These tumors of the thyroid gland have a behavior similar to follicular tumors. The distinction is made by the characteristic Hurthle cell, a cell with abundant eosinophilic cytoplasm caused by numerous mitochondria. Hurthle cells are derived from thyroid follicular cells.
Disease Associations Pathogenesis Laboratory/Radiologic/Other Diagnostic Testing Gross Appearance and Clinical Variants Histopathological Features and Variants Special Stains/Immunohistochemistry/Electron Microscopy Differential Diagnosis Prognosis Treatment Commonly Used Terms Internet Links
DISEASE ASSOCIATIONS CHARACTERIZATION THYROID CANCER
Hurthle cell carcinoma arising from thyroid papillary carcinoma.
Zwi LJ, Livolsi VA.
Department of Pathology, Faculty of Medicine and Health Science, University of Auckland, Auckland, New Zealand.
Endocr Pathol 2002 Fall;13(3):213-7 Abstract quote
Hurthle cell carcinoma of the thyroid is generally considered to be a subtype of follicular carcinoma.
We report a case of a small solitary usual-type papillary carcinoma of the thyroid, with metastatic tumor in cervical lymph nodes. The lymph node tumor consisted of both tall-cell papillary carcinoma and Hurthle cell carcinoma.
This suggests a closer relationship between papillary cell carcinoma and Hurthle cell tumors than previously appreciated.
Thyroiditis and oncocytic carcinoma: incidental association? A case report.
Pisani T, Bononi M, Pantellini F, Vecchione A, Giovagnoli MR.
Cytopathology Laboratory, Department of Experimental Medicine and Pathology, La Sapienza University, Rome, Italy.
Anticancer Res 2002 Nov-Dec;22(6B):3525-7 Abstract quote
BACKGROUND: Several studies have reported an association between Hashimoto's disease and thyroid carcinoma although the cause/effect relationship is still controversial.
CASE REPORT: In this paper we report the case of a 38-year-old female who first presented with a clinical history of Hashimoto's thyroiditis. Ultrasound examination showed a diffuse thyroid irregularity more pronounced in the right lobe. FNAC (Fine Needle Aspiration Cytology) was performed in this area, and the cytological diagnosis was "Hashimoto's thyroiditis". The patient underwent clinical follow-up. Two years later, an ultrasound examination showed a nodular lump in the area previously aspirated. A new FNAC evidenced a Hurthle cell neoplasia. Therefore, the patient underwent surgery. The histological diagnosis was "Hurthle cell carcinoma".
CONCLUSION: In the present case, the clinical and ultrasound history suggest the development of a malignant lesion strictly related to thyroiditis, as previously reported by other studies on papillary carcinoma. A cause-effect relationship between chronic lymphocytic thyroiditis and oncocytic neoplasia is still a matter of controversy. Therefore, patients suffering from chronic thyroiditis require a careful follow-up and, in case of nodules development, FNAC is recommended.
PATHOGENESIS CHARACTERIZATION E2F-1 TRANSCRIPTION FACTOR
E2F-1 Transcription Factor Is Overexpressed in Oxyphilic Thyroid Tumors.
Volante M, Croce S, Pecchioni C, Papotti M.
Department of Biomedical Sciences and Oncology, University of Turin, Torino, Italy.
Mod Pathol 2002 Oct;15(10):1038-43 Abstract quote
In thyroid tumors, several cell cycle regulators have been found to be altered or overexpressed, but no data exist on E2F transcription factors. Such factors (E2F-1 in particular) act as the final effectors in the retinoblastoma pathway but are also involved in apoptosis.
