Evaluation of Soft Tissue Tumors

By admin On Oct 6, 2024

Ovid: Oncology and Basic Science

Editors: Tornetta, Paul; Einhorn, Thomas A.; Damron, Timothy A.

Title: Oncology and Basic Science, 7th Edition

> Table of Contents > Section I
– Evaluation and Management of Musculoskeletal Oncology Problems > 2
– Evaluation of Soft Tissue Tumors

Evaluation of Soft Tissue Tumors

Carol D. Morris

Soft tissue tumors are heterogeneous in their behavior
and management. The vast majority of soft tissue tumors are benign,
with benign tumors outnumbering malignant tumors by a factor of at
least 100. This chapter deals with the general diagnostic and
management guidelines for both benign and malignant soft tissue tumors.
More specific information is available in each tumor-specific chapter.

Pathogenesis

Etiology

The etiology of most soft tissue tumors is largely
unknown. Environmental exposures, radiation, viral infection, and
genetic associations have all been implicated, though the developmental
associations are casual in most instances (Box 2-1).

Epidemiology

Benign
- True incidence is poorly reported
  - ~300/100,000
- Outnumber malignant soft tissue sarcomas by 100:1
Malignant
- ~8,700 cases/year in the U.S.
- Annual incidence ~1.5/100,000
  - 8/100,000 in individuals >80 years old
- Accounts for <1% of all cancers

Pathophysiology

While the pathophysiology of most soft tissue tumors
remains ambiguous, the past two decades have provided considerable
insight into the biology of these tumors in the form of cytogenetic and
molecular information. Chromosomal translocations or other chromosomal
aberrations have been reported for virtually every type of soft tissue
tumor. The more consistent genetic findings are outlined in Tables 2-1 and 2-2. In addition, a number of inherited conditions are associated with the development of soft tissue tumors (Table 2-3).

Classification

Soft tissue tumors are most commonly characterized
histologically according to the type of tissue they most closely
resemble. The most widely recognized classification is that

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of the World Health Organization (WHO), which was first published in 1969 and most recently updated in 2002.

Table 2.1 Cytogenetic and Molecular Genetic Alterations Seen in Benign Soft Tissue Tumors

Tumor	Genetic Alterations
Lipoma	12q13–15, 6p21–23, 13q11–22, 13q del
Desmoid	Trisomy 8, trisomy 20, APC gene mutations
Schwannoma	Monosomy 22
Neurofibroma	t(12;14)

Box 2-1 Etiologic Factors Reported in the Development of Soft Tissue Tumors

Environmental
   Trauma
   Chemical carcinogens (dioxin)
   Asbestos
   Surgical implants
Radiation
   Therapeutic
Viral Infection
   Human immunodeficiency virus (HIV)
   Cytomegalovirus (CMV)
   Human herpes virus (HHV)-8
   Epstein-Barr virus (EBV)
Genetic
   Neurofibromatosis
   Retinoblastoma
   Gardner’s syndrome
   Li-Fraumeni syndrome
Immunologic
   Therapeutic immunosuppression
   Stewart-Treves syndrome

The major histologic categories are:

Adipocytic
Fibroblastic
Fibrohistiocytic
Smooth muscle
Perivascular
Skeletal muscle
Vascular
Chondro-osseous
Uncertain differentiation

The major histologic categories are then divided into
benign, intermediate, and malignant groups. WHO recognizes over 60
subtypes of benign soft tissue tumors and over 50 subtypes of malignant
soft tissue tumors (sarcomas). It is not thought that the malignant
subtypes arise from the benign forms. For example, liposarcoma does not
arise from benign fat in lipoma but rather histologically exhibits
lipoblastic differentiation.

Diagnosis

Benign soft tissue tumors are fairly common and rarely
problematic. In contrast, soft tissue sarcomas are exceedingly rare but
diagnostically and therapeutically challenging. Unfortunately both
benign soft tissue tumors and soft tissue sarcomas have a deceptively
similar presentation, and as such a delay in the diagnosis of soft
tissue sarcoma is not uncommon (Table 2-4). While clinical and imaging features will help guide an appropriate work-up, any suspicious soft tissue mass must be biopsied.

