Classification Of Lung Carcinomas Research Articles

Cytohistopathological Association and the Use of a Dual Immunohistochemical Regimen in the Diagnosis of Lung Malignancies: A Cross-sectional Study

Introduction: Lung cancer is a highly aggressive malignancy that causes significant morbidity and mortality. The incidence of lung cancer has been increasing in the past few decades. Cytology aids in the initial evaluation and diagnosis of patients with lung cancer. Currently, the classification of lung carcinoma has expanded beyond small cell lung carcinoma and Non-Small Cell Lung Carcinoma (NSCLC). Precise subtyping of poorly differentiated NSCLC into adenocarcinoma and Squamous Cell Carcinoma (SCC) has a direct impact on patient management and prognosis. The morphologic diagnosis forms the basis and is further supplemented by a panel of immunohistochemical markers. Immunohistochemistry (IHC) is important in cases with poorly differentiated morphology or partial sampling. The IHC panel used includes Tumour Protein p63 (p63) and Thyroid Transcription Factor (TTF1) for subtyping lung cancer. Aim: The present study was conducted with the aim of studying the age and gender distribution, risk factors, cytohistopathological association, and formulating an effective IHC panel for the precise yet effective subtyping of poorly differentiated lung malignancies. Materials and Methods: This cross-sectional study included cases retrieved from the Archives of Pathology Department, SRM Medical College and Research Centre, Chennai, Tamil Nadu, India, between July 2012 and July 2016. The cases included had a diagnosis of lung malignancy (confirmed by cytology/biopsy) or were suspected of having malignancy based on clinical/radiological findings. The study period was from July 2015 to August 2016. The cytology and biopsy slides were reviewed, and the malignancy was classified according to the World Health Organisation (WHO) classification of lung malignancies (2021). IHC was performed on the cases using the markers p63 and TTF1 as a dual regimen. Diagnosis and subtyping of tumours were done based on histomorphology, and the tumours were reclassified based on IHC findings. The data were statistically analysed using SPSS software version 25 and the ROC curve. Results: The mean age of the patients was 60.9 years. The study included a total of 50 cases of lung carcinoma, with an average age of 60.9 years (ranging from 30 to 88 years). Among the cases, 35 (70%) had a positive smoking history. A concordant cytohistopathological association was observed in 26 (52%) of cases. Adenocarcinoma was the predominant subtype, accounting for 21 (42%) of cases. Tumour cells in adenocarcinoma showed positive staining for TTF-1, with the marker exhibiting 100% sensitivity and 83% specificity. In SCC, tumour cells were positive for p63, with the marker demonstrating 92% sensitivity and 82% specificity. Both markers showed effective sensitivity and specificity when used as a dual regimen. Conclusion: Although lung cancer is typically diagnosed in the elderly population, there has been an increase in cases among younger individuals due to urbanisation. Smoking remains an important risk factor for lung malignancy. Exfoliative cytology alone is not sufficient for the diagnosis of lung malignancies and should be supplemented with biopsy for more accurate results. Adenocarcinoma was found to be the most common subtype in our study. The IHC panel of p63 and TTF-1 proved to be an effective regimen for classifying poorly differentiated lung carcinomas.

Significance of Immunohistochemistry Testing in the Diagnosis and Subtyping of Lung Carcinomas- A Retrospective Study from a Tertiary Care Centre in Southern Rajasthan

