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Surgery Nov 2022Two-stage hepatectomy for bilobar colorectal cancer liver metastases is potentially curative for selected patients. Histological growth patterns of colorectal liver...
BACKGROUND
Two-stage hepatectomy for bilobar colorectal cancer liver metastases is potentially curative for selected patients. Histological growth patterns of colorectal liver metastases (desmoplastic, replacement, and pushing) have prognostic value. Our aim was to evaluate their association with pathologic response to preoperative treatment, second-stage hepatectomy completion, and survival in patients treated with a curative-intent 2-stage hepatectomy.
METHODS
In 67 patients planned for 2-stage hepatectomy, colorectal liver metastases resected from the first-stage hepatectomy were retrospectively evaluated for growth patterns and pathologic response according to Tumor Regression Grading, modified Tumor Regression Grading, and Blazer grading. Tumor Regression Grading 1 to 3, modified Tumor Regression Grading 1 to 3, and Blazer 0 and 1 defined good responders.
RESULTS
Desmoplastic growth patterns (GP) were more frequent among good responders (P < .001). Second-stage hepatectomy completion was associated with desmoplastic growth patterns and pathologic response on univariate analysis and multivariable analyses (P = .017 and P = .041, respectively). Median follow-up was 84 months (95% confidence interval: 53.4 [not reached]). Nondesmoplastic GP patients and nonresponders had a poorer overall survival (hazard ratio = 3.86, 95% confidence interval: 2.11-7.07, P < .001 and hazard ratio = 2.14, 95% confidence interval: 1.19-3.83, P = .009, respectively) on univariate analysis. Nondesmoplastic growth pattern was the only factor associated with a poorer overall survival on multivariable analysis (hazard ratio = 4.17, 95% confidence interval: 1.79-9.74, P < .001). Nondesmoplastic GP was also associated with a poorer recurrence-free survival (hazard ratio = 2.05, 95% confidence interval: 1.13-3.70, P = .017).
CONCLUSION
Desmoplastic GP could represent a useful morphological marker for early identification of patients who might benefit from 2-stage hepatectomy completion.
Topics: Colorectal Neoplasms; Hepatectomy; Humans; Liver Neoplasms; Nitrobenzoates; Prognosis; Retrospective Studies
PubMed: 36089423
DOI: 10.1016/j.surg.2022.06.032 -
The Journal of Clinical Investigation Mar 2020Mutations in APC promote colorectal cancer (CRC) progression through uncontrolled WNT signaling. Patients with desmoplastic CRC have a significantly worse prognosis and...
Mutations in APC promote colorectal cancer (CRC) progression through uncontrolled WNT signaling. Patients with desmoplastic CRC have a significantly worse prognosis and do not benefit from chemotherapy, but the mechanisms underlying the differential responses of APC-mutant CRCs to chemotherapy are not well understood. We report that expression of the transcription factor prospero homeobox 1 (PROX1) was reduced in desmoplastic APC-mutant human CRCs. In genetic Apc-mutant mouse models, loss of Prox1 promoted the growth of desmoplastic, angiogenic, and immunologically silent tumors through derepression of Mmp14. Although chemotherapy inhibited Prox1-proficient tumors, it promoted further stromal activation, angiogenesis, and invasion in Prox1-deficient tumors. Blockade of vascular endothelial growth factor A (VEGFA) and angiopoietin-2 (ANGPT2) combined with CD40 agonistic antibodies promoted antiangiogenic and immunostimulatory reprogramming of Prox1-deficient tumors, destroyed tumor fibrosis, and unleashed T cell-mediated killing of cancer cells. These results pinpoint the mechanistic basis of chemotherapy-induced hyperprogression and illustrate a therapeutic strategy for chemoresistant and desmoplastic CRCs.
Topics: Adenomatous Polyposis Coli Protein; Angiogenesis Inhibitors; Angiopoietin-2; Animals; Antineoplastic Agents, Immunological; Cell Line; Colorectal Neoplasms; Drug Resistance, Neoplasm; Homeodomain Proteins; Humans; Immunotherapy; Matrix Metalloproteinase 14; Mice; Neoplasms, Experimental; Neovascularization, Pathologic; Tumor Suppressor Proteins; Vascular Endothelial Growth Factor A
PubMed: 32015230
DOI: 10.1172/JCI129558 -
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 -
Anticancer Research Aug 2021Desmoplastic small round-cell tumor (DSCRT) in adults is an extremely rare (age-adjusted incidence 0.3 per million) and aggressive sarcoma with limited data for optimal... (Review)
Review
BACKGROUND
Desmoplastic small round-cell tumor (DSCRT) in adults is an extremely rare (age-adjusted incidence 0.3 per million) and aggressive sarcoma with limited data for optimal management.
