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Nature Communications Mar 2024Head and neck squamous cell carcinoma is the sixth most common cancer worldwide and has high heterogeneity and unsatisfactory outcomes. To better characterize the tumor...
Head and neck squamous cell carcinoma is the sixth most common cancer worldwide and has high heterogeneity and unsatisfactory outcomes. To better characterize the tumor progression trajectory, we perform single-cell RNA sequencing of normal tissue, precancerous tissue, early-stage, advanced-stage cancer tissue, lymph node, and recurrent tumors tissue samples. We identify the transcriptional development trajectory of malignant epithelial cells and a tumorigenic epithelial subcluster regulated by TFDP1. Furthermore, we find that the infiltration of POSTN fibroblasts and SPP1 macrophages gradually increases with tumor progression; their interaction or interaction with malignant cells also gradually increase to shape the desmoplastic microenvironment and reprogram malignant cells to promote tumor progression. Additionally, we demonstrate that during lymph node metastasis, exhausted CD8 T cells with high CXCL13 expression strongly interact with tumor cells to acquire more aggressive phenotypes of extranodal expansion. Finally, we delineate the distinct features of malignant epithelial cells in primary and recurrent tumors, providing a theoretical foundation for the precise selection of targeted therapy for tumors at different stages. In summary, the current study offers a comprehensive landscape and deep insight into epithelial and microenvironmental reprogramming throughout initiation, progression, lymph node metastasis and recurrence of head and neck squamous cell carcinoma.
Topics: Humans; Squamous Cell Carcinoma of Head and Neck; Carcinoma, Squamous Cell; Lymphatic Metastasis; CD8-Positive T-Lymphocytes; Ecosystem; Neoplasm Recurrence, Local; Head and Neck Neoplasms; Tumor Microenvironment
PubMed: 38519500
DOI: 10.1038/s41467-024-46912-6 -
Journal For Immunotherapy of Cancer Mar 2024Desmoplastic melanoma (DM) is a rare melanoma subtype characterized by dense fibrous stroma, a propensity for local recurrence, and a high response rate to programmed...
BACKGROUND
Desmoplastic melanoma (DM) is a rare melanoma subtype characterized by dense fibrous stroma, a propensity for local recurrence, and a high response rate to programmed cell death protein 1 (PD-1) blockade. Occult sentinel lymph node positivity is significantly lower in both pure and mixed DM than in conventional melanoma, underscoring the need for better prognostic biomarkers to inform therapeutic strategies.
METHODS
We assembled a tissue microarray comprising various cores of tumor, stroma, and lymphoid aggregates from 45 patients with histologically confirmed DM diagnosed between 1989 and 2018. Using a panel of 62 validated immune-oncology markers, we performed digital spatial profiling using the NanoString GeoMx platform and quantified expression in three tissue compartments defined by fluorescence colocalization (tumor (S100+/PMEL+/SYTO+), leukocytes (CD45+/SYTO+), and non-immune stroma (S100-/PMEL-/CD45-/SYTO+)).
RESULTS
We observed higher expression of immune checkpoints (lymphocyte-activation gene 3 [LAG-3] and cytotoxic T-lymphocyte associated protein-4 [CTLA-4]) and cancer-associated fibroblast (CAF) markers (smooth muscle actin (SMA)) in the tumor compartments of pure DMs than mixed DMs. When comparing lymphoid aggregates (LA) to non-LA tumor cores, LAs were more enriched with CD20+B cells, but non-LA intratumoral leukocytes were more enriched with macrophage/monocytic markers (CD163, CD68, CD14) and had higher LAG-3 and CTLA-4 expression levels. Higher intratumoral PD-1 and LA-based LAG-3 expression appear to be associated with worse survival.
CONCLUSIONS
Our proteomic analysis reveals an intra-tumoral population of SMA+CAFs enriched in pure DM. Additionally, increased expressions of immune checkpoints (LAG-3 and PD-1) in LA and within tumor were associated with poorer prognosis. These findings might have therapeutic implications and help guide treatment selection in addition to informing potential prognostic significance.
Topics: Humans; Melanoma; Programmed Cell Death 1 Receptor; CTLA-4 Antigen; Tumor Microenvironment; Actins; Proteomics; Biomarkers, Tumor
PubMed: 38519058
DOI: 10.1136/jitc-2023-008646 -
Journal For Immunotherapy of Cancer Mar 2024The survival benefit observed in children with neuroblastoma (NB) and minimal residual disease who received treatment with anti-GD2 monoclonal antibodies prompted our...
