Introduction: The classical type of well-differentiated thyroid cancer (WDTC) is the most common endocrine tumor with generally excellent prognosis. WDTC of the WHO stage 1 classification metastasizing to the vertebral column is not often seen for this neoplasm. Here, I present a case series of 14 individuals with aggressive classical type of WDTC.
Methods: To identify the most aggressive cases of classical type WDTC, I reviewed the medical records of 4,327 patients consecutively admitted and surgically treated in a single institution for thyroid pathology in the years 2008–2016. Demographic, pathological and outcome data were collected and reviewed.
Results: During the study period, 14 (4.02%) patients with aggressive forms of the classical type of WDTC were reviewed: 10 (2.87%) cases with papillary thyroid cancer (PTC) and 4 (1.14%) with follicular thyroid cancer (FTC). The median age at diagnosis was 61 years (31–84 years). Aggressive features such as extrathyroid extension 11/14 (78.57%), positive surgical margins 11/14 (78,57%), lymph node metastases 7/14 (50%), multifocality 6/14 (42.85%), regional tissue infiltration 11/14 (78.57%) and distant metastases 4/14 (28.57%) were observed. Long-term follow-up (median 40 months) demonstrated a high rate of locoregional recurrence in 12/14 (85.71%) individuals. Pulmonary and other distant metastases were observed in 4/14 (28.57%) patients, with mortality in 3/14 (21.42%) individuals.
Conclusion: In patients with classical type of WDTC characterized by excellent prognosis, extremely aggressive entities might be observed, making WDTC in some cases an unpredictable tumor.
Keywords: well-differentiated thyroid cancer, aggressive, metastases, multifocality
In recent decades, we have observed a tremendous rise in the prevalence of well differentiated thyroid cancer (WDTC), which is characterized by favorable prognosis.1–3 Papillary and follicular thyroid carcinomas (PTCs and FTCs) account for about 95% of all thyroid malignant tumors, forming the WDTC group.1,2 Both arise from follicular epithelial cells. The most common type is PTC, which owes its excellent prognosis to tumors of ≤1 cm in diameter, regardless of the existence of distant metastases. These tumors are defined as papillary thyroid microcarcinomas (PTMCs),3 and during recent years, they have become much more common.4,5 WDTCs often remain clinically silent for many years. Some of them are diagnosed during routine clinical examination followed by fine-needle aspiration biopsy (FNAB) and subsequently surgical treatment.6 The other tumors are diagnosed incidentally during histopathological examinations after surgery performed for benign thyroid disease.5,7 As with many other malignant tumors, thyroid cancers are classified according to the TNM classification proposed by the Union Internationale Contre le Cancer [UICC] and the American Joint Committee on Cancer [AJCC] 7th edition, 2010.8 As for the prognosis of WDTC, not only is clinical staging taken under consideration, but also factors such as age, gender, histological type and subtype, DNA euploidy, microvessel count, CD97, E-cadherin, telomerase activity, and capsular and vascular invasion.9 The authors of this study added that many WDTCs are not clearly defined in terms of tumor prognosis. However, it was estimated that WDTCs in patients under the age of 45 years have rather excellent prognosis and are classified according to the UICC classification as stage I, or, if distant metastases are observed, as stage II. Several years ago, due to the wide range of different prognoses in cases of classical type WDTCs, the American Thyroid Association (ATA) and the British Thyroid Association classified these tumors in the three categories of risk aggressiveness (low, middle, and high). The excellent prognosis of the majority of cases of WDTC is reflected in 5-year survival rates as high as 93%for women and 88% for men for all patients. Survival is poorer for patients over 45 years of age at the time of diagnosis and for those with distant metastases.10 According to the ATA guidelines, patients below 45 years with PTC and distant metastases have a 100% 5-year disease-specific survival, while those above 45 years with distant metastases have a 51% 5-year disease-specific survival.11 The clinically relevant features that define the classical type of WDTC with a low risk of aggressiveness are pT1a solitary or multiple, N0/Nx, pT1b N0/Nx, pT2 N0/Nx, pT3>4 cm N0/Nx, tumor diameter below 4 cm and intrathyroid, R0 or R1 resection, and M0. The features connected with a high risk of WDTC are pT4 and M1 or R2 resection.12 However, on the basis of our own observation and subsequent postsurgical follow-up, this risk stratification does not always correspond with clinical outcome. In addition to the previously mentioned suggestions that primary tumor size, extrathyroid extension, and distant metastases are strongly correlated with patient prognosis, we sometimes observe completely different situations. Some authors confirm overall excellent prognosis of classical type PTC, and the other types of PTC, such as tall cell variant, are considered independent poor prognostic factors.13 However, others do not agree with this opinion.14 They say that the higher risk for poor prognosis does not depend on the histopathological variant of PTC but rather on older age, larger tumor size, extrathyroidal extension and the higher stage, and grade of the tumor. Additionally, international guidelines do not accept histopathological variants of PTC such as tall cell carcinoma as higher risk factors.15 For example, the European Thyroid Association (ETA) and the ATA guidelines categorize the tall cell variant as a low and intermediate risk factor of PTC, respectively.16,17 In our study, we decided to evaluate patients with classical type WDTC. Generally, this type of WDTC is considered by all authors as one with the best prognosis. Currently, the incidence of WDTC has been increasing. The prognosis for this tumor is considered excellent; therefore, the general recommendations for surgical and adjuvant treatment might be less aggressive. We decided to present this case series of 14 individuals with the classical type of WDTC with adverse outcomes of surgical treatment so that we may now realize that they should be identified and treated aggressively with greater caution and attention.
PATIENTS AND METHODS
We performed a retrospective chart review of 4,327 patients consecutively admitted and surgically treated for thyroid pathology in the First Department and Clinic of General, Gastroenterological and Endocrine Surgery from January 1, 2008, to December 31, 2016. Demographic data, diagnostic results, clinical and histopathological characteristics, and outcomes were evaluated. As a main presurgical diagnostic test, all patients underwent UGFNAB. Clinical and pathological classification was performed according to the TNM classification criteria (7th Edition, 2010) by the AJCC.8 All of the operations were performed by the same team of surgeons, and histopathological specimens were examined by two pathologists experienced in thyroid malignancy. Histopathology reports were analyzed to determine tumor size, subtype, immunohistological staining, aggressive characteristics such as extrathyroidal extension, surgical margins, surrounding organs, tissue infiltration, and lymph node metastases. Details on postoperative course and follow-up data such as time to recurrence, length of follow-up, distant metastases, and patient mortality were collected. Only patients with classical type WDTC and aggressive pathological and clinical features were analyzed.