Trigger: LUQ mass • Primary defect is membrane instability due to

dysfunction or deficiency of red cell skeletal protein

WILM’S TUMOR (NEPHROBLASTOMA) Ankyrin mutations
 Wilms tumor, or nephroblastoma, is the most Alpha spectrin mutation
common childhood abdominal malignancy. The Beta spectrin mutation
median age at diagnosis of Wilms tumor (see the Protein 4.2 mutation
image below) is approximately 3.5 years. Band 3 mutation

Signs and symptoms Abnormalities of spectrin or ankyrin are the most

common molecular defects. Dominant defects have
 Asymptomatic abdominal mass (in 80% of children
been described in beta spectrin and band-3.
at presentation)
Recessive defects have been described in ankyrin.
 Abdominal pain or hematuria (25%)
 Urinary tract infection and varicocele (less common)
HEMATOLOGIC FEATURES
 Hypertension, gross hematuria, and fever (5-30%)
 Hypotension, anemia, and fever (from hemorrhage • Mild to moderate anemia
into the tumor; uncommon) • MCV is decreased, MCHC increased, RDW elevated
 Respiratory symptoms related to lung metastases (in • Reticulocytosis (RPI>2)
patients with advanced disease; rare) • Peripheral Blood Smear (PBS) revealspherocytosis.
About >15-20% of the RBCs are spherocytes
History • Direct antiglobulin test negative
• Increased osmotic fragility test
 The most common manifestation of Wilms tumor is
• Reduced survival of 51Cr labeled RBCssecondary to
an asymptomatic abdominal mass; an abdominal
splenic sequestration
mass occurs in 80% of children at presentation.
• Bone Marrow examination reveal Normoblastic
 Abdominal pain or hematuria occurs in 25%.
hyperplasia, increased iron
 Urinary tract infection and varicocele are less
• Eosin 5-maleimide dye staining with flow cytometry
common findings than these.
 Hypertension, gross hematuria, and fever are
DIAGNOSIS
observed in 5-30% of patients.
 A few patients with hemorrhage into their tumor may • Diagnosis of HS can be established from:
present with hypotension, anemia, and fever. Rare Positive family history
patients with advanced disease may present with Presence of typical clinical and laboratory features of
respiratory symptoms related to lung metastases. the disease:
─ Splenomegaly
Physical examination ─ spherocytes on the blood smear
─ Reticulocytosis
 Examination often reveals a palpable abdominal
─ Elevated mean corpuscular hemoglobin
mass.
concentration.
o Pay special attention to features of those
─ If these are present, no additional testing is
syndromes (WAGR syndrome and Beckwith-
necessary to confirm the diagnosis.
Wiedemann syndrome [BWS]) associated with
• If the diagnosis is less certain, the recommended tests
Wilms tumor (ie, aniridia, genitourinary
that have a high predictive value for Heriditary
malformations, and signs of overgrowth)
Spherocytosis (HS) are:
o The abdominal mass should be carefully
the flow cytometric EMA (eosin 5maleimide) binding
examined. Palpating a mass too vigorously
test
could lead to the rupture of a large tumor into
cryohemolysis test.
the peritoneal cavity.
Although no test for HS is 100% reliable, the EMA
binding test had a diagnostic sensitivity and
HEREDITARY SPHEROCYTOSIS
specificity of 93% and 98% respectively.
GENETICS
• The classic incubated osmotic fragility test can detect
• Autosomal dominant inheritance
the presence of spherocytes in the blood; however, it is
• No family history in 50% of cases
not specific to HS and may be abnormal in other
• Some are due to genetic mutations
hemolytic anemias.
