Update to the College of American Pathologists Reporting on Thyroid Carcinomas
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- Ghossein, R. Head and Neck Pathol (2009) 3: 86. doi:10.1007/s12105-009-0109-2
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Background The reporting of thyroid carcinomas follows the recommendations of the College of American Pathologists (CAP) protocols and includes papillary carcinoma, follicular carcinoma, anaplastic carcinoma and medullary carcinoma. Despite past and recent efforts, there are a number of controversial issues in the classification and diagnosis of thyroid carcinomas (TC) that, potentially impact on therapy and prognosis of patients with TC. Discussion The most updated version of the CAP thyroid cancer protocol incorporates recent changes in histologic classification as well as changes in the staging of thyroid cancers as per the updated American Joint Commission on Cancer staging manual. Among the more contentious issues in the pathology of thyroid carcinoma include the defining criteria for tumor invasiveness. While there are defined criteria for invasion, there is not universal agreement in what constitutes capsular invasion, angioinvasion and extrathyroidal invasion. Irrespective of the discrepant views on invasion, pathologists should report on the presence and extent (focal, widely) of capsular invasion, angioinvasion and extrathyroidal extension. These findings assist clinicians in their assessment of the recurrence risk and potential for metastatic disease. It is beyond the scope of this paper to detail the entire CAP protocol for thyroid carcinomas; rather, this paper addresses some of the more problematic issues confronting pathologists in their assessment and reporting of thyroid carcinomas. Conclusion The new CAP protocol for reporting of thyroid carcinomas is a step toward improving the clinical value of the histopathologic reporting of TC. Large meticulous clinico-pathologic and molecular studies with long term follow up are still needed in order to increase the impact of microscopic examination on the prognosis and management of TC.
KeywordsThyroidCarcinomaReportingCAPVascularCapsularInvasionMinimally invasiveWidely invasiveExtrathyroidExtensionMitosisNecrosisMarginsPapillary microcarcinomas
Despite advances in the last several decades in the diagnosis of thyroid cancers, there are still many problems and controversies related to the histopathology of thyroid carcinomas. These controversies impact on the prognosis and therapy of thyroid cancer patients, as well as, on the development of cutting edge research aimed at better outcome and quality of life for these patients. These contentious issues may directly impact on the pathologic reporting of these carcinomas. In the most updated version of the College of American Pathologists (CAP) protocol for the examination of specimens from patients with carcinomas of the thyroid, attempts were made to address some of these controversies. The goal was to produce a practical document providing for more clinically relevant pathology reports. The updated CAP protocol is essentially organized in a similar fashion to the previous edition with some modifications primarily but not exclusively based on the current CAP recommendations for the reporting of all cancers.
Among the controversial issues in thyroid pathology include (but are not limited to) the histopathologic interpretation of an encapsulated (well-differentiated) thyroid follicular neoplasm, specifically in determining which of these lesions does and which does not represent the follicular variant of papillary thyroid carcinoma [1, 2]. Controversies also relate to the concept of the less commonly occurring poorly-differentiated thyroid carcinoma. It is beyond the scope of the CAP protocol to provide guidelines for the histopathologic interpretation of thyroid cancers. Among the standard data elements required by the CAP, this paper addresses specific issues pathologists will confront relative to criteria of malignancy (e.g., invasiveness) and extrathyroidal extension (ETE). Unfortunately, even among the authors of the updated CAP Thyroid Cancer Protocol there was not uniformity in agreement on these issues. As such, the document echos the varying views on invasiveness and ETE. Although listed as recommended rather than required elements, mitotic activity and necrosis are important in potentially determining whether a given cancer represents a poorly-differentiated thyroid carcinoma. Finally, the issue of whether the identification of thyroid papillary microcarcinomas should engender the use of the CAP Thyroid Cancer Protocol will be discussed.
