Spinal extension exercises prevent natural progression of kyphosis.

UNLABELLED: The angle of kyphosis increases with age with the most rapid increase occurring between 50 and 60 years. The progression of kyphosis was prevented in women ages 50-59 years who performed extension exercises three times a week for one year. INTRODUCTION: The purpose of this study was to (1) measure the progression of the angle of kyphosis with age and (2) determine whether spinal extension exercises prevent progression of hyperkyphosis in women 50-59 years of age. METHOD: Part 1: Cross-sectional study of changes in posture with age, determined by measuring spinal curves in 250 women 30-79 years of age. Part 2: One-year prospective, descriptive analysis of the effect of extension exercises on posture in women 50-59 years of age. Depth of the cervical curve (CD), area under the thoracic curve (TA), and height were measured using a device developed at Kansas University Medical Center. Changes in CD and TA in women compliant with extension exercises were compared to those in non-compliant women. RESULTS: Kyphosis increases with age in healthy women, with the greatest difference observed between women 50 and 59 years of age. The progression of kyphosis was greater in women who did not perform extension exercises compared to those who performed extension exercises three times per week for 1 year. The difference in change in CD and TA between the two groups was highly significant (CD p = .0001, TA p = .0001). CONCLUSIONS: Kyphosis increases with age in healthy women. In this study the greatest difference in the angle of kyphosis was observed between the fifth and sixth decade. Exercises which strengthen the extensor muscles of the spine can delay the progression of hyperkyphosis in the group included in this study, i.e., women 50-59 years of age.

EGFR and PDGFR differentially promote growth in malignant epithelioid mesothelioma of short and long term survivors.

BACKGROUND: Malignant pleural mesothelioma (MPM) is an asbestos related tumour difficult to detect early and treat effectively. Asbestos causes genetic modifications and cell signalling events that favour the resistance of MPM to apoptosis and chemotherapy. Only a small number of patients, approximately 10%, survive more than 3 years. The aim of our study was to assess possible differences within signalling pathways between short term survivors (survival <3 years; STS) and long term survivors (survival >3 years; LTS) of MPM. METHODS: 37 antibodies detecting proteins engaged in cell signalling pathways, enforcing proliferation, antiapoptosis, angiogenesis and other cellular activities were investigated by tissue microarray (TMA) technology. RESULTS: Epidermal growth factor receptor (EGFR) was expressed stronger in LTS whereas platelet derived growth factor receptor (PDGFR) signalling was more abundant in STS. Expression of TIE2/Tek, a receptor for tyrosine kinases involved in angiogenesis, was differentially regulated via PDGFR and thus is more important in STS. Antiapoptosis was upregulated in STS by signal transducer and activator of transcription 1 (STAT1)-survivin and related molecules, but not in LTS. Our study provides novel insights into the regulatory mechanisms of signalling pathways in MPM, which differentially promote tumour growth in LTS and STS. CONCLUSION: We have demonstrated that small scale proteomics can be carried out by powerful linkage of TMA, immunohistochemistry and statistical methods to identify proteins which might be relevant targets for therapeutic intervention.

Is high-grade adenomatous hyperplasia an early bronchioloalveolar adenocarcinoma?

Atypical adenomatous hyperplasia (AAH) is a probable forerunner of bronchioloalveolar carcinoma (BAC) and pulmonary adenocarcinoma (AC) of mixed type. The present study analysed four low-grade AAHs, 13 high-grade AAHs, two BACs, nine mixed ACs, and one squamous cell carcinoma derived from 13 patients using comparative genomic hybridization. The average number of chromosomal aberrations was 1.2 in low-grade AAH, 9.6 in high-grade AAH, and 12.5 in AC. A high degree of overlap of genetic changes was found in high-grade AAH, BAC, and AC within individual patients. The high number of aberrations and the degree of shared aberrations found in high-grade AAH and AC raises questions about the separation of these two entities. In addition, in view of the monoclonal origin of multiple foci within the same patient, AAH may not be a precursor of AC in some cases, but rather may represent intraepithelial spread.

Chromosomal aberrations in a series of large-cell neuroendocrine carcinomas: unexpected divergence from small-cell carcinoma of the lung.

