Mesothelial

hyperplasia in
Cytology
Specimens
Philip T Cagle and Andrew Churg. Arch Pathol Lab Med. 2005:
129:1421-1427

.the primary diagnostic

challange facing the pathologist is
often wether a mesothelial
proliferation on a pleural biopsy
represents a malignancy or a
benign reactive hyperplasia.
Cytology
Cytology of Pleural Fluid, W

Michael MD

1. Cytopathologists are 1. Recognizing

frequently reluctant in mesothelial origin
making the diagnosis of 2. Distinguishing reactive
malignant from malignant
mesothelioma mesothelial cells
particularly in the 3. Distinguishing
absence of radiological mesothelioma from
findings non-mesothelial
2. When malignancy is malignancies
recognized, it is
sometimes
Pitfalls in differential
diagnosis

The main pitfalls in the differential

diagnosis include:
1- Reactive mesothelial cells versus
mesothelioma.
2- Reactive mesothelial cells versus
adenocarcinoma.
3- Mesothelioma versus adenocarcinoma.
4- Reactive lymphoid cells versus non-
Hodgkin's lymphoma.
PLEURAL FLUID

Four mechanisms result in cavity

effusions:
Transudate - low specific gravity fluid
crosses membrane barrier.
Exudate - inflammation allows fluid with
high cellular and protein component to
cross vessel walls.
Vessel or viscous rupture.
Collection and Preparation of
Pleural fluid Cell
Samples(routine)
1. fixative is not necessary, no significant alteration
of cell morphology noted if the specimen is
processed within 12 hr or kept referigerated at 4C
up to 72 hr
2. 3-4 smears are made by direct smearing of fluid
sedimentaion or by centrifugation( 5 minutes at
1800 rpm / 10 minutes at 1300 rpm / 6 minutes at
4000 rpm)
3. Smears are either fixed in 95% ethanol (stained by
Pap or HE), or air dried (stained with Romanowsky
technique or modified methods: Wright, Diff-quick,
Cancer cells in effusions as a
target of biological
investigations:
1- Cytology (routine pap & other cytochemical
stains).
2- Cell Block
3- Immunocytochemistry (testing the specificity
& reactivity of
various mABs).
4- EM (study of ultrastructural configuration of
cancer cells & other
cells and their mutual relationship).
5- Cytogenetic studies.
MESOTHELIUM

1. A membrane that forms the lining body

cavities
2. Origin: embrionic mesoderm
3. Sructure: monolayer of flattened
squamous-like epithelial cells
4. Function: to produce a lubricating fluid,
APC
MESOTHELIAL CELLS
CHARACTERISTIC
Uniform cell population
Monotonous , oval to round nuclei
Mononucleated cells with mostly centrally
placed nuclei
Evenly distributed fine powdery chromatin
Inconspicuous to prominent nucleoli
Multinucleation with anisonucleosis
Moderate amount of translucent cytoplasms
Two-zone cytoplasms
MESOTHELIAL CELLS
CHARACTERISTIC
A faint staining thin halo along the edge
(microvilli)
Fuzzy cell border (due to microvilli )
Peripheral blebs in Diff-Quick stained smears
Monolayer cell aggregates
Doublets or triplets with clasp-like articulation
Mesothelial windows between the cells
Occasional papillary groups
Balloning of cytoplasm with signet ring-like
MESOTHELIUM
monolayer of cells with:
Distinct cell borders
(mimicking the
appearance of
cobblestones),
A moderate amount of
cytoplasm, and
A central nucleus
Intracellular windowing.
Nuclear inclusions.
Cytoplasmic blebbing.

MESOTHELIUM From Wikipedia, the free

 MESOTHELIAL CELLS
FLAT MESOTHEL

PERIPHERAL ECTOPLASMA

INNER ENDOPLASM

CENTRAL TO SLIGHTLY
HYPERTROPHY
ECCENTRIC NUCLEUS

RUFFLED CELL BORDER

WITH BLEBS

Vinod B Shidham, Barbara F Atkinson in Cytopathologic diagnosis of serous fluids

Causes of Mesothelial
Hyperplasia
Radiation and
chemotherapy
Heart failure
Traumatic
Infection irritation(surgery)
Infarction Chronic
Liver disease inflammation
Underlying
Collagen disease neoplasm(causing
Renal irritation
disease/dialysis Foreign
Pancreatic disease substance(talc)
Reactive/Hyperplastic Mesothelium
Cytology of Pleural Fluid. Claire W Michael, M.D. The University
of Michigan
oShed as doublest or triplets with windows between
them
oFew papillary groups may be formed
oConnections by claps-like articulations are more
obvious
oCells are round to oval, 20-40m in diameter
oAbundant cytoplasm with endo-ectoplasmic
demarcation and peripheral submembranous
vacuoles
oCytoplasmic protrusions distal to cellular connections
Reactive/Hyperplastic Mesothelium

