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Hurthle cell carcinoma: a critical histopathologic appraisal.
J Clin Oncol. 2001 May 15;19(10):2616-25.
PURPOSE:
Controversy exists over the ability of morphology to predict the
biologic behavior of Hürthle cell carcinoma. The aim of this study was
to conduct a critical histopathologic review of Hürthle cell carcinoma
and to correlate morphologic parameters with clinical outcome.
PATIENTS AND METHODS: Patients with histologically confirmed Hürthle
cell carcinoma treated between 1940 and 2000 form the basis of this
study. Adenomas were excluded. Tumors of unknown malignant behavior ([UMB]
n = 17) had solid growth pattern, incomplete capsular invasion (Ci),
or both but no vascular invasion (Vi). Minimally invasive carcinomas
([MIC] n = 23) had one focus of intra- or extracapsular Vi, one focus
of complete Ci, or both. Widely invasive carcinomas ([WIC] n = 33)
demonstrated more than one focus of Vi, more than one focus of Ci, or
both. The primary end points were relapse-free survival (RFS) and
disease-specific survival (DSS). Rates of recurrence/death were
estimated by Kaplan-Meier method. The univariate influence of
prognostic factors on end points was analyzed by log-rank test, and
multivariate analysis was performed by Cox regression. RESULTS: Median
follow-up was 8 years. No patients with UMB or MIC relapsed or died of
disease. Of WIC, 73% relapsed and 55% died of disease. Age, size, and
extent of resection did not influence outcome. Adverse predictors of
RFS and DSS among WIC were extrathyroidal extension, nodal metastasis,
positive margin, and solid growth pattern (P <.05). Both Ci and Vi
were associated with worse DSS (P <.05). On multivariate analysis,
extrathyroidal extension and nodal metastases were independent
predictors of outcome (P <.05). CONCLUSION: Patients with Hürthle cell
carcinoma have a prognosis that is predicted by well-defined
histomorphologic characteristics. Unlike differentiated thyroid
cancer, nodal metastases predict a worse outcome in widely invasive
Hürthle cell carcinoma, as does extrathyroidal extension.
Hurthle cell carcinoma: a 60-year experience.Ann
Surg Oncol. 2002 Mar;9(2):197-203.
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.
Fine-needle
aspiration biopsy of Hurthle cell lesions of the thyroid gland: A
cytomorphologic study of 139 cases with statistical analysis.Cancer.
2006;108(2):102-9
BACKGROUND:
Lesions of the thyroid gland composed of Hurthle cells encompass
pathologic entities ranging from hyperplastic nodules with Hurthle
cell metaplasia to Hurthle cell carcinomas. The cytologic distinction
between these entities can be diagnostically challenging. Many
cytologic features of Hurthle cell lesions that distinguish neoplastic
Hurthle cell lesions requiring surgery from those that are benign and
nonneoplastic have been described, but with variable usefulness. This
is due, in part, to the small numbers of cases examined in previous
studies and the limited application of statistical analysis. A
morphologic study was made of 139 Hurthle cell lesions of the thyroid
gland and statistical analysis applied to identify a set of
cytomorphologic features that distinguish benign Hurthle cell lesions
(BHCL) from Hurthle cell neoplasms (HCN). METHODS: Fine-needle
aspiration biopsies (FNABs) of thyroid nodules with a predominant
Hurthle cell component and corresponding histologic followup were
included in the study. Cases were divided into BHCL and HCN groups on
the basis of the histologic diagnosis. All cases were reviewed to
assess the following 14 cytologic features: overall cellularity,
cytoarchitecture, percentage of Hurthle cells, percentage of single
cells, percentage of follicular cells observed as naked Hurthle cell
nuclei, background colloid, chronic inflammation, cystic change,
transgressing blood vessels (TBV), intracytoplasmic lumina, presence
of multinucleated Hurthle cells, nuclear to cytoplasmic ratio, nuclear
pleomorphism/atypia, and nucleolar prominence. The results were
evaluated by using univariate and stepwise logistic regression (SLR)
analysis; statistical significance was achieved at P-values < 0.05.
RESULTS: One hundred thirty-nine FNAB specimens, corresponding to 56
HCN and 83 BHCL, fulfilled the study criteria. Six of the 14 cytologic
features evaluated were shown by univariate analysis to be
statistically significant in predicting HCN: nonmacrofollicular
architecture (P < 0.001), absence of background colloid (P < 0.001),
absence of chronic inflammation (P < 0.001), presence of TBV (P <
0.001), > 90% Hurthle cells (P < 0.001), and >10% single Hurthle cells
(P = 0.014). The first four of these features were also shown to be
statistically significant in the SLR analysis (P = 0.005, 0.010,
0.016, and 0.045, respectively), and when all four of these features
were present HCN was correctly identified 86% of the time.
