Granulomatous

Inflammation of
Thyroid
By Kamlesh
Prajapati

Topics include :
Anatomy and Histology
Brief about Granuloma
Causes of granulomatous inflammation
in thyroid gland
All Specific entities

Anatomy- Thyroid gland

The thyroid gland is located in the anterior neck
region
adjacent to the larynx and trachea.
The thyroid gland is a bilobate endocrine gland
consists of two large lateral lobes connected by
an isthmus, a thin band of thyroid tissue.
The two lobes, each approximately 5 cm in
length, 2.5 cm in width, and 20 to 30 g in weight,
lie on either side of the larynx and upper trachea.

 The isthmus crosses anterior to the upper part of

the trachea. A pyramidal lobe often extends
upward from the isthmus.
A thin connective tissue capsule surrounds the
gland. It sends trabeculae into the parenchyma
that partially outline irregular lobes and lobules.
The thyroid gland develops from the endodermal
lining of the floor of the primitive pharynx.

Histology
The thyroid follicle is the structural and functional
unit of the thyroid gland.
A thyroid follicle is a roughly spherical cyst like
compartment with a wall formed by a simple
cuboidal or low columnar epithelium, the follicular
epithelium.
Hundreds or thousands of follicles that vary in
diameter from about 0.2 to 1.0 mm constitute
nearly the entire mass of the human thyroid
gland.

H E stain section
shows the colloidcontaining follicles
of the gland. Each
follicle consists of a
single layer of
epithelial cells
surrounding a
central mass of
colloid.
(Normal thyroid
follicle)

Granuloma ?
Pathophysiology
Is a type of chronic inflammation
Neutrophils usually remove agents that initiate an
acute inflammatory response by phagocytosis and
digestion. If an agent is indigestible, it provokes a
vicious cycle of acute inflammatory responses that
can cause local tissue damage.
The body deals with these reactions by forming
granulomas.

 The principle cells involved in granulomatous

inflammation are macrophages and
lymphocytes.

Macrophages live longer than neutrophils and

can phagocytose an indigestible agent. This
causes macrophage to lose their motility and
thus accumulate at the site of injury.

 Macrophages undergo structural changes and

become epithelioid cells (larger with more
cytoplasm, resemble epithelial cells).
These cells (50+) can fuse together and form
multinucleated giant cells. Lymphocytes
surround these cells. When the nuclei of these
giant cells form a horse show pattern, the cell is
named a Langhans Giant Cells.

Causes

Granulomatous (de Quervain) thyroiditis

Palpation thyroiditis
Tuberculosis
Sarcoidosis
Mycoses of various types
Postoperative
Histiocytic reaction to hemorrhage
Other causes of granuloma

 Granulomatous (de
Quervain) thyroiditis
Clinical Presentaion :
middle-aged women
Present with sore throat, painful deglutition, and
marked tenderness on palpation in the thyroid
region, often associated with fever and malaise.
Once the initial process has subsided, pressure
symptoms and/or mild hypothyroidism may
develop.

 Pathogenesis.
Granulomatous thyroiditis is believed to be triggered

by a viral infection.

The majority of patients have a history of an upper

respiratory infection just before the onset of
thyroiditis.
The disease has a seasonal incidence, with
occurrences peaking in the summer, and clusters of
cases have been reported in association with
coxsackie virus, mumps, measles, adenovirus, and
other viral infections.

 Although the pathogenesis of the disease is

unclear, one model suggests that it results from a
viral infection that leads to exposure to a viral or
thyroid antigen secondary to virus-induced host
tissue damage.
This antigen stimulates cytotoxic T lymphocytes,
which then damage thyroid follicular cells.
In contrast to autoimmune thyroid disease, the
immune response is virus-initiated and not selfperpetuating, so the process is limited.

 However, in the majority of cases there is

complete resolution. Because of the sometimes
asymmetric involvement of the gland, the disease
may be clinically confused with carcinoma.
Elevated serum levels of T4 and T3
complete suppression of 131I uptake are typical of
the initial phase of this disease.
associated with the HLA-B35 haplotype.

 Grossly, the process usually involves the entire

gland, but the enlargement is often asymmetric.

In a typical case, the gland is enlarged to

approximately twice its normal size.
In the advanced stage, the involved areas are
firm.

 Microscopically, areas of marked inflammation

and granulomas containing foreign body giant
cells are present.

It is characteristic for these granulomas to

surround follicles and for the multinucleated
giant cells (most of which are of histiocytic
nature) to engulf colloid.
The granulomas are not very distinct, and
caseation necrosis is consistently absent.

