WHO Classification Of Lung Tumors Research Articles

EGFR mutational status of primary Lung Adenocarcinoma in an Indian cohort based on 2015 WHO classification of lung tumors

Background: Epidermal growth factor receptor (EGFR) mutations have been known to be associated with adenocarcinoma, women, non- smokers and East-Asian ethnicity. This study was aimed to characterize the frequency of EGFR mutations and their association with histologic subtypes in primary lung adenocarcinoma in an Indian cohort. Methods: Two seventy-four cases were categorized using 2015 WHO classification of lung tumors. The frequency of each histologic subtype and cell type was correlated with EGFR exon sequences in a subset of 120 cases using polymerase chain reaction (PCR) gene sequencing. Results: The predominant biopsy categories in 274 cases were acinar 167(61%), solid 63(23%), mucinous 19(7%), lepidic 11(4%) and others 14(5%). EGFR mutations were detected in 49/120 (40.8%) including 3/5(60%) lepidic, 4/9(44.4%) papillary, 29/68(42.7%) acinar, 10/24(41.7%) solid and 1/13(7.7%) mucinous subtypes and were significantly associated with the cuboidal cell type (p=0.01). These mutations were common in women and non-smokers, although not statistically significant. Exon 19 mutations predominated in 36/49(73.4%). The majority, 213/263 (81%), were thyroid transcription factor 1(TTF-1) positive. The polygonal cell type and the solid subtype were frequent amongst stage IV tumors and smokers. Conclusions : EGFR mutations were most frequently seen with the lepidic and papillary subtypes, not associated with the mucinous subtype, more common in women and non-smokers and significantly associated with the cuboidal cell type. DOI: 10.21276/APALM.1372

Classification histomoléculaire des cancers pulmonaires : quoi de neuf en 2017 ?

The new 2015 WHO classification of lung tumors was based on multidisciplinary workshops involving clinicians, radiologists, geneticists and pathologists, and has included in the era of personalized medicine, the most recent data on lung tumor genetics. This histomolecular classification has provided a new grading system based on architectural subtyping for adenocarcinoma, which has been validated for the last 2 years, confirming the poor prognosis of solid and micropapillary adenocarcinoma, in contrast with the best prognosis of lepidic predominant adenocarcinoma, minimally invasive adenocarcinoma and in situ adenocarcarcinoma (ex bronchioloalveoalr carcinoma). A new grading system has been recently proposed for squamous cell carcinoma, mainly based on tumor budding, nest size and single cell migration pattern. A new concept of invasion, the STAS for Spread Through Alveolar Spaces is currently evaluated, small tumors with minimal resection having a tendency to recur when STAS could be demonstrated at the periphery of the tumor. The molecular testing algorithm proposed for small specimen has also evolved, including now PD-L1 immunohistochemistry, and new guidelines and reviews on the topic have been published, as well as an PD-L1 atlas edited by the IASLC. Finally, new insights have been provided in genetics for adenocarcinoma, neuroendocrine lung tumors and sarcomatoid carcinoma, leading to the discovery of new potential therapeutic targets.

