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Histological classification of lung cancer. Rays. 2004 Oct-Dec;29(4):353-5. A histological classification should provide guidelines for tumor diagnosis in order to evaluate patient prognosis and therapy. Pre-invasive lesions identified as precursors of invasive lung carcinoma are: squamous dysplasia/carcinoma in situ, atypical adenomatous hyperplasia and idiopatic pulmonary neuroendocrine cell hyperplasia. Squamous carcinoma and adenocarcinoma are the commonest types of lung carcinoma with the latter increasing in many countries mainly for changed smoking habits. Bronchioloalveolar carcinomas include exclusively noninvasive mucinous or non-mucinous tumors. Neuroendocrine tumors range from well differentiated neuroendocrine carcinoma (typical carcinoid) to intermediate grade (atypical carcinoma) to very aggressive poorly differentiated lesions (large cell neuroendocrine carcinoma and small cell carcinoma). The significance of associated pre-invasive lesions in patients resected for primary lung neoplasms.Eur J Cardiothorac Surg. 2004 Jul;26(1):165-72. OBJECTIVE: To evaluate the prevalence and clinico/prognostic significance of the presence of pre-invasive lesions in patients resected for primary lung neoplasm. METHODS: From 1993 to 2002, 1090 patients received resection for primary lung carcinomas. Of these, 73 presented an associated pre-invasive lesion in the surgical specimen distant from the primary tumour. Classification of pre-invasive lesions included Atypical Adenomatous Hyperplasia (AAH); Carcinoma In Situ (CIS) either diffuse or at the bronchial resection margin; Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH). Correlation between the presence of pre-invasive lesion and the following variables were calculated by logistic regression analysis: sex, age, median tumour size, histology, histologic differentiation, histologic evidence of invasiveness (vascular and perineural invasion), peritumoural lymphocytic infiltrate, pTNM, lobe location, history of previous malignancy. Survival rates were computed using Kaplan-Meier method and survival differences with the total patient population of resected lung carcinomas were tested using the log-rank method. RESULTS: There were 28 AAH, 42 CIS (5 at the bronchial resection margin) and 3 DIPNECH. Histology of the primary tumor included bronchioloalveolar carcinoma (9 patients), adenocarcinoma (19), squamous cell carcinoma (39), typical carcinoid tumour (3) and adenosquamous carcinoma (3). Overall prevalence of pre-invasive lesion was 6.7%. A strong correlation was found between the presence of AAH and the co-existence of either adenocarcinoma, bronchioloalveolar carcinoma or mixed adenocarcinoma-containing tumours (P = 0.00002) between CIS and squamous cell carcinoma (P = 0.009) and between DIPNECH and carcinoid tumours (P = 0.001). No significant correlation was found between the presence of any type of pre-invasive lesion and sex, age, median tumour size, histologic differentiation, histologic evidence of invasiveness, pTNM, lobe location and history of previous malignancy or the probability to develop a second primary lung carcinoma in the remaining lobe(s) after resection. Survival rates in the patients with AAH and CIS were not significantly different from those of patients without pre-invasive lesion (P = 0.3 and P = 0.1). CONCLUSIONS: Associated pre-invasive lesions in patients resected for primary lung neoplasms are not infrequent. AAH is associated with adenocarcinoma, CIS with squamous cell carcinoma, DIPNECH with typical carcinoid tumours. Our experience indicates that in these patients histology, stage distribution and survival do not differ from the total population of resected patients with lung tumors.
Classification of broncho-pulmonary cancers (WHO 1999).Rev