Large-cell neuroendocrine carcinoma (LCNEC) and small-cell lung cancer (SCLC) are high-grade neuroendocrine tumors of the lung. Despite different morphologic appearances, loss of heterozygosity and oncogene studies on LCNEC to date suggest genetic similarities. We analyzed 13 LCNEC and 5 mixed SCLC/LCNEC tumors by comparative genomic hybridization and subsequently compared our results with previously published data on 32 SCLCs. Comparison with SCLC showed several shared chromosomal aberrations, specifically losses of 3p, 4q, 5q, and 13q and gains of 5p. However, these aberrations are no special feature of neuroendocrine lung tumors but can also be found in other high-grade lung carcinomas. From this point of view, genetic similarities of LCNEC and SCLC are less important than the nonrandom changes that differ between these 2 tumor types. A gain of 3q observed in 66% of all SCLCs was detected only once in the LCNEC group. In contrast to the pure LCNEC, all mixed types with a SCLC component had a gain of 3q. Gains of 6p occurred more frequently in LCNEC. Deletions of 10q, 16q, and 17p were less frequent in LCNEC than in SCLC.

Olefin metatheses in metal coordination spheres: versatile new strategies for the construction of novel monohapto or polyhapto cyclic, macrocyclic, polymacrocyclic, and bridging ligands.

The broad applicability of the title reaction is established through studies of neutral and charged, coordinatively saturated and unsaturated, octahedral and square planar rhenium, platinum, rhodium, and tungsten complexes with cyclopentadienyl, phosphine, and thioether ligands which contain terminal olefins. Grubbs' catalyst, [Ru(=CHPh)(PCy3)2(Cl)2], is used at 2-9 mol% levels (0.0095-0.00042 M, CH2-Cl2). Key data are as follows: [(eta5-C5H4(CH2)6CH=CH2)Re(NO)(PPh3)-(CH3)], intermolecular metathesis (95 %); [(eta5-C5H5)Re(NO)(PPh3)(E(CH2CH=CH2)2)]+ TfO (E=S, PMe, PPh), formation of five-membered heterocycles (96-64%; crystal structure E = PMe); [(eta5-C5Me5)Re(NO)(PPh((CH2)6CH=CH2)2)(L)]n+ nBF4-(L/n = CO/1, Cl/0), intramolecular macrocyclization (94-89%; crystal structure L= Cl); fac-[(CO)3Re(Br)(PPh2(CH2)6CH=CH2)2] and cis-[(Cl)2Pt(PPh2(CH2)6CH=CH2)2], intramolecular macrocyclizations (80-71%; crystal structures of each and a hydrogenation product); cis-[(Cl)2Pt(S(R)(CH2)6CH= CH2)2], intra-/intermolecular macrocyclization (R=Et, 55%/24%; tBu, 72%/ <4%); trans-[(Cl)(L)M(PPh2(CH2)6CH=CH2)2] (M/L = Rh/CO, Pt/C6F5) intramolecular macrocyclization (90-83%; crystal structure of hydrogenation product, M=Pt); fac-[W(CO)3(PPh((CH2)6CH=CH2)2)3], intramolecular trimacrocyclization (83 %) to a complex mixture of triphosphine, diphosphine/ monophosphine, and tris(monophosphine) complexes, from which two isomers of the first type are crystallized. The macrocycle conformations, and basis for the high yields, are analyzed.

Prognostic significance of percentage of bronchioloalveolar pattern in adenocarcinomas of the lung.

