Lect 5 Thyroid Tumor

8/3/2019 Lect 5 Thyroid Tumor

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Pathology of the Thyroid

Gland

SMS 2023BY

Dr. Mohanad



Diseases of the Thyroid

Gland

• Congenital diseases

• Inflammation

• Functional abnormality• Diffuse and Multinodular goiters

• Neoplasia



Thyroid Neoplasms

I. Primary Tumours

• Epithelial

• Malignant Lymphomas

• Mesenchymal tumours

II. Metastatic Tumours



Solitary thyroid nodule

• Papillary carcinoma

• Follicular carcinoma

• Medullary carcinoma

• Follicular adenoma

• Hyperplastic (dominant) nodule

• Metastatic neoplasms

• FINE NEEDLE ASPIRATION CYTOLOGY



Typical Presentation of

Thyroid Cancer

• Painless lump

• Normal thyroid function tests

• Found on routine examination or by the patient

• Slow growth or no growth over several months

• Most thyroid cancers present in clinically euthyroid patients

who have normal thyroid function tests.

• These tests, including those measuring thyroid stimulating

hormone (TSH), thyroxine (T4), and triiodothyronine (T3),

are measurements of the functional status of the thyroid and

provide no information on the presence or absence of

structural disease of the thyroid (eg, nodules).



Epithelial Thyroid Neoplasms

• Tumours of follicular cells

Benign (adenomas)

• Follicular adenoma Malignant (carcinomas)

• Follicular carcinoma (10-20%)

• Papillary carcinoma (75-85%)

• Undifferentiated (anaplastic) carcinoma (<5%)

• Tumours of C-cells

Medullary thyroid carcinoma (MTC - 5%)



Types of Thyroid Cancer

• Papillary (80%-85%): develops from thyroid follicle cells in 1 or

both lobes; grows slowly but can spread

• Follicular (5%-10%): common in countries with insufficient

iodine consumption; lymph node metastases are uncommon

• Medullary: develops from C-cells, can spread quickly; sporadic

and familial types

• Anaplastic: develops from existing papillary or follicularcancers; aggressive, usually fatal

• Lymphoma: develops from lymphocytes; uncommon



Follicular Adenoma

• Benign, encapsulated tumor showing

evidence of follicular differentiation

• Common

• Predominantly young to middle women

• Presents as solitary thyroid nodule

• Painless nodular mass, cold on isotopic scan



Follicular Adenoma

Solitary, Variably

sized,

encapsulated, well-circumscribed with

homogenous gray-

white to red-brown

cut-surface+/- degenerative

changes



• Hemorrhage

• Oedema

• Fibrosis• Calcification

• Bone formation

(ossification)• Cystic degeneration



Follicular Carcinoma

• Second most common form, 10-20%

• Females > Males, average age ~ 45 - 55 yr

• Rare in children

• Solitary nodule, painless, cold on isotopic scan

• Widely invasive Vs minimaly invasive• 50% 10 yr survival Vs 90%10 yr survival

• Haematogenous route is preferred mode of spread



Follicular Carcinoma

• Solitary round or oval

nodule

• Thick capsule• Composed of follicles

• Capsular invasion or

vascular invasion

within our outsidecapsular wall



• Well-formed follicles

• Poorly-formed follicles

• Cribiform area

• Trabecular formations

• Predominantly solid growth

pattern

• Cytoplasmic clear changes

• Mitotic activity & nuclear

atypia



Follicular Thyroid Cancer

Solid invasive tumors,

usually solitary and

encapsulated

Usually stays in the thyroid

gland, but can spread to the

bones, lungs, and central

nervous system

Usually does not spread tothe lymph nodes Follicular Thyroid

Cancer



Follicular Thyroid Cancer

Diagnosis and Prognosis

• Most FTCs present as an asymptomatic neck

mass

• If caught early, this type of thyroid cancer isoften curable

Tumors >3 cm have a much higher mortality rate



Papillary Carcinoma

• Commonest thyroid malignancy, 75-85%

• Female:Male = 2.5:1

• Mean age at onset = 20 - 40 yr

• May affect children

• Prior head & neck radiation exposure

• Indolent, slow-growing painless mass cold on

isotopic scan• Cervical lymphadenopathy may be presenting

feature



Papillary Carcinoma

• Variable size (microscopic

to several cm)

