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The Journal of Veterinary Medical... Jun 2017A 10-year-old mixed breed dog was presented with a 0.8 cm diameter mass below the left eye region. The mass was surgically removed and processed for histopathological...
A 10-year-old mixed breed dog was presented with a 0.8 cm diameter mass below the left eye region. The mass was surgically removed and processed for histopathological examination. Microscopically, tumor cells proliferated in small lobules, nests and cords, and the tumor parenchyma was separated by desmoplastic stroma. Majority of the tumor cells were periodic acid-Schiff (PAS)-positive, and the desmoplastic stroma was densely collagenous and mucinous. Immunohistochemical results showed that the tumor cells were diffusely positive for cytokeratin 15, cytokeratin 19 and CD 34, while cytokeratin 8 reactivity was limited to the tumor cells proliferating in cords. Few tumor cells were positive for nestin. Based on the histopathological findings, the tumor was diagnosed as desmoplastic tricholemmoma.
Topics: Animals; Dermis; Diagnosis, Differential; Dog Diseases; Dogs; Female; Hair Diseases; Hair Follicle; Immunohistochemistry; Keratins; Skin Neoplasms
PubMed: 28458277
DOI: 10.1292/jvms.17-0178 -
Journal of Cancer Research and Clinical... Jul 2020Desmoplastic small round cell tumors (DSRCTs) are highly malignant and very rare soft tissue sarcomas with a high unmet need for new therapeutic options. Therefore, we...
PURPOSE
Desmoplastic small round cell tumors (DSRCTs) are highly malignant and very rare soft tissue sarcomas with a high unmet need for new therapeutic options. Therefore, we examined poly(ADP-ribose) polymerase 1 (PARP1) and Schlafen-11 (SLFN11) expression in DSRCT tumor tissue and the combination of PARP inhibitor olaparib with the alkylating agent temozolomide (TMZ) in a preclinical DSRCT model.
METHODS
PARP1 and SLFN11 have been described as predictive biomarkers for response to PARP inhibition. Expression of PARP1 and SLFN11 was assessed in 16 and 12 DSRCT tumor tissue samples, respectively. Effects of single-agent olaparib, and olaparib and TMZ combination treatment were examined using the preclinical JN-DSRCT-1 model. In vitro, single-agent and combination treatment effects on cell viability, the cell cycle, DNA damage and apoptosis were examined. Olaparib and TMZ combination treatment was also assessed in vivo.
RESULTS
PARP1 and SLFN11 expression was observed in 100% and 92% of DSRCT tumor tissues, respectively. Olaparib treatment reduced cell viability and cell migration in a dose-dependent manner in vitro. Drug synergy between olaparib and TMZ was observed in vitro and in vivo. Combination treatment led to a cell-cycle arrest and induction of DNA damage and apoptosis, even when combined at low dosages.
CONCLUSION
We show high PARP1 and SLFN11 expression in DSRCT tumor material and antitumor effects following olaparib and TMZ combination treatment in a preclinical DSRCT model. This suggests that olaparib and TMZ combination treatment could be a potential treatment option for DSRCTs.
Topics: Adolescent; Adult; Animals; Antineoplastic Agents; Apoptosis; Cell Line, Tumor; Cell Survival; Child; Desmoplastic Small Round Cell Tumor; Disease Models, Animal; Drug Synergism; Female; Gene Expression; Humans; Male; Mice; Nuclear Proteins; Phthalazines; Piperazines; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerase Inhibitors; Temozolomide; Xenograft Model Antitumor Assays; Young Adult
PubMed: 32279088
DOI: 10.1007/s00432-020-03211-z -
Cureus Aug 2020Desmoplastic trichoepitheliomas (DTEs) are benign cutaneous neoplasms that originate from the hair follicle and exhibit a preference for the facial region. This type of... (Review)
Review
Desmoplastic Trichoepithelioma: Histopathologic and Immunohistochemical Criteria for Differentiation of a Rare Benign Hair Follicle Tumor From Other Cutaneous Adnexal Tumors.