The updated CAP thyroid protocol is still a work in progress and a final consensus among the responsible authors has not been reached on all of the reporting data elements, including (but not limited to): (1) whether to report all identifiable foci of thyroid papillary microcarcinoma including incidentally identified foci or whether to limit reporting to only those foci that were detectable preoperatively (by clinical examination and/or radiographic evaluation); (2) whether to limit the use of the designation of thyroid papillary microcarcinoma to adults excluding such a designation for pediatric age groups. Consequently, the recommendations herein contained reflect the views of the author of this manuscript, as well as the senior author of the CAP protocol (Bruce M. Wenig MD1). Modifications to the recommendations in this manuscript based on a final consensus opinion of the entire panel may yet occur.
Criteria and Extent of Capsular and Vascular Invasion in Follicular Carcinoma and its Variants
Capsular Invasion (CI)
The diagnosis of papillary thyroid carcinoma is entirely predicated on the presence of diagnostic nuclear features. As such, the diagnosis of papillary thyroid carcinoma can be made in the presence of an encapsulated follicular neoplasm even in the absence of invasive growth. Once a given neoplasm invades its capsule and/or shows evidence of angioinvasion (intracapsular or beyond), that follicular epithelial cell lesion is malignant.
Angioinvasion or Lymph-Vascular Invasion
The CAP guidelines for all cancer protocols calls for the use of the term lymph-vascular invasion (LVI) which is the terminology used in the Thyroid Cancer Protocol as well as all the protocols for the reporting of carcinomas of the entire upper aerodigestive tract, including the oral cavity, pharynx (oro-, naso- and hypopharynx), sinonasal tract, larynx and salivary glands.
Extent of Capsular and Lymph-Vascular Invasion
Irrespective of one’s philosophy in regard to the definition of minimally invasive follicular carcinoma, the recommendation is that pathologists should report on the presence as well as the extent (focal, extensive) of capsular and lymph-vascular invasion. This approach has a dual advantage of collating the various terminologies suggested for these carcinomas, as well as and perhaps more importantly, providing a report that better assists the clinician in assessing recurrence risk and, therefore, in deciding on the extent of surgical intervention (e.g., completion thyroidectomy) and the use of postoperative RAI therapy.
Mitosis and Tumor Necrosis
From the above data, one can conclude that whatever definition is used for PDTC, it is very helpful to mention the presence of mitosis and tumor necrosis in the pathology report. It is however important to differentiate tumor necrosis from necrosis due to previous fine needle aspiration (FNA). Tumor necrosis has a “comedo-like” appearance composed of degenerating cytoplasm and punctuate, karyorectic nuclear debris (Fig. 4). In contrast, the presence of fibroblastic stromal reaction, evidence of hemorrhage or an identifiable needle tract in the necrotic area are attributable to reaction induced by prior FNA. Since the majority of thyroid cancers are well-differentiated lacking mitotic activity and necrosis, and the fact that PDTC is a rather uncommon diagnosis, the Thyroid Cancer Protocol recommends rather than requires the reporting of these data elements (i.e., mitotic activity and tumor necrosis).
While minimal extra-thyroid extension can be difficult to identify, extensive extra-thyroid extension is always obvious and easily diagnosed by the surgeon during the thyroidectomy. Extensive extrathyroid extension is defined by the presence of carcinoma well beyond the thyroid gland proper with direct invasion (i.e., not metastasis) into one or more of the following structures:subcutaneous soft tissues; adjacent viscera, including the larynx, trachea and/or esophagus; the recurrent laryngeal nerve, carotid artery or mediastinal blood vessels. Many studies have shown that carcinomas with extensive extra-thyroid extension have a much worse survival than those with minimal extra-thyroid extension [3, 23]. Moreover, some studies have found a similar outcome in patients with minimal versus no extra-thyroid extension .
Based on the above data, it is therefore mandatory to report on the extent (minimal versus extensive) of extrathyroid extension.
Few published studies have addressed the influence of margin status and patient outcome. Most surgeons, endocrinologists, and nuclear medicine specialists require knowledge of positive margins, i.e., tumor extending to surgical resection edge. While this makes intuitive sense and it is recommended that a positive margin be mentioned in the final pathology report, meticulous studies on the effect of positive margins and outcome in large series of patients with long-term follow-up are lacking.
