Annals of Surgical Oncology Cite Track
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Stojadinovic, A.
Right arrow Articles by Shaha, A. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Stojadinovic, A.
Right arrow Articles by Shaha, A. R.
Related Collections
Right arrow Other Endocrine
Annals of Surgical Oncology 9:197-203 (2002)
© 2002 Society of Surgical Oncology

ORIGINAL ARTICLES

Hürthle Cell Carcinoma: A 60-Year Experience

Alexander Stojadinovic, MD, Axel Hoos, MD, PhD, Ronald A. Ghossein, MD, Marshall J. Urist, Denis H. Y. Leung, PhD, Ronald H. Spiro, MD, Jatin P. Shah, MD, Murray F. Brennan, MD, Bhuvanesh Singh, MD and Ashok R. Shaha, MD

From the Departments of Surgery (AS, AH, MJU, RHS, JPS, MFB, BS, ARS), Pathology (RAG), and Biostatistics (DHYL), Memorial Sloan-Kettering Cancer Center, New York, New York.

Correspondence: Address correspondence and reprint requests to: Ashok R. Shaha, MD, Professor of Surgery, Head and Neck Service, Memorial Sloan-Kettering Cancer Center, 1275 York Ave., New York, NY 10021; Fax: 212-717-3302; E-mail: shahaa{at}mskcc.org


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
Background: The aim of this study was to define the clinical behavior and prognostic indicators of outcome in Hürthle cell cancer (HCC).

Methods: Diagnosis was confirmed for 56 patients with HCC treated between 1940 and 2000, who form the basis of this study. Primary end points were relapse-free survival (RFS) and disease-specific survival (DSS). Data were analyzed with the Kaplan-Meier method and by log-rank test.

Results: The extent of thyroid resection did not predict outcome. Recurrence was a significant predictor of tumor-related mortality. Significant adverse predictors of RFS and DSS were degree of invasion, size >4 cm, extrathyroidal extension, and initial nodal or distant metastases. The most significant predictor of outcome was extent of invasion. Eight-year RFS values for low- and high-risk groups were 100% and 24%. Corresponding rates of 8-year DSS were 100% and 58%.

Conclusions: Widely invasive HCC is an aggressive malignancy that identifies patients who are at high risk for recurrence and tumor-related death. Patients with HCC have a prognosis that is reliably predicted by degree of invasion, tumor size, extrathyroidal disease extension, and initial nodal or distant metastasis. Recurrence portends a poor outcome. High-risk patients and those with recurrence should be considered for adjuvant therapy.

Key Words: Hürthle cell • Thyroid cancer • Disease recurrence • Survival


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
The natural history of well-differentiated thyroid carcinoma has been studied extensively in recent decades. As a result, clinical and pathologic factors predictive of outcome have been well defined. Reliable prognostic scoring systems have been based on these variables. Prognostic factors (associated with increased mortality) in well-differentiated thyroid cancer include advanced age (>45 years), large (>4 cm) primary tumor size, follicular histology, high tumor grade, extrathyroidal extension, and distant metastases.1–4

The definition and natural history of Hürthle cell carcinoma (HCC) is not well understood. This is largely attributable to the rarity of disease, because these lesions represent <5% of all differentiated thyroid malignancies. Minimally invasive HCCs have essentially a benign clinical course, whereas the widely invasive form is a highly aggressive malignancy. This tumor heterogeneity has complicated characterization of prognostic variables. The biological behavior of HCC remains undefined because some investigators have considered these malignancies to be variants of follicular cancer and have included them in analyses of outcome predictors for follicular carcinomas.4–6

The aim of this study was to define the clinical behavior and prognostic indicators of outcome in a well-characterized cohort of patients with HCC. This analysis has enabled us to identify patients at low and high risk for recurrence and tumor-related mortality. We have found that outcome is reliably predicted by these well-defined prognostic factors.


