Random Lists of Common Questions Flashcards
Viruses that Cause Cancer
HPV - SCC of anogenital tract, cervical adenocarcinoma oropharyngeal SCC, sinonasal HPV-related multiphenotypic carcinoma
HHV8 - Kaposi sarcoma, Primary effusion lymphoma
EBV - NPC, HL, BL, gastric carcinoma
Hep B / C - HCC
Merkle cell polyomavirus - Merkel cell carcinoma
HTLV-1 - adult T cell lymphoma / leukaemia
Sarcomas that Metastasise to Lymph Nodes
SCARE
Synovial sarcoma
Clear cell sarcoma
Angiosarcoma
Rhabdomyosarcoma
Epithelioid sarcoma
Common Tumours that Metastasise to Bone
Breast
Lung
Thyroid
Kidney
Prostate
Tumours with Plasmacytoid Morphology
Plasma cell neoplasms (!) - myeloma, LPL
Lobular breast, diffuse gastric and urothelial (plasmacytoid variant)
Myoepithelial
Mesothelial
Melanoma
Osteoblastic
Rhabdoid tumours - INI1 / BRG1 lost
Subtypes of Amyloid
Amyloidosis refers to a heterogenous group of disorders characterised by extracellular deposition of non branching linear fibrils.
AL: Ig LC / Ig HC - plasma cell neoplasms
AA: Chronic infection or inflammation (e.g. autoimmune)
: Familial hereditary fever syndromes
ATTR: Hereditary or mutation associated
Non familial mutation form
B2 microglobulin: haemodialysis
A-Beta: Alzheimers disease, aging
Benefits of Synoptic Reporting
1) Standardised report that captures all the essential information required to stage, prognosticate and manage a patient. Acts as a checklist to remind pathologist of required elements and includes explanatory notes if needed.
2) Allows clear communication to the clinician / MDM.
3) Improved data capture for Cancer Registries etc. Data can used be re-purposed for cancer research & for population based research.
4) Evidence that structured reporting improves the quality of the pathology report and subsequently the delivery of adjuvant therapy and patient outcomes.
Define Quality Control and Quality Assurance
Quality Control (QC) refers to activities lab engages in to ensure that tests are working correctly and results are of high and reproducible standard. Aim = right test, for the right result, on the right patient, reported to the right doctor at the right time
External Quality Assurance/Assessment (EQA) aims to ensure that all laboratories testing the same sample will give the same result
Internal Quality Assurance (IQA) which monitors performance, drives improvement and supports collaborative on-going professional practice
Who are the ISO
International Organisation for Standardisation.
NGO. Integrated organisation composed of national standard bodies.
Lay down standards and protocols for laboratory practice (ISO 15189 for medical labs). Compliance with standards are assessed by IANZ and NPAAC.
Quality Control Measures at Cut up Bench
Cerebro system - QR codes and tracking of specimens
Correlation with clinical details and imaging
Checking three points of ID
One specimen on bench at a time
Alternate specimen types and use rotating system of biopsy inks for biopsy transfers
Rinsing instruments and cleaning board between specimens
Explain role of p57 in molar pregnancy
Poor interobserver variability between CHM, PHM and hydropic abortus on histology alone. Can use p57 IPX and FISH to distinguish these.
Partial mole:
p57 positive (nuclear expression in at least 10% of villous stromal cells and cytotrophoblasts)
NB: p57 also positive in normal fetus / hydropic abortus
FISH shows triploidy in partial mole
Complete mole:
p57 negative
FISH shows diploidy (diandric)
P57 negative in CHM because p57 is a paternally imprinted, maternally expressed gene and complete moles are diandric (dispermy, empty ova)
How to troubleshoot unexpected negative IPX
Double check you’ve stained the right block…
Look at controls on slide - check correct antibody has been used and that external and internal controls are working as expected.
If controls working then repeat IPX on different block.
If controls look iffy then IPX may have failed for technical reason: failure of fixation, failure of antigen retrieval, uneven dispersal across slide. Discuss with scientist and attempt on different block or consider alternate test.
Interpret MMR / BRAF in GIT
Loss of MLH1 / PMS2
- somatic promoter hypermethylation or
- germline loss of MLH1 (Lynch)
- > if BRAF positive, almost always due to promoter hypermethylation
- > if in doubt can request MLH1 promoter hypermethylation studies
Isolated loss of PMS2
Loss of MSH2 / MSH6
= both usually associated with germline loss / Lynch
Why is p16 overexpressed in HSIL?