MTE11.01 The Clinical Impact of the 2015 WHO Classification of Lung Tumors

MTE11.01 The Clinical Impact of the 2015 WHO Classification of Lung Tumors

IA01.04 Does Cytological Material Fit All - Lessons from EBUS/Bronchoscopy

In the diagnosis of lung cancer the primary diagnostic approach is microscopic evaluation of tissue biopsy. However, in many cases the only material for microscopic evaluation is cytological one. There are numerous types of cytological material in evaluation of lung tumors including sputum, bronchial brush, bronchial washing, transthoracic and transbronchial fine needle aspirates. Historically sputum was the most common diagnostic material but at present the most common types of cytological specimen are bronchial brush, and transthoracic or transbronchial FNAB. Nowadays worked out and recognized cytological criteria allows not only to diagnose carcinoma but in majority of cases to specify the histologic type of a tumor. This approach to microscopic diagnosis of lung carcinoma was incorporated to the latest WHO classification of lung tumors (ref). The key reason that cytodiagnosic criteria and terminology were included into WHO classification was that in about 30% cases of lung tumors the cytological specimen is the only material for microscopic evaluation. Similarly to evaluation of small tissue biopsies in cytopathology, in doubtful cases, immunocytochemistry may be implemented to determine histologic type of tumor. Most useful in evaluation of cytological specimen are IHC antibodies with nuclear presentation (e.g. p40 for squamous cell carcinoma and TTF1 for adenocarcinoma). Cytological material may be utilized in evaluation and in differential diagnosis between primary and metastatic lung tumor. The panel of the antibodies (e.g. CDX2, PSA, Melan A) may be used to indicate location of primary tumors mainly adenocarcinomas. Since cytological smears are of limited diagnostic value for immunocytochemistry, the so-called cell blocs technique is recommended. This technique allows to use larger panel of antibodies for immunohistochemical evaluation. Cytology become very useful for clinical staging of lung carcinoma routinely utilizing EBUS and EUS technique for obtaining material from parahilar and mediastinal lymph nodes. Cytological criteria are similar to that used for specimens obtained by transthoracic FNAB. In our center practice cooperation with adequately trained thorax surgeons provides adequate material for microscopic evaluation from EBUS and EUS obtained specimens in 94% cases. Currently one of the important task for pathologist in evaluating material from lung carcinoma is adequate selection of the material for molecular test. In case of lung carcinoma or to be specific lung adenocarcinoma â material is selected for evaluation of EGFR and K-RAS mutation. In our experience cytological material particularly fine needle aspirates - fulfill such demands. Percentages of tumors cells in the sample is often even higher than in tissue sections especially in fine needles of peripherally location lesions. Cytological material may be useful in evaluation of EGFR and K-RAS mutation as well as in determination of presence of translocations of ALK and ROS1 using FISH technique. Evaluation of ALK and ROS1 translocation remained in the hands of cytopathologists since the crucial point is the location of translocation in nuclei of tumors cells. Latest challenge for pathologists evaluating lung carcinoma specimen is to determine predictive criteria for immunotherapy in those tumors. At the moment it seems that cytological material may be not satisfactory for adequate evaluation of immunocytochemical expression of PD-L1 and PD-1. In summary cytological material from lung carcinoma is useful in establishing the firm microscopic diagnosis of malignancy, to determine histologic type and to be used for molecular tests. It also allows to differentiated between primary and metastatic lung malignancies as well as determined primary location of metastatic lung carcinoma. Cytological specimens obtained by EBUS and EBUS techniques are very useful in clinical staging of lung carcinoma. Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG eds. WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart. 4th ed. Lyon, France: IARC Press; 2015. cytology, lung carcinoma, molecular testing

P3.01-021 Reproducibility of Comprehensive Histologic Assessment and Refining Histologic Criteria in P Staging of Multiple Tumor Nodules: Topic: Morphology

Multiple tumor nodules (MTNs) are being encountered, with increasing frequency with the 8th TNM staging system recommending classification as separate primary lung cancers (SPLC) or intrapulmonary metastases (IM). Pathological staging requires assessment of morphological features, with criteria of Martini and Melamed supplanted by comprehensive histologic assessment of tumor type, predominant pattern, other histologic patterns and cytologic features. With publication of the 2015 WHO classification of lung tumors, we assessed the reproducibility of comprehensive histologic assessment and also sought to identify the most useful histological features. We conducted an online survey in which pathologists reviewed a sequential cohort of resected multifocal tumors to determine whether they were SPLC, IM, or a combination. Specific histological features for each nodule were entered into the database by the observing pathologist (tumor type, predominant adenocarcinoma pattern, and histological features including presence of lepidic growth, intra-alveolar cell clusters, cell size, mitotic rate, nuclear pleomorphism, nucleolar size and pleomorphism, nuclear inclusions, necrosis pattern, vascular invasion, mucin content, keratinization, clear cell change, cytoplasmic granuleş lymphocytosis, macrophage response, acute inflammation and emperipolesis). Results were statistically analyzed for concordance with submitting diagnosis (gold standard) and among pathologists. Consistency of each feature was correlated with final determination of SPLC vs. IM status (p staging) by chi square analysis and Fisher exact test. Seventeen pathologists evaluated 126 tumors from 48 patients. Kappa score on overall assessment of primary v. metastatic status was 0.60. There was good agreement as measured by Cohen’s Kappa (0.64, p<0.0001) between WHO histological patterns in individual cases with SPLC or IM status but proportions for histology and SPT or IM status were not identical (McNemar's test, p<0.0001) and additional histological features were assessed. There was marked variation in p values among the specific histological features. The strongest correlations (<0.05) between p staging status and histological features were with nuclear pleomorphism, cell size, acinus formation, nucleolar size, mitotic rate, nuclear inclusions, intra-alveolar clusters and necrosis pattern. Correlation between lymphocytosis, mucin content, lepidic growth, vascular invasion, macrophage response, clear cell change, acute inflammation keratinization and emperipolesis did not reach a p value of 0.05. Comprehensive histologic assessment shows good reproducibility between practicing lung pathologists. In addition to main tumor type and predominant patterns, nuclear pleomorphism, cell size, acinus formation, nucleolar size, and mitotic rate appear to be useful in distinguishing between SPLC and IM.

