Diagnosis Of Primary Lung Adenocarcinoma Research Articles

Immunohistochemistry comparison of Napsin A and CK7 expression in primary lung adenocarcinoma

Background: Lung cancer is the most common cancer worldwide and the leading cause of cancer-related death. Lung carcinomas are broadly divided into small cell carcinoma and non-small cell lung carcinoma (NSCLC). Non-small cell lung cancer accounts for 80% of lung cancers and lung adenocarcinoma is one of the main types of NSCLC. Here we studied the significance of the commonly used lung adenocarcinoma diagnostic markers, including TTF-1, Napsin A and CK7, in the diagnosis of lung adenocarcinoma using immunohistochemical (IHC) analysis.Aim: To evaluate and compare the significance of IHC markers, CK 7 and Napsin A in diagnosis of lung adenocarcinoma as far as specificity and reliability are concerned.Material and Methods: This study was conducted over a period of 5 years, from 2018 to 2022 which included all cases diagnosed as lung carcinoma on tissue biopsies and later subjected for IHC using relevant markers like CK7, TTF-1, Napsin-A, CK5/6, p63, Synaptophysin and Chromogranin A. 47 cases of lung adenocarcinoma were selected from the retrospective database of lung cancer.Results: Among the 47 cases of lung adenocarcinoma. IHC was done on 41 cases (87.23%). Immunocytochemistry (ICC) was done on 6 cases (12.8%). Lung adenocarcinoma IHC markers study shows CK 7 positive and Napsin-A negative in 21 cases (51.2%). CK 7 negative and Napsin-A positive only in 1 case (2.4%). Both are positive in 16 cases (39.0%) and both were negative in 3 cases (7.3%). ICC was studied in total 6 cases which show CK 7 positivity in 4 cases (66.7%). Only 2 case of ICC show Napsin-A positivity (33.3%).Conclusion: As far as IHC is concerned CK 7 is more reliable and specific than Napsin-A in diagnosis of primary lung adenocarcinoma.

Mass-forming extramedullary haematopoiesis of the liver mimicking metastases of lung cancer at initial presentation – a case report and literature review

Extramedullary haematopoiesis (EMH) of the liver is usually a diffuse process. However, it occasionally forms focal masses with non-specific imaging features, which may mimic metastatic deposits, especially in patients with active or previous malignancy.1 We report the case of a 79-year-old male ex-smoker who presented with shortness of breath and weight loss. Computed tomography showed two spiculated lung lesions and two hypoattenuating liver lesions, which were interpreted as primary lung tumours with liver metastases. Fine-needle aspiration cytology of the larger liver lesion unexpectedly revealed EMH without evidence of malignancy. Subsequent biopsies of the lung lesions established the diagnosis of primary lung adenocarcinoma. Disease stage was revised down because of the findings in the liver. There are a few previous case reports of mass forming EMH in the liver and at other sites mimicking metastases. It is postulated that EMH may develop in patients with solid malignancy, including lung cancer, due to secretion of haematopoietic growth factors by the primary tumour.2 Pathologists should be aware of this rare but recognised presentation of EMH.

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

BackgroundIt 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.MethodsIn 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.ResultsWe 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.ConclusionEvaluation of napsin A levels in ELF may be useful for distinguishing primary lung adenocarcinoma.

Colonic Metastasis with Anemia Leading to a Diagnosis of Primary Lung Adenocarcinoma.

Metastasis occurs with 50% of lung carcinomas, most commonly to lymph nodes, adrenal glands, liver, bone, and brain. It is extremely rare for lung cancer to present with symptoms of a gastrointestinal metastasis and even more so pertaining to the colon. To the best of our knowledge, only 12 such cases have been reported in the literature. We describe a case of a 71-year-old female presenting with refractory iron deficiency anemia that was found to have a lesion in the transverse colon. Pathology revealed adenocarcinoma of the lung and a subsequent lung lesion was discovered in a retrograde fashion.

