The value of immunohistochemistry of pleural biopsy specimens in the differential diagnosis between...

1
Absrracts /Lung Cancer 12 (1995) 265-329 only in 17% of breast carcinomas. The following remarks can bc drawn from this study: (1) some NSCLCs showed immunophcnotypic NE differentiation; (2) among all the markers used, NSE was the most sensitive (sensitivity, 100%) and chromogranin-A the most specific (speciticity, 100%). and (3) NSE and chromogranin-A appear to be the most valuable and useful indicators of probable ncuroendocrine differentiation in lung cpithelial tumors. Comparison of autopsy, clinical and death certificate diagnosis with particular reCeRnce to hug cancer. A View oftbe published data LAX PN. Statistics and Computing Ld, I7 Cedar Road, Sutfon, Surrey AFWS Suppl: 1994;102: l-42. Some clinicians and some epidemiologists appear to be under the illusion that techniques available for the diagnosis of internal diseases such as lung cancer have improved so much that autopsies are not necessary on the bodies of most people who die. Pertly for this reason, pertly for economic reasons and partly because clinicians fear litigation if autopsy shows that they tnxtcd patients for the wrong disease, autopsy rates have been falling in most developed countries. The object ofthe present review was to ascertain how much reliance can reasonably bc put on clinical diagnoses made and death certificates completed in the absence of autopsy data. In the case of lung cancer. high rates of false positive and false negative diagrwscs arc universally prevalent, with biases influencing these rates, so that smokers are more likely to be appropriately investigated for lung cancer, and false negatives are commoner in nonsmokers. All investigators who have compared clinical-based and autopsy-based death certiticates have concluded that higher autopsy rates are nccessaty and the results of one study suggest that a high autopsy rate in a hospital leads to improvements in the accuracy of clinical diagnoses. The extent to which diagnoses on death certificates that are dependent solely on clinical data are seriously inaccurate for internal diseases such as lung cs.nccr should engender caution in all who use mortality data to guide public health policies and to identify and quantify environmental risks to healths. The value of immuaohistocbemistry of pleural biopsy specimens in the differential diagosis between maligoant meaotklioma and metastatic carcinoma Grove A, Paulsen SM. Grcgcrscn M. Instirule of PaAology, tfolstebro Cenhul Hospital, DK-7500 Holslebro. Pathol Res Pratt 1994;190:104l-55. The aim ofthe present shrdywas to evaluate the aid of immune-histochemistry in the differential diagnosis behveen pleural malignant mcsothelioma (MM) and secondary pleural carcinoma in pleural biopsy specimens. A series of MM (epithcliel or biphasie type) (n = 39). and a scrics of secondaly pleural carcinomas (n = 25) were studied with a panel of monoclonal antibodies against Ber-EP4, CEA, and Lcu-MI (CDIS). Considering the markers one, two or three at a time, computer analysis was conducted to identify the immunophenotype with the highest sensitivity and specificity for both MM (n = 39) and sdencxxrcinoma (n = 19). The CWCDlS marker combination had the highest spcciticity @4M = lOOa/.; adenccarcinoma = 82,l%).and wnsitivity(MM = 82. I%;adcnoearcinoma = 100%) considering both categories of turnours. Positive reaction for CEA and/ or CD-1 5 was the best indicator of metastatic adenocarcinoma. Negative reaction for CWCD-I5 and Bcr-EP4KDI5 showed up to bc 100% spccitic for MM. Positive reaction for one, two or even all these antigens, however, occurred in nine tumours predetermined as MM according to their gross appcarancc, and absence ofother primary malignancies at autopsy. Ultrastructural examination (n = 7) of these tumours strongly supported the diagnosis in one case, and did by no means exclude the diagnosis MM in the other six cases. Neither did any of the turnours revcal ultrastructural signs of adenomatous differentiation, and they did not express PAS/diastase resistant globules, amylase or surf&ant. Anti-Bcr- EP4 was the antibody most frequently expressed in MM (n = 8). Until antibodies specitic for MM arc available, the limitation of immunohistochemistry to solve the diagnosis in all casts of pleural malignant tumours has to bc considered Utility ofcytokeratin immunwtaiaiog in separating puhomuy adenw carcinomas frum colonic adenocarcioomas by T S , Calalucc RD. Department ofPafho/ogy Msmuri Universify Medico/ Center, One Hospital Drive. Columbia, MO 65212. Am