Squamous Cell Carcinoma Histology Research Articles

Racial and ethnic disparities in nasopharyngeal cancer with an emphasis among Asian Americans.

118 Background: Nasopharyngeal cancer (NPC) is characterized by a distinct geographic distribution which reflects genetic predispositions, with highest incidence in Southeastern Asia and Southern China. It continues to cause a significant health burden among Asian Americans (AAs), which is a fast growing but understudied racial group. Prior studies investigating NPC combined all AA groups which may mask heterogeneities among AA subgroups. We aimed to examine the disparities in NPC by dividing AAs into four major ethnic groups - Chinese, Filipinos, Vietnamese, and Japanese Americans. Methods: NPC cases were identified from the Surveillance, Epidemiology, and End Result (SEER) 18 database from 1975-2016. Information regarding age, sex, race/ethnicity, education, income, % of foreign born, marital status, region of SEER registry, stage, histology, grade, surgery, chemotherapy, and radiation therapy were extracted. Multivariate-adjusted Cox proportional hazard regression and Fine-Gray sub-distribution hazard models were used to calculate overall and cause-specific mortality. SEER*Stat was used to calculated age-adjusted incidence. Results: Among a total of 11,737 NPC patients, 42.2% were non-Hispanic White (NHW), 10.7% non-Hispanic Black (NHB), 7.1% Hispanics, 18.9% Chinese, 7.6% Filipinos, 4.8% Vietnamese, 1.0% Japanese and 7.7% other Asians. AAs continue to have the highest NPC incidence among all racial groups despite of an overall decreasing trend. Japanese were significantly more likely to be diagnosed at localized stage, having low grade tumor and having keratinizing squamous cell carcinoma histology compared to other AAs. Compared to NHW, Filipino Americans had decreased mortality (HR = 0.90; 95%CI:0.84-0.98). Chinese (HR = 0.95; 95%CI: 0.90-1.01), and Vietnamese (HR = 0.94; 95%CI: 0.86-1.03) also observed marginally reduced mortality but not Japanese Americans (HR = 1.09; 95%CI: 0.90-1.32). No differences in NPC-specific mortality by race/ethnicity groups were found. In addition, Chinese, Filipino and Vietnamese Americans with NPC were less likely to die of other cancer and cardiovascular disease than NHW, but no such differences were observed among NHB, Hispanics or Japanese Americans. Conclusions: Asian Americans have been historically studied as one single racial group mostly due to limited sample size, despite that it is consistent of a diverse population with different genetic makeup, socioeconomic status, cultural background, health behaviors, and health care access. Our novel finding that significant disparities exist within AA NPC patients in regard to demographic and clinical features, overall and cause-specific mortality underlines the importance of adequate AA-subgroup specific sample size in future studies in order to understand the prognostic role of ethnicity in NPC, and advocates more ethnically and culturally tailored cancer care delivery.

Spindle cell squamous cell carcinoma exhibiting prominent neutrophil phagocytosis: a case report

BackgroundSpindle cell squamous cell carcinoma is an uncommon variant of squamous cell carcinoma; its diagnosis is sometimes challenging because it histopathologically resembles neoplastic or reactive spindle cell lesions of mesenchymal origins. Here, we report a rare case of spindle cell squamous cell carcinoma exhibiting prominent neutrophil phagocytosis.Case presentationA 69-year-old Japanese man presented with pain and a polypoid mass on the lower left gingiva. He had received chemoradiotherapy for squamous cell carcinoma of the buccal mucosa 15 years prior to this consultation. In addition, he was treated for mandibular osteonecrosis 6 years after chemoradiotherapy without evidence of cancer recurrence. A biopsy revealed atypical spindle or pleomorphic cells scattered in the edematous and fibrin-rich stroma; however, no malignant squamous components were apparent. These atypical cells frequently contained neutrophils within their cytoplasm that formed cell-in-cell figures. Immunohistochemically, the atypical cells were negative for cytokeratins, epithelial membrane antigen, and E-cadherin, but positive for p63, vimentin, and p53. Although these findings suggested spindle cell squamous cell carcinoma, it was difficult to reach a definitive diagnosis. Based on a clinical diagnosis of a malignant tumor, the patient underwent a hemimandibulectomy. The surgically resected specimen had a typical spindle cell squamous cell carcinoma histology consisting of biphasic spindle cells and conventional squamous cell carcinoma components. Moreover, the surgical specimen also exhibited spindle tumor cells that frequently included neutrophils, around which intense staining for lysosomal-associated membrane protein 1 and cathepsin B was observed. This suggested that the cell-in-cell figures represent active neutrophil phagocytosis by tumor cells, and not emperipolesis.ConclusionThe presence of neutrophil phagocytosis may be a potent indicator of malignancy.

