Intrapulmonary metastasis from primary pulmonary meningioma presenting as multiple cystic lesions: a case report.

BACKGROUND: Cystic lung lesions involving both lungs include a variety of diseases, such as pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis and pulmonary metastasis. Primary pulmonary meningioma accompanied with intrapulmonary metastasis was extremely rare and we were not aware of previous studies reporting with cystic radiological manifestation. CASE PRESENTATION: A 64-year-old female patient was admitted to our department for a mass located in right posterior mediastinum with multiple cystic pulmonary lesions. A thoracoscopic lung biopsy was performed and the diagnosis was confirmed as bilateral pulmonary metastasis from primary pulmonary meningioma. CONCLUSIONS: Intrapulmonary metastasis from a primary pulmonary meningioma may manifest as multiple thin-walled cystic lesions on computed tomography. Differential diagnosis of cystic pulmonary disease should include this situation. Our case shows the new CT manifestation of metastatic primary pulmonary meningioma and the importance of immunomolecular analysis.

Thoracic SMARCA4-deficient tumors: a clinicopathological analysis of 52 cases with SMARCA4-deficient non-small cell lung cancer and 20 cases with thoracic SMARCA4-deficient undifferentiated tumor.

Background: Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a distinct clinicopathological entity with an aggressive clinical course. Additionally, SMARCA4/BRG1 deficiency can be observed in a few patients with non-small cell lung cancer (NSCLC). We aimed to compare the clinicopathological, immunohistochemical and prognostic features of SMARCA4-deficient NSCLC (SMARCA4-dNSCLC) with those of thoracic SMARCA4-UT. Methods: Patients with BRG1-deficient tumors in the lung or thorax were enrolled in the study from the Department of Pathology of West China Hospital, Sichuan University, from January 2014 to June 2022. We retrospectively collected the clinicopathological and immunohistochemical features and outcomes of these patients. Results: Seventy-two patients had tumors in the lung or thorax with BRG1-deficient expression, including 52 patients with SMARCA4-dNSCLC and 20 patients with thoracic SMARCA4-UT. Among the patients with SMARCA4-dNSCLC, 98.1% were male, 85.7% were smokers, and 79.5% (35/44) had tumor-node-metas-tasis (TNM) III-IV tumors. Among the patients with thoracic SMARCA4-UT, all were males who smoked, and 93.75% (15/16) had TNM III-IV tumors. Pure solid architecture and necrosis were the predominant pathological features. Rhabdoid morphology was observed in some SMARCA4-dNSCLCs (10/52, 19.2%) and thoracic SMARCA4-UTs (11/20, 55%). In most patients with thoracic SMARCA4-UT, the tumors exhibited scattered weak expression or negative expression of epithelial markers, and positive expression of CD34 and Syn. Overall survival (OS) and progression-free survival (PFS) were not significantly different between patients with SMARCA4-dNSCLC and patients with thoracic SMARCA4-UT (p = 0.63 and p = 0.20, respectively). Conclusions: Thoracic SMARCA4-DTs include SMARCA4-dNSCLC and thoracic SMARCA4-UT. Both have overlapping clinicopathological features and poor prognosis. We hypothesize that thoracic SMARCA4-UT may be the undifferentiated or dedifferentiated form of SMARCA4-dNSCLC. However, further studies with larger cohorts and longer follow-up periods are needed.

Thoracic SMARCA4-deficient undifferentiated tumor: A clinicopathological and prognostic analysis of 35 cases and immunotherapy efficacy.

