Pathology Flashcards
Coomb’s test: direct vs indirect (how it works)
Direct: detects antibodies bound to RBC surface antigens, indicating immune mediated attack on RBC
Indirect: detects antibodies against RBCs present in patient’s serum (used for antibody screening)
Either is positive if agglutination occurs
Trichomonas: how many flagellum and where?
4 anterior, 1 posterior
First line treatment for HMB
LNG IUS (mirena) levonorgestrel releasing intrauterine system
Percentage of those who get VZV that develop pneumonitis?
<1%
Percentage risk of endometrial cancer with Lynch syndrome
40-60%
Type of ovarian cancer that is associated with mismatch repair deficiency (MMRD)
Clear cell carcinoma of ovary (rare subtype of epithelial ovarian ca.)
Post CS- absorbable sutures, nodule in stitch line, type of cell for inflammation here
Giant cell (Langerhan)
Management of HIV in pregnancy re: medications/ timing of commencing based on viral load/ CD4 counts
All women not on HAART (highly active anti-retroviral therapy) should commence:
* As soon as they are able to do so in the second trimester where the baseline viral load ≤30,000 HIV RNA copies/mL;
* At the start of the second trimester, or as soon as possible thereafter, in women with a baseline viral load of 30,000–100,000 HIV RNA copies/mL;
* Within the first trimester if viral load >100,000 HIV RNA copies/mL and/or CD4 cell count is less than 200 cells/mm3.
All women should have commenced cART by week 24 of pregnancy.
Subtype of lichen planus that causes painful ulceration
Erosive lichen Planus
Cells of Brenner Tumour
Epithelial stromal tumour; transitional epithelial cells with longitudinal nuclear grooves (coffee bean nuclei), lying in abundant fibrous storm
Most common type of Fallopian tube cancer
Epithelial (serous adenocarcinoma)
What is a keratin pearl in a vulval ulcer suggestive of?
Squamous cell carcinoma (vulval cancer)
Pathophysiology of bacterial vaginosis (bacteria)
Variable degrees of depletion of protective Lactobacillus species. Marked increase in other organisms especially anaerobes: Gardnella vaginalis, Mobincullus, Atopobium vaginale, mycoplasma, bacteroides
General risks of anti-epileptic drugs during pregnancy?
Increased risk of teratogenicity 3x.
Associated with NTDs, cleft lip/ palate, cardiac defects, urogenital defects, neonatal coagulopathies
Which AED has the worst teratogenic profile?
Valproate
Which AEDs are in the FDA pregnancy category D?
Valproate, carbamazepine, phenytoin
Which AEDs are in the FDA pregnancy category C?
Lamotrigine, topiramate, vigabatrin
Which AEDs are in the FDA pregnancy category B?
Levetiracetam, gabapentin
Organism causing gonorrhoea (name and appearance)
Neisseria gonorrhoeae: gram negative intracellular diplococci
Most common tumour of female urethra
TCC
Pathophysiology of Grave’s disease
Autoantibodies to the thyrotropin receptor (TRAb) that activate the receptor, thereby stimulating thyroid hormone synthesis and secretion as well as thyroid growth
Most common cause of hyperprolactinaemia
Pituitary microadenoma
Fevers, headache, lymphadenopathy, CMV IgG positive, IgM negative
Previous CMV infection.
IgM antibodies are produced by the body first in response to a CMV infection. They can be detected in the blood within a week or two after the initial exposure. IgM levels (titers) rise for a short time, then decline and usually fall below detectable levels after a few months. IgM antibody levels rise again when latent CMV is reactivated.
IgG antibodies are produced several weeks after the initial CMV infection. IgG levels rise during the active infection, then stabilize as the CMV infection resolves and the virus becomes inactive. Once exposed to CMV, you will have some measurable amount of CMV IgG antibody in your blood for the rest of your life, which provides protection from getting another primary infection (immunity).
Lung cancer, abdo pain, polyuria & hypercalcaemia
PTHrp produced by squamous cell lung cancer
Risk of miscarriage with amniocentesis
1%
Abe for UTI contraindicated in 3rd trimester/ close to term
Nitrofurantoin (risk of neonatal haemolysis)
Arias Stella reaction
An Arias-Stella reaction is a common gynaecological histological finding in curettage specimens of gestational endometrium describing a non-neoplastic lesion that is easily confused with uterine malignancy.
