High-risk Histopathologic Features Research Articles

Revisiting the Relationship Between Tumor Size and Risk in Well-Differentiated Thyroid Cancer.

Introduction: Large tumor size is associated with poorer outcomes in well-differentiated thyroid cancer, yet it remains unclear whether size >4 cm alone confers increased risk, independent of other markers of aggressive disease. The goal of this study was to assess the relationship between tumor size, other high-risk histopathological features, and survival in well-differentiated thyroid cancer and to evaluate the significance of 4 cm as a cutoff for management decisions. Methods: Patients with well-differentiated thyroid cancer were identified from the National Cancer Database (2010-2015) and categorized by tumor size (i.e., small [≤4 cm] or large [>4 cm]) and presence of high-risk histopathological features (e.g., extrathyroidal extension). First, propensity score matching was used to identify patients who were similar across all other observed characteristics except for small versus large tumor size, and a multivariable Cox proportional hazards model was used to estimate the relationship between tumor size and survival. Second, we assessed whether the presence of high-risk features demonstrates conditional effects on survival based on the presence of tumor size >4 cm using an interaction term. Finally, additional models assessed the relationship between incremental 1 cm increases in tumor size and survival. Analyses were repeated using a validation cohort from the Surveillance, Epidemiology, and End Results Program (2008-2013). Results: Of 193,133 patients in the primary cohort, 7.9% had tumors >4 cm, and 30% had at least one high-risk feature. After matching, tumor size >4 cm was independently associated with worse survival (HR 1.63, p < 0.001). However, tumor size >4 cm and one or more other high-risk features together yielded worse survival than either size >4 cm alone (MMD: 0.70, p < 0.001) or other high-risk features alone (MMD: 0.49, p < 0.001). When assessed in 1 cm increments, the largest increases in hazard of death occurred at 2 cm and 5 cm, not 4 cm. Results from the validation cohort were largely consistent with our primary findings. Conclusions: Concomitant high-risk features confer worse survival than large tumor size alone, and a 4 cm cutoff is not associated with the greatest increase in risk. These findings support a more nuanced approach to tumor size in the management of well-differentiated thyroid cancer.

High-risk histopathologic features in local advanced conjunctival melanoma.

To identify high-risk histopathologic and molecular features of local recurrence, nodal metastasis, distant metastasis (DM) and disease-specific death (DSD) in conjunctival melanoma (CoM). Ninety patients with pathologically diagnosed CoM between 2008 and 2023 were enrolled. Immunohistochemistry staining of BRAFV600E , NRASQ61R , CD117, PD-1 and PD-L1 was performed in 65 and 45 patients, respectively. Cox regression and Kaplan-Meier survival analysis were conducted to identify risk factors for local recurrence, nodal metastasis, DM and DSD. Pathologically, ulceration (hazard ratio [HR]: 3.170; 95% CI: 1.312-7.659; p = 0.01) and regression (HR: 3.196; 95% CI: 1.094-9.335; p = 0.034) were risk factors for DM. Tumour thickness ≥ 4 mm (HR: 4.889; 95% CI: 1.846-12.946; p = 0.001) and regression (HR: 4.011; 95% CI: 1.464-10.991; p = 0.007) were risk factors for DSD. For patients with tumour thickness < 4 mm, the presence of ulceration indicated a higher risk of nodal metastasis (log-rank p = 0.0011), DM (log-rank p = 0.00051) and DSD (log-rank p = 0.02). Patients with regression (+)/tumour-infiltrating lymphocytes (TILs) (+) had a higher risk for DM (log-rank p = 0.011) and DSD (log-rank p = 0.0032). Molecularly, the positive rate of BRAFV600E , NRASQ61R , CD117, PD-1 and PD-L1 was 40.00% (26/65), 43.08% (28/65), 70.77% (46/65), 46.67% (21/45) and 28.89% (13/45), respectively. Positive BRAFV600E was identified as an independent risk factor for DM (HR: 2.533; 95% CI: 1.046-6.136, p = 0.039). The expression level of BRAFV600E was positively correlated with vascular invasion (p = 0.01), as well as the expression levels of PD-1 (p = 0.038) and PD-L1 (p = 0.049). Tumour thickness ≥ 4 mm, ulceration, the coexistence of regression and TILs, and positive BRAFV600E were risk factors for poor prognosis of CoM patients. Besides, expression level of BRAFV600E was positively correlated with the expression levels of PD-1 and PD-L1.