Bronchioloalveolar (BA) carcinoma of the lung is considered to have a better prognosis than that of common adenocarcinomas of the lung. However, a minor component of the BA pattern is common in many lung adenocarcinomas and the criteria for designating an adenocarcinoma as BA are not well defined. We assessed the clinicopathologic features of 238 cases of lung adenocarcinoma with a partial or predominant BA pattern. Tumors were classified as BA if more than 75% of the tumor had a BA growth pattern. In other words, the tumor grew along pre-existing lung structures without invasion or destruction of parenchyma. Tumors with 50% to 75% BA pattern were considered mixed and tumors with less than 50% BA pattern were designated as solid/acinar (S/A). Fixed, paraffin-embedded tissue sections of each neoplasm were also assessed using immunohistochemical methods with a panel of antibodies specific for p53, retinoblastoma protein, p16, cyclin D1, and cyclin E, and the results were correlated with clinical and pathologic parameters. Our results show that the 5-year survival rate of patients with BA and mixed tumors, 63% and 60%, respectively, was significantly better than that of patients with S/A tumors (P =.026). Patients with BA tumors were more frequently women (55.9%) compared with patients with mixed (48.3%) and S/A (43.8%) tumors. Bronchioloalveolar and mixed tumors were similarly associated with tobacco use, 88.2% and 85%, respectively; slightly less than S/A tumors (93.8%). Clinical and pathologic parameters did not correlate with immunohistochemical results. In conclusion, patients with BA or mixed tumors have similar 5-year survival, better than that of patients with S/A tumors, suggesting that adenocarcinomas can be designated as BA when at least 50% of the tumor has a BA pattern.

Relationship between Epstein-Barr virus and lymphoepithelioma-like carcinoma of the lung: a clinicopathologic study of 6 cases and review of the literature.

Lymphoepithelioma-like carcinoma (LELC) is a rare form of lung cancer, usually encountered in Chinese patients. Similar to nasopharyngeal carcinoma, LELC of the lung is strongly associated with Epstein-Barr virus (EBV) infection in Asian patients, but there is controversy over whether an association exists in patients from Western countries. To determine whether such a relationship exists, we retrospectively studied 6 cases of primary LELC of the lung, all of which were in Western patients. There were 4 men and 2 women, ranging in age from 49 to 75 years. The tumors ranged from 1 to 4.5 cm in diameter. Four patients had stage I disease, 1 had stage IIb disease, and 1 had stage IIIa disease. All patients are alive without evidence of disease with a follow-up of 18 to 30 months. Formalin-fixed, paraffin-embedded tissue was stained with hematoxylin-eosin for routine evaluation and immunostained for keratin and leukocyte common antigen (LCA). LCA staining was performed to exclude large-cell lymphoma. Immunoperoxidase staining (1:500 clone CS1-4; Dako, Carpinteria, CA) and in situ hybridization were performed to detect EBV. Tumors consisted of solid nests of undifferentiated tumor cells in a syncytial arrangement surrounded by heavy lymphoplasmacytic infiltrate. Tumor cells stained positively for keratin but negative for LCA. All 6 cases were negative for EBV, suggesting no association between EBV and LELC in the Western population.

Atypical adenomatous hyperplasia of the lung: a probable forerunner in the development of adenocarcinoma of the lung.

An increasingly large body of work suggests that atypical adenomatous hyperplasia (AAH) of the lung may be a forerunner of pulmonary adenocarcinoma. Recognizing this fact, the World Health Organization now acknowledges the existence of AAH while noting difficulties that may be encountered in distinguishing AAH from the nonmucinous variant of bronchioloalveolar carcinoma. Regrettably, a universally acceptable definition of morphologic criteria for the diagnosis of AAH has not been achieved. This review of the literature examines the epidemiology, gross appearance, light microscopic findings, morphometry, immunohistochemistry, and molecular features of AAH and suggests a set of histopathologic features that may help the practicing pathologist identify this intriguing lesion. These features include the following: irregularly bordered focal proliferations of atypical cells spreading along the preexisting alveolar framework; prominent cuboidal to low columnar alveolar epithelial cells with variable degree of atypia but less than that seen in adenocarcinoma; increased cell size and nuclear-cytoplasmic ratio with hyperchromasia and prominent nucleoli, generally intact intercellular attachment of atypical cells with occasional empty-looking spaces between them without high cellularity and without tufting or papillary structures; and slight thickening of the alveolar walls on which the AAH cells have spread, with some fibrosis but without scar formation or significant chronic inflammation of the surrounding lung tissue. Several lines of evidence indicate that AAH is a lesion closely associated with adenocarcinoma of the lung, suggesting AAH may be involved in the early stage of a complex multistep carcinogenesis of pulmonary adenocarcinoma.

