Lung cancer-associated myofibroblasts reveal distinctive ultrastructure and function.

BACKGROUND: Cancer-associated stromal cells interact with carcinoma cells and thus participate in tumor growth. Our aim was to characterize the ultrastructure and contractile properties of stromal cells in collagen gel cultured from lung cancer of various histological types and from tumor-free lung. METHODS: Cells cultured from lung cancer (13 adenocarcinomas, six squamous cell carcinomas, one adenosquamous carcinoma, and one pleomorphic carcinoma) and tumor-free lung were analyzed by transmission electron microscopy and three-dimensional collagen gel contraction assays. The expression of α-smooth muscle actin (α-SMA), a recognized myofibroblast marker, was examined by immunoelectron microscopy from individual cells and by Western blotting from the whole cultured cell population. RESULTS: According to their ultrastructure, the cell lines were composed of fibroblastic and myofibroblastic cells. In electron microscopy, cells of lung cancer exhibited more myofibroblastic features displaying higher amounts of actin belts (p = 0.057) and α-SMA labeling (p = 0.010) than cells from tumor-free lung. Myofibroblasts cultured from lung cancer of smokers expressed less α-SMA labeling (p = 0.013) than counterparts from nonsmokers. Western blotting revealed that cancer-associated fibroblasts expressed more α-SMA (p = 0.006) than cells from tumor-free lung, whereas cells from tumor-free central lung of smokers showed less α-SMA (p = 0.039) than counterparts from nonsmokers. Cells cultured from cancer contracted more in collagen gel than those from tumor-free lung. The contractile capacity in collagen gel correlated with the frequency of extracellular component of fibronexus by transmission electron microscopy. CONCLUSIONS: Lung cancer-associated myofibroblasts are different both ultrastructurally and functionally when compared with cells cultured from tumor-free lung. Smoking altered myofibroblastic phenotype, regardless of their origin.

Low-grade adenosquamous carcinoma of the breast: imaging and histopathologic characteristics of this rare disease.

Low-grade adenosquamous carcinoma is a rare histologic subtype of breast carcinoma that has a variable mammographic and sonographic appearance, which overlaps with both benign and malignant neoplasms. Because of its lack of unique imaging features, a diagnosis of low-grade adenosquamous carcinoma is based on histopathology. The recognition of this entity is an important consideration in the differential diagnosis of breast masses and carries implications for prognosis, which is more favorable than other types of breast carcinoma.

Elastosis in lung carcinoma: immunohistochemical, ultrastructural and clinical studies.

Elastosis is the pathological finding of focal deposits of elastic fibers in abnormal amounts within tissue. It is well described in the case of infiltrating carcinoma of the breast, but elastosis in lung carcinoma has not been previously documented in detail. We investigated the characteristics of elastosis in lung carcinoma with light and electron microscopies, and immunohistochemistry for alpha-1-antitrypsin. A total of 184 surgically resected primary lung carcinomas were studied. Elastosis was detected in adenocarcinomas (85/106), squamous cell carcinomas (11/60) and adenosquamous carcinomas (5/7), but not in small-cell carcinomas (n = 4) or large-cell carcinomas (n = 5). The degree of elastosis in each case was divided into one of five grades, graded as 3+ to 1-. The score of elastosis was significantly higher in adenocarcinoma than that in squamous-cell carcinoma (P<0.01). In the cases of adenocarcinoma, the mean score of elastosis in the well-differentiated type (WD n = 43) was higher than that in the moderately differentiated (MD) (n = 39; P = 0.012) and poorly differentiated (PD) types (n = 24; P<0.01). The mean score of elastosis in MD adenocarcinoma was also higher than that in the PD type (P<0.01). Light- and electron-microscopic analyses revealed that these elastic fibers in elastosis were composed of aggregates of thick mature and fine immature elastic fibers, and were positive for alpha-1-antitrypsin. It is suggested that both degraded elastic fibers and newly synthesized fibers are contained in the elastosis of lung carcinoma. Although no significant evidence was detected to suggest any correlation between elastosis and the degree of tumor invasion, the survival curves of adenocarcinomas with elastosis showed a significantly improved prognosis than of those without elastosis in the cases of stages IA and IB (n = 52; P = 0.026).

Adenosquamous carcinoma of the tongue: report of a case with histochemical, immunohistochemical, and ultrastructural study and review of the literature.

