Table of Contents
Definition / general | Essential features | Terminology | Epidemiology | Radiology description | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Cytology images | Positive stains | Electron microscopy description | Electron microscopy images | Molecular / cytogenetics description | Differential diagnosis | Additional references | Board review style question #1 | Board review style answer #1Cite this page: Wei S. Oncocytic (Hürthle cell) tumors. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/thyroidhurthle.html. Accessed January 22nd, 2021.
Definition / general
- Follicular neoplasm with more than 75% oncocytic tumor cells
- Oncocytic appearance is due to accumulation of dysfunctional mitochondria
- Malignant if capsular and / or vascular invasion
- Tumor size, nuclear atypia, multinucleation, pleomorphism, mitoses or histologic pattern of the lesion are not determinants of malignancy (Arch Pathol Lab Med 2008;132:1241)
- Hematogenous metastases, 30% to lymph node (in contrast, rare in follicular carcinoma)
- No known exogenous risk factors for developing oncocytic tumors
Essential features
- Follicular neoplasm composed of more than 75% oncocytes
- Malignant if capsular and / or vascular invasion
- Malignant tumors have more aggressive behavior than conventional follicular carcinoma
Terminology
- Synonym: oncocytic cell is also called Hürthle, Askanazy and oxyphilic cells
- "Hürthle cell" is a misnomer - Dr. Hürthle originally used it to describe C cells instead of oncocytes
Epidemiology
- Carcinoma is more common in older men (mean age: 57 years)
Radiology description
- Similar to follicular adenoma / carcinoma
Prognostic factors
- Oncocytic adenoma is benign, no recurrence after excision
- Overall, oncocytic carcinoma is more aggressive than conventional follicular carcinoma, with higher frequency of extrathyroidal extension, local recurrence and metastasis to lymph nodes
- Mortality rate: 10 - 80%
- Worse prognosis: old age, tumor size > 4 cm and extensive vascular invasion
Case reports
- 21 year old man with Hürthle cell thyroid carcinoma and parathyroid carcinoma (J Clin Diagn Res 2015;9:OD08)
- 55 year old man with 3 year history of increasing neck mass (University of Pittsburgh: Neck Mass [Accessed 19 October 2017])
- 55 year old woman with phyllodes tumor metastatic to Hürthle cell adenoma (Arch Pathol Lab Med 2002;126:1233)
- 59 year old man with mixed oncocytic and mucinous secreting carcinoma (Arch Pathol Lab Med 2000;124:1547)
- 77 year old woman with metastasis to breast (Int Semin Surg Oncol 2008;5:14)
- 79 year old man with rapidly increasing lump on neck and colloid goiter 24 years ago (World J Surg Oncol 2004;2:27)
Treatment
- Adenoma: lobectomy
- Carcinoma: total thyroidectomy or radiation ablation
- Radioactive iodine: resistant compared to conventional follicular carcinoma
Gross description
- Most are more than 2 cm
- Prone to infarction or hemorrhage, especially after FNA or core biopsy
- Solitary, solid, bright brown to mahogany color, mostly encapsulated, lobulated, may have central scar
- Widely invasive tumors have irregular borders, may have satellite nodule / multinodular appearance
Gross images
Microscopic (histologic) description
- At least 75% of tumor cells are oncocytes with large size, distinct cell borders, deeply eosinophilic and granular cytoplasm, large nucleus with prominent nucleolus, complete loss of cell polarity
- Follicular, trabecular, solid or papillary growth patterns
- Occasional nuclear grooves or nuclear pseudoinclusions
- May have psammomatous-like calcifications without lamination in the lumen of follicle (papillary carcinoma has laminated psammoma body in the stroma)
- Random nuclear atypia common but not evidence for malignancy
- Carcinoma tends to have:
- Thicker capsule than that of adenoma
- Solid / trabecular rather than follicular pattern of growth
- Smaller cells with high N/C ratio, increased mitotic figures
- Can have clear cell changes due to dilated mitochondria
- Poorly differentiated oncocytic carcinoma: size > 4 cm, with tumor necrosis, numerous mitoses, foci of small tumor cells
Microscopic (histologic) images
Scroll to see all images:
Contributed by Shuanzeng Wei, M.D., Ph.D.
Contributed by Andrey Bychkov, M.D., Ph.D.
Contributed by Grace C.H. Yang, M.D.
Contributed by Mark R. Wick, M.D.
AFIP images
Adenoma:
Clear cell change:
Carcinoma:
Minimally invasive Hürthle cell carcinoma:
Images hosted on other servers:
Carcinoma:




Oncocytes with abundant eosinophilic granular cytoplasm (far right image is with intraluminal calcifications)
Minimally invasive Hürthle cell carcinoma:
Cytology description
- Highly cellular, 75% or more Hürthle cells (abundant granular cytoplasm, round nuclei, often prominent nucleoli), often discohesive cells, some enlarged and pleomorphic with intracytoplasmic lumens (empty vacuoles with magenta [Diff Quik], green [Pap] or no material); transgressing vessels (capillaries in clusters of Hürthle cells) (Arch Pathol Lab Med 2001;125:1031)
- No colloid, lymphocytes, histiocytes, plasma cells or ordinary follicular cells
- Cannot definitively diagnose malignancy based on cytologic material (Am J Clin Pathol 1993;100:231, Acta Cytol 2008;52:659) but malignant cases tend to have small or large cell dysplasia, nuclear crowding and discohesive cells (Diagn Cytopathol 2008;36:149)
- Metastatic tumors may have bland cytologic features (Diagn Cytopathol 2007;35:439)
Cytology images
Positive stains
- Thyroglobulin (moderate), TTF1, CK7 (CK20 negative)
- Poorly differentiated oncocytic carcinoma may be negative for TTF1 and thyroglobulin
Electron microscopy description
- Numerous large mitochondria
Electron microscopy images
Molecular / cytogenetics description
- Aneuploidy is common in oncocytic tumors, including chromosome gains and losses
- Deletions or mutation of mitochondrial DNA (mtDNA) coding for oxidative phosphorylation (OXPHOS) proteins, which leads to energy production defects and compensatory mitochondrial proliferation
- PTEN and TP53 mutations (Endocr Pathol 2015;26:365)
- MEN1 loss of function mutations in 4% of patients diagnosed with oncocytic thyroid carcinoma (J Clin Endocrinol Metab 2015;100:E611)
Differential diagnosis
- Hashimoto thyroiditis: abundant lymphocytes without distinct nodule
- Medullary carcinoma with Hürthle cell-like cells: calcitonin+, CEA+, thyroglobulin-
- Nodular goiter with prominent oncocytic cells: abundant colloid, follicular cells and histiocytes mixed with oncocytic cells
- Papillary thyroid carcinoma, oncocytic variant, Warthin-like variant, tall cell variant: with nuclear features of papillary carcinoma
Additional references
Board review style question #1
Which statement is not true for oncocytic carcinoma?
- More aggressive compared to conventional follicular carcinoma
- More resistant to radioactive iodine compared to conventional follicular carcinoma
- Not only metastases to bone or lung; can also spread to lymph node
- Oncocytic appearance is due to accumulation of dysfunctional mitochondria
- Risk factors include iodine deficiency and irradiation exposure
Board review style answer #1
E. Risk factors include iodine deficiency and irradiation exposure. There are no known exogenous risk factors for developing oncocytic tumors.