To analyze E2F-1 expression in thyroid neoplasms, we investigated 73 thyroid tumors, including 28 oxyphilic and 45 nonoxyphilic lesions, by immunohistochemistry, in parallel with other cell cycle-related proteins (p27, pRb, p53, and Ki67). p27, Ki-67, pRb, and p53 expression patterns generally overlapped the literature data. E2F-1 was expressed in all thyroid tumor types, both benign and malignant, with no statistical correlation with proliferative status (except for anaplastic carcinoma). A significantly higher percentage of tumor cells expressed E2F-1 in oxyphilic adenomas (71.5%) and oxyphilic carcinomas (66.1%) as compared with that of the corresponding nonoxyphilic lesions (30.8% and 34.5%, respectively; P <.05). These same tumors had a relatively low proliferative index. Therefore, because oxyphilic tumors of the thyroid show peculiar morphological, phenotypic, and ultrastructural features, possibly related to their particular metabolic conditions, it is possible that E2F-1 overexpression is linked to activities other than cell cycle entry in oxyphilic tumors.
In conclusion, E2F-1 is expressed in both benign and malignant thyroid tumors, thus suggesting a wide involvement of the retinoblastoma pathway in thyroid tumorigenesis. In addition, in oxyphilic tumors, more than two thirds of tumor cells express E2F-1, an event possibly linked to proapoptotic rather than proliferative signals in such neoplasms.
LABORATORY/RADIOLOGIC/OTHER TESTS CHARACTERIZATION Laboratory Markers Flow cytometry
Aneuploid tumors may behave more aggressively than diploid tumors
However, biologically and histologically benign tumors may also be aneuploid
20-50% of histologically malignant and aneuploid tumors are more aggressive biologically and clinically than diploid Hurthle cell tumors
GROSS APPEARANCE/CLINICAL VARIANTS CHARACTERIZATION General Solitary with complete or partial encapsulation
Brown to mahogany color
VARIANTS Extensive infarction Usually following fine needle aspiration
HISTOLOGICAL TYPES CHARACTERIZATION GENERAL
Hurthle cells have large cells with distinct cytoplasmic borders with voluminous granular cytoplasm, large nucleus, and prominent nucleolus
The histologic criteria to distinguish benign from malignant is the same criteria for follicular adenoma and carcinoma
Criteria for malignancy include:
Destructive capsular invasion
Hurthle cell carcinoma is a better gold standard than Hurthle cell neoplasm for fine-needle aspiration of the thyroid.
Department of Pathology, Baptist Hospital of Miami, Miami Florida.
Cancer 2002 Oct 25;96(5):261-6 Abstract quote
BACKGROUND: The majority of fine-needle aspirates of the thyroid that demonstrate a predominance of Hurthle cells are diagnosed as suspicious for Hurthle cell neoplasm. Only a minority of these patients are found to have carcinoma at the time of resection. In the current study, an attempt was made to define criteria that were more specific for Hurthle cell carcinoma without a loss in sensitivity.
METHODS: The literature was reviewed and 33 aspiration samples diagnosed as suspicious for a Hurthle cell neoplasm (4 nonneoplastic cases, 19 adenoma cases, and 10 carcinomas) were reexamined and reclassified based on criteria derived from the literature.
RESULTS: All Hurthle cell carcinomas could be identified using a total of five criteria: predominantly Hurthle cells and scant colloid and at least one of either small cell dysplasia (cytoplasmic diameter less than twice the nuclear diameter, with often quite bland cells), large cell dysplasia (greater than twice the variation in nuclear diameter; large cells typically demonstrate prominent nucleoli and irregular nuclear outlines), crowding (nuclei touching), and dyshesion (single cells). Three of 4 nonneoplastic aspiration samples (75%) and 7 of 19 Hurthle cell adenomas (37%) did not meet these criteria and could reliably be diagnosed as benign.
CONCLUSIONS: By focusing on criteria for Hurthle cell carcinoma rather than all Hurthle cell neoplasms, criteria can be developed that improve the specificity without a loss of sensitivity.
Diagnostic Utility of Intracytoplasmic Lumen and Transgressing Vessels in Evaluation of Hürthle Cell Lesions by Fine-Needle Aspiration
Yi J. Yang, MD, PhD and Kamal K. Khurana, MD
From the Department of Pathology, SUNY Upstate Medical University Hospital, Syracuse, NY.
