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1 Surgical Lymph Node Biopsy in the Diagnosis of Tuberculous Lymphadenopathy الخزع الجراحية للعقد اللمفاوية في تشخيص تضخم العقد اللمفاوية التدرني Dr. Ali Hussain Abd Sweilim MBChB CABMS (Surg.)* Dr. Riyadh Mustafa Murtadha MBChB MD FICMS (Med.)* * Collage of Pharmacy Karbala University Abstract: Background: Lymphadenopathy is a common problem in medical practice. Tuberculous lymphadenitis is among the commonest causes of lymphadenopathy in the developing world. Objectives: To describe the clinical presentations and the investigations for the diagnosis of lymphadenopathy. To study cases of tuberculous lymphadenitis with a view to determining the value of clinical and investigative diagnostic indices. Materials & Methods: A prospective observational study was conducted to describe the clinical presentations and the pathological diagnoses resulting from (76) surgical lymph node biopsies in patients (44 male, 3 female) with enlarged lymph nodes admitted to Al-Yarmouk Teaching Hospital in Baghdad (during the period from 1 st Jan. 001 to 31 st Dec. 00). Results: 30 patients out of 76 (39.4%) had Tuberculous Lymphadenitis, while 0 patients (6.3%) had Non-specific lymphadenitis, 1 patients (15.8%) had Lymphoma, 10 patients (13.1%) had Neoplastic metastases, and the rest 4 (5.4%) had other diagnoses like brucellosis & toxoplasmosis. The epidemiological, clinical, and investigative results of 30 patients with tuberculous lymphadenopathy were analyzed. While cervical lymphadenopathy predominated (60%), the classical clinical features of tuburculous infection both local and general were frequently absent. Almost only third of the cases (33.33%) had a normal ESR (< 0mm/hr) and only (30%) had lymphocytosis. A clinical diagnosis of tuberculous lymphadenopathy was accordingly made in only (18) patients (60%). Conclusion: This study emphasizes the need of a high index of diagnostic suspicion of tuberculosis when confronted with peripheral lymphadenopathy in developing countries, and the need of surgical LN biopsy in confirming the diagnosis. الخالصة : خلفية البحث: ذعخ اىؼقذ اىي فا ح اى ح ط ح شنيح شائؼح ف اىؼ و اىطث ؼرثز ذذر اىؼقذ اىي فا ح ا االسثاب ى ف اىؼاى اى ا. االهداف: دراسح اىصفاخ اىسز ز ح اىفح صاخ اى جزاج ىرشخ ص زظ ذعخ اىؼقذ اىي فا ح. طريقة البحث: ذ دراسح اىصفاخ اىسز ز ح اىرشخ ص اى س ج ىيؼقذ اىي فا ح ى )76( ز عا صاب ترعخ اىؼقذ اىي فا ح ف سرشف اى ز ك اىرؼي ف تغذاد ىيفرزج 001/1/1 ىغا ح 00/1/31 النتائج: ذث أ )%39.4( ما ا ؼا ذذر اىؼقذ اىي فا ح ت ا شنو اىر اب اىؼقذ اىي فا ح غ ز اى حذد )%6.3( ا ا ر اىؼقذ اىي فا ح االترذائ )اىي ف ا( فنا )%15.8( األ را اىثا ح اى رشزج إى اىؼقذ اىي فا ح )%13.1(. ذث أ ؼظ اىؼقذ اىي فا ح اى صاتح تاىرذر اىؼقذ اىزقث ح. م ا ى حظ غ اب اى شاخ اىسز ز ح اىرقي ذ ح ىيرذر ف ؼظ اى زظ س اء اى ظؼ ح أ اىج اس ح. ذ الحظح أ ؼذه ذزس ة مز اخ اىذ اىح ز E.S.R ى زذفغ ف )%33,33( اى زظ اى صات تاىرذر م ا أ )%30( اى زظ فقػ ىذ س ادج ف ػذد مز اخ اىذ اىث ط اىي فا ح )اىي ف سا د(. ىذىل ما اىرشخ ص اىسز ز ىرذر اىؼقذ اىي فا ح طاتق غ اىفحص اى س ج ف )%53,3( فقػ اى زظ اى صات. االستنتاجات: سيطد ذ اىذراسح اىع ء ػي اىحاجح إى ذ قغ األغثاء ىيرذر تشنو مث ز ىذ اى زظ اى صات ترعخ اىؼقذ اىي فا ح م اىرذر األ زاض اى رشزج ف اىذ ه اى ا ح ا قطز ا اىؼش ش. مذىل اىحاجح اى اىخشع اىجزاح ح ىيؼقذ اىي فا ح ىرثث د اىرشخ ص. Introduction: Tuberculosis is one of the most important infectious diseases in Iraq [1]. Several reports have alluded to the significance of tuberculosis in the developing world [,3]. The early involvement of lymphatic system in the pathogenesis of tuberculosis is universally known [4]. Clinical 7

