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| Year : 2013 | Volume
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| Issue : 2 | Page : 103-108 |
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| Spectrum of histopathologic diagnosis of lymph node biopsies: A descriptive study from a tertiary care center in South India over 5½ years |
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Arun Roy, Rakhee Kar, Debdatta Basu, Bhawana Ashok Badhe
Department of Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
Click here for correspondence address and email
| Date of Web Publication | 23-Sep-2013 |
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 Abstract | | |
Aims: Lymphadenopathy is a common clinical problem and biopsies undertaken to determine the cause of nodal enlargement may be neoplastic or non-neoplastic. The former are mainly lymphohematogenous malignancies and metastases while the causes of non-neoplastic lymphadenopathy are varied. This study was undertaken to determine the histopathological spectrum of lymphadenectomies. Materials and Methods: This was a descriptive cross-sectional study wherein 1010 cases of histologically diagnosed peripheral lymph node biopsies in the Department of Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry from January 2007 to June 2012 were reviewed. Surgical resection specimens with lymph node dissection were excluded from the study. Results: Neoplastic lesions were more common comprising 53% (535 cases) and included 32.1% (324 cases) of non-Hodgkin lymphoma, 12.4% (125 cases) of Hodgkin lymphoma and 8.5% (86 cases) of metastatic lesions. The non-neoplastic lesions were 47% (475 cases), which included 21.6% (218 cases) of non-specific reactive lymphoid hyperplasia, 6.8% (69 cases) of other reactive or specific lymphoid hyperplasia, 18% (182 cases) of tuberculous lymphadenitis, 0.6% (6 cases) of other granulomatous lesions. Conclusions: Lymph node biopsy plays an important role in establishing the cause of lymphadenopathy. Among the biopsied nodes, lymphomas were the most common (44.5%) followed by non-specific reactive hyperplasia (21.6%), tuberculous lymphadenitis (18%) and metastasis (8.5%). Keywords: Hodgkin lymphoma, lymphadenopathy, lymph node, non-Hodgkin lymphoma
How to cite this article:
Roy A, Kar R, Basu D, Badhe BA. Spectrum of histopathologic diagnosis of lymph node biopsies: A descriptive study from a tertiary care center in South India over 5½ years. Indian J Pathol Microbiol 2013;56:103-8 |
How to cite this URL:
Roy A, Kar R, Basu D, Badhe BA. Spectrum of histopathologic diagnosis of lymph node biopsies: A descriptive study from a tertiary care center in South India over 5½ years. Indian J Pathol Microbiol [serial online] 2013 [cited 2023 Sep 30];56:103-8. Available from: https://www.ijpmonline.org/text.asp?2013/56/2/103/118692 |
| Introduction | |  |
Lymphadenopathy is a common clinical problem and biopsies are usually undertaken to determine the cause of nodal enlargement, which may be neoplastic or non-neoplastic. The neoplastic disorders are mainly lymphohematogenous malignancies and metastases while the causes of non-neoplastic lymphadenopathy are more varied such as infections (bacterial, viral, fungal), drug reactions (including certain vaccines), lipid storage disorders and a wide variety of miscellaneous non-neoplastic lymphoproliferative disorders such as Castleman disease, Rosai Dorfman disease, Kimura disease, Kikuchi Fujimoto disease and systemic lupus erythematosus (SLE). Clinically, lymphadenopathy may be peripheral or visceral. Peripheral lymphadenopathies are easily detected by routine physical examination and are often biopsied as they are easily accessible for lymphadenectomy, which is a minor surgical procedure. Visceral lymphadenopathy on the other hand requires laparotomy or sophisticated imaging techniques for detection. 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 are often characterized by non-specific reactive or chronic inflammatory and fibrotic changes. [1]
However, there is a paucity of information on the spectrum of diseases affecting lymph nodes from this region. Hence this study was undertaken with the aim of evaluating the spectrum of histopathological diagnosis of peripheral lymph node biopsies.
