IPSO Practice Guidelines on Manangement of Lymph Node Enlargement in Children

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IPSO Practice Guidelines on Manangement of Lymph Node Enlargement in Children

Authors:
Ahmed Elgendy, Hafeez Abdelhafeez, Simone Abib

Disclaimer: The document, IPSO Practice Guidelines, and the information it contains are for authorized use by surgeons. IPSO cannot accept any liability and responsibility for any claims, loss or damage arising from the use of this document and its contents.
Version dated on 7 June 2020

Preoperative: evaluation, images, special needs, and biopsy need?

Lymphadenopathy is a condition in which lymph nodes are abnormal in size and consistency. The neck is the most common peripheral site of enlarged lymph nodes. A lymph node is considered enlarged if it is more than 1 cm in diameter if cervical or axillary, and more than 1.5 cm in diameter if inguinal. Peripheral lymphadenopathy is common in children and adolescents, and approximately 38–45% of healthy children have enlarged lymph nodes [1]. Conditions such as infections, reactive hyperplasia, autoimmune diseases, chronic inflammatory diseases, and malignancies are associated with lymph node enlargement.

The most common cause of cervical lymphadenopathy is viral upper respiratory tract infection. Differential viral etiologies also include Epstein–Barr virus (EBV) and cytomegalovirus (CMV). Group A beta-hemolytic streptococci and Staphylococcus aureus are the most common causes of bacterial cervical lymphadenitis in children. In addition, anaerobic bacteria from dental caries and periodontal disease are bacterial causes of lymphadenopathy. Therefore, evaluating the condition of teeth should always be part of the physical examination of children with enlarged lymph nodes on the neck. Cat scratch disease caused by Bartonella henselae can also cause lymphadenopathy, and thus the patient’s history should be studied for contact with cats. Atypical mycobacteria and Mycobacterium tuberculosis are important causes of subacute or chronic cervical lymphadenopathy. Immunocompromised patients should be tested for fungal infections. Parasitic infections, such as toxoplasmosis, can also cause lymphadenopathy. Paracoccidiomicosis and other infections that are typical in some countries should be investigated, depending on the patient’s country of origin. Furthermore, immunological diseases can cause lymph node enlargement (rheumatoid arthritis, mixed connective tissue disease, Sjögren syndrome, graft-versus-host disease). Other rarer conditions, such as lipid storage diseases, endocrine diseases, and Kawasaki disease, can also be a differential diagnosis.

Benign cervical masses such as dermoid and thyroglossal cysts in the midline, salivary gland enlargement, branchial cyst, and congenital torticollis are other differential diagnoses to be considered. Hodgkin lymphoma, non-Hodgkin lymphoma, neuroblastoma, leukemia, rhabdomyosarcoma, and metastatic diseases are the most frequent neoplasms associated with cervical lymph node enlargement. Therefore, pediatricians and pediatric surgeons need to rule out malignancy. A detailed history and careful physical examination are imperative steps in the initial evaluation of children presenting with peripheral lymphadenopathy.

Important information that needs to be included in the history are age, location, and duration of lymph node enlargement and its evolution (e.g., stable in size, growing, changing characteristics); associated symptoms (e.g., cough, pain, tenderness, fever, night sweats, weight loss); and association of upper respiratory tract infection, contact with cats, family history of tuberculosis (TB), and human immunodeficiency virus (HIV) status.

Physical examination should include the overall state of health (e.g., healthy, malnutrition, poor growth), location of lymph nodes (e.g., posterior cervical, supraclavicular, axilla, groin), characteristics of lymph nodes (e.g., tenderness, erythema, warmth, mobility, fluctuance, consistency, coalescence), presence of lymphadenopathy in other lymphatic chains outside the neck, hepatomegaly, and splenomegal. Certain nodes can be treated without being investigated. Obvious bacterial infections or reactions to infections within the drainage area need to be treated and followed up until resolution.

Furthermore, certain laboratory investigations should be conducted in case of general or specific clinical manifestations to exclude the presence of infectious etiology. Complete blood picture in addition to serological tests such as EBV, CMV, HIV, tuberculin skin tests, bartonella, and toxoplasmosis should be performed for suspected patients. Imaging studies are recommended in children with lymphadenopathy who present with progressively enlarging, firm, fixed nodes or with associated systemic features. Mediastinal involvement should be screened initially with a chest radiograph. Ultrasound is the preferred initial modality because of its real-time assessment without the need for general anesthesia. Moreover, it does not expose patients to ionizing radiation. Ultrasound gives data on the size, shape, and architecture for distinguishing benign from malignant nodes. In selected cases, computed tomography or magnetic resonance imaging can be used to gain further information. Ultrasound elastography can also be used as an adjunct tool for sonographic findings, which can improve the accuracy of predicting malignant lymph nodes [2]. Thick cortex with loss of fatty hilum, central necrosis, and a heterogeneous echo pattern with hyperechoic foci are suspicious characteristics in imaging modalities.