oNuclei are round to oval with slight variation

in size and chromatin distribution
oCell size vary slightly, only few cells are out of
proportion in size
oNucleoli may become prominent
oMultinucleated cells increase
oOccasional intranuclear inclusions are noted
 Mesothelial window in reactive mesothelial cells
Vinod B Shidham, Barbara F Atkinson in Cytopathologic diagnosis of serous fluids
Hyperplastic mesothelial cells
with slightly enlarged nuclei, micronucleoli and a clear space or
window between adjacent cells, present singly and in small clusters.
A cluster of highly atypical mesothelial cells showing
pleomorphic nuclei, prominent nucleoli and slight
nuclear molding.
A tight cluster of atypical mesothelial
cells with prominent nucleoli.
Mesothelioma
IMMUNO-CYTO/HISTO-CHEMISTRY
OF MESOTHELIAL CELLS
1. The distinction between reactive mesothelial hyperplasia (MH)
and malignant mesothelioma (MM) may be very difficult
based only on histologic and morphologic findings
2. Frank invasion is regarded as the most important
diagnostic feature of malignancy in surgical excision
specimensspecimens; however, this is not applicable to
cytologic examination of effusions
3. The cytologic features commonly used to identify
malignancy, including nuclear pleomorphism, macronucleoli,
large cellular aggregates, papillary-like tissue fragments, and
cell-in-cell engulfment, are helpful features but have limited
use in effusion, because they may also be present in florid
Mesothelioma:
markedly
cellular with
large cell balls
Mesotheliom
a with
papillary
groups
Mesotheliom
a
Nuclear atypia
Normal
mesothelia cell
Mesothelio
ma
Reactive
mesothelial
cells
Mesothelio
ma
Mesothelio
ma cell
block
Immunohistochemical Profile of
Mesothelium and Mesothelial Hyperplasia
ANTIGEN MH M ALV

Pancytoker 3+ 3+ 3+
AE1/3

Pancytoker 3+ 3+ 3+
CAM5.2

Calretinin 3+ 3+ -

D2-40 2+ 3+ -
CK5/6 1+ 2+ -
CK7 1+ M: mesothelium,
MH: mesothelial hyperplasia, 2+ ALV: alveolar3+
cell.
Modified from: T Terada.2+
CK8 Int J Clin Exp Pathol.
3+ 2011, 4(6): 631-638
-
Distinction
Between Benign Mesothelial Reactions
and Malignant Mesothelioma

Benign Atypical
Mesothelial Malignant
Antibody Proliferations Mesothelioma

Alberto M. Marchevsky. Arch Pathol Lab Med.

Keratin AE1/AE3 +/-

2008;132:397401
+++
Box plots of ki-67 LI average and LI
max in benign andmalignant pleural
disease.

ZM Taheri et al. Tanaffos 2006;

5(2): 9-12
Immunohistochemical Profile of
Mesothelium and Mesothelial Hyperplasia
ANTIGEN MH M ALV

Pancytoke
r AE1/3 3+ 3+ 3+

EMA - - 3+

Desmin - - -
MH: mesothelial hyperplasia, M: mesothelium, ALV: alveolar cell.
Modified from: T Terada. Int J Clin Exp Pathol. 2011, 4(6): 631-638
Summary
1/2
1. Mesothelial hyperplasia can caused by several
conditions and diseases
2. The diagnostic challange is wether the
mesothelial prolifereration represents a
malignancy or benign mesothelial reactive
hyperplasia
3. The cytologic features commonly used to
identify malignancy may also be present in
florid reactive MH.
Summary
2/2

4. To differentiate mesothelial hyperplasia from

mesothelioma based only on histologic and
morphologic findings is very difficult
5. A simple panel of immunochemistry can be
used to confirm the diagnosis of mesothelial
proliferation