2 lymphadenopathy is accordingly a frequent feature of tuberculosis and publications from both western hemisphere [5, 6] and Iraq [7] rate as the commonest non-respiratory form of the disease. Surgical lymph node biopsy thus plays an important role in the diagnosis of tuberculosis. The importance of lymph node biopsy in the investigation of clinical lymphadenopathy in Iraq is high because of the prevalence of lymphoma and Tuberculosis in Iraq. The studies from western hemisphere proved that malignancies were the leading cause of lymphadenopathy [8], while in developing countries tuberculosis proved to be commonest cause of lymphadenopathy. This study reviews 76 cases subjected to surgical lymph node biopsy and further analysis of 30 patients in whom the histological findings were those of tuberculous lymphadenitis with a view to determining the value of clinical and investigative diagnostic indices. Materials & Methods: Seventy six cases had undergone excisional lymph node biopsy at Al-Yarmouk Teaching Hospital in Baghdad from 1 st January, 001 to 31 st December 00. The biopsy procedure involved the removal of one or more entire lymph nodes by surgical operation under general anesthesia.the histological findings in each case were analyzed. Thirty cases in which pathological diagnosis was tuberculosis were studied further. The age and sex distribution were determined. The clinical features and investigations results were reviewed with particular reference to the manifestations and diagnosis of tuberculosis. Results: There were 0 males and 10 females among the 30 patients with tuberculous lymphadenitis. The male: female ratio being :1, while in non- TB patients the ratio was nearly equal. The patients ages ranged from years to 51 years (The mean age being 9 years). The age and sex distribution of the patients is depicted in Table 1. Table 1: A: Age and sex distribution of Tuberculous patients Age Males Females Total % Total B: Age and sex distribution of Non-Tuberculous patients Age Males Females Total % Total Thirty patients (39.4%) had tuberculous lymphadenitis, 1 patients (15.8%) had lymphoma, and 10 patients (13.1%) had metastatic tumour in lymph node. There were two cases of each toxoplasmosis and brucellosis. On 0 occasions (6.3%) the lymph node biopsy was helpful in that it excluded specific diseases and the histological features were Reactive Hyperplasia. The histological diagnoses of 76 cases subjected to lymph node biopsy are recorded in Table. 8

3 Table : Histological diagnosis of lymph node biopsy Histological diagnosis Tuberculosis Non specific lymphadenitis Lymphoma Metastasis Brucellosis Toxoplasmosis Total No. of cases The anatomical sites of the lymphadenopathy are catalogued in Table 3. Percentage 39.4 % 6.3 % 15.8 % 13.1 %.7 %.7 % 100 % Cervical lymphadenopathy was predominant in tuberculous cases, being seen in 18 patients (60%). Most of them had unilateral disease, bilateral lymphadenopathy being seen in only five cases. In addition to cervical lymphadenopathy, the axillary nodes were enlarged in 4 patients and inguinal nodes in. All three regions (cervical, axillary, and inguinal) were involved in 3 cases. A Single case had only inguinal, and had only axillary lymphadenopathy. Table 3 : Anatomical sites of Tuberculous Lymphadenopathy Sites of LN No. of cases Percentage Cervical Cervical and axillary Cervical and inguinal Cervical, axillary and inguinal Axillary Inguinal Total % 30 % 10 % 100 % Most of patients had more than one palpable enlarged lymph node at the site involved. The multiple nodes were however described as being matted on 15 occasions (50%). In 8 patients the enlarged nodes were specifically notes to be rubbery in consistency (6.6%). A clinical diagnosis of cold abscess was made in 5 cases. The scars of healed sinuses or ulcers were observed in two patients. The Characters of Lymph nodes in TB Cases are shown in Table 4 Table 4: The Characters of Lymph Nodes in TB Cases TB LAP Percentage Matted 15 50% Rubbery % Cold abscess % Sinus or ulcers 6.66% Total % Table 5 shows the prevalence of general symptoms suggestive of tuberculosis such as weight loss, pyrexia, night sweats and cough in all TB & non-tb cases. 9

