GREYS PRESENTATION

Dr. A. Mahanga2006

CASE HISTORY

31 year old Mrs B.M who presented with :• 2 week history of abdominal pain • Slow growing mass• 1 week history of epigastric pain, which

was non referred and worsening in intensity• No associated vomiting or nausea• No discoloration of eyes

SYSTEMIC ENQUIRY

• Cough for 2/52• LOW• LOA• Nightsweats• Fatigue

History...

• Pmhx : no D E A R T Hoff note , no previous TB+ TB contact

• Pshx : cholecystectomy - 1997

ON EXAMINATION

• Stable but appears chronically ill looking• Alert and orientated• Vitals : Apyrexial BP = 100 / 70

P : 90 not distressed• No jaundice, pallor, clubbing, oedema• small cervical lymph nodes. Axillary LN <

1cm. No inguinal / epitrochlear

ABDOMEN

• Distended• Fullness of epigastrium, RUQ• +/- 10 cm hepatomegaly, firm. Tender. No

nodules• 3 cm splenomegaly• Generalised abdo tenderness. - peritonitic• Bowel sounds present

Systems

• Cardiovascular : JVP nS1 S2 normal. NIF

• Respiratory : Trachea centralPercussion - resonantGood air entry bilaterally

• Cns : Alert, orientatedNo meningism/focal sns

Results - Blood

• FBC = 10.3 (94.8 / 29.9) , 7.21, 133• U+E = 130/3.5/104/23/4.0/75• LFT = 110/17/11/286/59/41• LDH = 1472• INR = 1.29

Ultrasound Abdo• Liver is littered with hypodense lesions in

all segments. Non cystic. (1.2 - 1.9cm )• Pancreas normal• Spleen - Large hypodense mass (non cystic)

3.1 x 2 x 3.4 cm. Hypodense lesionin splenic hilum.

A) ? HEPATOMA = RECOMMEND CT

CT ABDOMEN• Liver: A very large liver is seen. Poorly

defined masses seen throughout liver. No intra hepatic bile duct or vessel dilatation.

• Spleen: enlarged, with a large round hypodense lesion.

• Pancreas: normal• Kidneys: normal. Displaced inferiorly

RECOMMEND LIVER BIOPSY

Liver biopsy

• Liver tissue represented: Infiltrated by Non - Hodgkins lymphoma high grade B cell lineage

NONNON--HODGKINS HODGKINS LYMPHOMALYMPHOMA

Background• Malignancies of lymphoid cells arise

from cells of the immune system at different stages of differentiation.

• Common haemopoetic progenitor = lymphoid < T cells and B cells.

• They may present as leukaemias(primary involvement of bone marrow and blood ) or lymphomas ( solid tumour of the immune system ).

Epidemiology

• General decline in Hodgkins Disease rates in the past 20 years, making the disease only account for 1% of cancers.

• Non hodgkins however has increased by more than 70% in this same time.

• 54000 new cases of NHL diagnosed in USA in 2004.

• Age (40 - 70 ) > in elderly.

• M > F ( higher rates in men in locations epidemic of HIV )

• > in whites than in blacks or asians.• 7th in frequency world-wide amongst all

cancers.• NHL is increasing in frequency,

worldwide.

Pathophysiology

• NHL originate from lymphoid tissues (mainly lymph nodes, liver and spleen)

• The tumour cell line ie, B cell, T cell, hodgkins, correspond to the cellular components of antigen stimulated lymphoid tissue.

• There is clonal expansion of either B, T or natural killer cells.

• 85 % of NHL are of B cell origin.• Only 15 % are derived from Tcell/ nkc• Some are derived from macrophages.• Classification : B cell - precursor

maturelarge BBurkitts

T cell - precursor mature

Hodgkins - classicnodular

• The discovery of the Reed - Sternberg in the 20th century resulted in the distinguishing between HD and NHL.

• Furthermore the histological classification of NHL forms one of the most contentious issues in oncology

Working formulationLow grade lymphoma• Peripheral adenopathy ( painless)• Spontaneous regression can occur,

confusing with a transient infection.• Extranodal and B symptoms -

uncommon.• Cytopaenia if bone marrow involved• Fatigue and weakness if advanced.

Intermediate and high grade

• More varied clinical presentation.• Most patients have adenopathy• > 1/3 have extranodal involvement,

most commonly involving the GIT , skin, bone marrow, sinus, GUT, CNS.

