277681.116 -
Cancer Genomics & Proteomics Jan 2017Exosomes are important contributors to cell-cell communication and their role as diagnostic markers for cancer and the pathogenesis for cancer is under intensive... (Review)
Review
Exosomes are important contributors to cell-cell communication and their role as diagnostic markers for cancer and the pathogenesis for cancer is under intensive investigation. Here, we focus on their role in metastasis-related processes. We discuss their impact regarding promotion of invasion and migration of tumor cells, conditioning of lymph nodes, generation of premetastatic niches and organotropism of metastasis. Furthermore, we highlight interactions of exosomes with bone marrow and stromal components such as fibroblasts, endothelial cells, myeloid- and other immune-related cells in the context of metastases. For all processes as described above, we outline molecular and cellular components for therapeutic intervention with metastatic processes.
Topics: Adipocytes; Animals; Astrocytes; Cell Communication; Cell Movement; Disease Models, Animal; Endothelial Cells; Exosomes; Fibroblasts; Humans; Hyaluronan Receptors; Lung Neoplasms; Lymph Nodes; Melanoma; Neoplasm Invasiveness; Neoplasm Metastasis; Neoplasms; Stromal Cells; Tumor Microenvironment
PubMed: 28031234
DOI: 10.21873/cgp.20015