Hodgkin’s lymphoma

Rakesh Biswas

MD, Professor, Department of Medicine, People's College of Medical Sciences,

Bhanpur, Bhopal, India

A 25 year old lady

1 month of evening rise of temperature, night sweats and noticed a lump in her

neck

On examination pallor, generalized lymphadenopathy,

hepatosplenomegaly

I wasn't feeling well, still couldn't shake the cold that had been plaguing me for what seemed

like months.

But all in all, not feeling too bad, either.

It is required that anybody teaching in the schools have a clear tuberculosis

record.

After waiting several minutes, the nurse read my test site.

She said it seemed to her there was a little swelling that shouldn't be there,

and she asked me to wait and see the doctor.

I started to get a little bit nervous, I mean, Tuberculosis?

Was that possible?

The doctor brought me into her room and she examined me, and she said she could feel tumors in my neck. Had I

noticed them?

LymphomaClonal malignant disorders that are derived Clonal malignant disorders that are derived

from lymphoid cells: either precursor or from lymphoid cells: either precursor or mature T-cell or B-cellmature T-cell or B-cell

Majority are of B- cell originMajority are of B- cell origin

Divided into 2 main types :Divided into 2 main types :

1. 1. Hodgkin’s lymphomaHodgkin’s lymphoma

2. 2. Non - Hodgkin’s lymphomaNon - Hodgkin’s lymphoma

Hodgkin’s Disease

Histologically & clinically a distinct Histologically & clinically a distinct malignant diseasemalignant disease

Predominantly, B-cell diseasePredominantly, B-cell diseaseCourse of the disease is variable, Course of the disease is variable,

but the prognosis has improved but the prognosis has improved with modern treatmentwith modern treatment

Etiology

? Infection – ? Infection – EBVEBV

? Environmental factors? Environmental factors

REAL* Classification

Classic:Nodular SclerosisNodular SclerosisLymhocyte richLymhocyte richMixed CellularityMixed CellularityLymhocyte depletedLymhocyte depleted

Non-ClassicNodular Lymphocyte predominant Nodular Lymphocyte predominant

*REAL – Revised European,American,lymphoma

Clinical featuresBimodal age distribution :distribution :

young adults young adults ( 20-30 yrs)( 20-30 yrs) & elderly & elderly (> 50yrs) (> 50yrs) MMay occur at any ageay occur at any age

M > FM > FLymphadenopathyLymphadenopathy::

most often cervical region most often cervical region asymmetrical, discreteasymmetrical, discretepainless, non-tenderpainless, non-tenderelastic character on palpation ( rubbery)elastic character on palpation ( rubbery)not adherent to skinnot adherent to skin fluctuate in sizefluctuate in size

Contiguous spread via the lymphatic chain Contiguous spread via the lymphatic chain eg.eg.involvement of abdominal & thoracic involvement of abdominal & thoracic LNs LNs

Extra nodal disease - rareExtra nodal disease - rareHepatospleenomegalyHepatospleenomegaly

Constitutional symptoms ( Constitutional symptoms ( B symptoms ))Night sweats, Night sweats, sustained fever > 38 degree celsius,sustained fever > 38 degree celsius,loss of weight >10% of body weight in 6 moloss of weight >10% of body weight in 6 mo

Fever sometimes cyclical Fever sometimes cyclical (‘Pel-Ebstein fever’)Pain at the site of disease after drinking Pain at the site of disease after drinking

alcoholalcoholPallorPallorPruritis Pruritis Symptoms of Bulky (>10 cm) diseaseSymptoms of Bulky (>10 cm) disease

A zillion tests were done, blood drawn a zillion times, a zillion

questions by a million doctors.

Finally it was decided they would have to perform a biopsy

on one of the tumors to get a diagnosis.