   PATIENTS AND METHODS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 
A retrospective review was conducted of all available clinical, pathologic, treatment, and outcome information for 161 patients treated for HCC and observed at Memorial Sloan-Kettering Cancer Center over 60 years, from 1940 to 2000. Histopathologic slides were available for 102 patients. Only lesions demonstrating >75% follicular cells with oncocytic characteristics were included in the study group.7 Hürthle cell adenomas and nonencapsulated nodular aggregates of Hürthle cells were not included in this analysis. Tumors were characterized as Hürthle cell tumor of unknown malignant behavior (UMB), minimally invasive HCC, and widely invasive HCC according to our previously defined diagnostic criteria.8 Tumors with a solid or trabecular growth pattern that did not demonstrate vascular invasion, but did have partial thickness capsular involvement, were categorized as UMB. Tumors with a single focus of vascular invasion, a single focus of complete capsular invasion, or both were classified as minimally invasive HCC. Those tumors with more than one focus of intra- or extracapsular vascular invasion, more than one focus of complete capsular invasion, or both were classified as widely invasive HCC.

Comprehensive review of all available hematoxylin and eosin slides confirmed the diagnosis of UMB (n = 17), minimally invasive HCC (n = 23), and widely invasive HCC (n = 33) in 73 patients. Patients without available slides for review were excluded. Contrary to previous concerns raised by other investigators over the malignant potential of tumors defined as UMB, we demonstrated in an earlier study that these neoplasms have a benign natural history.8 As such, these tumors were excluded from this analysis. Thus, this clinical study is based on 56 patients with complete clinical data and histologically confirmed HCC.

The primary mode of treatment was surgical. Some patients received adjuvant radioiodine treatment or external beam radiotherapy for widely invasive carcinomas or locally advanced disease. Surgical treatment ranged from lobectomy and isthmusectomy to total thyroidectomy, with cervical lymphadenectomy in the presence of grossly pathologic lymph nodes.

Study end points were relapse-free survival (RFS) and disease-specific survival (DSS). The following clinical, pathologic, and treatment-related factors were correlated with study end points: (1) clinical factors: patient age at diagnosis (<=45 or >45 years) and sex; (2) pathologic factors: tumor size (<=4 cm or >4 cm), degree of invasion (minimally or widely invasive), focality (unifocal or multifocal), extrathyroidal extension (absent or present), initial regional nodal involvement (absent or present), and distant metastases at presentation; and (3) treatment-related factors: extent of thyroid resection (total or less than total thyroidectomy).

Associations between categorical variables were evaluated with Fisher’s exact test or {chi}2 tests where appropriate. Time to first disease relapse and disease-related mortality were calculated from the date of primary surgery. Only death as a result of HCC was considered as an end point in DSS calculations. All other deaths were censored in DSS analyses. RFS was calculated from the time of surgery to any disease recurrence. The rate of recurrence or death was estimated with the Kaplan-Meier method. Univariate influence of prognostic factors on study end points was analyzed with the log-rank test. Statistical analysis was performed with JMP software (JMP, Cary, NC). A P value <=.05 was considered significant.

The patient cohort consisted of 34 (60.7%) female and 22 (39.3%) male patients. The median age for the study population was 56 years (range, 9–94 years). The median follow-up for this patient cohort was 8 years.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
DISCUSSION
 CONCLUSION
 REFERENCES
 
The clinical variables of the study population consisting of HCC are listed in Table 1. Of the 44 patients with information about prior head and neck irradiation, 8 (14.3%) had exposure to ionizing radiation before presentation with HCC. There was no significant difference in RFS (P = .10) or DSS (P = .11) between those who were and were not exposed to prior head and neck irradiation.


View this table:
[in this window]
[in a new window]
  		TABLE 1. Patient, tumor, and treatment characteristics of Hürthle cell carcinoma (n = 56)
 
The distribution of prognostic factors according to type of tumor is listed in Table 2. There were 23 (41%) minimally invasive and 33 (59%) widely invasive carcinomas. The median age at presentation (51 vs. 61 years) was not statistically different between the two groups. The median tumor size for widely invasive HCC was significantly greater than that observed for minimally invasive HCC (4.5 vs. 3.0 cm; P = .03). Seventy-eight percent of minimally invasive and 25% of widely invasive cancers were <=4 cm in size (P <.001).


