Download - Malignant Mesothelioma : an overview
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Malignant Mesothelioma : an overview
Cesar A. Moran, MD
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Malignant Mesothelioma
• First described by Wagner in 1870. However, the terminology was controversial and terms such as “Endothelioma” were used to designate this tumor.
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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
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Malignant Mesothelioma
• Weiss in 1953 suggested that asbestos exposure was responsible for the induction of malignant mesothelioma.
– Weiss A. Medizinische 1953
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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.
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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
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Malignant Mesothelioma
• Clinical Features– Chest pain– Shortness of breath– Weight loss
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Radiological Features
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Radiological Features
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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
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Malignant Mesothelioma
• Epithelioid type:– Epithelioid– Tubulopapillary– Glandular– Myxoid– Clear cell– Deciduoid– Lipid rich
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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
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Malignant Mesothelioma
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Epithelioid Mesothelioma
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Tubulopapillary
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Mucinous
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Glandular
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Myxoid
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Clear Cell
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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
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Calretinin
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Am J Surg Pathol 2003; 27 (8): 1031.
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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
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Electron Microscopy
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What about asbestos bodies ??
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Is it always possible ??
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Malignant Mesothelioma
• Treatment:– Decortication– Extrapulmonary Pneumonectomy
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Variants & Mimickers
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Malignant Mesothelioma
• Differential Diagnosis– Pleuritis– Reactive Mesothelial Hyperplasia
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Pleuritis
• Acute or chronic• Pleural effusion• Thoracic pain
• Collagen vascular disease
• Trauma• Infections• Drug reactions
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Pleuritis
• Histological Features– Fibrin– Granulation tissue– Inflammatory reaction– Cellular atypia - mitotic figures
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Pleuritis
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Pleuritis
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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
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AMH vr Mesothelioma
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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
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Sarcomatoid Mesothelioma
• Histological variants:– Fibrosarcoma or MFH-like – Desmoplastic
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Sarcomatoid Mesothelioma
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Sarcomatoid Mesothelioma
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MFH-Like
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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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Desmoplastic Mesothelioma
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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.
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Fibrous Pleuresy
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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
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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
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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
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Biphasic Mesotheliomas
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Chondroid Differentiation
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Osteosarcomatous Differentiation
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Lymphohistiocytic
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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
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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
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Pseudomesotheliomatous Ca
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Ancillary Studies
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Carcinomatous Epitopes
Leu M1CEA
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Carcinomatous Epitopes
Ber-Ep4B72.3
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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