Investigations CBPCBP : :

Anemia ( normochromic / normocytic), eosinophilia, Anemia ( normochromic / normocytic), eosinophilia, neutrophilia, lymphopenianeutrophilia, lymphopenia

ESR -raisedESR -raised LFT- (liver infil / obs at porta hepatis)LFT- (liver infil / obs at porta hepatis) RFT- prior to treatmentRFT- prior to treatment Urate , Ca, Urate , Ca, LDH - adverse prognosisLDH - adverse prognosis CXR- mediastinal mass CXR- mediastinal mass CT thorax / abdomen / pelvis-for stagingCT thorax / abdomen / pelvis-for staging Other: Gallium scan, PET, Other: Gallium scan, PET, Lymphangiography , Lymphangiography ,

LaporotomyLaporotomy

LN FNAC / biopsyLN FNAC / biopsy : :

Malignant Malignant REED-STERNBERG ( RS) Cell: Bi-: Bi-

nucleate cell with a prominent nucleolus. Derived nucleate cell with a prominent nucleolus. Derived from B cell, at an early stage of differentiationfrom B cell, at an early stage of differentiation

Reactive background of eosinophils, Reactive background of eosinophils, lymphocytes, plasma cells lymphocytes, plasma cells

Fibrous tissueFibrous tissue

The operation was done on February third, my boyfriend's birthday.

I made him a card out of paper I had…

Hard to celebrate your boyfriend's birthday while getting ready to get

operated on.

REED-STERNBERG ( RS ) CellREED-STERNBERG ( RS ) Cell

REED-STERNBERG ( RS) CellREED-STERNBERG ( RS) Cell

The X-ray technician came out again, looking for me.

"We're not ready for you yet, the Doctors are still reading your chart, but

we wanted to make sure you didn't leave.

Just wait a few minutes and the doctor will be out to talk to you."

I've read in novels the expression "my heart sank" but I'm not sure I ever really felt that sort of thing until just

about then.

I'd been telling myself there was nothing to worry about, all was ok, but

this was a clear cut sign that something was very. very wrong

>10 cm

Bulky disease

LymphangiographyLymphangiography

Staging Stage I : Involvement of single LN region (I) or extra : Involvement of single LN region (I) or extra

lymphatic site (IAlymphatic site (IAEE ) ) Stage II : Two or more LN regions involved (II) or an Two or more LN regions involved (II) or an

extra lymphatic site and lymph node regions on the extra lymphatic site and lymph node regions on the same side of diaphragmsame side of diaphragm

Stage III : Involvement of lymph node regions on both Involvement of lymph node regions on both sides of diaphragm, with (IIIsides of diaphragm, with (IIIEE) or without (III) localized ) or without (III) localized extra lymphatic involvement or involvement of the extra lymphatic involvement or involvement of the spleen (IIspleen (IISS) or both (IIS) or both (IISEE) )

Stage IV : Involvement outside LN areas (Liver, bone Involvement outside LN areas (Liver, bone marrow)marrow)

AA : Absence of ‘B’ symptoms : Absence of ‘B’ symptoms BB : B symptoms present : B symptoms present

I had Stage IVb Hodgkin's Disease, a form of cancer of the lymph nodes.

Well, it's sort of hard to describe what hearing something like that does.

It seemed impossible that the nodes in my neck, and the masses that were supposedly

on my lungs were cancer.

How could that be? I just was amazed.

I said "this is unbelievable." and felt more or less detached, numb.

Treatment

RTRTChemoChemoBMT / SCTBMT / SCTAntibody treatment: Rituximab target CD-20Antibody treatment: Rituximab target CD-20SupportiveSupportive

Treatment - Guidelines Indications for RT:

Stage I diseaseStage I diseaseStage II disease with 3 or lesser areas involvedStage II disease with 3 or lesser areas involvedFor Bulky diseaseFor Bulky diseaseFor pressure problemsFor pressure problems

Indications for CTAll with B symptomsAll with B symptomsStage II disease with >3 areas involvedStage II disease with >3 areas involvedStage III and IV diseaseStage III and IV disease

Treatment Stage IA , Stage IIA with 3 or < 3 areas involved: : RadiotherapyRadiotherapy

Stage IB, Stage II A with > 3 areas , Stage IIB: : ChemotherapyChemotherapy every 3-4 weeks, 6-8 cycles; every 3-4 weeks, 6-8 cycles; either alone, or in combination with either alone, or in combination with radiotherapyradiotherapy

