Endobronchial Biopsy Specimens Research Articles

Fluticasone propionate induced alterations to lung function and the immunopathology of asthma over time

BACKGROUNDInhaled corticosteroids are the most widely used treatment for asthma, a disease characterised by both functional and immunopathological abnormalities. This study investigated the relative effects of inhaled corticosteroids on these...

Airway inflammation and severe asthma: abstract and commentary.

The role of inflammation in the pathogenesis of severe asthma chronically treated with high doses of glucocorticoids is poorly understood. Despite this, treatment has been aimed at advancing anti-inflammatory and immunomodulator therapy. This study was designed to evaluate both the presence and type of airway inflammation in patients with severe asthma. A prospective bronchoscopic study evaluated 14 severe, high-dose oral glucocorticoid dependent asthmatics. Bronchoalveolar lavage fluid was analyzed for cytology and inflammatory mediators. Endobronchial and transbronchial biopsies were performed in selected patients for morphometric evaluation of macrophage/monocytes, neutrophils, eosinophils and lymphocytes. These results were compared with lavage and endo- and transbronchial biopsy studies in normal controls and patients with moderate asthma. The concentration of eosinophils in bronchoalveolar lavage fluid was highest in the moderate asthmatics not on glucocorticoids, with very little difference between normal controls and severe asthmatics (significant difference among the groups, P=0.007). In contrast, the severe asthmatics demonstrated a twofold higher concentration of neutrophils in lavage than either the mild-moderate asthmatics, or the normal controls (P=0.032 among the groups, P<0.05 between the severe asthmatics and both controls). Similar results were obtained in the endobronchial and transbronchial biopsy specimens, which consistently showed significantly higher numbers of neutrophils in the severe asthmatics than in the control groups. The eicosanoid mediators, thromboxane and leukotriene B4, were also highest in the severe asthma group (differences among the groups, P=0.019 and P=0.023, respectively). These findings suggest that inflammation remains in severe symptomatic asthmatics despite treatment with high dose glucocorticoids which may be due to the severity of disease, glucocorticoid treatment, or other as yet undefined factors.

Changing cytologic and histologic utilization patterns in the diagnosis of 515 primary lung malignancies

BACKGROUND Over the last decade, the specimen types used to diagnose primary pulmonary malignancies at the authors' institution have changed in terms of their frequency of submission. METHODS The authors reviewed pathologic findings in 216 cases of primary lung carcinoma diagnosed during the years 1983-1984 (earlier period) and compared these with the findings in 299 cases diagnosed during the years 1993-1994 (later period). RESULTS The total number of transbronchial fine-needle aspirates (TBNA) increased from 13 to 206 (P < 0.0001), the total number of sputum (SP) samples declined from 236 to 36 (P < 0.0001), and the total number of forceps endobronchial biopsy (FBX) specimens increased from 61 to 119 (P = 0.0023) between the earlier period and the later period. The positivity rate of some specimen types was similar for these two periods (transthoracic percutaneous fine-needle aspirate [PFNA], 95% and 97%; bronchial washings, 61% and 60%), but the positivity of others improved by a statistically nonsignificant degree (bronchial brushings, 61-71%; FBX, 59-69%). The positivity of TBNA was 57% in 1993-1994. The collective positivity of bronchoscopic cytology specimens was significantly higher than simultaneous FBX during both periods (P = 0.0032), but bronchoscopic histology and cytology were complementary. The positivity of fiberoptic bronchoscopy (FOB) improved significantly, from 72% in 1983-1984 to 85% in 1993-1994 (P = 0.0059). During both periods, an equivalent proportion of patients were subjected to each of 3 major invasive sampling procedures (FOB, 70%; PFNA, 20%; open surgical biopsy, 10%). Fifteen patients were diagnosed by SP cytology without an invasive procedure in 1983-1984, but none were diagnosed by SP cytology in 1993-1994. CONCLUSIONS TBNA and increased utilization of FBX have displaced postbronchoscopy SP examination, generating higher positivity for FOB. Bronchoscopic cytology and histology were complementary, but radiologically guided fine-needle aspiration was the procedure with the highest positivity. Cancer (Cancer Cytopathol) 1997; 81:105-15. © 1997 American Cancer Society.

Bronchoscopic evaluation of severe asthma. Persistent inflammation associated with high dose glucocorticoids.

