Obscure Bleeding from a Metastatic Small Bowel Tumor Diagnosed Using Motorized Spiral Enteroscopy: A Case Study and a Literature Review.

Small bowel tumors are relatively rare, representing only around 5% of all gastrointestinal neoplasms, with a progressively increasing incidence. Currently, there are no established guidelines for diagnostic approaches, screening procedures, or management strategies for small bowel tumors. We present here the case of a patient with a rare type of metastatic tumor of the small bowel originating from primary lung adenocarcinoma who presented with abdominal pain, severe iron-deficiency anemia, and melena. The initial investigations, gastroscopy and colonoscopy, failed to identify the bleeding source. The obscure bleeding source and diagnosis were achieved through power motorized spiral enteroscopy (MSE), which allowed the visualization and biopsy of the tumor. Histopathological examination established the presence of a poorly differentiated non-mucinous adenocarcinoma originating from the lung. This case is reported to provide evidence of the efficiency of MSE in the diagnosis of small bowel tumors, with the method providing higher insertion depth in a reduced amount of time.

Diagnostic Value of Immunostaining for Thyroid Transcription Factor 1 (TTF1) and Paired Box 8 (PAX8) in Distinguishing Pulmonary Metastases of Mesonephric and Mesonephric-like Adenocarcinomas from Primary Lung Adenocarcinomas.

BACKGROUND/AIM: Both mesonephric adenocarcinoma (MA) and mesonephric-like adenocarcinoma (MLA) express thyroid transcription factor 1 (TTF1). TTF1 is also considered a highly sensitive and specific diagnostic marker for primary lung adenocarcinoma (PLA). However, distinguishing PLA from pulmonary metastatic MA/MLA (PMM) based on the expression of TTF1 alone can be difficult. This study aimed to investigate the expression of TTF1 and paired box 8 (PAX8) and assess their value in distinguishing PMM from PLA. PATIENTS AND METHODS: We reviewed the electronic medical records and pathology slides of eight PMM cases. We conducted immunostaining for TTF1 and PAX8 in 6, 8, and 21 cases of primary MA/MLA, PMM, and PLA, respectively. RESULTS: Two patients with stage IB uterine MLA developed lung metastases at 5 and 57 months after hysterectomy. Solitary pulmonary nodules were suspected to be primary lung cancer in two patients. Compared to primary tumors, all matched PMMs exhibited reduced TTF1 immunoreactivity. In contrast, the majority of PLAs showed uniform and intense TTF1 expression. All except one PMM exhibited diffuse and strong PAX8 expression, while only one PLA showed focal and weak PAX8 expression. CONCLUSION: Immunostaining for TTF1 and PAX8 can help in distinguishing PMM from PLA in the diagnosis of pulmonary lesions detected in patients with a history of MA/MLA.

Impact of RBM10 and PD-L1 expression on the prognosis of pathologic N1-N2 epidermal growth factor receptor mutant lung adenocarcinoma.

