Alveolar Cell Tumor Research Articles

Acute effects of 4-ipomeanol on experimental lung tumors with bronchiolar or alveolar cell features in Syrian hamsters or C3H/HeNCr mice.

4-Ipomenaol (IPO) has been shown to induce P-450-mediated necrosis of Clara cells in experimental animals, and clinical trials were initiated to treat people with bronchioloalveolar cancers with this novel drug. We therefore performed experiments to examine two different animal lung tumor models for acute IPO cytotoxicity: hamster Clara-cell-derived adenocarcinomas and mouse alveolar type II cell tumors. Clara cells serve as stem cells for airway cell renewal and, therefore, tumors derived from Clara cells may likewise differentiate into various bronchiolar cell types, or undergo squamous cell metaplasia. Bronchiolar cell tumors were induced in Syrian hamsters by a single weekly gavage with 6.8 mg N-nitrosomethyl-n-heptylamine (NMHA)/animal for 35 weeks. NMHA-induced bronchiolar tumors were classified as well-differentiated lepidic bronchioloalveolar carcinomas, acinar adenocarcinoma, adenosquamous carcinoma, and squamous-cell carcinoma. After 35 and 46 experimental weeks, control and carcinogen-treated hamsters were injected once with doses of 40-110 mg IPO/kg i.p. and necropsied 15-48 h later. Solid and papillary tumors with alveolar cell features were induced transplacentally in C3H/HeNCr mice, by treating pregnant animals on gestation day 16 with 0.5 mmol N-nitrosoethylurea/kg, i.p. Offspring of control and carcinogen-treated mice were injected at 2-3 months of age with 35 mg or 50 mg IPO/kg i.p. and necropsied either 24-48 h or 5 and 12 days after injection. Light microscopic studies were carried out to assess cytotoxic effects in various tissues in both hamsters and mice; in hamsters, additional ultrastructural studies were performed. When administered to hamsters, IPO induced moderate to severe cytotoxicity in normal and dysplastic bronchiolar lining cells, in most lepidic bronchioloalveolar carcinomas, and in some glandular areas of adenosquamous cell carcinomas. Susceptible cells included normal, anaplastic, and neoplastic nonciliated and some ciliated bronchiolar cells. Undifferentiated and squamous tumor cells were resistant to IPO, as were resident normal alveolar type II cells. However, some adenocarcinomas composed primarily of ciliated and mucous cells also showed no IPO-induced necrosis, indicating a deficiency in appropriate activating enzymes. In the mice, IPO induced bronchiolar cell necrosis and, at the high dose, also severe pulmonary edema. No cytotoxicity was observed in normal or hyperplastic alveolar epithelium, nor in either solid or papillary growth forms of mouse alveolar cell tumors.(ABSTRACT TRUNCATED AT 400 WORDS)

SO‐CALLED SCLEROSING HEMANGIOMA OF THE LUNG

Sclerosing hemangioma of the lung (SHL) was investigated immunohistochemically, histochemically and ultrastructurally with reference to cellular components associated with the histologic pattern: cuboidal cells in the papillary type, round cells in the solid type, flat cells in the hemorrhagic type and stromal cells in the sclerotic type. Immunohistochemically, cuboidal cells were positive for CEA, cytokeratin and EMA, whereas other cells were positive for EMA and vimentin. Immunoreactive factor-VIII-related antigen was confined to endothelial cells. Histochemically, cuboidal cells displayed alkaline phosphatase activity, but round cells showed ATPase activity. However, in spite of these different histochemical and immunohistochemical properties, morphological continuity was clearly revealed in immunostained sections; direct connection of spaces lined by cuboidal and flat cells, direct contact between cuboidal and stromal cells, and EMA expression of round cells associated with luminal structures were evident. Ultrastructurally, cuboidal cells were like alveolar cells. Flat and stromal cells showed microvillous protrusions and a discontinuous basement membrane, but some cells contained lamellar bodies. Solid cellular sheets consisted of various cells intermediate between cuboidal and flat or stromal cells. Direct apposition among these cells was evident. This morphological continuum confirms that each of these cell types are components of SHL as a whole. SHL may thus be merely sclerotic hemorrhagic alveolar cell tumor.

Silica-induced alveolar cell tumors in rats.

