The triple test refers to clinical, radiologic and pathologic evaluation of breast abnormalities (lesions) in order to establish a definitive diagnosis. The triple test has become the worldwide standard of care for the diagnosis and management of breast abnormalities. Concordance of all three arms of the test is required for definitive management.
The multidisciplinary approach to managing breast diseases has fostered a closer working relationship between the various disciplines involved in the diagnosis and treatment of breast diseases.
The role of a histopathologist/cytopathologist in the multidisciplinary team?
These are specialist pathologists trained in the microscopic evaluation of cellular (cytopathology) or tissue (histopathology) material for the purpose of making a diagnosis.
Pathologists may be directly involved in obtaining samples from the patient (e.g. FNA) or in the evaluation of tissue samples during surgery (intra-operative consultation/frozen section).
Current practice dictates that all radiologic abnormalities that are suspicious for malignancy must be evaluated microscopically. The purpose of pathologic evaluation is to confirm the presence or absence disease. In the presence of abnormality, the nature and type of disease is established. The absence of pathologic abnormality in samples that are adequately representative serves to reassure the patient.
Breast diseases include changes that are non-neoplastic or neoplastic in nature.
Non-neoplastic changes may be related to inflammation or proliferation which leads to changes in the different components and structure of breast tissue. These disease processes usually have no malignant potential, but the presence of some of these changes may allude to an increased risk of malignancy in the affected individual compared to the general population. The affected individuals may therefore require further investigation or more regular monitoring than the average population.
Neoplastic diseases (tumours) of the breast are classified into benign and malignant types.
Benign breast tumours generally form slow-growing, well delineated lumps. These tumours have no potential for spread or malignant change, but some may grow to significant size, causing localised tissue damage, disfigurement or discomfort.
Once a benign diagnosis has been definitively established using a minimally invasive procedure, further intervention may not be necessary except for specific indications. Despite the well-established natural history of benign neoplasms, the patient may elect to have the neoplasm removed.
Malignant tumours (cancers) include non-invasive neoplasms and invasive cancers. The former have cellular changes of malignancy but are still confined to the epithelium of breast ducts and/or lobules. Examples of these include ductal carcinoma in situ, lobular cancerisation and lobular carcinoma in situ.
Invasive tumours extend beyond the lining of the ducts and lobules and infiltrate the surround supportive tissue (stroma). These tumours are not only locally destructive but also have the ability to spread to lymph glands and other areas of the body.
In addition to the correct classification of the cancer type, important characteristics about the cancer are assessed by the pathologist, such the grade, proliferation rate and hormonal expression. These are attributes of the tumour that are likely to affect the treatment and outcome.
The clinical presentation and radiologic appearance determine the selection of the most appropriate type of biopsy for diagnosis.
The main types of biopsies include the following:
- Fine needle aspirate (FNA )biopsy
- Core needle biopsy (CNB)
- Stereotactic biopsy (FNA or core)
- Vacuum-assisted biopsy
- Incisional biopsy
- Excisional biopsy
There has been a gradual but concerted move towards using the least invasive means to establish a diagnosis and reducing the associated complications. Current recommendations discourage the use of open surgical biopsy (incisional and excisional) as a means of obtaining a tissue diagnosis, except in instances where less invasive biopsies are not possible.
The aim of a preoperative biopsy in the setting of a cancer diagnosis is to obtain sufficient information in order to plan oncologic treatment and to reduce the number of surgical operations or anaesthetic events.
The specimen obtained may either be cellular material, which is suitable for cytologic examination (FNA) or tissue for histologic examination.
The role of FNA in breast cancer diagnosis
The method for obtaining material for cytology is referred to as fine needle aspiration (FNA) biopsy. The material may be obtained by the referring doctor/surgeon, radiologist, pathologist or experienced technologist.
A thin (“fine”) needle with or without an attached syringe is used to draw (aspirate) cells from the area of concern. In patients that have palpable abnormalities, radiologic guidance may not be necessary. Ultrasound guided or stereotactic ((mammographic) FNA may be used for non-palpable and very small lesions.
The material is smeared and fixed onto a glass slide and is evaluated in the laboratory. Some of the material may be stained on site for adequacy and in some cases a provisional diagnosis may be possible. FNA is considered as a screening test for breast cancer diagnosis in some centres as part of the triple test. In specialised cytopathology centres, the FNA biopsy has a high sensitivity (98%) and a high specificity (97%). This method has been presented as a viable alternative to CNB, particularly where the expertise is available and resources are limited.
