Histopathological Evaluation of Lymph Node Biopsies : A Hospital Based Study

Background: Lymphadenopathy is a common manifestation of a large variety of disorders, both benign and malignant. It is essential to define the pattern of disorders presenting primarily as lymph node enlargement in a particular environment. Histopathological examination of the lymph node biopsies is a gold standard test in the distinction between reactive and malignant lymphoid proliferations as well as for detailed subtyping of lymphomas. We designed this study in our population for histopathological evaluation of lymph nodes that might be helpful for clinical management of these lesions. Objective: Histopathological evaluation of lymphadenopathy from excised specimen, in relation to age and sex of the patients, and distribution of the lymph nodes. Materials and Methods: It was a retrospective cross sectional study conducted in the department of Pathology, Enam Medical College & Hospital, Savar, Dhaka during the period from January 2006 to December 2010. Lymph node biopsies of all patients of both sexes and all age groups were included. Metastatic lymph nodes associated with evidence of primaries elsewhere in the body were excluded from the study. Total 191 lymph node biopsies were selected for histopathological evaluation. Among these 90 (47.12%) were from males and 101 (52.88%) were from females with male to female ratio being 1:2.1. The age of the patients ranged from 2 to 85 years with a mean age of 35.73 ± 18 years. Results: Cervical lymph nodes were the most common (56%) biopsied group. Of the 191 cases 59 cases (30.89%) were reactive lymphadenitis, 64 cases (33.5%) were tuberculosis, 2 cases (1.05%) were non-caseous granuloma, 11 cases (5.76%) were Hodgkin lymphoma, 22 cases (11.52%) were non-Hodgkin lymphoma, 24 cases (12.57%) were metastatic neoplasm and 9 cases (4.7%) were other lesions. Conclusion: Tuberculosis was the most common cause of lymphadenopathy, followed by reactive lymphadenitis and the cervical group of lymph nodes was most frequently affected.


Histopathological Evaluation of Lymph Node Biopsies:
A Hospital Based Study 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. 1,2mphadenopathy is a common clinical problem, and biopsies are usually undertaken to determine the cause of nodal enlargement.Various reports document tuberculosis and infectious etiology as major causes of lymph node enlargement, 3,4 whereas malignancies as a predominant cause in the developed countries. 5,6Increase in incidence of tuberculosis attributed to the advent and preponderance of HIV infection has been documented worldwide. 7,8,9nsidering the plethora of diseases that may cause lymphadenopathy, it is essential to define the pattern of disorders presenting primarily as lymph node enlargement in a particular environment. 10Pattern of lymph node enlargement is different in different age group.Metastatic deposit is common in adults whereas it is rare in children. 11,12Reactive hyperplasia to minor stimuli has been reported as a significant cause of lymphadenopathy in children. 13e intent of this study was etiological evaluation of lymphadenopathy, in relation to age and sex of the patients and pattern of lymph node distribution in lymph node biopsy samples received in the department of Pathology, Enam Medical College & Hospital.II.In this study, non-neoplastic lesions were more common comprising 70.16% (134 cases).TB was the most common cause of lymphadenopathy and accounts for 47.76% of all non-neoplastic lesions.

Materials and Methods
Females were more frequently affected compared to males with a female to male ratio of 1.78:1.Most of the patients (n=51; 79.7%) were between 11-40 years of age (Table III).Caseous granuloma was found in all of these cases.Noncaseating granuloma was seen in only two biopsies.
Malignancies comprised 29.8% (57 cases) of enlarged lymph node with lymphomas predominating accounting for 17.3%, making them collectively the third most prevalent cause of lymphadenopathy in this series.Among the lymphomas, non-Hodgkin lymphomas (NHLs) were more common with intermediate and high grade types being predominant (Table IV).Hodgkin lymphoma was predominantly observed in males (Table II).Mixed cellularity type was the most common subtype, seen in 7 cases (63.6%), followed by lymphocyte predominance and nodular sclerosis types (Table IV).