BACKGROUND
The survival benefit observed in children with neuroblastoma (NB) and minimal residual disease who received treatment with anti-GD2 monoclonal antibodies prompted our investigation into the safety and potential clinical benefits of anti-CD3×anti-GD2 bispecific antibody (GD2Bi) armed T cells (GD2BATs). Preclinical studies demonstrated the high cytotoxicity of GD2BATs against GD2+cell lines, leading to the initiation of a phase I/II study in recurrent/refractory patients.
METHODS
The 3+3 dose escalation phase I study (NCT02173093) encompassed nine evaluable patients with NB (n=5), osteosarcoma (n=3), and desmoplastic small round cell tumors (n=1). Patients received twice-weekly infusions of GD2BATs at 40, 80, or 160×10 GD2BATs/kg/infusion complemented by daily interleukin-2 (300,000 IU/m) and twice-weekly granulocyte macrophage colony-stimulating factor (250 µg/m). The phase II segment focused on patients with NB at the dose 3 level of 160×10 GD2BATs/kg/infusion.
RESULTS
Of the 12 patients enrolled, 9 completed therapy in phase I with no dose-limiting toxicities. Mild and manageable cytokine release syndrome occurred in all patients, presenting as grade 2-3 fevers/chills, headaches, and occasional hypotension up to 72 hours after GD2BAT infusions. GD2-antibody-associated pain was minimal. Median overall survival (OS) for phase I and the limited phase II was 18.0 and 31.2 months, respectively, with a combined OS of 21.1 months. A phase I NB patient had a complete bone marrow response with overall stable disease. In phase II, 10 of 12 patients were evaluable: 1 achieved partial response, and 3 showed clinical benefit with prolonged stable disease. Over 50% of evaluable patients exhibited augmented immune responses to GD2+targets post-GD2BATs, as indicated by interferon-gamma (IFN-γ) EliSpots, Th1 cytokines, and/or chemokines.
CONCLUSIONS
This study demonstrated the safety of GD2BATs up to 160×10 cells/kg/infusion. Coupled with evidence of post-treatment endogenous immune responses, our findings support further investigation of GD2BATs in larger phase II clinical trials.
Topics: Child; Humans; T-Lymphocytes; Neuroblastoma; Antibodies, Monoclonal; Antineoplastic Agents; Osteosarcoma
PubMed: 38519053
DOI: 10.1136/jitc-2023-008744 -
Turkish Archives of Pediatrics Jan 2024The aim of this study is to evaluate the demographic characteristics of patients diagnosed with Spitz nevus and to investigate potential distinctions in...
OBJECTIVE
The aim of this study is to evaluate the demographic characteristics of patients diagnosed with Spitz nevus and to investigate potential distinctions in clinicopathological findings of Spitz nevi in relation to age and location of the lesion.
MATERIALS AND METHODS
Clinical and histopathological findings of 32 patients who were diagnosed with Spitz nevus from our archives between 2010 and 2020 were obtained and evaluated retrospectively.
RESULTS
A total of 32 patients were included, of whom 19 (59.4%) were female and 15 (40.6%) were under the age of 18 years. Most of the lesions (14, 43.7%) were located on the upper extremity, followed by the lower extremity and the head and neck. The most common histological subtype was the compound variant. In the pediatric age group, the majority of the lesions were located on the upper extremity, and the most common histological subtypes were pigmented and compound variant. In adults, the lesions were chiefly located on the lower extremitiy and the most common histological subtype was the desmoplastic variant.
CONCLUSION
In this study, it was found that the location of the lesions and histopathological subtypes of Spitz nevi may differ in children and adults. Further studies incorporating genetic data and involving larger cohorts of patients are needed in order to determine these differences between age groups more clearly. The small sample size is the main limitation of this study Cite this article as: Uzunçakmak TK, Yücesoy SN, Önenerk AM, Özdil A, Engin B. Comparison of clinicopathological findings of spitz nevus in pediatric and adult patients. Turk Arch Pediatr. 2024;59(1):49-53.
PubMed: 38454260
DOI: 10.5152/TurkArchPediatr.2024.23154 -
Frontiers in Oncology 2024Intra-abdominal desmoplastic small round cell tumor (IDSRCT) is a rare entity (0.2-0.74 cases per million people per year), which predominantly occurs in young men. It...
BACKGROUND
Intra-abdominal desmoplastic small round cell tumor (IDSRCT) is a rare entity (0.2-0.74 cases per million people per year), which predominantly occurs in young men. It may present as an abdominal mass with pain, distention, and constipation. IDSRCT has a very poor prognosis, with 5-year overall survival estimated at 15%-30%. Diagnosis is made with tissue biopsy.
