fine needle cytology · • proliferative myositis • lipoblastoma • neurothekeoma • chondroid...
TRANSCRIPT
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Fine needle Cytologyof
Soft Tissue Lesions
Prof. Dr. med. Beata Bode-LesniewskaInstitute of Pathology and Molecular PathologyUniversity HospitalZurich, Switzerland
SGZyt 201714.10.2017 Saturday11.45-12.15
Diagnostic ApplicationsAdvantages and Limitations
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Clinical presentation
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Open (surgical) biopsy
Excisional biopsy (max 3-5 cm mass)
Incisional biopsy(>5 cm)
Needle biopsy
Core biopsyNeedle diameter
>1mm (18G)
Fine needle biopsyNeedle diateter
<1mm (24G)
Histology Histology Cytology
Tumor
Seroma
CELL BLOCK
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Interventional Cytopathology
Fähigkeitsausweis Sonographie (Proficiency Certificate)
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Division of Cytology, University Hospital ZurichFine needle biopsy
30% Lymph nodes25-30% Thyroid15-20% Lung
10% Soft tissue / Skin10% Salivary glands5% Pancreas (and liver)
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45-jährige Frauh/o NHL
Squamous cyst(trichilemmal cyst)
52-jähriger Mannh/o NHL
Melanoma
HMB45
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Z17.1317739 y; F
Mass in the muscles of the abdominal wall
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Z17.13177
ENDOMETRIOSIS
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Differential Diagnosisof soft tissue masses
• Hematoma• Infection (abscesses, granulomatous infection, etc..)
• Non-neoplastic lesions– Endometriosis– Hernias
• Non mesenchymal neoplasias– Benign– Malignant (infiltration form other structures)– Metastases (carcinoma, melanoma, lymphoma)
• Primary mesenchymal tumors– Primary diagnosis
• Benign• Malignant (sarcomas)
– Recurrences / Metastases
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USA 2016 (Ca Cancer J Clin; 2016; 66: 7-30)
- 1 685 210 new cancer diagnoses- 12 310 soft tissue sarcomas (0.7%)- 3 300 bone sarcomas (0.2%)- 249 360 breast carcinomas- 224 390 lung carcinomas- 142 520 colon carcinomas
Sarcomas – Epidemiology
Incidence of bone sarcoma: ~ 8 new cases pro 1 000 000 / y:
Switzerland ca 55-65, incl. ~15 osteosarcomas Germany : 600-700
Incidence of soft tissue sarcomas: ~ 25-30 new cases pro 1 000 000 / y:
Switzerland: ca 200-250 Germany: 2000 - 2500
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WHO 2013 «ClassificationSoft tissue and Bone Tumors»
Clinical presentation
Histopathology
Immunohistochemistry
Molecular genetics
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Genetic event in a precursor (stem) cell
- Translocation (Ewing sarcoma, synovial sarcoma, DFSP,. .)- SFT -> STAT6
- Amplification (ALT/WDLPS/DDLPS, sec. AS, paraos.OS)- mdm2 gene ampl -> mdm2
- Point mutation (ckit, GNAS, β-catenin)- nuclear beta-catenin expression
- Deletion (INI1)- Loss of INI1 expression
- ???? (others / unknown)
CYTOGENETICS & MOLECULAR BIOLOGY
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Cell suspensionFlow cytometry
Microbiology (steril)
Fresh frozen tissue (NGS)
Direct smearsCytomorphologyImmunocytochemistryFISH
Cell blocksImmunohistochemistryFISHPCR / NGS
US guidance CT guidance
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Cytoarchitectonic pattern of the primary soft tissue neoplasia
1. Spindle cell2. Myxoid3. Round cell4. Pleomorphic5. Epithelioid6. Mature tissue like
• Immunohistochemistry• Molecular genetics
(direct smears)(cell blocks)
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Spindel cell tumors
• Schwannoma• Nodular fasciitis• Desmoid / fibromatosis• Solitary fibrous tumor (SFT)• Proliferative myositis• Leiomyoma• (Intramuscular) hemangioma• Inflammatory myofibroblastic
tumor (IMT)
• Leiomyosarcoma• Synovial sarcoma• Gastrointestinal stroma tumor (GIST)• Embryonal / spindle cell
rhabdomyosarcoma• Malignant peripheral nerve sheath
tumor (MPNST)• Kaposi's sarcoma
• (Carcinoma)• (Melanoma)
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Neural tumors55 y old woman
Round mass in the left axilla
Radiating sensation tomiddle finger upon pressue
Neural tumor?
