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Child's Nervous System : ChNS :... Jul 2024Desmoplastic fibroma (DF) is an uncommon intermediate bone tumor rarely involving the skull with unidentified pathogenesis. We report the first case of pediatric... (Review)
Review
PURPOSE
Desmoplastic fibroma (DF) is an uncommon intermediate bone tumor rarely involving the skull with unidentified pathogenesis. We report the first case of pediatric temporoparietal cranial desmoplastic fibroma (DF) with a CTNNB1 gene mutation and review the previous literature.
CASE PRESENTATION
A 3-year-old boy had a firm, painless mass on the right temporoparietal region for 22 months. The cranial CT scan showed isolated osteolytic destruction in the outer plate and diploe of the right temporoparietal bone. Gross total resection of the lesion and cranioplasty were performed. After that, a growing epidural hematoma was observed so another operation was performed to remove the artificial titanium plate. Postoperative pathology indicated a DF diagnosis and molecular pathology suggested a missense mutation in exon 3 of the CTNNB1 gene (c.100G > A,p.Gly34Arg).
CONCLUSION
Pediatric cranial DF is rare and easy to be misdiagnosed before operation. For cranial DF, lesion resection can be performed and perioperative management should be strengthened. Mutations in the CTNNB1 gene might be one of the molecular pathologic features of DF.
Topics: Humans; Male; beta Catenin; Child, Preschool; Fibroma, Desmoplastic; Skull Neoplasms; Mutation; Tomography, X-Ray Computed
PubMed: 38635072
DOI: 10.1007/s00381-024-06375-y -
Quantitative Imaging in Medicine and... Apr 2024
Multimodality imaging of ureteral desmoplastic small round cell tumor: a case description and literature analysis of F-fluoro-2-deoxy-d-glucose positron emission tomography-computed tomography findings.
PubMed: 38617166
DOI: 10.21037/qims-23-1649 -
Cancer Letters Jun 2024Pancreatic ductal adenocarcinoma (PDAC) is a solid organ malignancy with a high mortality rate. Statistics indicate that its incidence has been increasing as well as the... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) is a solid organ malignancy with a high mortality rate. Statistics indicate that its incidence has been increasing as well as the associated deaths. Most patients with PDAC show poor response to therapies making the clinical management of this cancer difficult. Stromal cells in the tumor microenvironment (TME) contribute to the development of resistance to therapy in PDAC cancer cells. Cancer-associated fibroblasts (CAFs), the most prevalent stromal cells in the TME, promote a desmoplastic response, produce extracellular matrix proteins and cytokines, and directly influence the biological behavior of cancer cells. These multifaceted effects make it difficult to eradicate tumor cells from the body. As a result, CAF-targeting synergistic therapeutic strategies have gained increasing attention in recent years. However, due to the substantial heterogeneity in CAF origin, definition, and function, as well as high plasticity, majority of the available CAF-targeting therapeutic approaches are not effective, and in some cases, they exacerbate disease progression. This review primarily elucidates on the effect of CAFs on therapeutic efficiency of various treatment modalities, including chemotherapy, radiotherapy, immunotherapy, and targeted therapy. Strategies for CAF targeting therapies are also discussed.
Topics: Humans; Cancer-Associated Fibroblasts; Carcinoma, Pancreatic Ductal; Pancreatic Neoplasms; Tumor Microenvironment; Immunotherapy; Animals; Molecular Targeted Therapy
PubMed: 38615928
DOI: 10.1016/j.canlet.2024.216859 -
Dermatologic Surgery : Official... Apr 2024Desmoplastic trichoepithelioma (DTE) is an uncommon benign adnexal tumor that histologically may mimic malignant tumors including basal cell carcinoma and microcystic...
A Systematic Review of the Epidemiology, Clinical Characteristics, Treatment, and Outcomes for Desmoplastic Trichoepithelioma: Underscoring Mohs Micrographic Surgery in Management.
BACKGROUND
Desmoplastic trichoepithelioma (DTE) is an uncommon benign adnexal tumor that histologically may mimic malignant tumors including basal cell carcinoma and microcystic adnexal carcinoma.