• Common in people of northern European heritage
CLINICAL FEATURES
PATHOGENESIS
• Anemia and jaundice Not common among Filipinos but the most common
• Splenomegaly form of qualitative hemoglobin defects
• Presents in neonates with hyperbilirubinemia, Hemoglobin S - position 6 on the β chain has a
reticulocytosis, normoblastosis, spherocytosis, valine (nonpolar) substituted for the normal glutamic
negative DAT, splenomegaly acid (polar)
• Presents before puberty in most patients Carriers of the gene in Africa may be as high as 20-
• Diagnosis made much later in life 40% because when parasitized by Plasmodium
(causes malaria), cells containing HgbS will sickle
THALASSEMIAS (QUANTITATIVE) quickly, either killing the parasite or RBCs to be
• Syndromes that result from inherited abnormalities in sequestered in the spleen and destroyed.
globin synthesis that lead to decreases in the Therefore, having the gene provides a certain
production of hemoglobin protection against malaria
• Decreased globin chains → Low hemoglobin → It is usually only in the homozygous state that the
Anemia disease is so devastating
8-10% of African-American are carriers in the US,
CLINICAL FEATURES with .3-1.3 % being homozygous
• Failure to thrive in early childhood (Onset depends on
zygosity) CLINICAL FINDINGS
• Anemia • The disease is diagnosed early at about 6 months of
• Jaundice, gallstones age when hemoglobin F is replaced with HgbS rather
• Hepatosplenomegaly than hgb A
• Growth retardation, delayed puberty, endocrine The same time Beta thalassemia major would start
disturbances to manifest
• Skin bronzing • Homozygous individuals frequently do not live beyond
Repeated blood transfusion middle age
• Bone abnormalities • Chronic hemolytic anemia
Abnormal facies, prominence of malar eminence, due to extravascular hemolysis
frontal bossing, depression of the bridge of the RBC survival may decrease to 14 days
nose, exposure of upper central teeth Increased bilirubin turnover leads to gallstones
Hair on end appearance on skull radiograph • Hematologic complications that may occur are called
Fractures due to marrow expansion and abnormal crises. Three types of crisis may occur:
bone structure Aplastic crisis
Generalized skeletal osteoporosis ─ usually associated with infection and results in
temporary marrow aplasia due to overwork
LABORATORY FINDINGS Hemolytic crisis
Non-specific ─ sudden acute anemia
• Peripheral blood smear ─ in young children this may be due to splenic
Microcytic-hypochromic red cells, target cells, pooling
anisopoikilocytosis Vaso-occlusive or painful crisis
• Reticulocytosis ─ plugs of rigid sickle cells in the capillaries cause
• Heinz bodies (denatured proteins in RBC) tissue damage and necrosis and lead to organ
• Low MCV (mean corpuscular volume) dysfunction
• Low MCH (mean corpuscular haemoglobin) ─ This is the “hallmark” of sickle cell disease

Specific findings LABORATORY FINDINGS

• Hemoglobin electrophoresis • Normochromic, normocyticanemia
Beta thalassemia • 10-20% reticulocytes
─ Increased HbA2 >3.5% • 6-10 g/dLHgb
─ Increased HbF 30-100% • During crisis – marked anisocytosis and poikilocytosis
with target cells, fragmented cells, nucleated RBCs,
SICKLE CELL ANEMIA sickle cell
• Sickle cell disease • Basophilic stippling, Howell Jolly bodies and
Qualitative hemoglobin defect (vs Thalassemia siderocytes due to splenic hypofunction
which is more of quantitative) • Bone marrow – normoblastic hyperplasia
• Diagnosis – by a peripheral blood smear, hemoglobin
electrophoresis, solubility tests, sodium metabisulfite
will cause the cells to sickle by deoxygenating the
blood
PEDIATRIC RHABDOMYOSARCOMA
 Rhabdomyosarcoma (RMS) is the most common
soft tissue sarcoma in children, accounting for 4.5%
of all cases of childhood cancer. It is the third most
common extracranial solid tumor of childhood.
 Overall, the male-to-female ratio is 1.2-1.4:1.
Differences are observed according to the site of
primary disease.
o GU tract: The male-to-female ratio is 3.3:1 in
patients with bladder or prostate involvement
and 2.1:1 in rhabdomyosarcoma of the GU tract
without bladder or prostate involvement.
o Extremity: The male-to-female ratio is 0.79:1.
o Orbit: The male-to-female ratio is 0.88:1.
 Approximately 87% of patients are younger than 15
years, and 13% of patients are aged 15-21 years.
