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Title: Malignant%20Mesothelioma%20in%20Effusions%20and%20Fine%20Needle%20Aspirates

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Malignant Mesothelioma in Effusions and Fine
Needle Aspirates
Armando C. Filie, M.D. National Cancer Institute

No relationship exists that represents a possible
conflict of interest with respect to the content
of this presentation

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(No Transcript)
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OBJECTIVES

Objectives
Recognize the cytological features of malignant
mesothelioma (mesothelioma) in effusion samples
Recognize the cytological features of fine needle
aspirates of mesothelioma
Recognize the cytological features of major
lesions in the differential diagnosis of
mesothelioma
Familiarize with current ancillary studies in the
diagnosis of mesothelioma

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BLANK SLIDE

Mesothelioma
Malignant neoplasm of pleura, peritoneal cavity
and pericardium
Incidence of 2,500 cases/year (pleural)
Clinical Findings
age and presentation males, 6th-8th decade,
unilateral
pathogenesis asbestos exposure (latency of
20-50 years), ?simian vacuolating virus (SV40)
imaging findings CT scan pleural masse(s),
invasion by magnetic resonance imaging (MRI)
Diagnosis clinical history imaging findings
cytology(?)/biopsy

Mesothelioma
Prognosis and Treatment
poor prognosis
treatment surgery (most effective),
chemotherapy, radiotherapy (localized
recurrences), combine therapy
Histologic Types
epithelioid (epithelial) up to 17 subtypes
(deciduoid, clear cell, small cell, signet ring)
sarcomatoid 8 subtypes (fibrosarcomatous,
lymphohistiocytoid, MFH-like)
biphasic (mixed)
desmoplastic

Mesothelioma
Cytological Features in Effusions
sample preparation smear, cytocentrifugation,
thin layer, cell block (immunostains)
stains Diff-Quik, Papanicolaou

Mesothelioma
Cytological Features in Effusions
patterns epithelioid (malignant epithelial),
sarcomatous (sarcomatoid), anaplastic, biphasic
sarcomatoid mesothelioma differential diagnosis
spindle cell sarcomas
biphasic mesothelioma differential diagnosis
carcinomas (renal cell carcinoma)
anaplastic mesothelioma differential diagnosis
pleomorphic sarcomas
epithelioid mesothelioma most frequent pattern,
associated with effusion more frequently than
other patterns.

Mesothelioma in Effusions
Cytological Features of Epithelioid Mesothelioma
cellular sample
one cell population
clusters (scalloped border)
cell-in-cell formations
intercellular spaces
(windows)
two-tone cytoplasm
surface blebs
variable N/C ratio
multinucleation
macronucleoli

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Mesothelioma in Effusions Cytological Features
of Epithelioid Mesothelioma
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Mesothelioma in Effusions Cytological Features
of Epithelioid Mesothelioma
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Mesothelioma in Effusions
Differential Diagnosis
Metastatic carcinoma adenocarcinomas (lung,
breast, gynecologic tract, gastrointestinal
tract), may be the first manifestation of an
occult primary
Hematologic neoplasms B-cell lymphomas (diffuse
large B-cell), T-cell lymphomas (anaplastic large
cell), plasma cell neoplasms, primary effusion
lymphoma (PEL)
Melanoma may be the first manifestation of
disease
Others squamous cell carcinoma, mesothelial
cell lesions

Mesothelioma in Effusions
Cytological Features of Metastatic Adenocarcinoma
cellular sample
two cell population
clusters (smooth border)
cell-in-cell formations
high N/C ratio
multinucleation
macronucleoli
irregular nuclear contours
delicate/dense cytoplasm
vacuole(s) displacing the
nucleus

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Mesothelioma in Effusions Cytological Features
of Metastatic Adenocarcinoma
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Mesothelioma in Effusions
Cytological Features of Metastatic Melanoma
cellular sample
two cell population (?)
aggregates
cell-in-cell formations
low N/C ratio
multinucleation
macronucleoli
intranuclear cytoplasmic
inclusions
melanin pigment
vacuoles

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Mesothelioma in Effusions Cytological Features
of Metastatic Melanoma
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Mesothelioma in Effusions
Cytological Features of PEL
cellular sample
two cell population
variable N/C ratio
multinucleation
macronucleoli
dense basophilic
cytoplasm

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Mesothelioma in Effusions Cytological Features
of PEL
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Mesothelioma in Fine Needle Aspirates
Image-guided fine needle aspiration (FNA) may be
used for the initial diagnosis of mesothelioma
4 needle tract seeding for core-needle biopsy
with sensitivity of 86 (pleural)
FNA of metastatic mesothelioma (rare) scalp,
thyroid, cervical lymph node, axillary lymph
node, subcutaneous nodules, breast, liver
metastasis may be the first indication of
mesothelioma
inclusions of benign mesothelial cells in lymph
nodes
Mesothelial cell lesions of pleura solitary
fibrous tumor (most benign, rare malignant),
nodular pleural plaque, adenomatoid tumor, simple
mesothelial cyst, multicystic mesothelioma,
well-differentiated papillary mesothelioma,
localized malignant mesothelioma

