Low-stage Disease Research Articles

Natural course and effect of tafamidis treatment in real-life octogenarians with wild-type transthyretin cardiac amyloidosis: an international multi-centre analysis

Abstract Background and aims In real-life, wild-type transthyretin amyloid cardiomyopathy (ATTRwt-CM) is increasingly diagnosed in elderly patients above 80 years old. Nevertheless, specific data on natural course and outcome under tafamidis treatment in octogenarians are particularly scarce. We aimed to study tafamidis impact on mortality and its determinants in real-life ATTRwt-CM octogenarians. Methods International multi-centric cohort study of 710 consecutive ATTRwt-CM patients, stratified between octogenarians and non-octogenarians at diagnose and tafamidis naive or treatment. Mean follow-up was 2.2±1.8 years to all-cause mortality endpoint. Results The cohort consisted of 58.3% octogenarians (median 84 years, 74.2% male). Before tafamidis availability, natural course in octogenarians (148/257) versus non-octogenarians (109/257) was poor with 41% three-year and 70% five-year mortality versus 19% and 42%, respectively (p<0.001). Since tafamidis availability, 70.1% (253/361) octogenarians were initiated on tafamidis, less than 83.7% (231/276) non-octogenarians (p<0.001). Tafamidis discontinuation was similar (octogenarians 11.4%, non-octogenarians 7.9%, p=0.260). Overall tafamidis treated octogenarians had better survival than untreated octogenarians (p<0.001) and untreated non-octogenarians (p=0.026), with 23% three-year and 51% five-year mortality. Tafamidis treatment related to lower mortality in octogenarians (HR 0.37, 95%CI 0.20-0.67, p=0.001), after correcting for age, NAC stage and NYHA class, the other independent predictors. Propensity-score matching for those variables in 218 subjects confirmed tafamidis mortality benefit in octogenarians (p<0.001). Octogenarians had poorer survival under tafamidis, when initiated at ≥90 years old (p<0.001), NAC stage ≥3 (p=0.001) or NYHA class ≥3 (p=0.055). Conclusions Tafamidis treatment in real-life octogenarians independently improves survival, with better effect of early initiation at lower disease stage and age.Structured graphical abstractDistributions within age category

A temporal (phospho-)proteomic dataset of neurotrophic receptor tyrosine kinase signalling in neuroblastoma

Neurotrophic receptor tyrosine kinases (TrkA, TrkB, TrkC), despite their homology, contribute to the clinical heterogeneity of the childhood cancer neuroblastoma. TrkA expression is associated with low-stage disease and is often seen with spontaneous tumour regression. Conversely, TrkB is present in unfavourable neuroblastomas that often harbour amplification of the MYCN oncogene. The role of TrkC is less clearly defined, although some studies suggest its association with a favourable outcome. Understanding the differences in activity of Trk receptors that drive divergent clinical phenotypes as well as the influence of MYCN amplification on downstream Trk receptor signalling remains poorly understood. Here, we present a comprehensive label-free mass spectrometry-based total proteomics and phosphoproteomics dataset (432 raw files with FragPipe search outputs; available on PRIDE with accession number PXD054441) where we identified and quantified 4,907 proteins, 16,744 phosphosites and 5,084 phosphoproteins, derived from NGF/BDNF/NT-3 treated TrkA/B/C-overexpressing neuroblastoma cells with differential MYCN status. Analysing our dataset offers valuable insights into TrkA/B/C receptor signalling in neuroblastoma and its modulation by MYCN status; and holds potential for advancing therapeutic strategies in this challenging childhood cancer.

12327 Presenting Features of Papillary Thyroid Cancer with Hobnail Histology and Factors Associated with Advanced Disease at Presentation