Introduction: In the present era, the classification of lung carcinoma is not confined to Small Cell Lung Carcinoma (SCLC) and Non Small Cell Lung Carcinoma (NSCLC). Precise subtyping of lung carcinoma has a direct impact on patient management and prognosis. Further molecular study helps in identifying adenocarcinoma receptors, such as Epidermal Growth Factor Receptor (EGFR) and Anaplastic Lymphoma Kinase (ALK), which are useful in targeted therapy. Aim: To assess the role of Immunohistochemistry (IHC) in accurate diagnosis and subtyping of lung carcinoma and to analyse the prevalence of EGFR mutations and ALK rearrangement in lung adenocarcinoma. Materials and Methods: A retrospective hospital-based, observational study was conducted at the Department of Pathology of American International Institute of Medical Sciences, Udaipur, Rajasthan from January 2020 to August 2021. Total of 105 cases of guided core needle biopsies from lung and bronchoscopic biopsies were included. IHC markers were applied based on histopathological diagnosis from a panel of p63, Cytokeratin 7 (CK7), AE1/AE3, Thyroid Transcription Factor (TTF1), Napsin A, p40, synaptophysin, chromogranin, CD56 and Ki67. Adenocarcinoma cases were further analysed for EGFR mutations and ALK rearrangements. Data was tabulated and analysed statistically using Microsoft Excel to determine the percentage frequency distribution of cases. Results: Among 105, there were 88 males and 17 females and the mean age of the population was 60.57 years. The most prevalent subtype of lung malignancy was squamous cell carcinoma (44.7%) followed by adenocarcinoma (29.5%). The diagnostic accuracy of squamous cell carcinomas and adenocarcinomas on morphology was 93.1% and 84.6%, respectively and for small cell carcinoma it was 100%. Amongst 28 cases of adenocarcinoma, EGFR mutation was found in 46.42% cases whereas ALK mutation was found only in 21.42% cases. Conclusion: The study highlights the importance of IHC, and a substantial prevalence of EGFR mutations was found in patients with lung carcinoma.

VCNet: Hybrid Deep Learning Model for Detection and Classification of Lung Carcinoma Using Chest Radiographs.

Detection of malignant lung nodules from Computed Tomography (CT) images is a significant task for radiologists. But, it is time-consuming in nature. Despite numerous breakthroughs in studies on the application of deep learning models for the identification of lung cancer, researchers and doctors still face challenges when trying to deploy the model in clinical settings to achieve improved accuracy and sensitivity on huge datasets. In most situations, deep convolutional neural networks are used for detecting the region of the main nodule of the lung exclusive of considering the neighboring tissues of the nodule. Although the accuracy achieved through CNN is good enough but this models performance degrades when there are variations in image characteristics like: rotation, tiling, and other abnormal image orientations. CNN does not store relative spatial relationships among features in scanned images. As CT scans have high spatial resolution and are sensitive to misalignments during the scanning process, there is a requirement of a technique which helps in considering spatial information of image features also. In this paper, a hybrid model named VCNet is proposed by combining the features of VGG-16 and capsule network (CapsNet). VGG-16 model is used for object recognition and classification. CapsNet is used to address the shortcomings of convolutional neural networks for image rotation, tiling, and other abnormal image orientations. The performance of VCNeT is verified on the Lung Image Database Consortium (LIDC) image collection dataset. It achieves higher testing accuracy of 99.49% which is significantly better than MobileNet, Xception, and VGG-16 that has achieved an accuracy of 98, 97.97, and 96.95%, respectively. Therefore, the proposed hybrid VCNet framework can be used for the clinical purpose for nodule detection in lung carcinoma detection.

Prognostic impact of tumor-infiltrating lymphocytes and neutrophils in resected non-small cell lung carcinoma

