Lymphadenopathy, defined as an abnormal enlargement of lymph nodes, is a common clinical finding in both primary care and hospital settings. In elderly patients, its evaluation becomes more complex due to the wide spectrum of underlying causes, ranging from reactive hyperplasia and infections to malignancies such as lymphomas and metastatic carcinomas. Age-related immunosenescence, coupled with comorbidities and polypharmacy, often alters the clinical presentation, making diagnosis based solely on clinical examination unreliable [1].

The geriatric population (aged 60 years and above) is growing globally, particularly in developing countries like India, where infectious diseases such as tuberculosis (TB) still coexist with a rising incidence of cancer [2]. Tuberculous lymphadenitis remains a major cause of peripheral lymphadenopathy in endemic regions, particularly affecting cervical lymph nodes [3]. However, with increasing life expectancy and better diagnostic facilities, malignancies—both primary (e.g., lymphomas) and secondary (e.g., metastatic spread)—are being identified more frequently in this age group [4].

Histopathological evaluation remains the gold standard in diagnosing the etiology of lymphadenopathy. In elderly individuals, timely biopsy and accurate histopathological interpretation can drastically alter the clinical outcome, particularly when distinguishing between treatable infections and life-threatening malignancies [5]. Recent studies have emphasized the need for clinicopathological correlation to improve diagnostic accuracy and avoid unnecessary empirical treatments [6,7].

Moreover, systemic symptoms such as fever, night sweats, and unexplained weight loss (collectively known as "B symptoms") often provide crucial diagnostic clues, especially in cases of tuberculosis and lymphoma. However, in the elderly, these symptoms may be subtle or attributed to other chronic conditions, leading to misdiagnosis or delayed intervention [8].

Multicentric studies evaluating the pathological spectrum of lymphadenopathy in the elderly remain limited in India. This research gap calls for more inclusive and representative studies that take into account regional variations in disease incidence, healthcare access, and diagnostic infrastructure. This investigation aims to provide evidence-based guidance for clinicians managing lymphadenopathy in geriatric populations, particularly in resource-limited settings.

Study Design

This original research was designed as a prospective, observational, multicentric study.

Study Setting

The study was conducted at three tertiary care hospitals in India: KD Medical College, Mathura (Uttar Pradesh), KIMS Hospital, Bhubaneswar (Odisha), and MKCG Medical College, Berhampur (Odisha). These centers were selected for their high patient load and availability of advanced diagnostic and pathology services. Data collection and patient evaluation were standardized across all sites.

Participants

A total of 200 elderly patients (aged ≥60 years) presenting with clinically diagnosed lymphadenopathy were included in the study. These patients were enrolled consecutively over a period of 12 months from February 2023 to January 2024. All participants underwent detailed clinical examination and histopathological evaluation of lymph node samples obtained through biopsy or excision.

Inclusion Criteria

• Patients aged 60 years and above.
• Patients with clinically evident lymphadenopathy (cervical, axillary, inguinal, or generalized).
• Patients willing to provide informed written consent.
• Patients undergoing lymph node biopsy or excision as part of diagnostic workup.

Exclusion Criteria

• Patients below 60 years of age.
• Patients with known hematological malignancies already under treatment.
• Patients unwilling to participate or provide consent.
• Patients with inadequate or autolyzed biopsy samples unsuitable for histopathological analysis.

Bias

To minimize selection bias, consecutive patients meeting inclusion criteria were enrolled across all three centers. Observer bias was minimized by using standardized pathology reporting protocols and ensuring all histological examinations were performed by qualified pathologists who were blinded to the clinical diagnosis. Inter-observer variability was addressed through periodic review meetings and consensus reporting.

Data Collection

Data were collected using a pre-validated structured proforma. Clinical data included patient demographics, duration and location of lymphadenopathy, associated symptoms (e.g., fever, weight loss, night sweats), and any relevant medical history. Histopathological findings from lymph node biopsies were documented, including diagnosis (reactive, granulomatous, neoplastic, etc.), architectural patterns, and special stain results, if applicable.

Procedure

Each patient underwent thorough clinical assessment followed by biopsy of the affected lymph node. The tissue samples were fixed in 10% formalin and processed in the pathology department. Hematoxylin and eosin (H&E) staining was performed routinely, and special stains (e.g., Ziehl-Neelsen, PAS) were used as necessary. The histopathological findings were categorized, and clinicopathological correlation was made based on clinical presentation and final histological diagnosis.

Statistical Analysis

Data were entered and analyzed using IBM SPSS Statistics version 23.0. Descriptive statistics such as mean, standard deviation, and percentages were used to summarize demographic and clinical data. Chi-square test and Fisher’s exact test were applied to assess associations between clinical features and histopathological findings. A p-value of <0.05 was considered statistically significant.

Out of the 200 elderly patients included in the study, 118 (59%) were males and 82 (41%) were females, resulting in a male-to-female ratio of 1.4:1. The mean age of the study population was 68.4 ± 5.6 years, with the majority (43%) belonging to the 61–70 years age group.

Table 1: Age and Gender Distribution of Study Participants (n = 200)

Most participants (53%) were within the 60–70 age range. Males were predominant in all age groups.

Anatomical Site of Lymphadenopathy

The most commonly involved lymph node region was cervical (45%), followed by axillary (20%), inguinal (17%), and generalized (18%).

Table 2: Distribution of Lymphadenopathy Sites (n = 200)

Cervical lymphadenopathy was the most frequently encountered, especially in patients with tuberculosis or reactive changes.