Mal Respir. 2002 Sep;19(4):455-66 Pathology of lung cancer.Clin Chest Med. 2002 Mar;23(1):65-81, viii. This article reviews current concepts in pathologic classification of lung cancer based on 1999 World Health Organization (WHO)/International Association for the Study of Lung Cancer (IASLC) classification. Preinvasive lesions including squamous dysplasia/carcinoma in situ, atypical adenomatous hyperplasia and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia are discussed in addition to current concepts of bronchioloalveolar carcinoma and neuroendocrine tumors. The new World Health Organization classification of lung tumours. Eur Respir J. 2001 Dec;18(6):1059-68. Tumour classification systems provide the foundation for tumour diagnosis and patient therapy and a critical basis for epidemiological and clinical studies. This updated classification was developed with the aim to adhere to the principles of reproducibility, clinical significance, and simplicity in order to minimize the number of unclassifiable lesions. Major changes in the revised classification as compared to the previous one (WHO 1981) include the addition of two pre-invasive lesions to squamous dysplasia and carcinoma in situ; atypical adenomatous hyperplasia and diffuse idiopathic pulmonary neuroendocrine cell hyperplasia. Another change is the subclassification of adenocarcinoma: the definition of bronchioalveolar carcinoma has been restricted to noninvasive tumours. There has been substantial evolution of concepts in neuroendocrine lung tumour classification. Large cell neuroendocrine carcinoma (LCNEC) is now recognized as a histologically high grade non small cell carcinoma showing histopathological features of neuroendocrine differentiation as well as immunohistochemical neuroendocrine markers. The large cell carcinoma class has been enriched with several variants, including the LCNEC and the basaloid carcinoma, both with a dismal prognosis. Finally, a new class was defined called carcinoma with pleomorphic, sarcomatoid, or sarcomatous elements, which brings together a number of proliferations characterized by a spectrum of epithelial to mesenchymal differentiation. Immunohistochemistry and electron microscopy are invaluable techniques for diagnosis and subclassification, but our intention was to render the classification simple and practical to every surgical laboratory, so that most lung tumours could be classified by light microscopic criteria. An ultrastructural classification of carcinomas of the lung.Zhonghua Bing Li Xue Za Zhi. 1992 Oct;21(5):262-5. For the purpose of providing more accurate histological typing of lung carcinoma, it is necessary to classify carcinomas of the lung by electron microscopy. One hundred and fifty cases of resected lung carcinoma were examined under electron microscope. The results of ultrastructural typing of lung carcinoma were as follows: 1. carcinomas showed differentiated features of glandular and squamous epithelium, including squamous cell carcinoma (28 cases), adenocarcinoma (35 cases), and adenosquamous carcinoma (29 cases). Among them, some cases were associated with neuroendocrine differentiation. In addition, solid mucinous cell carcinoma (4 cases) and adenoid cystic carcinoma (2 cases) were seen. 2. Carcinomas showed differentiated features of bronchioloalveolar epithelium, subdividing into clara cell (9 cases), type II pneumocyte (3 cases), mucinous cell (5 cases) and mixed type (4 cases). 3. Carcinomas showed differentiated features of neuroendocrine cell (Kulchitsky cell), including well differentiated (carcinoid, 13 cases), intermediately differentiated (atypical carcinoid, 12 cases), and poorly differentiated (small cell carcinoma, 6 cases). Among them, some cases were associated with squamous differentiation. The ultrastructural classification was compared with histological classification of lung carcinomas and the differences between them are discussed. The World Health Organization histological typing of lung tumours. Second edition.Am J Clin Pathol. 1982 Feb;77(2):123-36. The WHO Histological Classification of Lung Tumours, published in 1967, has been revised. The main features are as follows: Squamous cell carcinoma (epidermoid carcinoma) has the same definition as in the original version, i.e., the identification of keratin and/or intercellular bridges by light microscopy. Three degrees of histological differentiation are described. Dysplasia and carcinoma in situ are discussed. Small cell carcinoma is divided into oat-cell carcinoma, an intermediate cell type and a category for oat-carcinomas combined with other major types. Adenocarcinoma includes the acinar, papillary and bronchiolo-alveolar forms and the solid carcinomas with mucus formation (previously, part of the large cell carcinoma group). Mesothelial tumours are divided into fibrous, epithelial and biphasic subtypes. A number of less common tumours and tumour-like lesions are defined. Histological typing of lung tumours.Tumori. 