An Arias-Stella reaction is due to hormonal hyperstimulation causing atypical endometrial glandular cells associated with the presence of viable chorionic tissue
It can present in normal physiologic conditions including pregnancy, postpartum and uterine abortion but is also associated with ectopic pregnancy, gestational trophoblastic disease, and uterine disease affecting the myometrium.
RMI
Combines ultrasound, menopausal status and ca125
RMI = (U) x (M) x Ca125
U- scores 1 point for each of the following characteristics: multilocular cysts, solid areas, metastases, ascites, bilateral lesions.
U = 0 (for an ultrasound score of 0), U = 1 (for an ultrasound score of 1), U = 3 (for an ultrasound score of 2 to 5)
M- premenopausal = 1, post-menopausal = 3 (women without period for 1 year or age >50 and hysterectomy)
If >200, discuss with gynaecological oncologist
How is melanoma prognosis assessed?
Breslow thickness (depth of lesion)
Which malaria parasite is the most dangerous?
P. falciparum
And most prevalent on African continent
PCOS biochemical markers
Increased insulin, decreased SHBG, high testosterone, high LH/oestrogen/ FSH, high prolactin (in 40% -caused by high estradiol)
Features of neonatal herpes
Localized skin infection
Encephalitis
Disseminated herpes infection— the most dangerous type. The virus is spread throughout the body and can affect multiple organs, including the liver, brain, lungs, and kidney.
Pregnant woman contracted CMV in 2nd trimester. Risk of neonatal congenital infection?
30-40% in 1st/2nd trimester
40-70% in 3rd
Amsel’s criteria for BV diagnosis
> =3 of:
clue cells on wet microscopy, vaginal pH >4.5, amine odor when vaginal fluid is exposed to 10% potassium hydroxide, and abnormal vaginal discharge.
pH interpretation of FBS
> 7.25 - Normal
Repeat in 1h if CTG remains abnormal
7.21 to 7.24 - Borderline (repeat in 30 minutes)
<7.2 - Abnormal (consider delivery)
Contraindications to FBS
Maternal infection e.g. HIV, HSV, hepatitis
Known fetal coagulopathy
Prematurity (<34 weeks)
Acute fetal compromise
JVP
Abnormalities & causes
Elevated JVP, normal waveform:
- RHF, fluid overload, bradycardia
Elevated JVP, no pulsation:
- SVC obstruction
Absent a-waves:
- AF
Paradoxical JVP (Kussmauls):
- Pericardial constriction
Large V wave, Absent X wave:
- Tricuspid regurgitation
Large A wave, slow Y descent:
- Tricuspid stenosis
Types of necrosis and organs/ environments it occurs in
Coagulative: Kidney, heart, adrenals, hypoxic
Liquefactive (Colliquative): Brain
Fat: Pancreas
Gangreous: GIT, peripheral limb
Caseous (granulomatous): TB
Features of metaplasia and dysplasia & neoplasia
Metaplasia:
- Reversible change of one differentiated cell type with another
- Cervical metaplasia where glandular epithelium is replaced by stratified squamous epithelium
Dysplasia:
- Abnormal change to cellular size, shape and/ or organisation
- Can progress to cancer
- Anisocytosis (unequal cell size)
- Poikilocytosis (abnormal cell shape)
- Hyperchromatism (pigmentation)
- Mitotic figures (increased cells currently dividing)
Neoplasia (cancer)
- Abnormal uncoordinated excess cell growth
- Nuclear enlargement
- Increased mitotic activity
- Loss of differentiation (polarity)
- Loss of cell cohesion
- Self simulating
acquired genetic alterations & activation of oncogenes/loss of TSG
paracrine, exocrine, endocrine factor production
incidence of choriocarcinoma in UK
1 in 45,000 pregnancies
ALP/ phosphate/ PTH profile in the following:
Myeloma
Calcium Alkali Syndrome
Sarcoidosis
Hyperthyroidism
Hyperparathyroidism
Malignancy
Vit D excess
Myeloma
Normal ALP
Normal/ high PO4
Normal/ high PTH
Calcium Alkali Syndrome
Normal ALP
Normal/ high PO4
Low PTH
Sarcoidosis
Normal/high ALP
Normal/ high PO4
Low PTH
Hyperthyroidism
Normal/high ALP
Normal/ high PO4
Low PTH
Hyperparathyroidism
Normal/ high ALP
Low PO4
High PTH
Malignancy
High ALP
Normal/ low PO4
Variable PTH
Vit D excess
Low ALP
High PO4
Low PTH
Which substance has been used as a tumour marker for granulosa cell tumour of the ovary?
