Background
Histological heterogeneity is thought to be important for prognosis of lung adenocarcinoma. We investigated to determine pathological features with prognostic value for recurrence of early ...stage lung cancer.
Methods
A total of 368 patients who underwent curative surgical resection for early stage lung adenocarcinoma between 2009 and 2012 were enrolled. Pathologic characteristics including the presence of visceral pleural invasion, micropapillary patterns, aerogenous spread, lymphovascular invasion, perineural invasion and necrosis were examined. The correlations between pathological factors and clinical outcomes were analysed to determine prognostic significance.
Results
Mean follow‐up was 43.0 months (±14.56, ranging from 0.0 to 73.9 months). Three‐year overall survival was 95.2% and disease‐free survival was 89.8%. The recurrence rate was 9.0% (33 patients) and the mortality rate was 6.0% (22 patients). The presence of a micropapillary pattern (P < 0.002), lymphatic invasion (P < 0.000), aerogenous spread (P < 0.000), vascular invasion (P = 0.036) and necrosis (P < 0.000) were negative prognostic factors of recurrence in univariate analysis. In multivariate analysis, only aerogenous spread had prognostic value (P = 0.020). The recurrence hazard ratio for the presence of aerogenous spread was 3.2 (95% confidence interval 1.20–8.47).
Conclusion
The presence of aerogenous spread was an independent pathological risk factor of recurrence in stage I lung adenocarcinoma. Micropapillary pattern had prognostic importance for recurrence in univariate analysis, but not in multivariate analysis.
We aimed to elucidate the evolutionary trajectories of gallbladder adenocarcinoma (GBAC) using multi-regional and longitudinal tumor samples. Using whole-exome sequencing data, we constructed ...phylogenetic trees in each patient and analyzed mutational signatures. A total of 11 patients including 2 rapid autopsy cases were enrolled. The most frequently altered gene in primary tumors was
and
(54.5%), followed by
(27.3%). Most mutations in frequently altered genes in primary tumors were detectable in concurrent precancerous lesions (biliary intraepithelial neoplasia BilIN), but a substantial proportion was subclonal. Subclonal diversity was common in BilIN (n=4). However, among subclones in BilIN, a certain subclone commonly shrank in concurrent primary tumors. In addition, selected subclones underwent linear and branching evolution, maintaining subclonal diversity. Combined analysis with metastatic tumors (n=11) identified branching evolution in nine patients (81.8%). Of these, eight patients (88.9%) had a total of 11 subclones expanded at least sevenfold during metastasis. These subclones harbored putative metastasis-driving mutations in cancer-related genes such as
,
, and
. In mutational signature analysis, six mutational signatures were identified: 1, 3, 7, 13, 22, and 24 (cosine similarity >0.9). Signatures 1 (age) and 13 (APOBEC) decreased during metastasis while signatures 22 (aristolochic acid) and 24 (aflatoxin) were relatively highlighted. Subclonal diversity arose early in precancerous lesions and clonal selection was a common event during malignant transformation in GBAC. However, selected cancer clones continued to evolve and thus maintained subclonal diversity in metastatic tumors.
Although immune checkpoints inhibitors have exhibited promising activity in clinical trials in non-small cell lung cancer (NSCLC) patients, the current programmed cell death-ligand 1 (PD-L1) assays ...are inconsistent in terms of the staining analysis and scoring system used. To verify the interchangeability of the available PD-L1 assays, we performed immunohistochemistry using three antibody clones used in clinical trials (22C3, SP263, and SP142) and the E1L3N clone as a laboratory developed test for 97 resected NSCLC specimens. Matched tissue microarray specimens were also stained. Staining with 22C3 yielded a greater proportion of stained tumor cells, whereas SP142 staining consistently labelled fewer tumor cells. However, when various cut-off criteria were applied, the positivity rates for PD-L1 were similar, with high concordance, under assay-specific cut-offs. Moreover, seven cases of discordant PD-L1 expression between the resected specimen and matched tissue microarray specimens were observed. In conclusion, despite of inter-assay variability of the PD-L1 status in NSCLC, the positivity rate appears to be similar under assay-specific criteria. Hence, an appropriate clinically defined algorithm or cut-off should be separately applied for each assay. Moreover, multiple biopsy specimens from different tumor areas should be obtained to reduce false results due to intratumoral heterogeneity in PD-L1 expression.
The current WHO classification of lung cancer states that a diagnosis of SCLC can be reliably made on routine histological and cytological grounds but immunohistochemistry (IHC) may be required, ...particularly (1) in cases in which histologic features are equivocal and (2) in cases in which the pathologist wants to increase confidence in diagnosis. However, reproducibility studies based on hematoxylin and eosin–stained slides alone for SCLC versus large cell neuroendocrine carcinoma (LCNEC) have shown pairwise κ scores ranging from 0.35 to 0.81. This study examines whether judicious use of IHC improves diagnostic reproducibility for SCLC.
