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Actas Dermo-sifiliograficas Jan 2022Desmoplastic melanoma (DM) accounts for 0.4% to 4% of all melanomas. These skin tumors are mainly formed by amelanotic spindled melanocytes immersed in an abundant... (Review)
Review
Desmoplastic melanoma (DM) accounts for 0.4% to 4% of all melanomas. These skin tumors are mainly formed by amelanotic spindled melanocytes immersed in an abundant collagen stroma and are classified as pure when the desmoplastic component accounts for at least 90% of the invasive tumor and as mixed or combined otherwise. DMs are more common in men (male to female ratio, 1.7 to 2:1), and the mean age at diagnosis is 66 to 69 years. The tumors tend to occur in chronically sun-exposed areas, often in association with lentigo maligna, and are difficult to recognize because they can resemble a scar, presenting as a firm, unpigmented papule or plaque with poorly defined borders. DMs also have a strong tendency to recur locally, and pure variants rarely spread to the lymph nodes. Nonetheless, recently published series suggest that patients with DM have a similar prognosis to those with nondesmoplastic melanoma of the same thickness. The clinical management of DM varies in certain aspects from that of other melanomas and is reviewed in this article.
PubMed: 35249710
DOI: 10.1016/j.ad.2021.06.004 -
The Journal of Pathology Feb 2023The FOS gene family has been implicated in tumourigenesis across several tumour types, particularly mesenchymal tumours. The rare fibrous tumour desmoplastic...
The FOS gene family has been implicated in tumourigenesis across several tumour types, particularly mesenchymal tumours. The rare fibrous tumour desmoplastic fibroblastoma is characterised by overexpression of FOSL1. However, previous studies using cytogenetic and molecular techniques did not identify an underlying somatic change involving the FOSL1 gene to explain this finding. Prompted by an unusual index case, we report the discovery of a novel FOSL1 rearrangement in desmoplastic fibroblastoma using whole-genome and targeted RNA sequencing. We investigated 15 desmoplastic fibroblastomas and 15 fibromas of tendon sheath using immunohistochemistry, in situ hybridisation and targeted RNA sequencing. Rearrangements in FOSL1 and FOS were identified in 10/15 and 2/15 desmoplastic fibroblastomas respectively, which mirrors the pattern of FOS rearrangements observed in benign bone and vascular tumours. Fibroma of tendon sheath, which shares histological features with desmoplastic fibroblastoma, harboured USP6 rearrangements in 9/15 cases and did not demonstrate rearrangements in any of the four FOS genes. The overall concordance between FOSL1 immunohistochemistry and RNA sequencing results was 90%. These findings illustrate that FOSL1 and FOS rearrangements are a recurrent event in desmoplastic fibroblastoma, establishing this finding as a useful diagnostic adjunct and expanding the spectrum of tumours driven by FOS gene family alterations. © 2022 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Topics: Humans; Fibroma, Desmoplastic; Fibroma; Gene Rearrangement; In Situ Hybridization; Soft Tissue Neoplasms; Ubiquitin Thiolesterase
PubMed: 36426824
DOI: 10.1002/path.6038 -
Cancer Science Sep 2023Desmoplastic reaction is a fibrosis reaction that is characterized by a large amount of dense extracellular matrix (ECM) and dense fibrous stroma. Fibrotic stroma around... (Review)
Review
Desmoplastic reaction is a fibrosis reaction that is characterized by a large amount of dense extracellular matrix (ECM) and dense fibrous stroma. Fibrotic stroma around the tumor has several different components, including myofibroblasts, collagen, and other ECM molecules. This stromal reaction is a natural response to the tissue injury process, and fibrosis formation is a key factor in pancreatic cancer development. The fibrotic stroma of pancreatic cancer is associated with tumor progression, metastasis, and poor prognosis. Reportedly, multiple processes are involved in fibrosis, which is largely associated with the upregulation of various cytokines, chemokines, matrix metalloproteinases, and other growth factors that promote tumor growth and metastasis. Fibrosis is also associated with immunosuppressive cell recruitment, such as regulatory T cells (Tregs) with suppressing function to antitumor immunity. Further, dense fibrosis restricts the flow of nutrients and oxygen to the tumor cells, which can contribute to drug resistance. Furthermore, the dense collagen matrix can act as a physical barrier to block the entry of drugs into the tumor, thereby further contributing to drug resistance. Thus, understanding the mechanism of desmoplastic reaction and fibrosis in pancreatic cancer will open an avenue to innovative medicine and improve the prognosis of patients suffering from this disease.