Abstract Disclosure: S.K. Majumdar: None. J. Sinard: None. The Hobnail subtype of papillary thyroid cancer (PTC) is reported to be a rare form of PTC that manifests with higher rates of extrathyroidal extension, metastases, disease recurrence, and mortality, when compared to classic PTC. We set out to characterize the clinical manifestations and initial pathologic findings of patients with PTC and hobnail histology at our institution. A retrospective search of pathology records from 1/2014 through 1/2024 was conducted to identify rare thyroid cancer variants including those with hobnail histology. An electronic medical record review was then performed to collect clinical information. The study was approved by our institutional IRB. A total of 15 patients with PTC of the hobnail subtype (≥ 30% features) or with hobnail features (< 30%) were identified: 8 hobnail subtype, 5 having hobnail features, 1 had hobnail and oncocytic features, 1 had hobnail and tall cell features. Sixty percent were female, mean age 50.6 years (SD 16.4), 67% white, 27% Hispanic, 6% black. Mean BMI was 29.4 kg/m^2 (SD 5.4), 33% had a history of prior or current smoking. Cancers were found incidentally in 33% of cases (3 after physical exam noting goiter or nodule), 53% presented with a newly noticed neck lesion, one of these presented with hoarseness and cough from tracheal invasion which was found later at surgery. Mean tumor size 2.65 cm (SD 1.7), 13 patients had 1 or more lymph nodes removed with at least one node being positive in 77% of cases. Rates of lymphatic invasion were 73% (33% extensive), vascular invasion 13%, and 13% had gross extrathyroidal extension. After initial surgery 60% had stage 1 disease, 27% stage 2, and 13% stage 3. One patient was changed to stage 4 upon the later discovery of lung metastases and this patient had 30% tall cell features on pathology. Three patients had T3 or T4 tumors, all of whom were from minority and vulnerable populations (2 non-English speaking Hispanic, 1 Black with mental illness), had significantly higher BMI than others (36.2 ± 4 vs 27.2 ± 4.5, p = 0.01), and tended to be older (67 ± 9.5 vs 46.5 ± 16, p = 0.057 ns). Long term follow up was limited since hobnail histology was only found in reports beginning in 2017 and became more frequent in 2022 and 2023. Although limited by case number, our findings show that patients who presented with the most advanced disease were from vulnerable populations, were older, and had higher BMI’s than those with lower stage disease. Also, coexistence of other variants, like tall cell changes, may impact presentation. Therefore, while PTC with hobnail histology is typically associated with more advanced disease presentations, psychosocial and other factors appeared to explain higher stage disease at presentation in our series. Presentation: 6/3/2024

Association of ATM and ARID1A in gastric carcinoma

BackgroundThe ataxia telangiectasia mutated (ATM) gene is involved in the repair of double-stranded DNA breaks and a component of the DNA damage repair pathway. Tumors with mutations or low expression of both ARID1A and ATM exhibit increased numbers of tumor-infiltrating lymphocytes and a favorable prognosis. However, the relationship between ATM and ARID1A in gastric carcinoma (GC) is unclear. MethodsWe used the mRNA expression data from the Asian Cancer Research Group to construct tissue microarrays (N = 249). Next-generation sequencing (NGS) databases of Samsung Medical Center (SMC) (N = 813) were used to compare genetic alterations. Tissue microarrays were used for ATM and ARID1A immunohistochemistry, and expressions were categorized as “low” and “high.” NGS data from TCGA-STAD (N = 431) were used as independent cohorts for genetic alterations validation. ResultsIn GCs, 32.1% (80/249) of the cases showed low ATM protein expression (ATMlow) and 20.9% (52/249) showed low ARID1A expression (ARID1Alow). ATMlow was significantly associated with older age (P <.01), gross type of tumor (P =.02), histology (P <. 01), lower incidence of perineural invasion (P =.04), lower disease stage (P <.01), microsatellite instability-high (P <.01), and ARID1Alow (P <.01). Furthermore, GCs in the SMC NGS database showed that ATM mutations were significantly correlated with ARID1A mutations (P <.01), and this finding remained significant in TCGA-STAD validation cohort (P <.01). ConclusionATMlow in GCs shows a characteristic clinicopathological feature that correlates strongly with ARID1Alow. ATM mutation was also associated with ARID1A mutations, highlighting the interactions between ATM and ARID1A in GC and suggesting a potential therapeutic target.

“Find Your Y”: histological differences in early stage (pT) and post-treatment (ypT) oesophageal adenocarcinoma with implications for salvage endoscopic resection

AimsCurrent guidelines offer limited strategies for managing recurrent/persistent oesophageal adenocarcinoma (EAC). Salvage endoscopic mucosal/submucosal resection (ER) shows promise in oesophageal squamous cell carcinoma, however its success in EAC is limited....