Endoscopic intermuscular dissection for locally advanced rectal cancer: A case report

BACKGROUND Endoscopic submucosal dissection is considered curative for patients with early rectal cancer when level of submucosal invasion is &lt; 1000 microns with favourable histopathological features. Recent data suggests even deeper submucosal invasion can potentially be curative if R0 resection can be achieved and when no high-risk histopathological features are seen in the resected specimen. To achieve R0 resection, deeper dissection is required. CASE SUMMARY A 66 year old New Zealand European male presented with 3 mo history of per rectal bleeding. He was referred for a colonoscopy test to investigate this further. This revealed a malignant appearing lesion in the rectum. Biopsies however showed high grade dysplasia only. Given endoscopic appearances suspicious for deep submucosal invasion, patient was consented for endoscopic intermuscular dissection (EID). The case was successfully performed, and the presence of muscularis propria was confirmed in the resected specimen. There were no complications and total procedure time was 124 min. Lesion was clear of radial margins however deep margins were positive confirming it was at least a pT2 cancer. Patient was recommended to have further treatment but could not have radical surgery due to comorbidities and instead was referred for long course chemoradiotherapy. CONCLUSION EID is a safe and feasible option for management of rectal cancer in highly selected patients.

Abstract LB267: Nitric oxide suppression by secreted frizzled-related protein 2 drives retinoblastoma

Abstract Retinoblastoma is a cancer of the infant retina primarily driven by the loss of the Rb tumor suppressor gene, which is undruggable. Here, we identified an autocrine signaling, mediated by secreted frizzled-related protein 2 (SFRP2), which suppresses nitric oxide and enables retinoblastoma growth. SFRP2 silencing resulted in rapid production of nitric oxide, leading to p53-dependent growth arrest of retinoblastoma cells. We show that coxsackievirus and adenovirus receptor (CXADR) is the cell surface receptor for SFRP2 in retinoblastoma cells, that CXADR functions as a "dependence receptor," transmitting a growth inhibitory signal in the absence of SFRP2, and that the balance between SFRP2 and CXADR determines nitric oxide production. Accordingly, high SFRP2 RNA expression correlates with high-risk histopathologic features in retinoblastoma. Targeting SFRP2 signaling by SFRP2-binding peptides or by a pharmacological inhibitor rapidly induced nitric oxide and profoundly inhibited retinoblastoma growth in orthotopic xenograft models. These results reveal a cytokine signaling pathway that regulates nitric oxide production and retinoblastoma cell proliferation, and is amenable to therapeutic intervention. Citation Format: Panneerselvam Jayabal, Xiuye Ma, Kathryn M. Bondra, Yidong Chen, Peter J. Houghton, Yuzuru Shiio. Nitric oxide suppression by secreted frizzled-related protein 2 drives retinoblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 2 (Clinical Trials and Late-Breaking Research); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(8_Suppl):Abstract nr LB267.

Nitric oxide suppression by secreted frizzled-related protein 2 drives retinoblastoma.