1981 Aug;67(4):253-72. The WHO Histological classification of Lung Tumours, published in 1967, has been revised. The main features are as follows: Squamous cell carcinoma (epidermoid carcinoma) has the same definition as in the original version, i.e., the identification of keratin and/or intercellular bridges by light microscopy. Three degrees of histological differentiation are described. Dysplasia and carcinoma in situ are discussed. Small cell carcinoma is divided into oat-cell carcinoma, an intermediate cell type and a category for oat-cell carcinomas combined with other major types. Adenocarcinoma includes the acinar, papillary and bronchiolo-alveolar forms and the solid carcinomas with mucus formation (previously part of the large cell carcinoma group). Mesothelial tumours are divided into fibrous, epithelial and biphasic subtypes. A number of less common tumours and tumour-like lesions are defined. Pulmonary carcinomas with pleomorphic, sarcomatoid, or sarcomatous elements: a clinicopathologic and immunohistochemical study of 75 cases. Am J Surg Pathol. 2003 Mar;27(3):311-24. We collected 75 primary pulmonary carcinomas with pleomorphic, sarcomatoid, or sarcomatous elements to better define their clinical, histologic, and immunohistochemical profile. The patient's age ranged from 42 to 81 years (mean 65 years), and the male-to-female ratio was 9.7:1. Sixty-nine patients (92%) were smokers. Cough and hemoptysis were the most frequent presenting symptoms. Fifty-nine patients (65%) died of disease: only stage significantly predicts overall survival (p = 0.0273). Microscopically, based on the WHO criteria, 58 cases were classified as pleomorphic carcinoma (51 with an epithelial component, 7 composed exclusively of spindle and giant cells), 10 as spindle cell carcinoma, 3 as giant cell carcinoma, 3 as carcinosarcoma, and 1 as pulmonary blastoma. Immunohistochemically, in the tumors composed exclusively of spindle and/or giant cells, thyroid transcription factor-1 (TTF-1) and cytokeratin 7 were positive in 55% and 70% of the cases, respectively, whereas surfactant protein-A was always negative. In pleomorphic carcinomas with an epithelial component, cytokeratin 7, TTF-1, and surfactant protein-A were positive in the sarcomatoid component in 62.7%, 43.1%, and 5.9% of the cases, respectively, whereas they were always negative in the sarcomatous part of carcinosarcomas and blastoma. In the epithelial component of pleomorphic carcinomas, cytokeratin 7, TTF-1, and surfactant protein-A were positive in 76.4%, 58.8%, and 39.2% of the cases, respectively, whereas the same antibodies did not react with the epithelial component of carcinosarcomas; in the case of blastoma, the epithelial part of the tumor was positive for cytokeratin 7 and TTF-1, whereas it was negative for surfactant protein-A. Cytokeratin 20 was always negative. In our opinion, this study: 1) supports the metaplastic histogenetic theory for this group of tumors; 2) shows that cytokeratin 7 and TTF-1, but not surfactant protein-A, are useful immunohistochemical markers in this setting; 3) confirms that stage is at the moment the only significant prognostic parameter, as in conventional non-small cell lung carcinomas; and 4) shows that this group of tumors has a worse prognosis than conventional non-small cell lung carcinoma at surgically curable stages I, justifying their segregation as an independent histologic type in the WHO classification. Surgery for young patients with lung cancer.Lung Cancer. 2003 Nov;42(2):215-20. OBJECTIVES: To investigate the relationship between the clinical features and prognosis in young patients with lung cancer who underwent resection. METHODS: Statistical analysis was employed on sex, age, symptoms, diagnosis, treatment and prognosis, in 92 young cases younger than 40 years old among 930 cases with primary lung cancer who underwent surgery from January 1978 to December 1996. RESULTS: There were 92 young patients with lung cancer, accounting for 9.89% of the total cases. They were 71 male and 21 female patients, with the ratio of 3.38:1.The histological types were 34 squamous cell carcinomas (37%), 30 adenocarcinomas (33%), 26 small cell carcinomas (28%), and two large cell carcinomas (2%). On TNM staging, there were 30 cases in stage I (32.6%), 30 in stage II (32.6%) and 32 in stage III (34.8%). Lobectomy was conducted in 54 patients (59%), pneumonectomy in 36 (39%) and wedge-shaped resection in two cases (2%). The rate of pneumonectomy in young patients was significantly higher than that of 18% in older patients (>40) with lung cancer (P<0.01). 