Lerner et al.
Pediatr Blood Cancer 2015;62:1942–1946
Follicular Variant Papillary Thyroid Carcinoma in a Pediatric Population Jonathan Lerner, MD,1 and Melanie Goldfarb, MD, MS, FACS, FACE2* Background. Follicular variant of papillary thyroid carcinoma (FVPTC) has been shown to be an intermediate entity between papillary (PTC) and follicular/Hurtle cell (FTC) thyroid carcinoma in adults. However, the tumor characteristics and prognosis of FVPTCs has not been studied in the pediatric population and is the focus of the current study Methods. All pediatric patients 19 years of age with differentiated thyroid cancer (PTC, FVPTC, or FTC) were identified from the SEER registry from 1988–2009. Patients were divided into groups based on their histology. Adjusted odds ratios (ORs) for demographic, tumor, and treatment characteristics, as well as hazard ratios (HRs) for overall (OS) and disease-specific survival (DSS) were calculated for FVPTC. Results. Of 1,956 patients, 445 (22.7%) had FVPTC. Compared to PTCs, FVPTCs were larger (OR: 2.03, CI:1.35– 3.06), node negative (OR: 2.26, CI:1.61–3.19), occurred more often
in patients 4 cm (HR: 13.92, CI:1.24–156.72) influenced OS for patients with FVPTC. There was no significant difference in OS or DSS between groups. Conclusions. In pediatric patients 19 years of age, FVPTCs have intermediate tumor features compared to PTC and FTC, but a similar OS and DSS. All pediatric patients with thyroid cancer require lifelong surveillance. However, FVPTCs >4 cm may warrant closer follow-up due to an increased risk of death. Pediatr Blood Cancer 2015;62:1942–1946. © 2015 Wiley Periodicals, Inc.
Key words: differentiated thyroid cancer; follicular variant; pediatric; SEER; survival
INTRODUCTION Thyroid cancer is one of the most rapidly rising malignancies in the United States, having nearly doubled in incidence from 1997 to 2007; this trend is observed in both children and adults.[1–3] Differentiated thyroid carcinomas (DTC) make up the vast majority of diagnosed malignancies and are classified by their histologic features.[4–6] The main histologic subtypes of DTC are papillary (PTC) and follicular/Hurtle cell carcinoma (FTC). However, research has shown that PTC is not a homogenous group, with only about 50% of tumors classified as PTC belonging to the “classical” type.[5,6] The follicular variant of papillary thyroid carcinoma (FVPTC) is the most commonly “non-classical” PTC diagnosed, compromising up to 22.5% of all PTCs, and as with other forms of DTC, is being diagnosed at an increasing rate. [1,2,6,7] Prior research has shown that pediatric DTC is a unique clinical entity from adult DTC, both in its presentation and behavior. Compared to adults, in patients younger than 18 years, diagnosis is typically made at a more advanced stage, with local extension in 20–60% of patients, cervical node involvement in 40–80%, and lung metastases in 20% of cases.[8–10] Moreover, children have more frequent local recurrences and later development of distant metastases. These differences are even more pronounced in pre-pubertal children as opposed to older adolescents.[11] However, despite the more aggressive presentation of pediatric DTCs, the overall survival of these patients remains excellent at >95%.[12,13] Despite the increasing prevalence of FVPTC, its status as a unique clinical entity with well-defined treatment protocols is controversial. As FVPTC displays histologic characteristics of both PTC and FTC, some believe that it possesses traits from both types of DTC and is, therefore, more aggressive than PTC.[14,15] A recent large study in adults suggested that FVPTC is an intermediate clinical entity between PTC and FTC and should be treated accordingly.[16] However, the tumor characteristics and prognosis of FVPTC have never been studied in a pediatric population. C 2015 Wiley Periodicals, Inc. DOI 10.1002/pbc.25623 Published online 1 July 2015 in Wiley Online Library (wileyonlinelibrary.com).
