Poorly differentiated thyroid carcinoma

doi:10.1053/j.semdp.2020.03.003

Seminars in Diagnostic Pathology

Volume 37, Issue 5, September 2020, Pages 243-247

https://doi.org/10.1053/j.semdp.2020.03.003 Get rights and content

Abstract

Poorly differentiated thyroid carcinoma (PDTC) is an aggressive form of follicular cell derived thyroid carcinoma with a prognosis intermediate between the indolent well differentiated thyroid carcinomas and the rapidly growing often fatal anaplastic carcinoma. While all investigators agree on the presence of this entity, there is disagreement in regard to its definition. In 2006, a set of criteria based solely on mitotic index ≥5/10 high power fields and/or tumor necrosis was proposed by a group of researchers from Memorial Sloan Kettering Cancer Center (MSKCC criteria) in New York. A year later, alternative diagnostic criteria of PDTC, so called the Turin proposal, were advocated by an international consensus group. The Turin proposal requires three criteria: 1) solid/trabecular/insular growth pattern; 2) absence of nuclear features of papillary carcinoma; and 3) at least one of the following three features: mitotic index ≥3/10 high power fields (HPFs), necrosis, or convoluted nuclei. In this review, we summarize the histology, diagnostic criteria (Turin proposal and MSKCC criteria) with their pros and cons, the prognostic factors, and molecular profile of PDTC, aiming to provide a practical and compreshensive review of this challenging entity.

Introduction

Poorly differentiated thyroid carcinoma (PDTC) is an uncommon type of thyroid follicular cell-derived carcinoma, accounting for 1-3% of all thyroid carcinomas diagnosed.¹ It carries an intermediate prognosis in between well-differentiated carcinoma (e.g. papillary carcinoma, follicular carcinoma and Hurthle cell carcinoma) and anaplastic carcinoma with a reported mortality of 38-57%.2, 3, 4, 5 Clinically, PDTC typically affects patients in their late 50s (median 59) and shows a higher male: female ratio of 1:1.6 compared with the 1:3 ratio of well-differentiated thyroid carcinoma.6, 7

In the past three decades, several key studies have been published aiming to establish the diagnostic criteria, prognostic factors and molecular signatures of PDTC. In the current review, we aim to summarize the evolution of PDTC, focusing specifically on the pathologic diagnostic aspect and genomics of this entity.

Section snippets

PDTC: History and diagnostic criteria

In 1907, Theodor Langhans was the first to describe a thyroid carcinoma with insular growth pattern, and he labeled the tumor “wuchernde Struma”⁸ in German or “proliferating goiter” in English . The term “poorly differentiated carcinoma of thyroid gland” was introduced into the English literature by Granner and Buckwalter in 1963.⁹ However, their histologic description of predominant small cell, giant cell, and spindle cell morphology is more akin to the contemporary description of anaplastic

Differential diagnosis

Because of the presence of solid growth pattern in many cases, PDTC can be confused with medullary thyroid carcinomas. The presence of colloid in some areas of the tumor should easily exclude medullary carcinoma. In difficult cases, immunostaining can reliably resolve the issue since PDTC are positive for thyroglobulin and PAX8 and negative for calcitonin, chromogranin and synaptophysin. In contrast, medullary carcinomas are positive for calcitonin and other neuroendocrine markers, rarely

Pathologic prognostic factors in PDTC

Using insular growth pattern or MSKCC parameters of high mitotic rate and/or tumor necrosis as the diagnostic criteria for PDTC, several groups have shown that the percentage of PDTC within a thyroid mass has no significant impact on overall survival4, 13, 23 and that any PDTC component in a well-differentiated thyroid carcinoma (e.g. papillary thyroid carcinoma and follicular thyroid carcinoma) independently incurs a worse prognosis.²⁴ Similarly, using Turin proposal, recent studies have shown

Genomics of PDTC

In the past decade, several studies have reported on the genetic profile of over 200 cases of PDTC using targeted next generation sequencing techniques19, 20, 32, 33, 34, 35 and their results are summarized in Table 2. Although these studies differ in term of the definition of PDTC, the genes included in next generation sequencing platforms, and the depth of coverage, several conclusions can be drawn from these studies.

First, similar to well-differentiated³⁶ and anaplastic thyroid carcinoma,19,

Treatment and follow up

Poorly differentiated thyroid carcinoma are considered aggressive forms of differentiated thyroid carcinomas and therefore categorized as at least intermediate risk by the latest American Thyroid Association (ATA) guidelines.⁴⁰ The initial management consists of total thyroidectomy followed by RAI therapy in the vast majority of cases.⁴⁰ Consideration should be given to use ¹⁸FDG-PET as part of the initial staging since a significant proportion of PDTC may not concentrate RAI13, 40 and are ¹⁸

Conclusions

The modern pathologic diagnostic criteria of PDTC are the Turin proposal and the MSKCC PDTC definition. PDTC diagnosed by the MSKCC criteria can be divided into two subgroups: The first set of tumors concord with the Turin criteria is enriched with RAS and EIF1AX mutations and had a metastatic tropism to distant sites; the second does not fullfill the Turin proposal, shows non-solid growth and/or nuclear features of papillary carcinoma, contains a high frequency of BRAF V600E mutation, and has

Disclosure Statement

No competing financial interests exist for all contributory authors.

Research reported in this publication was supported in part by the Cancer Center Support Grant of the National Institutes of Health/National Cancer Institute under award number P30CA008748. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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