57 patients (62%) received absolutely curative resection; 28 cases (30%), relatively curative resection; seven cases (8%), non-curative resection. The postoperative 5-year-survival was 46% (42/92), in comparison with 34% (288/838) in patients older than 40 receiving operation during the same period, with significant difference between the two groups (P<0.05). The 5-year-survivals in patients with squamous cell carcinoma, adenocarcinoma, small cell carcinoma and large cell carcinoma were 68% (23/34), 30% (9/30), 38% (10/26) and 0 (0/2), respectively. The survival in squamous cell cancer was markedly higher than in adenocarcinoma (P<0.01) and in small cell carcinoma (P<0.05). There was no significant difference between adenocarcinoma and small cell cancer. The 5-year-survivals in stage I, II and III were 63% (19/30), 53% (16/30) and 22% (7/32), respectively. There was no significant difference between stage I and II, while remarkable difference was found between stage I and III (P<0.01), and between stage II and III (P<0.05). The 5-year-survival in patients undergoing absolutely curative resection was 67% (38/57), and 14% (4/28) in patients with relatively curative resection, with significant difference (P<0.01). No patient survived longer than the 5th postoperative year in seven cases receiving non-curative resection. CONCLUSIONS: Young patients with lung cancer were more often seen in male than in female. Squamous cell carcinoma accounted for the most part, no statistical difference, however, compared with adenocarcinoma and small cell carcinoma. The pneumonectomy rate in young patients was remarkably higher than that in patients older than 40. The postoperative 5-year-survival in young patients was considerably higher than in patients older than 40 who underwent surgery during the same period. Favorable prognosis was seen in patients with squamous cell carcinoma and undergoing absolutely curative resection, while worse outcome in stage III cancer. Rare pulmonary tumors - a review of 32 cases. Oncology. 1998 Sep-Oct;55(5):431-4. In a review of pulmonary tumors diagnosed at our institute from 1976 to 1995, we found 20 malignant and 12 benign rare tumors, which accounted for 0.57 and 0.34% of all pulmonary tumors, respectively. The histological types of these rare malignant tumors were malignant lymphoma (6/20), carcinosarcoma (3/20), mucoepidermoid carcinoma (2/20), bronchial gland mixed tumor (2/20), adenocystic carcinoma (1/20), myoepithelioma (1/20), leiomyosarcoma (1/20), epitheloid hemangioendothelioma (1/20), hemangiopericytoma (1/20), malignant melanoma (1/20) and choriocarcinoma (1/20). Benign rare tumors involved papilloma (3/12), lipoma (3/12), leiomyoma (3/12), adenoma (1/12), fibroma (1/12), and meningioma (1/12). The clinical and pathological features of malignant tumors were roughly the same as those of common pulmonary carcinomas. In contrast, benign tumors were never larger than 3 cm and were more commonly located in the central parts of the lung, which explained the relatively frequent symptoms of wheezing and fever associated with obstructive pneumonia. Childhood primary pulmonary neoplasms.J Pediatr Surg. 1993 Sep;28(9):1133-6. Nine children (6 boys, 3 girls) were diagnosed with a primary endobronchial or pulmonary parenchymal neoplasm. The average age at diagnosis was 9 years. Presenting complaints included cough (7), fever (5), pulmonary infection (3), respiratory distress (3), weight loss (2), pain (2), and hemoptysis (1). Pulmonary x-rays showed persistent atelectasis, pneumonic infiltrates or mass lesions. A computed tomography scan was performed in 8. Five of six endobronchial tumors were diagnosed with bronchoscopy and biopsy. Treatment consisted of thoracotomy and pulmonary resection in 7 cases and laser resection