1. Dr. Rajesh Kumar
ATRICTRI
Bikaner

2. 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

3. 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

4. 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.

5. Local Symptoms of hodgkin’s lymphoma
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.

6. 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

7. 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

8. 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.

9. 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.

10. 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.

11. Alcohol-induced pain : Rarely, patients with Hodgkin’s
lymphoma complain of severe pain following alcohol
ingestion. The pain typically occurs within a few minutes after
the ingestion of even a small amount of alcohol. The
mechanism is unknown.
Abdominal pain : may be due to splenomegaly, Bowel
dysfunction due to adenopathy or bowel involvement or
hydronephrosis.
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.

12. 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.

13. 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.

14. 1. Lymph node enlargement
2. Cachexia
3. Anemia
4. Splenomegaly
5. Hepatomegaly
6. Jaundice. rarely

16. Patients in developing countries have more of
advanced disease (>50%) bulky disease (50%) and 'B'
symptoms (40-50%) at-initial presentation.
In Western countries, three fourth of newly diagnosed
children 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 to
the hospital, or to a more aggressive nature of the
disease, or to an altered host immune response
resulting in more aggressive clinical features.

19. 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; Lung
Bone marrow (low grade): Pancytopenia

20.  Systemic symptoms
Sweating, weight loss, itching
Metabolic complications: hyperuricemia,
hypercalcemia, renal failure
Compression syndrome:
Gut obstruction
Ascites
SVC obstruction
Spinal Cord Compression

21. 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)

23. Clinical differentiation
between
HL and NHL

24. 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

25. 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

26. 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

30. 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

31. Diagnosis-Lymphoma

32. 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

33. 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.

34. Physical examination- should note-
-Palpable node ( number, size, location, shape,
consistency-(Indian rubbery) , mobility )
-Palpable viscera

35. CBC, PBF, RFT, LFT, ESR, S.LDH, ALP, S.protein
Hematologic evaluation may reveal-
Anemia
Leucopenia /Leucocytosis
Lymphopenia
Thrombocytopenia-may be indicative BM
involvement

36. Thrombocytosis- often PNS effect
Anemia,leucocytosis, lymphopenia,
hypoalbumenia,
elevated LDH -adverse prognostic factor
especially if pt. in advanced stage 3-4)

37. 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

38. 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

39. 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
)

40. 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.

41. 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

42. 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

43. Gallium-67 isotope
Affinity for lymphomas
Good sensitivity/specificity
If treatment makes Ga scan negative, good
chance at lasting remission
May find occult disease

45. PET – positron emission tomography
FDG – 18-fluoro deoxy-glucose
Taken by actively metabolic cells
Good sensitivity/specificity

46. 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

48. 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%.

49. 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

50. 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

51. 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

52. Bone marrow-
-70% inv. in SLL & LPCL
-50% inv. in FL
-15% inv. in DLBCL
CSF cytology

53. Lymphoreticular System
Definitions
The lymphoid tissues in the body:
Lymphoid system
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)

54. Definition:
Fine needle = 22 gauge or smaller
Useful for :
 Reactive conditions e.g. infectious disease
 Metastatic tumors
 High grade lymphomas

55. 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.

56. Methods used for evaluation
Histology / cytology
Microbiologic (Bacteriologic) study
Immunohistochemistry
Cytogenetics and molecular genetics
Electron microscopy

57. 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 phagocytic
macrophages (cells with pale staining cytoplasm and tingible
bodies), 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.

58. Reactive lymphoid follicles with the mantle zone Neoplastic follicle

59. 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 drugs
especially 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..

60. Patients of all ages Risk Factors
Age >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.

61. Risk
Risk Group Factors
All ages Low (L) 0-1
Low-intermediate (LI) 2
High-intermediate (HI) 3
High (H) 4-5
Age-adjusted L 0
LI 1
HI 2
H 3
Shipp. Blood. 1994;83:1165.

62. 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

63. Follicular Lymphomas – 20-40% of adult NHL
Generally 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, purine
nucleoside analogues, monoclonal antibodies to
CD20
Becomes aggressive if progress to diffuse lymphoma
– but still not treatable .

65. 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

66. 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/madibular
mass
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 intrathecal
prophylaxis

67. Burkitt’s lymphoma

68. Hairy Cell Leukemia