ORIGINAL ARTICLE


https://doi.org/10.5005/jp-journals-10081-1444
Pediatric Infectious Disease
Volume 6 | Issue 4 | Year 2024

Utility of Fine Needle Aspiration Cytology in Bacille Calmette–Guerin Lymphadenitis: An Institutional Experience


Saba Naaz1, Sonam Sharma2https://orcid.org/0000-0001-9856-9542, Amrutha Aravind3, Mukul Singh4

1–4Department of Pathology, Vardhman Mahavir Medical College & Safdarjung Hospital, New Delhi, India

Corresponding Author: Sonam Sharma, Department of Pathology, Vardhman Mahavir Medical College & Safdarjung Hospital, New Delhi, India, Phone: +91 9991743193, e-mail: drsonamsharma@gmail.com

Received: 23 May 2024; Accepted: 05 September 2024; Published on: 05 November 2024

ABSTRACT

Background: The Bacille Calmette–Guerin (BCG) vaccine is a live attenuated vaccine that is a part of the National Immunization Program in India. It protects infants and children from tubercular meningitis and disseminated tuberculosis. It is usually a safe vaccine but can cause mild and severe adverse reactions including suppurative lymphadenitis as well as osteitis. BCG vaccine-induced regional lymphadenitis can be easily misdiagnosed and can lead to unnecessary therapeutic as well as surgical interventions. Fine needle aspiration cytology (FNAC) in such cases is a minimally invasive procedure for not only making an early and accurate diagnosis but can also have a curative role.

Aim: To study the utility of FNAC in BCG lymphadenitis and to create awareness regarding this entity.

Materials and methods: This study has been conducted for 3 years (December 2021 to December 2023). We analyzed 16 cases of BCG lymphadenitis diagnosed on FNAC. Their clinical presentation, cytomorphological features, and clinical outcomes were studied.

Results: Of all the 16 cases, 10 patients were males and 6 were females. The minimum age for the presentation was 5 months and the maximum was 2 years. The majority had left-sided axillary lymph node enlargement without any constitutional symptoms. FNAC yielded pus aspirates in 80% of cases. Cytological examination showed inflammatory cells (62.5%), reactive lymphoid cells (37.5%), and epithelioid cell granulomas with necrosis (18.7%), along with giant cells in 12.5% of cases. Ziehl–Neelsen staining for acid-fast bacilli was positive in 13 cases. On follow-up, lymphadenitis regressed in most of them within a few months of diagnosis.

Conclusion: Bacille Calmette–Guerin lymphadenitis is a benign condition that remits spontaneously within a few weeks without any treatment in most cases. A high index of suspicion, clinical history, and FNAC play an important role in its detection and management.

Keywords: Bacille Calmette–Guerin vaccine, Cytology, Lymphadenitis, Mycobacterium bovis

How to cite this article: Naaz S, Sharma S, Aravind A, et al. Utility of Fine Needle Aspiration Cytology in Bacille Calmette–Guerin Lymphadenitis: An Institutional Experience. Pediatr Inf Dis 2024;6(4):120–123.

Source of support: Nil

Conflict of interest: None

INTRODUCTION

Live attenuated vaccines use weakened organisms to immunize individuals, such as Bacille Calmette–Guerin (BCG) which employs a live attenuated strain of Mycobacterium bovis to protect against tuberculosis (TB). Since its inception in 1921, it has been included in the World Health Organization (WHO) immunization schedule since 1974.1 In India, the BCG vaccine is included in the National Immunization schedule. It is administered to all newborns intradermally at the left deltoid region within 1 month after birth.2 It reduces infection rate and hinders evolution to progressive disease.1 National and international health agencies aim to eradicate TB, with BCG vaccination playing a crucial role in this effort.2 One of the most significant impacts of the BCG vaccine is its ability to prevent tubercular meningitis and disseminated TB. Mild side effects, such as the development of a cutaneous nodule at the injection site, have been observed in a small number of children, occasionally causing subclinical self-limiting regional lymphadenitis.3 Some adverse effects observed in children include skin ulceration, lupoid reaction, eczema vaccinatum, and regional lymphadenitis or BCG adenitis. Rarely, life-threatening systemic complications such as anaphylaxis or disseminated infection have been reported.4

Bacille Calmette–Guerin lymphadenitis is “an ipsilateral regional lymph node enlargement presenting without the presence of fever and other constitutional symptoms developing within 2 years of vaccination.”5 Most cases are self-limiting and resolve independently, while a few may increase in size or develop suppuration.4 Nevertheless, recognizing this entity is crucial for accurately identifying and treating this disorder. The present study tries to elucidate the clinical cues and cytological findings of BCG lymphadenitis, underscoring the pivotal role of fine needle aspiration cytology (FNAC) in such scenarios to increase awareness of this condition and prevent misdiagnosis.