The role of inflammation in the pathogenesis of severe asthma chronically treated with high doses of glucocorticoids is poorly understood. Despite this, treatment has been aimed at advancing anti-inflammatory and immunomodulator therapy. This study was designed to evaluate both the presence and type of airway inflammation in patients with severe asthma. A prospective bronchoscopic study evaluated 14 severe, high-dose oral glucocorticoid dependent asthmatics. Bronchoalveolar lavage fluid was analyzed for cytology and inflammatory mediators. Endobronchial and transbronchial biopsies were performed in selected patients for morphometric evaluation of macrophage/monocytes, neutrophils, eosinophils and lymphocytes. These results were compared with lavage and endo- and transbronchial biopsy studies in normal controls and patients with moderate asthma. The concentration of eosinophils in bronchoalveolar lavage fluid was highest in the moderate asthmatics not on glucocorticoids, with very little difference between normal controls and severe asthmatics (significant difference among the groups, p = 0.007). In contrast, the severe asthmatics demonstrated a twofold higher concentration of neutrophils in lavage than either the mild-moderate asthmatics, or the normal controls (p = 0.032 among the groups, p < 0.05 between the severe asthmatics and both controls). Similar results were obtained in the endobronchial and transbronchial biopsy specimens, which consistently showed significantly higher numbers of neutrophils in the severe asthmatics than in the control groups. The eicosanoid mediators, thromboxane and leukotriene B4, were also highest in the severe asthma group (differences among the groups, p = 0.019 and p = 0.023, respectively). These findings suggest that inflammation remains in severe symptomatic asthmatics despite treatment with high dose glucocorticoids which may be due to the severity of disease, glucocorticoid treatment, or other as yet undefined factors.

Upregulation of αGM-CSF-receptor in nonatopic asthma but not in atopic asthma

Background: Intrinsic asthma is characterized by an increased number of activated eosinophils and macrophages and an increased expression of the hematopoietic growth factor granulocyte-macrophage colony-stimulating factor (GM-CSF) in the bronchial mucosa. Objective: This study was carried out to investigate the expression of αGM-CSF receptor (αGM-CSFr) messenger RNA and protein in the bronchial mucosa of patients with intrinsic or atopic asthma and of control subjects and to correlate the expression of αGM-CSFr to the number of EG2 + cells (eosinophils) and CD68 + cells (macrophages) and pulmonary function. Methods: Nineteen patients with stable asthma (9 with atopic and 10 with intrinsic asthma) and 22 normal control subjects (12 atopic and 10 nonatopic subjects) were recruited, and FEV 1 (percent predicted) and PC 20 were measured before bronchoscopy. Endobronchial biopsy specimens were obtained and examined for membrane-bound αGM-CSFr by using in situ hybridization and immunocytochemistry. Results: αGM-CSFr mRNA- and protein-positive cells were identified in biopsy specimens from all four groups studied. There was no significant difference in the number of cells expressing αGM-CSFr mRNA and protein in patients with atopic asthma compared with atopic and nonatopic control subjects. However, the numbers of αGM-CSFr mRNA- and protein-positive cells were significantly higher in nonatopic patients with asthma compared with atopic patients with asthma and atopic and nonatopic control subjects ( p < 0.001). In the patients with intrinsic asthma, the number of αGM-CSFr mRNA-positive cells per millimeter of basement membrane correlated with numbers of CD68 + cells ( r 2 = 0.87, p < 0.001) but not with EG2 + cells, and colocalization studies demonstrated that 80% of the cells expressing αGMCSFr mRNA were CD68 +. The expression of GM-CSF was also significantly increased in patients with intrinsic asthma compared with those with atopic asthma and control subjects ( p < 0.05). In addition, in intrinsic asthma, there was a correlation between αGM-CSFr mRNA and FEV 1 ( r 2 = 0.61, p < 0.05). Conclusion: These results demonstrate that elevated numbers of cells expressing αGM-CSFr can be detected in nonatopic asthma but not in atopic asthma and suggest that this increased expression is predominantly macrophage-associated and may play an important pathophysiologic role in intrinsic asthma. (J Allergy Clin Immunol 1997;99:666-72.)

