Cervical lymphadenopathy

medical lecture otolaryngology

1. Cervical lymphadenopathy

2. Lymph Nodes Anatomy Collection of lymphoid cells attached to both vascular and lymphatic systems Over 600 lymph nodes in the body

3. Anatomy Are small bean-shaped organs Each node has fibrous capsule & and has a hilum at one side. It receives many afferent vessels & gives efferent vessel from its hilum .

4. The lymph node is divided into an outer cortex and an inner medulla . Fibrous trabeculae extend from the deep surface of the capsule into the cortex to divide it into compartments. Fibrous trabeculae in the medulla are irregular & called medullary Cords . Lymphoid follicles form continuous row in the cortex and are absent in the medulla . Dr : Rabie Fahmy Zahran

5. Lymph Fluid similar in composition to blood plasma. Derived from blood plasma by filtration through capillary walls at the arterial end. As soon as the interstitial fluid enters the lymph capillaries, it is called lymph. Returning the fluid to the blood helps to maintain normal blood volume and pressure.

6. Function To provide optimal sites for the concentration of free or cell-associated antigens and recirculating lymphocytes – “sensitization of the immune response” To allow contact between B-cells, T-cells and macrophages Lymph nodes and other lymphatic organs filter the lymph to remove & destroy microorganisms and other foreign particles It returns excess interstitial fluid to the blood to maintain blood volume and blood pressure . Absorption of fat and fat-soluble vitamins from the digestive system by special lymph capillaries, called lacteals The lymph in the lacteals has a milky appearance due to its high fat content and is called chyle .

7. LYMPH NODES OF THE HEAD AND NECK CLASSIFICATION 1. Upper horizontal chain of nodes ( a) Submental (b) Submandibular (c) Parotid (d) Postauricular (e) Occipital (f) Facial

8. 2. Lateral cervical nodes. They include nodes, superficial and deep to sternocleidomastoid muscle and in the posterior triangle. (a) Superficial external jugular group (b) Deep group (i) Internal jugular chain (upper, middle and lower groups) (ii) Spinal accessory chain (iii) Transverse cervical chain

9. 3. Anterior cervical nodes (a) Anterior jugular chain (b) Juxtavisceral chain (i) Prelaryngeal (ii) Pretracheal (iii) Paratracheal

10. Submental nodes They lie on the mylohyoid muscle in the submental triangle, 2–8 in number. Afferents come from the chin, middle part of lower lip, anterior gums, anterior floor of mouth and tip of tongue . Efferents go to submandibular nodes and internal jugular chain.

11. Submandibular nodes They lie in submandibular triangle in relation to submandibular gland and facial artery. Afferents come from lateral part of the lower lip, upper lip,cheek , nasal vestibule and anterior part of nasal cavity, gums,teeth , medial canthus, soft palate, anterior pillar, anterior part of tongue, submandibular and sublingual salivary glands and floor of mouth. Efferents go to internal jugular chain.

12. Parotid nodes They lie in relation to the parotid salivary gland and are extraglandular and intraglandular . Preauricular and infraauricular nodes are part of the extraglandular group. Afferents come from the scalp, pinna, external auditory canal , face, buccal mucosa . Efferents go to internal jugular or external jugular chain . Postauricular nodes (mastoid nodes ) They lie behindthe pinna over the mastoid . Afferents come from the scalp, posterior surface of pinna and skin of mastoid. Efferents drain into infra-auricular nodes and into internal jugular chain.

13. Occipital nodes. They lie both superficial and deep to splenius capitus at the apex of the posterior triangle . Afferents come from scalp, skin of upper neck . Efferents drain into upper accessory chain of nodes . Facial nodes. They lie along facial vessels and are grouped according to their location. They are midmandibular, buccinator, infraorbital and malar (near outer canthus) nodes . Afferents come from upper and lower lids, nose, lips and cheek. Efferents drain into submandibular nodes.

14. LATERAL CERVICAL NODES Lateral Cervical Nodes a) Superficial group – it lies along external jugular vein and drains into internal jugular and transverse cervical nodes.

