Cytology of tumours Flashcards
List the 6 indications for cytology
- Lesion (nodule, mass, plaque) palpable externally or seen on imaging
- Organomegaly
- Cavitary effusion
- Cancer staging (lymph nodes, liver, spleen, BM)
- Pyrexia of Unknown Origin
- Test of choice for a bone marrow exam
What are the expectations of using cytology
- Identify inflammation
- Suspect or detect infection (with also preliminary morphologic identification)
- Detect neoplasia
- Differentiate between benign and malignant in most cases
- Identify cell of origin in many cases
Is specificity or sensitivity higher for cytology? What does this mean?
Sensitivity 75 – 89 %
Specificity 97 – 100%
- Therefore diagnosis of cancer are very likely to be true but need to be cautious if cancer is suspected but cytology non-confirmatory
- Results are often suggestive or supportive i.e. a guide to clinical decisions rather than a definitive answer
What questions should be asked when you are approaching examination of a cytology slide?
What is expected normally on the tissue/organ sampled?
1. Consider differentials for lesion
2. Adequate quality and cellularity?
3. Inflammation or neoplasia (or both?)
4. If inflammation, what type?
5. If neoplastic, what type?
6. Malignant or benign?
Describe staining of sample slides in house
Diff quik
Wear gloves
10 dips in each
Then rinse the slide
Describe the approach to the slide at 1x magnification (naked eye)
Is the slide labeled adequately?
Macroscopic appearance of sample
Staining? Distribution of material?
Describe the approach to the slide at 4-10x magnification
Scan all the slides and choose the most representative area of the slide
- Intact cells, thin region with good cytoplasmic/nuclear detail “sweet spot”
- Identify cell populations
What do ruptured cells on a sample indicate?
Incorrect sampling or smearing technique
Repeat applying less pressure
Use a needle-only technique
What does inadequate staining of a slide indicate?
Insufficient time
Inadequate drying prior to staining
Layer of cells too thick
Too close to histo pot… (formalin fumes exposure)
What is the predominant inflammatory cell seen in most cases?
Neutrophil
What other inflammatory cells may be seen?
Macrophages
Lymphocytes and plasma cells
Eosinophils
When using cytology for masses what kinds of cells might you see?
Epithelial cells - skin, gut, glandular
Mesenchymal - connective tissue, muscle
Round cells - mainly cells of the immune system
Which normal cells seen in inflammatory processes are often misinterpreted as malignant cells?
Reactive fibroblasts
If neoplasia is suspected from cytology, starting from low power how/what should you assess on the slide?
- Cell arrangement
- Cell shape
- Criteria of malignancy
- Cell types
What cell shapes might be seen?
Round
Polygonal
Spindle
Name the cell type seen in adenomas and carcinomas
Epithelial cells
How do epithelial cells appear on cytology
Cohesive - adhere to one another in clusters and clumps ‘islands of cells’
Well defined cell-cell junctions
Usually polygonal, cuboidal, columnar, round cells with round to oval nuclei
How do round cells appear on cytology
Non-adherent, individualized
‘Sea of round, discrete cells’
Usually round cells with round to oval nuclei
Size generally small relative to epithelial and spindle cells
Spindle/mesenchymal cells are seen with which tumour types?
Fibromas
Chondromas
How to spindle cells/mesenchymal cells present on cytology
Nonadherent - but may be loosely aggregated with matrix
Fusiform to stellate shaped cells with oval to elongate nuclei
Wispy cytoplasmic projections
Indistinct cell borders
Name 5 examples of round cell tumours
- Histiocytoma
- Plasma cell tumor
- Mast cell tumor
- Lymphoma
- Transmissible venereal tumor (not in UK)
What shape are mesenchymal cells?
Comet shaped/windmill arms
What is a lipoma, how would it appear on cytology?
Benign tumour
- Cannot distinguish from ‘normal’ subcutaneous adipose tissue
- Grapes of cells composed of one large ‘empty’ vacuole (it contained lipid before the staining process) and a small peripheralised nucleus
What are keratinising cyst?
Non-neoplastic, non-inflammatory
Often called sebaceous cysts (misnomer)
Benign biological behaviour
Cytologically identical to follicular tumours
What is sebaceous hyperplasia?
