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Diagnostic Cytopathology Apr 2024Oncocytic lesions of the thyroid are a heterogeneous group encompassing nonneoplastic and neoplastic entities ranging from benign to malignant and have traditionally... (Review)
Review
Oncocytic lesions of the thyroid are a heterogeneous group encompassing nonneoplastic and neoplastic entities ranging from benign to malignant and have traditionally been classified as separate entities in thyroid pathology. To illustrate the diversity of these thyroid lesions, we describe three cases of fine needle aspiration biopsies (FNAB) diagnosed as Bethesda Category IV: Follicular neoplasm, oncocytic type, under the 2017 Bethesda System for Reporting Thyroid Cytopathology (TBSRTC), with ThyroSeq v3 molecular testing and subsequent surgical excision.
PubMed: 38581413
DOI: 10.1002/dc.25314 -
BMC Cancer Apr 2024Patients from non-small cell lung cancer (NSCLC) controlled clinical trials do not always reflect real-world heterogeneous patient populations. We designed a study to... (Observational Study)
Observational Study
BACKGROUND
Patients from non-small cell lung cancer (NSCLC) controlled clinical trials do not always reflect real-world heterogeneous patient populations. We designed a study to describe the real-world patient characteristics and treatment patterns of first-line treatment in patients in the US with NSCLC.
METHODS
This was an observational, retrospective cohort study based on electronic medical records of US adults with locally advanced or metastatic disease in the ConcertAI Patient360 NSCLC database who initiated first-line treatment with anti-programmed cell death protein 1/programmed cell death ligand 1 (PD-1/PD-L1) therapy between July 2016 and December 2020. The analysis used patient attributes, clinical characteristics, and treatments from each patient's medical records.
RESULTS
A total of 2175 patients were eligible for analysis. The median age was 68 years, and 26.2% of the patients were ≥75 years old. At treatment initiation, 96.4% and 3.6% of the patients had Stage 4 and Stage 3 (B or C) NSCLC, respectively. The most common histology type was nonsquamous adenocarcinoma (66.4%), and 19.8% had Eastern Cooperative Oncology Group performance status ≥2. Immunosuppressive medications were being used by 17.7% of patients, and 11.0% were immunocompromised. Almost all patients had metastases: 64.6% had 1, 23.2% had 2, and 8.0% had ≥3 metastatic sites. Brain metastases were present in 22.9% of patients. Treatment evolution was observed with first-line standard of care shifting from single-agent immunotherapy in 2016 (90.2%) to combination immunotherapy and chemotherapy in 2020 (60.2%).
CONCLUSION
Between 2016 and 2020, the first-line treatment paradigm for advanced NSCLC in the US shifted from anti-PD-1/PD-L1 monotherapy to combination chemoimmunotherapy, with increasing biomarker testing. Further research in heterogeneous patient populations to characterize treatment strategies is warranted.
Topics: Adult; Humans; Aged; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; B7-H1 Antigen; Retrospective Studies; Immunotherapy
PubMed: 38580900
DOI: 10.1186/s12885-024-12126-8 -
Pathology International May 2024Whereas multifocality typically concerns papillary thyroid carcinoma (PTC) without specification of intrathyroidal metastatic or independent nature of tumor foci, the...
Whereas multifocality typically concerns papillary thyroid carcinoma (PTC) without specification of intrathyroidal metastatic or independent nature of tumor foci, the designation of the latter as Multi-UniFocal (MUF) may be relevant for select cases. A case series involving multifocal thyroid lesions with divergent histopathological morphology and/or molecular profile, with molecular evaluation of multiple individual tumor foci per patient based on a next-generation sequencing approach, was retrospectively reviewed. Twenty-five patient cases with multifocal thyroid lesions suggestive of MUF, with 2-6 (median 3) tumor foci per patient, were described. Tumor lesions comprised diverse histopathology, including PTC, (E)FVPTC, NIFTP, FA, FTC, and oncocytic. Morphologically similar and/or diverse tumor foci harbored different molecular alterations (suggestive of non-shared clonality); with(out) coexistent similar foci harboring identical molecular alterations; or (partly) shared molecular alterations. MUF was associated with chronic lymphocytic thyroiditis in almost half of the cases. The recognition of MUF may justify the independent clinical consideration per individual tumor focus; as separate lesions albeit within a multifocal context. The potential clinical relevance and prognostic value of MUF remain to be further established.
