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Alveolar Soft-Part Sarcoma: a Study of Improved imaging

Techniques

Alveolar soft-part sarcoma (ASPS) is a rare soft-tissue tumor that
accounts for approximately 0.51% of soft-tissue sarcomas (Portera 2001).
It arises mainly in children and young adults. Despite a relatively apathetic
clinical course, ASPS can migrate or metastasize into other parts of the
body, typically the lungs and the brain. Up to 79% of the patients develop
metastatic disease with a high proportion being resistant to conventional
chemotherapeutic regimens. ASPS is a sarcoma indicating that this cancer
initially arises from embryonic mesenchyme. ASPS has been the focus of
substantial interest for pathologists and clinicians due to its distinctive
microscopic features, ambiguous line of differentiation and erratic clinical
behavior. In the past several years, our understanding of the genetic
events underlying the pathogenesis of ASPS has greatly increased.

Christopherson, then a fellow in surgical pathology, is credited for
the original description of ASPS. With the publication of a study of 12
cases in 1952, Christopherson et al. started the descriptive term "alveolar
soft part sarcoma" for a rare soft-tissue tumor. This tumor normally
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occurred in the limbs of young women and followed a lengthy clinical
course with recurrent late metastases. It was defined histologically by the
presence of an organoid to pseudoalveolar pattern and large, eosinophilic
tumor cells. While Christopherson et al. did not describe the intra-
cytoplasmic crystalline structures that have become one of the symbols of
ASPS, they did quote an unpublished letter from Dr. Pierre Masson, who
noted the intra-cytoplasmic crystals (Christopherson 1952). Apparently
unknown to Christopherson and colleagues, ASPS had been described
one year previously by Smetana and Scott in a series of 14 cases retrieved
from the archives of the Armed Forces Institute of Pathology, as malignant
tumours of nonchromaffin paraganglia (Smetana 1951). They chose this
term because the tumors resembled non-physiologically active
paraganglia, postulating that primitive paraganglia-like structures may
perhaps normally occur in the somatic soft tissues (this hypothesis was
later discredited). Smetana and Scott also independently observed the
intra-cytoplasmic crystals of ASPS, describing them as rod-shaped,
coarse, basophilic bodies of unknown nature (Smetana 1951).

Most patients with alveolar soft part sarcoma have probably had the
cancer for a long period of time before it comes to medical attention. The
tumor grows slowly at first causing few symptoms long before a mass
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appears, thus, going undetected. By the time the tumor is big enough that
the patient feels a lump from the primary lesion and seeks out a physician
for help, the tumor has frequently spread, establishing small metastatic
colonies throughout the body, frequently found in the lungs and even the
brain. It is a malignant tumor that tends to spread relentlessly if not
completely removed by surgery. Many patients can live with disease for
years and even decades (Pappo, Parham et al. 1996). Metastasis has
been reported as long as 15 years after initial resection of the tumor.
Unlike other soft tissue sarcomas, ASPS also metastasizes to the brain,
and are described as a common feature of metastatic ASPS. Although
most patients with alveolar soft part sarcoma can never be rid of their
cancer completely, many can undergo repeated surgery over the years to
keep it somewhat at rest (Weis and Goldblum 2001).

Figure 1 Lowpower view of a typical alveolar softpart sarcoma, showing
an organoid, pseudoalveolar proliferation of large, eosinophilic cells and a
delicate capillary network.
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ASPS differs little in its appearance from case to case, and is in
some respects remarkable among softtissue neoplasms for the absence
of described variants. ASPS is characterized by uniform, organoid nests of
polygonal tumor cells, divided by fibro-vascular septa and delicate
capillarysized vascular channels. Diagnosis of ASPS requires clinicians
from different specialties, such as radiologists, pathologists, surgeon
oncologists, and medical oncologists (Keeffe 1983). Precise diagnosis and
treatment of this unusual tumor requires a high index of clinical suspicion
coupled with clinic-pathologic correlation via appropriate radiographic
studies. If the clinical or radiographic interpretation is equivocal, early
biopsy is essential to differentiate alveolar soft part sarcoma from
arteriovenous malformation.

