lymphadenopathy is an important finding in a large groups of patients. The doctor is confronted with a patient presenting with lymph node enlargement and the doctor need to decide is the lymph nodes normal or abnormal. Although the finding of lymphadenopathy some time give us a clue if the patients suffer from serious diseases or it is caused by infection or other benign conditions. Sometimes, we can diagnose the patients with lymphadenopathy depending on careful history and physical examination [1]. 

In the eighteenth century the human lymphatic anatomy has been studied already by Mascagui, Cruik shank and Sappy. Sappy illustrate anatomy of the lymphatic system in 1874. Sappy divide the body of human in to four regions by using two plains sagittal plain and horizontal plain at the L2 level. The lymph drains from these plains in to the same side of inguinal and axillary regions the thoracic duct which is the largest lymphatic vessel collect the lymph from the left side of the human body and from the abdomen and both lower limbs and this duct ends in the left subclavian vein, the right lymphatic trunk collect lymph from right side of the body and the thorax and head and this trunk ends to the right subclavian vein.

The immune response is the main function of lymphatic system because it produces antibodies and also filtration of foreign bodies and cancer cells also the lymphatic system represent the pathway to transfer cancer cell to other organs through the lymphatic vessels the staging and prognosis of malignant disease determined by the site of abnormal lymph nodes and a number of abnormal lymph nodes and if there is any associated diseases.

In localized lymphadenopathy we do a search for the lesion that cause this enlargement and excluding generalized lymphadenopathy other regions for lymph nodes enlargement. Supraclavicular nodes are always give as clue of malignancy. Two to four weeks follow up is mandatory in patients suffer from localized lymphadenopathy with suspicion of benign conditions. in cases of generalized lymphadenopathy, we must do to them clinical evaluation and and investigation is important and we need to choose the abnormal when we do FNA cytology and excisional biopsy because this selection make the pathologist results clear and give definitive diagnosis.

Patients Selection

This is a prospective study include (66) patients admitted to the baquba teaching hospital over and from general surgical outpatient clinic in a hospital a period of six months from 1st October 2014 to the 31st march 2015 with unknown cause of lymphadenopathy.

Evaluation of Patients

History: We take history from the patients. The history include age, sex, occupation, time of onset of swelling, if there is any associated symptoms such as fever, pain, weight loss, discharge from the node or from other site from the body.

Review of system is important to give us clue to the relation between the symptoms and under lying disease. History of smoking and taking alcohol and if there is any travelling history and past medical or surgical history, with history of chronic use of drugs.

Physical Examination

Physical examination is important to give us clue about the lymph node state, the site of lymph node if it's localized or generalized and the size of lymph node if more than 1 cm considered abnormal in the cervical region and more than 0.5 cm in epitrochlear region or more than 1.5 cm in the inguinal region and if the lymph node tender or not, the texture of lymph node if the node is soft or hard or fluctuated and if the lymph node separated or matted to gather and if lymph node fixed or mobile and the the state of the skin over the lymph node if there is any lesion or discoloration or discharge. 

The general examination of the patient is important to know the vital signs to the patient "pulse rate, blood pressure, temperature and respiratory rate" and if the patient anemic or jaundice or if there is finger clubbing and measure the body mass index to the patient.

The Systemic Examination

Important if there is systemic illness so we examine the head and neck first and and examine the lymph node as mention above and examination of the chest if there is any mass or crepitation or reduced air entry in the one or both sides of the lung.

The Abdominal Examination

We examine the abdomen by inspection first if it is distended or not and we notice the symmetry of the abdomen and if there is any bruising or discoloration of the skin and if there is any scar for previous operation. then we palpate the abdomen by superficial and deep palpation and we must evaluate the abdomen if it is soft or tender and if there is superficial mass or deep mass and if there is enlarged liver or spleen. And percussion of the abdomen if we suspect presence of ascites. Then auscultate the abdomen for presence or absence of bowel sound.