• Solid or cystic• Infiltrative or encapsulated

• Solitary or multicentric

(20%)



Papillary Thyroid Cancer

Characteristics

Unencapsulated tumor nodule with ill-defined margins

Tumor typically firm and solid

May present as nodal enlargement

Commonly metastasizes to neck and mediastinal lymphnodes

40% to 60% in adults and 90% in children

<5% of patients have distant metastases at time of

diagnosis

Lung is most common site



Papillary Carcinoma

• Papillae or follicles

• Psammoma bodies

• NUCLEAR

FEATURES***



Papillary Carcinoma

Nuclear Features

Optically clear (groundglass, Orphan Annie

nuclei)

Nuclear

pseudoinclusions or

nuclear grooves

Nuclear

microfilaments



This illustrative cell group shows cardinal features of papillary

carcinoma: nuclear grooves and pseudoinclusion



Lymph node with metastasis of papillary thyroid carcinoma

(middle/bottom of image)



Papillary Carcinoma

Prognosis

Excellent but following factors play importantrole: Age and sex

Size

Multicentricity

Extra-thyroid extension

Distant metastasis Total encapsulation, pushing margin of growth

& cystic change



Anaplastic Carcinoma

• Rare; < 5% of thyroid carcinomas

• Highly malignant and generally fatal < 1yr.

• Elderly ≈ 65 yrs; females slightly > males

• Rapidly enlarging bulky neck mass

• Dysphagia, dyspnoea, hoarseness




Large, firm, necrotic mass

Frequently replaces entire thyroid glandExtends into adjacent soft tissue, trachea

and oesophagus

Highly anaplastic cell on histology with: Giant, spindle,small or mix cell population

Foci of papillary or follicular differentiation




• Cellular pleomorphism

• +/- multinucleated giantcells

• High mitotic activity

• Necrosis




• Cellular variants

Squamoid

Spindle clee

Giant cell *Paucicellular

• 1. Neutrophilic infiltration

• 2. Prominent vascularization

• 3. Cartilaginous/osseous metaplasia

• Patterns of growth

Fascicular

Storiform

Palisading at the necrotic edges





Medullary Thyroid Carcinoma

(MTC)

• Malignant tumour of thyroid C cells

producing cacitonin

• 5 % of all thyroid malignancies

• Sporadic (80%)

• Rest in the setting of MEN IIA or B or as

familial without associated MEN syndrome




(MTC)

Sporadic MTC

Middle-aged adults Female:male = 1.3:1

Unilateral involvement of gland

+/- cervical lymph node metastases Indolent course with 60-70% 5-yr survival after

thyroidectomy



Multiple Endocrine Neoplasia

Types IIA & IIB

• Germ-line mutation in Ret protooncogene on

chromosome 10q11.2

• MEN IIA: MTC, phaeochromocytoma,

parathyroid adenoma or hyperplasia

• MEN IIB: MTC, phaeochromocytoma, mucosal

ganglioneuromas, Marfanoid habitus, other

skeletal abnormalities

C




(MTC)

Associated with MEN IIA

Younger patients in twenties

Multicentric and bilateral Slow growing

Associated with MEN IIB

Even younger patients in teens Aggressive with early metastasis

Poor prognosis

M d ll Th id C



Medullary Thyroid Cancer

Metastases

• Cervical lymph node metastases occur early

• Tumors >1.5 cm are likely to metastasize, often to

bone, lungs, liver, and the central nervous system

• Metastases usually contain calcitonin and stain for

amyloid



Gross:(MTC)

• solid, firm & non-encapsulated

but well circumscribed

• Continuous fibrous capsule (rare)• Located in the midportion of upper half of

the gland

• Corresponding to a greater concentration of C-cells



Medullary carcinoma of the thyroid

(MTC) is a distinct thyroid carcinoma

that originates in the parafollicular C

cells of the thyroid gland.

These C cells produce calcitonin.

