Mustaqueem, Hassan, and Agarwal: Evaluation of peripheral lymphadenopathy by fine needle aspiration cytology: Our experience at a tertiary care center


Introduction

Peripheral lymph nodes, located deep in the subcutaneous tissue are an important part of immune system as they clean antigens from the extracellular fluid.1 There are diverse etiologies of peripheral lymphadenopathy, ranging from benign reactive conditions (eg viral or bacterial infections including tuberculosis) to metastatic carcinomas and lymphomas.2 As the enlarged lymph nodes are easily accessible for fine needle aspiration cytology (FNAC), it permits rapid diagnosis with minimum intervention.3 Thus it allows a provisional diagnosis to be made at the patient’s initial presentation and helps to guide appropriate specialist referral and further investigations.

Aspiration of lymph node for diagnostic purpose was first reported in 1904 by Grieg & Gray in the diagnosis of trypanosomiasis. In 1921, Guthrie attempted to correlate lymph node aspiration cytology with various disease processes.4, 5, 6

The dilemma to approach a patient with peripheral lymphadenopathy, its evaluation and management, considering various differential diagnosis, prompted us to take up this study. We conducted this study to take evaluate the role of FNAC in the diagnosis of peripheral lymphadenopathy and to study the pattern and spectrum of diseases associated with them in different age groups and sex in this geographical area.

Materials and Methods

All FNA performed on patients with palpable lymph node enlargement in the Department of Pathology, Hind Institute of Medical Sciences, Barabanki between January 2018 to December 2019 were included in the study. A total of 331 cases were included in the study; out of which 176 were retrospective and 155 prospective. Relevant data including age, sex, clinical presentation and other relevant investigations were retrieved from records. The cytology smears of retrospective cases were retrieved from records of pathology department. In the prospective cases, aspirates were performed by cytology staff using 22-24 gauge needle by non-aspiration/aspiration technique. Routinely 2 aspirates were performed and direct smears were prepared. Slides were immediately immersed in 95% methanol for wet fixation and the remaining slides were air dried for dry fixation and stained with Haematoxylin and Eosin and Papanicolaou stains. Special stains like Ziehl Neelsen (ZN) stain for acid fast bacilli were used wherever required. Stained smears were examined under the microscope and results were analysed to study the spectrum of pathologies reported on FNAC.

At the end of study period, the data was analyzed using Advanced Excel software. Fischer’s exact test was used to check the association of age and sex with the cytodiagnosis. P-value ≤ 0.05 was considered as significant.

Results

This study analysed 331 cases of lymphadenopathy during the period January 2018 to December 2019. The age range of the patients was from 6 months to 75 years in which 58.3% were males and 41.7% were females. These cases were divided into 4 groups according to their age: group I (≤15 years), group II (16-35 years), group III (36-50 years) and group IV (>50 years). The maximum number of cases were in the age group ≤15 years.

It was observed that cervical region was the most common site of lymphadenopathy (67.07%), followed by axillary (11.18%), inguinal (9.97%) and supraclavicular (8.76%). 10 cases (3.02%) showed generalised lymphadenopathy.(Table 1)

Table 1

Distribution according to group of lymph nodes involved

Lymph node group

No. of Cases

Percentage

Cervical

222

67.07

Axillary

37

11.18

Supraclavicular

29

8.76

Inguinal

33

9.97

More than 1 group involved

10

3.02

Total

331

100

The cytomorphological patterns of lymph node lesions showed non-neoplastic lesions (83.69%) to be more common as compared to neoplastic lesions (16.31%). Out of 331 cases, maximum cases (38.67%) were of granulomatous lymphadenitis; followed by non-specific reactive lymphadenitis (36.25%) and suppurative lymphadenitis (8.76%). (Table 2)

Out of 128 cases of granulomatous lymphadenitis, ZN stain was used in every case and showed the presence of acid fast bacilli in 78/128 (60.94%) cases, whereas 50/128 (39.06%) cases did not reveal acid fast bacilli.

