Thyroid gland
Papillary carcinoma
Papillary carcinoma - General

Author: Shahidul Islam, M.D., Ph.D. (see Authors page)

Revised: 2 May 2017, last major update March 2009

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

PubMed Search: papillary carcinoma thyroid

Advertisement: Papillary Thyroid Cancer Trial

Cite this page: Papillary carcinoma - General. PathologyOutlines.com website. http://pathologyoutlines.com/topic/thyroidpapillary.html. Accessed May 24th, 2017.
Definition / general
  • 75 - 80% of thyroid carcinomas
  • Occult tumors in 6% at autopsy (1 to 10 mm), 46% multicentric, 14% with nodal metastases (Am J Clin Pathol 1988;90:72)
  • Occult tumors in up to 24% with other thyroid disease, but with male predominance (Mod Pathol 1996;9:816)
Epidemiology
  • Usually women (70%) of reproductive age
Clinical features
Radiology images

Images hosted on PathOut server:

CT scan with lymph node metastasis,
contributed by Mark R. Wick, M.D.

Prognostic factors
  • 10 year survival is 98%, similar to general population (versus 92% for follicular carcinoma); 100% if under age 20, even with nodal metastases
  • Cervical nodal involvement does NOT affect prognosis
  • 5 - 20% have local recurrences, 10 - 15% have distant metastases (lung, bones, CNS)

  • Poorer prognosis:
    • Age 40+ or elderly, male (possibly), local invasion (associated with higher incidence of nodal metastases, Arch Pathol Lab Med 1998;122:166), distant metastases (other sites worse than lung, Surgery 2008;143:35), large tumor size, multicentricity, tall cell, columnar or diffuse sclerosing variants
    • Poorly differentiated, anaplastic or squamous foci
    • Lymphatic invasion
Case reports
Treatment
  • Lobectomy, total thyroidectomy for high risk tumors
Gross description
  • Solid, white, firm, often multifocal (20%), encapsulated (10%) or infiltrative
  • Variable cysts, fibrosis, calcification
Gross images

Images hosted on PathOut server:

Contributed by Mark R. Wick, M.D.



AFIP Images:

Bisected thyroid lobe

Large tumor has invasive features

Tumor has abundant nodular fasciitis-like stroma

Metastasis to brain causing neurologic symptoms

Metastases to lymph node



Images hosted on other servers:

Multifocal tumor

Lobulated tumor with central scar and infiltrative borders

Yellow partially encapsulated tumor with granulated cut surface

White cut surface and irregular borders

Expansile gray white tumor

Microscopic (histologic) description
  • Complex, branching, randomly oriented papillae with fibrovascular cores associated with follicles
  • Usually dense fibrosis (Arch Pathol Lab Med 1993;117:645)
  • Papillae lined by cuboidal cells, nuclei are overlapping with finely dispersed optically clear chromatin (also called ground glass, Orphan Annie nuclei, not seen in cytology or frozen section material, Am J Surg Pathol 1979;3:31), micronucleoli, eosinophilic intranuclear inclusions (represent cytoplasmic invaginations) and nuclear longitudinal grooves (represent folding of redundant nuclear membrane, but nonspecific, Mod Pathol 1993;6:691)
  • Stromal elastosis in 66% (Hum Pathol 2005;36:474), often lymphatic invasion

  • Psammoma bodies:
    • In 50% of tumors in papillary stalk in fibrous stroma between tumor cells (usually not in neoplastic follicles)
    • Due to tumor cell necrosis
    • Fairly specific but may also be seen in metastases (Mod Pathol 1990;3:267)
    • Resembles inspissated colloid
    • Note: presence of psammoma body in neck or within cervical lymph node means papillary thyroid carcinoma must be ruled out; 75% are microscopically multifocal, often associated with tall cell variant (30%, Am J Clin Pathol 2003;119:90)

  • Spindle cell metaplasia:
    • Bland appearing spindle cells exhibiting fine chromatin, indistinct nucleoli and rare mitoses, minimal inflammation
    • Usually indolent (non infiltrative, Am J Clin Pathol 2002;117:199) but infiltrative tumors with low to intermediate grade may have aggressive behavior (Arch Pathol Lab Med 2004;128:87)

  • Variable:
    • Squamous metaplasia (15 - 40%), solid and trabecular areas, lymphocytes, histiocytes, multinucleate giant cells (of histiocytic origin, Am J Clin Pathol 1996;106:765), Langerhans cells, vascular invasion (5%)
    • Rarely mitotic figures or mucinous metaplasia

  • Hashimoto thyroiditis associated:
    • Prominent stromal desmoplasia, pseudovascular pattern (cystic spaces with thick hyalinized walls and focal papillary hyperplasia lined by flat and cuboidal epithelium) and marked obliteration of tumor by fibrosis
    • Atypical nodules (clear nuclei, occasional grooves, no nuclear pseudoinclusions) may represent a precursor lesion (Hum Pathol 2001;32:24)
Microscopic (histologic) images

Scroll to see all images.