The thyroid parenchyma contains a chronic

inflammatory infiltrate with a multinucleate giant
cell and a colloid follicle.

 Strong immunoreactivity for CA19-9 is found in

the late stage of the disease, whereas positivity
for CEA in the center of the granuloma is a
feature of the acute stage.

Cytological findings :

Diagnostic criteria

Multinucleate giant cells with numerous nuclei,

phagocytosed colloid,
Granulomatous aggregates of epithelioid cells,
Degenerating follicular cells, paravacuolar
granules,
Dirty smear background with cell debris, colloid,
neutrophils, lymphocytes and macrophages.

Huge multinucleate histiocytic giant cells, dirty

background of clumps of colloid, inflammatory
cells and degenerate epithelial cells

Mixed cell reaction; histiocytes, degenerating

epithelial cells and lymphocytes in a dirty
background with thin colloid

Large multinucleated giant cells; clumps of thick,

engulfed colloid (MGG, IP)

 Palpation thyroiditis
Palpation thyroiditis is the term that has been
proposed for a relatively common, clinically
insignificant, and grossly inconspicuous thyroid
process (also known as multifocal
granulomatous folliculitis).
In which collections of histiocytes (some of them
foamy), lymphocytes, and a few multinucleated
giant cells are seen within the lumen of
scattered thyroid follicles .

 In some of these follicles, the inflammatory

infiltrate disrupts the epithelium and extends
into the perifollicular region. These changes bear
no relationship to granulomatous (de Quervain)
thyroiditis.
Rather, they seem to be the result of minor
trauma to the gland, sometimes spontaneous
and sometimes thought to be induced by
vigorous palpation on physical examination,
hence the term palpation thyroiditis.

Palpation thyroiditis

 Tuberculosis
Tuberculosis of the thyroid gland is an extremely
rare disease. According to the literature, the
frequency of thyroid tuberculosis is 0.1%0.4%.
Extrapulmonary tuberculosis may have different
clinical manifestations and may be difficult to
diagnose.
In the thyroid gland, the tuberculous involvement
may be in two main forms. First, which is more
common, is miliary spread to the thyroid gland as a
part of generalized dissemination.

 Less common is focal caseous tuberculosis of

thyroid, presenting as a localized swelling
mimicking carcinoma, as cold abscess appearing
superficially, as multinodular goiter, or very rarely
as an acute abscess.
Thyroid tuberculosis can also manifest itself as a
common thyroid nodule or lump or as a nodule
with a cystic component.
The clinical presentation is often subacute, but it
may be acute in case of abscess or thyroiditis .

 The hypothyroidism is caused by extensive

glandular destruction by caseous necrosis.
In the literature, only three cases of
hypothyroidism due to thyroid TB have been
reported yet .
A past history of tuberculosis concomitant with
cervical lymphadenopathy and the sites of
tuberculous involvement might lead to the
correct clinical diagnosis.

 If mycobacterial infection is suspected, a chest Xray

and a tuberculin skin test (PPD) should be performed.
The diagnosis is made only after fine-needle
aspiration cytology (FNAC) or after histopathological
examination of the surgical specimen when FNAC is
negative.
The characteristic histological findings include
epithelioid cell granulomas with central caseous
necrosis, peripheral lymphocytic infiltration, and
Langhans giant cells.

 The simultaneous demonstration of acid fast

bacilli (AFB) makes diagnosis almost certain. In
this situation, a mycobacterial culture is helpful.

Tuberculosis

Smears examined show degenerated

inflammatory cells in a necrotic background.

Ziehl Nelson staining

 Initially, treatment of thyroid tuberculosis consisted of

antituberculous drugs combined with surgical removal
of the affected parts of the thyroid gland or surgical
drainage .
Now, it has been recognized that complete resolution
usually follows an appropriate antituberculous drug
treatment only .
But in cases with large abscess, surgical drainage or
resection followed by antituberculous treatment is
considered as sufficient, and further surgery is rarely
required.

 Sarcoidosis
Thyroid sarcoidosis is rarely diagnosed in vivo,
although non-caseating granulomas are found
post-mortem in up to 4.5% of sarcoidosis
patients.
In clinically significant thyroid sarcoidosis,
abnormalities in respect to gland morphology
(i.e., nodules, goiter, thyroiditis) and function
(hypo- and hyperthyroidism) may be isolated or
combined.

 A different criterion for categorizing thyroid

sarcoidosis patients is the involvement of other
organs; in this respect, concomitant sarcoidosis
manifestation in the lungs is more frequent than
isolated thyroid infiltration.

