Interpretation of the 2021 CSCO Guidelines for Diagnosis and Treatment of Differentiated Thyroid Cancer—Professor Liu Zhiyan's Analysis of Pathological Diagnosis

Introduction Pathology is the gold standard for diagnosis, and it plays an important role in the preoperative evaluation of differentiated thyroid cancer (DTC), the stratification of recurrence risk, and the guidance of clinical diagnosis and treatment
.

The "2021 Chinese Society of Clinical Oncology (CSCO) Guidelines for the Diagnosis and Treatment of Differentiated Thyroid Cancer)" (hereinafter referred to as the "Guide") absorbs the latest advances in the field of thyroid cancer based on China’s national conditions, and provides the latest updates for the diagnosis and treatment of DTC in China Supported by authoritative evidence1
.

Yimaitong specially invited Professor Liu Zhiyan from the Sixth People's Hospital of Shanghai Jiaotong University to interpret the pathological diagnosis part of the "Guide"
.

Expert profile Professor Liu Zhiyan, Director of the Department of Pathology, Shanghai Jiaotong University Sixth People's Hospital, Director of the Histopathology Research Office of the Limb Microsurgery Institute, Director of the Tumor Pathology Research Office, Master's Supervisor, Ph.
D.
, a visiting scholar from the University of Michigan, Chinese Medical Association Member of the Head and Neck Section of the Chinese Society of Pathology Member of the Professional Committee Member of the Thyroid Professional Committee of the Chinese Society of Clinical Oncology Pathology is of great value in the diagnosis of thyroid cancer, the presentation of possible etiological evidence or clues, the stratification of prognostic recurrence risk, the provision of systematic treatment basis, and the evaluation of curative effect
.

Pathological diagnosis methods mainly include cytological diagnosis (fine needle aspiration cytology), histological diagnosis (preoperative or recurrent tumor puncture with thick needle; intraoperative frozen pathological diagnosis; postoperative histopathology), cellular immunochemistry/immunohistochemistry , Molecular Pathology, Electron Microscopy
.

The "Guide" refines the recommended levels of pathological examinations at different stages, specifies the Bethesda diagnostic system of thyroid fine needle aspiration (FNA) cytology and its clinical treatment specifications, and emphasizes the importance of histological types and subtypes of thyroid cancer
.

Table 1: Recommended guidelines for pathological diagnosis methods at different stages.
Recommendations: According to different stages, select the appropriate pathological diagnosis method.
Interpretation 1: Preoperative UG-FNA is the first choice for identifying benign and malignant thyroid nodules.
Ultrasound guided fine needle aspiration (UG) -FNA) is suitable for the first diagnosis of suspected malignant thyroid nodules, considering recurrence, and the diagnosis of metastatic thyroid cancer
.

Preoperative FNA cell diagnosis has a high accuracy rate, which can effectively save medical insurance resources and reduce unnecessary diagnostic operations
.

The FNA standard cytology report generally adopts the Bethesda six-category report system of the United States
.

In countries and regions such as Europe, America, Japan and South Korea, UG-FNA cytology examination is one of the routine preoperative examination items
.

The "Guide" regards preoperative UG-FNA as a level I recommendation (category 1A).
This is the first time that preoperative FNA cytology is recommended in the Chinese guidelines with category 1A evidence
.

For Bethesda Ⅲ (AUS/FLUS), it is difficult to diagnose malignancy due to insufficient cellular and/or structural atypia.
Repeated FNA is difficult to solve this diagnostic problem, but molecular testing can help the diagnosis of papillary thyroid carcinoma
.

However, because Bethesda Ⅳ (FN/SFN, HCN/SHCN) diagnostic criteria need to clarify the characteristics of non-papillary carcinoma cells, it is also necessary to clarify vascular or capsular infiltration, which is difficult to evaluate by cytology and cannot be accurately diagnosed.
Follicular thyroid carcinoma (FTC) and eosinophilic carcinoma (HCC), such as molecular detection of high-risk mutations, may help the diagnosis of follicular adenocarcinoma
.

Interpretation 2: Intraoperative rapid frozen pathology and application of cell prints Intraoperative rapid frozen section diagnosis is recommended for the determination of lymph node metastasis, surgical margins, and parathyroid glands
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Intraoperative rapid frozen pathological examination has limited effect in the diagnosis and differential diagnosis of follicular tumors
.