Stage III & IV : ChemotherapyChemotherapy + + RadiotherapyRadiotherapy ( for bulky ( for bulky disease or palliation of symptoms)disease or palliation of symptoms)

Irradiation fields used in Hodgkin’s Lymphoma

Chemotherapy MOPP :

Nitrogen Mustard, Nitrogen Mustard, VVincristine (Oncovin), incristine (Oncovin), PProcarbazine, rocarbazine, PrPrednisoloneednisolone

ABVD: AAdriamycin, driamycin, BBleomycin, leomycin, VVinblastine, inblastine, DDacarbazineacarbazine

Higher dose for relapse or younger pts with poor Higher dose for relapse or younger pts with poor prognostic featuresprognostic features

After six cycles of chemotherapy, my CT scans still show masses on my

chest and in my neck.

On July 7, I had a meeting with my doctors, and was told that if I continued

with standard chemotherapy, my chances of being cured stand at less

than ten per cent.

Prognosis

Overall 10 yr survival – 80%Overall 10 yr survival – 80%

In long term survivors there is a risk ofIn long term survivors there is a risk ofsecondary malignancy: (secondary malignancy: (leukemia , NHL), Solid ), Solid

tumors- Lung, breast InfectionsInfectionsCardiac, pulmonary, endocrinal abnormalitiesCardiac, pulmonary, endocrinal abnormalities

International Prognostic Index (IPI)

AgeAgeAdvanced stage diseaseAdvanced stage diseasePerformance statusPerformance statusElevated LDHElevated LDHPresence of Extra nodal diseasePresence of Extra nodal disease

Non Hodgkin’s lymphoma

Incidence is increasingIncidence is increasingNHL>HDNHL>HDMedian age of presentation is Median age of presentation is 65-70 yrs65-70 yrsM>FM>FMore often clinically disseminated at More often clinically disseminated at

diagnosisdiagnosisB-cell-70% ; T-cell-30%B-cell-70% ; T-cell-30%

‘1990…Although I had been feeling fine, no different from normal, I was

worried about this lump in my neck that I had for several months.

I first thought it was just because I had some sort of infection, but it didn't go

away.

Clinical features Widely disseminated at presentation Widely disseminated at presentation Nodal involvementNodal involvement: :

Painless lymphadenopathyPainless lymphadenopathy, often cervical , often cervical region is the most common presentationregion is the most common presentation

HepatospleenomegalyHepatospleenomegaly ExtranodalExtranodal : :

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

Skin, Testis; Thyroid; Lung Bone marrow (low grade): (low grade): PancytopeniaPancytopenia

Systemic symptomsSystemic symptomsSweating, weight loss, itchingSweating, weight loss, itchingMetabolic complications:Metabolic complications:

hyperuricemia, hyperuricemia, hypercalcemia, hypercalcemia, renal failurerenal failure

Compression syndrome:Compression syndrome:Gut obstructionGut obstructionAscitesAscitesSVC obstructionSVC obstructionS/C CompressionS/C Compression

'The surgeon took a biopsy of the lump, taking a few cells out with a needle to be looked at under the microscope.

When the results came back a few weeks later, he told me that they

showed I had non-Hodgkin's lymphoma

Diagnosis and staging

Similar to HD Similar to HD plus, Bone marrow aspirate & trephineBone marrow aspirate & trephine Immunophenotyping : Monoclonal antibodies Immunophenotyping : Monoclonal antibodies

directed against specific lymphocyte associated directed against specific lymphocyte associated antigens antigens B B cell antigens ( CD 19, 20, 22); cell antigens ( CD 19, 20, 22); T cell antigens ( CD 2, 3, 5 & 7)T cell antigens ( CD 2, 3, 5 & 7)

Immunoglobulin determination: Ig G / IgM Immunoglobulin determination: Ig G / IgM praprotein markerpraprotein marker