Min-U-Sil5, a form of alpha quartz, has been shown to induce peripheral lung tumors in rats exposed to the dust by inhalation. The animals were exposed to a nominal particle concentration of 12.4 mg/m3 for 8 hr/day, 4 days/week, for 2 years. The induced tumors were large and peripheral, and, when examined by electron microscopy, were found to be composed predominantly of alveolar type II cells. These cells were found in papillary, acinar, and solid forms of the tumors and were characterized by lamellar inclusion bodies. This is in contrast to the mouse, in which the papillary form was associated with Clara cells and the acinar form was linked with the type II cell. In this study, the Clara cell was a minor component of the tumor mass. No clear risk is established in man linking silica exposure to increased lung tumor rates.

Association Between Cage Shelf Level and Spontaneous and Induced Neoplasms in Mice<xref ref-type="fn" rid="FN2">2</xref>

Data from a chronic feeding study with 2-acetylaminofluorene [(2-AAF) CAS: 53-96-3; N-fluoren-2-yl-acetamide] done on 20,880 female BALB/c mice were analyzed for associations between cage shelf level and occurrence of induced and spontaneous neoplasms. Each cage was maintained on a rack at a given shelf level throughout the experiment, allowing analysis of data by shelf level. Differences in the crude incidence of 2-AAF-induced liver and bladder neoplasms appeared to be shelf related, but these differences were small and disappeared when shelf-level analyses of time-to-tumor onset distributions were performed. There was evidence for a shelf-level influence on 5 of the 6 major spontaneous neoplasms noted. Time to onset of uterine polyps and reticulum cell sarcomas was significantly delayed on the top shelf of five of six animal rooms. Also, there was a significant delay in onset of lymphomas, adrenocortical adenomas, and lung alveolar cell tumors on the top shelf when data were combined from all six animal rooms, but these delays on the top shelf were significant in no more than two of six animal rooms when rooms were analyzed separately. There was no indication of any shelf-level influence on the development of harderian gland adenomas. In conclusion, shelf level is an environmental factor that should be considered in the design and analysis of carcinogenesis studies.

In vivo anti-tumor immunity detected by leukocyte adherence inhibition

The immune response of mice to a transplacentally induced alveolar cell tumor was studied with the leukocyte adherence inhibition (LAI) assay. The lung tumor, designated 85, was induced in a C3HfB/HeN (C3Hf) mouse by l-ethyl-l-nitrosourea (ENU). While a dose of 105 cells of this tumor does not grow in syngeneic C3Hf mice, it does grow readily in (A×C3Hf)F1 hybrid mice. The tumor possesses a tumor associated transplantation antigen (TATA) which cross-reacts with a normal tissue alloantigen in strain A/HeN (A) mice. Normal mice, tumor-immunized C3Hf mice, and tumor-bearing (A×C3Hf)F1 mice possessed peritoneal cells, the majority of which adhered rapidly to glass and resisted gentle washing. When incubated with an extract of the 85 tumor, peritoneal cells from tumor-immunized mice demonstrated marked inhibition of adherence (62.4%) compared to similarly incubated peritoneal cells of either normal mice (30.3%) or tumor bearing mice (37.1%). Specificity of the reactivity in the LAI assay was demonstrated with a neuroblastoma extract and peritoneal cells from neuroblastoma-immunized C3Hf mice. Peritoneal cells from lung tumor-immunized mice, but not tumor-bearing mice, responded to a lung extract from strain A mice. In contrast to the microcytotoxicity assay, the LAI assay is capable of distinguishing the effective anti-tumor response of tumor-immunized C3Hf mice from the ineffective immune response of tumor-bearing (A×C3Hf)F1 mice.

Human peripheral lung tumours: light and electron microscopic correlation.

Thirteen human peripheral lung tumours have been studied in both light and electron microscopy. They were classified as epidermoid carcinoma, mucus-secreting cell adenocarcinoma, and alveolar cell adenocarcinoma, the latter made up of granular pneumocytes. Alveolar cell cancer, as defined by ultrastructural features, could assume different gross histological patterns in light microscopy, and therefore electron microscopy is required for its identification.Since neither squamous nor mucous metaplasia was observed in any alveolar cell tumour, it is tentatively suggested that all peripheral lung tumours which lack these features may be derived from granular pneumocytes, irrespective of whether they appear to be adenocarcinomata or large cell carcinomata when examined by light microscopy.

