Fred Reyers, BVSc(Hons), MMedVet(KLD), MRCVS, Registered Pathologist (Clinical Pathology)
Fine needle aspiration biopsy (FNAB) cytology has important limitations. It is not, generally, a sensitive diagnostic method, with some exceptions. However, in competent hands it is, generally, a specific diagnostic method, with some exceptions. Consequently, FNAB-cytology is not always the ideal approach and in some instances other diagnostic approaches may be more appropriate. The clinician needs to have some idea, before relying on FNAB-cytology to rule in/out a possible diagnosis, whether the condition that he/she has in mind, in the tissue/organ affected, is suited to that diagnostic modality. This presentation lists the majority of the tissues/organs and gives an indication of the diagnostic usefulness of FNAB-cytology for neoplasia in each. On the basis of this listing, the clinician should be equipped to decide whether FNAB-cytology is worth doing or whether biopsy might not provide better information. The clinician is encouraged to use FNAB-cytology's strengths and to try to avoid FNAB-cytology when it is unlikely to resolve the diagnostic question.
To this end, this presentation will summarise the diagnostic advantages and/or pitfalls in a large number of organ systems or tissues.
Some Necessary Definitions
Poor sensitivity of a diagnostic modality means that if the patient has the disease you are quite likely to miss it using that modality. For example, transtracheal aspiration cytology (TTA) for pulmonary adenocarcinoma will seldom provide the clinician with a diagnosis, despite the presence of the tumour.
Alternatively, a diagnostic modality, with good sensitivity, will give a positive (diagnostic) result in a large proportion of patients that have the disease in question. For example, FNAB-cytology of enlarged lymph nodes in blastic malignant lymphoma, will, even in relatively inexperienced hands, yield a high level of confirmations.
Despite its generally poor sensitivity, FNAB-cytology is sensitive for picking up pathological reactions and processes that are reflected in widely distributed cellular patterns or reactions in the sampled tissue and reactions that are mostly independent of seeing the architectural effect of the process. For example, lymphoma, lymphoid reactive states, acute peritonitis, pleuritis, arthritis etc., are fairly consistently correctly diagnosed by FNAB-cytological means.
Good specificity means that the diagnostic conclusion would not be reached in patients that do not have the disease. For example, you are not going to find large numbers of highly anaplastic mast cells in a cutaneous nodule, in a patient that does not have mastocytoma.
Alternatively, a diagnostic modality with poor specificity will give a large number of false positive results. For example, pleural fluid aspirate analysis often leads to the incorrect conclusion of two neoplasms: mesothelioma and mediastinal lymphoma.
Despite its generally good specificity, FNAB-cytology is not specific (esp. for neoplastic indicators) in samples from tissues that tend to undergo very profound reactive change in response to a stimulus like inflammation. For instance, in pleuritis and peritonitis mesothelial cells undergo reactive transformation and appear malignant. Similarly, cystitis causes transitional epithelial cells to become quite markedly anaplastic; mammary gland cells in mastitis can appear malignant; and hepatitis causes hepatocytes to become anaplastic.
The term "diagnostic usefulness" is used to describe the combination of sensitivity and specificity.
Tissue-by-Tissue Listing of the Diagnostic Strengths and Weaknesses of FNAB-Cytology
Lymphoid Tissue (Peripheral and Mesenteric Lymph Nodes, GALT, Spleen, Mediastinum)
FNAB-cytology is reliable for reactive lymphadenopathy, hyperplasia, lymphadenitis, lymphoid neoplasia (esp. the most common high-grade, blastic lymphomas).
Less so for metastatic lymph node infiltration.
Avoid the submandibular lymph node if you can. Very often reactive and very often "contaminated" with glandular cells.
Spleen (Less So Than Lymph Node)
FNAB-cytology is fairly useful for reactive lymphoid states, hyperplasia, and splenitis (the latter is very rare actually).
Due to the large variety of proliferating cells that may be "normal" or expected in a spleen, lymphoid neoplasia is more difficult to diagnose than in lymph node aspirates and virtually confined to only the most common high-grade, blastic tumours or those lymphocytic tumours that totally overwhelm the spleen.
Sensitivity is not good for metastatic infiltration and poor for metastatic tumours in spleen. For instance, sensitivity is poor for haemangiosarcoma - even US-guided. However, finding anaplastic, metastatic cells in the spleen is unusual and constitutes a fairly specific finding.
Bone Marrow (Ideally Read with Concurrent Haemogram/Blood Smear)
Excellent sensitivity for marked/severe proliferative disease. Blood dilution is the main threat to a reliable diagnostic opinion.
Specificity dependent on experience.
Very poorly reproducible from day to day and from sampling site to sampling site.
Poor sensitivity for hypoplastic states (often just a thick blood smear and cannot be distinguished from blood dilution) but good specificity for hypoplastic states provided there is no excessive blood dilution.