The expression of cyclins D1 and E in predicting short-term survival in squamous cell carcinoma of the lung.

Cyclins D1 (cD1) and E (cE) are G1 phase cyclins believed to participate in the pathogenesis of malignancy. Overexpression of cD1 has been reported to influence prognosis in squamous cell carcinomas (SCC) of the larynx, but was not significant in a limited study of non-small cell lung cancers (NSCLC). Altered expression of cE has been proposed as another potential prognostic marker in malignancy but its possible role in NSCLC has not been elucidated. In order to determine the prognostic value of cD1 and cE in NSCLC, paraffin-embedded sections of 467 NSCLC were immunostained with monoclonal antibody to cD1 (1:500, PharMingen, San Diego, CA) and 400 NSCLC with MA to cE (1:2500, PharMingen) using an enhanced sensitivity avidin-biotin complex technique. The number of tumor cells with nuclear and/or cytoplasmic immunopositivity was graded on a scale of: 0 = less than 1%, 1 = 1 to 10%, 2 = 10 to 25%, 3 = 25 to 50%, 4 = 50 to 75%, 5 = more than 75%. Results were correlated with survival by Kaplan-Meier survival plot using Stat-View software (Abacus Concepts, Berkeley, CA). Overall, 426 NSCLC with cD1 and 360 NSCLC with cE had adequate follow-up (median, 76 mo) for survival analysis. Both cyclins independently showed significance in prognosis of SCC but not other cell types. For cD1, absence of immunostaining was associated with worse prognosis than any immunopositivity for all stages of SCC (P = .025). For cE, Stage I and II SCC with less than 50% immunopositivity had a worse prognosis (P = .029). Of 70 Stage I and II SCC immunostained for both monoclonal antibodies, 55% of patients with tumors that demonstrated both absence of cD1 staining and cE immunopositivity in less than 50% of cells were dead at 5 years compared to 35% of patients with tumors that demonstrated positive staining with cD1 and cE immunopositivity in more than 50% of cells. These results strongly suggest cD1 and cE can independently predict prognosis in early stage SCC. Worse prognosis was associated with loss of expression, consistent with mechanisms other than overexpression of these cyclins in the progression of SCC.

The separation of benign and malignant mesothelial proliferations.

The separation of benign from malignant mesothelial proliferations has emerged as a major problem in the pathology of the serosal membranes. For both epithelial and spindle cell mesothelial processes, true stromal invasion is the most accurate indicator of malignancy, but stromal invasion is often difficult to assess, especially in small biopsies. In the pleural cavity, deep penetration of a thickened and fibrotic pleura or penetration of mesothelial cells into the fat of the chest wall are good indicators of malignancy; however, superficial entrapment of mesothelial cells and glands by organizing effusions is common in benign reactions and needs to be distinguished from invasion. In the peritoneal cavity, invasion of fat or of organ walls is again the most reliable indicator of malignancy, but entrapment of benign cells in organizing granulation tissue or between fat lobules is frequent and confusing. Proliferations confined to the pleural or peritoneal space, particularly linear arrays of atypical mesothelial cells on the free surface, should not be called malignant in the absence of unequivocal invasion. Cytologic atypia is often not helpful in separating benign from malignant reactions, because benign processes are commonly atypical and mesotheliomas are often deceptively monotonous. Densely packed mesothelial cells within the pleural space are frequent in benign reactions, but densely packed mesothelial cells within the stroma favor a diagnosis of malignancy. Organizing effusions (fibrous pleurisy) typically show zonation with high cellularity and cytologic atypia toward the pleural space and increasing fibrosis with decreasing cellularity and lesser atypia toward the chest wall, whereas sarcomatous (including desmoplastic) mesotheliomas do not demonstrate this type of zonation. Elongated capillaries perpendicular to the pleural surface are seen in organizing effusions but are not a feature of sarcomatous mesotheliomas. The combination of a paucicellular storiform pattern, plus invasion of the stroma (including fat and adjacent tissues), or bland necrosis, overtly sarcomatous foci, or distant metastases, is required for the diagnosis of desmoplastic mesothelioma. Necrosis is usually a sign of malignancy but is occasionally seen in benign mesothelial reactions. Keratin staining is useful in indicating the distribution of mesothelial cells, and particularly in demonstrating penetration of mesothelial cells into the stroma or adjacent structures, but is of no help in separating benign and malignant proliferations because both are keratin-positive. Although both p53 and EMA staining have been proposed as markers of mesothelial malignancy, in our experience they are not helpful for the individual case.