Real-World Analysis of Breast Cancer Patients Qualifying for Adjuvant CDK4/6 Inhibitors

BackgroundAdjuvant CDK4/6 inhibitors abemaciclib and ribociclib improved disease-free survival (DFS) added to endocrine therapy in hormone receptor (HR)-positive HER2-negative early breast cancer (EBC), in monarchE (NCT03155997) and NATALEE (NCT03701334) trials respectively. We assessed the proportion and outcome of EBC patients qualifying for adjuvant CDK4/6 inhibitors in the real-world. MethodsConsecutive female patients with HR-positive HER2-negative EBC between 1997 and 2017 from the Australian Capital Territory and South-East New South Wales Breast Cancer Treatment Group registry were analyzed. Patients eligible for abemaciclib had ≥4 axillary nodes involved or 1-3 nodes plus primary >5 cm or grade 3. Ribociclib eligibility was defined as node-positive and node-negative with primary >5 cm or >2 cm grade 3. ResultsOf 3840 patients, 671 (17.5%) were abemaciclib-eligible and 1587 (41.3%) ribociclib-eligible . The 5-year DFS was 77% and 94% in abemaciclib-eligible and noneligible registry patients respectively (HR 2.6, 95% CI 2.26-3.05, P < .001). The 5-year DFS was 86% and 97% in ribociclib-eligible and noneligible registry patients respectively (HR 1.92, 95% CI 1.67-2.19, P < .001). Compared with monarchE trial patients, abemaciclib-eligible registry patients were older (median 55 years in registry vs. 51 years in trial), with lower nodal burden (≥4 nodes in 44% in registry vs. 60% in trial). There were more stage III cancers in NATALEE trial patients (60%) than ribociclib-eligible registry patients (24%). ConclusionsMany women with EBC will qualify for adjuvant CDK4/6 inhibitors (17.5% abemaciclib, 41.3% ribociclib) with resource and workforce implications. In the real-world setting, a greater proportion of adjuvant CDK4/6-eligible patients have lower stage disease, therefore the absolute benefit from treatment may be smaller than estimated by the trials.

Gastroesophageal signet ring cell carcinoma morbidity and mortality: A retrospective review.

Upper gastrointestinal (GI) signet ring cell carcinomas (SRCC) confer a poor prognosis. The benefit of operative intervention for this patient group is controversial in terms of overall survival. To investigate factors relating to survival in patients with upper GI SRCC. A retrospective, tertiary, single-centre review of patients who were diagnosed with oesophageal, gastroesophageal junction and gastric SRCC was performed. The primary outcome was to compare mortality of patients who underwent operative management with those who had nonoperative management. Secondary outcomes included assessing the relationship between demographic and histopathological factors, and survival. One hundred and thirty-one patients were included. The one-year survival for the operative group was 81% and for the nonoperative group was 19.1%. The five-year survival in the operative group was 28.6% vs 1.5% in the nonoperative group. The difference in overall survival between groups was statistically significant (HR 0.19, 95%CI (0.13-0.30), P < 0.001). There was no difference in survival when adjusting for age, smoking status or gender. On multivariate analysis, patients who underwent surgical management, those with a lower stage of disease, and those with a lower Charlson Comorbidity Index (CCI) had significantly improved survival. Well-selected patients with upper GI SRCC appear to have reasonable medium-term survival following surgery. Offering surgery to a carefully selected patient group may improve the outcome for this disease.

Molecular classification of metastatic and recurrent endometrial endometrioid carcinoma: prognostic relevance among low- and high-stage tumours.

Molecular classification according to The Cancer Genome Atlas (TCGA) improves endometrial endometrioid carcinoma (EEC) prognostication and has specific treatment implications; however, original data were skewed towards low-grade and low-stage tumours. Herein, we molecularly classify EECs metastatic at the time of diagnosis or with subsequently documented recurrent/metastatic disease to examine correlation with clinical outcomes. TCGA categories include POLE-mutated, microsatellite instability (MSI), p53 abnormal (p53 abnl) and no specific molecular profile (NSMP). POLE targeted sequencing at exons 9, 11, 13 and 14 and immunohistochemistry (IHC) for PMS2, MSH6 and p53 were performed to establish molecular classification. The distribution in our cohort of 141 EECs was similar to that generally reported in EEC, with nine POLE-mutated (6%), 45 MSI (32%), 16 p53 abnl (11%) and 71 NSMP (50%), with similar distributions between low- and high-stage cohorts. We demonstrate that when stratified by molecular subtype, disease-specific survival from the time of high-stage (stages III-IV) presentation or time of recurrence in low-stage (stages I-II) disease among metastatic and/or recurrent EEC is strongly associated with TCGA classification (high-stage P = 0.02, low-stage P = 0.017). Discordant molecular classification between primary and metastatic/recurrent tumours occurred in four of 105 (3.8%) patients, two related to PMS2/MSH6 IHC and two related to p53 IHC. We demonstrate that molecular classification is prognostically relevant not only at the time of diagnosis, but also at the time of recurrence and in the metastatic setting. Rare subclonal alterations occur and suggest a role for confirming TCGA classification in recurrent/metastatic tumours.