View this table:
[in this window]
[in a new window]
  		TABLE 2. Distribution of prognostic factors according to type of tumor: minimally invasive (Mi) versus widely invasive (Wi) Hürthle cell carcinomaa
 
The most common clinical presentation was that of a localized primary tumor, >1 to 4 cm in size (International Union Against Cancer/American Joint Committee on Cancer stage T2N0M0, 23 of 56 [41%]). T1 tumors were relatively rare (2 of 56; 4%). It is interesting to note that one patient presented with a 1-cm primary, widely invasive HCC—demonstrating both major capsular and vascular invasion—and synchronous lung metastases (T1N0M1).

There were five (9%) patients who had multifocal HCC, all with the widely invasive variant. RFS (P = .13) and DSS (P = .19) were not significantly different between patients with unifocal or multifocal disease. Twelve (21%) patients had synchronous microscopic foci of papillary thyroid carcinoma, six each with minimally invasive and widely invasive HCC. There was no significant difference in outcome between patients with and without synchronous papillary cancers (P = .17).

By definition, no patient with minimally invasive HCC had evidence of extrathyroidal disease extension, whereas tumor extended beyond the thyroid capsule in 19 (58%) of 33 widely invasive HCCs. When compared with patients with widely invasive HCC but without extracapsular invasion, extrathyroidal extension of disease was associated with significantly worse RFS (8-year RFS, 6% vs. 56%; P = .002) and DSS (8-year DSS, 33% vs. 94%; P = .01).

Initial regional nodal metastases were evident in seven (13%) patients. All seven of these patients had widely invasive HCC extending beyond the thyroid capsule. Each of these patients with initial nodal metastases developed subsequent disease recurrence, and 6 (86%) died of disease. When compared with patients with widely invasive HCC but no nodal disease at presentation, lymph node metastasis was associated with significantly higher rates of recurrence (8-year RFS, 0% vs. 34%; P = .002) and tumor-related mortality (8-year DSS, 0% vs. 79%; P < .001).

No patient with minimally invasive HCC developed distant metastases. Five patients with widely invasive cancers had distant metastasis evident at initial presentation. Patients with widely invasive HCC and synchronous distant metastatic disease had worse DSS than those with no systemic disease at the time of initial diagnosis (8-year DSS, 30% vs. 63%; P = .05). The median survival for those with systemic disease at initial diagnosis was 2.0 years, as opposed to 7.9 years for those patients with widely invasive HCC but without initial distant metastases.

Total thyroidectomy was performed in 22% (5 of 23) of patients with minimally invasive HCC and 36% (12 of 33) of those with widely invasive HCC (P = .24). Patients treated with less than total thyroidectomy were compared with those undergoing total thyroidectomy on the basis of age, tumor size, extrathyroidal disease extension, and degree of invasion. There was no significant difference in the proportion of these clinicopathologic variables among the two treatment groups. There was no significant difference in local control (P = .96) or survival (P = .71) between patients treated with total or less than total thyroidectomy for localized primary disease. For those with widely invasive HCC, the extent of resection did not alter the rate of recurrence (P = .48) or tumor-related mortality (P = .45).

No patient with minimally invasive HCC developed recurrence or died of disease. Recurrences and deaths were confined to patients with widely invasive carcinomas. Of the patients in the widely invasive group, 73% (24 of 33) developed recurrent disease, and 55% (18 of 33) experienced tumor-related mortality (P < .001 vs. minimally invasive HCC). Median RFS and DSS for the subset of patients with widely invasive HCC were 28 and 86 months, respectively.

Four patients with widely invasive HCC had local recurrence and underwent complete resection; two are alive free of disease, and two developed subsequent distant metastases; one of these patients died of disease. Five other patients developed synchronous local and regional nodal recurrence after a disease-free interval of 7 to 33 months. One of these five patients had unresectable recurrence, and four underwent complete resection. All five of these patients with synchronous locoregional recurrence after the primary operation had progression of HCC and died of disease 26 to 80 months after first relapse (Fig. 1).