15. b.Deep Group It consists of three chains, the internal jugular chain spinal accessory and Transverse cervical Internal jugular chain Lymph nodes of internal jugular chain lie anterior, lateral and posterior to internal jugular vein. Upper group (jugulodigastric node) – drains oral cavity, orpharynx, nasopharynx, hypopharynx , larynx and parotid. Middle group drains hypopharynx, larynx, throid, oral cavity, oropharynx. Lower jugular group drains larynx, thyroid and cervical oesophagus.

16. Spinal accessory chain Lies along the spinal accessory nerve. Spinal accessory chain drains the scalp, skin of the neck, the nasopharynx , occipital and postauricular nodes. Efferents from this chain drain into transverse cervical chain

17. Transverse cervical chain (supraclavicular nodes) It lies horizontally, along the trasverse cervical vessels, in the lower part of the posterior triangle. The medial nodes of the group called scalene nodes . Afferents to those nodes come from the accessory chain and also infraclavicular structures, e.d . breast, lung, stomach, colon, ovary and testis.

18. Anterior Cervical Nodes Anterior Cervical Nodes They lie between the two carotids and below the level of hyoid bone and consist of two chains: (a) Anterior jugular chian - It lies along anterior jugular vein and drains the skin of anterior neck. (b) Juxtavisceral chain – It consists of prelaryngeal pretracheal and paratracheal nodes

19. (i) Prelaryngeal node (Delphian node) lies on cricothyroid membrane and drains subgottic region of larynx and pyriform sinuses. (ii) Pretracheal nodes lie in front of the trachea, and drain thyroid gland and the trachea. Efferents from these nodes go to paratracheal, lower internal jugular and anterior mediastinal nodes. (iii) Paratracheal Nodes drain the thyroid lobes, subglottic larynx, tracha and cervical oesophagus

20. AJCC(American Joint Committee on Cancer) classification Level 1 –submental+ submandibular Level 2 –upper deep cervical nodes Level 3 –middle deep cervical nodes Level 4 –lower deep cervical nodes Level 5 –spinal accessory + transverse cervical Level 6 – pretracheal , prelaryngeal , paratacheal Level 7 –upper mediastinal nodes

21. Anatomic division Deep lateral cervical group Deep cervical chain Spinal accessory chain Transverse cervical chain Anterior cervical group Pretracheal Prelaryngeal Paratracheal Submental-Submandibular group Parotid group Retropharngeal group

22. Post cervical: scalp, neck skin of arms thorax cervical and axillary nodes (lymphoma, head/neck ca)

23. What is lymphadenopathy Lymph nodes that are abnormal in size > 1cm, consistency or number Localized – one area involved Generalized – two or more non-contiguous areas

24. Why do lymph nodes enlarge? Increase in the number of benign lymphocytes and macrophages in response to antigens Infiltration of inflammatory cells in infection (lymphadenitis) In situ proliferation of malignant lymphocytes or macrophages Infiltration by metastatic malignant cells Infiltration of lymph nodes by metabolite laden macrophages (lipid storage diseases)

25. Epidemiology 0.6% annual incidence of unexplained adenopathy in the general population 10% were referred to a subspecialist and 3.2 % required a biopsy and 1.1% had a malignancy

26. When to worry? Age Characteristics of the node Location of the node Clinical setting associated with lymphadenopathy

27. Age Children/young adults – more likely to respond to minor stimuli with lymphoid hyperplasia Lymph nodes in patients less than the age of 30 are clinically benign in 80% of cases whereas in patients over the age of 50 only 40% are benign Biopsies done in patients less than 25 yrs have a incidence of malignancy of <20% vs the over-50 age group has an incidence of malignancy of 55-80%

28. Clinical examination Localized adenopathy should prompt a search for an adjacent precipitating lesion and an examination of other nodal areas to rule out generalized lymphadenopathy. In general, lymph nodes greater than 1 cm in diameter are considered to be abnormal. Supraclavicular nodes are the most worrisome for malignancy. A three- to four-week period of observation is prudent in patients with localized nodes and a benign clinical picture.

