1.

4
CPC#2: Thyroid Gland: Follicular Adenoma
June 2015
Group 4
OUTLINE
I. Normal Anatomy and Histology
a. Anterior Triangle of the Neck
b. Thyroid Gland
i. Gross
ii. Histology
II. Case
a. Clinical History
b. Case Slides
c. Salient Features of the case
d. Approach to Diagnosis
e. Differential Diagnosis
i. Nodular Hyperplasia
ii. Follicular Variant Of Papillary Thyroid Carcinoma
iii. Minimally Invasive Follicular Carcinoma
iv. Hurthle Cell CA
v. Follicular Adenoma
f. Diagnosis
g. Management

NORMAL ANATOMY & HISTOLOGY

ANTERIOR TRIANGLE OF THE NECK

 Boundaries:
o Anterior: Midline of the neck  Common carotid artery
o Posterior: Anterior border of sternocleidomastoid o Passes through the anterior triangle, and bifurcates within the
o Superior: Lower margin of the body of the mandibles triangle into the external and internal carotid arteries.
 Internal jugular vein
o Drains blood from the head and neck
 Cranial nerves
o Facial [VII]
o Glossopharyngeal [IX]
o Vagus [X]
o Accessory [XI]
o Hypoglossal [XII]

NERVE SUPPLY
 comes from the right and left recurrent laryngeal nerves which
arise from the vagus nerve
o These nerves innervate all the intrinsic muscles of the larynx
EXCEPT for the cricothyroid muscles (innervated by the
external laryngeal nerves)
 The superior laryngeal nerves also arise from the vagus nerves.
o The internal branch of this nerve is sensory to the
supraglottic larynx
o external branch innervates the cricothyroid muscle

THYROID GLAND
GROSS

 Contains muscles, nerves, arteries, veins and lymph nodes

 the muscles in this part of the neck are divided as to where they lie
in relation to the hyoid bone:

Four suprahyoid muscles Four infrahyoid muscles

 Stylohyoid  Omohyoid
 Digastric  Sternohyoid
 Mylohyoid  Thyrohyoid
 Geniohyoid  Sternothyroid

 Located in the anterior portion of the neck

 Adult thyroid gland is a highly vascular, butterfly-shaped,
approximately 5cm by 5cm

Advento, Bautista, Bituin, Fabros 1 of 6

SURGICAL PATHOLOGY: THYROID CASE: FOLLICULAR ADENOMA 1.4

 Thyroid gland has a right lobe and left lobe connected by a narrow FOLLICULAR (PRINCIPAL) CELLS
isthmus  squamous to low-columnar in shape and are tallest when
o In approximately 50% of patients, another lobe, the stimulated
pyramidal lobe, may be present.  Active glands have more follicles of low columnar epithelium;
o The lobes extend up to the midthyroid cartilage superiorly glands with mostly squamous follicular cells are considered
lying adjacent to the carotid sheaths and laterally to the hypoactive
sternocleidomastoid muscles.  Secrete T4 and T3
 Normally, the thyroid gland weighs approximately 20g  Iodide is essential for the synthesis of the thyroid hormones;
o may vary according to a person’s body weight and iodine iodination occurs in the follicles at the colloid-follicular cell
intake interface
 A loosely connecting fascia derived from the partition of the deep
cervical fascia envelopes the thyroid gland. PARAFOLLICULAR CELLS
 The true capsule of the gland is a thin densely adherent fibrous
 a.k.a. C-cells
layer that sends out septa that invaginate into the gland forming
 Two to three times larger than follicular cells
pseudolobules that carry blood vessels, nerves and lymphatics.
 Pale-staining
 Secretes the hormones:
 Secrete calcitonin
o Thyroxine (T4) and triiodothyronine (T3): stimulate rate of
metabolism  Found individually or may form small clusters of cells at the
o Calcitonin: aids in decreasing blood calcium levels and periphery
facilitates the storage of calcium
 Composed of numerous spherical follicles
 The thyroid follicle is the structural and functional unit of the
thyroid gland

BLOOD SUPPLY
 superior thyroid arteries (arising from the external carotid
arteries)
 inferior thyroid arteries (arising from the thyrocervical trunk)
 thyroid ima artery (arising directly from the aorta; may be
innominate)

VENOUS DRAINAGE
 occurs via multiple small surface veins, which coalesce to form
three sets of veins
o superior & middle thyroid veins-(both drain directly into the
internal jugular vein)
o inferior thyroid veins (forms a plexus draining into the
brachiocephalic veins)

NERVE SUPPLY
 Sympathetic innervation of the thyroid gland comes from the
fibers of the superior and middle cervical sympathetic ganglia
while the parasympathetic fibers, on the other hand, are derived
from the vagus nerves.

