The Increasing Phenomena of Cervical Lymphadenopathy and Relations to Malignant and Chronic Diseases in Assiut and sohag populations.
Abstract
Background and aim: Cervical lymphadenopathy is one of the commonest presentations in inflammatory and neoplastic disorders. The aim is To determine the common causes of persistent cervical lymphadenopathy and Relations to Malignant and Chronic Diseases and to test a diagnostic approach. Patients and methods: This study was conducted at surgical departments in both AL -Azhar University, Assiut branch and Sohag unversity hospital, over 2 years period (February,2013 – January, 2015) to 146 patients [ 84 male (58%) and 62 female (52%)] between ages of 7 months and79 years with persistent lymph node enlargement. Persistent enlargement is defined as a lymph node > 1 cm in diameter, and > 2 weeks duration. The patients were divided into two groups, Group I, included the benign conditions and group II the malignant conditions. Case history, clinical signs, laboratory tests, imaging, treatment and clinical course were done . Results: this study were conducted on 146 patients [ 84 male (58%) and 62 female (52%)]. Group I, the benign conditions were 48 patients, while group II the malignant cases were 98 patients. Group I showed that (10.82%) of them were acute lymphadenitis, (14.58%) tubercular lymphadenitis: Tubercular lymphadenopathy was found with increasing frequency through adolescence (43.30%) to young adulthood (54.75%) & (48.18%) in adulthood. 10 children (20.38%) had lymph node abscess; 2 children (4.66%) had Epstein Barr virus infection, (45.83%) were hyperplasic lymph nodes. (2.02%) were secondary to moniliasis. While in the malignant Group, (71.42%) were Lymphoma and (2.04%) were Leukemic Lymphadenopathy.(2.04%) secondary to thyroid malignancy. Highest incidence of metastatic malignancy was seen in the fifth decade (8.4%). (12%) cases of metastatic tumours were in the age group of 31- 60 yrs., Conclusion: Both Persisting lymph nodes more than 4 weeks warrant acute cervical lymphadenopathy and Tuberculosis were a common cause of cervical lymphadenopathy.in pediatric and adolescent groups, metastatic and malignancies are noted from fourths to sixs decades.
Keywords: Cervical Lymphadenopathy, Lymphadenitis, Lymphadenopathy, Lymph node, Acute cervical lymphadenitis
Introduction
Peripheral lymphadenopathy is a common condition in the clinical practice of both the surgeons and physicians including the paediatricians. Easy accessibility of acquiring a sample for cytological or histological examination has made it an important component of practices of the pathologists as well. Even though, Fine needle aspiration cytology (FNAC) has been introduced in the laboratory diagnostics since last two or three decades (Handa et al., 2012). There are still many situation, where excision biopsies is mandatory, especially in suspected cases of lymphoproliferative disorders. Recent literature also cites a study on the role of ultrasound (US) guided core biopsy in the diagnosis and typing of lymphoma in the head and neck region (Burke et al., 2011).
Lymphadenopathy refers to any disease process involving lymph nodes that are abnormal in size and consistency. This condition has multiple etiologies, the most common of which are infection, neoplasia, and autoimmune diseases. Histological examination and surgical consultation are, however, often required to assist in the diagnosis and treatment of patients who do not respond to initial therapy or in whom there is an index of suspicion for a neoplastic process (Rajasekaran and Krakovitz, 2013). Despite the frequency of the problem in children, few original studies on the issue are recent. Most of the studies were conducted to define the causative agents.
lymphadenopathy is the most common cause of swelling in the neck and is one of the commonest presentations in inflammatory and neoplastic disorders. Etiological diagnosis of enlarged lymph nodes is of importance to the clinician as well as to the patients. FNAC has been successfully adopted as a special technique to diagnose the cause of lymphadenopathy and the method is now being adopted as a routine in most of the centres. Diagnosis is a simple, quick, inexpensive and is equally reliable procedure which can be used for diagnosis of lymphadenopathy. The human lymph nodes are susceptible to pathologic and physiologic changes and can, very commonly, be the first hallmarks of a disease. Palpable lymphadenopathy is a very common finding in any age group and can be observed in 38-45% of the population (Rajasekaran and Krakovitz, 2013). In the recent literature, there are a number of publications from all over the world on lymph node pathology, in the form of reviews, original articles and case reports and a literature review on enlarged neck lymph nodes (Burke et al., 2011).
