Histo Week 0 Flashcards
1
Q
What are the 3 main ways that breast disease can present?
A
- Breast lump
- Abnormal screening mammogram
- Nipple discharge
2
Q
How do we investigate breast disease?
A
- Clinical examination
- Imaging: sonography, mammography, MRI
- Pathology: cytopathology and/or histopathology
3
Q
Using breast cytopathology, the lesion is aspirated using a needle. What is it useful for investigating?
A
Nipple discharge and palpable lumps
4
Q
Aspirates of breast lumps from cytopathology are coded from…?
A
C1 - inadequate C2 - benign C3 - atypia (probably benign) C4 - suspicious of malignancy C5 - malignant
5
Q
Histopathology is better than cytopathology for investigating breast disease because it provides…
A
architectural and cellular detail
6
Q
Define duct ectasia
A
The inflammation and dilation of large breast ducts.
aetiology is unclear
7
Q
How does duct ectasia present?
A
Nipple discharge
Sometimes causes breast pain, breast mass and nipple retraction.
8
Q
Is duct ectasia benign or malignant?
A
Benign condition with no increased risk of malignancy
9
Q
In duct ectasia, nipple discharge is the usual presentation. What does cytology of nipple discharge show?
A
Proteinaceous material and inflammatory cells only
10
Q
Define acute mastitis
A
Acute inflammation in the breast
11
Q
When is acute mastitis often seen?
A
In lactating women due to cracked skin and stasis of milk
12
Q
Acute mastitis may also complicate what other condition?
A
Duct ectasis
13
Q
What is the usual bacterial organism involved with acute mastitis?
A
Staphylococci
14
Q
What is the presentation of acute mastitis?
A
Painful red breast
15
Q
What is the treatment for acute mastitis?
A
Drainage and antibiotics are usually curative
16
Q
Define fat necrosis and its causes
A
An inflammatory reaction to damaged adipose tissue
Caused by trauma, surgery, radiotherapy
17
Q
How does fat necrosis present?
A
A breast mass
18
Q
Is fat necrosis of the breast a benign or malignant condition?
A
Benign
19
Q
A group of alterations in the breast, that reflect normal and exaggerated responses to hormonal disease reflects which breast disease?
A
Fibrocystic disease
Very common with no increased risk for subsequent breast carcinoma
20
Q
What is the common presentation of fibrocystic disease?
A
Breast lumpiness
21
Q
What is a benign fibroepithelial neoplasm of the breast?
A
Fibroadenoma
Common
22
Q
What age do women typically present with fibroadenoma?
A
20-30yrs
23
Q
What is the common presentation of fibroadenoma?
A
Circumscribed mobile breast lump
20-30yr young women
24
Q
What is the curative treatment for fibroadenoma?
A
Simple ‘shelling out’
25
Define Phyllodes tumours
A group of potentially aggressive fibroepithelial neoplasms of the breast
Uncommon
26
Phyllodes tumours can arise within pre-existing......?
fibroadenomas
27
How do Phyllodes tumours present?
Enlarging masses
Women >50years
Most are benign, but some are more aggressive
28
Define intraductal papilloma
A benign papillary tumour arising within the ductal system of the breast
29
Where do (i) peripheral intraductal papillomas, and (ii) central intraductal papillomas arise?
(i) small terminal ductules
| (ii) larger lacteriferous ducts
30
Are intraductal papillomas common and what age group are they mostly seen in?
Common
40-60yrs women
31
What do central papillomas (arise from larger lacteriferous ducts) present with?
Nipple discharge
32
What do peripheral papillomas (arise from small terminal ductules) present with?
These remain clinically silent if small
33
What is the treatment for intraductal papillomas?
Excision of involved duct is curative
34
What is a benign sclerosing lesion characterised by a central zone of scarring, surrounded by a radiating zone of proliferating glandular tissue?
Radial scar
Common
These can range in size from tiny microscopic lesions to large apparent masses
35
What are radial scar lesions that are greater than 1cm sometimes called?
Complex sclerosing lesions
36
What is thought to be the cause of radial scars?
Exuberant reparative phenomenon in response to areas of tissue damage in the breast
37
What do radial scars usually present as?
Stellate masses on screening mammograms which may closely mimic a carcinoma
38
What is the treatment for radial scars?
Excision is curative
39
Proliferative breast diseases are a group of intraductal proliferative lesions. They increase the rest of developing what condition?
Invasive breast carcinoma
40
How do proliferative breast diseases present?