Adjuvant BRAF/MEK versus anti-PD-1 in BRAF-mutant melanoma: Propensity score–matched recurrence-free, distant metastasis-free, and overall survival analysis.

9573 Background: Adjuvant BRAF/MEK inhibitors (BRAF/MEKi) and immunotherapy with anti-PD-1 have become the standard of care for resected high-risk stage III and IV melanoma, but a head-to-head comparison is lacking. In our earlier study, we compared adjuvant BRAF/MEKi and anti-PD-1 in a nationwide cohort in the Netherlands. However, the follow-up was too limited for overall survival (OS) analysis. We present an updated analysis including OS with extended follow-up. Methods: We included all resected high-risk stage III melanoma patients treated with first-line adjuvant BRAF/MEKi and anti-PD-1 from the Dutch Melanoma Treatment Registry from 2018-2023. We performed a propensity score matched outcome analysis of 1- and 2-year recurrence-free survival (RFS), distant metastasis-free survival (DMFS), and OS. Grade ≥ 3 toxicity rates and discontinuation rates due to toxicity were described. Results: In total, 225 BRAF/MEKi-treated patients and 729 anti-PD-1-treated patients were included. BRAF/MEKi-treated patients had lower disease stages (16.4% versus 10.2% stage IIIA disease; p=0.01) and more comorbidities (76.0% versus 63.8%; p&lt;0.01) than anti-PD-1-treated patients. Median follow-up duration was 20.9 months. Two similar groups of 213 patients each were created by propensity score matching. Before matching, RFS and DMFS were significantly shorter in the anti-PD-1 treated patients, OS was not (Table). After matching, the 1- and 2-year RFS, DMFS and OS rates were not significantly different (Table). Toxicity data will be presented at the meeting. Conclusions: Our results suggest no significant differences in outcomes between adjuvant BRAF/MEKi and anti-PD-1 treatment in stage III melanoma.[Table: see text]

An analysis of post-operative thromboembolic events in patients diagnosed with gastro-esophageal cancer.

e16123 Background: Venous thromboembolism (VTE) commonly manifests as a postoperative complication of gastroesophageal cancer (GEC) surgery. However, guidelines seldom differentiate preventive approaches for postoperative VTE based on cancer types. Furthermore, there is a lack of research evaluating factors associated with the risk of thrombosis for patients diagnosed with GEC who undergo surgery. Herein, we aim to determine the incidence of VTE after GEC surgery and the clinical characteristics of the patients associated with VTE events. Methods: We retrospectively reviewed the charts of patients diagnosed with GEC and underwent gastrectomy/esophagectomy at Cleveland Clinic, OH, and Weston, FL, between 2005 and 2022. Patients who had non-malignant diseases or did not undergo invasive surgery were excluded. Of the 437 patients who underwent GEC surgery, only 375 met the inclusion criteria. Patients who developed a VTE event diagnosed by imaging studies within one year of GEC surgery were considered positive for the event. DVT prophylaxis (DDPX) was defined as the administration of anticoagulants, such as heparin and enoxaparin. The average length of DVT prophylaxis was 7 days. The chi-square test was used to assess the significant differences among the groups based on VTE status. Results: In this cohort of 375 patients, 54 (14.4%) patients experienced VTE. 43 patients (79.60%) who experienced a VTE event received DDPX, whereas 10 patients (18.50%) with VTE did not receive DDPX. Of the 321 patients who did not develop VTE, 251 patients (78.20%) received DDPX, while 66 patients (20.60%) did not receive DDPX. DDPX administration in both cohorts was not significantly different (p 0.868). Notably, 36 (66.7%) of the patients developed VTE events within 30 days following GEC surgery, with a subsequent significant decrease in VTE incidence beyond this timeframe (9.3%, 7.4%, 11.1%, and 5.5% in the 30-60-, 60-90, 90–180, and 180-365-day intervals, respectively, p &lt; 0.001). Among the patients who presented with gastrointestinal stromal and neuroendocrine tumors (7.50%), none of the patients developed a VTE event. Nevertheless, 19.35% of the 31 patients diagnosed with squamous cell carcinoma had a VTE within one year of GEC. Patients with Stage IV disease had a higher risk of VTE compared to lower-stage disease (25.95%, p 0.032). However, factors such as BMI, smoking status, type of surgery, treatment regimens, and ECOG score were not significantly associated with VTE. Conclusions: Patients diagnosed with GEC who underwent surgical intervention demonstrated a significant propensity for VTE, particularly within 30 days post-surgery. The rate of VTE incidence was not significantly different among the DPPX and non-DPPX cohorts, which could be attributed to the short duration of anticoagulation. Further studies are warranted to investigate the optimal duration of DDPX.

