[Proposed terms for endobronchial lesions in patients suspected of having a bronchial neoplasm]. / Propuesta de terminología de las lesiones endobronquiales en pacientes con sospecha de neoplasia bronquial.

Endoscopists describe lung cancer lesions using varying terminology. This study aimed to assess the probability of neoplastic disease in terms of endoscopic findings expressed in an original classification system. The endoscopic lesions were classified as infiltrations (superficial lesions without a clear border with normal mucosa) or masses (exophytic lesions easily distinguished from the bronchial wall). Each lesion was categorized according to 3 grades reflecting probability of malignancy. A grade I infiltration was a lesion presenting 1 of the following characteristics: loss of luster, increased thickness, or redness, with a smooth surface. A grade II infiltration presented 2 of the aforementioned characteristics, with a rough surface. A grade III infiltration presented 3 of those characteristics. A grade I mass was an exophytic lesion with a smooth surface, uniformly colored. A grade II mass presented a smooth surface of a distinct color, and a grade III mass had a rough surface and irregular coloring. We assessed 377 patients with suspicion of neoplasm. Twenty-three percent of the infiltrations were grade I carcinomas, 74% were grade II, and 95% were grade III. Twenty-three percent of masses were grade I, 77% were grade II, and 97% were grade III. The probability of malignancy increased significantly with grade (P< .001) for both types of lesion. In summary, there is a positive correlation between the terms used and the probability of carcinoma. Most grade III lesions were carcinomas, but apparently innocuous grade I lesions could be carcinomas in a significant number of cases.

Compromiso tumoral de vía aérea en pediatría / Pediatric airway compromise by tumors

Los tumores traqueo bronquiales son extremadamente infrecuentes en la edad pediátrica e incluyen lesiones benignas y malignas. Por la baja frecuencia en niños y sintomatología respiratoria inespecífica, la sospecha diagnostica es habitualmente tardía. El tratamiento de elección en la mayoría de ellos es la resección quirúrgica abierta, sin embargo, la remoción endoscopia podría estar indicada es casos muy seleccionados con histología benigna y de localización accesible.

Tracheobronchial tumors are extremely rare in children and include benign and malignant lesions. Due to the low frequency in children and nonspecific respiratory symptoms, diagnostic suspicion is usually late. The treatment of choice in most of them is open surgical resection, however, endoscopy removal could be indicated in highly selected cases with benign histology and accessible location.

Well-differentiated neuroendocrine carcinomas: the spectrum of histologic subtypes and various clinical behaviors.

The term "well-differentiated neuroendocrine carcinoma" was coined to describe a variety of demonstrably neuroendocrine tumors which were more aggressive (both with respect to their histologic appearance and their clinical course) than (typical) bronchial carcinoids but were also clearly distinguishable from small cell neuroendocrine carcinomas. This umbrella term encompasses a variety of tumors previously described by a variety of terms including "atypical" carcinoids, "malignant tumorlets," peripheral stage I small-cell carcinoma, as well as neoplasms described simply as "undifferentiated carcinoma" (prior to the recognition of their neuroendocrine properties). As such, this term is a broad term and is not simply synonymous with "atypical carcinoid." Over time, at least 3 subtypes have been identified based upon their histologic appearance and mitotic index, with correspondingly aggressive clinical courses.

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.

Bronchial-pulmonary adenocarcinoma subtyping relates with different molecular pathways.

Lung cancer is one of the most common cancers in the world with a high mortality rate. We analyzed 45 surgical samples of the adenocarcinoma, 13 with lymph node metastasis. APC, BCL2, chromogranin A, CK 5/6/18 (LP34), CK20, CK7, cyclin D1, EGFR, ERCC1, HER2, Ki67, LRP, MRP, P53, RB and TTF1 expressions were evaluated by immunohistochemistry (IHC). Higher Ki67, APC, ERCC1 expressions and lower TTF1 expression were identified in advanced stages (IIA and IIIA) of adenocarcinomas, which reflect a more aggressive, less differentiated, possibly a non-TRU adenocarcinoma. Acinar, micropapillary and BA/lepidic adenocarcinoma patterns were the most similar patterns and papillary was the most different pattern followed by solid pattern, according to expression of these markers. Different adenocarcinoma patterns are engaged with different molecular pathways for carcinogenesis, based on the differences of expression. Acinar, BA/lepidic and micropapillary showed higher TTF1 expression (type TRU), and papillary and solid patterns revealed less TTF1 expression, exhibiting a non-TRU/bronchial phenotype. Solid pattern revealed lower HER2 and higher EGFR and ERCC1 (this compared to papillary) expression; papillary higher HER2 and lower ERCC1 expressions; micropapillary higher RB expression; and acinar lower ERCC1 and higher EGFR expressions. Ciclin D1 seems to have more importance in acinar and BA/lepidic patterns than in micropapillary. ERCC1 protein expression in micropapillary, solid and BA/lepidic patterns may indicate DNA repair activation. Inhibition of apoptosis could be explained by BCL2 overexpression, present in all adenocarcinoma patterns. MRP-1 and LRP were overexpressed in all patterns, which may have implications for drug resistance. Further studies are needed to interpret these data regarding to therapy response in advanced staged bronchial-pulmonary carcinomas.