Arch Pathol Lab Med 2001;125:1031–1035. Abstract quote
Introduction. —Recent abstracts have emphasized the importance of recognizing intracytoplasmic lumen and transgressing vessels as useful criteria enabling distinction between Hürthle cells encountered in neoplastic and nonneoplastic thyroid aspirates. The purpose of this retrospective study was to evaluate if application of these criteria improves specificity and sensitivity of cytologic diagnosis of true Hürthle cell neoplasms.
Materials and Methods. —We retrospectively reviewed 30 fine-needle aspirates of thyroid with cytologic diagnosis of Hürthle cell neoplasms (13 cases) and nonneoplastic thyroid with prominent Hürthle cells (17 cases). All cases were evaluated for the presence of intracytoplasmic lumen and transgressing vessels and were reclassified as neoplastic or nonneoplastic based on the presence or absence of 1 or both of these criteria. Surgical follow-up was available in all cases.
Results. —Surgical follow-up in 13 cases of Hürthle cell neoplasms revealed Hürthle cell carcinoma (3 cases), Hürthle cell adenoma (6 cases), and Hashimoto's thyroiditis (4 cases). Seventeen cases with nonneoplastic diagnosis revealed Hürthle cell carcinoma (1 case), Hashimoto's thyroiditis (12 cases), and nodular goiter (4 cases). After application of the previously mentioned cytologic criteria, the cytologic diagnoses were reclassified as Hürthle cell neoplasms (13 cases) and nonneoplastic thyroid (17 cases). The true sensitivity of the test before and after the application of the criteria was 90% and 100%, respectively. The true specificity before and after the application of the cytologic criteria was 65% and 85%, respectively.
Conclusions. —Intracytoplasmic lumen and transgressing vessels are helpful features in distinguishing neoplastic and nonneoplastic Hürthle cell thyroid lesions. Use of these criteria may improve the specificity and sensitivity of the cytologic diagnosis.
Phyllodes Tumor Metastatic to Thyroid HurthleCell Adenoma.
Giorgadze T, Ward RM, Baloch ZW, LiVolsi VA.
Departments of Pathology, East Tennessee State University, Johnson City (Dr Giorgadze), the Craven Regional Medical Center, New Bern, NC (Dr Ward), and the University of Pennsylvania Medical Center, Philadelphia (Drs Baloch and LiVolsi).
Arch Pathol Lab Med 2002 Oct;126(10):1233-6 Abstract quote
We present a case of a malignant phyllodes tumor metastasizing to a Hurthle cell adenoma of the thyroid. A 55-year-old woman underwent mastectomy for a malignant phyllodes tumor. Two years later, she presented with a left thyroid mass, which was a single, circumscribed, soft, deep red-brown nodular lesion with an eccentric area of firmer consistency.
Histologically, the thyroid tumor was composed of 2 distinct types of cellular proliferation. Atypical spindle cells were infiltrating between the Hurthle cell cords and follicles in a fibrosarcomatous pattern. A battery of immunohistochemical stains was applied to both the thyroid and breast tumors for comparison.
Based on the histologic and immunophenotypic features of the fibrosarcomatous components of both the breast and thyroid tumors, we rendered a diagnosis of cystosarcoma phyllodes metastatic to Hurthle cell adenoma. To the best of our knowledge, this unusual case is a first report of tumor-to-tumor metastasis of a sarcoma to a primary thyroid neoplasm.
SPECIAL STAINS/IMMUNOPEROXIDASE/OTHER CHARACTERIZATION Electron microscopy (EM) Large mitochondria produced the characteristic cytoplasmic appearance
DIFFERENTIAL DIAGNOSIS KEY DIFFERENTIATING FEATURES Hurthle cells may be found in several conditions: Nodular goiter Nonspecific chronic thyroiditis Long-standing hyperthyroidism Chronic lymphocytic thyroiditis (Hashimoto's disease) Neoplasms May be incidental finding
Majority represent Hurthle cell change of preexisting follicular adenomatous nodules in goiters or thryoiditis
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSTIC FACTORS
The pathologic criterion for malignancy is more frequently met for Hurthle cell neoplasms than for other follicular tumors
NOTE: Size, nuclear atypia, multinucleation, cellular pleomorphism, mitoses, or histologic pattern are not predictive of behavior
30-40% of solitary encapsulated tumors will show invasive characteristics
Prognostic factors in patients with Hurthle cell neoplasms of the thyroid.
