Dr. Rajesh Kumar

ATRICTRI

Bikaner

I. Temprature

II. Night sweats

III. Weight loss ( >10% of body wt. in 6mths.)

IV. Loss of appetite

V. Pruritus (May be the presenting feature but

particularly asso. with Nodular sclerosis)

VI. Lethargy

Febrile-›99 -continue –no fluctuation eg typhoid,IE,Pn.

-intermittent-febrile for hrs only.eg septic

fever or Quatidian fever.

Remitent-≥2 F fluctuation but not touching base line

Relapsing fever-afebrile period more than a day -.

Tertian-EOD eg PV, PF

Quartan -4th day fever eg P Malarie.

Pel-Ebstein fever

I. 7-10 days fever folowed by afebrile period 7-10 days.

II. Saddle back 2-3 day fever than 2-3 day afebrile, eg. Dengue

III. Borrelia relapsing fever

Cancers

Lymphoma

Leukemia

Infections

HIV/AIDS, Mycobacterium avium-intracellulare infection

Tuberculosis

Infectious mononucleosis

Fungal infections (histoplasmosis, coccidioidomycosis)

Lung abscess

Infective endocarditis

Brucellosis

Endocrine disorders

Menopause, Premature ovarian failure

Hyperthyroidism

Diabetes mellitus (nocturnal hypoglycemia)

Endocrine tumors (pheochromocytoma, carcinoid)

Rheumatic disorders-Takayasu's arteritis

Temporal arteritis

Drugs-antidepressent, aspirin, PCM.

Lymphadenopathy :

Enlarged, painless superficial lymph nodes m/c complain

most often cervical region , unilateral mostly

asymmetrical, discrete

painless, non-tender

elastic character on palpation ( rubbery)

not adherent to skin

fluctuate in size

Cervical/Supraclavicular (60-80%),Axillary (10-20%) and Inguinal (6-12%)

Lymph node involvement is contiguous. Nodal distribution is centripetal.

Local Symptoms of hodgkin’s lymphoma

Submandibular lymph node

: Infections of head, neck, sinuses, ears, eyes, scalp, pharynx.

LD- Tongue, submaxillary gland, lips and mouth, conjunctivae

Submental lymph node

: Mononucleosis syndromes, Epstein-Barr virus, cytomegalovirus, toxoplasmosis, dental pathology such as periodontitis.

LD-Lower lip, floor of mouth, teeth, submental salivary gland, tip of tongue, skin of cheek.

Jugular lymph node

: Pharyngitis organisms, rubella

LD-Tongue, tonsil, pinna, parotid

Right supraclavicular lymph node-:Lung, retroperitoneal or gastrointestinalcancer,LD-Mediastinum, lungs, esophagus

Left supraclavicular lymph node-Lymphoma, thoracic or retroperitoneal cancer, bacterial or fungal infection. LD-Thorax, abdomen via thoracic duct.

Suboccipital lymph node-local infection. LD-Scalp and head

Posterior cervical lymph node

Tuberculosis, lymphoma,

LD- Scalp and neck, skin of arms and pectorals, thorax, cervical and axillary nodes

Peripheral lymph nodes:

In left supraclavicular LAP is more commonly associated with

abdominal involvement ( splenic involvement) then right side.

Thorax

Anterior mediastinum prime location for NS .

Lung involvement may occur by direct contiguity with direct

involvement or by hematogenous involvement, involvement in form

of nodules and irregular interstitial infiltration.

May presents with pleural effusion due to mediastinal compression

of vascular-lymphatic compression and direct pleural involvement.

SVC syndrome is rarely seen in HL.

Spleen, Liver and Upper abdomen

Spleen, splenic hilar nodes and celiac nodes are earliest

abdominal sites of involvement in infradiaphragmatic HL.

25% spleen not clinically enlarged even harbor occult HL

and half of spleen enlarged to be on physical examination

or on imaging assessment are histologically normal.