Patients and methods
This study was conducted at surgical departments in both AL -Azhar University hospital Assiut branch and Sohag hospitals, over two year period ( February,2013 – January, 2015 ) to 146 patients [ 84 male (58%) and 62 female ( 52%) ] between ages of 7 months and79 years with persistent lymph node enlargement. After taking concent from the patient or his relative .
The criteria for significant cervical lymphadenopathy in the study were lymph nodes in the cervical region >1 cm, matted or fixed lymph nodes, lymph nodes that were hard and rubbery on palpation, lymph nodes with a discharging sinus and two weeks or more duration . A detailed history was obtained and a thorough general physical examination and systemic examination carried out in all cases. All cases of cervical lymph nodes were confirmed histopathologically
The patients were divided into two groups, Group I, included the benign conditions and group II the malignant conditions.
The medical records, pathologic results, and imaging findings were reviewed. A database of 6 variables regarding sex, age, fever, number of involved regions, and location and size of the largest node was constructed. For the variable, size of node, 3 parameters including ML, maximal width (MW), and the ratio of MW to ML (Ratio) were recorded. A lymph node’s MW was measured at right angles to its longest length ( Fig:1 )
Figure1: Ultrasound showing picture of enlarged cervical Lymph node
Three parameters including ML, maximal width (MW), and the ratio of MW to ML (Ratio) were recorded. A lymph node’s MW was measured at right angles to its longest length
Consideration of whether symptoms and presentation are acute, subacute, or chronic is often helpful in establishing a differential diagnosis. Clearly, the definitions of these categories are arbitrary, and many infectious processes are associated with symptom duration that fits into more than one category.
In general, however, acute lymphadenitis, which can be 2 weeks in duration, is due to either a viral or bacterial invasion. Chronic lymphadenopathy is more likely to be due to a neoplastic process or invasion by an opportunistic organism. Sub acute lymphadenitis, which is 2 and 6 weeks in duration, encompasses a much broader group of potential etiologies. Most of these patients improve during a course of antibiotic therapy prescribed by their primary care physician.
Other important clinical information to obtain are the location (single or multiple sites) and progress of neck swelling (increasing, stable, or decreasing) and the presence of systemic symptoms (eg, fever, malaise, anorexia, weight loss, or arthralgia’s). More specific symptoms include skin changes and pain in the region of the nodal swelling, as well as at more distant sites. A history of recent upper respiratory tract symptoms, sore throat, ear pain, toothache, insect bites, superficial lacerations or rashes, and exposure to animals may suggest possible etiologies. In addition, a history of recent travel, exposure to individuals that are ill, and immunization status should be sought. Finally, patient age is another important consideration, since lymphadenopathy in young children is overwhelmingly due to infectious etiologies, whereas adenopathy due to neoplasia increases in the adolescent age group.
Laboratory tests are not commonly required as part of the workup for acute cervical lymphadenitis. Leukocyte counts and markers of inflammation (C-reactive protein and erythrocyte sedimentation rate) are usually abnormal but nonspecific. Although a left shift (i.e., increased percentage of immature white cells) on the leukocyte differential count suggests a bacterial etiology, this etiology frequently is suggested by the clinical presentation alone. Any material that has been aspirated due to fluctuance should be sent for culture and sensitivity. These cultures may show an organism that is resistant to prior antibiotic therapy, but occasionally they are negative due to eradication of the infectious agent by a prior course of antibiotics. Blood cultures should be obtained in any patient that appears toxic. Cultures of other sites that appear to be the primary site of the infection (eg, pharynx) should also be obtained, although results from pharyngeal cultures may not correlate with organisms isolated from a nodal abscess Immaging are somewhat necessary in patients with acute cervical lymphadenitis, but may occasionally document the primary site of an infection (eg, pneumonia, sinusitis, or dental caries). Plain radiographs are more valuable in the child with chronic or generalized adenopathy.
Plain radiographs of the chest may suggest involvement of mediastinal lymph nodes or the lungs and are indicated in all patients with respiratory symptoms. Chest radiographs with two views should also be obtained in any patient with either symptomatic or asymptomatic cervical adenopathy.
