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Archives of Pathology & Laboratory... Sep 2023It is important to recognize high-grade foamy gland prostatic adenocarcinoma with desmoplastic stroma given its aggressive clinical course with frequent metastases and...
CONTEXT.—
It is important to recognize high-grade foamy gland prostatic adenocarcinoma with desmoplastic stroma given its aggressive clinical course with frequent metastases and death.
OBJECTIVE.—
To review the morphology, immunohistochemistry, and prognosis for this rare subtype of prostate adenocarcinoma.
DESIGN.—
Twenty-four cases received for consultation from 2010 to 2021 were analyzed including needle biopsy (n = 21), transurethral resection (n = 2), and a cystoprostatectomy (n = 1).
RESULTS.—
Patients ranged in age from 40 to 89 years (mean, 67 years). On average, 8 cores per case were involved (mean 67% core involvement). Extraprostatic extension and seminal vesicle invasion were observed in 6 of 21 (29%) and 3 of 21 (14%) needle biopsy cases, respectively. Twenty of the 24 cases (83%) were Grade Group (GG) 5 with 4 of 24 (17%) being GG4. Tumor necrosis as a component of Gleason pattern 5 was observed in 21 of 24 cases (88%). Associated intraductal adenocarcinoma (IDC) was observed in 22 of 24 cases (92%), with 4 of 24 cases (17%) demonstrating extensive IDC. Diagnostic challenges were as follows: (1) sparse isolated cancer glands embedded in the dense desmoplastic stroma; (2) fragmented glands; and (3) aberrant staining for high-molecular-weight cytokeratin in a nonbasal cell pattern in all cases. PTEN loss was observed in 9 cases, and p53 nuclear accumulation was observed in 8 cases. Three patients were lost to follow-up. Overall, of the 16 patients with meaningful follow-up, 12 (75%) either had metastases or died from prostate cancer.
CONCLUSIONS.—
High-grade desmoplastic foamy gland adenocarcinoma is difficult to diagnose and grade and has a poor prognosis.
Topics: Male; Humans; Adult; Middle Aged; Aged; Aged, 80 and over; Prostate; Prostatic Neoplasms; Adenocarcinoma; Prostatectomy; Biopsy, Needle
PubMed: 36399606
DOI: 10.5858/arpa.2022-0165-OA -
International Journal of Surgical... Aug 2023Desmoplastic small round cell tumor (DSRCT) is a rare aggressive malignancy typically originating from the abdominal or pelvic cavity. DSRCT presenting as a primary head... (Review)
Review
Desmoplastic small round cell tumor (DSRCT) is a rare aggressive malignancy typically originating from the abdominal or pelvic cavity. DSRCT presenting as a primary head and neck tumor has rarely been described in the literature. We present three cases of DSRCT arising in the head and neck to further characterize its clinicopathological features. All three patients were male and aged 36, 30 and 17 years. The involved sites included the orbit (1 case) and submandibular gland (2 cases). The tumors ranged in size from 2.4 to 3.5 cm (mean, 2.1 cm). Histologically, all tumors showed irregular-shaped, variable-sized nests of small round cells deposited in an abundant desmoplastic stroma. Tumor cells contained scant amounts of eosinophilic cytoplasm and small hyperchromatic nuclei with inconspicuous nucleoli. Immunohistochemically, the tumors were positive for keratin (AE1/AE3) (3/3), desmin (3/3), vimentin (2/2), NSE (1/1) and EMA (1/1). Fluorescence in situ hybridization (FISH) analysis demonstrated the presence of and rearrangements in all three cases. All patients received surgery and adjuvant chemotherapy and/or radiotherapy. There was no evidence of recurrence and metastasis in two patients, and the third suffered lung metastasis. DSRCT arising in the head and neck represents an extremely rare condition. It is easily mistaken as poorly differentiated carcinoma due to similar morphology and expression of epithelial markers. Immunohistochemistry assay in conjunction with molecular detection of fusion will be helpful for arriving at an accurate diagnosis to avoid misdiagnosis and inappropriate treatment.
Topics: Male; Humans; Female; Desmoplastic Small Round Cell Tumor; In Situ Hybridization, Fluorescence; Head; Neck; Immunohistochemistry
PubMed: 36172631
DOI: 10.1177/10668969221117989 -
Medicina 2020Desmoplastic melanoma is a rare presentation of melanoma with a different clinical behavior compared to other histological variants. Its diagnosis in early stages is a...
Desmoplastic melanoma is a rare presentation of melanoma with a different clinical behavior compared to other histological variants. Its diagnosis in early stages is a challenge due to its variable clinical presentation, with a predominant dermal component and the frequent absence of pigment. Its histology is divided into pure and mixed type, and this classification has important prognostic implications. The average Breslow thickness at diagnosis is higher than in other melanoma variants. However, the tendency to lymph node metastasis is low.