PATIENTS AND METHODS
Retrospective analysis of patients with DSCRT diagnosis (2010-2020) was performed following Institutional Review Board approval. The follow-up period was from pathological diagnosis to the last patient contact. Endpoints were type of response and duration of response.
RESULTS
In the current analysis, first-line treatment in all cases was vincristine, anthracycline, and cyclophosphamide alternating with ifosfamide and etoposide (VAC-IE) with 100% response for a mean duration of 9.8 (range=5-12) months. Patients received 1-4 subsequent lines of therapy. All patients received temozolomide with irinotecan (50% partial response, duration 8-9 months). Two patients that underwent consolidative cytoreductive surgery with hyperthermic intraperitoneal chemotherapy had a longer survival (30.6 vs. 11.2 months). Patients suffered 100% mortality with a median survival was 17.8 (range=11.2-30.6) months.
CONCLUSION
While aggressive multimodality treatment is always warranted for DSCRT, the options are limited by the multicentric presentation, short-lived initial response and lack of established subsequent therapy portending a poor prognosis. Consolidative cytoreductive surgery following first-line therapy may improve survival.
Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cytoreduction Surgical Procedures; Desmoplastic Small Round Cell Tumor; Humans; Hyperthermic Intraperitoneal Chemotherapy; Male; Molecular Targeted Therapy
PubMed: 34281846
DOI: 10.21873/anticanres.15179 -
Dermatologic Surgery : Official... Mar 2022Perusal of the literature of cutaneous squamous cell carcinoma (SCC) reveals that the role of the desmoplastic subtype is indistinct. Data on local infiltration and...
BACKGROUND
Perusal of the literature of cutaneous squamous cell carcinoma (SCC) reveals that the role of the desmoplastic subtype is indistinct. Data on local infiltration and recurrence are inconsistent dependent on surgical technique, histological method, and investigated collective.
OBJECTIVE
The aim of the study was to analyze local infiltration and locoregional recurrence of the desmoplastic subtype under a uniform procedure.
METHODS AND MATERIALS
Between 2005 and 2015, 320 SCCs were analyzed and histological sections of all tumors were examined. Data collection included locoregional recurrence, metastasis rate, and tumor-specific death. The median follow-up was 36.5 months.
RESULTS
The desmoplastic subtype required significant more re-excisions (70.0% vs 23.9%, p < .001), more interventions until tumor-free margins were achieved (maximal 6 vs 2; p < .001), showed more widespread tumor infiltration with larger excisional margins (median 9 mm, 2-51 mm vs median 4 mm, 1-10 mm; p < .001), and a 5-fold higher local recurrence rate (26.7% vs 5.0%, p < .001). The metastasis rate (16.6% vs 2.3%, p < .001) was increased.
CONCLUSION
The desmoplastic subtype is characterized by a widespread local infiltration associated with perineural infiltration. It seems to be a marker for decreased histological detectability with a high rate of locoregional recurrence and metastasis.
Topics: Carcinoma, Squamous Cell; Humans; Lymphatic Metastasis; Neoplasm Recurrence, Local; Prognosis; Retrospective Studies; Skin Neoplasms
PubMed: 34966121
DOI: 10.1097/DSS.0000000000003324 -
The American Journal of Surgical... Dec 2022Five cases of a heretofore unreported rare variant of thymic carcinoma characterized by a striking resemblance to adamantinoma of the mandible are described. The tumors...