View larger version (23K):
[in this window]
[in a new window]
  		FIG. 1. Initial disease recurrence in patients (n = 33) with widely invasive Hürthle cell cancer (HCC). Five patients had synchronous local and regional metastases as the initial pattern of disease failure. Three patients with distant metastasis had synchronous locoregional recurrence. No patient with regional nodal or distant disease recurrence could be cured because all had disease progression, and the majority (16 of 20; 80%) died of disease. Of 24 patients who relapsed, 2 had salvage treatment and are alive free of disease after resection of isolated locally recurrent HCC.

 
Fifteen patients with widely invasive HCC developed distant metastases as a first disease relapse, three of whom had synchronous locoregional recurrence. A total of 20 patients developed distant metastasis during the course of their disease. The most frequent sites of metastases were lung (18 of 20; 90%) and bone (7 of 20; 35%). Three patients had synchronous lung and bone metastases, two had synchronous lung and liver metastases, and one had lung, liver, and colon metastases. Complete resection of all clinically apparent recurrent disease could be achieved in 5 of these 20 patients. All patients with distant metastasis developed disease progression; three are alive with advanced disease, and the remainder died. Time to death from diagnosis of distant metastases in four of the five patients with resectable disease was 33, 65, 189, and 392 months. For those with unresectable systemic disease, time from diagnosis to death ranged from 1 to 111 months.

Recurrence of disease was a significant predictor of tumor-related mortality (8-year DSS, 49%; P < .001). Seventy-five percent (18 of 24) of patients with recurrent HCC had died of disease at last follow-up. No patient with regional nodal or distant disease recurrence could be cured because all have had disease progression, and the majority (16 of 20; 80%) died of disease. Of 24 patients who relapsed, 2 had salvage treatment and were alive free of disease 94 and 262 months after resection of isolated locally recurrent HCC.

Univariate comparisons were made between categorical variables for the end points, RFS and DSS, for the entire study cohort (n = 56). Factors predicting outcome included widely invasive HCC, primary tumor size >4 cm, extrathyroidal extension of disease, and initial regional nodal and distant metastasis. The 8-year RFS and DSS are listed in Table 3. Widely invasive HCC was the single most powerful predictor of disease-related mortality.


View this table:
[in this window]
[in a new window]
  		TABLE 3. Relapse-free survival (RFS) and disease-specific survival (DSS) for Hürthle cell cancer (n = 56)
 
The patients were stratified according to degree of invasion into low- and high-risk groups. The low-risk group consisted of minimally invasive carcinomas. The single most important stratifier was the extent of invasion, because only widely invasive HCC demonstrated extrathyroidal extension and initial nodal or distant metastasis. The high-risk group was composed of patients with widely invasive HCC with or without size >4 cm, extrathyroidal extension, or initial nodal or distant metastasis (Table 4). Among widely invasive HCC, extracapsular extension and initial nodal or distant metastases were combined in the univariate analysis, and a significant difference in outcome was identified between those patients with extracapsular extension only and patients with both extension and initial nodal or distant metastasis. Widely invasive HCC with both extrathyroidal extension of disease and nodal or distant metastasis at initial presentation had the worst prognosis; 8-year RFS and DSS were both 0% for this group. Corresponding rates of RFS and DSS for widely invasive HCC and extrathyroidal extension only were 23% and 60%, respectively (P < .01). Outcome was well stratified on the basis of risk group because no patient in the low-risk group had a recurrence or died of disease, whereas 73% and 55% of high-risk patients relapsed and died, respectively (Table 4). High-risk HCC was associated with significantly higher tumor-specific mortality than low-risk cancers (Fig. 2). Eight year DSS was 100% and 58% (P < .001) for low- and high-risk HCC, respectively.


View this table:
[in this window]
[in a new window]
  		TABLE 4. Relapse and disease-specific mortality correlated with risk group categories
 


View larger version (12K):
[in this window]
[in a new window]
  		FIG. 2. Kaplan-Meier disease-specific survival among patients with low- and high-risk Hürthle cell carcinoma of the thyroid (n = 56). Eight-year survival for low- and high-risk groups was 100% and 58%, respectively (P < .001).