Background: Impact of RNA-binding motif protein 10 (RBM10) and programmed death-ligand 1 (PD-L1) on the postoperative prognosis of patients with epidermal growth factor receptor gene mutation (EGFR-Mt) lung adenocarcinoma with pathological lymph node metastasis is still unclear. Methods: Patients who underwent curative surgery for pN1-N2 EGFR-Mt lung adenocarcinoma (n=129) harboring the EGFR exon 19 deletion mutation (Ex19) (n=66) or EGFR exon 21 L858R mutation (Ex21) (n=63) between January 2010 and December 2020 were included in this retrospective study. The prognoses of patients with low/high cytoplasmic RBM10 expression and PD-L1 negativity/positivity based on immunohistochemistry (IHC) of resected specimens were compared using the log-rank test. The effects of RBM10 and PD-L1 expression on overall survival (OS) were examined via multivariable analysis using the Cox proportional hazards regression model. The effects of RBM10 and PD-L1 expression on progression-free survival (PFS) of EGFR-tyrosine kinase inhibitors (TKIs) therapy among patients with recurrent pN1-N2 EGFR-Mt lung adenocarcinoma (n=67) were examined using log-rank tests. Results: The RBM10 low expression group showed significantly better 5-year OS than the RBM10 high expression group (89.4% vs. 71.5%, P=0.020), and the PD-L1 negative group tended to have longer 5-year OS than the PD-L1 positive group (86.4% vs. 68.4%, P=0.050). Multivariable analysis showed that high RBM10 expression [hazard ratio (HR), 3.12; 95% confidence interval (CI): 1.19-8.17; P=0.021] and PD-L1 positivity (HR, 3.80; 95% CI: 1.64-8.84; P=0.002) were independent poor prognostic factors for OS. PFS of patients with relapse and first-line EGFR-TKI treatment was significantly better in the PD-L1-negative group than in the PD-L1-positive group (34.5 vs. 12.1 months, P=0.045). PFS of patients with Ex21 relapse and first-line EGFR-TKI treatment was significantly better in the RBM10 low expression group than in the RBM10 high expression group (25.5 vs. 13.0 months, P=0.025). Conclusions: High RBM10 expression and PD-L1 positivity are poor prognostic factors for OS in patients with pN1-N2 EGFR-Mt lung adenocarcinoma after curative surgery. In patients with recurrent pN1-N2 EGFR-Mt lung adenocarcinoma, PD-L1 and RBM10 expression may influence response to EGFR-TKIs.

Value of radiomics in differentiating synchronous double primary lung adenocarcinomas from intrapulmonary metastasis.

Background: Distinguishing synchronous double primary lung adenocarcinoma (SDPLA) from intrapulmonary metastasis (IPM) of lung cancer has significant therapeutic and prognostic values. This study aimed to develop and validate a CT-based radiomics model to differentiate SDPLA from IPM. Methods: A total of 153 patients (93 SDPLA and 60 IPM) with 306 pathologically confirmed lesions were retrospectively studied. CT morphological features were also recorded. Region of interest (ROI) segmentation was performed semiautomatically, and 1,037 radiomics features were extracted from every segmented lesion The differences of radiomics features were defined as the relative net difference in radiomics features between the two lesions on CT. Those low reliable (ICC <0.75) and redundant (r>0.9) features were excluded by intraclass correlation coefficients (ICC) and Pearson's correlation. Multivariate logistic regression (LR) algorithm was used to establish the classification model according to the selected features. The radiomics model was based on the four most contributing differences of radiomics features. Clinical-CT model and MixModel were based on selected clinical and CT features only and the combination of clinical-CT and Rad-score, respectively. Results: In both the training and testing cohorts, the area under the curves (AUCs) of the radiomics model were larger than those of the clinical-CT model (0.944 vs. 0.793 and 0.886 vs. 0.735 on training and testing cohorts, respectively), and statistically significant differences between the two models in the testing set were found (P<0.001). Meanwhile, three radiologists had sensitivities of 84.2%, 63.9%, and 68.4%, and specificities of 76.9%, 69.2%, and 76.9% in differentiating 19 SDPLA cases from 13 cases of IPM in the testing set. Compared with the performance of the three radiologists, the radiomics model showed better accuracy to the patients in both the training and testing cohorts. Among the three models, the radiomics model showed the best net benefits. Conclusions: The differences of radiomics features showed excellent diagnostic performance for preoperative differentiation between synchronous double primary lung adenocarcinoma from interpulmonary metastasis, superior to the clinical model and decisions made by radiologists.

A novel NGS-based diagnostic algorithm for classifying multifocal lung adenocarcinomas in pN0M0 patients.