in 2. The pathologic diagnoses were bronchial carcinoid (3), bronchial mucoepidermoid carcinoma (1), inflammatory pseudotumor (plasma cell granuloma) of the bronchus (2) and of the lung parenchyma (1), fibrosarcoma (1), and rhabdomyosarcoma (1). Postoperative chemotherapy was given only to the patient with pulmonary rhabdomyosarcoma; this child died. One child has developed a local recurrence while 7 children are alive and free of disease at an average of 2.4 years postresection. Pulmonary neoplasms are unusual in the pediatric age group and represent a wide spectrum of pathology. Including the present series, 383 tumors have been described. Seventy-six percent were malignant. Early investigation and surgical intervention are essential in children with persistent pulmonary symptoms or x-ray abnormalities. In most cases, the prognosis is excellent with complete surgical resection; however, malignancies other than bronchial adenoma are associated with significantly mortality. Rare pulmonary neoplasms. Mayo Clin Proc. 1993 May;68(5):492-8. We reviewed the clinical course and the results of various treatment modalities of 80 patients with rare pulmonary neoplasms, who constituted 0.8% of all patients with primary lung cancer treated at the Mayo Clinic from 1980 through 1990. The 50 male and 30 female patients had a median age of 60 years (range, 20 to 87). The histopathologic types of these rare pulmonary neoplasms were non-Hodgkin's lymphoma (41%), carcinosarcoma (20%), mucoepidermoid carcinoma (15%), malignant fibrous histiocytoma (5%), malignant melanoma (4%), fibrosarcoma (4%), leiomyosarcoma (4%), angiosarcoma (2%), hemangiopericytoma (2%), osteosarcoma (1%), and blastoma (1%). Follow-up was complete in all 80 patients, and the median duration of follow-up was 59 months (range, 15 to 130). Of the 80 patients, 63 (79%) underwent pulmonary resection. Of the other 17 patients, 8 underwent only bronchoscopy for diagnosis, 4 had unresectable disease at thoracotomy, 3 had metastatic disease on initial assessment, and 2 had mediastinal involvement detected on mediastinoscopy. Fifty-four patients (68%) received chemotherapy or radiation treatment (or both). The overall 5-year survival was 39%. The strongest factors that influenced survival were cell type and extent of disease at time of initial examination. Primary pulmonary neoplasms of childhood: a review.Ann Thorac Surg. 1983 Jul;36(1):108-19. Primary tumors of the lung rarely occur in children. However, 230 well-documented cases, including the 2 presented in this review, have been identified in the English-language literature. One hundred fifty-one tumors in these reports were classified as malignant lesions and 79 as benign neoplasms. Bronchial "adenomas" constituted the largest group; most of these lesions were of the carcinoid variety, and 8% were definitely malignant. Forty-seven cases of bronchogenic carcinoma were reported in children under 16 years of age, although there were few squamous cell tumors (12%). Fifty-six percent of the benign tumors were classified as inflammatory pseudotumor. Most of the children in this collective series were seen with symptoms related to bronchial irritation or obstruction, such as cough, hemoptysis, atelectasis, or pneumonitis. Respiratory distress was an unusual symptom that was often associated with large tumors seen in the neonatal period. Approximately 20% of the children were totally symptomatic. The limited survival data that are available indicate that leiomyosarcoma and mucoepidermoid carcinoma have a more favorable prognosis in children than in adults. Survival with bronchial carcinoid tumors (90%), bronchogenic carcinoma (30%), and pulmonary blastoma (45%) appears to parallel that for adults. The experience with pulmonary rhabdomyosarcoma, as described in this review, emphasizes the importance of early diagnosis and the use of combined modes of therapy in the approach to these malignancies. Despite the rarity of primary pulmonary neoplasms in children, this diagnosis should be considered in young patients with solitary pulmonary masses or persistent, atypical pulmonary symptoms. It is hoped that early diagnosis will result in an improved prognosis and prevent life-threatening complications.
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