HISTOLOGY

THYROID FOLLICLE
 Functional unit
 A spherical structure
 200 – 300 µm diameter
 Surrounded by a single layer of thyroid epithelial cells
 Consists of an outer simple epithelium of cuboidal follicular cells
 Encloses a central lumen filled with colloid (Figure 12 and 13)
 The hormones T4 and T3 are stored in the colloid, which is bound
to thyroglobulin

Advento, Bautista, Bituin, Fabros 2 of 6

SURGICAL PATHOLOGY: THYROID CASE: FOLLICULAR ADENOMA 1.4

CASE
CLINICAL HISTORY

The patient, D.T. is a 48 years old OFW from Samar with a 2-

year history of a 3 cm right sided, firm thyroid nodules. Clinical
impression is colloid goiter.

CASE SLIDES/DESCRIPTIONS

[D]
LPO

[A]
Scanner

[B]
Scanner
[E]
HPO
 (D) The solid tumor exhibiting distinct demarcation from the
collagenous thyroid capsule. No colloid noted.
 (E) Tumor cells are relatively monomorphic. No pseudoinclusions,
optical clearing, or grooves noted.

[C]
LPO

[F]
LPO

[G]
HPO

 (A&B) Thyroid with intact thick capsule.

 (A) Solid tumor penetrates the thyroid capsule. No extracapsular
extension noted.
 (C) Solid pattern of growth of the tumor with vascular invasion; no
extension of the tumor into the thyroid parenchyma. Normal
looking thyroid follicles. Hemorrhage is prominent.

 (F) Thyroid follicles containing hypereosinophilic colloid. No tumor

invasion observed. No significant lymphocytic infiltrate identified
 (G) Thyroid follicle containing hypereosinophilic colloid. Scalloping
(blue arrow) was noted. Follicular cells are cuboidal with
basophilic nucleus.

Advento, Bautista, Bituin, Fabros 3 of 6

SURGICAL PATHOLOGY: THYROID CASE: FOLLICULAR ADENOMA 1.4

SALIENT FEATURES OF THE CASE
 48 years old/Male
 2-year history of firm thyroid nodules, Right-Side
 Histologic examination (H and E Stain of the thyroid)
o The tumor was composed of a solid mass (non-cystic). The
tumor cells were relatively monomorphic.
o Vascular and capsular invasion without extracapsular
extension were observed.
o The tumor was well encapsulated by a thick fibrous capsule
with focal area of mushrooming
o Some areas of the thyroid capsule were noted to be thin.
o The thyroid parenchyma contained hypereosinophilic colloid
with prominent scalloping.
o Thyroid follicular cells with large, round, oval nuclei, abundant
cytoplasm without inclusion or grooves, or atypical cells.
o Lymphocytic infiltration was not identified. Hemorrhage was
prominent.
APPROACH TO DIAGNOSIS
 Hallmark: disturbed cytoarchitecture: follicular cells are
arranged predominantly in microfollicular or trabecular
arrangements
 Follicular cells are usually larger than normal
 Nuclear atypia or pleomorphism and mitoses are
uncommon
 A minor population of microfollicles can be present
CAT 5 Suspicious for Malignancy
 if only 1 or 2 characteristic features of PTC are present
 If they are only focal and not widespread throughout
the follicular cell population
 If the sample is sparsely cellular
CAT 6 Malignant
 Used whenever the cytomorphologic features are
conclusive for malignancy
 At least 6 groups of benign follicular cells are required for a thyroid
FNA specimen to be satisfactory for evaluation
o Each group is composed of at least 10 cells
o minimum size requirement for the groups allows one to
determine (by the evenness of the nuclear spacing) whether
they represent fragments of macrofollicles
 Exceptions to numeric requirement of benign follicular cells:
o specimen which contains abundant colloid is considered
adequate (and benign), even if 6 groups of follicular cells are
not identified, because a sparsely cellular specimen with
abundant colloid is, by implication, a predominantly
macrofollicular nodule, and, therefore, almost certainly
benign

