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Ultrastructure of well-differentiated adenocarcinomas of the lung with special reference to bronchioloalveolar carcinoma
25.5
sely related to degree of tumor differentiation, while GR content was slightly lower in poorly differentiated squamous cell carcinomas. GR content in squamous cell carcinoma increased slightly between Stages I and II and declined significantly in Stage II patients. This was not observed in adenocarcinoma, where GR content appeared to increase with stage of disease. Our results suggest that a significant incidence of specific, high affinity receptors for estrogen, androgen, and glucocorticoid is present in nonsmall cell carcinomas of the lung, which could provide a useful starting point for examining whether steroids influence the natural history of selected bronchogenic carcinomas.
secretory, and poorly differentiated. The cytologic features of these three types of bronchoioloalveolar carcinoma are presented and illustrated. Cytomorphologically, the three types of this tumor are distinctly different and their features are sufficiently distinctive fromthose of bronchogenic adenocarcinoma and metastatic adenocarcinomas to be of diagnostic value. Transthoracic fine-needle aspiration biopsy appears to be a definitive minimally invasive means of establishing the diagnosis of bronchioloalveolar carcinoma preoperatively and especially to be of value for those small peripheral cancers which are relatively inaccessible to direct method of study and are potentially surgically curable.
q,
Nonaspiration-Needle Smear Preparations of Pulmonary Lesions. A Comparison of Cytology and Histology. Strobel, S.L., Keyhani-Rofagha, S., O-Toole, R.V., Nahman, B.J. Division of Cytology, Department of Pathology, Ohio State University Columbus, OH 43210, U.S.A. Acta Cytol. 29: 1047-1052, 1985. Material for cytologic smears was obtained from pulmonary lesions in 146 patients at the Ohio State University between 1979 and 1984 using Rotex or Lee screw needles. Corresponding histologic specimens were available for comparison in 77 of these cases. Diagnosis of malignant neoplasms made by cytologic evaluation (55 cases) were confirmed by the corresponding histologic specimens in 93% of those cases. Possible explanations for the cytologic false-positive diagnoses of malignancy are presented. Correlations between the cytologic and histologic diagnoses of the morphologic type of tumor were 100% for adenocarcinoma, 75% for squamouscell carcinoma and 20% for large-cell undifferentiated carcinoma. The correlation was 100% for small-cell carcinoma when the histology specimen represented the tumor. Nonneoplastic benign lesions diagnosed cytologically had corresponding benign histologic diagnoses in 94% of the cases. These results compare favorably with those reported for other fine needle aspiration studies of pulmonary lesions. The advantages of using Rotex needles as compared to fine needle aspiration are discussed.
PATHOLOGY
Fine Needle Aspiration Cytology of Bronchi01oalveolar-Cell Carcinoma of the Lung. Silverman, J.F., Finley, J.L., Park, H.K. et al. Department of Clinical Pathology and Diagnostic Medicine, East Carolina University School of Medicine, Greenville, NC 27834, U.S.A. Acta Cytol. 29: 887-894, 1985. The fine needl~ aspiration cytology features of twelve peripherally located bronchioloalveolar cell carcinomas of the lung diagnosed by fine needle aspiration biopsy are described. A spectrum of cytomorphologic changes was appreciated, including classic groups showing uniform malignant cells having prominent depth of focus with a lack of significant nuclear molding. Other cells showed features of atypical alveolar macrophages and bronchial-lining cells. The smears demonstrated malignant cells arranged along alveolar septae and possessing hobnail-shaped nuclei. Two cases had associated psammoma bodies, and one case demonstrated optically clear nuclei in the malignant cells. This series stresses the fine needle aspiration features that aid in the recognition of this specific lung neoplasm and its differentiation from benign reactive pulmonary lesions, other primary lung cancers and metastatic tumors.