Topics: Humans; Pancreatic Neoplasms; Pancreas; Extracellular Matrix; Cytokines
PubMed: 37480223
DOI: 10.1111/cas.15890 -
The Pan African Medical Journal 2019The term desmoplastic infantile ganglioglioma was coined by VandenBerg et al in 1987. In their first report these authors referred to a rare, distinct brain tumor. About...
The term desmoplastic infantile ganglioglioma was coined by VandenBerg et al in 1987. In their first report these authors referred to a rare, distinct brain tumor. About 60 cases of desmoplastic infantile ganglioglioma have been described in the literature since its first description. We report a case of a 6-year-old girl who was admitted for seizure without family history. Magnetic resonance imaging scan showed a hypodense area in the right temporal region. A right temporal craniotomy was performed and the tumor was excised. The pathologic examination revealed the diagnosis of desmoplastic infantile ganglioglioma.
Topics: Brain Neoplasms; Child; Craniotomy; Female; Ganglioglioma; Humans; Magnetic Resonance Imaging; Seizures
PubMed: 31223403
DOI: 10.11604/pamj.2019.32.113.12669 -
BioRxiv : the Preprint Server For... Aug 2023The desmoplastic stroma in solid tumors presents a formidable challenge to immunotherapies that rely on endogenous or adoptively transferred T cells, however, the...
The desmoplastic stroma in solid tumors presents a formidable challenge to immunotherapies that rely on endogenous or adoptively transferred T cells, however, the mechanisms are poorly understood. To define mechanisms involved, we treat established desmoplastic pancreatic tumors with CAR T cells directed to fibroblast activation protein (FAP), an enzyme highly overexpressed on a subset of cancer-associated fibroblasts (CAFs). Depletion of FAPCAFs results in loss of the structural integrity of desmoplastic matrix. This renders these highly treatment-resistant cancers susceptible to subsequent treatment with a tumor antigen (mesothelin)-targeted CAR and to anti-PD1 antibody therapy. Mechanisms include overcoming stroma-dependent restriction of T cell extravasation and/or perivascular invasion, reversing immune exclusion, relieving T cell suppression, and altering the immune landscape by reducing myeloid cell accumulation and increasing endogenous CD8 T cell and NK cell infiltration. These data provide strong rationale for combining tumor stroma- and malignant cell-targeted therapies to be tested in clinical trials.
PubMed: 37090547
DOI: 10.1101/2023.04.13.536777 -
Disease Models & Mechanisms Jun 2023This study exploited a novel patient-derived xenograft (PDX) of desmoplastic small round cell tumor (DSRCT), which reproduces histomorphological and molecular...
This study exploited a novel patient-derived xenograft (PDX) of desmoplastic small round cell tumor (DSRCT), which reproduces histomorphological and molecular characteristics of the clinical tumor, to assess the activity of cytotoxic and targeted anticancer agents. Antitumor effect was moderate for doxorubicin, pazopanib and larotrectenib [maximum tumor volume inhibition (max TVI), 55-66%], while trabectedin had higher activity (max TVI, 82%). Vinorelbine, irinotecan and eribulin achieved nearly complete tumor growth inhibition (max TVI, 96-98%), although tumors regrew after the end of treatment. The combination of irinotecan with either eribulin or trabectedin resulted in complete responses, which were maintained until the end of the experiment for irinotecan plus trabectedin. Irinotecan-based combinations nearly abrogated the expression of proteins of the G2/M checkpoint, preventing cell entrance in mitosis, and induced apoptotic and necroptotic cell death. Consistently, irinotecan plus trabectedin resulted in reprogramming of DSCRT transcriptome, with downregulation of E2F targets, G2/M checkpoint and mitotic spindle gene sets. This study emphasizes the importance of patient-derived preclinical models to explore new treatments for DSRCT and fosters clinical investigation into the activity of irinotecan plus trabectedin.