Rhabdomyosarcoma rarely affects adults. Age-
related differences are observed for the different
sites of primary disease. Two age peaks tend to be
associated with different locations. Patients aged 2-6
years tend to have head and neck or GU tract
primary tumors, whereas adolescents aged 14-18
years tend to have primary tumors in extremity,
truncal, or paratesticular locations.
 Typical presentations by the location of
nonmetastatic disease are as follows:
o Orbit - Proptosis or dysconjugate gaze [2]
o Paratesticular - Painless scrotal mass
o Prostate - Bladder or bowel difficulties
o Uterus, cervix, bladder - Menorrhagia or
metrorrhagia
o Vagina - Protruding polypoid mass (botryoid,
meaning a grapelike cluster)
o Extremity - Painless mass
o Parameningeal (ear, mastoid, nasal cavity,
paranasal sinuses, infratemporal fossa,
pterygopalatine fossa) - Upper respiratory
symptoms or pain
EPIDERMOID CYST
 Epidermoid cyst — Epidermoid cysts, also called
epidermal cysts, epidermal inclusion cysts, or,
improperly, "sebaceous cysts," are the most
common cutaneous cysts.
 They can occur anywhere on the body and typically
present as skin-colored dermal nodules (picture
21B), often with a clinically visible central punctum
(picture 21A).
 The size ranges from a few millimeters to several
centimeters in diameter. Infected, fluctuant cysts
tend to be larger, more erythematous, and more
painful than sterile inflamed cysts, although an
intense inflammatory response to cyst rupture may
also present as a fluctuant nodule.
 The cyst wall consists of normal stratified squamous
epithelium derived from the follicular infundibulum.
 The cyst may be primary or may arise from the
implantation of the follicular epithelium in the dermis
as a result of trauma or from a comedone.
 Lesions may remain stable or progressively enlarge.
Spontaneous inflammation and rupture can occur,
with significant involvement of surrounding tissue
 The diagnosis of epidermoid cyst is usually clinical,
based upon the clinical appearance of a discrete
cyst or nodule, often with a central punctum, that is
freely movable on palpation
 The cyst wall consists of stratified squamous
epithelium similar to skin surface or infundibulum of
hair follicles. The cavity is filled with laminated layers
of keratinous material. In ruptured cysts, a foreign-
body inflammatory granulomatous reaction due to
the release of the cyst content into the dermis may
result in the formation of a keratin granuloma
SPLENIC DISORDERS
Normal splenic function — The spleen lies within the
peritoneal cavity in the posterior portion of the left upper
quadrant, below the diaphragm and adjacent to the 9th to
the 11th ribs, stomach, colon, and left kidney (figure 1),
with its hilum in close approximation to the tail of the
pancreas (figure 2). The spleen weighs 80 to 200 grams
and 70 to 180 grams in the normal adult male and
female, respectively, averaging about 150 grams, or
approximately 0.2 percent of body weight [4]. It is not
usually palpable, but may be felt in children,
adolescents, and some adults, especially those of
asthenic build.
The spleen is a major lymphopoietic organ, containing
approximately 25 percent of the total lymphoid mass of
the body; this component, as well as components of the
monocyte-macrophage system, can react and enlarge
quickly after the onset of infection or inflammation.
Under such circumstances, a spleen enlarged to scan
but not palpably enlarged may be a nonspecific marker
of inflammation similar to an elevated erythrocyte
sedimentation rate or other acute phase reactants.
(See "Acute phase reactants".)
A major function of the spleen is to remove particulates
(eg, opsonized bacteria, antibody-coated cells) from the
blood stream [5]. This function is most apparent when
the spleen has been removed, since splenectomized
patients are susceptible to bacterial sepsis, especially
with encapsulated organisms. This function is also
associated with trapping and destruction antibody-
coated platelets or red cells in patients with immune
thrombocytopenia (ITP) or autoimmune hemolytic
anemia, respectively. (See "Clinical features, evaluation,
and management of fever in patients with impaired
splenic function", section on 'Role of the spleen in
infection' and "Immune thrombocytopenia (ITP) in adults:
Clinical manifestations and diagnosis", section on
'Pathogenesis' and "Warm autoimmune hemolytic
anemia: Treatment", section on 'Splenectomy'.)