Inhibin
Metabolic abnormality seen in congenital hypertrophic pyloric stenosis.
When does it typically present?
Hypochloremic, hypokalemic metabolic alkalosis.
Typically presents 4-8 weeks of age
Describe histological appearance of endometrium
- In the proliferative/follicular phase
- Soon after ovulation (early secretory)
- Mid- secretory phase
- Late secretory phase
- In the menstrual phase
- Round to tubular glands with even spacing between them. Pseudostratified columnar cells in glands. Increased mitoses, tubular glands, increased vessel coiling
- Glands with subnuclear vacuolation in oedematous stroma. Mitoses present, but not as numerous as during proliferative phase
- stromal oedema and luminal secretion
- Decidualisation- periareterial stroma, increased spiral artery tortuosity, stromal granulocytes, no mitoses
- Stromal breakdown, aggregates of stromal cells mixed with inflammatory cells and blood.
Types of fibroid degeneration
Red/ Carneous (most common in pregnancy): pain, fever, leucocytosis. Haemorrhagic appearance.
Hyaline (most common- 60%): when the fibroid outgrows its blood supply. Ivolves presence of homogenous eosinophilic bands or plaques in the ECF, representing the accumulation of proteinaceous tissue.
MRI: difficult to distinguish. T1: isointense, T2: hypo intense
Cystic (4% of degen): extreme sequela of oedema. USS: hypoechooic or heterogeneous uterine mass with cystic areas.
MRI: cystic areas with portions of high T2 signal.
Myxoid (rare): filled with gelatinous material that can be difficult to distinguish from cystic.
Ectopic management
Expectant:
Pain free & stable
<35mm with no FH
hCG <1500 IU/L
Can return for F/U- hCG days 2, 4, 7, then weekly(should drop by >15% each time)
Methotrexate:
Pain free & stable
<35mm with no FH
hCG <5000 IU/L
No IUP
Can return for F/U- hCG measurement D4 and 7, then once per week until negative
Surgical:
Symptomatic/ clinically unstable
Sixe >35mm or FH or ruptured
Polymorphic eruption of pregnancy vs pemphigoid gestationis
Both itchy rashes.
Polymorphic eruption= itchy, bumpy rash in last 3 months of pregnancy, usually over abdomen. Clears with delivery.
More common in first pregnancy, white eomen, high BMI, multiple pregnancy and male foetus.
Pemphigoid gestationis (herpes gestationis)- itchy red rash.
Autoimmune disease associated with IgG against hemidesmosomal proteins, BPAG2 & BP180, present in skin basement membrane. AutoAb to amniotic basement membrane may cross-react with skin BPAG2 leading to the immune response.
Treatment (both): topical steroids and antihistamines, emollients.
Complete vs parțial molar pregnancy
Complete
Diploid (46XX most common)
Usually due to duplication of haploid sperm following fertilization of an empty ovum
No fetal tissue
Has the highest risk of malignancy (CM is15% vs. PM is 0.5%).