Table 2.2 Cytogenetic and Molecular Genetic Alterations Seen in Malignant Soft Tissue Tumors

Tumor	Translation	Involved Genes
Primitive neuroectodermal tumor (PNET)	t(11;22)	FLI1, EWS
Clear cell sarcoma	t(12;22)	ATF1, EWS
Extraskeletal myxoid chondrosarcoma	t(9;22)	CHN, EWS
Synovial sarcoma	t(X;18)	SSX1 or SSX2, SYT
Myxoid liposarcoma	t(12;16)	CHOP, TLS
Alveolar rhabdomyosarcoma	t(2;13)	PAX3, FKHR
Alveolar soft part sarcoma	t(X;17)	TFE3, ASPL
Dermatofibrosarcoma protuberans*	t(17;22)	COL1A1, PDGFB1
* In the WHO classification, dermatofibrosarcoma protuberans is classified as a skin tumor, but it may be encountered in the orthopaedic oncology setting.

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Table 2.3 Inherited Syndromes Associated with Soft Tissue Tumors

Syndrome	Associated Tumors
Bannayan-Riley-Ruvalcaba syndrome	Lipoma, hemangioma (hamartoma syndrome)
Beckwith-Wiedemann syndrome	Rhabdomyosarcoma, myxoma, fibroma (overgrowth syndrome)
Costello syndrome	Rhabdomyosarcoma (congenital anomaly/mental retardation syndrome)
Cowden disease	Lipoma, hemangioma (hamartoma syndrome)
Familial fibromatosis	Desmoid tumors
Li-Fraumeni syndrome	Various soft tissue sarcomas (or bone sarcomas)
Maffucci syndrome	Hemangioma, angiosarcoma (with enchondromas)
Mazabraud syndrome	Intramuscular myxoma (with fibrous dysplasia)
Neurofibromatosis-1	Neurofibromas, malignant peripheral nerve sheath tumors (MPNST)
Neurofibromatosis-2	Schwannoma
Proteus syndrome	Lipoma (overgrowth syndrome)
Retinoblastoma syndrome	Various soft tissue sarcomas
Rubinstein-Taybi syndrome	Myogenic sarcoma
Werner syndrome	Various soft tissue sarcomas

Physical Examination and History

Clinical Features

History

How long has the mass been present?

Masses present for long periods of time are most likely benign.
New masses arising over a short period of time raise malignancy suspicion.
Synovial sarcoma and clear cell sarcoma are classic exceptions (may be present for many years).

Any mass that persists for >4 weeks in the absence of clear-cut trauma warrants consideration of biopsy.

Table 2.4 Guidelines for the Clinical Presentation of Extremity Soft Tissue Masses

Parameter	Benign	Malignant	Comments
Pain	Rare*	Rare	Uncommon in the absence of nerve or bone invasion
Size	<5 cm	>5 cm
Location	Superficial (subcutaneous)	Deep to fascia	1/3 of soft tissue sarcomas are superficial.
Mobility	Mobile**	Fixed
Consistency	Soft	Firm
Growth	Stable	Enlarging	Synovial sarcoma and clear cell sarcoma can be very slow-growing.
* One benign soft tissue mass that typically presents with pain is an intramuscular hemangioma. ** Benign peripheral nerve sheath tumors are tethered to the nerve and therefore are mobile only medially and laterally but not proximally/distally.

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Is the mass enlarging?
- Enlarging masses indicate an active process.
- Patients often have difficulty assessing
  growth patterns, especially axial lesions (buttock, pelvis, shoulder
  girdle); they may not be noticed until of substantial size.
Is there any history of cancer?
- Certain malignancies may metastasize to the soft tissues with greater frequency:
  - Lung carcinoma
  - Melanoma
  - Lymphoma

Physical Examination

Always measure the size of the mass.
- Any mass >5 cm warrants biopsy!
- Any mass that increases in size over time warrants a biopsy!
Always assess depth.
- Any deep mass (involving fascia or deeper) warrants consideration of biopsy!
Determine mobility relative to surrounding structures.
- Any fixed mass warrants a biopsy!
Transilluminate superficial masses (rule out ganglion).
Palpate for tenderness.
Palpate to determine consistency (soft versus firm).
Check for pulsations, bruit.
Palpate adjacent blood vessels and bones.
Perform complete neurological examination.
Examine the abdomen for hepatomegaly or splenomegaly.
Examine entire extremity; check for satellite lesions.
Examine regional lymph nodes.

