Patricia Wasserman

Fine‐needle aspiration of thyroid nodules: A study of 4703 patients with histologic and clinical correlations

The Papanicolaou Society of Cytopathology recently proposed 6 diagnostic categories for the classification of thyroid fine‐needle aspiration (FNA) cytology. Using these categories, the experience with FNA from 2 institutions was studied with emphasis on cytologic‐histologic correlation, source of errors, and clinical management.

Thyroid fine-needle aspiration with atypia of undetermined significance

Atypia of undetermined significance is a controversial category in thyroid fine‐needle aspiration (FNA), not only for its questioned clinical utility, but also for its very existence as an expression of uncertainty. The current study was performed to investigate the potential impact of eliminating this category on the sensitivity and specificity for detecting thyroid neoplasms by FNA.

Paragangliomas: classification, pathology, and differential diagnosis.

This article discusses the paraganglion system and extra-adrenal paragangliomas. In particular, the clinicopathologic, immunohistochemical, and ultrastructural features of paragangliomas and neuroendocrine neoplasms of the larynx are presented with a discussion of the differential diagnosis.

Intracellular localization and intercellular heterogeneity of the human DNA repair protein O 6 -methylguanine-DNA methyltransferase

Abstract O6-Methylguanine-DNA methyltransferase (MGMT) is a DNA repair protein that removes alkyl adducts from DNA and may be important in tumor resistance to alkylation chemotherapy. MGMT was visualized in human cells and tumor tissues with monoclonal antibodies against MGMT and immunofluorescence microscopy, and fluorescent signals were quantified by digital image analysis. MGMT was found both in the cytoplasm and the nucleus, and in either locale the protein reacts with alkylated DNA bases and becomes inactivated and lost from the cell. Cell lines in culture and xenografts showed a broad normal distribution of nuclear MGMT levels, but human brain tumors often showed a skewed distribution, with a significant fraction of cells with high levels of MGMT. O6-Benzylguanine, a suicide substrate inactivator for MGMT activity, reduced MGMT in human cells and in a mouse xenograft to levels undetectable by antibody assay 1 h post-treatment. In melanoma specimens taken from a patient 3 h post-treatment with temozolomide, MGMT levels were reduced by 70%. This quantitative immunofluorescence assay can be used to monitor MGMT and its depletion in human tumors to improve the use of alkylating agents in cancer chemotherapy.

Parathyroid cyst : Current diagnostic and management principles

Parathyroid (PTH) cyst is a rare lesion. Only about 200 cases have been reported to date. The diagnosis of a PTH cyst is difficult, particularly in its differentiation from thyroid cyst. It has clinical significance because PTH cysts can mimic a thyroid mass and can be associated with hyperparathyroidism.

Endobronchial ultrasound-guided transbronchial needle aspirate (EBUS-TBNA): a proposal for on-site adequacy criteria.

This is a retrospective study of 48 patients who underwent EBUS‐TBNA procedure between the periods January 2008 to September 2009 at Long Island Jewish Medical Center. The study was undertaken with the following objectives: First, to define practical and useful on‐site adequacy criteria for EBUS‐TBNA samples; Second, to understand the diagnostic pitfalls associated with accurate interpretation of EBUS‐TBNA samples. EBUS‐TBNA procedure was able to diagnose 24/48 (50%) patients with malignancy, 1/48 (2%) suspicious for malignancy, 9/48 (19%) with granulomatous process, and 9/48 (19%) negative for disease. Only five cases (10%) could not be diagnosed with this procedure. Based on our experience, any smear with presence of > 5 low power fields (×100) with ≥ 100 lymphocytes in each and containing < 2 groups of bronchial cells/low power field (×100) can be considered adequate for evaluation. Also, the presence of germinal center fragments renders a smear adequate for evaluation, irrespective of the above mentioned criteria. Adequacy criteria are to be applied only to the smears not showing any identifiable pathology such as malignancy or granuloma. An understanding of diagnostic pitfalls associated with accurate interpretation of EBUS‐TBNA samples is essential to avoid false‐positive and false‐negative diagnosis. To conclude, an effective communication between the clinician and cytologist, an algorithmic approach to diagnosis, and the on‐site adequacy criteria proposed in this study can markedly improve the diagnostic yield of the procedure. Diagn. Cytopathol. 2011.

