thyroid tumor

Pathology of the Thyroid Gland

SMS 3023BY

Dr. Mohanad

Diseases of the Thyroid Gland

• Congenital diseases• Inflammation• Functional abnormality• Diffuse and Multinodular goiters• Neoplasm

Thyroid Neoplasms

I. Primary Tumors• Epithelial• Malignant Lymphomas• Mesenchymal tumors

II. Metastatic Tumors

Solitary thyroid nodule

• Follicular adenoma• Papillary carcinoma• Follicular carcinoma• Medullary carcinoma• Hyperplastic (dominant) nodule• Metastatic neoplasms

Typical Presentation of Thyroid Cancer (Clinical Symptoms)

Pain in the neck and sometimes in your ears. Difficulty swallowing, Difficulty breathing or constant wheezing. Hoarseness that is not related to a cold, A cough

that continues and is not related to a cold. 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),

Epithelial Thyroid Neoplasms

• Tumours of follicular cells Benign (adenomas)

• Follicular adenoma Malignant (carcinomas)

• Follicular carcinoma • Papillary carcinoma • Undifferentiated (anaplastic) carcinoma

• 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 follicular cancers; 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

Toxic Single Adenoma (TSA)

• TSA is a single hyper functioning follicular thyroid adenoma.

• Benign monoclonal tumor that usually is larger than 2.5 cm

• It is the cause in 5% of patients who are thyrotoxic

• Nuclear Scintigraphy scan shows only a single hot nodule

• TSH is suppressed by excess of thyroxines

• So the rest of the thyroid gland is suppressed

Common Symptoms

• Nervousness• Anxiety• Increased perspiration• Heat intolerance• Tremor• Hyperactivity• Palpitations• Weight loss despite increased appetite• Reduction in menstrual flow or oligo-menorrhea

Common Signs

• Hyperactivity, Hyper kinesis• Sinus tachycardia or atrial arrhythmia, AF, CHF• Systolic hypertension, wide pulse pressure• Warm, moist, soft and smooth skin- warm handshake• Excessive perspiration, palmar erythema, Onycholysis• Lid lag and stare (sympathetic over activity)• Fine tremor of out stretched hands – format's sign• Large muscle weakness, Diarrhea, Gynecomastia

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. minimally invasive• 50% 10 yrs. survival Vs. 90%10 yrs. survival• Haematogenous route is preferred mode of spread

Follicular Carcinoma

• Solitary round or oval nodule

• Encapsulated by Thick capsule

• Capsular invasion or vascular invasion within our outside capsular wall

• Composed of follicles;• Well-formed follicles• Poorly-formed follicles• Cribiform area or Trabecular

formations• Mitotic activity & nuclear

atypia

Follicular Thyroid Cancer

Usually stays in the thyroid gland, but can spread to the bones, lungs, and central nervous system

Usually does not spread to the lymph nodes

Follicular Thyroid Cancer

Follicular Thyroid Carcinoma

Follicular Adenoma• No Capsular invasion• Compressed normal thyroid usu. present external to capsule

Follicular Carcinoma• Capsular invasion present• May have vascular invasion

Follicular Thyroid CancerDiagnosis and Prognosis

• Most FTCs present as an asymptomatic neck mass

• If caught early, this type of thyroid cancer is often 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 yrs.• May affect children• Prior head & neck radiation exposure• Indolent, slow-growing painless mass • Cervical lymphadenopathy may be presenting

feature

Papillary Carcinoma

• Morphological Lesion• Variable size (microscopic

to several cm)• Solid or cystic• Infiltrative or encapsulated• Solitary or multicentric

(20%)

Papillary Thyroid Carcinoma

Papillary Thyroid CancerCharacteristics

Unencapsulated tumor nodule with ill-defined margins Tumor typically firm and solid May present as nodal enlargement Commonly metastasizes to neck and mediastinal lymph

nodes 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 (ground

glass, 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)

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 massFrequently replaces entire thyroid glandExtends into adjacent soft tissue, trachea

and oesophagusHighly anaplastic cell on histology with:

Giant, spindle,small or mix cell population Foci of papillary or follicular differentiation


• Cellular pleomorphism• +/- multinucleated giant

cells• 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 Middle-aged adults Female :male = 1.3:1 Unilateral involvement of gland +/- cervical lymph node metastases 5 % of all thyroid malignancies

• Sporadic (80%)• Rest in the setting of MEN IIA or B or as familial without

associated MEN syndrome


Germ-line mutation in Ret protooncogene on chromosome 10q11.2

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

Medullary Thyroid CancerMetastases

• 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

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


• Corresponding to a greater concentration of C-cells

• Solid, lobular or insular growth patterns

• Tumour cells round, polygonal or spindle-shaped


• Medium sized nucleus • Highly vascular stroma • Hyalinized collagen

Coarse calcification• Amyloid deposits stain

orange-red with Congo Red stain

• Amyloid deposits in many cases

Medullary Thyroid CarcinomaMicroscopic Features

• Amyloid stroma

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

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 therapy

• Tend to be locally invasive

Hürthle cell carcinoma expanding right IJV lumen, with adjacent smaller tumour 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

malignancies Large Cell Lymphoma of the

Thyroid

• Patients may have a history of diffuse goiter (probably the result of an autoimmune thyroiditis) that suddenly increases in size, and often diagnosed because of symptoms of airway obstruction.

• pain, hoarseness, dysphagia, dyspnea,

Primary Thyroid LymphomaCharacteristics 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 masses that develop over a period of time ranging from several days to a few weeks.

GrossCut surfaceSolid white with fish flesh appearance

MicroscopicMostly diffuse large cell typeSclerosis (focally prominent)Immunoblastic lymphomaLow grade lymphomas small/intermediate cellsDiffuse / follicular patternPacking of follicular lumina of lymphoma

Thyroid CarcinomaPrognosis

Excellent but following factors play important role: Age and sex Size Multicentricity Extra-thyroid extension Distant metastasis Total encapsulation, pushing margin of growth

& cystic change

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.

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 gradual process 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.

thyroid tumor

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