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5/21/2018
1
Malignant Mesothelioma : an
overview
Cesar A. Moran, MD
Malignant Mesothelioma
• First described by Wagner in 1870.
However, the terminology was controversial
and terms such as “Endothelioma” were
used to designate this tumor.
Malignant Mesothelioma
• DuBray and Rosson in 1920 introduced the
term “mesothelioma” after their observation
that these tumors arose from the surface of
parietal pleura.
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Malignant Mesothelioma
• Klemperer and Rabin in 1931, described
important features for these tumors, most of
them currently used in modern surgical
pathology
– The localized tumor connected to the pleura
was usually benign
– Malignant mesothelioma was usually diffuse
– High histological variability
Malignant Mesothelioma
• Weiss in 1953 suggested that asbestos
exposure was responsible for the induction
of malignant mesothelioma.
– Weiss A. Medizinische 1953
Malignant Mesothelioma
• Wagner et al in 1960 described cases of
mesothelioma in residents of Northwest
Cape Providence of South Africa and
reported strong association of asbestos
exposure and malignant mesothelioma.
– In two cases no history of asbestos exposure
was obtained.
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Malignant Mesothelioma
• In the past, it was a tumor of more unusual
occurrence, 0.1 - 0.01% of autopsies.
• Currently, there are about 2000 new cases
diagnosed in the USA each year.
• The frequency of asbestos exposure varies
depending on the population studied.
Malignant Mesothelioma
• Rare tumor
• Occurs in any age group
• More frequent in the 6th and 7th decade of
life
• 50 - 80% associated with asbestos fibers
Malignant Mesothelioma
• Clinical Features
– Chest pain
– Shortness of breath
– Weight loss
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Radiological Features
Radiological Features
Pathologic Staging
• TNM system
– T1-T4 = it will depend on the surgical
procedure performed (Extrapleural
peumonectomy, decortication, biopsy)
– N1-N3 (ipsilateral, contralateral,hilar,
mediastinal)
– M1 = Distant metastasis
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Gross Features
• Diffuse pleural
thickening
• White-tan tumor
• May be infiltrating
into intralobar
pulmonary septum
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Malignant Mesothelioma
• Histological Patterns
– Epithelioid
– Sarcomatoid
– Biphasic
– Unsual forms
Malignant Mesothelioma
• Epithelioid type:
– Epithelioid
– Tubulopapillary
– Glandular
– Myxoid
– Clear cell
– Deciduoid
– Lipid rich
Malignant Mesothelioma
• Malignant Mesothelioma In situ
– Is diagnosable only when invasion is demonstrable in the same specimen, in a follow-up biopsy, or at autopsy
– It should be considered proven only when unequivocal invasion is identified in a different area of the pleura
– this Dx should not be made in patients not expose to asbestos.
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Malignant Mesothelioma
Malignant Mesothelioma
Epithelioid Mesothelioma
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Tubulopapillary
Mucinous
Glandular
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Myxoid
Clear Cell
Ancillary Studies
• PAS w and w/o diastase
• Mucicarmine
• Keratin broad spectrum
• Keratin 5/6
• Calretinin
• D2-40
• Carcinomatous epitopes
– CEA, CD-15, B72.3, TTF-1
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Keratins
Calretinin
Am J Surg Pathol 2003; 27 (8): 1031.
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Conclusions:
From a practical viewpoint, a panel of four markers
usually allows for the distinction between epithelioid mesothelioma
and Adenocarcinoma - Calretinin and Keratin 5/6 -- CEA, MOC-31
Electron Microscopy
What about asbestos bodies ??
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Is it always possible ??
Malignant Mesothelioma
• Treatment:
– Decortication
– Extrapulmonary Pneumonectomy
Variants & Mimickers
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Malignant Mesothelioma
• Differential Diagnosis
– Pleuritis
– Reactive Mesothelial Hyperplasia
Pleuritis
• Acute or chronic
• Pleural effusion
• Thoracic pain
• Collagen vascular
disease
• Trauma
• Infections
• Drug reactions
Pleuritis
• Histological Features
– Fibrin
– Granulation tissue
– Inflammatory reaction
– Cellular atypia - mitotic figures
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Pleuritis
Pleuritis
Pleuritis
• Can immunohistochemistry help in
differentiating Mesothelioma from
Pleuritis?