HR HPV (subtypes 16 / 18) integrate into host genome
Production of viral oncoprotein E7 which binds to RB causing it to degrade
Without RB acting as a brake on the cell cycle, the CDKN2A gene can continue to produce p16 protein
When overexpressed p16 causes downstream effects on cellular proliferation and increased cell survival
NB: E6 viral oncoprotien binds to p53 with similar downstream effects
How to Decontaminate Cryostat
1) Speak to scientists - OHS for staff (should wear N95 for FZ, fill in incident form). Inform OT may be delay in results if only one cryostat.
2) PPE
3) Crytostat preparation - turn off to allow to warm to room temperature. Reomve everything (blades, knives, tools, sectionning debris etc.) disassemble anything with multiple components. Use isopropyl alcohol to clean.
4) Chemical disinfection once at room temperature. Follow manufacturers instructions. Some cryostats have UV disinfection built in.
5) Dry, lubricate, reassemble and then turn back. Don’t reuse until back at cold temperature.
Reasons for Performing Frozen Section
- Assess whether a structure is present or absent e.g. parathyroid gland
- Assess whether adequate lesional tissue is present for further assessment e.g. soft tissue incision biopsies
- To triage tissue for other studies e.g. microbiology, flow cytometry, tumour banking
- To change intraoperative management e.g. margin status H&N cancers, breast sentinel nodes
OPTIONS: just macroscopic assessment (+ / - surgeon), imprint or smear, freeze tissue
Reasons for Discordant Frozen Section Results
- Clinical details missing / unavailable
- Specimen labelling error
- Gross sampling error
- Technical issues in performing frozen section
- Misinterpretation of the frozen section - overcall, undercall or misclassify
- Frozen section negative, permanent sections from block positive
How to Stain a Frozen Section
Frozen sections are stained using a rapid H&E technique
Performed by scientists in lab but protocol on wall and stations clearly labelled with instructions if needed
- FIX with ethanol / methanol (30 secs)
- HAEMOTXYLIN (30 secs, rinse with water)
- HCL (10 secs, remove excess haemotoxylin)
- BLUE haematoxylin with AMMONIA (10 secs)
- EOSIN (15 secs)
- ETHANOL to clean slide then wash in XYLENE
Then coverslip slide.
Purpose of MDM
- A forum for communication
- allows all the pertinent data regarding a patients disease to be collated and discussed in order to make management decisions
- allows opportunity for dicussion between clinicians, radiologist, pathologists etc regarding challenging or unclear aspects of a case - Quality Tool
- provide an opportunity for internal audit of cases and to identify and discrepant or discordant findings
SRBCT’s in Adults
Lymphoma
Small cell NE carcinoma
Merkle cell carcinoma
Small cell melanoma
SRBCT’s in Young Adults / Some Children
DSRCT
Synovial sarcoma, poorly differentiated
Olfactory neuroblastoma
Small cell osteosarcoma
Mesenchymal chondrosarcoma
High grade myxoid liposarcoma
SRBCT’s in Children / Some Young Adults
Lymphoblastic lymphoma
Ewing sarcoma
CIC and BCOR rearranged sarcomas
Myeloid sarcoma
Neuroblastoma
Blastema predominant Wilms tumour
Alveolar RMS, solid variant
Medulloblastoma
Retinoblastoma
Hepatoblastoma, small cell variant
Most Common Metastases to Brain
Lung
Breast
Melanoma
Renal cell carcinoma
Colon
Thyroid
Critical Values in Anatomic Pathology
1) Cases with immediate clinical comsequences:
- crescents in >50% of gloms in kidney biopsy
- uterine contents without villi or trophoblast
- fat in endometrial curette or endoscopic polypectomy from colon
- malignancy in SVC obstruction
- neoplasms causing paralysis
- mesothelial cells in cardiac biopsy
- (acute) transplant rejection
2) Infections
- bacteria / fungi in CSF
- bacteria in heart valve / bone marrow
- invasive fungi in an immunocompromised patient
- HSV in cervical smear in a pregnant women
3) Unexpected / discrepant findings
- unexpected diagnosis of malignancy
- significant disagreement between frozen or prelim FNA and final diagnosis
- significant disagreement between original path and outside review
Common Laboratory Hazards
Blood, infectious agents, sharps
Falls, trips, slips, ergonomic injury
Chemical hazards and spills
Fire hazards
Electrical hazards
Biologic Hazards in the Laboratory
Blood borne illnesses:
Hep B, Hep C, Hep D, HIV
Immunisation where possible, handwashing, cover cuts, PPE
