Diffuse Malignant Mesothelioma

(Malignant Mesothelioma)

(Mesothelioma)

 

Epidemiology and Etiology:

    • >60y usually
    • M:F = 9:1
    • Prior asbestos exposure in >90%
      • Only 20% in women
      • Latency period 30-40y usually (rarely <15y)
    • Simian monkey virus 40 (SV40)
      • Old Polio vaccines\
      • Viral large T-antigen (Tag) inactivates P53 and RB
    • Other risk factors:
      • Therapeutic radiation
      • Intense pleural scarring

 

Common sites:

    • pleura
    • peritoneum
    • pericardium
    • tunica vaginalis
    • genital tract

 

Gross features:

    • early lesions:
      • macules, polyps, and nodules in the parietal pleura
    • extensive pleural effusion
    • fusion of visceral and parietal pleuras
    • lung ensheathed by thick layer of firm, gray-white, homogenous, nodular tumour (note: not pathognomonic)
      • extends into fissures
      • most or all of pleura involved
      • tumour more extensive basally than apically
    • sharply demarcated from lung parenchyma
      • if lung parenchyma involved, usually bulges into lung with pushing borders
    • concurrent pulmonary fibrosis (asbestosis) (20%)
    • myxoid / gelatinous occasionally
    • frequently spreads into underlying lung, through the diaphragm, and into the chest wall, mediastinum
      • also frequently spreads along needle tracks or biopsy sites
      • peritoneal seeding with ascites
      • intra-alveolar spread

 

Histologic features:

    • epithelioid:
      • bland usually
      • several different patterns present usually:
        • tubulopapillary
        • adenomatoid (microglandular)
          1. microcystic structures
          2. lace-like, adenoid cystic, or signet ring
        • sheet-like
        • less common patterns:
          1. small cell
          2. clear cell
          3. deciduoid
      • cuboidal, columnar, or flattened cells
      • eosinophilic cytoplasm
      • bland, relatively open nuclei usually
      • infrequent mitoses usually
      • stroma may be scanty to copious
      • may see:
        • anaplastic and / or tumour giant cells (pleomorphic mesothelioma)
    • sarcomoatoid mesothelioma:
      • spindle cells in fascicles or in a haphazard distribution
        • resembles fibrosarcoma most often (or MFH if pleomorphic)
      • bland to fairly anaplastic
      • may see:
        • areas resembling osteosarcoma, chondrosarcoma, or other sarcomas
    • desmoplastic mesothelioma (desmopastic component > 50%):
      • easily confused with benign organizing pleuritis
        • suggestive of malignancy:
          1. frankly sarcomatoid areas
          2. foci of bland collagen necrosis
          3. invasion of adipose tissue, skeletal muscle, or lung
            1. pankeratin stain may be helpful to highlight these invading cells
      • dense collagenized tissue
      • atypical cells arranged in a storiform or “patternless” pattern
        • haphazard arrangement of slit-like spaces
    • biphasic mesothelioma (30%):
      • epithelioid and sarcomatoid (at least 10% each)
    • lymphohistiocytoid mesothelioma
      • mimics non-Hodgkin lymphoma
    • small cell type:
    • deciduoid type:
    • undifferentiated type:
    • signs of asbestos exposure:
      • ferruginous bodies
        • deposition of protein and iron
      • asbestos plaques
    • cytology:
      • only detects the epithelioid type (sarcomatoid cells rarely shed into effusions)
      • very hard to differentiate from reactive mesothelail hyperplasia
      • sheets, clusters, morulae, or papillae
      • bland to pleomorphic (but very hard to differentiate from reactive mesothelial cells)
      • may see:
        • psammoma bodies

 

Immunophenotype:

Marker:

Sensitivity:

Specificity:

 

Calretinin

(usually neg in sarcomatoid mesothelioma)

 

WT-1

(usually neg in sarcomatoid) 

 

CK 5/6

(usually neg in sarcomatoid) 

 

Thrombomodulin

 

 

 

 

 

 

pankeratin (perinuclear accentuation)

Great

Usually positive even in sarcomatoid mesothelioma (patchy or diffuse)

Positive in organizing pleuritis

Usually negative in sarcomas 

CK7

 

 

CK20 (neg)

 

 

Mesothelin

 

 

Thrombomodulin

 

 

CEA (neg)

 

(Should be positive in adenocarcinoma) 

CD15 (neg)

 

 (Should be positive in adenocarcinoma) 

Ber EP4 (neg)

 

 (Should be positive in adenocarcinoma) 

B72.3 (neg)

 

 (Should be positive in adenocarcinoma) 

MOC 31 (neg)

 

 (Should be positive in adenocarcinoma) 

TTF-1 (neg)

 

 (positive in 70% of lung adenocarcinoma) 

PASD (neg)

Mucicarmine or alcian blue (pos)

With previous digestion by hyaluronidase (neg)

 

 

Sarcomatoid mesothelioma:

 

 

Vimentin

Maybe

 

Actin

Maybe

 

Desmin

Maybe

 

S-100

Maybe

 

 

Molecular features:

    • deletions in chromosomes 1p, 3p, 6q, 9p, or 22q (60-80%)
    • SV40 (simian virus 40) DNA (60-80%)

 

Other features:

    • EM (gold standard) – long microvilli with abundant tonofilaments but absent microvillous rootlets and lamellar bodies
      • Length:diameter > 10:1
      • Microvilli abutting extracellular collagen (seldom seen in adenocarcinoma)
      • Less useful in sarcomatoid mesothelioma
    • asbestos exposure is a risk factor
    • poor prognosis
      • mortality is practically 100%
      • sarcomatoid variant has shortest survival, epithelioid variant has the longest survival (only by a few months)

 

References:

    • Robbins 2005
    • WHO book 2004