Changing cytologic and histologic utilization patterns in the diagnosis of 515 primary lung malignancies

Over the last decade, the specimen types used to diagnose primary pulmonary malignancies at the authors' institution have changed in terms of their frequency of submission. The authors reviewed pathologic findings in 216 cases of primary lung carcinoma diagnosed during the years 1983-1984 (earlier period) and compared these with the findings in 299 cases diagnosed during the years 1993-1994 (later period). The total number of transbronchial fine-needle aspirates (TBNA) increased from 13 to 206 (P < 0.0001), the total number of sputum (SP) samples declined from 236 to 36 (P < 0.0001), and the total number of forceps endobronchial biopsy (FBX) specimens increased from 61 to 119 (P = 0.0023) between the earlier period and the later period. The positivity rate of some specimen types was similar for these two periods (transthoracic percutaneous fine-needle aspirate [PFNA], 95% and 97%; bronchial washings, 61% and 60%), but the positivity of others improved by a statistically nonsignificant degree (bronchial brushings, 61-71%; FBX, 59-69%). The positivity of TBNA was 57% in 1993-1994. The collective positivity of bronchoscopic cytology specimens was significantly higher than simultaneous FBX during both periods (P = 0.0032), but bronchoscopic histology and cytology were complementary. The positivity of fiberoptic bronchoscopy (FOB) improved significantly, from 72% in 1983-1984 to 85% in 1993-1994 (P = 0.0059). During both periods, an equivalent proportion of patients were subjected to each of 3 major invasive sampling procedures (FOB, 70%; PFNA, 20%; open surgical biopsy, 10%). Fifteen patients were diagnosed by SP cytology without an invasive procedure in 1983-1984, but none were diagnosed by SP cytology in 1993-1994. TBNA and increased utilization of FBX have displaced postbronchoscopy SP examination, generating higher positivity for FOB. Bronchoscopic cytology and histology were complementary, but radiologically guided fine-needle aspiration was the procedure with the highest positivity.

Changing cytologic and histologic utilization patterns in the diagnosis of 515 primary lung malignancies

BACKGROUND Over the last decade, the specimen types used to diagnose primary pulmonary malignancies at the authors' institution have changed in terms of their frequency of submission. METHODS The authors reviewed pathologic findings in 216 cases of primary lung carcinoma diagnosed during the years 1983-1984 (earlier period) and compared these with the findings in 299 cases diagnosed during the years 1993-1994 (later period). RESULTS The total number of transbronchial fine-needle aspirates (TBNA) increased from 13 to 206 (P < 0.0001), the total number of sputum (SP) samples declined from 236 to 36 (P < 0.0001), and the total number of forceps endobronchial biopsy (FBX) specimens increased from 61 to 119 (P = 0.0023) between the earlier period and the later period. The positivity rate of some specimen types was similar for these two periods (transthoracic percutaneous fine-needle aspirate [PFNA], 95% and 97%; bronchial washings, 61% and 60%), but the positivity of others improved by a statistically nonsignificant degree (bronchial brushings, 61-71%; FBX, 59-69%). The positivity of TBNA was 57% in 1993-1994. The collective positivity of bronchoscopic cytology specimens was significantly higher than simultaneous FBX during both periods (P = 0.0032), but bronchoscopic histology and cytology were complementary. The positivity of fiberoptic bronchoscopy (FOB) improved significantly, from 72% in 1983-1984 to 85% in 1993-1994 (P = 0.0059). During both periods, an equivalent proportion of patients were subjected to each of 3 major invasive sampling procedures (FOB, 70%; PFNA, 20%; open surgical biopsy, 10%). Fifteen patients were diagnosed by SP cytology without an invasive procedure in 1983-1984, but none were diagnosed by SP cytology in 1993-1994. CONCLUSIONS TBNA and increased utilization of FBX have displaced postbronchoscopy SP examination, generating higher positivity for FOB. Bronchoscopic cytology and histology were complementary, but radiologically guided fine-needle aspiration was the procedure with the highest positivity. Cancer (Cancer Cytopathol) 1997; 81:105-15. © 1997 American Cancer Society.

Immunopathological changes in the airways of stable lung transplant recipients.

BACKGROUND: Pathological obliterative bronchiolitis, characterised by inflammation and occlusion of airways, is a serious complication of lung transplantation. Endobronchial biopsy (EBB) provides a means of examining transplanted airways. This study...