MATERIALS AND METHODS

In this retrospective and descriptive study, we meticulously analyzed 16 cases of BCG lymphadenitis diagnosed by FNAC over 3 years (December 2021 to December 2023). All children who had recently received BCG inoculation and presented with an enlarged regional lymph node were included in the study. Informed consent was obtained from parents/guardians of the cases. FNAC was performed using a 23-gauge black needle in each case, employing a to-and-fro technique. Each case was analyzed for clinical and cytomorphological features. Both May–Grunwald–Giemsa (MGG) and Ziehl–Neelsen (ZN) stains, along with control slides, were examined in all the cases. All patients have been followed up. The data was tabulated in an Excel sheet, and an appropriate statistical analysis using percentage calculation was done.

RESULTS

Over the last 3 years, there have been 16 documented cases of BCG lymphadenitis. The age at presentation ranged from 5 months to 2 years, with a male-to-female ratio of 1.6 to 1. The most common presentation was enlargement of the left axillary lymph node, observed in 14 cases (87.5%). Two cases presented with left cervical lymph node enlargement. No other constitutional symptoms were present in any of the cases. The swelling ranged in size from 1 to 3 cm in diameter. In all 16 cases, a BCG scar was observed on the left arm (Fig. 1). The swellings were present on the same side as the BCG scar in all cases. On FNAC, frank pus was obtained in all cases except two, which yielded blood mixed aspirate. Some cases showed regression of swelling after aspiration. Cytomorphological features revealed the presence of polymorphs in 10 cases (62.5%), a reactive lymphoid population in 6 cases (37.5%), and epithelioid cell granulomas in 3 cases (18.7%), along with giant cells in 2 cases (12.5%). The necrotic background was seen in all cases except two with blood mixed aspirate. In 13 cases (81.2%), the ZN stain for acid-fast bacilli (AFB) was positive (Fig. 2). All these patients showed localized lymph node swelling and did not exhibit multisystemic involvement. None of these patients required surgical excision. On follow-up, swelling spontaneously resolved within a few weeks in 13 cases (81.2%), while it persisted in 3 cases. Two cases underwent repeat aspiration, and one case was lost to follow-up. The results are summarized in Table 1.

Figs 1A to D: (A) BCG scar on the left arm of a 2-year-old child; (B) Ipsilateral enlarged axillary lymph node in the same child; (C) BCG vaccine-induced left axillary lymphadenitis in an infant; (D) Ultrasonography showing heterogeneously hypoechoic lesion in the left axilla

Figs 2A to D: (A) Well-formed epithelioid cell granuloma (MGG, 20×); (B) Multinucleated giant cell against a reactive population of lymphoid cells (MGG, 20×); (C) Degenerating granuloma in a necrotic background (MGG, 20×); (D) Beaded AFB (ZN stain, 100×)

Table 1: Clinical features of all cases of BCG lymphadenitis
S. no. Age (months) Sex Laterality Site Size (cm) Aspirate Follow-up
1 5 Male Left Axilla 2 Pus Resolved
2 5 Male Left Axilla 1 Pus Resolved
3 5 Male Left Axilla 3 Pus Resolved
4 6 Female Left Axilla 1 Pus Resolved
5 6 Male Left Axilla 3 Pus Resolved
6 6 Male Left Axilla 2.5 Pus Lost
7 7 Female Left Axilla 1.5 Pus Resolved
8 8 Female Left Axilla 1 Pus Persisted
9 8 Male Left Axilla 1 Pus Resolved
10 9 Female Left Axilla 1 Pus Resolved
11 12 Female Left Axilla 1.5 Pus Resolved
12 12 Male Left Cervical 2 Pus Resolved
13 12 Male Left Cervical 2.5 Pus Persisted
14 15 Male Left Axilla 2 Blood mixed Resolved
15 18 Male Left Axilla 2 Pus Resolved
16 24 Female Left Axilla 1 Blood mixed Resolved

