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.

Diagnostic Challenges in Cytology

Cytology of Pleural Fluid, W Michael MD

1. Cytopathologists are
frequently reluctant in
making the diagnosis
of malignant
mesothelioma
particularly in the
absence of radiological
findings
2. When malignancy is
recognized, it is
sometimes

1. Recognizing
mesothelial origin
2. Distinguishing reactive
from malignant
mesothelial cells
3. Distinguishing
mesothelioma from
non-mesothelial
malignancies

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.
5- Site of the primary tumor.

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:

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
ECCENTRIC NUCLEUS

RUFFLED CELL BORDER

WITH BLEBS

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

HYPERTROPHY

Causes of Mesothelial Hyperplasia

Heart failure
Infection
Infarction
Liver disease
Collagen disease
Renal disease/dialysis
Pancreatic disease

Radiation and
chemotherapy
Traumatic
irritation(surgery)
Chronic inflammation
Underlying
neoplasm(causing
irritation
Foreign substance(talc)

Reactive/Hyperplastic Mesothelium
Cytology of Pleural Fluid. Claire W Michael, M.D. The University
of Michigan

o Shed as doublest or triplets with windows between

them
o Few papillary groups may be formed
o Connections by claps-like articulations are more
obvious
o Cells are round to oval, 20-40m in diameter
o Abundant cytoplasm with endo-ectoplasmic
demarcation and peripheral submembranous
vacuoles
o Cytoplasmic protrusions distal to cellular connections

Reactive/Hyperplastic Mesothelium
o Nuclei are round to oval with slight variation in
size and chromatin distribution
o Cell size vary slightly, only few cells are out of
proportion in size
o Nucleoli may become prominent
o Multinucleated cells increase
o Occasional 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

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

ALV

Pancytoker AE1/3

3+

3+

3+

Pancytoker CAM5.2

3+

3+

3+

Calretinin

3+

3+

D2-40

2+

3+

CK5/6

1+

2+

CK7

1+

2+

3+

CK8

2+

3+

EMA

3+

Vimentin
Desmin

3+
1+
MH: mesothelial hyperplasia, M: mesothelium, ALV: alveolar cell.
- Int J Clin Exp Pathol. 2011,
Modified from: T Terada.
4(6): 631-638

Immunohistochemistry for the Distinction

Between Benign Mesothelial Reactions and
Malignant Mesothelioma

Antibody
Keratin AE1/AE3
EMA
p53
Desmin

Benign Atypical
Mesothelial
Proliferations

Malignant
Mesothelioma

+/+/+/+++

+++
+++
+++
+/-

Alberto M. Marchevsky. Arch Pathol Lab Med.

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

ALV

Pancytoker
AE1/3

3+

3+

3+

EMA

3+

Desmin

10%
20%

1%

1%

p53
Ki-67

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