At the present time, there is no need to report the distance of tumor to closest resection margin. Indeed, there is no data to date on the prognostic value of close margins as an independent or co-variable.
Lymph Node Metastases
Although controversy still exists in regard to the prognostic value of nodal metastases in papillary thyroid carcinomas, the reporting on lymph node status is mandatory since positive nodal metastases most often lead to RAI therapy. The pathologist should also comment on the presence or absence of extranodal extension since the latter was shown to increase the risk for distant metastases and death .
Papillary Thyroid Microcarcinoma
This variant of papillary thyroid carcinoma is defined as any focus measuring ≤1 cm.  Such papillary thyroid microcarcinomas usually are incidentally identified in thyroid glands removed for other reasons. There is general agreement that no additional therapy is needed for these incidentally identified foci of thyroid papillary microcarcinoma and, in order to avoid overtreatment, it is worthwhile to consider indicating in the pathology report that these foci have an extremely favorable prognosis and should not be used as a reason for additional therapy (e.g., completion thyroidectomy and RAI). Given their rather common identification in all thyroid gland resections and their indolent biologic behavior, it is not the recommendation of the CAP Thyroid Cancer Protocol to issue a protocol for each case in which incidental papillary thyroid microcarcinomas are found. An exception to such practice would be considered in those examples of papillary thyroid carcinomas measuring ≤1 cm but representing the primary reason a lobe/gland was removed. The tumor could have been discovered clinically (palpable, visible nodule) or by imaging. Given the more sophisticated diagnostic (e.g., imaging) modalities currently available, smaller (i.e., <1 cm) lesions are being identified and resected. In such circumstances, where the primary reason for thyroid surgery is to excise a subcentimeter focus of PTC, then reporting should follow the CAP Thyroid Protocol.
Although usually extremely indolent, papillary thyroid microcarcinomas may exceptionally behave aggressively with spread to lymph node or distant sites . Such aggressive papillary thyroid microcarcinomas usually harbor their metastases at presentation . The presence of two or more foci of papillary thyroid microcarcinonas, and aggressive features related to the primary tumor such as lymph-vascular invasion, extra-thyroid extension and “aggressive” morphology (e.g., tall cell features) may trigger full blown treatment including total thyroidectomy and RAI therapy. Such management does not appear to be justified at this time as there is insufficient data in the literature (long term follow-up) on these papillary thyroid microcarcinomas with “aggressive” features in the primary to justify such a therapeutic approach. It is our recommendation that the designation of papillary thyroid microcarcinoma should not be applied to children and adolescents under 19 years old as a significant number of these subcentimeter papillary carcinomas occurring in the pediatric population display extrathyroidal extension and distant metastases .
The updated CAP protocol is a step toward improving the clinical value of the pathologic reporting of thyroid carcinomas. An accurate assessment of the extent of invasion of the tumor capsule, especially lymph-vascular invasion, is an important element in the reporting of thyroid carcinomas. Meticulous microscopic examination of TC is no longer an academic exercise but a necessity in the management of these malignancies. Proliferative assessment of the tumor (i.e., mitosis and necrosis) is of high prognostic value in the determination of a poorly-differentiated thyroid carcinoma. The extremely indolent behavior of papillary thyroid microcarcinoma should be communicated to the clinician in order to avoid overtreatment.
There are still unresolved issues in the histopathologic diagnosis of thyroid carcinomas. Large clinico-pathologic studies with long term follow up are still needed in order to increase the impact of histopathology on the prognosis and management of TC. With the advent of molecular diagnostics the anticipation is that many of these controversial issues will be resolved but until that time, pathologists must rely on morphology in the assessment and reporting of thyroid carcinomas.
Bruce M. Wenig, M.D is Professor of Pathology and Chairman, Department of Pathology and Laboratory Medicine, Beth Israel Medical Center and St. Luke’s and Roosevelt Hospitals, New York NY.