The classification of multifocal lung adenocarcinomas (MLAs), including multiple primary lung adenocarcinomas (MPLAs) and intrapulmonary metastases (IPMs), has great clinical significance in staging and treatment determination. However, the application of molecular approaches in pN0M0 MLA diagnosis has not been well investigated. Here, we performed next-generation sequencing (NGS) analysis in 45 pN0M0 MLA patients (101 lesion pairs) who were initially diagnosed as having MPLA by comprehensive histologic assessment (CHA). Five additional patients with intrathoracic metastases were used as positive controls, while 197 patients with unifocal lung adenocarcinomas (425 random lesion pairs) were used as negative controls. By utilizing a predefined NGS criterion, all IPMs in the positive control group could be accurately classified, whereas 13 lesion pairs (3.1%) in the negative control cohort were misdiagnosed as IPMs. Additionally, 14 IPM lesion pairs were diagnosed in the study group, with at least 7 misdiagnoses. We thus developed a refined algorithm, incorporating both NGS and histologic results, that could correctly diagnose all the known MPLAs and IPMs. In particular, all IPMs identified by the refined algorithm were diagnosed to be IPMs or suspected IPMs by CHA reassessment. The refined algorithm-diagnosed MPLAs patients also had significantly better progression-free survival than the refined algorithm-diagnosed IPMs (p < 0.0001), which is superior to conventional NGS or CHA diagnoses. Overall, we developed an NGS-based algorithm that could accurately distinguish IPMs from MPLAs in MLA patients. Our results demonstrate a promising clinical utility of NGS to complement traditional CHA-based MLA diagnosis and help determine patient staging and treatment.

One-stage resection of four genotypes of bilateral multiple primary lung adenocarcinoma: A case report.

BACKGROUND: The incidence of multiple primary lung cancer (MPLC) in China is 0.52%-2.45%. Most primary lung cancer cases have reported two lesions or three in rare cases. We report a rare case of bilateral simultaneous multiple primary lung adenocarcinoma of four different genotypes. CASE SUMMARY: A 58-year-old woman was admitted to our hospital on June 29, 2021, and upon physical examination, four multiple pulmonary nodules were identified in both lungs. Further computed tomography (CT) images revealed the presence of ground glass nodules, predicted to be high-risk cancer lesions by artificial intelligence. With the guidance of three-dimensional reconstruction of preoperative CT images, the nodules were resected under thoracoscopy. Postoperative pathological investigation revealed that the nodule types were adenocarcinoma in situ, invasive alveolar adenocarcinoma, and microinvasive adenocarcinoma. The excised nodules were further sequenced using high-throughput sequencing (semiconductor sequencing method) of 26 lung cancer genes to confirm that the four lesions were not homologous. The patient was discharged on postoperative day 8, that is, on July 15, 2021. One month later, she returned to the hospital for follow-up and reexamination. Chest CT examination showed that she had recovered well, and no obvious exudation and effusion were found in both pleural cavities. Evaluation of postoperative pulmonary function showed that her forced vital capacity was 1.40 L (preoperative value, 2.27 L) and forced expiratory volume was 1.24 L (preoperative value, 2.23 L). CONCLUSION: The surgical plan for multiple pulmonary nodules should be carefully considered. For carefully selected patients with concurrently occurring multiple lung nodules in both lungs, sublobectomy is a safe and feasible plan for concurrent bilateral resection of the lesions. Genetic sequencing is necessary for MPLC diagnosis and treatment.

Prognostic factors for relapse-free survival in stage IB-IIIA primary lung adenocarcinoma by epidermal growth factor receptor mutation status.

