Cytopathology of Follicular Cell Nodules

Abstract

This article corresponds to a lecture delivered during the Endocrine Pathology Society symposium held in Boston on 21 March 2015 (104th USCAP meeting, March 21-27). It focuses on the importance of cytopathology in endocrine thyroid pathology and the limits and pitfalls of diagnosis in follicular cell lesions. Lights and shadows are present in each diagnostic technique: Fine needle aspiration has imposed itself as a gold standard in thyroid nodules thanks to its easiness of execution and high cost-effectiveness ratio. A milestone in this field is represented by the National Cancer Institute (NCI) Thyroid Fine Needle Aspiration (FNA) State of the State of the Science Conference hosted in October 22-23, 2007 by the NCI, followed by a series of documents published in Diagnostic Cytopathology and Cytojournal (2008) as well as in an atlas entitled: The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC): terminology and criteria (2010, Springer). "Gray" zones still remain, causing difficulties and anxiety to the cytopathologist when facing challenging cases. Each diagnostic category of TBSRTC is analyzed and discussed in a concise fashion with special emphasis on challenging cases such as atypia of undetermined significance (AUS), suspicion for follicular neoplasms (SFNs), diagnoses of papillary thyroid carcinoma (PTC) in Hashimoto thyroiditis and follicular variant of papillary carcinoma (FVPTC). Our aim was to better define and clarify the spectrum of follicular cell lesions in thyroid nodule samplings and to underline the diagnostic limits in order to avoid pitfalls. New emerging molecular biology techniques may represent useful tools in selected morphological challenging cases and lead to new therapeutic approaches in line with drug-tailored therapy and personalized medicine.

Ancillary molecular testing of indeterminate thyroid nodules

“…[1][2][3][4][5] The remaining nodules (20% to 25%) represent the "gray zone" of follicular/indeterminate lesions that belong to indeterminate categories according to TBSRTC. [6][7][8][9][10][11][12][13][14][15][16][17][18] Difficulties and limitations in morphologically discriminating whether these nodules are benign or malignant entities has led to unnecessary surgical resections (lobectomy or total thyroidectomy) and has raised health care costs accordingly. 4,5 Patients with indeterminate nodules that undergo surgical resection often turn out to have benign thyroid nodules or only indolent neoplasms, including NIFTP.…”

“…[1][2][3][4][5][6][7][8][9][10] Several authors have demonstrated that the likelihood of an SFN/FN nodule being neoplastic is 65% to 85%, whereas that for the ROM is significantly lower (25% to 40%). [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18] Most of these malignancies are interpreted histologically as PTC ( Fig. 1), comprising mostly FVPC (Table 3).…”

Correspondence of cytological and histopathological diagnoses in diagnostic category V of the Bethesda system: “suspicious for malignancy”

“…The Endocrine Pathology Society proposed a formal reclassification, treating NI-FVPTC as a benign neoplasm [34]. The researchers analyzed 5 studies from 5 institutions, [9,35,36]. Moreover, they concluded that after reclassification due to the decrease in RM there should be an indication for lobectomy instead of a thyroidectomy in many cases [9].…”

The diagnosis of cancer in thyroid fine needle aspiration biopsy. Surgery, repeat biopsy or specimen consultation?

“…Fine needle aspiration is invariably the best method of preoperative diagnostics and rational triage of patients to surgical treatment or observation [5,14]. In the case of DC VI ("malignant" diagnosis), the recommended treatment is thyroidectomy.…”

“…Special attention has recently been given to the encapsulated non-invasive follicular variant of papillary thyroid carcinoma: NI-FVPTC due to its indolent course. It is proposed to treat this tumor as an adenoma [14,17,37,38,39]. It is often difficult, though, to assess the capsular invasion if the patient had multiple biopsies and the capsule has features that cause difficulties in distinguishing between capsular damage and invasion.…”