Nineteen lung pathologists studied interactive digital images of 79 tumors, predominantly neuroendocrine lung tumors. Images of resection and biopsy specimens were used to make diagnoses solely on the basis of morphologic features (level 1), morphologic features along with requested IHC staining results (level 2), and all available IHC staining results (level 3).
For the 19 pathologists reading all 79 cases, the rate of agreement for level 1 was 64.7%, and it increased to 73.2% and 77.5% in levels 2 and 3, respectively. With IHC, κ scores for four tumor categories (SCLC, LCNEC, carcinoid tumors, and other) increased in resection samples from 0.43 to 0.60 and in biopsy specimens from 0.43 to 0.64.
Diagnosis using hematoxylin and eosin staining alone showeds moderate agreement among pathologists in tumors with neuroendocrine morphology, but agreement improved to good in most cases with the judicious use of IHC, especially in the diagnosis of SCLC. An approach for IHC in the differential diagnosis of SCLC is provided.
Since the 2015 WHO classification was introduced into clinical practice, immunohistochemistry (IHC) has figured prominently in lung cancer diagnosis. In addition to distinction of small cell versus ...non–small cell carcinoma, patients’ treatment of choice is directly linked to histologic subtypes of non–small cell carcinoma, which pertains to IHC results, particularly for poorly differentiated tumors. The use of IHC has improved diagnostic accuracy in the classification of lung carcinoma, but the interpretation of IHC results remains challenging in some instances. Also, pathologists must be aware of many interpretation pitfalls, and the use of IHC should be efficient to spare the tissue for molecular testing. The International Association for the Study of Lung Cancer Pathology Committee received questions on practical application and interpretation of IHC in lung cancer diagnosis. After discussions in several International Association for the Study of Lung Cancer Pathology Committee meetings, the issues and caveats were summarized in terms of 11 key questions covering common and important diagnostic situations in a daily clinical practice with some relevant challenging queries. The questions cover topics such as the best IHC markers for distinguishing NSCLC subtypes, differences in thyroid transcription factor 1 clones, and the utility of IHC in diagnosing uncommon subtypes of lung cancer and distinguishing primary from metastatic tumors. This article provides answers and explanations for the key questions about the use of IHC in diagnosis of lung carcinoma, representing viewpoints of experts in thoracic pathology that should assist the community in the appropriate use of IHC in diagnostic pathology.
Pulmonary blastoma is an extremely rare and highly aggressive tumor. Only a few hundred cases of pulmonary blastoma have been reported. In other cases, a definitive diagnosis is often made through ...surgical resection. The use of preoperative histopathological sampling in diagnosing was of limited value because of the variety of pulmonary blastoma histology. And there was no literature that the first biopsy was attempted with medical thoracoscopy for diagnosis.
A 65-year-old man presented to our hospital with pleural effusion and lung mass.
The patient was initially diagnosed with dedifferentiated chondrosarcoma by medical thoracoscopic biopsy but the final diagnosis was pulmonary blastoma through bilobectomy.
Medical thoracoscopy, and video-assisted thoracoscopic surgery (bilobectomy) followed by adjuvant chemotherapy.
After surgical resection of the tumor, adjuvant chemotherapy has been performed 5 cycles at 3 weeks intervals, and there was no evidence of recurrence on follow-up computed tomography performed 4 months after surgery.
Medical thoracoscopy is useful for the diagnosis of indeterminate pleural effusion; however, caution is needed when confirming rare malignancies, such as pulmonary blastoma. Although surgical resection is the treatment of choice, appropriate adjuvant chemotherapy to improve the prognosis may be necessary if there is pleural metastasis.
Every patient with advanced non–small cell lung cancer (NSCLC) should be tested for targetable driver mutations and gene arrangements that may open avenues for targeted therapy. As most patients with ...NSCLC in the advanced stage of the disease are not candidates for surgery, these tests have to be performed on small biopsies or cytology samples. A growing number of other genetic changes with targetable mutations may be treatable in the near future. To identify patients who might benefit from novel targeted therapy, relevant markers should be tested in an appropriate context. In addition, immunotherapy of lung cancer is guided by the status of programmed death-ligand 1 expression in tumor cells. The variety and versatility of cytological specimen preparations offer significant advantages for molecular testing; however, they frequently remain underused. Therefore, evaluating the utility and adequacy of cytologic specimens is important, not only from a lung cancer diagnosis, but also for the large number of ancillary studies that are necessary to provide appropriate clinical management. A large proportion of lung cancers is diagnosed by aspiration or exfoliative cytology specimens; thus, optimizing strategies to triage and best use the tissue for diagnosis and biomarker studies forms a critical component of lung cancer management. In this review, we discuss the opportunities and challenges of using cytologic specimens for biomarker testing of lung cancer and the role of cytopathology in the molecular era.
