Lymphoma

Lymphoma: Tumours of lymphoid tissues which represent abnormal proliferation of B

or T cells.

Majority are of B cell origin e.g. lymph node, spleen, and mucosal-associated lymphoid

tissue (MALT).

Lymphomas are B- or T-cell neoplasms that typically result in the enlargement of lymph

nodes; however, the spleen, bone marrow, and other tissues may also be infiltrated.

The expansion of malignant cell clone causes a partial or complete loss of normal lymph

node architecture and progressive enlargement of lymph nodes

These malignancies of lymphoid cells range from the most indolent to the most

aggressive human malignancies

The predominant pathological manifestations are in extramedullary tissue (lymph node)

These cancers arise from cells of the immune system at different stages of differentiation,

resulting in a wide range of morphologic, immunologic, and clinical findings.

Types of Lymphoma

Lymphomas can be classified histologically or clinically

Histologically they are divided into

Hodgkin’s lymphoma (HL)

Non hodgkin’s lymphoma (NHL)

Classification of Hodgkin's lymphoma

Is based on histopathology findings of lymph nodes

RYE classification categorizes Hodgkin's lymphoma into four types

Lymphocyte predominant (many lymphocytes & Reed-Sternberg cells)

Mixed cellularity (more Reed-Sternberg cells mixed with heterogeneous pop of

reactive cells)

Lymphocyte depleted (increased Reed-Sternberg cells & decreased reactive cells)

Nodular sclerosing

Histopathological Classification of Hodgkin’s Lymphoma

Classification Description

Lymphocyte-rich

or Lymphocytic

predominance

Is a rare subtype (5% of cases) show many features which may cause

diagnostic confusion with nodular lymphocyte-predominant B-cell non-Hodgkins

lymphoma (B-NHL). This form also has the most favorable

prognosis. Involving particularly peripheral lymph nodes.

Mixed-cellularity Is a common subtype (25% of cases) and is composed of numerous

classic RS cells admixed with numerous inflammatory cells including

lymphocytes, histiocytes, eosinophils, and plasma cells without

sclerosis. This type is most often associated with EBV infection and

may be confused with the early, so-called 'cellular' phase of nodular

sclerosing. More common in men, with systemic (B) symptoms.

Lymphocyte

depleted

Is a rare subtype, composed of large numbers of often pleomorphic RS

cells with only a few reactive lymphocytes which may easily be confused

with diffuse large cell lymphoma. Many cases previously classified

within this category would now be reclassified under anaplastic large

cell lymphoma. It is seen in HL associated with HIV.

Nodular sclerosing Is the most common subtype and is composed of large tumor nodules

showing scattered lacunar classical RS cells set in a background of

reactive lymphocytes, eosinophils, and plasma cells with varying

degrees of collagen fibrosis/sclerosis. Typically seen in young females,

involving particularly lymph nodes in the mediastinum and neck.

Classification of Non-Hodgkin’s lymphoma is father divided into three subtypes on the

basis of their proliferation rate.

Low grade lymphoma

Intermediate grade lymphoma

High grade lymphomas

 

Clinically lymphomas are classified according to their clinical presentations

Hodgkin’s lymphomas present with

Painless, progressive enlargement of the LNs, Spleen & general lymphoid tissue

More often localized to a single axial group of nodes (cervical, mediastinal and paraaortic)

Extra-nodal involvement is uncommon (does not involve extranodal areas)

Orderly spread by contiguity rarely involve the mesenteric nodes

Non Hodgkin’s Lymphoma presents present with

More frequent involvement of multiple peripheral nodes

Extra-nodal involvement is common

Non-contiguous spread mesenteric node commonly involved

Epidemiology and Predisposing The factor of Hodgkin's Lymphoma

Epidemiology

• Is more common in whites than in blacks

• More common in males than in females (female to male ratio is 2:1)

• A bimodal distribution of age at diagnosis has been observed

• One peak incidence occurring in patients in their 20s and the other in their 80s

Predisposing Factors

• Infection by HIV is a risk factor for developing Lymphocyte depleted Hodgkin's disease.

• There is an association between infection with Epstein Barr Virus (EBV) and Hodgkin's

disease.

Epidemiology of Non-Hodgkin's Lymphomas

• Are more frequent in the elderly (Common above 50 years) although it can also occur in

young children and adults

• More frequent in men than women

• More prevalent than Hodgkin's lymphoma

Predisposing Factors of Non-Hodgkin's Lymphomas

• Patients with both primary and secondary immunodeficiency states are predisposed to

developing non-Hodgkin's lymphomas e.g. HIV infection, use of radiotherapy &

chemotherapy for other cancer treatment and prolonged use of steroids such as in arthritis

• A number of environmental factors have been implicated in the occurrence of non-

Hodgkin's lymphoma, including

Infectious agents e.g. HTLV-1, EBV, Helicobacter pylori, HCV, and Human herpes

virus type 8

Chemical exposures

Medical treatments.

• Exposure to agricultural chemicals and an increased incidence in non-Hodgkin's

lymphoma has been reported

• HTLV-I infects T cells and leads directly to the development of adult T cell lymphoma

(ATL) in a small percentage of infected patients.

• The the cumulative lifetime risk of developing lymphoma in HTLV infected patients is 2.5%.