4 Table 5: General symptoms in cases of TB and non-tb lymphadenopathy Symptoms TB cases Non-TB cases No. % No. % Fever Weight loss Night sweats Cough Total symptomatic Total asymptomatic Total All cases No % The known duration of lymphadenopathy was not more than year in the majority of cases 80%, the shortest being a fortnight and in this group the mean duration was 5.5 months. Only Two patients gave a family history of tuberculosis. No other patient admitted a contact history of the disease. The results of some Laboratory Investigations done for TB and non-tb cases is shown in Table 6 Table 6: Laboratory Investigations of TB and non-tb cases Table 6-A: Total White Blood Cells (WBC) WBC TB cases Non-TB cases No. % No. % Normal (4-11 x 10 3 ) 1 40% % >11 x % 4 5.% < 4 x % % Total % % Table 6-B: Erythrocyte sedimentation rate (ESR) ESR TB cases Non-TB cases No. % No. % 0mm/hr % 1-40mm/hr 1 40% % 41-60mm/hr 6 0% % > 60mm/hr 6.6% % Total % % The total white cell count of 30 patients ranged from x 10 3 with a mean value of 6.17 x The differential count revealed a lymphocyte percentage greater than (35%) in 9 patients (30.0%). The range of lymphocyte percentage was (13-63%) and the mean was (34%). Four patients (5.%) had a polymorphonuclear leukocytes percentage over (70%), the range for 30 patients being (4-78%) and the mean was (56%).The erythrocyte sedimentation rate (E.S.R.) in one hour was below 10mm in 8 out of 30 patients (0.66%) and above 60mm in patients (6.6%), the highest rate being 80mm. The mean E.S.R. for tuberculous lymphadenopathy patients in this series was 5.5mm.Chest X-ray (CXR) was done for all patients; only 4 out of 30 patients (13.33) had evidence of pulmonary TB in their CXR. Discussion: 30

5 Tuberculosis is still a major health problem in Iraq [9]. Lymphatic spread from the primary complex is an integral component of the pathogenesis of tuberculosis. Lymphadenopathy is consequently a characteristic feature of the disease and frequently comprises the only clinical manifestation of tuberculous infection[10].the total number of tuberculous lymphadenopathy recorded in Iraq was (63) cases in 00 which represent (5.3%) of all recorded cases of tuberculosis. Chest and Respiratory Diseases Institute in Baghdad reported that peripheral lymphadenopathy accounted for (18.3%) of cases of extrapulmonary tuberculosis [11].This study has shown that tuberculous lymphadenopathy was the histological report on as much as (39.4%) of surgical lymph node biopsy. Lymphoma and metastatic malignancy were the pathological finding in (15.5%) and (13.8%) respectively. The study thus illustrated that while reticuloendothelial neoplasia and disseminated carcinoma compete with tuberculosis for the diagnostic decision in cases where lymphadenopathy dominates the clinical picture in Baghdad, tuberculosis maintains the foremost position whatever the age of the patient.this conclusion contrast with clinical experience in developed countries of the western hemisphere where as a rule: "any lymph node enlargement in an adult of more than cm diameter is likely to be due to secondary spread from a malignant growth" [1], While in India 75% of lymphadenopathy was tuberculous [13,14]. In this study, Cervical TB Lymphadenopathy was predominant (60%) compared with other study in Saudi Arabia which revealed that Cervical TB Lymphadenopathy constituting (80%) of the involved sites[15].a high index of diagnostic suspicion with reference to tuberculosis must therefore be kept by the clinician in Iraq when dealt with cases of established lymphadenopathy. While