MTC has a genetic association with

multiple endocrine neoplasia (MEN)

type 2A an



Medullary Thyroid Carcinoma (MTC)

• Histology same for

sporadic & familial

• Solid, lobular or

insular growth

patterns

• Tumour cells round,

polygonal or spindle-shaped

• Amyloid deposits in

many cases

M d ll Th id C i




(MTC)

• Medium sized nucleus

• Highly vascular

stroma

• Hyalinized collagen

Coarse calcification

• Amyloid deposits stain

orange-red withCongo Red stain



Hürthle Cell Cancer

• A variant of follicular

cancer that tends to be

aggressive

• Represents about 3% to 5%

of all types of thyroid cancer

High power magnification

Hü thl C ll C



Hürthle Cell Cancer

Prognosis

• May be benign or malignant, based on

demonstration of vascular or capsular

invasion

• Malignancies tend to have a worse

prognosis than other follicular tumors and

rarely respond to 131I therapy

• Tend to be locally invasive



Hürthle cell carcinoma expanding right IJV lumen, with adjacent smallertumour mass. Note cells with uniform round nuclei and abundant granular

cytoplasm (haematoxylin and eosin × 200).



Primary Thyroid Lymphoma

• A rare type of thyroid

cancer

Affects fewer than 1 in 2

million people

• Constitutes 5% of thyroid

malignanciesLarge Cell Lymphoma of the

Thyroid

• Patients may have a history of diffuse goiter (probably theresult of an autoimmune thyroiditis) that suddenly increases in

size, and often diagnosed because of symptoms of airway

obstruction.

• pain, hoarseness, dysphagia, dyspnea,

P i Th id L h



Primary Thyroid Lymphoma

Characteristics and Diagnosis

• Develops in the setting of pre-existing

lymphocytic thyroiditis

• Often diagnosed because of airway obstruction

symptoms

• Tumors are firm, fleshy, and usually pale

•The tumors usually appear as rapidly enlarging massesthat develop over a period of time ranging from several

days to a few weeks.



GrossCut surface

Solid white with fish flesh appearance

MicroscopicMostly diffuse large cell type

Sclerosis (focally prominent)Immunoblastic lymphomaLow grade lymphomas

small/intermediate cellsDiffuse / follicular pattern

Packing of follicular lumina of

lymphoma

Prognosis of Thyroid



Prognosis of Thyroid

Carcinomas

Papillary Best prognosis

Follicular

Medullary

Anaplastic Worst prognosis



Secondary Tumours

• Direct extensions from: larynx, pharynx,

oesophagus etc.

• Metastasis from:renal cell carcinoma, large intestinal

carcinoma, malignant melanoma, lung

carcinoma, breast carcinoma etc.

T t t f Th id C



Treatment of Thyroid Cancer

Summary

• Papillary and follicular thyroid cancer

Generally excellent prognosis

Risk for recurrence for as long as 30 years

• Initial management Surgery and radioactive iodine

LT4 suppressive therapy

• Follow-up Physical examination

Radioactive iodine scans

Serum Tg

TSH and T4





Q-1-A 39-year-old woman presented with a large solid, firm nodules,

painless swelling in her neck. The enlargement had been a gradualprocess over 2 years. She had no other symptoms and felt generally

well. On examination, her thyroid was diffusively enlarged and had a

rubbery consistency. There were no signs of thyrotoxicosis or of thyroid

failure.

Thyroid function tests showed that she was euthyroid; T3 was 1.2nmol/l

(NR 0.8-2.4), T4 was 12nmol/l (NR 9-23) and TSH was 6.3mU/l (NR

0.4-5mU/l). However, her serum contained high titre antibodies to

thyroid peroxidase (1/64000; 4000iu/ml).

A biopsy revealed thyroid tissue within the mediastinal lymph node.A. What is the most likely diagnosis is?

B. Describe the histological lesion.

C. Mention the most common factor related to the development of the

disease.



Q-2-A-Subacute (granulomatous) thyroiditis or de quervian

thyroiditis.

B-Subacute painless lymphocytic (painless or silent) thyroiditis.

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Lect 5 Thyroid Tumor

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