Patients with early-stage cervical cancer have an increased risk of preterm birth in a population-based cohort study

<h3>Objectives:</h3> Cancer therapy can impact not only fertility but also the course of a subsequent pregnancy. Over 40% of women with cervical cancer will be diagnosed prior to age 45 and many will have not completed childbearing. Those with early-stage disease are eligible for fertility-sparing surgery (FSS), which is increasingly utilized. We sought to evaluate obstetric outcomes among cervical cancer patients in a population-based cohort. <h3>Methods:</h3> This is a population based retrospective study of women age 18-45 years with a history of (FIGO 2009) stage IA1-IB1 cervical cancer reported to the California Cancer Registry (CCR) for the years 2000-2012. CCR data were linked to the 2000-2015 California Office of Statewide Health Planning and Development (OSPHD) birth and discharge datasets to establish a linked database with both oncologic characteristics and obstetric outcomes. Exposure status was defined as cervical cancer patients who conceived at least 3 months after fertility-sparing surgery (FSS) and delivered after 23 weeks gestational age (GA). The primary outcome was preterm birth, and only the first pregnancy following cancer diagnosis was considered. Secondary outcomes included growth restriction, fetal demise, neonatal morbidity (any of the following: need for respiratory support within 72 hours of life, hypoxic-ischemic encephalopathy, seizure, sepsis/pneumonia, meconium aspiration syndrome, birth trauma, and intracranial or subgaleal hemorrhage), and severe maternal morbidity (SMM) as defined by the CDC. Propensity score was used to match similar women in 2 groups in a 1:2 ratio (when possible) of cases to controls: group 1: women who conceived at least 1 year prior to their cervical cancer diagnosis; group 2: healthy controls. Wald statistics and logistic regression were used to evaluate outcomes. <h3>Results:</h3> Of the 4087 patients who were 18-45 years at time of cervical cancer diagnosis, 40.9% (n=1671) had a recorded pregnancy. Of those, 113 conceived following FSS and were primarily non-Hispanic White (52.2%) followed by Hispanic (31.9%) with a median age of 32 years (29-36). The majority had squamous cell carcinoma histology (62.8%), and of those with known type of surgery (97.3%), 90.9% had a LEEP or conization and 9.1% had a trachelectomy. Prematurity rates prior to 32 and 37 weeks were 5.3% and 26.5% respectively, and the live birth rate was 99.1%. Propensity score matching yielded 213 group 1 controls and 226 group 2 controls. Cervical cancer was associated with higher odds of preterm birth before 32 weeks compared to healthy controls (OR 4.17 95% CI 1.023-16.99), but not compared to control group 1, and higher odds of preterm birth before 37 weeks compared to both control groups (OR 2.39, 95% CI 1.34-4.25; OR 3.94, 95% CI 2.10^-7.38, control 1, 2 respectively). There were no differences between the groups in rates of: growth restriction (5th or 10th percentile), fetal demise, and delivery via cesarean section. Neonatal morbidity was more common among the cervical cancer cohort compared to both control groups (OR 2.69, 95% CI 1.29-5.64; OR 2.3, 95% CI 1.15-4.72, control 1,2 respectively). <h3>Conclusions:</h3> In a population-based cohort, patients who conceived at least 3 months following surgery for early-stage cervical cancer had a high live birth rate, but higher odds of preterm delivery and consequent neonatal morbidity compared to matched controls who had a pregnancy prior to their diagnosis as well as healthy controls.

Molecular profiling and characteristics of non-small-cell lung cancer patientsin Georgia.

Aims: In patients with advanced non-small-cell lung cancer, the correlation between histopathology, smoking status, driver oncogene mutations and PD-L1 overexpression were investigated. Patients and methods: A total of 202 patients were identified. Research was done in Georgia. Results: EGFR mutations were detected in 6% of the tested cases (12/187) and five out of 12 EGFR+ cases had histology consistent withsquamous cell carcinoma. No statistically significant correlation was observed between PD-L1 expression, smoking status and clinicopathological characteristics. However, the correlation between smoking status and histologywas statistically significant (p = 0.0264), as never-smokers had ahigher incidence of adenocarcinomahistology. Conclusion: The study showed asmall percentage of EGFR mutationsassociated with adenocarcinomahistology and revealed a solid existence of this mutation in squamous cell carcinomahistology. A higher incidence of adenocarcinomahistology was observed in never-smokers.

Patients with early-stage (T1-2N0) adenosquamous lung cancer have worse long-term survival compared to patients with early-stage lung adenocarcinoma or squamous cell histology.

