1 / 33

Malignant Mesothelioma in Effusions and Fine Needle Aspirates

Malignant Mesothelioma in Effusions and Fine Needle Aspirates. Armando C. Filie, M.D. National Cancer Institute. No relationship exists that represents a possible conflict of interest with respect to the content of this presentation. OBJECTIVES. Objectives

wolfe
Download Presentation

Malignant Mesothelioma in Effusions and Fine Needle Aspirates

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Malignant Mesothelioma in Effusions and Fine Needle Aspirates Armando C. Filie, M.D. National Cancer Institute No relationship exists that represents a possible conflict of interest with respect to the content of this presentation

  2. 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

  3. 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

  4. 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

  5. Mesothelioma • Cytological Features in Effusions • sample preparation: smear, cytocentrifugation, thin layer, cell block (immunostains) • stains: Diff-Quik, Papanicolaou

  6. 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.

  7. 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

  8. Mesothelioma in Effusions Cytological Features of Epithelioid Mesothelioma

  9. Mesothelioma in Effusions Cytological Features of Epithelioid Mesothelioma

  10. 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

  11. 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

  12. Mesothelioma in Effusions Cytological Features of Metastatic Adenocarcinoma

  13. 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

  14. Mesothelioma in Effusions Cytological Features of Metastatic Melanoma

  15. Mesothelioma in Effusions Cytological Features of PEL • cellular sample • two cell population • variable N/C ratio • multinucleation • macronucleoli • dense basophilic cytoplasm

  16. Mesothelioma in Effusions Cytological Features of PEL

  17. 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

  18. 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

  19. Mesothelioma in Fine Needle Aspirates Cytological Features of Mesothelioma in FNAs

  20. 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

  21. 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)

  22. Mesothelioma in Fine Needle Aspirates Cytological Features of Lung BAC in FNAs

  23. 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)

  24. 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

  25. Mesothelioma (Ancillary Studies) Mesothelial cell (Mesothelioma) Markers HBME-1 CK 5/6

  26. 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

  27. Mesothelioma (Ancillary Studies) Adenocarcinoma Markers B72.3 CA19.9 Ber-EP4

  28. 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

  29. Mesothelioma (Ancillary Studies) Hematopoietic and other markers HHV8 TTF-1 CK 7

  30. 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

  31. Mesothelioma (Ancillary Studies) Molecular Tests • SELDI-TOF in FNAs and fluid samples of 8 MM, 4 RCC, 3 reactive effusions

  32. 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

More Related