The spleen also serves as a quality control mechanism
for red cells, removing senescent and/or poorly
deformable red cells from the circulation. This "culling"
function is taken advantage of when splenectomy is
employed as treatment for hereditary spherocytosis.
(See "Hereditary spherocytosis", section on
'Splenectomy'.)
As part of this quality control function, the spleen also
removes particles from within circulating red cells (ie, its
"pitting" function), such as nuclear remnants (Howell-
Jolly bodies), insoluble globin precipitates (Heinz
bodies), and normally-occurring endocytic vacuoles. Of
clinical importance, Howell-Jolly bodies appear in
circulating red cells when the spleen has been surgically
removed or has reduced function (ie, hyposplenism),
and subsequently disappear when and if splenic
function returns, as in the following circumstances:
●Splenosis due to the growth of splenic implants
resulting from the spillage of cells from the splenic
pulp during splenectomy or following trauma to the
abdomen. (See 'Splenosis' below.)
●Growth of preexisting accessory spleen(s) or
splenic implants following splenectomy, classically
(albeit rarely) described in patients with immune
thrombocytopenia (ITP) or autoimmune hemolytic
anemia (AIHA) undergoing a late relapse after
successful splenectomy [6,7].
●Improvement in splenic function, as seen in some
patients with sickle cell anemia following successful
allogeneic hematopoietic cell transplantation [8] or
institution of a chronic transfusion program in
children or young adults [9,10].
Cysts and pseudocysts — A splenic cyst (or multiple
cysts) may be noted as an incidental finding on
conventional imaging techniques, or as a result of
evaluation of a patient with left upper quadrant pain, left
shoulder pain, abdominal enlargement, or splenomegaly.
A vast number of abnormal conditions, many of which
are rare, may be associated with such cysts, including
[71-73]:
●Post-traumatic cysts/pseudocysts, including cystic
splenosis
●Hydatid (echinococcal) cysts
●Congenital cysts
●Epidermoid, mesothelial cysts
●Hemangioma, lymphangioma
●Polycystic kidney disease with splenic cysts
●Splenic peliosis
●Cystic metastasis to the spleen
Some splenic cysts may remain unchanged for many
years, while others may enlarge slowly, enlarge to
massive proportions, rupture, bleed, or become
secondarily infected. Since non-parasitic splenic cysts
are rare, there is no evidence-based information
regarding their optimal surgical management [74].
For those with symptomatic cysts, or cysts that are
enlarging over time, a number of radiologic and surgical
procedures are available for investigating the probable
diagnosis [74-76]. Available options for those with non-
parasitic cysts include percutaneous procedures (eg,
biopsy, aspiration, drainage), or more direct surgical
interventions such as decapsulation/cyst wall unroofing,
partial or total splenectomy. However, only splenectomy
provides diagnostic certainty, which is rarely clinically
justified.
Treatment of echinococcal cysts is discussed
separately.
Splenic infarction — Splenic infarction occurs when the
splenic artery or one or more of its sub-branches
become occluded with an infected or bland embolus or
clot. Affected patients classically present with acute left
upper quadrant pain and tenderness, although atypical
presentations are common. As an example, in a study of
26 patients with splenic infarction seen at a single
medical center, the following clinical and laboratory
features were noted [50]:
●Left-sided abdominal pain: 48 percent; abdominal
pain was absent in 16 percent
●Fever >38°C: 36 percent
●Left upper quadrant abdominal tenderness: 36
percent; abdominal tenderness was absent in 32
percent
●Nausea or vomiting: 32 percent
●Splenomegaly: 32 percent
 ●Elevated serum lactate dehydrogenase (LDH): 71
percent
●White blood cell count >12,000/microL: 56
percent
Symptoms — The presence or absence of symptoms
due to an enlarged spleen depends on many factors,
such as the acuteness and nature of the underlying
illness, as well as the size of the spleen. Thus, a
minimally enlarged spleen secondary to an acute viral
infection may be quite tender, while a markedly enlarged
spleen in one of the chronic myeloproliferative disorders
(eg, polycythemia vera, primary myelofibrosis) may be
totally asymptomatic unless there is an episode of
splenic infarction.
