INVESTIGATIONS OF LYMPHOMA

GENERAL BLOOD TESTS FBE / CBC U&E LFT ESR LDH Beta 2 microglobulin Protein electrophoresis HIV and HTLV II serology

FBE Look for:anaemia, WCC, lymphopenia,

neutrophilia/ neutropenia, eosinophiliaHodgkin disease NHL

RBC Anaemia: anaemia of chronic disease / bone marrow infiltration / autoantibodies (positive warm Coombs test)

Anaemia: bone marrow infiltration/ autoimmune hemolysis/ bleeding/ anaemia of chronic disease

WBC Leukopenia due to bone marrow infiltrationLymphocytosis with circulating malignant cells

Platelet Platelet counts may be increased or decreased

Thrombocytopenia due to bone marrow infiltration or autoimmune cytopenias

Others Cytopenias: common in advance stages

Pancytopenia due to bone marrow infiltration or autoimmune cytopenias

U&E Check serum creatitine and renal function: ureteric

obstruction secondary to lymph node enlargement can cause renal impairment

Check calcium, phosphate, and sodium Check renal function prior to treatment

Hodgkin disease NHL

Hypercalcaemia Hypercalcaemia (in acute adult T-cell lymphoma)

Hypernatraemia

Check serum creatinine for nephrotic syndrome (rare)

Patient may have renal impairment due to obstruction (lymph node enlargement)

LFTHodgkin disease NHLALP due to the presence of liver or bone involvement.

Abnormal due to hepatic involvement, hypermetabolic tumour growth, chronic inflammation

ESR Elevated in Hodgkin's disease and NHL fairly non-specific and should not be

used for screening

LDH Bad prognosis if it is increase in

Hodgkin’s disease and NHL

BETA 2 MICROGLOBULIN may be elevated and correlates with a

poor prognosis in NHL

PROTEIN ELECTROPHORESIS Hodgkin disease NHL Increase gamma

globulin Monoclonal

gammopathy Hypogammaglobulinemi

a

HIV AND HTLV II SEROLOGY HIV serology is done because antiviral

therapies can improve disease outcomes in HIV-positive patients in NHL and HD.

In NHL, HIV serology is done for patients with diffuse large cell immunoblastic or small noncleaved histologies.

HTLV II serology is done for adult T-cell lymphoma-leukemia

IMAGING Structural imaging (Conventional

method of staging) CT (neck to pelvis) MRI CXR

Functional imaging PET scan Gallium scan

Bone scan

CT (NECK TO PELVIS)

It is the most widely used test for initial staging, assessing treatment response, and conducting follow-up care

Possible abnormal findings include enlarged lymph nodes, hepatomegaly and/or splenomegaly, lung nodules or infiltrates, and pleural effusions.

Mediastinal lymphadenopathy, is a very common finding in classic Hodgkin disease, although it is uncommon in Nodular Lymphocyte-Predominant Hodgkin's Disease

Ct's showed lypmhadenopathy in the left inguinal node and the left iliac fossa

MRI

MRI is done when there is a suspicion of CNS involvement eg primary CNS lymphoma, or vertebral body involvement by lymphoma

CXR CXR is more indicated for NHL eg for

identification of hilar or mediastinal adenopathy, pleural or pericardial effusions, and parenchymal involvement

PET SCAN considered to be essential to the initial

staging of Hodgkin disease can be used for the initial evaluation of

patients with NHL more useful for post-treatment

evaluation to differentiate early recurrences or residual disease from fibrosis or necrosis.

PET SCAN Appears to be sensitive for detecting NHL in

extranodal sites Reliability to detect bone marrow involvement

is questioned Better than gallium and equal to CT to detect

disease sites in intermediate to high grade NHL and Hodgkin’s

PET scan has a higher predictive value for relapse than classic CT scan imaging

Scarce availability so x always practical

GALLIUM SCAN (NUCLEAR MEDICINE) the use is nearly all replaced by PET

scan

Increased uptake of gallium in inguinal lesion before treatment

BONE SCAN It is done if suspected BM involvement

eg bone pain or elevated ALP In NHL, one lesions are particularly

associated with the acute form of adult T-cell lymphoma-leukemia and diffuse large B-cell lymphomas

HISTOLOGY Light microscopy and H&E are the

mainstay of pathologic diagnosis Flow cytometry: marked increased in

monoclonal cells indicate lymphoma Immunoperoxidase: special staining

using specific marker antibody to determine the type of lymphoma

SPECIFIC CD MARKERCells MarkersT cell CD3, CD4, CD8B cell CD20, immunoglobulin on surfaceHodgkin’s lymphoma

CD45

NK cells CD16, CD56Lymphoblast Terminal deoxynucleotidyl

transferaseAll lymphocytes CD34

HISTOLOGY Lymph node sample

Fine needle aspiration Needle-core biopsy / incisional biopsy Excision biopsy

Bone marrow sample Trephine / biopsy Aspirate

Biopsy of extranodal sites Lumbar puncture Staging laparotomy Pleural effusion sampling

LYMPH NODE SAMPLEFine needle aspiration

Needle-core biopsy / incisional biopsy

Excision biopsy

- can be used as initial diagnosis of HD

- insufficient for establishing a diagnosis of NHL

Has a limited role in establishing a diagnosis of NHL.