Fine needle aspiration cytology (FNAC) may be an option for pathological diagnosis in the pediatric population, as it is a minimally invasive procedure. Older children may be cooperative, and the use of topical anesthetic creams aids the procedure. Suitable conditions to perform fine needle aspiration biopsy at established facilities can facilitate the process and be a more efficient way of diagnosing the cause of lymphadenopathy and avoiding the need for theater time and a general anesthetic. However, when performing FNAC, several limitations can be encountered, such as insufficient material for examination, false-negative results, and the need for an experienced pediatric pathologist and sedation or general anesthesia in some patients. These factors suggest that relying on FNAC alone is inconclusive [5]. If FNAC gives a clear and precise diagnosis, the patients are treated accordingly, but if patients have equivocal, “reactive,” or indeterminate results, they need to undergo an open biopsy. Eventually, open biopsy remains the standard and precise procedure to obtain a tissue diagnosis of lymphadenopathy in children.

Surgical goals

If the primary diagnostic work-up cannot identify the valid cause of peripheral lymphadenopathy, a definitive histopathological diagnosis is required. Children who present with persistent enlarged lymph nodes for more than 4 weeks despite being administered empirical antibiotics should be prepared to undergo a surgical biopsy [3]. The possibility of malignancies usually drives surgeons to make this decision, and predictors include long duration (no decrease in size in 4–6 weeks or no resolution in 8–12 weeks), multiple levels of lymphadenopathy, supraclavicular location, hard or fixed nodes, increase in size over 2 weeks, suspicious radiological signs, and increased nodal size (>2 cm) [4]. Concomitant clinical manifestations such as weight loss, organomegaly, persistent or unexplained fever and night sweats, in addition to older age of patients (>10 years) should be added to the aforementioned criteria for nodal biopsy. Sometimes, the surgeon’s role is to only drain the cervical abscess.

Pitfalls

  1. Preoperative evaluation of mediastinum enlargement should be performed before a child is given general anesthesia, due to the risk of ventilation problems and death during induction, when there is a significative mediastinum mass. In this situation, the surgeon should look for peripheral lymph nodes that can be biopsied under local anesthesia or pleural effusion, so that a thoracocentesis diagnosis can be made. If there are no peripheral lymph nodes to biopsy, the anesthesiologist should be aware of the risks and do whatever possible to prevent complications.
  2. Sometimes, more than one biopsy may be needed to diagnose Hodgkin lymphoma. To avoid that situation, the surgeon should ensure that a representative lymph node is biopsied. If the diagnosis is “reactive” or inconclusive on the open biopsy, the patient should be followed up until the case is resolved or it is further investigated.
  3. It is important to note that patients from countries where TB and HIV are prevalent may have concurrent different diagnoses.

Surgery

Open excisional biopsy is the procedure of choice to obtain adequate tissue samples for histopathological assessment. The largest node, decided by clinical examination and preoperative imaging, should be removed completely with an intact capsule for a precise pathological result.

Complications

Surgical biopsy is often a safe procedure; however, some complications such as bleeding, hematoma formation, nerve injuries (spinal accessory or marginal mandibular), infection, and risks associated with general anesthesia may occur.

Conclusions

  • Enlargement of peripheral lymph nodes is a very common finding in children and adolescents.
  • Predictive factors should be correlated by careful analysis of history, examinations, and radiological findings to make a decision about biopsy.
  • Open surgical biopsy is the cornerstone of diagnosing pediatric lymphadenopathy with an equivocal etiology, as the accuracy of results using FNAC still remains unclear.

References

  1. Niedzielska G, Kotowski M, Niedzielski A, et al. Cervical lymphadenopathy in children: incidence and diagnostic management. Int J Pediatr Otorhinolaryngol. 2007; 71: 51-56.
  2. Zakaria OM, Mousa A, AlSadhan R, et al. Reliability of sonoelastography in predicting pediatric cervical lymph node malignancy. Pediatr Surg Int. 2018; 34(8):885-890.
  3. Celenk F, Baysal E, Aytac I, et al. Incidence and predictors of malignancy in children with persistent cervical lymphadenopathy. Int J Pediatr Otorhinolaryngol. 2013; 77(12):2004-7.
  4. Nolder AR. Paediatric cervical lymphadenopathy: when to biopsy? Curr Opin Otolaryngol Head Neck Surg. 2013; 21(6):567-70.
  5. Locke R, Comfort R, Kubba H. When does an enlarged cervical lymph node in a child need excision? A systematic review. Int J Pediatr Otorhinolaryngol. 2014; 78(3):393-401.
  6. Rajasekaran K, Krakovitz P. Enlarged neck lymph nodes in children. Pediatr Clin N Am 2013; 60:923–936.
  7. Robert Kliegman Joseph St. Geme. Nelson Textbook of Pediatrics, 21st Edition. Robert M. Kliegman, Bonita F. Stanton, Joseph W. St. Geme, Nina F. Schor, and Richard E. Behrman. Chapter 484, 1724-1724.e6. Elsevier. 19th April 2019.