this suspicion may be enhanced by other allegedly characteristic clinical features of tuberculosis and by the commonly expected results of investigative procedures relevant to the disease, the diagnostic decision must not be determined by their absence, as what is found in a study done in USA that constitutional symptoms were rare [16]. In this study as much as (46.08%) of patients had none of general symptoms supportive of a diagnosis of tuberculosis like : weight loss, low-grade fever, night sweats and chronic cough.clinical teaching frequently emphasize, that tuberculous lymph nodes are typically: "matted" while "rubbery" consistency is described of lymphomatous lymphadenopathy, while in this study: matted node 50%, rubbery node 6.6%, cold abscess and sinus 3.4%.Almost a third of the cases had a normal ESR and in those in whom the rate was elevated the rise was usually moderate the mean value for the series being 5.5 mm/hr. The classically expected lymphocytosis in tuberculosis was seen in only (34%).Radiological evidence of pulmonary tuberculosis were present in only (13.3%) of Chest X-Ray of patients, as compared to (7%) of patients in Saudi Arabia [15].Tuberculine test and TB culture were not included in our study because of unavailability at the time of study, while Fine Needle Aspiration Cytology (FNAC) was not done because of its lower diagnostic yield as was seen in a study in Saudi Arabia which gave only (46%) positivity of FNAC [15].Although the prevalence of tuberculosis in developing countries is well known, a clinical diagnosis of tuberculosis was made in only (60% = 18 patients) of the patients in this study who were subsequently proven to have tuberculous lymphadenopathy by surgical biopsy. Recommendations: This study emphasizes the need for an increased awareness of the probability of tuberculous lymphadenopathy as a likely diagnosis in cases of chronic lymph nodes enlargement, despite the absence of general features of the disease and the lack of the expected results of standard investigative procedures.a high index of diagnostic suspicion and its prompt confirmation by lymph node biopsy would lead to early effective therapy and the reduction of the incidence of this debilitating disease thereby enhancing the development of those parts of the world where it is still prevalent. 31

6 References: 1. I.U.A.T. "International Union Against Tuberculosis". Conference in Baghdad, Raviglione MC, Kochi A. "Global epidemiology of tuberculosis" JAMA 1995 ; 73 : W.H.O. / T.B. / 1991 "First Program Report and Future plan ". 159:. 4. Seal ME : "The pathology of tuberculosis". Br. J. Hosp. Med. 1971: Enderson DA, Dorken E. "Non-respiratory tuberculosis in Canada". Am. J. Epidemiol 1980, 11 : Monie RD, Hunter A.M, Kilpatrick GS : "Management of extra-pulmonary tuberculosis in South and Wales". Br. Med. J. 198, 85: Chest and respiratory Diseases Institute. "Tuberculosis Annual Report In Iraq, 00". 8. Martin DA, James OA. "Clinical oncology". nd ed. London (UK): Chruchill Livingstone Inc., 000, P Al-Khamese A.S. "T.B. in children", Iraq Med. 198 ; 30 : Innes JA: "Non respiratory tuberculosis". Medicine International 1984, : Ibrahim M: "Cervical lymph node biopsy", Saudi Med. Journal. 00, 3: Cady B: "Evaluation of neck mass". North Am ; 50 : Bowling MC. "Lymph node specimens": Achieving technical excellence laboratory Med 1979; 10 : Kissane M. Gephardt GN. "Lymphadenopathy in childhood" Hum. Pathol. 1974; 5: Memish ZA et al Clinico-diagnostic experience with tuberculous lymphadenitis in Saudi Arabia : Clin Microbiol Infect. 000 Mar;6(3): Artenstein AW et al Isolated peripheral tuberculous lymphadenitis in adults: current clinical and diagnostic issues : Clin Infect Dis Apr;0(4):

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