1. 림프절병증
내과 4년차 한재준

2. 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

3. 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.

4. 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

5. 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.

6. 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

7. 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

8. 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

9. 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

10. 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

11. Approach to the patient

12. 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

13. 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

14. 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

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

16. 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

17. 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

18. 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

19. 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)

20. 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

21. 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.

22. 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

23. 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.

24. 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.

25. 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.

26. 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.

27. 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

28. 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.

29. 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

30. 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

31. 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.