• EBV is associated with the development of Burkitt's lymphoma in central Africa and the

occurrence of aggressive non-Hodgkin's lymphomas in immunosuppressed patients in

western countries.

• Infection of the stomach by the bacterium Helicobacter pylori induce the development

of gastric MALT (mucosa-associated lymphoid tissue) lymphomas.

Clinical Features of Lymphoma

• Localized Adenopathy (lymphadenopathy)

 Especially in a cervical region most common mode of presentation

 These are usually painless and of rubbery consistency

• Systemic symptoms

 Occur in 25% of pt

 Fever (temperature >380C)

 Drenching night sweat

 Weight loss over 10% of body weight in 6 months

 Others: anorexia, lassitude, anaemia, pruritis

 Hepatomegaly or splenomegaly

 Occasionally alcohol induces pain at the site of enlarged lymph nodes

 Symptoms due to involvement of other organs e.g. lung-cough and breathlessness.

Clinical Features of Non-Hodgkin’s Lymphoma (NHL)

• Peripheral lymphadenopathy

• Most patients present with painless, superficial lymph node enlargement

• Extra-nodal presentation may involve

 Gastro-intestinal tract

 Lung

 Brain

 Testes

 Thyroid and skin (mycosis fungoides)

• Non –specific symptoms

 Fever

 Sweats

 Anorexia

 Weight loss

 Anemia

Differential Diagnosis, Investigation and Treatment of Lymphoma

Differential Diagnosis of HL

• TB Adenitis

• Chronic lymphocytic leukemia

• Non-Hodgkin’s lymphoma

• Secondary malignancies e.g. breast, stomach, and lungs

Differential Diagnosis of NHL

• HL

• TB Adenitis

• Chronic lymphocytic leukemia

Investigations for HL

• The important investigations for HL and NHL are not available in dispensaries and health

centers and therefore referring the patient suspected of having HL and NHL is necessary.

• The following (in general) can be done at hospital levels

 Investigation- to confirm the diagnosis and staging

 Blood count –may be normochromic, normocytic anemia, lymphopenia

 Raised erythrocyte sedimentation rate (ESR)

 Renal function test and liver function test

 Serum lactate dehydrogenase raised level is an adverse prognostic factor

 CAR show mediastinal widening with or without lung involvement

 Bone marrow aspirate

 Lymph node biopsy- confirmatory

 CT scans show intrathoracic involvement in 70% of cases

Investigations of NHL

• Full blood count

 Normochromic normocytic anemia

 Elevated white blood cells or neutropenia and thrombocytopenia are suggestive of

bone marrow infiltration.

• ESR may be elevated

• Urea and electrolytes

• Lumber puncture

• Bone marrow aspirate or Biopsy

• Lymph node biopsy

• CXR and CT scans of chest, abdomen, and pelvis

Treatment of HL

• Treatment depending on the type of lymphoma and the stage of diseases

This can be achieved at specialized hospital levels and not at primary health care facility

levels.

• Assigned by a combination of clinical findings & laboratory tests

• Definitive staging often require exploratory laparotomy with splenectomy

• Radiotherapy

• Involved nodes + next node group i.e local disease

• Chemotherapy can be used as salvage

CMT 05102 Internal Medicine I NTA Level 5 Semester 1 Student Manual

Session 15: Leukaemia and Lymphoma 166

• Chemotherapy for relapse after radiotherapy

• Cyclical combination chemotherapy

 All stage 4 disease

 Many stage 3

 Pt with localized bulky disease

Treatment for NHL

 Treatment of lymphomas varies greatly depending on tumor stage, histology (i.e.,

whether low, intermediate, or high-grade), symptoms, performance status, patient's age,

and co-morbidities.

 The Ann Arbor staging system is the most commonly used staging system for patients

with lymphomas

 Staging is important in selecting a treatment and also for prognosis. CT scan is

commonly used for staging. Lymphomas are staged from stage I-IV

 In this system stages I-IV can be appended by A or B designations. Patients with A

disease do not have systemic symptoms. The B designation is applied in patients with any

of the following symptoms:

 Unexplained loss of more than 10% of body weight in the preceding 6 months before

diagnosis

 Unexplained fever with the temperature above 38°C

 Drenching night sweats.

Stages of Non-Hodgkin’s Lymphomas

 Stage I

 Involves a single lymph node region (I) or localized involvement of a single

extra lymphatic organ or site (IE).

 Stage II

 Involves 2 or more lymph node regions on the same side of the diaphragm (II) or

localized involvement of a single associated extra lymphatic organ in addition to

criteria for stage II (IIE).

 Stage III

 Involves lymph node regions on both sides of the diaphragm (III) that also may be

accompanied by localized involvement of an extra lymphatic organ or site (IIIE),

spleen (IIIS), or both (IIISE).

 Stage IV

 Represents disseminated or multifocal involvement of one or more extra lymphatic

sites with or without associated lymph node involvement or isolated extra lymphatic

organ involvement with distant (non-regional) nodal involvement.

 Subscript letters designate involvement of extra lymphatic organs, as follows: L, lung; H,

liver; P, pleura; O, bone; M, bone marrow; and D, skin. The designation E is used when

extra-nodal lymphoid malignancies arise in tissues that are separate from but near the

major lymphatic aggregates.

 Treatment modalities include

 Medical treatment

 Radiotherapy

 Surgical treatment

 Bone marrow transplantation                                                                                 

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