Ultrasound characteristics of thyroid nodules diagnosed as follicular neoplasms by fine-needle aspiration cytology. A prospective study with histological correlation.

UNLABELLED: Cytopathological evaluation has been proven useful in the diagnostic work-up of "cold" nodules. The cytological diagnosis of follicular neoplasm usually requires histology to exclude malignancy. The objective of this prospective study was to test the hypothesis that ultrasound examinations show distinct characteristics in a subgroup of nodules which may attest the benign nature of a follicular neoplasm. PATIENTS, METHODS: 56 patients (45 women, 11 men) were included in the study. All patients had a "cold" nodule which was diagnosed as follicular neoplasm. Consecutive histology revealed follicular adenomas (FTAs) (n = 44), follicular carcinomas (FTCs) (n = 7) and papillary carcinomas (PTCs) (n = 5), including follicular variant papillary carcinomas (fv PTCs) (n = 4). Ultrasound examinations were performed preoperatively. The ultrasound examinations were evaluated with respect to seven characteristics. RESULTS: In 21 % of patients a follicular neoplasm was associated with a malignant and in 79 % of patients with a benign tumor as compared with histology. The ultrasound characteristics size ≤ 2 ml, round shape and homogeneous structure revealed significant differences for FTAs, FTCs and PTCs with p < 0.001, p = 0.003 and p = 0.027, resp. With respect to the benign nature of a follicular neoplasm maximum values for sensitivity and specificity were 0.75 and 0.83. Multivariate discriminant analysis revealed that ultrasound criteria were suitable to discriminate between benign vs. malignant nodules and among FTAs, FTCs and PTCs with correlation coefficients of r = 0.53 and r = 0.74, resp. CONCLUSIONS: in selected patients with higher operative risks and cytological diagnosis of follicular neoplasm ultrasound parameters may be helpful to assume a benign nature of the neoplasm and thus avoid the necessity of a histological work-up.

CSF cytology--the ongoing dilemma to distinguish neoplastic and inflammatory lymphocytes.

To evaluate different morphological criteria for the distinction between inflammatory and neoplastic lymphocytes in the cerebrospinal fluid (CSF). Forty-two cytospin preparations of CSF from patients with confirmed CSF involvement by aggressive B-cell lymphoma or acute leukemia were compared with 26 samples of inflammatory diseases. CSF cytology was analyzed morphologically for preselected parameters of cell, cytoplasm and nucleic appearance, and the presence of mitoses or apoptoses. None of the evaluated parameters sharply discerns neoplastic and inflammatory changes. However, neoplastic cells were significantly larger. Moreover, irregular shape and pointed borders of the cytoplasm, and deep notches in the nucleus were significantly more frequent in neoplastic than in inflammatory lymphocytes. No single parameter is sufficient to detect neoplastic lymphocytes. Considering a combination of cell size and irregular shape of cell and nucleus, however, may improve the diagnostic accuracy of CSF dissemination by aggressive hematological malignancies.

Establishment and characterization of two distinct malignant mesothelioma cell lines with common clonal origin.

We describe two newly established malignant mesothelioma (MM) cell lines derived from a pleural effusion of a male. One cell line, designated as MM-Z03E, reveals an epithelioid cobblestone morphology, while the second one, designated as MM-Z03S and subcloned after in vivo selection, exhibits a sarcomatoid storiform growth pattern. Both cell lines showed the immunologic profile characteristic for MM (i.e., expression of cytokeratin, CK18, calretinin, and vimentin in both phenotypes). Cytogenetics, multicolor fluorescence in situ hybridization, comparative genomic hybridization, and oligonucleotide array CGH were performed on both cell lines. Aberrations shared by both cell lines included chromosomal losses of 1q34 approximately qter, 4, 9p, 10p, 13, 14, 16q, 18, and 22, as well as a complex structural aberration involving chromosome 17. Aberrations exclusive to MM-Z03E included gains of 3q11q27 and 5p, while gain of 9q and losses of 3q27qter, 11q, and 18 in MM-Z03S were exclusive to MM-Z03E. Both cell lines were able to develop solid transplant tumors in nude mice within 16 weeks, and immunophenotyping of tumor xenografts revealed an overall retained expression profile of the markers used. Remarkably, one xenograft from MM-Z03E revealed overexpression of p53 and widely invasive growth. In conclusion, both cell lines are useful in vivo and in vitro model systems to study the underlying genetic mechanisms of biphasic differentiation in MM, which can be of certain value considering the increasing relevance of assessing MM tumor biology for the clinical management of this disease.