Ultrasound: “snowstorm” diagnosis
- Need for chemo afterwards is 15%
Partial
Triploid (e.g. 69 XXY)
Two haploid paternal gene sets and 1 maternal haploid gene set (dispermic fertilization of an ovum)
Evidence of fetus or RBCs
Medical evacuation may be necessary if large fetal tissues
- Need for chemo afterwards is 0.5%
Histological features of malignancy
Mitoses
↑nuclear: cytoplasm ratio
Abnormal differentiation
Disrupted architecture
Breach of BM by malignant cells
Metastasize
IOTA benign vs malignant USS rules
Benign
Unilocular cyst
If solid components, largest solid <7mm
Acoustic shadowing
Smooth multilocular tumour with largest diameter <10cm
No blood flow
Malignant
Irregular solid tumour
Ascites
At least 4 papillary structures
Irregular multilocular solid tumour with largest diameter >10cm
Very strong blood flow
Endometrial cancer
- Type 1 vs Type 2
- Age at presentation
- Prognosis
- Most common spread
- Staging & 5 year survival
Type 1
- Younger perimenopausal women with unopposed oestrogen
- Risk factors include obesity, HRT, nulliparity, PCOS, early menses/ late menopause
- Endometriod carcinoma (pre-malignant phase is atypical hyperplasia)
Type 2
- Older post menopausal women
- Non endometriosis (serous carcinoma)
Typically present age 50-60 as PMB
Most commonly spread to external iliac LN
Staging:
Stage 1 (85-90% 5Y survival)
1A: limited to uterus, invasion <1/2 myometrium
1B: limited to uterus, invasion >1/2 myometrium
Stage 2 (65%)
Cervical stromal invasion
Stage 3 (45-60%)
Invasion beyond uterus, but confined to pelvis
3A: invasion of uterine serosa, adnexa and peritoneal fluid
3B: Vaginal invasion
3C: Nodal involvement (C1= pelvic, C2 = para-aortic)
Stage 4 (15%)
Distant metastasis
4A: Invasion of mucosa of rectum/ bladder
4B: Distant including abominal mets or inguinal LN
Tumour markers in ovarian masses
Ca-125
LDH, AFP, HCG if <40 years with complex ovarian mass (germ cell tumours)
Types of primary ovarian ca. & tumour markers
Epithelial (85%)
- Serous (75%)- psammoma bodies
- Mucinous (CEA, TATI)L pseudomyxoma peritonei
- Brenner’s
- Clear cell
- Differentiated
- Endometrioid
- FIbroma
Stromal (5%)
- Sertoli-Leydig (testosterone secreting)
- Thecofibroma
- Granulosa (oestrogen secreting, inhibin A, 50% show Call-Exner bodies)
Germ cell (5%)- 50% show Schiller-Duval bodies
- Germinoma (yolk sac tumour)
- Endodermal sinus tumour (secretes AFP and alpha anti-trypsin)
- Choriocarcinoma
- Teratoma
- Embyronal E.G. Dysgerminoma (secretes LDH)
Benign ovarian masses
Primary malignant ovarian masses
Secondary malignant ovarian
Benign ovarian masses
- Functional cysts
- Serous cystadenoma
- Mucinous cystadenoma
- Mature teratoma (commonest ovarian tumour- 40%, bilateral in 10-15%)
Primary malignant ovarian masses
- Germ cell tumour
- Epithelial carcinoma
- Sex cord tumour
Secondary malignant ovarian
- Spread from breast/ GI/ peritoneal carcinoma
- Krukenberg = ovarian ca from GI primary cancer, mucin-secreting signet ring cells.
Meig’s syndrome
Ascites, pleural effusion and ovarian fibroma or thecoma (1% cases)
Ovarian cancer:
- Staging & 5 year survival
- Peak incidence
- Common sites of spread
Stage 1
Limited to 1 or both ovaries
1A: involves 1 ovary, peritoneal washings negative
1B: involves both ovaries, peritoneal washings negative
1C: capsule ruptures, peritoneal washings positive
Stage 2
Pelvic extensions
2A: implants on uterus
2B: implants on pelvic structure
2C: peritoneal washings positive
Stage 3: peritoneal implants beyond pelvis or with extension to small bowel/ omentum
3A: microscopic implants
3B: Macroscopic implants <2cm
3C: Macroscopic implants >2cm
Stage 4: distant mets
5 year survival for all stages is 35-45%
Peak incidence 55-74y
Commonly spreads to pelvic/ peritoneal cavity and para-aortic LN
CIN I to III
CIN I: dysplasia confined to basal 1/3 of squamous epithelium
CIN II: dysplasia confined to basal 2/3 of squamous epithelium
CIN III: full thickness epithelial dysplasia
What is the transition zone on the cervix? What is its clinical significance?
The region where the endocervical columnar epithelium has undergone squamous metaplasia and is bounded proximally by the new SQJ and distally by the original SQJ.
