Thyroid gland
Papillary thyroid carcinoma
Main variants
Tall cell


Topic Completed: 26 August 2020

Minor changes: 22 September 2020

Copyright: 2002-2020, PathologyOutlines.com, Inc.

PubMed Search: Papillary carcinoma [title] tall cell variant

Livia Florianova, M.D., M.Sc.
Marc Pusztaszeri, M.D.
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Page views in 2020 to date: 3,812
Cite this page: Florianova L, Pusztaszeri M. Tall cell. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/thyroidtallcellvariant.html. Accessed September 29th, 2020.
Definition / general
  • Papillary thyroid carcinoma (PTC) variant characterized by presence of ≥ 30% of tall cells (2 - 3 times taller than wide) with abundant granular eosinophilic (oncocytic-like) cytoplasm and the typical nuclear changes of PTC
  • Variable diagnostic criteria over time with significant interobserver variability (Thyroid 2017;27:1498)
  • Often underrecognized (Thyroid 2008;18:1179, Thyroid 2007;17:655)
  • First described in 1976 (Cleve Clin Q 1976;43:207)
Essential features
  • The most common aggressive variant of papillary thyroid carcinoma, characterized by tall cells occupying ≥ 30% tumor and well developed papillary thyroid carcinoma nuclear features
  • Usually requires more aggressive treatment and closer disease surveillance
  • BRAF V600E mutation present in most cases
  • Papillary thyroid carcinomas with tall cell features (≥ 10% tall cells) have worse prognosis than those without tall cells; more than 10% tall cells in a tumor should be reported in final pathology reports
Terminology
  • 2017 WHO classification of tumors of endocrine organs requires ≥ 30% of tall tumor cells to define this variant
  • Variable diagnostic criteria over time
    • WHO 2017 (current): 2 - 3x height / width cells occupying ≥ 30% tumor
    • WHO 2004 (outdated): 3x height / width cells occupying ≥ 50% tumor
  • If tall cell features are > 10% but < 30%, the tumor should be designated as PTC with tall cell features (Endocr Relat Cancer 2015;22:419)
ICD coding
  • ICD-10: C73 - malignant neoplasm of thyroid gland
  • ICD-O: 8260/3 - papillary carcinoma of thyroid
Epidemiology
Sites
  • Thyroid
  • Exceedingly rare at other sites, e.g. ectopic thyroid tissue in thyroglossal duct (see case reports below)
Pathophysiology
Etiology
  • Sporadic in most cases
  • Shared risk factors with most other variants of PTC
  • Ionizing radiation and pre-existing benign thyroid disease
Clinical features
  • Asymptomatic or enlarging neck mass
  • May present as an incidental thyroid nodule
  • Local symptoms (dysphagia, hoarseness, stridor) may be present for more advanced cases with vocal cord paralysis or tracheal compression
  • Thyroid function tests at the time of diagnosis are typically normal
Diagnosis
  • Gold standard for the diagnosis of the tall cell variant is histopathologic evaluation of thyroid resection specimens
  • Nevertheless, tall cell features may be recognized on fine needle aspiration cytology
Laboratory
Radiology description
Radiology images

Images hosted on other servers:

Tall cell variant in 19 year old woman

Prognostic factors
Case reports
Treatment
  • Total thyroidectomy in most cases
  • With or without neck lymph node dissection with or without radioiodine therapy in selected cases
  • BRAF targeted therapy may be beneficial in selected advanced cases (J Endocr Soc 2017;1:285, Lancet Oncol 2016;17:e468)
Gross description
  • Tend to be large (> 5 cm)
  • Extrathyroidal extension may be grossly apparent
Gross images

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

Entire lobe

Muscular invasion

Frozen section description
  • Frozen section is usually not indicated
  • Standard of care is to perform preoperative fine needle aspiration to establish the diagnosis of PTC and to determine the most appropriate surgical procedure
Microscopic (histologic) description
  • Usually unencapsulated and infiltrative
  • Growth patterns
    • Papillary is the most common
    • Trabecular (due to closely packed papillae) and follicular
    • Areas of tram track or railroad track-like appearance on lower power
  • Intricate, well formed, long papillae lined by single layer of tall columnar cells (cell height is 2 - 3 times their width)
    • Depending on the plane of sectioning, cells may appear wide rather than tall
    • Well developed and easily identifiable nuclear features of PTC: enlarged nuclei with numerous grooves and pseudoinclusions
    • Sharply delineated cell borders with intensely eosinophilic and finely granular cytoplasm
  • Tall cell features / pattern are frequently seen in the areas of extrathyroidal invasion of PTC
  • Psammoma bodies uncommon
  • Absent features: nuclear stratification, squamoid morules
  • May exhibit prominent vascular invasion, mitotic activity
  • Often found as a well differentiated component within anaplastic (undifferentiated) carcinomas and poorly differentiated thyroid carcinomas (Thyroid 2011;21:493)
  • May be associated with lymphocytic thyroiditis
Microscopic (histologic) images