Cytologic Diagnosis of Bronchioloalveolar Carcinoma by Fine-Needle Aspiration Biopsy. Tao, L.-C., Weisbrod, G.L., Pearson, F.G. et al. Department of Pathology, Toronto General Hospital, Toronto, Ont. M5G IL7, Canada. Cancer 57: 1565-1570, 1986. From 1970 to June 1984, 275 patients with bronchioloalveolar carcinoma were admitted to the Toronto General Hospital. Of these, 181 (190 aspiration biopsies, including nine repeat samples) had this diagnosis made following the use of transthoracic fine-needle aspiration biopsy. Based on the cytomorphologic features observed in the aspiration preparations, the tumor was subclassified into three types; nonsecretory
Ultrastructure of Well-Differentiated Adenocarcinomas of the Lung with Special Reference to Bronchioloalveolar Carcinoma. Eimoto, T., Teshima, K., Shirakusa, T., Kikuchi, M. Departments of Pathology and Surgery, Fukuoka University School of Medicine, Fukuoka University School of Medicine, Fukuoka 814-01, Japan. Ultrastruct. Pathol. 8: 177190, 1985. The cytologic phenotypes of 20 we~l-differentiated pulmonary adenocarcinomas were
256
determined by electron microscopy. On examination of more than 100 cells in each case, the tumors were classified according to the predominant cell types. Nine cases (45%) were of mucous cell type, further divided into 7 cases of bronchial surface epithelial cell type, 1 case of bronchial gland cell type, and 1 case of metaplastic bronchiolar goblet cell type. The remainder included 5 cases (25%) of Clara cell type, 2 cases (10%) of type II cell type, and 4 cases (20%) of mixed cell type. The predominant histologic pattern by light microscopy was 'typically' bronchioloalveolar (Manning et al.'s type i) in the metaplastic goblet cell tumor and papillary in most Clara cell-type tumors, while it was glandular in bronchial surface and bronchial gland cell types, although variable in type II cell or mixed cell type. Therefore, bronchioloalveolar carcinomas, when histologically defined inclusive of papillary tumors, present cytologic phenotypes also related to the bronchioloalveolar epithelium, i.e., metaplastic goblet or Clara or type II cell subtypes, which is in accordance with some previous reports. These tumors could be distinguished from the other (glandular) adenocarcinomas that show primarily bronchial mucous cell differentiation. Morphologic Variations of Small Cell Lung Cancer. A Histopathologic Study of Pretreatment and Posttreatment Specimens in 104 Patients. Sehested, M., Hirsch, F.R., Osterlind, K., Olsen, J.E. Department of Pathology, Fineen Institute, DK-2100 Copenhagen, Denmark. Cancer 57: 804-807, 1986. A consecutive series of 104 autopsies on patients treated in protocol for small cell carcinoma of the lung (SCCL) was studied with respect to (i) metastatic pattern at autopsy in relation to pretreatment WHO 1981 classification, and (2) extent and significance of non-SCLC tumor tissue at autop~ sy. The only significant difference in the metastatic pattern at autopsy between patients with pretreatment oat cell or intermediate subtype was metastases to the brain. Thus, the frequency of brain metastases was 17/35 (49%) in patients with oat cell type compared to 2/18 (11%) in patients with intermediate type (P < 0.05). At au~ topsy 13 of 98 patients (13%) had nonSCCL tumor tissue in at least one site. These patients had a significantly shorter survival (P = 0.020) compared to patients with pure SCCL at autopsy. Furthermore, none of these 13 patients had obtained complete remission. Whether these morphologic variations had been present at the pretreatment stage of the disease or were due to the chemotherapeutic treatment could not be solved in the present study. However,
the results might indicate that mixed SCCL/ non-SCCL histology is a negative prognostic factor in the treatment of SCCL. Prospective studies including more extensive pretreatment tissue sampling seem to be required. Morphometric Study of Adenocarcinoma and Hyperplastic Epithelial Lesions in the Peripheral Lung. Kodama, T., Biyajima, S., Watanabe, S., Shimosato, Y. Pathology Division, National Cancer Center Research Institute, Chuo-ku, Tokyo 104, Japan. Am. J. Clin. Pathol. 