CONCLUSIONS: In the current study of 139 FNAB specimens of thyroid
Hurthle cell nodules, 14 cytologic features were examined and 6 were
found to be statistically significant in identifying HCN. The
following four features, when found in combination, were found to be
highly predictive of HCN: nonmacrofollicular architecture, absence of
colloid, absence of inflammation, and presence of TBV.
Hürthle cell
carcinoma: a clinicopathological study of thirteen cases.
Nucl Med Commun. 2006 Apr;27(4):377-9.
BACKGROUND:
Hürthle cell carcinoma (HCC) of the thyroid is a variant of follicular
cancer which has been considered by many as a more aggressive disease
than the usual well-differentiated carcinoma of the thyroid. AIM: To
investigate the clinico-pathologic characteristics, treatment and
outcome of Hürthle cell carcinoma. MATERIAL AND METHODS: During a
7-year period, 13 patients (seven male, six female; mean age at
diagnosis 48.4+/-13.2 years) with HCC were treated and monitored at
the Ankara University. The measured diameter of the tumours varied
from 1 to 6 cm in diameter with pathological examination. Three of the
HCC had extra thyroid invasion, five had intrathyroid invasion, and
five were encapsulated. One of the patients had a history of low-dose
external radiation to the head and neck in childhood. Treatment
consisted of a total thyroidectomy in 12 patients, and a near total
thyroidectomy in one patient. At surgery, lymph node metastases were
present in three patients and lymph node dissection were performed in
these patients. Distant metastases were detected in only one patient
(lung metastasis). RESULTS: All patients had radioiodine ablation
therapy for residual thyroid tissue. Twelve of the 13 patients were
ablated with a single dose of 131 I (3.7-5.5 GBq). A second dose of
radioiodine therapy was required in only one patient who had lung
metastases and this patient is still being followed up. After a median
follow-up period of 85 months, there was no recorded mortality due to
the disease and 12/13 of the patients were categorized as disease free
(criteria for ablation were a negative I whole-body scan and very low
serum thyroglobulin levels). CONCLUSION: We did not find higher
incidences of local recurrences, distant metastases or mortality rates
compared to well differentiated thyroid carcinomas. HCC of the thyroid
and well differentiated thyroid carcinomas have similar biological
behaviour. Their treatment should be similar, including total or
near-total thyroidectomy plus modified cervical node dissection when
there is lymph node involvement. Radioactive iodine therapy and
suppressive laevothyroxin therapy should follow.
Prognostic factors
in patients with Hürthle cell neoplasms of the thyroid.
Cancer. 2003 1;97 (5):1186-94.
BACKGROUND:
Hürthle cell neoplasms, often considered a variant of follicular
thyroid neoplasms, represent 3% of thyroid carcinomas. Only a handful
of publications have focused on the biologic behavior, prognostic
factors, and treatment outcomes of Hürthle cell carcinoma. The
objective of the current study was to identify the clinical and
pathologic features of Hürthle cell carcinomas that predict disease
progression or death. METHODS: The authors reviewed medical records of
patients who were treated for Hürthle cell carcinoma (HCC) and Hürthle
cell adenoma (HCA) at The University of Texas M. D. Anderson Cancer
Center from March 1944 to February 1995, including follow-up
information. The pathologic diagnosis was confirmed by one of the
authors. RESULTS: The authors identified 127 patients with Hürthle
cell neoplasms, 89 patients with HCC and 38 patients with HCA. Seven
patients with HCC had foci of anaplastic thyroid carcinoma. Survival
for this subgroup was worse compared with the overall group and was
analyzed separately. The HCC group was significantly older (age 51.8
years vs. age 43.1. years) and had larger tumors (4.3 cm vs. 2.9 cm)
compared with the HCA group. No differences were seen in gender or
previous radiation exposure. Forty percent of patients in the HCC
group died of thyroid carcinoma, whereas no patients in the HCA group
died of the disease. There has been no improvement in all-cause and
disease specific mortality in the past 5 decades for patients with
these neoplasms. Conventional staging systems predicted mortality with
minor differences. Of the patients with known metastasis, 38% showed
radioiodine uptake. Univariate analysis identified older age, higher
disease stage, tumor size, extraglandular invasion, multifocality,
lymph node disease, distant metastasis, extensive surgery, external
beam radiation therapy, and chemotherapy as factors that were
associated with decreased survival. Tumor encapsulation was associated
with improved survival. Although radioactive iodine treatment had no
overall effect on survival, subgroup analysis showed that patients who
received radioactive iodine for adjuvant ablation therapy had better
outcomes compared either with patients who did not receive radioactive
iodine or with patients who received radioactive iodine as treatment
for residual disease. Multivariate analysis indicated that older age
and larger tumor size predicted worse survival through an association
with worse behaving tumors (multifocal, less encapsulated, and with
extraglandular invasion). The decreased survival in patients with
lymph node metastases may be explained by its association with distant
metastases. The association of extensive surgery, external beam
radiation therapy, and chemotherapy with worse survival also
disappeared once those factors were analyzed together with other
prognostic factors, such as distant metastases. CONCLUSIONS: Several
clinical and pathologic prognostic factors were identified in patients
with HCC and HCA. Older age and larger tumor size predicted reduced
survival. Radioactive iodine therapy may confer a survival benefit
when it is used for adjuvant ablation therapy, but not when residual
disease is present. The authors could not demonstrate a survival
benefit for the use of extensive surgery, external beam radiation
therapy, or chemotherapy.
