림프절병증 내과 4년차 한재준.

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림프절병증 내과 4년차 한재준

Introduction Lymphadenopathy may be a primary or secondary manifestation of numerous disorders. A. In primary care practice More than 2/3 of patients with LAP have nonspecific causes or upper respiratory illnesses (viral or bacterial) <1% have malignancy ! B. In one study- referred for evaluation of LAP 84% had a “benign” diagnosis 16% had a malignancy lymphoma or metastatic adenocarcinoma Of the benign LAP: 63% had a nonspecific or reactive etiology Remained: infectious mononucleosis, toxoplamosis, or tuberculosis

Introduction Is it abnormal ? Soft, flat, submandibular nodes (<1cm) are often palpable in healthy children and young adults. Healthy adults may have palpable inguinal nodes of up to 2cm, which are considered normal.

Some conditions simulating lymph node enlargement Lymphangioma Graves disease Cystic hygroma Hashimoto thyroiditis Hemangioma Parotid swelling Brachial cleft cyst Thyroid goiter Thyroglossal duct cyst Granular cell tumor Laryngocele Esophageal diverticulum

Lymphatic system Lower part of the body, left side of the head, left arm, part of the chest The thoracic duct Between Left internal jugular v. and left subclavian v. Right side of the neck and head, right arm, parts of the right thorax Right lymphatic duct Between right internal jugular v. and right subclavian v.

병태생리 항원에 반응하는 동안 양성 림프구와 대식세포의 수적 증가 림프절을 침범하는 감염증에서 염증세포들에 의한 침윤(림프선염) 생체정상부위의 악성 림프구나 대식세포의 증식 전이성 악성 세포에 의한 림프절의 침윤 지질 저장성 질환에서 대사물을 적재한 대식세포의 림프절 침윤

Diseases associated with lymphadenopathy 1. Infectious diseases   a. Viral—infectious mononucleosis syndromes (EBV, CMV), infectious hepatitis, herpes simplex, herpesvirus-6, varicella-zoster virus, rubella, measles, adenovirus, HIV, epidemic keratoconjunctivitis, vaccinia, herpesvirus-8   b. Bacterial—streptococci, staphylococci, cat-scratch disease, brucellosis, tularemia, plague, chancroid, melioidosis, glanders, tuberculosis, atypical mycobacterial infection, primary and secondary syphilis, diphtheria, leprosy   c. Fungal —histoplasmosis, coccidioidomycosis, paracoccidioidomycosis   d. Chlamydial —lymphogranuloma venereum, trachoma   e. Parasitic —toxoplasmosis, leishmaniasis, trypanosomiasis, filariasis   f. Rickettsial —scrub typhus, rickettsialpox, Q fever

Diseases associated with lymphadenopathy 2. Immunologic diseases   a. Rheumatoid arthritis   b. Juvenile rheumatoid arthritis   c. Mixed connective tissue disease   d. Systemic lupus erythematosus   e. Dermatomyositis   f. Sjögren's syndrome   g. Serum sickness   h. Drug hypersensitivity—diphenylhydantoin, hydralazine, allopurinol, primidone, gold, carbamazepine, etc.   i. Angioimmunoblastic lymphadenopathy   j. Primary biliary cirrhosis   k. Graft-vs.-host disease   l. Silicone-associated   m. Autoimmune lymphoproliferative syndrome

Diseases associated with lymphadenopathy 3. Malignant diseases   a. Hematologic —Hodgkin's disease, non-Hodgkin's lymphomas, acute or chronic lymphocytic leukemia, hairy cell leukemia, malignant histiocytosis, amyloidosis   b. Metastatic —from numerous primary sites 4. Lipid storage diseases —Gaucher's, Niemann-Pick, Fabry, Tangier 5. Endocrine diseases —hyperthyroidism

