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

Clinical presentation

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

Interventional Cytopathology

Fähigkeitsausweis Sonographie (Proficiency Certificate)

Division of Cytology, University Hospital ZurichFine needle biopsy

30% Lymph nodes25-30% Thyroid15-20% Lung

10% Soft tissue / Skin10% Salivary glands5% Pancreas (and liver)

45-jährige Frauh/o NHL

Squamous cyst(trichilemmal cyst)

52-jähriger Mannh/o NHL

Melanoma

HMB45

Z17.1317739 y; F

Mass in the muscles of the abdominal wall

Z17.13177

ENDOMETRIOSIS

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

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

WHO 2013 «ClassificationSoft tissue and Bone Tumors»

Clinical presentation

Histopathology

Immunohistochemistry

Molecular genetics

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

Cell suspensionFlow cytometry

Microbiology (steril)

Fresh frozen tissue (NGS)

Direct smearsCytomorphologyImmunocytochemistryFISH

Cell blocksImmunohistochemistryFISHPCR / NGS

US guidance CT guidance

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)

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)

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

39j; M (Z17.13136-7)Slowly growing nodule on the lower thoracic wall, present since many years

PAP HE CD34

Z17.13136

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

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 )

60 y old woman

Slightly painful swellig of the distal upper arm

Intramuscular myxoma

Intramuscular myxoma

44 y old man

Long standing, slowly growing swelling of the thigh

Myxoid liposarcoma

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

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

Myxofibrosarcoma (high grade)

PAP DiffQuik Cell block

Extraskeletal myxoid chondrosarcoma

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

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)

64 y old, woman

FNA direct smear (PAP)

FNA cell block mib1

FNA cell block mdm2

FNA cell block mdm2 gene FISH

Dediferentiated liposarcoma; high grade

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

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

FISH SS18(SYT)

Synovial sarcoma (poorly differentiated)

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)

75 y old, woman

S100CK

Epithelioid sarcoma (proximal type)

FNA cell block INI1 (loss of expression)

Mature tissue-like

• Fatty tissue– lipoma– well differentierted liposarcoma

• Cartilage– chondroma– well differentiated chondrosarcoma

• Muscle– Leiomyoma– Rhabdomyoma

• Peripheral nerves– Ectopic meningeoma– Ganglioneuroma

50 y; W

Lipoma

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

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

60 y; W

Swelling of the neck; s/o lymph node clinically

Intramuscular nodular fasciitis

Fibromatosis (desmoid tumor)

68 y; W

Large longstanding and slowly progr. mass on the neck

• 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

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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