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.

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.

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

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

Gross Features

• Diffuse pleural thickening

• White-tan tumor• May be infiltrating

into intralobar pulmonary septum

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.

Malignant Mesothelioma

Malignant Mesothelioma

Epithelioid Mesothelioma

Tubulopapillary

Mucinous

Glandular

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

Keratins

Calretinin

Am J Surg Pathol 2003; 27 (8): 1031.

Conclusions:

From a practical viewpoint, a panel of four markersusually allows for the distinction between epithelioid mesotheliomaand Adenocarcinoma - Calretinin and Keratin 5/6 -- CEA, MOC-31

Electron Microscopy

What about asbestos bodies ??

Is it always possible ??

Malignant Mesothelioma

• Treatment:– Decortication– Extrapulmonary Pneumonectomy

Variants & Mimickers

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

Pleuritis

Pleuritis

Pleuritis

• Can immunohistochemistry help in

differentiating Mesothelioma from

Pleuritis?

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

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

Sarcomatoid Mesothelioma

MFH-Like

MFH-Like

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

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

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

Mesotheliomas

• Other types of Mesotheliomas include:– Biphasic (Epithelioid - Sarcomatoid)– Chondroid differentiation– Osteosarcomatous differentiation– Lymphohistiocytic

Biphasic Mesotheliomas

Chondroid Differentiation

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

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

Pseudomesotheliomatous Ca

Pseudomesotheliomatous Ca

Ancillary Studies

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

Questions