They are microscopic lesions which usually produce NO symptoms
41
How are proliferative breast diseases diagnosed?
In breast tissue (that was removed for other reasons)
| Or on screening mammograms if they calcify
42
Usual epithelial hyperplasia is a marker for slightly increased risk (1.5-2.0 relative risk) for which condition?
Invasive breast carcinoma
n.b. the epithelial hyperplasia is not a direct precursor lesion to this, but only increases the risk.
43
Flat epithelial atypia (FEA) is also called...?
atypical ductal carcinoma
44
Flat epithelial atypia (FEA) may be the earliest morphological precursor to which condition?
Low grade ductal carcinoma in situ
FEA increases the relative risk by 4 of developing cancer
45
In situ lobular neoplasia is a risk factor for ....?
Subsequent invasive breast carcinoma
| 7-12 increased relative risk
46
Ductal carcinoma in situ (DCIS) is common. Its incidence has increased since...
the introduction of breast screening programmes
47
Define ductal carcinoma in situ (DCIS)
A neoplastic intraductal epithelial proliferation in the breast with an inherent, but not inevitable, risk of progression to invasive breast carcinoma
48
85% of cases of ductal carcinoma in situ (DCIS) are detected by...?
Mammography as areas of microcalcification
49
10% of patients with ductal carcinoma in situ (DCIS) present with clinical findings such as...?
Breast lump
Nipple discharge
Eczematous change of the nipple (Paget's disease of the nipple)
50
Ductal carcinoma in situ (DCIS) can be histologically subclassified into ...?
Low grade
Intermediate grade
High grade
51
What is the treatment for ductal carcinoma in situ (DCIS)?
Surgical excision
Complete excision with clear margins is curative
Recurrence is more likely with extensive disease and high grade DCIS
52
How common are invasive breast carcinomas?
They are the most common cancer in women
| Lifetime risk of 1 in 8
53
Define invasive breast carcinomas
A group of malignant epithelial tumours which infiltrate within the breast and have the capacity to spread to distant sites
54
What are risk factors associated with increased risk of invasive breast carcinomas?
```
Early menarche
Late menopause
Age (most cases occur in older women)
Increased weight
High alcohol consumption
Oral contraceptive use
Postitive FH
```
55
About 5% of invasive breast carcinomas show clear evidence of inheritance. Mutations in which gene can cause a lifetime risk of them by up to 85%?
BRCA gene
56
What do low grade breast carcinomas tend to arise from?
- Low grade ductal carcinoma in situ (DCIS) or in situ lobular neoplasia
- 16q loss
57
What do high grade breast carcinomas tend to arise from?
- High grade ductal carcinoma in situ (DCIS)
| - Complex karyotypes with many unbalanced Chr aberrations
58
How do invasive breast carcinomas present?
Symptomatically with a breast lump
| Increasing number of asymptomatic cases are detected on screening mammography
59
How are basal-like carcinomas are histologically characterised?
Sheets of markedly atypical cells
Prominent lymphocytic infiltrate
Central necrosis
60
How are basal-like carcinomas are immunohistochemically characterised?
Positive for 'basal' cytokeratins
| CK5/6 and CK14
61
What is the progression of basal-like carcinomas?
They have the propensity to vascular invasion and distant metastatic spread
62
All invasive breast cancers are graded histologically by assessing which 3 things?
1) Tubule formation
2) Nuclear pleomorphism
3) Mitotic activity
Each is scored from 1-3. Grade 1 (well differentiated) is the lowest w/ 3-5points.
63
All invasive breast carcinomas are assessed for receptor status in which 3 receptors?
1. Oestrogen receptor (ER)
2. Progesterone receptor (PR)
3. Her2
64
Invasive breast carcinomas that are ER/PR positive and Her2 negative tend to be graded as....?
Low grade tumour
65
Invasive breast carcinomas that are ER/PR positive and Her2 positive tend to be graded as....?
High grade tumour
66
What is the receptor status of basal-like carcinomas often?
ER/PR/Her2 negative
| Triple negative
67
What is the single most important prognostic factor for breast carcinomas?
Status of axillary lymph nodes
Other factors: tumour size, histological type, grade
68
What is the aim of the NHS Breast Screening Programme?
Mammogram aims to pick up DCIS or early invasive carcinomas
47-73yr women every 3 years
Looks for abnormal calcification or masses
69
Core biopsies taken from the breast as part of the NHS screening programme are given B codes from 1-5 which represent what?