Liver involvement is uncommon and always associated

with infiltration of spleen.

Retroperitoneal lymph node

Involvement early in course of inguinal presentation of

HL while relativly late in course of supradiaphragmatic

HL.

Bone marrow

is rarely involved at the time of diagnosis.

Patients with advanced stage disease, systemic

symptoms and MC or LD histology have a

higher risk of bone marrow involvement.

Bone: osseous involvement of HL produces

osteoblastic reaction.

Liver, skin and CNS are rarely involved in HL.

Alcohol-induced pain : Rarely, patients with Hodgkin’slymphoma complain of severe pain following alcoholingestion. The pain typically occurs within a few minutes afterthe ingestion of even a small amount of alcohol. Themechanism is unknown.

Abdominal pain : may be due to splenomegaly, Boweldysfunction due to adenopathy or bowel involvement orhydronephrosis.

Bone pain: in the area of bone destruction or invasion or diffuse marrow infiltration.

Neurogenic pain : by spinal cord compression,plexopathies, nerve root infiltration, meningeal involvement and complicating by varicella zoster.

Symptoms related to mass:

1. Mediastinal mass:

retrosternal chest pain, cough, or shortness of

breath.

2. Retroperitoneal lymphadenopathy

discomfort and pain in the paravertebral or

loin regions, particularly in the supine

position. often with psoas muscle invasion.

CNS involvement rare <1 % .

Bone marrow involvement uncommon (<10 %)

, in HL bone marrow involvement adversely

affects the prognosis.

Pel Ebstein fever is periodic and uncommon

but characteristic of HL.

1. Lymph node enlargement

2. Cachexia

3. Anemia

4. Splenomegaly

5. Hepatomegaly

6. Jaundice. rarely

Patients in developing countries have more ofadvanced disease (>50%) bulky disease (50%) and 'B'symptoms (40-50%) at-initial presentation.

In Western countries, three fourth of newly diagnosedchildren have early disease at presentation (stage I-II)and only one fourth of the patients have advanced(stage III-IV) disease.

The cause for such differences remains unknown.

It might be related to a delay in reporting tothe hospital, or to a more aggressive nature of thedisease, or to an altered host immune responseresulting in more aggressive clinical features.

Widely disseminated at presentation

Nodal involvement: Painless lymphadenopathy, often cervical region is the most common presentation

Hepatospleenomegaly

Extranodal : Intestinal lymphoma ( abdominal pain, anemia, dysphagia); CNS ( headache, cranial nerve palsies, spinal cord compression) ;

Skin, Testis; Thyroid; LungBone marrow (low grade): Pancytopenia

Systemic symptoms

Sweating, weight loss, itching

Metabolic complications: hyperuricemia, hypercalcemia, renal failure

Compression syndrome:

Gut obstruction

Ascites

SVC obstruction

Spinal Cord Compression

Patients may present with some emergent problem(s) that require immediate intervention and therapy. These include:

Spinal cord compression

Pericardial tamponade

Hypercalcemia (eg, adult T cell leukemia-lymphoma)

Superior or inferior vena cava obstruction

Hyperleukocytosis (eg, B or T cell lymphoblastic leukemia/lymphoma)

Acute airway obstruction (eg, mediastinal lymphoma)

Lymphomatous meningitis and/or CNS mass lesions

Hyperuricemia and tumor lysis syndrome

Hyperviscosity syndrome (eg, lymphoplasmacytic lymphoma with Waldenstrom macroglobulinemia)