New insights into the pathogenesis of severe corticosteroid-dependent asthma

Severe asthma is characterized by persistent T-cell activation, as demonstrated in both peripheral blood and bronchial mucosa. Endobronchial biopsy specimens of patients with severe, corticosteroid-dependent asthma revealed increased expression of CD25+ on mucosal T cells. Increased immunoreactivity for IL-5 further supports the evidence that the inflammatory response is orchestrated by T H2-type T cells. Peripheral blood eosinophils and total serum IgE levels were increased in the absence of allergen and despite optimal treatment. The chemokine IL-8 may also be an aggravating factor in severe asthma; as well as being a potent chemotactic and activating factor for neutrophils, it may also be chemoattractant for eosinophils. We have recently detected increased levels of free IL-8 in the peripheral blood of patients with chronic severe asthma but not in healthy control subjects or in patients with mild asthma, even after allergen challenge. In patients with severe asthma there may be an imbalance between IL-8 production and the blocking capacity of IL-8 autoantibodies. Higher levels of IL-8 complexed to IgA autoantibody and increased numbers of activated T cells were also found in patients with unstable asthma compared with patients who had severe but stable disease. We conclude that IL-8 may provide an additional marker of asthma severity and corticosteroid responsiveness. (J A LLERGY C LIN I MMUNOL 1996;98:S22-6.)

Expansion of bronchial epithelial cell populations by in vitro culture of explants from dysplastic and histologically normal sites.

The genetic and phenotypic properties of cells which ultimately give rise to carcinoma of the lung are not well defined in part because of unavailability of preneoplastic cells from well-characterized dysplastic sites. In order to expand bronchial epithelial cell populations from patients at high risk for lung cancer, endobronchial biopsy specimens were explanted onto collagen- and fibronectin-coated dishes and cultured in serum-free, chemically defined media. One hundred forty-nine biopsy pairs were obtained from smokers and from healthy volunteers for culture and histologic evaluation. The histologic appearances of mucosa adjacent to the site of the cultured biopsies ranged from normal through varying degrees of noninvasive squamous dysplasia to invasive carcinoma. Confluent monolayers of pure epithelial cells were obtained from 68% of the cultured explants. Sites exhibiting high-grade dysplasia were 51% more likely to yield successful cultures than sites exhibiting normal histology (13 of 14 cultures successful versus 52 of 83 cultures successful, P < 0.02). Cultures had a maximum proliferative life span of 81 days and none of the cultures spontaneously became immortalized. Immunolabeling studies revealed that all cultured epithelial cells, regardless of the in situ histologic appearances of the mucosa at the biopsy site, strongly expressed keratin and epidermal growth factor receptor, weakly expressed transferrin receptor and human folate receptor, and were negative for neural cell adhesion molecule and human leukocyte antigen DR (HLADR). Ploidy and karyotypic analyses were performed in a limited number of explants from normal and dysplastic sites and all were found to be diploid without karyotypic abnormality. We conclude that pure bronchial epithelial cell populations can be routinely expanded from histologically normal and dysplastic sites by tissue culture of biopsy explants and that the expanded cell populations may represent a library of normal and preneoplastic cells which are suitable for immunophenotypic, ploidy, genetic, or functional analyses.

New insights into the pathogenesis of severe corticosteroid-dependent asthma

Severe asthma is characterized by persistent T-cell activation, as demonstrated in both peripheral blood and bronchial mucosa. Endobronchial biopsy specimens of patients with severe, corticosteroid-dependent asthma revealed increased expression of CD25+ on mucosal T cells. Increased immunoreactivity for IL-5 further supports the evidence that the inflammatory response is orchestrated by TH2-type T cells. Peripheral blood eosinophils and total serum IgE levels were increased in the absence of allergen and despite optimal treatment. The chemokine IL-8 may also be an aggravating factor in severe asthma; as well as being a potent chemotactic and activating factor for neutrophils, it may also be chemoattractant for eosinophils. We have recently detected increased levels of free IL-8 in the peripheral blood of patients with chronic severe asthma but not in healthy control subjects or in patients with mild asthma, even after allergen challenge. In patients with severe asthma there may be an imbalance between IL-8 production and the blocking capacity of IL-8 autoantibodies. Higher levels of IL-8 complexed to IgA autoantibody and increased numbers of activated T cells were also found in patients with unstable asthma compared with patients who had severe but stable disease. We conclude that IL-8 may provide an additional marker of asthma severity and corticosteroid responsiveness. (J ALLERGY CLIN IMMUNOL 1996;98:S22-6.)

Endobronchial Needle Aspiration in the Diagnosis of Small-Cell Carcinoma

Endobronchial biopsy specimens of small-cell carcinoma often exhibit extensive crush artifact that precludes definitive diagnosis. Occasionally, cytologic study from the brushings and washings is also nondiagnostic, contributing to the frustration of the bronchoscopist. We reviewed our experience with this problem over the past 4 years. We identified five cases in which an endobronchial needle aspirate proved critical in establishing the diagnosis of small-cell carcinoma. We believe endobronchial needle aspiration is a valuable adjunct in the diagnosis of endobronchial small-cell carcinoma.