Desmoplastic trichoepitheliomas (DTEs) are benign cutaneous neoplasms that originate from the hair follicle and exhibit a preference for the facial region. This type of neoplasm is characterized by accelerated growth, with vigorous histologic and immunohistochemical features that may be confused with other skin cancers. Thus, the objective of this study is to establish a definitive diagnosis that can be widely used. This review was systematically carried out and includes case series and studies to establish valuable data that can be used for research. The articles were sought in PubMed, MEDLINE, and Google Scholar using the keywords "desmoplastic trichoepithelioma," "morphea basal cell carcinoma," "microcystic adnexal carcinoma," "syringoma," and "cutaneous breast carcinoma." From a total of 65 journal articles, we chose 42 studies describing the clinical features, etiology, histopathology, and immunohistochemical characteristics of tumors. After quality assessment, 10 studies were selected, representing the differentiating features among the four mentioned cutaneous tumors. The differential diagnosis of DTE also includes other cutaneous and follicular tumors. At present, there is no standardized grading system for trichogenic tumors, although several symptomatic terms have been offered. More recently, immunohistochemistry and histopathological studies support the differentiation between the above-mentioned cutaneous tumors. However, additional research needs to be conducted to obtain complete information regarding the specific distinct traits of the indicated cutaneous tumors.
PubMed: 32923292
DOI: 10.7759/cureus.9703 -
Frontiers in Oncology 2019Malignant tumors are highly heterogeneous and likely contain a subset of cancer cells termed cancer stem cells (CSCs). CSCs exist in a dynamic equilibrium with their... (Review)
Review
Malignant tumors are highly heterogeneous and likely contain a subset of cancer cells termed cancer stem cells (CSCs). CSCs exist in a dynamic equilibrium with their microenvironments and the CSC phenotype is tightly regulated by both cell-intrinsic and cell-extrinsic factors including those derived from their surrounding cells or stroma. Many human solid tumors like breast, lung, colorectal and pancreatic cancers are characterized by a pronounced stromal reaction termed "the desmoplastic response." Carcinoma-associated fibroblasts (CAFs) derived either from resident fibroblasts or tumor-infiltrating mesenchymal stem cells (MSCs) are a major component of the stroma in desmoplastic cancers. Recent studies identified subpopulations of CAFs proficient in secreting a plethora of factors to foster CSCs, tumor growth, and invasion. In addition, cytotoxic therapy can lead to the enrichment of functionally perturbed CAFs, which are endowed with additional capabilities to enhance cancer stemness, leading to treatment resistance and tumor aggressiveness. When recruited into the tumor stroma, bone-marrow-derived MSCs can promote cancer stemness by secreting a specific set of paracrine factors or converting into pro-stemness CAFs. Thus, blockade of the crosstalk of pro-stemness CAFs and MSCs with CSCs may provide a new avenue to improving the therapeutic outcome of desmoplastic tumors. This up-to-date, in-depth and balanced review describes the recent progress in understanding the pro-stemness roles of CAFs and tumor-infiltrating MSCs and the associated paracrine signaling processes. We emphasize the effects of systemic chemotherapy on the CAF/MSC-CSC interplay. We summarize various promising and novel approaches in mitigating the stimulatory effect of CAFs or MSCs on CSCs that have shown efficacies in preclinical models of desmoplastic tumors and highlight the unique advantages of CAF- or MSC-targeted therapies. We also discuss potential challenges in the clinical development of CSC- or MSC-targeted therapies and propose CAF-related biomarkers that can guide the next-generation clinical studies.
PubMed: 31417869
DOI: 10.3389/fonc.2019.00688 -
Cells Apr 2021Desmoplastic tumors correspond to a unique tissue structure characterized by the abnormal deposition of extracellular matrix. Breast tumors are a typical example of this... (Review)
Review
Desmoplastic tumors correspond to a unique tissue structure characterized by the abnormal deposition of extracellular matrix. Breast tumors are a typical example of this type of lesion, a property that allows its palpation and early detection. Fibrillar type I collagen is a major component of tumor desmoplasia and its accumulation is causally linked to tumor cell survival and metastasis. For many years, the desmoplastic phenomenon was considered to be a reaction and response of the host tissue against tumor cells and, accordingly, designated as "desmoplastic reaction". This notion has been challenged in the last decades when desmoplastic tissue was detected in breast tissue in the absence of tumor. This finding suggests that desmoplasia is a preexisting condition that stimulates the development of a malignant phenotype. With this perspective, in the present review, we analyze the role of extracellular matrix remodeling in the development of the desmoplastic response. Importantly, during the discussion, we also analyze the impact of obesity and cell metabolism as critical drivers of tissue remodeling during the development of desmoplasia. New knowledge derived from the dynamic remodeling of the extracellular matrix may lead to novel targets of interest for early diagnosis or therapy in the context of breast tumors.