BACKGROUND: Thoracic SMARCA4-deficient undifferentiated tumor (SMARCA4-UT) is a recently recognized distinct clinicopathological entity according to the fifth edition of the 2021 World Health Organization Classification (WHO) for thoracic tumors. Thoracic SMARCA4-UTs are diagnostically challenging to diagnose, especially on small biopsies. METHODS: We identified 35 thoracic SMARCA4-UTs from the Department of Pathology of West China Hospital, Sichuan University, between January 2017 and December 2022. In the present study, we summarized the clinicopathological features, prognostic significance and immunotherapy efficacy of thoracic SMARCA4-UTs. RESULTS: All 35 patients were male, and 88.6 % were smokers. The left upper lobe (25.7 %) and mediastinum (20.0 %) were the most affected sites. 17.1 % of the patients received surgical treatment. 30.4 % of the patients were stage III, and 69.6 % were stage IV. Solid architecture (100 %), rhabdoid morphology (51.4 %) and necrosis (42.9 %) were the common histological features. Immunohistochemical staining revealed CD34 and synaptophysin positivity in most patients (76.9 % and 65.2 %, respectively). Patients had unfavorable outcomes. Patients who received immunotherapy had better OS and PFS than those who did not (p = 0.007 and p = 0.02, respectively). Five patients were evaluated for immunotherapy efficacy, and four of those patients were negative expression of PD-L1. Cases 1-4 presented TIL counts ranging from 20 to 1000/HPF. Case 5 presented TIL counts of 5-10/HPF. Mutations in SMARCA4 were confirmed in cases 4 and 5, and the TMB was 5.98 and 5.03 mutations/Mb, respectively. Case 1 achieved a CR, cases 2-4 achieved a PR, and case 5 had a PD. Five patients who received immunotherapy were all alive, with OS ranging from 10.7 to 33.6 months. CONCLUSIONS: Thoracic SMARCA4-UTs exhibited an aggressive clinical course, presented solid architecture with or without necrosis and/or rhabdoid morphology, and frequently expressed CD34 and synaptophysin. Some thoracic SMARCA4-UTs appear to be associated with responsiveness to immunotherapy, suggesting the need for validation in larger series.

Gastric SMARCA4-deficient undifferentiated tumor (SMARCA4-UT): a clinicopathological analysis of four rare cases.

BACKGROUND: SMARCA4, as one of the subunits of the SWI/SNF chromatin remodeling complex, drives SMARCA4-deficient tumors. Gastric SMARCA4-deficient tumors may include gastric SMARCA4-deficient carcinoma and gastric SMARCA4-deficient undifferentiated tumor (SMARCA4-UT). Gastric SMARCA4-UT is rare and challenging to diagnose in clinical practice. The present report aims to provide insight into the clinicopathological characteristics and genetic alterations of gastric SMARCA4-UTs. RESULTS: We retrospectively reported four rare cases of gastric SMARCA4-UTs. All four cases were male, aged between 61 and 82 years. These tumors presented as ulcerated and transmural masses with infiltration, staged as TNM IV in cases 1, 2 and 4, and TNM IIIA in case 3. Pathologically, four cases presented solid architecture with undifferentiated morphology. Cases 2 and 3 showed focal necrosis and focal rhabdoid morphology. Immunohistochemical staining showed negative expression of epithelial markers and deficient expression of SMARCA4. Furthermore, positivity for Syn (cases 1, 2 and 3) and SALL4 (cases 1 and 2) were observed. Mutant p53 expression occurred in four cases, resulting in strong and diffuse staining of p53 expression in cases 1, 2 and 4, and complete loss in case 3. The Ki67 proliferative index exceeded 80%. 25% (1/4, case 4) of cases had mismatch repair deficiency (dMMR). Two available cases (cases 1 and 3) were detected with SMRACA4 gene alterations. The response to neoadjuvant therapy was ineffective in case 1. CONCLUSIONS: Gastric SMARCA4-UT is a rare entity of gastric cancer with a poor prognosis, predominantly occurs in male patients. The tumors are typically diagnosed at advanced stages and shows a solid architecture with undifferentiated morphology. Negative expression of epithelial markers and complete loss of SMARCA4 immunoexpression are emerging as a useful diagnostic tool for rare gastric SMARCA4-UTs.

Case Report: Gastrointestinal neuroendocrine carcinoma with SMARCA4 deficiency: a clinicopathological report of two rare cases.

