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Year : 2017  |  Volume : 10  |  Issue : 4  |  Page : 343-348  

Spectrum of lymph node lesions as determined by histopathology

Department of Pathology, Dr. D. Y. Patil Medical College, Hospital and Research Centre, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India

Date of Submission29-Dec-2016
Date of Acceptance30-Jul-2017
Date of Web Publication4-Sep-2017

Correspondence Address:
Bedarshi Banerjee
Department of Pathology, Dr. D. Y. Patil Medical College and Hospital, Pimpri, Pune - 411 018, Maharashtra
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Source of Support: None, Conflict of Interest: None


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Background and Objective: Lymph node lesions form a wide range of spectrum, exhibiting manifestations in both hematopoietic tissue and lympho reticular system. It is necessary to document the same spectrum in a particular region to understand the trend and diseases occurring frequently in that region. The range encompasses benign reactive changes to frank malignant lymphoma and metastatic deposits. Histopathology is considered to be the gold standard and its relevance to clinical diagnosis is studied here. Materials and Methods: A total of 200 cases were studied retrospectively in this study. Samples received were either biopsy or node resection specimens, and clinical history was recorded for each of them. Immunohistochemistry and special stains were performed as and when required. Results: Clinical diagnosis had a diagnostic accuracy of 71% approximately using histopathology as the gold standard. Most of the benign diseases were either reactive or tubercular lymphadenitis, whereas non-Hodgkin Follicular lymphoma had the maximum incidence among lymphomas. Conclusion: This study concluded that cervical group of superficial lymph nodes are most frequently encountered as palpable nodal swellings. The clinical suspicion of malignancy remains high in most of the cases due to the matted and enlarged presentation of lymph nodes. Histopathology revealed that only 33.5% of the cases to be malignant of which the most common was Follicular Lymphoma (non-Hodgkin type). The clinical accuracy of diagnosing malignant lesions thus coming to 71% approximately.

Keywords: Clinico-pathological correlation, histopathological spectrum, lymph nodes, lymphoma

How to cite this article:
Pagaro PM, Banerjee B, Khandelwal A, Pandey A, Gambhir A. Spectrum of lymph node lesions as determined by histopathology. Med J DY Patil Univ 2017;10:343-8

How to cite this URL:
Pagaro PM, Banerjee B, Khandelwal A, Pandey A, Gambhir A. Spectrum of lymph node lesions as determined by histopathology. Med J DY Patil Univ [serial online] 2017 [cited 2024 Feb 24];10:343-8. Available from:

  Introduction Top

The lymph nodes are an integral part of the immune system, a complex system whose job is to adequately deal with foreign substances.[1] Lymph, an ultrafiltrate of blood, traverses from the afferent lymph vessels, through the sinuses, and out the efferent vessels. The sinuses are studded with macrophages, which remove 99% of all delivered antigens.[2] As lymph nodes deal with antigens, their histology reflects the activity of the immune system; the nature of the antigen not only determines whether a reaction will be mounted against it but also determines what effector cells will be employed. This will be reflected in the morphology of the lymph nodes. Lesions can be both proliferative and nonproliferative and can be treatment-related or not. It is considered gold standard in diagnosis and determines the treatment protocol, thus aiding the surgeon.

Most of the studies conducted earlier did not cover the entire spectrum of lymph nodal lesions, or were too early to reflect the changes in the pattern of diseases affecting the same, postimplementation of newer treatment modalities, including directly observed treatment short course and chemotherapeutic agents, including the change in cyclophosphamide, doxorubicin, oncovin, and prednisolone regime with newer alkylating drugs. Furthermore, a significant understanding of the lymphoma and Langerhans cell morphology, the emergence of the concept of follicular dendritic and reticulum cell sarcoma and their understanding and grouping them together with diffuse large B cell lymphoma (DLBCL) (on similar morphologic and prognostic grounds), reflects the change in the pathological spectrum of the same.

Most studies on lymphoma did not take these entities together, and so a variation in distribution is probable. Furthermore, most of the studies in the recent past, were carried out in Japan, or Middle Eastern part of the world; a study in the Indian subcontinent on similar lines was rare. The aim of this study was to evaluate various lymph node lesions in our department of pathology, through histopathological study. The main objective was to find out the incidence of nonneoplastic, neoplastic, and metastatic lesions in the lymph nodes, as diagnosed by histopathological examination (HPE) and to determine their incidence with respect to age, radiological, clinical and pathological features, in a tertiary center of the Indian subcontinent.