| Materials and Methods | | |
This was a descriptive cross-sectional study of 1010 cases of peripheral lymph node biopsies diagnosed in the Department of Pathology in a large tertiary care teaching hospital in South India from January 2007 to June 2012. Cases were retrieved from the departmental archives and were reviewed. In all patients, biopsy was performed as an out-patient procedure with minimal morbidity and no mortality. The clinical details were noted from histopathology requisition form. Sections from formalin fixed, paraffin embedded blocks and stained with H and E, stains were studied in all cases. Special stains including Ziehl Neelsen, periodic acid Schiff and Gomori's methenamine silver were used where indicated. Immunohistochemistry (IHC) was performed using relevant antibodies according to the histomorphological features. The panel of antibodies included cluster of differentiation (CD)3, CD5, CD10, CD15, CD20, CD23, CD30, CD56, CD68, Leukocyte Common Antigen (LCA), Epithelial membrane antigen, cytokeratin, Bcl-2, Bcl-6, cyclin D1, kappa light chain, lambda light chain, Ki-67, TdT, smooth muscle actin, desmin, vimentin, Human Melanoma Black (HMB)-45, synaptophysin, chromogranin and S100. IHC was performed by avidin-biotin peroxidase method with pre-treatment by microwave heating. All lymphoma cases were classified according to standard World Health Organization classification of hemato-lymphoid malignancies (2008). En bloc lymph node dissection in known cases of primary or associated with evidence of primaries elsewhere in the body was excluded from the study.
| Results | | |
A total of 1010 lymph node biopsies were received during the period under review, accounting for 1.5% of all surgical biopsy specimens. Out of these, 63.2% (638 cases) were males and 36.8% (372 cases) females giving a male to female ratio of 1.7:1. The age range was 1-84 years in case of male and 1-87 years in case of female. Most cases were seen in the age group of 11-30 years (354 cases, 35%) and the least cases were seen in the age group above 70 years (30 cases, 3%). Out of 1010 lymph node biopsies analyzed, neoplastic lesions were more common comprising 53% (535 cases), which included 32.1% (324 cases) of non-Hodgkin lymphoma (NHL), 12.4% (125 cases) of Hodgkin lymphoma (HL) and 8.5% (86 cases) of metastatic lesions. The non-neoplastic lesions were 47% (475 cases), which included 21.6% (218 cases) of non-specific reactive lymphoid hyperplasia, 6.8% (69 cases) of other reactive or specificlymphoid hyperplasia, 18% (182 cases) of tuberculous lymphadenitis, 0.6% (6 cases) of other granulomatous lesions [Figure 1]. | Figure 1: Distribution of different types of lesions on lymph node biopsy. HL = Hodgkin Lymphoma, NHL = Non-Hodgkin lymphoma, FH = Follicular hyperplasia, SH = Sinus histiocytosis, PH = Paracortical hyperplasia, TB. = Tuberculosis
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Among the non-neoplastic lesions, reactive lesions were by far most common accounting for 60.4% (287 cases). There was male preponderance and male to female ratio was 1.8:1. Common age group affected was 11-20 years. Among the non-specific reactive lymphoid hyperplasia, majority, i.e., 40% (190 cases) was follicular hyperplasia, 3.8% (18 cases) were sinus histiocytosis and 2.1% (10 cases) were paracortical hyperplasia. The rest 14.5% (69 cases) had other specific patterns of lymphoid hyperplasia or lymphadenopathy in 12% (57 cases) and included 4 (0.8%), 11 (2.3%), 1 (0.2%), 19 (4%), 6 (1.3%), 1 (0.2%), 2 (0.4%), 2 (0.4%), 11 (2.3%) cases of infarcted node, human immunodeficiency virus associated lymphadenopathy, SLE lymphadenopathy, dermatopathic lymphadenopathy, Kikuchi Fujimoto disease, Kimura disease, hyalinized node, Rosai Dorfman disease and Castleman disease respectively and 12 cases (2.5%) were not otherwise specified or categorized. [Figure 2]. | Figure 2: Gender and percentage distribution of different types of non-neoplastic lesions on lymph node biopsy
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Tuberculous lymphadenitis comprising 38.3% (182 cases) of non-neoplastic lesions and the second most common histologic pattern encountered occurred predominantly in young adult female and 80% (146 cases) occurred before the age of 40 years with a peak between 21 and 30 years with slight female preponderance (M:F = 0.87:1). Other granulomatous lesions included two cases of sarcoidosis, two cases of cat scratch disease and two cases of toxoplasmosis [Figure 2].