The WHO 2015 classification of lung tumours: Evolution of tumour classification in lung cancer

There are many important changes in the 2015 WHO classification of lung tumours, reflecting the numerous advances in tumour genetics and therapy over the past decade.1 A classification system for small biopsies and cytology is provided for the first time, with emphasis on integration of molecular testing and usage of a limited panel of immunohistochemistry when needed. Adenocarcinoma classification has changed significantly with definitions for adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA), and discontinuation of the term bronchioloalveolar carcinoma. Invasive adenocarcinomas are classified according to the predominant pattern, shown to have prognostic significance and also to predict response to adjuvant chemotherapy. These changes will also likely impact on the next TNM staging system in terms of multiple primary tumours and measurement of tumour invasive size. Large cell carcinoma is now restricted to resected tumours that lack clear morphological and immunohistochemical differentiation, with reclassification of those that do to solid adenocarcinoma and non-keratinising squamous cell carcinoma. Squamous cell carcinoma classification is simplified to keratinising, non-keratinising and basaloid subtypes, with the non-keratinising tumours ideally requiring immunohistochemical confirmation. Criteria for diagnosing neuroendocrine tumours remain essentially unchanged but these tumours are now grouped in one category. There are many important changes in the 2015 WHO classification of lung tumours, reflecting the numerous advances in tumour genetics and therapy over the past decade.1 A classification system for small biopsies and cytology is provided for the first time, with emphasis on integration of molecular testing and usage of a limited panel of immunohistochemistry when needed. Adenocarcinoma classification has changed significantly with definitions for adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA), and discontinuation of the term bronchioloalveolar carcinoma. Invasive adenocarcinomas are classified according to the predominant pattern, shown to have prognostic significance and also to predict response to adjuvant chemotherapy. These changes will also likely impact on the next TNM staging system in terms of multiple primary tumours and measurement of tumour invasive size. Large cell carcinoma is now restricted to resected tumours that lack clear morphological and immunohistochemical differentiation, with reclassification of those that do to solid adenocarcinoma and non-keratinising squamous cell carcinoma. Squamous cell carcinoma classification is simplified to keratinising, non-keratinising and basaloid subtypes, with the non-keratinising tumours ideally requiring immunohistochemical confirmation. Criteria for diagnosing neuroendocrine tumours remain essentially unchanged but these tumours are now grouped in one category.

Carcinomes épidermoïde, basaloïde et adénosquameux pulmonaires

The precise distinction between adenocarcinoma and squamous cell carcinoma (SqCC) has become very important for determining the appropriate therapy for patients and more specifically to drive the use of tyrosine kinase inhibitors, pemetrexed, anti-VEGF monoclonal antibody and crizotinib. Squamous pearls and distinct intercellular bridges identify keratinizing SqCC. In non-keratinizing SqCC, immuno-histochemistry is required. Recent studies have shown p40 and TTF1 to be the two best markers of SqCC and adenocarcinoma respectively. Many morphological variants of SqCC have been described. Basaloid SqCC is a poorly differentiated epithelial tumor lacking squamous morphology but showing immuno-histochemical expression of squamous makers. The pronostic of basaloid carcinoma is considered poorer than that of other non-small cell lung cancers. Adenosquamous carcinoma shows components of both SqCC and adenocarcinoma. Both components must be clearly identified either on H&E or by immuno-histochemistry. The adenocarcinoma components justified a screening for gene rearrangements. Finally, the recent WHO classification of lung tumors did not change the criteria applying for the grading of preinvasive bronchial lesion.