Clinical response following adjuvant Temozolomide in a patient with primary cerebral lymphoma.

A 69-year-old female patient was treated for primary CNS-lymphoma (PCNSL) starting from August 2002. As her general condition allowed no high-dose methotrexate (MTX) therapy, radiotherapy was administered as a first-line treatment. CSF involvement could be managed by intrathecal Ara-C. Her general condition and cognitive status stabilized, but did not improve for 3 months. Therefore, oral chemotherapy with Temozolomide 200 mg/m2 was initiated. After two courses, which were tolerated without any problems, the patient's Karnofsky performance index had improved from 40% to 50%, the Mini-Mental Status rose from 16 to 27/30. The CSF-cell count was elevated again to 23 cells/l without signs of meningeal relapse. Unfortunately, the patient died unexpectedly from suspected pulmonary embolism. We conclude that adjuvant Temozolomide chemotherapy can improve the general condition and cognition in patients with PCNSL even when the general condition is poor. Long-term effects and neurotoxicity remain to be analysed in prospective trials, as well as the efficacy in leptomeningeal disease.

Real-time reverse transcription-polymerase chain reaction assay for GA733-2 mRNA in the detection of metastatic carcinoma cells in serous effusions.

Cytomorphologic and immunocytologic examination alone provide only limited sensitivity for the detection of metastatic carcinoma cells in many cases of serous effusions. The specificity of conventional reverse transcription-polymerase chain reaction (RT-PCR) methods for detection of epithelial gene transcripts is low owing to the ectopic expression of many such genes in nonepithelial cells. For the detection of metastatic carcinoma cells, we describe a quantitative real-time RT-PCR assay for GA733-2 messenger RNA encoding an epithelial glycoprotein (EGP-2) that binds to the monoclonal antibody BerEP4. With serial dilutions of BerEP4-positive SK-BR-3 breast carcinoma cells, the RT-PCR assay was able to detect 10 carcinoma cells in a background of 10(6) lymphoid cells compared with 10(2) to 10(3) carcinoma cells detectable by immunocytologic examination. We analyzed 51 serous effusions, including 25 malignant metastatic effusions, by the real-time RT-PCR assay. Receiver operating characteristic curve analyses demonstrated a sensitivity of 96% corresponding to a specificity of 98% for a correct diagnosis of metastatic effusions. These results provide evidence that the GA733-2 real-time RT-PCR assay is a specific and sensitive tool for the detection of metastasis of BerEP4-positive primary tumors in serous effusion specimens.

The potential value of comparative genomic hybridization analysis in effusion-and fine needle aspiration cytology.

Comparative genomic hybridization (CGH) is a molecular cytogenetic technique that provides an overview on chromosomal imbalances within the whole tumor cell genome. This method has yet not been applied in effusion cytology. We performed CGH analysis in malignant effusions, fine needle aspirates, and imprint smears from eight ovarian adenocarcinomas, three breast carcinomas, one colon adenocarcinoma, and three malignant mesotheliomas. In part, CGH analysis from fresh frozen tissue and classic karyotyping served as controls. In this series, 14/15 cytologic specimens were suitable for extraction of high molecular weight DNA sufficient for reliable CGH analysis. CGH profiles from cytologic material were equal or even more significant in comparison with corresponding fresh frozen tumor samples. We conclude that CGH analysis from cytologic specimens may support the primary cytologic diagnosis of malignancy, especially in the differential diagnosis of benign proliferating mesothelium, malignant mesothelioma, and metastatic adenocarcinoma. CGH analysis of metastatic lesions may provide information on the site of the primary tumors and detects cytogenetic imbalances affecting oncogenes and tumor suppressor genes involved in tumor progression and metastatic spread.