International Journal of Health Sciences and Research Vol.10; Issue: 10; October 2020 Website: www.ijhsr.org Review Article ISSN: 2249-9571

Cervical : A Review

Rupali Verma1, Shriya Khera2

1M.D.S- Oral Medicine and Radiology, 2Senior Research Associate, Maulana Azad Institute of Dental Sciences, New Delhi

Corresponding Author: Rupali Verma

ABSTRACT

Cervical enlargement may be an incidental finding on examination in a patient seeking oral health care, or may be associated with a patient’s complaint. The condition is generally not a disease by itself; rather, it may be a symptom of one of many possible underlying problems. It may be localized, limited or generalized in location and/ or acute, subacute or chronic in duration. The etiologies for cervical lymphadenopathy fall under a wide range of spectrum and usually history and physical examination alone may lead to diagnosis. But, unexplained cervical lymphadenopathy is a cause of concern for the physician as it could be a manifestation of an underlying malignancy. However, a methodological approach to lymphadenopathy can disclose the accurate diagnosis causing minimal discomfort to the patient and also less time consuming for the physician. This article reviews the common causes of lymphadenopathy and presents a methodical clinical approach to a patient with cervical lymphadenopathy.

Key Words- Cervical lymphadenopathy, Clinical Evaluation, Differential Diagnosis, Benign, Malignant.

INTRODUCTION glycoprotein-laden macrophages. When this The human body has about 600 occurs, lymph nodes may be detected lymph nodes which play the role of filtering clinically. Thus, lymphadenopathy is the the lymph fluid as it circulates throughout term used to describe the clinical sign of the body. The prime function of lymph node swelling of the lymph nodes. Lymphadenitis is to deal with antigen, whether this is in the is the pathologic term for of form of organisms or other particulate the lymph nodes.1 material, or even soluble antigen. The lymph The lymph nodes are strategically nodes contain T and B cells along with placed along the drainage of tissue and body Antigen Presenting Cells which are called fluids with neck containing nearly 2/3rd of the dendritic cells. They form the part of the the total lymph nodes of the body. Cervical immune system and function to fight off lymphadenopathy is quite significant in that disease and infections.3,6,11. there are numerous etiological agents and is Lymphadenopathy (LAP) refers to an index of spread of infection and the lymph nodes that are abnormal in size malignancy.6 When cervical (usually greater than 1 cm) consistency or lymphadenopathy is detected, a cause can number.4,11 In general, there are two sometimes be determined by careful mechanisms of lymphadenopathy- medical history, thorough physical hyperplasia and infiltration. The former examination, judicious selection of occurs in response to immunologic or laboratory tests and, if necessary, a lymph infectious stimuli, and the latter is the result node .1 of infiltration by various cell types, including cancer cells, lipid cells, or

International Journal of Health Sciences and Research (www.ijhsr.org) 292 Vol.10; Issue: 10; October 2020 Rupali Verma et.al. Cervical lymphadenopathy: a review

EPIDEMIOLOGY- TB to 50%. In general practice, less than The exact incidence of lymphadenopathy is one percent of patients with LAP have unknown, due to inadequate literature but malignant disease, often due to in the number varies from 38-45%. In tropical younger children and Hodgkin's disease in areas, is the main cause of adolescents. It has been reported that the benign LAP with vast social and massive prevalence of malignancy is 0.4% in economic implications. Additionally, patients under 40 years and 4% in those increasing cases of HIV in TB patients has over 40 years of age in the primary care increased the incidence of extrapulmonary setting.3,11.

DEFINITION AND CLASSIFICATION-

Pathologic lymph node >1 cm in adults. >2 cm in pediatric patients, is considered abnormal.

Generalized Enlargement of more than two noncontiguous lymph node groups. Localized Limited to one group; cervical involved more than others. Dermatopathic Lymphadenopathy associated with skin diseases.

Acute <2 weeks in duration. Subacute 2-6 weeks in duration. Chronic >6 weeks in duration.

ETIOLOGY- The etiologies of lymphadenopathy can be remembered by MIAMI mnemonic-

MALIGNANCIES Kaposi’s Sarcoma, , , multiple myelomas with amyloidosis, skin neoplasms, metastatic from primary sites. INFECTIONS Bacterial , Cat-scratch disease, Chancroid, Cutaneous infections (staphylococcus or streptococcus), Viral Lymphogranuloma venerum, primary and secondary , Tuberculosis, Tuleremia, Typhoid fever. Fungal Adenovirus, , Hepatitis, Herpes Zoster, Human Immunodeficiency Virus, Infectious Granulomatous Mononucleosis, . Others , Coccidiomycosis, Paracoccidiodomycosis. Berylliosis, Silicosis. Helminthic, Rickettsial, Lyme disease, Scrub typhus, . AUTOIMMUNE Dermatomyositis, Rheumatoid Arthritis, Sjogrens Syndrome, Stills Disease, Systemic Lupus Erythematosus. DISORDERS MISCELLANEOUS/ Angiofollicular lymph node hyperplasia (), Histiocytosis, , Kikuchi UNUSUAL lymphadenitis, Kimura disease, , Silicosis, Lipid Storage diseases, Endocrine disease (hyperthyroid, adrenal insufficiency, thyroiditis), Severe hypertriglyceridemia. IATROGENIC Medications, Serum Sickness.