DIFFERENTIAL DIAGNOSIS

NODULAR HYPERPLASIA
 Nodular hyperplasia is the most common thyroid disease and the
most common benign condition mistaken for a thyroid tumor.
 The thyroid undergoes a series follicular cell hyperplasia and
involution/hyperinvolution involving all of the lobules and causing
enlargement of the gland and formation of nodules.
 Gross: the thyroid with nodular hyperplasia is enlarged and its
shape distorted. The thyroid capsule may be stretched but is intact.
 Microscopic: there is a wide range of appearances. Vascularization
inside the nodules is usually prominent

RULE IN
Epid 48 y/o (more common in adults)
Gross Thyroid capsule may be stretched but is intact
Micro  Vascularization inside the nodules
 Follicular size is variable

RULE OUT
Epid Male>women
Gross  Thyroid enlarged and its shape distorted, one lobe being
frequently larger than the other
 On XS
o multiple nodules seen
o some surrounded by a partial or complete capsule
o Secondary changes in the form of hemorrhage,
calcification, and cystic degeneration are common
Micro  Presence of encapsulation
 Compression of adjacent structures
BETHESDA SYSTEM FOR REPORTING THYROID
 No Sanderson Polsters were seen in the actual slide.
CAT 1 Nondiagnostic or Unsatisfied  Follicles in the actual slide varied in size but are not largely
 Cystic fluid only dilated.
 Virtually acellular specimen  Epithelial cells lining the follicles are not flattened.
CAT 2 Benign  There are no hyperplastic nodules.
 Consistent with a benign follicular nodule
 An adequately cellular specimen composed of
varying proportions of colloid benign follicular cells FOLLICULAR VARIANT OF PAPILLARY THYROID CARCINOMA
arranged as microfollicle fragments  Papillary thyroid carcinoma (PTC) is the most common type of
CAT 3 Atypia of Undertermined Significance or Follicular Lesion malignant thyroid tumor constituting more than 70% of thyroid
of Undetermined Significance malignancies
 Not easily classified into the benign, suspicious, or  The cause of PTC is believed to be environmental, genetic, and
malignant categories hormonal in nature.
CAT 4 Follicular Neoplasm or Suspicious for a Follicular
Neoplasm