Table 2

Spectrum ofnon neoplastic and neoplastic lesions

Cytodiagnosis

No. of Cases

Percentage

Non-neoplastic lesions

Non-specific reactive Lymphadenitis

120

36.25

Granulomatous Lymphadenitis

128

38.67

Suppurative Lymphadenitis

29

8.76

Neoplastic Lesions

Metastatic Carcinoma

43

12.99

Non Hodgkin’s Lymphoma

8

2.41

Hodgkin’s Lymphoma

3

0.90

Amongst the neoplastic lesions, metastatic carcinoma was the most commonly seen lesion (12.99%); as compared to 8 cases (2.41%) of NHL and only 3 cases (0.90%) of HL. The metastatic lesions showed squamous cell carcinoma (62.79%) more frequent than poorly differentiated carcinoma (25.58%) and adenocarcinoma (11.63%). (Table 3 )

Table 3

Distribution of various types of metastatic lesions

Metastatic Lesion

No. of cases

Percentage

Squamous cell carcinoma

27

62.79

Adenocarcinoma

5

11.63

Poorly differentiated carcinoma

11

25.58

Table 4

Correlation of age withcytodiagnosis

Diagnosis on FNAC

≤ 15 years

15 to 35 years

36 to 50 years

> 50 years

p-value

Non-specific reactive Lymphadenitis

64

25

20

11

<0.05

Granulomatous Lymphadenitis

42

55

23

8

Suppurative Lymphadenitis

11

10

4

4

Lymphoproliferative disorder

-

2

3

6

Metastatic Carcinoma

-

1

15

27

[i] Fisher’s exact test was applied.

[ii] p-value significant as it was <0.05.

Agewise distribution of cytomorphological patterns of diagnosed cases showed that non-specific reactive (53.33%) and suppurative lymphadenitis (37.93%) were more commonly seen in ≤15 years. Granulomatous lymphadenitis (42.96%) was more common in 15-35 years age group. Amongst the neoplastic lesions, metastatic carcinoma (62.79%) and NHL (75%) were more common in >50 years. 2/3 cases (66.67%) of HL were seen in 15-35 years age group. (Table 4)

Table 5

Correlation of gender withcytodiagnosis

Diagnosis on FNAC

Male

Female

p-value

Non-specific reactive Lymphadenitis

83

37

<0.05

Granulomatous Lymphadenitis

55

73

Suppurative Lymphadenitis

18

11

Lymphoproliferative disorder

8

3

Metastatic Carcinoma

29

14

[i] Fisher’s exact test was applied.

[ii] p-value significant as it was <0.05.

Genderwise distribution of cytomorphological patterns of diagnosed cases showed that non-specific reactive 83/120 (69.17%) and suppurative lymphadenitis 18/29 (62.07%) were more common in males as compared to granulomatous lymphadenitis 73/128 (57.03%) which was more common in females. 29/43 cases (67.44%) of metastatic carcinoma were seen in males. 6/8 (75%) cases of NHL and 2/3 cases (66.67%) of HL were seen in males. (Table 5)

Figure 1

Granulomatous lymphadenitis showing group ofepithelioid histiocytes in a background of caseous necrosis. H and E x 1000

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Figure 2

Metastatic carcinoma with abscess showing fragment of malignant epithelial cells in a background of purulent exudates. H and E x 400

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Figure 3

Non-Hodgkin’s Lymphoma showing highly cellular monomorphous population of atypical lymphoid cells. Leishman x 400

https://s3-us-west-2.amazonaws.com/typeset-prod-media-server/2cacdb50-4813-473f-ac9c-fa68ac2bed38image3.png
Figure 4

Hodgkin Lymphoma showing binuclearReedsternberg cell in a background of small lymphocytes. H and E x 1000

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Figure 5

Metastatic squamous cell carcinoma showing scattered malignant squamous cells exhibiting cytoplasmic keratinization. H and E x 1000

https://s3-us-west-2.amazonaws.com/typeset-prod-media-server/2cacdb50-4813-473f-ac9c-fa68ac2bed38image5.png
Figure 6

Metastatic adenocarcinoma showing cluster of malignant epithelial cells exhibiting glandular differentiation. H and E x 1000

https://s3-us-west-2.amazonaws.com/typeset-prod-media-server/2cacdb50-4813-473f-ac9c-fa68ac2bed38image6.png

Discussion

FNAC is a valuable diagnostic technique in the evaluation of cases of superficial lymphadenopathy. The categorization of the causes of lymphadenopathy into reactive, inflammatory and lymphoproliferative could be reliably done by FNAC. A high sensitivity (71.4%) and specificity (91.5%) of FNAC was reported in previous studies for the evaluation of lymphadenopathy.7 The use of this technique has limited the need for excision of enlarged lymph nodes, especially in cases of reactive and tubercular lymphadenitis where conservative management can be offered to patient just on the basis of cytological diagnosis. However potential cytological misdiagnosis may occur, either in lymphomas that present an apparently admixed cell pattern (false negative cases) or in reactive proliferations in which atypical cells are identified (false positive cases).8 In such cases, the cytological diagnosis should be followed by histological evaluation for accurate diagnosis and subtyping and grading in cases of primary lymphoproliferative disorders.

