Get Permission Samin, Ahmad, Mittal, Awasthi, and Nasir: Role of hematological and inflammatory marker in granulomatous compared to non-granulomatous lymphadenitis


Introduction

Lymph node enlargement in local and systemic infectious cases is seen as lymphadenopathy. Lymphadenopathy describes the expansion of lymph gland, which brings about non-malignant, malignant & metastatic disease. Non-neoplastic lymphadenopathies mostly include granulomatous lymphadenitis, follicular hyperplasia, and other causes of reactive lymph node enlargement. An enlarged cervical lymph node is a typical finding in clinical examinations performed in medical practices. Lymphoproliferative disorder or an infection may cause lymphocytes that are intrinsic to the lymph node to proliferate, causing the lymph node to swell. Lymph node harbors various kinds of lymphoid cells which are physiologically in direct connection with bone marrow and peripheral blood. In pathological terms, such diseases are mentioned as hematolymphoid pathologies. Granulomatous lymphadenitis can be due to various etiologies for example tuberculosis, leprosy, sarcoidosis, autoimmune inflammation, fungal infection, protozoal infection, some neoplasm and even due to reaction against any foreign bodies. Epithelioid cell granulomas are a collection of modified macrophages under the influence of interleukin 2 and interferon-gamma secreted by TH-1 cells along with some intermingled lymphocytes and fibroblasts at the periphery.1 Granulomatous lymphadenitis is most frequently brought on by tuberculosis in underdeveloped nations like India.2 Epithelioid cell granulomas can be caseating or non-caseating depending upon etiology. Tubercular granulomas are mostly caseating type.3 TBL is difficult to identify and frequently occurs in conjunction with other chronic diseases that provide erratic physical and laboratory results. Diagnostic imaging and cytological/histological examination of cervical lymph nodes need to be excised on the path of conclusion. TBL has been connected to altered levels of many cytokines, interleukin 1 and 17 mediators in serum or plasma.4, 5 Neopterin, C reactive protein (CRP), and beta 2 macroglobulin are just a few of the biochemical parameters that have been employed to evaluate therapeutic monitoring, find persistent culture positivity, diagnose radiological problems, find disseminated mycobacterial disease, and more definitely, to distinguish tuberculosis from cancer.6 Necrotizing non-granulomatous lymphadenitis is a symptom of several illnesses. Inappropriate therapy that might have negative consequences on the patient could result from incorrect understanding of this pathological phrase. Systemic lupus erythematosus (SLE/lupus lymphadenitis) and other infections are prominent prevalent infectious and inflammatory disorders that produce necrotizing lymphadenitis, which excludes mycobacterial infections like tuberculosis (TB). Numerous studies on chronic inflammatory diseases, including tuberculosis (TB), have concentrated on white blood cell (WBC) count, platelets, and various relative ratios of different blood's white cells can be identified by their monocyte/lymphocyte ratio (MLR), neutrophil/lymphocyte ratio (NLR), and platelet/lymphocyte ratio (PLR). Elevated MLR in peripheral blood was described as indicator of TB progression in newborns and adults who are HIV-positive. The NLR ratio was antiquated and shown to predict possibility of TB in persons with HIV as well as aid to distinguish between pulmonary TB and bacterial community-acquired pneumonia.7 Neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) rates calculated according to hemogram data in patients with a white blood cell count within the normal range can be used to evaluate systemic inflammation. Patients with autoimmune diseases, rheumatic disorders, malignancies, and diabetes have a higher PLR. Neutrophil to lymphocyte ratio (NLR) is a straightforward marker of the systemic inflammatory response in intensive care patients. It has also been identified as an unrelated prognostic factor for non-infectious disorders, such as acute myocardial infarction, stroke, and a variety of malignancies.8, 9, 10 Additionally, NLR has been demonstrated to be self-sufficient predictor of both short as well as long term death in critically sick patients. 11

Consequently, we wanted to find out and interpret quantitative levels of these parameters in granulomatous lymphadenitis and reactive lymphadenopathy and will try to find out any association with the disease.

Materials and Methods

Study design

It was a clinical prospective study that was done in the Department of Pathology, Teerthanker Mahaveer Medical College and Research Centre.

Study setting

The data utilized in this study has been anonymized to protect the identities of the individuals involved. The study was conducted from August 2020 to September 2022. Research was approved by Institutional Ethical Committee

Sample size

The study comprised a total of 150 neck mass cases. Research participants were categorized as granulomatous and reactive lymphadenitis according to their cytological report.

Method of data collection

A comparison of different laboratory parameters was performed among these 2 categories. A CBC was conducted on Sysmex XN‑10, CRP was measured on a semi-automated analyzer 300, and ESR by the Westergren method. We studied parameters such as TLC(Total leucocyte count), DLC(Differential Leucocyte Count), NLR(Neutrophil Lymphocyte Ratio), PLR(Platelet Lymphocyte Ratio), ESR(Erythrocyte Sedimentation Rate), and CRP(C-Reactive Protein).