8550 Background: Survival outcomes for patients with adenosquamous carcinoma of the lung are not well understood by virtue of reduced prevalence. The objective of this study is to compare the long-term survival among patients with adenocarcinoma, squamous cell carcinoma and adenosquamous carcinoma of the lung. Methods: Overall survival of all patients with adenosquamous carcinoma, squamous cell carcinoma, and adenocarcinoma who received guideline-concordant treatment for T1-2N0M0 from 2004-2017 in the National Cancer Data Base was assessed using Kaplan-Meier analysis, multivariable Cox proportional hazard analysis, and propensity score-matched analysis. Results: Among patients who met study criteria (N = 88,983), there were 2,469 (2.77%) patients with adenosquamous, 60,148 (67.59%) with adenocarcinoma and 26,366 (29.63%) with squamous cell carcinoma histology. In patients who had T1-T2 N0 M0 disease, adenosquamous carcinoma was associated with significantly worse 5-year overall survival (58.9% [95%CI:56.6%-61.1%]) when compared with adenocarcinoma (72.4% [95% CI:72.0%-72.8%]) and squamous cell carcinoma (62.6% [95% CI:61.9%-63.3%]). In multivariable Cox proportional hazards analysis, adenocarcinoma (HR 0.81 [95% CI:0.76-0.87], p &lt; 0.001) and squamous cell carcinoma (HR 0.86 [95% CI:0.80-0.92], p &lt; 0.001) continued to be associated with significantly better survival when compared to adenosquamous carcinoma histology. A propensity score-matched analysis of 1,854 adenocarcinoma and 1,854 adenosquamous patients who were well matched by 17 common prognostic covariates (including tumor size and comorbidities) found that adenosquamous histology (57.2% [95% CI:54.7%-59.6%]) was associated with worse survival when compared to adenocarcinoma (63.0% [95% CI:60.6%-65.4%]). An additional propensity score-matched analysis of 1,852 squamous cell carcinoma and 1,852 adenosquamous patients matched by the same covariates demonstrated that adenosquamous carcinoma (57.1% [95%CI:54.6%-59.6%]) was associated with worse survival when compared with squamous cell carcinoma (64.0% [95% CI:61.5%-66.4%]). Conclusions: Early stage adenosquamous carcinoma of the lung is associated with worse overall survival compared to its individual histologic components of adenocarcinoma or squamous cell carcinoma. These observations in both the unmatched and propensity matched patient cohorts invoke consideration of multimodality therapy for these early tumors.

Comparison of Lobectomy and Sublobar Resection for Stage IA Elderly NSCLC Patients (≥70 Years): A Population-Based Propensity Score Matching's Study.

BackgroundTo investigate the differences in survival between lobectomy and sub-lobar resection for elderly stage I non-small-cell lung cancer (NSCLC) patients using the Surveillance, Epidemiology, and End Results (SEER) registry.MethodThe data of stage IA elderly NSCLC patients (≥ 70 years) with tumors less than or equal to 3 cm in diameter were extracted. Propensity-matched analysis was used. Lung cancer-specific survival (LCSS) was compared among the patients after lobectomy and sub-lobar resection. The proportional hazards model was applied to identify multiple prognostic factors.ResultsA total of 3,504 patients met criteria after propensity score matching (PSM). Although the LCSS was better for lobectomy than for sub-lobar resection in patients with tumors ≤ 3 cm before PSM (p < 0.001), no significant difference in the LCSS was identified between the two treatment groups after PSM (p = 0.191). Multivariate Cox regression showed the elder age, male gender, squamous cell carcinoma (SQC) histology type, poor/undifferentiated grade and a large tumor size were associated with poor LCSS. The subgroup analysis of tumor sizes, histologic types and lymph nodes (LNs) dissection, there were also no significant difference for LCSS between lobectomy and sub-lobar resection. The sub-lobar resection was further divided into segmentectomy or wedge resection, and it demonstrated that no significant differences in LCSS were identified among the treatment subgroups either. Multivariate Cox regression analysis showed that the elder age, poor/undifferentiated grade and a large tumor size were a statistically significant independent factor associated with survival.ConclusionIn terms of LCSS, lobectomy has no significant advantage over sub-lobar resection in elderly patients with stage IA NSCLC if lymph node assessment is performed adequately. The present data may contribute to develop a more suitable surgical treatment strategy for the stage IA elderly NSCLC patients.

Preoperative nutritional status is associated with the prognosis for lung cancer.

We investigated whether preoperative nutritional indicators predicted the prognosis for patients with early-stage non-small cell lung cancer. Data for stage I or stage IIA non-small cell lung cancer without lymph node metastasis patients who received anatomical lung resection and were followed-up at least five years after surgery (n=286) were analyzed. We calculated geriatric nutritional risk index, prognostic nutritional index, controlling nutritional status score, and modified Glasgow prognostic score. Multivariate Cox proportional hazard model adjusting for age, BMI, complication, pathological stage, histology of squamous cell carcinoma, T factor, diffusing capacity for carbon monoxide, surgery and smoking status was fitted to evaluate the association between these nutritional indicators and mortality and recurrence within five years. After adjusted for covariates other than type of surgery and diffusing capacity for carbon monoxide, controlling nutritional status of ≥3 was significantly associated with mortality (hazard ratio (HR) = 2.68, 95% confidence interval (CI) = 1.02, 7.01). The association remained marginally significant by adjusting for type of surgery and diffusing capacity for carbon monoxide (HR = 2.44, 95% CI = 0.92, 6.45). controlling nutritional status of ≥3 was significantly associated with recurrence (HR = 2.60; 95% CI: 1.20, 5.61) after adjusting for all covariates. Other nutritional indices did not predict the prognosis in multivariate analysis. Preoperative high controlling nutritional status score was marginally and significantly associated with mortality and recurrence of non-small cell lung cancer patients after lung resection.

