Programmed Death Ligand-1 (PD-L1) Expression in Cervical Squamous Cell Carcinoma: Does it Correlate With Outcomes?

Cervical cancer is one of the most common gynecological malignancies. Upregulation of programmed death ligand-1 (PD-L1), an immunoregulatory protein, is associated with an adverse outcomes in several malignancies. Most studies evaluating PD-L1 expression in cervical squamous cell carcinoma (CSCC) lack data on outcomes. In this study, we correlate PD-L1 expression with clinicopathologic factors and clinical outcomes in invasive CSCC. Seventy-three cases of CSCC from 2010 to 2018 were immunostained for PD-L1. A combined positive score (CPS) of ≥1 and ≥10 was correlated with age, stage, and survival outcomes. Kaplan-Meier curves for progression-free survival and overall survival were plotted and compared using the log-rank test. Cox regression analysis was performed to identify significant prognostic factors (2-tailed P <0.05 was considered statistically significant). With CPS ≥1 or ≥10 as the cut-off, PD-L1 was positive in 52/73 (71.2%) and 23/73 (31.5%) of cases, respectively. PD-L1 positive patients present at a higher stage of disease, especially those with CPS ≥10. With CPS of ≥10 as the cut-off, the 5-yr progression-free survival and 5-yr overall survival were significantly lower ( P = 0.034 and 0.012, respectively). Only stage was statistically significant for worse overall survival on multivariate analysis. PD-L1 positive patients present at a higher stage of disease, and stage is an independent prognostic indicator for adverse outcomes in CSCC. This study highlights the potential of PD-L1 targeted therapy in patients with CSCC.

Bilateral breast Rosai-Dorfman disease screen detected by mammography.

Rosai-Dorfman disease (RDD) is a proliferative disorder of histiocytes typically found in nodal sites and commonly observed in females. Patients often present with systemic symptoms such as fever, lymphadenopathy, and weight loss. However, extra-nodal disease has been identified in locations including the skin and subcutaneous tissue. We present a case of a 59-year-old female presenting with abnormal bilateral findings on screening mammography, who was found to have a rare presentation of Rosai-Dorfman disease.

Gastric submucosal mass lesions.

PURPOSE OF REVIEW: Gastric submucosal mass lesions are a collection of tumours that arise in the stomach and are deep to the mucosal layer. Distinct from gastric epithelial carcinomas, these tumours are generally more indolent. They are often found incidentally on upper endoscopy. Most often they present as smooth protuberant masses covered by normal intact gastric mucosa. The majority are asymptomatic. Endoscopic ultrasound (EUS) is frequently employed to further characterize the lesions. EUS can be diagnostic of some lesions, such as lipomas, and can be used to guide fine needle aspiration to diagnose others. Adding to the traditional management approaches of observation and surgical resection, numerous new and emerging endoscopic therapies are now being used to resect these gastric tumours. RECENT FINDINGS: This review focuses on evolving strategies in the diagnosis and management of submucosal mass lesions. Although surgical intervention was once the lone option for intervention, there are an increasing number of endoscopic therapies. There have also been advancements in neoadjuvant therapies and in distinguishing the malignant potential of submucosal mass lesions. SUMMARY: Gastric submucosal lesions are common. EUS is frequently indicated in the evaluation and diagnosis. For tumours for which observation is not recommended, novel endoscopic therapies may offer less invasive management options.

Risk Stratification of Prostatic Adenocarcinoma Metastatic to the Lymph Nodes.

CONTEXT.­: The pathologic nodal staging of prostatic adenocarcinoma is binary for regional lymph nodes. Stages pN0 and pN1 indicate the absence or presence of regional nodal metastasis, respectively, whereas patients with metastasis to nonregional lymph nodes are staged as pM1a. OBJECTIVE.­: To determine the risk of recurrence of pN1 prostatic adenocarcinoma patients based on the extent of nodal tumor burden. DESIGN.­: We retrospectively reviewed pN1 patients with prostatic adenocarcinoma managed with radical prostatectomy seen between 2011 and 2019. Kaplan-Meier and Cox regression analyses were performed to compare disease-free survival. RESULTS.­: Ninety-six patients were included (median [interquartile range] age, 62 years [57-67 years]; 70 of 96 [73%] White). On univariate analysis, age >65 years (P = .008), ≥2 positive regional lymph nodes (P < .001), and a maximum size of the tumor deposit ≥2 mm (P = .004) were significantly associated with an unfavorable outcome. Controlling for age, stage, metastatic deposit size, margin status, and the presence of extranodal extension, patients with ≥2 positive regional lymph nodes were 3.03 times more likely (95% confidence interval, 1.39-6.60; P = .005) to have an unfavorable outcome. Patients with pN1M1a stage showed a disease-free survival similar to that of pN1M0 patients, after controlling for the number of positive regional lymph nodes (P = .36). CONCLUSIONS.­: Overall, pN1 patients with ≥2 positive regional lymph nodes are 3 times more likely to have an unfavorable outcome. The results suggest a benefit in further stratifying patients with metastatic prostatic adenocarcinoma to the lymph nodes into prognostically significant risk categories that could help the treating clinicians tailor subsequent patient follow-up and therapy.