When present, symptoms of an enlarged spleen may
include one or all of the following:
●Pain, a sense of fullness, or discomfort in the left
upper quadrant
●Pain referred to the left shoulder
●Pleuritic pain
●Early satiety, due to encroachment on the
adjacent stomach
Acute pleuritic-like pain and tenderness in the left upper
quadrant in the presence of fever suggests the presence
of perisplenitis or splenic abscess, most likely due to
infection originating elsewhere in the body (eg, sepsis,
infective endocarditis). Splenic abscess may be
accompanied by a left pleural effusion [48] or by splenic
infarction if due to septic emboli [44]. Some patients with
splenic infarction have an associated friction rub over the
infarcted area. (See 'Splenic disorders' above
and "Causes of abdominal pain in adults".)
SPLENIC SIZE AND PALPABILITY — The median
splenic weight in adults is about 150 grams [4,85]. It is
not usually palpable, but may be felt in children,
adolescents, and some adults, especially those of
asthenic build [86]. A spleen becomes palpable not only
as a result of its size, but also its texture. Ordinarily, the
spleen is a soft organ, but a spleen infiltrated with
lymphoma or one with extramedullary hematopoiesis
(eg, a myeloproliferative disorder) is much firmer and
thus easier to feel. (See 'Normal splenic
function' above.)
Physical examination — A number of studies have
shown wide interobserver variability in the ability to
appreciate an enlarged spleen, which is generally not
associated with the level of clinical experience [87].
There are at least six different palpation and percussion
maneuvers available. Only two of these will be
discussed here: abdominal palpation and percussion of
Traube's semilunar space. The interested reader is
referred to the literature and textbooks of physical
examination techniques for further information on this
subject [55,87-89].
Palpation method — The most frequent errors made in
examination of the spleen involve incomplete relaxation
of the abdominal musculature of the patient and the
musculature of the examiner's hand(s). Effectiveness in
palpating the spleen can be maximized by remembering
that the major error in splenic palpation is due to
pressing too hard on the patient's abdomen, and by
paying attention to the following:
●With the patient supine, allow the patient to feel
the examining hand on the abdomen before
pressing down, and to become adjusted to its
presence. Do not suddenly increase pressure
during palpation, as an enlarged spleen may be
quite tender (particularly if it has enlarged quickly)
and the patient may be reluctant to allow the
examination to continue.
●Make sure that the patient is relaxed, with arms at
the sides of the abdomen. If the arms are raised,
this may stiffen the abdominal musculature and
make examination more difficult.
●Relaxation of the patient can be improved if the
legs and neck are slightly flexed. Relaxation of the
examiner can be improved by being comfortably
seated in a chair alongside the patient's bed or
examining table, with the examiner on the patient's
right side, the right hand doing the palpation and
the left hand underneath and supporting the
patient's left lower posterior rib cage.
A spleen that is only minimally enlarged will be quite
movable with respiration, and may be palpable only at
the end of inspiration. Using a light touch, with the skin
depressed under the left costal margin, a minimally
enlarged spleen can be felt as a rounded edge with the
consistency of normal liver, which slips under the
examiner's fingers at the end of inspiration and back on
expiration.
Since the spleen is normally a posterior structure,
increased sensitivity can occasionally be obtained by
placing the patient in the right lateral decubitus position,
with knees and neck flexed. This maneuver also
increases relaxation of the abdominal musculature and
rotates the spleen to a more anterior position. One study
suggested that this additional maneuver was not useful
when it followed examination of the patient in the supine
position [55]. However, it is this authors' experience that
some spleens not palpable with the patient in the supine
position are felt with the patient in the right lateral
decubitus position.
With greater degrees of enlargement, the spleen rotates
to a more anterior and rightward position, and may
extend downward into the pelvis. Under these
circumstances, the lower pole of the spleen may not be
easily felt (since it is well below the left costal margin),
and splenomegaly is appreciated either by palpating at
successively lower levels on the left side of the abdomen
or by palpating the medial edge of the spleen. The
presence of a notch or indentation on the medial splenic
edge is a further indication that the mass is spleen and
not the left kidney or a pancreatic pseudocyst.
In more extreme cases, the enlarged spleen extends
across the midline, and may even be palpable in the
right upper quadrant. The presence of exquisite splenic
tenderness suggests the presence of infarction or
perisplenitis in such massively enlarged spleens.