Result

In our study, out of a total of 150 cases, 75 were classified as granulomatous and 75 cases as reactive lymphadenitis. In the studied population, there were 70.7% females and 44% males. As indicated in Table 1, our study found a female preponderance in both study groups as indicated in Table 1. The average age of the study group was 27.55±0.91 in granulomatous lymphadenitis and 26.32±16.60 in non-granulomatous. All laboratory parameters in the two groups of lymphadenitis are shown in Table 1 indicating differences in their mean values. Hematological parameters such as NLR, PLR and CRP were significantly increased in patients of granulomatous disease and showed statistical significance with disease severity (P < 0.001) whereas other parameters such as TLC, ESR was not significant.

Table 1

Granulomatous lymphadenitis

Non-granulomatous lymphadenitis

P-value

Age

27.55±0.91

26.32±16.60

0.614

Sex

Male

29.3%

48%

0.019

Female

70.7%

52%

TLC

13158.01±603.1

11667.73±1248.1

0.353

ESR

22.48±5.63

22.72±7.22

0.821

NLR

6.15±3.17

3.76±2.64

0.001

PLR

(1.74±0.63) x104

(1.30±0.73) x 104

0.001

CRP

11.71±19.69

2.97±4.07

0.001

Discussion

Nothing stood out different in mean age between the groups with granulomatous lymphadenitis (27.55years ±12.91SD) and non-granulomatous lymphadenitis (26.32years ±16.60SD). With an overall mean age of 29.04 ± 19.14 years, the findings revealed that 23.4%, 65.2%, and 11.3% of the study participants were in the age groups of fewer than 14 years, 15-59 years, and 60 years, respectively.

Females were significantly more among granulomatous lymphadenitis group (70%) compared to non-granulomatous lymphadenitis group(52%). T Sagirgolu et al. (2017)12 and Rohini et al (2016),13 confirmed through a study that mean TLC in cases of lymphadenopathy is higher than in control groups (0.008) but in the present study, there was no significant difference in mean TLC between non-granulomatous lymphadenitis (11667.73±1248.12) and granulomatous lymphadenitis groups(13158.01±603.56). The mean Lymphocyte was significantly more among non-granulomatous lymphadenitis (24.37±11.07 vs 16.01±6.83). The mean Neutrophil was significantly more among the granulomatous lymphadenitis group (79.53±8.09vs 69.03±13.14). This may be due to an equal rise of TLC in cases of granulomatous and reactive lymphadenitis due to superadded infection and it is balanced in both cases or this difference has occurred due to geographical variation in the pattern of disease. It was found in the current research that there was no significant difference in mean ESR between non-granulomatous lymphadenitis (22.72±7.22) and granulomatous lymphadenitis (22.48±5.63) groups and this output does not match with Rohini et al. (2016),13 who assessed hematological parameters in tuberculosis groups versus control. The result of which stated that there was raised ESR in tubercular groups than in control. This may be due to the small sample size in recent study.

Dirican et al (2014),14 found that NLR is considerably greater in sarcoidosis patients compared to healthy control and also stated that patients with extrapulmonary involvement had higher NLR levels. This study is in accordance with the present study where NLR is remarkably more among granulomatous (6.15±3.17) compared to non-granulomatous lymphadenitis(3.76±2.64) category. Additionally, recognized as a diagnostic indicator of bacterial infection is lymphocytopenia.15 This study does not match the output of a recent study where the granulomatous lymphadenitis group had increased NLR. Therefore, it is proposed that NLR could be predictive of bacterial infections and stressful situations. The lack of differences in NLR levels between TB lymphadenitis and controls in our investigation may indicate that parenchymal infiltration is a possible cause of NLR increase. Singh et al.16 (2017) investigated found that hematological changes associated with tuberculosis and found thrombocytosis in cases of pulmonary tuberculosis groups. This means PLR will be more in cases with pulmonary tuberculosis and this research matches result of recent study where PLR was significantly more in cases of granulomatous (1.74±0.63) compared with non-granulomatous (1.30±0.73) lymphadenitis. This probably explains the pulmonary manifestation in our study group of granulomatous lymphadenopathies. In line with the research of Rohini et al. (2016) there was a significant difference in mean CRP between the groups with granulomatous lymphadenitis (11.71±19.09) and non-granulomatous lymphadenitis (2.97±4.07),13 and Ştefanescu et al,17 (2021) where there was continuous elevation of CRP in tuberculosis patients as stated that continuous elevation CRP, is linked with a chronic inflammatory condition.

Conclusion

Haematological markers have been examined in a number of trials to determine their value in predicting the likelihood that TB illness would develop, detecting active tuberculosis infections, and tracking treatment response. For the proper identification of active TB, there has to be a significant adjustment made to the way conventional blood tests are used. Measures and ratios for complete blood counts have been proposed as hallmark indicators in inflammatory or infectious diseases, such as pulmonary tuberculosis.