Medications causing Lymphadenopathy:- Allopurinol Phenytoin Atenolol Primidone Captopril Pyrimethamine Carbamazepine Quinidine Gold Trimethoprim/ Sulfamethoxazole Hydralazine Sulindac Penicillins

CLASSIFICATION- Localized Lymphadenopathy- Head and Neck- Infection is a common cause of head and cervical lymphadenopathy. In children, acute and self-limiting viral illnesses are the most common etiologies of lymphadenopathy. Supraclavicular adenopathy in adults and children is associated with high risk of intra-abdominal malignancy and must be evaluated promptly.

International Journal of Health Sciences and Research (www.ijhsr.org) 293 Vol.10; Issue: 10; October 2020 Rupali Verma et.al. Cervical lymphadenopathy: a review

Preauricular nodes: Drain scalp, skin Differential diagnosis: Submandibular nodes: Scalp infections, mycobacterial Drain oral cavity infection Differential diagnosis: Malignancies: Mononucleosis, upper Skin neoplasm, lymphomas, head and neck respiratory infection, SCCs. mycobacterial infection, toxoplasma, cytomegalovirus, dental disease, rubella Posterior cervical nodes: Malignancies: Drain scalp, neck, upper thoracic Squamous cell carcinoma of skin the head and neck, lymphomas, Differential diagnosis: leukemias Same as preauricular nodes

Supraclavicular nodes: Drain gastrointestinal tract, Anterior cervical nodes: genitourinary tract, pulmonary Drain larynx, tongue, oropharynx, Differential diagnosis: anterior neck Thyroid/laryngeal disease, Differential diagnosis: mycobacterial/fungal infections Same as submandibular nodes Malignancies: Abdominal/thoracic

Infraclavicular Highly suspicious of Non- Hodgkin . lymphadenopathy Epitrochlear lymphadenopathy >5 mm is pathologic Suggestive of lymphoma or melanoma; infections of upper extremity, sarcoidosis and secondary syphilis. Axillary lymphadenopathy Infectious or granulomatous; breast adenocarcinomas, skin neoplasms, lymphomas, leukemias, Kaposi’s sarcoma. Inguinal lymphadenopathy Infections, sexually transmitted diseases, penile and vulvar SCCs, melanoma.

Generalized Lymphadenopathy- It is fatigue, and prolonged malaise are the other defined as the enlargement of more than two symptoms. non-contiguous lymph node groups. It is HIV infection is frequently more likely than localized lymphadenopathy associated with generalized LAP. It may to result from serious infections, also increase the risk of TB. The HIV autoimmune diseases, and disseminated initially involves the cervical, axillary, and malignancy. It usually merits specific occipital nodes and is not tender. In this testing to determine the diagnosis.4 situation, lymph nodes enlargement may last Generalized LAP is rarely seen in for more than 2-3 months. Drug reaction is malignancies; however, it is usually seen in characterized by fever, rash, arthralgia and non- Hodgkin's lymphoma, whereas generalized LAP. Hodgkin's disease is distinguished by the Generalized lymph node localized involvement of the lymph nodes. enlargement is common and is usually a The Epstein-Barr virus typically non-specific aspect of systemic lupus involves the bilateral posterior cervical, erythematosus. It is frequently detected in axillary, and inguinal lymph nodes, the cervical, axillary, and inguinal regions. distinguishing it from the other causes of Whereas lymph node necrosis is the pharyngitis. LAP appears in the first week characteristic histological finding, reactive of exposure and then gradually subsides follicular hyperplasia is the most frequent over two to three weeks. Low-grade fever, histopathologic finding in lymph node

