Overview and update on molecular testing in non-small cell lung carcinoma utilizing endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples

Lung carcinoma remains one of the most frequent and aggressive human neoplasms. Fortunately, in the last decades, the increasing knowledge of the molecular mechanisms leading to cancer development has allowed the use of targeted therapies with improvement of prognosis in many patients. Clinical management has also changed after the introduction of endobronchialultrasonographic bronchoscopy that allows a conservative staging of lung tumors, avoiding the need of mediastinoscopy for lymph node staging. Lung pathologists and cytopathologists are facing the challenge of giving the more comprehensive prognostic and predictive information with ever smaller tissue or cytological samples. The aim of this review is to summarize the molecular testing for non-small cell lung carcinoma and how pathologists can contribute to the patient's outcome with a conscious management of biological samples.     

Accumulation of methotrexate and methotrexate polyglutamates in lymphoblasts at diagnosis of childhood acute lymphoblastic leukemia: a pilot prognostic factor analysis

Lymphoblasts in bone marrow samples, obtained from 43 children with acute lymphoblastic leukemia at diagnosis, were incubated with 1.0 mumols/L [3H] methotrexate for 24 hours in vitro. Nonexchangeable methotrexate and methotrexate polyglutamates were separated and quantitated. Event-free survival at 5 years was 38% +/- 9% for all 43 patients (27 failures), and 44% +/- 10% for the 35 with non-T, non-B- cell acute lymphoblastic leukemia (20 failures). Of these 35 children, those whose lymphoblasts accumulated more than 100 pmol methotrexate and 500 pmol methotrexate polyglutamates per billion cells experienced better 5-year event-free survival than those whose lymphoblasts did not (65% +/- 12% v 22% +/- 9%, P = .010). This difference characterized "good-risk" patients who were female (P = .014), less than age 7 at diagnosis (P = .005), or had low initial white blood cell counts (less than 20 X 10(9)/L, P = .018). Findings were similar for the 43 children with acute lymphoblastic leukemia and for the "good-risk" children in this total group. Thus, the ability of lymphoblasts to accumulate methotrexate and form methotrexate polyglutamates may be important to the curative properties of current therapy of acute lymphoblastic leukemia in children, particularly for "good-risk" patients. In such patients, inherent rather than acquired drug resistance may be the initial event leading to treatment failure.     

Lymphangiomas in children: MR imaging

Seventeen lymphangiomas in 15 patients were imaged with magnetic resonance (MR) to define the nature, extent, and anatomic relationships of these lesions. The MR and pathologic findings were then compared to determine the histologic basis for the signal-intensity characteristics of these lesions. The signal intensity of 13 lesions was similar to or slightly less than that of muscle on T1-weighted images and greater than that of fat on T2-weighted images. This appearance correlated with the presence of ectatic lymphatic channels containing clear fluid on histologic section. Four lymphangiomas had high signal intensity, approximately equal to that of fat, on T1-weighted images, reflecting the presence of clotted blood or small cystic spaces with a higher ratio of fat to fluid. Sixteen of 17 lesions had visible septations on MR images. The authors' experience suggests that most lymphangiomas have a characteristic appearance on MR images. The information obtained with MR imaging can help in providing a preoperative diagnosis, in planning surgical resection, and in defining recurrence.     

Granulocytic sarcoma of the brain: a case report and review of the literature

Granulocytic sarcoma (chloroma), a rare tumor usually associated with myelogenous leukemia, is capable of invading the meninges or brain parenchyma. Radiologic findings in a case of granulocytic sarcoma of the brain, as well as those in 11 previously reported cases of intracranial leukemic masses, are interpreted. On computed tomographic scans, the lesions can appear isodense or hyperdense, edema and necrosis are variable, and there is uniform enhancement following intravenous administration of contrast material. There may be some affinity for the posterior fossa.     

Human erythrocyte antigens: II. The In(Lu) gene regulates expression of an antigen on an 80-kilodalton protein of human erythrocytes

We have previously shown that a murine monoclonal antibody (A3D8) identifies a human erythrocyte protein antigen whose expression is regulated by the Lutheran inhibitor [In(Lu)] gene. In the present study, we demonstrated by immunoprecipitation and Western blot techniques that the antigen defined by A3D8 was on an 80-kD erythrocyte membrane protein. A second 170-kD protein was coprecipitated with the 80-kD protein but failed to show antigen activity by Western blot analysis. The 170-kD protein, when analyzed by sodium dodecyl sulfate- polyacrylamide gel electrophoresis in two dimensions, was composed of 50- and 30-kD disulfide-linked subunits. In(Lu) Lu[a-b-) erythrocytes differed from Lu(a+b+) or Lu(a-b+) erythrocytes in that In(Lu) deoxycholate erythrocyte membrane extracts contained trace amounts of immunoprecipitable 80-kD protein compared with detergent-solubilized erythrocyte membrane extracts prepared from Lu(a+b+) or Lu(a-b+) subjects.     

High incidence of monoclonal proteins in the serum and urine of chronic lymphocytic leukemia patients

Chronic lymphocytic leukemia (CLL) is generally considered a nonsecretory B cell immunoproliferative disorder. Conventional electrophoretic and immunoelectrophoretic methods have revealed serum monoclonal proteins in less than 10% of these patients. However, there is increasing experimental evidence from in vitro studies demonstrating that CLL cells may secrete immunoglobulins, particularly free light chains. We examined the serum and urine of 36 consecutive CLL patients for monoclonal proteins using sensitive immunochemical methods (high resolution agarose gel electrophoresis combined with immunofixation). The results obtained were correlated with the Rai stage, quantitative immunoglobulin levels, and lymphocyte membrane immunoglobulin phenotype of the leukemic cells. Twenty-three monoclonal proteins were identified in the serum or urine of 22 patients, an incidence of 61%. Six patients had serum monoclonal proteins, seven had only urinary monoclonal proteins, and nine had monoclonal proteins in serum and urine. In every instance the monoclonal protein was the same light chain type as expressed on the leukemic cells. Our findings suggest that the monoclonal proteins observed in the serum or urine of CLL patients are secretory products of the tumor cells and that their discovery is a function of the sensitivity of the method used for their detection.     

Ureteral and renal pelvic metastases from renal cell carcinoma

Six patients with ureteral or renal pelvic metastases from renal cell carcinoma (RCC) were studied radiologically. Correlation with surgical and histologic findings confirmed renal venous involvement in 5 and lymphatic invasion in 3 patients. The possible role of nephroureterectomy or secondary ureterectomy in patients with RCC is discussed in the background of our cases, as are prior reports of this finding.