Thyroid & parathyroid
Other thyroid malignancies
Langerhans cell histiocytosis


Topic Completed: 1 June 2021

Minor changes: 1 June 2021

Copyright: 2014-2021, PathologyOutlines.com, Inc.

PubMed Search: Langerhans cell histiocytosis[TI] thyroid

Jijgee Munkhdelger, M.D., Ph.D.
Andrey Bychkov, M.D., Ph.D.
Page views in 2020: 300
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Cite this page: Munkhdelger J, Bychkov A. Langerhans cell histiocytosis. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/thyroidlch.html. Accessed August 2nd, 2021.
Definition / general
  • Langerhans cell hystiocytosis (LCH) is a clonal neoplastic proliferation of langerin / CD1a / S100 positive dendritic cells (Langerhans-like cells)
    • LCH cells initially thought to arise from the epidermal or mucosal derived Langerhans cell due to the morphologic, immunophenotypic and ultrastructural similarities; however, gene expression profiling showed that LCH cells are not derived from terminally differentiated Langerhans cells but rather share a closer kinship with dendritic cells of the bone marrow (Blood 2017;130:176)
  • Thyroid involvement is rare
    • 100+ morphologically verified cases published as case series and case reports
  • Can occur as a primary disease or secondary involvement in systemic disease
Essential features
  • Rare histiocytic neoplasm with occasional involvement of thyroid, either a part of systemic dissemination or isolated
  • Proliferation of LCH cells (CD1a / S100 / langerin positive histiocytes with convoluted nuclei) on inflammatory, typically eosinophil rich background
Terminology
  • Not recommended / obsolete terminology:
    • Morphological: eosinophilic granuloma; histiocytosis X
    • Clinical: Hand-Schüller-Christian disease; Letterer-Siwe disease
ICD coding
  • ICD-O:
    • 9751/1 - Langerhans cell histiocytosis, NOS
    • 9751/3 - Langerhans cell histiocytosis, disseminated
Epidemiology
  • Isolated thyroid involvement is extremely rare
  • Secondary involvement is more common
  • LCH incidence: 5 - 9 per million children, 1 - 2 per million adults (Blood 2020;135:1319)
  • Age range: 2 months to 55 years
    • Childhood onset and adult onset LCH
    • Young age (< 20 years) at initial presentation in systemic disease, older age in isolated disease (Endocr Pathol 2002;13:227)
  • Slight male predilection (Br J Haematol 2016;174:887)
Sites
Pathophysiology
Etiology
Diagrams / tables

Images hosted on other servers:
Risk factor model Risk factor model

Risk factor model

Clinical features
  • Diffuse enlargement or unilateral thyroid nodule
  • Commonly associated with Hashimoto thyroiditis
  • Presenting features of systemic LCH are variable and depend on the index organ involved: bone pain, fracture, skin rash, lymphadenopathy, diabetes insipidus and more (Blood 2020;135:1319)
Diagnosis
  • Fine needle aspiration cytology aided by immunostaining
    • If immunocytochemistry is not available, immunostaining in suspicious cases can be performed on core needle biopsy
  • Histologic evaluation of surgical specimen, if surgery performed
  • History of systemic LCH in multiorgan disease
Laboratory
Radiology description
  • Cold nodule on thyroid scan
  • Ultrasonography: heterogeneous or hypoechoic mixed density nodules (Int J Clin Exp Pathol 2014;7:1229)
    • Nonspecific
  • Increased uptake on FDG-PET
Radiology images

