the adenosquamous lung carcinoma: clinicla and pathological characteristics

1
Abstracts/Lung Cancer 13 (1995) 185-232 199 has been well documented in the literature, it has been primarily in the form of single case reports. Consequently, it has been difficult until recently to determine their prevalence, clinical behavior, treatment, and spectrum of histopathologic features. Moreover, because of the rarity with which these tumors occur, one needs to be familiar with their diverse histopathologic features to comfortably arrive at the correct diagnosis. Because of their close histological similarities to their salivary gland counterparts, careful clinical evaluation is necessary to establish the primary nature of these tumors in the lung and to rule out the possibility of a metastasis. Another feature that may generate difficulties in interpretation is that some of these tumors may share certain histo- pathologic and some immunohistochemical features with each other. This may pose s serious problem, particularly when dealing with small biopsy samples. Therefore, the use of special studies such as electron microscopy and routine histochemistry may be beneficial and must be used in addition to conventional microscopy and immunohistochemistry to corroborate the diagnosis. In essence, the diagnosis of these tumors requires a combined approach that must include a detailed clinical history, a reasonably sized sample for histopathologic evaluation, histochemical and immunohistcchemical studies, and an ultrastructural examination. Proliferative potential and ~53 overexpression in precursor and early stage lesions of broncbioalveolar lung carcinoma Kitamura H, Kameda Y, Nakamura N, Nakatani Y, Inayama Y, Iida M- I et al. Department of Pathologv School of Medicine, Yokohama City University. 3-9 Fukuura, Kanasawa ku, Yokohama 236. Am J Pathol 1995;l46:816-87. To elucidate the pathogenesis of bronchioloalveolar lung carcinoma (BAC), we evaluated the lesion size, growth fraction, and ~53 overexpression of atypical adenomatous hyperplasia (AAH) and early stage BAC. AAH was classitied as showing low grade or high grade atypia. AAH-like carcinoma, presumably very early stage BAC, was distinguished from AAH in that it exhibited remarkable atypia suggestive of malignant potential and from overt BAC in that it lacked unequivocal malignant features, including invasive/destructive growth. The growth fraction was determined immunohistochemically in terms of the Ki-67 labeling index. The overexpression of ~53 was evaluated by assessing the nuclear accumulation of immunoreactive ~53 protein. Both the lesion size and the growth fraction increased from low grade AAH, to high grade AAH, to AAH-like carcinoma, and to overt adenocarcinoma. The overexpression of ~53 in AAH-like carcinoma was similar to that in overt adenocarcinoma and was more frequent than that in AAH. Our findings indicate that AAH, AAH-like carcinoma, and overt BAC represent diiferent categories, although the cellular events occurring in these lesions presumably represent a continuous spectrnm ofthe changes that are reflected in the cytomorphology and lesion size. The findings here suggest that AAH and AAH-like carcinomas constitute a population of heterogeneous lesions representing different steps toward overt BAC. Plow cytometric analysis of c-myc oncoprotein in non-small- cell lung carcinoma: Comparison with inununohistochemical results De Santis L, Mangili F, Sassi I, Di Rocco M, Rossi C, Cantaboni A. Cattedra Anatomia/Istologia Patolog., IRCCS H San Raffaele, I/is Olgettina 60, 20132h4ilano. Anal Cell Pathol 1995;8:247-7. c-myc oncoprotein expression was evahrated in 36 non-small-cell lung carcinomas using immunohistochemical and flow cytometric analysis. Formalin fixed and paraRin embedded material was used. The same monoclonal antibody (mouse anti-human c-myc) was employed both for immunohistochemistry and flow cytometry. For the immunohistochemical evaluation we calculated the percentage of stained cells on 200 neoplastic cells. c-myc oncoprotein was measured using flow cytometry by linking the monoclonal with a secondary FITC- conjugated antibody; for each sample 20000 events were analysed and the percentage of cells positive for green fluorescence was calculated. DNA content was obtained by pmpidium iodide staining. Results showed a high correlation between immunohistochemical and cytometric data, suggesting that flow cytometry could be used as an alternative to immunohistochemistry in wahmting nuclear antigens. Moreover, using flow cytometry information on DNA content can be obtained simuhaneously. Divergent differentiative histogenetic lines in lung tumors: Identification of histotypes with pure or mixed ultrastructural phenotype and their prognostic significance Taccagni GL, Revere E. Terreni MR Gambini S, Cantaboni A. Catt. Anatomia/Istologia Patologica, Istituto Scienti$co H San Raflaele, Universita degli Studi di Milano, Ma Olgettina 60, 20132 Milano. Ultrastruct Pathol 1995;19:61-73. We performed an electron microscopic study of 50 lung tumors, previously diagnosed by light microscopy, and compared the results of the two techniques. Data analysis identified two ultrastructural phenotypes: pure and mixed. The former was characterizedby a constant differentiative pattern and the latter by diverging differentiative histogenetic lines. We observed six differentiative lines as follows: squamous, glandular, neuroendocrine, villopodial, intestinal, and apocrine sudoriparous. Features of divergent differentiative lines were observed in 36 cases (64%). throughout the histotypes, sometimes with coexpression of more than one differentiation in a single case and/or cell. Adenocarcinoma was the histotype most frequently observed in pure form whereas most squamous cell carcinomas showed a mixed phenotype. This suggests that the histotype of the different lung tumors arises from a single glandular phuipotent cell, able to differentiate toward divergent differentiative lines. The clinical stage at onset and at the end of the follow-up indicates that the biologic behavior of lung tumors varies according to whether the ultrastmctural phenotype is pure or IlliXl2.d. The adenosquamous lung carcinoma: Clinical and pathological characteristics Hofmann H-S, Knolle J, Neef H. Cardio-Thoracic Sutgety, Martin- Luther-Univ. Halle-Wittenberg, E Grube St,: 40, Halle 06097. J cardiovase slug 1994;35:543-7. The adenosquamous carcinoma is a rare combined tumour of non- small cell lung cancer (NSCLC). The survival prognosis of surgically treated patients with adenosquamous carcinoma and patients with squamous cell carcinoma, large cell carcinoma or adenocarcinoma were compared during a study. ‘Bvo hundred and seventy-five patients who had been treated surgically because of primary lung cancer in the Department of Thoracic-Surgery at the Martin-Luther-University Halle- Wittenberg between 1980 and 1989 were evaluated. The Eve year survival study of 172 patients who underwent resection because of squamous cell carcinoma was 450/o, the one of patients with adeno- carcinoma (n = 84) was 27%. 26% was the five year survival rate of the patients (n = 9) with large cell carcinoma. of 13 patients (4%) with adenosquamous carcinoma none survived five years after surgical tmat- ment. The two year survival rate was 28%. The presented results demon- strate the poor survival prognosis of patients suffering from adeno- squamous carcinoma and ask for an adjuvant therapy.