The prognostic impact of tumor-infiltrating lymphocytes (TILs) has been determined in non-small cell lung carcinoma; however, there is no standardized method for counting TILs. In this report, we applied the method proposed by the International Immuno-Oncology Biomarkers Working Group for the assessment of TILs to count the number of tumor-infiltrating neutrophils (TINs). We then analyzed the association between TIL counts, TIN counts, and clinicopathological factors in lung cancer. We retrospectively analyzed a series of 1191 Japanese patients with resected lung adenocarcinoma and squamous cell carcinoma, which were restaged according to the eighth edition of the TNM staging system. Tumors were classified according to the 2015 WHO classification of lung carcinoma. Recurrence-free probability (RFP) and overall survival (OS) were analyzed using the log-rank test and Cox proportional hazard model. Using multivariate analysis for patient outcome in patients with adenocarcinoma, high TIN counts were an independent prognostic factor for worse RFP (hazard ratio [HR]: 1.94, p<0.001) and worse OS (hazard ratio [HR]: 1.75, p=0.006). On the other hand, TIL counts were not related to patient outcome. We have demonstrated that high TINs are unfavorable prognostic markers for resected lung adenocarcinoma. In resected lung squamous cell carcinoma, TIL and TIN counts were not related to patient prognosis. It has been suggested that the immune response to cancer cells may differ depending on the histological type. An understanding of how neutrophils are programmed to perform protumor activities is necessary for the future design of targeted immunotherapies.

Molecular target therapeutics of EGF-TKI and downstream signaling pathways in non-small cell lung cancers.

Lung carcinoma (LC) is the third most common cancer diagnosis and accounted for the most cancer-related mortality worldwide in 2018. Based on the type of cells from which it originates, LC is commonly classified into non-small cell lung cancers (NSCLC) and small cell lung cancers (SCLC). NSCLC account for the majority of LC and can be further categories into adenocarcinoma, large cell carcinoma, and squamous cell carcinoma. Accurate classification of LC is critical for its adequate treatment and therapeutic outcome. Since NSCLC express more epidermal growth factor receptor (EGFR) with activation mutations, targeted therapy EGFR-tyrosine kinase inhibitors (TKIs) have been considered as primary option of NSCLC patients with activation EGFR mutation. In this review, we present the genetic alterations, reported mutations in EGFR, and TKIs treatment in NSCLC patients with an emphasis on the downstream signaling pathways in NSCLC progression. Among the signaling pathways identified, mitogen activation protein kinase (MAPK), known also as extracellular signal-regulated protein kinase (Erk) pathway, is the most investigated among the related pathways. EGFR activation leads to the autophosphorylation of its kinase domain and subsequent activation of Ras, phosphorylation of Raf and MEK1/2, and the activation of ERK1/2. Phosphatidylinositol 3-kinase (PI3K)/Akt is another signal pathway that regulates cell cycle and has been linked to NSCLC progression. Currently, three generations of EGFR TKIs have been developed as a first-line treatment of NSCLC patients with EGFR activation and mutation in which these treatment options will be further discussed in this review. The Supplementary Appendix for this article is available at http://links.lww.com/JCMA/A138.

The Significant Impact of Immunohistochemistry in the Classification of Lung Carcinoma on Small Biopsies

Background : There are limitations of histomorphology in the appropriate categorization of lung carcinoma where immunohistochemistry can confirm the morphological diagnosis and may add value in the poorly differentiated and undifferentiated tumors. The aim of the study was to assess the role of immunohistochemistry in classifying lung carcinoma on small biopsy samples. Methods and Material: A retrospective hospital based, observational study was conducted on cases of lung carcinoma diagnosed by core needle or bronchoscopic biopsies over a 3- year period. After evaluation of clinical findings and H&amp;E sections, all biopsies were evaluated by immunohistochemical staining. The immunohistochemistry panel included cytokeratin cocktail, CK7, CK 20, TTF1, Napsin A, CK5/6, p40, synaptophysin, chromogranin, CD 56. Result: Out of 78 cases, the mean age was 58 +/- 11 years. Most prevalent malignancy type was adenocarcinoma (30, 38.1%). Adenocarcinoma cases were positive for CK7 (25/26, 96%), Napsin A (24/26, 92%), TTF1 (15/30, 50%) and negative for CK 20. Squamous cell carcinoma cases showed positivity for p40(18/22, 82%) and CK 5/6 (17/22.71%).Small cell carcinoma showed positivity for neuroendocrine markers synaptophysin (5/7,71%) and chromogranin(4/7, 57%) and CD 56 (6/7cases (85%).88% of small cell carcinomas,75% of adenocarcinomas and 72 % of squamous cell carcinomas were accurately diagnosed by morphology. Morphologic prediction was poor in the NSCC NOS group (0%) and poorly differentiated carcinomas (64%), which were finally, diagnosed by immunohistochemistry.In the morphologically diagnosed cases, immunohistochemistry confirmed the diagnosis. Conclusion: Thus, morphology added with immunohisto chemistry provides a crisp diagnosis thereby improving therapeutic efficacy

