European Journal of Cardiovascular Medicine

Lymph node is an essential organ of the human immune system. Lymphadenopathy is a sign noticed when a lymph node increases in size and number or atypical in consistency [1]. The causes of lymphadenopathy are numerous Few of them varies from benign reactive lymphoid hyperplasia to malignant diseases and the most common cause is benign lymphadenopathy (90%), including reactive hyperplasia (60%), followed by infectious or inflammatory lymphadenitis (30%). Infectious or inflammatory lymphadenitis includes Kikuchi- Fujimoto disease (KFD), tuberculosis, sarcoidosis, infectious mononucleosis, toxoplasmosis, human immunodeficiency virus infection, cat-scratch disease, drug (phenytoin) reaction, and others [1,2]. Malignant lymphadenopathies only comprise 10% of the cases, which include primary lymphomas (3%), including diffuse large B-cell lymphoma/anaplastic large cell lymphoma, follicular lymphoma (FL), mantle cell lymphoma (MCL), peripheral T-cell lymphoma (PTCL), and Hodgkin’s lymphoma (HL). Metastatic carcinomas account for 7% of cases and include squamous cell carcinoma primarily from oral carcinoma, metastatic papillary thyroid carcinoma, adenocarcinomas primarily from lung or breast, and poorly differentiated squamous cell, small cell, or any primary unknown carcinoma  [2]. It is very difficult to diagnose the cause of lymphadenopathy based solely on history, physical examination, or ultrasound alone. Fine needle aspiration cytology (FNAC) is very cost effective and rapid process, therefore,is vastly utilized as a primary diagnostic tool to examine enlarged lymph nodes and to exclude involvement of alternative organs, such as the salivary gland, head, neck, or other subcutaneous masses. It is also a minimally invasive approach that allows fast diagnosis and treatment. There are few complications that have been reported for FNAC, including hemorrhage, nerve damage, and vasovagal reactions in head and neck lymph node procedures [4]. Finally, FNAC is a cost-effective procedure, especially in developing countries.

In the year 2020, a new classification was proposed at the 20^th International Congress of Cytology in Sydney based on classification and reporting of Lymph node cytology [5]. The main motive of this classification was to give consensus and proper guidelines to facilitate communication among cytopathologists, surgeons, clinicians and other health care providers [6,9]. Sydney classification categorises Lymph node lesions in 5 categories L1-L5 using microscopic features. The main limitation of this system is its inability to differentiate between Lymphoma and Metastasis.

So, this study aims to proposed improvised version of Sydney classification along with use of Sydney classification to give diagnosis in our setup.

This was a retrospective cross sectional study of lymph node cytology collected  from 1 January 2020 to 30 July 2021 in Geetanjali Medical College and Hospital Udaipur Raj. and 1 January 2023 to 31 January 2024 in Ananta Institute Of Medical Sciences and Research Centre Rajsamand Rajasthan, and the results were reported using the Sydney System  into 5 groups from L1 to L5. To measure diagnostic accuracy and the risk of malignancy for each  diagnostic category, the diagnoses were compared with the corresponding radiological diagnoses. The statistical tools used were calculation of sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV).

Study Procedure

In all the cases the FNA and USG were performed with patient consent, under aseptic conditions with 23 gauge needle. The superficial and palpable lymph node aspirations were taken blindly and for non palpable and deep lymph nodes, image guidance was taken, mostly by ultrasonography guided FNA.

Atleast two air dried and three wet fixed smears were made and stained with Papanicolaou & field stains. Additional smears were made in suspected cases of tuberculosis and stained with ziehl nelson stain. The smears were reported and classified into 5 different diagnostic categories based on the proposed Sydney system of reporting [5].The first diagnostic level included cases from L1-L5 [5]:

L1: inadequate/non diagnostic

L2: benign

L3: atypical cells of undetermined significance/atypical lymphoid cells of uncertain significance (AUS/ALUS)

L4: suspicious

L5: malignant

And L6 category to differentiate between lymphoma and metastasis.

To assess the diagnostic accuracy the FNA diagnosis, each diagnostic category was compared with histopathologic diagnosis, immunohistochemistry and radiological diagnosis; when no biopsy,no immunohistochemistry was performed, clinical follow-up was checked. Out of a total 210 FNA, data of 88 histopathological cases were available.

Total of 210 cases were chosen for the study from a total of 300 FNACs performed for lymphadenopathy since they had radiological correlation. The L1, L2, L3, L4, and L5 categories were assigned to all of them respectively. We found 95.2% concordance in benign diseases, 85.9% concordance (metastasis) and 50% concordance (lymphoma) with radiological findings. 70% cases which were diagnosed in L3 category were diagnosed radiologically correct. 100% inconclusive cases were diagnosed on radiological scans. This study proposed here revised version of Sydney classification by adding 1 more category L6 of Lymphoma to it based on radiological and microscopy findings.

