Thyroid gland
Other thyroid carcinoma
Oncocytic (Hürthle cell) tumors

Author: Shuanzeng Wei, M.D., Ph.D. (see Authors page)

Revised: 30 October 2017, last major update October 2017

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: Hürthle cell oncocytic thyroid [title]

Cite this page: Wei, S. Oncocytic (Hürthle cell) tumors. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/thyroidhurthle.html. Accessed December 13th, 2017.
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
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
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

Images hosted on PathOut server:

AFIP images:

Adenoma with massive infarct

Carcinoma has focal capsular invasion



Images contributed by Dr. Mark R. Wick:

Carcinoma

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 random 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:


Images hosted on PathOut server:

Images contributed by Dr. Shuanzeng Wei:

Vascular invasion



Images contributed by Dr. Andrey Bychkov:

Follicular thyroid carcinoma (oncocytic variant)

Oncocytes



Images contributed by Dr. Grace C.H. Yang:

Hürthle cell adenoma, 2x H&E

Hürthle cell adenoma, 4x H&E

Hürthle cell adenoma, 10x H&E

Hürthle cell adenoma, 40x H&E



Images contributed by Dr. Mark R. Wick:

Adenoma with atypia

Hürthle cell carcinoma images



Adenoma (AFIP):

Oncocytic adenoma has follicular pattern

Massive infarct due to fine needle biopsy

Pseudo-angiosarcomatous pattern

Well developed papillary growth pattern

Cytoplasm has fine,
homogeneously
distributed
granularity


Psammomatous-like calcifications in follicular lumina

Tumor has hyalinized area near capsule

Tumor has focal cells with large hyperchromatic nuclei

Focal papillary formations



Clear cell change (AFIP):

Gradual transition from oncocytic to clear cells

Both patterns exist in same cell

Sharp demarcation
between clear
and oncocytic cells



Carcinoma (AFIP):

Capsular invasion

Vascular invasion

Trabecular pattern


Multinodular pattern

Nesting pattern resembles insular carcinoma

Pseudopapillary formations due to tangential sectioning

Pulmonary metastasis
of tumor with
trabecular
growth pattern



Minimally invasive Hürthle cell carcinoma (AFIP):

Fine needle biopsy induced necrosis



Images hosted on other servers:

Psammomatous-like
calcifications in
Hürthle cell
neoplasm (fig 3)



Carcinoma:

Capsular invasion

Oncocytes with abundant eosinophilic granular cytoplasm (far right image is with intraluminal calcifications)

No capsular invasion evident


Tumor in internal jugular vein

Various images

Microfollicles

Metastasis to breast

Cells have
eosinophilic
cytoplasm and
prominent nucleoli

Vascular invasion (fig B)


Mixed oncocytic and mucinous secreting carcinoma

Ki67, mucus secreting carcinoma

p53, mucus secreting carcinoma

Ki67 and cyclin D1



Minimally invasive Hürthle cell carcinoma:

Intracapsular vascular invasion (fig 1)

Vascular invasion (fig 2)

Distant metastasis to femur (fig 3)

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

Images hosted on PathOut server:

Images contributed by Dr. Grace C.H. Yang:

Hürthle cell adenoma, 10x Diff Quik

Hürthle cell adenoma, 2x Pap stain

Hürthle cell adenoma, 10x Pap stain



Images hosted on other servers:

Various images

Microfollicles of carcinoma

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

Images hosted on PathOut server:

AFIP images:

Dilated mitochondria have reduced cristae

Cytoplasm packed
with large mitochondria
with myelin figures



Images contributed by Dr. Mark R. Wick:

Carcinoma



Images hosted on other servers:

Cytoplasm is packed with mitochondria

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
Board review question #1
Which statement is not true for oncocytic carcinoma?

  1. More aggressive compared to conventional follicular carcinoma
  2. More resistant to radioactive iodine compared to conventional follicular carcinoma
  3. Not only metastases to bone or lung; can also spread to lymph node
  4. Oncocytic appearance is due to accumulation of dysfunctional mitochondria
  5. Risk factors include iodine deficiency and irradiation exposure
Board review answer #1
E. Risk factors include iodine deficiency and irradiation exposure. There are no known exogenous risk factors for developing oncocytic tumors.