Cell proliferation and histologic classification of bronchogenic carcinoma.

The rate of cell proliferation of 99 bronchogenic carcinomas (94 primary tumors and 5 metastases) was evaluated from the labeling index after in vitro incorporation of [3H]thymidine; the rate was then correlated with the histologic tumor type according to the classification of the World Health Organization (WHO). Cell proliferation was significantly slower in adenocarcinoma (WHO type III) than in squamous cell carcinoma (WHO type I), small cell anaplastic carcinoma (WHO type II), and large cell carcinoma (WHO type IV). Cells proliferated at a significantly higher rate in large cell carcinoma than in the squamous cell type, whereas no significant difference was observed between the other cell types. Dedifferentiated forms of squamous cell carcinomas had a higher rate of cell proliferation than did differentiated forms of the same cell type. Metastases of small cell anaplastic carcinoma did not differ in cell proliferation from primary tumors of the same cell type.

Luminal plasma membrane organization in rat urinary bladder urothelium after direct exposure in vivo to N-methyl-N-nitrosourea.

Adult female rat urinary bladders were exposed to N-methyl-N-nitrosourea in vivo. After 12 weeks, urothelial hyperplasia was established. Ultrastructural changes of the luminal plasma membrane were studied with thin sectioning and freeze-fracturing techniques. The mosaic pattern which is a characteristic specialization of the normal luminal plasma membrane and of cytoplasmic vesicles disappeared. The plasma membrane of the transformed urothelium was indistinguishable from an undifferentiated membrane in the following respects: thickness; apparent symmetry in cross-section; and distribution of intramembranous particles. Zonulae occludentes became permeable to colloidal lanthanum and appeared disassembled, while desmosomes developed concomitantly. These membrane changes implicate increased permeability and less adaptability of urothelial function to mechanical stress caused by bladder volume changes. The increased desmosome formation may indicate that squamous metaplasia is a feature of early malignant urothelium transformation. It is proposed that N-methyl-N-nitrosourea treatment induces a change in the plasma membrane assembly and specialization.

Effect of BAY K 8644 on cytosolic free calcium in isolated rabbit gall-bladder epithelial cells.

Rabbit gall-bladder epithelial cells were isolated by a combination of Ca2+ omission, enzymatic treatment, and mechanical detachment and had a viability of 96-98% and well preserved morphology. Measurements of cytosolic free Ca2+ concentration ([Ca2+]i) in these cells with the Ca2+-fluorescent indicator fura-2 demonstrated a resting [Ca2+]i level of 115 +/- 12 nM. When used in concentrations which inhibit rabbit gall-bladder isosmotic NaCl absorption (1-100 microM), the Ca2+-channel activator BAY K 8644 caused a dose-dependent increase in the epithelial [Ca2+]i to a maximal value of 850 nM. The effect was dependent on extracellular Ca2+, and was not altered by 1 microM L-verapamil. Depolarization of the epithelial cells with KCl had no effect on [Ca2+]i. The results suggest that BAY K 8644 activates a Ca2+ influx which is not dependent on voltage-gated channels. Cytosolic Ca2+ may be involved in the regulation of isosmotic NaCl absorption in the mammalian gall-bladder.

Kaposi's sarcoma in liver transplant recipients on FK506: two case reports.

We report two cases of Kaposi's sarcoma (KS) after orthotopic liver transplantation for cirrhosis of the liver related to hepatitis C virus. Both cases were Saudi-born Arabs who were negative for human immunodeficiency virus; one patient was receiving FK506 plus prednisolone, and the other patient was receiving FK506. One patient died of fulminant multicentric KS. The other patient, with lesions confined to the lower limbs, is still alive. These are the first case reports of KS in liver transplant recipients in the Kingdom of Saudi Arabia and, to our knowledge, these are the first case reports of KS in liver transplant recipients on FK506. All previous reports were related to either cyclosporine or conventional immunosuppressive therapy, i.e., azathioprine plus prednisolone.

Intracardiac rhabdomyosarcoma: transesophageal echocardiographic findings and diagnosis.