Clinical differentiation

between

HL and NHL

s.no. HL NHL

1 Frequency Less common (30%) More common (70%)

2 age Bimodal peaK Any age

incresing with age

3 B- symptoms Early & prominent Late & not prominent

4 Dissemination Unifocal origin

Well localised at dx

Multicentric origin

Widespread at dx

5 splinomegaly More common Less common

6 GIT involvement uncommon common

7 CNS involvement uncommon common

8 BM involvement Late Early

9 Alcohol test common uncommon

10 anaemia Late Early

sn HL NHL

11 pruritus Common lesscommon

12.a LN involvment-

-presention

90% nodal

10% extra nodal

60% nodal

40% extra nodal

b Size Smaller Larger

c Rate of growth Slow Fast

d Consistency Rubbery elastic Variegated or ferm

e Matting Rare May be seen

f Local temp. N May be raised

g Tendernes Absent May be present

h Waldeyer`s ring Less common More common

i Epitrochlear nodes Less common More common

j Mediastinal LN More common Less common

Stage is the term used to describe the extent of tumor that has spread through the body( I and II are localized where as III and IV are advanced.

Each stage is then divided into categories A, B, and E

A: No systemic symptoms

B: Systemic Symptoms such as fever, night sweats and weight loss

E: Spreading of disease from lymph node to another organ

Stage I: limited or generalized plaques without adenopathy

or histologic involvement of lymph nodes

Stage II: limited or generalized plaques with adenopathy, or

cutaneous tumors without adenopathy; without histologic

involvement of lymph nodes or viscera

Stage III: generalized erythroderma, with or without

adenopathy; without histologic involvement of lymph nodes

or viscera

Stage IV: histologic involvement of lymph nodes or viscera

with any skin lesions; with or without adenopathy

Diagnosis-Lymphoma

History- a careful history of pt. should be taken,

including especially emphasis on presence of

B- symptoms these –

Unexplained fever

Drenching night sweats

Wt.loss greater than 10% of body wt in last 6

months

Other symptoms- should be noted these-

alcohol intolerance- pain in area of nodal

involvement after taking alcohol occur in about

8% of case of HL

Pruritis

Fatigue

Respiratory problem like- SOB, Dyspnoea etc.

Physical examination- should note-

-Palpable node ( number, size, location, shape,

consistency-(Indian rubbery) , mobility )

-Palpable viscera

CBC, PBF, RFT, LFT, ESR, S.LDH, ALP, S.protein

Hematologic evaluation may reveal-

Anemia

Leucopenia /Leucocytosis

Lymphopenia

Thrombocytopenia-may be indicative BM

involvement

Thrombocytosis- often PNS effect

Anemia,leucocytosis, lymphopenia,

hypoalbumenia,

elevated LDH -adverse prognostic factor

especially if pt. in advanced stage 3-4)

S.ALP level- may be non specific marker of tumor

activity, hepatic& bone marrow involvement and

bone disease

ESR- may correlate with response to treament &

subsequent disease activity & a prognostic factor

for limited disease (stage 1-2)

Other marker- S.Ca+, LDH, beta2 microglobulin

HBV-for chemo.-Rituximab

Chest radiograph – PA & Lateral view

Mediastinal adenopathy may be assess by -

measurement of maximum width of mediastinal

mass divided by maximum intra-thoracic

diameter near the level of diaphragm on

standing PA chest radiograph

When this ratio exceeds 1:3,disease defined as

Bulky

Other definition of bulky mediastinal

adenopathy

A nodal mass > 10 cm & a ratio of mediastinal

mass to chest diameter at T5-6 exceeding 0.35

this employed in EORTC (European

organization for reaserch & treatment of cancer

)

Abdominal & pelvic CT scan- indicated to note the presence of enlarge LN in retro-peritoneal area, hepatospleno-megaly, or focal nodules in spleen & liver.

LN usually enlarged on CT if their short axis measurement exceeds 1 cm

-LN inv. if LA >1.5 cm

or LA >1.1 & SA >1.0 cm

-LN uninv. if both axis <1.0 cm

2-D echocardiography for anthracycline CT.