DISCUSSION

The Universal Immunization Program in India includes BCG vaccination in its ambit. BCG vaccine helps prevent the development of severe forms of TB such as meningitis and disseminated TB.1,2 Nevertheless, it may lead to skin induration and scarring. BCG is a live vaccine, and the live attenuated organism can spread to lymph nodes, potentially leading to an asymptomatic subclinical lymphadenopathy in some cases. However, this lymphadenopathy resolves within a few weeks.3 Therefore, in patients with BCG lymphadenitis, it is frequently observed that ipsilateral axillary and supraclavicular lymphadenitis is common. There are two manifestations of BCG lymphadenitis: non-suppurative and suppurative. The non-suppurative form of BCG lymphadenitis improves spontaneously without treatment and simple follow-up might suffice. The suppurative lymphadenitis presents as an erythematous soft swelling devoid of other constitutional symptoms and may require surgical intervention.2 In our series, 62.5% (10 out of 16) of cases presented within the first year of life. This is lower compared to other studies.2,6,7 13 out of 16 (81.2%) cases in our study presented with suppuration, which is higher compared to the study by Pal et al. (40%) and Johri et al. (57.1%), but lower compared to the study done by Jain et al. (86.7%).2,6,7 Male predominance was reported in 10 out of 16 cases, similar to all the studies mentioned above. In our study, 14 out of 16 cases (87.5%) observed axillary lymph nodes on the same side. This finding is consistent with the study by Jain et al. (86.7%), but lower than the results reported by Pal et al. (100%) and Johri et al. (100%).2,6,7 In our study, polymorphs were seen in 10 cases (62.5%), and necrosis was seen in almost all cases except two, which is almost similar to the studies done by Jain et al. and Vagasiya et al.6,8 The reactive lymphoid population in our study were found in 6 cases and epithelioid cell granulomas in 3 cases, both of which are lower as compared to other studies.6,8 ZN stain for AFB was found to be positive in 13 cases (81.2%) in our study which is higher as compared to the study by Johri et al. (57.1%) and Pal et al. (36%) but lower as compared to the study by Jain et al. (86.7%).2,6,7 All these findings are summarized in Table 2.

Table 2: Comparison with other studies documented in the literature
Studies Age of presentation within 1 year Male predominance Suppurative adenitis Left axillary lymph node Positive AFB
Present study 62.5% 62.5% 81% 87.5% 81.2%
Jain et al.6 100% 73% 86.7% 86.7% 86.7%
Johri et al.7 85% 71% 57.1% 100% 57.1%
Pal et al.2 100% 56.6% 40% 100% 36%

Differentiating BCG lymphadenitis from tubercular lymphadenitis is perplexing, however, TB is unlikely to present as a single enlarged axillary lymph node.2 In our study, FNAC caused regression of lymphadenitis in 13 cases (81.2%), after aspiration and reaspiration, which is lower as compared to Pal et al. who reported a regression in 91.67% after aspiration or reaspiration and higher as compared to the study done by Jain et al. which shows the efficacy of 73.3%.2,6

The role of FNAC in differentiating all lymph node lesions has been extensively studied in the literature. It has been a boon as it is a cost-effective, rapid, reliable, and non-invasive technique for diagnosis and ancillary testing.9-13 Likewise, cytology is also pivotal in diagnosing BCG lymphadenitis and preventing unnecessary medical/surgical treatment. Hence, it is both therapeutic as well as diagnostic in BCG lymphadenitis. It prevents sinus formation and spontaneous lymph node rupture in such cases. Additionally, a quick remission of suppurative lymphadenitis is facilitated by needle aspiration. FNAC-treated patients show superior outcomes and speedier recovery, however, very few studies have been documented in this regard.14 Nevertheless, the present study underscores the efficacy of FNAC in the diagnosis as well as management of BCG lymphadenitis.

For suppurative BCG lymphadenitis, an excision biopsy is an effective and curative method for removing the diseased lymph node, promoting early recovery and improved wound healing. However, in addition to the dangers of surgical manipulation which are significantly higher in children than the adults the patients may also suffer the risks of general anesthesia. Researchers have reported that most of the cases get resolved by fine needle aspiration and reaspiration, therefore excision biopsy should be kept reserved for non-healing cases only or when repeated aspirations fail.2

CONCLUSION

A high index of clinical suspicion for BCG lymphadenitis is required in cases of recently vaccinated children presenting with isolated ipsilateral lymph node enlargement to avoid any misdiagnosis. In such a scenario, FNAC plays an important role by clinching an accurate diagnosis and acting as an exceptional therapeutic intervention in both non-suppurative as well as suppurative lymphadenitis.

ORCID

Sonam Sharma https://orcid.org/0000-0001-9856-9542

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