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Ossification of lung tissue is a rare phenomenon, which can be found in association with carcinoid tumors of the lung or pulmonary blastomas. Very rarely, ossifications are observed in lung metastases of extrathoracal epithelial tumors. In these cases, the most probable primary focus is a colorectal adenocarcinoma. Our question was, whether ossifications in lung metastases are pathognomonic for colorectal adenocarcinomas and how they can be pathogenetically arranged. A total of 15 lung metastases with ossifications from 5 patients suffering from a colorectal adenocarcinoma were examined by means of immunohistochemistry. Thereby, we found an increased expression of bone morphogenetic protein (BMP) 2/4 and osteonectin in tumor cells, as well as an increased stromatogenous expression of collagen type III. We conclude that there is strong evidence of a primary colorectal adenocarcinoma when ossifications in lung metastases are found. In these cases, a common metastatic spread of tumor cells and tumor stroma seems to be probable.

In the course of a prospective multicenter study, 40 (26 squamous cell and 14 adenocarcinomas) patients with stage IIIA and IIIB non-small cell lung cancer (NSCLC) were submitted to surgery after neoadjuvant radiochemotherapy. Pretherapeutic clinical lymph node status was compared to the lymph node involvement established in the resection specimens. Therapy-induced tumor regression was classified according to a three-step tumor regression grading system. In 29 patients (72.5%) a downward shift in lymph node involvement could be established,whereas in 27.5% ( n=11) pretherapeutic lymph node status was maintained. Of 26 patients with post-therapeutic N0 or N1 status, 21 revealed less than 10% vital tumor tissue in the resection specimens (regression grades IIb or III). Patients with post-therapeutic N0 or N1 lymph node status were found to have a survival benefit compared to patients with N2 lymph node involvement, though this difference was not statistically significant (p=0.27). On the other hand, tumor regression showed a significant correlation to the overall survival period (p=0.02). Thus, therapy-induced tumor regression grading seems to be a more precise method to predict the outcome of the disease.

We reexamined biopsy and resection specimens from seven patients with histologically established primary diagnosis of small-cell lung cancer (SCLC) which showed previously undetected adenocarcinomatous differentiation after chemotherapy. Adenocarcinoma was diagnosed in the same part of the lung as was SCLC before treatment in five cases and in contralateral location in two. Two tumors showed heterogeneous differentiation with small-cell and adenocarcinomatous components, and five had only adenocarcinoma. The interval between histological evidence of SCLC and adenocarcinoma was 3 months-5 years. From the specific findings in the respective patients we can offer two possible explanations for changing differentiation in SCLC after chemotherapy: (a) a primarily heterogeneously differentiated tumor with selection of adenocarcinomatous component under chemotherapy, and (b) an independently developed adenocarcinoma after successful chemotherapy of SCLC, as patients with treated SCLC are known to have an increased risk of non-SCLC. However, therapy-induced alteration of differentiation seems much more unlikely. These findings should be considered in diagnosis and therapy of SCLC to allow early and appropriate reaction to non-SCLC components.

Background: Previous research has demonstrated that adenocarcinoma is the leading cell type among patients with early age onset lung carcinoma. An increase in adenocarcinoma at the expense of squamous cell carcinoma in general was observed in recent years and may be due to the smoking of filtered cigarettes., Methods: To rule out whether shifts in smoking patterns or other etiologic factors are responsible for the high rates of adenocarcinoma in young patients, personal interviews regarding smoking, occupation, and family history of cancer were conducted in 251 young patients (age < or =45 years) and 2009 older patients (ages 55-69 years) with histologically confirmed lung carcinoma from selected study clinics in Germany between 1990 and 1996., Results: Young male patients were found to have significantly more adenocarcinomas (41%) than older male patients (28%), whereas adenocarcinomas were dominant in young and older women (43% and 47%, respectively). Because smoking patterns were different between young and older patients, the authors stratified for comparable levels of smoking exposure. Histology did not differ in never smokers (dominance of adenocarcinomas in both age groups) and in male heavy smokers (dominance of squamous cell carcinomas in both age groups), whereas young male low dose smokers showed significantly more cases of adenocarcinoma than older low dose smokers. A family history of lung carcinoma was significantly higher in young patients compared with older patients, but no association with histologic type was observed., Conclusions: The results of the current study show that differences in the histologic type of lung carcinoma based on age at onset can be explained in part by differences in smoking patterns. However, there still are unknown factors that appear to favor the development of adenocarcinoma in the young.