The role of pulmonary metastasectomy for pulmonary metastasis from head and neck cancer

The incidence rate of distant metastasis from head and neck (HN) cancers is 4.2–58.8%. The lung is the most common site of distant metastasis, and pulmonary metastasectomy (PM) can be performed in selected patients with pulmonary metastasis originating from HN cancers. However, due to the small number of study objectives, the knowledge on PM treatment of pulmonary metastasis from HN cancers remains insufficient, and the optimal management of pulmonary metastasis from HN cancer is unclear. Patients with pulmonary metastasis from HN cancer who underwent PM have a better prognosis than those who did not, with reported 5-year overall survival rates after PM of 20.9–59.4%. A histology of squamous cell carcinoma, incomplete resection, a short disease-free interval (DFI), and the oral cancer have been identified as factors predicting a worse prognosis after PM in this patient population. As a systemic therapy, longer overall survival has been achieved using immune check point inhibitors compared with standard single-agent therapies. Since the clinical and morphological diagnoses of pulmonary metastasis from HN cancers are often difficult, molecular techniques can provide useful information for the differential diagnosis between pulmonary metastasis from HN cancers and primary lung cancers. In cases of suspected pulmonary metastasis from HN cancer, the surgical strategy should be determined based on the patient’s clinical background.

MicroRNA expression profiling and biomarker validation in treatment-naïve and drug resistant non-small cell lung cancer

BackgroundIn the absence of targetable mutations or immune checkpoints, cisplatin-doublet chemotherapy remains the standard of care in non-small cell lung cancer (NSCLC). Drug resistance has however become a significant clinical challenge. Exploring a role for small non-coding microRNAs (miRNA) as biomarker candidates in cisplatin resistant (CisR) lung cancer is lacking and warrants further investigation.MethodsmiRNA expression profiling was assessed in a panel of cisplatin sensitive and resistant NSCLC cell lines and validated by qPCR. Modulation of altered miRNAs was studied using antagomiRs and pre-miRs while functional assays were used to assess cisplatin response. The translational relevance of these miRNAs as potential biomarkers was assessed in serum and matched normal and tumour lung tissues from chemo-naïve NSCLC patients, in addition to xenograft formalin-fixed paraffin-embedded (FFPE) tumours derived from cisplatin sensitive and resistant cell lines.ResultsDifferential expression of a 5-miR signature (miR-30a-3p, miR-30b-5p, miR-30c-5p, miR-34a-5p, miR-4286) demonstrated their ability to distinguish between normal and tumour lung tissue and between NSCLC histologies. In squamous cell carcinoma (SqCC), tissue miRNA expression was associated with poor survival. miR-4286 showed promise as a blood-based diagnostic biomarker that could distinguish between adenocarcinoma and SqCC histologies. In a xenograft model of cisplatin resistance, using 7-9 week old female NOD/SCID mice (NOD.CB17-Prkdcscid/NCrCrl), a 5-miRNA panel showed altered expression between sensitive and resistant tumours.ConclusionsThis study identified a panel of miRNAs which may have diagnostic and prognostic potential as novel biomarkers in lung cancer and furthermore, may have a predictive role in monitoring the emergence of resistance to cisplatin.

Prognostic value of the number of the metastatic lymph nodes in locally early-stage cervical cancer: squamous cell carcinoma versus non-squamous cell carcinoma