Discussion
Patients presenting with enlargement of the lymph nodes is one of the most common problems in clinical practice. 14Lymphadenopathy offers an important diagnostic clue to the etiology of the underlying condition.The cause of lymphadenopathy often cannot be ascertained on clinical grounds alone.Excision biopsy of the lymph node provides material to establish an early diagnosis and is a vital part of the management. 15 this study, cervical lymph nodes were the most frequently biopsied constituting 56% of nodal biopsies.This is consistent with virtually all other lymph node studies.In agreement with other studies benign lesions were more frequent comprising 70.2% of lymph node enlargement and malignant lesions constituted 29.8%. 15,16In contrast, a study done by Olu-Eddo AN et al 10 revealed malignancy being the predominant lesion constituting 55% of cases.The higher incidence of malignant tumors are also documented in the western series. 5,6,18berculosis was the commonest cause of lymphadenopathy in this study accounting for 33.5%.Tuberculosis has also been reported by several authors as the predominant lesion in adults in the tropics. 3,4The studies performed in other developing countries also showed TB lymphadenitis being the most common cause of lymphadenopathy. 16,19,20The high incidence of TB has been attributed to the low socio-economic status and the attendant poor standard of living in the third world countries. 21 the western countries, infections like TB have become rare and malignancies including lymphoma are the predominant causes of lymph node enlargement. 5,6The higher rates of tuberculosis in some African countries like Zambia is due to their higher HIV infection rates, tuberculosis being an AIDS-defining illness. 8Different other studies also revealed predominance of TB due to higher HIV infection. 9In the last three decades, HIV/AIDS has also been responsible for the resurgence of tuberculosis.Coincident with the AIDS epidemic, the incidence of tuberculosis has risen dramatically.Worldwide, almost a third of all deaths in AIDS patients are attributable to tuberculosis.Prior to the HIV pandemic, tuberculosis was declining due to improved living standards. 7We could not analyze the HIV status in patients with TB because test for HIV was not done.
In this study, TB affected mainly the cervical group of lymph nodes of young adult females with maximum at 21-30 years and 80% of the patients were between 11-40 years of age.Only 11% patients with TB lymphadenitis were above 40 years of age.These results are consistent with the findings of other authors. 3,4,10,21A study from Turkey showed that the most common site of extrapulmonary TB lymphadenitis was intrathoracic lymph nodes followed by cervical lymph nodes. 22ke Asian and North African populations, in the USA tubercular lymphadenitis was found to be more common in females as compared to males. 23 Malignant tumors constituted 29.8% cases with lymphoma accounting for 17.3%, making them collectively the third commonest cause of lymphadenopathy.These are consistent with the findings of other authors. 10,17,18However, some other authors found predominance of metastatic neoplasms among the malignancies. 15,20Among the lymphomas, NHLs were more common comprising 11.5% of lymphadenopathies while HL constituted 5.76%.Other studies also document a preponderance of NHL over HL. 10,15 In the western world NHL is reported to be three to four times more common than HL.The much higher proportion of NHL in the western world may be partly explained by racial and genetic factors. 27termediate and low grade lymphomas accounted for over 80% NHL in the USA 27 , whereas high and intermediate grades were predominant in our study comprising 91%.In contrast to these studies, Naseem SS et al 19 found predominance of HL over NHL (72 cases versus 27 cases).
Hodgkin lymphoma showed marked predilection for the cervical group of lymph nodes with a striking male to female ratio of 10:1.These findings corroborate with other findings. 4,10The mixed cellularity type is the most common pattern in the current study, in agreement with other studies. 17,19 the present study, metastatic tumors was the fourth commonest cause of lymphadenopathy constituting 12.57% cases, which is similar to the study of Shrestha AK et al. 16 In agreement with others, majority of the patients (62.5%) were above the age of 45 years.4,16 Out of 24 metastatic lesions, adenocarcinoma and squamous cell carcinomas were common comprising 37.5% and 25% respectively.The distribution of metastatic lymph nodes among both sexes depends upon the tumor type (primary), as metastatic lymph nodes in patients with breast carcinoma will be seen more in female patients and vice versa.13 The varied etiology of lymphadenopathy observed at our tertiary care center, as documented by histopathological evaluation, was comparable to studies conducted in other developing countries.TB was the most common cause of lymphadenopathy, followed by reactive lymphadenitis and presented mostly with cervical lymphadenopathy.Females were frequently affected by TB as compared to males.In both HLs and NHLs males were frequently affected than females. Amng the HLs, mixed cellularity was the commonest subtype and among the NHLs, intermediate grade lymphomas were more common.Among metastatic tumors, adenocarcinoma and squamous cell carcinoma were frequent.

Fig 1 .
Fig 1. Age and sex distribution of the patients Cervical lymph nodes were the most commonly biopsied group (56%), followed by axillary, abdominal and inguinal group of lymph nodes (TableI).The overall diagnostic yield in 191 biopsies was 64.4% with abdominal lymph nodes giving the highest yield (67.9%) and the submental group giving the least diagnostic yield.Among the different spectrum of lesions, 65.2% cases of TB, 57.6% of reactive lesions, 42.4% of lymphoma, 50% of metastatic neoplasms and 44.4% of other specific causes of lymphadenitis were found in the cervical group of lymph nodes.

Table I :
Distribution of various histopathologic diagnoses according to lymph node location and diagnostic yield in each group TB=Tuberculosis; HL=Hodgkin lymphoma; NHL=Non-Hodgkin lymphoma Diagnostic yield of each group is defined as: (Number of biopsies with specific histopathologic findings in this group/Total number of biopsies of the same group) × 100

Table II :
Age and sex distribution of 191 patients with lymphadenopathy Distribution of various histological diagnoses, mean age values and sex distribution are shown in Table

Table IV :
Nodal lymphomas in 33 patients

Table III :
Histological diagnosis and age of 191 patients with lymph node biopsies 25o cases of granulomas lacking caseation or other specific features were seen in this review.These possibly were early tuberculosis before the development of caseous necrosis.Both of these were negative for acid-fast bacilli (AFB).These results differ from that of Attah EB 24 , Sibanda et al25and Moore et al 26 who found reactive change highest followed by TB.Attah EB reported 33% of reactive change and 30% of TB, Sibanda et al found 33% of reactive change and 26.7% of TB and Moore et al found 47.8% of reactive lesions and 36.3%cases of TB.