29. The body has approximately 600 lymph nodes, but only those in the submandibular, axillary or inguinal regions may normally be palpable in healthy people . 1  Lymphadenopathy refers to nodes that are abnormal in either size, consistency or number. There are various classifications of lymphadenopathy, but a simple and clinically useful system is to classify lymphadenopathy as “generalized” if lymph nodes are enlarged in two or more noncontiguous areas or “localized” if only one area is involved. 

30. First, are there localizing symptoms or signs to suggest infection or neoplasm in a specific site ? Second, are there constitutional symptoms such as fever, weight loss, fatigue or night sweats to suggest disorders such as tuberculosis, lymphoma, collagen vascular diseases, unrecognized infection or malignancy ? Third, are there epidemiologic clues such as occupational exposures, recent travel or high-risk behaviors that suggest specific disorders? Fourth , is the patient taking a medication that may cause lymphadenopathy? Some medications are known to specifically cause lymphadenopathy (e.g., phenytoin [Dilantin]), while others, such as cephalosporins, penicillins or sulfonamides, are more likely to cause a serum sickness-like syndrome with fever, arthralgias and rash in addition to lymphadenopathy

31. Characteristics of the node Nodes lasting less than 2 weeks or greater than one year with no progression of size have a low likelihood of being neoplastic – excludes low grade lymphoma Cervical nodes – up to 56% of young adults have adenopathy on clinical exam Inguinal adenopathy is common – up to 1-2 cm in size and often benign reactive nodes

32. Characteristics of the node Consistency – Hard/Firm vs Soft/Shotty; Fluctuant Mobile vs Fixed/Matted Tender vs Painless Clearly demarcated Size When to worry – 1.5-2cm in size Epitroclear nodes over 0.5cm; Inguinal over 1.5cm Duration and Rate of Growth Mobile vs fixed Symmetrical vs asymmetrical

33. Consistency Stony hard : typical of cancer usually metastatic Firm rubbery : can suggest lymphoma Soft : infection or inflammation Fluctuant : Suppurated nodes. Matting : . A group of nodes that feels connected and seems to move as a unit is said to be “matted.” Nodes that are matted can be either benign (e.g., tuberculosis, sarcoidosis or lymphogranuloma venereum ) or malignant (e.g., metastatic carcinoma or lymphomas ).

34. Pain/Tenderness When a lymph node rapidly increases in size, its capsule stretches and causes pain. Pain is usually the result of an inflammatory process or suppuration, but pain may also result from hemorrhage into the necrotic center of a malignant node. The presence or absence of tenderness does not reliably differentiate benign from malignant nodes

35. size in one series  of 213 adults with unexplained lymphadenopathy, no patient with a lymph node smaller than 1 cm 2  (1 cm × 1 cm) had cancer, while cancer was present in 8 percent of those with nodes from 1 cm 2  to 2.25 cm 2  (1 cm × 1 cm to 1.5 cm × 1.5 cm) in size, and in 38 percent of those with nodes larger than 2.25 cm 2  (1.5 cm × 1.5 cm). In children, lymph nodes larger than 2 cm in diameter (along with an abnormal chest radiograph and the absence of ear, nose and throat symptoms) were predictive of granulomatous diseases (i.e., tuberculosis, cat-scratch disease or sarcoidosis) or cancer (predominantly lymphomas).

36. Location of the node The anatomic location of localized adenopathy will sometimes be helpful in narrowing the differential diagnosis. For example, cat-scratch disease typically causes cervical or axillary adenopathy, infectious mononucleosis causes cervical adenopathy and a number of sexually transmitted diseases are associated with inguinal adenopathy  .