Contributed by Livia Florianova, M.D., M.Sc. and Marc Pusztaszeri, M.D.

Tram track pattern

Papillary architecture

Elongated papillae

Solid architecture

Trabecular architecture


Tall cells

Oncocytic-like cytoplasm

Extrathyroidal extension

Microcarcinoma with infiltrative borders


Nuclear features

HBME-1

Galectin 3


Cytokeratin 19

BRAF V600E



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

Long papillae with tall cells

Tram track pattern

Virtual slides

Images hosted on other servers:

Tall cell variant

Tall cell variant

Cytology description
  • Tall cell features may be recognized by cytology (see below) but a definitive diagnosis of a tall cell variant requires histologic evaluation (see definition)
  • Tall / polygonal cells whose height is 2 - 3 times their width (Diagn Cytopathol 2019;47:452)
  • Well defined granular eosinophilic or dense cytoplasm
  • Nuclei with grooves and pseudoinclusions which can resemble soap bubbles due to multiple pseudoinclusions in the same nucleus (Diagn Cytopathol 2002;27:143, Diagn Cytopathol 2019;47:452)
  • Palisaded arrangement and solid clusters
  • Cells at the periphery of clusters show a tapering cytoplasmic tail to the outside (cytoplasmic elongation or tadpole cell-like)
  • Individual detached cells may show a spindle-like shape or tombstone appearance (both luminal and basal cell borders are horizontal) (Diagn Cytopathol 2019;47:452)
  • Lymphocytes may also be present (Acta Cytol 2004;48:325, Diagn Cytopathol 2019;47:452)
Cytology images

Contributed by Papanicolaou Society and the Bethesda System for Reporting Thyroid Cytopathology, Manon Auger, M.D., C.M., Livia Florianova, M.D., M.Sc. and Marc Pusztaszeri, M.D.

Giemsa

Papanicolaou

Soap bubble nuclear pseudoinclusions


Tall cells

Papillae (cell block)

Tall cells (cell block)

Positive stains
Electron microscopy description
Molecular / cytogenetics description
Videos

High grade and poorly differentiated and anaplastic thyroid carcinoma


Ultrasound of tall cell variant of PTC

Sample pathology report
  • Thyroid, left lobe, fine needle aspiration:
    • Satisfactory for evaluation
    • Malignant (Bethesda diagnostic category VI)
    • Papillary thyroid carcinoma, favor tall cell variant
  • Thyroid, left lobe, left hemithyroidectomy:
    • Papillary thyroid carcinoma, classic type with tall cell features (20%) (see synoptic report)
  • Thyroid, total thyroidectomy:
    • Papillary thyroid carcinoma, tall cell variant (see synoptic report)
Differential diagnosis
Board review style question #1

Which of the following statements concerning the tall cell variant of papillary thyroid carcinoma is correct?

  1. It usually has an indolent clinical course
  2. Most cases are associated with a RAS mutation
  3. Patients are usually older adults
  4. The tumor is positive for TTF1, synaptophysin and calcitonin
  5. Tumor cells are stratified and only focal areas show characteristic papillary thyroid carcinoma nuclear features
Board review answer #1
C. Patients are usually older adults

Comment Here

Reference: Papillary carcinoma, tall cell variant
Board review style question #2

Which of the following diagnostic features are associated with the tall cell variant of papillary thyroid carcinoma?

  1. A dense lymphocytic infiltration of tumor stroma
  2. Cells with granular eosinophilic cytoplasm and nuclei with a soap bubble appearance on cytology
  3. Focal positivity for GATA3
  4. Infrequent nuclear grooves and pseudoinclusions
  5. High nucleus to cytoplasm ratio
Board review answer #2
B. Cells with granular eosinophilic cytoplasm and nuclei with a soap bubble appearance on cytology

Comment Here

Reference: Papillary carcinoma, tall cell variant
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