 

   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
CONCLUSION
 REFERENCES
 
This study was conducted on a well-characterized patient cohort with histologically confirmed HCC that was treated and observed at a single institution. Extent of invasion, tumor size, extrathyroidal extension, and initial nodal or distant metastases were predictors of RFS and DSS. Prognosis for HCC was reliably predicted by these prognostic factors, because 8-year survival rates were 100% and 58% for low- and high-risk cancers, respectively. The most significant stratifier for outcome among the entire study cohort was extent of invasion, namely, widely invasive carcinoma.

Risk group stratification for well-differentiated thyroid carcinoma according to prognostic factors is well established.1–4 The natural history of HCC has been incompletely defined, given the rarity of this type of thyroid malignancy. A previous analysis of patients with follicular carcinoma treated at our institution included 59 HCCs characterized as follicular variants in accordance with the World Health Organization classification.4 That study identified that the Hürthle cell variant was an independent outcome predictor on multivariate analysis. HCC is now considered a distinct pathologic entity.9

Prognostic criteria for HCC have been defined on the basis of analysis of small patient cohorts. The Lahey Clinical experience with 44 HCCs demonstrated that the previously defined AMES (age, distant metastases, extrathyroidal extension, tumor size) criteria predicted outcome with this tumor type.10 Their low-risk patients were defined as all women <51 years old and all men <41 years old without distant metastasis and all older patients with tumors <5 cm in size and no extrathyroidal extension, if papillary carcinoma, and no major capsular invasion, if follicular carcinoma. Ten-year survivals in that study for patients with low- and high-risk HCC were 95% and 50%, respectively.

In this study, age was not found to predict outcome. Our risk group definitions were based on those variables that were found to be significant predictors of RFS and DSS. Adverse prognostic variables for survival included tumors of widely invasive HCC with or without tumor size >4 cm, extrathyroidal extension of disease, and nodal or distant metastases at initial diagnosis. No patient with a low-risk tumor had a recurrence or died of disease. Despite the lack of significant prognostic influence of age, the 10-year survival on the basis of risk group for this study (low risk, 100%, vs. high risk, 48%) cohort is strikingly similar to that reported by the Lahey Clinic.

Other investigators have reported that size is predictive of malignancy for Hürthle cell neoplasms.11,12 In the report of Carcangiu et al.13 report of 153 Hürthle cell tumors (90 benign, 35 indeterminate, and 28 carcinoma), no patient with carcinoma had a primary tumor <1 cm in size, and most (75%) were >5 cm in diameter. In a study of 57 patients with Hürthle cell neoplasms (37 adenoma and 20 carcinoma) at the Johns Hopkins Hospital, primary tumor size was found to be predictive of malignancy.14 The likelihood of malignancy with tumors <=1, >1 to 4, and >=4 cm was 17%, 23%, and 65%, respectively, in that study; however, only 15% of carcinomas were <4 cm in size. In this study, two patients with widely invasive HCC had primary tumors <=1 cm, one of whom had synchronous distant metastases. Seventy-five percent of primary widely invasive HCCs in this cohort were >4 cm. These findings underscore the fact that small (<=1 cm) HCCs may, albeit rarely, demonstrate aggressive biological behavior.

In a previous study that correlated histopathologic findings with patient outcome, we found that the natural history of Hürthle cell tumors with minimal or incomplete capsular invasion, so-called UMB, is uniformly benign.8 Thus, these nonmalignant variants were excluded from this analysis. We have also excluded the ubiquitous Hürthle cell lesion as a benign tumor characterized by nonencapsulated aggregates of oncocytic cells. Our findings further underscore the benign behavior of cases in this study with only one focus of capsular or vascular invasion defined as minimally invasive HCCs. The lower median age and smaller tumor size in the minimally invasive group suggest that these tumors may be precursors of widely invasive HCC, but we are not aware of any data in the literature to support this hypothesis. During a follow-up period of 8 years, no patient with minimally invasive HCC had a recurrence or died of disease. Investigators at the Mayo and Lahey Clinics have similarly found that patients with minimally invasive follicular carcinomas and HCCs are not at risk for recurrence or death.5,10