Retinoblastoma is a cancer of the infant retina primarily driven by loss of the Rb tumor suppressor gene, which is undruggable. Here, we report an autocrine signaling, mediated by secreted frizzled-related protein 2 (SFRP2), which suppresses nitric oxide and enables retinoblastoma growth. We show that coxsackievirus and adenovirus receptor (CXADR) is the cell-surface receptor for SFRP2 in retinoblastoma cells; that CXADR functions as a "dependence receptor," transmitting a growth-inhibitory signal in the absence of SFRP2; and that the balance between SFRP2 and CXADR determines nitric oxide production. Accordingly, high SFRP2 RNA expression correlates with high-risk histopathologic features in retinoblastoma. Targeting SFRP2 signaling by SFRP2-binding peptides or by a pharmacological inhibitor rapidly induces nitric oxide and profoundly inhibits retinoblastoma growth in orthotopic xenograft models. These results reveal a cytokine signaling pathway that regulates nitric oxide production and retinoblastoma cell proliferation and is amenable to therapeutic intervention.

Basal Cell Carcinoma of Breast Metastasis to Axillary Lymph Node: A Case Report and Comprehensive Literature Review

Basal cell carcinoma (BCC) metastasis incidence is rare and occurs in advanced, neglected, recurrent tumors or tumors with high risk histopathologic features like perineural invasion. The mainstay of management remains surgical excision with clear margins wherever possible followed by radiotherapy. We are presenting a case of metastatic BCC of an uncommon site i.e., anterior shoulder with metastasis to axillary lymph nodes and to review literature regarding the current standard of management.

Lag time, high-risk histopathological features, metastasis, and survival interrelation in retinoblastoma: a perspective from lower-middle income country.

To investigate the impact of lag time to metastasis and survival rates among patients with retinoblastoma. This retrospective study was conducted with 52 patients from the Department of Ophthalmology and the Department of Pediatrics of Dr. Sardjito General Hospital, between 1st January 2014 and 31st December 2020. Lag time was defined as the time delay between the first sign of retinoblastoma to the diagnosis of retinoblastoma. The subjects with lag time > one year were included in the case group, while the subjects with lag time < one year were included in the control group. The lag time was significantly correlated with American Joint Committee on Cancer and Intraocular Classification of Retinoblastoma staging of retinoblastoma (P=0.005 and P=0.006, respectively). The lag time was also significantly correlated with both metastasis event [odds ratio (OR): 5.06, 95%Cl: 1.56-16.44, P=0.006] and mortality (OR: 4.54, 95%Cl: 1.37-15.07, P=0.011). The follow-up was continued for 32 subjects for 3y after initial diagnoses. Survival analysis revealed a significant difference among these two groups (P=0.021). Furthermore, lag time was significantly correlated with survival of retinoblastoma (r=-0.53, P=0.046). The study highlights the importance of lag time between the onset of first symptoms and the time of retinoblastoma diagnosis which significantly contribute to metastasis and mortality of patients with retinoblastoma. Examinations for the early detection of retinoblastoma should be performed for individuals at-risk to minimize lag time and improve the outcomes.

The Role of Bone Marrow in Baseline Investigations for Advanced Intraocular Retinoblastoma

Objective: To assess the rationale for bone marrow biopsy/aspiration as a part of a routine systemic workup in advanced intraocular retinoblastoma (RB) in relation to high-risk histopathological post-enucleation features. Methods: A retrospective observational study was conducted at the Department of Pediatric Hematology and Oncology of the Children’s Hospital, Lahore, Pakistan. Data regarding demographics, clinical presentations, staging workup, and treatment strategies of all the newly diagnosed retinoblastoma cases registered at our centre from January 2018 to December 2019 were collected. Statistical analysis was performed using IBM SPSS statistics version 22. Results: Of the 61 patients, 41 (67%) showed unilateral disease, while bilateral and trilateral involvement was found in 17 (28%) and three (5%) cases, respectively. The mean age of presentation in our cohort was 25 months (median: 24 months; range: &lt;1–72 months). Amongst 81 eyes (61 patients), tumours were limited to an intraocular location in 54 eyes (46 patients). In this group, 42 eyes (38 patients) underwent enucleation. Adverse histopathology was found only in nine (23.68%) patients. None of the patients with the intraocular disease, with or without adverse histopathological features in enucleated eyes, were found to have bone marrow (BM) involvement. For 15 patients with extraocular disease, five (33%) patients were found to have bone marrow involvement based on initial investigations. Conclusion: Our study did not show any correlation between bone marrow positivity and advanced intraocular groups D/E RB. Therefore, BM evaluation can be avoided in this subset of patients with retinoblastoma at presentation, while stage III and IV patients (International Retinoblastoma Staging System IRSS) must be evaluated for metastasis. This will reduce the risks of biopsy to the patients and the burden on services. Keywords: Retinoblastoma, Bone Marrow Involvement, Intraocular disease.