Background: Gastrointestinal neuroendocrine carcinoma (GI NEC) is a rare but highly malignant neoplasm with an aggressive clinical course. SMARCA4 is one of the subunits of the SWI/SNF chromatin remodeling complex. SMARCA4 deficiency can occur rarely in subsets of NECs. Reports of the clinicopathological features of GI NECs with SMARCA4 deficiency are limited. Methods: In this study, we retrospectively reported two rare cases of GI NEC with SMARCA4 deficiency and described the clinicopathological, radiographic and histopathological features. Results: Case 1 was a 43-year-old male with a stage cT3NxM1, IV tumor. Case 2 was a 64-year-old female with a stage cT4aN1M0, IIIA tumor. Both tumors presented as ulcerated masses with infiltration. Pathological examination indicated a solid architecture with poorly differentiated morphology, and complete loss of SMARCA4 (BRG1) was found. Immunohistochemical staining showed positivity for Syn, CgA and CD56. The Ki-67 index was 90% and 70%, respectively. None of the cases had mismatch repair (MMR) deficiency. Case 1 received treatment with chemotherapy and anti-PD-1 immunotherapy. He did not respond to treatment, and died 9 months later. Case 2 received neoadjuvant chemotherapy before surgical treatment, and the tumor showed TRG3 in response to neoadjuvant chemotherapy, chemotherapy and anti-PD-1 immunotherapy were continued after surgical resection. There was no evidence of disease for 10 months. Conclusions: GI NEC with SMARCA4 deficiency is a rare entity of gastric NEC. SMARCA4 may be a promising targetable and prognostic biomarker. BRG1 immunohistochemical staining could be performed for GI NECs. Further studies with a larger cohort will be needed.

Stromal micropapillary pattern and CD44s expression predict worse outcome in lung adenocarcinomas with micropapillary pattern.

OBJECTIVES: This study aims to investigate the clinicopathologic characteristics of lung adenocarcinoma with micropapillary pattern (MPP) and the expression of CD44s and CD44v6 in MPP. METHODS: A total of 202 patients diagnosed with primary lung adenocarcinoma with MPP were included. We estimated the proportion of MPP in each tumor tissue and divided MPP into aerogenous micropapillary pattern (AMP) and stromal micropapillary pattern (SMP). The expression of CD44s and CD44v6 was estimated by immunohistochemical staining. Clinicopathologic data were collected from the patients' medical records. We also collected patients' follow-up data and used PFS (progression-free survival) as a survival indicator. RESULTS: Lung adenocarcinoma with MPP had a high risk of pleural invasion, lymph node metastasis, in advanced TNM stage, and a high rate of EGFR mutation. The presence of SMP indicated a higher rate of pleural invasion, lymphovascular invasion, lymph node metastasis, and a worse PFS compared with pure AMP. We found high expression of CD44s in micropapillary, especially in AMP, while the absence of CD44s expression indicated shorter survival, which was an independent unfavorable factor for PFS. CONCLUSIONS: Lung adenocarcinoma with micropapillary pattern indicated an unfavorable prognosis, which had two different pattens, AMP and SMP. SMP indicated a worse survival than AMP, and was an independent unfavorable factor for PFS. So, AMP/SMP subclassification is necessary to evaluate patient's prognosis. Furthermore, the absent expression of CD44s in micropapillary indicated shorter survival, especially in patients with EGFR mutation. Herein, CD44s may be a biological marker for micropapillary lung adenocarcinoma.

Persistent Pulmonary Interstitial Emphysema With Respiratory Infection: A Clinicopathological Analysis of Six Cases and Detection of Infectious Pathogens by Metagenomic Next-Generation Sequencing (mNGS).