Advento, Bautista, Bituin, Fabros 4 of 6

SURGICAL PATHOLOGY: THYROID CASE: FOLLICULAR ADENOMA 1.4

 ret/PTC rearrangements are common in classic papillary thyroid RULE IN

carcinoma (PTC) and PAX8-PPARγ and ras mutations in follicular Epid 48 y/o (More common in adults, female)
thyroid carcinoma. Gross  Most grow well into the parenchyma in a multinodular
 FV cases demonstrated a significantly higher prevalence of tumor fashion
encapsulation, angiovascular invasion, and poorly differentiated  Most are well encapsulated throughout
areas and a lower rate of lymph node metastases. Micro  Pattern of growth can be follicular or solid
 FV of papillary carcinoma has a distinct set of molecular  Capsular Invasion and vascular Invasion may be prominent
alterations and is characterized by a high frequency of ras point
mutations (Zhu, 2014). RULE OUT
Epid
RULE IN Gross
Epid Median age is 44 years old Micro  Follicles are not separated by fibrous septa and do not form
Gross - papillary structures
Micro  presence of tumor cells arranged almost entirely in a  No inspissated intraluminal colloids or psamomma bodies
follicular pattern with the nuclear features identical to that of were seen
PTC  Tumor cells are relatively monomorphic with no inclusions.
 Strongly eosinophilic colloid with scalloped edges, and the No bizarre forms were seen
presence of abortive papillae
 Specimen showing a hypereosinophilic colloid and
scalloping. Clear cells and overlapping is absent DIAGNOSIS
FOLLICULAR ADENOMA
RULE OUT
 Follicular adenoma is the most common thyroid neoplasm
Epid Male (FVPTC is more common in women; F:M ratio is 6:1)
o Generally, patients with this type of lesion are euthyroid
Gross  can be quite variable – ranging from firm solid to cystic
and only presents with a thyroid lump or a solitary nodule.
 Some show dystrophic calcification and occasional bone
o The ratio of incidence of follicular adenoma is 5 times
formation.
greater than its malignant type; however it is more
 The size of the nodule ranges from minute (<1mm) to
common in females.
several centimeters and multicentricity is common.
o Patients with larger tumors may present with dyspnea,
Micro  hypereosinophilic colloid can be observed with scalloping
coughing or choking spells, hoarseness, or dysphagia as a
 overlapping of the nuclei, pseudoinclusions, and
psammoma bodies were not present result of compression of the trachea, recurrent laryngeal
nerve, or esophagus. They may complain of neck pain as a
result of sudden tumor enlargement from intratumoral
hemorrhage or cystic degeneration.
MINIMALLY INVASIVE FOLLICULAR CARCINOMA
o Rare patients may present with hyperthyroidism.
 Follicular carcinoma comprises about 10-15% of thyroid  Hyperthyroidism usually does not occur until the
malignancies with a female predilection (WHO, 2004). adenoma is greater than 3cm in size that is why
 Minimally invasive follicular carcinoma is a subtype of follicular there are no evident symptoms on the patient
carcinoma. except for the colloid goiter.
 Gross: the tumor is encapsulated with a pattern of growth that o It is surrounded by a thin fibrous capsule that is grossly or
resembles an adenoma, although a predominantly solid pattern of microscopically complete.
growth may be seen in some cases  Gross: It is firm, rubbery, homogenous, round or oval and benign
 The diagnosis of malignancy relies on capsular or vascular encapsulated tumor of the thyroid gland.
invasion. There must be full thickness of capsular invasion and the  Microscopic: It is simple to distinguish histologically, as its
blood vessel should be of venous calibre located immediately cytologic features are different from the surrounding gland and
outside the capsule rather than within the tumor. usually shows no signs of compression and is composed mainly of
 A tumor that has already invaded the original capsule occasionally follicles that are smaller than those of the normal gland. Nodular
has formation of a second or third capsule. hyperplasia can be eliminated in the fact that its capsule is
RULE IN incomplete, variable follicular size and largen than those in the
Epid 48 years old surrounding gland.
Gross Unifocal  Adenomas can be in various forms and may exhibit patterns singly
Micro  Solid growth pattern or in combination: normofollicular (simple), macrofollicular
 Capsular invasion (colloid), microfollicular (fetal), and trabecular/solid (embryonal)
 Vascular invasion (Rosai, et al).
 No invasion of adjacent thyroid parenchyma  General Rule: The larger the follicles, the less likely that the lesion
 Fairly uniform cells is a follicular adenoma or a follicular carcinoma.
 Nuclei lack features of typical papillary carcinoma
 Psammoma bodies are absent RULE IN
Epid 48 y/o (More common in adults, female)
RULE OUT Gross  Colloid Goiter
 Firm, encapsulated, bulges when fresh, compresses
Epid Male
adjacent thyroid
Gross Firm palpable nodules
 Variable size (1-10cm)
Micro
Micro  Solid pattern of tumor
 Architecturally and cytologically different from surrounding
HURTLE CELL CA gland, surrounding thyroid tissue shows signs of
 An oncocytic cell of the thyroid gland, which is inaccurately compression
designated as Hurthle cells is described as round cells with  Encapsulated
cytoplasmic granularity due to the accumulation of mitochondria.  Closely packed follicles, trabeculae or solid sheets
 The granularity has a deeply eosinophilic granularity in H&E  Round to Oval Monomorphic Cells showing no inclusions or
stained sections. grooves.
 Currently, the WHO Committee for Histological Typing of Thyroid  Capsular Mushrooming (Invasion)
Tumors do not view these tumors as a distinct type; rather, they  Vascular Invasion
place them in a specific existing tumor categories depending on
their type of growth.
RULE OUT
Epid Male
 However, Rosai and Ackerman thought otherwise based on the
biological and morphological characteristics of the tumor. Gross
Micro

