Download approach to the patient with lymphadenopathy and splenomegaly

APPROACH
TO THE PATIENT
WITH
LYMPHADENOPATHY AND
SPLENOMEGALY
‫‪NHL‬‬
‫اهداف اختصاصي ‪:‬‬
‫‪HD‬‬
‫‪-1‬مشخصات كلي‬
‫‪ -1‬تعريف‬
‫‪DD -2‬‬
‫‪-2‬اپيدميولوژي‬
‫‪ -3‬برخورد‬
‫‪-3‬پاتولوژي‬
‫‪-4‬تعريف و اتيولوژي‬
‫‪-4‬تشخيص‬
‫‪-5‬طبقه بندي‬
‫‪STAGING -6‬‬
‫‪-5‬تظاهر‬
‫‪-7‬تظاهرات‬
‫‪-6‬پيش آگهي‬
‫‪-8‬پيش آگهي‬
‫‪-7‬درمان‬
‫‪-9‬درمان‬
APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY
PHYSIOLOGY AND ANATOMY
Lymph nodes are populated predominantly by
macrophages,
dendritic cells,
B lymphocytes, and
T lymphocytes.
B lymphocytes are located primarily in the
follicles and perifollicular areas,
T lymphocytes are found primarily in the
interfollicular or paracortical areas of the lymph
node.
APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY
PHYSIOLOGY AND ANATOMY
In young childrenpalpable lymphadenopathy is the rule.
who are continuously undergoing exposure to new
antigens,
In fact, the absence of palpable lymphadenopathy would
be considered abnormal
In adults, lymph nodes larger than 1 to 2 cm in diameter
are generally considered abnormal.
However, lymph nodes 1 to 2 cm in diameter in the groin
are sufficiently frequent to often be considered "normal.“
APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY
Generalized immune proliferation and lymphadenopathy
can occur with a
systemic disorder of the immune system,
disseminated infection, or
disseminated neoplasia.
Malignancies of the immune system might be manifested
as:
localized or
disseminated lymphadenopathy.
APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY
more than two-thirds of patients with LAP have :
nonspecific causes or upper respiratory illnesses (viral
or bacterial),
fewer than 1% have a malignancy
in another study :16% had a malignancy
(lymphoma or metastatic adenocarcinoma)
Thus, the vast majority of patients with lymphadenopathy
will have a nonspecific etiology requiring few diagnostic
tests.
APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY
Differential diagnosis of lymphadenopathy
TABLE 178–1. CAUSES OF LYMPHADENOPATHY
Infection
Bacterial (e.g., all pyogenic bacteria, cat-scratch disease, syphilis,
tularemia)
Mycobacterial (e.g., tuberculosis, leprosy)
Fungal (e.g., histoplasmosis, coccidioidomycosis)
Chlamydial (e.g., lymphogranuloma venereum)
Parasitic (e.g., toxoplasmosis, trypanosomiasis, filariasis)
Viral (e.g., Epstein-Barr virus, cytomegalovirus, rubella, hepatitis, HIV)
Benign disorders of the immune system (e.g., rheumatoid arthritis,
systemic
APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY
TABLE 178–1. CAUSES OF LYMPHADENOPATHY
lupus erythematosus, serum sickness,
drug reactions such as to phenytoin,
Castleman's disease, sinus histiocytosis with massive lymphadenopathy,
Langerhans'cell histiocytosis,
Kawasaki syndrome, Kimura's disease)
Malignant disorders of the immune system (e.g., chronic and acute myeloid
and
lymphoid leukemia, non-Hodgkin's lymphoma, Hodgkin's disease,
angioimmunoblastic-like
T-cell lymphoma, Waldenström's macroglobulinemia, multiple myeloma with
amyloidosis, malignant histiocytosis)
Other malignancies (e.g., breast carcinoma, lung carcinoma, melanoma, head
and
neck cancer, gastrointestinal malignancies, germ cell tumors, Kaposi's
sarcoma)
Storage diseases (e.g., Gaucher's disease, Niemann-Pick disease)
Endocrinopathies (e.g., hyperthyroidism, adrenal insufficiency, thyroiditis)
Miscellaneous (e.g., sarcoidosis, amyloidosis, dermatopathic lymphadenitis)
APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY
TABLE 178–2. MOST FREQUENT CAUSES OF LYMPHADENOPATHY
IN ADULTS IN AMERICA
Unexplained
Infection
In drainage area of infection (e.g., cervical adenopathy with
pharyngitis)
Disseminated (e.g., mononucleosis, HIV infection)
Immune disorders (e.g., rheumatoid arthritis)
Neoplasms
Immune system malignancies (e.g., leukemia and lymphomas)
Metastatic carcinoma or sarcoma
APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY
FACTORS TO CONSIDER IN THE DIAGNOSIS OF
LYMPHADENOPATHY
Associated systemic symptoms
Patient age
History of infection, trauma, medications, travel
experience, previousmalignancy, etc.