OBJECTIVE
To present a systematic review of the epidemiology, clinical characteristics, treatment, and outcome data on DTEs, with emphasis on comparing Mohs micrographic surgery (MMS) with other treatments.
METHODS
Using the OVID platform, MEDLINE and Embase were searched from inception for studies providing original data on DTEs.
RESULTS
A total of 338 cases of DTE from 61 articles were included. No recurrence/persistence (0%) was reported following MMS (n = 24, mean follow-up of 41.9 months), 13.1% with standard excision (n = 38, mean follow-up 16.9 months), and 2.1% for electrosurgery/cautery (n = 49, follow-up 3-72 months). 100% recurrence/persistence for imiquimod (n = 2) and liquid nitrogen (n = 4) were identified. In patients who underwent biopsy only, there was a 12.5% recurrence/persistence (n = 32, mean follow-up 16.5 months). Overall, duration of follow-up varied from 2 months to 6 years for the various management strategies.
CONCLUSION
Data are limited regarding DTE outcomes. In this review, surgical modalities, specifically MMS, had the lowest rates of recurrence/persistence compared with other options. Given that most lesions are found on cosmetically sensitive locations, MMS seems to be the optimal management strategy for actively managing DTEs.
PubMed: 38595132
DOI: 10.1097/DSS.0000000000004194 -
Biomolecules & Therapeutics May 2024Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis owing to its desmoplastic stroma. Therefore, therapeutic strategies targeting this tumor stroma should be... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis owing to its desmoplastic stroma. Therefore, therapeutic strategies targeting this tumor stroma should be developed. In this study, we describe the heterogeneity of cancer-associated fibroblasts (CAFs) and their diverse roles in the progression, immune evasion, and resistance to treatment of PDAC. We subclassified the spatial distribution and functional activity of CAFs to highlight their effects on prognosis and drug delivery. Extracellular matrix components such as collagen and hyaluronan are described for their roles in tumor behavior and treatment outcomes, implying their potential as therapeutic targets. We also discussed the roles of extracellular matrix (ECM) including matrix metalloproteinases and tissue inhibitors in PDAC progression. Finally, we explored the role of the adaptive and innate immune systems in shaping the PDAC microenvironment and potential therapeutic strategies, with a focus on immune cell subsets, cytokines, and immunosuppressive mechanisms. These insights provide a comprehensive understanding of PDAC and pave the way for the development of prognostic markers and therapeutic interventions.
PubMed: 38590092
DOI: 10.4062/biomolther.2024.029 -
The American Journal of Surgical... Jun 2024Next-generation sequencing (NGS) is increasingly being utilized as an ancillary tool for diagnostically challenging melanocytic neoplasms. It is incumbent upon the...
Next-generation sequencing (NGS) is increasingly being utilized as an ancillary tool for diagnostically challenging melanocytic neoplasms. It is incumbent upon the pathology community to perform studies assessing the benefits and limitations of these tools in specific diagnostic scenarios. One of the most challenging diagnostic scenarios faced by skin pathologists involves accurate diagnosis of desmoplastic melanocytic neoplasms (DMNs). In this study, 20 expert melanoma pathologists rendered a diagnosis on 47 DMNs based on hematoxylin and eosin sections with demographic information. After submitting their diagnosis, the experts were given the same cases, but this time with comprehensive genomic sequencing results, and asked to render a diagnosis again. Identification of desmoplastic melanoma (DM) improved by 7%, and this difference was statistically significant ( P <0.05). In addition, among the 15 melanoma cases, in the pregenomic assessment, only 12 were favored to be DM by the experts, while after genomics, this improved to 14 of the cases being favored to be DM. In fact, some cases resulting in metastatic disease had a substantial increase in the number of experts recognizing them as DM after genomics. The impact of the genomic findings was less dramatic among benign and intermediate-grade desmoplastic tumors (BIDTs). Interobserver agreement also improved, with the Fleiss multirater Kappa being 0.36 before genomics to 0.4 after genomics. NGS has the potential to improve diagnostic accuracy in the assessment of desmoplastic melanocytic tumors. The degree of improvement will be most substantial among pathologists with some background and experience in bioinformatics and melanoma genetics.