To clarify the prognostic value of the number of metastatic lymph nodes (mLNs) in squamous and non-squamous histologies among women with node-positive cervical cancer. One hundred ninety-one node-positive cervical cancer patients who had undergone radical hysterectomy plus systematic pelvic and para-aortic lymphadenectomy followed by concurrent radiochemotherapy were retrospectively reviewed. The prognostic value of the number of mLNs was investigated in squamous cell carcinoma (SCC) v (n = 148) and non-SCC (n = 43) histologies separately with univariate log-rank test and multivariate Cox regression analyses. In SCC cohort, mLNs > 2 was significantly associated with decreased 5-year disease-free survival (DFS) [hazard ratio (HR) = 2.06; 95% confidence interval (CI) 1.03-4.09; p = 0.03) and overall survival (OS) (HR = 2.35, 95% CI 1.11-4.99; p = 0.02). However mLNs > 2 had no significant impact on 5-year DFS and 5-year OS rates in non-SCC cohort (p = 0.94 and p = 0.94, respectively). We stratified the entire study population as SCC with mLNs ≤ 2, SCC with mLNs > 2, and non-SCC groups. Thereafter, we compared survival outcomes. The non-SCC group had worse 5-year OS (46.8% vs. 85.3%, respectively; p < 0.001) and 5-year DFS rates (31.6% vs. 82.2%, respectively; p < 0.001) when compared to those of the SCC group with mLNs ≤ 2. However, the non-SCC group and the SCC group with mLNs > 2 had similar 5-year OS (46.8% vs. 65.5%, respectively; p = 0.16) and 5-year DFS rates (31.6% vs. 57.5%, respectively; p = 0.06). Node-positive cervical cancer patients who have non-SCC histology as well as those who have SCC histology with mLNs > 2 seem to have worse survival outcomes when compared to women who have SCC histology with mLNs ≤ 2.

Incidence rates and contemporary trends in primary urethral cancer

PurposeWe assessed contemporary incidence rates and trends of primary urethral cancer.MethodsWe identified urethral cancer patients within Surveillance, Epidemiology and End Results registry (SEER, 2004–2016). Age-standardized incidence rates per 1,000,000 (ASR) were calculated. Log linear regression analyses were used to compute average annual percent change (AAPC).ResultsFrom 2004 to 2016, 1907 patients with urethral cancer were diagnosed (ASR 1.69; AAPC: -0.98%, p = 0.3). ASR rates were higher in males than in females (2.70 vs. 0.55), respectively and did not change over the time (both p = 0.3). Highest incidence rates were recorded in respectively ≥75 (0.77), 55–74 (0.71) and ≤54 (0.19) years of age categories, in that order. African Americans exhibited highest incidence rate (3.33) followed by Caucasians (1.72), other race groups (1.57) and Hispanics (1.57), in that order. A significant decrease occurred over time in Hispanics, but not in other race groups. In African Americans, male and female sex-stratified incidence rates were higher than in any other race group. Urothelial histological subtype exhibited highest incidence rate (0.92), followed by squamous cell carcinoma (0.41), adenocarcinoma (0.29) and other histologies (0.20). In stage stratified analyses, T1N0M0 stage exhibited highest incidence rate. However, it decreased over time (−3.00%, p = 0.02) in favor of T1-4N1-2M0 stage (+ 2.11%, p = 0.02).ConclusionUrethral cancer is rare. Its incidence rates are highest in males, elderly patients, African Americans and in urothelial histological subtype. Most urethral cancer cases are T1N0M0, but over time, the incidence of T1N0M0 decreased in favor of T1-4N1-2M0.

ESOPHAGEAL CANCER IN SOUTH INDIA; AN INSTITUTIONAL 5-YEARS RETROSPECTIVE ANALYSIS ON ITS CLINICOPATHOLOGY AND RISK FACTORS OF DISTANT METASTASIS

Context: Esophageal cancer (EC) is highly fatal malignancy with considerable geographical variation in its distribution, etiologies, histopathological subtypes, and mortality. Methods: A retrospective analysis was performed to study the clinicopathology, and risk factors of distant metastasis (DM) among 255 cases of EC treated between January 2015 and December 2019 in a tertiary cancer center in south India. Statistical analysis: Chi-square test and multivariate analysis (MVA) were used for analysis. P &lt; 0.05 was considered signicant. Results: The median age at diagnosis of EC was 57 years, higher for male. Younger EC patients (≤ 40 years) constituted 8.2%, and were commonly female, non-smoker, non-alcoholic, squamous cell carcinoma (SCC). Male: female ratio was 1.67:1. Lower thoracic esophagus was the commonest site. SCC was the commonest histology. Adenocarcinoma (ADC) was common among older age, male, esophagogastric junction (EGJ), high grade tumor, and carried higher risk of DM. ADC had higher propensity for liver metastasis, whereas SCC for lung metastasis. MVA showed the risk factors associated with DM were poor performance status (PS), delayed diagnosis, EGJ tumor, ADC histology, high grade tumor. Conclusion: Lower thoracic esophageal location and SCC histology remains the commonest type of EC in southern part of India. Younger EC patients are commonly female, nonsmokers, non alcoholic, SCC. ADC is common in male, older age. EGJ tumor are commonly ADC, high grade, and carries higher risk of DM, which warrants early diagnosis, aggressive systemic therapy in this subset of patients for improving the survival.

Comparison Between Urothelial and Non-Urothelial Urethral Cancer.