B1 - normal
B2 - benign abnormality
B3 - lesion of uncertain malignant potential
B4 - suspicious of malignancy
B5 - malignant (B5a = DCIS, B5b = invasive carcinoma)
70
What is enlargement of the male breast called?
Gynaecomastia
This is benign with no risk of malignancy
71
What age groups does gynaecomastia occur in?
Pubertal boys
| Older men >50
72
What are causes of gynaecomastia?
Idiopathic or associated with drugs (both therapeutic and recreational)
73
What are the histological presentations of gynaecomastia?
Breast ducts show epithelial hyperplasia with finger-like projections extending into duct lumen
Periductal stromal is cellular and oedematous
74
Carcinoma of the male breast is rare (0.2% of all cancers). What is the median age of diagnosis and the presentation?
65yrs old
Palpable lump
Histologically, similar features to female breast cancers
75
What are neutrophils associated with?
Acute inflammation
76
What are lymphocytes and plasma cells are associated with?
Chronic inflammation
| i.e. lymphomas
77
What are eosinophils associated with?
Allergic reactions
Parasitic infections
Tumours e.g. Hodgkin's disease
78
What are macrophages associated with?
```
Late acute inflammation
Chronic inflammation (including granulomas)
```
79
Caseating granulomas seen histologically indicate which disease?
Tuberculosis
80
Carcinomas are tumours of what cell type?
Epithelial cells
81
What are the 3 types of carcinomas?
1. Squamous cell carcinoma
2. Adenocarcinoma
3. Transitional cell carcinoma (uncommon)
82
What do squamous cell carcinomas show histologically?
Keratin production
| Intracellular bridges
83
What do squamous cell carcinomas show histologically?
Mucin production
| Glands
84
What are 6 sites of origin of squamous cancers?
```
Skin
Head and neck
Oesophagus
Anus
Cervix
Vagina
```
85
What are some sites of origin of adenocarcinomas?
```
Lung
Breast
Stomach
Colon
Pancreas etc
```
86
Pigmented tumours are highly likely to be....?
Melanoma
| but not always!
87
A histological liver biopsy shows positive results for Prussian Blue Iron Stain. What is the likely diagnosis?
Haemochromatosis
88
Amyloid deposits in the glomerulus can be detected using which histochemical stain?
Congo red
Positive with amyloid deposits (shows apple green birefringence)
89
Immunoperoxidase is a useful immunohistochemical stain that can work out....?
The type of tumour e.g.
carcinoma vs lymphoma
Type of carcinoma
90
Cytokeratin is what type of immunohistochemical stain?
Epithelial marker
Detects the type of tumour
91
CD45 is what type of immunohistochemical stain?
Lymphoid marker
Positive result (brown) when added = confirms that the tumour is a lymphoma
92
CK20 and CK7 are what types of immunohistochemical stains?
Adenocarcinoma marker
93
Giant multinuclear cells seen on histology with ulcerated epithelial between oesophagus and the stomach suggest which infection?
Herpes simplex
n.b. giant cells can be caused by other infections like chicken pox. Immunostaining can complex HSV.
94
What is an example of an autoimmune disease that is organ specific with organic specific antigens?
Penicious anaemia
Auto-antibodies against intrinsic factor are present so we cannot absorb vitamin B12
95
What is an example of an autoimmune disease that is organ specific without organic specific antigens?
Primary biliary cirrhosis
Presents with impaired LFTs (high ALP)
96
What are some examples of multisystem autoimmune diseases?
SLE
Rheumatoid arthritis
Scleroderma
Sjorgren's syndromes
97
SLE involves a combination of manifestations (which may not all occur) in which regions?
- Skin
- Oral ulcers
- Joints
- Neurological
- Serositis
- Renal (proteinuria)
- Haematological (pancytopaenia)
- Immunological
98
Anti-antibodies in SLE can be detected by ELISA. Which 3 antibodies are present in SLE?
Anti-dsDNA (most useful)
Anti-smith (most specific, but not sensitive)
Anti-histone (present in drug-related SLE e.g. use of hydralazine for CVS disease may induce SLE)
99
How does SLE affect the kidney?
Thickens glomerular capillaries
Wire-loop appearance of capillaries with thick pink walls pathologically
Capillary walls thicken due to immune complex deposition in the basement membrane
100
What is Libman-sacks endocarditis?
Non-infective endocarditis (may be in patients with SLE)
CVS presentations e.g. emboli, murmur, chest pain
Vegetations deposited on the vales are inflammatory, not due to bacteria (unlike in infective endocarditis)
101
What autoimmune condition is characterised by fibrous and excess collagen in the body?