Topics: Humans; High-Throughput Nucleotide Sequencing; Melanoma; Skin Neoplasms; Observer Variation; Female; Male; Reproducibility of Results; Predictive Value of Tests; Middle Aged; Adult; Aged; Pathologists; Biomarkers, Tumor
PubMed: 38590014
DOI: 10.1097/PAS.0000000000002226 -
Cancer Research May 2024Desmoplastic small round cell tumors (DSRCT) are a type of aggressive, pediatric sarcoma characterized by the EWSR1::WT1 fusion oncogene. Targeted therapies for DSRCT...
UNLABELLED
Desmoplastic small round cell tumors (DSRCT) are a type of aggressive, pediatric sarcoma characterized by the EWSR1::WT1 fusion oncogene. Targeted therapies for DSRCT have not been developed, and standard multimodal therapy is insufficient, leading to a 5-year survival rate of only 15% to 25%. Here, we depleted EWSR1::WT1 in DSRCT and established its essentiality in vivo. Transcriptomic analysis revealed that EWSR1::WT1 induces unique transcriptional alterations compared with WT1 and other fusion oncoproteins and that EWSR1::WT1 binding directly mediates gene upregulation. The E-KTS isoform of EWSR1::WT1 played a dominant role in transcription, and it bound to the CCND1 promoter and stimulated DSRCT growth through the cyclin D-CDK4/6-RB axis. Treatment with the CDK4/6 inhibitor palbociclib successfully reduced growth in two DSRCT xenograft models. As palbociclib has been approved by the FDA for the treatment of breast cancer, these findings demonstrate the sensitivity of DSRCT to palbociclib and support immediate clinical investigation of palbociclib for treating this aggressive pediatric cancer.
SIGNIFICANCE
EWSR1::WT1 is essential for desmoplastic small round cell tumors and upregulates the cyclin D-CDK4/6-RB axis that can be targeted with palbociclib, providing a targeted therapeutic strategy for treating this deadly tumor type.
Topics: Animals; Humans; Mice; Cell Line, Tumor; Cell Proliferation; Cyclin-Dependent Kinase 4; Cyclin-Dependent Kinase 6; Desmoplastic Small Round Cell Tumor; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Oncogene Proteins, Fusion; Piperazines; Protein Kinase Inhibitors; Pyridines; RNA-Binding Protein EWS; WT1 Proteins; Xenograft Model Antitumor Assays; Mice, Inbred NOD
PubMed: 38588409
DOI: 10.1158/0008-5472.CAN-23-3334 -
Cureus Mar 2024Retroperitoneal fibrosis (RPF), also referred to as Ormond's disease, is a rare fibroinflammatory condition characterized by abnormal fibrous tissue deposition in the...
Retroperitoneal fibrosis (RPF), also referred to as Ormond's disease, is a rare fibroinflammatory condition characterized by abnormal fibrous tissue deposition in the retroperitoneal space, which traditionally presents with ureteral obstruction. Nonetheless, our case report showcases an exceptional instance involving a 70-year-old female patient who presented with symptoms suggestive of colonic obstruction, an unusual presentation that is not commonly associated with RPF. Although RPF has established associations with autoimmune conditions such as immunoglobulin G4-related disease and systemic lupus erythematosus, its connection to colonic obstruction remains undocumented in the medical literature. Our patient is a 70-year-old female who presented with constipation, anemia, and fecal occult blood. Her past medical history included a hysterectomy due to fibroids, right breast lumpectomy, type 2 diabetes mellitus, subclinical hyperthyroidism, hypertension, and obesity. Upon physical examination, the patient's abdomen appeared protuberant but was non-tender to palpation. Bowel sounds were normal, and there was no distension. Notably, there was no tenderness in the right or left costovertebral angles, nor was there any guarding. Workup with colonoscopy could not be completed due to the inability to pass a colonoscope beyond the rectosigmoid junction. Further workup with barium enema confirmed an apple core lesion seen in the rectosigmoid concerning for a neoplastic or inflammatory process. Finally, a computed tomography scan of the abdomen and pelvis showed a 7.1 cm right pelvic mass