In our experience of 331 cases, the pattern of non-neoplastic lesions consists of reactive hyperplasia, granulomatous lymphadenitis and suppurative lymphadenitis. Malignant lesion includes metastatic carcinoma, non-Hodgkin’s lymphoma (NHL) and Hodgkin’s lymphoma (HL).

The age group which was studied ranged from 6 months to 75 years with maximum cases in ≤15 years which is comparable with the study of Pandey P et al. However Shilpa G et al, Patel MM et al and Kumar H et al.9, 10, 11, 12 found maximum number of cases in the age group 21-30. The variation may be due to different population density or geographic variation.

In the present study, the incidence in male (58.3%) was more than that in females with male to female ratio (1.4:1). Similar male preponderance was noted by Patel MM and Kumar N et al.10, 11

The most frequent site of FNAC was cervical region (67.07%), followed by axillary region (11.18%). Similar findings were also observed by Wilkinson AR et al, Shah PC et al and Mohanty R et al.13, 14, 15 The reason behind this may be the easy accessibility of cervical lymph nodes for examination and evaluation.

Cytomorphologic patterns obtained in this study were predominantly non-neoplastic (83.69%) as compared to neoplastic lesions (16.31%). Amongst the non-neoplastic lesions, granulomatous lymphadenitis was the most common pattern (46.21%), followed by non-specific reactive lymphadenitis (43.32%) and suppurative lymphadenitis (10.47%). Similar findings were observed by Shilpa G et al, Shah PC et al and Wahid F et al.9, 14, 16 This high rate of granulomatous lymphadenitis is because of high incidence of tuberculosis in this geographical area. However Pandey P et al, Mohanty R et al and Shrivastav A et al12, 15, 17 found reactive lymphadenitis as the most common cytological pattern.

In our study, granulomatous lymphadenitis was most frequently seen in 15-35 years age group; whereas non-specific reactive lymphadenitis was more commonly seen in ≤15 years. Shrivastav A et al17 have shown similar findings in their study. However study by Thomas JO et al18 shows tubercular lymphadenitis to be more common in ≤20 years age group. This may be due to difference in population density.

Amongst the neoplastic lesions, the most common lesion was of metastatic carcinoma (43/54); followed by NHL (8/54). Only 3 cases of HL were detected in this study.

Amongst the metastatic lesions, squamous cell carcinoma was the most common variant seen. A similar finding was reported by Shah PC et al, Mamatha K et al and Mohan A et al.19, 20 This correlates with the higher incidence of upper aerodigestive tract malignancy in India, possibly due to habbit of tobacco chewing in Indian population. However, Ghartinagar et al21 showed relatively higher incidence of metastatic adenocarcinoma in their study.

Most common age group presenting with metastatic carcinoma was ≥50 years (27/43); followed by 35-50 years. This finding was in concordance with the finding of Ghartinagar et al21 and Agarwal et al.22 The possible reason may be because advanced age group is itself a risk factor for carcinoma.

Lymphoproliferative disorders formed a very small proportion (3.31%) of the total pathologies reported, a finding which correlates with other studies.9, 13, 14 However Dowerah et al23 reported a higher incidence of 10.6% cases of lymphoma in their series. This variation may be due to difference in demographics, environmental and genetic influence.

We further advised histopathological examination in these cases, but excision biopsy was done in only 5 cases – 4 NHL and 1 HD; which showed concordant results. Rest of the cases were lost in follow up.

Conclusion

To summarize, FNAC is a valuable and reliable screening tool in outpatient department. It helps to categorize the patients into 2 groups; one which can be treated conservatively without requiring histopathological assessment and the other which requires further hisopathological assessment and other ancillary tests for diagnosis. Hence the use of this rapid technique allows a provisional diagnosis to be made at patient’s initial presentation and helps to guide the clinician to manage the patients accordingly. Our statistical data suggests the role of different etiologies in different age groups varying from reactive to metastatic. So it is emphasised that we must keep in mind the higher possibility of neoplastic lesions in ≥50 years age group and should take up ancillary studies on the cytological samples itself for definite diagnosis. This will not only save the time, but is also cost effective; a point to be considered in a developing country like ours.

Conflict of Interest

The authors declare that there are no conflicts of interest in this paper.

Source of Funding

None.

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Article History

Received : 24-03-2021

Accepted : 20-05-2021

Available online : 03-08-2021


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https://doi.org/10.18231/j.ijmpo.2021.014


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