scholarly journals Next-Generation Sequencing of a Cohort of Pulmonary Large Cell Carcinomas Reclassified by World Health Organization 2015 Criteria

2015 ◽  
Vol 140 (4) ◽  
pp. 312-317 ◽  
Author(s):  
Brandon R. Driver ◽  
Bryce P. Portier ◽  
Dina R. Mody ◽  
Michael Deavers ◽  
Eric H. Bernicker ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Large Cell Carcinoma ◽  
Large Cell ◽  
World Health ◽  
Mutation Profile ◽  
Nonkeratinizing Squamous Cell Carcinoma ◽  
Health Organization ◽  
Squamous Cell Carcinoma Group

The classification of pulmonary large cell carcinoma has undergone a major revision with the recent World Health Organization (WHO) 2015 Classification. Many large cell carcinomas are now reassigned to either adenocarcinoma with solid pattern or nonkeratinizing squamous cell carcinoma based on immunopositivity for adenocarcinoma markers or squamous cell carcinoma markers, respectively. Large cell carcinomas that are negative for adenocarcinoma and squamous cell carcinoma immunomarkers are now classified as large cell carcinoma with null immunohistochemical features (LCC-N). Although a few studies investigated the mutation profile of large cell carcinomas grouped by immunostain profile before the publication of the new WHO classification, investigation of tumors previously diagnosed as large cell carcinoma and reclassified according to the 2015 WHO classification has not, to our knowledge, been reported.Context.— To determine the mutation profiles of pulmonary large cell carcinomas reclassified by WHO 2015 criteria.Objective.— Archival cases of non–small cell lung carcinoma with large cell carcinoma morphology (n = 17) were reclassified according to 2015 WHO criteria. To determine mutation profile, we employed Ion Torrent (Life Technologies, Carlsbad, California)–based next-generation sequencing (50 genes; more than 2800 mutations) in addition to real-time quantitative reverse transcription polymerase chain reaction for ALK translocation detection.Design.— Two of 17 cases (12%) were reclassified as LCC-N, and both had mutations—BRAF D594N in one case and KRAS G12C in the other case. Seven of 17 cases (41%) were reclassified in the adenocarcinoma with solid pattern group, which showed one KRAS G12C and one EGFR E709K + G719C double mutation in addition to mutations in TP53. Eight of 17 cases (47%) were reclassified in the nonkeratinizing squamous cell carcinoma group, which showed mutations in PIK3CA, CDKN2A, and TP53. No ALK translocations or amplifications were detected.Results.— The adenocarcinoma with solid pattern group showed mutations typical of adenocarcinoma, whereas the nonkeratinizing squamous cell carcinoma group showed mutations typical of squamous cell carcinoma. Both LCC-N cases had mutations associated with adenocarcinoma, supporting the hypothesis that LCC-N is related to adenocarcinoma.Conclusions.—

Pulmonary Large Cell Carcinoma Lacking Squamous Differentiation Is Clinicopathologically Indistinguishable From Solid-Subtype Adenocarcinoma

2013 ◽  
Vol 138 (5) ◽  
pp. 626-635 ◽  
Author(s):  
David H. Hwang ◽  
David P. Szeto ◽  
Anthony S. Perry ◽  
Jacqueline L. Bruce ◽  
Lynette M. Sholl
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Clinical Features ◽  
Squamous Cell ◽  
Lung Tumor ◽  
Neuroendocrine Differentiation ◽  
Large Cell Carcinoma ◽  
Large Cell ◽  
World Health ◽  
Thyroid Transcription Factor 1

