Fine Needle Aspiration Cytology of Cervical Lymphadenopathy: Is There Anything Different At South Coastal Region of India?

Background: Cervical lymphadenopathy is one of the commonest clinical presentations of the patients in all age groups. FNAC is simple, inexpensive and minimally invasive procedure that can be used as an outpatient procedure for diagnosing lymphadenopathy cases. Aims and Objective: To assess the various causes of cervical lymphadenopathy through FNAC and to see the distribution of various lesions with respect to age and gender and to correlate with histopathological findings. Materials and Methods: The present Analytical cross-sectional study was conducted in the Department of Pathology, Mahatma Gandhi Medical College and Hospital, Pondicherry from January 2010 to July 2016.FNAC was done by standard procedure. All the slides were reviewed and diagnosis was rendered. Cytology findings were compared with histopathological diagnosis where-ever excision biopsy


Introduction
Cervical lymphadenopathy is one of the commonest clinical presentations of all age groups attending the outpatient department. [1] The various etiologies for cervical lymphadenopathy are broadly categorized as microbial infections & their breakdown products, malignancies, iatrogenic conditions, autoimmune disorders. [2] The general approach to cervical lymphadenopathy includes: detailed clinical evaluation, fine needle aspiration cytology and open biopsy. [3] FNAC has become an important diagnostic tool for initial and rapid diagnosis and management of patients having lymphadenopathy, owing to its simplicity, reliability, early availability of results and it, being a minimally invasive procedure. It is a primary method for diagnosing whether lymphadenopathy is due to reactive, infective or metastatic causes, thereby avoiding unnecessary excisional biopsy and aiding in rapid onset of therapy. [3,4] The cytomorphological features obtained through FNAC correlates well with histological appearance. Thus, FNAC is considered as an ideal method for diagnosing the nature of lesions. [5,6] The diagnosis of metastatic tumor to the lymph node by cytomorphological pattern is highly reliable and it is a sole indicative procedure for evaluating primary tumor in case of the occult primary. [7,8,9] In case of non-neoplastic lesions, the varied morphological patterns can mimic the other reactive conditions and it can lead to multiple differential diagnosis. [10,11,12] In case of primary lymphoid malignancies, FNAC is mainly used to assess the tumor staging and to recognize the residual and recurrence of lymphoid malignancy.

Materials and Methods
The present Analytical study on 411 patients with cervical lymphadenopathy was done at the Department of Pathology, Mahatma Gandhi Medical College and Research Institute over a period of 6.5 years from January 2010 to July 2016 after obtaining clearance from institutional Human ethics committee.
Aspirations from All cervical lymph nodes were included in the study i.e submental, submandibular, (level Ia, Ib) and posterior triangle including supraclavicular lymphnodes (level V). The relevant clinical details were noted from the accompanying requisition forms and/or from the patient case records. Clinical data including age, gender, clinical diagnosis, site and duration, consistency and any organ involvement like hepatosplenomegaly were noted. The cytology slides of all cases were examined to determine the cyto-morphological features. Cytology findings were compared with histopathological diagnosis wherever excision biopsy was done. The efficacy of FNAC was tested by using statistical test like Sensitivity, Specificity, Diagnostic accuracy, Positive predictive value and Negative predictive value after cyto-histopathology correlation. Unpaired t test was applied to compare our findings with other studies and p value <0.05 was considered as significant.