We studied the relation between various histological types of lung cancer and the number of years of cessation from smoking using data from a recently completed case-control study in Northern Germany. In this context we wanted to answer the question whether smoking cessation is a specific symptom of small cell lung cancer. Defining current smokers as the reference group the odds ratios decreased with years of cessation. Based on the analysis of all male cases and controls in our study, former smokers who stopped smoking 6-10 years ago had an odds ratio of 0.97 (95% confidence interval (C.I.) = 0.65-1.45), ex-smokers with 11-20 years of smoking cessation had a reduced risk of 0.55 (95% C.I. = 0.38-0.79), and for more than 20 years of cessation we found an odds ratio of 0.25 (95% C.I. = 0.16-0.40). Moreover, these calculations are also presented for the major groups of histological types of lung cancer. Our data show that there is no evidence for the presumption that cases with small cell lung cancer stop smoking earlier than cases with other histological types: in no other histological category we found such a big part of current smokers.

In 50 lung cancers (25 small cell lung cancers, 17 squamous cell carcinomas, 8 adenocarcinomas) pulmonary, mediastinal and cervical lymph node-metastases were analyzed. Lymph-node "skipping" was demonstrated in 46% of the investigated tumors. In seven of these cases the lymph nodes were skipped, which showed complete hyalinization as a consequence of preexisting anthracosilicosis. In 5 other tumors additional lymph nodes with preserved structure were skipped by the metastatic process. Fibrosis of lymphatic tissue after tuberculosis or exposure to ionizing radiation were further reasons for lymph-node skipping. The skipping of intact lymph nodes can be explained by anatomically demonstrable intra- and perinodal short circuit connections. Apart from that, preexisting lymph node changes (silicosis, fibrosis) play an important part.

In the scope of a prospective multi-centre study after neoadjuvant combined chemotherapy (carboplatin, ifosfamide, etoposide, vindesine) and radiotherapy (45 Gy) 40 resection specimens of locally advanced non-small-cell lung cancer were analysed in order to establish reproducible pathological/anatomical results of tumour regression. Resection specimens of 28 squamous cell carcinomas and 12 adenocarcinomas were investigated using serial sections of the primary lesion. The mean age of the patients was 57 years. The results were compared to spontaneous regressive changes in a control group of 50 untreated non-small-cell lung cancers. Marked scarry fibrosis in the region of the former primary tumour, concentric foci of fresh tumour necroses and surrounding foam cell clusters with transition into vascular granulation tissue could be established as characteristic features of therapy-induced tumour regression, whereas untreated carcinomas revealed necroses with adjoining vital tumour tissue. Using a three-step regression system, 3 tumours could be classified as grade I (no or only slight tumour regression), 10 tumours as grade IIA (marked but incomplete tumour regression, more than 10% vital tumour tissue), 20 tumours as grade IIB (less than 10% vital tumour tissue) and 7 tumours as grade III (complete tumour regression without vital tumour tissue). After a median follow-up period of 32.3 months in patients with grade IIB or III tumour regression ("responders") the median survival time of 27.9 months was found to be significantly longer than in patients with grade I or IIA tumour regression ("non-responders") with a median survival period of 13.7 months (log-rank test, P = 0.020). The resection specimens analysed, which were obtained 7 weeks (on average) after the end of radiochemotherapy, did not show specific changes due to preoperative therapy, but quite characteristic histological alterations in the former tumour area were registered, which had been induced by combined neoadjuvant radiation and chemotherapy. The grade of therapy-induced tumour regression could be shown to be a significant prognostic factor in non-small-cell lung cancer.

A study was undertaken to analyse the type and extent of pathological changes in the pulmonary arteries in non-small cell malignant tumours of the lung. Large-section histological preparations were made from 33 squamous cell carcinomas and 30 adenocarcinomas (T1 and T2 tumours) and classified according to tumour margin area (zone 1), intermediate area (zone 2) and tumour centre (zone 3). Transmural tumour growth with intraluminal cell formations in the pulmonary artery branches were found in the centre of all adenocarcinomas and 86% of squamous cell carcinomas, involving subsegment, prelobular and lobular arteries. Obstructive and obliterative changes in the pulmonary arteries as the result of tumour compression and secondary fibrosing changes predominantly occurred in the centre of all tumours. They were less common and less marked in zones 1 and 2. -Pulmonary artery branches in lung tumours of stages T1 and T2 showed marked infiltrating, obliterative and secondary inflammatory changes as far as complete vascular occlusions. These observations indicate that cytotoxic drugs, introduced via the systemic circulation, cannot reach and therefore not exert their effects in extensive areas of tumour.