CASE DESCRIPTION
We present a case of a 28-year-old man with a history of schizophrenia and depression who presented to an emergency room (ER) in November 2022 with constipation and pelvic pain. The patient was sent home with a bowel regimen after radiography showed no obstruction. He re-presented for evaluation due to persistent pain. A computerized tomography scan of the abdomen and pelvis (CT A/P) revealed numerous pelvic masses with severe colitis, bilateral moderate hydronephrosis, and metastatic disease in the liver. A colonoscopy showed a mass extending 3 cm from the anus to 10 cm causing a partial obstruction. Biopsy was read as squamous cell carcinoma (SCC). The patient was subsequently admitted to our institution with pelvic pain, nausea, and vomiting. Colorectal surgery performed a colectomy with end-ileostomy due to colonic obstruction. He was evaluated by a medical oncologist, with previous slides requested for review. Initial review was concerning metastatic basaloid SCC with neuroendocrine features and a Ki67 of 70%. Given his recent abdominal surgeries, chemotherapy was delayed until February 2023 when he was started on reduced dose carboplatin and paclitaxel. Tumor specimen was sent for next generation sequencing (NGS) and programmed death-1 ligand 1 (PD-L1) testing. NGS results returned after the first dose of chemotherapy was given and showed a t(11;22) EWSR-WT1 translocation characteristic of desmoplastic small round cell tumor. The patient was supported in the hospital and discharged with oncology follow-up.
DISCUSSION
As seen in this case, pathology review is essential to ensuring correct diagnosis and appropriate treatment plan. This is especially true when the clinical scenario does not match the listed pathology. Additional diagnostics such as NGS are invaluable in establishing correct diagnosis.
PubMed: 38440227
DOI: 10.3389/fonc.2024.1260474 -
Cureus Feb 2024Desmoplastic small round cell tumor (DSRCT) is a rare, highly aggressive malignancy predominantly affecting adolescents and young adults. We report a case of multifocal...
Desmoplastic small round cell tumor (DSRCT) is a rare, highly aggressive malignancy predominantly affecting adolescents and young adults. We report a case of multifocal DSRCT in an 11-year-old male who presented with complaints of unilateral forehead swelling, proptosis, and ophthalmoplegia for four months along with abdominal pain and dysphagia for six months. A whole-body computed tomography revealed widespread lesions in the skull, orbit, thorax, and abdomen with local infiltration. Ultrasound-guided biopsy of the forehead lump was performed. Based on histopathological and immunohistochemical investigations, it was diagnosed to be a DSRCT with multifocal presentation. The patient underwent chemo-radiation but unfortunately succumbed to neutropenic sepsis and renal failure. DSRCT is a very rare, highly aggressive malignancy with an extremely poor prognosis. Orbital presentations are even rarer, with less than 10 such cases currently described in English medical literature.
PubMed: 38440042
DOI: 10.7759/cureus.53504 -
Cureus Jan 2024Desmoplastic small round cell tumors (DSRCT) are very rare and aggressive diseases typically present with abdominal or retroperitoneal masses. We present a case of a...
Desmoplastic small round cell tumors (DSRCT) are very rare and aggressive diseases typically present with abdominal or retroperitoneal masses. We present a case of a young female who presented with ST-segment elevation myocardial infarction and cardiac tamponade and who was found to have DSRCT. The patient was coded at the emergency department. Left heart catheterization showed normal coronary arteries, and pericardiocentesis removed 1,260 mL of bloody pericardial effusions. The patient was stabilized, and a positron emission tomography scan revealed left intrahilar, hilar, and cardiophrenic masses with associated hypermetabolic right hilar, left hilar, subcarinal, costophrenic, aortopulmonary, paratracheal, and mediastinal lymphadenopathy. Cardiac magnetic resonance imaging showed multiple masses visualized in the pericardium, one mass anterior to the right ventricular outflow tract/pulmonary artery, and a second mass adjacent to the right ventricular apex. Computed tomography abdomen/pelvis showed no evidence of metastatic malignancy in the abdomen/pelvis. A biopsy of lung mass and lymph nodes showed desmoplastic small round cell tumors with sarcoma fusion gene detected (Ewing sarcoma RNA-binding protein 1-Wilms' tumor 1). We performed cycle 1 of chemotherapy, including doxorubicin, vincristine, and cyclophosphamide, and the patient was transferred to an oncology center for further care. This case suggested that one of the differential diagnoses of lung and pericardium masses at a young age can be desmoplastic small round cell tumors. This case also highlighted that ST-segment elevation myocardial infarction can be secondary to neoplasm, especially at a young age besides myocardial infarction.