Transesophageal echocardiography (TEE) was performed on a 41-year-old woman who presented with a cerebrovascular accident. TEE confirmed the presence of a morphologically bizarre biatrial tumor with precarious, vigorous motion throughout the cardiac cycle. Surgical intervention was decided on, and the patient underwent cardiac surgery for tumor excision 16 hours after TEE. Intraoperative frozen section diagnosis was spindle cell sarcoma, and subsequent immunohistochemical analysis showed the tumor to be a rhabdomyosarcoma. The data are presented here, and the role of TEE to establish a preoperative diagnosis of intracardiac tumor is discussed.

Electron microscopy of ultrasound-guided fine-needle biopsy specimens.

A prospective 3-year study was undertaken in order to assess the value of electron microscopy (EM) as a supplement to routine light microscopy (LM) in ultrasound-guided fine-needle biopsy of suspected abdominal and retroperitoneal tumours. Eight-six of the 899 ultrasound-guided fine-needle biopsies performed during this period were supplemented with EM using the following indications: metastatic lesions with unknown primary tumour, primary retroperitoneal tumours, tumours with atypical clinical histories and where the primary LM evaluation was unable to determine tumour cell type. Two methods of obtaining material for EM were tested, namely, fine-needle aspiration and fine-needle histological biopsy (Surecut). Both methods yielded suitable material for EM evaluation in approximately 80% of the 76 cases where tumour cells were identified by LM. However, it was technically easier to process material for EM when obtained by fine-needle histological biopsy. The results of the 62 cases where suitable material for EM was obtained were grouped according to the histopathological and clinical value of the diagnosis. In 23 cases (37%) EM was without additional diagnostic value. In 12 cases (19%), EM supplied a more precise histopathological diagnosis, but the diagnostic gain was without clinical significance. In 27 cases (44%) EM was of significant clinical value, as the diagnosis by itself was enough to change the investigative procedure and/or the treatment of the patient.

Ultrasound-guided, histological, fine-needle biopsy from suspect parathyroid tumours: success-rate and reliability of histological diagnosis.

Ultrasound-guided, fine-needle tissue biopsies were performed in 60 suspected parathyroid tumours in 55 consecutive patients with biochemically proven hyperparathyroidism. The specimens were randomly arranged and re-read "blind" by two pathologists. The interobserver agreement, corrected for chance agreement, was 0.92 (= kappa coefficient). Twenty-three of the 60 suspect parathyroid tumours were verified histologically following surgery. No diagnostic errors were seen but the percentage of insufficient biopsies from suspect parathyroid tumours or surgically verified parathyroid tumours was high (45 and 47%, respectively). We conclude that a reliable tissue diagnosis can be made by ultrasound-guided, fine-needle tissue biopsy. However, when the material is insufficient for histological diagnosis, we recommend the additional use of ultrasound-guided, fine-needle aspiration for cytology or parathyroid hormone determination.

Fine-needle aspiration biopsy of Ki-1-positive anaplastic large-cell lymphoma.

Five cases of Ki-1-positive anaplastic large-cell lymphoma diagnosed by fine-needle aspiration biopsy are reviewed, and cytologic, histologic, and ultrastructural findings in these cases are correlated. In all cases, the diagnosis of anaplastic large-cell lymphoma was suggested on the basis of the morphological appearance in aspiration smears. This diagnosis was confirmed by immunohistochemistry, which revealed strong positivity of most of the cells by Ki-1 antibody. Two of the lymphomas were T-cell type, one was B-cell type, and the remaining 2 were composed of null cells. In 2 cases, intracytoplasmic inclusions were seen in some of the tumor cells in aspiration smears. These were ultrastructurally correlated with large lysosomal bodies of variable morphology. Fine-needle aspiration combined with immunohistochemistry may be an effective technique for diagnosing this neoplasm.

Primary diagnosis and REAL/WHO classification of non-Hodgkin's lymphoma by fine-needle aspiration: cytomorphologic and immunophenotypic approach.