Diseases associated with lymphadenopathy 6. Other disorders   a. Castleman's disease (giant lymph node hyperplasia)   b. Sarcoidosis   c. Dermatopathic lymphadenitis   d. Lymphomatoid granulomatosis   e. Histiocytic necrotizing lymphadenitis (Kikuchi's disease)   f. Sinus histiocytosis with massive lymphadenopathy (Rosai-Dorfman disease)   g. Mucocutaneous lymph node syndrome (Kawasaki's disease)   h. Histiocytosis X   i. Familial mediterranean fever   j. Severe hypertriglyceridemia   k. Vascular transformation of sinuses   l. Inflammatory pseudotumor of lymph node   m. Congestive heart failure

Approach to the patient

Medical history Symptoms Sex Occupation Exposure of pets sore throat, cough, fever, night sweats, fatigue, weight loss, or pain in the nodes should be sought Sex Occupation Exposure of pets Sexual behavior Use of drugs: diphenylhydantoin Age children and young adults- viral or bacterial upper respiratory tract infections, infectious mononucleosis, toxoplasmosis, tuberculosis After age 50 the incidence of malignant disorders increase

Physical examination Extent of lymphadenopathy (localized or generalized) Size of nodes Texture Presence or absence of nodal tenderness Signs of inflammation over the node Skin lesions Splenomegaly ENT exam. adult patients with cervical adenopathy or history of tobacco use

The lymph nodes most accessible to inspection and palpation The “necklace” of nodes Parotid and retropharyngeal (tonsillar) Submandibular Submental Sublingual (facial) Superficial anterior cervical Superficial posterior cervical Preacuricular and postauricular Sternomastoid Occipital Supraclavicular

The lymph nodes most accessible to inspection and palpation The arms Axillary Epitrochanter (cubital) The legs Superficial superior inguinal Superficial inferior inguinal Occassionally, popliteal

Site of lymphadenopathy Generalized adenopathy has been defined as involvement of three or more noncontiguous lymph node areas. Generalized LAP is frequently associated with nonmalignant disorders such as Infectious mononucleosis,Epstein-Barr virus,Cytomegalovirus Toxoplasmosis,AIDS,other viral infections SLE, and mixed connective tissue disease Acute and chronic lymphocytic leukemia & malignant lymphomas

Site of lymphadenopathy Occipital adenopathy infection of the scalp Preauricular adenopathy conjunctival infections and cat-scratch disease The most frequent site of regional adenopathy is the neck Upper respiratory infections Oral and dental lesions Infectious mononucleosis Metastatic cancer from head and neck, breast, lung, thyroid primaries

Site of lymphadenopathy Enlargement of supraclavicular and scalene node is always abnormal These LNs drain regions of the lung and retroperitoneal space, they can reflect lymphomas, other cancers, or infectious processes arising in these areas. Virchow’s node is an enlarged SCN infiltrated with metastatic cancer from gastrointestinal primary Lung, breast, testis, or ovarian cancers Tuberculosis, sarcoidosis, and toxoplasmosis

Site of lymphadenopathy Axillary adenopathy Due to injuries or localized infections of the ipsilateral upper extremity Melanoma or lymphoma, breast cancer Inguinal lymphadenopathy Usually secondary to infections or trauma of the lower extremities and may accompany sexually transmitted disease (lymphogranuloma venereum, primary syphilis, genital herpes, or chancroid) Lymphomas and metastatic cancer from rectum, genitalia, or lower extremities (melanoma)

The size of the lymph nodes Nodes<1.0cm2 in area almost always secondary to benign, nonspecific reactive causes Retrospective analysis of younger patients(9-25 years) who had a lymph node biopsy a maximum diameter of >2cm - Predicting malignant or granulomatous disease A lymph node size 2.25cm2 - the best size limit for distinguishing malignant or granulomatous lymphadenopathy from other causes of lymphadenopathy node<1.0cm2 should be observed after excluding infectious mononucleosis and/or toxoplasmosis unless there are symptoms and signs of an underlying systemic illness

The texture of the lymph nodes Described as Soft firm Rubbery hard Discrete matted Tender movable Fixed Tenderness: capsule is stretched during rapid enlargement usually secondary to an inflammatory process. Some malignant disease such as acute leukemia may produce rapid enlargement and pain in the nodes.