FNA biopsy is a cheaper option to a core needle biopsy (CNB) and does not require processing, resulting in a shorter time to diagnosis than a CNB. Part of the material may be assessed on site for adequacy and a provisional diagnosis may be established.
FNA also has become a biopsy of choice in assessing axillary lymph nodes of patients with lumps that are radiologically and clinically suspicious for malignancy. FNA material may be used to prepare cell blocks which allow for ancillary investigations such as hormonal receptor studies.
FNA readily distinguishes solid from cystic breast lesions. The type of fluid obtained usually gives an indication of the underlying lesion with bloody aspirates commonly associated with more sinister disease processes. The latter, however serves a guide with material from the wall of the cyst yielding more clinically useful information. Correlation with the clinical and radiologic appearance should take precedence over the appearance of fluid aspirated.
FNA may prevent circumvent the need for a tissue biopsy in patients with suspected recurrent disease where a definitive diagnosis has previously been established. The major limitation of FNA biopsy compared to CNB is its inability to distinguish non-invasive from invasive cancers.
Assessment of papillary lesions by FNA is fraught with difficulty and often requires histologic evaluation. While some centres regard FNA confirmation of malignancy as sufficient grounds for treatment, the majority require tissue biopsy confirmation. A major factor relating to FNA is that the quality of the material is highly dependent on the experience and skill of the aspirator. Poor material increases the rate of non-diagnostic specimen and possible the false negative rate.
Even in centres with experienced cytopathologists, false negative rates of up to 36% have been reported in patients with palpable lumps. The false negative rate is higher in the absence of expertise, non-palpable lumps, tumours with low cellularity lesions and specific cancer types (e.g. lobular carcinoma).
The role of the core needle biopsy
Core needle biopsy CNB is currently the gold standard for diagnosis of breast diseases, in particular, breast cancer. This is a less invasive and less expensive procedure compared to the open surgical biopsy. There is a lower rate of complications such as infection and haematoma formation compared to open surgical biopsies.
A 12 to 14-gauge hollow needle/biopsy or gun is generally used. The number of cores obtained may range from 3 to 5 depending on a number of factors, including the size of the lesion.
CNB may not require radiologic guidance for palpable lumps, with deep-seated, small as well as non-palpable lesions requiring image guidance. Mammographic (stereotactic) and ultrasound guidance is generally used for the latter group of lesions.
CNB has generally a higher accuracy and a lower false negative rate than FNA, particularly when obtained with imaging assistance. CNB has an advantage over FNA in the distinction of invasive from non-invasive tumours.
The tissue obtained by CNB allows for the diagnosis, grading and performance of prognostic markers. Grading is an important determinant of patient outcome and influences treatment decisions. While several FNA-based grading systems for breast cancer have been proposed, there is currently no universally accepted grading system.
The tissue obtained by CNB can be stored permanently for future reference and further testing should this become necessary. In common with other biopsy types CNB require tissue processing and therefore take longer than FNA.
Risks and complications of FNA and CNB
Patients should be made aware of the limited, but inherent risks associated with any biopsy procedure. CNB and FNA both have inherent complications (pain, haematoma, infection) and pitfalls (tissue distortion, sampling errors, diagnostic errors).
Complications may occur despite measures taken by the clinicians to mitigate these risks. These risks are relative less with FNA and CNB compared to other forms of biopsies. Follow up or repeat biopsies may be necessary in cases where the abnormality is missed by the initial biopsy (especially with small lesions). Repeat biopsies or open surgical biopsies may be necessary where there is discordance between the clinical, radiologic and pathologic appearance; or in cases where sufficient material cannot be obtained by other means.
The results of FNA and CNB may necessitate further surgical intervention in the form of excision. It is therefore important to note that biopsies, by their nature, may represent a small part of the lesion, In some disease entities (especially cancers) the tissue may vary from one part of the tumour to another. Assessment of the entire excision following a CNB may therefore result in a change in some parameters such as the grading and prognostic parameters.
In some instances lesions that are very small in size and may be completely removed by the CNB biopsy. In this situation the CNB becomes the only permanent record of the abnormality. Further excision may show biopsy-related changes with no residual disease.