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Page 1: The adenosquamous lung carcinoma: Clinicla and pathological characteristics

Abstracts/Lung Cancer 13 (1995) 185-232 199

has been well documented in the literature, it has been primarily in the form of single case reports. Consequently, it has been difficult until recently to determine their prevalence, clinical behavior, treatment, and spectrum of histopathologic features. Moreover, because of the rarity with which these tumors occur, one needs to be familiar with their diverse histopathologic features to comfortably arrive at the correct diagnosis. Because of their close histological similarities to their salivary gland counterparts, careful clinical evaluation is necessary to establish the primary nature of these tumors in the lung and to rule out the possibility of a metastasis. Another feature that may generate difficulties in interpretation is that some of these tumors may share certain histo- pathologic and some immunohistochemical features with each other. This may pose s serious problem, particularly when dealing with small biopsy samples. Therefore, the use of special studies such as electron microscopy and routine histochemistry may be beneficial and must be used in addition to conventional microscopy and immunohistochemistry to corroborate the diagnosis. In essence, the diagnosis of these tumors requires a combined approach that must include a detailed clinical history, a reasonably sized sample for histopathologic evaluation, histochemical and immunohistcchemical studies, and an ultrastructural examination.

Proliferative potential and ~53 overexpression in precursor and early stage lesions of broncbioalveolar lung carcinoma Kitamura H, Kameda Y, Nakamura N, Nakatani Y, Inayama Y, Iida M- I et al. Department of Pathologv School of Medicine, Yokohama City University. 3-9 Fukuura, Kanasawa ku, Yokohama 236. Am J Pathol 1995;l46:816-87.

To elucidate the pathogenesis of bronchioloalveolar lung carcinoma (BAC), we evaluated the lesion size, growth fraction, and ~53 overexpression of atypical adenomatous hyperplasia (AAH) and early stage BAC. AAH was classitied as showing low grade or high grade atypia. AAH-like carcinoma, presumably very early stage BAC, was distinguished from AAH in that it exhibited remarkable atypia suggestive of malignant potential and from overt BAC in that it lacked unequivocal malignant features, including invasive/destructive growth. The growth fraction was determined immunohistochemically in terms of the Ki-67 labeling index. The overexpression of ~53 was evaluated by assessing the nuclear accumulation of immunoreactive ~53 protein. Both the lesion size and the growth fraction increased from low grade AAH, to high grade AAH, to AAH-like carcinoma, and to overt adenocarcinoma. The overexpression of ~53 in AAH-like carcinoma was similar to that in overt adenocarcinoma and was more frequent than that in AAH. Our findings indicate that AAH, AAH-like carcinoma, and overt BAC represent diiferent categories, although the cellular events occurring in these lesions presumably represent a continuous spectrnm ofthe changes that are reflected in the cytomorphology and lesion size. The findings here suggest that AAH and AAH-like carcinomas constitute a population of heterogeneous lesions representing different steps toward overt BAC.

