Thyroid & parathyroid
Cytology
Bethesda system
Oncocytic neoplasm
Editor-in-Chief: Debra L. Zynger, M.D.
Last author update: 7 May 2020
Last staff update: 12 December 2024 (update in progress)
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PubMed Search: Hurthle cell neoplasm
Table of Contents
Definition / general | Essential features | Terminology | Clinical features | Diagnosis | Case reports | Cytology description | Cytology images | Treatment | Sample cytology report | Videos | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Suzuki A, Bychkov A. Oncocytic neoplasm. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/thyroidhurthlecellneoplasm.html. Accessed December 22nd, 2024.
Definition / general
- Bethesda category IV - Hürthle, “follicular neoplasm, Hürthle cell type / suspicious for a follicular neoplasm, Hürthle cell type (FNHCT/SFNHCT)” is used for cases with a cellular aspirate that consists exclusively of Hürthle cells (Thyroid 2017;27:1341)
- Hürthle cells are thyroid follicular cells with oncocytic appearance characterized by large hyperchromatic nuclei with prominent nucleoli and abundant granular eosinophilic cytoplasm
- Cases cytologically suspected for Hürthle cell adenoma and Hürthle cell carcinoma are included
- The final diagnosis is made histologically because capsular or vascular invasion are the essential criteria of Hürthle cell carcinoma
Essential features
- Includes cases with most of the follicular cells showing abundant fine granular cytoplasm (Hürthle cells)
- Frequency 1.2 - 8.75%, resection rate 30.1%, risk of malignancy 10 - 40%
- The most common histopathological diagnosis is Hürthle cell adenoma and Hürthle cell carcinoma, followed by multinodular goiter and Hashimoto thyroiditis
Terminology
- The term “suspicious for a follicular neoplasm, Hürthle cell type (SFNHCT)” may be more convenient than “follicular neoplasm, Hürthle cell type (FNHCT)” because some nodular goiter or Hashimoto thyroiditis (i.e. nontumor) cases are included in this category
- Hürthle cells are also known as oxyphilic, oncocytes or Askanazy cells (Oncologist 2011;16:1380)
- In the Bethesda System for Reporting Thyroid Cytopathology, FNA specimens that are suspicious for a Hürthle cell neoplasm are distinguished from those suspicious for a non-Hürthle cell follicular neoplasm (Ali: The Bethesda System for Reporting Thyroid Cytopathology, 2nd Edition, 2018)
- Striking morphologic difference between the cytologic patterns of follicular and Hürthle cell neoplasms
- Follicular and Hürthle cell carcinomas may be genetically different neoplasms (Onco Targets Ther 2016;9:6873)
- WHO histological classification also has a separate chapter for Hürthle (oncocytic) cell tumors
Clinical features
- Frequency: 1.2 - 8.75% (J Clin Diagn Res 2013;7:1051, Int J Surg 2013;11:898)
- Resection rate: 30.1% (Int J Surg 2013;11:898)
- Rate of neoplastic lesion after resection: 75 - 84% (Eur J Endocrinol 2013;169:649)
- Risk of malignancy: 10 - 40% (Ali: The Bethesda System for Reporting Thyroid Cytopathology, 2nd Edition, 2018)
- The most common histopathological diagnosis is Hürthle cell adenoma and Hürthle cell carcinoma (77.3%), followed by multinodular goiter (13.3%) and Hashimoto thyroiditis (6.6%) (Eur J Endocrinol 2013;169:649)
- Distinction between Hürthle cell adenoma and Hürthle cell carcinoma is based upon histologic evidence of transcapsular or vascular invasion (World J Surg 2010;34:836)
- Hürthle cell carcinomas represent 15 - 20% of all follicular carcinomas (American Registry of Pathology: Tumors of the Thyroid Glands, Atlas of Tumor Pathology, 1st Edition, 2016)
Diagnosis
- Aspirates are at least moderately cellular and are composed exclusively of Hürthle cells
- Aspirates composed entirely of Hürthle cells with abundant fine granular cytoplasm should be diagnosed as FNHCT/SFNHCT
- Excluded from this category:
- Sparsely cellular aspirates composed entirely of oncocytes that could be interpreted as atypia of undetermined significance or follicular lesion of undetermined significance
- Moderately or markedly cellular aspirates composed entirely of non-atypical Hürthle cells with abundant colloid; it is acceptable to interpret the sample as benign
- Specimen with partial or minimal Hürthle cell differentiation should be diagnosed as follicular neoplasm / suspicious for a follicular neoplasm rather than FNHCT/SFNHCT
- Aspirates with Hürthle cells showing nuclear features of papillary carcinoma should be classified as malignant
Case reports
- 16 year old girl with Hürthle cell carcinoma in an autonomous thyroid nodule (Pediatr Radiol 1995;25:568)
- 36 year old woman with medullary carcinoma of thyroid mimicking Hürthle cell neoplasm on cytology (Diagn Cytopathol 2019;47:943)
- 42 year old man with papillary Hürthle cell tumor (Acta Cytol 1996;40:311)
- 55 year old man with a novel nonsense EIF1AX mutation identified in a Hürthle cell carcinoma (Endocrine 2018;62:492)
- 69 year old man with recurrent Hürthle cell carcinoma (Head Neck 1994;16:64)
- 71 year old woman with EIF1AX mutation in a Hürthle cell carcinoma (Endocr Pathol 2018;29:27)
- 82 year old man with Hürthle cell carcinoma with extensive tumor necrosis (Zhonghua Yi Xue Za Zhi (Taipei) 1999;62:111)
- 85 year old woman with anaplastic thyroid carcinoma developing from a Hürthle cell tumor (Acta Cytol 2001;45:761)
Cytology description
- Abundant finely granular cytoplasm
- Blue or gray pink (Romanowsky), green (Papanicolaou), pink (H&E)
- Nuclei
- Round
- Enlarged, central or eccentrically located
- Prominent nucleolus
- Binucleation (common)
- Small cells with high nuclear / cytoplasmic (N/C) ratio (small cell dysplasia) (Cancer 2002;96:261)
- Large cells with more than two times anisonucleosis (large cell dysplasia) (Cancer 2002;96:261)
- Predominantly isolated cells but sometimes arranged in crowded, syncytial-like clusters
- Little or no colloid
- No lymphocytes or plasma cells
- Transgressing vessels (capillaries passing through clusters of Hürthle cells), seen occasionally (Arch Pathol Lab Med 2001;125:1031)
- Sometimes intracytoplasmic colloid inclusions (Arch Pathol Lab Med 2001;125:1031)
Cytology images
Contributed by Ayana Suzuki, C.T.
