Lymphoma :

is a neoplasm related to lymphocyte which are of 2 types; B and T lymphocytes,

lymphoma is one of the differential diagnoses when you have patient with
lymphadenopathy.
Differential Diagnosis for lymphadenopathy:
1) Infections: TB (most important), viruses and Brucellosis.
Note: when TB or Brucellosis is suspected Never forget to ask your patient if
anyone related to him has similar symptoms.
2) Tumors: lymphomas (Hodgkin's or Non-Hodgkin's) and Metastatic cancers.
3) CTD (connective tissue diseases): SLE.
4) Sarcoidosis; Erythema nodosum (tender and red nodules on the shin) is one of

the finding in sarcoidosis and commonly asked question in the MiniOsce exam,
and the next step if you see Erythema nodosum is to order chest X-Ray where you
find Bilateral Hilar lymphadenopathy (important point).

OSCE Station
Patient presented to you with lymphadenopathy what are the important points you
will look for??
History
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 Site; local infection will cause localized lymph node swelling.

Painful or not; Infections and high grade lymphoma are painful.
Progression in size; lymphomas rabidly increase in size, but in Hodgkin's
lymphoma the size is fluctuating so you might feel the swelling but the next time you
examine no swelling will be detected or it will be smaller.
Constitutional symptoms; if the patient has lymphoma then it will be called B
symptoms that are:
1 ) Significant night sweats
2 ) Fever (usually its a low grade ,sometimes > 38.5 c).
3 )Weight loss of >10% body weight last 6 months.
Local symptoms: Most important are the respiratory symptoms i.e. SOB and
Cough.
Examination
Examine the affected lymph node; Site, shape, size, consistency, mobility of the
enlarged L.N and whether it is fixed to the skin or not also if tender.
Other sites affected: all lymph node groups.
Spleen involvement (very important).

Investigation
CBC and differential WBCs count: helpful in Acute leukemia and CLL, patients
might come with reactive result in which all component are increased other might
come with lymphocytosis only.
Excisional lymph node biopsy: This is the most important test.
Flowcytometry: Looking for the markers on the cells weather it is B or T cells.
Cytogenetics: important test and depend on the type of the lymphoma.

Investigations for Tumor lysis syndrome which is is a group of metabolic

complications that can occur after treatment of cancer, usually lymphomas and
leukemias, and sometimes even without treatment. These complications are caused by

the break-down products of dying cancer cells and include :

1-hyperkalemia 2-hyperphosphatemia, 3-hyperuricemia, 4-hyperuricosuria,
5-hypocalcemia, and consequent acute uric acid nephropathy and acute renal failure.
Elevated LDH level: seen in 1.Muscular diseases. 2. Cardiac diseases.
3. Lymphoma. 4. Acute leukemia. and 5. Hemolytic anemia.
Elevated ESR level especially in the late stages.
Immunoglobulin deficiency especially CLL
LFT (liver function test): determine if the liver is involved, or if the lymph node
swelling makes pressure on the bile duct.
KFT: most important test for Tumor lysis Syndrome.
Bone Marrow biopsy: for staging and diagnosis

****
Rule: Hodgkin's lymphoma Nodal (but could be extranodal).
Non-Hodgkin's lymphoma can be anywhere so first presentation could
be in the bone marrow.
****

Hodgkin's lymphomas
Nodular sclerosis HD: The most common type, frequently associated with
mediastinal mass, and hilar lymphadenopathy, in addition to the neck, it is common in
females, Good prognosis, most in stage I & II.

Non-Hodgkin's lymphomas
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Diffuse large B-cell lymphoma: This is the most common seen type of lymphoma
and it is classified as aggressive high grade lymphoma, usually symptomatic and

extranodal involvement is common, it is treated aggressively using chemotheraby and now

Rituximab

is used widely nowadays and it is a monoclonal antibody against CD20

lymphocytes causing cytotoxic effect, other use of Rituximab is as immunosuppressive

agent in organ transplantation and it is also used in autoimmune diseases as in SLE.
Side effects of Rituximab include: Anaphylactic reaction (its protein components),
immunosupression etc

Chronic lymphoid leukemia:

It is the most common low grade lymphoma and the majority of patients are
asymptomatic and might be discovered incidentally as this is the commonest leukaemia,
it is called leukemia because there is immature cells in the peripheral blood, occurring
predominantly in later life and increasing in frequency with advancing years (median age
of presentation between 65 and 67 years) as It results from the clonal expansion of small
lymphocytes and is almost invariably (95%) B cell in origin and most of the patients have
their bone marrow involved, CLL might progress into high grade lymphoma where
it changes into a fast-growing diffuse large B cell lymphoma and this is known as
Richter's transformation -syndrome-, not all patients need treatment some pf them might
stay stable for 10 years even without treatment, so treatment in those patients depend on
the symptoms and the progression in the Lymphocyte count in the CBC also Hb and
platelets and these are the indications for treatment.