• B symptoms more common (30-40%)

GIT lymphoma

• Primary CNS lymphomas are high grade neoplasms of B cell origin.

• Most CNS lymphomas are large cell / immunoblastomas.

• NHL accounts for 1 % of all CNS lymphomas

• These are commonly associated with immunosuppression.

CNS lymphoma

Who gets lymphomas?

• Immunodeficiency : HIVtransplantsinherited immune d.

• Environment : medical treatments, infectious diseasesagricultural chem.

• Hodgkins disease

•Infections

• HTLV : infects T cells, T cell lymphoma• EBV : Burkitts lymphoma. Aggressive

NHL in immune suppressed. Majority of CNS lymphomas are associated with EBV.

• HIV• HELICOBACTER PYLORI : gastric malt• HEP C : lymphoplasmacytic lymphoma

Burkitts in a child

Genes

• A large number of translocations and mutations play a role in the differentiation of a tumour.

• In 30 % of pts with large B cell lymphoma there is a translocation t(14/18) -chromosome 18, which results in suppression of apoptosis( cell death ) and tumour formation.

An approach to the patient

• Good history• Physical findings:

Peripheral lymph nodesSplenomegaly (40 %)HepatomegalyAbdominal / testicular massSkin lesions ( T cell lymphoma )

Lab. studies

• FBC with diff count and platelets• Counts may be normal in early stage.• Anaemia, TCP, leucopaenia,

pancytopaenia may occur with bone marrow infiltration.

• Lymphocytosis• Thrombocytosis

Chemistry

• Raised LDH ( poor prognostic factor )• Abnormal LFT ( hepatic involvement )• Hypercalcaemia ( acute form of T cell

lymphoma)• HIV• Raised B2 microglobulin• Monoclonal gammopathy

Imaging

• CXR - 25% + nodes, effusion• Ultrasound abdomen• CT scan - neck, chest, abdo, pelvis • Bone scan - in bone pain / > ALP• Gallium scans• Upper GI series with follow through• MRI

Procedures

• Biopsy - Lymph nodesFNA ( generally insufficient )heamotoxylin and eosin stain

• BMAT - not routine for diagnosis• Biopsy of extranodal sites• LP for CSF exam : in suspected primary

cns lymphoma, hiv, neuro abn.

Staging- Ann arbor

Differential diagnosis

• Infectious mononucleosis• Metastatic disease : carcinoma

melanomasarcoma

• Benign lymph node infiltrates, eg : TB, bacterial, fungal and viral infections

• Collagen vascular diseases

HIV and lymphoma

• NHL most common lymphoma in HIV.• 2 types : a) systemic CD4 > 50

b) CNS CD4 < 50• The risk of developing systemic NHL is

60 - 200 x greater than general population

• Symptoms are commonly confused with most other infections common in HIV.

HAART

• Although the incidence of various opportunistic infections as well as KS have fallen since the introduction of HAART, effects on NHL is unclear.

• Metanalysis of studies with 14936 HIV + pts showed that the relative risk of development of NHL in the era of HAART compared to pre-haart was statistically insignificant. (p = 0.58 )

Treatment

Treatment

• CHOP = combination chemotherapy • Cyclophosphamide, vincristine,

prednisone, doxorubicin.• Stage 1/2 : treated with 3- 4 cycles of

chemo then radiotherapy.• Cure rates are 80 - 90 % stage 1

60 - 70 % stage 2

Treatment cont..

• Stage 2 (bulky), 3, 4 = 6-8 cycles of combination chemotherapy eg. CHOP often with Rituximab.

• If the pt responds initially, 70 % may achieve complete remission.

• 50 - 70 % may be cured• Those that do not respond require

salvage treatment.

• NB: the long term disease free interval inpatients is < 10 %

• Studies have proved that pts with early stage NHL could be treated with a short course of chemo of lesser intensity, without irradiation of primary sites.(nejm oct 30 1997.)

• Thomas. P. MiIller - investigated the use of chemo vs the use of chemo and radiotherapy in int./ high grade NHL

• This trial however showed that patients who received 3 cycles of CHOP and radiotherapy had better progression of disease and better overall survival than the use of chemo alone.(nejm July 1998)

• Index case patient, sent to Greys.• She had routine Ct scans for staging• Sent to oncology, and later discharged for

palliative management

Guess what he has??

Thank you

References

• Harrison’s: Principles of internal medicine• New England journal of medicine• Oncology channel• Research article, D.A Estrada and team,

haematology, oncology, cancer care specialists. E-medicine.