#2918 Genetic background of kidney graft cancer

Abstract Background and Aims Renal cell carcinoma (RCC) is one of the most prevalent cancer in kidney transplant recipient (KTR). Majority of RCC occurs in native kidney as opposed to kidney graft. The genetic background of RCC in native kidneys has been determined implicating the clinical importance. Method This single-center cohort study aimed to identify genetic background of kidney graft RCC and outcome in KTR who underwent single kidney transplantation between January 2000 and December 2020 and manifested kidney graft RCC. Genetic analysis (NGS) from peripheral blood-derived genomic DNA (gDNA) was performed in both the recipient and donor using cancer-predisposition panel CZECANCA (CZEch CAncer paNel for Clinical Application). Results The calculated incidence of kidney graft RCC was 0.43%. Of the eighteen KTR with manifested kidney graft RCC, fifteen KTR and donors underwent NGS. The average patient age at transplantation was 50.3 years (median 54; 5-67 years) and 66 years (median 66; 24-79 years) at the diagnosis of kidney graft RCC. The mean donor age at transplantation was 39.7 years (median 42; 7-68 years) and graft age at kidney graft RCC diagnosis 50.2 years (median 46; 20-83 years). The mean follow-up after RCC diagnosis was 47 months (median 39.1; 0-112 months). The most prevalent was papillary RCC (n=8) followed by clear cell RCC (n=6) and renal pelvis urothelial RCC (n=1). Thirteen RCC were low stage (pT1a/b) disease, one was pT3 and one was unknown stage. Majority of RCC were higher graded. No cancer-predisposition gene was found in KTR or his donor. Conclusion Kidney graft RCC is very rare. NGS cancer-predisposition panel CZECANCA has not detected any genetic predisposition for kidney graft RCC. Further research is needed to assess clinical relevance of genetic testing for cancer risk in KTR.

Thrombocytosis Is a Poor Prognostic Factor in Those Treated With Chemoradiation for Advanced Cervical Cancer [ID 2683596

INTRODUCTION: Prior to the addition of chemotherapy to radiation, thrombocytosis was seen as a poor prognostic factor for women with advanced cervical cancer. The objective of this study was to see in the chemoradiation era whether thrombocytosis was still a prognostic factor. METHODS: An IRB-approved study was performed analyzing all patients with cervical cancer receiving primary chemoradiation (cisplatin) as therapy over a 10-year period. Minimum follow-up was 30 months. Records were examined for initial platelet count at diagnosis, stage, grade, histology, and survival. Only patients receiving chemoradiation with stage IIa–IVb cervical cancer were studied and included in the final analysis. RESULTS: Two hundred nine with cervical cancer were diagnosed with 173 treated with primary chemoradiation. The most common stage was IIIb (88; 50.9%). The mean platelet counts of those receiving chemoradiation were significantly higher (396k/mL; 95% CI, 376–416k) than those with lower-stage disease (313k/mL; 292–334k) (P&lt;.001). Of the 173 patients, 42 (24.3%) had a platelet count &gt;450k/mL and 24 (13.9%) had a platelet count &gt;500k/mL. Patients who died of disease had significantly higher initial platelet counts (mean 433k/mL; 95% CI, 407–458k) than those who were alive at the completion of follow-up (mean 326k/mL; 95% CI, 303–350k). None of the patients with an initial platelet count greater than 500k/mL was alive at the time of follow-up. CONCLUSION: High platelet count at initial diagnosis is a poor prognostic factor in those with cervical cancer treated by primary chemoradiation.

Addressing racial disparities in prostate cancer pathology prediction models: external validation and comparison of four models of pathological outcome prediction before radical prostatectomy in the multiethnic SEARCH cohort.