BACKGROUND: Pathological stage IB-IIIA lung adenocarcinoma with an epidermal growth factor receptor (EGFR) mutation (Mt) has a high recurrence rate even after complete resection. However, there have been few reports on the risk factors for Mt recurrence. This study aimed to analyze the clinicopathological factors related to the relapse-free survival (RFS) of patients with pathological stage IB-IIIA primary lung adenocarcinoma with and without an EGFR mutation. METHODS: Patients who underwent curative surgery for Mt (n = 208) harboring the EGFR exon 21 L858R point mutation or EGFR exon 19 deletion mutation and EGFR mutation wild-type lung adenocarcinoma (Wt, n = 358) between January 2010 and December 2020 were included. Patients who received adjuvant EGFR-tyrosine kinase inhibitors were excluded. The prognostic factors for RFS were analyzed using a multivariable Cox regression analysis. RESULTS: The 5-year RFS rates in the Mt and Wt groups were 43.5 and 52.3%, respectively (p = 0.907). Prognostic factors for RFS in the Mt group included smoking history (hazard ratio [HR], 1.49; p = 0.049), blood vessel invasion (HR, 1.84; p = 0.023), and lymph node metastasis (HR, 1.96; p = 0.005). However, adjuvant chemotherapy was not a prognostic factor (HR, 1.02; p = 0.906). In contrast, positron emission tomography (PET) max standardized uptake value (SUV) ≥ 6.0 (HR, 1.53; p = 0.042), lymphatic vessel invasion (HR, 1.54; p = 0.036), lymph node metastasis (HR, 1.79; p = 0.002), and adjuvant chemotherapy (HR, 0.60; p = 0.008) were prognostic factors for RFS in the Wt group. CONCLUSIONS: Prognostic factors for RFS in stage IB-IIIA primary lung adenocarcinoma differ by epidermal growth factor receptor mutation status. The impact of adjuvant chemotherapy on RFS also differed by EGFR mutation status.

Gene expression of Nectin-4 and its clinical significance in dogs with primary lung adenocarcinoma.

BACKGROUND: Canine primary lung adenocarcinoma (CPLA) is suspected by radiography or computed tomography; however, since there are no tumour markers, early diagnosis is difficult, and the prognosis is poor due to increased tumour volume. Nectin-4 has been reported to be expressed in human lung, ovarian, and pancreatic cancers and promotes tumour growth. It has been reported to be a tumour marker and prognostic factor, and oncolytic virotherapy is being investigated using nectin-4 as a therapeutic target. OBJECTIVES: The purpose of this study was to investigate the expression of Nectin-4 in CPLA and its clinical significance in dogs with pulmonary adenocarcinomas. METHODS: The relationships between Nectin-4 expression and signalling, tumour volume, tumour weight, and prognosis were analyzed in 34 CPLA patients. RESULTS: The expression of canine Nectin-4 (high Nectin-4) was found in 25 of 34 cases (73%), and Nectin-4 expression levels did not show any significant associations with gender, body weight, and tumour stage. However, there was a significant positive correlation between Nectin-4 expression and tumour volume (r = 0.623, p < 0.05) and tumour weight (r = 0.735, p < 0.05). Regarding prognosis, the median survival time was 427 days in high Nectin-4 cases and 420 days in cases with no Nectin-4 expression. CONCLUSION: Our study demonstrated that Nectin-4 is highly expressed in CPLA. In addition, nectin-4 might be a tumour growth factor in CPLA and thus is a promising biomarker for CPLA. Further investigations on nectin-4 in CPLA are warranted for its diagnosis and novel targets for oncolytic virotherapy.

Primary lung adenocarcinoma complicated with lung hamartoma: A case report and literature review. / åŽŸå‘æ€§è‚ºè ºç™Œåˆå¹¶è‚ºé”™æž„ç˜¤1ä¾‹å¹¶æ–‡çŒ®å¤ä¹ .

The clinical data for a patient with primary lung adenocarcinoma complicated with pulmonary hamartoma, who admitted to Zunyi Medical University Hospital in September 2020, was retrospectively analyzed. The 62-years-old male visited outpatient service because of dysphagia in March 2015, and the pulmonary nodules were found. In September 2020, the computed tomography indicated the enlarged nodule in the lower lobe of left lung with lobulation, and there was ground glass nodule in the upper lobe of left lung. After thoracoscopic wedge surgery, the primary pulmonary adenocarcinoma in the upper lobe of left lung and pulmonary hamartoma in the lower lobe of left lung were confirmed by pathology. Whole exon sequencing revealed that kinesin family member 20B (KIF20B) gene was not expressed in lung adenocarcinoma, but was expressed in pulmonary hamartoma. The clinical manifestations of lung adenocarcinoma complicated with pulmonary hamartoma was not typical, which could locate in the same side and different sides of the lung. The imaging manifestations of the 2 kinds of tumors were diverse and can not be completely distinguished. The pathological examination after surgery is the gold standard, and the possibility of malignant transformation of pulmonary hamartoma should be warned.