Location: cervical, supraclavicular, epitrochlear,
axillary, intrathoracic(hilar versus mediastinal), intraabdominal (retroperitoneal versus mesentericversus
other), iliac, inguinal, femoral
Localized versus disseminated
Tenderness/inflammationSizeConsistency
APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY
LYMPH NODE EVALUATION.
a careful history
a thorough physical examination
laboratory tests
imaging studies to determine the extent
and
character of the
lymphadenopathy
age of the patient
The occurrence of fever, sweats, or
weight
loss
of a site of infection, a particular
medication, a travel history, or a previous
malignancy.
APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY
physical examination
localized or generalized
size of nodes
Texture
presence or absence of nodal tenderness
signs of inflammation over the node
skin lesions
splenomegaly.
APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY
Generalized adenopathy has been defined
as
involvement of three or
more
noncontiguous lymph
node areas.
generalized lymphadenopathy
is
frequently associated
with
nonmalignant
disorders
APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY
physical examination
(localized or generalized), size of nodes, texture, presence or absence of nodal
tenderness, signs of inflammation over the node, skin lesions, and splenomegaly.
Generalized adenopathy has been defined as involvement of three or more
noncontiguous lymph node areas.
generalized lymphadenopathy is frequently associated with nonmalignant disorders
The site of localized or regional adenopathy
Nodes <1.0 cm2 in area (1.0 ´ 1.0 cm or less) are almost always secondary to
benign, nonspecific reactive causes.
Patients with node(s) <1.0 cm2 should be observed after excluding infectious
mononucleosis and/or toxoplasmosis unless there are symptoms and signs of an
underlying systemic illness.
APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY
METHODS OF LYMPH NODE EVALUATION
Physical examination
Imaging
Chest radiography
Lymphangiography
Ultrasonography
Computed tomography
Magnetic resonance imaging
Gallium scanning
Positron emission tomography
Sampling
Needle aspiration
Cutting needle biopsy
Excisional biopsy
APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY
lymph nodes that are tender are more likely to be due to
an infectious process,
whereas painless adenopathy raises the concern of
malignancy.
Lymph node consistency
lymph nodes containing metastatic carcinoma are rock
hard,
lymph nodes containing lymphoma are firm and
rubbery,
lymph nodes enlarged in response to an infectious
process are soft.
The larger the lymph node, the more likely a serious
underlying cause exists, and lymph nodes greater than 3
to 4 cm in diameter in an adult are very concerning
APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY
Chest radiographs provide the most economical and easiest method to
assess mediastinal and hilar lymphadenopathy but are not as accurate as
CT of the chest.
lymphangiography provides an extremely accurate assessment of the
lower abdominal lymph nodes and, because of retained contrast material,
allows repeat examinations and assessment of the response to therapy.
CT and ultrasound provide the most useful ways to assess abdominal
and retroperitoneal lymphadenopathy
ultrasound has the advantage of being less expensive and not requiring
radiation exposure.