Extent of thyroidectomy has been an area of controversy in the management of HCCs. Thompson et al.11 at the University of Michigan have advocated total thyroidectomy for all Hürthle cell neoplasms. This recommendation is based on an observed tumor-related mortality of 44% (11 of 25) in patients with Hürthle cell neoplasms, 3 of which were initially considered benign. These and other authors have argued that the lack of histopathologic criteria to predict biological behavior and the 15% to 35% incidence of multifocality support the role of total thyroidectomy in this disease.14,15

Contrary to these reports, our recent critical histopathologic appraisal of HCC demonstrates that morphology is a powerful predictor of clinical outcome.8 Tumors with a solid or trabecular growth pattern without complete capsular or any degree of vascular invasion (UMB) and those with a solid/trabecular or follicular growth pattern and a single focus of vascular invasion, capsular invasion, or both (minimally invasive HCC) did not exhibit aggressive behavior. Moreover, no patient with UMB or minimally invasive HCC was found to have multifocal disease, whereas 15% (5 of 33) of widely invasive carcinomas were multifocal. Given the benign natural history of Hürthle cell UMB and minimally invasive carcinomas, lobectomy alone is appropriate treatment.

Recurrence of HCC represents a formidable treatment challenge. Disease recurrence is associated with extremely poor outcome (8-year DSS, 49%). In this study, only 2 (8.3%) of 24 patients with recurrent HCC were cured of disease, and 75% had died of disease by the time of the last clinical follow-up. The two patients that were curable by reoperation had isolated local recurrence of disease. Thus, no patient with regional nodal or distant disease recurrence could be cured. For those whose disease recurred, the median time to first relapse was 20 months; however, there was considerable variation in the time to recurrence, from <1 year to >10 years, thereby underscoring the importance of lifelong follow-up in patients with HCC.

Because most HCCs do not concentrate radioiodine, ablative doses of radioactive iodine have not been effective in salvage treatment of patients with locoregional or distant disease recurrence. Although external beam radiotherapy is useful in the setting of unresectable disease, it is not curative. There are no chemotherapy agents that have proven efficacy with systemic HCC. Octreotide has been ineffective for the treatment of metastatic HCC.16 The significant risk of relapse with high-risk HCC (73%) and the lack of effective adjuvant local or systemic therapies provide an adequate basis for an aggressive initial surgical approach to widely invasive carcinomas. Thus, total thyroidectomy should be considered for HCCs demonstrating more than a single focus of complete capsular invasion, vascular invasion, or both (i.e., widely invasive HCC), with or without extracapsular extension or nodal/distant metastasis. If total thyroidectomy is performed for more aggressive forms of HCCs, one may consider iodine dosimetry and ablation with the hope that there may be some follicular component in which radioiodine may be beneficial.


   CONCLUSION
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
REFERENCES
 
Minimally invasive HCC defines a benign phenotype. Significant predictors of outcome of HCCs are the extent of invasion, size >4 cm, extrathyroidal extension, and initial nodal or distant metastasis. Patients with low-risk cancers did not experience recurrence or die of disease, whereas 73% of high-risk group patients relapsed and 55% died of disease. This risk group analysis supports an individualized treatment approach based on extent of invasion. Lobectomy alone is adequate therapy for low-risk patients. Total thyroidectomy is recommended for the high-risk patient to allow ease of follow-up and detection of recurrent disease. Adjuvant therapy options are limited, but it would seem prudent to consider external beam radiotherapy for locally advanced (widely invasive) cancers with or without nodal metastases. The role of radioiodine remains unclear. Current chemotherapy for advanced disease is poor, but it may be considered for the high-risk patient in the setting of a controlled clinical trial.