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Ultrasound

Ultrasound

MRI

MRI

FDG-PET

Prognostic factors
Case reports
Treatment
Gross description
  • Focal of diffuse involvement
  • Variable sized nodules
  • Similar to other noncystic thyroid nodules
Microscopic (histologic) description
  • Nodular or diffuse proliferation of LCH cells
  • LCH cells characteristic of disease are histiocytoid cells recognized by their grooved, convoluted, indented or lobed nuclei (Arch Pathol Lab Med 2015;139:1211, Thyroid 2001;11:697, Mod Pathol 1996;9:145)
    • Nuclear appearance is often described as resembling coffee beans, horseshoes or kidneys
    • Nuclear atypia is absent or minimal
    • Mitoses variable, not correlated with aggressiveness
    • Cytoplasm is moderately abundant and slightly eosinophilic
    • Unlike epidermal Langerhans cells, LCH cells are oval in shape and devoid of dendritic cell processes
  • Typical background includes eosinophils with a variable amount of neutrophils, lymphocytes and occasional multinucleated giant cells
    • Rarely, eosinophilic abscesses may be formed
  • Temporal trend
    • In early lesions, LCH cells predominate, along with eosinophils and neutrophils
    • In late lesions, the LCH cells are decreased in number, with more foamy macrophages and increased fibrosis
    • In most cases, at least some LCH cells can be found
  • Effacement of the surrounding thyroid parenchyma due to infiltration of thyroid follicles by LCH cells
  • Chronic lymphocytic thyroiditis is common
  • Neoplastic cells can extend beyond thyroid capsule and occasionally spread to cervical lymph nodes (Case Rep Pathol 2014;2014:184237)
  • Thyroid carcinoma may coexist and even collide with LCH (Endocr Pathol 2010;21:274, Case Rep Pathol 2014;2014:184237)
Microscopic (histologic) images

Contributed by Somboon Keelawat, M.D. and Jijgee Munkhdelger, M.D., Ph.D.
Discrete nodule

Discrete nodule

Eosinophils

Eosinophils

Follicular stuffing

Follicular stuffing

LCH cells

LCH cells

LCH cells and eosinophils

LCH cells and eosinophils


Langerin

Langerin

CD1a

CD1a

Thyroglobulin

Thyroglobulin

Virtual slides

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Thyroid LCH

Thyroid LCH

Cytology description
Cytology images

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FNA smear FNA smear

FNA smear

S100 and CD1a

S100 and CD1a

Positive stains
Negative stains
Electron microscopy description
  • Birbeck granules are characteristic cytoplasmic inclusions (Blood 2020;135:1319)
    • Rod to flask to tennis racket shaped
    • 200 - 400 nm long x 33 nm wide
    • Zipper-like appearance due to a median striated line
  • Electron microscopy is less often used today
    • Replaced by immunostains
    • Birbeck granules present in a variable percentage of LCH cells
Electron microscopy images

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Birbeck granules Birbeck granules

Birbeck granules

Molecular / cytogenetics description
Sample pathology report
  • Thyroid gland, total thyroidectomy:
    • Histiocytic proliferation with eosinophil rich inflammatory background, consistent with Langerhans cell histiocytosis (see comment)
    • Comment: The immunohistochemical stains are positive for CD1a / S100 and negative for thyroglobulin in the histiocytes. These findings support the above diagnosis. Clinical correlation (history, systemic involvement) is recommended.
Differential diagnosis

Differential diagnosis of thyroid LCH
Entity Potential pitfall Morphological hallmark IHC profile
Rosai-Dorfman disease Histiocytic origin; S100+ Histiocytes with emperipolesis CD1a-, CD207-
Lymphoma Lymphocyte rich neoplasm Monotonous proliferation of atypical lymphoid cells B or T lineage markers+;
CD1a-, CD207-
Papillary thyroid carcinoma Grooved and indented nuclei; BRAF mutation Papillary and follicular patterned epithelial tumor TTF1 / Tg+;
LCH immunophenotype-
Hashimoto thyroiditis Lymphocyte rich background obscuring LCH cells Lymphocytic infiltration LCH immunophenotype-
Anaplastic thyroid carcinoma Unusual morphology Marked pleomorphism LCH immunophenotype-
Board review style question #1

What is a widely used IHC marker for Langerhans cell histiocytosis?

  1. CD1a
  2. CD20
  3. Cytokeratin
  4. Thyroglobulin
  5. TTF1
Board review style answer #1
Board review style question #2
What is the most common molecular alteration in Langerhans cell histiocytosis?

  1. BRAF V600E mutation
  2. EGFR mutation
  3. RAS family mutations
  4. TERT promoter mutation
  5. TP53 mutation
Board review style answer #2
A. BRAF V600E mutation

Comment Here

Reference: Langerhans cell histiocytosis
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