This article is a brief review of diagnostic error in thyroid cytopathology and histopathology with a discussion of more general medicolegal aspects of error in histopathology and cytopathology ...relevant to thyroid pathology. Pre-operative ultrasound guided thyroid FNA cytology is the standard pre-operative investigation for thyroid nodules. FNA is effective in triaging thyroid nodules. The cytological features of papillary thyroid carcinoma are readily identified in FNA specimens. Needle core biopsy may also be useful in some circumstances if fine-needle aspiration is unhelpful. Errors tend to occur in thyroid pathology due to a number of relatively well-known diagnostic pitfalls. Strategies to reduce diagnostic errors include careful attention to known pitfalls and the clinical history. Previous fine-needle aspiration or core biopsy may produce artefacts that can mimic capsular invasion. Other helpful strategies include double or consensus reporting of suspected problematic lesions, e.g. follicular tumour of uncertain malignant potential vs. minimally invasive follicular thyroid carcinoma, sampling of the whole lesion capsule if capsular or vascular invasion is suspected and judicious use of additional levels and immunostains if vascular or lymphatic invasion is suspected. The importance of multidisciplinary case review is also highlighted.
Background
The UK Royal College of Pathologists Thy terminology for reporting thyroid fine‐needle aspiration cytology (FNAC), first published in 2009 is used throughout the United Kingdom and ...Ireland, in some parts of Italy and Switzerland and elsewhere. There is no review of the literature or meta‐analysis of the risk of malignancy (ROM) in the various categories of the UK Thy terminology. The goal of this study was to establish the published ROM for each Thy category and compare the results with other existing terminology systems for which similar meta‐analyses are available.
Methods
A comprehensive literature search of online databases was conducted in May 2019 to examine the ROMs for histologically proven nodules with preoperative FNAC classified according to the UK Thy terminology.
Results
Twenty‐five articles were identified that showed results of both cytology and histology. Twelve of these articles were excluded to prevent a selection bias because they showed data in just 1 Thy category. In the remaining 13 articles, the pooled ROMs were as follows: Thy1, 12% (95% confidence interval CI, 5%‐22%); Thy2, 5% (95% CI, 3%‐9%); Thy3, 22% (95% CI, 18%‐26%); Thy3a, 25% (95% CI, 20%‐31%); Thy3f, 31% (95% CI, 24%‐39%); Thy4, 79% (95% CI, 70%‐87%); and Thy5, 98% (95% CI, 97%‐99%).
Conclusions
This meta‐analysis shows results comparable to those of meta‐analyses of other internationally recognized reporting terminologies for the pooled ROMs for surgically excised nodules in the various Thy reporting categories. There is comparatively little difference (only 6%) between the pooled ROMs of Thy3a and Thy3f surgically excised nodules.
A meta‐analysis of the risk of malignancy using the UK Thy terminology describes the published results for patients undergoing thyroid surgery. It demonstrates that the UK terminology is comparable to other international terminologies for the risk of malignancy for patients undergoing surgery in the various Thy subcategories and that the UK terminology is robust and clinically useful.
In diagnostic cytology, the known site‐specific false positive rates at various anatomical sites for the risk malignancy (ROM) when a confirmed malignant diagnosis is made are comparatively well ...documented. ROM figures for diagnostic cytology specimens may vary according to the anatomical site of the specimen, the exact nature of the specimen received, the staining method(s) used, and the use of additional laboratory techniques including molecular profiling; furthermore, they often differ to some extent from institution to institution, between differing cytologists within the same institution, and over time. A brief literature review for a selected group of routine diagnostic cytology specimens shows a published ROM for a confirmed malignant diagnosis as follows: bile duct brushings, ~99% (range, 97%‐100%); breast fine needle aspiration, 98.5% (range, 92%‐100%); serous effusion fluid, 98.9% (range, 90%‐100% although lower for squamous cell carcinoma, mesothelioma, and lymphoma), pulmonary endobronchial ultrasound cytology, ~99% (range, 86.6%‐100%); thyroid FNA, 98% (range, 97%‐99% if NIFTP tumors are excluded), salivary gland FNA, ~90%; (range 57%‐100%) and lateral neck cyst FNA, ~99% (range, 95.5%‐100%). Because most diagnostic cytology specimens have a small but accepted false‐positive rate, this information is vitally important for the clinical management of patients and for shared patient decision making. In our view, the known false‐positive rate for a given diagnostic cytology specimen could be included within the cytology report to assist in explaining the limitations of the diagnostic cytology interpretation and help facilitate the clinical decision‐making process.
