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Slide 1 - Malignant Mesothelioma in Effusions and Fine Needle Aspirates No relationship exists that represents a possible conflict of interest with respect to the content of this presentation Armando C. Filie, M.D. National Cancer Institute
Slide 2 - ppt slide no 2 content not found
Slide 3 - OBJECTIVES Objectives Recognize the cytological features of malignant mesothelioma (mesothelioma) in effusion samples Recognize the cytological features of fine needle aspirates of mesothelioma Recognize the cytological features of major lesions in the differential diagnosis of mesothelioma Familiarize with current ancillary studies in the diagnosis of mesothelioma
Slide 4 - BLANK SLIDE Mesothelioma Malignant neoplasm of pleura, peritoneal cavity and pericardium Incidence of 2,500 cases/year (pleural) Clinical Findings age and presentation: males, 6th-8th decade, unilateral pathogenesis: asbestos exposure (latency of 20-50 years), ?simian vacuolating virus (SV40) imaging findings: CT scan [pleural masse(s)], invasion by magnetic resonance imaging (MRI) Diagnosis: clinical history + imaging findings + cytology(?)/biopsy
Slide 5 - Mesothelioma Prognosis and Treatment poor prognosis treatment: surgery (most effective), chemotherapy, radiotherapy (localized recurrences), combine therapy Histologic Types epithelioid (epithelial): up to 17 subtypes (deciduoid, clear cell, small cell, signet ring) sarcomatoid: 8 subtypes (fibrosarcomatous, lymphohistiocytoid, MFH-like) biphasic (mixed) desmoplastic
Slide 6 - Mesothelioma Cytological Features in Effusions sample preparation: smear, cytocentrifugation, thin layer, cell block (immunostains) stains: Diff-Quik, Papanicolaou
Slide 7 - Mesothelioma Cytological Features in Effusions patterns: epithelioid (malignant epithelial), sarcomatous (sarcomatoid), anaplastic, biphasic sarcomatoid mesothelioma differential diagnosis: spindle cell sarcomas biphasic mesothelioma differential diagnosis: carcinomas (renal cell carcinoma) anaplastic mesothelioma differential diagnosis: pleomorphic sarcomas epithelioid mesothelioma: most frequent pattern, associated with effusion more frequently than other patterns.
Slide 8 - Mesothelioma in Effusions Cytological Features of Epithelioid Mesothelioma cellular sample one cell population clusters (scalloped border) cell-in-cell formations intercellular spaces (“windows”) two-tone cytoplasm surface blebs variable N/C ratio multinucleation macronucleoli
Slide 9 - Mesothelioma in Effusions Cytological Features of Epithelioid Mesothelioma
Slide 10 - Mesothelioma in Effusions Cytological Features of Epithelioid Mesothelioma
Slide 11 - Mesothelioma in Effusions Differential Diagnosis Metastatic carcinoma: adenocarcinomas (lung, breast, gynecologic tract, gastrointestinal tract), may be the first manifestation of an occult primary Hematologic neoplasms: B-cell lymphomas (diffuse large B-cell), T-cell lymphomas (anaplastic large cell), plasma cell neoplasms, primary effusion lymphoma (PEL) Melanoma: may be the first manifestation of disease Others: squamous cell carcinoma, mesothelial cell lesions
Slide 12 - Mesothelioma in Effusions Cytological Features of Metastatic Adenocarcinoma cellular sample two cell population clusters (smooth border) cell-in-cell formations high N/C ratio multinucleation macronucleoli irregular nuclear contours delicate/dense cytoplasm vacuole(s) displacing the nucleus
Slide 13 - Mesothelioma in Effusions Cytological Features of Metastatic Adenocarcinoma
Slide 14 - Mesothelioma in Effusions Cytological Features of Metastatic Melanoma cellular sample two cell population (?) aggregates cell-in-cell formations low N/C ratio multinucleation macronucleoli intranuclear cytoplasmic inclusions melanin pigment vacuoles
Slide 15 - Mesothelioma in Effusions Cytological Features of Metastatic Melanoma
Slide 16 - Mesothelioma in Effusions Cytological Features of PEL cellular sample two cell population variable N/C ratio multinucleation macronucleoli dense basophilic cytoplasm
Slide 17 - Mesothelioma in Effusions Cytological Features of PEL
Slide 18 - Mesothelioma in Fine Needle Aspirates Image-guided fine needle aspiration (FNA) may be used for the initial diagnosis of mesothelioma 4% needle tract seeding for core-needle biopsy with sensitivity of 86% (pleural) FNA of metastatic mesothelioma (rare): scalp, thyroid, cervical lymph node, axillary lymph node, subcutaneous nodules, breast, liver metastasis may be the first indication of mesothelioma inclusions of benign mesothelial cells in lymph nodes Mesothelial cell lesions of pleura: solitary fibrous tumor (most benign, rare malignant), nodular pleural plaque, adenomatoid tumor, simple mesothelial cyst, multicystic mesothelioma, well-differentiated papillary mesothelioma, localized malignant mesothelioma