Correlation between clinical presentations, radiological findings and high risk histopathological features of primary enucleated eyes with advanced retinoblastoma at Queen Sirikit National Institute of Child Health: 5 years result.

To evaluate the correlation between clinical presentations, radiological findings and high risk histopathological features of primary enucleated eyes in patients with advanced retinoblastoma at a tertiary child hospital in Thailand. We retrospectively reviewed the medical records of patients who were treated with primary enucleation of tumor eyes between 2015-2020. Demographic data, radiological assessment, and histopathological findings were collected. The association between clinical presentations and high-risk histopathological features in the primary enucleated eyes were evaluated. The radiological findings, which showed characteristic of high risk features, were compared with the histopathological findings. Thirty-three enucleated eyes were enrolled in this study. The mean age at diagnosis was 23.12 months. Most patients had unilateral group E retinoblastoma, with no difference in sex and laterality of the eye. Leukocoria was the most common presentation, followed by proptosis and uveitis. Older age at presentation were statistically associated with post laminar cribrosa optic nerve invasion (P-value 0.0027) and high-risk histopathological features in enucleated eyes (P-value 0.0032). Clinical presentations with proptosis were statistically associated with post laminar cribrosa optic nerve invasion, while leukocoria and uveitis were statistically associated with anterior segment invasion. Unifocal intraocular mass with necrosis was the most common histopathological finding. High-risk features were found in 45% of primary enucleated eye. The sensitivity and specificity of magnetic resonance imaging (MRI) for detected optic nerve invasion in retinoblastoma patients were 75% and 54%, respectively. Patients with unilateral retinoblastoma who presented with older age related to high-risk features after enucleation. Ophthalmic examination with slitlamp is the best way for detection of anterior segment invasion. Choroidal invasion was unable to predict with clinical presentation. MRI was the better imaging for detection of post laminar cribrosa optic nerve invasion.

Development and Validation of Multiparametric MRI-based Radiomics Models for Preoperative Risk Stratification of Endometrial Cancer.

Background Stratifying high-risk histopathologic features in endometrial carcinoma is important for treatment planning. Radiomics analysis at preoperative MRI holds potential to identify high-risk phenotypes. Purpose To evaluate the performance of multiparametric MRI three-dimensional radiomics-based machine learning models for differentiating low- from high-risk histopathologic markers-deep myometrial invasion (MI), lymphovascular space invasion (LVSI), and high-grade status-and advanced-stage endometrial carcinoma. Materials and Methods This dual-center retrospective study included women with histologically proven endometrial carcinoma who underwent 1.5-T MRI before hysterectomy between January 2011 and July 2015. Exclusion criteria were tumor diameter less than 1 cm, missing MRI sequences or histopathology reports, neoadjuvant therapy, and malignant neoplasms other than endometrial carcinoma. Three-dimensional radiomics features were extracted after tumor segmentation at MRI (T2-weighted, diffusion-weighted, and dynamic contrast-enhanced MRI). Predictive features were selected in the training set with use of random forest (RF) models for each end point, and trained RF models were applied to the external test set. Five board-certified radiologists conducted MRI-based staging and deep MI assessment in the training set. Areas under the receiver operating characteristic curve (AUCs) were reported with balanced accuracies, and radiologists' readings were compared with radiomics with use of McNemar tests. Results In total, 157 women were included: 94 at the first institution (training set; mean age, 66 years ± 11 [SD]) and 63 at the second institution (test set; 67 years ± 12). RF models dichotomizing deep MI, LVSI, high grade, and International Federation of Gynecology and Obstetrics (FIGO) stage led to AUCs of 0.81 (95% CI: 0.68, 0.88), 0.80 (95% CI: 0.67, 0.93), 0.74 (95% CI: 0.61, 0.86), and 0.84 (95% CI: 0.72, 0.92), respectively, in the test set. In the training set, radiomics provided increased performance compared with radiologists' readings for identifying deep MI (balanced accuracy, 86% vs 79%; P = .03), while no evidence of a difference was observed in performance for advanced FIGO stage (80% vs 78%; P = .27). Conclusion Three-dimensional radiomics can stratify patients by using preoperative MRI according to high-risk histopathologic end points in endometrial carcinoma and provide nonsignificantly different or higher performance than radiologists in identifying advanced stage and deep myometrial invasion, respectively. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Kido and Nishio in this issue.