Background: Persistent pulmonary interstitial emphysema (PPIE) is known to be related to mechanical ventilation and preterm. However, PPIE is also reported rarely in non-ventilated and full-term infants. Its relationship with respiratory infection is rarely reported in the literature. PPIE is difficult to diagnose and always mimics other congenital thoracic malformations (CTMs), such as congenital cystic adenomatoid malformation (CCAM). Objective: The objective of this study was to evaluate clinicopathological and radiographic features of PPIE with respiratory infection and to detect the possible infectious pathogens. Methods: From January 2011 to December 2019, six cases were confirmed pathologically with PPIE from a large cohort of 477 resected CTMs in West China Hospital of Sichuan University. Clinical and radiographic features were obtained from patients' medical records and follow-up. The present study aimed to analyze clinicopathological and radiographic features and to detect the infectious pathogens by metagenomic next-generation sequencing (mNGS). Results: The six PPIE cases included four girls and two boys, ranging from 2 months to 5 years; 100% (5/5) of the available cases were full-term and without mechanical ventilation. CCAM were suspected in 66.7% (4/6) patients; 66.7% (4/6) cases affected a single lobe, and 33.3% (2/6) cases affected both lung lobes. Clinically, all six PPIEs were presented with symptoms of respiratory infection and diagnosed with pneumonia. All six patients were treated by surgery after anti-infective treatment. The pathologic characteristics showed lung cysts with variable size along the bronchovascular bundles, the cysts had a discontinuous fibrotic wall with a smooth inner surface lined with uninucleated and/or multinucleated macrophages. Streptococcus pneumoniae was detected in patient No. 1. Human beta-herpesvirus 5 was detected in patient No. 2. Neisseria mucosa, Neisseria sicca, Prevotella melaninogenica, Prevotella histicola, and Fusobacterium nucleatum were detected in patient No. 5, and no infectious pathogen was detected in 50% (3/6, No. 3, No. 4, and No. 6) of cases. Conclusion: Six rare cases of PPIE with respiratory infection were treated by surgery after anti-infective treatment. All five available cases were full-term infants without mechanical ventilation. The histological characteristics of PPIE were the wall of cysts composed of a thin layer of discontinuous fibrous tissue and lined with uninucleated or/and multinucleated macrophages.

Pulmonary large cell carcinoma with neuroendocrine morphology shows genetic similarity to large cell neuroendocrine carcinoma.

BACKGROUND: Large cell neuroendocrine carcinoma (LCNEC) is a high-grade malignant pulmonary neuroendocrine tumour. The distinction of pulmonary large cell carcinoma (LCC) and LCNEC is based on the presence of neuroendocrine morphology and the expression of at least one neuroendocrine marker in at least 10% of tumour cells in the latter. According to the current classification, LCC with neuroendocrine morphology and without neuroendocrine marker expression is classified as LCC. This subgroup we have named LCNEC-null and aimed to analyze its characteristics. METHODS: 31 surgical samples resected in West China Hospital of Sichuan University between 2017 to 2021 were collected, including 7 traditional LCCs, 11 LCNEC-nulls and 13 LCNECs. Each case was conducted to immunohistochemistry and 425-panel-NGS. RESULTS: Compared to other LCCs, detailed analysis of LCNEC-nulls revealed biological features similar to those of LCNECs, especially for immunohistochemistry and molecular analysis: 1. diffusive, coarse granular and high expression of Pan-CK; 2. rare PD-L1 expression; 3. High rate of p53 expression and Rb deficiency 4. abundant genetic alterations are similar to LCNEC. All characteristics above deviated from traditional LCC, indicating they have the same origin as LCNEC. Furthermore, LCNEC could be genetically divided into two subtypes when we reclassified LCNEC-null as LCNEC, and the mutational type and prognosis differed significantly. CONCLUSIONS: We consider that LCNEC-null should be reclassified as LCNEC based on analysis above. In addition, two genetic types of LCNEC with different prognosis also indicate two mechanism of tumour formation.

Primary pulmonary lymphoepithelioma-like carcinoma is characterized by high PD-L1 expression, but low tumor mutation burden.

