Malignant%20Mesothelioma%20in%20Effusions%20and%20Fine%20Needle%20Aspirates

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
(No Transcript)
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

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

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

6

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

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.

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

9
Mesothelioma in Effusions Cytological Features
of Epithelioid Mesothelioma
10
Mesothelioma in Effusions Cytological Features
of Epithelioid Mesothelioma
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

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

13
Mesothelioma in Effusions Cytological Features
of Metastatic Adenocarcinoma
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

15
Mesothelioma in Effusions Cytological Features
of Metastatic Melanoma
16

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

17
Mesothelioma in Effusions Cytological Features
of PEL
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

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

20
Mesothelioma in Fine Needle Aspirates Cytological
Features of Mesothelioma in FNAs
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

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)

23
Mesothelioma in Fine Needle Aspirates Cytological
Features of Lung BAC in FNAs
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)

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
26
Mesothelioma (Ancillary Studies) Mesothelial
cell (Mesothelioma) Markers
HBME-1
CK 5/6
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
28
Mesothelioma (Ancillary Studies) Adenocarcinoma
Markers
B72.3
CA19.9
Ber-EP4
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
30
Mesothelioma (Ancillary Studies) Hematopoietic
and other markers
HHV8
TTF-1
CK 7
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

32

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

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