Using ultrasound examination of the spleen as a gold
standard (criteria described above), a number of studies
have compared the various palpation and percussion
techniques for evaluating splenic size. Major conclusions
from all of these studies are the insensitivity of available
techniques, wide interobserver variability, and the
complementary value of combinations of techniques (ie,
palpation plus percussion). Specific observations in
individual studies can be summarized:
●Palpation of the spleen was significantly more
accurate in lean versus obese individuals [55].
●Sensitivity and specificity of percussion of
Traube's semilunar space were 62 and 72 percent,
respectively [91].
●The specificity of direct splenic palpation was 92
percent, with a positive predictive value of 92
percent [89].
●The combination of positive results on percussion
of Traube's space (ie, dullness to percussion) and
positive palpation had a sensitivity and specificity of
46 and 97 percent, respectively [55].
If palpation maneuvers convince the examiner that the
spleen is enlarged, this high degree of specificity
suggests that follow-up scanning to confirm the finding is
not necessary. However, scanning may still be useful to
document baseline splenic involvement and size in
preparation for treatment, or to document the presence
of other abnormalities (eg, infiltrative disease of other
abdominal organs, intraabdominal lymphadenopathy).
Splenic imaging for size estimation — There is a
reasonably close correlation between splenic weight and
splenic size on external scanning. This was illustrated in
a retrospective study of 81 patients who had undergone
a total of 101 abdominal ultrasound examinations within
four months of death and whose spleens were weighed
during autopsy; the splenic weight in grams was equal to
(0.43 x length x width x thickness) for measurements in
centimeters [94].
A number of criteria have been proposed to define the
size of the normal spleen in adults using these
procedures:
●Ultrasound – The spleen is considered to be
normal in size if its length is <13 cm [87] or its
thickness is ≤5 cm on ultrasound examination [95].
In one study of healthy stem cell donors, mean
values for splenic length and width were 10.8 and
3.6 cm, respectively [96]. The mean predictive
errors for repeated ultrasound measurements of
splenic length and width were 1.5 and 1.9 mm,
respectively.
●Plain film – The spleen is normal in size if it is not
seen on the abdominal plain film, if it is <5 cm in
width, or if it is less than 85 percent of the size of
the normal kidney [92]. It is considered enlarged if
it is >6 cm wide or >13.6 cm long, or if (length x
width) is >75 cm2.
●Liver-spleen colloid scanning – The spleen is
normal in size if its length on the posterior view of
the liver-spleen scan is ≤13 cm [97]. It is
considered enlarged if the posterior length is >14
cm, or if the lateral scan area exceeds 80 cm 2 [92].
In one study, 98 of 100 spleens with a posterior
length ≤13 cm on colloid scanning weighed less
than 250 grams and were normal at postmortem
examination [97].
●CT or PET/CT scanning – The spleen is
enlarged if its length is >10 cm [98]. In one study
this value had a sensitivity, specificity, and
accuracy of 81, 90, and 88 percent, respectively.
Nevertheless, a palpable spleen usually means the
presence of significant splenomegaly. As a general rule,
a spleen has to be increased in size by at least 40
percent before it becomes palpable [99]. However, it has
been estimated that 20 percent of spleens with an
estimated weight of more than 900 grams are not
palpable [93].
Massively enlarged spleen — A spleen enlarged such
that its lower pole is within the pelvis, or which has
crossed the midline into the right lower or right upper
abdominal quadrants is considered to be massively
enlarged. There are only a few conditions that cause this
degree of splenic enlargement, each of which discussed
elsewhere on the appropriate topic reviews:

●Chronic myeloid leukemia

●Myelofibrosis, primary or secondary to
polycythemia vera or essential thrombocytosis
●Gaucher disease
●Lymphoma, usually indolent, including hairy cell
leukemia [106]
●Kala-azar (visceral leishmaniasis)
●Hyperreactive malarial splenomegaly syndrome,
also called tropical splenomegaly syndrome [107]
●Beta thalassemia major or severe beta
thalassemia intermedia
●AIDS with Mycobacterium avium complex [105]