Prognostic implications of calbindin-D28k expression in lung cancer: analysis of 452 cases.

Calbindin D28k (Ca-D28k) acts as a buffering system to maintain cellular calcium homeostasis and is thought to play a role in inhibiting apoptosis. The goals of this study were to assess CA-D28k expression in lung carcinomas and to correlate these results with patient survival. A total of 452 lung carcinomas were immunostained with a monoclonal antibody specific for Ca-D28K using an avidin-biotin peroxidase technique. The number of cells with nuclear staining was graded semiquantitatively into one of five groups: 0, fewer than 10%, 10 to 25%, more than 25 to 50%, more than 50 to 75%, and more than 75%. Results were correlated with patient survival using Kaplan-Meier survival curves. A total of 335 of 452 (74%) lung carcinomas were positive for Ca-D28k. There was no statistically significant difference in the prevalence of Ca-D28k expression in tumors of different histologic type. Kaplan-Meier survival analysis revealed that for patients with adenocarcinoma, those with Ca-D28k-positive tumors had a better overall survival than patients with Ca-D28k-negative tumors (P = .036). This difference was also significant for patients with Stages I and II adenocarcinomas (P = .033). No statistically significant difference in prognosis was observed for patients with Stages III and IV adenocarcinomas or for patients with other lung carcinoma types of varying stage. Ca-D28k is commonly expressed in lung carcinomas of all histologic types. For patients with localized adenocarcinoma of the lung, Ca-D28k expression correlated with improved survival. No correlation between Ca-D28k expression and patient survival was found for disseminated adenocarcinoma and for other histologic types of lung carcinoma.

Mycobacterial DNA in recurrent sarcoidosis in the transplanted lung--a PCR-based study on four cases.

Sarcoidosis is a systemic granulomatous inflammation, which may be caused by mycobacteria other than M. tuberculosis complex (MOTT) in one-third of cases. A few cases of recurrent sarcoidosis in the transplanted lung have been reported. However, mycobacteria have been excluded by acid-fast stains only. We investigated four cases of recurrent sarcoidosis in lung transplant patients. Using PCR for the insertion sequence 6110 of Mycobacterium tuberculosis complex and a second PCR for the mycobacterial chaperonin (65-kDa antigen coding sequence), we looked for mycobacterial DNA. In three cases sequence analysis was also performed. One patient was negative for mycobacterial DNA in explanted, but positive for M. tuberculosis DNA in transplanted lung, qualifying this case as M. tuberculosis infection in the transplant. Three patients were negative for M. tuberculosis DNA, but were positive for MOTT-DNA in both explanted and transplanted lungs. In these three patients sequence identity of the amplified sequences before and after transplantation was proven, which rules out mycobacteriosis. Recurrent sarcoidosis does occur, but can only be proven by the exclusion of mycobacterial DNA. In cases of recurrent MOTT-DNA-positive sarcoidosis the diagnosis cannot be confirmed except by proof of sequence identity. Probably MOTT-DNA-positive sarcoidosis is more likely to recur in a transplanted lung.

Unilocular retroperitoneal cyst of mesothelial origin presenting as a renal mass.