Investigations

Hematological Study: We do to the patients’ blood test "Complet Blood Count" to evaluate the state of blood components in the body and if there is any increase or decrease in the number of white blood cells and if there is any change in the hemoglobin or hematocrits and we need evaluate the number of platelets if increase or decrease. And also we need to evaluate the functions of kidneys and liver by using biochemical tests "blood urea, serum critinine, alkaline phosphatase, total serum bilirubin and direct, indirect bilirubin".

Imaging Study

Ultrasound: We use the U/S to confirm the diagnosis of Lymphadenopathy and describe its content and site, size, texture and relation with the surrounding tissue.

C.T. scan and M.R.I

Important in the identification of the deep lymph node and identify other mass may be the cause of Lymph node enlargement and we can demonstrate the state of other intra-abdominal organs if there is enlargement or metastasis.

Cytology and Histopathology

Fine Needle Aspiration Cytology (F.N.A.): F.N.A. cytology allows the pathologist to see the cells aspirated from the lesion and done by hand of expert pathologist.

Technique

Fine-Needle Aspiration (FNA) is a simple office procedure that requires a few minutes to complete. It is ideal to have the cytotechnologist and pathologist available at the time of the aspiration. This allows an immediate assessment of the adequacy of the specimen. If insufficient cells have been obtained, the aspirate can be repeated. Sometimes the diagnosis can be made immediately. 

The skin that overlies the mass is prepared with a prepackaged, sterile, alcohol preparation sponge that contains 70% isopropyl alcohol. For right-handed surgeons, the mass is grasped with the left hand and held in a fixed and stable position. 

A 10-mL disposable syringe with an attached 23-gauge needle is placed just under the skin surface. Negative suction is applied to the syringe. The negative pressure is created and maintained by pulling the syringe plunger back. The mass is entered and multiple passes are made without exiting the skin surface.

Approximately 6 passes through the mass are recommended. If a cyst is encountered, it should be completely evacuated, with fluid and capsules sent for cytology. Recall that the cyst fluid may "dilute" the specimen and make cytologic interpretation impossible. Accordingly, aspirating the solid portions of the mass is ideal. The vacuum on the syringe is then released and the skin is exited. 

Histopathology

We take excisional or incisional biopsy from the patients after we putting the patient in proper position in order to make the Lymph nodes obvious and under general anesthesia or local anesthesia using xylocaine 2% skin infiltration with full aseptic technic skin over the L.N. opened parallel to the skin cresses in order to avoid scar formation then opened other layers (subcutaneous layer and muscle) till reach the target node and try to excise the L.N. without crushing the node or we take apart of lymphnode (incisional biopsy) and we put drain if we need and close the wound in layers . And we put the lymph node in formalin to preserve the texture of lymph node till the lymph node reach to histopathologist.

Inclusion Criteria

• With age group from one year to 60 years old admitted to surgical word as a case of L.N. enlargement without knowing the disease that cause this enlargement

• Duration of lymph node enlargement from (2-4 weeks) from first visit if the lymph node remains in the same size or increase in the size and if there is any sign of infection we included in the study

• If there is suspicion of malignancy (hard, fixed, matted to gather lymph nodes or if there is alternation to the general condition to the patient like weight loss, anemia) in despite to the size of lymph node and duration of observation

• The size of L.N. more than 1 cm in the cervical or axillary nodes and more than 1.5 cm in the inguinal L.N

 Exclusion Criteria

• Resolving there L.N. swelling from the period from two to four weeks

• With L.N. enlargement less than 1 cm in the cervical and axillary regions and with less than 1.5 cm in the inguinal region

• Not follow the notes of senior

• Refuse the lines of management and advices from senior

• With diagnosed disease that cause L.A.P (Figure 1, 2)

Figure 1: Structured Questionnaire Used for Data Collection, Including Demographic Details, Symptom Profile, Medical and Surgical History, Medication Intake, Lymph Node Characteristics and Examination Findings

Figure 2: Clinical Assessment and Investigation Proforma Documenting Lymph Node Examination Findings, Associated Manifestations, Laboratory Investigations, Imaging Studies and Histopathological Evaluation

Statistical Analysis

Statistical analysis was performed by using chi-square test we considered tabulated chi-square 9.21 on Standard Deviation (SD)² and chi-square by using the formula:

X2 = SUM (observed-expected)²/expected

Descriptive of qualitative variables as a number or percentage.