Context Pulmonary large cell carcinoma (LCC) includes tumors not readily diagnosed as adenocarcinoma (ADC) or squamous cell carcinoma on morphologic grounds, without regard to immunophenotype, according to the World Health Organization (WHO). This ambiguous designation may cause confusion over selection of mutation testing and directed therapies. Several groups have proposed the use of immunohistochemistry (IHC) to recategorize LCC as ADC or squamous cell carcinoma; however, it remains unclear if strictly defined LCCs are a clinicopathologically distinct lung tumor subset. Objective —To compare the pathologic, molecular, and clinical features of 2 morphologically similar tumors: solid-subtype ADC and LCC. Design Tumors were included on the basis of solid growth pattern; tumors with squamous or neuroendocrine differentiation were excluded. Solid ADC (n = 42) and LCC (n = 57) were diagnosed by using WHO criteria (5 intracellular mucin droplets in ≥2 high-power fields for solid ADC) and tested for KRAS, EGFR, and ALK alterations. Results —Both solid ADC and LCC groups were dominated by tumors with “undifferentiated”-type morphology and both had a high frequency of thyroid transcription factor 1 expression. KRAS was mutated in 38% of solid ADCs versus 43% of LCCs (P = .62). One ALK-rearranged and 1 EGFR-mutated tumor were detected in the solid ADC and LCC groups, respectively. There were no significant differences in clinical features or outcomes; the prevalence of smoking in both groups was greater than 95%. Conclusions Other than a paucity of intracellular mucin, LCC lacking squamous or neuroendocrine differentiation is indistinguishable from solid-subtype ADC. We propose the reclassification of these tumors as mucin-poor solid adenocarcinomas.

scholarly journals Incorporation of differentiated dysplasia improves prediction of oral leukoplakia at increased risk of malignant progression

2020 ◽  
Vol 33 (6) ◽  
pp. 1033-1040 ◽  
Author(s):  
Leon J. Wils ◽  
Jos B. Poell ◽  
Ilkay Evren ◽  
Marit S. Koopman ◽  
Elisabeth R. E. A. Brouns ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
World Health Organization ◽  
Cell Carcinoma ◽  
Malignant Transformation ◽  
Squamous Cell ◽  
Malignant Progression ◽  
Oral Leukoplakia ◽  
World Health ◽  
Oral Lesions ◽  
Health Organization

AbstractOral leukoplakia is the most common oral potentially malignant disorder with a malignant transformation rate into oral squamous cell carcinoma of 1–3% annually. The presence and grade of World Health Organization defined dysplasia is an important histological marker to assess the risk for malignant transformation, but is not sufficiently accurate to personalize treatment and surveillance. Differentiated dysplasia, known from differentiated vulvar intraepithelial neoplasia, is hitherto not used in oral dysplasia grading. We hypothesized that assessing differentiated dysplasia besides World Health Organization defined (classic) dysplasia will improve risk assessment of malignant transformation of oral leukoplakia. We investigated a retrospective cohort consisting of 84 oral leukoplakia patients. Biopsies were assessed for dysplasia presence and grade, and the expression of keratins 13 (CK13) and 17, known to be dysregulated in dysplastic vulvar mucosa. In dysplastic oral lesions, differentiated dysplasia is as common as classic dysplasia. In 25 out of 84 (30%) patients, squamous cell carcinoma of the upper aerodigestive tract developed during follow-up. Considering only classic dysplasia, 11 out of 56 (20%) patients with nondysplastic lesions progressed. With the incorporation of differentiated dysplasia, only 2 out of 30 (7%) patients with nondysplastic lesions progressed. The risk of progression increased from 3.26 (Hazard ratio, p = 0.002) when only classic dysplasia is considered to 7.43 (Hazard ratio, p = 0.001) when classic and differentiated dysplasia are combined. Loss of CK13, combined with presence of dysplasia, is associated with greater risk of malignant progression (p = 0.006). This study demonstrates that differentiated dysplasia should be recognized as a separate type of dysplasia in the oral mucosa and that its distinction from classic dysplasia is of pathological and clinical significance since it is a strong (co)prognostic histopathological marker for oral malignant transformation. In oral lesions without dysplasia and retained CK13 staining the risk for progression is very low.

scholarly journals A Case of Synchronous Triple Primary Lung Cancers Composed of Adenocarcinoma, Squamous Cell Carcinoma and Large Cell Carcinoma in the Right Lung.