MATERIALS AND METHODS Data Source and Cohort Selection Data for this study were obtained from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database, which has been extensively described elsewhere.[17,18] The 18 SEER registries currently cover approximately 28% of the total US population and include the states of Connecticut, Hawaii, Iowa, New Mexico, Kentucky, Louisiana, New Jersey, and Utah; the metropolitan areas of Atlanta, Detroit, and San Francisco-Oakland; Los Angeles County, the four-county area of San Jose-Monterey, and greater California; the 13-county area of Seattle-Puget Sound; rural as well as greater Georgia; and the Alaska Native tumor registry.[19] The populations in these areas are generally representative of the US population as a whole, although they are somewhat more urban and racially diverse. Cases of pathologically confirmed PTC, FVPTC, and FTC diagnosed between 1988 and 2009 in patients 19 years of age were
PTC, papillary thyroid cancer; FTC, follicular thyroid cancer; FVPTC, follicular variant of papillary thyroid cancer; OS, overall survival; DSS, disease specific survival; OR / HR, odds ratio / Hazard ratio; RAI, radioiodine; TTx, total thyroidectomy; LN, Lymph nodes 1
School of Medicine, University of Southern California Keck, Los Angeles, California; 2John Wayne Cancer Institute/Providence St. John’s Medical Center, Santa Monica, California Conflict of interest: Nothing to declare. Presented at American College of Surgeons Clinical Congress, San Francisco, CA, October 2011. Correspondence to: Melanie Goldfarb, Assistant Professor of Surgery, Endocrine Surgery, John Wayne Cancer Institute/Providence, St. John’s Medical Center, 2200 Santa Monica Blvd, Santa Monica, CA 90404. E-mail: [email protected]
Received 10 March 2015; Accepted 14 May 2015
Follicular Variant Papillary Thyroid Carcinoma
1943
TABLE I. Characteristics of Study Population
Demographics Gender Male Female Year of diagnosis 1988–1999 2000–2009 Age at diagnosis 0–14 years old 15–19 years old Ethnicity Black White Other DTC is secondary malignancy SEER region Midwest Northeast South West Treatment Surgery Partial thyroidectomy Total thyroidectomy No Surgery Unknown surgical status Radioactive iodine Lymph nodes removed No Yes Unknown Tumor features Tumor size (mean) >4 cm Distant metastases Positive lymph nodes Unknown nodal status Multifocal Extrathyroidal extension SEER summary stage Localized Regional Distant
PTC
FVPTC
FTC
232 (17.5%) 1,092 (82.5%)
86 (19.3%) 359 (80.7%)
28 (15.0%) 159 (85.0%)
338 (25.5%) 986 (74.5%)
123 (27.6%) 322 (72.4%)
57 (30.5%) 130 (69.5%)
305 (23.0%) 1,019 (77.0%)
129 (29.0%) 316 (71.0%)
48 (25.7%) 139 (74.3%)
P-value 0.408
0.292 0.039a
Pediatr Blood Cancer 2015;62:1942–1946
Follicular Variant Papillary Thyroid Carcinoma in a Pediatric Population Jonathan Lerner, MD,1 and Melanie Goldfarb, MD, MS, FACS, FACE2* Background. Follicular variant of papillary thyroid carcinoma (FVPTC) has been shown to be an intermediate entity between papillary (PTC) and follicular/Hurtle cell (FTC) thyroid carcinoma in adults. However, the tumor characteristics and prognosis of FVPTCs has not been studied in the pediatric population and is the focus of the current study Methods. All pediatric patients 19 years of age with differentiated thyroid cancer (PTC, FVPTC, or FTC) were identified from the SEER registry from 1988–2009. Patients were divided into groups based on their histology. Adjusted odds ratios (ORs) for demographic, tumor, and treatment characteristics, as well as hazard ratios (HRs) for overall (OS) and disease-specific survival (DSS) were calculated for FVPTC. Results. Of 1,956 patients, 445 (22.7%) had FVPTC. Compared to PTCs, FVPTCs were larger (OR: 2.03, CI:1.35– 3.06), node negative (OR: 2.26, CI:1.61–3.19), occurred more often
in patients 4 cm (HR: 13.92, CI:1.24–156.72) influenced OS for patients with FVPTC. There was no significant difference in OS or DSS between groups. Conclusions. In pediatric patients 19 years of age, FVPTCs have intermediate tumor features compared to PTC and FTC, but a similar OS and DSS. All pediatric patients with thyroid cancer require lifelong surveillance. However, FVPTCs >4 cm may warrant closer follow-up due to an increased risk of death. Pediatr Blood Cancer 2015;62:1942–1946. © 2015 Wiley Periodicals, Inc.