Topics: Aged; Biopsy; Diagnosis, Differential; Female; Humans; Male; Melanoma; Middle Aged; Skin Neoplasms
PubMed: 32442943
DOI: No ID Found -
Magyar Onkologia Sep 2019Colorectal carcinomas are heterogeneous in their morphologic, immunologic and molecular aspects. The smooth and sharply demarcated medullary carcinomas present with an... (Review)
Review
Colorectal carcinomas are heterogeneous in their morphologic, immunologic and molecular aspects. The smooth and sharply demarcated medullary carcinomas present with an expansive border and high tumor stroma ratio. The high load of cancer neoantigens as a consequence of microsatellite instability results in numerous reactive regional lymph nodes. In contrast, the low grade, MSS type carcinomas are spiculated, desmoplastic and hard, frequently with smaller and sometimes also desmoplastic lymph node metastases. This macroscopic and histological heterogeneity is mirrored on the immunohistochemical and molecular level and is decisive from prognostic and predictive point of view. As immunotherapy opened a new front in the therapy of colorectal cancer, the pathology report has to quantify and qualify the characteristics of the tumor microenvironment, the peritumoral and intratumoral lymphoid infiltration and tumor stroma ratio in order to improve patient selection.
Topics: Colorectal Neoplasms; Humans; Immunotherapy; Lymphatic Metastasis; Microsatellite Instability; Prognosis; Tumor Microenvironment
PubMed: 31533138
DOI: No ID Found -
Journal of Nanobiotechnology Apr 2024Tumors desmoplastic microenvironments are characterized by abundant stromal cells and extracellular matrix (ECM) deposition. Cancer-associated fibroblasts (CAFs), as the... (Review)
Review
Tumors desmoplastic microenvironments are characterized by abundant stromal cells and extracellular matrix (ECM) deposition. Cancer-associated fibroblasts (CAFs), as the most abundant of all stromal cells, play significant role in mediating microenvironments, which not only remodel ECM to establish unique pathological barriers to hinder drug delivery in desmoplastic tumors, but also talk with immune cells and cancer cells to promote immunosuppression and cancer stem cells-mediated drug resistance. Thus, CAFs mediated desmoplastic microenvironments will be emerging as promising strategy to treat desmoplastic tumors. However, due to the complexity of microenvironments and the heterogeneity of CAFs in such tumors, an effective deliver system should be fully considered when designing the strategy of targeting CAFs mediated microenvironments. Engineered exosomes own powerful intercellular communication, cargoes delivery, penetration and targeted property of desired sites, which endow them with powerful theranostic potential in desmoplastic tumors. Here, we illustrate the significance of CAFs in tumors desmoplastic microenvironments and the theranostic potential of engineered exosomes targeting CAFs mediated desmoplastic microenvironments in next generation personalized nano-drugs development.
Topics: Cancer-Associated Fibroblasts; Exosomes; Tumor Microenvironment; Humans; Animals; Neoplasms; Drug Delivery Systems; Extracellular Matrix; Antineoplastic Agents
PubMed: 38644492
DOI: 10.1186/s12951-024-02452-1 -
Melanoma Management Sep 2021
PubMed: 34900219
DOI: 10.2217/mmt-2020-0013 -
Biomaterials Feb 2020Solid tumors, especially desmoplastic tumors, are characterized by a dense fibrotic stroma composed of abundant cancer-associated fibroblasts and excessive extracellular... (Review)
Review
Solid tumors, especially desmoplastic tumors, are characterized by a dense fibrotic stroma composed of abundant cancer-associated fibroblasts and excessive extracellular matrix. These physical barriers seriously compromise drug delivery to tumor cells, leading to suboptimal treatment efficacy and resistance to current tumor-centric therapeutics. The need to overcome these problems has driven extensive investigations and sparked the flourish of anti-stromal therapy, particularly in the field of nanomedicines. In this paper, we firstly review the major components of the tumor stroma and discuss their impact on drug delivery. Then, according to the different stromal targets, we summarize the current status of anti-stromal therapy and highlight recent advances in anti-stromal nanomedicines. We further examine the potential of nano-enabled anti-stromal therapy to enhance the anti-tumor efficacy of other therapeutic modalities, including chemotherapy, immunotherapy, phototherapy and radiotherapy. Finally, the potential concerns and future developments of anti-stromal nanomedicines are discussed.