Lopez-Penabad L, Chiu AC, Hoff AO, Schultz P, Gaztambide S, Ordonez NG, Sherman SI.
Department of Endocrine Neoplasia and Hormonal Disorders, The University of Texas M. D. Anderson Cancer Center, Houston, Texas.
Cancer 2003 Mar 1;97(5):1186-94 Abstract quote
BACKGROUND: Hurthle 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 Hurthle cell carcinoma. The objective of the current study was to identify the clinical and pathologic features of Hurthle cell carcinomas that predict disease progression or death.
METHODS: The authors reviewed medical records of patients who were treated for Hurthle cell carcinoma (HCC) and Hurthle 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 Hurthle 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 Hurthle cell carcinoma of the thyroid gland.
Division of Otolaryngology, Brigham and Women's Hospital, 333 Longwood Ave, Boston, MA 02115, USA.
Arch Otolaryngol Head Neck Surg 2003 Feb;129(2):207-10 Abstract quote
OBJECTIVE: To determine factors that affect survival in patients with Hurthle cell carcinoma of the thyroid gland.
METHODS: Data for all cases of Hurthle 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 Hurthle 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 Hurthle cell carcinoma.
RESULTS: We identified 555 cases of nonmetastatic Hurthle 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 Hurthle 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 Hurthle 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 Hurthle 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 Hurthle cell carcinoma.
Hurthle cell tumors of the thyroid gland. Personal experience and review of literature.
Bononi M, De Cesare A, Cangemi V, Fiori E, Galati G, Giovagnoli MR, Izzo L, Cimitan A, Meucci M, Cavallaro A.
Department of General Surgery, Pietro Valdoni University of Rome La Sapienza, Via Talete no. 45, 00124 Roma, Italy.
Anticancer Res 2002 Nov-Dec;22(6B):3579-82 Abstract quote
BACKGROUND: Oncocytic cell neoplasm of the thyroid is currently recognized as a histological entity, but doubts still exist about its clinical and evolutionary categorization. Controversies concern occurrence and frequency of malignant forms, natural history and therapeutic strategies.
MATERIALS AND METHODS: The authors report six cases of Hurthle cell tumor. Five cases were adenoma, one was carcinoma. Morpho-functional pre-operative evaluation and inter-operative histopathological test were performed in all patients. One patient underwent lobectomy (absence of unusual characteristics of the adenoma Hurthle cell) and five underwent total thyroidectomies (1 carcinoma). All patients were treated with suppressive hormonal therapy.
RESULTS: No mortality and morbidity was recorded. All patients are undergoing follow-up (adenomas: average 64.2 months; carcinoma: 132 months) and none of them show recurrent symptoms.
DISCUSSION: Hurthle cell tumors can be diversified in adenoma and carcinoma. Almost all reports classify oncocytic nodules as malignant when capsular and/or vascular invasion is present or when there is peri-thyroid tissue infiltration or lymphatic or hematic metastases. A clear differentiation between adenoma and carcinoma is determined by a histological test. Also an intra-operative histopathological analysis is sometimes unable to show minimal signs of invasion. Conflicting observations about the biological behaviour of Hurthle cell neoplasm lead to different therapeutic strategies. The authors believe lobectomy is the treatment of choice when a clear histological diagnosis of adenoma has been made. When carcinoma is diagnosed or when doubts exist after intraoperative histological test, the authors recommend total thyroidectomy followed by scintigraphic test and preventive radio-active therapy. All patients should be treated with suppressive hormonal therapy and undergo periodic check-ups.
TREATMENT Total thyroidectomy for malignant tumors
Hemithryoidectomy for benign tumors
Diagnostic Surgical Pathology Third Edition. Sternberg S. editor. Lippincott Williams Wilkins. 1999
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