BackgroundTo test the effect of variant histology relative to urothelial histology on stage at presentation, cancer specific mortality (CSM), and overall mortality (OM) after chemotherapy use, in urethral cancer.Materials and MethodsWithin the Surveillance, Epidemiology and End Results (2004–2016) database, we identified 1,907 primary variant histology urethral cancer patients. Kaplan-Meier plots, Cox regression analyses, cumulative incidence-plots, multivariable competing-risks regression models and propensity score matching for patient and tumor characteristics were used.ResultsOf 1,907 eligible urethral cancer patients, urothelial histology affected 1,009 (52.9%) vs. squamous cell carcinoma (SCC) 455 (23.6%) vs. adenocarcinoma 278 (14.6%) vs. other histology 165 (8.7%) patients. Urothelial histological patients exhibited lower stages at presentation than SCC, adenocarcinoma or other histology patients. In urothelial histology patients, five-year CSM was 23.5% vs. 34.4% in SCC [Hazard Ratio (HR) 1.57] vs. 40.7% in adenocarcinoma (HR 1.69) vs. 43.4% in other histology (HR 1.99, p < 0.001). After matching in multivariate competing-risks regression models, variant histology exhibited 1.35-fold higher CSM than urothelial. Finally, in metastatic urethral cancer, lower OM was recorded after chemotherapy in general, including metastatic adenocarcinoma and other variant histology subtypes, except metastatic SCC.ConclusionAdenocarcinoma, SCC and other histology subtypes affect fewer patients than urothelial histology. Presence of variant histology results in higher CSM. Finally, chemotherapy for metastatic urethral cancer improves survival in adenocarcinoma and other variant histology subtypes, but not in SCC.

The Outcomes of Multi-Disciplinary Treatment of Esophageal Cancer in Vajira Hospital

Background: Esophageal cancer is one of the most fatal and difficult-to-treat cancer. Multi-modality management is the key to success of improving outcomes, however, which modality is the most proper is difficult to determine. Objective: To evaluate the overall survival (OS) of patients with early or locally-advanced (E/LA) esophageal carcinoma treated in Vajira Hospital. The outcomes of the multi-modality management among patients with E/LA diseases were evaluated. Materials and Methods: The retrospective analyses of esophageal carcinoma patients who attended at Vajira Hospital between January 1, 2012 and December 31, 2016 were performed. Results: There were 86 patients with complete medical records. The median age was 60.5 years (IQR 52 to 66). Sixty-five patients (75.6%) presented with E/LA diseases. Most of the patients had primary site at thoracic part of esophagus (58 patients, 67.4%) and had squamous cell carcinoma histology (84 patients, 97.7%). Tri-modality treatment including neoadjuvant chemoradiation and esophagectomy for clinically fitted patients without evidence of mediastinal involvement and non-regional lymph node metastasis resulted in the best survival outcome [28.56 months (IQR 10.64 to 46.47)]. The OS of patients with E/LA disease was only 9.15 months (IQR 4.49 to 23.02). Male patients, non-cervical site, and non-surgical treatment were associated with the worse OS. Conclusion: The outcomes of patients with esophageal carcinoma treated in a real-world practice is still not impressive. Tri-modality management would be the best paradigm; however, it is suitable for well-selected patients. Keywords: Esophageal cancer, Multi-modality treatment, Real-world practice

EGFR Protein Expression Relates with Tumor Histology, Methylation Status of EGFR and HPV16 E6 Viral Load in Oropharyngeal Carcinoma.

The epidermal growth factor receptor (EGFR) pathway is important in tumorigenesis of oropharyngeal carcinoma (OPC). However, the molecular mechanisms contributing to EGFR expression in OPC are not well-known. To detect relating factors and clinicopathological impact of EGFR protein expression in OPC, gene amplification/loss, point mutations including synonymous mutations, and promoter methylation of EGFR, and the viral genome load of human papillomavirus type 16 (HPV16)-E5, -E6, and -E7, after extracting HPV16-related OPCs with qPCR of HPV16-E6 and E7, were investigated in 74 OPC surgical cases, including 52 HPV-related (HPV-OPC) and 22 HPV-unrelated (nHPV-OPC). Immunohistochemical (IHC) data of EGFR expression (high, weak, and negative), validated by the qPCR of EGFR mRNA, were compared with molecular, viral, and clinicopathological data of patients. All nHPV-OPC cases were EGFR-IHC-high, whereas 21.2%, 65.4%, and 13.5% of HPV-OPC cases showed EGFR-IHC-high, -weak, -negative (p < 0.01), respectively. In HPV-OPC cases, EGFR-IHC-weak/negative status was related to promoter methylation of EGFR (p = 0.009), but not with gene amplification/loss or the point mutation of EGFR and was more often seen in HPV16-OPC cases (p = 0.049). Among HPV16-OPC cases, EGFR-IHC-weak/negative was related to high E6 expression. EGFR protein-loss was related to the tumor histology of non-keratinizing squamous cell carcinoma (SCC) (p = 0.035) but not with patient prognosis. In conclusion, decreased EGFR protein expression was more frequent in HPV-OPC than in nHPV-OPC and was related to EGFR methylation, infection of HPV16, and the viral genome load of HPV16-E6. Clinicopathologically, it was related to the tumor histology of non-keratinizing SCC.