Scleroderma (also called systemic sclerosis)
n.b. the localised form of excess collagen in the skin is termed morphea
102
Does diffuse scleroderma (systemic sclerosis) involve the truncal skin?
Yes
103
What antibodies are involved in diffuse scleroderma (systemic sclerosis)?
Anti-DNA topoisomerase (Scl70)
104
What antibodies are involved in limited form scleroderma (systemic sclerosis)?
Anti-centromere antibodies
105
Does limited scleroderma (systemic sclerosis) involve the truncal skin?
No
106
What are the main clinical features of limited scleroderma (systemic sclerosis)?
```
CREST:
Calcinosis
Raynauds
Eosophageal dysmotility
Sclerodactyl
Teleagiectasis
```
Other: nail-fold capillary dilatation, microstomia, intimal artery wall proliferation and thickening (onion skin on histology), microthrombi
107
What pattern is seen on immunofluroescence diagnosis of scleroderma?
Nucleolar pattern
108
What will mixed connective tissue disease show on antibody testing?
Speckled pattern of ANA test
109
How does dermatomyositis clinically persent?
High CK
Tender and inflamed muscles
Gottron's papules
110
How does sarcoidosis present?
- Skin: lupus pernio, erythema nodosum
- Lung: BHL, fibrosis, lymphocytosis
- Eyes: uveitis, keratoconjunctivitis
- Neuro/CNS: meningitis, cranial nerve lesions
- Liver: hep, cholestasis, cirrhosis
- Parotids: bilateral enlargement
- Joints
- Lymphadenopathy
- Heart
111
Bilateral enlargement of the parotids can occur in sarcoidosis. What are 2 other causes of bilateral enlargement?
Alcohol
| Sjorgrens syndrome
112
What is the pathological hallmark of sarcoidosis?
Non-caseating granuloma
(A ball of macrophages with epilethialoid cells Some fuse to form giant multi-nucleate cells with horse-shoe shaped nuclei)
113
What are 3 biochemical changes that may be seen in sarcoidosis?
1. Hypergammaglobulinaemia
2. High ACE
3. Hypercalcaemia (vit D hydroxylation by activated macrophages)
114
What type of vasculitis is temporal arteritis?
Large vessel vasculitis
115
What type of histology is shown in temporal arteritis?
Narrowing of lumen, multiple granulomas, lymphocytic infiltration of tunica media, multinucleate giant cells
116
What type of vasculitis is Kawasaki's disease?
Medium vessel vasculitis
117
What are the clinical presentations of Kawasaki's disease?
Fever
Erythema of palms and soles (desquamation)
Conjunctivitis
Lymphadenopathy
Coronary arteries may be affected (high MI risk)
Otherwise this is a self-limiting disease.
118
What type of vasculitis is Polyarteritis nodosa?
Medium vessel vasculitis
119
What are the pathology of Polyarteritis nodosa?
Necrotising arteritis
Infiltration of polymorphs, lymphocytes and eosinophils around the vessels
Arteritis is focal and sharply demarcated
Heals by fibrosis
Nodular appearance on angiograms due to small aneurysms
120
What arteries does polyarteritis nodosa (medium vessel vasculitis) often affect?
Renal and mesenteric arteries
121
Granulomatosis with polygangiitis (Wegner's) shows hallmark features in which 3 regions?
1. ENT
2. Lungs
3. Kidneys
122
What are 3 types of ANCA-associated small vessel vasculitis?
1. Microscopic polyangiitis
2. Granulomatosis with polygangiitis (Wegner's)
3. Eosinophilic granulomatosis with Polyangiitis (Churg-Strass)
123
What antibodies are associated with Granulomatosis with polygangiitis (Wegner's)?
Cytoplasmic ANCA (C-ANCA)
which is directed against the proteinase-3 antigen
124
What antibodies are associated with Eosinophilic granulomatosis with Polyangiitis (Churg-Strass)?
Perinuclear ANCA antibodies (P-ANCA)
which are directed against myeloperoxidase antigen
125
When considering endocrine pathology, how can we classify the diseases i.e. into regions?
- Pituitary
- Thyroid gland
- Parathyroid glands
- Adrenal glands (cortex, medulla)
- Multiple endocrine neoplasia syndromes
126
The anterior pituitary gland has epithelial cells that are derived from where...?
Oral cavity
127
The anterior pituitary gland secretes trophic hormones under the control of factors from where?