Topics: Humans; Thyroid Neoplasms; Female; Male; Middle Aged; Adult; Retrospective Studies; Aged; Thyroid Cancer, Papillary; Thyroid Gland; Hashimoto Disease; Carcinoma, Papillary; High-Throughput Nucleotide Sequencing
PubMed: 38558427
DOI: 10.1111/pin.13421 -
Cancer Cytopathology Jun 2024DICER1 mutations and PTEN alterations are increasingly detected by thyroid fine-needle aspiration (FNA). Both are associated with nodular thyroid disease and cancer. The... (Comparative Study)
Comparative Study
BACKGROUND
DICER1 mutations and PTEN alterations are increasingly detected by thyroid fine-needle aspiration (FNA). Both are associated with nodular thyroid disease and cancer. The authors analyzed a large comparative thyroid FNA cohort with DICER1 mutation or PTEN alteration.
METHODS
A total of 117 thyroid FNAs with DICER1 or PTEN alterations were retrieved from the databases of two academic medical institutions. Demographic, clinical, and radiologic data were collected; FNA slides were analyzed for 29 cytomorphologic features.
RESULTS
Of 117 thyroid FNAs, 36 (30.8%) had DICER1 mutation and 81 (69.2%) showed PTEN alteration. The DICER1 cohort had 33 (91.7%) females and three (8.3%) males (mean, 40.9 years); 61.8% had multinodular disease. FNAs were classified as atypia of undetermined significance (AUS), 23 (63.9%); follicular neoplasm (FN), 12 (33.3%); and malignant, 1 (2.8%). The PTEN subgroup had 66 (81.5%) females and 15 (18.5%) males (mean, 55.2 years) with increased multinodular disease (93.8%, p = .0016). PTEN FNAs had greater cytologic diversity: non-diagnostic, 2 (2.5%); benign, 5 (6.2%); AUS, 44 (54.3%); FN, 24 (29.6%); and malignant, 6 (7.4%). Both DICER1 and PTEN cases showed a range of resected tumor subtypes. The DICER1 cohort included thyroblastoma, and the PTEN group included anaplastic carcinoma. The cytomorphology of DICER1 and PTEN cases showed overlapping features, especially microfollicular patterns. Minor cytomorphologic differences included papillary patterns in DICER1 (p = .039), and oncocytic changes (p < .0001) in PTEN.
CONCLUSIONS
DICER1 and PTEN FNAs reveal many cytologic similarities. DICER1 patients are younger, and PTEN patients had multinodular disease. Awareness of these genetic cohorts can identify patients at risk for thyroid cancer.
Topics: Humans; Ribonuclease III; PTEN Phosphohydrolase; Male; Female; Thyroid Nodule; Biopsy, Fine-Needle; DEAD-box RNA Helicases; Adult; Middle Aged; Mutation; Thyroid Neoplasms; Aged; Young Adult; Adolescent
PubMed: 38558329
DOI: 10.1002/cncy.22811 -
JAMA Oncology May 2024Despite the clear potential benefits of neoadjuvant therapy, the optimal neoadjuvant regimen for patients with high-risk resectable melanoma (HRRM) is not known. (Comparative Study)
Comparative Study Meta-Analysis
IMPORTANCE
Despite the clear potential benefits of neoadjuvant therapy, the optimal neoadjuvant regimen for patients with high-risk resectable melanoma (HRRM) is not known.
OBJECTIVE
To compare the safety and efficacy of dual checkpoint inhibitors with anti-programmed cell death protein-1 (anti-PD1) therapy in a neoadjuvant setting among patients with HRRM.
DESIGN, SETTING, AND PARTICIPANTS
In this pooled analysis of clinical trials, studies were selected provided they investigated immune checkpoint inhibitor treatment, were published between January 2018 and March 2023, and were phase 1, 2, or 3 clinical trials. Participant data included in the analysis were derived from trials evaluating the efficacy and safety of anti-PD1 monotherapy and the combination of anti-cytotoxic T lymphocyte-associated protein-4 with anti-PD1 in the neoadjuvant setting, specifically among patients with HRRM.
INTERVENTIONS
Patients were treated with either anti-PD1 monotherapy; dual checkpoint inhibition (DCPI) with a conventional dose of 3-mg/kg ipilimumab and 1-mg/kg nivolumab; or DCPI with an alternative-dose regimen of 1-mg/kg ipilimumab and 3-mg/kg nivolumab.
MAIN OUTCOMES AND MEASURES
The main outcomes were radiologic complete response (rCR), radiologic overall objective response (rOOR), and radiologic progressive disease. Also, pathologic complete response (pCR), the proportion of patients undergoing surgical resection, and occurrence of grade 3 or 4 immune-related adverse events (irAEs) were considered.