Probability p-value: 

• p-value>0.01 was considered insignificant

• p-value<0.01 was considered significant

The Age Distribution

Total number of patients with lymphadenopathy (66) included in this study, patients age ranged from one year to sixty years old. The most common age group involve between 31-40 years (21 case 31.9%) and 41-50 years (14 case 21.3%) mean age is 35.5 and less common age group involve is 21-30 years only three cases 4.5% as shown in the Table 1.

Geographic and Sex Distribution

The most common patients with lymphadenopathy came from rural area (50 cases 75.8 %) with rural to urban ratio 3:1 and In this study male patients more than female patients (male 38 cases 57.6%) while female patients (28 cases) 24.2% and ratio Male : Female, 1.35:1 as shown in Table 2,3 and Figure 3.

Family and Travellar History

In the current study we found (61 cases) 92.4 % have no family history of enlarge lymph nodes while only (6 cases) 7.6 % associated with family history and only (3 case) 4.5% have history to traveller to other countries and (63 cases) 95.5% have no history to travel as shown in Table 4,5.

Associated Symptoms and Lymphadenopathy

Most patient in current study associated with other symptoms. There are (49 cases) 74.2% presented with other symptoms such as fever, anemia, weight loss and other symptoms and (17 cases) 25.8 %, the ratio between other symptom presented with L.A.P. or not about 3:1.

Table 1: Age Distribution of the Patients with Lymphadenopathy

Table 2: The Geographic Distribution of Patients with Lymphadenopathy

Table 3: The Distribution of Patients with Lymphadenopathy According to Gender

This symptoms distributed between fever, swelling, weight loss and most common associated symptoms is presented swelling (40 cases) 31.2% and fever (31 cases) 24.3% and we found jaundice less common symptoms present (6 cases) 4.6% and also we found patients with anemia (13 cases) 10.2% and weight loss (10 cases) 7.8% and night sweat (9 cases) 7.1%, also we found there are many patients presented with more than one symptoms like fever with anemia or fever with malaise and anemia with weight loss or with jaundice and swelling with fever etc (Table 6,7 and Figure 4,5).

The Anatomical Site of Lymph Nodes

The lymph nodes swelling either localized or generalized, the most anatomical site involve in current study is cervical region (29 cases) 43.9 % then the axillary region (20 cases) 30.3% while generalized lymphadenopathy (11 cases) 16.7% and less area involve in this study is inguinal region (two cases) 3% as shown in Table 8, Figure 6.

FNA Cytology 

We send all patients in current study to do FNA cytology study and the results was being most of the patient’s benign condition (43 cases) 65.2% and the second group of patients was malignant conditions (17 cases) 25.8% and there is six cases found suspicious (about 9%). then we give treatment for benign cases only (10 cases) respond to medical treatment and 33 cases not respond to medical treatment. when we use chi-square for illustrated the significance we found the calculated X2 = 22.495 and tabulated X2 = 9.21 on degree of freedom = 2 and this show the calculated X2 >tabulated X2 and this mean there is a difference between calculated and tabulated X2 and the p-value<0.01, SO FNA cytology significant in diagnosis of conditions of lymphadenopathy (Table 9, Figure 7).