Five cases of a heretofore unreported rare variant of thymic carcinoma characterized by a striking resemblance to adamantinoma of the mandible are described. The tumors occurred in 4 women and 1 man aged 58 to 76 years (mean: 67.8 y); they arose in the anterior mediastinum and measured from 5.3 to 12.0 cm in greatest diameter (mean: 8.9 cm). Presenting symptoms included chest pain, shortness of breath, and in 2 patients, pleural effusion. One tumor was asymptomatic and discovered incidentally. Histologically, the tumors were extensively desmoplastic, and the cellular proliferation was characterized by multiple islands of squamous epithelium with striking peripheral palisading of nuclei and central areas containing clear cells resembling a stellate reticulum. Areas of preexisting spindle cell thymoma were identified in 2 cases; these areas gradually merged with the higher-grade component of the lesion. Cystic changes were noted in 3 cases. Immunohistochemical studies in 3 cases showed the tumor cells were positive for cytokeratins, p40 and p63, and all showed a high proliferation rate (>50% nuclear positivity) with Ki-67. Next-generation sequencing was performed in 2 cases that showed amplification of the AKT1 gene (copy numbers 6 and 13). Clinical follow-up in 3 patients showed recurrence and metastasis after 1 and 2 years; 1 patient passed away 2 years after diagnosis due to the tumor. Desmoplastic adamantinoma-like thymic carcinoma represents an unusual histologic variant of thymic carcinoma that needs to be distinguished from metastases from similar tumors to the mediastinum.
Topics: Female; Humans; Male; Adamantinoma; Ameloblastoma; Biomarkers, Tumor; Epithelium; Hyperplasia; Keratins; Thymoma; Thymus Neoplasms; Middle Aged; Aged
PubMed: 35993584
DOI: 10.1097/PAS.0000000000001947 -
Clinical & Experimental Metastasis Jun 2022Distinct Histopathological Growth Patterns can be identified in liver metastases from melanoma, breast and colorectal cancers. For each of these distinct liver...
BACKGROUND
Distinct Histopathological Growth Patterns can be identified in liver metastases from melanoma, breast and colorectal cancers. For each of these distinct liver metastasis types the HGP has proven a biomarker for survival after partial hepatectomy, with the desmoplastic type marking favourable prognosis. Whether HGPs can be considered a pan-cancer phenomenon remains unknown. This study therefore evaluates the presence of HGPs and their prognostic value across non-colorectal non-neuroendocrine liver metastases.
METHODS
A retrospective multicentre cohort study was performed in patients who underwent curative intent resection of non-colorectal non-neuroendocrine liver metastasis. HGPs were assessed on Haematoxylin and Eosin slides according to consensus guidelines and classified as desmoplastic or non-desmoplastic. Overall- and recurrence-free survival were evaluated using Kaplan-Meier and multivariable Cox regression analysis.
RESULTS
In total, 132 patients with liver metastasis from 25 different tumour types were eligible for analysis, of which 26 (20%) had a desmoplastic HGP. Five-year OS and RFS (95%CI) were 53% (36-78%) versus 40% (30-53%), and 33% (19-61%) versus 15% (9-27%) for patients with desmoplastic compared to non-desmoplastic metastases, respectively (p = 0.031 & p = 0.004). On multivariable analysis (adjusted HR [95%CI]) a desmoplastic HGP was prognostic for both OS (0.46 [0.25-0.86]) and RFS (0.38 [0.21-0.69]).
CONCLUSIONS
This study demonstrates that HGPs apply to liver metastases across a wide variety of primary tumour origins. They hold a prognostic value in these cases, suggesting that HGPs could represent a pan-cancer biomarker for survival after surgical resection of liver metastases.
Topics: Cohort Studies; Colorectal Neoplasms; Hepatectomy; Humans; Liver Neoplasms; Prognosis; Retrospective Studies
PubMed: 35124739
DOI: 10.1007/s10585-022-10153-y -
Case Reports in Orthopedics 2020Desmoplastic fibroblastoma (DFB) is an uncommon, benign, soft tissue tumor. The tumor most often presents as a slowly growing, painless soft tissue mass and is usually...
Desmoplastic fibroblastoma (DFB) is an uncommon, benign, soft tissue tumor. The tumor most often presents as a slowly growing, painless soft tissue mass and is usually small. There have been only a few reports of patients with DFB who presented with bone invasion. Herein, we report the case of a 66-year-old woman with DFB with bone invasion in her left axilla. A lump under the left axilla was detected and was associated with pain and limited range of motion (ROM) of the shoulder. Computed tomography showed a soft tissue mass with invasion of the adjacent left humerus. Magnetic resonance imaging revealed a lesion with low signal intensity on T1- and T2-weighted images, and weak internal enhancement on postcontrast T1-weighted images with fat suppression. Histologic evaluation of a preoperative needle biopsy revealed DFB with FOSL1 expression. The tumor was marginally excised. Postoperative outpatient follow-up demonstrated a significant improvement in pain and ROM of the shoulder and no recurrence after 1 year. Even though DFB with bone invasion can cause pronounced clinical symptoms with pain and limited ROM, we conclude that simple excision is an adequate treatment.
