Quo vadis? Evolving trends in fine-needle aspiration cytology practice: A personal perspective

Dear Editor,

Fine-needle aspiration cytology (FNAC) is a diagnostic method that underwent a long and challenging journey before it gained acceptance in medical communities and is gradually becoming more widely adopted.

FNAC was first widely employed in large series at New York Memorial Hospital during the 1930s, but later diminished in appeal mainly because the medical community, still new to histopathology, was uncertain about the diagnostic accuracy of cells collected from a few drops of fluid using a needle rather than from surgically obtained tissue samples.

FNAC was virtually revived in the 1950s and 1960s due to the efforts of some Scandinavian pioneers (Zajicek, Franzen, Esposti, and Löwhagen). During these years, FNAC was performed only on palpable masses, but later (after the 1970s), its use began with ultrasound (US) guidance.^[1]

US-guided FNAC is a practical, cost-effective, and reliable method with high diagnostic accuracy for the initial diagnosis of US-detected non-palpable masses in various organs, especially the breast, thyroid, head and neck, and lymph nodes.^[2] Further, in their paper to pay tribute to the late Franzen, Waisman et al. stated that Franzen and his colleagues expanded the organ spectrum to include transrectal prostate fine needle cytology; in fact, Franzen created a specialized aspiration device for this purpose.^[3]

Subsequently, the combination of FNAC with advanced imaging techniques such as computed tomography and magnetic resonance imaging enabled access to deep-seated organs. FNAC has become an essential triage tool for deep lesions, such as those in the lungs, mediastinum, and abdominal organs (including the pancreas, kidneys, liver, and intra-abdominal lymph nodes). This approach has helped avoid more invasive biopsy procedures and has played a role in the technique’s revival, widespread acceptance, and global popularity.^[4]

During the 1990s, image-guided core-needle biopsy (IG-CNB) gained popularity as it has higher sensitivity and specificity than FNAC for diagnosing breast lesions. IG-CNB is now the preferred diagnostic method for the pre-operative assessment of breast lesions in most institutions in the USA, the UK, and Europe. It is advantageous for assessment of pre-invasive breast lesions, for which FNAC is inadequate; for pre-operative in situ invasive differentiation; and for obtaining information regarding immunohistochemical (IHC) markers and molecular tumor analysis to ensure appropriate treatment.^[5]

Initially, FNAC was most commonly performed on the breast. Today, almost no breast FNAC is performed in most hospitals in western countries or in my own country because of changing trends in breast carcinoma treatment methods (breast-preserving approaches, targeted therapy, and neoadjuvant chemotherapy followed by breast-preserving surgery). FNAC is used for large cystic lesions, recurrence, sentinel nodes, and metastatic lymph nodes in some centers.^[6]

The popularity has shifted toward core needle biopsy (CNB), which was first performed on the breast, but has now expanded to other internal organs. With advances in lung cancer treatments, tissue samples or histology are now favored over cytology; therefore, CNB has replaced FNAC for IHC staining and molecular testing, which are essential for diagnosis and current treatment protocols. CNB is also useful for obtaining sufficient tissue for diagnosing metastatic lesions in the lungs.^[7] Although some hospitals prefer a combination of FNA and CNB for evaluating lung lesions, many centers consider CNB sufficiently compelling because of limited facilities in cytopathology laboratories and high workloads in interventional radiology departments.^[8]

The preference for lymph node FNAC has varied over time among specialists. Hematologists and oncologists often favor excisional biopsy over lymph node FNAC. In some advanced academic hospitals with experienced cytopathologists, ENT specialists sometimes choose FNAC as the first-line diagnostic method for lymph nodes. Over time, ENT specialists also gradually favored CNB for the treatment of lymph nodes.^[9]

Finally, IG-CNB has replaced FNAC in the diagnosis of internal organs, such as the liver, kidneys, intra-abdominal masses, soft-tissue lesions, and lymph nodes. The reasons for this shift are that FNAC has sometimes been inadequate for diagnosing and subtyping these lesions. Moreover, CNB enables pathologists to observe the involvement of the lesion within the tissue. It also enables the use of broad IHC markers for differential diagnosis and molecular analyses on tissue samples when needed for targeted treatments.^[10]

Unfortunately, the present-generation pathology residents often complete their residency without undergoing cytology of the breast, lung, or other internal organs. One solution to this problem is performing FNAC followed by CNB during the same session, at least for selected cases, if not routinely.

However, the success of this approach depends on mutual interest and collaboration between the pathology and interventional radiology departments. When such cooperation is established, FNAC with rapid on-site evaluation (ROSE) can be followed by CNB of the breast, lung, and other intra-abdominal organs during a single visit. Implementing this technique not only improves cytology training for pathologists but also enhances diagnostic accuracy through the expansion of the range of materials examined.

A literature review revealed several publications describing the use of a combination of FNAC and CNB for lung and breast lesions. However, CNB is often preferred as the first-choice method due to the abovementioned practical reasons. This practice can be revived and encouraged through mutual interest, cooperation, and projects between the pathology and radiology departments.^[8,11]

Endobronchial US-guided fine-needle aspiration (FNA) and endoscopic US-FNA for pancreatic lesions are outside the scope of this discussion. However, these two FNA methods still retain their diagnostic value.

Current role of FNAC.

Despite the decline of the use of FNAC for lesions at various sites, FNAC is currently widely used in the evaluation of lesions in two organs, the thyroid and salivary glands, in daily medical practice.

The next generation sequencing (NGS) technology enables molecular analysis in FNAC samples. However, the global use of NGS is currently limited.^[12]

The primary reason for this is that CNB is unsuitable for use in these two organs due to their anatomical structure and proximity to vascular and neural networks. Although a few publications have reported attempts to use CNB for salivary gland and thyroid lesions, its widespread application has been limited by potential complications.^[13,14]

Thyroid and salivary gland lesions are commonly seen in daily medical practice, and FNAC remains the preferred initial diagnostic method for lesions in both sites. Therefore, the most common FNAC samples encountered by cytopathologists and pathologists are the thyroid and salivary glands.

In the questionnaire titled, “Which subjects would you like to be included in our training program?” “thyroid and salivary gland FNAC” ranked first among trainees and young pathologists of the Turkish Cytopathology Society for the 2025-26 academic year.

The implementation of standardized reporting systems for thyroid (Bethesda) and salivary gland (Milan) cytopathology has improved communication between pathologists and the clinicians involved.^[15] However, limitations remain, such as non-diagnostic aspirates and indeterminate cytologic features. These challenges can be overcome through close collaboration between operators (radiologists/clinicians) and cytopathologists. The use of ancillary techniques, such as cell blocks and IHC, along with the incorporation of molecular analyses in thyroid cytology whenever possible can also help address these limitations.

On the other hand, FNAC still plays an essential role as an economic first-line tool in the diagnosis of infectious and neoplastic diseases in “low and lower-middle income” countries where CNB and other ancillary diagnostic techniques are limited. However, establishing FNAC services requires training of cytopathologists and education of clinicians in the use of FNAC in these countries.^[16]

However, the author, who has more than 30 years of post-fellowship experience in cytopathology, believes that maintaining the value of FNAC depends on the dedication of both the cytopathologist and the histopathologist interpreting cytology reports as well as on establishing a dual cooperation with the radiologist during the procedure.^[17]