The sarcoid involvement of the thyroid remains

clinically insignificant. The emergence of gland
disorders (change in function or morphology) is not
associated with pain. The process is mild and
frequently leads to hypothyroidism.

 However, sporadically, sarcoidosis can cause pain

and compression symptoms, and may coexist with
thyroid cancer.
One should also bear in mind that papillary thyroid
carcinoma may cause a sarcoid-type reaction in
the gland. Therefore, in patients with suspected
thyroid sarcoidosis, thorough diagnosis and
observation are necessary.
Often, particularly due to the diagnostic
difficulties, surgery is indicated.

 Mycoses
Mycoses of various types have been described,
most of them occurring in immunocompromised
hosts.
In many of these cases, the tissue changes are
characterized by necrosis and acute inflammation
rather than granuloma formation.
Although it would be expected that fungal
infection would produce granulomatous reactions
in the thyroid, most instances show an acute
necrotizing reaction or no reaction at all.

 Since the patients with fungal thyroiditis

frequently are immunosuppressed, the
appropriate reaction may be lacking.
Two fungal infections, one is coccidoidomycosis
and second is actinomycoses whose clinical
symptoms resemble sub acute thyroiditis.

 Actinomycoses
Actinomyces species are a very rare cause of
acute suppurative thyroiditis. There is a rare case
of actinomycotic thyroiditis in Korean literature.
In which 23 year old young adult man with
pyriform sinus fistula presented with general
weakness and neck pain.
Thyroid ultrasonography showed an ill-defined
area of heterogeneous hypoechogenicity in the
left lobe of the thyroid gland.

The cytological smear shows characteristic sulfur

granules.

 Postoperative
necrotizing granuloma
Rare, occur in less than 0.5 % of surgical cases.

Postoperative necrotizing granulomas,

vaguely simulating rheumatoid nodules and
morphologically similar to those more commonly
seen in the prostate and bladder, have been
observed within the thyroid.

 Postoperative necrotizing thyroiditis is related to

a trauma of the thyroid, through vigorous
manipulation of the gland at surgery.
It could be through repeated fine needle
aspiration.
Such manipulation could induce an acute
thyroiditis, which in turn may lead to
thyrotoxicosis or to a necrotizing thyroiditis.

 Histiocytic reaction to
hemorrhage
In adenomatous nodules, occasionally in
neoplasms, and in nodular goiters, hemorrhage and
an associated inflammatory response are seen.
A macrophage reaction near areas of hemorrhage
and inflammation is usual. Often the histiocytic
contain cytoplasmic iron.
These areas are usually focal in a gland showing
another lesion (nodule, tumour, etc.) and should
not present diagnostic problems for the pathologist.

 Foreign body giants cells can be seen in

common thyroid lesions : around hemorrhage
and cholesterol debris in nodular goiter, in
papillary carcinomas and in chronic lymphocytic
thyroiditis.
The findings of giant cells in FNA cytology
sample may raise the diagnostic differential of
subacute thyroiditis versus chronic lymphocytic
thyroiditis.

 However, in chronic thyroiditis giant cells are

few, and numerous lymphocytes and oncocytes
are found.
The pattern in subacute thyroiditis is usually
one of acute inflammatory cells and
mononuclear as well as multinucleated
histiocytes.

 Other causes of
granulomas in thyroid
Granulomatous vasculitis : Vessels in the thyroid
may be involved in systemic vasculitides.
Foreign material : Foreign material occasionally
find its way to the thyroid via a lymphatic route.
( Ex. Patient with (Teflon) implants for vocal cord
paralysis.

REFERENCES
Ross Histology Text and atlas 6th edition
Rosai and Ackermans surgical pathology, 9e
and 10th edition.
Sternbergs Diagnostic surgical pathology, 5th
and 6th edition.
Robbins and Cotran pathological basis of
disease, 9e edition
Orell & Sterretts Fine needle aspiration
biopsy 5th edition
Pathology of thyroid lesion, Major problem in
pathology series.

 Uzma Majid and Najmul Islam .Thyroid Tuberculosis:

A Case Series and a Review of the Literature Journal
of Thyroid Research Volume 2011, Article ID 359864
Piotr Kmie1, Marta Lewandowska : Two cases of
thyroid sarcoidosis presentation as painful,
recurrent goiter in patients with Graves disease
;Endocrinol Metab. 2012;56/3
Hyun Ju Choi,Bo Won Kim,Min Ji Shin A Case of
Actinomycotic Thyroiditis in an Adult with Piriform
Sinus Fistula :,Endocrinol Metab. 2012
Sep;27(3):222-226.