Factors released by the hypothalamus
128
What are the effects of the hypothalamic factors on the anterior pituitary gland?
(i) TRH
(ii) PIF (dopamine)
(iii) CRH
(iv) GHRH and somatostatin
(v) GnRH
(i) TRH stimulates TSH
(ii) PRF (dopamine) inhibits prolactin
(iii) CRH stimulates ACTH
(iv) GHRH stimulates, and somatostatin inhibits GH
(v) GnRH stimulates FSH and LH
129
Define hyperpituitarism
Excess secretion of trophic hormones
| Usually due to functional adenoma
130
Define hypopituitarism
Deficiency of trophic hormones
131
How is hyperpituitarism classified?
Originally by the morphological character of the predominant cell, but now it is classified on the basis of the hormones produced (detected by immunohistochemistry)
132
What is the order of type of cells affected by pituitary adenoma?
```
Prolactin cell (20-50%)
ACTH cell (10-15%)
Gonadotroph cell (10-15%)
GH cell (5%)
Mixed GH/prolactin (5%)
TSH (1%)
Other (35%)
```
133
What % of intracranial pituitary adenomas present clinically with symptoms?
10%
| adults in 4-6th decade usually
134
Pituitary adenomas are classed as microadenomas at what size?
<1cm
135
What % of pituitary adenomas are discovered incentally in autopsies?
25%
136
What are the clinical effects of prolactinomas (a functioning pituitary adenoma)?
Amenorrhoea
Galactorrhea
Loss of libido
Infertility
usually diagnosed early in females of reproductive age
137
What are the clinical effects of growth hormone adenomas (a functioning pituitary adenoma)?
Pre-pubertal children = gigantism
Adults = acromegaly
Diabetes mellitus
Muscle weakness
Hypertension
Congestive heart failure
138
What are the clinical effects of corticotroph cell adenomas (a functioning pituitary adenoma)?
Corticotroph = ACTH
Cushing's syndrome
139
What are most cases of hypopituitarism caused by?
1. Non-secretory pituitary adenomas
2. Ischaemic necrosis
3. Ablation of pituitary by surgery or irradiation
140
Hypopituitarism can be caused by non-secretory pituitary adenomas, ischaemic necrosis or ablation of pituitary by surgery/radiation. Give the causes of ischaemic necrosis.
- Most commonly post-partum (Sheehan's syndrome)
- DIC
- Sickle cell anaemia
- Increased ICP
- Shock
141
What are main clinical manifestations of anterior pituitary hypofunction e.g. for deficiencies in (i) GH, (ii) gonadotrophins, (iii) TSH and ACTH, (iv) prolactin?
(i) Children have growth failure (pituitary dwarfism)
(ii) Gonadotrophin deficiency causes amenorrhoea and infertility in women; decreased libido and impotence in men
(iii) TSH and ACTH deficiency induce hypothyroidism and hypoadrenalism
(iv) Prolactin def causes a failure of post-partum lactation
142
What hormones are released by the posterior pituitary gland?
Two peptides:
1. Antidiuretic hormone (ADH or vasopressin)
2. Oxytocin
143
What are the 2 posterior pituitary syndromes that involve ADH?
Diabetes insipidus
| Syndrome of inappropriately high ADH (SIADH)
144
Pituitary tumours can cause local mass effects. Compression of the optic chiasm can lead to ....?
Bitemporal hemianopia
145
As well as bitemporal hemianopia, what other local mass effects of pituitary tumours are important?
- High ICP signs and symptoms
| - Obstructive hydrocephalus
146
What is the aim of the thyroid gland producing T4 and T3 to be released into the circulation?
To increase the basal metabolic rate
147
Thyroid glands (as well as the follicular epithelial cells producing T4/3), they contain parafollicular or 'C' cells with what function?
Synthesis of calcitonin
This promotes calcium absorption by the skeletal system
148
Define goitre
Enlargement of the thyroid
149
When can non-toxic goitre (enlargement of the thyroid) occur?
- Impaired synthesis of thyroid hormone (e.g. iodine def)
- Puberty (esp in females)
- Ingestion of substances that prevent thyroid hormone synthesis (e.g. brassicas
- Hereditary enzyme defects
150
How does multinodular goitre occur?
Simple thyroid enlargement may be transformed into a multi-nodular pattern.
This may reach massive size
151
What can multinodular goitre result in?