The Revised European American lymphoma (REAL) and World Health Organization (WHO) classification of non-Hodgkin's lymphoma (NHL) relies on the constellation of cytologic, phenotypic, genotypic, and clinical characteristics of NHL. For the most part, the classification does not rely on architectural pattern for classification of neoplasms. This classification makes it possible to diagnose and classify lymphomas by fine-needle aspiration (FNA). In this study, we attempted to evaluate the accuracy of FNA in diagnosing and classifying NHL within the context of the REAL/WHO classifications. Cases included only those in which FNA was the primary diagnosis, followed by a surgical biopsy for confirmation. Flow cytometry (FCM) for phenotyping was carried out whenever material was available. Two groups of pathologists were identified. Group A consisted of pathologists with background training in cytopathology and/or hematopathology (three pathologists). Group B consisted of experienced surgical pathologists with no training in cytopathology and/or hematopathology (four pathologists). Seventy-four cases were included in the study. FCM phenotyping was performed in 53 cases (71%). Large cell lymphoma constituted 63% of the cases. The remaining lymphomas included Burkitt's, small lymphocytic, lymphoblastic, follicle center cell, Ki-1, mantle cell, marginal zone, and natural killer cell lymphoma. The diagnosis of lymphoma was rendered for all cases. The correct classification was seen in 63% of the cases. Classification was more accurate in immunophenotyped than in nonimmunophenotyped cases (84% vs 33%; P = 0.00004). Group A pathologists showed higher incidence of proper classification than group B (80% vs 56%; P = 0.046). The diagnosis and classification of NHL can be achieved in a large number of cases on FNA material. This accuracy can be increased if cytomorphologic criteria are established for different entities of NHL aided by FCM for phenotyping.

Lymphatic capillaries of the periosteum: do they exist?

Normal periosteum from 12 humans was examined for the presence of lymphatic capillaries using immunohistochemistry (light microscopy) and transmission electron microscopy. Both techniques failed to demonstrate lymphatic capillaries suggesting that periosteum is devoid of these structures.

Collagen fibres in otosclerosis and in osteogenesis imperfecta tarda. A light and electron microscopic study.

Skin biopsies taken from patients with osteogenesis imperfecta tarda and otosclerosis were compared blind by light- and electron microscopy with similar biopsies taken from normal volunteers in an effort to find common pathological features in the collagen fibres from the two patient groups, thus corroborating the theory that osteogenesis imperfecta and otosclerosis might be due to a common genetic anomaly in the form of a mesenchymal hypoplasia. We were not able to find differences in structure or quantity of the collagen-, elastic- or reticular fibres between normals and the two patient groups. We cannot, on the basis of our previous work and on the present morphological investigation, give support to the above-mentioned theory.

Spindle cell carcinoma of the larynx.

Histology, histogenesis, biology and treatment of the rare spindle cell carcinoma of the larynx are presented. The histogenesis of spindle cell tumours has been much debated, but electron microscopic investigations have shown that most of the laryngeal lesions are squamous epithelial carcinomas that have undergone transformation to a spindle cell pattern. As confusion with supporting tissue neoplasms may occur in the light microscope, the use of the electron microscope in differential diagnostics is recommended.

Fibrous histiocytoma of the larynx.

We present a case of fibrous histiocytoma of the larynx in a young female who presented eight years ago and is still alive and well with no evidence of any regional invasion or distant metastasis. This rare lesion has been described in 30 cases previously of which 26 were malignant and four benign. Our case is unusual in a sense that histologically it has not been possible to determine its exact biological behaviour and growth potential. However, clinically it behaved as a low-grade malignant tumour.

Syndrome of camptodactyly, arthropathy and coxa vara (CAC syndrome).

Three Saudi children (two female, one male) are described who presented with familial arthropathy associated with congenital camptodactyly. This rare but recognized clinical entity has a variable clinical presentation and may be associated with pericarditis and coxa vara. Camptodactyly was observed in the neonatal period in all patients, while joint swelling was observed between the third and 11th month. Pericarditis was suspected in the referral hospital in one patient but was not subsequently confirmed at our institution, raising the possibility that pericarditis may be reversible. Radiological examination of the hips showed coxa vara with short femoral neck in all patients. Synovial biopsy in the three patients revealed proliferating synovial epithelium with moderate fibrocollagenous densities and multinucleated giant cells, occasional lymphocytes or neutrophils but no plasma cells were identified. This is the first series of this familial arthropathy with a triad of camptodactyly, arthropathy and coxa vara (CAC syndrome) in Saudi Arabia which is to be considered in patients where more than one family member has juvenile arthritis.