J Clin Pathol 1994;102:764-7. Adenocarcinomas of uncertain origin arc a frequent problem for surgical pathologists. To determine the utility of immunostaining for cytokeratin 7 and cytokeratin 20 in the separation of pulmonary adcnocarcinomas from colonic adenoearcinomas, we studied routinely processed, forms&-fixed tissue from I5 1 of these tumors using commercially available monoclonsl antibodies and an avidin-biotin immunohistochemical technique. Used alone, neither cytokeratin 7 immunostaining orcytokeratin 20 immunostaining reliably separated thcsc tumors. However, the immunophcnotype of cytokeratin 7 positivelcytokeratin 20 negative was seen in 86% of the pulmonary adcnoearcinomas, and in 0% of the colonic adenccarcinomas. Conversely, the cytokeratin 7-negative/cytokeratin 20- positive immunophenotype was seen in 77% of the colonic carcinomas, and in 0% of the pulmonary tumors. In conclusion, cytokcratin ‘Ilcytokeratin 20 immunostaining patterns may be helpful in separating pulmonary sdenocarcinomas from colonic adenocarcinomas. Ptdmonary blastomu. Report on two cawa and litrature review Schmidt W. Lcifeld H. Hoer PW. Dcwald-Schmidt M. Abreilung fur Pneumologie, Hildegardtiankenhaus. Hildegardstrasre 2. D-55131 Main Atemwegs-Lunge&r 1994,20:615-21. WC report on hvo cases of II pulmonary blastoma, in a I7 years old man and an I8 years old woman. The histological diagnosis has been ditlicult and could only be settled up by a consensus of pathologists. In the first case the tumor has bscn characterized as an epithclial leiomyoblastoma, which has yet only been described in the stomach, not in the lungs. Despite of intensive chemo- and radiotherapy resp.. following primary surgery in the second cast, in no patient a remission could be gained. They died in a pcrmancnt progression of their tumor 10 and 9 months resp. et?er diagnosis. Our wses are compared with 96 ones of the litcratur, in which more often remissions have been reported. In small tumors primaty resections, followed by chemc- and radiotherapy, in children additional radiation of the brain, is recommended. Advances in pathobiological research oo lung carcinoma Noguchi M. Deparbnen: ofPaorhology N&ma/ Cancer Center Res. Insr. 5-I- I Tsukji, Chuo-ku, Tokyo 104. Jpn J Cancer Chemother 1994;21:2549-54. Histological examination revealed that many peripheral type papillary adenocarcinomas appear to develop from atypical adenomatous hypcrplssia (AAH), which can be called adenoma or in situ sdenocarcinoma, and progress stepwise. Molecular-biologically, loss of hetcrozygosities of 3, 11 and 17 chromosomes, point mutation of ras oncogene and ~53 anti-oncogenc, amplitication of myc oncogene, and overexpression of erbB2 oncogene arc related to lung cancer development. Especially, ras and ~53 gene abnormalities are closely associated with poor prognosis of lung adenocarcinoma. Future molecular- biological examinations should focus on AAH and/or early stage adcnocarcinoma of the lung, in order to clarify the gene abnormality at the early stage of lung carcinogenesis. Impactofneumendoctine differentiation in mm-small cell lungcancer: ‘Ibe LCSG experience Linnoila RI, Piantadosi S, Ruckdeschel JC. BPRL%NCI 96iUMedical Cenfer Dc Rockville. MD 21710. Chest 1994;106:Suppl:367S-71s. Non-small cell lung cancers with neurcendcwine differentiation (NSCLC- NE) may demonstrate biologic behavior intermediate behvan non-small cell lung canner (NSCLC) and small cell lung cancer (SCLC) with impact on prognosis. We studied the expression of four welldefined neurcendocrine (NE) markers: neuron-specific en&se @SE), chromogranin A, Leu-7, gastrin- releasing peptide, and a panel of three non-NE markers, including vimcntin, and the epithelial markers csrcino-embryonic antigen (CEA) by immunohistochcmistry, and mucin by histcchemistry in 237 rcsccted NSCLCs from patients on six LCSG protocols. Twenty-nine (12%) tumors were positive for 2 or more NE markers An NE differentiation score was calculated but failed to correlate with recurrence as did other combinations of markers. However, the presence of tissue staining for CEA was strongly associated with improved survival (p=O.Ol I), whereas the presence. of mucin was associated with a worse outcome (p<O.OOl). Individually, CFA and mucin remained prognostic even when come&d for stage, histologic features, and performance status. We conclude that NE differentiation is not predictive of recurrence in patients with resected NSCLC but data on patterns of CEA and mucin expression may improve prognostication and permit rational design of new therapeutic approaches.

