Thyroid & parathyroid

Papillary thyroid carcinoma

Main variants

Diffuse sclerosing


Editorial Board Member: Andrey Bychkov, M.D., Ph.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Livia Florianova, M.D., M.Sc.
Marc Pusztaszeri, M.D.

Topic Completed: 17 December 2020

Minor changes: 2 June 2021

Copyright: 2003-2021, PathologyOutlines.com, Inc.

PubMed Search: papillary carcinoma [title] WITH diffuse sclerosing

Livia Florianova, M.D., M.Sc.
Marc Pusztaszeri, M.D.
Page views in 2020: 3,896
Page views in 2021 to date: 3,518
Cite this page: Florianova L, Pusztaszeri M. Diffuse sclerosing. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/thyroiddiffusesclerosing.html. Accessed September 22nd, 2021.
Definition / general
  • Papillary thyroid carcinoma (PTC) variant characterized by diffuse involvement of one or both thyroid lobes with dense sclerosis, abundant psammoma bodies, solid foci with associated squamous metaplasia, chronic lymphocytic thyroiditis background and extensive lymphatic invasion
  • First described in 1985 by Vickery et al. (Semin Diagn Pathol 1985;2:90)
Essential features
  • Diffuse sclerosing variant of PTC (DSV PTC) is an uncommon variant of PTC highly prevalent in female pediatric / young patients and in patients with history of radiation exposure
  • Characterized by diffuse involvement of thyroid lobes, extensive lymphatic invasion, sclerosis, abundant psammoma bodies, squamous metaplasia and background thyroiditis
  • Has distinct clinical, pathological and molecular profiles when compared with conventional PTC
  • Aggressive subtype of PTC associated with frequent extrathyroidal extension, cervical lymph node metastasis, greater incidence of distant metastasis (5 - 15%) and more frequent recurrence than conventional PTC, however, mortality rates are similar to classic PTC
ICD coding
  • ICD-O: 8260/3 - papillary carcinoma of thyroid
  • ICD-10: C73 - malignant neoplasm of thyroid gland
Epidemiology
Sites
Pathophysiology
  • Clonal neoplastic proliferation of thyroid follicular cells, usually with a specific driver mutation, mainly RET / PTC rearrangements resulting in the activation of the RAS / RAF / MAPK pathway (see Molecular / cytogenetics description below)
Etiology
Clinical features
Diagnosis
  • Workup is similar to any thyroid mass / nodule
    • Ultrasound with fine needle aspiration cytology
    • CT scan may be useful to evaluate extrathyroidal extension and lymph node metastases
  • Diagnosis is made via histological examination of a resection specimen
    • Fine needle aspiration cytology can raise a suspicion of DSV PTC and influence surgical decision making
Laboratory
Radiology description
  • Most cases show diffuse, scattered microcalcifications ("snowstorm appearance") with or without associated suspicious masses and underlying heterogeneous hypoechogenicity (Clin Radiol 2007;62:382)
  • Ultrasound features correlate with numerous psammoma bodies and lymphocytic infiltration on histology (Korean J Radiol 2010;11:579)
  • Cervical lymphadenopathy is frequently present at the time of the ultrasound examination (Korean J Radiol 2010;11:579)
Radiology images

Images hosted on other servers:
Ultrasonographic features of DSV PTC Ultrasonographic features of DSV PTC Ultrasonographic features of DSV PTC

Ultrasonographic features

Prognostic factors
Case reports
Treatment
Gross description
Gross images

AFIP images
Diffuse growth and fibrosis

Diffuse growth and fibrosis



Images hosted on other servers:
Fibrotic cut surface

Fibrotic cut surface

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
Microscopic (histologic) images

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

Lymphocytic infiltrate

Papillary pattern

Papillary pattern

Dense fibrosis

Dense fibrosis

Dense sclerosing fibrosis

Dense sclerosing fibrosis


Infiltrative growth

Infiltrative growth

Nuclear features

Nuclear features

Psammoma bodies and sclerosis Psammoma bodies and sclerosis

Psammoma bodies and sclerosis

Solid pattern

Solid pattern


Squamous morule Squamous morule

Squamous morule

Lymphovascular invasion

Lymphovascular invasion

Lymph node metastasis Lymph node metastasis

Lymph node metastasis



Contributed by Andrey Bychkov, M.D., Ph.D.
Multiple tumor nodules

Multiple tumor nodules

Fibrosis and lymphocytic infiltration

Fibrosis and lymphocytic infiltration

Large psammoma bodies

Prominent sclerosis

Thick fibrous bands

Extensive squamous metaplasia

Virtual slides

Images hosted on other servers:
Papillary thyroid carcinoma, diffuse sclerosing type

