Appendix cancer differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Soroush Seifirad, M.D.[2]

Overview

Appendix cancer must be differentiated from benign appendix lesions (mucocele, acute appendicitis), colorectal cancers, adenexal masses (ovarian tumors), and carcinoid tumors of the other organs.

Differentiating appendix cancer from other Diseases

Diseases Clinical manifestations Para-clinical findings
Symptoms Physical examination
Lab Findings Imaging Histo-

pathology

Abdo-
minal
pain
Change in girdle size Bowel

freq-

uency

Other

symptoms

Abdo-
minal
mass
Abdo-
minal
tender-
ness
Other

physical

exami-

nation

findings

5-HIAA
and/or
CgA
Other lab findings CT scan MRI Utra-

sounography

Other

diagnostic

studies

and

imaging

modalities

Appendix cancer Adeno-

carcinoma1

+/- -/+ - - -
  • Soft
    tissue
    thickening
  • Wall
    irregularity
  • Presence
    of
    pseudo-
    myxoma
    peritonei
  • Calcification
  • Internal
    septations
  • Peri
    appendiceal
    fat
    stranding
    and
    intra-
    peritoneal
    free fluid
    which is a
    nonspecific
    finding
  • Cystic
    lesion
  • Diffusion
    weighted
    MRI
    has
    been
    shown to
    be
    the
    modality
    of choice
    for
    peritoneal
    carcino-
    matosis
  • Increased
    fluid
    signal on
    T2 weighted sequence
  • Soft
    tissue
    mass in
    the
    appendix
  • Invasion to
    the other
    structures
  • Dilated
    appendix
  • Peri-
    appendiceal
    fluid
    collection
  • Distinct
    appendix
    wall
    layers
Positron
emission
tomography

(PET)
Gross
pathology
:
  • Gray/yellow
    color
  • Cystic
    structures
    with
    angiolymphatic
    invasion
  • Appendix
    might be
    buried
    within
    the mass

Microscopic
pathology:

IHC:

  • MUC 2
  • MUC5AC
  • CK 8/18
  • CK 13
  • CK 19
  • CK 20
Carcinoid

tumor2

+/- - - - +

Ki67:
a reliable
marker of
cell
proliferation

Gross
pathology
:
  • Prevalent
    at the
    tip of
    appendix
  • Generally
    less than
    1 cm
  • Gray or
    yellow
  • Well-
    demarcated
    firm
  • Intramural
    nodules
    that may
    narrow or
    obliterate
    appendiceal
    lumen
  • Proximal
    tumors
    may cause
    obstruction
    and
    appendicitis

Microscopic
pathology:

  • Insular
    growth
    pattern
    of solid
    islands of
    uniform
    polygonal
    cells with
    minimal
    pleomorphism
  • Retraction
    of
    peripheral
    tumor
    cells from
    stroma
  • Angio-
    lymphatic
    invasion
    is common
  • Granular
    eosinophilic
    cytoplasm
    with either
    diffusely
    scattered
    or
    peripherally
    clumped
    granules
  • Two types
    of well
    differentiated
    tumors:
    EC cell
    (serotonin
    producing)
    and rarely
    L-cell
    (enteroglucagon
    or
    peptide YY
    producing)

IHC:

  • Might be
    positive for
    S100
Goblet

cell

carcinoid

+ +/- +/- +
  • Ascites
  • Shifting
    dullness
  • May
    appear
    anemic
+/- Unfortunately,
compared to the other carcinoid tumors of appendix,
GCC is more aggressive and
patients with GCC generally present at higher stages.
Hence, in addition to
the above mentioned
general findings for appendix cancers,
imaging studies should
look for evidences of peritoneal involvement,
bone metastasis, lymphadenopathy,
and metastatic lesions
in ovaries and/or prostate.

Gross
pathology
:

  • No gross
    tumor might
    be present
  • Thickened
    appendiceal
    wall

Microscopic
appearance:

  • GCC Generally
    spares mucosa
    and
    infiltrates
    muscularis
    propria
    and
    peri-
    appendiceal
    fat
  • Tumor
    cell clusters
  • Crypt-like
    structures
  • Tubules of
    mucus-secreting
    cells distended
    with mucin
    resembling
    goblet cells
  • Eosinophilic
    cytoplasm
    resembling
    carcinoid
    tumors
  • Pools of
    extracellular
    mucin
  • Scattered
    Paneth cells
    in tumors
    with crypt
    like
    structures
  • Extensive
    perineural
    invasion
  • Carcinomatous
    growth
    pattern:
  • Cribriform
    growth
    pattern,
    solid
    sheets of
    infiltrating
    signet ring
    cells
  • Nuclear
    pleomorphism
  • Increased
    mitotic
    activity
Diseases Abdo-
minal
pain
Change in girdle size Bowel

freq-

uency

Other

symptoms

Abdo-
minal
mass
Abdo-
minal
tender-
ness
Other

physical

exami-

nation

findings

5-HIAA
and/or
CgA
Other lab findings CT scan MRI Utra-

sounography

Other

diagnostic

studies

and

imaging

modalities

Histo-

pathology

Appendix Mucocele Mucosal

hyperplasia

- - -
  • Generally asympto-
    matic
  • Benign
    even
    after
    rupture
- +/- N/A - N/A
  • low
    attenuation
    well
    defined
    mass in
    RLQ
    near
    cecum
  • Inflammation
    is the key to
    distinguish
    between
    appendicitis
    and
    mucocele
  • Wall
    thickness
    does not
    distinguish
    between
    malignant
    and
    benign
    mucocele
  • Intramural
    nodule
    is a sign of
    neoplastic
    lesions. 4
Rounded
right iliac
fossa mass
  • T1: The
    signal
    depends
    on
    the mucin
    concen-
    tration,
    may be
    from
    hypointense
    to
    isointense
  • T2:
    Hyperintense
  • Histo-
    logically
    benign
  • Dilated
    fluid
    filled
    appendix
    in the
    RLQ.
  • Thin
    appendiceal
    wall
  • A focus
    of
    hyper-
    echogenicity
  • Since
    generally
    there is
    no inflammation
  • Surrounding
    fat
    is normal.
  • No peri-
    appendiceal
    fluid or
    collection
N/A Similar
to
hyperplastic
colon
polyp
Simple

or

retention

cyst

- - - - +/- - - N/A Degenerative
epithelial
changes
because of
obstruction
Mucinous cyst-

adenomas

+/- +/-
  • Generally asympto-
    matic
  • Rupture
    may
    lead
    to
    Pseudo-
    myxoma
    peritonei
+/- +/- If develop

pseudo-
myxoma
peritonei
:

-
  • Histo-
    logically
    benign
  • Similar
    to
    colon
    adenomatous
    polyps or
    villous
    adnomas
Mucinous cystadeno-

carcinomas

+/- +/- +/- +/- - -
  • Glandular
    invasion
    into the
    stoma
  • Pseudo-
    myxoma
    peritonei
Diseases Abdo-
minal
pain
Change in girdle size Bowel
freq-
uency
Other

symptoms

Abdo-
minal
mass
Abdo-
minal
tender-
ness
Other

physical
exami-
nation
findings

5-HIAA
and/or
CgA
Other lab findings CT scan MRI Utra-
sounography
Other
diagnostic
studies
and
imaging
modalities
Histo-

pathology

Ovarian cancer +/- +/- +/- + +/- -
  • Adnexal
    mass
  • Adenexal
    Cyst
    (simple
    or
    complex)
  • Fluid
    accumulation
  • Endometrial
    thickening
  • Calcification
  • Pleural
    effusion
  • Peritoneal
    involvement
  • Lympha-denopathy
  • Adnexal
    mass
  • Adenexal
    cyst
    (simple
    or
    complex)
  • Except for
    Thecoma,
    ovarian
    masses
    are
    generally hyperintense
    on T1 and
    hypo or
    sointense
    on
    T2 imaging
  • Fluid
    accumulation
  • Endometrial
    thickening
  • Calcification
  • Pleural
    effusion
  • Peritoneal
    involvement
  • Lympha-
    denopathy
  • Adnexal
    mass
  • Adenexal
    cyst
    (simple
    or
    complex)
  • Fluid
    accumulation
  • Increased
    Doppler
    flow
  • Endometrial
    thickening
  • Calcification
N/A Depends
on the
tumor type.
You may
find the
details
here.
Colorectal cancer +/- +/- + +/- Colonoscopy

Adeno-

carcinoma

Carcinoids

-/+(Carcinoid tumors)
  • Tumor
    mass
    and
    the
    extension
    of
    tumor to
    other
    structures
Generally
not
recommended:
may
evaluate
liver metastasis
or presence
of fluid
in abdominal
cavity, but it is
neither
sensitive
nor
specific.
PET
scan
,
Endoscopy,
Colonoscopy,