International Journal of Health Sciences and Research (www.ijhsr.org) 294 Vol.10; Issue: 10; October 2020 Rupali Verma et.al. Cervical lymphadenopathy: a review lesions in systemic lupus erythematosus Environmental, travel-related, patients. animal and insect exposure, tobacco and alcohol use as well as occupational history DIFFERENTIAL DIAGNOSIS should be ascertained. Chronic medication Three models are available to categorize use, infectious exposures, immunization peripheral LAP. status should also be reviewed. The family 1) Using the acronym "CHICAGO" helps history may also be helpful in identifying to consider all causes. the familial causes such as Li-Fraumeni C→ Cancers: Hematologic malignancies: Syndrome or lipid storage diseases. Hodgkin's disease, Non Hodgkin's The patient’s past medical history lymphoma, Leukemia should reveal the setting in which Metastatic: Breast tumor, Lung, Kidney, lymphadenopathy is present. A history of others malignancy or infection could point to a H→ Hypersensitivity syndromes: Serum recurrence. sickness, Drugs A family history of malignant I→ Infections: Viral (EBV, CMV, HIV), disorders may raise the physician’s Bacterial (TB,) Fungal, Protozoan, suspicion to distinct etiologies of LAP such Rickettsial (Typhus), Helminths as breast carcinomas, melanoma, and C→ Connective Tissue disorders: SLE, RA, dysplastic nevus syndrome. Also, if LAP Dermatomyositis lasts less than two weeks or over one year A→ Atypical lymphoproliferative disorders: without increasing in size, the probability of Castleman’s Disease, Wegener’s. malignancy is quite low. G→ Granulomatous: Histoplasmosis, Mycobacterial infections, Cryptococcus, ASSOCIATED SIGNS AND Berylliosis, Cat scratch disease, Silicosis SYMPTOMS- O→ Others A thorough review of systems is important in the evaluation of peripheral 2) Using the letters of alphabet, although it lymphadenopathy. Constitutional symptoms makes the categorization too long. such as fatigue, weight loss, malaise and 3) Using the region of lymph node fever, rapid enlargement or tenderness of enlargement and its localization provides the mass, or overlying erythema should be useful information about causes. noted to find a possible etiology.8,9. Most malignant neck masses in chil- DIFFERENTIAL DIAGNOSIS ON dren are asymptomatic and are not painful. BASIS OF PALPATION- However, acute infection in a necrotic, Cystic soft Cold Abscess malignant lymph node can also occur. An Firm Syphilis Rubbery Hodgkin’s Lymphoma upper respiratory tract infection preceding Matted Tuberculosis the onset of the mass suggests possible Stony hard Carcinoma reactive lymphadenopathy or a secondary

infection of a congenital cyst. Constitutional HISTORICAL CLUES- type B symptoms such as fever, malaise, A clinician’s diagnostic skills are weight loss, and night sweats suggest a strongly based on his/ her ability to elicit a possible malignancy. Lymphadenopathy complete history of present illness. Age, with high fever, bilateral conjunctivitis, and time of presentation, duration of symptoms, oral mucosal changes with a strawberry underlying diseases, and circumstances in tongue likely represents Kawasaki disease. which LAP was detected are of great value.

International Journal of Health Sciences and Research (www.ijhsr.org) 295 Vol.10; Issue: 10; October 2020 Rupali Verma et.al. Cervical lymphadenopathy: a review

CLINICAL FEATURES- LOCATION Identify the anatomical location (cervical, submandibular, submental, supraclavicular, occipital, preauricular, auricular, axial inguinal.) Single or multiple nodes Localized or disseminated nodes If palpable; unilateral or bilateral CONSISTENCY Firm Soft Rubbery Rock hard Movable Fixed SIZE <1 cm2, >1 cm2 If bilateral; check for symmetry SYMPTOMS Asymptomatic Tender Associated with systemic symptoms

DIAGNOSIS- Following comprehensive history taking and physical examination, the existing algorithm can guide the physicians for further evaluation of patients with peripheral LAP.

International Journal of Health Sciences and Research (www.ijhsr.org) 296 Vol.10; Issue: 10; October 2020 Rupali Verma et.al. Cervical lymphadenopathy: a review

1) LABORATORY INVESTIGATIONS- If additional information is required, then CBC and specific markers may also be needed.

2) IMAGING- Imaging can evaluate LAP more accurately than physical The American College of Radiology examination. recommends ultrasonography as the initial  Chest radiography. imaging choice for cervical  Ultrasonography is a useful imaging tool lymphadenopathy in children up to 14 years in the assessment of the number, size, of age and CT for persons older than 14 site, shape, margins, and internal years. structure in patients with peripheral 3) INVASIVE- LAP. Tissue diagnosis is the gold standard in the 11  Color Doppler ultrasonography has been evaluation of LAP. used in the assessment of lymph node Fine Needle Aspiration and Core Needle enlargement since the beginning of the Biopsy can aid in the diagnostic evaluation 1970s. It can evaluate the vascular of lymph nodes when etiology is unknown pattern, displacement of vascularity, or enlarged lymph nodes have not vascular resistance, and pulsatility responded to antibiotic and has been present 3,4. index; which can help differentiate for 2-6 weeks’ duration. between old and new LAP. Excisional Biopsy to be performed if the  CT scan and magnetic resonance FNAC results are negative, however the imaging (MRI) are more useful in the clinical findings are strongly suggestive of 3 evaluation of the retropharyngeal, malignancy. thoracic and abdominopelvic cavity or suspected malignancy and their accuracy RISK FACTORS FOR MALIGNANCY- mainly depends on the size of the lymph these should be considered as guidelines for nodes. early referral for biopsy to rule out  ECG/ECHO based on clinical findings if malignancy. Kawasaki is suspected to rule out any  Age older than 40 years. complications.3,11.  Duration of LAP greater than 4-6 weeks.

