Introduction Lymph node (LN) fine needle aspiration cytology (FNAC) is a safe, quick, inexpensive, reliable, and minimally invasive technique for the diagnosis of lymphadenopathies. Recently, an international committee of experts proposed guidelines for the performance, classification, and reporting of LN‐FNAC: the Sydney System. We set out to analyse the diagnostic performance of the Sydney System in a retrospective study. Methods We retrieved 1458 LN‐FNACs, reformulated the diagnoses according to the Sydney System, and compared them to the histological control where available (n = 551, 37.8%). Results The risk of malignancy for each of the five categories was 66.7% for inadequate/insufficient, 9.38% for benign (overall: 0.84%), 28.6% for atypical, 100% for suspicious and 99.8% for malignant. LN‐FNAC showed a sensitivity of 97.94%, a specificity of 96.92%, a positive predictive value of 99.58%, and a negative predictive value of 86.30%. Conclusions These data support the usage of LN‐FNAC as an agile first‐level technique in the diagnosis of lymphadenopathies. The Sydney System supports and enhances this role of LN‐FNAC, and its adoption is encouraged. In negative cases, coupled with ancillary techniques, LN‐FNAC can reassure the clinician regarding the benignity of a lymphadenopathy and indicate the need for clinical follow‐up, which will catch possible false negatives. In positive cases, LN‐FNAC can provide sufficient information, including predictive biomarkers, to initiate management and obviate the need for subsequent, more invasive procedures. Given its speed, minimal invasiveness, and low cost, LN‐FNAC can be performed in most cases, even when more invasive techniques are not feasible.

<b><i>Background:</i></b> Despite their sometimes deceivingly bland appearance, some small-cell lymphomas are very aggressive and the prognosis of patients depends on a prompt diagnosis that allows the initiation of appropriate therapy. <b><i>Summary:</i></b> The present review discusses the salient cytological features of the most common aggressive small-cell lymphomas and then proceeds to analyze their main diagnostic criteria, including the usage of ancillary techniques. <b><i>Key Messages:</i></b> Lymph node fine-needle aspiration cytology is a fast, safe, cheap, minimally invasive, and accurate procedure that can be used for a prompt and accurate diagnosis of lymphomas.

Pleomorphic liposarcoma (PLPS) is the rarest liposarcoma subtype, with high-local recurrence and metastasis rates. Fine-needle aspiration cytology (FNAC) is successfully used in the diagnosis of primary or metastatic soft tissue tumors, but liver metastases of PLPS diagnosed by FNAC have never been reported. The cytological diagnosis depends on the identification of lipoblasts with sharply defined cytoplasmic vacuoles indenting and distorting the nucleus in the context of a pleomorphic tumor and in a proper clinical and imaging context. Despite its aggressive behavior, hematogenous liver metastases are rare, with just one case reported in literature. A case of PLPS liver metastasis and concomitant primary tumor diagnosed by FNAC and core needle biopsy is herein described.

COVID‐19 vaccine‐associated clinical lymphadenopathy (C19‐LAP) and subclinical lymphadenopathy (SLDI), which are mainly detected by 18F‐FDG PET‐CT, have been observed after the introduction of RNA‐based vaccines during the pandemic. Lymph node (LN) fine needle aspiration cytology (FNAC) has been used to diagnose single cases or small series of SLDI and C19‐LAP. In this review, clinical and LN‐FNAC features of SLDI and C19‐LAP are reported and compared to non‐Covid (NC)‐LAP. A search for studies on C19‐LAP and SLDI histopathology and cytopathology was performed on PubMed and Google Scholar, on 11 January 2023. Reports on LN‐FNAC of C19‐LAP were retrieved. A total of 14 reports, plus one unpublished case of C19‐LAP observed in our institution, diagnosed by LN‐FNAC were included in a pooled analysis and compared to the corresponding histopathological reports. In total, 26 cases were included in this review, with a mean age of 50.5 years. Twenty‐one lymphadenopathies assessed by LN‐FNAC were diagnosed as benign, and three cases as atypical lymphoid hyperplasia; the latter were subsequently confirmed as benign (one by repetition of LN‐FNAC, two by histological control). One case of mediastinal lymphadenopathy in a patient suffering from melanoma was reported as reactive granulomatous inflammation, while one unsuspected case was diagnosed as metastasis from melanoma. In all cases, the cytological diagnoses were confirmed by follow‐up or excisional biopsy. The high diagnostic value of LN‐FNAC in excluding malignant processes was extremely useful in this context and may be particularly valuable when CNB or histological excisions are difficult to perform, as was the case during Covid lockdowns.

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Fine-needle aspiration cytology (FNAC) is commonly used to obtain a pre-surgical pathological diagnosis in many organs, but its cost-effectiveness in lymphadenopathy has not been studied yet. We calculated the cost and diagnostic accuracy of a diagnostic algorithm that uses FNAC as a first-line procedure and compared it to a purely surgical approach in 545 consecutive lymphadenopathies. In 74% of the cases, FNAC alone can obtain a sufficiently detailed diagnosis, avoiding the surgical biopsy. In doing so, the average cost of diagnosis is cut to less than one-third, the patient avoids an invasive procedure and the diagnosis is reached earlier. In conclusion, the systematic use of lymph node-FNAC in the initial assessment of lymphadenopathy is clinically and economically advantageous as it avoids surgical biopsies in cases where cytology can suffice.

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