37. Location of the node Supraclavicular lymphadenopathy Highest risk of malignancy – estimated as 90% in patients older than 40 years vs 25% in those younger than 40 yrs Right sided node – cancer in mediastinum, lungs, esophagus Left sided node (Virchow’s) – testes, ovaries, kidneys, pancreas, stomach, gallbladder or prostate Paraumbilical node ( Sister mary Joseph’s ) Abdominal or pelvic neoplasm

38. Location helps guide differential dx • Lateral neck most common site for metastatic disease from UADT - upper neck anterior/deep to SCM • Midline neck masses likely related to thyroid, elevates with swallowing Concerning features : • any abnormality in other area of head and neck - skin/scalp/ear lesions, mucosal lesion of nasal cavity, oral cavity, pharynx, larynx • enlarging or hard mass • fixation to surrounding structures (skin, SCM, mandible) • single, asymmetric node/mass ~ > 2 cm • mass in supraclavicular fossa or parotid • neurologic abnormalities (cranial nerves) • multiple rapidly growing nodes may suggest lymphoma

39. Location of the node Epitroclear nodes Unlikely to be reactive Isolated inguinal adenopathy Less likely to be associated with malignancy

40. Generalized Lymphadenopathy Malignancy – lymphoma, leukemia, Kaposi’s sarcoma, metastases Autoimmune – SLE, RA, Sjogren’s syndrome, Still’s disease, Dermatomyositis Infectious – Brucellosis, Cat-scratch disease, CMV, HIV, EBV, Rubella, Tuberculosis, Tularemia, Typhoid Fever, Syphilis, viral hepatitis, Pharyngitis Other – Kawasaki’s disease, sarcoidosis, amyloidosis, lipid storage diseases, hyperthyroidism, necrotizing lymphadenitis, histiocytosis X, Castlemen’s disease

41. Unexplained Generalized lymphadenopathy Always requires an evaluation Start with CXR and CBC Review Medications PPD (TB test), RPR(Rapid plasma reagin , a blood test for syphilis) , Hepatitis screen, ANA, HIV No yield on above test: Biopsy from most abnormal node.

42. persistent generalized lymphadenopathy Enlargement of the lymph nodes that persists for at least three months in at least two extrainguinal sites is defined as persistent generalized lymphadenopathy and is common in patients in the early stages of HIV infection . Other causes of generalized lymphadenopathy in HIV-infected patients include Kaposi's sarcoma, cytomegalovirus infection, toxoplasmosis, tuberculosis, cryptococcosis, syphilis and lymphoma

43. Clinical Setting symptoms – fever, night sweats, weight loss, Fatigue, Pruritis Evidence of other medical conditions – connective tissue disease Young patient – mononucleosis type of syndrome

44. History Identifiable cause for the lymphadenopathy? Localizing symptoms or signs to suggest infection/neoplasm/trauma at a particular site URTI, pharyngitis, periodontal disease, conjunctivitis, insect bites, recent immunization etc Constitutional symptoms(fever , night sweats, weight loss, Fatigue, Pruritis) Epidemiological clues Occupational exposures, recent travel, high-risk behaviour Medications – serum-sickness syndrome

45. Physical Exam Full nodal examination – nodal characteristics Organomegaly Localized – examine area drained by the nodes for evidence of infection, skin lesions or tumours

46. Drugs Allopurinol Atenolol Captopril Carbamazepine Gold Hydralazine Penicillins Phenytoin Primidone Pyrimethamine Quinidine Trimethoprim/Sulfamethozole Suldinac

47. Management Identify underlying cause and treat as appropriate – confirmatory tests Generalized adenopathy – usually has identifiable cause Localized adenopathy 3-4 week observation period for resolution if not high clinical suspicion for malignancy Biopsy if risk for malignancy - excisional

48. Radiographic Investigation of the Head and Neck Masses MRI – Magnetic Resonance Imaging can clearly highlight soft tissue pathologies better than the C.T. Scan. It uses a magnetic field rather than x-rays (radiation). CT SCAN – Computed tomography is less accurate than M.R.I for the soft tissue examination, but is very useful to locate bony tumors and their dimensions and extensions. C.T with contrast is used to enhance the visibility of abnormal tissue during examination. PET (Positron Emission Tomography) and SPECT (Single Photon Emission Tomography) are useful after diagnosis to help determine the grade of a tumor or to distinguish between cancerous and dead or scar tissue. They involve injection with a radioactive tracer. Gallium scanning