The most frequent clinical issue associated with cervical lymphadenopathy is tuberculosis in our geographical region. Females are more commonly involved. Important warning signs and symptoms include organomegaly, consistency, fixed lymph nodes, and B symptoms which should be taken into account while evaluating lymphadenopathy but hematological parameters like DLC and biochemical parameters like CRP can give us some clue prior to FNAC for the presence of granulomatous and non-granulomatous lymphadenitis. It will assist the treating physician, particularly at the primary care level, in thinking systematically about early case identification and preventing diagnostic delays in instances like tuberculosis. It may be very beneficial for basic healthcare providers at the urban and rural levels, where advanced diagnostic tools to identify lymph node illnesses are often not yet accessible owing to budget limitations. Inflammatory markers NLR and PLR are new and can be used to differentiate Granulomatous and non-granulomatous infections. Further, trials should be made with increased sample size. Many lymphadenopathy patients had vague symptoms and required further testing to get a definitive diagnosis. Additional research may be done by including a large number of patients.

Source of Funding

None.

Conflcit of Interest

None.

References

1 

V Kumar A Abbas J Aster J Turner S Robbins R Cotran Robbins & Cotran Pathologic Basis of Disease10th edElsevierHaryana2020

2 

C Ozdemir S Sokucu S Onur Can neutrophil/lymphocyte ratio and platelet/lymphocyte ratio be used in differential diagnosis of Stage I sarcoidosis from tuberculosis lymphadenopathy?Eurasian J Pulmonol2020201226

3 

GR Kathamuthu K Moideen NP Kumar R Sridhar D Baskaran S Babu Altered systemic levels of acute phase proteins in tuberculous lymphadenitis and modulation after treatmentPLoS One2020155e0233426

4 

T Mustafa KA Brokstad SG Mfinanga HG Wiker Multiplex Analysis of Pro- or Anti-Inflammatory Serum Cytokines and Chemokines in relation to Gender and Age among Tanzanian Tuberculous Lymphadenitis PatientsTuberc Res Treat20152015561490

5 

GR Kathamuthu K Moideen D Bhaskaran G Sekar R Sridhar B Vidyajayanthi Reduced systemic and mycobacterial antigen-stimulated concentrations of IL-1β and IL-18 in tuberculous lymphadenitisCytokine2017906672

6 

V Sharma HS Mandavdhare S Lamoria H Singh A Kumar Serial C-reactive protein measurements in patients treated for suspected abdominal tuberculosisDig Liver Dis201850655962

7 

IR Nair S Balan P Phalak M Daniel Clinicopathologic spectrum of necrotizing lymphadenitisIndian J Pathol Microbiol2020631603

8 

S Balta S Demirkol M Unlu Z Arslan T Celik Neutrophil to lymphocyte ratio may be predict of mortality in all conditionsBr J Cancer20131091231256

9 

S Balta C Ozturk E Kurtoglu The neutrophil-lymphocyte ratio is not enough to describe inflammatory conditionEur Arch Otorhinolaryngol20142716183940

10 

I Kushner ML Broder D Karp Control of acute phase response. Serum C-reactive protein kinetics after acute myocardial infarctionJ Clin Invest197861223542

11 

C Cray J Zaias NH Altman Acute phase response in animals: a reviewComp Med200959651726

12 

S Güzelsoy Sağıroğlu S Sarıca N Bilal I Orhan A Erdoğan M Kılıç The investigation of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio in children with pathological cervical lymphadenopathyENT Updat20177299

13 

K Rohini MS Bhat PS Srikumar AM Kumar Assessment of Hematological Parameters in Pulmonary Tuberculosis PatientsIndian J Clin Biochem20163133325

14 

N Dirican C Anar S Kaya HA Bircan HH Colar M Cakir The clinical significance of hematologic parameters in patients with sarcoidosisClin Respir J201610329

15 

DH Wyllie ICJW Bowler TEA Peto Relation between lymphopenia and bacteremia in UK adults with medical emergenciesJ Clin Pathol20045799505

16 

KJ Singh G Ahluwalia SK Sharma R Saxena VP Chaudhary M Anant Significance of haematological manifestations in patients with tuberculosisJ Assoc Physicians India20014978890

17 

S Ştefanescu R Cocoş A Turcu-Stiolica B Mahler AD Meca AMC Giura Evaluation of prognostic significance of hematological profiles after the intensive phase treatment in pulmonary tuberculosis patients from RomaniaPLoS One2021164e0249301



jats-html.xsl


This is an Open Access (OA) journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

  • Article highlights
  • Article tables
  • Article images

Article History

Received : 12-02-2023

Accepted : 13-03-2023


View Article

PDF File   Full Text Article


Copyright permission

Get article permission for commercial use

Downlaod

PDF File   XML File   ePub File


Digital Object Identifier (DOI)

Article DOI

https://doi.org/10.18231/j.ijpo.2023.009


Article Metrics






Article Access statistics

Viewed: 1117

PDF Downloaded: 245



Medical Abbreviation List