Cytology Reporting System for Lung Cancer from the Japan Lung Cancer Society and Japanese Society of Clinical Cytology: An Interobserver Reproducibility Study and Risk of Malignancy Evaluation on Cytology Specimens

Introduction: The classification of lung carcinoma is based on small biopsies and/or cytology in 80% of patients with non-small cell carcinoma. However, there is no widely accepted classification system for respiratory cytology. The Japan Lung Cancer Society (JLCS) and Japanese Society of Clinical Cytology (JSCC) have proposed a new four-tiered cytology reporting system for lung carcinoma with the following categories: (1) “negative for malignancy,” (2) “atypical cells,” (3) “suspicious for malignancy,” and (4) “malignancy.” Objective: The aim of this work was to perform an interobserver reproducibility study to confirm the utility of the four-tiered reporting system on respiratory cytological samples. Methods: We analyzed 90 cytological samples obtained with bronchoscopy. Seven observers classified these cases into each category by reviewing one Papanicolaou-stained slide per case according to the three-, four-, and five-tiered reporting systems. Results: The interobserver agreement was fair in the three- (κ = 0.50), four- (κ = 0.45), and five-tiered (κ = 0.45) reporting systems. However, the four-tiered reporting system provided more precise information than the three-tiered reporting system in patient management. The risk of malignancy in the four-tiered reporting system was also stratified well: 19.3% for “negative for malignancy,” 45.6% for “atypical cells,” 74.7% for “suspicious for malignancy,” and 88.1% for “malignancy.” Conclusions: The reporting system proposed by the JLCS and JSCC was designed to enhance the communication between clinicians and pathologists and among different institutions. It is simple and applicable to cytological diagnosis of any respiratory diseases. We propose establishing an international classification for respiratory cytology, harmonizing the reporting systems proposed by different countries.

Automatic Detection and Classification of Lung Carcinoma using Image Processing Techniques in Lab VIEW

Lung cancer screening saves human lives by detecting cancer earlier, when it may be treated more successfully. The most familiar methods for the diagnosis of lung cancer includes bronchoscope guided BronchoAlveolar Lavage (BAL) samples and the CT scan. In this paper, we propose a technique to automatically analyze the microscopic images of BAL samples and CT scan images in the same platform. This method will help in reducing the manual intervention and provides many useful parameters such as location, size and number of clusters present in the images. We have processed the images using the specialized software in LabVIEW, NI vision Assistance. The detection is done with the microscopic images of BAL and the stages are classified with the analysis of CT scan images. For this, separate algorithms have been developed using Vision Assistant and the common user interface has been designed using LabVIEW.

Current classification of lung carcinoma. Histological, immunophenotypic, molecular and clinical considerations

In recent years, the rapid technological development and the better knowledge of genetic and molecular aspects in medicine have allowed a better approach to understand, diagnose and treat various oncological diseases. Regarding lung carcinoma, there has been a remarkable evolution from the first classifications, which were purely morphological, to the last one issued in 2015. This last classification includes histological, immunophenotypic, molecular genetics, clinical and radiological information, which allows a better evaluation and therapeutic management of these patients. In the present article, the first classifications of lung carcinoma to the last one are reviewed, and the most relevant changes and the importance of the molecular genetics findings are examined for a better clinical and therapeutic approach.

Best Practices Recommendations for Diagnostic Immunohistochemistry in Lung Cancer

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.