49. Fine Needle Aspirate Safe Convenient, less invasive, quicker turn-around time especially beneficial for verification of lymphoid origin of the enlarged growth and in differentiating between metastatic, infectious, reactive and lymphomatous causes of lymphadenopathy. It also helps in the determination of the extent of tumor; detection of recurrence; monitoring of the course of disease; obtaining of material for special studies such as microbiological cultures, immunological or genetic studies as well as electron microscopy. Furthermore Most patients with a benign diagnosis on FNA biopsy do not undergo a surgical biopsy overall sensitivity was 92.7%, specificity 98.5 %

50. If the LN are not palpable, endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) has been shown to accurately diagnose mediastinal lymph node pathology with diagnostic accuracy of 84% endobronchial ultrasound guided transbronchial needle aspiration (EBUS-TBNA) have been shown to be highly sensitive and specific in the diagnosis of mediastinal and hilar lesions

51. Limitations of FNA: the lack of proper tissue sample to run special studies including cytogenetics, flow cytometry, electron microscopy, the potential risk of seeding a tract with malignancy as a result of FNA

52. BIOPSY Can be done by bedside, open surgery , mediastinoscopy FNA cannot distinguish between lymphomas (nodal architecture needs to be intact) The preservation of nodal architecture is critical to the proper diagnosis of lymphadenopathy, particularly when differentiating lymphoma from benign reactive hyperplasia Biopsy should be avoided in patients with probable viral illness because lymph node pathology in these patients may sometimes simulate lymphoma and lead to a false-positive diagnosis of malignancy. The diagnostic yield of the biopsy can be maximized by obtaining an excisional biopsy of the largest and most abnormal node (which is not necessarily the most accessible node). If possible, the physician should not select inguinal and axillary nodes for biopsy, since they frequently show only reactive hyperplasia .  Patients should be cautioned to remain alert for the reappearance of the nodes because lymphomatous nodes have been known to temporarily regress .

53. TB abscess Treatment should be started following the national TB Guidelines.

54. Thank you

55. Creating a Differential C hicago

56. C hicago Cancer Heme. malignancies: Hodgkin, NHL, acute and chronic leukemia , waldenstroms , multiple myeloma ( plastmocytomas) Metastatic: solid tumor breast, lung, renal, cell ovarian.

57. c H icago Hypersensitivity syndromes Serum sickness. Serum sickness like illness. Drugs Silicone Vaccination Graft vs Host

58. Ch i cago Infections Viral Bacterial Protozoan Mycotic Rickettsial (typhus) Helminthic (filariasis)

59. VIRAL EBV…mono spot test CMV….cmv titers, immunsuppresed, transplant recipient, recent blood transfusion HIV…IV drug use, high risk sexual behavior Hepatitis….IV drug use Herpes Zoster….superficial cutaneous nodules

60. Bacterial Staph/strep: cutaneous source, lymphadenitis Cat scratch: bartonella hensalae, two weeks after inoculation Mycobacterium: TB and non-tb, host characteristics (HIV, foreign born, low socioeconomic status, homo….)

61. Spirochete Syphilis: Treponema pallidum Primary localized inguinal lymph nodes and secondary, non-treponemal, treponemal Lyme disease( the most common tick-borne disease caused by Borrelia )

62. Protozoan Toxoplasmosis: ELISA assay, intracellular protozoan toxoplasmosis gondii….bilateral, symmetrical, non-tender cervical adenopathy …consider undercooked meat, reactivation in immun-compromised host

63. chi c ago Connective Tissue Disease Rheumatoid Arthritis SLE Dermato-myositis Mixed connective tissue disease Sjogren

64. chic a go Atypical lymphoproliferative disorders Castleman’s disease. Wegener's granulomatosis ( a form of vasculitis that affects the lungs, kidneys and other organs..) Angio-immuonplastic lymph-adenopathy with dysproteinemia.

65. chica G o Granulomatous Histoplasmosis. Mycobacterial infections. Cryptococcus. Silicosis: coal, foundry, ceramics, glass. Berylliosis: metal, alloys. Cat Scratch .

66. chicag O OTHER……. RARE Kikuchi (histiocytic necrotizing lymphadenitis ( non-cancerous enlargement of the lymph nodes) Rosi Dorfman disease (sinus histiocytosis with massive lymphadenopathy, is a rare, benign disorder of unknown etiology ) Kawasaki disease.