Cytological examination of cell prints of surgical specimens can help determine the characteristics of papillary thyroid carcinoma nucleus (nucleus size and size, nuclear membrane irregularity, ground glass nucleus), medullary carcinoma nucleus (pepper-salt nucleus), in papillary thyroid carcinoma and marrow It is of great significance in the differential diagnosis of follicular carcinoma and follicular tumor
.

Interpretation 3: Routine pathological examinations should be performed after surgery to distinguish histopathological types.
According to the WHO classification of thyroid tumors, DTC mainly includes papillary thyroid carcinoma (PTC), FTC and HCC2
.

For cases with PTC morphology, if possible, further report histological subtypes that may indicate a poor prognosis, such as high cell subtype, columnar cell subtype, solid type and stud subtype, etc.
; if it contains corresponding tumors If the components fail to meet the diagnostic criteria of a certain subtype, the proportion of histological subtypes that suggest a poor prognosis should be indicated
.

Most of the vascular invasion of PTC is lymphatic invasion, while FTC and HCC are more prone to vascular invasion.
In addition to vascular invasion, HCC can also have lymphatic metastasis
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For cases with FTC and HCC morphology, the number of tumor thrombi in blood vessels needs to be assessed
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For lymph node metastasis, the size of the largest lesion, whether it is micrometastasis, and whether the metastatic lymph node has extracapsular invasion should be assessed
.

Table 2: Preoperative thyroid fine needle aspiration cytology Bethesda diagnostic system and clinical treatment guidelines Recommendation: Emphasize the application of molecular diagnosis in Bethesda Ⅲ/Ⅳ Interpretation 1: Molecular detection, auxiliary diagnosis In recent years, with molecular biology With the rapid development of thyroid nodules, molecular detection has played an increasingly important role in the differentiation of benign and malignant thyroid nodules
.

The "Guide" recommends Bethesda Ⅲ (AUS/FLUS, cell atypical lesions of ambiguous significance/follicular lesions of undetermined significance) and Bethesda Ⅳ (FN/SFN, follicular tumors or suspicious follicles) for FNA For sexual tumors; HCN/SHCN, eosinophilic tumors or suspected eosinophilic tumors) molecular testing (Class 2A), including some specific genetic mutations (such as BRAF V600E, RET/PTC, RAS, PAX8/PPARγ, etc.
)
.

The results of molecular testing need to be interpreted by pathologists in conjunction with FNA cytology results and postoperative pathological features
.

Interpretation 2: Molecular testing helps evaluate the risk of recurrence and formulate treatment plans.
In addition to assisting diagnosis, molecular testing has important guiding significance in the stratification of recurrence risk of thyroid cancer and the formulation of treatment plans
.

Genes such as BRAF, RAS, and RET are key genes in the MAPK and PI3K-AKT signaling pathways.
Mutations or rearrangements of these genes play an important role in the occurrence and development of thyroid cancer.
In addition, mutations in the TERT promoter and mutations in the TP53 gene, etc.
It is also of great significance in the progression of thyroid cancer
.

Studies have shown that BRAF/RAS and TERT promoter double mutations have a synergistic effect, which is more aggressive than single-gene BRAF or RAS or TERT mutations in thyroid cancer3
.

Not only that, genetic mutations (such as BRAF mutations, etc.
) can affect the efficacy of iodine therapy in patients
.

The prerequisite for precision treatment is accurate diagnosis.
For advanced patients, molecular testing can help accurately identify the people who benefit from targeted drugs
.

The guidelines recommend that for advanced, aggressive, and life-threatening tumors, genomic testing for genetic mutations (ALK, NTRK, RET, dMMR, MSI, TMB, etc.
) is recommended
.

Reference materials 1.
Chinese Society of Clinical Oncology Guidelines Working Committee.
Chinese Society of Clinical Oncology (CSCO) Guidelines for Diagnosis and Treatment of Differentiated Thyroid Cancer (2021) [M].
People's Medical Publishing House 2.
LLOYD RV, OSAMURA RY, KLoPPEL G, et al ,WHO classification of tumours: Patholog and genetics of tumours of endocrine organs[J].
Lyon: IARC,20173.
Luo Dingyuan, Liao Jianwei.
Guangdong expert consensus on gene detection and clinical application of thyroid cancer (2020 edition)[J].
Chinese General Surgery Literature (Electronic Edition),2020,14(03):161-168.
4.
Liu Zhiyan.
Morphological lineage and molecular biological characteristics of differentiated thyroid cancer[J].
Chinese Journal of Pathology.
2020,49,(3):284- 288.