RESULTS
Among 573 patients enrolled in 6 clinical trials, neoadjuvant therapy with DCPI was associated with higher odds of achieving pCR compared with anti-PD1 monotherapy (odds ratio [OR], 3.16; P < .001). DCPI was associated with higher odds of grade 3 or 4 irAEs compared with anti-PD1 monotherapy (OR, 3.75; P < .001). When comparing the alternative-dose ipilimumab and nivolumab (IPI-NIVO) regimen with conventional-dose IPI-NIVO, no statistically significant difference in rCR, rOOR, radiologic progressive disease, or pCR was noted. However, the conventional-dose IPI-NIVO regimen was associated with increased grade 3 or 4 irAEs (OR, 4.76; P < .001). Conventional-dose IPI-NIVO was associated with greater odds of achieving improved rOOR (OR, 1.95; P = .046) and pCR (OR, 2.99; P < .001) compared with anti-PD1 monotherapy. The alternative dose of IPI-NIVO also was associated with higher odds of achieving rCR (OR, 2.55; P = .03) and pCR (OR, 3.87; P < .001) compared with anti-PD1 monotherapy. The risk for grade 3 or 4 irAEs is higher with both the conventional-dose (OR, 9.59; P < .001) and alternative-dose IPI-NIVO regimens (OR, 2.02; P = .02) compared with anti-PD1 monotherapy.
CONCLUSION AND RELEVANCE
In this pooled analysis of 6 clinical trials, although DCPI was associated with increased likelihood of achieving pathological and radiologic responses, the associated risk for grade 3 or 4 irAEs was significantly lower with anti-PD1 monotherapy in the neoadjuvant setting for HRRM. Additionally, compared with alternative-dose IPI-NIVO, the conventional dose of IPI-NIVO was associated with increased risk for grade 3 or 4 irAEs, with no significant distinctions in radiologic or pathologic efficacy.
Topics: Female; Humans; Antineoplastic Combined Chemotherapy Protocols; Immune Checkpoint Inhibitors; Ipilimumab; Melanoma; Neoadjuvant Therapy; Nivolumab; Programmed Cell Death 1 Receptor
PubMed: 38546551
DOI: 10.1001/jamaoncol.2023.7333 -
JCO Precision Oncology Mar 2024Current guidelines for the management of metastatic non-small cell lung cancer (NSCLC) without driver mutations recommend checkpoint immunotherapy with PD-1/PD-L1... (Observational Study)
Observational Study
PURPOSE
Current guidelines for the management of metastatic non-small cell lung cancer (NSCLC) without driver mutations recommend checkpoint immunotherapy with PD-1/PD-L1 inhibitors, either alone or in combination with chemotherapy. This approach fails to account for individual patient variability and host immune factors and often results in less-than-ideal outcomes. To address the limitations of the current guidelines, we developed and subsequently blindly validated a machine learning algorithm using pretreatment plasma proteomic profiles for personalized treatment decisions.
PATIENTS AND METHODS
We conducted a multicenter observational trial (ClinicalTrials.gov identifier: NCT04056247) of patients undergoing PD-1/PD-L1 inhibitor-based therapy (n = 540) and an additional patient cohort receiving chemotherapy (n = 85) who consented to pretreatment plasma and clinical data collection. Plasma proteome profiling was performed using SomaScan Assay v4.1.
RESULTS
Our test demonstrates a strong association between model output and clinical benefit (CB) from PD-1/PD-L1 inhibitor-based treatments, evidenced by high concordance between predicted and observed CB ( = 0.98, < .001). The test categorizes patients as either PROphet-positive or PROphet-negative and further stratifies patient outcomes beyond PD-L1 expression levels. The test successfully differentiates between PROphet-negative patients exhibiting high tumor PD-L1 levels (≥50%) who have enhanced overall survival when treated with a combination of immunotherapy and chemotherapy compared with immunotherapy alone (hazard ratio [HR], 0.23 [95% CI, 0.1 to 0.51], = .0003). By contrast, PROphet-positive patients show comparable outcomes when treated with immunotherapy alone or in combination with chemotherapy (HR, 0.78 [95% CI, 0.42 to 1.44], = .424).
CONCLUSION
Plasma proteome-based testing of individual patients, in combination with standard PD-L1 testing, distinguishes patient subsets with distinct differences in outcomes from PD-1/PD-L1 inhibitor-based therapies. These data suggest that this approach can improve the precision of first-line treatment for metastatic NSCLC.