Essential for diagnosis of HD and NHL

Histopathologic image of Hodgkin's lymphoma. CD30 (Ki-1) immunostain.

Histopathologic image of Hodgkin's lymphoma. Lymph node biopsy. H & E stain.

Malignant B-cell lymphocytes seen in Burkitt's lymphoma, stained with hematoxylin and eosin (H&E) stain

Histopathology of diffuse large B-cell lymphoma occurring in the tonsil. H&E stain.

Histopathology of diffuse large B-cell lymphoma occurring in the tonsil. CD20 (L26) immunostain.

BONE MARROW SAMPLE (TREPHINE/ASPIRATE)

lymphoma in the bone marrow is often patchy, so bilateral bone marrow biopsies is indicated

HD: Bone marrow involvement is more common in elderly

individuals, in patients with advanced-stage disease, in the presence of systemic symptoms, and in patients with a high-risk histology.

A bone marrow biopsy can be omitted in patients with stage I Hodgkin disease (Hodgkin's lymphoma) and some patients with stage II disease without hematologic abnormalities. 

For NHL, bone marrow sampling is done for staging rather than diagnosis

BONE MARROW TREPHINE Sensitive for the presence of lymphoma at light

microscopy level when there are sufficient cells to be identified by the pattern they form or number of cells present

Sensitivity can be increased by using CD marker to identify subgroup of lymphocytes, but because lymphocytes are normally present in BM, the pattern and number are important.

PCR to detect presence of translocation or oncogenes can increase the sensitivity and give better measure of prognosis

BIOPSY OF EXTRANODAL SITES In some patients with NHL, the

extranodal sites are the primary presenting sites, and the most common site is the GI tract.

LUMBAR PUNCTURE (if symptoms or signs of CNS involvement are present)

CNS involvement with Hodgkin disease (Hodgkin's lymphoma) is exceedingly rare

In patient with NHL, it should be performed if Diffuse aggressive NHL with bone marrow, epidural,

testicular, paranasal sinus, nasopharyngeal involvement, or patient with two or more extranodal sites of disease.

High-grade lymphoblastic lymphoma High-grade small noncleaved cell lymphomas (eg,

Burkitt and non-Burkitt types) HIV-related lymphoma Primary CNS lymphoma Patients with neurologic signs and symptoms

STAGING LAPAROTOMY involves splenectomy with biopsies of

the liver and lymph nodes in the para-aortic, mesenteric, portal, and splenic hilar regions.

Rarely done

PLEURAL EFFUSION SAMPLING Sampling of a pleural effusion by

thoracentesis and examination of the cells obtained may be useful in the evaluation of Hodgkin disease (Hodgkin's lymphoma).

STAGING: ANN ARBOR CLASSIFICATION

Stage I a single lymph node area (I) or single extranodal site (IE).

Stage II 2 or more lymph node areas on the same side of the diaphragm (II or IIE).

Stage III lymph node areas on both sides of the diaphragm (III or IIIE or IIIs or IIIS)

Stage IV disseminated or multiple involvement of the extranodal organs.Involvement of the liver or the bone marrow is considered stage IV disease.

B The presence of 1 or more of the following: Fever (temperature >38°C) Drenching night sweats Unexplained loss of more than 10% of body weight

within the preceding 6 months

A Absence of the above

X The presence of bulky disease

E Contiguous involvement of extranodal sites (eg, involvement of the lung parenchyma due to direct extension of large mediastinal lymphadenopathy)

IN PATIENTS WITH STAGE I OR II DISEASE, THE FOLLOWING FACTORS ARE CONSIDERED UNFAVOURABLE AND, IF PRESENT, WILL INCREASE THE INTENSITY OF THE RECOMMENDED INITIAL THERAPY: Large mediastinal adenopathy An ESR result (a general marker of inflammation) 50 mm/h or

higher, if the patient is otherwise asymptomatic OR ESR > 30 if hv B symptoms

More than 3 sites of disease involvement The presence of B symptoms The presence of extranodal disease Age above 50 at diagnosis