Understanding the PAD and cytology reports in the cancer patient Flashcards
Cytology techniques: A fine needle aspirate can be performed using either
the aspiration or fenestration technique.
The character of the mass may lend itself more to one technique versus the
other.
Using both techniques on the same mass may improve diagnostic yield.
Always preform several aspirates in the same lesion (min. 3 pokes in different directions).
Cytology often provides useful diagnostic information in many, but not all cases.
aspiration vs fenestration technique in cytology
Aspiration technique involves simply inserting the needle into the lesion while gently aspirating with a syringe.
Simple FNA meaning fenestration technique involves repeated insertions of a needle into the tissue, WITHOUT a syringe attached. Withdraw the needle, attach the syringe, and expel the sample onto a slide.
Cytology benefits and trouble shooting.
Cytology is usually very good in cutaneous lesions and a positive result
very reliable. Very high positive predictive value (97%).
Lower negative predictive value (approx. 65%)
This means that you can be confident that a report diagnosing a tumor will be
reliable.
However, a report reporting negative results can be due to insufficient
material, aspiration performed in the wrong area of a neoplasia or in a region
with local inflammation and/or necrosis.
If poor exfoliation, consider aspiration – if using fenestration technique, or increase size of the needle.
Is sedation required for FNA?
Nope, Can mostly be performed on unsedated animals but never perform aspiration in the oral cavity on non-sedated/anesthetized animals!
Local topical anesthetics can be useful in oral and or face locations.
Fast turnaround of results if you stain and look at them yourself.
Air dried samples very stable
Cytoimmunochemistry possible, but communicate with the lab in advance.
Molecular techniques also available to improve diagnostics. Can often be used even on stained samples.
PARR very useful and also works on cats!
(PCR for Antigen Receptor Rearrangements to determine if a population of cells is the result of the clonal expansion of B or T cells, which usually, but not always, implies lymphoid neoplasia aka lymphoma.)
Grading will typically not work with what type of samples?
on cytology
Cytological grading in K9 MCT still inconclusive – reports either overestimate
or underestimate grading in cutaneous MCT in dogs.
However, skilled clin pathologist can give you very good clues to the nature of
the lesion.
Cytology language to become familiar with. (13)
Anisokaryosis
Prominent, multiple, and variable sized nucleoli
Increased N:C ratio (is commonly associated with precancerous dysplasia as well as with malignant cells.)
Nuclear pleomorphism/molding
Coarse or atypical chromatin pattern
High mitotic index
Atypical mitoses
Multinucleation
Basophilic cytoplasm
Round cell tumors (Lymphoma, Mast cell tumor, Histiocytoma, TVT, Plasma cell)
Epithelial tumors
Mesenchymal tumors
Melanomas
Tingible body macrophages are very typical to lymphomas.
Lymphoglandular bodies are bits of cytoplasm from degraded neoplastic lymphoma cells.
Tissue biopsy.
If the cytology is not definitive, and/or if a major resection is planned, a tissue biopsy may be indicated prior to treatment.
It is important to keep in mind that the biopsy tract should not interfere with
a future definitive resection. Tumor can be seeded into the biopsy tract.
Biopsy benefits and trouble shooting.
Biopsy is typically needed for adequate grading. This is because many grading systems include features such as invasion
and localization (e.g. cutaneous vs sub cutaneous). These features cannot be analyzed in cytology slides.
It is important to go deep enough with the biopsy in suspected soft tissue
sarcomas to avoid undergrading – The pseudo capsule is really annoying!
Also important to consider taking several biopsies from lesions, especially if larger, to avoid unspecific answers – May hit necrotic and hypoxic areas!
Remember that the pathologist grade the tumor based on the location having the highest grade. Grade normally I-III, where high grade always are equal to a worse outcome.
This is the reason why tumors are frequently re-graded when the final
resection is analyzed.
Tissue biopsy language.
Mitotic index
Differentiation
Invasion
Localization
Tubulin formation (cytoskeleton)
Nucleoli – size and numbers
Intravascular tumor emboli
Immunohistochemistry
Origin of cell type
Biopsy language,
Mitotic index (MI)
Often the most consistent negative prognostic marker in all tumors.