Figure 3: Geographic Distribution in Patient with Lymphadenopathy

Table 4: Family History of Patients with Lymphadenopathy

Table 5: Traveller History of Lymphadenopathic Patients 

Figure 4: Correlation Between Associated Symptoms and Lymphadenopathy

Figure 5: Associated Symptoms in Patients with Lymphadenopathy

Figure 6: The Anatomical Site of Enlarged Lymphnode

Excisional Biopsy Results

We do excisional biopsy to confirm the diagnosis to the benign condition in FNA results but not respond to treatment we found there are 3 cases 9.1% malignant conditions and 30 cases 90.9 % benign condition, When we do excisional biopsy to the suspicious and malignant results with FNA cytology found that the suspicious condition 6 cases divided in to one case 16.7% benign condition and other (5 cases) 83.3% malignant condition and in the malignant state in FNA cytology biopsy found that one case benign and 16 cases 94.1% malignant . and when we use chi-square test for illustrated for the significance of excisional biopsy for the diagnosis of diseases. we found calculated X2 = 29.14 and tabulated X2 = 9.21 on the degree of freedom 2 and we notice that calculated X2 >tabulated X2 and this mean there is a difference between calculated and tabulated X2 and the p-value<0.01. 

Figure 7: F.N.A. Cytology Results

Table 6: Correlation Between Associated Symptoms and Patients with Lymphadenopathy

Table 7: Distribution of Associated Symptoms to the Patients Presented with L.A.P

Table 8: The Anatomical Site of Lymphadenopathy

Table 9: Results of FNA Cytology

SO excisional biopsy significant in diagnosis of conditions of lymphadenopathy. And because the calculated X2 for excisional biopsy more than calculated X2 for FNAC, so the excisional biopsy best in the diagnosis of diseases than FNA cytology (Table 10, Figure 8).

Histopathological Results of Excisional Biopsy

In excisional biopsy done to the patients (56 cases) we found the most common patients with reactive hyperplasia (13 cases 23.2%) and second most common conditions is acute lymphadenitis (10 cases) 17.8%, T.B. lymphadenitis (9 cases) 16% and for malignant conditions we found the non-Hodgkin lymphoma (8 cases) 14.3% then secondary metastasis (7 cases) 12.5% then Hodgkin lymphoma (6 cases) 10.7% and less common patients with leukemia (3 cases 5.5%) as shown in Table 11, Figure 9.

Figure 8: The Excisional Biopsy Results

Figure 9: Excisional Biopsy Results

Figure 10: Benign Conditions in Patients with Lymphadenopathy

Table 10:   The Histopathological Results in Excisional Biopsy to the Suspicious and Malignant and Benign (Not Respond to Treatment) Conditions in FNA Cytology

Table 11: The Histopathological Results of Excisional Biopsy

In this study and from FNA cytology and excisional biopsy we found 42 patients with benign conditions and most patient with reactive hyperplasia (17 cases 40.5%) and patients in with acute lymphadenitis (13 cases) 30.9% and patients with T.B. lymphadenitis (12 cases 28.6%) (Table 12, Figure 10).

The Primary Origin of Lymph Nodes Metastasis

In this study found 7 cases secondary metastasis to the lymph node and when we follow up with patients to search the primary origin of cancer we found the most common origin is breast (3 cases 42.9 %) and stomach carcinoma (2 cases 28.7%) and we don't find the origin (unknown origin) for one case 14.2% as shown in Table 13.

Table 12: Benign (Non Malignant) Condition Patients with Lymphadenopathy 

Table 13:   The Primary Origin of Cancer to the Secondary Metastasis Lymphadenopathy

In this review of 66 patients with lymphadenopathy we do to them FNA cytology and excisional biopsy. in this study the main age group involved with lymphadenopathy 31 years–40 year with number of patients 21 (31.9%) and this agree with kais sabri 1998 which conclude that the main age group is middle age groups (14 cases).

And disagree with Adeswa noma olu eddo, Caroline Edijana [2,3], which conclude that the main age group (16 years–30 year) because in our study most patients visit us to surgical outpatient clinic complaining of enlarge lymph nodes from 31 years-40 years [4]. 

And in this study the patients came from rural areas more than those came from urban 50 case 75.8% and this agree with kais sabi 1998 that conclude the patients come from rural areas more common than urban 35 cases came from rural areas [5]. 

In current study we conclude the male gender is predominant 38 cases 57.6% and this agree with Adeswa noma olu eddo, Caroline Edijana which conclude male gender is predominant 48 case 60% and Male : Female ratio 1.5:1 [6].