Images hosted on PathOut server:

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

Pseudonuclear inclusion

Pseudonuclear inclusions and large vesicular nucleus

True papillae with multiple branching

Arborizing papilla

Tall cell variant

Nuclear enlargement, crowding / overlapping


Necrotic degeneration

Psammoma bodies

Giant cells

Giant cells within lumen of papillary structure

Different kinds of giant cells

Cancer deposits in perithyroidal fat


Residual tumor in thyroid bed

Clear cell change

Clear cell change

Subtotal involvement with solid and cystic coalescing foci

Cystic degeneration

Large collapsed cystic lymph node


Papillary structures in cystic space

Submucosal spread of PTC

Tumor deposit due to spread of PTC

Lymphoid tissue replaced by papillary thyroid carcinoma

High grade progression

Encapsulated metastatic deposit


PAS-D staining of PTC with laryngeal invasion

Mucicarmine staining of PTC with laryngeal invasion

Diffuse positive staining for CK19, Galectin-3 and HBME-1

CK19: demarcation between cancer tissue and adjacent thyroid

CK19: Prominent membranous and cytoplasmic staining

Galectin-3: intrathyroidal cancer spread


Galectin-3: Cytoplasmic and nuclear staining

HBME-1: Tumor interface

HBME-1: Striking membranous staining

AE1 / AE3 expression in PTC

BRAF V600E mutant protein diffusely expressed by tumor and in cancer but not in normal tissue


BRAF V600E mutant protein: diffuse cytoplasmic staining

H&E: large psammoma bodies in sclerotic stroma

PTC with ossification

PTC follicular variant with ossification

Nuclear pseudo-inclusions

Vesicular nuclei of thyroid follicles similar to PTC nuclei


Follicular adenoma, mimics of PTC nuclei

Distorted nuclei due to technical / processing artifact

Formation of vesicular appearing nuclei

Papillary thyroid carcinoma with Orphan Annie eye nuclei

Concentric layers of calcium deposition in tumor stroma

Psammoma bodies, laminated calcifications


Evolution in psammoma body in PTC

Psammoma bodies in benign appearing thyroid

Follicular adenoma progressing to papillary cancer

Encapsulated papillary microcarcinoma

Extrathyroidal extension

Minimal extrathyroidal extension


Extrathyroidal extension, muscle invasion

Extrathyroid extension, intramuscular growth

Cancer deposits in skeletal muscle

Metastatic PTC with extranodal extension

Extranodal extension

Large tumor embolus in thyroid vein


TTF1

PAX8



Contributed by Mark R. Wick, M.D.:

Classical type

In cervical lymph node



AFIP Images:

Papillae show hyalinization of stroma

Papillary pattern on left, follicular pattern on right

Glomeruloid pattern due to tight packing of papillae

Solid growth pattern with ground glass nuclei


Typical low power appearance

Typical growth pattern

High grade papillary carcinoma

Multicentric focus of papillary carcinoma



Nuclear features (AFIP):

Various images

Different fixatives

Papillae are lined
by cuboidal to low
columnar cells



Psammoma bodies (AFIP):

Heavily calcified with well defined concentric laminations

Numerous psammoma bodies

Single necrotic cell in center has beginning calcification


Psammoma body in normal appearing thyroid

In center of papillae

In tumor with solid growth but with ground glass nuclei

Psammoma bodies
are embedded in dense,
fibrous tissue



Other features (AFIP):

Marked lymphocytic infiltrate

Vascular invasion (unusual finding)

Clear cell change

Clear cell change (follicular variant)

Squamous metaplasia with keratin pearl



With other disorders (AFIP):

Papillary carcinoma in Hashimoto thyroiditis

Papillary carcinoma in follicular adenoma



Invasion / metastases (AFIP)

Cervical lymph node - marginal sinus

Lung metastasis - exuberant papillary architecture

Cervical lymph node with follicular growth pattern



Stain images (AFIP):

Thyroglobulin+ in cytoplasm

Keratin+



Images hosted on Flickr:

Contributed by Dr. Grace Yang



Psammoma bodies:

Contributed by Semir Vranic, M.D.



Images hosted on other servers:

Architectural patterns:

Papillary architecture with fibrovascular cores

Low power papillary architecture

Papillary architecture with ground glass nuclei

Papillary architecture

Various images



Nuclear features:

Ground glass nuclei and nuclear grooves



Psammoma bodies:

Ground glass nuclei
and psammoma bodies



Other features:

Aggressive spindle cell transformation

Squamous cell metaplasia



With other disorders:

Arising from
thyroglossal duct cyst



Invasion / metastases:

Parathyroid gland invasion

Capsular invasion (van Gieson)

Cervical lymph node

Pituitary gland metastasis



Stain images:

CK19

HBME1 and CK19

Virtual slides

Images hosted on other servers:

Various images

Cytology images

Images hosted on PathOut server:

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

Pink intranuclear cytoplasmic inclusion vs. intranuclear bubbles

Microfollicle, enlarged nuclei and single intranuclear inclusion

Positive stains
Negative stains
Electron microscopy description
  • Highly indented nuclear membrane with pseudoinclusions and multilobation
  • Clusters of large interchromatin granules, nucleoli have microfibrillar cortex with segregation of their components
  • Also dense RNA containing microspherules in nucleoli (Arch Pathol Lab Med 1978;102:635)
Electron microscopy images

Images hosted on PathOut server:

Tall cuboidal cells (AFIP)

Tumor was metastatic to lymph node (AFIP)

Molecular / cytogenetics description
  • Either:
    1. BRAF point mutations (30%, associated with older age, classic morphology or tall cell variant, advanced stage or extrathyroidal extension)
    2. RET / PTC rearrangements at 10q11.2 (45%, associated with younger age, classic morphology, frequent psammoma bodies, nodal metastases; RET encodes a tyrosine kinase not normally expressed by thyroid follicular cells, rearrangement may cause constitutive expression) or
    3. RAS point mutations (associated with follicular variant of PTC, low rate of nodal metastases, Am J Surg Pathol 2006;30:216); RET amplification is associated with radiation induced tumors (Hum Pathol 2007;38:621)
Molecular / cytogenetics images

Images hosted on other servers:

RET-PTC1 rearrangement

Videos


"Histopathology Thyroid - Papillary carcinoma" by John R. Minarcik, M.D.


"Histopathology Thyroid - Hashimoto thyroiditis, papillary carcinoma" by John R. Minarcik, M.D.
Differential diagnosis