The Utility of Fiberoptic Bronchoscopy in the Evaluation of the Solitary Pulmonary Nodule

To determine the value of routine, preoperative, fiberoptic bronchoscopy (FB) for diagnosing and treating patients (pts) with solitary pulmonary nodules (SPNs), we retrospectively reviewed the records of all pts with SPNs undergoing FB at Walter Reed Army Medical Center between January 1986 and December 1989. We defined SPNs radiographically as < or = 6 cm peripheral pulmonary lesions completely surrounded by pulmonary parenchyma. Of 191 charts reviewed, 91 (72 bronchogenic carcinomas [BC], 7 carcinoid tumors, 12 benign) constitute the study population. Fifty-four charts were eliminated because preoperative, clinical-radiologic staging revealed advanced (greater than stage I) BC or extrathoracic malignancy metastatic to the lung (44), the clinicians suspected benign disease and elected medical followup (3), the pt had medically inoperable disease (3), or the pt refused surgery (4). Forty-six charts were incomplete or unavailable. Fiberoptic bronchoscopy revealed one unsuspected vocal cord carcinoma and no occult synchronous BCs. Five pts had submucosal or endobronchial tumors and biopsy specimens showed BC in four of five tumors from which specimens were taken. Four of 66 (6 percent) cytologic evaluations of bronchial brushings or washings diagnosed BC. In pts shown at surgery to have BC, 9 of 30 transbronchial lung biopsy (TBBx) specimens showed BC. Diagnostic yield of TBBx specimens was not improved in the pts who underwent biopsies under fluoroscopic guidance. The 16 FB specimens positive for BC concurred 100 percent with the surgical specimens. The FB findings did not obviate the need for surgery nor alter the surgical stage of BC. A preoperative diagnosis of malignancy did not affect operative time or operative procedure, because many pts required frozen-section biopsy of mediastinal lymph nodes prior to lung resection. At our institution, routine, preoperative FB did not measurably benefit pts with SPNs.

Pathology of asthma and its clinical implications

Although detailed histopathologic studies have described the inflammatory processes present in fatal asthma, until recently the pathology of less severe forms of the disease has been less well understood. Now a series of important studies has extended our understanding of the pathophysiology of mild asthma. Studies that examine sputum or fluid obtained by bronchoalveolar lavage from mildly asthmatic subjects revealed findings consistent with an active inflammatory process within the airways. The histopathologic examination of endobronchial biopsy specimens from stable asthmatic patients has shown that inflammatory cell infiltration of the mucosa is a distinctive feature of mildly asthmatic subjects requiring only intermittent inhaled β-agonist therapy. These studies have also shown that marked tissue disruption may occur early in the natural history of mild asthma. These investigations have demonstrated that asthma is a disease characterized by acute and chronic inflammatory changes within the airways and that in many respects the histopathologic features of mild allergic asthma are similar to those observed in fatal asthma. The therapeutic implications of these findings are that management of mild asthma should be directed toward resolving this inflammatory process. There is now sufficient evidence to suggest that anti-inflammatory drugs such as cromolyn sodium, inhaled corticosteroids, and nedocromil sodium be used earlier in the course of the disease and that the use of these therapeutic agents should not be limited to patients with severe forms of asthma. This may be particularly important in view of the increasing awareness of the potential problems associated with the overreliance on β-agonist therapy in patients with asthma.

Polypoid Endobronchial Lesions: A Manifestation of Bacillary Angiomatosis

Polypoid endobronchial lesions occurred in a patient with acquired immunodeficiency syndrome (AIDS) with recent fever, skin lesions, lymphadenopathy, lung infiltrates, and pleural effusions. His condition improved with antimicrobials and vincristine. After therapy ceased, skin lesions recurred and gastroesophageal mucosal lesions developed. Bacillary angiomatosis was identified during retrospective analysis of skin and endobronchial biopsy specimens.

Primary Endobronchial Actinomycosis in Association with Foreign Body Aspiration

A 66-year-old diabetic man presented with a bilobar pneumonia two months after aspiration of a chicken bone. Flexible fiberoptic bronchoscopy demonstrated a mass in the bronchus intermedius. Histologic examination of endobronchial biopsy specimens revealed bone fragments, vegetable matter, and sulfur granules containing Actinomyces organisms. The patient responded to bronchoscopic removal of the foreign body and penicillin therapy. To our knowledge, the association of actinomycotic infection with an aspirated endobronchial foreign body has not previously been reported.