The absolute rate when it is considered prognostic varies among tumor types.
Please make sure that it is reported in the standard format mitoses/10 HPF (high power field).
If only reported per HPF you must multiply with 10 to compare to most publications considering prognosis.
Biopsy language,
Differentiation
Together with mitotic index this is most important to understand the biological behavior of the tumor.
Mostly reported as high, moderately and low differentiation.
The worst prognosis is usually tumors that show anaplastic appearance.
Then the pathologist cannot decide cell of origin, sometimes not even after
immunohistochemistry.
Biopsy language,
Invasion
When tumor cells invade other tissues this usually indicates worse prognosis.
Typically soft tissue sarcomas (STS) have a pseudocapsule (fooling the surgeon) that on histopath contains branches of tumor cells anchored in surrounding tissue.
Sometimes satellites of tumors can be found outside the central tumor – called skip metastases also characteristic for soft tissue sarcomas.
Biopsy language,
Localization
If the tumor is situated in the cutis, subcutis or intramuscular this can impact on the level of grading.
Some tumors behave biologically different depending on localization.
Hemangiosarcomas in the skin carry a good prognosis in dogs compared to localization in the spleen or right auricle where survival times is much shorter.
Biopsy language,
Tubulin formation
Cell skeleton and mitotic features that are used in e.g. K9 mammary tumor grading system.
Biopsy language,
Nucleoli – size and numbers
As in cytology, size and numbers of nucleoli are described
Typically larger nucleoli and/or increased numbers are reported in more malignant
tumors
Biopsy language,
Intravascular tumor emboli
If tumor cells are found in blood/lymph vessels this is a clear indication of
metastatic spread
This have been reported to worsen prognosis in many tumors both in dogs and cats
Many times this finding supports the use of adjuvant chemotherapy even if “clean
margins” are reported
Biopsy language,
Immunohistochemistry and origin of cell type
A laboratory method that uses antibodies to check for certain antigens (markers) in a sample of tissue. The antibodies are usually linked to an enzyme or a fluorescent dye. Often used if differentiation of the cells are poor.
Very useful to differentiate sarcomas from carcinomas, where vimentin is
positive for sarcomas whereas keratin is used to define carcinomas and epithelial cell origin.
In poorly pigmented melanomas immunohistochemistry is valuable
to confirm the tumor type.
Typically amelanotic melanomas are considered having a worse prognosis, likely correlating to a lower differentiation.
Low differentiated mast cells often lacks the typical granules and even here special staining are used .
The mitotic index can be better understood if immunohistochemistry also is preformed.
well differentiated mast cells and eosinophil thus low grade mast cell tumor suspected but can’t be confirmed with only cytology
with atypical location as its on tongue mucosa and not on skin like usual for MCT.
e.g. squamous cell carcinomas are more common on the tongue
mammary adenocarcinoma
mammary tumor cytology is often overinterpreted due to the affect of hormone cyclicity on the tissues and cells.
feline mammary hyperplasia with ulceration
Treatment involves removal of the progesterone source. Administration of antiprogestins or ovariohysterectomy for animals in diestrus.
NB For cytology on soft tissue sarcomas, remember…
STS normally exfoliates less and may need larger bore needles for successful FNA.
Refine prognosis by…?
Grading cannot be done based on cytology alone.
Grading often needed to refine prognosis, hence the use of BOTH cytology and histopathology.
Larger lesions need pre-operative biopsy, to motivate extensive surgery that may induce post operative effects on body function or cosmetics.
Grade normally I-III, where high grade indicate a…
a worse outcome.
Please remember that highly differentiated tumors are ? grade, where low
differentiated tumors (anaplastic) are ? grade.
Please remember that highly differentiated tumors are LOW grade, where low
differentiated tumors (anaplastic) are HIGH grade.
High grade indicates a worse outcome.
Cytology will NOT normally increase risk of spreading the tumor – but its not recommended to perform intra-abdominal ultrasound guided aspiration for what 2 types of suspected neoplasia?
bladder tumors or ovarian neoplasia