Plow cytometric analysis of c-myc oncoprotein in non-small- cell lung carcinoma: Comparison with inununohistochemical results De Santis L, Mangili F, Sassi I, Di Rocco M, Rossi C, Cantaboni A. Cattedra Anatomia/Istologia Patolog., IRCCS H San Raffaele, I/is Olgettina 60, 20132h4ilano. Anal Cell Pathol 1995;8:247-7.

c-myc oncoprotein expression was evahrated in 36 non-small-cell lung carcinomas using immunohistochemical and flow cytometric analysis. Formalin fixed and paraRin embedded material was used. The same monoclonal antibody (mouse anti-human c-myc) was employed both for immunohistochemistry and flow cytometry. For the

immunohistochemical evaluation we calculated the percentage of stained cells on 200 neoplastic cells. c-myc oncoprotein was measured using flow cytometry by linking the monoclonal with a secondary FITC- conjugated antibody; for each sample 20000 events were analysed and the percentage of cells positive for green fluorescence was calculated. DNA content was obtained by pmpidium iodide staining. Results showed a high correlation between immunohistochemical and cytometric data, suggesting that flow cytometry could be used as an alternative to immunohistochemistry in wahmting nuclear antigens. Moreover, using flow cytometry information on DNA content can be obtained simuhaneously.

Divergent differentiative histogenetic lines in lung tumors: Identification of histotypes with pure or mixed ultrastructural phenotype and their prognostic significance Taccagni GL, Revere E. Terreni MR Gambini S, Cantaboni A. Catt. Anatomia/Istologia Patologica, Istituto Scienti$co H San Raflaele, Universita degli Studi di Milano, Ma Olgettina 60, 20132 Milano. Ultrastruct Pathol 1995;19:61-73.

We performed an electron microscopic study of 50 lung tumors, previously diagnosed by light microscopy, and compared the results of the two techniques. Data analysis identified two ultrastructural phenotypes: pure and mixed. The former was characterizedby a constant differentiative pattern and the latter by diverging differentiative histogenetic lines. We observed six differentiative lines as follows: squamous, glandular, neuroendocrine, villopodial, intestinal, and apocrine sudoriparous. Features of divergent differentiative lines were observed in 36 cases (64%). throughout the histotypes, sometimes with coexpression of more than one differentiation in a single case and/or cell. Adenocarcinoma was the histotype most frequently observed in pure form whereas most squamous cell carcinomas showed a mixed phenotype. This suggests that the histotype of the different lung tumors arises from a single glandular phuipotent cell, able to differentiate toward divergent differentiative lines. The clinical stage at onset and at the end of the follow-up indicates that the biologic behavior of lung tumors varies according to whether the ultrastmctural phenotype is pure or IlliXl2.d.

The adenosquamous lung carcinoma: Clinical and pathological characteristics Hofmann H-S, Knolle J, Neef H. Cardio-Thoracic Sutgety, Martin- Luther-Univ. Halle-Wittenberg, E Grube St,: 40, Halle 06097. J cardiovase slug 1994;35:543-7.

The adenosquamous carcinoma is a rare combined tumour of non- small cell lung cancer (NSCLC). The survival prognosis of surgically treated patients with adenosquamous carcinoma and patients with squamous cell carcinoma, large cell carcinoma or adenocarcinoma were compared during a study. ‘Bvo hundred and seventy-five patients who had been treated surgically because of primary lung cancer in the Department of Thoracic-Surgery at the Martin-Luther-University Halle- Wittenberg between 1980 and 1989 were evaluated. The Eve year survival study of 172 patients who underwent resection because of squamous cell carcinoma was 450/o, the one of patients with adeno- carcinoma (n = 84) was 27%. 26% was the five year survival rate of the patients (n = 9) with large cell carcinoma. of 13 patients (4%) with adenosquamous carcinoma none survived five years after surgical tmat- ment. The two year survival rate was 28%. The presented results demon- strate the poor survival prognosis of patients suffering from adeno- squamous carcinoma and ask for an adjuvant therapy.