A rare case of oral adenosquamous carcinoma in a 78-year-old woman is reported. The tumor occurred in her tongue and metastasized to the submandibular and cervical lymph nodes. Histologically, the tumor showed invasive growth involving the submucosal and muscle layers. Its solid carcinomatous nests exhibited ductal differentiation in the deeper aspects and squamous differentiation toward the surface. Histochemical examination revealed an accumulation of acid mucopolysaccharide in the ductal lumina, and the ductal cells were immunohistochemically positive for carcinoembryonic antigen, epithelial membrane antigen, cancer antigen 15-3 and Ulex europaeus agglutinin I. Ultrastructurally, tonofibrils, desmosomes and numerous cytoplasmic processes were common features of the tumor cells. In addition, true glandular structures and pseudocysts were seen in areas. Clinical features of 13 adenosquamous carcinomas in the literature were analyzed.

[Objective histological grading of squamous and adenosquamous lung cancer]. / Objektiv histologisk gradering af planocellulaer og adenoskvamøs lungecancer.

The prognostic value of quantitative histopathological parameters was evaluated in 55 consecutively treated patients with operable lung carcinoma of squamous and adenosquamous cell type. Using a projection microscope, estimates were obtained of mean nuclear volume (vV(nuc)), mean nuclear profile area, nuclear profile density, nuclear volume fraction, and mitotic profile frequency. Patient sex, age, and clinical stage was recorded. Single-factor analyses showed a prognostic significance of clinical stage and patient age (2p < or = 0.03), whereas sex was marginally significant (2p = 0.09). Of the quantitative histopathological parameters only estimates of vV(nuc) were of prognostic significance (2p = 0.02), in that small nuclear volumes were associated with the worst prognosis. In a multivariate Cox analysis, clinical stage, age, and vV(nuc) were found to be of significant, independent prognostic value. Thus, the present study indicates that vV(nuc) is of prognostic value, independent of clinical stage. The parameter is highly reproducible and easily obtained using unbiased stereology, and may be of future importance in the management of lung cancer patients.

Objective malignancy grading of squamous cell carcinoma of the lung. Stereologic estimates of mean nuclear size are of prognostic value, independent of clinical stage of disease.

BACKGROUND: The prognostic value of quantitative histopathologic parameters was evaluated in 55 consecutively treated patients with operable lung carcinoma of squamous (N = 39) and mixed, adenosquamous (N = 16) cell type. Patients alive were followed for at least 12 years. METHODS: Using a projection microscope and a simple test system in fields of vision systematically selected from the whole tumor area of one routine section, five quantitative histopathologic variables were estimated: the mean nuclear volume, the mean nuclear profile area, the density of nuclear profiles, the volume fraction of nuclei to tissue, and the number of mitotic profiles per 10(3) nuclear profiles. For each patient, information was recorded regarding sex, age at diagnosis, and clinical stage of disease. RESULTS: Single-factor analyses showed that a favorable prognosis was associated with early clinical stages (Stages I and II) and young age (P < or = 0.03), and that females tended to do better than males (P = 0.09). Estimates of the mean nuclear volume were of prognostic significance (P = 0.02), small nuclei being associated with the worst prognosis. In a multivariate Cox analysis, clinical stage, age, and mean nuclear volume were found to be parameters of significant, independent prognostic value. CONCLUSIONS: The present feasibility study indicates that estimates of the mean nuclear volume are of prognostic value, independent of the clinical stage of disease. This quantitative histopathologic variable is highly reproducible and easily obtained using an unbiased stereologic method. Thus, the mean nuclear volume may be a parameter of future importance in the clinical management of patients with carcinoma of the lung.

Adenosquamous carcinoma of the thyroid: a case report and review of the literature.

A case of mixed squamous cell carcinoma and papillary adenocarcinoma of the thyroid in a 75-year-old woman is described. Review of 19 reported adenosquamous carcinoma including the present case revealed that they tended to occur in the sixth and seventh decades of life with an average age of 63.84 years and without sexual predilection. Local invasion and metastases of this highly fatal neoplasm are common.

Neuroendocrine component of different types of the pulmonary carcinoma.

One hundred and seventy lung tumors were examined: 155 squamous cell carcinoma, 12 adenocarcinomas and 3 mixed adenosquamous carcinoma. In electron microscopic examination the neuroendocrine cells were found: in 31 cases of squamous carcinoma, in 9 cases of adenocarcinoma, and 1 case of mixed adenosquamous carcinoma.