Results
Total 411 patients of all age groups with cervical lymphadenopathy were included in this study and the peak occurrence was observed in 3 rd decade of life accounting for 23.6%(97 cases).We observed that non-neoplastic lesions were common in the 3 rd decade with female preponderance, in contrast with metastatic lesions which were more common in the 7 th decade with male preponderance.
In the present study, out of 411 cases, majority of the patients presented with left sided cervical lymphadenopathy with frequency of 55.7%and right sided involvement in 40.4%. Bilateral involvement was seen in 3.9%cases. Out of total 411 cases, non-neoplastic lesions were more common accounting for 75.1%, followed by neoplastic 22% and non-diagnostic 2.9%.In non-neoplastic lesions, chronic reactive lymphadenitis was found to be the most common pathological lesion(34.6%) followed by granulomatous lesion(30%) [Fig1]. Distribution of remaining non-neoplastic cases was shown in Table  1.Ninetycytology cases showed neoplastic lesions and were further grouped into metastatic, Hodgkin's and non-Hodgkin's lymphomas. Out of these, metastatic lesions were more common with an occurrence of 87.7%.The occurrence of metastatic Adenocarcinoma and Squamous cell carcinoma showed equal frequency in our study with 62 cases (39.2%) each. Metastasis occurred from primary carcinoma in breast, stomach, colon, rectum, and lung.[ Fig  2&3]The occurrence of metastatic thyroid carcinoma in our study was 13.92%. [Fig 4] The youngest patient in our study was 5 year girl presented with nodular enlargement of thyroid with multiple group of cervical lymph node enlargement over a period of 6 months. In 3 cases, ultrasonography revealed multiple cystic areas admixed with solid areas which were diagnosed as metastasis from papillary carcinoma of thyroid, correlating with cytological diagnosis. In our study, metastatic malignant melanoma was reported in one case. Clinically, a 65 year old male patient presented with 4 x3 cm, raised, ulcerated wound present in the right plantar aspect of the foot for a duration of six months with multiple groups of lymph node involvement. On aspiration, highly cellular smear shows scattered and few clusters of polygonal shaped cells with eosinophilic cytoplasm with vesicular nuclei with prominent nucleoli. Both intracellular and extracellular melanin pigmentation is seen. Background shows Melanophage and melanin. [Fig 5] Cytologically, 5 cases were diagnosed as Non-Hodgkin's lymphoma. The age group ranged from 32 to 60 years with male preponderance. Cytologically, 6 cases were diagnosed as Hodgkin's lymphoma, majority of patients were in 2 nd and 3 rd decade with male preponderance. Clinically, all patients presented with cervical lymph node enlargement. Two patients presented with splenomegaly. Microscopically, 4 cases showed Classic Reed Sternberg cell and two cases showed mononuclear cells morphology.

Correlation of Cytological Diagnosis with Histopathology:
In this study period, 411 cases of cervical lymphnode were referred to Department of pathology for aspiration.Out of these, 12 smears were inadequate or non-diagnostic, hence exclude from further evaluation.