The 2015 WHO classification of lung tumors.

The 2015 WHO classification of lung tumors.

Update on large cell carcinomas of the lung

Large cell carcinoma of the lung is defined in the 2004 WHO classification as an undifferentiated malignant epithelial tumour that lacks the cytologic features of small cell, squamous or adenocarcinoma. The concept of large cell carcinoma is often criticized as a waste basket category. In the forthcoming revision of the WHO classification of lung tumours, most of the variants are reallocated to other tumour types. The details will be discussed. The existence of primary lung tumours which are morphologically undifferentiated when fully examined in the context of a surgically resected lesion (large cell NOS or not otherwise specified) is undeniable. Whilst the term large cell carcinoma seems perfectly reasonable for these cases, there is disquiet regarding this situation, driven in part by the concept of NSCLC-NOS as applied in diagnosis in the small biopsy/cytology setting and also by the observation that some large cell carcinomas shared immunohistochemical or molecular genetic features with either adenocarcinomas or squamous cell carcinomas. Thus, in the forthcoming WHO classification, the category of large cell carcinoma is a much reduced rump of morphologically undifferentiated carcinomas (not small cell carcinoma and not sarcomatoid/pleomorphic carcinoma), which lack definitive immunohistochemical features which reallocate the tumour to either squamous cell or adenocarcinoma. This debate is to a large extent a matter of definitions. We have moved away from a purely morphological definition, and incorporated into the definition of both squamous cell and adenocarcinoma, some immunohistochemical features which may define a tumour type in the absence of morphological features.

Adenokarzinome der Lunge - die neue Klassifikation

The new, interdisciplinary IASLC/ATS/ERS classification of lung adenocarcinoma has achieved a considerable impact since its publication in the year 2011. It separates tumours into preinvasive, minimally invasive and invasive subtypes. The preinvasive lesions atypical, adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS) together with the minimally invasive adenocarcinoma (MIA), have an excellent prognosis after complete resection with 100 % survival. It enables a reproducible tumour grading by the determination of the predominant histological growth pattern which could be confirmed in several follow-up studies. Thereby the mixed subtype was eliminated which formerly represented about 80 % of all adenocarcinomas. Similarly, the terms bronchioloalveolar adenocarcinoma and bronchioloalveolar tumour growth were eliminated because they represented several distinct entities, specifically the in-situ lesions AAH and ACIS as well as the non-in-situ/invasive tumours like minimally invasive adenocarcinoma, lepidic predominant adenocarcinoma (LPA) and invasive mucinous adenocarcinoma (IMA). Although the classification is based on data from tumour resections it accommodates the fact that most tumours are diagnosed on biopsies and cytological specimens and includes recommendations for an efficient work-up to preserve tissue for molecular testing. Furthermore, the morphological analysis may provide hints for molecular changes including mutations with therapeutic relevance that may enable targeted molecular diagnostics. This review presents essentials facts of the new classification that will be part of the next WHO classification of lung tumors and its follow-up publications.

The Study on Gene Amplification of EGFR in Bronchioloalveolar Carcinoma and Conventional Adenocarcinoma of the Lung.

Patients with adenocarcinoma of the lung have disproportionately response to the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). The aim of this study is to analyze the difference of EGFR gene amplification in bronchioloalveolar carcinoma (BAC), adenocarcinma mixed subtype and conventional adenocarcinoma of the lung and provide some information to clinical therapies. Lung cancer cases were collected and reviewed from the archives of the Department of Pathology, Chinese PLA General Hospital during the time period from 2004 to 2006. The definite diagnosis of BAC based on 2004 WHO classification of lung tumors was made by two pathologists. Fluorescence in situ hybridization (FISH) was performed to detect EGFR gene amplification in pure BAC, adenocarcinma mixed subtype and conventional adenocarcinoma. Conventional adenocarcinoma had higher EGFR amplification compared with pure BAC and adenocarcinma mixed subtype (Chi-square=11.632, P<0.05). EGFR gene amplification was found in 45.45% of conventional adenocarcinoma, 14.81% in pure BACs, and 22.58% in adenocarcinma mixed subtype. EGFR gene amplification was observed as scattered signals in most cases. EGFR gene amplification was seen more frequently in the invasive components than in BAC. EGFR gene amplification might be associated with the development of adenocarcinoma of the lung.

