malignant mesothelioma : an overview · malignant mesothelioma : an overview cesar a. moran, md...

5/21/2018

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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.


• 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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• 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


• Weiss in 1953 suggested that asbestos

exposure was responsible for the induction

of malignant mesothelioma.

– Weiss A. Medizinische 1953


• 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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• 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.


• Rare tumor

• Occurs in any age group

• More frequent in the 6th and 7th decade of

life

• 50 - 80% associated with asbestos fibers


• 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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• Histological Patterns

– Epithelioid

– Sarcomatoid

– Biphasic

– Unsual forms


• Epithelioid type:

– Epithelioid

– Tubulopapillary

– Glandular

– Myxoid

– Clear cell

– Deciduoid

– Lipid rich


• 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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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 ??


• Treatment:

– Decortication

– Extrapulmonary Pneumonectomy

Variants & Mimickers

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• 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


• Histological variants:

– Fibrosarcoma or MFH-like

– Desmoplastic


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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)



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• 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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• 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


• 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

malignant mesothelioma : an overview · malignant mesothelioma : an overview cesar a. moran, md...

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