BBA / Incident form if exposed - OHS will test staff and source (with consent) at time of incident and in 3/12
Other Infectious Agents:
Prions, TB, Covid
PPE (N95), open in biosafety cabinet, fix for > 48 hours
Name some Chemical Hazards in the Laboratory
Acetone – flammable liquid
Acetic acid – combustible liquid
Concentrated acids (hydrochloric, nitric, sulfuric) - corrosive
Concentrated bases (sodium hydroxide, ammonium hydroxide) - corrosive
Dyes such as auramine O, basic fuchsin and Congo red - carcinogenic
Toluene - neurotoxic and carcinogenic
Ethanol – flammable liquid
Xylene - toxic and flammable
Formaldehyde - irritant and carcinogenic
What is Contained in the Safety Data Sheets for Chemicals
Identification of Substance
Hazard(s) Identification
Composition/Information on Ingredients
First-Aid Measures
Fire-Fighting Measures
Accidental Release Measures
Handling and Storage
Exposure Controls/Personal Protection
Physical and Chemical Properties
Stability and Reactivity
Toxicological Information
Non mandatory: Ecological Information, Disposal Considerations, Transport Information, Regulatory Information
How To Manage a Formalin Spill or Exposure
1) Report the incident to the person in charge of the laboratory, alert others and assist anyone who is contaminated.
2) For large chemical spills, consult the appropriate SDS or product label for specific measures, e.g. for a flammable liquid this may include:
Avoid breathing vapors
Remove all sources of ignition
Evacuate the area immediately
3) Arrange for the safe cleanup of the chemical
Smaller spills may be absorbed with paper towels while wearing gloves and other PPE. Decontaminate the area and wash hands. Larger spills need formal spill kit with absorbent material.
4) If exposed to chemical:
For contact exposure, flush copiously with water and remove any contaminated clothing.
If the eyes or mucous membranes are involved, flush with water for at least 10 minutes
If severe burns are involved, apply cold wet cloths, gauze, or paper towels, and immediately seek medical attention.
What to Include on Label for Chemicals that have been Decanted or Newly Prepared
Name of reagent
Reagent concentration
Initials of person who prepared the reagent
Date of preparation
Expiration date
Special storage requirements
Difference Between a Fume Hood and a Biosafety Cabinet
(Chemical) Fume Hood:
Used for dangerous chemicals
Protects the user
No HEPA filter
Exhausets air outside the building
Biosafety Cabinet:
Used for infectious biologic agents
Protect the user, the environment and the material
Has a HEPA filter
Does not exhaust air outside (without decontamination)
Advantages and Disadvantages of Smear versus Frozen
Smear / Imprint
Uses less tissue
Quicker
No frozen section artefacts
But…. no architecture, can’t give size (e.g. breast metastasis)
Frozen Section
Can see architecture and relationships of structures
Can give size of deposits and measure distances
But... uses up more tissue for FFPE and frozen artefacts
Viral Inclusions
Nuclear inclusions are generally associated with DNA viruses (HSV, CMV, JC, BK, adenovirus)
CMV also has cytoplasmic speckles.
RNA viruses don’t usually have inclusions (except measles)
Nuclear inclusions fall into two morphologic categories:
Cowdry A: eosinophilic owls’eye e.g. CMV
Cowdry B: smudge cells with ground glass chromatin e.g. HSV
Other viral effects:
Koilocytes in HPV
Warthin-Finkeldey giant cells in measles
How to Calculate Area of Field of View
- Take eye piece field number (22) and divide by objective magnification (40x) to give diameter of field of view (0.55mm)
- Take diameter, halve it and then use π r2 to calculate FOV. area e.g 0.55mm field diameter gives a FOV area of 0.237 mm2
- To convert mm2 to HPF: X mm2 divided by FOV area = HPF. e.g. 2mm2 divided by 0.237 = 8.4HPF
Types of Rosettes
Homer Wright Rosettes
Fibrillary processes point to centre, but no true lumen or vessel
Pathognomonic for neuroblastic tumours
Perivascular Pseudorosettes
Fibrillary processes point to centre containing a vessel
Seen in ependymomas
Luminal Type Rosettes
Polarise around a central lumen which is formed by apical borders of cells, e.g NET’s and Flexner-Wintersteiner rosettes seen in RB
How to See if Specimen (or Floater) matches a Patient
Barr bodies (if different genders…)
A, B, H blood group antigen IHC
MSI PCR to see if profile matches
HLA antigen testing