PubMed: 32547801
DOI: 10.1155/2020/9780263 -
Acta Dermatovenerologica Croatica : ADC Jul 2020Dear Editor, Desmoplastic melanoma (DM) is a rare histological subtype of melanoma, usually presenting as a slowly-growing, amelanotic, discoid, and/or firm lesion...
Dear Editor, Desmoplastic melanoma (DM) is a rare histological subtype of melanoma, usually presenting as a slowly-growing, amelanotic, discoid, and/or firm lesion composed of spindle cells with abundant collagen (1). It is more common on sun-exposed areas, especially on head and neck in elderly patients (2). Regional lymph node involvement is reported to be less frequent than in other cutaneous melanomas (3). Desmoplastic melanoma can clinically mimic a wide spectrum of benign and malignant lesions, including Bowen's disease, desmoplastic nevus, basal cell carcinoma, squamous cell carcinoma, lentigo maligna, dermatofibrosarcoma protuberans, peripheral nerve sheath tumors, cysts, or hypertrophic/keloid scars (4). Regarding its appearance, at the time of diagnosis DM frequently presents as advanced lesions with deep infiltration. A 60-year-old man presented with an one-year history of an asymptomatic, erythematous, well-defined plaque in the right lumbar region (Figure 1). Dermatological examination revealed a 5×5 cm, pink/red infiltrated plaque accompanied by a 6 mm dark-brown melanocytic lesion. Dermoscopically, atypical vascular structures in the form of linear, irregular, and dotted vessels, milky-red areas, and atypical pigment network, and streaks were observed near the melanocytic lesion (Figure 2). A 4 mm punch biopsy was performed on the erythematous plaque next to the melanocytic lesion, and a dermal-based, paucicellular proliferation of atypical spindle cells without melanin in a sclerotic stroma was found histologically (Figure 3, a). Immunohistochemically, dermal spindle cells were stained with S-100 and HMB45 antibodies (Figure 3, b). The patient was histologically diagnosed with melanoma, of the desmoplastic subtype. The lesion was totally excised with 2 cm clear margins. A diagnosis of nonulcerated nodular melanoma with a Breslow thickness of 4 mm and a mitotic index 1/mm2 was established. Sentinel lymph node biopsy revealed no metastases. No systemic metastases were detected in PET-CT scanning and cranial magnetic resonance imaging. The patient remained under follow-up and has been free of any local recurrence or primary or systemic metastasis for 3 years. Dermoscopic characteristics of DM are not well known, probably due to it not being considered a melanocytic lesion. Debarbieux et al. first reported the dermoscopic features of desmoplastic melanoma in six cases (5). They found that only half of the cases presented one classical feature of a melanocytic lesion, whereas the other cases were diagnosed based on the presence of figures of regression such as white scar-like and "peppering", multiple (>4) color, and melanoma-related vascular patterns (five out of six) such as linear-irregular vessels and milky-red areas (5). In the largest DM case series, Jaime et al. reported that all DM featured at least 1 melanoma-specific structure, with atypical vascular structures being the most common (6). Similarly, in our patient dermoscopy showed an atypical pigment network and streaks, atypical vascular structures, and milky-red areas, which is predictive for melanoma. We reported this case to serve as a reminder to consider desmoplastic melanoma in the differential diagnosis of pink tumoral lesions despite its rarity and atypical localization.
Topics: Dermoscopy; Diagnosis, Differential; Humans; Male; Melanoma; Middle Aged; Skin Neoplasms
PubMed: 32650855
DOI: No ID Found -
Biomedicines Oct 2020Pancreatic adenocarcinoma (PDAC) originates in the glandular compartment of the exocrine pancreas. Histologically, PDAC tumors are characterized by a parenchyma that is... (Review)
Review
Pancreatic adenocarcinoma (PDAC) originates in the glandular compartment of the exocrine pancreas. Histologically, PDAC tumors are characterized by a parenchyma that is embedded in a particularly prominent stromal component or desmoplastic stroma. The unique characteristics of the desmoplastic stroma shape the microenvironment of PDAC and modulate the reciprocal interactions between cancer and stromal cells in ways that have profound effects in the pathophysiology and treatment of this disease. Here, we review some of the most recent findings regarding the regulation of PDAC cell invasion by the unique microenvironment of this tumor, and how new knowledge is being translated into novel therapeutic approaches.
PubMed: 33050151
DOI: 10.3390/biomedicines8100401