Basaloid adenocarcinoma. A new variant of pulmonary adenocarcinoma

The 2004 WHO classification of lung tumours recognised basaloid carcinoma as a variant of squamous and large cell carcinoma. We report a unique case of primary pulmonary adenocarcinoma with a basaloid component. An 82-year-old man underwent pulmonary lobectomy for a 2.8 cm tumour. The patient is disease-free 13 months after diagnosis. Histologically, an invasive carcinoma having a glandular and a solid component was observed. The former was an adenocarcinoma with mucus containing spaces lined by columnar mucinous cells and basaloid cells. The solid component was an organoid proliferation of basaloid-type cells, as in cutaneous basal cell carcinoma. Basaloid cells, but not mucinous cells, were immunoreactive for high molecular weight cytokeratins (CK), CK 7 and, focally, for TTF-1. High Ki67 index, p53 and EGFR expression were also found. This tumour is unique in several respects: (1) The solid areas resemble a conventional basaloid carcinoma, except for the presence of small mucin-containing spaces. (2) The mucinous adenocarcinoma areas contain two layers of columnar and basaloid cells. (3) Both components are neoplastic based on cell morphology, invasive properties and phenotypic profile. These findings indicate that a basaloid variant of adenocarcinoma is also existing in the spectrum of basaloid carcinomas of the lung.

Bronchial Typical Carcinoid Tumors

The current WHO classification of lung tumors recognizes bronchial typical carcinoid as low-grade neuroendocrine tumors. These tumors grow slowly but can metastasize to regional nodes (4 to 20%) and more rarely to extrathoracic sites. Symptoms are usually related to local compression and obstruction of the bronchial tree. Paraneoplastic syndrome can be present (carcinoid syndrome, Cushing's syndrome, acromegaly). Preoperative diagnosis is usually obtained with bronchoscopic biopsy. Computed tomography and somatostatin receptor scintigraphy are useful in the preoperative staging. Only selected cases can be treated endoscopically with laser resection. The complete surgical resection remains the only therapy with curative intent in the majority of patients. Parenchyma-sparing resections are indicated whenever possible. Overall survival after surgery is excellent (5-year rate, 87 to 100%) with low recurrence rate (2 to 11%). N-status and type of resection seem not to affect prognosis. Local relapse can be treated successfully with surgery, whereas distant metastases have a poor prognosis even after chemotherapy.

Evolving Concepts in the Pathology and Computed Tomography Imaging of Lung Adenocarcinoma and Bronchioloalveolar Carcinoma

To review recent advances in pathology and computed tomography (CT) of lung adenocarcinoma and bronchioloalveolar carcinoma (BAC). A pathology/CT review panel of pathologists and radiologists met during a November 2004 International Association for the Study of Lung Cancer/American Society of Clinical Oncology consensus workshop in New York. The purpose was to determine if existing data was sufficient to propose modification of criteria for adenocarcinoma and BAC as newly published in the 2004 WHO Classification of Lung Tumors, and to address the pathologic/radiologic concept of diffuse/multicentric BAC. Solitary small, peripheral BACs have an excellent prognosis. Most lung adenocarcinomas with a BAC pattern are not pure BAC, but rather adenocarcinoma, mixed subtype with invasive patterns. This applies to tumors presenting with a diffuse/multinodular as well as solitary nodule pattern. The percent of BAC versus invasive components in lung adenocarcinomas appears to be prognostically important. However, a consensus definition of "minimally invasive" BAC with a favorable prognosis could not be achieved. While recognition of a BAC component is possible, the diagnosis of BAC with exclusion of invasive adenocarcinoma cannot be made by small biopsy or cytology specimens. There is a need to work toward a mutual understanding and consensus between pathologists, clinicians, and researchers with the use of the term BAC versus adenocarcinoma. Future studies should make some attempt to quantitate these components and/or other features such as size of scar, size of invasive component, or pattern of invasion. Hopefully, this work will allow definition of a category of adenocarcinoma, mixed subtype with predominant BAC/minimal invasion and a favorable prognosis.