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Atypical Mesothelial Hyperplasia
• AMH
– No evidence of
infiltration into
adjacent tissue
– Lack of increase
mitotic activity or
cellular atypia
– Inflammatory infiltrate
• fibrin
• Mesothelioma
– Infiltration into
adjacent tissue, I.e.,
adipose tissue
– Cellular atypia
– Mitotic activity
AMH vr Mesothelioma
Immunohistochemistry in AMH
• Keratin +
• Calretinin +
• Keratin 5/6 +/-
• CEA, B72.3, CD15, TTF-1 negative
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Sarcomatoid Mesothelioma
• The tumor should have more than 50% of
this histology
• Represents approximately 10% of
malignant mesotheliomas
• Similar clinical and radiological features as
those previously described for epithelioid
mesotheliomas
Sarcomatoid Mesothelioma
• Histological variants:
– Fibrosarcoma or MFH-like
– Desmoplastic
Sarcomatoid Mesothelioma
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Sarcomatoid Mesothelioma
MFH-Like
MFH-Like
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Desmoplastic Mesothelioma
• Diagnostic Criteria:
– Invasion of chest wall or lung
– Foci of bland necrosis
– Frankly sarcomatoid foci
– Distant metastases (very rare)
Desmoplastic Mesothelioma
Desmoplastic Mesothelioma
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Sarcomatoid Mesothelioma
• The most important differential diagnosis is
with either a metastasis or a primary
sarcoma of the pleura and more importantly
with fibrous pleuresy.
Fibrous Pleuresy
Fibrous Pleuresy
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Sarcomatoid Mesothelioma
• Immunohistochemical Features
– It has very little value
– Namely to rule out other sarcomas
– Broad spectrum Keratin is helpful, mainly in
identifying invasion into adjacent tissue
– Cannot help in distinguishing it from fibrous
pleuresy
Fibrous Pleuresy vr
Mesothelioma
• FP
– Increased cellularity
under effusion, more
fibrotic away from
effusion “zonation”
– Atypical cells
– Capillaries
perpendicular to
pleural surface
– Organizing pleuritis
• Mesothelioma
– No zonation
– Bland appearance
– Capillaries
inconspicuous
– Stromal invasion
– Sarcomatoid foci
– Bland Necrosis
Sarcomatoid Mesothelioma
• Treatment
– In some medical centers, the diagnosis of
Sarcomatoid mesothelioma is not follow by
surgical treatment
– Extrapleural pneumonectomy is being
performed more frequently
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Mesotheliomas
• Other types of Mesotheliomas include:
– Biphasic (Epithelioid - Sarcomatoid)
– Chondroid differentiation
– Osteosarcomatous differentiation
– Lymphohistiocytic
Biphasic Mesotheliomas
Chondroid Differentiation
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Osteosarcomatous Differentiation
Lymphohistiocytic
Is there a role for Molecular
Biology
• FISH analysis for p16 (CDKN2A probe):
– Homozygous Deletion
• Very helpful in establishing a diagnosis
• Not all mesotheliomas will have the deletion (30-
50%).
– Heterozygous
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Adenocarcinoma
Pseudomesotheliomatous
Adenocarcinoma
• Harwood in 1976 reported a form of peripheral carcinoma of lung characterized by diffuse neoplastic involvement of pleura
• Clinically, radiologically, grossly and histologically similar to pleural mesothelioma
• Later named Pseudomesotheliomatous Adenocarcinoma
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Pseudomesotheliomatous Ca
Pseudomesotheliomatous Ca
Ancillary Studies
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Carcinomatous Epitopes
Leu M1CEA
Carcinomatous Epitopes
Ber-Ep4B72.3
Mesothelioma vr AdenoCa
• Mesothelioma
– Poor prognosis
– Chemotherapy
– Extrapulmonary
pneumonectomy
– Survival about 12
months
• Adenocarcinoma
– Poor prognosis
– Chemotherapy
– Survival about 18
months
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Questions