Haigan ◽  
1996 ◽  
Vol 36 (2) ◽  
pp. 147-154 ◽  
Author(s):  
Yuichiro Takeda ◽  
Masahiro Seike ◽  
Shigeto Kawachi ◽  
Tatsurou Watanabe ◽  
Shouji Kudoh ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Large Cell Carcinoma ◽  
Large Cell ◽  
Lung Cancers ◽  
The Right

Lung Cancer - Part I

2019 ◽  
Author(s):  
Jeffrey Crawford ◽  
John Strickler
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Small Cell Lung Cancer ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Large Cell Carcinoma ◽  
Large Cell ◽  
Small Cell ◽  
Small Cell Lung

In the United States, lung cancer is the second most common cancer, surpassed only by prostate cancer in men and breast cancer in women. But lung cancer is the leading cause of cancer deaths, accounting for 29% and 26% of all cancer-related deaths in men and women, respectively. The four major pathologic cell types of lung cancer are small cell carcinoma, adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Because they have overlapping clinical behaviors and responses to treatment, adenocarcinoma, squamous cell carcinoma, and large cell carcinoma are generally grouped together in the category of non–small cell lung cancer (NSCLC). This review discusses both NSCLC and small cell lung cancer (SCLC), including lung cancer in those who have never smoked, prevention of lung cancer, with sections on diagnosis, biomarkers, treatment, and supportive care.  This review contains 7 figures, 10 tables, and 74 references. Keywords: lung cancer, mediastinoscopy, chemoradiotherapy, TNM staging system, pulmonary parenchyma, segmentectomy

Lung Cancer - Part I

2019 ◽  
Author(s):  
Jeffrey Crawford ◽  
John Strickler
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Small Cell Lung Cancer ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Large Cell Carcinoma ◽  
Large Cell ◽  
Small Cell ◽  
Small Cell Lung

In the United States, lung cancer is the second most common cancer, surpassed only by prostate cancer in men and breast cancer in women. But lung cancer is the leading cause of cancer deaths, accounting for 29% and 26% of all cancer-related deaths in men and women, respectively. The four major pathologic cell types of lung cancer are small cell carcinoma, adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Because they have overlapping clinical behaviors and responses to treatment, adenocarcinoma, squamous cell carcinoma, and large cell carcinoma are generally grouped together in the category of non–small cell lung cancer (NSCLC). This review discusses both NSCLC and small cell lung cancer (SCLC), including lung cancer in those who have never smoked, prevention of lung cancer, with sections on diagnosis, biomarkers, treatment, and supportive care.  This review contains 7 figures, 10 tables, and 74 references. Keywords: lung cancer, mediastinoscopy, chemoradiotherapy, TNM staging system, pulmonary parenchyma, segmentectomy

Lung Cancer Part II

2019 ◽  
Author(s):  
Jeffrey Crawford
Keyword(s):  
Lung Cancer ◽  
Squamous Cell Carcinoma ◽  
Small Cell Lung Cancer ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Cell Lung Cancer ◽  
Large Cell Carcinoma ◽  
Large Cell ◽  
Small Cell ◽  
Small Cell Lung

In the United States, lung cancer is the second most common cancer, surpassed only by prostate cancer in men and breast cancer in women. But lung cancer is the leading cause of cancer deaths, accounting for 29% and 26% of all cancer-related deaths in men and women, respectively. The four major pathologic cell types of lung cancer are small cell carcinoma, adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Because they have overlapping clinical behaviors and responses to treatment, adenocarcinoma, squamous cell carcinoma, and large cell carcinoma are generally grouped together in the category of non–small cell lung cancer (NSCLC). This review discusses treatment of both NSCLC and small cell lung cancer (SCLC). This review 2 figures, 19 tables, and 90 references. Keywords: lung cancer, mediastinoscopy, chemoradiotherapy, TNM staging system, pulmonary parenchyma, segmentectomy

scholarly journals CYFRA21-1 tests in the diagnosis of non-small cell lung cancer: A meta-analysis