Total 210 lymph node fine needle aspiration smears were reviewed during study period; in which 81.3% were percutaneous aspiration and 18.7% image guided aspirations were taken in GMCH. The mean age of patients was 42 years with age range from 18 years to 65 years. Out of which, 126 (40.3%) were male and 184 (59.6%) were females. Most common site for FNA was cervical lymph nodes, comprising 77.6% cases. Second most common site was axillary lymph nodes with 13.5% cases, followed by submandibular lymph nodes 12.3% cases and 10.4% cases from other sites including submental, supraclavicular, infraclavicular and inguinal lymph nodes [Table/Fig.-3].

A total of 0.06% in total of both centres were reported as non diagnostic/inconclusive (L1). The majority of them showed only blood and no cellularity and rest cases showed only necrosis. Benign (L2) cytologic diagnosis was seen in 52.3% cases, which included cases of granulomatous lymphadenitis, non specific lymphadenitis, reactive lymphadenitis and necrotising lymphadenitis. Atypia of undetermined significance (AUS) (L3) included 0.04% in both centres with atypical lymphoid and atypical epithelial population. Suspicious of malignancy-category L4 cytological diagnosis were rendered 0.02% cases in total including suspicious for malignancy and L5 includes 30.95% of metastasis of various organs as of oral cavity SCC adenocarcinoma of breast,thyroid and lung [Table/Fig. 5,6a,b,c,d]. If we consider L6 as of only lymphomas including both Hodgkin and Non-Hodgkin were 2.85% in both centres [Table/Fig. 2].

Among all FNAC cases 3 of positive cases of metastasis, 2 lymphomas were missed, 1 suppurative abscess was diagnosed as malignant lesion in AIMS on radiology but was diagnosed correctly in FNAC as confirmed by histopathology reports. 1 case of Rosai dorfmann and 1 case of suppurative lymohadenitis were missed on radiology in GMCH. 2 Lymphomas were diagnosed as reactive lymphadenitis and 4 metastasis were missed on radiology reports in GMCH . All inconclusive cases were diagnosed in GMCH on radiology correctly.

Total 6 cases of AIMS and 4 cases of GMCH were missed. The sensitivity for the present study for Sydney system of reporting was 94% and specificity of 96%. The cytological correlation was done with radiological findings.

After the successful establishment of Bethesda system for cervical [6] and thyroid cytology [7] and Milan system for salivary gland cytology [8], in 2020 proposal of Sydney system for lymph node was proposed to keep uniform reporting and better communication [9]. The present study showed the diagnostic accuracy of Sydney system in Fine needle aspiration cytology of lymph node pathologies.

In the present study, 67.5% (n=131) patients were having cervical lymphadenopathy, both unilateral as well as bilateral. A study by Robert F suggested 55% of lymphadenopathy occurs at head and neck region [15] Similar findings were also suggested by Gupta P et al., Vigilar E et al., [10, 11].

In the present study, L2 category showed more prevalence (77.6%) which could be due to low sample size and also could be due to increased prevalence of tuberculosis in the area where study has been conducted. On the contrary, studies by Gupta P et al., Vigilar E et al., [10,11] showed equal distribution between benign and malignant lesion catagories .

On the contrary, in a study by Gupta P et al., 35 cases out of 304 cases 11.51% were found to be malignant [10].

Maximum discordant results (false negative) results were found in category L3, L5 where 3 cases were reported as atypical lymphoid and non lymphoid cells which later were diagnosed as Non Hodgkin’s lymphoma in 6 cases and metastasis from epithelial malignancy in one of the case. Where as in study of Gupta P et al., [10], total 16 cases were discordant in the category L3 .In the category L5, the sub typing of the Non Hodgkin’s lymphoma were followed-up with histopathological examination. Due to lack of other ancillary methods like flowcytometry and cell block preparation, those results could not be correlated.

Table 3 – Various studies had done showing comparisons between various sites of lymphadenopathies among them and present studies.

Table 4 - Various studies had done showing comparisons between statistics values among them and present studies.

The sensitivity of lymph node FNA in the malignant lesions is variable and it has range from 75-99% [12] while other studies have found that core biopsies for suspicious lymph nodes are more useful in diagnosing malignant lymph node lesions [13]. The present study showed sensitivity and specificity of diagnosing FNA lymph node lesion by using Sydney system of reporting to be as 95.23% and 94.11%, respectively which is similar to the other studies by Vigilar E et al., and Cupato A et al., [10, 11, 14] [Table -4].

The proposed Sydney system of reporting and classification of lymph node cytology helps in achieving uniformity and accessibility. This appears to be the first time, the    Sydney system has been introduced in this region in patient care, and this can improve the clinicians understanding of the risk of malignancy and subsequent care.This System can be modified by adding Radiological diagnosis in defining it and adding 1 more final category L6 of Lymphoma diagnosis.We need more researches and studies to prove validity of Sydney Classification.

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