Certain widely used pathological outcome prediction models that were developed in tertiary centers tend to overpredict outcomes in the community setting; thus, the Michigan Urological-Surgery Improvement Collaborative (MUSIC) model was developed in general urology practice to address this issue. Additionally, the development of these models involved a relatively small proportion of Black men, potentially compromising the accuracy of predictions in this patient group. We tested the validity of the MUSIC and three widely used nomograms to compare their overall and race-stratified predictive performance. We extracted data from 4139 (1138 Black) men from the Shared Equal Access Regional Cancer Hospital (SEARCH) database of the Veterans Affairs health system. The predictive performance of the MUSIC model was compared to the Memorial-Sloan Kettering (MSK), Briganti-2012, and Partin-2017 models for predicting lymph-node invasion (LNI), extra-prostatic extension (EPE), and seminal vesicle invasion (SVI). The median PSA of Black men was higher than White men (7.8 vs. 6.8 ng/ml), although they were younger by a median of three years and presented at a lower-stage disease. MUSIC model showed comparable discriminatory capacity (AUC:77.0%) compared to MSK (79.2%), Partin-2017 (74.6%), and Briganti-2012 (76.3%), with better calibration for LNI. AUCs for EPE and SVI were 72.7% and 76.9%, respectively, all comparable to the MSK and Partin models. LNI AUCs for Black and White men were 69.6% and 79.6%, respectively, while EPE and SVI AUCs were comparable between races. EPE and LNI had worse calibration in Black men. Decision curve analysis showed MUSIC superiority over the MSK model in predicting LNI, especially among Black men. Although the discriminatory performance of all models was comparable for each outcome, the MUSIC model exhibited superior net benefit to the MSK model in predicting LNI outcomes among Black men in the SEARCH population.

Association between Medicaid Expansion and Cutaneous Melanoma Diagnosis and Outcomes: Does Where You Live Make a Difference?

Early detection and standardized treatment are crucial for enhancing outcomes for patients with cutaneous melanoma, the commonly diagnosed skin cancer. However, access to quality health care services remains a critical barrier for many patients, particularly the uninsured. Whereas Medicaid expansion (ME) has had a positive impact on some cancers, its specific influence on cutaneous melanoma remains understudied. The National Cancer Database identified 87,512 patients 40-64 years of age with a diagnosis of non-metastatic cutaneous melanoma between 2004 and 2017. In this study, patient demographics, disease characteristics, and treatment variables were analyzed, and ME status was determined based on state policies. Standard univariate statistics were used to compare patients with a diagnosis of non-metastatic cutaneous melanoma between ME and non-ME states. The Kaplan-Meier method and log-rank tests were used to evaluate overall survival (OS) between ME and non-ME states. Multivariable Cox regression models were used to examine associations with OS. Overall, 28.6 % (n = 25,031) of the overall cohort was in ME states. The patients in ME states were more likely to be insured, live in neighborhoods with higher median income quartiles, receive treatment at academic/research cancer centers, have lower stages of disease, and receive surgery than the patients in non-ME states. Kaplan-Meier analysis found enhanced 5-year OS for the patients in ME states across all stages. Cox regression showed improved survival in ME states for stage II (hazard ratio [HR], 0.84) and stage III (HR, 0.75) melanoma. This study underscores the positive association between ME and improved diagnosis, treatment, and outcomes for patients with non-metastatic cutaneous melanoma. These findings advocate for continued efforts to enhance health care accessibility for vulnerable populations.

Micronodular thymoma with lymphoid stroma: As benign as it sounds.

Micronodular thymoma (MNT) is a rare subtype of thymoma (reported incidence is approximately 1-5%). We report a case received as a core biopsy from the "right lung mass" of a 31-year-old female. CT scan showed an 8.1 cm large well-defined mass lesion in the right middle lobe, causing indentation and mild compression of the right atrium. Microscopically, the biopsy showed a thymic neoplasm comprised of multiple discrete and coalescing nodules of bland epithelioid tumor cells separated by an epithelial cell-free lymphocyte-rich stroma. On immunohistochemistry, cytokeratin highlighted the thymic epithelial cells. The lymphoid cells showed a naive T-cell phenotype (TdT+ CD 3+). It is worthwhile recognizing this rare variant of thymoma as almost all the patients present with localized low stage disease with rare/no reports of recurrences or distant metastases.

Cortical-sparing chronic traumatic encephalopathy (CSCTE): a distinct subtype of CTE.