Cribriform Subtype is an Independent Predictor of Recurrence and Survival After Adjustment for the Eighth Edition of TNM Staging System in Patients With Resected Lung Adenocarcinoma

IntroductionAt present, cribriform arrangements are regarded as a pattern of acinar adenocarcinoma. However, recent studies have indicated that clinical outcomes for lung adenocarcinoma patients with cribriform subtype are unfavorable. To validate the prognostic significance of the cribriform pattern, we analyzed a series of 735 Japanese patients with resected lung adenocarcinoma, which was restaged according to the eighth edition of the TNM staging system. MethodsTumors were classified in accordance with the 2015 WHO classification of lung carcinomas. The cribriform pattern was defined by invasive back-to-back fused tumor glands with poorly formed glandular spaces or invasive tumor nests of tumors cells that produce glandular lumina. Recurrence-free probability (RFP) and overall survival (OS) was analyzed using the log-rank test and the Cox proportional hazards model. ResultsAfter the addition of the cribriform pattern, 54 of 90 acinar-predominant tumors were reclassified as cribriform subtype. Five-year RFP for patients with the cribriform subtype (51%) was lower than it was for patients with acinar and papillary subtype (81% and 80%, respectively) but was comparable to that for patients with solid subtype (48%). Five-year OS for patients with the cribriform subtype (49%) was lower than it was for patients with acinar and papillary subtype (90% and 81%, respectively). On multivariate analysis adjusted for the eighth edition of the TNM staging system, the cribriform subtype was an independent prognostic factor of a worse RFP and OS. ConclusionsWe have validated that the cribriform subtype is an independent factor of poor prognosis in patients with resected lung adenocarcinoma.

Uncommon Types of Lung Carcinoma With Mixed Histology: Sarcomatoid Carcinoma, Adenosquamous Carcinoma, and Mucoepidermoid Carcinoma.

- Lung tumors are histologically heterogeneous, but classification of lung carcinoma has prognostic impact and increasingly, specific molecular correlates. - To update the gross, microscopic, and molecular pathology of unusual lung carcinomas to assure accurate classification. In entities with mixed histology, the recognition of specific features or rare patterns is critical to diagnosis. These diagnoses can identify tumors with aggressive clinical behavior, and diagnostic pitfalls can therefore result in underdiagnosis of these already rare entities. Incorrect classification of more indolent tumors into the more aggressive categories can also occur. In the area of molecular pathology, these unusual tumors have a specific spectrum of molecular alterations. - PubMed searches for lung and sarcomatoid carcinoma, pleomorphic carcinoma, blastoma, carcinosarcoma, and adenosquamous and mucoepidermoid carcinoma were undertaken and this information was integrated with clinical experience of the author. - These uncommon carcinomas have specific clinicopathologic features, and attention to their gross and microscopic pathology leads to classification with important associated molecular findings.

The diagnostic value of TTF1, P63, HMWK [34βE12], CK7, and CD56 immunostaining in classification of lung carcinoma

The histologic distinction of small cell from non-small cell lung carcinoma and correct identification of all subtypes of lung carcinoma are very important in treatment management. The main method for histologic classification of lung tumors is based on morphology. However, in small bronchoscopic biopsies in particular, distinction is very difficult upon morphology alone. The current study aimed at evaluating the utility of a panel of antibodies, consisting of thyroid transcription factor (TTF-1), P63, high molecular weight keratin [HMWK (34βE12)], cytokeratin (CK7), and cluster of differentiation (CD56) for accurate distinction of bronchogenic carcinomas. Bronchoscopic biopsies of 60 lung carcinoma cases including 20 small cell carcinomas, 20 adenocarcinomas, and 20 squamous cell carcinomas (SCCs) with typical morphologic features were selected. All these cases were immunohistochemically stained for TTF-1, P63, HMWK (34βE12), CK7, and CD56. All immunostained slides were scored as either positive or negative. The mean age of the patients was 60 years; ranged from 35 to 81. Sixteen patients were female and 44 were male. All adenocarcinomas were positive for CK7 and most of them (18/20; 90%) were positive for TTF-1. Most of small cell lung carcinomas were positive for TTF-1 (17/20; 85%), and CD56 (18/20; 90%). All squamous cell carcinomas (SCCs) were negative for TTF-1, but most of them were positive for HMWK (34βE12) and P63. The obtained data showed that TTF-1, P63, CK7, CD56 and/or 34βE12 represent a useful panel of antibodies to identify lung carcinoma subtypes in small bronchoscopicbiopsies.