If possible, visually guided (fibroscopic) FNA aspirates should be obtained.
Cytobrushing is a good second choice but may "miss" significant pathology that is not superficial. These techniques yield poor sensitivity but fair specificity for neoplasia.
Nasal flushes have low sensitivity for neoplasia but good sensitivity for rhinitis.
If rhinitis is present, the specificity for neoplasia becomes poor and, unfortunately, intranasal neoplasia is often associated with secondary inflammation. The fact that adenocarcinoma is more common than adenoma (which is rare), does help improve the specificity somewhat.
Large-breed dogs and dolicocephalic breeds are predisposed to intranasal neoplasia.
FNAB-cytology is sensitive for effusive intrabronchial/bronchiolar and even alveolar (TTA more so than BAL) pathology, but only fair for peribronchial/bronchiolar infiltration.
Pulmonary FNAB-cytology (even US-guided) is generally of poor sensitivity but of good specificity.
FNAB-cytology is not very reliable for chronic obstructive airway disease and poor for focal lung densities such as neoplasms and abscesses, though reasonably specific. Despite that, FNAB-cytology may be the only reasonable recourse because biopsy is generally not feasible.
Soft Tissues (Connective) Including Muscle
Poor sensitivity for most connective tissue. Cells tend to "resist" aspiration, often just yielding a poor blood slide.
Good specificity for the tissue cell line (i.e., mesenchymal), but cell type blurs as anaplasia increases, eventually just a "spindle-cell type."
Group name for tumours is the "soft tissue sarcomas," despite some being very hard/tough.
Fair to good sensitivity for prostatitis.
Fair to poor sensitivity for neoplasia with poor specificity. Reactive epithelial changes are common in prostatitis. Despite this, FNAB-cytology is better than nothing - because biopsy is not a reasonable alternative.
Washings and prostatic massage are disastrously confusing.
Fair to good sensitivity for diffuse conditions such as lipidosis and steroid hepatopathy.
Fair sensitivity for overwhelming toxic/hypoxic degeneration.
Poor diagnostic usefulness for focal disease such as focal/miliary hepatitis, neoplasia (I and II) which is slightly better if US guided for secondary neoplasia but still poor for primary (esp. adenoma).
Poor diagnostic usefulness for cholangitis/cholangiohepatitis and abysmally poor for cirrhosis, PVA and MVD.
Poorly sensitive for most common renal pathology (CIN, GN etc.).
Fairly sensitive for rare renal lymphoma.
Can see renal lipidosis but of doubtful diagnostic use (liver is more reliable).
Bone and Skeletal
FNAB-cytology is fairly sensitive for osteo- and chondrosarcoma. Ideally, one should aspirate from the centre of lesion because that is where the focus of proliferation is situated, unlike most other tumours where one should sample tangentially into the interface between proliferating and normal tissue.
FNAB-cytology is quite specific for skeletal neoplasms.
Bladder aspirate sediment cytology has good sensitivity for cystitis but poor sensitivity for neoplasia. In addition, this cytology has poor specificity for neoplasia - especially when inflammation is present.
Ultrasound-guided FNA can be useful. Fair sensitivity for generic "neoplasia." Fair to good specificity for "generic" neoplasia.
Poor specificity for neoplasia that is specific to the adrenal gland.
Cells are inclined to be very fragile.
Poor sensitivity for neoplasia although it improves with US-guided FNA and is best with laparotomy.
Poor specificity for neoplasia.
Rectal swabs/brush may be useful, but, generally, have poor sensitivity and poor specificity for most diagnostic purposes.
Body Cavities (Pleural, Peritoneal)
The use of a cytocentrifuge significantly enhances the diagnostic usefulness.
Good sensitivity for pleuritis/peritonitis.
Poor sensitivity for neoplasia.
Poor specificity for neoplasia - especially for the diagnosis of mesothelioma.
Fair sensitivity for mastitis.
Poor specificity for neoplasia.
Before submitting FNAB-cytology, stop and consider:
What pathology/process do I have in mind? (i.e., what am I expecting the cytologist to rule in/out for me?)
Is it worth doing FNAB-cytology, knowing the weaknesses and strengths of the technique for this pathology/process in this organ or tissue?
Would biopsy (needle or excision, provided that it is logistically feasible) not provide better information?
Use FNAB-cytology's strengths.
Try to avoid FNAB-cytology when it is unlikely to resolve your question.
FNAB-cytology can provide useful, almost immediate diagnostic information for the clinician, seeking to rule in or rule out the possibility of neoplasia. However, FNAB-cytology has strengths and weaknesses that vary very markedly from tissue to tissue. Some forms of neoplasia are easily and reliably identified in certain tissues or organs (such as poorly differentiated, large cell malignant lymphoma in lymph node aspirate smears), while others are often missed (such as soft-tissue sarcomas) and even diagnosed in error (such as mesothelioma).