Primary pulmonary lymphoepithelioma-like carcinoma (PLELC) is a rare subtype of non-small cell lung cancer (NSCLC). There are few reported studies on the relationship between programmed death ligand-1 (PD-L1) expression and genomics features of this distinct NSCLC subtype. Our study aimed to investigate the expression levels of PD-L1 to determine their clinical value and to identify genetic alterations in PLELC. Fifty-nine PLELC patients, whose clinical information and pathology results were available, were included in this study. Immunohistochemical analysis of PD-L1 was performed in all cases. Specimens of 37 PLELCs and 3 metastatic nasopharyngeal carcinomas (NPCs) of the lung, resected within the previous 3 years, were chosen for mutation analysis, using next-generation sequencing of 425 genes. PLELC patients in the present study were mainly non-smoking females, with a high frequency of PD-L1 positivity in their tumors. Positivity rates were 96.6 %, 91.5 %, 83.1 %, and 61.0 % at tumor proportion scores (TPSs)≥ 1%, 5%, 10 %, and 50 %, respectively. Moreover, we observed that PD-L1 expression was higher in specimens stored for ≤ 3 years and in tumor cells with vesicular nucleus morphology at a TPS ≥ 50 %. Mutation analysis suggested a relatively high frequency of TP53 mutations and MCL1 copy number variation, but low tumor mutation burden (TMB) (ranging from 0 to 6.9, median of 1.1 mutation per megabase) and similarity of gene alteration with NPCs. However, no specific germline mutation was detected in PLELC patients. Additionally, survival analysis showed that patients in the early stages (stage I and II) had higher progression-free survival rates (P = 0.035) and those with tumors containing obvious stroma fibrosis tended to have worse prognosis (P =  0.008). However only stage was shown to be the independent prognostic factor (P = 0.008, HR=4.807, 95 %CI:1.508-15.323).PLELC is a subtype of lung cancer with distinct clinicopathological and genetic features, especially characterized by high PD-L1 expression and low TMB.

Distribution of PD-L1 expression and its relationship with clinicopathological variables: an audit from 1071 cases of surgically resected non-small cell lung cancer.

BACKGROUND: Programmed death ligand 1 (PD-L1) was reported to predict the response of immunotherapy; however, the association between PD-L1 expression and clinicopathologic characteristics has yet to be elucidated in non-small cell lung cancer (NSCLCs). MATERIALS AND METHODS: We reviewed PDL1 expression investigated by immunohistochemical analysis using FFPE tissue in a total of 1071 cases of primary or metastatic NSCLC tissues analyzed between 2015-2017, and evaluated the association between PD-L1 expression and the clinicopathologic characteristics. RESULTS: PD-L1 expression was observed in 361 (33.7%) cases with positive staining in at least 1% tumor cells and 116 (10.8%) cases had positive staining in ≥50% tumor cells. The PD-L1 positive prevalence was significantly higher in squamous cell carcinoma (SCC) than in adenocarcinoma (AD). In the AD subgroup, PD-L1 expression on tumors was higher in males and smokers, and with high histologic grade, relative high T, N, M status, advanced AJCC stage, and in ALK rearrangement patients. However, EGFR mutated patients showed relatively lower PD-L1 expression than wild type patients. CONCLUSION: This study revealed the unique distribution of PD-L1 expression with clinicopathologic features in East Asian NSCLCs in a single, large cohort of patients. Since immunohistochemistry of the PD-L1 protein (PD-L1 IHC) is the only clinically approved predictive biomarker for anti-PD-1/-PD-L1 therapy currently, our outcomes could help to stratify patients to ensure selection of those who would most benefit from PD-1/PD- L1 inhibitor therapy.

Mixed Adenoneuroendocrine Carcinoma of the Gallbladder.

Mixed adenoneuroendocrine carcinoma rarely occurs in the gallbladder. Most cases of cholecystic mixed adenoneuroendocrine carcinoma have been reported from Asia, North American, and Europe; however, there is scarce literature available on this tumor in other populations. Here, we report a case of mixed adenoneuroendocrine carcinoma in a Melanoderm woman who was initially suspected to have gallbladder cancer. No specific symptoms or abnormal blood test results were observed preoperatively. Magnetic resonance imaging revealed a 7-cm hypointense mass in the gallbladder fossa, which invaded the surrounding liver segments. Radical cholecystectomy, partial liver resection, and regional lymphadenectomy were performed. Finally, she was diagnosed as mixed adenoneuroendocrine carcinoma of the gallbladder upon postoperative pathological examination and immunohistochemical staining. She received six cycles of systemic chemotherapy and somatostatin treatment and survived 21 months after surgery. Our case highlights the fact that mixed adenoneuroendocrine carcinoma of the gallbladder can occur in African populations as well. Surgical approach combined with adjuvant chemotherapy and somatostatin treatment may contribute a relatively good survival outcome.