Chronic traumatic encephalopathy (CTE) is a neurodegenerative disease caused by repetitive head impacts (RHI) and pathologically defined as neuronal phosphorylated tau aggregates around small blood vessels and concentrated at sulcal depths. Cross-sectional studies suggest that tau inclusions follow a stereotyped pattern that begins in the neocortex in low stage disease, followed by involvement of the medial temporal lobe and subcortical regions with significant neocortical burden in high stage CTE. Here, we define a subset of brain donors with high stage CTE and with a low overall cortical burden of tau inclusions (mean semiquantitative value ≤1) and classify them as cortical-sparing CTE (CSCTE). Of 620 brain donors with pathologically diagnosed CTE, 66 (11%) met criteria for CSCTE. Compared to typical high stage CTE, those with CSCTE had a similar age at death and years of contact sports participation and were less likely to carry apolipoprotein ε4 (p<0.05). CSCTE had less overall tau pathology severity, but a proportional increase of disease burden in medial temporal lobe and brainstem regions compared to the neocortex (p's<0.001). CSCTE also had lower prevalence of comorbid neurodegenerative disease. Clinically, CSCTE participants were less likely to have dementia (p= 0.023) and had less severe cognitive difficulties (as reported by informants using the Functional Activities Questionnaire (FAQ); p<0.001, meta-cognitional index T score; p=0.002 and Cognitive Difficulties Scale (CDS); p<0.001,) but had an earlier onset age of behavioral (p=0.006) and Parkinsonian motor (p=0.013) symptoms when compared to typical high stage CTE. Other comorbid tauopathies likely contributed in part to these differences: when cases with concurrent Alzheimer dementia or frontal temporal lobar degeneration with tau pathology were excluded, differences were largely retained, but only remained significant for FAQ (p=0.042), meta-cognition index T score (p=0.014) and age of Parkinsonian motor symptom onset (p=0.046). Overall, CSCTE appears to be a distinct subtype of high stage CTE with relatively greater involvement of subcortical and brainstem regions and less severe cognitive symptoms.

Social factors and age play a significant role in cervical cancer and advanced-stage disease among Danish women

BackgroundFor cervical cancer (CC), the implementation of preventive strategies has the potential to make cervical cancer occurrence and death largely avoidable. To better understand the factors possibly responsible for cervical cancer, we aimed to examine possible differences in age and social parameters as well as screening status between women with low- or high-stage cervical cancer and matched controls.MethodsThrough the Danish Cancer Registry (DCR), women diagnosed with cervical cancer in Denmark between 1987 and 2016 were included. These were age- and residence-matched in a 1:5 ratio with controls from the general female population. The study population was sub grouped into a low-stage subpopulation with women with early-stage cervical cancer and matched controls and a high-stage subpopulation with women with late-stage cervical cancer and matched controls. Age and social parameters were compared within the subpopulations as well as between low- and high-stage cases. For part of the study population, screening attendance was examined to compare differences in adherence.ResultsOverall, we found that the risk of cervical cancer is significantly increased in socially disadvantaged women and not least non-attenders in screening. Interestingly, the high-stage subpopulation was significantly older than the low-stage subpopulation (p < 0.001), and when examining the impact of age further, we found that for cervical cancer cases, the risk of having low-stage disease decreases significantly with increasing age, whereas the risk of having high-stage disease increases significantly with increasing age. In the screening cohort, significantly less cases than controls were attenders in screening with the most pronounced differences seen in the old subpopulation (women aged 50–64 years) and in the high-stage subpopulation (p-values all < 0.001). Interestingly, when examining the risk of CC for attenders and non-attenders, we demonstrated that many social parameters continue to influence the risk of cervical cancer, even in women attending screening.ConclusionsOlder women, socially disadvantaged women, and non-attenders in screening are particularly vulnerable in terms of developing cervical cancer, especially high-stage disease. Therefore, improvements in the participating rate in screening as well as a revision of the current screening guidelines are needed.

Mucosal Melanoma Clinical Management and Prognostic Implications: A Retrospective Cohort Study.

Mucosal melanoma (MM) is an uncommon melanoma subtype affecting mucosal surfaces of the head and neck, anorectal region, and vulvovaginal area. We aimed to present our experience at a tertiary-level hospital regarding MM diagnosis, management, monitoring of progression, mutations, and outcome predictors. We performed a registry-based cohort study including MM cases diagnosed from 2012 to 2022 and retrospectively characterized somatic mutations on BRAF, NRAS and c-KIT. We employed Kaplan-Meier curves, log-rank tests, and Cox regression analysis to explore prognostic factors and survival outcomes in a cohort of 35 patients, mainly women (63%) with a median age of 70 years. Predominantly, MM occurred in the vulvovaginal region (48.6%). At diagnosis, 28.6% had lymph node involvement, and 31.4% also had distant metastasis. Mutations in BRAF and c-KIT were identified in 3/35 (9%) and 2/6 patients (33%), respectively. Surgery was performed in 71.4% of patients, and most received systemic treatment (65.7%). Lower disease stage, thinner Breslow depth, and surgical resection were associated with improved overall survival. Notably, age, sex, radiotherapy, and BRAF mutant status did not affect survival. Standard management typically involves immunotherapy. Cases with BRAF or c-KIT mutations may be considered for targeted therapies. Unfortunately, MM prognosis remains unfavorable, with a less than 50% survival rate at 2 years.