Neoadjuvant and adjuvant therapy for local excision of rectal cancer

Local excision (LE) for early-stage rectal cancer is an attractive option compared to total mesorectal excision (TME), as it avoids many of the significant comorbidities and adverse functional outcomes associated with TME. However, LE for tumors with high-risk histopathologic features can lead to unacceptably high rates of local and distant recurrence. Neoadjuvant or adjuvant chemoradiotherapy can mitigate those risks in certain clinical settings and may expand the number of patients who can be safely treated with an organ-preserving approach. In this chapter, we will explore the available date supporting the use of neoadjuvant and adjuvant chemoradiation (CRT) for the treatment of high-risk early-stage rectal cancer and will discuss future studies that aim to answer some of the ongoing clinical questions related to this practice.

Completion Total Mesorectal Excision After Transanal Local Excision of Early Rectal Cancer: A Systematic Review and Meta-analysis.

Completion total mesorectal excision is recommended when local excision of early rectal cancers demonstrates high-risk histopathological features. Concerns regarding the quality of completion resections and the impact on oncological safety remain unanswered. This study aims to summarize and analyze the outcomes associated with completion surgery and undertake a comparative analysis with primary rectal resections. Data sources included PubMed, Cochrane library, MEDLINE, and Embase databases up to April 2021. All studies reporting any outcome of completion surgery after transanal local excision of an early rectal cancer were selected. Case reports, studies of benign lesions, and studies using flexible endoscopic techniques were not included. The intervention was completion total mesorectal excision after transanal local excision of early rectal cancers. Primary outcome measures included histopathological and long-term oncological outcomes of completion total mesorectal excision. Secondary outcome measures included short-term perioperative outcomes. Twenty-three studies including 646 patients met the eligibility criteria, and 8 studies were included in the meta-analyses. Patients undergoing completion surgery have longer operative times (standardized mean difference, 0.49; 95% CI, 0.23-0.75; p = 0.0002) and higher intraoperative blood loss (standardized mean difference, 0.25; 95% CI, 0.01-0.5; p = 0.04) compared with primary resections, but perioperative morbidity is comparable (risk ratio, 1.26; 95% CI, 0.98-1.62; p = 0.08). Completion surgery is associated with higher rates of incomplete mesorectal specimens (risk ratio, 3.06; 95% CI, 1.41-6.62; p = 0.005) and lower lymph node yields (standardized mean difference, -0.26; 95% CI, -0.47 to 0.06; p = 0.01). Comparative analysis on long-term outcomes is limited, but no evidence of inferior recurrence or survival rates is found. Only small retrospective cohort and case-control studies are published on this topic, with considerable heterogeneity limiting the effectiveness of meta-analysis. This review provides the strongest evidence to date that completion surgery is associated with an inferior histopathological grade of the mesorectum and finds insufficient long-term results to satisfy concerns regarding oncological safety. International collaborative research is required to demonstrate noninferiority. CRD42021245101.