In this review, we discuss why it may be useful to include the risk of malignancy in nongynecologic cytopathology reports, using as examples the known risks of a false‐positive malignancy result for bile duct brushings, pleural fluid cytology, endobronchial ultrasound cytology, and fine needle aspiration of thyroid, salivary gland, lateral neck cysts, and breast. We also discuss the implications for shared patient care.
Thyroid cancer therapy is increasingly tailored to patients' risk of recurrence and death, placing renewed importance on pathologic parameters. The International Collaboration on Cancer Reporting ...(ICCR), an organization promoting evidence-based, internationally agreed-upon standardized pathology data sets, is the ideal conduit for the development of a pathology reporting protocol aimed at improving the care of patients with thyroid carcinomas.
An international expert panel reviewed each element of thyroid pathology reporting. Recommendations were made based on the most recent literature and expert opinion.The data set uses the most recent World Health Organization (WHO) classification for the purpose of a more clinically and prognostically relevant nomenclature. One example is the restriction of the term minimally invasive follicular carcinoma to tumors with capsular invasion only. It reinforces the already established criteria for blood vessel invasion adopted by the most recent WHO classification and Armed Forces Institute of Pathology fascicle. It emphasizes the importance of the extent of blood vessel invasion and extrathyroid extension to better stratify patients for appropriate therapy. It is the first data set that requires pathologists to use the more recently recognized prognostically powerful parameters of mitotic activity and tumor necrosis. It highlights the importance of assessing nodal disease volume in predicting the risk of recurrence.The ICCR thyroid data set provides the tools to generate a report that will guide patient treatment in a more rational manner aiming to prevent the undertreatment of threatening malignancies and spare patients with indolent tumors the morbidity of unnecessary therapy. We recommend its routine use internationally for reporting thyroid carcinoma histology.
Background
Correlation of cytologic and ultrasound findings is extremely valuable for the cytopathologist in management of thyroid nodules.
Methods
Ultrasound scans (US) of all thyroid FNA taken over ...a 13 month period and reported by a single cytologist were reviewed at the time of reporting, focusing on aspirates that were non‐diagnostic/unsatisfactory, equivalent to Bethesda Class I, UK Royal College of Pathologists Class Thy1 or Thy1c.
Results
FNA cases 68 (40.7%) were classified as Thy1, equivalent to Bethesda Class I. US of 3 Thy1 cases were not available for review. On cytologist US review 9 cases were classified as pure cystic, 28 as mixed cystic/solid, 12 as predominantly solid/focally cystic and 16 as purely solid. 27 (41.5%) of cases on cytological assessment were Thy1 and showed no evidence of a cyst on US, 17 (26.1%) were Thy1/Thy1c showing features suggestive of a possible cyst and 21 (32.3%) were Thy1c showing definite features of a cyst. Fifteen of 16 (93.7%) of pure solid cases on US were Thy1, equivalent to Bethesda Class I and all 9 (100%) of cases that were pure cystic on US were reported as Thy1c—equivalent to Bethesda Category I—cyst fluid only (P < .001).
Conclusion
Cytopathologist review of thyroid US is extremely useful and can be helpful in triaging patients for further management in cases of solid, mixed cystic and/or solid, and pure cystic thyroid lesions with non‐diagnostic/unsatisfactory thyroid FNA.
Although growing evidence points to highly indolent behavior of encapsulated follicular variant of papillary thyroid carcinoma (EFVPTC), most patients with EFVPTC are treated as having conventional ...thyroid cancer.
To evaluate clinical outcomes, refine diagnostic criteria, and develop a nomenclature that appropriately reflects the biological and clinical characteristics of EFVPTC.
International, multidisciplinary, retrospective study of patients with thyroid nodules diagnosed as EFVPTC, including 109 patients with noninvasive EFVPTC observed for 10 to 26 years and 101 patients with invasive EFVPTC observed for 1 to 18 years. Review of digitized histologic slides collected at 13 sites in 5 countries by 24 thyroid pathologists from 7 countries. A series of teleconferences and a face-to-face conference were used to establish consensus diagnostic criteria and develop new nomenclature.
Frequency of adverse outcomes, including death from disease, distant or locoregional metastases, and structural or biochemical recurrence, in patients with noninvasive and invasive EFVPTC diagnosed on the basis of a set of reproducible histopathologic criteria.