The texture of the lymph nodes Nodes involved by lymphoma large, discrete, symmetric, rubbery, firm, mobile, and nontender. Nodes containing metastatic cancer hard, nontender, and nonmovable because of fixation to surrounding tissues. The coexistance of splenomegaly systemic illness such as infectious mononucleosis, lymphoma, acute or chronic leukemia, SLE, sarcoidosis, toxoplasmosis, cat-scratch disease, or other common hematologic disorders

Symptom-directed diagnostic workup Nonsuperficial presentations (thoracic or abdominal) of adenopathy Thoracic adenopathy: routine chest radiography workup for superficial adenopathy cough or wheezing from airway compression hoarseness from recurrent laryngeal nerve involvement dysphagia from esophageal compression swelling of the neck,face or arms secondary to compression of the superior vena cava or subclavian vein.

Differential diagnosis of mediastinal and hilar adenopathy Primary lung disorders and systemic illnesses that characteristically involve mediastinal or hilar nodes. In the young: infectious mononucleosis and sarcoidosis In endemic regions: histoplasmosis can cause unilateral paratracheal lymph node involvement that mimics lymphoma Tuberculosis also cause unilateral adenopathy In older patients: primary lung cancer(especially among smokers), lymphomas, metastatic carcinoma(usually lung), tuberculosis, fungal infection, and sarcoidosis.

Enlarged intraabdominal or retroperitoneal nodes are usually malignant. tuberculosis may present as mesenteric lymphadenitis These masses usually contain lymphomas or, in young men, germ cell tumors.

Lab investigation Chest X-ray usually negative Presence of a pulmonary infilatrate or mediastinal LAP suggest tuberculosis, histoplasmosis, sarcoidosis, lymphoma, primary lung cancer, or metastatic cancer CT and MRI are comparably accurate (65-90%) in diagnosis of metastasis of cervical LNs. Ultrasonography Determine the long axis, short axis, and ratio L/S L/S ratio <2.0 has a sensitivity & specificity of 95% in patients with head and neck cacner.

Lymph node biopsy Prompt biopsy: if the patient’s history and physical findings suggest a malignancy- for example, Solitary, hard, nontender cervical node in an old patient who is chronic user of tobacco Supraclavicular adenopathy Solitary or generalized adenopathy that is firm, movable, and suggestive of lymphoma

Lymph node FNA Fine-needle aspiration should not be performed as the first diagnostic procedure. Most diagnosis require more tissue than such aspiration can provide, and it often delays a definitive diagnosis. FNA should be reserved for thyroid nodules confirmation of relapse in patients whose primary diagnosis is known.

Lymph node biopsy A. 9~25 years of age who had a node biopsy performed. Positive predictive value: >2cm, abnormal CXR Negative predictive value: recent ENT symptoms B. evaluated 220 LAP patients in a hematology unit lymph node size, location (supraclavicular or nonsupraclavicular), age (>40years or <40years), texture (hard or nonhard), tenderness Positive predictive value: >40years, supraclavicular locations, node size>2.25cm2, hard texture, lack of pain or tenderness Negative predictive value: <40 years, node size<2.25cm2, nonhard texture, tender or painful nodes

Lymph node biopsy Open biopsy Fine needle aspiration for cytology Histologic examination of intact tissue: presence of abnormal cells & abnormal node architecture (useful for the diagnosis of lymphomas) False negative: when the wrong node is taken (not uncommon) Fine needle aspiration for cytology Most useful when searching for recurrence of cancer False negative: substantial due to sampling error Core needle biopsy Provides tissue for special studies and some information on architecture & relatively low-morbidity, inexpensive alternative to open biopsy

Conclusion Most LAP patients do not require a biopsy, and at least half require no lab. studies. If the patient’s history and physical findings point to a benign cause for LAP, then careful follow-up at a 2- to 4- week interval can be employed. The patient should be instructed to return for reevaluation if the node increases in size. Antibiotics are not indicated for LAP unless strong evidence of a bacterial infection is present. Glucocorticoids should not be used to treat LAP because their lympholytic effect obscures some diagnosis.