Histopathological Spectrum

Histopathological examination revealed that reactive lymphoid hyperplasia (30%) was the most common finding, followed by tuberculous lymphadenitis (28%), metastatic carcinoma (22%), non-Hodgkin’s lymphoma (12%), and Hodgkin’s lymphoma (8%).

Table 3: Histopathological Diagnosis of Lymph Node Biopsies (n = 200)

Benign causes were slightly more prevalent than malignant ones. Tuberculosis was a common cause, even in elderly patients.

Correlation of Clinical Features with Histopathology

Fever, weight loss, and night sweats were significantly associated with tuberculosis and lymphomas (p < 0.05). Painless, firm lymph nodes were commonly seen in malignancies.

Table 4: Association of Clinical Features with Histopathological Findings

Systemic features (fever, night sweats, weight loss) showed a strong correlation with tuberculous and lymphomatousetiology. Malignancies were often painless.

Malignant vs Non-Malignant Lesions

Malignant lymphadenopathy accounted for 42% of cases, while non-malignant causes accounted for 58%.

Table 5: Malignant vs Non-Malignant Causes of Lymphadenopathy

Though non-malignant causes were more frequent, malignancies made up a significant proportion (nearly 1 in 2), indicating the importance of histopathological evaluation in elderly patients.

In this multicentric observational study involving 200 elderly patients presenting with lymphadenopathy, a comprehensive analysis was performed to correlate clinical findings with histopathological diagnoses. The study population comprised more males (59%) than females (41%), with a mean age of 68.4 years. The highest frequency of cases was observed in the 60–70 years age group, emphasizing the vulnerability of early elderly individuals to lymph node pathology.

Cervical lymphadenopathy emerged as the most commonly affected anatomical site (45%), followed by axillary (20%) and inguinal (17%) regions. Generalized lymphadenopathy was present in 18% of the participants. This pattern aligns with clinical expectations, where cervical lymph nodes are commonly involved due to frequent exposure to upper respiratory infections and tuberculosis.

Histopathological examination revealed that benign conditions slightly outnumbered malignant ones, with reactive lymphoid hyperplasia (30%) and tuberculous lymphadenitis (28%) being the most frequent non-malignant causes. Among malignancies, metastatic carcinoma (22%) was the most prevalent, followed by non-Hodgkin’s lymphoma (12%) and Hodgkin’s lymphoma (8%). Overall, 42% of the lymphadenopathy cases were due to malignancy, highlighting a substantial burden of cancer-related lymph node disease in the geriatric population.

Clinically, certain features such as fever, weight loss, and night sweats showed strong statistical association with tuberculosis and lymphomas (p < 0.05), which are classically linked to systemic symptoms. Conversely, painless, firm lymph node swelling was significantly associated with malignant etiologies, especially metastatic deposits and lymphomas.

The results emphasize the diagnostic importance of histopathological confirmation in elderly patients, as clinical features alone may be misleading. Though infections like tuberculosis remain common even in older adults, the high incidence of malignancies necessitates timely biopsy and evaluation. Moreover, systemic symptoms should prompt suspicion for specific pathologies, particularly lymphoma and tuberculosis.

Several studies conducted after 2018 have expanded the understanding of lymph node pathology in elderly populations presenting with lymphadenopathy. A three-year study focusing on elderly patients aged 60 years and above found that reactive lymphadenitis was the most common cause of lymphadenopathy, followed closely by metastatic deposits, with squamous cell carcinoma being the predominant metastatic type. Tubercular and suppurative lymphadenitis were also observed, with males showing higher rates of both reactive and malignant lesions. Fine needle aspiration cytology (FNAC) was validated as a rapid and effective screening method for initial diagnosis in elderly patients with lymph node enlargement [9].

In a related study involving 100 patients with lymphadenopathy, the highest incidence was tubercular lymphadenitis (62.5%), particularly among younger adults, though some elderly were included. The study reaffirmed the diagnostic utility of FNAC and recommended histopathological biopsy especially when FNAC results were inconclusive or non-specific [10]. Another retrospective analysis of 131 lymph node cytology samples found that while reactive lymphadenitis was the most common pathology overall (42%), malignancies such as metastatic carcinoma were more common in older age groups, supporting a trend of increasing malignant etiologies with advancing age [11].

A 2023 investigation on cervical lymphadenopathy supported these findings, reporting that metastatic carcinoma was the most frequent malignant lesion among patients aged 40 and above. The study confirmed strong concordance between FNAC and histopathological examination and emphasized FNAC as the primary diagnostic tool, with histopathology reserved for confirmation [12]. Similarly, a study analyzing 174 cases found reactive lymphadenitis in 35 patients and metastatic carcinoma in 28, with FNAC yielding a sensitivity of 100% and specificity of 96.9% for tubercular lymphadenitis, and slightly higher specificity for metastatic malignancies [13].

Another hospital-based study from 2025 found metastatic carcinoma and lymphoma to be the dominant etiologies in patients over 50 years, reinforcing the need for region-specific diagnostic algorithms. The authors emphasized the importance of correlating cytological findings with clinical and demographic data to better guide diagnosis and management in elderly populations [14].

This study demonstrates a nearly equal distribution of benign and malignant causes of lymphadenopathy in the elderly. It underscores the relevance of integrating clinical signs with pathological confirmation for accurate diagnosis and early intervention, especially in resource-limited settings where empirical treatment is common.

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