There were 125 cases of HL, which accounted for 12.4% of all lymph node biopsies and constituted 27.8% of all lymphomas. The most common age group was between 11 and 20 years of age with male preponderance (M:F = 2.5:1). Nodular sclerosis (NS) was the most common subtype of HL [Table 1]. | Table 1: Age and gender distribution of patients and subtypes of Hodgkin lymphoma
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There were 324 cases of NHL, which accounted for 32.1% of all lymph node biopsies and constituted 72.2% of all lymphomas. Out of these, 63.6% (206 cases) occurred after the age of 40 years with a peak between 51 and 60 years and male preponderance (M:F = 2.2:1). Among 324 cases of NHL, T-cell lymphoma comprised 38% (123 cases) and B-cell lymphoma 54% (175 cases) with diffuse large B-cell lymphoma (DLBCL) being the most common subtype comprising 29.3% (95 cases). Other subtypes of B cell lymphomas were, 6.8% (22 cases) of follicular lymphoma (FL), 1.85% (6 cases) of burkitt lymphoma, 0.3% (1 case) of lymphoplasmacytic lymphoma (LPL), 2.8% (9 cases) of marginal zone lymphoma (MZL), 4% (13 cases) of mantle cell lymphoma (MCL), 3.7% (12 cases) of chronic lymphocytic lymphoma/small lymphocytic lymphoma (CLL/SLL), 2.8% (9 cases) of T-cell/histiocyte-rich large B-cell lymphoma and 2.5% (8 cases) of precursor B-lymphoblastic lymphoma.
The T-cell NHLs were 10.5% (34 cases) of anaplastic large cell lymphoma (ALCL), 17.3% (56 cases) of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), 1.85% (6 cases) of angioimmunoblastic T-cell lymphoma (AITL), 0.9% (3 cases) of adult T-cell lymphoma/leukemia (ATLL) and 7.4% (24 cases) of precursor T-lymphoblastic lymphoma. The natural killer (NK)-T cell lymphoma and histiocytic/dendritic cell neoplasm comprised 0.3% (1 case) each respectively. Twenty four (7.4%) cases could not be further sub-classified due to outside slides having been submitted for review with non-availability of blocks or due to non-contributory IHC, possibly due to poor antigenic preservation. Out of these, 14 cases were high grade, 6 cases were intermediate and 4 cases were low grade NHLs [Table 2]. | Table 2: Age and gender distribution of patients and subtypes of non-Hodgkin lymphoma
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Metastases constituted the remaining malignancies representing 8.5% of total lymph node biopsies. The majority of cases were found within the age group 40-70 years (55 cases, 64%). The male:female ratio was 1.6:1. Out of 86 cases of metastatic lymphadenopathies, 18.6% (16 cases) were squamous cell carcinoma, 31.4% (27 cases) were adenocarcinoma, 19.7% (17 cases) were poorly differentiated carcinoma, 11.6% (10 cases) were undifferentiated carcinoma, 1.2% (1 case) each of malignant melanoma, medullary thyroid carcinoma, seminoma and small round cell tumor respectively, 2.3% (2 cases) of rhabdomyosarcoma, anaplastic thyroid carcinoma and small cell carcinoma respectively and 3.5% (3 cases) of neuroendocrine carcinoma and papillary thyroid carcinoma respectively [Table 3]. | Table 3: Age and gender distribution of patients with metastatic lesions
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| Discussion | | |
Palpable lymph nodes offer an important diagnostic clue to the etiology of the underlying condition. Though fine needle aspiration cytology is commonly used to establish the etiological diagnosis, excision biopsy of the lymph node remains the "gold standard" for diagnosis. [2],[3],[4] Our study shows that males were more commonly affected; patients with benign etiology were younger, whereas those with malignant etiology were older.
The present study showed lymphomas were the most common cause of lymphadenopathy (44.5%) followed by non-specific reactive hyperplasia (21.6%), tuberculous lymphadenitis (18%) and metastatic nodes (8.5%). Among the lymphomas, NHL was more common comprising 72.2% of all lymphoma while HL constituted 27.8%. In the Western world NHL is reported to be 3 to 4 times more common than HL and the incidence is rising while that of HL is falling. [5],[6],[7] The higher proportion of NHL in the Western world than here in India, may be partly explained by racial and genetic factors as comparative studies in the United States document higher incidence among Whites than Blacks.