Slide 19 - Mesothelioma in Fine Needle Aspirates Cytological Features of Mesothelioma in FNAs cellular aspirate clusters and flat sheets papillary groups (core) acinar/tubular groups single cells intercellular spaces round/polygonal shape spindle cells (sarcomatoid, biphasic) small cytoplasmic vacuoles multinucleation
Slide 20 - Mesothelioma in Fine Needle Aspirates Cytological Features of Mesothelioma in FNAs
Slide 21 - Mesothelioma in Fine Needle Aspirates Differential Diagnosis Epithelioid: carcinoma - lung (adenocarcinoma and bronchoalveolar carcinoma [BAC]), ovary and peritoneal serous carcinoma; mesothelial cell lesions; thymoma; epithelioid sarcomas, reactive mesothelial proliferations Sarcomatoid: mesothelial cell lesions, desmoid tumor, schwannoma, spindle cell sarcomas Biphasic: thymoma, synovial sarcoma, desmoplastic small round cell tumor, pleuropulmonary blastoma Anaplastic: pleomorphic sarcomas
Slide 22 - Mesothelioma in Fine Needle Aspirates Cytological Features of Lung BAC in FNAs monolayer sheets papillae single cells round nuclei nuclear grooves and pseudoinclusions nuclear crowding/overlapping pleomorphic cells mucin (mucinous)
Slide 23 - Mesothelioma in Fine Needle Aspirates Cytological Features of Lung BAC in FNAs
Slide 24 - Mesothelioma (Ancillary Studies) Histochemical stains: mucin (Alcian blue, mucicarmin) Electron microscopy: long microvilli (meso), short (adeno) FISH: detection of chromosomal alterations Hyaluronic acid levels in effusion samples Immunocytochemistry: most commonly used may be applied to cytocentrifuged samples, smears, thin layer samples, cell blocks (preferred) panel of mesothelial cell and adenocarcinoma markers: 2 meso and 2 adeno markers or 1/2 meso and 3 adeno markers other markers: hematopoietic markers, melanoma markers, site “specific” markers (TTF-1, PSA, PAP, CDX-2, GCDFP-15, thyroglobulin)
Slide 25 - Mesothelioma (Ancillary Studies) Mesothelial cell (Mesothelioma) Markers calretinin: neuron-specific calcium binding protein (neural tissues and a few other cell types like mesothelial cells) cytokeratin 5/6: intermediate filament (mainly keratinized and non-keratinized squamous cell carcinoma) Others: HBME-1, WT1,Mesothelin, Podoplanin calretinin
Slide 26 - Mesothelioma (Ancillary Studies) Mesothelial cell (Mesothelioma) Markers HBME-1 CK 5/6
Slide 27 - Mesothelioma (Ancillary Studies) Adenocarcinoma Markers B72.3: antibody detects a tumor associated protein Ber-EP4: antibody against epithelial adhesion molecule CA19.9: antibody against Lewisa blood group antigen Others: mCEA, CD15, MOC-31 B72.3
Slide 28 - Mesothelioma (Ancillary Studies) Adenocarcinoma Markers B72.3 Ber-EP4 CA19.9
Slide 29 - Mesothelioma (Ancillary Studies) Melanoma markers: HMB45, Mart-1, KBA62, S100 Hematopoietic markers: LCA, L26, CD38, HHV8 Others: TTF-1, PSA and PAP, GCDFP-15, thyroglobulin HMB45 Mart-1
Slide 30 - Mesothelioma (Ancillary Studies) Hematopoietic and other markers HHV8 TTF-1 CK 7
Slide 31 - Mesothelioma (Ancillary Studies) Molecular Tests Gene expression (quantitative RT-PCR) Proteomics: protein complement of the genome (serum - early cancer diagnosis), potential in cytopathology Surface enhanced laser desorption/ionization time of flight (SELDI-TOF): protein profile in cytology samples (Fetsch et al, 2002) Initial set: 5 renal cell carcinomas, 9 metastatic melanomas, 6 reactive effusions Unknown set: 4 renal cell carcinomas, 8 metastatic melanomas, 3 reactive effusions
Slide 32 - Mesothelioma (Ancillary Studies) Molecular Tests SELDI-TOF in FNAs and fluid samples of 8 MM, 4 RCC, 3 reactive effusions
Slide 33 - Mesothelioma in Effusions and FNAs SUMMARY Cytological features of mesothelioma in effusions and FNAs overlap with those seen in other benign and malignant lesions (adenocarcinoma) Some cytologic features of mesothelioma are not often present in cytology samples of lesions that should be considered in the differential diagnosis Ancillary studies are important in supporting the diagnosis of mesothelioma (immunocytochemistry, electron microscopy) Diagnosis of mesothelioma has prognostic, treatment and legal implications
 

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