Programmed Death Ligand-1 Expression Is Associated With Poorer Survival in Anal Squamous Cell Carcinoma.

CONTEXT.­: Upregulation of programmed death ligand-1 (PD-L1), an immunoregulatory protein, is associated with an adverse outcome in several malignancies. Very few studies have evaluated PD-L1 expression in invasive anal squamous cell carcinoma (ASCC). OBJECTIVE.­: To assess PD-L1 expression in patients with ASCC and correlate it with clinicopathologic factors and clinical outcomes. DESIGN.­: Fifty-one cases of ASCC were immunostained for PD-L1. PD-L1 expression by combined positive score and tumor proportion score was correlated with age, sex, HIV status, HIV viral load, CD4 count, stage, and outcomes. Kaplan-Meier curves for overall survival were plotted and compared using the log-rank test. Cox regression analysis was performed to identify significant prognostic factors (2-tailed P < .05 was considered statistically significant). RESULTS.­: PD-L1 was positive in 24 of 51 cases (47%) by combined positive score and in 18 of 51 (35%) by tumor proportion score. The median cancer-specific survival and 5-year overall survival were significantly lower in PD-L1+ patients. Age, sex, HIV status, HIV viral load, stage, and cancer progression were not significantly different between the 2 groups. CD4 count of more than 200/µL was significantly higher in PD-L1+ patients. PD-L1+ status remained statistically significant for worse overall survival on multivariate analysis. CONCLUSIONS.­: PD-L1+ status is an independent adverse prognostic factor for overall survival in ASCC. This study highlights the potential of PD-L1 targeted therapy in better management of ASCC.

Diagnosing Anal Squamous Intraepithelial Lesions With and Without p16: An Interobserver Variability Study.

OBJECTIVE: Morphologic diagnosis and grading of anal squamous intraepithelial lesions (ASILs) are challenging. In this study, we investigated interobserver variability and p16 utility in accurately grading anal SIL. MATERIALS AND METHODS: Six pathologists evaluated the degree of SIL on hematoxylin and eosin slides from 146 anal biopsies, followed by the review of both p16 and hematoxylin and eosin slides in cases where p16 was previously performed. κ was calculated in the following 4 ways: (A) 4-tiered diagnosis (negative for SIL [NSIL], anal intraepithelial neoplasia [AIN 1, AIN 2, AIN 3]); (B) 3-tiered diagnosis (NSIL and AIN 1 [pooled], AIN 2, AIN 3); (A) 3-tiered diagnosis (NSIL, low-grade SIL, high-grade SIL [HSIL]); and (D) 2-tiered diagnosis (no HSIL, HSIL). RESULTS: There is only moderate agreement with a 4-tiered diagnosis with or without p16 (κ = 0.48-0.57). There is substantial agreement when AIN 2 and AIN 3 are pooled as HSIL in cases with or without p16 review (κ = 0.71-0.78). There is almost perfect agreement with a 2-tiered diagnosis of negative for HSIL and HSIL both in cases where p16 was used and where p16 was not required, with the best agreement for a 2-tiered diagnosis with concurrent p16 review. CONCLUSIONS: This study highlights the importance of a judicious use of p16 for diagnosis. When there is no need for p16 by the Lower Anogenital Squamous Terminology guidelines, interobserver agreement was substantial to almost perfect with a 2-tiered diagnosis. However, when its use is indicated but it is not performed or reviewed, the agreement is much lower even with a 2-tiered diagnosis. Rational use of p16 will ensure diagnostic accuracy and the best possible patient care.