Transcript of The value of immunohistochemistry of pleural biopsy specimens in the differential diagnosis between...

Page 1: The value of immunohistochemistry of pleural biopsy specimens in the differential diagnosis between malignant mesothelioma and metastatic carcinoma

Absrracts /Lung Cancer 12 (1995) 265-329

only in 17% of breast carcinomas. The following remarks can bc drawn from this study: (1) some NSCLCs showed immunophcnotypic NE differentiation; (2) among all the markers used, NSE was the most sensitive (sensitivity, 100%) and chromogranin-A the most specific (speciticity, 100%). and (3) NSE and chromogranin-A appear to be the most valuable and useful indicators of probable ncuroendocrine differentiation in lung cpithelial tumors.

Comparison of autopsy, clinical and death certificate diagnosis with particular reCeRnce to hug cancer. A View oftbe published data LAX PN. Statistics and Computing Ld, I7 Cedar Road, Sutfon, Surrey AFWS Suppl: 1994;102: l-42.

Some clinicians and some epidemiologists appear to be under the illusion that techniques available for the diagnosis of internal diseases such as lung cancer have improved so much that autopsies are not necessary on the bodies of most people who die. Pertly for this reason, pertly for economic reasons and partly because clinicians fear litigation if autopsy shows that they tnxtcd patients for the wrong disease, autopsy rates have been falling in most developed countries. The object ofthe present review was to ascertain how much reliance can reasonably bc put on clinical diagnoses made and death certificates completed in the absence of autopsy data. In the case of lung cancer. high rates of false positive and false negative diagrwscs arc universally prevalent, with biases influencing these rates, so that smokers are more likely to be appropriately investigated for lung cancer, and false negatives are commoner in nonsmokers. All investigators who have compared clinical-based and autopsy-based death certiticates have concluded that higher autopsy rates are nccessaty and the results of one study suggest that a high autopsy rate in a hospital leads to improvements in the accuracy of clinical diagnoses. The extent to which diagnoses on death certificates that are dependent solely on clinical data are seriously inaccurate for internal diseases such as lung cs.nccr should engender caution in all who use mortality data to guide public health policies and to identify and quantify environmental risks to healths.

The value of immuaohistocbemistry of pleural biopsy specimens in the differential diagosis between maligoant meaotklioma and metastatic carcinoma Grove A, Paulsen SM. Grcgcrscn M. Instirule of PaAology, tfolstebro Cenhul Hospital, DK-7500 Holslebro. Pathol Res Pratt 1994;190:104l-55.

The aim ofthe present shrdywas to evaluate the aid of immune-histochemistry in the differential diagnosis behveen pleural malignant mcsothelioma (MM) and secondary pleural carcinoma in pleural biopsy specimens. A series of MM (epithcliel or biphasie type) (n = 39). and a scrics of secondaly pleural carcinomas (n = 25) were studied with a panel of monoclonal antibodies against Ber-EP4, CEA, and Lcu-MI (CDIS). Considering the markers one, two or three at a time, computer analysis was conducted to identify the immunophenotype with the highest sensitivity and specificity for both MM (n = 39) and sdencxxrcinoma (n = 19). The CWCDlS marker combination had the highest spcciticity @4M = lOOa/.; adenccarcinoma = 82,l%).and wnsitivity(MM = 82. I%;adcnoearcinoma = 100%) considering both categories of turnours. Positive reaction for CEA and/

or CD-1 5 was the best indicator of metastatic adenocarcinoma. Negative reaction for CWCD-I5 and Bcr-EP4KDI5 showed up to bc 100% spccitic for MM. Positive reaction for one, two or even all these antigens, however, occurred in nine tumours predetermined as MM according to their gross appcarancc, and absence ofother primary malignancies at autopsy. Ultrastructural examination (n = 7) of these tumours strongly supported the diagnosis in one case, and did by no means exclude the diagnosis MM in the other six cases. Neither did any of the turnours revcal ultrastructural signs of adenomatous differentiation, and they did not express PAS/diastase resistant globules, amylase or surf&ant. Anti-Bcr- EP4 was the antibody most frequently expressed in MM (n = 8). Until antibodies specitic for MM arc available, the limitation of immunohistochemistry to solve the diagnosis in all casts of pleural malignant tumours has to bc considered

Utility ofcytokeratin immunwtaiaiog in separating puhomuy adenw carcinomas frum colonic adenocarcioomas by TS, Calalucc RD. Department ofPafho/ogy Msmuri Universify Medico/ Center, One Hospital Drive. Columbia, MO 65212. Am J Clin Pathol 1994;102:764-7.

