Approach to Approach to LymphadenopathLymphadenopath

yyDr. Vishal KukretiDr. Vishal Kukreti

February 20, 2007February 20, 2007

Case 1Case 1 25 year old female25 year old female 3 month history of B-symptoms, 3 month history of B-symptoms,

progressive anemia (normocytic), new progressive anemia (normocytic), new adenopathy – not painful but progressive adenopathy – not painful but progressive over weeks, weight lossover weeks, weight loss

Physical exam – diffuse adenopathy 2-3 Physical exam – diffuse adenopathy 2-3 cm in size, oral ulceration - ?HSV, no cm in size, oral ulceration - ?HSV, no organomegalyorganomegaly

Laboratory Investigations – Hemoglobin Laboratory Investigations – Hemoglobin 60, MCV of 80, low WBC, normal platelet 60, MCV of 80, low WBC, normal platelet count, normal biochemistry – high LDHcount, normal biochemistry – high LDH

Case 2Case 2 83 yo Female83 yo Female Otherwise healthyOtherwise healthy 5 years ago presented with painful right 5 years ago presented with painful right

submandicular node – 3X3 cm – given ABx and submandicular node – 3X3 cm – given ABx and followed for a few months – slight decreasefollowed for a few months – slight decrease

FNA done – reactiveFNA done – reactive Node persisted over months – excisional Node persisted over months – excisional

biopsy – reactive adenopathybiopsy – reactive adenopathy 6 months ago – recurrent right submandicular 6 months ago – recurrent right submandicular

node – matted, slowly increased in size – now node – matted, slowly increased in size – now 3X3cm3X3cm

ObjectivesObjectives

Approach to AdenopathyApproach to Adenopathy Who to investigateWho to investigate When to investigateWhen to investigate How to define risk for underlying How to define risk for underlying

malignancymalignancy

Lymph NodesLymph Nodes AnatomyAnatomy

Collection of lymphoid cells attached to both vascular Collection of lymphoid cells attached to both vascular and lymphatic systemsand lymphatic systems

Over 600 lymph nodes in the bodyOver 600 lymph nodes in the body FunctionFunction

To provide optimal sites for the concentration of free or To provide optimal sites for the concentration of free or cell-associated antigens and recirculating lymphocytes cell-associated antigens and recirculating lymphocytes – “sensitization of the immune response”– “sensitization of the immune response”

To allow contact between B-cells, T-cells and To allow contact between B-cells, T-cells and macrophagesmacrophages

Lymphadenopathy - node greater than 1cm in sizeLymphadenopathy - node greater than 1cm in size

Why do lymph nodes Why do lymph nodes enlarge?enlarge?

Increase in the number of benign Increase in the number of benign lymphocytes and macrophages in response lymphocytes and macrophages in response to antigensto antigens

Infiltration of inflammatory cells in Infiltration of inflammatory cells in infection (lymphadenitis)infection (lymphadenitis)

In situ proliferation of malignant In situ proliferation of malignant lymphocytes or macrophageslymphocytes or macrophages

Infiltration by metastatic malignant cellsInfiltration by metastatic malignant cells Infiltration of lymph nodes by metabolite Infiltration of lymph nodes by metabolite

laden macrophages (lipid storage laden macrophages (lipid storage diseases)diseases)

EpidemiologyEpidemiology

0.6% annual incidence of 0.6% annual incidence of unexplained adenopathy in the unexplained adenopathy in the general populationgeneral population

10% were referred to a subspecialist 10% were referred to a subspecialist and 3.2 % required a biopsy and and 3.2 % required a biopsy and 1.1% had a malignancy1.1% had a malignancy

When to worry?When to worry?

AgeAge Characteristics of the nodeCharacteristics of the node Location of the nodeLocation of the node Clinical setting associated with Clinical setting associated with

lymphadenopathylymphadenopathy

AgeAge

Children/young adults – more likely to Children/young adults – more likely to respond to minor stimuli with lymphoid respond to minor stimuli with lymphoid hyperplasiahyperplasia Lymph nodes in patients less than the age of Lymph nodes in patients less than the age of

30 are clinically benign in 80% of cases 30 are clinically benign in 80% of cases whereas in patients over the age of 50 only whereas in patients over the age of 50 only 40% are benign40% are benign

Biopsies done in patients less than 25 yrs Biopsies done in patients less than 25 yrs have a incidence of malignancy of <20% vs have a incidence of malignancy of <20% vs the over-50 age group has an incidence of the over-50 age group has an incidence of malignancy of 55-80%malignancy of 55-80%

Characteristics of the Characteristics of the nodenode

Nodes lasting less than 2 weeks or Nodes lasting less than 2 weeks or greater than one year with no greater than one year with no progression of size have a low likelihood progression of size have a low likelihood of being neoplastic – excludes low grade of being neoplastic – excludes low grade lymphomalymphoma

Cervical nodes – up to 56% of young Cervical nodes – up to 56% of young adults have adenopathy on clinical examadults have adenopathy on clinical exam

Inguinal adenopathy is common – up to 1-Inguinal adenopathy is common – up to 1-2 cm in size and often benign reactive 2 cm in size and often benign reactive nodesnodes

Characteristics of the Characteristics of the nodenode

Consistency – Hard/Firm vs Soft/Shotty; Consistency – Hard/Firm vs Soft/Shotty; FluctuantFluctuant

Mobile vs Fixed/MattedMobile vs Fixed/Matted Tender vs PainlessTender vs Painless Clearly demarcatedClearly demarcated SizeSize

When to worry – 1.5-2cm in sizeWhen to worry – 1.5-2cm in size Epitroclear nodes over 0.5cm; Inguinal over Epitroclear nodes over 0.5cm; Inguinal over