Topics: Antineoplastic Agents; Drug Delivery Systems; Humans; Immunotherapy; Nanomedicine; Neoplasms
PubMed: 31918228
DOI: 10.1016/j.biomaterials.2019.119745 -
Journal of Clinical Medicine Nov 2022Cholangiocarcinoma (CCA) is an aggressive neoplasia with an increasing incidence and mortality. It is characterized by a strong desmoplastic stroma surrounding cancer... (Review)
Review
Cholangiocarcinoma (CCA) is an aggressive neoplasia with an increasing incidence and mortality. It is characterized by a strong desmoplastic stroma surrounding cancer cells. Cancer-associated fibroblasts (CAFs) are the main cell type of CCA stroma and they have an important role in modulating cancer microenvironments. CAFs originate from multiple lines of cells and mainly consist of fibroblasts and alpha-smooth muscle actin (α-SMA) positive myofibroblast-like cells. The continuous cross-talking between CCA cells and desmoplastic stroma is permitted by CAF biochemical signals, which modulate a number of pathways. Stromal cell-derived factor-1 expression increases CAF recruitment to the tumor reactive stroma and influences apoptotic pathways. The Bcl-2 family protein enhances susceptibility to CAF apoptosis and PDGFRβ induces fibroblast migration and stimulates tumor lymphangiogenesis. Many factors related to CAFs may influence CCA prognosis. For instance, a better prognosis is associated with IL-33 expression and low stromal IL-6 (whose secretion is stimulated by microRNA). In contrast, a worst prognosis is given by the expression of PDGF-D, podoplanin, SDF-1, α-SMA high expression, and periostin. The maturity phenotype has a prognostic relevance too. New therapeutic strategies involving CAFs are currently under study. Promising results are obtained with anti-PlGF therapy, nintedanib (BIBF1120), navitoclax, IPI-926, resveratrol, and controlled hyperthermia.
PubMed: 36362726
DOI: 10.3390/jcm11216498 -
International Journal of Surgical... Sep 2023. Tumour budding and desmoplastic reactions in peritumoural stroma are features of the tumour microenvironment that are associated with colorectal cancer prognosis but...
. Tumour budding and desmoplastic reactions in peritumoural stroma are features of the tumour microenvironment that are associated with colorectal cancer prognosis but have not been as thoroughly examined in gastric cancer. We aimed to further characterize the prognostic role of tumour budding and desmoplastic reaction in gastric adenocarcinoma with intestinal differentiation. . 76 curative gastrectomy specimens were identified, excluding post-neoadjuvant cases or cases with >50% diffuse-type histology. Tumour budding was defined and graded according to the International Tumor Budding Consensus Conference recommendations and desmoplastic reaction was classified as described by Ueno et al 2017. Tumour budding and desmoplastic reaction were analyzed for associations with pathologic features and clinical outcomes. . Tumour budding was associated with pT ( < .001), pN ( < .004), overall stage ( < .001), LVI ( < .001) and PNI ( = .002). Desmoplastic reaction was associated with pT ( < .001), pN ( = .005), overall stage ( = .031) and PNI ( < .001), but not LVI. Survival analysis showed decreased overall survival (OS) and recurrence-free survival (RFS) for intermediate and high grade tumour budding ( = .031, .014 respectively). Immature stroma was significantly associated with RFS but not OS. Neither tumour budding nor desmoplastic reaction were independent predictors of OS or RFS on multivariate analysis in this cohort. . Tumour budding and desmoplastic reaction were associated with known pathologic risk factors. Prognostically, tumour budding was associated with OS and RFS while desmoplastic reaction was associated with RFS only. Our data suggest that tumour budding and desmoplastic reaction have prognostic value in intestinal-type gastric adenocarcinoma.
Topics: Humans; Prognosis; Stomach Neoplasms; Neoplasm Staging; Adenocarcinoma; Survival Analysis; Retrospective Studies; Tumor Microenvironment
PubMed: 35726174
DOI: 10.1177/10668969221105617 -
Nano Letters Nov 2022The desmoplastic stroma imposes a fatal physical delivery barrier in pancreatic ductal adenocarcinoma (PDAC) therapy. Deconstructing the stroma components hence...
The desmoplastic stroma imposes a fatal physical delivery barrier in pancreatic ductal adenocarcinoma (PDAC) therapy. Deconstructing the stroma components hence predominates in stroma-targeting approaches, but conflicting outcomes have sometimes occurred due to the multifaceted nature of the stroma. Here, we constructed two sub-20-nm nanomedicines based on a so-called "next-wave" antifibrotic halofuginone (HF) and the tumoricidal paclitaxel (PTX) for enhanced PDAC chemotherapy. This was achieved by coassembling methoxy poly(ethylene glycol)--poly(caprolactone) with ketal-linked HF- and PTX-derived prodrugs. HF nanomedicine and PTX nanomedicine had excellent prodrug-nanocarrier compatibility and exhibited greatly improved pharmacokinetic profiles and high tumor accumulation. HF nanomedicine pretreatment restored stromal homeostasis and considerably facilitated the distribution of PTX nanomedicine and its penetration into carcinoma cells, leading to positive modulation of the infiltration of cytotoxic T cells and significant regression of tumor growth in two PDAC models. Our nanomedicine-based stromal remodeling strategy appears promising for treating desmoplastic malignancies.
Topics: Humans; Nanomedicine; Pancreatic Neoplasms; Carcinoma, Pancreatic Ductal; Paclitaxel; Prodrugs; Homeostasis; Cell Line, Tumor
PubMed: 36279310
DOI: 10.1021/acs.nanolett.2c03663