Histopathological and Cytopathological Correlations of Percutaneous Testis Biopsy and Open Testis Biopsy in Infertile Men

A testis biopsy is used to assess quantitatively testicular spermatogenesis in infertile patients. Recently, several reports have used less invasive, percutaneous methods to obtain testis tissue. Percutaneous testis biopsies and touch imprints, immediately followed by open testis biopsies, were performed on 24 testes (19 patients) to ascertain whether they could provide the same histological information as an open biopsy. The technique of percutaneous testis biopsy using a core biopsy system is described. Comparison of the percutaneous and open biopsy histological diagnoses revealed a 95% correlation. The percutaneous method using 1 pass through the testis failed to provide adequate tissue in 2 of 24 patients. Touch imprints obtained by the percutaneous method also provided a 95% correlation compared with the open method (2 of 24 touch imprints were lost during processing and, thus, were not evaluated). Percutaneous testis biopsies and touch imprints provide adequate tissue for histological and cytological evaluation, with excellent correlation with biopsies obtained by the traditional open methods. Percutaneous testis biopsy and touch imprint may be performed in an office setting, thus obviating the need to perform an open biopsy in the operating room.

Clinical impact of second opinion in thyroid fine needle aspiration cytology (FNAC): A study of 922 interinstitutional consultations†

Interinstitutional consultation in pathology has shown to improve patient safety by detecting interpretive errors that may significantly impact clinical management. We conducted a study of 922 cases of thyroid FNAC slides, referred to our institution over a 2‐year period, to assess the magnitude of discrepancies and determine the clinical impact of second opinion. Disagreements were categorized as none, minor or major, the latter two defined as one‐ or two‐step deviations respectively on the NCI diagnostic categories scale. There were 122 disagreements (13%), including 44 major and 78 minor. Seventy‐five patients underwent a change in management based on second opinion, in conjunction with clinical and radiologic findings (age, size of nodule, family history, ultrasonographic appearance, and solitary versus multiple nodules). The second opinion was supported on follow‐up in 57% of major discrepancies, and the initial diagnosis was concurrent with the surgical diagnosis in 7% cases. The remainder (36%) of major discrepancy cases did not undergo surgery, precluding tissue confirmation. Critics have alleged increased costs due to interinstitutional consultations. However, cost avoidance from lost wages, potential surgical complications, and litigation is not easily quantified. Using a simplified calculation to objectively measure the costs associated with changed diagnoses, we estimate that second opinion of these 922 cases resulted in potential cost saving of

O6-Methylguanine-DNA Methyltransferase in Normal and Malignant Tissue of the Breast

940,166 based on current Medicare reimbursement codes. Our study indicates the need for a quality‐control program of outside thyroid FNA slides, especially in “high discrepancy categories” as discussed in the article. Diagn. Cytopathol. 2011;.

Aetiology of non‐diagnostic renal fine‐needle aspiration cytologies in a contemporary series

An important component of high-dose chemotherapy/autologous bone marrow support regimens for adjuvant treatment of breast cancer is carmustine. Preclinical studies have shown that the level of the DNA repair protein O6-methylguanine-DNA methyltransferase is correlated with the resistance of cultured human tumor cells to this drug, but little is known about transferase levels of breast tissue in vivo. We measured the DNA repair activity in 80 tissue samples from 65 patients, including normal, abnormal, benign, and malignant specimens. Wide interindividual variations was observed and average transferase levels were similar in normal and benign tissue. However, transferase levels were significantly elevated in stage I-IV disease. In addition, the frequency of samples with no detectable transferase was greatly reduced in this malignant group, and transferase was positively correlated with the presence of positive nodes, a marker for disease progression. In contrast, transferase levels were not correlated with age or estrogen receptor status, and the levels in normal tissue did not vary between patients with benign or malignant disease. These results suggest that this DNA repair activity may be increased in breast cancer relative to normal tissue and encourage further study of the predictive value of transferase measurements in high-dose chemotherapy/autologous bone marrow transplant for breast cancer.