85: 146151, 1986. Mean nuclear areas (MNA) were calculated morphometrically in ten cases of well-differentiated adenocarcinoma, ten cases of atypical alveolar cuboidal cell hyperplasia (AAH), and five cases of alveolar cuboidal cell hyperplasia (AH) and were compared with each other. In cases of adenocarcinoma, the MNA were significantly larger than those of AAH and AH, and t3ae standard diviation (SD) of nuclear area was greater in adenocarcinoma than that in AAH and AH, thus implying greater 'scatter' of the nuclear areas in the former tham the latter two. The MNA and the SD of nuclear area in AH were smallest in these three groups. In one case each of AAH and adenocarcinoma, there were two different populations of nuclear size in the same lesions, that is, histograms~,showed both adenocarcinoma and AAH in the same tumor. Through the use of the morphometric method, many cases of AAH were easily distinguishable from adenocarcinoma cases, and there were two cases in which foci of adenocarcinoma and AAH coexisted. The Frequency 0f Distribution According to Histological Types of Lung Cancer in the Tracheobronchial Tree. Histologie und Lokalisation beim Bronchialkarzinom. Celikoglu, S.I., Aykan, T.B., Karayel, T. et al. Pulmonologische Abteilung der Medizinischen Klinik, Istanbul Universitesi Cerrahpasa Tip Fakultesi jc Hastaliklar, Istanbul, Turkey. Prax, Klin. Pneumol. 39: 817-818, 1985. Based on an analysis of 355 patients with bronchial carcinoma, we can conclude that there are two main groups of bronchial carcinomas; of these, the squamous-cell carcinoma and small-cell carcinoma will be found preferably in the upper lobes, whereas there are other carcinomas - among them the adenocarcinomas - that do not seem to have any predilective location. The first group, namely, the squamous-cell carcinoma and the small-cell carcinoma, are attributed to smoking, and hence they will be found mainly in the upper lobes, similar to other inhalative diseases of the upper airways and lungs. U1trastructural and I m m m o h i s t o c h e m i c a l Pea-
sely related to degree of tumor differentiation, while GR content was slightly lower in poorly differentiated squamous cell carcinomas. GR content in squamous cell carcinoma increased slightly between Stages I and II and declined significantly in Stage II patients. This was not observed in adenocarcinoma, where GR content appeared to increase with stage of disease. Our results suggest that a significant incidence of specific, high affinity receptors for estrogen, androgen, and glucocorticoid is present in nonsmall cell carcinomas of the lung, which could provide a useful starting point for examining whether steroids influence the natural history of selected bronchogenic carcinomas.
secretory, and poorly differentiated. The cytologic features of these three types of bronchoioloalveolar carcinoma are presented and illustrated. Cytomorphologically, the three types of this tumor are distinctly different and their features are sufficiently distinctive fromthose of bronchogenic adenocarcinoma and metastatic adenocarcinomas to be of diagnostic value. Transthoracic fine-needle aspiration biopsy appears to be a definitive minimally invasive means of establishing the diagnosis of bronchioloalveolar carcinoma preoperatively and especially to be of value for those small peripheral cancers which are relatively inaccessible to direct method of study and are potentially surgically curable.
q,
Nonaspiration-Needle Smear Preparations of Pulmonary Lesions. A Comparison of Cytology and Histology. Strobel, S.L., Keyhani-Rofagha, S., O-Toole, R.V., Nahman, B.J. Division of Cytology, Department of Pathology, Ohio State University Columbus, OH 43210, U.S.A. Acta Cytol. 29: 1047-1052, 1985. Material for cytologic smears was obtained from pulmonary lesions in 146 patients at the Ohio State University between 1979 and 1984 using Rotex or Lee screw needles. Corresponding histologic specimens were available for comparison in 77 of these cases. Diagnosis of malignant neoplasms made by cytologic evaluation (55 cases) were confirmed by the corresponding histologic specimens in 93% of those cases. Possible explanations for the cytologic false-positive diagnoses of malignancy are presented. Correlations between the cytologic and histologic diagnoses of the morphologic type of tumor were 100% for adenocarcinoma, 75% for squamouscell carcinoma and 20% for large-cell undifferentiated carcinoma. The correlation was 100% for small-cell carcinoma when the histology specimen represented the tumor. Nonneoplastic benign lesions diagnosed cytologically had corresponding benign histologic diagnoses in 94% of the cases. These results compare favorably with those reported for other fine needle aspiration studies of pulmonary lesions. The advantages of using Rotex needles as compared to fine needle aspiration are discussed.
