L36 Endocrine pathology - Pituitary and Thyroid Flashcards
There is overlapping features of adenoma and carcinoma
such as pleomorphism, capsular/vascular invasion.
meaning that histology is not useful
(except in?)
What serves as the most accurate diagnostic criteria?
Except in
- Papillary thyroid carcinoma
- Neuroblastoma
Metastasis as the most accurate diagnostic criteria
Causes for hyperpituitarism? (5)
Which cause is the most common?
- Adenoma (MC)
- Hyperplasia
- Carcinoma
- Ectopic production e.g. SCLC
- Hypothalamic diseases
What are the causes for hypopituitarism? (4)
MC for adult and child?
- Non-functioning adenoma (MC in adult): mass effect
- Rathke cleft cyst (MC in child) :from Rathke’s pouch (embryonic remnant of anterior pituitary)
- Ischemic injury: Sheehan syndrome (postpartum necrosis of anterior pituitary)
- Inflammation (e.g. TB), irradiation (chemotherapy of NPC)
List possible consequences of mass effect of the pituitary gland. Briefly explain too. (5)
- Hypopituitarism: loss of all normal pituitary cell types/ isolated excess in hormone from tumor
- Bitemporal hemianopia: compression on optic chaism
- Ophthalmoplegia: compression of CN3,4,6
- Headache: stretching of diaphragm sella, raised ICP (due to obstruction to CSF drainage)
- Pituitary apoplexy: sudden onset of neurological dysfunction due to bleeding into or impaired blood supply of pituitary gland at the base of the brain
(apoplexy = bleeding in internal organs with symptoms)
What do you expect to see on X-ray when there is a mass effect caused by pituitary gland?
Sellar expansion, bony erosion.
Name the types of pituitary adenomas. (3)
- Functioning = with multuple/single trophic hormones
- Non-functioning
- Prolactinoma (MC)
- Gonadotroph adenoma
- Null cell adenoma: non-functioning (2nd MC)
What are macroadenoma and microadenoma?
Macroadenoma >1cm
Microadenoma <1cm
- confirmed to sella, thus producing no mass effect-induced symptoms
Pituitary adenomas
A. They are invasive to adjacent bones, dura and brain
B. They are not metastatic
C. They may have hemorrhagic foci
D. There is clonal expansion of primitive stem cell usually in the anterior pituitary, thus monoclonal in origin
E. Reticulin stain is used to distinguish adenoma (+ve) from normal gland (-ve)
All except E!
E: Reticulin stain is used to distinguish adenoma (-ve) from normal gland (+ve)
B: thus they are different from carcinoma
Other than reticulin stain, what can be used to investigate pituitary adenomas?
IHC for anterior pituitary hormones
- IHC +ve for a particular hormone in adenoma does not mean that tumor is actively secreting that normal
- therefore functional aspect of the pituitary adenoma cannot be assessed by histopathology
Thyroid gland disorder are classified by morphology (diffuse, multiple nodular, diffuse) and thyroid status.
List Ddx for hyperthyroidism. (7)
- Grave’s disease
- Toxic multinodular goitre (Plummer’s disease)
- Toxic adenoma
- De Quervain thyroiditis (subacute, viral infection like mumps)
- Subacute lymphocytic thyroiditis
- Struma ovarri (teratoma)
- Factitious thyrotoxicosis (overdose)
List Ddx for hypothyroidism? (3)
- Cretinism in neonates (severely impaired physical and mental development) or myxoedema in adults
- Hashimoto’s thyroiditis
- Iodine deficiency
A patient has a neck lump that is diffuse and non-toxic.
What is the possible diagnosis?
Simple goitre/colloid goitre/ diffuse goitre
Simple goitre/colloid goitre/ diffuse goitre contains enlarged follicles with ?
Colloid
A nodular goitre can be solitary or multiple. The patient can appear to be euthyroid or hyperthyroid (if toxic multi nodular).
Regressive changes such as calcification, fibrosis and hemorrhage can be picked up by?
USG
Cause of Grave’s disease?