Radiographic Features

Plain Radiographs

Plain radiographs of the affected area
are important for the evaluation of soft tissue mineralization and bony
involvement. In addition, any patient with a mass suspicious for soft
tissue sarcoma should have a chest x-ray.
Any soft tissue sarcoma can present with soft tissue calcifications.
The most common masses with soft tissue mineralization:
- Myositis ossificans (more mature mineralization around periphery)
- Hemangioma (small, round, well-defined phleboliths; Fig. 2-1)
- Synovial sarcoma (variable pattern of mineralization)
- Well-differentiated liposarcoma
- Extraskeletal chondrosarcoma
- Extraskeletal osteogenic sarcoma (centrally mature mineralization; Fig. 2-2)

Computed Tomography (CT)

There are four main reasons to obtain a CT scan in patients with soft tissue masses:

CT scan of the chest for staging in soft tissue sarcoma

Figure 2-1 Soft tissue phleboliths. Diagnosis: Hemangioma.

Figure 2-2 Soft tissue mineralization. Diagnosis: Extraskeletal osteogenic sarcoma.

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Figure 2-3
MRI versus CT scan in the evaluation of adjacent bone involvement in a
patient with soft tissue sarcoma in the leg. The CT scan (A) clearly shows loss of cortex, whereas the MRI (B) is more ambiguous.

Evaluation of underlying bony involvement (Fig. 2-3)
Evaluation of the primary tumor in patients with contraindication to magnetic resonance imaging (MRI)
Evaluation of pattern of mineralization (Fig. 2-4)

Magnetic Resonance Imaging

MRI is the imaging modality of choice in
the diagnosis and therapeutic planning of soft tissue tumors. It is
superior to other imaging modalities in determining size, location, and
anatomic relationships to neurovascular structures in multiple planes.
For soft tissue sarcomas, MRI is useful
for evaluating preoperative radiation or chemotherapy responses and for
detecting local recurrences.

In general, most tumors demonstrate dark signal on T1-weighted images and bright signal on T2-weighted images (Fig. 2-5).

Figure 2-4
Mineralized soft tissue mass in the pelvis. CT scan nicely demonstrates
a zonal pattern of ossification with more mature mineralization
peripherally, consistent with myositis ossificans.

Tumors that do not follow this usual signaling pattern have a narrow differential (Table 2-5).

MRI alone cannot differentiate benign tumors from malignant ones. Lipomas and synovial cysts/ganglions are exceptions.
- Lipomas have a characteristic appearance
  on MRI, with uniform homogenous fatty signal on all sequences and loss
  of signal on the fat-suppression sequences (Fig. 2-6).
- Cysts have homogenous fluid signal with only peripheral enhancement.
Helpful hints when evaluating soft tissue masses on MRI:
- Any deep heterogeneous mass or any heterogeneous mass >5 cm regardless of location is a soft tissue sarcoma until proven otherwise.
- Cysts do not demonstrate central enhancement with gadolinium (Fig. 2-7).
- Not all small masses near a joint
  (especially the knee and wrist) are ganglions. Unfortunately, small
  soft tissue sarcomas can occur in and around joints. When in doubt,
  obtain an MRI with contrast to differentiate cystic masses from solid
  masses (Fig. 2-8).
- Just because some of the tissue has the
  same signal as fat does not make it a lipoma. True lipomas are
  homogenous on all sequences, are isointense with the subcutaneous fat
  on all sequences, and uniformly suppress with fat suppression (see Fig. 2-6).
  Well-differentiated to moderately differentiated liposarcomas have
  areas of signal consistent with normal fat but admixed with nonfatty
  signal (Fig. 2-9).

Staging

Staging systems are a way to predict a tumor’s biological potential and hence its clinical behavior, which in turn aids

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clinicians in outlining treatment strategies for a given patient.
Staging systems guide the diagnostic work-up, the type of local
control, the need for adjuvant treatments, and a long-term follow-up
strategy.

Figure 2-5 A typical MRI appearance of a soft tissue sarcoma in the arm. (A) The mass displays dark signal on the T1-weighted image, which is isointense with the adjacent muscle. (B)
On the T2-weighted image, the mass displays bright signal relative to
the surrounding normal tissues. On both sequences, there is
considerable heterogeneity, which is more obvious on the T2 image.

All patients with suspicious soft tissue
masses require MRI and biopsy. (The importance of biopsy choice and
technique is discussed in Chapter 3.)
All patients with suspected sarcoma require MRI, chest x-ray, CT scan of the chest, and biopsy.

Benign

Staging systems for benign soft tissue tumors are not well developed or widely used.
Most benign tumors have limited local
recurrence potential and distant metastases are exceedingly rare. As
such, evaluations of the extent of disease are unnecessary, and when
surgery is necessary, local excision alone is usually curative.