MRI and gallium scanning are not first-line studies for the assessment of
lymphadenopathy
APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY
Gallium scans
presence of active lymphoma in patients with lymphadenopathy and a proven
diagnosis
Fine-needle aspiration
currently popular and is often an accurate way to diagnose infection or
carcinoma
it is inappropriate as an initial diagnostic maneuver for lymphoma.
Cutting needle biopsies
will occasionally provide sufficient material for an unequivocal diagnosis and
subtyping of the lymphom
excisional biopsy,
which is most likely to provide the pathologist with adequate material to
perform histologic, immunologic, and genetic studies, is the most appropriate
approach.
APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY
AN APPROACH TO THE PATIENT WITH LYMPHADENOPATHY
AN APPROACH TO THE PATIENT WITH LYMPHADENOPATHY
1. Does the patient have a known illness that causes lymphadenopathy?Treat and
monitor for resolution.
2. Is there an obvious infection to explain the lymphadenopathy (e.g., infectious
mononucleosis)?Treat and monitor for resolution.
3. Are the nodes very large and/or very firm and thus suggestive of
malignancy?Perform a biopsy.
4. Is the patient very concerned about malignancy and unable to be reassured
thatmalignancy is unlikely? Perform a biopsy.
5. If none of the preceding are true, perform a complete blood count and if it
isunrevealing, monitor for a pre-determined period (usually 2 to 6 weeks).If the
nodes do not regress or if they increase in size, perform a biopsy.
APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY
AN APPROACH TO THE PATIENT WITH LYMPHADENOPATHY
come to medical attention in several ways
felt a lymph node in the neck, axilla, or groin
an unexpected finding on routine physical examination or as part
of the evaluation of another complaint.
Finally, patients might be found to have unexpected
lymphadenopathy on imaging studies of the chest or abdomen.
The approach to a patient complaining of newly discovered
lymphadenopathy in the neck, axilla, or groin will depend on the
size, consistency, and number of enlarged lymph nodes and the
patient's general health
a biopsy might be done more quickly in a patient who is very
anxious about malignancy or who needs a definitive diagnosis
expeditiously.
APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY
AN APPROACH TO THE PATIENT WITH LYMPHADENOPATHY
Biopsy might be done more
quickly in a patient who is
very anxious about
malignancy or who needs a
definitive diagnosis
expeditiously.
GENERAL ASPECTS OF LYMPHOID MALIGNANCIES
ETIOLOGY AND EPIDEMIOLOGY
Hodgkin's disease
The cell of origin of
suggests that most are of B cell origin.
Hodgkin's disease is more common in whites than in blacks
more common in males than in females
A bimodal distribution of age at diagnosis has been observed,
with one peak incidence occurring in patients in their 20s
and the other in those in their 80s
younger age groups diagnosed in the United States largely have the
nodular sclerosing subtype
Elderly patients, patients infected with HIV, and patients in third world
countries more commonly have mixed-cellularity Hodgkin's disease or
lymphocyte-depleted Hodgkin's disease
Infection by HIV is a risk factor for developing Hodgkin's disease. In
addition, an association between infection by EBV and Hodgkin's disease
has been demonstrated
GENERAL ASPECTS OF LYMPHOID MALIGNANCIES
ETIOLOGY AND EPIDEMIOLOGY
non-Hodgkin's lymphomas
have increased in frequency in the United States at the rate of 4% per year
since 1950.
more frequent in the elderly and more frequent in men
Patients with both primary and secondary immunodeficiency states are
predisposed to developing non-Hodgkin's lymphomas.
HIV infection;
patients who have undergone organ transplantation
patients with inherited immune deficiencies,
the sicca syndrome
rheumatoid arthritis
GENERAL ASPECTS OF LYMPHOID MALIGNANCIES
ETIOLOGY AND EPIDEMIOLOGY
non-Hodgkin's lymphomas
various subtypes differ geographically
T cell lymphomas are more common in Asia
follicular lymphoma are more common in western countries.
angiocentric nasal T/natural killer (NK) cell lymphoma has a striking
geographic occurrence, being most frequent in Southern Asia and parts of
Latin America.
human T cell lymphotropic virus (HTLV) I is seen particularly in southern
Japan and the Caribbean.