Clinical manifestations?
Strongly associated with what MHC class II cell surface receptor?
Autoimmune cause
Clinical manifestations - Triad
- Diffuse thyrotoxic goitre
- Infiltrative ophthalmology (thyroid eye signs)
- Infiltrative dermopathy (pretibial myxoedema)
associate with HLA-DR3
What is the pathogenesis of Grave’s disease?
- TSI (thyroid stimulating immunoglobulin) stimuates TSH receptor
- Thyroid stimulating antibodies mimics TSH to stimulate oversecretion of thyroid hormone
- other autoantibodies targeting
2. TPO (thyroid peroxidase)
- Thyroglobin
What would you expect to see histologically in Grave’s disease?
What would you expect to see in extraocular muscles in Grave’s disease?
Diffuse hyperplasia of follicular epithelium with T-cell infiltration
- bland-looking thyroid follicles
Extraocular muscles
-Lymphocytic infiltrates, muscular destruction
Cause of Hashimoto’s thyroiditis?
Clinical manifestations?
Autoimmune
(usually associated with other autoimmune diseases)
Initial thyrotoxicosis - Hashitoxicosis due to gland destruction (transient thyrotoxicosis)
Null cell adenoma
A. Is chromophobic
B. no PAS positivity
C. No lead hemtoxylin positibity
D. no carmoisine positivity
E. Electron microscopy can reveal their morphogenesis
F. 2nd MC non-functioning pituitary adenoma
All except E
- cannot
chromophobic = resist to staining with dyes
_______________ is also known as subacute granulomatous thyroiditis/ giant cell thyroiditis
De Quervain’s thyroiditis
How can the thyroid eye signs and pretibial myxoedema be explained?
Increase amount of glycosaminoglycan, T-cell infiltration
Hashimoto thyroiditis - chronic lymphocytic thyroiditis
Strongly associated with?
Increases risk of?
Associated with HLA-DR3,5
Increases risk of B-cell non-hodgkin lymphoma in thyroid (esp. MALToma)
What can be seen histologically in Hashimoto thyroiditis?
- Abundant Hurthle cells (oxyphilic cell metaplasia)
(Oncocytic cells (originating from follicular cells) in the thyroid are often called Hürthle cells, due to cellular enlargement characterized by an abundant eosinophilic (pink) granular cytoplasm as a result of accumulation of altered mitochondria.)
- Widespread infiltration of lymphocytes and plasma cells
- Fibrosis
- Follicular atrophy
others:
- well-formed germinal centers
Which hyperthyroidism disease is associated with diffuse and symmetrically enlarged thyroid with intact capsule?
Hashimoto thyroiditis
Grave’s: one-sided
Which disease is associated with hyperthyroidism preceded by URTI?
What kind of inflammation does it cause?
De Quervain thyroiditis
- Viral origin
- subacute granulomatous inflammation
What are the differences between Hashimoto and De Quervain thyroiditis? (2)
- Without follicular atrophy
- Without oxyphil metaplasia
A thyroid nodule is likely to be neoplastic if? (5)
The patient is
- young
- male
The nodule is
- solitary
- solid
- cold (non-functioning) (RAI uptake)
What are the 2 types of thyroid adenomas?
- Follicular adenoma
- Hurthle cell adenoma
*10% of follicular adenoma progresses into follicular carcinoma
We look for ______________ or _________ to exclude carcinoma?
Capsular invasion
Vascular invasion
Name the 4 thyroid carcinomas in descending order of occurrence.
