Zubair W. Baloch

Laboratory medicine practice guidelines. Laboratory support for the diagnosis and monitoring of thyroid disease.

Guidelines Committee: The preparation of this revised monograph was achieved with the expert input of the editors, members of the guidelines committee, experts who submitted manuscripts for each section and many expert reviewers, who are listed in Appendix A. The material in this monograph represents the opinions of the editors and does not represent the official position of the National Academy of Clinical Biochemistry or any of the co-sponsoring organizations. The National Academy of Clinical Biochemistry is the official academy of the American Association of Clinical Chemistry. Single copies for personal use may be printed from authorized Internet sources such as the NACB’ s Home Page (www.nacb.org), provided it is printed in its entirety, including this notice. Printing of selected portions of the document is also permitted for personal use provided the user also prints and attaches the title page and cover pages to the selected reprint or otherwise clearly identifies the reprint as having been produced by the NACB. Otherwise, this document may not be reproduced in whole or in part, stored in a retrieval system, translated into another language, or transmitted in any form without express written permission of the National Academy of Clinical Biochemistry (NACB, 2101 L Street, N.W., Washington, DC 20037-1526). Permission will ordinarily be granted provided the logo of the NACB and the following notice appear prominently at the front of the document: Reproduced (translated) with permission of the National Academy of Clinical Biochemistry, Washington, DC Single or multiple copies may also be purchased from the NACB at the address above or by ordering through the Home Page (http://www.nacb.org/ ).

Diagnostic terminology and morphologic criteria for cytologic diagnosis of thyroid lesions: A synopsis of the National Cancer Institute Thyroid Fine‐Needle Aspiration State of the Science Conference

The National Cancer Institute (NCI) sponsored the NCI Thyroid Fine‐needle Aspiration (FNA) State of the Science Conference on October 22–23, 2007 in Bethesda, MD. The two‐day meeting was accompanied by a permanent informational website and several on‐line discussion periods between May 1 and December 15, 2007 (http://thyroidfna.cancer.gov). This document summarizes matters regarding diagnostic terminology/classification scheme for thyroid FNA interpretation and cytomorphologic criteria for the diagnosis of various benign and malignant thyroid lesions. (http://thyroidfna.cancer.gov/pages/info/agenda/). Diagn. Cytopathol. 2008;36:425–437.

The Bethesda System for Reporting Thyroid Cytopathology: A Meta-Analysis

Objective: We aimed to investigate the validity of the Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) through meta-analysis. Study Design: All publications between January 1, 2008 and September 1, 2011 that studied TBSRTC and had available histological follow-up data were retrieved. To calculate the sensitivity, specificity and diagnostic accuracy, the cases diagnosed as follicular neoplasm, suspicious for malignancy and malignant which were histopathologically confirmed as malignant were defined as true-positive. True-negative included benign cases confirmed as benign on histopathology. The nondiagnostic category was excluded from the statistical calculation. The correlations between the 6 diagnostic categories were investigated. Results: The publications review resulted in a case cohort of 25,445 thyroid fine-needle aspirations, 6,362 (25%) of which underwent surgical excision; this group constituted the basis of the study. The sensitivity, specificity and diagnostic accuracy were 97, 50.7 and 68.8%, respectively. The positive predictive value and negative predictive value were 55.9 and 96.3%, respectively. The rates of false negatives and false positives were low: 3 and 0.5%, respectively. Conclusions: The results of meta-analysis showed high overall accuracy, indicating that TBSRTC represents a reliable and valid reporting system for thyroid cytology.

Follicular-Patterned Lesions of the Thyroid The Bane of the Pathologist

This review focuses on follicular-patterned lesions of the thyroid gland and their differential diagnosis. Included are a discussion of the features differentiating follicular adenoma from adenomatous or hyperplastic nodule and follicular adenoma from follicular carcinoma and the follicular variant of papillary thyroid carcinoma. The cytologic and histologic characteristics are described, and criteria for diagnosing the major follicular lesions are reviewed.

Fine-needle aspiration of follicular patterned lesions of the thyroid: Diagnosis, management, and follow-up according to National Cancer Institute (NCI) recommendations

The National Cancer Institute (NCI) State of the Science Conference on thyroid fine‐needle aspiration (FNA) proposed that follicular patterned lesions can be divided into two diagnostic categories; follicular lesion of undetermined significance/Atypia of undetermined significance (FLUS/AUS) and suspicious for follicular neoplasm/follicular neoplasm (SFON/FON). The former group can benefit from repeat FNA (RFNA) to achieve a more definitive diagnosis and the latter should undergo surgical excision for histologic characterization (adenoma vs. carcinoma). In this study, we report the combined experience from our institutions with thyroid FNA cases that can be placed into NCI‐designated thyroid FNA diagnostic categories for follicular patterned lesions.

Immunohistochemical Expression of Galectin-3 in Benign and Malignant Thyroid Lesions

CONTEXT The expression of galectin-3, a human lectin, has been shown to be highly associated with malignant behavior of thyroid lesions. DESIGN We studied the immunohistochemical expression pattern of galectin-3 in a variety of follicular-derived thyroid lesions (13 benign and 62 malignant), including Hürthle cell and follicular carcinoma, papillary carcinomas and variants, and anaplastic and poorly differentiated carcinomas. RESULTS Immunoreactivity was strongest in papillary thyroid carcinomas, whereas staining was less intense in Hürthle cell and anaplastic carcinomas, and even weaker in the follicular variant of papillary thyroid carcinoma. Staining was absent or weak in the 3 follicular thyroid carcinomas and was negative in both insular carcinomas. In several tumors, staining was stronger at the advancing invasive edge of the lesion than in the central portion of the tumor. Galectin-3 was also expressed focally and weakly in reactive follicular epithelium and entrapped follicles in chronic lymphocytic thyroiditis. A variety of thyroid lesions showed prominent endogenous, biotin-like activity, which could cause flaws in interpretation if a biotin-detection system were used. CONCLUSION We conclude that galectin-3 immunostaining, when used in biotin-free detection systems, may be useful as an adjunct to distinguish benign from malignant thyroid lesions.