We report the first 2 cases, to our knowledge, of retroperitoneal cysts with features of mesothelial differentiation that clinically mimic renal masses. The first lesion occurred in a 71-year-old man who presented with flank pain. Ultrasound and magnetic resonance imaging studies showed a unilocular cystic structure arising from the upper pole of the left kidney. The second lesion was in a 44-year-old woman who presented with left flank pain. Imaging studies revealed an 8-cm hemorrhagic cyst at the lower pole of the left kidney. Histologic examination of the nephrectomy specimens in each case revealed a unilocular cyst with intracystic and pericystic hemorrhage. In each case, the cyst was lined by a single layer of cells with ample eosinophilic cytoplasm and benign nuclear features without mucinous or müllerian differentiation. Histochemical staining showed Alcian blue positivity on the cell surface, which was sensitive to hyaluronidase digestion. Intracytoplasmic mucin, however, was not detected. Immunostaining showed that the cyst lining cells were positive for keratin, vimentin, HBME-1, WT1, and thrombomodulin but negative for carcinoembryonic antigen, B72.3, Leu-M1, and BerEP4. The first case was positive for calretinin, whereas the second was negative. These findings support the mesothelial nature of the cysts.

Differential expression of thyroid transcription factor 1 in small cell lung carcinoma and Merkel cell tumor.

The distinction between metastatic small cell lung carcinoma (SCLC) and Merkel cell tumor is difficult by routine histology, prompting the search for specific markers that could separate these neoplasms. Thyroid transcription factor 1 (TFF-1) is a homeodomain containing transcription factor expressed in the normal airway epithelium. The expression of TTF-1 has also been shown in adenocarcinomas and small cell carcinomas of the lung. However, the utility of TTF-1 to differentiate between SCLC and Merkel cell tumor has not yet been investigated. In this study, paraffin sections of 36 SCLCs and 21 Merkel cell tumors were analyzed for the presence of immunoreactive TTF-1 and cytokeratin 20 (CK20), a marker previously demonstrated in Merkel cell tumors. Monoclonal TTF-1 and CK20 antibodies were used with a biotin-streptavidin detection system. Immunostaining for TTF-1 was observed in 97% of SCLCs and in no Merkel cell tumors. Immunoreactivity for CK20 was demonstrated in 76% of Merkel cell tumors and 3% of SCLCs. These data indicate that TTF-1 is a sensitive (97%) and specific (100%) marker for SCLCs and can be used to differentiate SCLCs from Merkel cell tumors.

Differential retinoblastoma and p16(INK4A) protein expression in neuroendocrine tumors of the lung.

BACKGROUND: Neuroendocrine neoplasms of the lung represent a wide spectrum of phenotypically and biologically distinct entities. Their histopathologic diagnosis, which carries therapeutic and prognostic significance, may sometimes be difficult because of their overlapping features. We previously demonstrated that large cell neuroendocrine carcinomas (LCNECs) and small cell lung carcinomas (SCLCs) failed to show positive nuclear staining of RB protein (RB-), whereas typical and atypical carcinoids (TCs and ACs) showed nuclear RB immunostaining (RB+). METHODS: In the current study, a series of 58 surgically resected lung tumors, of which 33 tumors were initially diagnosed as SCLCs and 25 as TCs or ACs, were studied for RB and p16 protein expression by immunohistochemistry. They were also reviewed for their pathologic diagnosis; the reviewers were blinded to the RB and p16 protein status. RESULTS: Nineteen tumors were diagnosed as TCs, 5 as ACs, 7 as LCNECs, and 27 as SCLCs. Three of seven LCNECs were RB+, whereas the other four were RB-. In contrast, all 19 TCs were RB+ and all 27 SCLCs were RB-. In addition, two of five ACs were RB+, whereas the other three were RB-. Interestingly, all 3 RB+ LCNECs and the 1 RB+ AC tested failed to show nuclear staining of p16 protein in any tumor cells (p16-), although some normal stromal cells showed nuclear staining of p16 protein (p16+) as positive internal controls, indicating loss of p16 function in these tumors. It is also noteworthy that the three RB+ LCNECs were initially diagnosed as SCLCs and one of the RB- ACs was initially considered a TC. With the exception of TCs, tumors were significantly more prevalent among heavy smokers with >20 pack-years compared with nonsmokers and light smokers with < or = 20 pack-years (P < 0.01). CONCLUSIONS: These findings suggest that all SCLCs and LCNECs have abnormalities in the p16:RB pathway, as do at least certain ACs, whereas the p16:RB pathway is normal in TCs.

Oncocytic mucoepidermoid carcinoma of the trachea.