High-Grade Neuroendocrine Carcinoma of the Ampulla of Vater

We describe the clinical and pathologic features of 14 cases of high-grade neuroendocrine carcinoma (HGNEC) of the ampulla of Vater classified according to WHO classification of lung tumors into small cell carcinoma (SCC, 6 cases) and large cell neuroendocrine carcinoma (LCNEC, 8 cases) types. The immunohistochemical findings were compared with those of 13 cases of primary poorly differentiated ampullary adenocarcinomas (PDACA) lacking neuroendocrine morphology. The mean age of 10 males and 4 females was 70 years. The mean tumor size was 2.5 cm. Ten of 13 patients had lymph node metastases (mean, 2.3 nodes involved). Documented sites of distant metastases included brain and liver. Overall, 64% of patients with ampullary HGNEC died of disease (mean follow-up, 14.5 months). Four patients had no evidence of disease after resection (mean, 20 months). Half of the tumors were associated with adenomas of the adjacent mucosa, 2 with high-grade dysplasia. Two HGNECs were combined with a conventional adenocarcinoma and another with a squamous cell carcinoma component. By immunohistochemistry, the HGNECs were positive for cytokeratins (AE1/AE3, 100%; Cam5.2, 67%; CK7, 87%; CK20, 38%), similar to the pattern found in PDACAs. p27 expression was lost in 1 case of HGNEC and in all PDACAs. Retinoblastoma (Rb) protein expression was lost in 60% of HGNECs and in none of the PDACA cases. In conclusion, HGNECs of the ampulla are rare (2%-3% of ampullary tumors in our material). The clinical course parallels that of their pulmonary counterparts and appears to be worse than that of locally advanced ampullary adenocarcinomas. The association with adenoma and or conventional adenocarcinoma components may suggest a common pathway in the initial carcinogenesis of these two types of tumors. Loss of Rb expression, a characteristic finding in pulmonary SCCs, is present in almost half of ampullary HGNECs. In contrast, p27 expression is lost in PDACAs and retained in most HGNECs. Thus, there are differences in the molecular phenotypes of these two types of ampullary carcinoma, supporting the distinction of poorly differentiated carcinomas with a neuroendocrine phenotype from those without.

Feasibility of the new WHO classification of pulmonary neuroendocrine tumours.

Primary pulmonary neuroendocrine tumours present a heterogeneous group of tumours causing problems in diagnosis and treatment. The new WHO classification of lung tumours was published in 1999 in order to improve this situation by combining morphology, immunohistochemistry and clinical background for diagnosis. The aim of our study was to evaluate the feasibility of this classification and to discuss the consequences of modified diagnostic criteria. 50 cases of neuroendocrine tumours and 50 poorly differentiated lung tumours diagnosed in the years 1981-1994 were independently evaluated by three pathologists. The diagnosis of all 27 typical carcinoids (TC) was given by all authors, however, no unanimous agreement was achieved in one of three atypical carcinoids (AC) and two of four large cell neuroendocrine carcinomas (LCNEC). While typical and atypical carcinoids can be distinguished by the number of mitoses or presence of necrosis it was found that the most difficult diagnostic factor for large cell neuroendocrine carcinoma is the recognition of its light-microscopic neuroendocrine features. In consequence it must be distinguished not only from atypical carcinoid or small cell lung carcinoma (SCLC), but also from poorly differentiated carcinoma. Immunohistochemistry is important for the diagnosis of this entity but also for nonsmall cell lung carcinoma with neuroendocrine differentiation (of which 1 case was detected in our series) There was agreement on the diagnosis of small cell carcinomas in all but one case. The results indicate the excellent reproducibility of the WHO classification.

Feasibility of the new WHO classification of pulmonary neuroendocrine tumours.