  Materials and Methods Top

The study was carried out in the Department of Pathology of a teaching Medical College, Hospital and Research Centre. Institutional Ethical Committee permission was obtained before start of the study. The study was a retrospective study covering the period of 2 years.

Inclusion criteria

The study included 200 excised/biopsized lymph node specimens.

Exclusion criteria

Cases where histopathological studies were inconclusive, due to the lack of adequate material, or other causes.

In all patients, biopsy was performed as an outpatient procedure with minimal morbidity and no mortality. The clinical details were noted from histopathology requisition forms. 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 differentiation, 5, 10, 20, 23, 30, and 34, leukocyte common antigen, epithelial membrane antigen, cytokeratin, Ki-67, smooth muscle actin, desmin, vimentin, human melanoma black-45, chromogranin and S100. IHC was performed by avidin-biotin peroxidase method with pretreatment by microwave heating.

All lymphoma cases were classified according to the standard World Health Organization (WHO) classification of hematolymphoid malignancies. For the diagnostic criterion of each pathology, guidelines of the WHO published in 2008 were followed.

Statistical analysis

The validity of clinical diagnoses was ascertained by calculating sensitivity, specificity, and positive and negative predictive values with their 95% confidence intervals (CI) using histopathology as the gold standard.

  Results Top

Totally 200 cases were considered in the present study. Maximum cases were observed in the age group of 41–50 years, whereas least was above 70 years [Table 1].
Table 1: Age-wise distribution of cases in study group

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Gender-wise, female cases (51%) were slightly more than male cases (49%).

Ultrasound was not done in all the cases. Among the available cases, the incidence of reactive hyperplasia and malignant changes observed by ultrasonography (USG) were comparable [Table 2].
Table 2: Ultrasonography finding wise distribution of cases in study group

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Clinical diagnosis mostly attributed the lymph nodal enlargement as metastasis from primary, followed by reactive hyperplasia. Approximately 30% were diagnosed as tubercular lymphadenitis.

To summarize, slightly greater number of lymph nodes were considered clinically malignant than benign [Table 3].
Table 3: Clinical Diagnosis wise categorization of cases into benign or malignant

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HPE examination was considered gold standard in this study. It revealed most of the cases to be reactive lymphadenitis, followed by slightly lower number of tubercular lymphadenitis. Two cases of follicular hyperplasia were also diagnosed, which was not apparent on fine needle aspiration cytology (FNAC). Six cases of Hodgkin lymphoma and 16 cases of non-Hodgkin lymphoma (NHL) were also diagnosed. Kikuchi's disease, Kimura's disease, and Sarcoidosis were also diagnosed but very few. Two cases of Castleman disease and one of toxoplasmosis were also diagnosed [Table 4]. [Figure 1],[Figure 2],[Figure 3],[Figure 4],[Figure 5] show some illustrative HPE findings.
Figure 1: Follicular hyperplasia: Microphotograph showing lymphoid follicles of varying size and shape. The mantle zone is preserved in most of the follicles (H and E × 40)

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Figure 2: Burkitt's Lymphoma: Higher power showing medium-sized tumor cells with occasional squaring of cytoplasm. Cells have round to oval nuclei with several small basophilic nucleoli (H and E × 400)

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Figure 3: Castleman Disease: Higher power showing hyalinization of germinal center and prominent vascularization. There is concentric layering of lymphocytes at the periphery resulting in an “Onion – skin” appearance (H and E × 400)

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Figure 4: Lymphoblastic lymphoma: Microphotograph showing diffuse and relatively monomorphic pattern of proliferation of lymphoid cells with scant cytoplasm and round nucleus (H and E × 400)

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Figure 5: Hodgkin Lymphoma- Mixed Cellularity: Microphotograph showing several diagnostic R-S cells admixed with polymorphic lymphoid infiltrate rich in eosinophils (H and E × 400)

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Table 4: Hstopathological examination finding wise distribution of cases in the study group

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The most common type of lymphoma observed was follicular type NHL [Table 5].
Table 5: Number of various types of lymphomas in the 200 cases studied

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Further cases were categorized into benign and malignant on the basis of histopathological findings, which showed approximately 2/3rd malignant and 1/3rd benign cases [Table 6].
Table 6: Histopathological examination finding wise categorization of cases into benign or malignant

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Out of 106 cases diagnosed clinically as malignant, 58 came out to be truly malignant on HPE. Conversely, of 94 cases diagnosed as benign, 85 were truly benign.