In this study there is (61 cases) 92.4% have no family history of lymphadenopathy and this agree with adeswa noma olu eddo, Caroline Edijana where there are (254 cases) 71.2 % have no family history of disease [7,8].

In current study there is (49 cases) 74.2% presented with associated symptoms and this agree with Kais Sabri 1998 which concluded that there are (36 cases) 72.4% presented with associated symptoms [9,10].

In this study we found many patients with clinical presentations the most common presenting symptoms is swelling (40 cases) 31.2% and the second most common symptoms is fever (31 cases) 24.3% and this agree with kais Sabri which conclude the most common symptom is swelling ( 35 cases ) 70% and the second most common presenting symptoms is fever (6 cases) 12% and also agree with Maria Christine, Robert Dennis which conclude that the most common clinical presentation is mass or swelling (18 case) 82% and the second most common clinical presentation is fever (5 cases) 23% and in this study the less common clinical presentation concluded is jaundice (6 cases) 4.6 % which dis agree with study which concluded that the less common presenting symptoms is pruritis, hoarseness of voice and dysphagia (one case) to each symptom 2% to each because of our study deals with most groups of lymph nodes in the body while deals with only cervical lymph nodes and Disagree with Maria Christine , Robert Dennis which concluded that less common presenting symptoms is abdominal pain and coldness (one case) to each because of in our study involve all age groups while Maria Christine, Robert Dennis deals with child hood age groups [11,12].

In current study we found that the cervical region the most common anatomical site of enlarged lymph node (29 cases) 43.9% and this agree with Esam Abbas [13], which conclude the most common anatomical region for lymph node enlargement is cervical region (61 cases) 42.6% and also agree with Maria Christine, Robert Dennis which conclude that the cervical region is most common region (17 cases) 78% and in this study the second most common site of lymphadenopathy is axillary region (20 cases) 30.3% and this agree with Sumyra Khurshide Qadri Khurshide Qadri et al. which (248 case) 15.7% [14].

And in current study the less common site of lymph nodes enlargement is inguinal region (2 cases) 3% and this agree with kirti M Rathod, Smita A Shah [15], which conclude that the less anatomical region presenting with lymphadenopathy is inguinal region (8 cases) 5.7% and disagree with Maria Christine, Robert Dennis which conclude that the axillary and supraclavicular region is less common anatomical site than inguinal region (one case) to each 4% while the inguinal region (3 cases)14% because in our study we deal's with all age groups while in study of Maria Christine, Robert Dennis deal with childhood age groups [16].

In current study when we do FNA cytology we found the benign common condition is malignant condition (17 cases) 25.8% and suspicious condition (6 cases) 9% and this disagree with which concluded that the most common condition is malignant condition (24 case) 48% and benign (23 cases) 46% with suspicious condition (3 cases) 6% because the study of Kais Sabri done in Bagdad teaching hospital which is specialized center and include center of oncology so most patient with malignant condition visit this center in order to complete their management and this explain the raise in malignant condition in Kais Sabri study [17]. 

And when we do excisional biopsy to FNA benign condition (33 cases) which is not respond to treatment and (6 cases) FNA cytology suspicious and (17 cases) FNA cytology malignant we found that benign conditions more common (32 cases) and malignant condition (24 case) and this disagree with which have (29 cases) malignant and (21 cases) benign depending on excisional biopsy because the study of Kais Sabri done in Bagdad teaching hospital which is specialized center and include center of oncology so most patient with malignant condition visit this center in order to complete their management and this explain the raise in malignant condition in Kais Sabri study [18,19]. 

In current study the histopathological results of excisional biopsy done to the patients with lymphadenopathy conclude that the most common patient with (non-specific) reactive hyperplasia (13 cases) 23.3% and this agree with Essam Abbas [13], which conclude that the patient with reactive hyperplasia is most common (45 cases) and disagree with adeswa noma olu eddo, Caroline Edijana [3], that conclude the most common patient presented with T.B. lymphadenitis (125 cases) 35% because of T.B. is not an endemic in our community . and the second most common finding is acute lymph adenitis (10 cases) 17.8% and this disagree with Essam Abbas [13], which conclude that the second most common finding is T.B. lymphadenitis (34 cases) because of the economic blockade on our country at that time (1995) which reduce the income to the citizens and this will reflect on the general health of the peoples and poor hygiene to the peoples and this lead to increase the incidence of some diseases like T.B [20]. 