The metastatic origin of alveolar-cell tumour of the lung.

The metastatic origin of alveolar-cell tumour of the lung.

Bronchiolar-cell carcinoma.

Bronchiolar carcinoma is a recognized clinical and pathologic entity. The radiologic findings are not specific, but permit the consideration of the diagnosis in many cases. While it is undoubtedly true that the x-ray appearance is extremely varied, the findings are completely understandable if they are classified according to the stage of development of the tumor. In its behavior, location, and relatively benign histology, bronchiolar carcinoma is quite different from bronchogenic carcinoma. The authors are reporting 16 cases (Table I) to illustrate the various features of the condition. Cases of intrinsic bronchogenic carcinoma or with primary adenocarcinoma elsewhere in the body have been excluded. Synonyms: The most common synonyms for bronchiolar carcinoma are: alveolar-cell carcinoma, pulmonary adenomatosis, papillary adenocarcinoma, and mucous carcinoma. Others are: primary multiple carcinoma, multicentric papillary adenocarcinoma of the lungs, columnar-cell carcinoma, alveolar-cell tumor, malignant adenomatosis, and multiple nodular carcinoma. Still others are mentioned by Liebow (15). Definition: Bronchiolar carcinoma is a primary lung tumor probably originating in the terminal bronchioles (Herbut, 10) in the peripheral portions of the lung. It has a relatively benign histologic appearance and is composed of tall columnar or cuboidal mucus-secreting cells lying on an intact alveolar septum. It does not, as a rule, destroy the normal pulmonary tissue. We are making no distinction between this tumor and pulmonary adenomatosis. Etiology The etiology of bronchiolar carcinoma is unknown. It is a primary lung tumor with a distinctive histologic pattern and pathogenesis, setting it apart from other pulmonary neoplasms. Its relation to Jaagsiekte (probably a virus infection) in sheep, chronic inflammations (Beaver and Shapiro, 2), and possibly to irritating fumes such as smog and tobacco smoke, is of interest. None of these, however, has been established as the cause of bronchiolar carcinoma in man (Storey et al., 25). Pathology Gross: Small tumors are found in the peripheral portion of the lung. Rarely major bronchi may be invaded late in the course of the disease. There are no favorite sites; all lobes and either or both lungs may be involved. The tumors may be multiple or solitary, varying in size from those measuring a few millimeters in diameter to extremely large tumors involving the whole lung. A large mass may be present in one section and multiple small nodules may be found in another section or sections. The cut surface is moderately firm, gray-tan to yellow-brown in color. Mucus may exude from the cut surface. Nodular tumors may extend to the pleura. Pleural effusions may be present and be serosanguineous. Focal atelectases are not uncommon, but collapse of major bronchopulmonary segments, lobes, or a whole lung is rare.

Pulmonary adenomatosis (alveolar cell tumour): A case with an unusual cavitating lung lesion

Summary A case of pulmonary adenomatosis, with unusual features of ( a )) cavitation and ( b )) a prolonged survival rate since discovery of the lesion, is recorded.

The significance of cell types in bronchogenic carcinoma.

