Transcript Case report from ASH

Case report from ASH
Lymphadenopathy.
Dr. Tariq Roshan
History
 A 60 year-old man complains
of a new lump in the right
groin for the past six weeks.
 What are the major
pathophysiologic
mechanisms for lymph node
enlargement?
 Is the lymph node tender.
 Have you felt swollen lymph
nodes in this or another area
before?
 Do you have fever or
drenching sweats or loss of
more then 10% of your body
weight?
History
 Have you traveled to foreign countries?
 Have you had any of the following:
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change in bowel movements
pain in the abdomen
blood in the stools or black tarry stools
fullness in the stomach
inability to eat a full meal (early satiety)?
 Have you ever: Abused intravenous drugs?
 Shared needles with other people?
 Had anal receptive sexual intercourse?
 Had heterosexual intercourse with multiple partners?
 Did you receive blood or blood product
transfusions prior to 1985?
History
 Have you noticed unusual bleeding, easy
bruising or red spots in the skin?
 Have you noticed any sores on your penis
or abnormal discharge from your penis?
 Do you have any pain, redness, or swelling
in your leg?
 No I have not noticed any pain, redness, or swelling in
my leg.
 Cellulitis can cause inguinal adenopathy.
Pathophysiolgy.
 A lymph node may enlarge in response to
an infection, a non-specific inflammatory
reaction, or a malignant growth of its cells.
Is the lymph node tender.
 The node is not painful
 Lymph nodes that become enlarged as a
result of infection are usually tender to
touch, whereas malignant lymph nodes do
not hurt. In addition, infectious nodes can be
erythematous and warm.
Have you felt swollen lymph nodes
in this or another area before?
 Yes, I have noted other enlarged nodes, but
my groin area concerns me the most.
 Infections most often cause localized
lymphadenopathy. Disseminated
lymphadenopathy is more likely due to a
malignancy but can be due to
 HIV
 EBV.
 Malignant lymphadenopathy can also wax
and wane, sometimes for months before a
final diagnosis is made.
Do you have fever or drenching
sweats or loss of more than 10% of
your body weight?
 No, I have not had fevers, or sweats.
However, I have lost 8 pounds over the past
6 months.
 One or more of these symptoms is present
in many patients with lymphoma. The
classic “B” symptoms of lymphoma are
– Temperature greater than 380C,
– Drenching night sweats
– Unintentional loss or 10% of body weight over 6 months.
Have you traveled to foreign
countries?
 I have lived in Texas all my life, and have not
recently traveled outside Texas.
 This is an important question in order to rule out
infectious etiologies which might be acquired in
other countries.
 Some of these may cause disseminated
lymphadenopathy or signs that might be mistaken
for a malignancy.
 Tuberculosis.
 Histoplasmosis.
 I have none of these problems.
– The gasterointestinal tract is a very common
site of primary extranodal lymphoma
presentation. It can also be a place of spread of
lymphoma. In addition, enlarged spleen can
give left upper quadrant pain or early satiety.
 The patient reported none of these risk
factors for HIV
– HIV may cause disseminated lymphadenopathy.
In addition people with HIV infection have a 300
fold increased risk of developing high-grade
NHL.
 No I don’t have a problem with any of that.
 Spontaneous bleeding can ocure if the platelet count
is < 10,000/ cub. mm, either due to consumption or
due to underproduction from a bone marrow that is
replaced by a malignant process.
 I have none of these symptoms.
 Squamous cell carcinoma of the penis can cause
inguinal adenopathy.
 Venereal diseases including syphilis, chancroid,
genital herpes, and lymphogranuloma venereum, can
also cause inguinal adenopathy.
Physical Exam
 A 60 year-old man complains of a new lump
in the right groin for the past six weeks.
 What should you look for on his physical
exam that would help you to narrow the
differential diagnosis? Name several lymph
node areas that you should examine.
 Cervical, supraclavicular, axillary, epitrochlear, and
inguinal.
 Be sure to examine the tonsils and spleen as well, as
these are also lymphoid tissues
Physical Examination
 General: Well nourished man in no acute distress.
 HEENT: Pale mucosa, no scleral icterus, no orpharyngeal lesions, no
tonsillar enlargement.
 Lungs - Clear to auscultation and rhythm.
 Heart - Regular rate without murmur.
 Abdomen - spleen enlarged to 6 cm below the costal margin, firm and
non tender to palpation. The liver is enlarged.
 Musculoskeletal - Normal.
 Genitourinary - Normal male genitals without lesions on the penis or in
the perirectal area.
 Neurological - normal.
 Lymphatics - generalized adenopathy. The nodes range from 1.5 cm to
4 cm in diameter, are rubbery and not tender to palpation.
 Skin - normal.
 What do you think now?
 Generalized rubbery adenopathy and significant splenomegaly. These findings
point to a systemic disease rather than a localized infection.
Differential diagnosis at this point
Differential Diagnosis
The following diagnoses should be considered at this point.