Primary pulmonary neuroendocrine tumours present a heterogeneous group of tumours causing problems in diagnosis and treatment. The new WHO classification of lung tumours was published in 1999 in order to improve this situation by combining morphology, immunohistochemistry and clinical background for diagnosis. The aim of our study was to evaluate the feasibility of this classification and to discuss the consequences of modified diagnostic criteria. 50 cases of neuroendocrine tumours and 50 poorly differentiated lung tumours diagnosed in the years 1981-1994 were independently evaluated by three pathologists. The diagnosis of all 27 typical carcinoids (TC) was given by all authors, however, no unanimous agreement was achieved in one of three atypical carcinoids (AC) and two of four large cell neuroendocrine carcinomas (LCNEC). While typical and atypical carcinoids can be distinguished by the number of mitoses or presence of necrosis it was found that the most difficult diagnostic factor for large cell neuroendocrine carcinoma is the recognition of its light-microscopic neuroendocrine features. In consequence it must be distinguished not only from atypical carcinoid or small cell lung carcinoma (SCLC), but also from poorly differentiated carcinoma. Immunohistochemistry is important for the diagnosis of this entity but also for nonsmall cell lung carcinoma with neuroendocrine differentiation (of which 1 case was detected in our series) There was agreement on the diagnosis of small cell carcinomas in all but one case. The results indicate the excellent reproducibility of the WHO classification.

Small cell lung carcinoma (SCLC): a clinicopathologic study of 100 cases with surgical specimens.

Separation of small cell lung carcinoma (SCLC) from nonsmall cell lung carcinoma (NSCLC) is a critical distinction to be made in the diagnosis of lung cancer. However, the diagnosis of SCLC is most commonly made on small biopsies and cytologic specimens, and practicing pathologists may not be familiar with all its morphologic guises and frequent combination with NSCLC elements, which may be seen in larger specimens. Following the most recent WHO classification of lung tumors and with the hope of identifying prognostic markers, we examined in detail the histology of 100 surgical biopsies or resections with a diagnosis of SCLC from the AFIP and pathology panel of the International Association for the Study of Lung Cancer (IASLC). Multiple clinical and histologic features were studied by Kaplan-Meier analysis. Neuroendocrine architectural patterns, including nested and trabecular growth, with peripheral palisading and rosette formation were common in SCLC. Necrosis and apoptotic debris was prominent in all cases, but crush artifact was infrequent. Cell size in surgical biopsy specimens appears larger than in bronchoscopic biopsy specimens and occasional cells may show prominent nucleoli and vesicular nuclear chromatin, but this does not preclude the diagnosis of SCLC. A high percentage of cases (28%) showed combinations with NSCLC, with large cell carcinoma the most common, followed by adenocarcinoma and squamous cell carcinoma. Because of the frequency of a few scattered large cells in SCLC, we arbitrarily recommend that at least 10% of the tumor show large cell carcinoma before subclassification as combined SC/LC. However, combined SCLC is easily recognized if the additional component consists of other NSCLC subtypes such as adenocarcinoma or squamous cell carcinoma, so no percentage requirement is needed. Stage remained the only predictor of prognosis.

Ultrastructure of Neoplastic Cells in Different Histologic Subtypes of Pulmonary Adencocarcinoma

57 pulmonary adenocarcinomas were classified according to the WHO Classification of Lung Tumours. 55 cases were primary adenocarcinomas and two were metastases from the gastrointestinal tract. The acinar, papillary and bronchiolo-alveolar carcinomas were well or moderately differentiated and the solid adenocarcinomas were poorly differentiated tumours secreting mucus in intracytoplasmic vacuoles. All tumours, including the two metastases, were analyzed by transmission electron microscopy. Most of the acinar, papillary and all bronchiolo-alveolar adenocarcinomas contained a great or moderate number of secretory granules which were pale fibrillar or dense homogeneous. Among the solid adenocarcinomas there were no tumours with a great number of secretory granules. The surface fine structure of the metastatic carcinomas differed from those of the primary adenocarcinomas, having a brush-border instead of microvilli. The ultrastructure of the primary adenocarcinomas resembled the normal surface epithelial cells of bronchi and bronchioli, and two papillary adenocarcinomas contained lamellar bodies similar to granular pneumocytes. Instead of dividing into four different subtypes pulmonary adenocarcinomas can be classified according to histological grading.

Epidermoid bronchial carcinoma in dogs and cats

In seven cats and four dogs of different ages, an epidermoid pulmonary carcinoma has been described. This tumour originates from the orifices or the proximal sections of the ducts of the bronchial glands. The carcinoma, which usually shows no keratinization, penetrates the bronchial mucosa, submucosa and the peribronchial tissue. There is no mucus. Occasionally in the peribronchial neoplastic areas there are adenoid formations, comparable to the combined carcinoma of the WHO classification of lung tumours. Metastases have been restricted to the bronchial lymph nodes.