MAML2 gene rearrangement occurs in all Warthin-like mucoepidermoid carcinoma: A reappraisal in a series of 29 cases

BackgroundWarthin-like Mucoepidermoid carcinoma (MEC) is a new and rare morphological variant of MEC, with only a few case reports in the literature. The clinicopathological, molecular features and bio-behaviors of Warthin-like MEC has not been studied extensively. We reappraisal all Warthin-like MEC patients diagnosed and treated at our hospital. MethodsPatient characteristics including clinicopathological features, genetic aberrations, treatment, and prognostic information were assessed and evaluated. ResultsTwenty-nine Warthin-like MEC patients were identified, 19 patients were female (65.5 %), and 10 were male (34.5 %). The patients’ age varied widely from 8 to 68 years (mean 42.3 years). Genetic aberrations of MAML2 rearrangement were detected in all Warthin-like MEC patients, which suggesting this genetic event is the unique feature of Warthin-like MEC. Twenty-five patients (86.2 %) were assessed as having a low-stage disease (I/II), and four (13.8 %) as having high-clinical stage disease (III/IV). More than half of the patients (16/29) underwent only partial sialoadenectomy; 2 patients underwent extended sialoadenectomy, and 11 patients underwent extended sialoadenectomy with cervical lymph node dissection. After a median follow-up time of 73 months (5–128 months), Twenty-eight patients were alive without recurrence at the end of the follow-up period, one patient died 1 year after surgery due to lung metastasis. ConclusionOur data suggested that most Warthin-like MEC exhibited mild clinicopathological course and less aggressive bio-behavior, and an aggressive bio-behavior seemed to be very rare. In addition, in the salivary gland, MAML2 rearrangement seems to be a unique molecular feature of salivary Warthin-like MEC.

Analyzing factors associated with the receipt of surgery in clear cell sarcoma.

447 Background: Clear cell sarcoma (CCS) is a ultrarare soft tissue sarcoma, which is highly aggressive and associated with a poor prognosis. CCS is histologically characterized by clear cells, representative of intracellular glycogen accumulation. Primary tumors commonly arise from tendinous sheaths or aponeuroses in the upper and lower extremities—the most common site being around the ankles. Average age at diagnosis is 25 years old. 5-year survival is between 40 and 60%. CCS is the result of fusion gene EWSR1/ATF1. Multimodal therapy, including wide surgical excision with radiotherapy, is often used to treat CCS. Chemotherapy may be used if patients are not eligible for surgery. No significant study has analyzed the factors which predict the utilization of wide surgical excision. This study aims to describe the factors involved in the receipt of this surgery. Methods: The National Cancer Database (NCDB) was used to identify patients diagnosed with CCS from 2004 to 2020 using histology codes 9044 as assigned by the Commission on Cancer Accreditation program. Kaplan-Meier, ANOVA Chi-Square, and Logistic Regression tests were performed, and data were analyzed using SPSS version 27. Statistical significance was set at α = 0.05. Results: 669 patients with CCS formed the initial sample. Of these patients, 466 patients (69.7%) received a surgical procedure of the primary site. Additionally, 14 patients (2.09%) received radiation and 69 patients (10.31%) received adjuvant chemotherapy. The receipt of surgery was associated with a marked increase in median survival ( 91.5 months vs. 8.525 months; p&lt;0.05). Surgical resection with clear margins was achieved in 409 patients (61.14%), of whom experienced improved survival compared to patients with residual tumor burden. Each additional year of age in a patient conferred a 2.4% decrease in likelihood of the patient receiving surgery. Lower stage disease was significantly more likely to be treated surgically (OR 11.4; p&lt;0.001), while stage IV disease and abdominal primary site tumors were associated with lower rates of surgery. Facility type (academic vs. nonacademic), insurance, or distance travelled for care had no effect on rates of surgery. Conclusions: As a significant portion of CCS patients receive surgical treatment, this study confirms that tumor resection is associated with increased overall survival of patients with CCS. Improved survival with surgery correlates with clear surgical margins and full tumor resection. It appears that patients are more likely to be treated surgically if their disease is of lower stage. Patients with abdominal primary site tumors or stage IV disease are less likely to receive surgery. This research serves as the beginning of developing standardized treatment plans for CCS patients. Further studies are needed to better understand the factors involved in receiving surgery and other treatment modalities as part of CCS treatment.