CLL/SLL formed 3.7% of all lymphoma cases (6.9% of all B-cell lymphoma), a proportion that is similar to or lower than those seen in most developed countries and some Asian countries. However, it is higher than in Hong Kong and Korea. [8],[9],[10],[11] Our study included only those CLL/SLL patients who had a lymph node biopsy as a part of the workup. MZL (nodal) constituted 2.8% of all NHL cases (5.1% of all B-cell lymphoma). FL accounted for 6.8% of all NHL cases (12.6% of all B-cell lymphoma). This reiterates the reported low frequency of FL in developing countries and Asia. [11],[12],[13],[14] The epidemiological factors (either genetic or environmental) responsible for this low frequency of FL remain to be elucidated. MCL forming only 4% of NHL cases (7.4% of all B-cell lymphoma) was rarer than in the most developed countries. Its proportion is closer to the reported 3% from Hong Kong. [8] DLBCL accounting for 29.3% (54.3% of all B-cell lymphoma) is the single largest subset of NHLs seen in India. In a study by Naresh et al. [15] DLBCL comprised 34% of all NHL.
T-cell and NK cell neoplasms accounted for 38.3% of all NHL. Reports from Hong Kong and Shanghai quote T/NK-cell lymphomas to collectively constitute 25% and 28% of all NHLs. [16],[17] The most common subtypes of mature T-cell lymphomas were PTCL-NOS constituting 17.3% of all NHL (45.2% of all T-cell lymphoma), ALCL comprising 10.5% of all NHL (27.4% of all T-cell lymphoma), AITL accounting for 1.8% of all NHL (4.8% of all T-cell lymphoma) and adult T-cell lymphoma/leukemia accounting for 0.9% of all NHL (2.4% of all T-cell lymphoma).
Among the precursor neoplasms, (B and T lymphoblastic lymphomas), which comprised 9.9% of all NHLs, we found that T-cell lymphoblastic lymphoma, accounting for 7.4% of all NHL cases (19.4% of all T-cell lymphoma), was relatively more frequent compared with other studies where the reported frequency has been lesser than 3% [9],[10],[18] and was higher than B lymphoblastic lymphoma. In a report by Advani et al. [19] lymphoblastic lymphoma (irrespective of immunophenotype) formed 7.5% of all NHLs. The factors that might be responsible for this increased frequency of T-cell lymphoblastic lymphoma are unknown.
Among HL, nodular sclerosis was the most common subtype comprising 39.2% of cases. In USA and Europe it comprises 70% of classical HL; however, rate varies greatly among other geographical regions and the risk is the highest among those with high socio-economic status.
Tuberculosis has been reported by several authors as the predominant cause of lymph node enlargement in adults in the tropics. [20],[21] In our study tuberculous lymphadenitis was the third common cause of lymphadenopathy, constituting 18% of all cases. In the Western countries, infections like tuberculosis have become rare and malignancies including lymphoma are now the predominant causes of lymph node enlargement. [22],[23]
Non-specific reactive hyperplasia was second most common pattern encountered constituting 21.6% of cases in our study. In the United States, non-specific reactive hyperplasia is a common cause of lymphadenopathy comprising nearly half of all cases. [24],[25] The relative absence of tuberculosis and earlier diagnosis of malignancies before the onset of nodal metastases may explain the prominence of reactive hyperplasia in the Western world.
Metastases comprised the remaining nodal malignancies constituting 8.5% of all lymph nodes biopsies. Among them, metastatic adenocarcinoma was the most common. In the United states metastases comprising 29% of peripheral lymph nodal enlargement, second only to reactive hyperplasia. [24],[25]
| Conclusion | | |
Lymph node biopsy plays an important role in establishing the cause of lymphadenopathy. A diagnosis of lymphoma was the most common cause of biopsied lymphadenopathy in our study with NHL comprising 32.1% and HL comprising 12.4%. T/NK cell lymphomas show a greater prevalence compared with other studies. Among the NHL, DLBCL was most common and among the HL, nodular sclerosis (NS) was the most common. Among the non-neoplastic etiologies, reactive hyperplasia was most common followed by tuberculous lymphadenitis.
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Correspondence Address:
Rakhee Kar
Department of Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry - 605 006
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0377-4929.118692
[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3] |
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