PATHOLOGY
Fine Needle Aspiration Cytology of Bronchi01oalveolar-Cell Carcinoma of the Lung. Silverman, J.F., Finley, J.L., Park, H.K. et al. Department of Clinical Pathology and Diagnostic Medicine, East Carolina University School of Medicine, Greenville, NC 27834, U.S.A. Acta Cytol. 29: 887-894, 1985. The fine needl~ aspiration cytology features of twelve peripherally located bronchioloalveolar cell carcinomas of the lung diagnosed by fine needle aspiration biopsy are described. A spectrum of cytomorphologic changes was appreciated, including classic groups showing uniform malignant cells having prominent depth of focus with a lack of significant nuclear molding. Other cells showed features of atypical alveolar macrophages and bronchial-lining cells. The smears demonstrated malignant cells arranged along alveolar septae and possessing hobnail-shaped nuclei. Two cases had associated psammoma bodies, and one case demonstrated optically clear nuclei in the malignant cells. This series stresses the fine needle aspiration features that aid in the recognition of this specific lung neoplasm and its differentiation from benign reactive pulmonary lesions, other primary lung cancers and metastatic tumors.
Cytologic Diagnosis of Bronchioloalveolar Carcinoma by Fine-Needle Aspiration Biopsy. Tao, L.-C., Weisbrod, G.L., Pearson, F.G. et al. Department of Pathology, Toronto General Hospital, Toronto, Ont. M5G IL7, Canada. Cancer 57: 1565-1570, 1986. From 1970 to June 1984, 275 patients with bronchioloalveolar carcinoma were admitted to the Toronto General Hospital. Of these, 181 (190 aspiration biopsies, including nine repeat samples) had this diagnosis made following the use of transthoracic fine-needle aspiration biopsy. Based on the cytomorphologic features observed in the aspiration preparations, the tumor was subclassified into three types; nonsecretory
Ultrastructure of Well-Differentiated Adenocarcinomas of the Lung with Special Reference to Bronchioloalveolar Carcinoma. Eimoto, T., Teshima, K., Shirakusa, T., Kikuchi, M. Departments of Pathology and Surgery, Fukuoka University School of Medicine, Fukuoka University School of Medicine, Fukuoka 814-01, Japan. Ultrastruct. Pathol. 8: 177190, 1985. The cytologic phenotypes of 20 we~l-differentiated pulmonary adenocarcinomas were
256
determined by electron microscopy. On examination of more than 100 cells in each case, the tumors were classified according to the predominant cell types. Nine cases (45%) were of mucous cell type, further divided into 7 cases of bronchial surface epithelial cell type, 1 case of bronchial gland cell type, and 1 case of metaplastic bronchiolar goblet cell type. The remainder included 5 cases (25%) of Clara cell type, 2 cases (10%) of type II cell type, and 4 cases (20%) of mixed cell type. The predominant histologic pattern by light microscopy was 'typically' bronchioloalveolar (Manning et al.'s type i) in the metaplastic goblet cell tumor and papillary in most Clara cell-type tumors, while it was glandular in bronchial surface and bronchial gland cell types, although variable in type II cell or mixed cell type. Therefore, bronchioloalveolar carcinomas, when histologically defined inclusive of papillary tumors, present cytologic phenotypes also related to the bronchioloalveolar epithelium, i.e., metaplastic goblet or Clara or type II cell subtypes, which is in accordance with some previous reports. These tumors could be distinguished from the other (glandular) adenocarcinomas that show primarily bronchial mucous cell differentiation. Morphologic Variations of Small Cell Lung Cancer. A Histopathologic Study of Pretreatment and Posttreatment Specimens in 104 Patients. Sehested, M., Hirsch, F.R., Osterlind, K., Olsen, J.E. Department