In comparing the accuracy of clinical diagnosis to histopathology, with respect to the determination of benign and malignant lesions, the sensitivity was 86.57% (95% [CI] 76.4, 92.77), whereas specificity was 63.91% (95% CI 55.46, 71.58). Positive predictive value was modest at 54.72% (95% CI 45.24, 63.86). The negative predictive value was 90.43% (95% CI 64.88, 77.31). The accuracy of clinical diagnosis when compared to HPE was thus 71.50% (95% CI 64.88, 77.31) [Table 7].
Table 7: Association between clinical diagnosis and histopathological examination findings in study group

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  Discussion Top

The predominant age of presentation in our study was 41–50 years, whereas only 3% was over 70 years of age. In this study, female was slightly more than male (51% and 49%, respectively). A study had been done by Khan et al.,[3] which showed males were more commonly affected than females. Similar observation of male dominance was found in another study. This difference could be attributed to the fact that the location of this study was in an urban population where more female gender patients visit tertiary health care compared to a rural population where still females are oppressed in our country.

The median age of NHL in Asian countries is significantly lower, compared to the population-based registration in western countries. The Hematological Malignancy Research Network reported that the median age of their patients was 68-year-old.[4] However, the median age in Asian countries is about 54 years old in Iranian patients was 55-year-old,[5] in the Korean patients 52 years,[6] in Taiwan 54 years,[7] and in a previous study in Japan 54.5 years, but in a recent study in Japan it was 66 years.[8] In this study, the median age of presentation of NHL was 53 years.

In the latter study, a maximum number of lymph node biopsies was from a cervical group of lymph nodes followed by axillary, and the least common group of superficial lymph node involved was inguinal lymph nodes as they found cervical group of lymph node as the most commonly involved nodes. This is comparable to our study where 39% (highest) were from cervical lymph node, and least was from hilar lymph node (0.5%) (Image guided).

USG findings mostly revealed reactive lymph nodes. The clinical diagnoses revealed metastasis from the primary tumor (39%) as the most common cause of lymphadenopathy. It is obvious that the clinician would request for FNAC and/or HPE only when he or she suspects such grave and serious malignant conditions where operative procedure is indicated.

The knowledge of the pattern of lymphadenopathy in a given geographical region is essential for making a confident diagnosis or suspecting a disease. Tuberculosis is one of the most common cause of lymphadenopathy in developing countries such as Nepal and India and should be considered in every case of granulomatous lymphadenopathy unless proved otherwise.

It has been reported by several authors that tuberculosis is one of the predominant cause of lymph node enlargement in adults in tropics like India. A study by Khan et al.[3] and Umer et al.[9] found tuberculosis in 33.3% and 55.4%, respectively. The variation of tuberculosis in percentage might be due to geographic variation, number of patients included in the study and immunological status of the patients. Recently, HIV infection has emerged as a cofactor for tuberculosis emergence. Nonspecific reactive hyperplasia of lymph node tissue was second most common lesion seen in our study with 20% of all cases. As seen in the study by Lee et al.[7] nonspecific reactive hyperplasia is the foremost cause of lymphadenopathy.

In this study, NHL-T cell subtype was only 2% compared to NHL-B cell subtype (6%). This is comparable to other studies. It is also to be noted that we found Follicular NHL as the most common subtype in our study. In a previous study in Japan, the incidence rate of FL was 6.7%,[10] but a recent study in Japan found a relatively high rate of FL (19%) similar to that of western countries (11–30).[8]

The most common subtype of T cell lymphoma in Asia is reported to be Natural Killer T cell lymphoma and Adult T-cell leukemia/lymphoma.[11] This variation may reflect exposure or genetic susceptibility to pathogenic agents such as Epstein-Barr virus and HTLV1 in Asian countries.

A major subtype of T cell lymphoma reported from western countries is also seen in Asia, albeit at a lower rate.[12] Essential differences in the incidence and distribution of major NHL subtypes among different geographic areas were seen which seems to be related to host, racial and environmental differences,[13] but changes in these differences in recent reports, indicate that environmental factors probably are more important than the genes. We found one case of T cell Lymphoblastic lymphoma, presenting at 22 years of age.

Immunologic characterization of NHL although B-cell lymphomas are constantly more common worldwide, T-cell lymphomas are proportionally more common in Asia than in western countries.[14] Despite a higher percentage of T-cell lymphomas in Asians compared with westerns, the absolute incidences of T-NHL in HTLV1 non endemic areas, and western countries are quite similar when calculated by age-adjusted incidence.[8],[15],[16]

In some studies like a recent study in Mashhad, Iran,[5] there was a higher rate of aggressive NHL especially, DLBCL which occurs more frequent than others. It may be related to the etiology of DLBCL such as immune deficient conditions and their treatments which in most instances caused aggressive NHL, and we should consider that a comparative excess of DLBCL resulting in a deficit of follicular lymphoma. In our study, we found three cases of DLBCL.