Solitary pulmonary papillomas in adults: a clinicopathologic and in situ hybridization study of 14 cases combined with 27 cases in the literature.

Solitary endobronchial papillomas in adults are rare neoplasms. Only sporadic cases have been documented. The histologic classification of these tumors remains problematic, and little is known about their clinical behavior. The clinical and pathologic features of 13 endobronchial papillomas and a single endobronchiolar papilloma were reviewed. In situ hybridization for human papillomavirus (HPV) types 6/11, 16/18, and 31/33/51 was performed on seven cases. Twenty-seven additional well-documented cases were identified in a literature review. Human papillomavirus studies were performed in four of the previously reported cases. The 41 neoplasms combined from the Armed Forces Institute of Pathology and literature review were divided into three groups according to their histologic features. Thirty-one of 41 (76%) patients were men. The ages of the patients ranged from 26 to 74 years (median, 57 years). Three morphologically distinct histologic types were recognized; 27 squamous cell papillomas, 7 glandular papillomas, and 7 mixed squamous and glandular papillomas. Squamous papillomas: 23 of 27 (85%) patients were men, and the median age was 54 years. Six of eleven (55%) of these patients smoked. Twenty-six lesions were exophytic and a single lesion had an inverted pattern. Seven of 24 (29%) lesions featured cytologic atypia and 5 of 24 (14%) had viral cytopathic effect. Five of seven (71%) cases examined for HPV DNA were positive. Three of 18 (17%) recurred. Glandular papillomas: Four of seven (57%) patients were women. The mean age was 67 years. One of five (20%) patients smoked. Five lesions were central, and two were peripheral. Four lesions had columnar epithelium, and three had ciliated epithelium. One of six (17%) lesions recurred. Mixed papillomas: five of seven (71%) patients were men. The median age was 64 years. Three of five (60%) patients smoked. Three of seven (43%) lesions featured cytologic atypia. Four of five lesions were examined for HPV DNA and all were negative. No lesions recurred. This study demonstrates that solitary endobronchial papillomas can be separated into three distinct morphologic categories. Squamous cell and mixed papillomas are predominantly lesions of male smokers in their 6th decade. Although cytologic atypia is observed in many cases, the rarity of these tumors and difficulty in separating papillomas from endobronchial papillary squamous carcinomas make generalizations regarding the risk of progression to carcinoma tenuous at best. Human papillomavirus appears to play a pathogenetic role in some squamous cell papillomas, but not in mixed papillomas, yet its presence in the squamous lesions does not correlate with recurrence or malignancy. The first report of an inverted squamous cell papilloma indicates clinical features similar to the more common exophytic squamous cell papillomas. Glandular papillomas, the rarest of all endobronchial papillomas, are found in an older age group than squamous and mixed papillomas, and most-patients are nonsmokers. Based on these findings, all endobronchial papillomas should be completely excised.

Relationship between length of longitudinal extension and maximal depth of transmural invasion in roentgenographically occult squamous cell carcinoma of the bronchus (nonpolypoid type).