Mechanical effects including dysphagia and airway obstruction
A hyperfunctioning nodule may develop to hyperthyroidism
152
Define thyrotoxicosis
Hypermetabolic state caused by elevataed circulating levels of free T3 and T4
153
What are primary causes of thyrotoxicosis?
- Graves' disease
- Hyperfunctioning multinodular goitre
- Hyperfunctioning adenoma
- Thyroiditis
154
What are secondary causes of thyrotoxicosis?
TSH secreting pituitary adenoma (rare)
155
Define struma ovarii
Ovarian teratoma with ectopic thyroid
i.e. induces hyperthyroidism. This is very rare
156
Define factitious thyrotoxicosis
Exogenous thyroid intake
This induces hyperthyroidism. This is very rare.
157
What is the most common cause of endogenous hyperthyroidism?
Graves' disease
158
Graves' disease can consist of a triad that involves....?
1. thyrotoxicosis
2. infiltrative ophthalmopathy (with exophthalmos in up to 40%)
3. infiltrative dermopathy (pretibial myxoedema) in minority of cases
159
What is the epidemiology of Graves' disease?
Primarily younger adults
| F:M 7:1
160
Autoimmune disorders of the thyroid span a continuum with what diseases at each end of the spectrum?
Graves' disease (hyperthyroidism)
Hashimoto's disease (hypothyroidism)
Autoantibodies against thyroid antigens are present in both but different specificities result in different functional consequences.
161
What are causes of primary hypothyroidism?
- Postablative (after surgery/RAI therapy)
- Autoimmune (Hashimoto's thyroiditis)
- Iodine deficiency
- Congenital biosynthetic defect
162
What are causes of secondary hypothyroidism?
Pituitary or hypothalamic failure
| uncommon
163
What is the most common cause of hypothyroidim?
Hashimoto's thyroiditis
Autoimmune disease
164
What is the epidemiology of Hashimoto's thyroidism?
45-65years
| F:M 15:1
165
What is the main clinical presentation of Hashimoto's thyroiditis (the commonest cause of hypothyroidism)?
Painless enlargement of thyroid
166
Are adenomas of the thyroid benign or malignant?
Adenomas are BENIGN neoplasms of follicular epithelium
Only a small % cause thyrotoxicosis.
167
Carcinomas of the thyroid are uncommon and account for what % of solitary thyroid nodules
<1%
168
Are solitary nodules or multiple nodules of the thyroid more neoplastic?
Solitary nodules are more often neoplastic than multiple nodules
169
Are solid nodules or cystic nodules of the thyroid more neoplastic?
Solid nodules are more likely to be neoplastic than cystic nodules
170
Are nodules of the thyroid in younger patients or older patients more neoplastic?
Nodules in younger patients are more likely to be neoplastic than in older patients
171
Are nodules of the thyroid in males or females more neoplastic?
Nodules in males are more likely to be neoplastic than those in females
172
Are nodules of the thyroid that do not take up radioactive iodine (i.e. 'cold' nodules) or 'hot' nodules more neoplastic?
'Cold' nodules are more commonly neoplastic than ‘hot’ nodules
173
Morphology of thyroid nodules will give the best diagnosis and level of neoplasm. This can be determined using which 2 techniques?
Fine needle aspiration cytology
| Histology
174
Are adenomas of the thyroid usually solitary or multiple?
Solitary
175
What is the general appearance of adenomas of the thyroid?
Well-circumscribed lesion that compresses the surrounding parenchyma
Well-formed capsule
176
Why is it important to examine the capsule of adenomas of the thyroid?
It is important to examine the capsule for invasion to exclude follicular carcinoma.
177
Carcinoma of the thyroid typically occurs in adults, and accounts for <1% cancer deaths. What are the 4 types of carcinoma of the thyroid?
1. Papillary (75-85%)
2. Follicular (10-20%)
3. Medullary (5%)
4. Anaplastic (<5%)
178
Describe the pathogenesis for carcinoma of the thyroid?
- Genetic: including MEN
| - Environment: ionising radiation (mostly papillary carcinomas)
179
Papillary carcinomas of the thyroid can occur at any age. What can be seen on histopathology?
1. Papillary architecture
2. Optically clear nuclei
3. Intranuclear inclusions
4. ±Psammoma bodies
n.b. diagnosis of papillary carcinoma is based upon the nuclear features (2 and 3 above)
180
Papillary carcinomas are non-functional and present with what signs and symptoms?
Painless mass in neck
| ± Metastasis in cervical lymph node
181
What is the 10 year survival for papillary carcinomas of the thyroid?
10 yr survival up to 90%
182
Describe follicular carcinoma morphology and pathology?