Advento, Bautista, Bituin, Fabros 5 of 6

SURGICAL PATHOLOGY: THYROID CASE: FOLLICULAR ADENOMA 1.4

MANAGEMENT  High risk, based on patient factors (age >45 y, history of head
SURGICAL MANAGEMENT and neck radiation, family history of thyroid cancer)

The initial treatment for cancer of the thyroid is surgical. The RAI ablation is not recommended for the following:
exact nature of the surgical procedure to be performed depends for  Small (< 1 cm), solitary tumors
the most part on the extent of the local disease (Santacroce, 2015).  Multifocal tumors when all foci are < 1 cm
Primary considerations for surgery are the following:
 Size/diameter
 Extrathyroidal involvement or distant metastases THYROID-STIMULATING HORMONE (TSH) REPLACEMENT THERAPY
 Age of the patient (levothyroxine)
 Patient preference
 Nodal involvement  Thyroid hormone is ONLY given for treatment of hypothyroidism,
After FNA result and diagnostic procedures according to the which occurs in one third of patients following thyroid lobectomy
National Comprehensive Cancer Network (NCCN) guidelines, primary  This entails taking 2.5-3.5 mcg/kg of L-T4 every day.
treatment must be considered (NCCN guidelines, 2013). The primary  The thyroxine is given in the dose necessary to inhibit thyrotropin
treatment and their indications recommended by the guideline are to a value of 0.1-0.5 mU/L. This treatment plan is generally
the following: successful.
 However, a 10-year recurrence rate of 20-30% may be seen in older
Surgical management of thyroid tumors. patients, in patients with primary tumors greater than 4 cm in
RECOMMENDED diameter, and in patients where tumor has spread beyond the
INDICATION
TREATMENT thyroid boundaries and where lymph node involvement is
Total  Primary tumor is more than 1 cm in widespread.
Thyroidectomy diameter.  Adverse effects include:
 If there is extrathyroidal involvement and o Atrial fibrillation
distant mestastases o Osteopenia
 Patient preference ( patient wishes to avoid o Anxiety
a second completion thyroidectomy should o Other manifestations of thyrotoxicosis.
the pathologic review reveals cancer
[Santacrose, 2015])
Central Neck  Clinically apparent (ultrasound detected) FOLLOW UP
Dissection /biopsy proven disease
(Level VI)  If lymph node involvement is positive  A serum TSH level is obtained 4–6 weeks after surgery to assess
for hypothyroidism.
Lateral Neck  Same indication as CND (Level VI)  A yearly neck examination, cervical ultrasound exam, and a
Dissection  Preservation of cervical sensory nerves must screening serum TSH level are recommended for follow-up.
(Levels II, III, IV, be considered
Vb, include level
I and Via if
clinically
involved)
Lobectomy plus  Invasive cancer (extensive vascular invasion)
isthmusectomy  Minimally invasive cancer
 Benign tumor
 Papillary carcinoma

 Thyroid lobectomy and isthmusectomy is definitive treatment

for patients with a benign follicular adenoma and patients with
minimally invasive follicular cancer.

MEDICAL TREATMENT
(NCCN Guidelines, 2013)

Patients with a final diagnosis of follicular adenoma require no

additional therapy. Surgery, may be followed by treatment with
radioiodine and thyroxine therapy.

RADIOACTIVE IODINE ABLATION

Postoperative whole-body scintigraphy scan may identify

previously unrecognized disease and influence staging. If residual
disease is found, adjuvant therapy with radioactive iodine (RAI) may
be considered. Ablation of residual normal thyroid tissue facilitates
early detection of recurrence based on serum thyroglobulin
measurement and/or RAI whole-body scan.

RAI ablation is indicated for patients with any of the following:

 Large (>4 cm) tumors
 Known distant metastasis
 Gross extrathyroid extension

RAI ablation may be considered for tumors with the following

characteristics:
 Moderate-size (1-4 cm) and node positive
 Grossly multifocal
 Aggressive, based on histology

Advento, Bautista, Bituin, Fabros 6 of 6