This study was designed to verify our hypothesis that there are two different growth types in roentgenographically occult squamous cell carcinoma of the bronchus. Serial blocks prepared from the entire bronchial tree of 83 resected specimens of occult carcinoma were used for the evaluation of the relationship between the length of longitudinal extension and the maximal depth of transmural invasion. We prepared a length-depth diagram of 92 lesions, including multifocal carcinomas, which confirmed that there are at least two types: Most of these lesions are of the creeping type, which shows a marked superficial growth; the minority are of the penetrating type, which shows a marked downward growth. The diagram suggests that occult carcinoma has a propensity either for longitudinal growth along the bronchial lumen or for transmural growth into the bronchial wall at the time of occurrence. It is likely that the penetrating type grows rapidly and becomes advanced in a short time. Identification of longer lesions of the creeping type is occasionally problematical both at bronchoscopy and at surgical treatment. The stump is usually positive for carcinoma unless frozen sections or imprint specimens of the margin of resection are examined, because it is frequently difficult to identify the proximal end of extension by bronchoscopy.

Bronchial carcinoid tumors.

Bronchial carcinoid tumors, termed (incorrectly) "bronchial adenomas" in the past, are uncommon pulmonary neoplasms. These tumors are currently classified as neuroendocrine in origin because of their potential to form and sometimes secrete a variety of chemical substances. Overall, approximately 75% of bronchial carcinoid tumors arise in the lobar bronchi, 10% occur in the main-stem bronchi, and 15% originate in the periphery of the lung. Well-differentiated carcinoid tumors constitute almost 90% of all bronchial carcinoids. Atypical carcinoid tumors have a higher malignant potential than do typical bronchial carcinoids. The carcinoid syndrome is rarely, if ever, associated with carcinoids limited to the tracheobronchial tree. Occasionally, Cushing's syndrome due to ectopic hormone production is caused by bronchial carcinoid tumors. More than 75% of bronchial carcinoids are detected on conventional posteroanterior chest roentgenograms. Computed tomography may help disclose small neoplasms that are occult on conventional roentgenography, particularly in the assessment of patients who have Cushing's syndrome due to ectopic hormone production. Pulmonary resection is the treatment of choice for bronchial carcinoids. The prognosis is related to the pathologic grade and stage of the tumor.

Bronchial carcinoid tumours: a study on clinicopathological features and role of octreotide scintigraphy.

Several authors proposed the stage at diagnosis and some histopathological features as prognostic factors of bronchial carcinoids. However, since large tumour diameters or nodal metastases are frequently associated to aggressive histology, their prognostic role is unclear. To investigate the relationships between the clinicopathological parameters at diagnosis and outcome, 21 patients were analysed. Overall 26% of the radically resected patients recurred. Recurrences and disease-specific mortality were related to atypical histology and, only in cases with typical histology, to the presence of hilar or mediastinal lymph node metastases. These prognostic factors were valuable independently of the size of the primary tumour, that was remarkably homogeneous, always less than 3 cm, thus not predictive of recurrence. Moreover we evaluated the role of somatostatin receptor scintigraphy, a diagnostic tool only preliminary studied in this field. Scintigraphy with 111In-octreotide revealed the primary tumours at diagnosis (8/8), the increase in tumour size in two unresected patients, and all the cases of recurrent or metastatic disease (5/11), sometimes before the appearance of symptoms. These results suggest the usefulness of histology and nodal status as prognostic factors in clinical practice. Somatostatin receptor scintigraphy turns out to be a powerful diagnostic tool, for an accurate staging and an early diagnosis of recurrence in bronchial carcinoids.

Neuroendocrine tumors of the bronchopulmonary tract: a reappraisal of their classification after 20 years.

This article is an overview of the classification of pulmonary neuroendocrine neoplasms, their presentation, their pathologic appearance, and their clinical management. In addition, the original classification, based on histologic features, is reassessed in the light of newer areas in study, including neurosecretory products, neuroendocrine markers, ultrastructural studies, ploidy analysis, cell adhesion markers, apoptosis, oncogene mutation analysis, and genetic alterations. The histologic classification proposed in 1983 remains the single most valuable factor in establishing the diagnosis and, together with the TNM status, the prognosis of this group of interesting neoplasms.

[Radiological study of the topography and morphology of pulmonary cancer]. / Studio radiologico sulla topografia e morfologia del cancro polmonare

This study proposes a radiological, topographical and morphological classification of primary carcinoma of the lung based on a large radiographic case-series of the National Cancer Institute of Milan checked anatomopathologically. The aim is to standardise the X-ray findings and so make for easier understanding and more rewarding cooperation among those engaged on the diagnosis and treatment of this tumor. The classification of lung cancer into central and peripheral only is felt, in the light of present knowledge, to be inadequate. It is therefore suggested that central lung cancers be divided into purely endobronchial, endoperibronchial and exobronchial, taking into account both the repercussions on ventilation and extracentral spread. For peripheral lung carcinomas more detailed morphological and topographical features are considered in order to pinpoint the tumor and its hilomediastinal spread, especially in the case of paracentral tumors. A brief reference is made to the more relevant radiodiagnostic procedures.

