Disclosures I have nothing to disclose. Spindle cell sarcomas of - - PowerPoint PPT Presentation

1

Spindle cell sarcomas of soft tissue:

Beyond herringbones and fibrosarcoma

Andrew Horvai, MD, PhD Clinical Professor, Pathology

Disclosures

I have nothing to disclose.

Introduction Introduction

Bick EM. Ann Surg 1935; 101(2):759-65.

2

Introduction

• Fibrosarcoma: Malignant tumor, composed of

fibroblasts with variable collagen and, in classical cases, a herringbone architecture (WHO, 2002)

• Fibrosarcoma: Malignant tumor, composed of

fibroblasts with variable collagen and, in classical cases, a herringbone architecture. It is a diagnosis of exclusion (WHO, 2013)

• Problem: What is the definition of a fibroblast?

Fisher, C., et al. (2002). Adult Fibrosarcoma. WHO Pathology and Genetics Tumours of Soft Tissue and Bone: 100-101. Folpe, A. L. (2013). Adult fibrosarcoma. WHO Classification of Tumours of Soft Tissue and Bone: 91-92.

Introduction

0% 10% 20% 30% 40% 50% 60% 70% 1936 1974 1989 2010

Fibrosarcoma as % of soft tissue sarcomas

Meyerding H et al. Surg Gynecol Obstet 1936; 62: 1010-1019. Pritchard DJ et al. Cancer 1974; 33(3):888-97. Scott SM et al. Cancer 1989; 65(4):925-31. Bahrami A, Folpe AL. Am J Surg Pathol 2010;34(10):1504-13

Questions

• 1. How have tumors formerly known as fibrosarcoma

been reclassified?

• 2. Are there any true fibrosarcomas?

Monophasic synovial

sarcoma

Malignant peripheral

nerve sheath tumor

Adult fibrosarcoma Undifferentiated

spindle cell sarcoma

Spindle cell

rhabdomyosarcoma

Infantile fibrosarcoma Myxofibrosarcoma Sclerosing epithelioid

fibrosarcoma

Low-grade

fibromyxoid sarcoma

Dermatofibrosarcoma protuberans (DFSP) Fibrosarcomatous DFSP

Looks like fibrosarcoma Called fibrosarcoma

3

Monophasic synovial sarcoma

• Clinical

Young adults 80% extremity, but can arise anywhere 5 year survival 36-76%, chemotherapy + surgery

• Pathology

Highly uniform spindle cells, short fascicles, occasionally

herringbone

Hyperchromatic nuclei Branching vessels, calcification

• IHC

Keratin, EMA – at most focal, patchy S100 in ~30% CD34 negative

• Genetics

t(X;18), SS18-SSX fusion

Monophasic synovial sarcoma Monophasic synovial sarcoma Monophasic synovial sarcoma

4

Monophasic synovial sarcoma EMA Keratin SS18 break apart FISH

Malignant peripheral nerve sheath tumor (MPNST)

• Clinical

Middle aged adults, post-radiation 50% in NF1 patients, 50% sporadic Prognosis related to grade

• Pathology

Tight fascicular pattern is only one of many Tapering, hyperchromatic nuclei More mitotic activity (>5/10) and pleomorphism than SS Herniation into vessels, pre-existing benign NF

• IHC

~50% S100 or SOX10, usually very focally Keratin, desmin, EMA, CD34 usually negative H3K27 Me3 loss

• Genetics

No reproducible changes

Prieto-Granada CN et al. Am J Surg Pathol 2015 (epub).

Malignant peripheral nerve sheath tumor

5

Malignant peripheral nerve sheath tumor Malignant peripheral nerve sheath tumor Malignant peripheral nerve sheath tumor: herniation into vessels Malignant peripheral nerve sheath tumor S100 SOX10

6

Fibrosarcomatous DFSP

• Clinical

Trunk, proximal extremity mid-age, > 5cm Synchronous or metachronous DFSP Controversial if prognosis worse than DFSP after complete

excision

• Pathology

Usually precursor DFSP can be found at periphery

Normal epidermis, uniform storiform, “Swiss cheese”

Transition to fascicular, herringbone, hypercellular area High mitotic activity (>7 / 10 hpf), necrosis

• IHC

CD34 positive but weaker than DFSP

• Genetics

t(17;22)(q21;q13) COL1A1:PDGFβ fusion

DFSP Fibrosarcoma Dermatofibrosarcoma protuberans Fibrosarcomatous DFSP

7

Fibrosarcomatous DFSP Fibrosarcomatous DFSP DFSP + Fibrosarcoma CD34

Adult fibrosarcoma “undifferentiated spindle cell sarcoma”

• Clinical

Trunk, proximal extremity mid-age Deep soft tissue Poor prognosis (<55% 5 year survival)

• Pathology

Monomorphic spindle cells Fascicles, herringbone and/or storiform Rarely fibromatosis like areas Collagen can be wispy or keloidal

• IHC

Negative except focal SMA

• Genetics

Variable

8

Adult Fibrosarcoma Adult Fibrosarcoma Keratin SMA CD34 Caldesmon S100 CD10 … and more Adult Fibrosarcoma Adult Fibrosarcoma

9

Adult Fibrosarcoma Adult Fibrosarcoma

Infantile fibrosarcoma

• Clinical

Very rare, distal extremity but wide distribution Congenital (1/3rd) to 1 year Relatively good prognosis, does not correlate with grade

• Pathology

Highly cellular, monomorphic ovoid to spindled Herringbone to sheets HPC-like vessels

• IHC

Negative, weak focal SMA

• Genetics

t(12;15) ETV6:NTRK3 Same as congenital pulmonary fibrosarcoma, congenital

mesoblastic nephroma

Also in secretory breast cancer and AML

Infantile Fibrosarcoma

10

Infantile Fibrosarcoma Infantile Fibrosarcoma Infantile Fibrosarcoma

Ancillary tests summary

Synovial sarcoma MPNST FS in DFSP Infantile FS Adult FS Keratin Rare cells

• S100

Weak, patchy Weak, patchy

• CD34
• Rare cells

Weak

• Other

SS18 FISH SOX10 PDGF FISH ETV6 FISH

11

Take-home messages

• 1. Adult fibrosarcoma is a diagnosis of exclusion
• 2. Some diagnoses that retain the diagnosis of

“fibrosarcoma” are not uniformly herringbone

• 3. Most herringbone spindle cell neoplasms in adults

can be classified as synovial sarcoma, MPNST or fibrosarcomatous DFSP

• 4. Immunohistochemistry and, in some cases,

genetics are needed in most cases to classify these tumors