Follicular neoplasm, Hürthle cell type
Hürthle cell clusters
Oncocytes and histiocytes
Contributed by Grace C.H. Yang, M.D.
Hürthle cell adenoma, Diff-Quik
Hürthle cell adenoma, Pap stain
Hürthle cell adenoma, Pap stain
Treatment
- Diagnostic lobectomy (Thyroid 2016;26:1)
- Molecular testing with available gene panels is generally not helpful in identifying Hürthle cell carcinomas and distinguishing them from adenomas (Cancer Cytopathol 2018;126 Suppl 8:654)
- Patients with FNHCT/SFNHCT who have benign Afirma Gene Expression Classifier (GEC) result may be spared an unnecessary lobectomy (Endocr Pract 2018;24:622)
Sample cytology report
- Dx / category: follicular neoplasm, Hürthle cell (oncocytic) type
- Cellular aspirate consisting of abundant isolated oncocytes in the absence of colloid
- Dx / category: suspicious for a follicular neoplasm, Hürthle cell (oncocytic) type
- Cellular aspirate of follicular cells with Hürthle cell features, in addition occasional nuclear grooves and focal papillary architecture are seen
- The findings raise the possibility of a Hürthle cell neoplasm with mild nuclear irregularity but a papillary carcinoma cannot be excluded
- Dx / category: suspicious for a follicular neoplasm, Hürthle cell (oncocytic) type
- Cellular aspirate composed of cells with abundant granular cytoplasm
- The findings raise the possibility of a Hürthle cell neoplasm but a parathyroid tumor cannot be excluded
- Correlation with clinical findings, imaging and biochemistry might be helpful
Videos
Case 1
Case 2
Oncocytic lesions by Z. Baloch (2020)
Differential diagnosis
- Mutinodular goiter:
- Flat, cohesive sheets of Hürthle cell admixed with normal follicular cells and a moderate to abundant amount of colloid (Cancer Cytopathol 2014;122:241)
- Chronic thyroiditis:
- Lymphocytes predominate over Hürthle cells
- Data suggest that the criteria for FNHCT/SFNHCT have a lower predictive value for malignancy in the settings of chronic thyroiditis (Am J Clin Pathol 2011;135:139)
- Oncocytic variant of papillary carcinoma:
- Nuclear features specific for papillary carcinoma, i.e. nuclear enlargement, pale chromatin, grooves and intranuclear pseudoinclusions
- A few Hürthle cell neoplasms exhibit some of the architectural and nuclear features of papillary carcinoma (diagnosed either as FNHCT/SFNHCT or “suspicious for malignancy”) (Malays J Pathol 2015;37:49)
- Medullary carcinoma:
- Presence of salt and pepper chromatin, intranuclear pseudoinclusions but absence of prominent nucleolus; metachromasy on Romanowsky stains
- Calcitonin and chromogranin +, thyroglobulin - (Endocr J 2017;64:1099)
- Calcitonin measurement using needle washout fluid is helpful (Endocr J 2017;64:1099)
- Parathyroid adenoma:
- Monomorphous cytoplasm with round nuclei and salt and pepper chromatin
- GATA3, chromogranin, synaptophysin and parathyroid hormone +, thyroglobulin and TTF1 - (Endocr J 2016;63:621)
- Parathyroid hormone measurement using needle washout fluid is helpful
- GEC can recognize the expression profile of parathyroid lesions (Diagn Cytopathol 2017;45:526)
Additional references
Board review style question #1
Which finding is not helpful in distinguishing medullary carcinoma from a Hürthle cell neoplasm?
- Salt and pepper chromatin
- Metachromasia in Romanowsky stain
- Calcitonin measurement using needle washout fluid
- PTH value measurement using needle washout fluid
- Calcitonin immunostaining
Board review style answer #1
D. PTH value measurement using needle washout fluid; PTH value measurement is useful for parathyroid lesions
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Reference: Hürthle cell neoplasm
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Reference: Hürthle cell neoplasm
Board review style question #2
What is the most likely diagnosis of this thyroid aspirate?
- Chronic thyroiditis
- Adenomatous nodule
- Hürthle cell neoplasm
- Medullary carcinoma
- Parathyroid adenoma
Board review style answer #2
D. Medullary carcinoma; salt and pepper chromatin indicates medullary carcinoma
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Reference: Hürthle cell neoplasm
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