Three years after heart transplantation and immunosuppressive therapy, a 66-year-old man suffered from dyspnea and showed symptoms mainly due to right heart failure. Malignant tumor cells were discovered within extensive pleural effusion. Computed tomography revealed two lesions of the liver suspicious of metastases, and recurrent blood in the stools was evident. The patient deteriorated rapidly and died 3 weeks after admission. Autopsy findings included an adenocarcinoma of the cecum (grade II) with metastases to the liver. High-grade immunoblastic non-Hodgkin's lymphoma of plasmoblastic differentiation was diagnosed, located within the mediastinal soft tissues and infiltrating the peri- and myocardium. Mesenteric lymph nodes were enlarged with histological verification of malignant lymphoma. The lymphatic tumor masses had caused considerable compression of the heart and vessels, leading to the signs of cardiac failure. The development of metastasizing colonic carcinoma and high-grade immunoblastic non-Hodgkin's lymphoma 3 years after heart transplantation and immunosuppressive therapy must be considered an unusual combination. Malignent lymphomas following heart transplantation have been described several times.

Immunohistochemical investigations on tumours of the lung and pleura led to an enlarged knowledge about the characterization of the tumours biology and the typical morphological feature of lung tumours. A helpful tool was the elaboration of monoclonal antibodies against different cellular proteins and proliferation markers which revealed a detailed information on proliferation tendency and immunological reaction of the tumour. The most informative parameter in adenocarcinomas was the distinguished expression of the carcino embryonic antigen (CEA). The immunohistochemical investigations are helpful for the differentiation of primary and secondary lung- and pleural tumours, but also pointed out a high heterogeneity of malignant lung tumours. Nevertheless the present tumour markers--be considered to give an indication for diagnosis, therapy and prognosis of the development of the disease--have to be correlated with clinical and biochemical data for further estimation of their value.

In a case-control study to examine the risk factors for bronchial carcinoma, 194 histologically confirmed cases of lung cancer and twice the number of controls (194 hospital controls, 194 population controls) were covered. In addition, the histological material obtained from 139 patients was assessed by a reference pathologist. In 107 cases (77%) the data coincided with the findings by the hospital pathologists. In women, young patients and persons with better general job qualifications adenocarcinomas and other bronchial carcinomas were seen more often and small-cell carcinomas as well as squamous cell carcinomas were rarer. Smoking did not entail any significant difference in respect of bronchial carcinoma risk. There was a significant risk increase among persons occupationally exposed to polycyclic aromatic hydrocarbons, arsenic, chromium, nickel and radionuclides in respect of squamous cell and small-cell carcinomas but not of adenocarcinomas and other histological types of carcinoma.

In the diagnosis of a so-called scar carcinoma, one of the accepted morphological characteristics is the deposition of dust in tumours of the lung. In 50 bronchial carcinomas in former miners and patients not occupationally exposed to dust, the cause and significance of such lesions were investigated in autopsy and surgical material. Impregnation with dust must be considered to be a secondary phenomenon of the infiltrative tumour growth. Such depositions depend upon previously present dust depositions in the pulmonary parenchyma and on the localisation of the tumour, and reveal a clear correlation with the histological type and degree of differentiation of the tumour.

The categorization of lung tumors into histologically defined groups and subtypes is based on morphometric criteria, on various degrees of tumoral differentiation and growth patterns. Light microscopic examination of different sections of one and the same tumor reveals in more than 30% of the cases investigated a qualitative and quantitative heterogeneous cell and tumor growth pattern, which is further proved by additional immunohistochemical, electronmicroscopic and DNA-flow cytometry studies. According to observations on the ultrastructural level mixed or combined morphologic features signaling abnormal differentiation patterns in preneoplastic lesions of the bronchial mucosa were visible. So-called amphicrine cells containing mucous vacuoles as well as granules of neurosecretory type were found in basal cell and goblet cell hyperplasia. Squamous-type cells predominate in epidermoid metaplasia and in dysplasia. Cells containing mucous granules or tonofilaments and scant granules of dense core-type suggestive of squamous neurosecretory differentiation were present in all lesions. The ultrastructural features were correlated with the bronchial carcinoma cell heterogeneity and histogenesis.

The reaction patterns in 80 adenocarcinomas of the lung were examined with PAP-method using a monoclonal antibody against keratin and one against carcinoembryonic antigen (CEA) and a polyclonal antiserum against CEA. Almost all tumors showed a positive reaction to the antibodies which, however, varied quantitatively. Even though a reliable correlation of positive immunohistochemical reaction with the different light microscopical types was not possible according to WHO subtypes and degrees of differentiation, specific localization of the reaction within the tumor cells was seen with increasing differentiation. There was no correlation between the immunohistochemical reactions and 14 clinically measured plasma CEA levels. The plasma CEA level not only depends on CEA production by the tumor but also on other factors.

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