of Pathology, Fineen Institute, DK-2100 Copenhagen, Denmark. Cancer 57: 804-807, 1986. A consecutive series of 104 autopsies on patients treated in protocol for small cell carcinoma of the lung (SCCL) was studied with respect to (i) metastatic pattern at autopsy in relation to pretreatment WHO 1981 classification, and (2) extent and significance of non-SCLC tumor tissue at autop~ sy. The only significant difference in the metastatic pattern at autopsy between patients with pretreatment oat cell or intermediate subtype was metastases to the brain. Thus, the frequency of brain metastases was 17/35 (49%) in patients with oat cell type compared to 2/18 (11%) in patients with intermediate type (P < 0.05). At au~ topsy 13 of 98 patients (13%) had nonSCCL tumor tissue in at least one site. These patients had a significantly shorter survival (P = 0.020) compared to patients with pure SCCL at autopsy. Furthermore, none of these 13 patients had obtained complete remission. Whether these morphologic variations had been present at the pretreatment stage of the disease or were due to the chemotherapeutic treatment could not be solved in the present study. However,
the results might indicate that mixed SCCL/ non-SCCL histology is a negative prognostic factor in the treatment of SCCL. Prospective studies including more extensive pretreatment tissue sampling seem to be required. Morphometric Study of Adenocarcinoma and Hyperplastic Epithelial Lesions in the Peripheral Lung. Kodama, T., Biyajima, S., Watanabe, S., Shimosato, Y. Pathology Division, National Cancer Center Research Institute, Chuo-ku, Tokyo 104, Japan. Am. J. Clin. Pathol. 85: 146151, 1986. Mean nuclear areas (MNA) were calculated morphometrically in ten cases of well-differentiated adenocarcinoma, ten cases of atypical alveolar cuboidal cell hyperplasia (AAH), and five cases of alveolar cuboidal cell hyperplasia (AH) and were compared with each other. In cases of adenocarcinoma, the MNA were significantly larger than those of AAH and AH, and t3ae standard diviation (SD) of nuclear area was greater in adenocarcinoma than that in AAH and AH, thus implying greater 'scatter' of the nuclear areas in the former tham the latter two. The MNA and the SD of nuclear area in AH were smallest in these three groups. In one case each of AAH and adenocarcinoma, there were two different populations of nuclear size in the same lesions, that is, histograms~,showed both adenocarcinoma and AAH in the same tumor. Through the use of the morphometric method, many cases of AAH were easily distinguishable from adenocarcinoma cases, and there were two cases in which foci of adenocarcinoma and AAH coexisted. The Frequency 0f Distribution According to Histological Types of Lung Cancer in the Tracheobronchial Tree. Histologie und Lokalisation beim Bronchialkarzinom. Celikoglu, S.I., Aykan, T.B., Karayel, T. et al. Pulmonologische Abteilung der Medizinischen Klinik, Istanbul Universitesi Cerrahpasa Tip Fakultesi jc Hastaliklar, Istanbul, Turkey. Prax, Klin. Pneumol. 39: 817-818, 1985. Based on an analysis of 355 patients with bronchial carcinoma, we can conclude that there are two main groups of bronchial carcinomas; of these, the squamous-cell carcinoma and small-cell carcinoma will be found preferably in the upper lobes, whereas there are other carcinomas - among them the adenocarcinomas - that do not seem to have any predilective location. The first group, namely, the squamous-cell carcinoma and the small-cell carcinoma, are attributed to smoking, and hence they will be found mainly in the upper lobes, similar to other inhalative diseases of the upper airways and lungs. U1trastructural and I m m m o h i s t o c h e m i c a l Pea-