Mesothelioma in Fine Needle Aspirates
Cytological Features of Mesothelioma in FNAs
cellular aspirate
clusters and flat sheets
papillary groups (core)
acinar/tubular groups
single cells
intercellular spaces
round/polygonal shape
spindle cells (sarcomatoid,
biphasic)
small cytoplasmic vacuoles
multinucleation

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Mesothelioma in Fine Needle Aspirates Cytological
Features of Mesothelioma in FNAs
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Mesothelioma in Fine Needle Aspirates
Differential Diagnosis
Epithelioid carcinoma - lung (adenocarcinoma
and bronchoalveolar carcinoma BAC), ovary and
peritoneal serous carcinoma mesothelial cell
lesions thymoma epithelioid sarcomas, reactive
mesothelial proliferations
Sarcomatoid mesothelial cell lesions, desmoid
tumor, schwannoma, spindle cell sarcomas
Biphasic thymoma, synovial sarcoma,
desmoplastic small round cell tumor,
pleuropulmonary blastoma
Anaplastic pleomorphic sarcomas

Mesothelioma in Fine Needle Aspirates
Cytological Features of Lung BAC in FNAs
monolayer sheets
papillae
single cells
round nuclei
nuclear grooves and
pseudoinclusions
nuclear crowding/overlapping
pleomorphic cells
mucin (mucinous)

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Mesothelioma in Fine Needle Aspirates Cytological
Features of Lung BAC in FNAs
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Mesothelioma (Ancillary Studies)
Histochemical stains mucin (Alcian blue,
mucicarmin)
Electron microscopy long microvilli (meso),
short (adeno)
FISH detection of chromosomal alterations
Hyaluronic acid levels in effusion samples
Immunocytochemistry most commonly used
may be applied to cytocentrifuged samples,
smears, thin layer samples, cell blocks
(preferred)
panel of mesothelial cell and adenocarcinoma
markers 2 meso and 2 adeno markers or 1/2 meso
and 3 adeno markers
other markers hematopoietic markers, melanoma
markers, site specific markers (TTF-1, PSA,
PAP, CDX-2, GCDFP-15, thyroglobulin)

Mesothelioma (Ancillary Studies)
Mesothelial cell (Mesothelioma) Markers
calretinin neuron-specific calcium binding
protein (neural tissues and a few other cell
types like mesothelial cells)
cytokeratin 5/6 intermediate filament (mainly
keratinized and non-keratinized squamous cell
carcinoma)
Others HBME-1, WT1,Mesothelin, Podoplanin

calretinin
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Mesothelioma (Ancillary Studies) Mesothelial
cell (Mesothelioma) Markers
HBME-1
CK 5/6
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Mesothelioma (Ancillary Studies)
Adenocarcinoma Markers
B72.3 antibody detects a tumor associated
protein
Ber-EP4 antibody against epithelial adhesion
molecule
CA19.9 antibody against Lewisa blood group
antigen
Others mCEA, CD15, MOC-31

B72.3
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Mesothelioma (Ancillary Studies) Adenocarcinoma
Markers
B72.3
CA19.9
Ber-EP4
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Mesothelioma (Ancillary Studies)
Melanoma markers HMB45, Mart-1, KBA62, S100
Hematopoietic markers LCA, L26, CD38, HHV8
Others TTF-1, PSA and PAP, GCDFP-15,
thyroglobulin

HMB45
Mart-1
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Mesothelioma (Ancillary Studies) Hematopoietic
and other markers
HHV8
TTF-1
CK 7
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Mesothelioma (Ancillary Studies)
Molecular Tests
Gene expression (quantitative RT-PCR)
Proteomics protein complement of the genome
(serum - early cancer diagnosis), potential in
cytopathology
Surface enhanced laser desorption/ionization
time of flight (SELDI-TOF) protein profile in
cytology samples (Fetsch et al, 2002)
Initial set 5 renal cell carcinomas, 9
metastatic melanomas, 6 reactive effusions
Unknown set 4 renal cell carcinomas, 8
metastatic melanomas, 3 reactive effusions

Mesothelioma (Ancillary Studies)
Molecular Tests
SELDI-TOF in FNAs and fluid samples of 8 MM, 4
RCC, 3 reactive effusions

Mesothelioma in Effusions and FNAs
SUMMARY
Cytological features of mesothelioma in effusions
and FNAs overlap with those seen in other benign
and malignant lesions (adenocarcinoma)
Some cytologic features of mesothelioma are not
often present in cytology samples of lesions that
should be considered in the differential
diagnosis
Ancillary studies are important in supporting the
diagnosis of mesothelioma (immunocytochemistry,
electron microscopy)
Diagnosis of mesothelioma has prognostic,
treatment and legal implications