Interobserver agreement among histological patterns and diagnosis in lung adenocarcinomas

The aim of this study was to investigate the interobserver agreement in determination of the dominant histological pattern and the final diagnosis in lung adenocarcinomas. A total of 12 patients with a diagnosis of primary lung adenocarcinoma were included in the study. Twelve pathologists from eight study centers were asked first to determine the dominant histological pattern in these cases and then to decide whether the final diagnosis was in situ, minimally invasive or invasive adenocarcinoma. The kappa value for the agreement in determining the dominant pattern among the pathologists was 0.36 (p < 0.001), with the values for the lepidic, acinar, papillary, solid, micropapillary patterns and mucinous character of adenocarcinoma being 0.34, 0.28, 0.30, 0.80, 0.16 and 0.38 respectively (p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001, p < 0.001). None of the cases was diagnosed as in situ adenocarcinoma. On the other hand, the kappa value for the agreement in differentiating minimally invasive from invasive adenocarcinoma among reviewers was 0.17 (p < 0.001). The agreement among pathologists in determining the subtype of lung adenocarcinomas that depends on the identification of the dominant pattern was at intermediate level. In addition, the agreement in deciding whether the case is minimally invasive or invasive, was at low level. The criteria defining the histological patterns should be clarified and described in more detail. Educational activities and larger multicenter studies might be helpful in improving the agreement and standardization.

Value of napsin A and thyroid transcription factor-1 in the identification of primary lung adenocarcinoma

Napsin A is a newly discovered functional aspartic proteinase that is expressed in normal lung parenchyma in type II pneumocytes and is thought to be associated with primary lung adenocarcinoma. Thyroid transcription factor-1 (TTF-1) is a widely used relatively restricted marker for lung adenocarcinoma. The present study aimed to compare the usefulness of napsin A with TTF-1 for the identification of primary lung adenocarcinoma. Immunohistochemical expression of napsin A and TTF-1 was analyzed in 351 lung cancer tissues, including 27 metastases. Napsin A was expressed in 180 of 212 (84.9%) primary lung adenocarcinomas, while no expression was noted in all 27 metastatic lung cancer specimens, including 19 metastatic adenocarcinomas. In contrast, TTF-1 expression was not only noted in 179 of 212 (84.4%) primary lung adenocarcinomas, but also in 12 of 18 (66.7%) small-cell carcinomas and some of the squamous carcinomas, as well as in one metastatic adenocarcinoma from the thyroid. The sensitivity and specificity of napsin A for primary lung adenocarcinoma (84.9 and 93.8%, respectively) were higher than the sensitivity and specificity of TTF-1 (84.4 and 83.9%, respectively). By combining napsin A and TTF-1, sensitivity increased to 91.0%. Furthermore, the sensitivity and specificity expression was associated with gender, smoking history, performance status, pathological type, primary tumor size and nodal metastasis. Therefore, napsin A is a useful novel marker in the differential diagnosis of primary lung adenocarcinoma.

Alkaline phosphatase, cytokeratin 7, cytokeratin 8 in the diagnosis of primary lung adenocarcinoma from 148 pleura fluids specimens.

Adenocarcinomas are the most common cause of malignancy in pleura fluids. Usual primary sites include the lung, breast, gastrointestinal tract, and genitourinary tracts. Predicting the site of origin of an adenocarcinoma can be difficult due to overlapping morphologic characteristics. We investigated the use of alkaline phosphatase (AP), Cytokeratin7 (CK7) Cytokeratin8 (CK8) to distinguish adenocarcinomas of lung in 148 body cavity fluid samples. Overall results for primary lung adenocarcinomas, demonstrated CK8 reactivity in 106 (72%) of 148 cases. 95 primary lung carcinoma samples (65%) were positive for CK7. AP was expressed in 81% of primary lung adenocarcinomas. Positive immunoreactivity for AP was characterized by a red, diffusely apical cytoplasmic staining in tumor cells that ocurred singly or in groups. There was a significant difference between AP, CK 7 and CK 8 expressions in primary lung adenocarcinomas (P=0.02; Chi-squared test). The sensitivity of AP, CK8, CK7 as a marker for primary lung adenocarcinomas were 82%, 72%, 64%, respectively. Thus the AP positive staining largely confirmed the cytologic diagnosis of lung adenocarcinoma.