Correlation of clinical and radiological predictors of retinoblastoma with high-risk histopathological features.

Retinoblastoma (RB) tumors having high-risk histopathologic features (HRFs) have an increased risk of metastasis and disease relapse. However, RB has not been studied widely in Pakistan. Therefore, we evaluated the association of clinical, histopathologic, and radiological findings with HRFs in patients with RB who were treated at the Indus Health & Hospital Network in Karachi, Pakistan. We enrolled treatment-naïve patients with RB who received upfront enucleation from September 2017 to February 2021. We evaluated enucleated eyes with the Intraocular Classification of Retinoblastoma system and classified HRFs as invasion of the anterior chamber, including the iris and ciliary body, or massive invasion of the choroid, sclera, or optic nerve (postlaminar and/or up to the transection line). Of 117 patients with RB treated at our institution during the study period, 54 received upfront enucleation. Unilateral disease was present in 92.6% of cases. The most frequent disease signs and symptoms included the presence of vitreous seeds (30.6%) and leukocoria (100%), respectively. The most frequent HRFs and radiological findings comprised massive choroidal invasion (15.1%) and anterior chamber enhancement (66.7%), respectively. The majority (62.9%) of patients did not exhibit any HRFs. Female sex, pseudohypopyon, iris neovascularization, buphthalmos, and glaucoma had significant predictive ability for HRF occurrence. Pseudohypopyon, iris neovascularization, buphthalmos, and glaucoma are important clinical factors that should be taken into consideration before the management of RB. Early recognition of high-risk histopathological and radiological features is essential for appropriate treatment of RB.

Survival outcomes of unilateral retinoblastoma based on pathological risk stratification-experience at a tertiary care centre in Pakistan.

Retinoblastoma (RB) is the most common childhood intraocular malignancy. In high-income countries over the past decade, upfront enucleation for unilateral RB is least favoured due to other alternatives that can help in globe preservation, but in low-middle income countries it is still the preferred option due to lack of resources and expertise. The treatment of RB after enucleation is tailored based on the histopathological risk features, as adjuvant chemotherapy with high-risk features reduces the risk of metastasis. The aim of our study was to analyse the survival outcomes of adjuvant therapy based on histopathological risk stratification in patients who underwent upfront enucleation for unilateral RB with advanced disease. A retrospective study was carried out at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Pakistan. A total 113 patients (aged 3 months till 16 years) diagnosed with unilateral RB who had upfront enucleation from July 2009 till January 2019 were included in this study. The mean age of diagnosis was 37.4 months (±24.5) and male-to-female ratio of 1.3:1. The most common clinical presentation was leukocoria (74.3%). Patients who underwent enucleation had advanced disease; group D present in 62.8% followed by group E (32.7%). Histopathology revealed high-risk features in 29 patients (25.7%) and intermediate risk in 54 patients (47.8%). Disease progression and relapse was seen in patients with high-risk histopathological features. The 4-year over-all survival and EFS observed for this cohort was 74% and 71%. Awareness about the early symptoms among the general population and health care personnel at a nationwide level is needed to facilitate early detection and lessen disease related morbidity and mortality.

Retinoblastoma outcomes: a global perspective

Retinoblastoma outcomes: a global perspective

The role of adjuvant radiotherapy in locally advanced T4 mandible squamous cell carcinoma in the N0 patient: a single centre experience