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Differential diagnosis
of generalized adenopathy:
Reactive hyperplasia due to HIV
Secondary syphilis
Epstein-Barr virus (mononucleosis)
Tuberculosis
Lymphoma
Cytomegalovirus
Brucillosis
Toxoplasmosis
Sarcoidosis
Differential diagnosis
of localized inguinal adenopathy:
Cat-scratch fever (bartonella)
Herpes simplex type II
What lab studies should be
requested?
 CBC, peripheral blood smear & platelet count
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WBC 2000/ml
Hemoglobin 8.3 g/dl
Platelets 80,000 /ml
The peripheral smear does not show abnormal lymphoid cells.
– A low hemoglobin could due to marrow replacement with
lymphoma, or to iron deficiency anemia secondary to blood loss
through the gastrointestinal tract.
– Platelets could drop due to:
 splenic sequestration by the enlarged spleen
 ITP (which can be associated with lymphomas)
 lack of production due to extensive marrow infiltration by lymphoma a
combination of the above.
 There will be evidence of peripheral blood involvement by
lymphoma in some patients.
Lab studies
 Serum chemistries
– Normal.
 Liver and renal chemistries will be abnormal if these organs are
involved or obstructed by lymphoma. Spontaneous tumor lysis
syndrome, (elevated serum potassium, phosphate, and uric
acid, and low serum calcium) is almost never present at
presentation of lymphoma, but can happen with therapy if the
lymphoma is rapidly proliferating or presenting with bulky
disease or with a leukemic picture.
 LDH 250 (0-190)
 B2 microglobin 1.5ng/ml(0-2.5 ng/ml)
 Pretreatment serum levels of LDH and ß2 microglobulin are
elevated in many patients with lymphoma. In general, a higher
LDH value correlates with a higher proliferative rate.
Lab studies
 Hemoccult testing of stool
– Negative
 Hemoccult testing of the stool is important as some
patients with lymphoma will have GI involvement at
diagnosis.
Radiograph.
 What radiographic
procedures would you
recommend?
– CT scan chest,
abdomen, and pelvis
with administration of
both oral and
intravenous contrast.
– The abdominal CT
scans in this patient
show diffuse
involvement of the
retroperitoneal nodes.
Laboratory Studies and
Procedures
 Diagnostic Procedures: What diagnostic
procedure(s) should be done?
– Diagnostic Procedures
– Lymph node biopsy
 Should this be a:
 Fine needle aspirate?
 Core needle biopsy?
 Excisional biopsy?
– Bone marrow aspirate and biopsy
 Why does the patient need both an aspirate & biopsy of
the bone marrow?
 In patients with accessible peripheral lymph
nodes, an excisional biopsy (surgical removal of
the entire lymph node) is strongly preferred over a
fine needle aspirate or a core needle biopsy. An
excisional biopsy provides more tissue for
evaluation and permits the hematopathologist to
evaluate the architecture of the lymph node. A fine
needle aspirate (although useful in the evaluation
of thyroid nodules and breast cysts) is not
adequate for the evaluation of possible lymphoma.
 The aspirate and biopsy provide complementary
information.
The aspirate shows the morphology (appearance)
of the cells in the marrow in detail, and can be
sent for flow cytometry.
The biopsy shows the cellularity of the marrow
(proportion of the marrow space occupied by
cells), and can look for replacement of the marrow
with fibrosis, tumor cells, or granuloma.
List of studies that you should
request on the lymph node.
– Histopathology
 Findings for this patient
– Flow Cytometry
 Findings for this patient
– Molecular Studies
 Findings for this patient
– Culture
 Findings for this patient
Histopathology
 To evaluate the size and
appearance of the lymphoid
cells, and whether these cells
involve the node in a nodular
(follicular) or diffuse pattern.
 May also proceed with
immunocytochemistry. This
means staining the lymph node
with monoclonal antibodies
specific for B or T lymphocytes,
followed by a second antibody
tagged with a visible label such
as horseradish peroxidase.
Flow Cytometry
 The laboratory reports the following
characteristics for this patient Coexpression
of CD5-CD19, negative CD23, positive
FMC-7
Molecular Studies
 Depending on the results of the initial
histopathology and flow cytometry data, these
studies may include an evaluation for
immunoglobulin gene rearrangement (a
characteristic of B cell lymphomas), T cell receptor
rearrangement (a characteristic of T-cell
lymphomas), or specific oncogenes associated
with certain lymphoma subtypes.
 The laboratory reports the following characteristics for this
patient Cytogenetics shows a translocation t(11;14)(q13;q32).
The fluorescent in situ hybridization technique (FISH) also
detects the cyclin D1 translocation.
Culture
 If an infectious cause of adenopathy is in the
differential diagnosis, the node can be sent
to the microbiology laboratory for culture.
 The lab reports no infectious process present.
Bone marrow aspirate.
Diagnosis.
The findings lead to the diagnosis of
Mantle cell lymphoma.
Mantle Cell Lymphoma.
 The definite diagnosis.
 Histopathologic.
 Necessary to diffrentiate between Mantle zone pattern, follicular
and diffuse variants.
 Phenotypically
 CD 20 and CD 5 co-expression.
 CD 23 negative and FMC-7 positive.
 CD 10 negative.
 Important D/D
 Small lymphocytic lymphoma,
 Follicular small cleaved cell lymphoma
 Lymphoblastic lymphoma.