Alkaline phosphatase, cytokeratin 7, cytokeratin 8 in the diagnosis of primary lung adenocarcinoma from 148 pleura fluids specimens.

Alkaline phosphatase, cytokeratin 7, cytokeratin 8 in the diagnosis of primary lung adenocarcinoma from 148 pleura fluids specimens.

Evidence-Based Criteria to Help Distinguish Metastatic Breast Cancer From Primary Lung Adenocarcinoma on Thoracic Frozen Section

The distinction between primary lung adenocarcinoma and metastatic breast carcinoma in patients with a history of breast cancer is difficult by frozen section (FS) analysis. Our experience with 129 FSs from 121 patients with a pulmonary nodule and a history of breast cancer was reviewed. The pretest odds ratio of primary pulmonary carcinoma/metastatic breast carcinoma was 2.6. The incidence of 12 histopathologic features was assessed in a "training set" composed of 20 FSs, 10 with primary lung adenocarcinoma and 10 with metastatic breast cancer. A differential diagnosis model composed of significant pathologic features that favor the diagnosis of primary lung adenocarcinoma (acini, lepidic growth, nuclear pseudoinclusions, and scar) or metastatic breast carcinoma (comedonecrosis, solid nests, trabecular architecture, and cribriform growth) was identified. The external validity of this model was successfully tested by challenging 19 pathologists and trainees with a test set of 20 unknown FSs, supporting the clinical applicability of the diagnostic model.

A rare tumoral combination, synchronous lung adenocarcinoma and mantle cell lymphoma of the pleura

BackgroundCoexistence of adenocarcinoma and mantle cell lymphoma in the same or different anatomical sites is extremely rare. We present a case of incidental discovery of primary lung adenocarcinoma and mantle cell lymphoma involving the pleura, during an axillary thoracotomy performed for a benign condition.Case presentationA 73-year old male underwent bullectomy and apical pleurectomy for persistent pneumothorax. A bulla of the lung apex was resected en bloc with a scar-like lesion of the lung, which was located in proximity with the bulla origin, by a wide wedge resection. Histologic examination of the stripped-off parietal pleura and of the bullectomy specimen revealed the synchronous occurrence of two distinct neoplasms, a lymphoma infiltrating the pleura and a primary, early lung adenocarcinoma. Immunohistochemical and fluorescence in situ hybridization assays were performed. The morphologic, immunophenotypic and genetic findings supported the diagnosis of primary lung adenocarcinoma (papillary subtype) coexisting with a non-Hodgkin, B-cell lineage, mantle cell lymphoma involving both, visceral and parietal pleura and without mediastinal lymph node involvement. The neoplastic lymphoid cells showed the characteristic immunophenotype of mantle cell lymphoma and the translocation t(11;14). The patient received 6 cycles of chemotherapy, while pulmonary function tests precluded further pulmonary parenchyma resection (lobectomy) for his adenocarcinoma. The patient is alive and without clinical and radiological findings of local recurrence or distant relapse from both tumors 14 months later.ConclusionThis is the first reported case of a rare tumoral combination involving simultaneously lung and pleura, emphasizing at the incidental discovery of the two coexisting neoplasms during a procedure performed for a benign condition. Any tissue specimen resected during operations performed for non-tumoral conditions should be routinely sent for pathologic examination.