PubMed: 38435931
DOI: 10.7759/cureus.53333 -
OncoTargets and Therapy 2024Desmoplastic small round cell tumor (DSRCT) is a rare and highly aggressive malignancy. Most patients are diagnosed at a late stage with poor prognosis. The treatment...
Desmoplastic small round cell tumor (DSRCT) is a rare and highly aggressive malignancy. Most patients are diagnosed at a late stage with poor prognosis. The treatment usually includes combined intensive chemotherapy, cytoreductive surgery, radiotherapy, and targeted therapy. Due to the low incidence rate and dismal survival, there is currently a lack of case reports on DSRCT with concurrent leukemia. We report a case of a young patient who achieved disease stabilization for 14 months after receiving 6 cycles of chemotherapy and whole abdominal radiation therapy (WART), followed by consolidation treatment with anlotinib. However, the treatment was terminated due to the development of Acute Myeloid Leukemia-M5 (AML-M5). Multimodal therapy may provide a survival benefit for rare tumors that lack standard treatment. However, intensive chemotherapy and extensive radiotherapy carry a risk of inducing secondary malignancies. This is the first reported case of concurrent DSRCT and AML-M5 with short intervals between onset.
PubMed: 38435840
DOI: 10.2147/OTT.S434286 -
Journal of Stomatology, Oral and... Feb 2024Desmoplastic fibroma (DF) is a rare benign bone tumor adopting an aggressive behavior, representing a challenge for clinical and radiographic diagnosis. This case report...
Desmoplastic fibroma (DF) is a rare benign bone tumor adopting an aggressive behavior, representing a challenge for clinical and radiographic diagnosis. This case report focused on a 31-year-old man with a large mandibular lesion with severe displacements of the mandibular teeth. Only a combination of paraclinical findings allows a definitive diagnosis to be made. Cervicofacial MRI revealed a low T1 signal intensity with peripheral enhancement after Gadolinium, and T2 hyperintense signal, while PET scan showed a moderate metabolism. Bone biopsy with immunohistochemical analysis allowed for definitive diagnosis of DF after eliminating the main differential diagnosis (fibrous dysplasia, fibrosarcoma, desmoid tumor, and osteosarcoma). The patient was successfully treated by large mandibular resection and reconstruction with a free-fibular bone flap".
PubMed: 38431083
DOI: 10.1016/j.jormas.2024.101805 -
Indian Journal of Pathology &... Apr 2024Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide with 878,348 new cases. Cancer-associated fibroblasts (CAFs) are the predominant...
Evaluation of the significance of tumor stromal patterns and peri-tumoral inflammation in head and neck squamous cell carcinoma with special reference to the Yamamoto-Kohama classification.
INTRODUCTION
Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide with 878,348 new cases. Cancer-associated fibroblasts (CAFs) are the predominant cell type in tumor stroma and are important promoters of tumor progression.
OBJECTIVE
The aim of the study was to evaluate the pattern of desmoplastic stromal reaction and peri-tumoral inflammatory infiltrate with the histological grade and clinical data.
MATERIALS AND METHODS
A total of 60 cases of HNSCC were included in the study. The hematoxylin and eosin (H and E)-stained sections from all cases were examined by two experienced pathologists for the grade, nature of stomal reaction (SR), peri-tumoral inflammatory infiltration, Yamamoto-Kohama classification grade, worst pattern of invasion (WPOI), depth of invasion (DOI), and other histopathological parameters. Correlation analysis was conducted using the Chi-square test. P- value less than 0.05 was considered statistically significant.
RESULTS
Immature SR was not observed in any of the well-differentiated squamous cell carcinoma (SCC) cases. However, one (3.7%) case of moderately differentiated SCC and two (28.6%) cases of poorly differentiated SCC showed signs of immature SR. In the case of the higher grades of the YK classification, specifically grades 4C and 4D, a more profound depth of tumor cell invasion, equal to or exceeding 10 mm, was evident in six (66.67%) and two (28.57%) cases, respectively. Additionally, among the seven (11.7%) cases classified as poorly differentiated carcinoma, three (42.85%) displayed a WPOI score of 5.
CONCLUSION
SR and the tumor invasive pattern in HNSCC are related to prognosis and may indicate tumor aggressiveness.
Topics: Humans; Female; Male; Squamous Cell Carcinoma of Head and Neck; Middle Aged; Head and Neck Neoplasms; Aged; Inflammation; Adult; Cancer-Associated Fibroblasts; Aged, 80 and over; Carcinoma, Squamous Cell; Stromal Cells
PubMed: 38427768
DOI: 10.4103/ijpm.ijpm_426_23