(!) Note: Old patients with Herpes zoster virus should be considered significantly as
it could be indication of malignancy.

cell

lymphoma

(Mycosis

Fungoides) :
is the most common form of cutaneous Tcell lymphoma. It generally affects the
skin, but may progress internally over time.
Mycosis fungoides was The name mycosis

fungoides is somewhat misleading, The disease, however, is not a fungal infection but
rather a type of non-Hodgkin's lymphoma.

Note: Some infections cause tumors as EPV which causes Burket's Lymphoma also HIV
can cause lymphoma on the other hand Chronic H.pylori infection can cause
MALTOMA(low grade lymphoma) in the stomach. Some immunosuppressive agents can
cause B-cell lymphoma as Cysclosporine which is prescribed in kidney transplantation.
Follicular lymphoma
It is a low grade lymphoma as CLL but it is Associated with BCL-2 gene rearrangement
t(14;18) t:translocation, it is usually asymptomatic, and it has the same line of
management for CLL.

*******
Clinical presentation :

Manifestations of the disease depend on the

grade of the disease so the low grade
lymphomas are asymptomatic and the findings
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In this microscopic picture you can see

lymphocytosis, Blast cells are the cells
with scanty Cytoplasm.

could be localized to an increase in the WBCs count with mild generalized lymph node
swelling including the mediastinal, abdominal and supraclavicular lymph nodes.
Some patients may come with Bone marrow failure, so it is important to investigate for
the involvement of the bone marrow as it is important for the diagnosis and the staging
where it is considered stage 4b if the Bone marrow is involved, one more additional

benefit is in the treatment where high dose chemotherapy is considered if the bone marrow
is free.

CNS involvement is commonly seen in non-Hodgkin's lymphoma (T-cell and Burket's

lymphomas) and Acute lymphocytic leukemia so we might give prophylactic intrathecal
chemotherapy in such cases.

(?) What chemotherapeutic agents that can be given safely intrathecally??

(Very important memorize by heart)
1. Methotrexate 2.Citrapine 3.Steroids.

(Note: Vincristine isn't safe)

Memorize these drugs and their side effects it is important to do so:

Anthracyclines cardiomyopathies
Cyclophosphamide (commonly used) hemorrhagic cystitis
Bleomyocin pulmonary fibrosis
Vincristin neuropathies, neurological complications.
Doxorubicin
Steroid given in patient with lymphoid malignancy because of it is suppressive effect
on lymphocytes.

Note: Radiotherapy and bone marrow transplantation (auto- & allogenic) are also
considered in the treatment of lymphoma.

Chemotherapy cause bone marrow suppression, after a period of time the patient will
have hemolysis and pancytopenia or thrombocytopenia (it is also caused by ITP,
hypersplenism or Marrow failure).
Bone fracture is one of the clinical manifestations if bone is involved, other
manifestation is pericardial effusion.

Staging :
Stage I Involvement of a single lymph node region (I) or of a single
extralymphatic organ or site, in such cases the treatment with chemotherapy will
be limited to few courses or radiotherapy alone.
Stage II Involvement of 2 or more lymph node regions on the same side of the
diaphragm, or localized involvement of the extra lymphatic organ or site and 1 or
more lymph node regions on the same side of the diaphragm.
Stage III Involvement of lymph node regions on both side of the diaphragm.
Which may be accompanied by localized involvement of extralymphatic organs or
site (IIIE), or by
Stage IV Diffuse or disseminated involvement of I or more extra lymphatic
organs or tissues with or without associated lymph node enlargement, involvement
of liver or bone marrow is always considered stage IV .

Designations applicable to any disease state

A Absence of B symptoms
B Presence of B symptoms and it is considered advanced stage.
E Involvement of an extra nodal site by local extension from a nodal site.
X Bulky disease mediastinal widening greater than one third diameter of the chest
at T6-7, or > 10 cm in any single dimension.
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Multiple Myeloma :

Presence of more than 15% plasma cells in the bone marrow and presence of monoclonal
immunoglobulin (most common Ig G) secreted by plasma cells where there is billions of
immunoglobulins this is known as paraprotinemia and monoclonal bands are prominent
on electrophoresis and all are useless, and the main clinical presentation in this case is
Bone pain and pathological fractures due to Osteoclast activation by plasma cells which
causes lytic bone lesions and collapse fracture especially in the vertebrae and ribs.
On investigation those patients will have Normocytic anemia, elevated total protein level
but low albumin, Hypercalcemia, elevated ESR level and Kidney Function test maybe
consistent with renal failure.

What are the causes of hypercalcemia?

Multiple myeloma
Bone metastasis
Thyroid adenoma
Vitamin D toxicity
Iatrogenic (calcium containing drugs)
Paraneoplastic syndrome
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Paget's disease (osteoclastic phase)

Renal failure (by causing secondary hyperparathyroidism)
etc
How to manage Hyprcalcemia?
First line of management is Hydration with normal saline because the
patient is dehydrated.
Salt intake
Bisphosphonates are pyrophosphate analogues with high affinity for
bone and act by inhibition of the osteoclastic activity (e.g.pamedronate).
Calcitonin
Continuous monitoring of Mg+ and K+ to prevent depletion.

The End

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B
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