Discussion
Among the different groups of lymph nodes, cervical group is easy to access by FNAC and therefore it plays a major role in establishing rapid diagnosis. FNAC also plays important role in diagnosing the etiology of cervical lymph node enlargement due to early availability of results, better patient compliance and minimal trauma. [13] The diagnosis obtained through FNAC very well correlates with histopathological diagnosis after excision biopsy. [14] The gender distribution of cases in our study showed clear female preponderance with a male: female ratio of 1:1.7 in adulthood. Similar findings were noted by other authors. [15][16][17][18] However, paediatric and older age group showed male predominance in our study.
In the present study, we observed that non-neoplastic lesions were common in the 3 rd decade whereas neoplastic lesions were more common in 6 th to 7 th decade. Findings of our study showed correlation with the study conducted by Dukare et al, Pavithra et al and Kumar et al. [19,20,21] In our study, left sided cervical lymph node lesions were most commonly involved in both neoplastic and nonneoplastic lesions with an frequency of 55.7%, whereas right sided lesions accounted for 40.4%.Similar findings were noted by Attaullah et al. [17] In the current study, we observed that non-neoplastic lesions was the most common cause of cervical lymph node enlargement accounting for 74.5%. In other studies, similar findings were observed with frequency of non-neoplastic lesion ranging from 70 to 90%. [19,22,23] Among non-neoplastic lesions, reactive lymphadenitis was the most common pattern with an occurrence of 34.6%, which showed mild preponderance over granulomatous lymphadenitis (30.04%).Other studies also showed majority cases belonging to reactive lymphadenitis ranging from 50% to 70%. Our study showed 63% cases of granulomatous Annals of Pathology and Laboratory Medicine, Vol. 4, Issue 4, July-August, 2017 lymphadenitis, which was higher than other studies, which reported these cases ranging from 25 to 30% [13,23,24,] .This difference was found to be statistically significant using unpaired t test with p value <0.0001.In the present study, one cytologically diagnosed granulomatous lymphadenitis turned out to be Non-Hodgkin's Lymphoma on histopathology accounting for false negativity probably due to non availability of architecture on cytology or sinus histiocytes aspirated on smear appeared as ill formed granulomas.
In the neoplastic lesions, metastatic lesions accounted for 87.78%.Similar findings were noted by other authors. [19,20] Among metastatic lesions, both adenocarcinoma and squamous cell carcinoma has the occurrence rate of about 39.4% each, followed by thyroid carcinoma 13.9%. Most of the Indian studies observed that, metastatic lesion in cervical lymph node was mainly due to squamous cell carcinoma followed by adenocarcinoma. [20,25] But, in our study, adenocarcinoma showed the same frequency with that of squamous cell carcinoma(SCC). As SCC is common in head and neck region and we get less number of cases of this region in our hospital, metastatic adenocarcinoma in supraclavicular lymphnode showed equal proportion with SCC as compared to other studies. Ghartimagar et al also reported higher frequency of metastatic adenocarcinoma over squamous cell carcinoma in their study. [26] [ Table 3]. In our study, Metastatic thyroid carcinoma (predominantly papillary carcinoma) showed higher frequency of 13.9% as compared to other studies which showed frequency ranging from 2 to 5%. [20,26] [ Table 3].Unpaired t test showed significant statistical difference with p value <0.0001.This could be due to higher iodinated salt intake because of our coastal region as documented in literature thatincreased iodine supplementation increases risk for thyroid malignancy, particularly Papillary thyroid carcinoma(PTC). [27] Similar findings were noted by Indian studies mentioning environmental conditions and dietary habits i.e diet rich in fish may be contributing factor for wide spread distribution of PTC occurring in coastal areas of Tamilnadu, Andhra Pradesh& Kerala which are iodine rich and the iodine content of soil is thought to modify the development of these cancers. [28] Previous studies conducted in our hospital also showed higher frequency of thyroid carcinomas predominantly papillary carcinomas which needs further molecular studies. [29] In neoplastic lesions, apart from metastasis, Hodgkin's and Non-Hodgkin's Lymphoma showed frequency of 6.6% and 5.5% respectively. Similar findings were observed by other authors. [21,23,30] In our study, one cytologically diagnosed Non-Hodgkin's lymphoma turned out to be granulomatous lymphadenitis accounting for false positive diagnosis probably due to inadequate sampling or sampling predominantly of germinal centre centroblastic cells or large atypical cell appearance due to drying artifact because of late fixation. Thus, cytology has limitations in diagnosing Lymphomas due to non-availability of complete architecture for complete assessment. Also, diagnostic accuracy is said to be lower for lymphomas compared to metastatic malignancy. [31] In our study, the overall diagnostic accuracy of FNAC in diagnosing cervical lymph node lesions was 97% with sensitivity 97%, specificity 95%, positive and negative predictive value to be 97% and 95% respectively which was comparable with other studies. In other studies, sensitivity ranged from 90% to 99% and specificity from 70 to 100%. [15,32,33]

Conclusion
Fine needle aspiration cytology offers a simple, safe, quick and minimally invasive technique which can be performed as an outpatient department procedure for rapid diagnosis of neoplastic and non-neoplastic lesions of cervical lymph nodes for better patient care management. Our study showed high sensitivity, specificity and diagnostic accuracy, thus making it reliable investigation in further management of cervical lymphnode lesions. Also, significant findings in our study were higher frequency of granulomatous lymphadenitis in non-neoplastic lesions and higher occurrence of metastatic thyroid carcinoma in this rural tertiary healthcare centre located at iodine sufficient eastern coastal region of South India.