Thyroid gland
Papillary thyroid carcinoma
Rare variants
Oncocytic


Topic Completed: 7 April 2020

Minor changes: 23 September 2020

Copyright: 2003-2020, PathologyOutlines.com, Inc.

PubMed search: oncocytic [title] "papillary carcinoma" thyroid

See also: Warthin-like variant

Shipra Agarwal, M.D.
Andrey Bychkov, M.D., Ph.D.
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Cite this page: Agarwal S, Bychkov A. Oncocytic. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/thyroidoncocytic.html. Accessed October 29th, 2020.
Definition / general
  • Rare type of papillary carcinoma (PTC) characterized by nuclear features of papillary carcinoma and oncocytic / oxyphilic / Hürthle cell like cytoplasm (mitochondria-rich)
  • Oncocytic changes can be seen in other thyroid cancer (Hürthle cell carcinoma, medullary carcinoma) and in other variants of papillary carcinoma (tall cell variant, Warthin-like variant)
Essential features
  • Papillary carcinoma with oncocytic cytoplasm
  • Abundant altered mitochondria on ultrastructural examination
  • Must differentiate from other oncocytic thyroid tumors, especially tall cell papillary thyroid carcinoma
Terminology
  • Papillary carcinoma, oxyphilic variant
  • Papillary carcinoma, Hürthle cell variant
ICD coding
  • ICD-0: 8342/3 - Papillary carcinoma, oxyphilic cell
  • ICD-10: C73 - Malignant neoplasm of thyroid gland
Epidemiology
Sites
  • Either lobe or isthmus of thyroid gland, also in ectopic thyroid tissue, e.g., thyroglossal cyst or struma ovarii
Pathophysiology
  • Increasing accumulation of somatic mitochondrial DNA mutations, upregulation of energy pathways (pyruvate synthesis, Krebs cycle, electron transport chain) and mitochondrial related pathways (Mitochondrion 2019;46:123)
Clinical features
Diagnosis
  • Preoperative fine needle aspiration cytology
  • Histopathological examination of tumor post resection
Radiology description
Radiology images

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Ultrasound

Prognostic factors
Case reports
Treatment
Gross description
Gross images

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Well encapsulated soft mass

Microscopic (histologic) description
  • Usually papillary, can be follicular, rarely solid (Nikiforov: Diagnostic Pathology and Molecular Genetics of the Thyroid, 3rd Edition, 2019, Clin Endocrinol (Oxf) 2016;85:797, Acta Cytol 2019:1)
  • Composed of oncocytic (oxyphilic, Hürthle) cells
    • Polygonal cells with well defined cell borders
    • Abundant, dense eosinophilic, granular cytoplasm
    • Can be discohesive, similar to Hürthle cell tumors (adenoma / carcinoma)
  • Nuclear features
    • Nuclear enlargement, round to oval nuclei
    • Nuclear membrane with irregular contour, nuclear grooves, frequent intranuclear pseudoinclusions
    • Chromatin clearing / chromatin margination / Orphan-Annie nuclei / ground glass nuclei
    • Prominent nucleoli, may be hidden due to above nuclear changes
    • Nuclear overlapping is uncommon (Acta Cytol 2019:1)
  • Ideally should be purely oncocytic, however cut off of for proportion of oncocytic cells is not established
  • Psammoma bodies may be found
Microscopic (histologic) images

Contributed by Andrey Bychkov, M.D., Ph.D.

Nucleoli and pseudoinclusions

Oncocytic cells with pseudoinclusions

Cytology description
  • Cellular aspirate
  • Monotonous population of polygonal cells arranged as sheets, clusters, papillae or single
  • More than 75% of cells have oncocytic changes of dense cytoplasm and well defined cell borders (Acta Cytol 2019:1)
  • Nuclear enlargement, fine powdery chromatin, nuclear grooves, prominent intranuclear pseudoinclusions
Cytology images

Contributed by Shipra Agarwal, M.D.

Loose clusters of oncocytic cells

Predominant oncocytic cells

Intranuclear inclusions

Positive stains
Negative stains
Electron microscopy description
Molecular / cytogenetics description
Sample pathology report
  • Thyroid, total thyroidectomy:
    • Papillary thyroid carcinoma, oncocytic variant, left lobe, 1.5 cm (see synoptic report)
Differential diagnosis
Board review style question #1

    Which of the following is a typical finding on ultrastructural examination of this thyroid tumor?

  1. Abnormal mitochondria
  2. Filament-ribosomal complexes
  3. Membrane bound crystals
  4. Neurosecretory granules
  5. Paranuclear whorls of intermediate filaments
Board review answer #1
A. Abnormal mitochondria. This is oncocytic variant of papillary thyroid carcinoma. The cells of have abundant abnormal mitochondria, displaying stacks of parallel cristae, filamentous bundles and woolly densities.

Reference: Oncocytic variant

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Board review style question #2
    Oncocytic variant of papillary thyroid carcinoma is typically associated with which of the following molecular alterations?

  1. BRAFV600E mutation
  2. Mitochondrial DNA mutations
  3. PAX8/PPARγ translocation
  4. RAS mutations
  5. TERT promoter mutations
Board review answer #2
B. Mitochondrial DNA mutations. Oncocytic papillary thyroid carcinomas show accumulation of mitochondrial DNA mutations. BRAFV600E mutation can be found in oncocytic papillary thyroid carcinoma but is much more prevalent in tall cell variant of papillary thyroid carcinoma. PAX8/ PPARγ translocation and RAS mutations are usually associated with follicular variant of papillary thyroid carcinoma. TERT promoter mutations have been reported to occur with increasing frequency in cases with de-differentiation.

Reference: Oncocytic variant

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