Hepatic Paragonimiasis Mimicking Hepatocellular Carcinoma.

Paragonimiasis is a parasitic lung infection caused by lung flukes of the genus Paragonimus. Ectopic infection may occur but rarely involves the liver. Here, we report a case of hepatic paragonimiasis in a Chinese man who was initially suspected to have hepatocellular carcinoma. He had been previously diagnosed with chronic hepatitis B. No specific symptoms or abnormal blood test results were observed, except for a significant rise in serum alfa-fetoprotein. Magnetic resonance imaging revealed a 12-cm mass with inhomogeneous signal intensity at the left lobe of the liver. Laparoscopic left hemihepatectomy was performed. He was finally diagnosed as hepatic paragonimiasis upon pathological examination and antibody serology. The postoperative course was uneventful. He received a standard course of praziquantel and recovered well. Our case is unique in its tumor-like characteristic and protrudes the difficulty of differential diagnosis with both benignant and malignant hepatic diseases by imaging studies or non-specific symptoms. Hepatic paragonimiasis is unusual; however, it should be considered in the differential diagnosis of liver malignancy by clinicians.

Myoepithelial carcinoma of the nasopharynx: Rare case report with clinicopathologic and immunohistochemical features review of literature.

BACKGROUND: Myoepithelial carcinoma is a rare salivary carcinoma, which most often arises from the major salivary glands. Only a few cases of myoepithelial carcinoma of the nasopharynx have been reported, thus, the treatment guideline and prognosis remain undefined. METHODS: We reported a case of nasopharyngeal myoepithelial carcinoma in a 31-year-old man. The tumor cells showed specific cell types and arrangements histologically, which were immunoreactive with myoepithelial markers. The patient received surgical excision with transpalatal approach. A literature review of previous cases was also presented. RESULTS: The patient reflected residual tumor 4 weeks later. After concurrent chemoradiotherapy (CRT), the tumor reduced and remained stable without signs of progression. CONCLUSION: The nasopharyngeal mass with spindled, plasmacytoid, epithelioid, and clear cell types, was suggested to raise the suspicion of myoepithelial carcinoma in order to diagnose and treat early. The wide surgical excision followed by optimal adjuvant therapy might offer a mode of treatment with better survival results.

[Influence of Different Therapies on EGFR Mutants by Circulating Cell-free DNA of Lung Adenocarcinoma and Prognosis].

BACKGROUND: Epidermal growth factor receptor (EGFR) gene mutation is closely related to the EGFR-TKI target treatment and prognosis of lung adenocarcinoma patients. The mutation status of EGFR is limited by tissue detection. The purpose of this study was to investigate the difference of EGFR mutants in plasmacirculating cell-free DNA (cfDNA) obtained from patients with non-small cell lung cancer (NSCLC) in three groups: pre-therapy, after traditional chemotherapy and targeted therapy. The aim of this study was to analyze whether the plasma cfDNA could effectively determine the EGFR mutations and monitor the drug resistant gene T790M, as well as its prognostic prediction value in patients with targeted therapy. METHODS: ARMS (amplification refractory mutation system)-PCR was used to detect EGFR mutations in 107 (50 of pre-therapy, 29 after traditional chemotherapy and 28 after targeted therapy) cases of paired plasma and tumor tissue specimens, followed by comparing their concordance. The sensitivity, specificity and the prognostic value of plasma cfDNA detection were also observed. RESULTS: The total rate of EGFR mutation was 56% (60/107) in all plasma samples and 77.6% (83/107) in corresponding tumor tissues. Completely the same mutants and wild-type EGFR were found in 68.2% cases of paired specimens. The sensitivity of plasma cfDNA detection was 72.3% and the specificity was up to 100%. Patients were sub-categorized according to therapy. The results showed that the highest consistent rate of cfDNA and tumor tissues was found in the group of pre-therapy (74%, 37/50). Whereas, the lowest consistent rate was observed in the targeted therapy group (57.1%, 16/28). It indicated that the targeted treatment could change the EGFR status in plasma cfDNA. Further analyses on inconsistent cases in this group revealed that 50% of them were compound EGFR mutations with T790M. Thereby, it suggested that targeted therapy might induce the emergence of drug resistance gene T790M. This speculation was confirmed by survival analyses. Based on plasma cfDNA results, patients with T790M mutant had significantly worse progression-free survival (PFS) and overall survival (OS). CONCLUSIONS: For EGFR testing, ARMS-PCR on plasma cfDNA is a promising methodology with the highest specificity and effective sensitivity. It is useful for EGFR testing in patients before treatment, especially the late-stage patients. Simultaneously, plasma cfDNA could be used to monitor the drug resistant mutation, T790M status and predict prognosis after targeted therapy.