Usually splenomegaly & hepatomegaly alone

can not represent involvement by HL

Often enlarged spleen not involved at the time

of presentation

But presence of focal nodules usually indicative

of involvement by HL

Overall accuracy rate for detection of HL in

spleen is 58% by CT scan

Sensitivity, specificity, & overall accuracy rate

of CT in identifying nodal disease is -65% ,

92%, & 87%

A CT scan of neck may be indicated if

irradiation to cervical node given, --

to identify their precise location for treatment

planning

Gallium-67 isotope

Affinity for lymphomas

Good sensitivity/specificity

If treatment makes Ga scan negative, good

chance at lasting remission

May find occult disease

PET – positron emission tomography

FDG – 18-fluoro deoxy-glucose

Taken by actively metabolic cells

Good sensitivity/specificity

FDG-PET scan used in initially staging in HL &

largely replaced Gallium imaging for that

purpose

More sensitive than CT & Gallium imaging &

more convenient than Gallium because shorter

duration between injection & scanning ( 1hr.

Vs. 48to72hr )

Useful as follow-up study to evaluate residual

detected by CT scan

MRI– it main value in staging evaluation of

women during pregnency

Bx. a needle bx. of posterior iliac crest bone

marrow may be indicated in pt. with B-symptom

or clinical evidence of sub-diaphragmtic

disease.

Overall incidence of BM involvement by HL

only 5-10%.

Evaluation of ejection fraction for doxorubicin containing regimens-2D-Echo.

Pulmonary function test if ABVD or BEACOPP used.

Pneumococcal, H.flu, & meningococcal vaccines, if splenic RT indicated.

HIV test

Pregnancy test if women of child bearing age

Counseling for fertility, smoking cessation & psychological destress

HBV

FNAC -LN

Excisional biopsy is preferred to show nodal

architecture

(follicular vs diffuse).

Immunohistochemistry to confirm cells are lymphoid

LCA (leukocyte common antigen)

Monoclonal staining with Igk or Igl

Flow cytometry:

CD 19, CD20 for B cell lymphomas

CD 3, CD 4, CD8 for T cell lymphomas

Chromosome changes

14;18 translocation in follicular lymphoma

bcl-2 oncogene

t(8;14), t(2;8), t(8;22) in Burkitt’s lymphoma

c-myc oncogene

t(11;14) in mantle cell lymphoma

cyclin D1 gene

Bone marrow-

-70% inv. in SLL & LPCL

-50% inv. in FL

-15% inv. in DLBCL

CSF cytology

Definitions

The lymphoid tissues in the body:

Primary (central) lymphoid tissues i.e. thymus and bone marrow where lymphocytes

differentiate from

Secondary (peripheral) lymphoid tissues including lymph nodes, spleen, and gut

(mucosal)-associated lymphoid tissues (MALT)

Lymphoreticular System

Lymphoid system

Definition:

Fine needle = 22 gauge or smaller

Useful for :

Reactive conditions e.g. infectious disease

Metastatic tumors

High grade lymphomas

Core needle biopsy is adequate for the

diagnosis of metastatic carcinoma , but for

primary lymphoid disorders so far not

recommended.

Incisional biopsy is also not preferable in

primary lymphoid disorders.

Exicional biopsy of (whole) node with intact

capsule by sharp dissection is highly useful for

demonstration of nodal architecture, therefore

most favorable.

Methods used for evaluation

Histology / cytology

Microbiologic (Bacteriologic) study

Immunohistochemistry

Cytogenetics and molecular genetics

Electron microscopy

I. Follicular hyperplasia:

Caused by stimulation that activate humoral immunity

Increased and enlargement of large B cell rich germinal centres(secondary follicles) covered by a layer of resting B cell (the mantle zone)

Follicular center cells comprising the large proliferating lymphocytes (centroblasts), smaller cells having cleaved nuclear contour (so-called cleaved cells or centrocytes) and phagocyticmacrophages (cells with pale staining cytoplasm and tingiblebodies), some T cells and others. Eg. rheumatoid arthritis, toxoplasmosis, and the early stages of HIV infection.