Barium enema

  • Depends
    on the
    tumor
    type.
    You will
    find more
    information
    here
Pseudomyxoma

peritonei

+ + Bloating - + Ascites

Shifting dullness

-
  • Nonspecific
  • Depends
    on the
    etiology
    of the
    disease
  • Low-
    attenuation
    Scalloping
    of the
    visceral
    surfaces
    differentiates
    pseudo-
    myxoma

    from other
    causes of
    peritonitis.
  • Typically
    does not
    invade
    visceral
    organs
    or spread
    by lymphatic
    or
    hemato-
    genous
    routes
    unlike
    mucinous
    carcino-
    matosis

Charact-
erized
by a mass
which is
hypointense
on
T1-weighted
MRI
and
hyperintense
on
T2-weighted
MRI.
MRI has
better
sensitivity
in
detecting
ascites
fluid
and
mucocele.

  • The echoes
    within
    pseudo-
    myxoma
    peritonei

    are not
    mobile.
  • Echogenic
    septations
    within
    the
    gelatinous
    ascites.
  • Scalloping
    of the
    hepatic
    and
    splenic
    margins
18F-FDG
PET scan
  • Depending
    on
    WHO
    classification,
    whether it is
    low or high
    grade
    with
    cellular atypia
    or acellular mucin.
    ( DPAM, PMCA)
  • Gelatinous
    ascites
    in peritoneum
    and
    visceral
    organs,
    usually
    underneath
    the right
    hemidiaphragm,
    liver.
  • Omental cake

IHC:

Carcinoid syndrome -/+ - - - + Depends
on the
tumor
type:
Depends on the
primary tumor location and type
  • Salt
    and
    pepper
    nuclei
  • Cellular
    uniformity
  • Central
    ovoid
    nucleus
  • Presence of
    ribbons,
    trabeculae,
    nesting,
    glands,
    gyriform,
    pseudorosettes
  • Insulinoma
    (Amyloid
    deposition)
  • Somatostatinom
    (Psammoma
    bodies)
  • Hyaline
    globules

IHC:

  • Synaptophysin
    (almost
    always,
    strongly
    and
    diffusely
    expressed )
  • CGA
  • CD56 and PGP
    ( less
    specific)
  • PDX1
  • ISL1
Appendicitis 3 PU,
RLQ
- Nausea
&
vomiting
,
decreased

appetite

+/- + -
  • Appendiceal
    wall
    thickening
    /perforation
  • Peri-
    appendiceal
    inflammation,
    fluid
    accumulation,
  • Fat
    stranding
Increased
fluid
signal
on T2
weighted
sequence
Evidences
of
inflammation
  • Dilated
    appendix
  • Peri-
    appendiceal
    fluid
    collection
  • Distinct
    appendix
    wall
    layers
Tc-99m
labeled
anti-
CD15
antibodies
Evidences
of
inflammation
Diseases Abdo-
minal
pain
Change in girdle size Bowel

frequ- f ency

Other

symptoms

Abdo-
minal
mass
Abdo-
minal
tender-
ness
Other

physical

exami-

nation

findings

5-HIAA
and/or
CgA
Other lab findings CT scan MRI Utra-

sounography

Other

diagnostic

studies

and

imaging

modalities

Histo-

pathology

1 Adenocarcinomas usually present with appendicitis, barely they might present with Pseudomyxoma peritonei; meanwhile pseudomyxoma peritonei is more prevalent in perforated mucocele, goblet cell tumor or high stages of adenocarcinoma.

2 Generally appendix carcinoids are asymptomatic, they were only become symptomatic if they metastasize to the liver, or in rare cases make an obstruction and present with appendicitis which is quit uncommon in appendiceal carcinoids compared to appendiceal adenocarcinoma. Any patient with carcinoid syndrome should be evaluated for appendix carcinoids.

3 Every patient with appendicitis should be evaluated for appendix cancer, 0.5 in 100 appendicitis cases are because of appendix cancer.

4 Imaging is not a reliable method to distinguish between neoplastic and non-neoplastic lesions, hence every patient should undergo surgery, appendectomy and histopathologic evaluation of the lesion

*Abbreviations: RLQ: Right Lower Quadrant, AFP: Alpha-fetoprotein, HCG: Human chorionic gonadotropin, LDH: Lactate Dehydrogenase, CEA: Carcinoembryonic antigen, CA-125: Cancer antigen 125, 5-HIAA: Urinary 5-hydroxyindoleacetic acid , CgA: Serum Chromogranin A ,PU: Periumbelical, TR: Tricuspid regurgitation

References