Although oropharyngeal squamous cell carcinoma (OPSCC) with human papillomavirus (HPV) infection has a good prognosis, the accurate prediction of survival and risk of treatment failure is essential ...to design deintensification regimens. Here, we investigated estrogen receptor α (ERα) as a prognostic biomarker with therapeutic implications in OPSCC alongside factors associated with HPV infection.
We performed immunohistochemistry for ERα and p53 using formalin-fixed, paraffin-embedded tissues and assessed the HPV status using p16 immunohistochemistry and HPV DNA testing in 113 consecutive patients with OPSCC treated with surgical resection or radiotherapy/chemoradiotherapy.
ERα expression and p53 alteration was observed in 35.4% and 21.2% OPSCCs; 45.6% and 1.3% p16+/HPV+ OPSCCs; and 11.5% and 76.9% p16- OPSCCs, respectively. These data suggest that OPSCC pathogenesis varies with HPV status. Furthermore, ERα expression was associated with improved overall survival (OS) in both HPV+ (p16+/HPV+ OPSCC) and p16+ (p16+ OPSCC irrespective of HPV status) models (p = 0.005 and p = 0.006, respectively) and with improved OS adjusted for stage (p = 0.037, hazard ratio: 0.109, 95% confidence interval 0.013-0.871) in the p16+ model.
ERα is a potential predictive biomarker for improved survival in both HPV+ and p16+ OPSCC models.
Radiogenomic features are predictive of anaplastic lymphoma kinase (ALK) rearrangement in surgically resected non-small cell lung cancer (NSCLC).
ALK rearrangement was screened by fluorescent in situ ...hybridization in 497 patients with resected NSCLC. Of these, 198 patients screened for both ALK and epidermal growth factor receptor (EGFR) mutation were enrolled. Clinicopathologic findings, survival after surgical procedure, computed tomographic (CT) features, and maximum standardized uptake value according to different genotypes were investigated with univariate and multivariate analyses. A receiver operating characteristic (ROC) curve analysis was performed to quantify the predictive value of these factors.
The prevalence of ALK positivity in resected NSCLC was 5.0% (25 of 497). Patients with ALK rearrangement showed significant differences in terms of patient's age (p = 0.006 for ALK versus EGFR, and 0.04 for ALK versus wild type WT/WT, respectively), solid lesion (p = 0.0074 for ALK versus EGFR), degree of contrast enhancement (p = 0.0006 for ALK versus EGFR), and lesion margin (p = 0.0011 for ALK versus EGFR, and 0.0314 for ALK versus WT/WT, respectively) compared with EGFR mutant and WT/WT cohorts. Multivariate analysis revealed that young age, solid lesion, lobulated margin, and hypoattenuation at contrast-enhanced CT scan were independent predictors of ALK positivity (p = 0.027, 0.046, 0.001, 0.021, respectively). The area under the ROC curve of the predictive model was 0.832, which suggests good discrimination.
ALK-rearranged lung cancer has characteristic clinical and imaging features compared with EGFR mutant or WT/WT cohorts. Our findings suggest that young age, lobulated margin, solid lesion, and hypoattenuation at contrast-enhanced CT scan are important predictors of ALK-rearranged lung cancer.
Summary Background Focal ground-glass opacity (GGO) is becoming a major concern because of its possible association with lung cancer. In this study, we analyzed the long-term progression of GGOs that ...persisted for more than 2 years. Methods We reviewed focal GGOs identified by thin-section computed tomography that persisted for more than 2 years. Results We enrolled a total of 114 patients with 175 GGO lesions. The median patient age was 61 years (range, 37–92 years) and 42 (36.8%) patients were male. Mean initial GGO size was 7.8 ± 4.4 mm. Median follow-up duration was 45 months. Forty-six (26.3%) GGOs had significant size increases (≥2 mm in the longest diameter) with a mean volume doubling time of 1041 days. In a multivariate analysis, large size (≥10 mm), the presence of a solid portion (mixed GGO) and old age (≥65 years) were risk factors for significant size increase, with odds ratios (95% CI) of 6.46 (2.69–15.6), 2.69 (1.11–6.95) and 2.55 (1.13–5.77), respectively. GGOs with character changes from pure to mixed or mixed to solid showed more rapid volume expansion. Conclusions GGOs which persisted for several years showed an indolent course. Large lesions with a solid portion and GGOs in male or elderly individuals may be cause for more concern, as these factors were associated with size increase. Resection should be considered if GGOs show character changes, as these may be associated with rapid size progression.
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