[Biological variables and stratification of patients with inoperable non-small-cell bronchial cancer: recommendations for future trials]. / Variables biologiques et stratification des patients atteints de cancer bronchique non à petites cellules non opérés: recommandations pour de futurs essais.

OBJECTIVE: To identify, through a review of the literature, the laboratory variables that would allow a more accurate stratification of unresected non small-cell lung cancer patients who participate in clinical trials. METHOD: Systematic review, without meta-analysis, following the recommendations of the International Federation of Clinical Chemistry and Laboratory Medicine, and taking into account the Consolidated Standards of Reporting Trials statement. RESULTS: Of 1106 publications retrieved, we were able to include only fourteen studies in our review. Available evidence would support the use of several laboratory variables as prognostic covariables to stratify non resected non small-cell lung cancer patients in clinical trials, but blood haemoglobin would be the only one that could be recommended on a routine basis, and only in patients treated with radiotherapy (three studies out of three). The possible consequences in terms of therapeutic decision of haemoglobin measurements remain however to be clarified. CONCLUSION: Until better designed studies are published, a number of arguments would support the pre-treatment measurements of the following variables in patients participating in clinical trials: blood haemoglobin, white blood cell count with differential, serum LDH, albumin, calcium, and NSE. Further studies would also be necessary to support the addition to this list, of other tumour markers (including Cyfra 21-1), and/or measurements during or after treatment.

[Epidemiologic study of 1665 cases of bronchogenic neoplasms collected at the S. Luigi Gonzaga Hospital between 1973 and 1979]. / Studio epidemiologico su 1665 casi de neoplasie broncogene raccolte all' Ospedale "S. Luigi Gonzaga" fra il 1973 e il 1979.

Data regarding 1,665 cases of benign and malignant lung cancers are examined and frequency behaviour analysed by histological type, sex, age groups and site of onset. Results are compared with other reported data and it is concluded that there is a considerable increase in dyskaryokinesis in both sexes, especially females (particularly epidermoid forms), and that there is a shift in maximum incidence towards more advanced age groups. No variation was seen, however, with respect to the frequency of bronchial tree localisation.

[Classification of broncho-pulmonary cancers (WHO 1999)]. / Classification des cancers broncho-pulmonaires (OMS 1999).

Tumour classification systems provide the foundation for tumour diagnosis and patient therapy and a critical basis for epidemiological and clinical studies. This updated classification was developed with the aim to adhere to the principles of reproducibility, clinical significance, and simplicity in order to minimize the number of unclassifiable lesions. Major changes in the revised classification as compared to the previous one (WHO 1981) include the addition of two pre-invasive lesions to squamous dysplasia and carcinoma in situ: atypical adenomatous hyperplasia (AAH) and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. Another change is the subclassification of adenocarcinoma: the definition of bronchioloalveolar carcinoma has been restricted to non-invasive tumours. There has been substantial evolution of concepts in neuroendocrine lung tumour classification. Large cell neuroendocrine carcinoma (LCNEC) is now recognized as a histologically high-grade non-small cell carcinoma showing histopathological features of neuroendocrine differentiation as well as immunohistochemical neuroendocrine markers. The large cell carcinoma class has been enriched with several variants, including the large cell neuroendocrine carcinoma and the basaloid carcinoma, both of which have a poor prognosis. Finally, a new class has been defined called carcinoma with pleomorphic, sarcomatoid, or sarcomatous elements, which gathers a number of proliferations characterized by a spectrum of epithelial to mesenchymal differentiation. Immunohistochemistry and electron microscopy are invaluable techniques for diagnosis and subclassification, but our intention was to render the classification simple and practical to every surgical laboratory so that most lung tumours can be classified by light microscopic criteria.

[Bronchopulmonary carcinoids: neoplasms with attenuated malignancy or true and proper malignant tumors?]. / Carcinoidi broncopolmonari: neoplasie a malignità attenuata o veri e propri tumori maligni?