Topics: Humans; B7-H1 Antigen; Carcinoma, Non-Small-Cell Lung; Immune Checkpoint Inhibitors; Lung Neoplasms; Programmed Cell Death 1 Receptor; Proteome; Proteomics
PubMed: 38513170
DOI: 10.1200/PO.23.00555 -
Journal of Medical Case Reports Mar 2024Cystadenoma of the salivary glands is a rare benign clinical condition affecting both major and minor salivary glands equally. It constitutes approximately 2% of total...
BACKGROUND
Cystadenoma of the salivary glands is a rare benign clinical condition affecting both major and minor salivary glands equally. It constitutes approximately 2% of total neoplasms and 4.2-4.7% of benign formations in minor salivary glands. Typically presenting as a slow-growing, painless neoplasm, it can be distinguished from Cystadenolymphoma (Whartin's Tumor) by the absence of lymphoid elements in histological examination. While mostly located in the oral cavity and oropharynx, it can also be found in sinonasal mucosa, and rare cases have been identified in the larynx.
CASE PRESENTATION
A 75-year-old Caucasian woman presented to the ear, nose, and throat department with complaints of dysphonia and headaches persisting for several months. Dysphonia had developed months after an unspecified vocal cord surgery elsewhere. Flexible laryngoscopy identified a left-sided cystic swelling affecting the supraglottic space, leading to respiratory obstruction and dysphonia. Head and neck computed tomography confirmed a 1.9 × 1.7 cm bilobed cystic mass originating from the left Morgagni ventricle. Microlaryngoscopy with CO laser excision and biopsy revealed a histopathological diagnosis of oncocytic papillary cystadenoma. Post-surgery, the patient fully recovered from dysphonia, with no significant complications noted. Long-term clinical surveillance was advised to detect potential recurrences promptly.
CONCLUSION
Ectopic minor salivary gland tumors, both benign and malignant, should be taken into consideration as potential differential diagnosis for any swelling arising within the upper digestive tract mucosa. Ears, nose, and throat clinical examination completed by videolaryngoscopy can easily point out the location of the mass. Imaging is mandatory for differential diagnosis and for surgical planning. Surgical excision can provide both diagnosis and definitive cure.
Topics: Female; Humans; Aged; Cystadenoma, Papillary; Dysphonia; Salivary Glands; Salivary Gland Neoplasms; Larynx
PubMed: 38504337
DOI: 10.1186/s13256-024-04425-2 -
Head and Neck Pathology Mar 2024Oncocytoid salivary tumors include several entities such as oncocytoma, Warthin tumor, secretory carcinoma (SC), salivary duct carcinoma (SDC), acinic cell carcinoma... (Review)
Review
BACKGROUND
Oncocytoid salivary tumors include several entities such as oncocytoma, Warthin tumor, secretory carcinoma (SC), salivary duct carcinoma (SDC), acinic cell carcinoma (AciCC), oncocytic mucoepidermoid carcinoma (OMEC), intraductal carcinoma, and epithelial myoepithelial carcinoma (EMC). This review investigates the differential diagnosis of oncocytoid salivary tumors and explore the role of newly described immunostains as valuable tools for their diagnosing and potentially guiding treatment options.
METHODS
We assess the utility of incorporating new immunohistochemical markers in routine practice to aid in diagnosing oncocytoid salivary tumors and potentially provide treatment options.
RESULTS
In SDC, AR and Her2 immunostains are utilized as diagnostic tools and biomarkers for selecting patients who might benefit from Androgen-deprivation therapy (ADT) and HER2-targeted therapy. Furthermore, nuclear Pan-Trk immunostaining can aid in diagnosing SC. Additionally, NR4A3 immunostaining has been shown high sensitivity and specificity in identifying AciCC in both surgical and cytologic specimens. Similarly, RAS Q61R mutant-specific immunostaining, detected in EMC, may offer a cost-effective diagnostic marker for this tumor. Although further studies are required to evaluate the role of BSND, this marker has been reported to be positive in Warthin tumor and oncocytoma, aiding in differentiating them from other oncocytoid tumors, particularly OMEC. In addition, BRAFV600E mutant-specific immunostaining can serve as a diagnostic and potentially therapeutic marker for oncocytic intraductal carcinoma in mutation positive cases.