In locally advanced oral squamous cell carcinoma (OSCC), namely that showing invasion of the mandible, demonstrating no high-risk (e.g. extranodal extension, positive margin) or intermediate-risk histopathological features (e.g. perineural invasion, lymphovascular invasion), the additional benefit of postoperative radiotherapy (PORT) currently remains uncertain. A retrospective review covering the period between January 1, 2010 and December 31, 2019 was conducted to identify patients from a single UK centre with locally advanced invasive mandibular OSCC defined as pT4a, with no nodal or distant metastasis (N0 M0). The primary outcome was to determine the disease-free survival and overall survival rates in the surgery + PORT group, in comparison to the surgery only group. Twenty-eight eligible patients were identified, with 13 patients in the surgery + PORT group and 15 patients in the surgery only group. A single patient in the surgery + PORT group developed disease recurrence and subsequently died (1/13) (median follow-up 5.24 years, range 2.13–10.71 years). No patient in the surgery only group developed disease recurrence or died (0/15) (median follow-up 5.13 years, range 1.37–10.93 years). It may be reasonable to consider omitting PORT in pT4a pN0 M0 OSCC of the mandible in patients who demonstrate no high- or intermediate-risk histopathological features, following multidisciplinary team discussion.

Defining High-risk Retinoblastoma

High-risk histopathologic features of retinoblastoma are useful to assess the risk of systemic metastasis. In this era of globe salvage treatments for retinoblastoma, the definition of high-risk retinoblastoma is evolving. To evaluate variations in the definition of high-risk histopathologic features for metastasis of retinoblastoma in different ocular oncology practices around the world. An electronic web-based, nonvalidated 10-question survey was sent in December 2020 to 52 oncologists and pathologists treating retinoblastoma at referral retinoblastoma centers. Anonymized survey about the definition of high-risk histopathologic features for metastasis of retinoblastoma. High-risk histopathologic features that determine further treatment with adjuvant systemic chemotherapy to prevent metastasis. Among the 52 survey recipients, the results are based on the responses from 27 individuals (52%) from 24 different retinoblastoma practices across 16 countries in 6 continents. The following were considered to be high-risk features: postlaminar optic nerve infiltration (27 [100%]), involvement of optic nerve transection (27 [100%]), extrascleral tissue infiltration (27 [100%]), massive (≥3 mm) choroidal invasion (25 [93%]), microscopic scleral infiltration (23 [85%]), ciliary body infiltration (20 [74%]), trabecular meshwork invasion (18 [67%]), iris infiltration (17 [63%]), anterior chamber seeds (14 [52%]), laminar optic nerve infiltration (13 [48%]), combination of prelaminar and laminar optic nerve infiltration and minor choroidal invasion (11 [41%]), minor (<3 mm) choroidal invasion (5 [19%]), and prelaminar optic nerve infiltration (2 [7%]). The other histopathologic features considered high risk included Schlemm canal invasion (4 [15%]) and severe anaplasia (1 [4%]). Four respondents (15%) said that the presence of more than 1 high-risk feature, especially a combination of massive peripapillary choroidal invasion and postlaminar optic nerve infiltration, should be considered very high risk for metastasis. Responses to this nonvalidated survey conducted in 2020-2021 showed little uniformity in the definition of high-risk retinoblastoma. Postlaminar optic nerve infiltration, involvement of optic nerve transection, and extrascleral tumor extension were the only features uniformly considered as high risk for metastasis across all oncology practices. These findings suggest that the relevance about their value in the current scenario with advanced disease being treated conservatively needs further evaluation; there is also a need to arrive at consensus definitions and conduct prospective multicenter studies to understand their relevance.

High-Risk Histopathologic Features of Retinoblastoma Treated at a Tertiary Hospital in West Java, Indonesia

Purpose: To evaluate the histopathological characteristics of clinically advanced retinoblastoma (RB) and its relationship with tumor differentiation. Methods: This was a cross-sectional study of primary enucleated group D/E intraocular RB using medical records from 2017 to 2020 in a tertiary referral hospital. Cases with incomplete histopathological results were excluded. Tumors were classified into well, moderately, and poorly differentiated and undifferentiated. High-risk histopathological features were classified as per Thaung and Karaa [Community Eye Health. 2018;31(101):17–3]. Results: This study included 121 patients (129 eyes), of which 32.2% were diagnosed at 25–36 months. High-risk features (HRFs) were found in 100/129 eyes, and of 73 complete histopathological results, the 2 most common HRFs were postlaminar optic nerve invasion and massive choroidal invasion. RB was poorly differentiated in 69.9% and well differentiated in 12.3% of eyes. There was no statistically significant association between any HRFs and tumor differentiation, with age >2 years associated with tumor differentiation (p < 0.05). Conclusion: The frequency of HRFs is 77.5% of primary enucleated eyes, mainly poorly and undifferentiated cells, particularly in children aged >2 years old.