International Journal of Health Sciences and Research (www.ijhsr.org) 297 Vol.10; Issue: 10; October 2020 Rupali Verma et.al. Cervical lymphadenopathy: a review

 Generalized LAP. Contemporary Medical Research 2016;  Male sex. 3(4):1207-1210. 2. Mohan Kumar Mili, Jyotirmoi Phookan. A  Supraclavicular location. clinico-pathological study of cervical  Node not returned to baseline after 8-12 lymphadenopathy. Int J Dent Med Res 2015; weeks. 1(5):24-27.  Lymph nodes are non-tender, firm or 3. Shahrzad Mohseni, Abolfazl Shojaiefard, hard; >2 cm in size or are progressively Zhamak Khorgami, Shahriar Alinejad, Ali enlarging. Ghorbani, Ali Ghafouri. Peripheral Lymphadenopathy: Approach and Diagnostic  Axillary nodes are involved (in absence Tools. Iran J Med Sci. 2014;39(2):158-170. of local infection or dermatitis). 4. Heidi L. Gaddey, Angela M. Riegel.  Systemic signs- fever, night sweats, Unexplained Lymphadenopathy: Evaluation weight loss, hepatosplenomegaly. and Differential Diagnosis. Am Fam  White race.4,3. Physician. 2016; 94(11):896-903. 5. T. Sambandan, R. Christeffi Mabel. Cervical

Lymphadenopathy- A Review. JIADS 2011; CONCLUSION- 2(1):31-33. Lymphadenopathy is a common 6. Prasadrao Dasari, Satyanarayanamurthy occurrence and should be duly noted and a Varanasi, Surjkumar Pattnayak, Nagababu, systemic approach should be followed to Nandini. Cervical Lymphadenopathy: A diagnose the cause which further helps in Prospective Study in Rajiv Gandhi Institute of determining a proper treatment course for Medical Sciences, Srikakulam, Andhra Pradesh. International Journal of Scientific the patient. Mostly, history and physical Study. 2016; 4(5):233-238. examination can reveal the etiology for the 7. Ernesta Parisi, Michael Glick. Cervical same and hence should be taken into lymphadenopathy in the dental patient: A consideration while examination. Diagnosis review of clinical approach. Quintessence Int of less obvious causes can often be made 2005; 36: 423-436. after considering the patient’s age, duration 8. Jeremy D. Meier, Johannes F. Grimmer. and all other risk factors, and whether Evaluation and Management of Neck Masses in Children. Am Fam Physician. 2014; constitutional signs are present. When the 89(5):353-358. cause of lymphadenopathy remains 9. Andrew W. Bazemore, Douglas R. Smucker. unexplained, a three- to four- week Lymphadenopathy and Malignancy. Am Fam observation period is appropriate when the Physician 2002;66:2103-10. clinical setting indicates a high probability 10. Dong Gyu Na, Hyo Keun Lim, Hong Sik of benign disease. Once biopsy has been Byun, Hong Dae Kim, Young Hyeh Ko, Jeong chosen, ideally the largest, most suspicious, Hwan Baek. Differential Diagnosis of Cervical Lymphadenopathy: usefulness of and most accessible node is selected, taking Color Doppler Sonography. American Journal into account differing diagnostic yields by of Roentgenology 1997; 168:1311-1316. site. Although the advent of new techniques 11. Robert Ferrer. Lymphadenopathy: Differential has increased the sensitivity and specificity Diagnosis and Evaluation. Am Fam Physician. of FNAC, excisional biopsy remains the 1998;58(6):1313-1320. diagnostic procedure of choice. Thus, a case 12. Athira Aruna Ramadas, Renju Jose, Beena with cervical lymphadenopathy has to be Varma, Marina Lazar Chandy. Cervical Lymphadenopathy: Unwinding the hidden evaluated carefully to prevent any truth. Dent Res J (Isfahan).2017;14(1):73-78. misdiagnosis. How to cite this article: Verma R, Khera S. REFERENCES Cervical lymphadenopathy: a review. Int J Health 1. Sachin Darne, Trusha Rajda. Cervical Sci Res. 2020; 10(10):292-298. lymphadenopathy in children- a clinical approach. International Journal of

******

International Journal of Health Sciences and Research (www.ijhsr.org) 298 Vol.10; Issue: 10; October 2020