Topics: Animals; Breast Neoplasms; Carcinogenesis; Extracellular Matrix; Female; Humans; Protein-Lysine 6-Oxidase; Signal Transduction
PubMed: 33946660
DOI: 10.3390/cells10051046 -
Annals of Coloproctology Feb 2019We evaluated the relationship of cancer-associated fibroblasts (CAFs) and desmoplastic reactions with cancer invasiveness and long-term outcomes in patients with...
PURPOSE
We evaluated the relationship of cancer-associated fibroblasts (CAFs) and desmoplastic reactions with cancer invasiveness and long-term outcomes in patients with colorectal cancer (CRC).
METHODS
Histologic evaluation of mature CAFs and desmoplasia was performed by observing the collagen fiber structure and fibroblast cytomorphology in the intratumoral stroma and invasive front of CRC tissues. Cancer-cell invasiveness was evaluated using lymphatic invasion, vascular invasion, perineural invasion, tumor budding, and tumor growth patterns. Overall survival and systemic recurrence were analyzed. A network analysis was performed between CAF maturation, desmoplastic reaction, and cancer invasiveness.
RESULTS
The proportions of mature CAFs in the intratumoral stroma and the invasive front were 57.6% and 60.3%, respectively. Epidermal growth factor receptor (EGFR) overexpression was significantly higher in the mature CAFs in the invasive front as compared to immature CAFs. Lymphatic invasion increased as the number of mature fibroblasts in the intratumoral stroma increased. Tumor budding was observed in almost half of both mature and immature stroma samples and occurred more frequently in infiltrating tumors. On network analysis, well-connected islands were identified that was associated with EGFR overexpression, CAF maturation, and infiltrating tumor growth patterns leading to tumor budding.
CONCLUSION
The maturity of CAFs and desmoplastic reactions were associated with cancer invasion. However, the cytomorphologic characteristics of CAFs were insufficient as an independent prognostic factor for patients with CRC.
PubMed: 30879282
DOI: 10.3393/ac.2018.09.10 -
Cancers Jun 2022The deposition of collagen-rich desmoplastic tissue is a well-documented feature of the solid tumor microenvironment (TME). However, efforts to target the desmoplastic... (Review)
Review
The deposition of collagen-rich desmoplastic tissue is a well-documented feature of the solid tumor microenvironment (TME). However, efforts to target the desmoplastic extracellular matrix (ECM) en masse, or collagen molecules more specifically, have been met with mixed and sometimes paradoxical results. In this review, we posit that these discrepancies are due-at least in part-to the incredible diversity of the collagen superfamily. Specifically, whereas studies of "collagen-targeting" approaches frequently refer to "collagen" as a single molecule or relatively homogeneous molecular family, 28 individual collagens have been identified in mammalian tissues, each with a unique structure, supramolecular assembly pattern, tissue distribution, and/or function. Moreover, some collagen species have been shown to exert both pro- and anti-neoplastic effects in the desmoplastic TME, even within the same cancer type. Therefore, herein, we describe the diversity of the collagen family in normal tissues and highlight the context-specific roles of individual collagen molecules in desmoplastic tumors. We further discuss how this heterogeneity relates to the variable efficacy of "collagen-targeting" strategies in this setting and provide guidance for future directions in the field.