2019 ◽  
Vol 34 (3) ◽  
pp. 251-261 ◽  
Author(s):  
Lei Fu ◽  
Rong Wang ◽  
Ling Yin ◽  
Xiaopu Shang ◽  
Runtong Zhang ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Lung Adenocarcinoma ◽  
Cell Carcinoma ◽  
Likelihood Ratio ◽  
Squamous Cell ◽  
Meta Analysis ◽  
Positive Likelihood Ratio ◽  
Negative Likelihood Ratio ◽  
Large Cell Carcinoma ◽  
Large Cell

Objective: The aim of the study was to evaluate the diagnostic value of soluble fragment of cytokeratin 19 (CYFRA21-1) tests in detecting non-small cell lung cancer (NSCLC), including squamous cell carcinoma, lung adenocarcinoma, and large cell carcinoma. Methods: The relevant studies were identified from PubMed, Embase and the Cochrane Library before November 2018. Summary estimates for sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of CYFRA21-1 tests for the diagnosis of NSCLC were calculated using the random effects model. A summary receiver operating characteristic (SROC) curve was used to assess the overall effectiveness of the test. Meta-DiSc 1.4 and Stata11.0 were applied to the statistical analysis. Publication bias was detected using Egger’s test. Results: A total of 22 studies consisting of 7910 NSCLC patients (squamous cell carcinoma/lung adenocarcinoma/large cell carcinoma) and 2630 benign lesions patients that met the inclusion criteria were included. The meta-analysis showed that CYFRA21-1 tests had a relatively high accuracy for squamous cell carcinoma detection and a lower accuracy for lung adenocarcinoma detection. The overall sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, and diagnostic odds ratio of CYFRA21-1 tests for squamous cell carcinoma detection were 0.72 (95% confidence interval (CI) 0.70, 0.74), 0.94 (95% CI 0.92, 0.95), 9.73 (95% CI 7.06, 13.40), 0.37 (95% CI 0.29, 0.47), and 27.30 (95% CI 17.68, 42.16), respectively. The area under the SROC curve was 0.9171 (Q* = 0.8500). No publication bias was tested in the squamous cell carcinoma (P = 0.567) and lung adenocarcinoma (P = 0.378) groups. Conclusions: CYFRA21-1 tests might be appropriate for detecting squamous cell carcinoma.

Vindesine in the Treatment of Squamous Cell Carcinoma (Who I), Adenocarcinoma (Who III), and Large Cell Carcinoma (who IV) of the Lung

1982 ◽  
Vol 68 (6) ◽  
pp. 531-535 ◽  
Author(s):  
Eros Ferrazzi ◽  
Yittorina Zagonel ◽  
Orazio Vinante ◽  
Enzo Galligioni ◽  
Giovanni L. Pappagallo ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Single Agent ◽  
Previous Treatment ◽  
Large Cell Carcinoma ◽  
Large Cell ◽  
Pretreated Patients ◽  
Previously Treated ◽  
Histologic Types

The antineoplastic activity of vindesine was evaluated in 57 patients with non-small-cell carcinoma of the lung. 53 patients were fully evaluable for response and toxicity. Twenty-seven patients had squamous cell carcinoma (WHO I), 14 had adenocarcinoma (WHO III), and 12 had large cell carcinoma (WHO IV). Forty percent of patients were previously treated. Vindesine was administered at a weekly i.v. dose of 3 mg/m2. Partial remissions were observed in 2 of 12 patients with large cell carcinoma and in 1 of 27 patients with squamous cell carcinoma. Among 14 patients with adenocarcinoma, 3 minor responses were observed. Drug-related toxic effects (mainly leukopenia with manageable and reversible neurotoxicity) required modification of dose in 41 % of patients: this finding and previous treatment may have adversely affected the response rate. It is concluded that vindesine as a single agent has some activity in large cell carcinoma. Activity in the other histologic types was minimal but not totally absent and deserves further evaluation, possibly in non-pretreated patients.

Sign in / Sign up

Export Citation Format

Share Document