1.5cm1.5cm Duration and Rate of GrowthDuration and Rate of Growth

Location of the nodeLocation of the node

Supraclavicular lymphadenopathy Supraclavicular lymphadenopathy Highest risk of malignancy – estimated as Highest risk of malignancy – estimated as

90% in patients older than 40 years vs 90% in patients older than 40 years vs 25% in those younger than 40 yrs25% in those younger than 40 yrs

Right sided node – cancer in Right sided node – cancer in mediastinum, lungs, esophagusmediastinum, lungs, esophagus

Left sided node (Virchow’s) – testes, Left sided node (Virchow’s) – testes, ovaries, kidneys, pancreas, stomach, ovaries, kidneys, pancreas, stomach, gallbladder or prostategallbladder or prostate

Paraumbilical node (Sister Joseph’s)Paraumbilical node (Sister Joseph’s) Abdominal or pelvic neoplasmAbdominal or pelvic neoplasm

Location of the nodeLocation of the node

Epitroclear nodesEpitroclear nodes Unlikely to be reactiveUnlikely to be reactive

Isolated inguinal adenopathyIsolated inguinal adenopathy Less likely to be associated with Less likely to be associated with

malignancymalignancy

Clinical SettingClinical Setting

B symptoms – fever, night sweats, B symptoms – fever, night sweats, weight lossweight loss

FatigueFatigue PruritisPruritis Evidence of other medical conditions Evidence of other medical conditions

– connective tissue disease– connective tissue disease Young patient – mononucleosis type Young patient – mononucleosis type

of syndromeof syndrome

HistoryHistory

Identifiable cause for the Identifiable cause for the lymphadenopathy?lymphadenopathy? Localizing symptoms or signs to suggest Localizing symptoms or signs to suggest

infection/neoplasm/trauma at a particular siteinfection/neoplasm/trauma at a particular site URTI, pharyngitis, periodontal disease, conjunctivitis, URTI, pharyngitis, periodontal disease, conjunctivitis,

insect bites, recent immunization etcinsect bites, recent immunization etc

Constitutional symptomsConstitutional symptoms Epidemiological cluesEpidemiological clues

Occupational exposures, recent travel, high-risk Occupational exposures, recent travel, high-risk behaviourbehaviour

Medications – serum-sickness syndromeMedications – serum-sickness syndrome

Physical ExamPhysical Exam

Full nodal examination – nodal Full nodal examination – nodal characteristicscharacteristics

OrganomegalyOrganomegaly Localized – examine area drained by Localized – examine area drained by

the nodes for evidence of infection, the nodes for evidence of infection, skin lesions or tumoursskin lesions or tumours

Approach to Approach to LymphadenopathyLymphadenopathy

Localized – one area involvedLocalized – one area involved Generalized – two or more non-Generalized – two or more non-

contiguous areascontiguous areas

Generalized Generalized LymphadenopathyLymphadenopathy

Malignancy – lymphoma, leukemia, Kaposi’s Malignancy – lymphoma, leukemia, Kaposi’s sarcoma, metastasessarcoma, metastases

Autoimmune – SLE, RA, Sjogren’s syndrome, Autoimmune – SLE, RA, Sjogren’s syndrome, Still’s disease, DermatomyositisStill’s disease, Dermatomyositis

Infectious – Brucellosis, Cat-scratch disease, Infectious – Brucellosis, Cat-scratch disease, CMV, HIV, EBV, Rubella, Tuberculosis, CMV, HIV, EBV, Rubella, Tuberculosis, Tularemia, Typhoid Fever, Syphilis, viral Tularemia, Typhoid Fever, Syphilis, viral hepatitis, Pharyngitishepatitis, Pharyngitis

Other – Kawasaki’s disease, sarcoidosis, Other – Kawasaki’s disease, sarcoidosis, amyloidosis, lipid storage diseases, amyloidosis, lipid storage diseases, hyperthyroidism, necrotizing lymphadenitis, hyperthyroidism, necrotizing lymphadenitis, histiocytosis X, Castlemen’s diseasehistiocytosis X, Castlemen’s disease

DrugsDrugs

AllopurinolAllopurinol AtenololAtenolol CaptoprilCaptopril CarbamazepineCarbamazepine GoldGold HydralazineHydralazine PenicillinsPenicillins

PhenytoinPhenytoin PrimidonePrimidone PyrimethaminePyrimethamine QuinidineQuinidine Trimethoprim/Trimethoprim/

SulfamethozoleSulfamethozole SuldinacSuldinac

ManagementManagement

Identify underlying cause and treat Identify underlying cause and treat as appropriate – confirmatory testsas appropriate – confirmatory tests

Generalized adenopathy – usually Generalized adenopathy – usually has identifiable causehas identifiable cause

Localized adenopathyLocalized adenopathy 3-4 week observation period for 3-4 week observation period for

resolution if not high clinical suspicion resolution if not high clinical suspicion for malignancyfor malignancy

Biopsy if risk for malignancy - excisionalBiopsy if risk for malignancy - excisional

Fine Needle AspirateFine Needle Aspirate

Convenient, less invasive, quicker Convenient, less invasive, quicker turn-around timeturn-around time

Most patients with a benign Most patients with a benign diagnosis on FNA biopsy do not diagnosis on FNA biopsy do not undergo a surgical biopsyundergo a surgical biopsy

ConclusionsConclusions

Lymphadenopathy – initial presenting Lymphadenopathy – initial presenting symptomsymptom

Reactive vs MalignantReactive vs Malignant ProbabilityProbability HistoryHistory Physical ExamPhysical Exam

Biopsy if not resolved in 3-4 weeks for low Biopsy if not resolved in 3-4 weeks for low risk patientsrisk patients

Biopsy all high risk patients – excisional Biopsy all high risk patients – excisional biopsybiopsy