Topics: Humans; Trabectedin; Irinotecan; Desmoplastic Small Round Cell Tumor; Heterografts; Antineoplastic Agents
PubMed: 37158111
DOI: 10.1242/dmm.049649 -
Journal of Pharmacy & Bioallied Sciences Jul 2023Desmoplastic ameloblastoma (DA) is a rare variant of conventional ameloblastoma. It accounts for only 4%-13% of all ameloblastomas. DA was included in the World Health...
Desmoplastic ameloblastoma (DA) is a rare variant of conventional ameloblastoma. It accounts for only 4%-13% of all ameloblastomas. DA was included in the World Health Organization Classification of Head and Neck Tumors (WHO-2005) as a variant of ameloblastoma with specific clinical, imaging, and histological features. The desmoplastic variant of ameloblastoma usually appears in the anterior and premolar regions as a mixed radiolucent and radiopaque lesion, sometimes resembling a benign fibro-osseous lesion.Ameloblastoma is a locally aggressive tumor that may cause recurrence and in rare cases, malignant transformation with repeated postsurgical recurrences. In this paper, we present a case of a 28-year-old female with swelling in the left upper jaw, a biopsy of which turned out to be DA.
PubMed: 37654261
DOI: 10.4103/jpbs.jpbs_44_23 -
Frontiers in Oncology 2021Desmoplastic small round cell tumor (DRSCT) is a highly aggressive primitive sarcoma that primarily affects adolescent and young adult males. The 5-year survival rate is... (Review)
Review
Desmoplastic small round cell tumor (DRSCT) is a highly aggressive primitive sarcoma that primarily affects adolescent and young adult males. The 5-year survival rate is 15-30% and few curative treatment options exist. Although there is no standard treatment for DSRCT, patients are most often treated with a combination of aggressive chemotherapy, radiation, and surgery. Targeted therapy inhibitors of PDGFA and IGF-1R, which are almost uniformly overexpressed in DSRCT, have largely failed in clinical trials. As in cancer in general, interest in immunotherapy to treat DSRCT has increased in recent years. To that end, several types of immunotherapy are now being tested clinically, including monoclonal antibodies, radionuclide-conjugated antibodies, chimeric antigen receptor T cells, checkpoint inhibitors, and bispecific antibodies (BsAbs). These types of therapies may be particularly useful in DSRCT, which is frequently characterized by widespread intraperitoneal implants, which are difficult to completely remove surgically and are the frequent cause of relapse. Successful treatment with immunotherapy or radioimmunotherapy following debulking surgery could eradiate these micrometasteses and prevent relapse. Although there has been limited success to date for immunotherapy in pediatric solid tumors, the significant improvements in survival seen in the treatment of other pediatric solid tumors, such as metastatic neuroblastoma and its CNS spread, suggest a potential of immunotherapy and specifically compartmental immunotherapy in DSRCT.
PubMed: 34869013
DOI: 10.3389/fonc.2021.772862 -
World Journal of Gastroenterology Jul 2022Liver is the most common site of metastases of colorectal cancer, and liver metastases present with distinct histopathological growth patterns (HGPs), including... (Review)
Review
Liver is the most common site of metastases of colorectal cancer, and liver metastases present with distinct histopathological growth patterns (HGPs), including desmoplastic, pushing and replacement HGPs and two rare HGPs. HGP is a miniature of tumor-host reaction and reflects tumor biology and pathological features as well as host immune dynamics. Many studies have revealed the association of HGPs with carcinogenesis, angiogenesis, and clinical outcomes and indicates HGP functions as bond between microscopic characteristics and clinical implications. These findings make HGP a candidate marker in risk stratification and guiding treatment decision-making, and a target of imaging observation for patient screening. Of note, it is crucial to determine the underlying mechanism shaping HGP, for instance, immune infiltration and extracellular matrix remodeling in desmoplastic HGP, and aggressive characteristics and special vascularization in replacement HGP (rHGP). We highlight the importance of aggressive features, vascularization, host immune and organ structure in formation of HGP, hence propose a novel "advance under camouflage" hypothesis to explain the formation of rHGP.
Topics: Cell Proliferation; Colorectal Neoplasms; Humans; Liver Neoplasms; Neovascularization, Pathologic
PubMed: 36051338
DOI: 10.3748/wjg.v28.i26.3101