Adenocarcinomas of uncertain origin arc a frequent problem for surgical pathologists. To determine the utility of immunostaining for cytokeratin 7 and

cytokeratin 20 in the separation of pulmonary adcnocarcinomas from colonic adenoearcinomas, we studied routinely processed, forms&-fixed tissue from I5 1 of these tumors using commercially available monoclonsl antibodies and an avidin-biotin immunohistochemical technique. Used alone, neither cytokeratin 7 immunostaining orcytokeratin 20 immunostaining reliably separated thcsc tumors. However, the immunophcnotype of cytokeratin 7 positivelcytokeratin 20 negative was seen in 86% of the pulmonary adcnoearcinomas, and in 0% of the colonic adenccarcinomas. Conversely, the cytokeratin 7-negative/cytokeratin 20- positive immunophenotype was seen in 77% of the colonic carcinomas, and in 0% of the pulmonary tumors. In conclusion, cytokcratin ‘Ilcytokeratin 20 immunostaining patterns may be helpful in separating pulmonary sdenocarcinomas from colonic adenocarcinomas.

Ptdmonary blastomu. Report on two cawa and litrature review Schmidt W. Lcifeld H. Hoer PW. Dcwald-Schmidt M. Abreilung fur Pneumologie, Hildegardtiankenhaus. Hildegardstrasre 2. D-55131 Main Atemwegs-Lunge&r 1994,20:615-21.

WC report on hvo cases of II pulmonary blastoma, in a I7 years old man and an I8 years old woman. The histological diagnosis has been ditlicult and could only be settled up by a consensus of pathologists. In the first case the tumor has bscn characterized as an epithclial leiomyoblastoma, which has yet only been

described in the stomach, not in the lungs. Despite of intensive chemo- and radiotherapy resp.. following primary surgery in the second cast, in no patient a remission could be gained. They died in a pcrmancnt progression of their tumor 10 and 9 months resp. et?er diagnosis. Our wses are compared with 96 ones of the litcratur, in which more often remissions have been reported. In small tumors primaty resections, followed by chemc- and radiotherapy, in children additional radiation of the brain, is recommended.

Advances in pathobiological research oo lung carcinoma Noguchi M. Deparbnen: ofPaorhology N&ma/ Cancer Center Res. Insr. 5-I- I Tsukji, Chuo-ku, Tokyo 104. Jpn J Cancer Chemother 1994;21:2549-54.

Histological examination revealed that many peripheral type papillary adenocarcinomas appear to develop from atypical adenomatous hypcrplssia (AAH), which can be called adenoma or in situ sdenocarcinoma, and progress stepwise. Molecular-biologically, loss of hetcrozygosities of 3, 11 and 17 chromosomes, point mutation of ras oncogene and ~53 anti-oncogenc, amplitication of myc oncogene, and overexpression of erbB2 oncogene arc related to lung cancer development. Especially, ras and ~53 gene abnormalities are closely associated with poor prognosis of lung adenocarcinoma. Future molecular- biological examinations should focus on AAH and/or early stage adcnocarcinoma of the lung, in order to clarify the gene abnormality at the early stage of lung carcinogenesis.

Impactofneumendoctine differentiation in mm-small cell lungcancer: ‘Ibe LCSG experience Linnoila RI, Piantadosi S, Ruckdeschel JC. BPRL%NCI 96iUMedical Cenfer Dc Rockville. MD 21710. Chest 1994;106:Suppl:367S-71s.

Non-small cell lung cancers with neurcendcwine differentiation (NSCLC- NE) may demonstrate biologic behavior intermediate behvan non-small cell lung canner (NSCLC) and small cell lung cancer (SCLC) with impact on prognosis. We studied the expression of four welldefined neurcendocrine (NE) markers: neuron-specific en&se @SE), chromogranin A, Leu-7, gastrin- releasing peptide, and a panel of three non-NE markers, including vimcntin, and the epithelial markers csrcino-embryonic antigen (CEA) by immunohistochcmistry, and mucin by histcchemistry in 237 rcsccted NSCLCs from patients on six LCSG protocols. Twenty-nine (12%) tumors were positive for 2 or more NE markers An NE differentiation score was calculated but failed to correlate with recurrence as did other combinations of markers. However, the presence of tissue staining for CEA was strongly associated with improved survival (p=O.Ol I), whereas the presence. of mucin was associated with a worse outcome (p<O.OOl). Individually, CFA and mucin remained prognostic even when come&d for stage, histologic features, and performance status. We conclude that NE differentiation is not predictive of recurrence in patients with resected NSCLC but data on patterns of CEA and mucin expression may improve prognostication and permit rational design of new therapeutic approaches.