Well differentiated
- Papillary (80% ‘P’opular)
- Follicular (10%)
- Medullary (MTC) (5%)
- Anaplastic (‘A’ged >60y. 1%)
Papillary carcinoma of thyroid
A. Occurs in young adult <50
B. Slow growing and non-functioning
C. Region LN metastasis is common at the time of diagnosis
D. most commonly associated with BRAF mutation
E. Related to radiation exposure in childhood.
All of the above
C: Tracheo-esophageal nodes - Level VI
D: others: RET, RAS - molecular testing is not routine
How is papillary carcinoma of thyroid diagnosed? (4)
By nuclear morphology by FNAC
- Crowding of nuclei (displaced, irregular)
- Orphan Annie eyes sign - optically clear nucleus
- Nuclear groove (=longitidinal groove in the middle like coffee bean),
nuclear pseudo-inclusion (= part of the cytoplasm extending into nuclei)
Other than nuclear morphology of papillary carcinoma of thyroid, what else is examined? (2)
- Papillary differentiation
- Psammoma bodies (dystrophic calcification) - non-specific
** but diagnosis depends on ATYPICAL CYTOLOGY still
Is thyroidectomy required in papillary carcinoma of thyroid?
Total thyroidectomy +/- neck dissection is required!
- potential of multi-focal lesions
Follicular carcinoma of thyroid
A. Young and middle age groups >50
B. 3:1 female predominance
C. Is a solitary cold nodule
D. Common LN involvement
E. Metastasize through blood to lung, bone and liver
F. Nuclear morphology has no role in diagnosis
All correct except D
- Rare! due to E
B: Female predominance is in both papillary and follicular thyroid carcinoma
F: only in Papillary carcinoma
Follicular carcinoma of the thyroid may be related to iodine deficiency.
Follicular adenoma is not a risk factor.
Fusion gene such as _______ would be seen.
PAX8-PPARgamma1
How to differentiate follicular adenoma and carcinoma?
FNAC diagnostic for follicular carcinoma. T/F?
Hurthe cell variant shows good/worse prognosis?
Capsular or vascular invasion,
FNAC is not diagnostic! (cannot use it to distinguish adenoma/carinoma)
worse
Anaplastic carcinoma of thyroid is in the aged (elderly), in endemic goitre area.
- Aggressive
- Anaplastic cells (giant cells, spindle cells, squamous cells, small cells)
- _________ mutation is common?
- Slowly/ Rapidly enlarging neck mass?
TP53 mutation;
Rapidly > palliative treatment
Aggressive: very poor prognosis, usually associated with Hx of CA thyroid
Medullary carcinoma of thyroid is a disease of the C cells, and it is an ____________ tumor associated with _________ familiy history.
_________ gene has to be screened for family!
- Neuroendocrine
- MEN2 (familial type)
- RET gene mutation
There is C-cell hyperplasia in Medullary thyroid carcinoma.
________ and ______ are stained by IHC,
with _______ deposits histologically.
Calcitonin and CEA (carcinoembryonic antigen);
Amyloid (calcitonin peptides)
Medullary carcinoma of thyroid
A. Serum Ca is low due to calcitonin
B. It is sporadic in >50 y and familial in <30y patients
C. Somatostatin, serotonin and vasoactive intestinal peptides can be found
D. It can be solitary or multiple
E. C-cell hyperplasia only in familial cases
All except A
- Calcitonin has weak effect on [Ca] in this case (normally will be low)
IHC expression correlates with actual hormonal status in pituitary diseases.
Not necessarily!
Main investigations for thyroid mass? (3)
USG + Fine needle aspiration (FNA) + Thyroid function test
- also radioactive iodine uptake
- serum free/total T3,4, sensitive TSH
What system is used to report thyroid cytopathology by FNAC in papillary carcinoma?
How many classes are there?
Bethesda System
Class I to VI (6 classes)
Bethesda System
Class I: non-diagnostic - malignancy risk depends on USG
Management?
Repeat FNA with USG
Bethesda System
Class II: Benign
- 0-3% malignancy risk
- FU as management
Class III: Atypic of undetermined significance (AUS)
- 3-5% malignancy risk in HK
Management?
Repeat FNA
Bethesda System
Class IV: suspicious for follicular neoplasm
- 25% malignancy
Management?
Surgical lobectomy (starting from class IV)
Bethesda System
Class V: suspicious for malignancy
- 70% malignancy
Management?
Total thyroidectomy or surgical lobectomy
Class VI in Bethesda system means ? Management?
Malignancy (99%) e.g. papillary histology
> Total thyroidectomy