Second Primary Lung Adenocarcinoma After Intensity-Modulated Radiotherapy for Nasopharyngeal Carcinoma.

Objective: The improvement of the efficacy of intensity-modulated radiotherapy (IMRT) for nasopharyngeal cancer (NPC) has prolonged the survival of patients, and the incidence of the second tumor has gradually increased. Among them, second primary lung adenocarcinoma (SPLAC) attributes the highest incidence. This study aimed to determine the long-term risk of SPLAC in NPC patients after IMRT. Methods: From May 2005 to May 2018, a total of 1,102 non-metastatic NPC patients who received IMRT in our hospital were enrolled, and the incidence and efficacy of SPLAC were followed up in the long term. Results: Over a median follow-up period of 66 months, a total of 22 cases of SPLAC were observed, with an incidence of 2.0%. The 1-, 2-, 3-, 4-, and 5-year cumulative risks of SPLAC were 0.4%, 0.7%, 0.8%, 1.1%, and 1.7%, respectively. During follow-up, 90.9% (20/22) of the SPLAC detected was in early stage, and the recurrence rate of surgery alone was 5.3% (1/19). Conclusion: In NPC patients, the proportion of SPLAC after IMRT was similar to that of the normal population, and most of them were found in early stage during follow-up, with good surgical efficacy.

Primary lung adenocarcinoma complicated with lung hamartoma: A case report and literature review / 中南大学学报(医学版)

The clinical data for a patient with primary lung adenocarcinoma complicated with pulmonary hamartoma, who admitted to Zunyi Medical University Hospital in September 2020, was retrospectively analyzed. The 62-years-old male visited outpatient service because of dysphagia in March 2015, and the pulmonary nodules were found. In September 2020, the computed tomography indicated the enlarged nodule in the lower lobe of left lung with lobulation, and there was ground glass nodule in the upper lobe of left lung. After thoracoscopic wedge surgery, the primary pulmonary adenocarcinoma in the upper lobe of left lung and pulmonary hamartoma in the lower lobe of left lung were confirmed by pathology. Whole exon sequencing revealed that kinesin family member 20B (KIF20B) gene was not expressed in lung adenocarcinoma, but was expressed in pulmonary hamartoma. The clinical manifestations of lung adenocarcinoma complicated with pulmonary hamartoma was not typical, which could locate in the same side and different sides of the lung. The imaging manifestations of the 2 kinds of tumors were diverse and can not be completely distinguished. The pathological examination after surgery is the gold standard, and the possibility of malignant transformation of pulmonary hamartoma should be warned.

Primary lung adenocarcinoma with gross calcification and suspected bone formation.

Calcification in a lung tumor suggests that it is a benign tumor such as a hamartoma or a sclerosing lung cell tumor. In contrast, carcinoid, lung cancer, carcinosarcoma, and sarcoma rarely harbor calcification. Primary lung adenocarcinomas with gross calcification that is suggestive of bone formation are very rare. It is difficult to distinguish between calcification and bone formation purely on the basis of image definitive diagnosis of bone formation being difficult in the absence of a large surgical specimen. Lung cancers with bone formation are exceedingly rare: to the best of our knowledge, only 13 cases have been reported. Careful attention is needed when differentiating between benign and malignant tumors. Here, we report a case of primary lung adenocarcinoma with gross calcification that was suggestive of bone formation.

[Impact of Smoking on the Histological Subtype and Outcome of the Primary Lung Adenocarcinoma].

