The follicular variant of papillary thyroid carcinoma (FVPTC) is a common subtype of papillary thyroid carcinoma. Few studies have compared the clinical behavior and treatment outcome of patients with FVPTC with the outcome of patients with pure papillary carcinoma (PTC). A retrospective study was performed to identify the influence of FVPTC compared with PTC on therapeutic variables, prognostic variables, and survival.
A clinicopathologic analysis of 243 patients with papillary carcinoma was performed. One hundred forty-three tumors were PTC, and 100 tumors were FVPTC. The following variables were evaluated: age at diagnosis, tumor size, stage of tumor, treatment, capsular invasion, and survival.
The median follow-up was 11.5 years. The median age was 43 years in the PTC group and 44 years in the FVPTC group. The median tumor size, disease stage, and type of initial surgery and iodine 131 ablation were similar. More patients had capsular invasion by the tumor and less metastases to cervical lymph nodes in the FVPTC group. The actuarial survival of patients age < 40 years was higher compared with the survival of patients age > 50 years in both groups. The 21-year overall actuarial survival was 82% in patients with PTC and 86% in patients with FVPTC (P value not significant).
Approximately 90% of malignant thyroid tumors are well differentiated and are classified as papillary thyroid carcinoma (PTC; 80%) or follicular carcinoma (10%), based on the predominant histologic pattern.1 The follicular variant of PTC (FVPTC), which also is classified as mixed tumor, is a common subtype of papillary carcinoma. Microscopically, papillary carcinomas are characterized by the presence of papillae, and the follicular variant contains a variable area of both papillary and follicular histology.2 The term mixed papillary and follicular carcinoma no longer is used. Historically, FVPTC has been regarded as more aggressive compared with pure PTC.3 Some reports suggest that pulmonary metastases are more common in FVPTC compared with pure PTC.4 To our knowledge, there are few data in the literature comparing the clinical behavior and treatment outcome of patients with FVPTC and patients with papillary carcinoma.5 Prognostic factors published for patients with papillary carcinoma always are based on the analysis of FVPTC and PTC together.6 The objective of this retrospective comparative study was to determine the behavior, treatment, prognostic factors, and long-term survival of patients who have FVPTC compared with patients who have PTC.
MATERIALS AND METHODS
The records of 243 patients with a histologic diagnosis of papillary carcinoma of the thyroid who were treated at the Northern Israel Oncology Center at Rambam University Hospital between 1970 and 1992 were reviewed. Tumors were classified as pure PTC by the presence of papillae. The nuclei of papillary carcinoma are enlarged and ovoid and contain thick nuclear membranes, small nuclei that often are pressed against the nuclear membrane, intranuclear grooves, and intranuclear cytoplasmic inclusions. The nuclei frequently overlap each other (World Health Organization classification system).7 Criteria for the diagnosis of FVPTC include pure follicular architecture occupying at least 80% of the neoplasm and at least 2 nuclear features typical of papillary carcinoma. All slides were analyzed and read by a committee of experienced pathologists from Rambam University Hospital using modern, acceptable criteria.
The initial staging procedure included physical examination, complete blood count, routine serum chemistries, serum thyroxine, triiodothyronine, thyroid-stimulating hormone, chest radiograph, radionuclide imaging, ultrasound, and serum thyroglobulin. TNM classification and staging were performed according to the criteria of the American Joint Committee on Cancer.8
Patients' records were reviewed for gender, age, histology, tumor size, capsular invasion, extent of primary surgery, results of postoperative radioiodine scanning, and treatment with radioactive iodine. Initially, metastatic disease was diagnosed if metastases were present at the time of diagnosis of the primary tumor or within 3 months after diagnosis. Occult carcinoma was diagnosed if the greatest tumor dimension measured ≤ 1 cm.
All patients had undergone either total or subtotal thyroidectomy (total lobectomy on the side of the initial lesion combined with a contralateral subtotal lobectomy). A total body scan was done 5–6 weeks postsurgery in all patients. The type of surgery and the disease stage of all patients were determined after discussing postoperative radionuclide imaging and ultrasound finding with the patient's surgeon. Patients with positive iodine 131 (I131) uptake after 24 hours received I131 for ablation of the remnant in the thyroid bed.
Statistical analyses were performed by the Kaplan–Meier method. Differences between proportions were tested by using chi-square analysis, and between means were tested by using the Student t test. P values ≤ 0.05 (based on one test) were considered statistically significant.
Of 243 patients with papillary carcinoma, 143 patients (59%) had PTC, and 100 patients (41%) had FVPTC (Table 1). The median age was 43 years (range, 11–78 years) in the PTC group and 44 years (range, 17–81 years) in the FVPTC group. The female:male ratio was 1.9:1.0 in the PTC group and 2.8:1.0 in the FVPTC group. Tumor size and stage at diagnosis were comparable in both groups. Capsule invasion by tumor was found in 31% of patients in the PTC group and in 38% of patients in the FVPTC group (P value not significant [NS]). More cervical lymph node metastases were found at the time of diagnosis in the PTC group compared with the FVPTC group (32% vs. 22% respectively; P value NS). The most common metastatic site was lungs followed by bones. Multifocality was observed in 25% of patients in the PTC group and in 33% of patients in the FVPTC group. Occult tumor was observed in 8% of patients in both groups. All patients underwent surgery. Initial surgery was total thyroidectomy in 46% of patients and subtotal thyroidectomy in 54% of patients in the PTC group compared with 40% of patients and 60% of patients, respectively, in the FVPTC group.