attached to the bladder and cecum, moderate right hydroureteronephrosis, and a 5.2 cm left adnexal mass with soft tissue changes narrowing the sigmoid colon. The next step was to take the patient for an exploratory laparotomy. During exploratory laparotomy, extensive adhesions and desmoplastic reactions were observed in the pelvic region, involving the sigmoid colon, bladder, cecum, and appendix. Two firm masses were identified in the retroperitoneum, one located in the left lower quadrant (LLQ) adherent to the posterior wall of the sigmoid colon and one in the right lower quadrant (RLQ) adherent to the posterior wall of the cecum. Three specimens were sent to pathology for further examination: a portion of the sigmoid colon, a resection from the RLQ mass, and a resection from the LLQ mass. Pathology reported dense fibrotic masses with abscess-like formation, reactive in nature and of unclear etiology, and negative for malignancy. They were negative for fibromatosis (β-catenin negative), and IgG4+/IgG+ was approximately 5%. Interestingly, the LLQ mass also contained remnants of the fallopian tube and ovary and benign cystic changes. This case report presents a unique and atypical presentation of RPF, deviating from the conventional presentation of ureteral obstruction. The patient's initial symptoms suggested colonic obstruction, a clinical scenario rarely linked to RPF. This case underscores the significance of considering diverse clinical presentations when diagnosing RPF, thereby expanding our comprehension of the condition's clinical spectrum and ultimately refining patient care and management.
PubMed: 38586788
DOI: 10.7759/cureus.55621 -
Medicine Apr 2024Desmoplastic small round cell tumor (DSRCT) is a rare and rapidly metastasizing soft tissue sarcoma, distinguished by its unique cell morphology and pleomorphic... (Review)
Review
RATIONALE
Desmoplastic small round cell tumor (DSRCT) is a rare and rapidly metastasizing soft tissue sarcoma, distinguished by its unique cell morphology and pleomorphic differentiation.
PATIENT CONCERNS
This report describes the case of an 18-year-old male diagnosed with abdominopelvic DSRCT exhibiting metastases to the peritoneum, liver, pleura, bone, and muscle. The patient primarily presented with symptoms of incomplete intestinal obstruction and an abdominal mass.
DIAGNOSES
Colonoscopy revealed lumen stenosis caused by external compression mass. Contrast-enhanced computed tomography and 18F-fluorodeoxyglucose positron emission tomography/computed tomography revealed multiple lesions in the abdominopelvic cavity. A needle biopsy of an abdominal wall lesion established it as a malignant tumor, origin unknown. Immunohistochemical staining post-surgery showed positive results for Cytokeratin (CK), CK7, Desmin, Vimentin, Caudal type homeobox 2 (CDX2), and Ki-67. Fluorescence in situ hybridization analysis revealed an Ewing sarcoma breakpoint region 1/EWS RNA binding protein 1 (EWSR1) rearrangement, and next-generation sequencing identified an EWSR1-Wilms tumor protein 1 (WT1) gene fusion.
INTERVENTIONS
The patient underwent laparoscopic exploratory surgery, which encompassed biopsy, ascites drainage, adhesion lysis, reinforcement of weakened sections of the small intestinal walls, and repositioning of twisted intestines. Postoperatively, the treatment protocol included fasting, rehydration, gastrointestinal decompression, and parenteral nutrition. However, the patient did not received chemotherapy.
OUTCOMES
The patient declined further treatment and deceased in early November.
LESSONS
This case highlights the nonspecific nature of DSRCT symptoms. In clinical practice, it is crucial to meticulously evaluate unexplained intestinal obstruction in young patients, considering DSRCT as a differential diagnosis to avoid delays in diagnosis.
Topics: Male; Humans; Adolescent; Desmoplastic Small Round Cell Tumor; In Situ Hybridization, Fluorescence; Soft Tissue Neoplasms; Intestinal Obstruction; Oncogene Proteins, Fusion
PubMed: 38579065
DOI: 10.1097/MD.0000000000037664