CONCLUSION
Oncocytoid salivary tumors may have overlapping morphologies, posing diagnostic challenges for pathologists. Recently described immunohistochemical markers may offer valuable tools for diagnosing and potentially guiding treatment options for these tumors.
Topics: Male; Humans; Adenoma, Oxyphilic; Adenolymphoma; Immunohistochemistry; Diagnosis, Differential; Carcinoma, Intraductal, Noninfiltrating; Androgen Antagonists; Biomarkers, Tumor; Prostatic Neoplasms; Salivary Gland Neoplasms; Carcinoma, Acinar Cell; Carcinoma, Ductal; Breast Neoplasms; Carcinoma
PubMed: 38502259
DOI: 10.1007/s12105-024-01622-9 -
The American Journal of Surgical... May 2024Recurrent gene fusions are common in salivary gland tumors including benign tumors, such as pleomorphic adenoma (PA) and myoepithelioma (ME). In cases where chromosomal...
Recurrent gene fusions are common in salivary gland tumors including benign tumors, such as pleomorphic adenoma (PA) and myoepithelioma (ME). In cases where chromosomal rearrangement is identified in the pleomorphic adenoma gene 1 (PLAG1) gene, different gene partners are found. Oncocytic metaplasia, characterized by oncocytes with abundant eosinophilic granular cytoplasm and hyperchromatic nuclei, is a well-known phenomenon in salivary gland neoplasms. However, the pure oncocytic variant of PA/ME showed PLAG1 gene rearrangements involving various gene partners at the molecular level, without any recurrent fusion being found. Our study includes 20 cases of PA/ME, with 11 females and 9 males. The age of patients ranged from 37 to 96 years, with a median age of 62.8 years. Most tumors originate from the parotid gland. The median size of the tumor was 26.5 mm (range: 13 to 60 mm). Among the 20 cases, 14 were a pure oncocytic variant of PA/ME, whereas 6 cases showed focal oncocytic or oncocytic-like aspects. Molecular studies on 20 cases of PA/ME were conducted. A novel recurrent ZBTB47-AS1::PLAG1 fusion was identified in 6 of 12 cases with pure oncocytic metaplasia, whereas the other cases had PLAG1 gene fusion with different gene partners. The transcriptomic analysis of the cases harboring ZBTB47-AS1::PLAG1 fusion demonstrated that these tumors have a distinct molecular profile from conventional PA/ME. This study reveals a unique subset in the oncocytic PA/ME spectrum characterized by pure oncocytic morphology with larger oncocytic cells and recurrent ZBTB47-AS1::PLAG1 fusion. It also highlights the transcriptomic distinctness of salivary gland adenomas with pure oncocytic metaplasia in the spectrum of salivary gland neoplasms. Further studies are needed to better understand the oncocytic variant of PA/ME and to determine the true nature of oncocytic cells in PA/ME.
Topics: Male; Female; Humans; Middle Aged; Adult; Aged; Aged, 80 and over; Adenoma, Pleomorphic; Myoepithelioma; DNA-Binding Proteins; Salivary Gland Neoplasms; Gene Fusion; Adenoma, Oxyphilic; Metaplasia
PubMed: 38497430
DOI: 10.1097/PAS.0000000000002206 -
Journal of Experimental & Clinical... Mar 2024Immune-checkpoint inhibitors (ICIs) have showed unprecedent efficacy in the treatment of patients with advanced non-small cell lung cancer (NSCLC). However, not all...
BACKGROUND
Immune-checkpoint inhibitors (ICIs) have showed unprecedent efficacy in the treatment of patients with advanced non-small cell lung cancer (NSCLC). However, not all patients manifest clinical benefit due to the lack of reliable predictive biomarkers. We showed preliminary data on the predictive role of the combination of radiomics and plasma extracellular vesicle (EV) PD-L1 to predict durable response to ICIs.
MAIN BODY
Here, we validated this model in a prospective cohort of patients receiving ICIs plus chemotherapy and compared it with patients undergoing chemotherapy alone. This multiparametric model showed high sensitivity and specificity at identifying non-responders to ICIs and outperformed tissue PD-L1, being directly correlated with tumor change.
SHORT CONCLUSION
These findings indicate that the combination of radiomics and EV PD-L1 dynamics is a minimally invasive and promising biomarker for the stratification of patients to receive ICIs.
Topics: Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; B7-H1 Antigen; Radiomics; Multiomics; Prospective Studies; Biomarkers, Tumor; Immunotherapy; Extracellular Vesicles
PubMed: 38486328
DOI: 10.1186/s13046-024-02997-x