GENERAL ASPECTS OF LYMPHOID MALIGNANCIES
ETIOLOGY AND EPIDEMIOLOGY
non-Hodgkin's lymphomas
environmental factors
infectious agents,
chemical exposures
medical treatments
Patients treated for Hodgkin's disease can develop non-Hodgkin's
lymphoma
agricultural chemicals
GENERAL ASPECTS OF LYMPHOID MALIGNANCIES
ETIOLOGY AND EPIDEMIOLOGY
non-Hodgkin's lymphomas
HTLV-I infects T cells
directly to the development of adult T cell lymphoma (ATL) in a small
percentage of infected patients.
cumulative lifetime risk of developing lymphoma in an infected patient is
2.5%.
transmitted by infected lymphocytes ingested by nursing babies of infected
mothers, blood-borne transmission, or sexually
The median age of patients with ATL is about 56 years, emphasizing the
long latency.
GENERAL ASPECTS OF LYMPHOID MALIGNANCIES
ETIOLOGY AND EPIDEMIOLOGY
non-Hodgkin's lymphomas
EBV
Burkitt's lymphoma in Central Africa and the occurrence of aggressive
non-Hodgkin's lymphomas in immunosuppressed patients in western
countries
EBV infection is strongly associated with the occurrence of extranodal
nasal T/NK cell lymphomas in Asia and South America.
GENERAL ASPECTS OF LYMPHOID MALIGNANCIES
ETIOLOGY AND EPIDEMIOLOGY
non-Hodgkin's lymphomas
HIV
predisposes to the development of aggressive, B cell non-Hodgkin's
lymphoma
overexpression of interleukin 6 by infected macrophages
Helicobacter pylori
Infection of the stomach by the bacterium
induces the development of gastric MALT (mucosa-associated lymphoid
tissue) lymphomas.
The bacterium does not transform lymphocytes to produce the lymphoma;
instead, a vigorous immune response is made to the bacterium and the
chronic antigenic stimulation leads to the neoplasia.
GENERAL ASPECTS OF LYMPHOID MALIGNANCIES
ETIOLOGY AND EPIDEMIOLOGY
non-Hodgkin's lymphomas
Chronic hepatitis C virus
lymphoplasmacytic lymphoma
Human herpesvirus 8 is associated with primary effusion lymphoma
in HIV-infected persons and multicentric Castleman's disease, a diffuse
lymphadenopathy associated with systemic symptoms of fever, malaise, and
weight loss.
TABLE 179–2. COMPARISON OF THE WORKING FORMULATION AND THE WORLD HEALTH ORGANIZATION
CLASSIFICATION OF LYMPHOID NEOPLASMS
WHO CLASSIFICATION
WORKING FORMULATION
B-Cell Neoplasms
T-Cell Neoplasms
Low Grade
A. Small lymphocytic consistent with CLL
B-cell CLL/SLL
B. Follicular, predominantly small cleaved cell
Follicular lymphoma, grade I
C. Follicular, mixed small cleaved and large cell
Follicular lymphoma, grade II
Intermediate Grade
D. Follicular, large cell
Follicular lymphoma, grade III
E. Diffuse, small cleaved cell
Mantle cell lymphoma
F. Diffuse, mixed small and large cell
Large B-cell lymphoma (rich in T cells)
Peripheral T cell, unspecified
G. Diffuse, large cell
Diffuse large B-cell lymphoma
Peripheral T cell, unspecified
H. Large cell immunoblastic
Diffuse large B-cell lymphoma
Peripheral T cell, unspecified
I. Lymphoblastic
Precursor B lymphoblastic
Precursor T lymphoblastic
J. Small non-cleaved cell
Burkitt's
Non-Burkitt's
Burkitt's lymphoma
High Grade
CLL = chronic lymphocytic leukemia; SLL = small lymphocytic lymphoma.