Key words: differentiated thyroid cancer; follicular variant; pediatric; SEER; survival
INTRODUCTION Thyroid cancer is one of the most rapidly rising malignancies in the United States, having nearly doubled in incidence from 1997 to 2007; this trend is observed in both children and adults.[1–3] Differentiated thyroid carcinomas (DTC) make up the vast majority of diagnosed malignancies and are classified by their histologic features.[4–6] The main histologic subtypes of DTC are papillary (PTC) and follicular/Hurtle cell carcinoma (FTC). However, research has shown that PTC is not a homogenous group, with only about 50% of tumors classified as PTC belonging to the “classical” type.[5,6] The follicular variant of papillary thyroid carcinoma (FVPTC) is the most commonly “non-classical” PTC diagnosed, compromising up to 22.5% of all PTCs, and as with other forms of DTC, is being diagnosed at an increasing rate. [1,2,6,7] Prior research has shown that pediatric DTC is a unique clinical entity from adult DTC, both in its presentation and behavior. Compared to adults, in patients younger than 18 years, diagnosis is typically made at a more advanced stage, with local extension in 20–60% of patients, cervical node involvement in 40–80%, and lung metastases in 20% of cases.[8–10] Moreover, children have more frequent local recurrences and later development of distant metastases. These differences are even more pronounced in pre-pubertal children as opposed to older adolescents.[11] However, despite the more aggressive presentation of pediatric DTCs, the overall survival of these patients remains excellent at >95%.[12,13] Despite the increasing prevalence of FVPTC, its status as a unique clinical entity with well-defined treatment protocols is controversial. As FVPTC displays histologic characteristics of both PTC and FTC, some believe that it possesses traits from both types of DTC and is, therefore, more aggressive than PTC.[14,15] A recent large study in adults suggested that FVPTC is an intermediate clinical entity between PTC and FTC and should be treated accordingly.[16] However, the tumor characteristics and prognosis of FVPTC have never been studied in a pediatric population. C 2015 Wiley Periodicals, Inc. DOI 10.1002/pbc.25623 Published online 1 July 2015 in Wiley Online Library (wileyonlinelibrary.com).
MATERIALS AND METHODS Data Source and Cohort Selection Data for this study were obtained from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database, which has been extensively described elsewhere.[17,18] The 18 SEER registries currently cover approximately 28% of the total US population and include the states of Connecticut, Hawaii, Iowa, New Mexico, Kentucky, Louisiana, New Jersey, and Utah; the metropolitan areas of Atlanta, Detroit, and San Francisco-Oakland; Los Angeles County, the four-county area of San Jose-Monterey, and greater California; the 13-county area of Seattle-Puget Sound; rural as well as greater Georgia; and the Alaska Native tumor registry.[19] The populations in these areas are generally representative of the US population as a whole, although they are somewhat more urban and racially diverse. Cases of pathologically confirmed PTC, FVPTC, and FTC diagnosed between 1988 and 2009 in patients 19 years of age were
PTC, papillary thyroid cancer; FTC, follicular thyroid cancer; FVPTC, follicular variant of papillary thyroid cancer; OS, overall survival; DSS, disease specific survival; OR / HR, odds ratio / Hazard ratio; RAI, radioiodine; TTx, total thyroidectomy; LN, Lymph nodes 1
School of Medicine, University of Southern California Keck, Los Angeles, California; 2John Wayne Cancer Institute/Providence St. John’s Medical Center, Santa Monica, California Conflict of interest: Nothing to declare. Presented at American College of Surgeons Clinical Congress, San Francisco, CA, October 2011. Correspondence to: Melanie Goldfarb, Assistant Professor of Surgery, Endocrine Surgery, John Wayne Cancer Institute/Providence, St. John’s Medical Center, 2200 Santa Monica Blvd, Santa Monica, CA 90404. E-mail: [email protected]
Received 10 March 2015; Accepted 14 May 2015
Follicular Variant Papillary Thyroid Carcinoma
1943
TABLE I. Characteristics of Study Population
Demographics Gender Male Female Year of diagnosis 1988–1999 2000–2009 Age at diagnosis 0–14 years old 15–19 years old Ethnicity Black White Other DTC is secondary malignancy SEER region Midwest Northeast South West Treatment Surgery Partial thyroidectomy Total thyroidectomy No Surgery Unknown surgical status Radioactive iodine Lymph nodes removed No Yes Unknown Tumor features Tumor size (mean) >4 cm Distant metastases Positive lymph nodes Unknown nodal status Multifocal Extrathyroidal extension SEER summary stage Localized Regional Distant
PTC
FVPTC
FTC
232 (17.5%) 1,092 (82.5%)
86 (19.3%) 359 (80.7%)
28 (15.0%) 159 (85.0%)
338 (25.5%) 986 (74.5%)
123 (27.6%) 322 (72.4%)
57 (30.5%) 130 (69.5%)
305 (23.0%) 1,019 (77.0%)
129 (29.0%) 316 (71.0%)
48 (25.7%) 139 (74.3%)
P-value 0.408
0.292 0.039a