Table 2.5 Tumors Other Than Those with Low T1/high T2* That Have Specific Mri Signaling Characteristics

High T1	Low T1, Low T2
Lipoma	Fibromatosis
Well-differentiated liposarcoma	Diffuse giant cell tumor (pigmented villonodular synovitis)
Hemangioma (with serpiginous vascular channels)	Clear cell sarcoma
Acute hemorrhage	Rind around chronic hematoma
*The only tumor with low T1/high T2 that can be specifically diagnosed by MRI is a cyst, the diagnosis of which is confirmed by the absence of any central enhancement after gadolinium administration.

Intermediate

In 2002, WHO subdivided intermediate
tumors into two categories: intermediate–locally aggressive and
intermediate–rarely metastasizing.
Intermediate–locally aggressive tumors tend to cause local problems and recur locally.
- Examples include desmoid tumors and atypical lipomatous tumors.
- Histologically, they demonstrate an infiltrative pattern.
- Often, wide surgical excision is
  necessary, particularly with desmoid tumors, although on occasion even
  this is inadequate to achieve local control.
Intermediate–rarely metastasizing tumors
can also display locally aggressive characteristics but demonstrate the
ability to give rise to distant disease, though to a lesser degree than
fully malignant tumors (on the order of ~2%).
- Examples of such tumors are hemangiopericytoma and giant cell tumor of soft tissues.

Malignant

Staging systems for soft tissue sarcomas
rely on histologic grade, size of the tumor, anatomic location of the
tumor, and the degree of regional and distant disease.
The primary staging system used for soft tissue sarcomas was developed by the American Joint Committee on Cancer (AJCC) (Table 2-6).

The histologic grading is a complex endeavor that has evolved through the years.

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Figure 2-6 Intramuscular lipoma. (A) On the T1-weighted image, the intramuscular mass is the same signal as the subcutaneous fat. (B)
On the fat-suppression T2 image, the mass remains homogenous with a
uniform loss of signal. Post-contrast enhanced images would not show
any enhancement.

Grading incorporates the mitotic index
(number of mitoses per high-power field), extent of spontaneous
necrosis, and the degree of tumor differentiation, cellularity, and
pleomorphism.

The anatomic location of the tumor refers
to the location of the tumor relative to the deep fascia and is termed
superficial or deep.

The size of the tumor has significant prognostic importance.

Figure 2-7 This parameniscal cyst demonstrates homogenous dark signal and bright signal on the T1-weighted (A) and T2-weighted (B and C) images, respectively. (C)
With the administration of gadolinium contrast, note the lack of
central enhancement, with enhancement peripherally only. The
enhancement pattern is characteristic for cystic structures.

For the purposes of the AJCC staging system, tumors >5 cm are deemed large and those <5 cm are deemed small.
Tumors >10 cm have been shown to carry an even worse prognosis, but this information has not formally

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been incorporated into a formal staging system, though it is used for stratification in clinical trials.

Figure 2-8 (A)
This small, well-encapsulated mass near the knee joint demonstrating
homogenous high signal on the T1-weight fat-suppressed image could
easily be mistaken for a cyst. (B)
Contrast administration reveals heterogeneous, central enhancement,
proving this is a solid mass. Biopsy revealed an extraskeletal myxoid
chondrosarcoma.

Figure 2-9 (A)
On this T1-weighted image, the subcutaneous soft tissue mass overlying
the deltoid displays areas of high signal with intensity similar to the
adjacent subcutaneous fat. (B) On the
fat-suppression image, while some of the mass displays similar loss of
signal, there are persistent areas of high signal, which indicates the
mass is not simply a lipoma. Diagnosis: Well-differentiated liposarcoma.

The presence or absence of distant metastases carries tremendous prognostic significance.
- Most distant spread from soft tissue
  sarcomas occurs in the lungs, while lymph node, bone, and other organ
  involvement is far less common.

Table 2.6 Ajcc Staging System for Soft Tissue Sarcoma

Stage	Size	Depth*	Grade	Metastases
I	Any	Any	Low	No
II	<5 cm, any depth OR >5 cm, superficial		High	No
III	>5 cm	Deep	High	No
IV	Any	Any	Any	Yes
* Depth is termed superficial (above the deep fascia) or deep (deep to the deep fascia). Retroperitoneal tumors are considered deep. From AJCC Cancer Staging Handbook, 6th ed. New York: Springer, 2002.