Physicians dealing with diseases of the thorax have long been aware that carcinoma of the lung varies greatly in its clinical manifestations, and that certain types of bronchogenic carcinoma are much more amenable to surgical eradication than others. The great frequency with which bronchogenic carcinoma occurs and its apparent increasing incidence make it essential to determine as far as possible the various factors that may influence the course of the disease. In discussing bronchogenic carcinoma, it is first essential to define what Is included by the term. Bronchogenic carcinoma is a primary carcinoma of the lung which is presumed to originate in the mucosa of the bronchi. Metastatic carcinoma of the lung, adenoma of the bronchus, and alveolar cell tumor must be distinguished from bronchogenic carcinoma, for not only are their clinical course and prognosis different from those of bronchogenic carcinoma, but they have an entirely different source of origin. The results of early studies that were carried out to classify carcinoma of the lung solely on the basis of grade of malignancy of the tumor according to the method of Broders were soon found to be of little or no clinical, surgical or prognostic value. It has long been recognized that true bronchogenic carcinoma may assume a variety of form’s, and many terms have been utilized by pathologists to describe these various changes. This lack of uniformity in terminology has made an understanding of the significance of cell types in carcinoma of the lung difficult. It Is only since sufficient surgical and necropsy material has become available that it is possible to study and correlate the clinical course of the disease with survival following operative intervention and to devise a workable histologic classifIcation. In order to study the problem of the significance of cell types of bronchogenic carcinoma, the records of 1,000 cases of proved carcinoma of the lung, taken at random from the files of the Mayo Clinic, were reviewed. In each case, the diagnosis of carcinoma of the lung was based on the examination of bronchoscopic specimens, specimens taken for biopsy at the time of thoracotomy for inoperable neoplasms, and surgical specimens obtained by lobectomy or pneumonectomy. This series did not include any case in which there was evidence of carcinoma elsewhere in the body or in which there was a chance that the pulmonary lesion might be metastatic. �Read at the Joint Session of the First International Congress of Bronchoesophagology and the Second International Congress on Diseases of the Chest of the American College of Chest Physicians, Rio de Janeiro, Brazil, August 24 to 30, 1952.

Esophageal carcinoma with alveolar cell tumor of the lung.

A case, believed to be unique, of alveolar cell tumor of the lung in association with squamous cell carcinoma of the esophagus is presented. It is believed that the absence of a primary cancer elsewhere should not be one of the criteria for making the diagnosis of alveolar cell tumor of the lung.

Alveolar Cell Tumor of the Lung

Alveolar cell tumors of the lung are rare and present symptoms which are often atypical and misleading. This tumor occurs in two forms, i.e. nodular or miliary variety and a diffuse or pneumonic type. A case is reported in whom an alveolar cell tumor existed for a period of 11 years before death occurred. Symptoms had been attributed to unresolved pneumonia throughout the major part of its course. Excisional surgery, where possible, is the treatment of choice but roentgen therapy is of aid in the inoperable case. Metastases usually occur only to regional lymph nodes. In the case presented, distant metastases were also found.

Pulmonary adenomatosis; report of two cases.

PULMONARY adenomatosis is a rare tumor of the lung characterized by the presence of tall columnar mucus-secreting cells lining the alveolar walls, without evidence of bronchial origin or of primary adenocarcinoma elsewhere. In the past few years there has been a marked increase in the number of reported cases, with two recent reviews of the literature1 , 2 and numerous pathological discussions.A considerable difference of opinion exists concerning pulmonary adenomatosis, or alveolar-cell tumors of the human lung, including complete disbelief in the existence of this condition as a separate entity.3 The question of the existence of a true alveolar epithelium has . . .

Atypical Pulmonary Inflammatory Reactions

1) A series of 10 cases has been presented with atypical pulmonary inflammatory reactions, probably of viral origin, that resemble closely those seen in chicken pox, rheumatic fever, and in primary atypical pneumonia. 2) The pulmonary changes failed to produce a clearcut clinical syndrome. As a rule, they supervened upon other diseases, predominantly cardiovascular disturbances. 3) The lesions include fibrinoid swelling of the walls of alveoli and blood vessels, septal-cell proliferation, mononuclear-cell exudate, hyaline membranes, occasional peppering with neutrophils, fibrinous plugs, fibrinophagia, Masson bodies, and bronchiolitis obliterans. Inclusion bodies were not seen. 4) The inclusion of these reactions, thus described, among the larger group of atypical pneumonias of diverse etiology appears justified on the ground of their histologic pattern. 5) Presence of Masson bodies should no longer be considered as occurring only in rheumatic pneumonia. 6) Diffuse progressive interstitial pulmonary fibrosis, pulmonary adenomatosis, and alveolar-cell tumor of the lung may result from such atypical pulmonary inflammatory reactions.

Cytologic Diagnosis of Bronchogenic Carcinoma

SUMMARY Our experience with cytologic diagnosis of bronchogenic carcinoma has been summarized. To date in more than 400 cases of bronchogenic carcinoma the diagnosis has been made cytologically with a false positive error of approximately 2 per cent. In our experience the false negative error has been approximately 30 per cent. Of 80 consecutive surgically removed bronchogenic carcinomas, 10 per cent were peripherally placed showing slight or no gross communication with the bronchial tree. Cytologic examination in the case of these peripherally located tumors gave negative results. Cytologic studies are of value in the diagnosis of alveolar-cell tumor but of no value in bronchial adenoma or cylindroma.