Follicular morphology
May be well-demarcated with minimal invasion
OR clearly infiltrative
183
When is there a peak incidence for follicular carcinomas?
Middle age
184
Where do follicular carcinomas of the thyroid usually metastasise to?
Via the bloodstream
| To lungs, bone, liver
185
What is the pathogenesis of medullary carcinomas of the thyroid?
- Neuroendocrine neoplasm derived from parafollicular C cells
- 80% sporadic (adults 50-60yrs)
- 20% familial (younger patients, MEN)
186
Anaplastic carcinomas of the thyroid typically occur in what age group of patients?
Elderly patients
187
Is anaplastic carcinoma of the thyroid severe?
Very aggressive
Metastasis is common
Most cases have death within 1 year due to local invasion
188
Where do the parathyroid glands derive from?
Usually 4 parathyroid glands derive from developing pharyngeal pouches
189
Where are the 4 parathyroid glands usually close to?
Upper and lower poles of thyroid
| But may be in the thymus or antetrior mediastinum
190
Parathyroid gland activity is controlled by what?
The level of free calcium in blood
191
What stimulates the release of PTH from parathyroid glands?
Low calcium in blood
192
What are 5 main functions of PTH?
1. Activates osteoclasts
2. Increases renal tubular calcium reabsorption
3. Increases conversion of Vit D to its active form
4. Increases urinary phosphate excretion
5. Increases intestinal calcium absorption
193
What are the causes of hyperparathyroidism in order of commonest?
1. Solitary adenoma (80-90%)
2. Hyperplasia of all 4 glands i.e. sporadic or component of MEN1 (10-20%)
3. <1% carcinoma
194
What is the most common cause of clinically silent hypercalcaemia?
Hyperparathyroidism
195
Hyperparathyroidism shows what biochemical changes?
- Increased level of serum ionised calcium
| - High PTH (in comparison with hyperCa2+ due to non-parathyroid diseases)
196
What are the clinical features of primary hyperparathyroidism?
Bones, stones, abdo groans, psychic moans
- Bone resorption with thinning of cortex and cyst formation (osteitis fibrosa cystica)
- Renal stones, obstructive uropathy
- GI disturbances (constipation, pancreatitis, gallstones)
- CNS (depression, lethargy, seizures)
- Neuromuscular abnormalities and weakness
- Polyuria and polydipsia
197
In primary hyperparathyroidism, there is high Ca2+ and PTH. The high levels of Ca2+ induce bone resorption with thinning of cortex and cysts (osteitis fibrosa cystica) which may lead to what?
Fractures
198
What causes secondary hyperparathyroidism?
- Any condition associated with chronic depression of serum calcium e.g. vit D def
- Renal failure is the commonest cause
199
What is the presentation of (i) parathyroid glands and (ii) bone changes in secondary hyperparathyroidism?
(i) PTH glands are enlarged; may be asymmetrical
(ii) Bone changes are the same as primary disease with bone resorption, thinning of cortex and cysts with increased fracture risk.
200
What are the causes of hypoparathyroidism?
Surgical ablation
Congenital absence
Autoimmune
201
What are the clinical manifestations of hypoparathyroidism?
- Neuromuscular irritability - tingling, muscle spasms, tetany
- Cardiac arrhythmias
- Fits
- Cataracts
202
Within the adrenal gland, what hormone(s) are secreted from the zona glomerulosa?
Aldosterone
203
Within the adrenal gland, what hormone(s) are secreted from the zona fasciculata?
Glucocorticoids
204
Within the adrenal gland, what hormone(s) are secreted from the zona reticularis?
Androgens
| Glucocorticoids
205
Within the adrenal gland, what hormone(s) are secreted from the medulla?
Noradrenaline
| Adrenaline
206
Adrenocortical hyperfunction results in what conditions?
- Cushing's syndrome = excess glucocorticoids
- Hyperaldosteronism
- Virilising syndromes = excess androgens
207
What are the clinical features of Cushing's syndrome?
```
Hypertension and weight gain
Truncal obesity
'Moon' facies
Buffalo hump
Cutaneous striae
```
208
What are most cases of Cushing's syndrome caused by?
Administration of exogenous glucocorticoids
| adrenal glands are atrophic
209
Most Cushing's syndrome cases are caused by exogenous admin of steroids. What is the commonest endogenous cause of Cushing's syndrome?