Clinicopathological and immunohistochemical profile of non-small cell lung carcinoma in a tertiary care medical centre in South India

Background:Lung cancer is a highly aggressive malignancy causing high morbidity and mortality. An increasing incidence of lung cancer has been observed in India. Currently, the classification of lung carcinoma has gone beyond small cell lung carcinoma and non-small cell lung carcinoma (NSCLC). Precise subtyping of poorly differentiated NSCLC into adenocarcinoma and squamous cell carcinoma has a direct impact on patient management and prognosis. With this background, many molecules are under study for developing targeted therapies. Epidermal growth factor receptor (EGFR) is one such biomarker considered to be useful in targeted therapy for adenocarcinoma.Objective:The aim of this study was to subtype poorly differentiated NSCLC based on the expression of thyroid transcription factor-1 (TTF-1) and p-63 and to evaluate EGFR expression in adenocarcinomas.Materials and Methods:A retrospective analysis of 84 cases of poorly differentiated carcinomas of the lung was performed. Paraffin sections were immunostained with TTF-1 and p-63 and the tumors were subtyped. EGFR expression was assessed in adenocarcinomas by immunohistochemistry.Results:Fifty-five percent of the NSCLC were adenocarcinoma, with a peak incidence between 61 and 70 years of age and a male predominance. EGFR was expressed in 89% of the adenocarcinomas.Conclusions:Poorly differentiated non-small cell carcinoma can be subtyped by immunohistochemical markers and hence has a direct impact on the current therapeutic strategies.

The Classification of Lung Carcinoma: Time to Change the Morphology-Based Approach?

Morphology still remains the cornerstone in lung cancer classification and always has been accompanying pathologists in their daily activity, even though several ancillary techniques have been incorporated over time to improve diagnostic, prognostic, and predictive capabilities in lung cancer. Currently, we are also faced with a global rethinking of lung cancer care, especially once novel therapy strategies have been made available on the basis of the diverse characteristics of tumors. Although morphology still remains a not easily replaceable tool for lung cancer classification, we are now challenged by the need of offering clinicians more detailed subtyping of non-small-cell lung cancer especially in event of limited diagnostic material, poorly differentiated tumors, or unresectable lesions. Close integration of improved morphology, immunohistochemistry, and molecular tests will be able to not only sharpen our diagnostic algorithms and prognostic and predictive potentialities but also get insights into several lung cancer biology issues, such as histogenesis and new classification schemes.

The Diagnostic Value of TTF-1, CK 5/6, and p63 Immunostaining in Classification of Lung Carcinomas

This study was aimed to evaluate the utility of a panel of antibodies, consisting of thyroid transcription factor-1 (TTF-1), p63, and cytokeratins (CK) 5/6 for distinguishing between small cell lung carcinoma (SCLC) and nonsmall cell lung carcinoma, as well as for identifying glandular or squamous differentiation in small tissues obtained by bronchoscopy. Bronchoscopic biopsies of 77 lung carcinoma cases with easily recognizable morphologic features were included in this study. All the cases were immunohistochemically stained for p63, CK5/6 [indicators of squamous cell carcinoma (SCC)] and TTF-1 [indicator of SCLC and adenocarcinoma (AC)]. Although, 28 SCLC displayed TTF-1 positive, p63 negative immunoprofile, most of the SCC (32/39) had the opposite immunoprofile. All of the 10 ACs were negative for p63 and most of them (8/10) were negative for CK5/6. p63 and CK 5/6 seem to be useful for differentiating AC and SCLC from SCC with 100% specificity and 82% sensitivity, 89% specificity and 79% sensitivity, respectively. It seems that to achieve histologic typing of lung cancer as accurate as possible, TTF-1 in combination with p63 and CK 5/6 might be useful components of immunohistochemical analysis of poorly differentiated lung carcinomas in biopsy tissues.