Ultrasonography (US) is the most frequently obtained and the most useful diagnostic imaging study. High-resolution US is used to assess nodal morphology, longitudinal
and transverse diameter, and internal architecture. One potential drawback of US, however, is its lack of absolute specificity and sensitivity in ruling out neoplastic processes as the cause of nodal enlargement.Nuclear medicine scanning is helpful in the evaluation of lymphomas.
Despite the potential benefits of FNAB, open biopsy remains the gold standard for histologic diagnosis of cervical lymphadenopathy in the pediatric population.1 When open biopsy is indicated, the largest node should be completely excised, with the capsule intact to preserve tissue architecture
Results
Our study included 146 cases, was conducted at surgical departments in both AL -Azhar University hospital, Assiut branch and Sohag hospitals, over two year period ( February,2013 – January, 2015 ) to 146 patients [ 84 male (58%) and 62 female ( 52%) ] between ages of 7 months and79 years with persistent lymph node enlargement. All had persistent lymph node enlargement based on our previous definition Age and sex distribution is shown in Table 1
Table 1
Age group (years) Male cases Female cases Total Percentage
0.7 – 10 11 9 20 13.69%
11 – 20 12 10 22 15.06%
21 – 30 11 8 19 13.01%
31 -40 14 10 24 16.43%
41 -50 14 9 23 15.75%
51-60 12 8 20 13.69%
61 – 70 7 5 12 18.21%
71 -79 4 3 7 4.79%
Total 84 (58%) 62 ( 52 %) 146
Table 1 : Showing age and sex distributions of all cases.
This study were conducted on 146 patients [ 84 male (58%) and 62 female (52%)]. Group I, the benign conditions were 48 patients, while group II the malignant cases were 98 patients. Group I showed that (10.82%) of them were acute lymphadenitis, (14.58%) tubercular lymphadenitis: Tubercular lymphadenopathy was found with increasing frequency through adolescence (43.30%) to young adulthood (54.75%) & (48.18%) in adulthood. 10 children (20.38%) had lymph node abscess; 2 children (4.66%) had Epstein Barr virus infection, (45.83%) were hyperplasic lymph nodes. (2.02%) were secondary to moniliasis. While in the malignant Group, (71.42%) were Lymphoma and (2.04%) were Leukemic Lymphadenopathy.(2.04%) secondary to thyroid malignancy. Highest incidence of metastatic malignancy was seen in the fifth decade (8.4%). (12%) cases of metastatic tumours were in the age group of 31- 60 yrs., ( Table 2) demonstrate Benign and Malignant pathological types in cases with cervical Lymphadenopathy.
Benign or Malignant pathologic type No. Percentage
Benign
n.=48 Tuberculosis
Lymphoproliferative disorders
Postvaccination of tuberculosis
Castleman disease
Secondary to Epstein-Barr virus
to specific infection
Nonspecific reactive hyperplasia
Secondary to Monilia
7
2
3
1
2
10
22
1
14.58%
4.66%
6.25%
2.08%
4.66%
20.83%
45.83%
2.08%
Malignant
n. 98 Hodgkin and non–Hodgkin lymphoma
Metastatic disease from solid tumor
Leukemia
Nasopharyngeal carcinoma
Thyroid cancer
Rhabdomyosarcoma
Malignant germ cell tumor
lymphohistiocytosis
70
20
2
1
2
1
1
1 71.42%
20.4%
2.04%
1.02%
2.04%
1.02%
1.02%
1.02%
Table 2: Benign and Malignant pathological types in cases with cervical Lymphadenopathy
Discussion
Cervical lymphadenopathy is a common presentation in most cases, the primary care and hospital setting. Park states that 90% of children aged 4-8 yrs have palpable cervical lymph nodes.(Pizzo et al., 2014) According to Larsson et al 38- 45% of otherwise healthy children have palpable cervical lymph nodes.(Bhargava et al. 2002)
The differential diagnosis of a persistent neck lump in children is different from adults because of increased incidence of congenital anomalies and infectious diseases and rarity of malignant disorder. In our study we excluded congenital anomalies and limited our research to persistently enlarged lymph nodes. It is widely accepted that the absence of clinical signs of inflammatory disease, negative laboratory testing and progressive reduction of size of lymph node indicate reactive hyperplasia (Fazal-I-wahid, et,Al 2013)The study indicates that reactive inflammatory changes are the commonest pathology in children as confirmed by other studies. Our observation indicates also that most cases of lymphadenopathy are self-limited and require no treatment. Failure of resolution after 4 weeks might be an indication for diagnostic histology. Most researches indicate that bilateral lymphadenopathy is more likely to be reactive in nature but our study cannot confirm that because in 58% of patients, the enlargement was unilateral.(Knight, et al., 2013 ).