S100
Schwannoma
S100
H&E Cell blockPAP
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39j; M (Z17.13136-7)Slowly growing nodule on the lower thoracic wall, present since many years
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PAP HE CD34
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Z17.13136
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Spindle cell neoplasms• Clinical context
– (Rule out non mesenchymal)
• Cell density– Low cellurarity of the FNA in experienced hands may be
used as a diagnostic hint (fibromatosis?)• Cell cohesion• Cell type
– Monomorph– Pleomorph
• Apply necessary auxillary methods– Immunohistochemistry– Mostly molecular – FISH / RT-PCR / NGS
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Myxoid mesenchymal Tumors • Myxoma (juxtaarticular, intramuscular, superficial, aggressiv)• Nodular fasziitis• Neurofibroma / Schwannoma• Spindel cell lipoma• Proliferative myositis• Lipoblastoma• Neurothekeoma• Chondroid lipoma• Sacrococcygeal myxopapillary ependymoma
• Myxoid liposarcoma• Myxofibrosarcoma• Extraskelettal myxoid chondrosarcoma• Low grade fibromyxoid sarcoma (Evans tumor)• Ossifying fibromyxoid tumor• Rare variants of leiomyo-, rhabdomyo-sarcomas, MPNST and DFSP
• (carcinoma and melanoma metastases)• (infiltration of the soft tissue by primary bone tumors, such as chondrosarcoma,
chordoma )
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60 y old woman
Slightly painful swellig of the distal upper arm
Intramuscular myxoma
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Intramuscular myxoma
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44 y old man
Long standing, slowly growing swelling of the thigh
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Myxoid liposarcoma
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Type of liposarcoma (LPS)
Well differentiated LPS(30-40% of LPS)
Dedifferentiated LPS(15-20% of LPS)
Myxoid LPS
Round cell LPS
(30-50% of LPS)
Pleomorphic LPS(~15% of LPS)
Genetic aberration
Amplification 12q 13-15inkl. MDM2 und CDK4 genes
Translocation t(12;16) FUS/CHOP
or t(16;22) EWSR1/CHOP
Complex karyotype
MG
G1
G2-3
G1-2
G3
G3
Grading
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FUS/DDTI3
b actin
1 2 3 4
1. M04.5192. neg control3. pos control4. neg control
138 bp
174 bp
Myxoid liposarcomaRT-PCR t(12;16) on the cell block
FUS gene (exon 7); chromosome 16 DDTI3 gene (exon 2); chromosome 12
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Myxofibrosarcoma (high grade)
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PAP DiffQuik Cell block
Extraskeletal myxoid chondrosarcoma
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Myxoid neoplasms• Clinical context
• Cell density• Cell type
– Monomorph– Pleomorph
• Blood vessels present?• Type of extracellular matrix
• Apply necessary auxillary methods– Mostly molecular – FISH / RT-PCR / NGS
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Pleomorphic Tumors• Pleomorphic undifferentiated sarcoma• Dedifferentiated (high grade) liposarcoma• Pleomorphic leiomyosarcoma• Pleomorphic malignamt nerve sheath tumor (MPNST)• Extraskeletal osteosarcoma• Angiosarcoma• Pleomorphic rhabdomyosarcoma• Pleomorphic liposarcoma
• (Carcinoma metastasis)• (Melanoma metastasis)• (Anaplastic large cell lymphoma)
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64 y old, woman
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FNA direct smear (PAP)
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FNA cell block mib1
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FNA cell block mdm2
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FNA cell block mdm2 gene FISH
Dediferentiated liposarcoma; high grade
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Round cell Neoplasia