Prevalence of programmed death ligand-1 in patients diagnosed with non-small cell lung cancer in Lebanon.

Introduction:Programmed death ligand-1 expression has been shown to be a good predictor of response to cancer therapy with checkpoint inhibitors. Its expression varies among different tumor types and among non-small cell lung cancer patients with different clinical and demographic characteristics. The prevalence and determinants of programmed death ligand-1 expression have been previously reported from various regions of the world, but data from Lebanon are lacking. This study examines the prevalence and the clinical, demographic and pathological predictors of programmed death ligand-1 expression in patients diagnosed with non-small cell lung cancer in Lebanon.Methods:Medical records of 180 patients diagnosed with primary non-small cell lung cancer at our institution and tested for programmed death ligand-1 expression were reviewed. Clinical, demographic and pathological information were collected and correlated with programmed death ligand-1 expression using the chi-square test and logistic regression.Results:One hundred eleven of the 180 non-small cell lung cancer tumor samples tested positive for programmed death ligand-1 expression (61.7%). 27.2% of those tumor samples expressed programmed death ligand-1 in 1%–49% of tumor cells, while 34.4% of tumor samples expressed programmed death ligand-1 in 50% or more of their cells. Squamous histology and advanced stage were significant predictors of programmed death ligand-1 expression (odds ratio = 2.79, 95% confidence interval [1.13–6.90], p = 0.012 and odds ratio = 2.48, 95% confidence interval [1.23–4.99], p = 0.044, respectively).Conclusion:Similar to reports from other populations, our results suggest that programmed death ligand-1 expression in non-small cell lung cancer is highly prevalent in the Lebanese population, especially in patients with advanced stage at diagnosis or squamous cell carcinoma histology. Because of the small sample size, while more that 60% of the patients are Lebanese, the results of this article cannot be extrapolated to the Middle Eastern and the Levantine population.

Survival rate of cervical cancer from a study conducted in India

Objectives: The incidence and mortality rates of cervical cancer in the world are 13.1/105 and 6.9/105, respectively. In India, it is estimated that there are 96,922 new cervical cancer cases and 60,078 deaths and ranked second among women cancers. The incidence and mortality rates are 14.7/105 and 9.2/105, respectively, although the incidence varies within Indian population. The majority of these cervical patients report at a late-stage of disease in health-care facility due to lack of awareness. A premier tertiary cancer hospital in Mumbai conducted the present survival-study. The aim of the study was to assess the various factors that determine the survival outcomes by age at diagnosis, role of comorbidities, stage of disease, and treatment. Material and Methods: The main source of information was patients’ medical records from which the data were abstracted, and active follow-up was undertaken. 1678 cases diagnosed between the years 2006 and 2008 at Tata Memorial Hospital are analyzed using actuarial method for obtaining survival rates and log-rank tests for comparison of survival groups. Results: The 5-year survival rate was 76.0% for those aged ≤50 years, 73.3% for non-residents, 74.4% for literates, and 81.8% for Christians and 72.5% for those with squamous cell carcinoma histology; those with no comorbidities had marginally better survival than their counter-parts. The survival rates were 83.5%, 80.6%, 66.0%, and 37.1% for Stage I, Stage II, Stage III, and Stage IV, respectively. The best survival outcomes were for those treated with only surgery (95.6%), or in combination with either radiotherapy (90.6%) or with radiotherapy and chemotherapy (85.5%). Involvement of either nodes/sites had poorer survival than those with no-involvement. In the multivariate analysis, only stage of the disease emerged as a significant prognosis factor. Conclusion: The study concluded that younger patients, early stage of disease, non-involvement of any sites/ nodes, and radiotherapy either alone or in combination with other treatment type provided better outcomes. Early detection and prevention strategies are keys to obtain better outcomes.

CYLD-mutant cylindroma-like basaloid carcinoma of the anus: a genetically and morphologically distinct class of HPV-related anal carcinoma