OBJECTIVE: To explore the effect of smoking on the histological subtype and prognosis of patients with lung adenocarcinoma (LAC) in China. METHODS: According to the new International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society(IASLC/ATS/ERS)classification, 266 donors with primary LAC were reclassified. The correlation between clinicopathological factors including smoking status and the histological subtype was analyzed, and survival analysis was used to analyze the prognosis of primary LAC. RESULTS: There were four main histological subtypes including acinar predominant adenocarcinoma (APA) 30.1%, papillary predominant adenocarcinoma (PPA) 26.7%, solid predominant adenocarcinoma (SPA) 25.9%, and lepidic predominant adenocarcinoma (LPA) 11.7%.Smoking was associated with the histological subtype.The proportion of smokers was significantly higher than non-smokers in the SPA group, and the proportion of non-smokers was higher in other subtypes group. Cox regression model showed that the histological subtype and TNM stage were the independent predictors of prognostic in all patients.TNM stage was the predictor of postoperative survival in both smokers and non-smokers, and histological subtypes was the predictor only in smokers (ß=0.898, RR=2.455). Compared with the non-SPA group, the prognosis of the SPA group was significantly worse. CONCLUSION: Smoking is associated with SPA subtype, which affect the prognosis of primary LAC.

Clinical analysis of 56 cases of simultaneous bilateral video-assisted thoracoscopic surgery for bilateral synchronous multiple primary lung adenocarcinoma.

BACKGROUND: Bilateral synchronous multiple primary lung adenocarcinoma (BSMPLA) is a rapidly increasing disease for which timely and accurate treatment is required. We describe our experience which we hope to establish optimal therapeutic options for patients with BSMPLA. METHODS: This study aimed to explore the feasibility and safety of simultaneous bilateral video-assisted thoracoscopic surgery (VATS) in 56 patients who received histological diagnoses of BSMPLA at our hospital between January 2016 and January 2018. In this retrospective analysis of clinical outcomes, we observed no serious postoperative complications or perioperative death. RESULTS: Four and 28 patients respectively underwent bilateral lobectomy and lobectomy with contralateral sublobar resection, whereas the remaining 24 patients underwent bilateral sublobar resection. Sublobar resection means anatomical segmentectomy or wedge resection. The mean postoperative hospital stay duration was 5.39±2.67 days. Postoperative complications comprising persistent air leakage for more than 5 days was observed in 8 (14.2%) of 56 patients. No severe postoperative complications or deaths occurred. CONCLUSIONS: Our results suggest that simultaneous bilateral VATS is feasible, safe, and reproducible. This therapeutic strategy appears to confer considerable benefits on patients with BSMPLA.

Napsin A levels in epithelial lining fluid as a diagnostic biomarker of primary lung adenocarcinoma.

BACKGROUND: It is crucial to develop novel diagnostic approaches for determining if peripheral lung nodules are malignant, as such nodules are frequently detected due to the increased use of chest computed tomography scans. To this end, we evaluated levels of napsin A in epithelial lining fluid (ELF), since napsin A has been reported to be an immunohistochemical biomarker for histological diagnosis of primary lung adenocarcinoma. METHODS: In consecutive patients with indeterminate peripheral lung nodules, ELF samples were obtained using a bronchoscopic microsampling (BMS) technique. The levels of napsin A and carcinoembryonic antigen (CEA) in ELF at the nodule site were compared with those at the contralateral site. A final diagnosis of primary lung adenocarcinoma was established by surgical resection. RESULTS: We performed BMS in 43 consecutive patients. Among patients with primary lung adenocarcinoma, the napsin A levels in ELF at the nodule site were markedly higher than those at the contralateral site, while there were no significant differences in CEA levels. Furthermore, in 18 patients who were undiagnosed by bronchoscopy and finally diagnosed by surgery, the napsin A levels in ELF at the nodule site were identically significantly higher than those at the contralateral site. In patients with non-adenocarcinoma, there were no differences in napsin A levels in ELF. The area under the receiver operator characteristic curve for identifying primary lung adenocarcinoma was 0.840 for napsin A and 0.542 for CEA. CONCLUSION: Evaluation of napsin A levels in ELF may be useful for distinguishing primary lung adenocarcinoma.

Sole metastatic pulmonary nodules from breast cancer simulating primary lung adenocarcinoma: Two case reports.