PubMed: 35804902
DOI: 10.3390/cancers14133132 -
Current Oncology (Toronto, Ont.) Mar 2023Desmoplastic small round cell tumor is a very rare and highly aggressive soft tissue sarcoma, usually presenting with multiple intra-abdominal tumors in young males.... (Review)
Review
Desmoplastic small round cell tumor is a very rare and highly aggressive soft tissue sarcoma, usually presenting with multiple intra-abdominal tumors in young males. Patients present with advanced disease and the overall survival is dismal. Multiple studies report relatively favorable outcomes with multimodal treatment consisting of chemotherapy, surgery and radiotherapy. If resection is feasible, complete cytoreductive surgery is the cornerstone of surgical treatment. The benefit of hyperthermic intraperitoneal chemotherapy in addition to cytoreductive surgery is unclear, and few studies have evaluated this option. We sought to identify the role of hyperthermic intraperitoneal chemotherapy in patients with intra-abdominal desmoplastic small round cell tumor. Our review of the available literature revealed no clear survival benefit in performing hyperthermic intraperitoneal chemotherapy after cytoreductive surgery.
Topics: Male; Humans; Hyperthermic Intraperitoneal Chemotherapy; Desmoplastic Small Round Cell Tumor; Peritoneal Neoplasms; Combined Modality Therapy; Sarcoma
PubMed: 37185412
DOI: 10.3390/curroncol30040299 -
Oncoimmunology 2023Tertiary lymphoid structures (TLS) are ectopic lymphoid structures that can arise in human cancers and are associated with improved overall survival (OS) and response to...
Tertiary lymphoid structures in desmoplastic melanoma have increased lymphocyte density, lymphocyte proliferation, and immune cross talk with tumor when compared to non-desmoplastic melanomas.
Tertiary lymphoid structures (TLS) are ectopic lymphoid structures that can arise in human cancers and are associated with improved overall survival (OS) and response to immune checkpoint blockade (ICB) in several cancers, including non-desmoplastic metastatic melanoma (NDMM). Desmoplastic melanoma (DM) has one of the highest response rates to ICB, and we previously identified that primary DM (PDM) contains TLS. Despite the association of TLS with survival and ICB response, it is unknown whether TLS or associated markers of immune activity can differ between PDM and NDMM. We hypothesized that PDM would contain higher frequencies of TLS than NDMM, that T and B-cell densities and proliferation would be greater in TLS of PDM than TLS of NDMM, and that proliferation rates of T and B-cells in PDM TLS would be concordant with those of intratumoral lymphocytes. We found that four features of TLS in PDM distinguish them from TLS in NDMM. TLS were peritumoral in NDMM but intratumoral in PDM. CD8 T-cell and CD20 B-cell densities and proliferative fractions were higher in PDM TLS than NDMM TLS. Additionally, the proliferative fractions of T- and B-cells were concordant between the TLS and tumor site in PDM and discordant in NDMM. Collectively, these data suggest that TLS and associated immune markers can differ across melanoma subsets and suggest that PDM TLS may be more immunologically active and have enhanced immune cell trafficking between tumor and TLS compared to NDMM.
Topics: Humans; Biomarkers; CD8-Positive T-Lymphocytes; Cell Proliferation; Melanoma; Tertiary Lymphoid Structures
PubMed: 36632563
DOI: 10.1080/2162402X.2022.2164476 -
Journal of the Korean Association of... Apr 2018Desmoplastic melanoma of the oral cavity is an extremely rare condition that is often confused on initial diagnosis with non-melanotic benign lesion or spindle cell...
OBJECTIVES
Desmoplastic melanoma of the oral cavity is an extremely rare condition that is often confused on initial diagnosis with non-melanotic benign lesion or spindle cell tumors. The purpose of this article was to raise awareness of the disease using a literature review.
MATERIALS AND METHODS
We analyzed 19 desmoplastic melanoma cases reported in the literature and added our experience. Data on clinical, histopathology, treatment, and survival were retrieved and analyzed. Survival analysis was by the Kaplan-Meier method.
RESULTS
Initial clinical and histopathological features were indistinctive, and a definite diagnosis of desmoplastic melanoma at initial assessment was possible in only 23.5% of cases. Among tests, immunohistochemical studies for S-100 and vimentin were all positive. The 5-year disease-free survival rate for oral desmoplastic melanoma was 0%, and the 5-year overall survival rate was 55.0%.
CONCLUSION
Oral desmoplastic melanoma has a high percentage of initial misdiagnosis and propensity for local recurrence. Thus, careful initial diagnosis and adequate surgery may result in improved overall survival.
PubMed: 29732311
DOI: 10.5125/jkaoms.2018.44.2.66