HIVHIV

Classification

REALREALClinical / Working FormulationClinical / Working Formulation

Low gradeLow grade Inermediate gradeInermediate grade High gradeHigh grade

Classification

Low grade

Proliferation: LowProliferation: Low

Course:Course: Indolent Indolent

Symptoms: -veSymptoms: -ve

Treatment: Not curable Treatment: Not curable

High grade

HighHigh

Rapid, fatal(un-Rx)Rapid, fatal(un-Rx)

+ve+ve

Potentially CurablePotentially Curable

StagingSimilar to HD

Etiology Cannot be attributed a single causeCannot be attributed a single cause Chromosomal translocationsChromosomal translocations: t (14, : t (14,

18)18)

Infection:Infection: Virus:Virus:EBV, HTLV,HHV-8, HIVEBV, HTLV,HHV-8, HIV Bacteria: H.Pylori - Gastric lymphomaBacteria: H.Pylori - Gastric lymphoma

Immunology: Immunology: Congenital immunodeficiency,Congenital immunodeficiency, Immunocompromised patients - Immunocompromised patients - HIV, organ transplantationHIV, organ transplantation

'When I went back a couple of weeks later, he said that the results showed I

had stage I indolent follicular non-Hodgkin's lymphoma, which is a slow-

growing form of the disease.

He said that the good news was that only one lymph node was affected and

that I had no B symptoms.

So, he suggested that I have radiotherapy on the swollen lymph

node in my neck to make it go away.

Because I had heard so many stories about how radiotherapy can

make you sick and your hair fall out, I was quite worried

'In the end, I didn't have any real side effects, apart from feeling a bit tired, and the lump in my neck went away

completely.

After a check-up a couple of weeks later, the haematologist told me that I should come back every 6 months for another CT scan to make sure that the non-Hodgkin's lymphoma hadn't come

back.

Management

Low grade: Asymptomatic : No treatment ; Asymptomatic : No treatment ;

RadiotherapyRadiotherapy for localised disease (Stage 1); for localised disease (Stage 1); Chemotheraphy: mainstay is Chemotheraphy: mainstay is

ChlorambucilChlorambucil; Initial response good , but ; Initial response good , but repeated relapses, median survival 6-10 yrs; repeated relapses, median survival 6-10 yrs; Newer: Fludarabine, 2-CdA (Chlorodeoxyadenosine)Newer: Fludarabine, 2-CdA (Chlorodeoxyadenosine)

Monoclonal antibody: RituximabMonoclonal antibody: Rituximab SCT/BMTSCT/BMT

In 1994, when I was between my CT appointments, I found another lump in my neck, so I called up the specialist hospital and they told me to come back early for my next scan.

At the same time, they did the bone marrow test and the LDH blood test again.

When I went back to see the haematologist, he told me that they had found…

…swollen lymph nodes in my chest and my armpit, as well as my neck,

…which really worried me, although he said the disease had not spread to my bone marrow.

Aggressive ( high / intermediate grade):

ChemotherapyChemotherapy: mainstay : mainstay CHOP -every 3 weeks, at least -every 3 weeks, at least 6 cycles 6 cycles Cyclophosphamide, yclophosphamide, Doxorubicin oxorubicin HHydrochloride, ydrochloride, Vincristine, incristine, Prednisolononerednisolonone

'We talked about what treatment I should have, and the doctor said that,

as I had radiotherapy on my neck before, and now other lymph nodes

were involved, I couldn't have the same treatment again.

However, he offered me chemotherapy instead, and I was given the treatment

over the next six months.

High risk cases with poor prognostic High risk cases with poor prognostic factors or relapse : factors or relapse : High dose chemotherapy High dose chemotherapy combined with autologous BMT / SCTcombined with autologous BMT / SCT

Monoclonal antibodyMonoclonal antibody

With CNS involvement / leukemic relapse : With CNS involvement / leukemic relapse : Similar to ALLSimilar to ALL

Prognosis

Low grade : Median survival –10 yrsLow grade : Median survival –10 yrsHigh Grade:High Grade:

Increasing age, advanced stage, concomitant Increasing age, advanced stage, concomitant disease, raised LDHdisease, raised LDH,,T- cell phenotypeT- cell phenotype : Poor : Poor prognosisprognosis