TABLE 179–1. WORLD HEALTH ORGANIZATION CLASSIFICATION OF NEOPLASTIC DISEASES OF THE HEMATOPOIETIC AND LYMPHOID
TISSUES: LYMPHOID NEOPLASMS
B-Cell Neoplasms
Precursor B-cell lymphoblastic leukemia/lymphoma*
Mature B-cell neoplasms
B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma
B-cell prolymphocytic leukemia
Lymphoplasmacytic lymphoma
Splenic marginal zone B-cell lymphoma
Hairy cell leukemia
Extranodal marginal zone B-cell lymphoma of the mucosa-associated lymphoid tissue type
Mantle cell lymphoma
Follicular lymphoma
Nodal marginal zone lymphoma with or without monocytoid B cells
Diffuse large B-cell lymphoma
Burkitt's lymphoma
Plasmacytoma
Plasma cell myeloma
T-Cell Neoplasms
Precursor T-cell lymphoblastic lymphoma/leukemia
Mature T-cell and NK cell neoplasms
T-cell prolymphocytic leukemia
T-cell large granular lymphocytic leukemia
NK cell leukemia
Extranodal NK/T-cell lymphoma, nasal and nasal type
Mycosis fungoides/Sézary syndrome
Primary cutaneous anaplastic large cell lymphoma
Subcutaneous panniculitis-like T-cell lymphoma
Enteropathy-type intestinal T-cell lymphoma
Hepatosplenic g/d T-cell lymphoma
Angioimmunoblastic T-cell lymphoma
Peripheral T-cell lymphoma (unspecified)
Anaplastic large cell lymphoma, primary systemic type
Adult T-cell lymphoma/leukemia (HTLVI+)
NK = natural killer; HTLV = human T-cell leukemia virus.
*The most common B- and T-cell malignancies are in bold.
Modified from Jaffe E, Bernard C, Harris N, et al: Proposed World Health Organization classification of neoplastic diseases of hematopoietic and
lymphoid tissues. Am J Surg Pathol 21:114, 1997.
TABLE 179–4. ANN ARBOR STAGING SYSTEM
Stage I
Involvement of a single lymph node region (I) or a single extralymphatic
organ or site (IE)
Stage II
Involvement of two or more lymph node regions on the same side of the
diaphragm (II) or localized involvement of an extralymphatic organ or site
(IIE)
Stage
III
Involvement of lymph node regions on both sides of the diaphragm (III) or
localized involvement of an extralymphatic organ or site (IIIE), the spleen
(IIIS), or both (IIISE)
Stage
IV
Diffuse or disseminated involvement of one or more extralymphatic
organs with or without associated lymph node involvement
Identification of the presence or absence of symptoms should be noted with each
stage designation. A = asymptomatic; B = fever, sweats, or weight loss greater than
10% of body weight.
HODGKIN'S DISEASE
Nodular Lymphocyte-Predominant Hodgkin's Disease
CLASSIC HD
LP
NST
MCT
LD
APPROACH TO THE PATIENT SPLENOMEGALY
PHYSIOLOGY AND ANATOMY.
the largest lymphatic organ
function
the primary immune response
filter for the blood
removing from the circulation senescent red cells,
Removing blood cells and other cells coated with immunoglobulins
Red pulp
occupies more than half the volume of the spleen
is the site where senescent red cells are identified and destroyed and red cell
inclusions are removed by a process known as pitting
In the absence of splenic function, inclusions known as Howell-Jolly bodies are
seen in circulating red blood cells
White pulp
of the spleen contains macrophages, B lymphocytes, and T lymphocytes,
participates in the recognition of microorganisms and foreign proteins, and
is involved in the primary immune response
APPROACH TO THE PATIENT SPLENOMEGALY
PHYSIOLOGY AND ANATOMY.