舌下神経麻ひを契機に発見された肺腺癌の１例

A case of lung adenocarcinoma with incipient symptoms of paralysis of the hypoglossal nerve is reported, with an emphasis on clinical features.A 52-year-old woman presented with disturbance of tongue movement at the Department of Oral and Maxillofacial Surgery, Komaki City Hospital. The tongue deviated towards the right on protrusion. The clinical diagnosis was paralysis of the hypoglossal nerve with suspicion of a lesion in the base of the skull. On CT and MRI of the head, a bone defect with a tumor was observed in the base of the skull. Bone scintigraphy revealed several hot spots in the thoracic vertebrae. Multiple bone metastases were suspected. A thoracoabdominal CT scan and chest roentgenogram showed a mass in the left lower lobe. The patient was finally given a diagnosis of primary lung adenocarcinoma and multiple bone metastases. Respecting the patient's will, we performed palliative therapy. The lung adenocarcinoma with metastases to the brain and bone has recently grown. The number of patients with cranial nerve disorders caused by metastatic lung adenocarcinomas, is considered to be increasing. Therefore, oral and maxillofacial surgeons should closely observe patients, taking into account important general diseases related to oral symptoms.

Aspartic proteinase napsin is a useful marker for diagnosis of primary lung adenocarcinoma.

Napsin A is an aspartic proteinase expressed in lung and kidney. We have reported that napsin A is expressed in type II pneumocytes and in adenocarcinomas of the lung. The expression of napsin was examined in 118 lung tissues including 16 metastases by in situ hybridisation. Napsin was expressed in the tumour cell compartment in 33 of 39 adenocarcinomas (84.6%), in two of 11 large cell carcinomas and in one lung metastasis of a renal cell carcinoma. Expression of napsin was found to be associated with a high degree of differentiation in adenocarcinoma. Immunohistochemistry was performed for three proteins currently used as markers for lung adenocarcinoma : surfactant protein-A, surfactant protein-B and thyroid transcription factor-1. Thyroid transcription factor-1 showed the same sensitivity (84.6%) as napsin for adenocarcinoma, whereas surfactant protein-A and surfactant protein-B showed lower sensitivities. Among these markers, napsin showed the highest specificity (94.3%) for adenocarcinoma in nonsmall cell lung carcinoma. We conclude that napsin is a promising marker for the diagnosis of primary lung adenocarcinoma.

Napsin A, a member of the aspartic protease family, is abundantly expressed in normal lung and kidney tissue and is expressed in lung adenocarcinomas

A pair of 35 kDa polypeptides (TAO1/TAO2) are expressed in more than 90% of all primary lung adenocarcinomas but not in other major malignancies. Mass spectrometry of tryptic peptides showed that TAO1/TAO2 is identical to napsin A, a recently described member of the aspartic proteinase family. The site of processing of pronapsin A to the mature form was located. Napsin expression was detected in human lung adenocarcinoma tumors, compatible with the marker nature of TAO1/TAO2 in the diagnosis of primary lung adenocarcinoma. This is important since identification of markers which can distinguish primary lung adenocarcinomas from distant metastases is desirable. Northern blot analysis showed expression of napsin also in normal lung and kidney tissue, and in situ hybridization showed expression in type II alveolar cells of the lung. This protease is concluded to have a specific functional role in the normal alveolar epithelium and is a candidate protease for the proteolytic processing of surfactant precursors.

Detection of Surfactant Protein-A Gene Transcript in the Cells from Pleural Effusion for the Diagnosis of Lung Adenocarcinoma

PURPOSE: To determine whether detecting surfactant protein-A (SP-A) gene transcript in the cells from pleural effusion is useful for the diagnosis of lung adenocarcinoma. PATIENTS AND METHODS: We performed reverse transcription polymerase chain reaction (RT-PCR) analysis of SP-A gene transcript in the cells of pleural effusion from 42 consecutive patients with pleural effusion, including 7 patients with primary lung adenocarcinoma before their treatments. RESULTS: A cDNA segment of SP-A was amplified from the pleural fluid cells of all patients with primary lung adenocarcinoma, indicating the presence of the SP-A gene transcript. None of the remaining patients, including those with metastatic lung adenocarcinoma, showed positive for the SP-A gene transcript. CONCLUSION: These findings indicate that RT-PCR analysis of the SP-A gene transcript in pleural effusion is useful for the diagnosis of primary lung adenocarcinoma.