Table 1. Clinical and Pathologic Characteristics of Patients with Papillary Thyroid Carcinoma
No. of patients (%)
AJCC: American Joint Committee on Cancer.
No. of patients
Age at diagnosis (yrs)
Tumor size (cm)
Capsular tumor invasion
Lymph node metastases at diagnosis
Type of surgery
One hundred thirty-two patients (92%) in the PTC group and 94 patients (94%) in the FVPTC group were treated with 30–100 mCi I131 (median dose, 54 mCi) for ablation of postoperative remnant thyroid tissue. The therapeutic I131 dose administered for the treatment of distant metastases was 150–200 mCi. All patients received continuous replacement therapy with thyroxine. Twenty-one patients (10 patients with PTC and 11 patients with FVPTC) also received external irradiation with 5000 centigrays to the lower area of the neck and the upper mediastinum because of tumor extension to surrounding tissues or organs.
At a median follow-up of 138 months (range, 48–288 months), patient age < 40 years at the time of diagnosis was the strongest prognostic factor for survival in both groups. The 21-year actuarial survival rate was 100% in patients age < 40 years, 95% in patients age 40–50 years, and 51% in patients age > 50 years (P = 0.001) in the PTC group (Fig. 1). In the FVPTC group, the 21-year actuarial survival rate was 97% in patients age < 40 years, 88% in patients age 40–50 years, and 71% in patients age > 50 years (P < 0.01) (Fig. 2). The actuarial 21-year survival for all 143 patients in the PTC group 82% compared with 86% (100 patients) in the FVPTC group (P value NS) (Fig. 3). The actuarial 21-year survival rate for all patients was 83%. The survival of patients who underwent total thyroidectomy, compared with patients who underwent subtotal thyroidectomy, was similar in both groups. Gender was not found to influence survival significantly when it was corrected for age at diagnosis.
PTC is the most common form of thyroid malignancy (80%).9 The major subtype of papillary carcinoma is FVPTC.6 Tielens et al. reported that 13% of papillary carcinomas were FVPTC, whereas others reported that > 50% were FVPTC.10 In the current study, 41% of patients with papillary carcinoma had FVPTC, and 59% had PTC.
To our knowledge, few studies in the literature have compared clinical parameters, treatment outcome, and survival in patients with FVPTC and patients with PTC. Our study showed that the 21-year overall survival of the 2 groups was comparable: 86% in the FVPTC group compared with 82% in the PTC group. These results are similar to the results published by Mazzeferri and Jhiang11 and others in the literature,12 although the survival reported by those authors did not separate patients with FVPTC from patients with PTC.
The most important prognostic factor affecting survival in patients with well-differentiated thyroid carcinoma is age.13, 14 The current results were similar to the results from most previous multivariate studies showing that increasing patient age at the time of initial diagnosis has an independent and unfavorable influence on survival.15 Patients age > 40 years and, in other studies, patients age 45–50 years have a higher rate of recurrence and lower survival rate compared with younger patients.11, 16 Figures 1 and 2 show better survival in patients age < 40 years compared with patients age 40–50 years in both the PTC group and the FVPTC group (P value NS) and a significantly longer survival compared with patients age > 50 years (P ≤ 0.001 and P ≤ 0.01, respectively). In the current study, it appears that the 21-year overall survival rate for women age > 50 years was higher in the FVPTC group compared with the PTC group (71% vs. 51%), although the survival of the two groups together (all patients and all ages) was similar.
Tielens et al. reported that FVPTC tumors tend to be smaller compared with PTC tumors and are more likely to be encapsulated.5 In the current study, tumor size was comparable in both groups (Table 1). There was no difference in multifocality and stage of tumors between the two groups. More capsular invasion was found in the FVTCP group (38% vs. 31%; P value NS).
In the current study, cervical lymph node metastases were less common in the FVPTC group compared with the PTC group (22% vs. 32%; P value NS). Most distant metastases were in the lungs; and, compared with some previous studies, there was no evidence that pulmonary or other distant spread of disease occurred more frequently in patients who had FVPTC compared with patients who had PTC.17
The optimal extent of surgery is debated, perhaps because of the confounding effect of medical therapy.11 However, there were similar percentages of patients who underwent total thyroidectomy and patients who underwent subtotal thyroidectomy in both groups, and no difference was found in survival between the total thyroidectomy group and the subtotal thyroidectomy group. Ninety-two percent of patients with PTC and 94% of patients with FVPTC were treated with I131 for ablation of remnant thyroid tissue (cumulative dose, 52 mCi). Ablation was successful after a single I131 dose in 91% of patients with PTC and in 92% of patients with FVPTC. Others demonstrated that successful ablation of the thyroid tissue occurred in 80% of patients after an I131 dose ranging from 30 mCi to 200 mCi.5, 18, 19
In conclusion, FVPTC is a common subtype of papillary carcinoma. Patients with FVPTC and patients with PTC showed similar clinical characteristics and prognostic factors. Survival was comparable in both groups. The same treatment strategy is required for patients with FVPTC and patients with PTC.