Mobility, softness and tenderness are almost always associated with reactive changes, which is similar to observation by other researchers. We found that ultrasound is a valuable diagnostic tool for showing the size, shape and echotexture of lymph nodes. A homogenous echotexture, oval shape, central necrosis, blurred margins were associated with reactive hyperplasia in most cases, while a non-homogenous echotexture suggests other diagnosis. Nevertheless U/S should not be considered as a definitive mean to rule out neoplasia in patients with persistent lymphadenopathy.
The initial approach to determining the cause of cervical lymphadenopathy includes thorough history-taking and complete physical examination ( van den Brekel,et al., 2010 ) . However, if the initial investigation does not reveal the cause of cervical lymphadenopathy, the physician has difficulty in determining immediate excision biopsy or observation . Considering that enlargement of cervical lymph nodes is the first manifestation of severe systemic disease in a significant number of cases, the cervical lymph node biopsy represents an important diagnostic procedure . However, it is impossible to perform the excision biopsy for all cases of pediatric cervical lymphadenopathy. In addition, the excision biopsy may be performed under general anesthesia, which may result in complications (Qadri et al., 2012). FNAC is developing into a feasible option in diagnosing pediatric neck masses. In addition, the use of flow cytometry and immunocytochemistry has been developed over the time period studied, and now is used regularly with FNAC in the diagnosis of lymphoma ( Park, et al,. 2011 ) . The low specificity might also have reflected the somewhat small sample size. In our study, one false negative result occurred in the diagnosis of pediatric cervical lymphadenopathy. In the false negative case, the patient was diagnosed with a reactive lymphadenopathy, which eventually proved to be a Non-Hodgkin’s lymphoma. This result may be due to sampling errors, lack of adequate material, or difficulty in distinguishing reactive cells from malignant cells (Nolder, et al., 2013) . However, the pediatricians required us to perform the excision biopsy, because the patient had symptoms, laboratory test results, and physical examination results consistent with malignant lymphoma. Therefore, joint decision-making between surgeons and pediatricians is crucial ( Munson, et al., 2008). FNAC provides clear and reliable guidance as to which further investigations should be planned. In addition, FNAC may be help to avoid an unnecessary procedure and its potential complications ( Karadeniz, et al., 2012). However, it is important to recognize that the final histopathologic results after surgical treatment may in rare cases, such as encountered in the present study, differ from the results of FNAC. If there is any suspicion of malignancy or in cases of persistent lymphadenopathy, an excision biopsy should be performed. In summary, we suggest that FNAC would decrease unnecessary biopsy for patients with benign diseases and hasten biopsy in patients likely to have malignant diseases, avoiding the delay of diagnosis and treatment. We also suggest that FNAC be used in combination with history and clinical examination for accurate diagnosis . In addition, we demonstrate the importance of joint decision-making between surgeons and pediatricians to determine the necessity of excision biopsy ( S. Anne, et al., 2008). The limiting factors of this study are the small sample size and retrospective review. Therefore, prospective study or multicenter study is needed. In the future, new flow cytometry and immunochemistry can be developed and improved the accuracy of FNAC in the diagnosis of pediatric cervical lymphadenopathy ( J. Wang, et al., 2010).
Conclusion
Cervical lymphadenopathy in Assiut and Sohage areas is largely inflammatory and infectious in etiology, especially tuberculus Lymphadenitis. Although in some patients it may be related to neoplastic disease. It is important for the surgeon to be aware of the clinical manifestations and specific etiologies of this condition, as well as the diagnostic approaches and therapeutic options currently available. Close follow-up is required to monitor the need for either additional diagnostic tests or biopsy if the patient fail to respond to appropriate initial therapy.
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