TZ is where CIN occurs and needs to be sampled/ visualised by smear/ colposcopy
Cervical cancer staging
Stage I
Limited to cervix
1A1: depth <3mm, length <7mm
1A2: depth 3-5mm, length <7mm
1B1: lesion <4cm
1B2: lesion >4cm
Stage 2
Invades beyond uterus, but not to pelvic wall or lower 1/3 of vagina
2A: without parametrial invasion
2B: with parametrial invasion
Stage 3
Extends to pelvic side wall or lower 1/3 vagina or hydronephrosis
Stage 4
Extends beyond true pelvis
4A: invades mucosa of bladder and rectum
4B: distant mets
Features of TB on endometrial biopsy
Focal areas of ulceration, caseous necrosis and haemorrhage
Two most common cancers associated with endometriosis
Clear cell carcinoma
Endometriod carcinoma
Cell death associated with cytoplasmic blebbing
Apoptosis
Best way to detect receptor status in breast ca.?
Immuno-histochemistry (using Abs against the different receptors)
Wound healing
- inflammatory phase
- Lasts 2-3d
- Local vasoconstriction
- Thrombus formation and fibrin mesh
- Platelets line the damaged endothelium and release ADP/ PDGF/ cytokines/ histamine/ 5HT/ prostaglandins
- ADP causes thrombus aggregation
- Cytokines attract lymphocytes and macrophages - Proliferative phase
- d3- week 3
- Increased fibroblast activity produces collagenase type 3 and ground substance
- Angiogenesis
- Re-epithelialisation of wound surface
- Formation of granulation tissue - Remodelling
- Maturation of collagen (type 1 replaces type 3)
- Decrease in wound vascularity
- Wound contraction
Process of healing by primary intention
NOT an acute inflammatory reaction
- Fibrin rich haematoma develops
- Neutrophils appear at the margins within 24h and move towards fibrin clot
- Movement of epithelial cells from wound edge deposit a basement membrane in 24-48h
- Macrophages replace neutrophils by D3
- Granulation tissue invasion
- Neovascularisation (max D5)
- Fibroblast proliferation at week 2
- Scar is devoid of inflammatory cells by week 4
Cells that dominate in acute inflammation in first 24h, then 48h
Neutrophils dominate in first 6-24h
Largely replaced by monocytes in 24-48h
What is a tamm-horsfall protein?
A major protein in normal urine and the primary component of waxy nephron casts (common in ATN).
It is secreted by renal tubular epithelial cells.
What is clear cell adenocarcinoma of the vagina/ cervix?
Who is at risk?
What else are they at risk of?
Rare cancer of vagina/ cervix
Daughters of women treated with diethylstilbestrol during pregnancy (used to prevent miscarriages- non-steroidal oestrogen medication)
Also at risk of vaginal adenosis (presence of glandular epithelium in vagina)
Which is the most common non-epithelial vaginal cancer?
Rhabdomyosarcoma
What is the risk of developing SCC in vulval lichen sclerosis?
<5%
What is Paget’s disease of the vulva?
Adenocarcinoma in situ
Most common solid benign tumour of ovary
Fibroma
Most common benign epithelial ovarian tumour
Serous cyst adenoma
Proportion of Brenner tumours of the ovary that are malignant
5%
What type of gene is BRCA 1/2
Tumour suppressor genes
Histology of fibroma
Characterised by spindle cells with central nucleus and no nuclear atypia
Fibromas with > 3 mitoses per 10 high power fields are considered fibrosarcomas
What type of necrosis is ATN?
Coagulative
Most common site for vulval cancer
Labia majora
What type of antibodies is lichen planus associated with?
Typical features of lichen sclerosis including histology?
Extracellular matrix protein-I antibodies (60-80%)
Smooth porcelain-white plaques on the vulva.
Peri-anal skin involvement.
Narrowing of Introits
Hyperkeratosis
Fissuring
doesn’t typically involve vaginal mucosa
Histology
- Atrophy of epidermis
- Hyperkeratosis
- Loss of normal rete ridge pattern in epidermis
- Lymphocytic infiltrate in dermal-epidermal junction
What type of antibodies is lichen planus associated with?
anti-basement membrane antibodies
4 main groups of Lichen Simplex
Underlying dermatoses
Systemic conditions
Environmental factors
Psychiatric disorders
Probability of sarcomatous change occurring in a fibroid
1 in 500
Size differentiation between micro and macroprolactinoma
10mm diameter