Novel gene mutations in well-differentiated fetal adenocarcinoma of the lung in the next generation sequencing era.

OBJECTIVES: Since well-differentiated fetal adenocarcinoma of lung (WDFA) is an extremely rare subtype of invasive lung adenocarcinoma, histologic features, biomarkers and molecular aberrant of it are not fully determined. This article aims to investigate the clinic-pathologic details and potential driver genes of WDFA. MATERIALS AND METHODS: Two cases of WDFA were selected from a large cohort of 730 cases of primary adenocarcinoma of the lung resected in West China Hospital of Sichuan University between January 2016 and June 2017, retrospectively. Both of them were conducted to immunohistochemical profile and gene mutation analysis by using 56-parelle-NGS. RESULTS: Microscopically, besides conventional histologic characteristics of WDFA, such as well-differentiated glands composed of obvious glycogen-rich cells and squamoid morules formation, remarkable proliferation of benign fibrous tissue, focal necrosis and mitoses were found. Unlike the common adenocarcinomas of the lung, WDFAs showed nuclear/cytoplasmic expression of ß-catenin, diffuse expression for TTF-1, and focal for Napsin A. Furthermore, molecular analysis demonstrated two novel missense gene mutations of BRCA2 and TSC2, as well as the classical CTNNB1 gene mutation and silent mutation of DDR2 gene. CONCLUSIONS: This report presents the first case with two novel gene mutations of the WDFA, suggesting that in addition to ß-catenin, BRCA2 and TSC2 might play some important roles in up-regulation of Wnt signaling pathway. Moreover, use of NGS technique is helpful to understand the biology of this rare neoplasm and provide the potential gene for targeted therapy.

High concordance of EGFR mutation status between sputum and corresponding tissue specimens of late-stage lung cancers using amplification refractory mutation system-PCR.

BACKGROUND: To gain sufficient tumor tissue for EGFR mutations analysis is of prime clinical importance. Therefore, the objective of present study was to assess whether sputum is suitable for EGFR testing and to assess the consistency between sputum and tissue specimens. METHODS: This analysis included 37 paired sputum and tissue specimens obtained from late-stage lung cancer patients followed by EGFR analysis using the ARSM-PCR method, and 11 sputum specimens of COPD were added as negative control. RESULTS: 35 out of 37 (94.6%) patients with lung cancer were found to have tumor cells in the sputum specimen using the LCT method and extracted adequate DNA for EGFR testing. In contrast, only five out of 11 cases of COPD (45.5%) were isolated with sufficient DNA (P<0.001). Among sputum testing, higher EGFR mutation was significantly associated with NCSLC and ADC (40%, 10/25), stage IV (45.5%), and non-smoking status (43.8%). Compared with corresponding tissue specimens, the accuracy, specificity, and sensitivity of EGFR mutation analysis in sputum specimens were demonstrated as 97.1%, 96%, and 90.9%, respectively. Interestingly, a significantly high frequency of L858R in exon 21 was found (P<0.001) in all types of EGFR mutants both on sputum and tissue specimens. CONCLUSIONS: The findings of the current study suggest a high concordance between sputum and tissue specimens, reflecting the important potential of sputum specimens for EGFR mutant detection in patients with late-stage lung cancer using the ARSM-PCR method.