It can be confused morphologically with follicular lymphomas . Findings that favor a diagnosis of follicular hyperplasia are

(1) the preservation of the lymph node architecture, with normal lymphoid tissue between germinal centers;

(2) variation in the shape and size of the lymphoid nodules;

(3) a mixed population of lymphocytes at various stages of differentiation; and

(4) prominent phagocytic and mitotic activity in germinal centers.

Neoplastic follicleReactive lymphoid follicles with the mantle zone

II. Paracortical (lymphoid) hyperplasia:

Caused by stimulation of cellular immunity

Widening of T cell regions of the node

Paracortical or interfollicular areas containing activated T cells (immunoblasts) and others. viral infections (such as EBV), following certain vaccinations (e.g., smallpox), and in immune reactions induced by certain drugsespecially phenytoin, hydralazine, allopurinol.

III. Sinus histiocytosis or Reticular hyperplasia:

Histiocytes = tissue cells, in this meaning includes macrophages and dendritic cells (Langerhans cells) along the sinusoidsSinus histiocytosis is often encountered in lymph nodes draining cancers and may represent an immune response to the tumor or its products..

Patients of all ages Risk FactorsAge >60 years

PS 2-4

LDH level Elevated

Extranodal involvement >1 site

Stage (Ann Arbor) III-IV

Patients 60 years (age-adjusted)PS 2-4

LDH Elevated

Stage III-IV

Shipp. N Engl J Med. 1993;329:987.

All ages Low (L) 0-1Low-intermediate (LI) 2High-intermediate (HI) 3High (H) 4-5

Age-adjusted L 0LI 1HI 2H 3

Risk

FactorsRisk Group

Shipp. Blood. 1994;83:1165.

Diffuse Large Cell Lymphoma –40- 50% of NHL

Most of B cell origin

Dual age peak: twenties and sixties

Rapidly enlarging, symptomatic mass at a single site

Commonly extranodal: GI, skin, bone, brain – although

liver, spleen and marrow not often involved at

presentation

Requires intensive therapy and CNS prophylaxis.

Express B cell markers-CD19, CD20, CD22, CD79a.

Types-

a. germinal center B cell

b. activated B cell sub-type

c. primary mediastinal

Follicular Lymphomas – 20-40% of adult NHLGenerally low grade

Usually age > 50 years

Characteristic t(14;18) in 90% of cases

Generalized, painless, lymphadenopathy. Spleen and marrow often involved at time of diagnosis (75%).

Long natural history (6-8 years) – but not affected by treatment

Treatment options: watchful waiting, purinenucleoside analogues, monoclonal antibodies to CD20

Becomes aggressive if progress to diffuse lymphoma – but still not treatable .

Lymphoblastic Lymphoma 40% of all childhood lymphomas: mostly males under 20 years

high grade lymphoma; closely related to T-cell Acute Lymphocytic Leukemia – and treated accordingly

present with a rapidly progressive mediastinal mass (50-70%)

early bone marrow spread, and onward to blood and meninges

Small Lymphocytic Lymphoma

4% of all NHL

older age group

generalized lymphadenopathy with enlarged liver and spleen

The only non-follicular low-grade lymphoma

prolonged survival – but not treatable

Mantle Cell Lymphoma B-Cell tumor believed to arise from the mantle of the follicle (as opposed to the other lymphomas that arise from the middle)

Older males: disseminated disease

Aggressive and incurable

T(11; 14) - cyclin D1 driven monoclonal expansion

Burkitt’s Lymphoma Endemic in parts of Africa – presents with maxillary/madibularmass

North America – presents with a progressive abdominal mass

Children and young adults (30% of childhood NHL)

Fastest growing human neoplasm

Intensive chemotherapy: 50% long term survival

20-30% risk of CNS involvment – provide intrathecalprophylaxis

Burkitt’s lymphoma

Hairy Cell Leukemia