The authors, in reporting their series of 6 bronchopulmonary carcinoids, dwell upon the criteria used to classify such neoplasms pointing out the related diagnostic problems. The presence of metastases and/or local recurrences as well as the impossibility to define the aggressiveness of the tumor brought the authors to consider such tumors as malignant. They conclude for a surgical approach which should be conservative: segmentectomy and lobectomy in elective procedures, whereas pneumonectomy and endoscopic resection should be reserved to particular cases.

[Metastasizing bronchial carcinoids]. / Metastaziruiushchie kartsinoidy bronkhov.

Bronchial carcinoids develop metastases approximately in 22 per cent of cases. Metastases can develop in all anatomical forms of the growth. Histologically, metastasizing tumors may be of a different structure: a) typical histoarchitectonics and cytology; b) atypical histoarchitectonics but without cell atypism; c) typical histoarchitectonics associated with cytologic atypism; d) histoarchitectonic atypism associated with cytologic atypism. There is no dependence between an anatomical form of the growth and histological structure. But secondary changes in the lung are directly dependent on the localization and anatomical form of the growth. In Fontana silverring and diazol rose staining secretory granules in the tumor cells cytoplasm, as a rule, are not revealed, including the cases with carcinoid syndrome.

Variability of Ki67 labeling index in multiple neuroendocrine tumors specimens over the course of the disease.

BACKGROUND: The Ki67-LI is a valid surrogate for biologic behavior of neuroendocrine tumors (NETs), with higher levels associated with aggressive behavior. The World Health Organization (WHO) classifies NETs according to Ki67-LI (G1: <3%; G2 : 3-20%; G3: >20%). Little is known about the evolution of NETs histologic characteristics over the disease course. We sought to evaluate variations in Ki67-LI throughout NETs disease course. METHODS: We retrospectively reviewed the Sunnybrook Odette Cancer Center NET database for patients with multiple pathology specimens. Primary outcome was the WHO NET class based on Ki67-LI for each specimen. We assessed change in WHO class between specimens. RESULTS: Forty-three patients were retrieved, of which 39 had specimens from the primary tumor and a metastatic focus, and 4 had specimens from multiple metastatic foci. Sixteen (37.0%) were identified with Ki67-LI falling in different WHO classes on distinct biopsies. For 12 (75.0%) of those 16 patients, Ki67-LI showed enough variability for WHO class to be upstaged: 5 (31%) from G1 to G2, 2 (13%) from G2 to G3, and 5 (31%) from G1 to G3. CONCLUSION: When multiple pathology specimens were available, Ki67-LI varied throughout NETs disease course, with a majority of cases upgraded to a higher WHO class. If confirmed, this finding may have implications in how neuroendocrine tumors are monitored and treated. Further research is warranted to confirm these findings, understand better the underlying mechanisms of Ki67 variability, and define its relationship to prognosis.

Endobronchial lipomatous tumors: clinicopathologic analysis of 12 cases with molecular cytogenetic evidence supporting classification as "lipoma".

Lipomatous lesions rarely involve the bronchial tree, and detailed morphologic and molecular cytogenetic analysis of these tumors is lacking. The clinicopathologic features of 12 endobronchial lipomatous neoplasms were studied, with ancillary fluorescence in situ hybridization performed in subsets of cases for CPM, which is amplified in atypical lipomatous tumors/well-differentiated liposarcomas (ALT/WDL), and HMGA1 and HMGA2, which are often rearranged in lipomas. The cases occurred predominately in older men (91%) (age range 44 to 80 y, mean 65 y). Most patients (80%) had a former or current history of heavy smoking (20 to 100 pack-years). Three patients had concurrent pulmonary squamous cell carcinoma, and 1 had a history of multiple lung cancers. Most lesions were small (<2.5 cm) and discovered incidentally. A subset of tumors showed atypical morphologic features that would be suggestive of ALT/WDL in soft tissue sites, including regions of fibrosis and scattered hyperchromatic stromal cells. However, all cases with atypia were CPM negative and behaved in a clinically benign manner. Seven cases were tested for HMGA1 and HMGA2 rearrangement; 4 showed HMGA2 rearrangement, and 1 showed HMGA1 rearrangement, consistent with lipomas. Two cases were negative for HMGA1/2 rearrangements. We conclude that endobronchial lipomatous neoplasms represent lipomas, even in the presence of morphologic features suggestive of ALT/WDL. Ancillary fluorescence in situ hybridization testing may be very valuable in the analysis of these rare tumors, as true ALT/WDL seem to be very rare or nonexistent at this anatomic site.