Postoperatively determined high-risk histopathologic features in papillary thyroid carcinoma initially eligible for thyroid lobectomy: a game changer.

Recent clinical practice guidelines consider thyroid lobectomy a viable alternative for low-risk papillary thyroid carcinoma PTC measuring 1-4 cm in size. We aimed to assess the likelihood of finding postoperatively determined high-risk histopathologic features that would lead to the recommendation of completion thyroidectomy. A retrospective review of patients who underwent total thyroidectomy for PTC measuring 1-4 cm in size between Jan 2012 and Jan 2018 was conducted. Patients with pre-operative high-risk characteristics were excluded: history of radiation exposure, positive family history, clinically suspicious cervical lymphadenopathy, and gross extrathyroidal extension (ETE). A hypothetical group of 245 patients remained eligible for lobectomy. The pathology specimens from the cancer-containing lobes were evaluated for high-risk features: aggressive histology, capsular and/or vascular invasion, microscopic ETE, and multifocality. A subgroup analysis was performed with 2 cm being the cut-off size. The average age was 39 years with 73% being females. Mean cancer size was 16 mm. Evaluation of the cancer-containing lobe for high-risk features revealed: aggressive histology (33%), ETE (12%), capsular invasion (33%), vascular invasion (17%), and ipsilateral multifocality (30%). The cumulative risk of having ≥1 high-risk feature mandating completion thyroidectomy was 59%. The risk was considerably higher for lesions ≤2 cm compared to larger lesions (64% vs.48%; p = 0.049; RR = 1.3). A considerable proportion of patients initially eligible for lobectomy have high-risk features that only become evident at pathology. Therefore, a comprehensive approach is advocated to determine the extent of surgery for PTC incorporating patient preferences regarding risks and benefits.

Clinical outcomes and prognosis of Thai retinoblastoma patients.

Retinoblastoma (RB) outcomes in Thailand are unfavorable compared to those of developed countries. This study aims to determine whether the clinical outcomes of patients with RB significantly improved after the implementation of new therapeutic approaches and which clinical factors affect survival and globe-saving outcomes. The medical records of patients newly diagnosed with RB and treated at Siriraj Hospital between January 2005 and December 2018 were reviewed retrospectively. Clinical data, treatments, and outcomes were collected and analyzed. In 194 eyes (144 patients), leukocoria was the most common presenting feature (76.8%); 129 (66.5%) eyes were staged in group E of the International Classification of Intraocular Retinoblastoma. Of the 149 enucleated eyes, 35 had high-risk histopathological features, mostly choroidal invasion; 45 eyes (23.2%) could be salvaged. The 5-year overall survival rate was 90.3%, an improvement compared to the previous study. The 5-year enucleation-free survival rates of Groups A and B, C, D and E were 100%, 83.1%, 36.7% and 16.6% respectively. Factors associated with a lower survival rate were interval from symptom onset to diagnosis >3months (hazard ratio (HR): 5.8: 95% confidence interval (CI): 1.637, 20.579) and buphthalmos (HR: 12.57: 95% CI: 3.936, 40.153). Factors associated with high-risk features were secondary glaucoma (HR: 11.016: 95% CI: 1.24, 98.10) and pseudohypopyon (HR: 14.110: 95% CI: 2.16, 92.05). Survival rates and globe-saving rates appear to have improved; however, advanced-stage presentation remains the major hindrance. Further studies with a larger cohort and longer follow-up are warranted.