Rare reports of anal carcinoma (AC) describe histologic resemblance to cutaneous cylindroma, but mutations in the tumor suppressor CYLD, the gene responsible for familial and sporadic cylindromas, have not been systematically investigated in AC. Here, we investigate CYLD-mutant AC, focusing on molecular correlates of distinct histopathology. Comprehensive genomic profiling (hybrid-capture-based DNA sequencing) was performed on 574 ACs, of which 75 unique cases (13%) harbored a CYLD mutation. Clinical data, pathology reports, and histopathology were reviewed for each CYLD-mutant case. The spectrum of CYLD mutations included truncating (n = 50; 67%), homozygous deletion (n = 10; 13%), missense (n = 16; 21%), and splice-site (n = 3; 4%) events. Compared with CYLD-wildtype AC (n = 499), CYLD-mutant ACs were significantly enriched for females (88% vs. 67%, p = 0.0001), slightly younger (median age 59 vs. 61 years, p = 0.047), and included near-universal detection of high-risk HPV sequences (97% vs. 88%, p = 0.014), predominantly HPV16 (96%). The CYLD-mutant cohort also showed significantly lower tumor mutational burden (TMB; median 2.6 vs. 5.2 mut/Mb, p < 0.00001) and less frequent alterations in PIK3CA (13% vs. 31%, p = 0.0015). On histopathologic examination, 73% of CYLD-mutant AC (55/75 cases) showed a striking cylindroma-like histomorphology, composed of aggregates of basaloid cells surrounded by thickened basement membranes and containing characteristic hyaline globules, while only 8% of CYLD-wildtype tumors (n = 34/409) contained cylindroma-like hyaline globules (p < 0.0001). CYLD-mutant carcinomas with cylindroma-like histomorphology (n = 55) showed significantly lower TMB compared with CYLD-mutant cases showing basaloid histology without the distinctive hyaline globules (n = 14) (median 1.7 vs. 4.4 mut/Mb, p = 0.0058). Only five CYLD-mutant cases (7%) showed nonbasaloid conventional squamous cell carcinoma histology (median TMB = 5.2 mut/Mb), and a single CYLD-mutant case showed transitional cell carcinoma-like histology. Within our cohort of ACs, CYLD mutations characterize a surprisingly large subset (13%), with distinct clinical and genomic features and, predominantly, a striking cylindroma-like histopathology, representing a genotype-phenotype correlation which may assist in classification of AC.

Abstract PO-088: A deep-learning based approach to assess heterogeneity of histologies in non-small cell lung cancer

Abstract Adenosquamous carcinomas of the lung carry a poor prognosis compared to other non-small cell lung cancers (NSCLC) (Tian. 2017, Baine et al. 2018, Wood et al. 2017, 2015 WHO Classification of Lung Tumors). Adenosquamous carcinoma (ASC) has features of both Adenocarcinoma (ADC) and Squamous cell carcinoma (SCC) in the same tumor. The incidence of ASC varies between studies but is estimated to account for 0.4 to 4% of all lung cancers (2015 WHO Classification of Lung Tumors). Diagnosis of these cancers depends on several factors including adequate sampling of the tumor, careful review and objective interpretation of histologic criteria. An automated method for light microscopy review could help standardize and speed up correct identification of this important subtype and lead to better targeted therapies. In addition, an automated technique to quantify the relative contributions of histologies in heterogeneous tumors would lead to a better understanding of tumor biology. 476 tissue samples from NSCLC patients were scanned at 0.5pixel/um resolution, and the tumor area was selected by a pathologist. Each slide tumor area was divided into smaller image ‘patches’ of 512 × 512 pixels. We trained a Convolution Neural Network based on the Inception V3 and Resnet18 architecture using transfer learning and weakly-supervised learning, to classify tissue patches using the whole-slide level labels. Once the network was trained, a patch-level prediction was performed on 20 unseen test slides. A whole-slide diagnosis was performed by choosing the most common histology predicted among all patches extracted for each slide. In addition, a patch-based heatmap was created to identify the heterogeneity of histologies within a single tissue sample. The model’s whole slide prediction of ADC or SCC histologies on the test set, matched the pathologist’s whole-slide diagnosis, with an F1-score of 0.91 at the individual tile level and 1.0 (perfect) in slide level. The trained model also identified a few likely adenosquamous carcinomas, where slides were found to have patches with features from both ADC and SCC at high proportions. We are currently examining whether samples identified as heterogeneous can be confirmed by pathologists’ visual inspection, and whether we can visualize the network features that contribute to the patch-level classification decision. The development of an algorithm to identify mixed histologic subtypes may enable better selection of patients responsive to drug treatment and elucidate the biological mechanism leading to tumor heterogeneity. Citation Format: Reheman Baikejiang, Jennifer Giltnane, Eloisa Fuentes, Cleopatra Kozlowski. A deep-learning based approach to assess heterogeneity of histologies in non-small cell lung cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-088.

Spindle cell carcinoma arising in a skin graft of the tongue: A case report

AbstractSpindle cell carcinoma (SpCC) exhibits dual features of malignancy, with the histology of squamous cell carcinoma and sarcoma‐like proliferation of spindle cells. SpCC development in the oral region has rarely been reported. Skin grafts are frequently applied to defects following superficial cancer resection. We encountered an extremely rare case of SpCC that developed in the central part of a skin graft, which was applied after superficial tongue cancer resection. SpCC may develop on skin grafts and is not limited to the oral mucosa in the oral cavity. Therefore, long‐term observation should be done carefully because skin grafts change over time.