Received for publication February 6, 2001. Accepted for publication September 25, 2001.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 PATIENTS AND METHODS
 RESULTS
 DISCUSSION
 CONCLUSION
 REFERENCES
 

  1. Hay ID, Grant CS, Taylor WF, McConahey WM. Ipsilateral lobectomy versus bilateral lobar resection in papillary thyroid carcinoma: a retrospective analysis of surgical outcome using a novel prognostic scoring system. Surgery 1987; 102: 1088–95.[Medline]
  2. Cady B, Ross R. An expanded view of risk group definition in differentiated thyroid carcinoma. Surgery 1988; 104: 947–53.[Medline]
  3. Shah JP, Loree TR, Dharker D, et al. Prognostic factors in differentiated carcinoma of the thyroid gland. Am J Surg 1992; 164: 658–61.[Medline]
  4. Shaha AR, Loree TR, Shah JP. Prognostic factors and risk group analysis in follicular carcinoma of the thyroid. Surgery 1995; 118: 1131–8.[CrossRef][Medline]
  5. Van Heerdan JA, Hay ID, Goellner JR, et al. Follicular thyroid carcinoma with capsular invasion alone: a nonthreatening malignancy. Surgery 1992; 112: 1130–8.[Medline]
  6. Rao RS, Parikh HK, Desmane VH, et al. Prognostic factors in follicular carcinoma of the thyroid: a study of 198 cases. Head Neck 1996; 18: 118–26.[Medline]
  7. Rosai J, Caracangui M, DeLellis R. Tumors of the thyroid gland.In: Rosai J, Sobin L, eds. Atlas of Tumor Pathology. 3rd series: Fascicle. Washington, DC: Armed Forces Institute of Pathology, 1992: 337, 1192.
  8. Stojadinovic A, Ghossein RA, Hoos A, et al. Hürthle cell carcinoma: a critical histopathological appraisal. J Clin Oncol 2001; 19: 2616–25.[Abstract/Free Full Text]
  9. Masood S, Auguste LJ, Westerbank A, et al. Differential oncogenic expression in thyroid follicular and Hürthle cell carcinomas. Am J Surg 1993; 166: 366–8.[CrossRef][Medline]
  10. Sanders LE, Silverman M. Follicular and Hürthle cell carcinoma: predicting outcome and directing therapy. Surgery 1998; 124: 967–74.[Medline]
  11. Thompson NW, Dunn EL, Batsakis JG, Nishiyama RH. Hürthle cell lesions of the thyroid gland. Surg Gynecol Obstet 1974; 139: 555–60.[Medline]
  12. Chen H, Nicol TL, Zeiger MA, et al. Hürthle cell neoplasms of the thyroid: are there factors predictive of malignancy? Ann Surg 1998; 227: 524–6.
  13. Carcangiu ML, Bianchi S, Savino D, et al. Follicular Hürthle cell tumors of the thyroid gland. Cancer 1991; 68: 1944–53.[CrossRef][Medline]
  14. Rosen IB, Luk S, Katz I. Hürthle tumor behavior: dilemma and resolution. Surgery 1985; 98: 778–83.
  15. Grossman RF, Clark OH. Hürthle cell carcinoma. Cancer Control 1997; 4: 13–7.[Medline]
  16. Zlock DW, Greenspan FS, Clark OH, et al. Octreotide therapy in advanced thyroid cancer. Thyroid 1994; 4: 427–31.[Medline]



This article has been cited by other articles:


Home page
 JNMHome page
D. A. Pryma, H. Schoder, M. Gonen, R. J. Robbins, S. M. Larson, and H. W.D. Yeung
Diagnostic Accuracy and Prognostic Value of 18F-FDG PET in Hurthle Cell Thyroid Cancer Patients
J. Nucl. Med., August 1, 2006; 47(8): 1260 - 1266.
[Abstract] [Full Text] [PDF]

Home page
 Arch Otolaryngol Head Neck SurgHome page
E. L. Maxwell, C. E. Palme, and J. Freeman
Hurthle Cell Tumors: Applying Molecular Markers to Define a New Management Algorithm
Arch Otolaryngol Head Neck Surg, January 1, 2006; 132(1): 54 - 58.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Stojadinovic, A.
Right arrow Articles by Shaha, A. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Stojadinovic, A.
Right arrow Articles by Shaha, A. R.
Related Collections
Right arrow Other Endocrine

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS