Orthopaedic Surgery - Epithelioid and Synovial Sarcoma

Basics

Epithelioid sarcoma and synovial sarcoma are:

High-grade malignant soft-tissue tumors

that most commonly affect:

Adolescents and young adults.

Both may recur locally and metastasize, particularly to the:

Lungs.

Epithelioid sarcoma has an additional notable tendency toward:

Regional lymph-node metastasis.

Epithelioid Sarcoma

Epithelioid sarcoma is a rare aggressive soft-tissue sarcoma with a predilection for the:

Distal upper extremity

particularly the:

Hand

Wrist

and

Forearm.

It is among the characteristic sarcomas of the hand and upper extremity.

Age

Epithelioid sarcoma most often occurs in:

Young patients

typically between approximately:

15 and 40 years of age.

Clinical Behavior

Epithelioid sarcoma is notable for:

Local recurrence

Regional lymphatic spread

and

Pulmonary metastasis.

Because of its superficial appearance and sometimes indolent course, it may initially be mistaken for:

Inflammatory

Granulomatous

or other benign lesions.

Synovial Sarcoma

Synovial sarcoma is a:

High-grade malignant soft-tissue tumor

that frequently develops near:

Large joints

and other para-articular structures.

Despite its name, it does not arise primarily from normal synovium.

True intra-articular involvement is:

Uncommon, historically reported in only about 5% of cases.

Typical Locations of Synovial Sarcoma

Approximate historical distribution includes:

Lower extremity – about 60%

Upper extremity – about 25%

Trunk – about 10%

Head and neck – about 10%

The lower extremity, particularly around the:

Knee

is a common location.

Prevention

There is no established preventive strategy for either:

Epithelioid sarcoma

or

Synovial sarcoma.

No specific modifiable environmental cause has been clearly identified.

Epidemiology

Soft-tissue sarcomas collectively are uncommon malignancies.

Historical estimates described approximately:

10,000 new soft-tissue sarcomas per year in the United States

at the time of the source data.

Epithelioid and synovial sarcomas together make up only a minority of all:

Soft-tissue sarcomas.

Epithelioid Sarcoma Epidemiology

Characteristic epidemiologic features include:

Young age

and

Upper-extremity predominance.

Synovial Sarcoma Epidemiology

Synovial sarcoma most frequently affects patients between approximately:

15 and 40 years of age.

A slight male predominance has historically been reported, with a male-to-female ratio of approximately:

1.2:1.

Risk Factors

No well-established acquired risk factors are known for either tumor.

Genetics

Epithelioid Sarcoma

No simple inherited genetic predisposition has been established.

A characteristic molecular abnormality is loss of function of:

SMARCB1/INI1

in most conventional epithelioid sarcomas.

Synovial Sarcoma

Synovial sarcoma is characterized by a specific chromosomal rearrangement involving chromosomes:

X and 18.

The classic translocation is:

t(X;18)(p11;q11).

Fusion Genes

This rearrangement produces fusion between:

SS18, historically called SYT, on chromosome 18

and an:

SSX gene

on the X chromosome.

Common fusion products include:

SS18-SSX1

and

SS18-SSX2.

This molecular finding is highly characteristic of:

Synovial sarcoma.

Pathophysiology

Both tumors arise from uncontrolled proliferation of:

Malignant soft-tissue cells.

Metastatic Spread

The predominant hematogenous site of metastasis is the:

Lung.

Lymphatic Spread

Regional lymphatic metastasis is especially important in:

Epithelioid sarcoma.

Synovial sarcoma can also metastasize, although pulmonary spread is particularly important clinically.

Superficial Epithelioid Sarcoma

When epithelioid sarcoma arises superficially, it may present as a:

Firm subcutaneous nodule.

The lesion may eventually:

Ulcerate through the skin.

Deep Epithelioid Sarcoma

Deep tumors may be firmly attached to:

Muscle

Tendon

Fascia

or other deep structures.

Etiology

No definite etiologic factor has been identified for either:

Epithelioid sarcoma

or

Synovial sarcoma.

Associated Conditions

No consistent associated medical disorder is recognized.

Diagnosis

Diagnosis requires:

Clinical assessment

Cross-sectional imaging

and

Tissue biopsy.

Because many benign masses can resemble a sarcoma, biopsy planning should be coordinated with the:

Definitive orthopaedic oncology team.

Signs and Symptoms

The most common presentation is a:

Soft-tissue mass.

Pain

Approximately:

Half of patients

may experience pain.

Other lesions may remain:

Painless

for a prolonged period.

Growth Pattern

The mass may demonstrate:

Slow progressive enlargement

or

More rapid growth.

Some patients report that the lesion has been present for:

Months or years

before diagnosis.

History

Important historical features include:

Duration of the mass

Change in size

Rate of growth

Pain

Skin ulceration

Previous attempted excision

and

Neurologic or vascular symptoms.

A history of a supposedly benign mass that repeatedly recurs should raise concern for:

Malignancy.

Physical Examination

Carefully document the:

Size

Location

Depth

Consistency

Mobility

and relationship to surrounding structures.

Depth

Determine whether the lesion is:

Superficial to fascia

or

Deep to fascia.

Deep masses generally warrant greater concern for:

Soft-tissue sarcoma.

Mobility

Determine whether the tumor is:

Mobile

or

Fixed to underlying tissue.

Skin Examination

Inspect for:

Erythema

Ulceration

Discoloration

Tethering

or other changes in the overlying skin.

Lymph-Node Examination

Regional lymph-node basins should be examined carefully, especially in patients with suspected:

Epithelioid sarcoma.

Laboratory Tests

There are no specific routine blood tests that establish the diagnosis.

Laboratory studies may be obtained as part of:

General oncologic evaluation

or preoperative assessment.

Imaging

Imaging defines the:

Anatomic extent

of the primary tumor and evaluates for:

Metastatic disease.

Plain Radiographs

Radiographs of the involved region may identify:

Bone erosion

Cortical destruction

Periosteal reaction

Soft-tissue mineralization.

Mineralization in Synovial Sarcoma

Calcification or mineralization within the tumor has historically been described in approximately:

20% of synovial sarcomas.

This may provide a useful radiographic clue in a:

Young patient with a periarticular soft-tissue mass.

MRI

MRI is the most useful local imaging study.

It defines:

Tumor size

Depth

Relationship to fascia

Muscle involvement

Bone involvement

Neurovascular relationships

and the overall extent necessary for:

Biopsy and surgical planning.

CT

CT is important for staging, particularly evaluation of the:

Chest

for pulmonary metastases.

Nodal Imaging

When lymphatic spread is a concern, imaging may include regional nodal basins such as the:

Axilla

Pelvis

or other drainage regions depending on the primary tumor location.

Biopsy

A properly planned:

Core-needle biopsy

is generally required before definitive treatment.

Biopsy Principles

The biopsy tract should be positioned so that it can later be:

Removed en bloc with the definitive tumor resection.

Poorly planned biopsy or unplanned excision can contaminate:

Additional tissue planes

and complicate limb-preserving surgery.

Sentinel Lymph-Node Evaluation

Because epithelioid sarcoma has a relatively strong tendency toward:

Lymph-node spread

sentinel lymph-node biopsy or other nodal assessment may be considered in selected patients.

Pathological Findings

Epithelioid Sarcoma

Characteristic findings include:

Nodular growth pattern

Central necrosis

Cells with epithelioid morphology

and loss of:

INI1/SMARCB1 expression

on immunohistochemical staining.

Synovial Sarcoma Histologic Types

Histologic patterns include:

Monophasic spindle-cell type

Biphasic type

Poorly differentiated type

and, rarely,

Predominantly epithelial forms.

Biphasic Synovial Sarcoma

The biphasic form contains both:

Epithelial-appearing cells

and

Spindle or fibrous components.

Monophasic Synovial Sarcoma

The monophasic form consists predominantly of:

Spindle cells.

Molecular confirmation can be especially useful when histology overlaps with other sarcomas.

Differential Diagnosis

The differential diagnosis of a soft-tissue mass is broad and includes numerous:

Benign

and

Malignant lesions.

Epithelioid Sarcoma Differential Diagnosis

Epithelioid sarcoma may be confused clinically or pathologically with:

Granuloma annulare

Rheumatoid nodule

Squamous cell carcinoma

Necrotizing infectious granuloma

Necrobiosis lipoidica

and other inflammatory or epithelial lesions.

Synovial Sarcoma Differential Diagnosis

Synovial sarcoma may resemble:

Other spindle-cell sarcomas

Malignant peripheral nerve sheath tumor

Fibrosarcoma

Leiomyosarcoma

and some benign periarticular masses.

Molecular testing for the:

SS18-SSX fusion

can help confirm the diagnosis.

Treatment

Treatment should be coordinated through a:

Multidisciplinary sarcoma center.

The major goals are:

Local tumor control

Prevention or treatment of metastatic disease

and

Preservation of limb function when oncologically safe.

Surgery

Wide surgical excision with:

Negative margins

is the cornerstone of local treatment.

Surgical Margin

The tumor should be removed with an appropriate cuff of:

Normal surrounding tissue

whenever anatomically feasible.

Inadequate initial excision increases the risk of:

Local recurrence.

Limb Preservation

Modern treatment allows:

Limb-sparing surgery

in the great majority of patients.

Historical series reported limb preservation in more than:

90% of cases.

Amputation

Amputation is occasionally necessary when:

Negative margins cannot otherwise be obtained

or when tumor extensively involves critical:

Nerves

Blood vessels

or other unreconstructable structures.

Lymph-Node Surgery

Clinically or radiographically abnormal lymph nodes should be:

Biopsied and treated appropriately.

Confirmed nodal disease may require:

Regional lymph-node dissection.

This is especially relevant in:

Epithelioid sarcoma.

Radiation Therapy

Radiotherapy is frequently combined with surgery for:

High-grade

Deep

or otherwise high-risk soft-tissue sarcomas.

Radiation Timing

Radiation may be delivered as:

Preoperative external-beam radiation

Postoperative external-beam radiation

or, less commonly,

Brachytherapy.

The choice depends on:

Tumor size

Location

Surgical plan

Wound-healing considerations.

Preoperative Radiation

Preoperative radiation may allow:

Smaller treatment fields

and lower total dose but is associated with an increased risk of:

Early wound-healing complications.

Postoperative Radiation

Postoperative radiation may reduce immediate wound complications but typically requires treatment of a:

Larger field

and may contribute to more:

Late fibrosis

and

Joint stiffness.

Chemotherapy

Systemic chemotherapy may be considered because both tumors can develop:

Pulmonary metastases.

Synovial Sarcoma Chemotherapy

Synovial sarcoma is among the soft-tissue sarcomas that may demonstrate meaningful sensitivity to:

Ifosfamide-containing chemotherapy regimens.

Treatment is individualized according to:

Tumor size

Grade

Metastatic risk

Patient age

and overall health.

Epithelioid Sarcoma Systemic Therapy

Systemic therapy may be used for:

Advanced

Metastatic

or

Unresectable disease.

Treatment strategies should be directed by a:

Sarcoma medical oncologist.

Physical Therapy

Rehabilitation is often necessary after surgery and radiation to restore:

Range of motion

Strength

Gait or upper-extremity function

and overall limb use.

Follow-Up

Patients require:

Long-term oncologic surveillance

because both local recurrence and distant metastases may occur after treatment.

Pulmonary Surveillance

The lungs are the most important site of distant metastasis.

Historical surveillance protocols included chest CT approximately every:

3–4 months for the first 2–3 years

then about every:

6 months until 5 years

followed by:

Annual imaging.

Current schedules are individualized according to tumor risk and oncology protocols.

Local Surveillance

MRI with contrast of the involved region may be obtained periodically to evaluate for:

Local recurrence.

Older protocols often used MRI approximately every:

6 months during the first 2–3 years.

Multidisciplinary Referral

Patients should be managed by a team that may include:

Orthopaedic oncologist

Medical oncologist

Radiation oncologist

Musculoskeletal pathologist

Radiologist

Plastic or reconstructive surgeon

Physical therapist

Prognosis

Prognosis depends on:

Tumor size

Depth

Histologic grade

Completeness of excision

Presence of metastasis

and specific tumor biology.

Epithelioid Sarcoma Prognosis

Epithelioid sarcoma has a substantial risk of:

Local recurrence

and

Lymphatic or pulmonary metastasis.

Historical series reported disease-free survival around:

40–50%

in some cohorts, although outcomes vary considerably with stage and treatment.

Poor Prognostic Features in Epithelioid Sarcoma

Historically unfavorable features include:

Tumor larger than 5 cm

Deep location

High mitotic activity

Tumor necrosis

Vascular invasion

Proximal rather than distal location

Inadequate initial excision

and, in some reports,

Male sex.

Synovial Sarcoma Prognosis

Localized synovial sarcoma can have favorable outcomes when:

Complete local control is achieved

and

Pulmonary metastasis does not develop.

Historical 5-year survival estimates have ranged approximately:

50–80%.

Favorable Features in Synovial Sarcoma

Historically favorable factors include:

Younger age

Tumor size less than 5 cm

Absence of poorly differentiated components.

Unfavorable Features in Synovial Sarcoma

Unfavorable factors include:

Age over approximately 40 years

Tumor size greater than 5 cm

Poorly differentiated histology

Metastatic disease.

Complications of Treatment

Potential complications of surgery and radiation include:

Delayed wound healing

Infection

Arthrofibrosis

Loss of motion

Soft-tissue fibrosis

Neurovascular injury

and impaired limb function.

Wound Complications

Wound-healing problems are particularly relevant when surgery is combined with:

Radiation therapy.

Joint Stiffness

Tumors near joints and postoperative or radiation-induced fibrosis may produce:

Arthrofibrosis

and reduced:

Range of motion.

Recurrence

Local recurrence remains an important oncologic complication, particularly after:

Inadequate initial excision

or positive margins.

Metastatic Disease

The major metastatic concern is spread to the:

Lungs.

Epithelioid sarcoma also requires particular attention to:

Regional lymph nodes.

Patient Monitoring

Surveillance should assess:

Wound healing

Limb function

Range of motion

Local recurrence

Regional lymph nodes

and

Pulmonary metastases.

Because late recurrence can occur, follow-up is generally:

Long term.

Key Principle

Epithelioid and synovial sarcomas are rare, high-grade soft-tissue malignancies that commonly affect young patients and require treatment in a specialized multidisciplinary sarcoma setting.

Epithelioid sarcoma classically affects the:

Distal upper extremity

and has a notable tendency toward:

Local recurrence and lymph-node metastasis.

Synovial sarcoma commonly develops near major joints and is characterized molecularly by:

t(X;18) with an SS18-SSX fusion.

The foundation of treatment is:

Wide surgical excision with negative margins, frequently combined with radiotherapy, while systemic therapy is considered according to tumor type, size, stage, and metastatic risk.