Consensus diagnostic criteria for EFVPTC were developed by 24 thyroid pathologists. All of the 109 patients with noninvasive EFVPTC (67 treated with only lobectomy, none received radioactive iodine ablation) were alive with no evidence of disease at final follow-up (median range, 13 10-26 years). An adverse event was seen in 12 of 101 (12%) of the cases of invasive EFVPTC, including 5 patients developing distant metastases, 2 of whom died of disease. Based on the outcome information for noninvasive EFVPTC, the name "noninvasive follicular thyroid neoplasm with papillary-like nuclear features" (NIFTP) was adopted. A simplified diagnostic nuclear scoring scheme was developed and validated, yielding a sensitivity of 98.6% (95% CI, 96.3%-99.4%), specificity of 90.1% (95% CI, 86.0%-93.1%), and overall classification accuracy of 94.3% (95% CI, 92.1%-96.0%) for NIFTP.
Thyroid tumors currently diagnosed as noninvasive EFVPTC have a very low risk of adverse outcome and should be termed NIFTP. This reclassification will affect a large population of patients worldwide and result in a significant reduction in psychological and clinical consequences associated with the diagnosis of cancer.
Thyroid fine‐needle aspiration cytology (FNA) and histopathology can be subjective areas of medical diagnosis and subject to different interpretations. On the basis of the authors' personal ...experience, 12 recommendations with potential to improve clinical decision making, ensure quality, and reduce diagnostic error in thyroid FNAC and histopathology are presented. 1) use a standardized reporting terminology for thyroid FNAC; 2) understand and explain to service users the limitations of cytology and the standardized thyroid FNAC reporting terminology used; 3) the cytopathologist should review all relevant clinical and ultrasound findings, if feasible; 4) include the risk of malignancy in all FNAC reports if feasible; 5) collect data to calculate the local institutional risk of malignancy for FNAC if feasible; 6) accept that nondiagnostic FNAC will include small numbers of carcinomas; 7) use rapid on‐site evaluation and/or educational sessions for aspirators if the nondiagnostic aspiration rate is high; 8) know the diagnostic pitfalls of both cytology and histopathology; 9) use special immunohistochemical and molecular techniques that are evidence‐based; 10) make use of second opinions, either in‐house or interinstitutional; 11) multidisciplinary discussion of cases before surgery or therapy is invaluable; and, finally, 12) manage patient and clinician expectations of thyroid cytology and histopathology. These 12 recommendations may assist in quality‐improvement initiatives and may reduce diagnostic errors in thyroid cytology and histopathology. Thyroid multidisciplinary case discussion remains the principal, overarching method for error reduction and for providing high‐quality clinical decision making.
This review discusses the reasons for diagnostic error in thyroid cytology and histopathology and provides 12 recommendations for cytology and histopathology to improve quality and reduce the likelihood of clinical diagnostic errors. For each of the 12 recommendations, the rationale is explained together with the overarching requirement for multidisciplinary case discussion if there is clinical or diagnostic uncertainty.
The encapsulated and noninvasive follicular variant of papillary thyroid carcinoma has been recently reclassified as noninvasive follicular thyroid neoplasm with papillary-like nuclear features ...(NIFTP). These tumors demonstrate indolent behavior. This change in nomenclature will have great clinical impact by avoiding overtreatment of patients with NIFTP lesions who in the past were diagnosed with thyroid carcinoma and typically received completion thyroidectomy followed by radioactive iodine ablation. The pathologic diagnosis of NIFTP requires surgical removal of the thyroid lesion or the lobe harboring it, and thorough sampling of the complete interface between the tumor capsule and the thyroid parenchyma, to exclude foci of invasion. From a cytologic point of view, the unequivocal differential diagnosis between NIFTP and infiltrative follicular variant of papillary thyroid carcinoma in fine-needle aspiration is close to impossible based on cellular and architectural features. Therefore, use of adjunct molecular testing on fine-needle aspiration specimens may be essential for the preoperative diagnosis of low-risk tumors such as NIFTP for appropriate patient management. This review discusses and summarizes the existing known literature on molecular characteristics of NIFTP tumors, so far reported, including cases retrospectively classified or prospectively diagnosed as NIFTP. Brief reference is also made to new and promising approaches applicable to the diagnosis of this tumor.
PDF
