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DHANYA A N 8th term

Hodgkins lymphoma
It is a unique form of lymphoid malignancy characterised by pleomorphic lymphocyte infiltrate interspersed by malignant multinuclear giant cell(RS cell). Thomas hodgkin in his historic paper entitled On Some Morbid Appearances of the Absorbent Glands and Spleen presented to the Medical Society London on jan 10, 1832 described this disease for the first time. It is said that the hodgkins reed-sternberg cell are clonal lymphoma cells derived from B-cells, hence the term hodgkins lymphoma is preferred over the hodgkins disease.

Etiology and Epidemiology


Hodgkins lymphoma is more common in whites than in blacks and

more common in males than in females.


There is a bimodal age distribution with one peak in mid to late 20s and

the other one in 80s.


Majority of patients in developing countries are associated with Epstien

Barr virus in RS-cells. Chronic stimulation due to EBV infection is postulated to results in pleomorphic infiltration, some of the cell undergo malignant transformation subsequently.
Infection by HIV is also a risk factor for developing hodgkins

lymphoma.
Rarely hodgkins lymphoma can be familial.

Clinical features and Physical Examination


The usual presentation is with painless lymphadenopathy, commonly in

cervical region(76%). On examination these have rubbery feel.


Other areas of involvement include lymphoid tissue in

mediastinum(60%), abdomen and groin, axilla and spleen(20-25%)


Less common site include liver, bone marrow, extra nodal soft tissue,

lungs,pleura, pericardium and waldeyers ring.


Constitutional symptoms commonly termed as B symptoms indicate B

systemic disease, they are unexplained wt loss(>10% in last 6 months),


unexplained fever(>38 degree c >3 days), drenching night sweats.
Symptoms like pruritus,pain in enlarged lymph nodes, pel ebstein fever

are uncommon.

Classification
Diagnosis of hodgkins lymphoma requires demonstration of Reed Sternberg

cells in the biopsy. These RS cells are large multinucleated giant cells with a clear halo around prominent nucleoli(caterpillar or owl eye appearance), which are

scattered in a background rich in lymphocytes, histiocytes, eosinophils and


plasma cells effacing the normal lymhoid architecture. Based on the relative preponderance of these cells as well as the degree of sclerosis or fibrosis, WHO classified hodgkins lymphoma as follows
Nodular lymphocyte predominant hodgkins lymphoma Classical hodgkins lymphoma

-nodular sclerosis

-mixed cellularity
-lymphocyte rich -lyphocyte depleted

Nodular lymphocyte predominant hodgkins lymphoma.

Nodular sclerosis classical hodgkins lymphoma

Mixed cellularity classical hodgkins lymphoma

Lymphocyte rich classical hodgkins lymphoma

Lymphocyte depleted classical hodgkins lymphoma

Staging
Ann Arbor staging system
I Involvement of a single lymph node region or a single extralymphatic

organ or site(IE)
II- Involvement of two or more lymph node region on the same side of

the diaphragm(II) or localised involvement of an extralymphatic organ or site(IIE)


III- Involvement of lymph node region on both sides of diaphragm(III)

or localised involvement of an extralymphatic organ or site(IIIE) or spleen(IIIS) or both(IIISE)


IV- Diffuse or disseminated involvement of one or more extralymphatic

organs with or without associated lymph node involvement. Bone marrow n liver involvement are always stageIV.

Diagnosis and Laboratory Evaluation


Mandatory procedures
History- Fever, wt loss and night sweat Physical examination- Measurements of all palpable LN with biopsy of

doubtful nodes Complete blood count and biochemistry including LDH Chest x-ray CT scan of thorax, abdomen and pelvis Tissue excision biopsy and aspiration Optional procedures Post nasal space x-ray if cervical nodes are involved Liver biopsy Radioisotope bone scan if stage IV Pleural cytology if there is pleural effusion PET scan Staging laparotomy,lymphangiography and gallium scan

Differential Diagnosis
Non hodgkins lymphoma
Infectious mononucleosis Tubercular lymphadenitis