TABLE 178–6. CAUSES OF SPLENOMEGALY
Infection
Bacterial (e.g., endocarditis, brucellosis, syphilis, typhoid, pyogenic abscess)
Mycobacterial (e.g., tuberculosis)
Fungal (e.g., histoplasmosis, toxoplasmosis)
Parasitic (e.g., malaria, leishmaniasis)
Rickettsial (e.g., Rocky Mountain spotted fever)
Viral (e.g., Epstein-Barr virus, cytomegalovirus, HIV, hepatitis)
Benign disorders of the immune system (e.g., rheumatoid arthritis with
Felty's syndrome, systemic lupus erythematosus, drug reactions such as
to phenytoin, Langerhans' cell histiocytosis, serum sickness)
APPROACH TO THE PATIENT SPLENOMEGALY
PHYSIOLOGY AND ANATOMY.
TABLE 178–6. CAUSES OF SPLENOMEGALY
Malignant disorders of the immune system (e.g., acute or chronic myeloid
or lymphoid leukemia, non-Hodgkin's lymphoma, Hodgkin's disease,
Waldenström's macroglobulinemia, angioimmunoblastic-like T-cell
lymphoma, malignant histiocytosis)
Other malignancies (e.g., melanoma, sarcoma)
Congestive splenomegaly (e.g., portal hypertension secondary to liver disease,
splenic or portal vein thrombosis)
Hematologic disorders (e.g., autoimmune hemolytic anemia, hereditary
spherocytosis, thalassemia major, hemoglobinopathies, elliptocytosis,
megaloblastic anemia, extramedullary hematopoiesis)
Storage diseases (e.g., Gaucher's disease)
Endocrinopathies (e.g., hyperthyroidism)
Miscellaneous (e.g., sarcoidosis, amyloidosis, tropical splenomegaly, cysts)
APPROACH TO THE PATIENT SPLENOMEGALY
PHYSIOLOGY AND ANATOMY.
EVALUATION OF SPLENIC SIZE AND FUNCTION.
TABLE 178–7. METHODS FOR EVALUATION OF THE SPLEEN
Physical examination
Imaging
Ultrasonography
Computed tomography
Liver-spleen scanningGallium scanning
Positron emission tomography
BiopsyNeedle aspiration
Splenectomy
Laparotomy (total or partial splenectomy)
Laparoscopy
APPROACH TO THE PATIENT SPLENOMEGALY
PHYSIOLOGY AND ANATOMY.
an important skill, but it is not easily learned
the existence of a splenic rub on inspiration can lead to the diagnosis of splenic
infarct.
In general, a splenic "biopsy" involves splenectomy, which can be performed at
laparotomy or with laparoscopy
a splenectomy done via laparoscopy leads to maceration of the organ and reduces
the diagnostic information.
APPROACH TO THE PATIENT SPLENOMEGALY
PHYSIOLOGY AND ANATOMY.
AN APPROACH TO THE PATIENT WITH SPLENOMEGALY
1. Does the patient have a known illness that causes splenomegaly(e.g.,
infectious mononucleosis)? Treat and monitor for resolution.
2. Search for an occult infection (e.g., infectious endocarditis),
hematologicdisorder (e.g., hereditary spherocytosis), occult liver disease (e.g.,
cryptogeniccirrhosis), autoimmune disease (e.g., systemic lupus
erythematosus),or storage disease (e.g., Gaucher's disease). If found, manage
appropriately.
3. If systemic symptoms are present and suggest malignancy and/or focal
replacement of the spleen is seen on imaging studies and no other site is
available for biopsy,splenectomy is indicated.
4. If none of the above are true, monitor closely and repeat studies until
thesplenomegaly resolves or a diagnosis becomes apparent.
APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY
AN APPROACH TO THE PATIENT WITH SPLENOMEGALY
presentation
left upper quadrant pain or fullness or
of early satiety
catastrophic symptoms of splenic rupture
unexplained cytopenias
incidentally on physical examination
The presence of a palpable spleen on physical examination is almost always
abnormal.
The one exception to this rule is a palpable spleen tip in a slender, young
woman
In general, the presence of a palpable spleen should be considered a serious
finding and an explanation should be sought.
APPROACH TO THE PATIENT WITH LYMPHADENOPATHY AND SPLENOMEGALY