Diagnosis and typing of lung carcinomas by cytopathologic methods. A review of 108 cases

A correlative review was made of the type of cytology specimens (sputum, bronchial washing and bronchial brushing) together with the corresponding histopathologic specimens of 108 patients. One hundred patients had primary pulmonary carcinomas diagnosed histopathologically (84) or clinically (16); 5 had carcinomas metastatic to the lungs and 3 had apparently false-positive cytologic results for lung cancer. The correlative review was used to determine the diagnostic reliability of pulmonary cytopathologic techniques in the detection and classification of lung carcinomas (i.e., the sensitivity and accuracy). The overall sensitivities of sputum, bronchial washing and bronchial brushing cytology were 60%, 66% and 77%, respectively (p less than 0.05). Bronchial brushing had a higher sensitivity (80%) for peripheral and metastatic lesions than did sputum (37%) or bronchial washing (60%). The overall accuracies of sputum, bronchial washing and bronchial brushing cytology were 79%, 75% and 76%, respectively, which is not statistically different. Regardless of the sampling methods, cytologic typing of squamous-cell and small-cell carcinomas was highly accurate but was less satisfactory for the other types of lung carcinomas. In the 16 cases in which endoscopic biopsies were either not attempted or gave negative results, one or more pulmonary cytologic specimens showed malignant cells. It is concluded that: (1) pulmonary cytopathologic techniques have excellent sensitivity and accuracy in the diagnosis of lung carcinomas; (2) they may establish the diagnosis of pulmonary carcinomas when endoscopic biopsies give negative results; and (3) they are particularly helpful in cases in which endoscopic biopsies suffer from a low yield (peripheral lesions) or create a considerable danger to the patients (iatrogenic hemorrhage).

Classification of lung carcinomas in the dog and cat.

A total of 218 lung carcinomas from dogs and cats were examined histologically. The tumors were classified into adenocarcinoma, squamous-cell carcinoma, bronchial gland carcinoma, and alveolar-cell carcinoma. We believe that adenocarcinoma should be subdivided into differentiated and undifferentiated types because the two are distinct histologically and vary in frequency in the cat and dog. It is also important to recognize bronchial gland carcinoma, a distinct histological type, and to subdivide alveolar-cell carcinoma into three separate types: anaplastic small-cell and large-cell types, and adenomatosis type.

Cytological criteria for a histogenetic classification of bronchogenic carcinomas

Although pulmonary cytology has been quite successful in the diagnosis of well differentiated epidermoid carcinomas (wdEC) and well differentiated adenocarcinomas, cytological accuracy is very poor for various forms of poorly differentiated epidermoid carcinomas (pdEC) and poorly differentiated adenocarcinomas (pdAC) as well as large cell carcinomas (LCC), giant cell carcinomas (GCC), and undifferentiated carcinomas (UC). Using routine light microscopic descriptions based mainly upon cellular form and size, human and hamster pulmonary tumors have been previously classified illogically, with little reference to their histogenesis. A new classification of lung carcinomas, based upon cell of origin, utilizes specific morphological features of various tumor types at the cellular level. Ultrastructural and histochemical techniques reveal that the majority of lung tumors are derived from mucous and/or basal cells. Studies in our laboratories on the histogenesis of epidermoid metaplasia, carcinoma in situ, and regeneration have shown the transformation of mucous cells to nonkeratinizing squamous metaplastic cells which may undergo keratinization.