Eridothelin immunoreactivity of airway epithelium in asthmatic patients

There is extensive pharmacological and physiological evidence that endothelin-1 influences airway calibre. In mammals, endothelin receptors occur on airway smooth muscle, local storage and release of the peptide have been demonstrated, and inhalation of endothelin-1 induces bronchoconstriction. To investigate the relation between endothelins and asthma the expression of this peptide in endobronchial biopsy specimens was examined immunohistochemically with an antiserum against endothelin-1. Biopsy specimens from 17 asthmatic patients and 11 atopic and non-atopic healthy controls revealed striking differences, with endothelin expression being evident in airways epithelium and vascular endothelium in 11 of the 17 asthmatic patients but in only 1 of 11 controls. These results suggest that endothelins may play a part in the exaggerated bronchomotor tone of asthma.

Infiltration of the lower respiratory tract by helper/inducer t lymphocytes in htlv-1-associated adult t-cell leukemia/lymphoma

The human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia/lymphoma (ATLL), a disorder in which periperal blood and multiple organs are infiltrated by malignantly transformed T lymphocytes. We investigated the nature of pulmonary disease in a patient with serologic evidence of HTLV-1 infection. In this case, endobronchial biopsy specimens showed infiltration of the bronchial mucosa by pleomorphic cells exhibiting a high degree of nuclear irregularity. These cells were morphologically identical in appearance to malignant cells found in peripheral blood and infiltrating the dermis, expressed the OKT4/Leu3 phenotype and the receptor for interleukin 2, and, by analogy to gene rearrangement studies on leukemic blood cells, were monoclonal in origin. However, in situ hybridization of endobronchial biopsy specimens with fulllength HTLV-1 probes failed to detect retroviral RNA or proviral DNA. These studies indicate that T lymphocytic involvement of the lower respiratory tract in HTLV-1-associated ATLL is characterized by expression of a malignant phenotype despite the inability to document actual cellular infection with this retrovirus by a molecular hybridization technique.

SUBEPITHELIAL FIBROSIS IN THE BRONCHI OF ASTHMATICS

The epithelial basement membrane and underlying collagen were examined by immunohistochemistry and electron microscopy in endobronchial biopsy specimens from 8 asthmatic and 3 control subjects. There was an excess of interstitial collagens beneath the basement membrane in the asthmatic subjects. There was no evidence of any epithelial contribution to this abnormality, nor was there any correlation with epithelial damage, disease duration, or severity. These findings contradict the long-held notion of basement membrane thickening in asthma and indicate that the subepithelial fibrosis is a result of fibroblast activation rather than bronchial epithelial cell dysfunction.

Neural markers in carcinoma of the lung.

Small cell carcinoma (SCC) is considered to be of neuroendocrine origin. Neurone specific enolase (NSE) and PGP 9.5 are markers of neural and neuroendocrine differentiation. S-100 protein is a marker of glial differentiation. The expression of these markers in endobronchial biopsy and lung tumour resection specimens was studied to see if any diagnostic, prognostic or therapeutic implications would emerge. Zamboni fixed endobronchial tumour biopsy specimens from 20 patients were examined. Twelve of these were cases of SCC and 8 were non-SCC. Of the 12 SCC, 7 were positive for NSE, 6 for PGP 9.5 and 5 for S-100 protein. Cases which showed a positive reaction for NSE had a mean survival of 9.1 months compared with 3.9 months for those with a negative reaction, but the number of cases is too small to assign any statistical significance. There was no difference in survival times between positive and negative reactors for PGP 9.5 and S-100 protein. All 8 cases of non-SCC showed positive reactions to all three markers. Of 32 formalin fixed lung tumour resection specimens 6 were cases of SCC, 25 non-SCC and 1 a chemodectoma. Three of the 6 cases of SCC showed positive staining for NSE, 3 for PGP 9.5 and 1 for S-100 protein. Of the 25 non-SCC, 10 were positive for NSE, 12 for PGP 9.5 and 6 for S-100 protein. The 1 chemodectoma stained positively for all three markers. Neuroendocrine markers are of little value in differentiating SCC from non-SCC. Positive staining for NSE in SCC may be an indicator of prolonged survival but further investigation is required.