Raised, hairless, cauliflower shaped
Cytologically identical to sebaceous adenomas
Describe hair follicle tumours
- Group of related benign tumors
- Often cystic therefore accumulate keratin and cellular debris
- Cytology cannot differentiate specific type (and from cysts) but most have similar benign biological behaviour
Once we have established an interpretation of neoplasia and classified it we should try to decide if the neoplasia is benign or malignant - list the criteria of malignancy
- Hypercellularity (in mesenchymal tumours)
- Pleomorphism (anisocytosis, anisokaryosis)
- High/variable N:C ratio
- Multinucleation
- Karyomegaly
- Mitoses (especially if atypical)
- Nuclear moulding (rapid cell growth)
- Large, angular, or variably sized nucleoli
Define anisocytosis
RBCs that are unequal in size
Define anisokaryosis
Variation of nuclear size and shape from cell to cell
Define karyomegaly
The condition of a cell’s nucleus being abnormally enlarged
Describe how malignant cells are differentiated from hyperplastic/benign cells
- Variable sized cells
- Large, multiple, prominent and irregularly shaped nuclei
- Nuclear chromatin is abnormally clumped
- High mitosis rate
Do malignant or benign cells exfoliate well?
Malignant
How is the malignancy criteria used to confirm a malignant tumour?
Minimum 3 criteria, nuclear are stronger
- Adapt to the specific organ/cell type
- Allow some with inflammation and in histiocytes
Which tumours may be described as ‘confusing tumours’ as they are not easily classified as round, epithelial or spindle?
- Endocrine and neuroendocrine tumours
- Histiocytic sarcoma, chrondrosarcoma and osteosarcoma: maybe round or spindle
- Melanoma = the great imitator - undifferentiated melanocytes
- Inflammation and fibroblasts
Describe the features and cytological appearance of a histiocytoma
- Dome shaped, alopecic, may be ulcerated
- Tends to regress in a few weeks
- Often (but not only) in young dogs
- Light blue cytoplasm fading into the background
- Small lymphocytes often present and may predominate at later stages!
- Sometimes difficult to differentiate from plasma cell tumour and lymphoma
Describe the features and cytological appearance of lymphoma
Round cells with high nucleus to cytoplasm ratio
Large blasts (larger than a neutrophil)
Monomorphic population
Describe the features and cytological appearance of a mast cell tumour
- Mast cells have magenta granules in the cytoplasm
- Poor granulation can be due to poor differentiation (more aggressive tumour)
- Sometimes granules do not stain well with Diff Quik!
- Submit some unstained slides
Describe the features and cytological appearance of a plasmacytoma
- Cutaneous plasmacytoma is usually benign
- Can be well differentiated to pleomorphic (most commonly)
- Deep blue cytoplasm, perinuclear halo, eosinophilic borders
- Round, eccentric nucleus
Describe the features and cytological appearance of a histiocytic sarcoma
- Can arise from any tissue
- Arises from interstitial dendritic cells
- Usually marked cell pleomorphism with karyomegaly and multinucleation
- Localised or disseminated
Describe the features and cytological appearance of a trichoblastoma
Benign skin tumour
Scant amount of cytoplasm
Uniform nuclei
Describe the features and cytological appearance of a sebaceous adenoma
Raised cauliflower alopecic lesions
Clusters of cohesive heavily vacuolated cells
Cannot differentiate from hyperplasia on cytology
Describe the features and cytological appearance of a hepatoid gland tumour
- Usually benign
- Cutaneous mass perianal or along thighs
- Clusters of “hepatoid” cells: similar to hepatocytes
- Surrounded by few ‘reserve’ cells
- Smaller and higher N:C ratio and oval nuclei
Describe the features and cytological appearance of a squamous cell carcinoma
- Usually ulcerated lesions, highly malignant behaviour
- Often metastasis to lymph nodes already present
- Polygonal cells with variable tendency to cohesion
- Typically marked pleomorphism (variable shape)
- Often secondary neutrophilic inflammation
Describe the features and cytological appearance of an anal sac adenocarcinoma
- Anal sac apocrine glands
- Classically ‘naked nuclei’ appearance
- Often cells form rosettes and ‘rows’
- Sheets of bland-looking cells but high metastatic potential!
- Check lymph nodes!
Describe the features and cytological appearance of a soft tissue sarcoma
- Cytologically all appear similar
- May be difficult to distinguish from reactive fibroplasia
- Histopathology may be needed
- Histology needed for grading and identification of specific type
- Dogs: Perivascular and nerve sheath tumor, Fibrosarcoma
- Cats: Fibrosarcoma/injection site sarcoma
Describe the features and cytological appearance of a melanoma
- Usually benign and well differentiated in haired skin
- Often malignant in nailbeds, oral cavity
- Variable amounts of dark pigment
- May mimic epithelial, round cell or spindle cell tumour