PTC, diffuse sclerosing type

Cytology description
  • Moderately to highly cellular with scant or absent colloid
  • Neoplastic cells are often arranged in 3 dimensional ball-like clusters from which protruding hobnail cells can be frequently observed (Cytopathology 2014;25:199)
  • In contrast to conventional PTC, there is less chromatin pallor (slightly coarser chromatin) and fewer nuclear grooves and nuclear pseudoinclusions (Cytopathology 2014;25:199)
  • Squamous metaplastic changes: flat, polygonal shaped cells with sharply demarcated cell membranes, fitting together like jigsaw pieces (without overt keratinization) (Cytopathology 2014;25:199)
  • Numerous lymphocytes and psammoma bodies present in the background (Cytopathology 2014;25:199)
  • Cytological differential diagnosis includes chronic lymphocytic thyroiditis, PTC Warthin-like variant and lymphoma
Cytology images

Contributed by Livia Florianova, M.D., M.Sc., Marc Pusztaszeri, M.D. and Manon Auger, M.D.C.M.
3D ball-like clusters

3D ball-like clusters

Protruding hobnail cells

Protruding hobnail cells

Squamous metaplasia

Squamous metaplasia

Cytological atypia

Cytological atypia

3D ball-like clusters

3D ball-like clusters

Psammoma body

Psammoma body


Cytological and architectural atypia

Cytological and architectural atypia

Cytological atypia

Cytological atypia

Cytological and architectural atypia

Cytological and architectural atypia

Psammoma bodies and lymphocytes

Psammoma bodies and lymphocytes

Nuclear features

Nuclear features

Psammoma bodies and lymphocytes

Psammoma bodies and lymphocytes

Positive stains
Molecular / cytogenetics description
Sample pathology report
  • Thyroid, left lobe, fine needle aspiration:
    • Satisfactory for evaluation
    • Malignant (Bethesda Diagnostic Category VI)
    • Papillary thyroid carcinoma, favor diffuse sclerosing variant
  • Thyroid, total thyroidectomy:
    • Papillary thyroid carcinoma, diffuse sclerosing variant (see synoptic report)
Differential diagnosis
  • Chronic lymphocytic thyroiditis (with squamous metaplasia)
    • No psammoma bodies
    • Reactive atypia; no well developed nuclear features of PTC
    • No solid clusters
    • No lymphovascular invasion or metastasis, unless it is associated with PTC
  • PTC Warthin-like variant
    • Usually one tumor mass instead of multiple tumor foci diffusely involving one or both thyroid lobes
    • Oncocytic tumor cells
    • Usually no solid clusters, psammoma bodies or squamous metaplasia
Board review style question #1

Which of the following statements is true about the diffuse sclerosing variant of papillary thyroid carcinoma (PTC)?

  1. Extrathyroidal extension and lymph node metastasis are usually not detected
  2. Not considered an aggressive type of papillary thyroid carcinoma
  3. Patients are usually older than those with classical papillary thyroid carcinoma
  4. Presents as a solitary thyroid nodule in which calcifications are infrequent
  5. Shows a high 10 year disease specific survival
Board review style answer #1
E. Shows a high 10 year disease specific survival. Despite being an aggressive variant of PTC with some adverse prognostic features, mortality rates are similar to those of classical PTC with 93% disease specific survival at 10 years.

Comment Here

Reference: Papillary thyroid carcinoma, diffuse sclerosing variant
Board review style question #2

What is the most common molecular alteration found in the diffuse sclerosing variant of papillary thyroid carcinoma?

  1. ALK translocation
  2. BRAF V600E mutation
  3. ETV6 / NTRK rearrangement
  4. RAS mutation
  5. RET / PTC rearrangement
Board review style answer #2
E. RET / PTC rearrangement. RET / PTC rearrangements are common (~ 60%), including RET / PTC1 (28 - 46%) and RET / PTC3 (14 - 16%). Overall, BRAF V600E is uncommon (0 - 24%), except in Korea (50 - 61%). ALK translocation is also uncommon (13%). RAS mutation and ETV6 / NTRK rearrangement have not been reported in diffuse sclerosing variant of papillary thyroid carcinoma.

Comment Here

Reference: Papillary thyroid carcinoma, diffuse sclerosing variant
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