Primary hypothalamic-pituitary disease with increased ACTH (>50%)
i.e. Cushing's disease
ACTH-producing pituitary adenoma. Some have hyperplasia of ACTH secreting cells in pituitary. Adrenal glands show nodular cortical hyperplasia.
210
Steroids are the commonest exogenous cause of Cushing's syndrome. The commonest endogenous cause is ACTH-dependent i.e. pituitary adenoma (Cushing's disease). What are other endogenous causes that are less common?
1. Primary adrenal solitary neoplasm i.e. adenoma or carcinoma. (30%)
2. Bilateral hyperplasia
211
Steroids are the commonest exogenous cause of Cushing's syndrome. What are some less common exogenous causes of Cushing's syndrome?
Secretion of ectopic ACTH by non-endocrine tumours
Most commonly small cell carcinoma of the lung. Adrenals will show bilateral hyperplasia.
212
What are the causes of primary hyperaldosteronism?
1. Aldosterone secreting adenoma – Conn’s syndrome (35%)
| 2. Bilateral adrenal hyperplasia (60%)
213
Hyperaldosteronism accounts for <1% causes of hypertension but why is it important to recognise?
Surgically correctable
214
What are the 2 important clinical manifestations of hyperaldosteronism?
Hypertension
| Hypokalaemia
215
Adrenogenital syndromes may be associated with neoplasms (carcinoma>adenoma). They are defined by an excess of what?
Androgens
216
Congenital adrenal hyperplasias are a group of disorders with what mode of inheritance?
Autosomal recessive
217
Congenital adrenal hyperplasias involve autosomal recessive hereditary defects in enzymes involved with what processes?
Cortisol biosynthesis
218
Congenital adrenal hyperplasias involve autosomal recessive hereditary defects in enzymes involved with cortisol biosynthesis. Less cortisol results in what?
Decreased cortisol results in:
Increased ACTH
Adrenal stimulation
Increased androgen synthesis
219
What age do congenital adrenal hyperplasias typically present?
Childhood
| Or less commonly in adults
220
Adrenal insufficiency can be primary, or secondary to reduced ACTH. Secondary causes include...?
- Non-functional pituitary adenomas
| - Other lesions of pituitary or hypothalamus including infarction
221
Primary adrenal insufficiency may be acute or chronic. Acute causes include...?
- Sudden withdrawal of corticosteroid therapy
- Haemorrhage (neonates)
- Sepsis with DIC (Waterhouse-Friderichson syndrome)
222
Primary adrenal insufficiency may be acute or chronic. Chronic causes include...?
- Autoimmune (75-90%)
- TB
- HIV
- Metastatic tumour (esp lung and breast)
- Rarely amyloid, fungal infections, haemochromatosis, sarcoidosis
223
Adrenocortical neoplasms include adenomas and carcinomas.
(i) Are the adenomas mostly functional or non-functional?
(ii) What conditions are the adenomas usually associated with?
(i) Adrenocortical adenomas are mostly non-functional
| (ii) May be associated with Cushing's syndrome or Conn's syndrome
224
Adrenocortical neoplasms include adenomas and carcinomas.
(i) Are the carcinomas common
(ii) How big are they?
(ii) What conditions are the carcinomas usually associated with?
(i) Adrenocortical carcinomas are rare
(ii) Usually large
(iii) More commonly associated with virilising syndrome than adenomas
225
What is the function of the adrenal medulla?
Secretes catecholamines in response to signals from the sympathetic nervous system
226
The most important diseases involving the adrenal medulla are neoplasms such as....?
Phaeochromocytoma
| Neuroblastoma
227
Phaeochromocytomas secrete what hormones and result in what key clinical finding?
Catecholamines are released
Hypertension occurs
Surgically correctable
228
What are the 4 features that follow the 'rule of 10s' involving phaeochromocytomas?
1. 10% arise in association with familial syndromes
2. 10% are bilateral
3. 10% are malignant
4. 10% of catecholamine-secreting tumours arise outside adrenals (paragangliomas)
229
What are the familial syndromes that 10% of phaeochromocytoma cases arise in association with?
MEN2A
MEN2B
von Hippel-Lindau disease
Sturge-Weber syndrome
230
Define multiple endocrine neoplasia (MEN) syndromes
A group of diseases resulting in proliferative lesions (hyperplasias, adenomas and carcinomas) of multiple endocrine organs
231
Do tumours in multiple endocrine neoplasia (MEN) syndromes occur at a younger or older age than sporadic tumours?
Occur at a younger age than sporadic tumours
Usually more aggressive than sporadic tumours too.