The characteristic radiological signs of primary lung adenocarcinoma include notching, lobulation, spicular formation, pleural indentation and a bronchus leading to the nodule (bronchus sign). However, metastatic tumors rarely display such characteristics. We herein present two cases of breast cancer with sole metastatic pulmonary tumors recurring ~20 years after surgery for breast cancer. These patients exhibited radiographic signs specific to primary lung adenocarcinoma. Pulmonary metastatic nodular lesions occur through hematogenous spread; therefore, obtaining pathological specimens by transbronchial biopsy may be challenging. In our patients, however, obtaining pathological specimens by transbronchial biopsy was feasible and it ultimately confirmed the diagnosis of lung metastasis from previously treated breast cancer. To the best of our knowledge, no similar cases are reported in the English medical literature. Therefore, metastatic breast cancer may exhibit the characteristic radiological signs of pulmonary lung adenocarcinoma and, although rare, pulmonary metastasis from breast cancer should be considered even in the presence of irregularly shaped pulmonary nodule(s) following long-term disease-free survival.

Arginase-1 and HepPar-1 expression in fine-needle aspiration specimens of primary lung adenocarcinoma.

INTRODUCTION: Arginase-1 is a novel immunohistochemical (IHC) marker for hepatocellular differentiation. The purpose of this study was to evaluate the expression of Arginase-1 and HepPar-1 in lung adenocarcinoma to assess the potential value of these markers for diagnosing metastatic lung tumors, especially to the liver in fine-needle aspiration specimens. MATERIALS AND METHODS: Forty-four cytology specimens of lung adenocarcinoma, obtained by endobronchial ultrasound-guided fine-needle aspiration were retrospectively reviewed. IHC stains for Arginase-1 and HepPar-1 were performed on formalin-fixed paraffin-embedded cell blocks. Tissue from confirmed hepatocellular carcinoma was used as the positive control. TTF-1 IHC stain was performed in all cases. RESULTS: All 44 lung adenocarcinoma cases (100%) were negative for Arginase-1, whereas HepPar-1 expression was detected in 3 (7%) of lung adenocarcinomas and negative in 41 (93%). The 3 HepPar-1-positive lung adenocarcinoma cases demonstrated positive TTF-1 IHC stain performed on the same cell block. Although both Arginase-1 and HepPar-1 are useful diagnostic IHC markers to differentiate metastatic lung adenocarcinoma from hepatocellular carcinoma, Arginase-1 IHC stain shows better specificity than HepPar-1 does (Arginase-1 specificity 100% and HepPar-1 specificity 93%). CONCLUSIONS: Arginase-1 IHC can be used in combination with other markers in the workup of metastatic lung adenocarcinoma, especially to the liver.

Warranting investigation of primary lung adenocarcinoma in patients with an extrapulmonary malignancy and lung nodules due to high frequency.

OBJECTIVES: To distinguish primary lung adenocarcinoma (PLA) from metastatic adenocarcinoma/malignancy to optimize therapy. METHODS: We investigated the utility of thyroid transcription factor 1 (TTF-1) and napsin A in distinguishing PLA from metastatic adenocarcinoma/malignancy and assessed the frequency of PLA in patients with extrapulmonary malignancy/adenocarcinoma (PLA-EPM/EPA). RESULTS: TTF-1 and napsin A identified PLA in PLA-EPM/ EPA with a sensitivity of 89.4% and 93.3% and a specificity of 93.9% and 94.7%, respectively. PLA was confirmedin 47.4% of PLA-EPM and 40.2% of PLA-EPA. Overall, 38.5% of patients with PLA had EPM. The common organs for PLA-EPA were breast (35.8%), colon (13.2%), and others, whereas the common organs resulting in pulmonary metastasis were the colon (32.8%), breast (28.1%), and others. A patient with a smoking history and without EPM had a higher chance of having PLA. Multiple nodules are not a reliable indication of metastatic adenocarcinoma. CONCLUSIONS: Our results firmly support the role of TTF-1 and napsin A in identifying PLA-EPM/EPA. We reason that all new lung nodules in patients with a history of EPM should be screened using these techniques due to the high frequency of PLA-EPM, which will affect treatment and prognosis of patients with EPM/EPA.