Cytologic Diagnosis of Bronchogenic Carcinoma

SUMMARY Our experience with cytologic diagnosis of bronchogenic carcinoma has been summarized. To date in more than 400 cases of bronchogenic carcinoma the diagnosis has been made cytologically with a false positive error of approximately 2 per cent. In our experience the false negative error has been approximately 30 per cent. Of 80 consecutive surgically removed bronchogenic carcinomas, 10 per cent were peripherally placed showing slight or no gross communication with the bronchial tree. Cytologic examination in the case of these peripherally located tumors gave negative results. Cytologic studies are of value in the diagnosis of alveolar-cell tumor but of no value in bronchial adenoma or cylindroma.

Alveolar cell tumour of the lung: Report of a case

Summary o 1. A case of alveolar cell tumour is described. 2. Diagnosis presents great difficulty, as the picture is indistinguishable from that of bronchial new growth. 3. Certain unusual features in the course of the disease and negative findings on investigation may at least lead to the inclusion of this condition in the differential diagnosis. 4. The balance of opinion appears to favour a bronchiolar origin of the tumour, but its unusual characteristics warrant a separate description.

Roentgenologic and Pathologic Aspects of Pulmonary Tumors Probably Alveolar in Origin

Among primary tumors of the chest, pulmonary alveolar-cell tumors are believed to be of relatively rare occurrence. They are characterized by their apparent independence of the bronchial system and by evidence of circumscribed or diffuse intra-alveolar origin and growth. In a recent review of lung tumors, Shinall (5) mentions that, during a five-year period, he did not see a single definite instance of carcinoma arising from the pulmonary alveoli. While the comparative scarcity of this type of tumor is not questioned, its infrequent observation may be due, at least in part, to the intrinsic difficulties of premortem radiologic and clinical diagnosis. The purpose of this report is to present six probable cases of alveolar-cell tumor and to discuss their differentiation from bronchiogenic and metastatic lung tumors and from infections with a similar x-ray appearance. Case 1: G. D., a 49-year-old baker, was first seen on May 10, 1940, complaining of cough, pain in the chest, and loss of weight for the past five months. Previous and family histories were not significant. The physical examination showed the patient to be cyanotic, dyspneic, and emaciated. Resonance was impaired over the bases of both lungs, especially on the left, where the breath sounds were diminished. The roentgenogram showed a large pleural effusion on the left and small scattered radiopacities in the right lung, suggestive of metastatic tumor invasion. (Due to the death of the roentgenologist, the roentgenograms are no longer available.) Bronchoscopy failed to show any obstruction. The symptoms increased in severity and, according to the roentgenologic report, pathologic changes became more visible in the left chest. Death occurred Sept. 5, 1940. Autopsy: The left pleural cavity contained 800 c.c., the right 100 c.c., of yellow fluid. Both lungs were studded with firm gray nodules, measuring about 0.3 cm. in diameter and occasionally coalescing. Bronchi and bronchioles were free from tumor. Liver and adrenals showed nodules similar to those in the lungs. Microscopic Examination: The nodules were composed of anaplastic columnar cells that lined fairly well preserved alveolar walls. The cells often formed papillary projections; some cells contained dust particles or pigment. Mitosis was infrequent. Occasional bronchi revealed nests of tumor cells in the submucosa. Thrombosis, inflammation, and early abscess formation were seen in one section. Metastases, mostly in a glandular pattern, were found in the hilar lymph nodes, liver, and adrenals. Case 2: L. C., a 53-year-old woman, entered the hospital on June 24, 1943, complaining of blurred vision, difficulty in articulation, drowsiness, and loss of weight. Her mother had died at sixty-five of a brain tumor. The past personal history was noncontributory. The patient was emaciated, with lungs normal to percussion and auscultation.

Malignant adenomatosis (alveolar cell tumour) of the lung

An example of malignant adenomatosis (alveolar cell tumour) of the lung is described occurring in a human subject. The literature is discussed and similarities to adenomatosis of sheep and some other animals are noted. These tumours appear to be true alveolar growths, and they show individually a series of stages from purely benign to highly malignant characteristics.