And disagree with adeswa noma olu eddo, Caroline Edijana [3], that conclude the second most common cause is non-specific reactive hyperplasia 56 cases 15.6% because of non–specific reactive hyperplasia is endemic in Nigeria where Adesuwa Noma Ola, Carolina Edijana 2011 established them study and less common result in current study is leukemia 3 cases 5.5% and this agree with Essam Abbas [13], that concluded the leukemia is less common finding (4 cases) [21].

In this study we found the histopathological results regarding to malignant changes the most common is non-hodgkin lymphoma (8 cases) 14.3% then secondary metastasis (7 cases) 12.5% then Hodgkin lymphoma (6 cases ) 10.7% then leukemia (3 cases) 5.5% and this agree to the study Essam Abbas [13], that conclude the most common is non-Hodgkin (26 cases) 38.8% then secondary metastasis (25 cases ) 37.3% then Hodgkin lymphoma (12 cases) 19.4% and less common leukemia (4 cases ) 4.5 % and the current study disagree with adeswa noma olu eddo, Caroline Edijana [3] that conclude the most common malignant in histopathological study is secondary metastasis (80 cases) 22.4% then non-hogkins lymphoma (56 cases) 15.7% then hogkins lymphoma (37 cases)10.4% and this because of lymphoma is common disease in our country and early diagnosis of primary cancer and treat the primary cause reduce the incidence of secondary metastasis to lymph nodes [22,23]. 

In this study we search about primary origin of secondary metastasis to lymph nodes we found the most common is breast carcinoma (3 cases) 42.9% then the carcinoma of stomach is second most common (2 cases) 28.7% and disagree with which conclude that the most common primary site is lung , stomach and intestine (3 cases) 23.08% to each then second most common site is breast (2 cases) 15.4% and this occur because the breast cancer is common problem in our hospital while the patients with carcinoma of the lung go to specialized center for this condition [24,25].

• The key factors considered when evaluating a patient with lymphadenopathy include the age of the patient, location of lymphadenopathy and associated symptoms

• Lymphadenopathy a serious condition because we found significant number of cases malignant 

• A significant lymph node is more than 1.5 cm in size

• Lymphadenopathy may be the first (and sometimes) the only presentation of underlying disease

• Most common type of malignancy in patients with lymphadenopathy is lymphomas 

• We should not depend on clinical examination only to diagnose lymph node and we should depend on other diagnostic modalities such as ultra sound and C.T. scan

• FNA cytology is useful triage for the rapid and definitive diagnosis of tuberculosis but may miss malignancy

• In patients with lymphadenopathy and associated with symptoms such as unexplained fever and weight loss which give us suspicion of underlying malignancy the excisional biopsy is gold standard to reach to definitive diagnosis

Recommendation

• We recommend to do excisional biopsy as soon as possible to patients with highly suspicion of malignancy (don't wait 4-6 weeks) in order to early reach to diagnosis and early management of malignancy if present

• We recommend to open postgraduate studies in histopathology (MD., PHD. Degrees) in order to increase the number of histopathologist and reduce the shortage of this branch in the hospitals

• We recommend to open specialized centers of histopathology and FNA cytology in the hospitals and increase the number of workers in this field and increase their skills and experience by making workshops and clinical sections, meeting and conferences and this will reflect positively on the time required the results to appear and the accuracy of the results

• We recommend to open a histological subsidiary in the operation theaters in order to do frozen section histology and give the surgeon the diagnosis within minutes (intra operative) to help the surgeon to making diagnosis and make decision intra operatively and making definitive management with in one suction 

• we recommend to increase health education to peoples about the lymph nodes and their importance and the disease affected lymph nodes and the importance of visiting physicians when there is swelling in this nodes.

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