Histomorphological patterns of lesions in lymph node biopsies

Introduction: Lymph node biopsies are routinely performed for the evaluation of lymphadenopathies. Tuberculosis and other infections are the major causes of lymphadenopathy in developing countries. The pattern of lymph node enlargement is different for different age groups. Malignancies are common in adults as compared


Introduction
Lymph nodes are discrete ovoid lymphoid structures present throughout the body. They drain lymph from different parts of the body and become involved in many pathological conditions. Lymphadenopathy refers to an abnormal change in size, shape, or consistency of lymph nodes. The causes may be broadly divided into neoplastic and non-neoplastic. Non-neoplastic causes include infections, drug reactions, lipid storage disorders, and non-specific inflammatory conditions. 1 Clinically, lymphadenopathy may be peripheral or visceral. Peripheral lymphadenopathies are easily detected by general physical examination and are often biopsied as they are easily accessible for lymphadenectomy.
However, visceral lymphadenopathy requires laparotomy or imaging assistance. 2 Among the peripheral nodes, those in the upper part of the body (cervical, supraclavicular, axillary) are preferentially biopsied than lower limb nodes (popliteal, inguinal, or femoral), as the former are more likely to yield definitive diagnosis whereas the latter is often characterized by non-specific reactive or chronic inflammatory and fibrotic changes. 1,2 Lymph node biopsies are routinely performed for the evaluation of lymphadenopathies. Tuberculosis and other infections are a major cause of lymphadenopathy in developing countries especially in regions where HIV is common, whereas in developed countries; non-specific reactive hyperplasia predominates. 3 The pattern of lymph node enlargement is also different for different age groups. Malignancies are more common in adults as compared to children. Reactive hyperplasia to minor stimuli is a significant cause of lymphadenopathy in children. 1,4 Generally in primary health care, patients older than 40 years with lymphadenopathy, without any obvious cause, have chances of malignancy about 4% and in patients under 40 years of age, this chance is about 0.4%. 5 Considering numerous causes of lymphadenopathy, it has become essential to define diseases presenting with lymph node enlargement. The intent of this study is the etiological evaluation of lymphadenopathy, in relation to age and gender of patients and pattern of lymph node distribution in biopsy samples.

Materials and Methods
This descriptive, cross-sectional study was conducted to study different causes of lymphadenopathy in our setup, and to correlate site and size of lymphadenopathy with the histopathological diagnosis. A total of 163 patients who underwent lymph node biopsies were included in this hospitalbased, non-interventional study. The specimens obtained were processed for histopathological examination. All the lymph node biopsy specimens received from January 2015 till June 2018 were included. Specimens with incomplete records were excluded from the study. A pre-designed proforma was used to record all the demographic and laboratory data including age, gender, site of biopsy, size of largest lymph node biopsied, and a clinical diagnosis made based on morphology and cut section appearance.
Age-wise distribution of lymphadenopathy is given in Table-I   To check the relationship between gender and lymph node lesions we applied Chi-square test. We tested the hypothesis "There is no association among female gender and lymph node lesion" against the alternative "There is association among female gender and thyroid lesion" at 0.05 level of significance. The results were X2=163, df=1, p-value=0.000. As the p-value <0.05, we rejected our null hypothesis of no association between female gender and lymph node lesion.
In this study, all lesions were divided into two groups: neoplastic or non-neoplastic. Neoplastic lesions were 22 accounting for 13.50% of all the lesions. The majority of these lesions were in the age group ≥ 60years. Most common among neoplastic lesions were metastatic lesions followed by Hodgkin lymphoma, non-Hodgkin lymphoma, and unclassified lymphoproliferative disorders respectively. Age-wise distribution of neoplastic disorders is given in Table-III.
Non-neoplastic lesions were 122 accounting for 74.84% of all the lesions. The peak age group was 10-19 years. The most common non-neoplastic lesion was reactive hyperplastic lymphadenopathies followed by tuberculous granulomatous lesions and other granulomatous lesions respectively. In 19 cases (11.65%), biopsies were either unremarkable or non-lymphoid tissue was biopsied. The most frequently biopsied lymph node group was abdominal lymph nodes followed by cervical, inguinal, and axillary lymph nodes respectively. In 30 cases, sites other than these were biopsied. Diagnostic yield for each lymph node group was calculated by the given formula: Diagnostic yield = (number of biopsies with specific histopathological findings ÷ total number of biopsies) × 100 The abdominal lymph node group gave the highest diagnostic yield while the group giving the lowest diagnostic yield was the axillary lymph node group.   Statistical comparison was made between size of lymphadenopathy among neoplastic and nonneoplastic lesions using Chi-square test which revealed significant relationship between size of lymphadenopathy and type of lesion. The most common histopathological diagnosis in this study was reactive hyperplasia (50.3%) followed by tuberculous granulomatous lesions (23.3%), metastatic lesions (6.1%), Hodgkin's lymphoma (3%), non-Hodgkin's lymphoma (2.4%), unclassified lymphoproliferative disorders (1.8%) and other granulomatous lesions (1.2%) respectively. 19 biopsies (11.6%) were unremarkable. Similarly, in studies conducted by Kasturi et al 9 and Abdul Ghafoor et al 10 , benign lesions were found to be more common than malignant lesions. Neoplastic lesions were found to be more common in the study by Roy et al 7 conducted in India, may be because the study was conducted in a setting that works as a referral center where specialized diagnostic techniques are used for malignancy detection. In our study, the most common benign lesion causing lymphadenopathy was reactive hyperplasia (50.3%) followed by granulomatous lymphadenopathy (24.5%). Similarly, in a study by Zahir ST et al 6 , lymphadenopathy due to reactive hyperplasia (62.5%) was found to be more common than due to infectious etiology (15.9%). Reactive hyperplasia was also more common in studies conducted by Moore et al 5 12 , the most common site of the biopsy was cervical lymph nodes. This might be due to the easy accessibility of cervical lymph nodes for biopsy. In our study, the most common biopsies were of abdominal lymph nodes. This may be because many of these samples were obtained during surgeries performed on the abdomen. Most cases of lymphomas were diagnosed on biopsies taken from the cervical region (77.7%). Cervical and abdominal lymph nodes were found to be the commonest sites for metastatic deposits (80% cases of metastatic lymphadenopathy). Many sources have revealed that lymphadenopathy in the supraclavicular region and some other places has increased risk of malignancy. However, in study by Zahir ST et al 6 , no significant relationship between pathologic findings and site of the biopsy was seen.
In the present study, abdominal lymph nodes and cervical lymph nodes gave the highest diagnostic yield (90% and 88% respectively), while axillary lymph nodes gave the lowest diagnostic yield (75%). In a study by Atiqur Rahman et al 12 , abdominal and axillary lymph nodes gave the highest diagnostic yield (67.9%), while submental and submandibular lymph nodes gave poor diagnostic yield. This might be because there were only fewer biopsies taken from the submental and submandibular regions in the given study.

Conclusion
Reactive hyperplasia and tuberculosis are the most common of histomorphological patterns of lymph node biopsies in developing countries accounting for 50.3% and 23.3% respectively. Malignancy and lymphomas are other common causes. Moreover, the abdominal lymph node group gave the highest diagnostic yield. Different methods are employed for the diagnosis of lymph node lesions such as FNAC, core needle biopsy but excision of lymph nodes and study after routine H&E staining is the gold standard in differentiating neoplastic from non-neoplastic lesions. However, in reaching a definite diagnosis as well as in the further classification of lymphomas, immunohistochemical markers must be applied.