Most of the studied metastatic nodes were metastatic squamous cell carcinoma followed by metastatic adenocarcinoma. In this study, the most common histological type was metastatic squamous cell carcinoma followed by metastatic breast carcinoma. Similar findings had been documented by other researchers.

  Conclusion Top

This retrospective study thus showed that the predominant age of presentation of lymph nodal lesions was between 41 and 50 years, accounting for 22.5%

The most common site of lymph nodal enlargement was cervical accounting for 39% of the total. Axillary lymph node followed it, and the least of 0.5% was observed in pelvic and hilar lymph nodes.

Most of the lymph nodes presented as multiple and most of them were matted/fixed along with being tender. Thus, it shows that the trend is implicating on clinicians to think more in lines of malignancy and/or tuberculosis, rather than benign or reactive changes. This being one of the reasons why the accuracy of clinical diagnosis came low (we got more benign lesions on pathological examination). Thus, the presenting symptoms have misled to false diagnoses.

The clinical diagnoses gave most of the lesions as malignant or metastasis from primary, while USG concluded that reactive changes were slightly more prevalent than malignant changes. This picture is helpful in one way as a high degree of clinical suspicion helps avoid missing a malignant lesion completely. It is also to be concluded that the accuracy of clinical diagnosis was 71% only when compared to HPE.

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Conflicts of interest

There are no conflicts of interest.

  References Top

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Khan AH, Hayat AS, Baloch GH, Jaffery MH, Soomro MA, Siddiqui S. Study of FNAC in cervical lymphadenopathy. World Appl Sci J 2011;12:1951-4.  Back to cited text no. 3
Smith A, Roman E, Howell D, Jones R, Patmore R, Jack A, et al. The Haematological Malignancy Research Network (HMRN): A new information strategy for population based epidemiology and health service research. Br J Haematol 2010;148:739-53.  Back to cited text no. 4
Mozaheb Z, Aledavood A, Farzad F. Distributions of major sub-types of lymphoid malignancies among adults in Mashhad, Iran. Cancer Epidemiol 2011;35:26-9.  Back to cited text no. 5
Ko YH, Kim CW, Park CS, Jang HK, Lee SS, Kim SH, et al. REAL classification of malignant lymphomas in the republic of Korea: Incidence of recently recognized entities and changes in clinicopathologic features. Hematolymphoreticular Study Group of the Korean Society of Pathologists. Revised European-American Lymphoma. Cancer 1998;83:806-12.  Back to cited text no. 6
Lee MY, Tan TD, Feng AC, Liu MC. Clinicopathological analysis of malignant lymphoma in Taiwan, defined according to the World Health Organization classification. Haematologica 2005;90:1703-5.  Back to cited text no. 7
Aoki R, Karube K, Sugita Y, Nomura Y, Shimizu K, Kimura Y, et al. Distribution of malignant lymphoma in Japan: Analysis of 2260 cases, 2001-2006. Pathol Int 2008;58:174-82.  Back to cited text no. 8
Umer MF, Mehdi SH, Muttaqi AE, Hussain SA. Presentation and aetiological aspect of cervical lymphadenopathy at Jinnah Medical College Hospital Korangi, Karachi. Pak J Surg 2009;25:224-6.  Back to cited text no. 9
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Shih L, Liang D. Non-Hodgkin's lymphomas in Asia. Hematol Oncol Clin North Am 1991;5:983.  Back to cited text no. 12
Atichartakarn V, Kurathong S, Nitiyanand P, Kiatikajornthada N, Petchclai B, Ou D, et al. Alpha chain disease in the Thai man. Southeast Asian J Trop Med Public Health 1982;13:120-6.  Back to cited text no. 13
Müller AM, Ihorst G, Mertelsmann R, Engelhardt M. Epidemiology of non-hodgkin's lymphoma (NHL): Trends, geographic distribution, and etiology. Ann Hematol 2005;84:1-12.  Back to cited text no. 14
Au WY, Ma SY, Chim CS, Choy C, Loong F, Lie AK, et al. Clinicopathologic features and treatment outcome of mature T-cell and natural killer-cell lymphomas diagnosed according to the World Health Organization Classification scheme: A single center experience of 10 years. Ann Oncol 2005;16:206-14.  Back to cited text no. 15
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  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]

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