• Ewing sarcoma• Round cell liposarcoma• Poorly differentiated synovial sarcoma• Alveolar rhabdomyosarcoma• Mesenchymal chondrosarcoma• Neuroblastoma• Melanotic neuroectodermal tumor• Rhabdoid tumor• Desmoplastistic, small- und round cell
tumor (DSRCT)
• (NHL)• (Small cell carcinoma)• (Melanoma)
Immunhistochemistry
Molecular genetics
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Cytokeratin (AE1/AE3) Vim MIB 1EMA
CD99 Prog-Rec S100 Calretinin
Negativ:
-Synaptophysin, Chromogranin-CD10, CD34-CK5/6; D2-40, WT1-Desmin, Actin, Myogenin-TTF1, RCC, Brst1, NY-BR1
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FISH SS18(SYT)
Synovial sarcoma (poorly differentiated)
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Epithelioid Tumors
• Granular cell tumor
• Epithelioid sarcoma• Alveolar sarcoma of soft tissue• Clear cell sarcoma of soft tissue• Epithelioid hemangioendothelioma• Paraganglioma• Rhabdoid tumor• Synovial sarcoma• Rare epitheloid variants:
– Angiosarcoma– Malignant peripheral nerve sheath tumor (MPNST)– Leiomyosarcoma
• (Carcinoma metastasis) • (Melanoma metastasis)• (Mesothelioma)
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75 y old, woman
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S100CK
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Epithelioid sarcoma (proximal type)
FNA cell block INI1 (loss of expression)
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Mature tissue-like
• Fatty tissue– lipoma– well differentierted liposarcoma
• Cartilage– chondroma– well differentiated chondrosarcoma
• Muscle– Leiomyoma– Rhabdomyoma
• Peripheral nerves– Ectopic meningeoma– Ganglioneuroma
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50 y; W
Lipoma
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42 y, man
• 10 y previously excision of a welldifferentiated liposarcoma on the neck
• History of several weeks of slowly growingmass in the operation area
• MRI mass with fatty signal
• FNA PAP: Adipocytes
• mdm2 gene FISH: Amplification
Dg: ReccurrenceAtypical lipomatous tumor (ALT)
synWell differenciated liposarcoma (WDLPS)
mdm2 FISH
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Type of liposarcoma (LPS)
Well differentiated LPS(30-40% of LPS)
Dedifferentiated LPS(15-20% of LPS)
Myxoid LPS
Round cell LPS
(30-50% of LPS)
Pleomorphic LPS(~15% of LPS)
Genetic aberration
Amplification 12q 13-15incl. MDM2 und CDK4 genes
Translocation t(12;16) FUS/CHOP
or t(16;22) EWSR1/CHOP
Complex karyotype
MG
G1
G2-3
G1-2
G3
G3
Grading
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60 y; W
Swelling of the neck; s/o lymph node clinically
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Intramuscular nodular fasciitis
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Fibromatosis (desmoid tumor)
68 y; W
Large longstanding and slowly progr. mass on the neck
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• Undisputable value– Inflammation / infection, – Metastases and recurrences
• Diagnostic of primary mesenchymale neoplasia– Controversial –
• Rare• Lack of expertise
– Pitfalls• pseudo-sarkomatous prolifarations• Hypocelullar / collagen rich tumors
• Acceptancy growing – prevention of „whoops“ ops– Sensitivity for malignancy 95%– Specifity for sarcoma 58-95%– False positiv 0-5%– False negativ 2-15%
Cytology of Soft Tissue Masses
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RequirementsDIFFERENTIAL DIAGNOSIS
• High quality cytologic samples– Advantages of the direct smears– Application of the same specturm of the auxillary
methods, as in the histology (cell block!!)
• Clinical presenations (age, gender, topography,…)
• Multidisciplinary collaboration
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www.klinische_pathologie.usz.ch
www.zytologie.usz.ch