Survival and
prognosis in Hürthle cell carcinoma of the thyroid gland.
Arch Otolaryngol Head Heck Surg. 2003 ;129(2):207-10.
OBJECTIVE: To
determine factors that affect survival in patients with Hürthle cell
carcinoma of the thyroid gland. METHODS: Data for all cases of Hürthle
cell carcinoma that occurred between January 1, 1988, and December 31,
1998, were extracted from the Surveillance, Epidemiology, and End
Results database. Clinical data regarding age, sex, tumor size,
primary site extension, nodal involvement, and vital status were
tabulated. Patients with distant metastases were excluded, and
Kaplan-Meier survival analysis was conducted. Survival data for
patients with Hürthle cell carcinoma were compared with data for a
control group of patients with follicular cell carcinoma matched for
age, sex, tumor size, and local disease extension. Cox multivariate
regression analysis was conducted to determine the effect of predictor
variables on overall survival in Hürthle cell carcinoma. RESULTS: We
identified 555 cases of nonmetastatic Hürthle cell carcinoma (mean age
at diagnosis, 55.9 years; women, 67.9%). The primary tumor was
intrathyroidal in 83.8% of patients, whereas 11.2% had minor local
extension. Mean tumor size was 3.5 cm. Mean, 5-year, and 10-year
survival for Hürthle cell carcinoma was 109 months, 85.1%, and 71.1%,
respectively. Mean survival for 411 matched patients with follicular
cell carcinoma was 113 months, which was not statistically different
from that of patients with Hürthle cell carcinoma (P =.47, log-rank
test). On multivariate analysis, increasing age at diagnosis, male
sex, and increasing tumor size were statistically significant
predictors of poor survival; degree of primary site extension did not
affect survival. CONCLUSIONS: Overall survival for Hürthle cell
carcinoma is similar to that of comparably staged follicular cell
carcinoma. Increasing age, male sex, and increasing tumor size
substantially diminish survival in patients with Hürthle cell
carcinoma.
Hurthle cell neoplasms of the thyroid.
Laryngoscope.
2002;112(12):2178-80.
OBJECTIVES/HYPOTHESIS: Hurthle cell tumors are a variant of follicular
cell neoplasms. The purpose of the study was to determine the
reliability of intraoperative frozen-section analysis for diagnosing
Hurthle cell carcinoma and Hurthle cell neoplasm and to evaluate age,
gender, and tumor size differences in the incidence of Hurthle cell
carcinoma. STUDY DESIGN: Retrospective chart review. METHODS: The
records of all patients undergoing thyroid surgery at Long Island
Jewish Medical Center (Long Island Campus of the Albert Einstein
College of Medicine, New Hyde Park, NY) from 1990 to 2000 were
reviewed. Patients were identified whose final pathological finding
was Hurthle cell neoplasm or Hurthle cell carcinoma. Age at diagnosis,
gender, tumor size, and correlation between frozen-section analysis
and final pathological finding was determined. RESULTS: One hundred
sixteen patients had Hurthle cell tumors on final pathological finding
(49 had Hurthle cell carcinoma and 67 had Hurthle cell neoplasm).
Eleven of these patients had incidental papillary carcinoma. There
were 24 men and 92 women. Sixty-seven percent of the men (16 of 24)
and 36% of the women (33 of 92) had Hurthle cell carcinoma on final
pathological finding. The mean ages for Hurthle cell neoplasm and
Hurthle cell carcinoma groups were 53 (median age, 50 y) and 58 years
(median age, 61 y), respectively. One hundred eleven patients had
intraoperative frozen-section analysis. Of the 49 patients with
Hurthle cell carcinoma, 9 (19%) were diagnosed by frozen-section
analysis, 36 (75%) had indeterminate frozen-section analysis, 3 (6%)
were discovered to have papillary carcinoma on frozen-section
analysis, and 1 did not have a frozen-section analysis. Multivariate
analysis indicated that size correlated with malignancy and that
gender did not (P =.0015). CONCLUSIONS: In the study population, only
19% of patients were discovered to have Hurthle cell carcinoma on
frozen-section analysis. Sixty-seven percent of men with Hurthle cell
neoplasm had malignancies, compared with 36% of women, and this
difference was statistically significant.
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