Encapsulated Follicular Variant of Papillary Thyroid Carcinoma with Bone Metastases

Although true follicular thyroid carcinoma is known to metastasize via the bloodstream and give rise to bone and lung metastases, such a pattern of spread is rare in papillary thyroid carcinoma. The follicular variant of papillary thyroid carcinoma (FVPTC) is believed to behave in a clinical manner similar to usual or classical papillary cancer and to follow a similar indolent course.There have been a few reports of “aggressive” FVPTC wherein follicular patterned tumors with nuclear features of papillary carcinoma have metastasized hematogenously; these neoplasms have been diffusely invasive or multicentric in the thyroid.We report five cases of FVPTC, which were encapsulated and simulated grossly and microscopically follicular adenomas. In two of these, the primary was discovered after clinical presentation of bone metastases. In three others, bony metastases (without other nonosseous metastases) arose 7 to 17 years after thyroid lobectomy for lesions initially diagnosed as follicular adenoma. In retrospect, these three encapsulated lesions had vascular invasion. We wish to bring attention to these innocuous-appearing lesions, which, although sharing nuclear features of papillary cancer, behave clinically in an unexpectedly malignant fashion.

Adenoid cystic carcinoma with high-grade transformation: a report of 11 cases and a review of the literature.

High-grade transformation of adenoid cystic carcinoma (ACC) (previously referred to as dedifferentiation) is a rare phenomenon that does not fit into the traditional ACC grading schemes. The importance and minimal criteria for distinction from solid (grade III) ACC are not well established. We report 11 new cases and review the literature to further define the profile of this tumor. The median age was 61 years (range: 32 to 72 y) with a male predominance (male to female ratio of 1.75:1). The most commonly involved sites were sinonasal (4/11) and submandibular (4/11). Lymph nodes were pathologically positive in 4/7 (57.1%) cases. Distant metastases to the lung (n=2) and soft tissue of the shoulder (n=1) were observed. Five of 9 patients (55.6%) died, all within 5 years with a median overall survival of 12 months. Histologically, ACC with high-grade transformation was distinguished from conventional ACC by nuclear enlargement and irregularity, higher mitotic counts, and the loss of the biphasic ductal-myoepithelial differentiation. Useful supportive criteria were prominent comedonecrosis and fibrocellular desmoplasia. The most common morphologies for the high-grade component were poorly differentiated cribriform adenocarcinoma and solid undifferentiated carcinoma. Micropapillary and squamoid patterns were occasionally present. Ki-67 and p53 labeling indices were elevated in the high-grade components, though c-kit and cyclin-D1 were not. ACC–high-grade transformation is a highly aggressive salivary gland tumor with a variety of histologic patterns. The high propensity for lymph node metastases suggests a role for neck dissection in patients with this rare tumor.

Relative accuracy of fine-needle aspiration and frozen section in the diagnosis of lesions of the parotid gland

Both fine‐needle aspiration (FNA) and frozen section (FS), although useful in preoperative and intraoperative management, have their advantages and pitfalls when used in the diagnosis of salivary gland lesions. The accuracy of each of these modalities has been assessed separately in many studies; a direct comparison of these techniques on a large cohort has not been well studied. Herein, we determine the relative accuracies of both FNA and FS in the diagnosis of salivary gland lesions.

Thyroid nodules with FNA cytology suspicious for follicular variant of papillary thyroid carcinoma: Follow-up and management

Thyroid nodules diagnosed as follicular neoplasm on fine‐needle aspiration biopsy (FNAB) may represent hyperplastic/adenomatous nodules, follicular adenoma or carcinoma, and follicular variants of papillary thyroid carcinoma (FVPTC) on histologic follow‐up. In our laboratory, we attempted to identify a subset of cases which showed cellular specimens with focal features (nuclear chromatin clearing, membrane thickening, and rare grooves) suspicious for the follicular variant of papillary thyroid carcinoma. These cases are reported as follicular‐derived neoplasms with nuclear features suspicious for FVPTC to distinguish them from those diagnosed as follicular neoplasm. This study documents our experience with 52 cases so diagnosed and followed prospectively with histologic follow‐up. A neoplastic nodule was confirmed in 45/52 cases (86%), of which 40 were malignant (77%). FVPTC was identified in 35/52 cases (67%). Four cases were usual papillary carcinoma, 3 were follicular adenoma, 2 were Hürthle‐cell adenoma, and 1 was insular carcinoma. In 7 cases, the subsequent histologic findings were nonneoplastic (5 hyperplastic nodules and 2 colloid nodules). Our prospective study shows that in cellular smears from thyroid nodules, a careful search for the nuclear features of papillary carcinoma should be performed, and it is appropriate to diagnose cases as suspicious for FVPTC if the nuclear features of papillary carcinoma are focal. The surgical management of this group may include an intraoperative confirmation of cytologic diagnosis by scrape preparation and/or frozen section in order to avoid a second surgical intervention for completion thyroidectomy. Diagn. Cytopathol. 2000; 23:380–385.