We report a rare case of an oncocytic mucoepidermoid carcinoma of the trachea, which presented in a 78-year-old woman with hemoptysis. Oncocytic cells comprised the majority of this low-grade lesion and demonstrated granular cytoplasmic phosphotungstic acid-hematoxylin staining as well as strong immunohistochemical reactivity to antimitochondrial antibody. Most tracheobronchial tumors with oncocytic change are carcinoid tumors. To our knowledge, this is the first oncocytic mucoepidermoid carcinoma of the trachea reported. This diagnosis was facilitated by histochemical and immunohistochemical studies.

Utility of surfactant protein B precursor and thyroid transcription factor 1 in differentiating adenocarcinoma of the lung from malignant mesothelioma.

Differentiation of malignant mesothelioma from adenocarcinoma, particularly from a lung primary, remains a difficult diagnostic problem. Surfactant protein B precursor (pro-SP-B) and thyroid transcription factor 1 (ITF-1) are expressed selectively in the normal respiratory epithelium and in adenocarcinomas of the lung. In this study, we evaluated the utility of pro-SP-B and ITF-1 in distinguishing pulmonary adenocarcinomas and malignant mesotheliomas. Immunoreactivity for pro-SP-B and TTF-1 was examined in paraffin sections of 370 primary lung carcinomas (208 adenocarcinomas, 101 squamous cell carcinomas, and 61 large cell carcinomas) and 95 malignant mesotheliomas, using a pro-SP-B antiserum and a monoclonal TTF-1 antibody with a biotin-streptavidin detection system. Immunostaining for pro-SP-B was detected in 57% of adenocarcinomas, and 20% of large cell carcinomas. Immunoreactivity for TTF-1 was shown in 76% of adenocarcinomas and 26% of large cell carcinomas. Malignant mesotheliomas and squamous cell carcinomas did not stain with either antibody. The expression of pro-SP-B and TTF-1 in adenocarcinomas of the lung but not in malignant mesotheliomas shows that pro-SP-B and TTF-1 staining is useful in differentiating these neoplasms.

Metastatic carcinoma of the prostate mimicking primary carcinoid tumor of the lung and mediastinum.

Although prostatic carcinomas rarely present as intrathoracic metastases, they may occasionally exhibit clinical and radiographic findings suggestive of a primary pulmonary carcinoid, particularly when they have a cribriform pattern. This report describes three patients who presented with lung and mediastinal neoplasms initially diagnosed as primary carcinoid tumors. These tumors were later proven to be metastatic prostate carcinoma by the use of immunohistochemical studies, including stains for chromogranin, carcinoembryogenic antigen and prostate specific antigen. These findings emphasize the importance of considering metastatic prostate adenocarcinoma in the differential diagnosis of carcinoid or neuroendocrine carcinoma with a cribriform pattern.

The diagnosis of desmoplastic malignant mesothelioma and its distinction from fibrous pleurisy: a histologic and immunohistochemical analysis of 31 cases including p53 immunostaining.

We studied 31 patients with fibrotic pleural lesions and classified them as desmoplastic malignant mesothelioma (DMM) or fibrous pleurisy (FP) using predetermined histologic criteria, including a paucicellular fibrotic pleural lesion with a storiform pattern or the "patternless pattern " of Stout, plus 1 or more of the following: invasion of chest wall or lung, bland necrosis, frankly sarcomatoid areas, and distant metastases. Staining for p53 was performed in 22 cases. Follow-up was obtained on all cases and compared with the histologic diagnoses. For 24 cases, the consensus diagnosis was DMM; 19 of these displayed frankly sarcomatoid areas, 16 showed invasion, and 8, bland necrosis. Of the 24, 23 patients died of disease and 1 was alive with disease. The remaining 7 cases were classified as FP, and all were alive without disease. The concordance among 3 pathologists using the criteria was excellent. Staining for p53 was more common in DMM than in FP, but the difference was not statistically significant. The concordance in interpreting the p53 stains by the same 3 pathologists was moderate. The distinction between DMM and FP in a predominantly fibrotic pleural lesion can be made in most cases with adequate sampling and the use of specific criteria.