Bronchogenic carcinoma
Head and neck squamous cell carcinoma Sarcoidosis

Cat scratch disease


Infection in draining area(ENT or skin)

Prognostic Factors
Adverse prognostic factors apart from advanced stage

in hodgkins lymphoma include Age- >50 yr ESR- >50 Large mediastinal mass and four or more involved regions Depending on these, three prognostic groups have been identified Early stage favorable group include stage I, II with none of the above adverse prognostic factor Early stage unfavorable group include stage I, II with one or more of the adverse risk factors Advanced stage include stage III, IV, serum albumin <4 gm%, presence of B symptoms.

Treatment strategies in patients with hodgkins lymphoma based on stage of disease and patients age
Young patients Early stage favorable RT alone- extended field(30-36Gy) Elderly patient

Chemotherapy(2cycles of ABVD) and involved field RT


Chemotherapy(4cycles of ABVD) and involved field RT Only chemotherapt(68cycles)

Early stage unfavorable

Chemotherapy(8cycles)+ involved field RT


Chemotherapy (8cycles) with or without consolidation local RT(2036Gy)

Advanced stages

Treatment
Radiotherapy- It offers effective regional control of disease in

patients with hodgkins lymphoma. The mantle field comprises of submandibular, cervical, supraclavicular, infraclavicular, axillary, mediastinal, subcarinal and hilar lymph node and this is used for supra-diaphragmatic disease. Para-aortic, splenic and pelvic field radiations are used for infra-diaphragmatic disease. Involved field radiation is commonly used in the present era of combined modality treatment, the field comprises the entire involved lymph node regions.

Chemotherapy After the discovery of cytotoxic effect of

nitrogen mustard in 1940, a number of different drugs were developed and showed efficacy in hodgkins lymphoma. The first breakthrough four drug combination was developed in 1967 i.e MOPP(mechlorethamine, vincristin,

procarbazine, prednisalone) achieving cure in more than


50% patients with stage III, IV disease. Thereafter many chemotherapy regimens like COPP, ABVD(doxorubicin,

bleomycin, vinblastine, dacarbazine) have been evaluated.


ABVD regimen is associated with less myelotoxicity, less incidence of secondary leukaemias and infertility and has been established as the standard chemotherapy regimen.

Combined modality therapy- It include radiotherapy and

chemotherapy aiming at overcoming the tumor resistance,

improving the outcome, reducing the toxicity with either


modality. With combination chemotherapy, the dose of radiation for non bulky site can be reduced to 20 Gy and even the size of the RT portal can de decreased from extended field to involved field. It is recommended that chemotherapy always precede the radiotherapy. Advantage include early effective treatment of systemic disease, delay in induction of irreversible loss of bone marrow function, potential to use smaller RT field.

High dose chemotherapy with stem cell support- It is extensively

used in patients with relapsed and refractory hodgkins lymphoma. BEAM(BCNU, etoposide, cytocine arabinoside, melphalan) is one of the commnly used high dose conditioning chemotherapy regimen. Combination chemotherapy regimen used as salvage therapy in relapsed or residual disease include MINE, DHAP, ESHAP, ICE, mini BEAM, dexa BEAM. With the

combination treatment modalities 5-yr survival of 70-80% has


been achieved in patients with advanced stage hodgkins lymphoma.
Newer modalities of therapy- Monoclonal antibodies,

radioimmunoconjugates, cellular therapy, newer chemotherapeutics like gemcitabin, vinorelbine are also used.

Treatment related complication


Potentially fatal

-Acute myeloid leukaemia -Diffuse high grade NHL -Solid tumors(mostly lung and breast tumor) -Overwhelming bacterial sepsis following splenectomy or splenic irradiation Potentially serious -Myocardial damage from radiation and anthracyclines -Lung fibrosis -Sterility -growth abnormalities in children -opportunistic disease and psychological problems Usually minor -Chemical or clinical hypothyroidism -long term alteration of lymphocyte function

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