ASPS tumors appear to be hyper vascular on angiography and
computed tomographic scan (CT scan), with a compact tumor stain and
roundabout, dilated draining veins (Keefe). Magnetic resonance imaging
typically exhibits high signal intensity of tumor on both T1- and T2-
weighted images (Temple et al 1994). Three-phase bone scans with
administration of 26.4 mCi and Tc-99m oxidronate sodium (Tc-99m HDP)
can also be used to show the vascularity of the tumor in selected cases
(Khameh 2007).
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Tumor sizes usually ranges between 3 and 8 cm, but cases of ASPS
up to 20 cm have been reported. Macroscopically, the tumor tissue is pale
gray or yellowish in color and has a soft consistency. ASPS often
represents a diagnostic challenge. Due to the epithelioid appearance of the
neoplastic cells and their pseudoalveolar pattern of growth, ASPS may
look like a wide variety of neoplastic conditions, such as metastatic renal
cell carcinoma, paraganglioma, granular cell tumor, and melanoma
(Mackay 1998).

ASPS chromosomal translocation not only has provided critical
information about the pathogenesis of the disease but has also led to
rational molecular targeted therapy evaluation. Most series reported in the
literature suggest that ASPS chemo-sensitivity is modest, providing a
compelling rationale underlying a major role for surgery in localized
disease. The existence of withdrawn metastases is quite common in
ASPS; however, even the largest currently published ASPS clinical series
does not define the optimal treatment for metastatic ASPS disease
(Lieberman 1989). In the meantime, new molecular targeted therapies,
such as antiangiogenic approaches and tyrosine kinase inhibitors, include
the most encouraging new approaches for the treatment of ASPS, a
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shattering tumor which unfortunately seems to emerge in patients who
otherwise would be just on the verge of normal adult life (Torres 2010).
Due to ASPS resistance to chemotherapy, hundreds of thousands of
dollars are spent per individual on surgery and different clinical trials.
Again, there is no real cure for ASPS.

Computed tomography (CT) and magnetic resonance imaging (MRI)
are the current highest level of general development in the proper staging,
evaluation of loco-regional involvement, presence of necrotic areas,
infiltration and surrounding tissue, and surgical and bi-optical planning and
as such are the main instruments used in identifying ASPS. Digital
subtraction angiography, a type of fluoroscopy technique used to clearly
visualize blood vessels in a bony or dense soft tissue environment, is also
used (Kim et al 2005). Images are produced using contrast medium by
subtracting a 'pre-contrast image' or the mask from later images, once the
contrast medium has been introduced into a structure. CT is more sensitive
in the detection of bone cortical thinning and cortical invasion, while MRI is
useful to evaluate partition, intra-articular tumor extension, and for the
depiction of bone marrow edema (Stramare et al 2013).

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Although ASPS currently has no cure, discovering it before it
spreads, can significantly increase survival chances. The issue with the
current techniques is not necessarily with the individual instruments
themselves. The issue is that one imaging modality is simply inefficient in
detecting ASPS. A case report Ultrasonographic and MR Findings of
Alveolar Soft Part Sarcoma (Lai 2013) uses a modality not normally used:
combining the MRI and CT with Ultrasnography. This is a promising
approach to earlier detection of ASPS. The imaging modalities for this
tumor include plain film, sonography, computed tomography (CT), and
magnetic resonance imaging (MRI). ASPS commonly show equal or higher
signal intensity to muscle on T1-weighted images and high signal intensity
on T2-wighted images, with intra- and extratumoral flow voids. Marked
enhancement is seen after gadolinium administration (Lai et al 2009).
Sonographic findings of ASPS reveal well-circumscribed hypoechoic lesion
with hypervascularity. No resistive index (RI) of color Doppler ultrasound
(CDUS) for ASPS has previously been reported.

The paper presents the sonographic, CDUS and MRI findings of
ASPS in the right lower limb of a 19-year-old female. Microscopy revealed
large tumor cells with vesicular nuclei, prominent nucleoli, and granular
cytoplasm, clustered in well-defined nests separated by delicate fibrous
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tissue. Unenhanced T1-weighted MRI of ASPS usually show equal or
higher signal intensity to muscle, and T2-weighted MRI shows very high
signal intensity. Intra- and extratumoral flow voids are seen on both T1-
and T2-weighted images, representing enlarged feeding arteries and
draining veins. Marked enhancement is seen after gadolinium
administration.


There are a few reports describing the sonographic findings of
ASPS, which are as follows: well circumscribed hypo-echoic lesions with
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hyper-vascularity and without sound through transmission or acoustic
enhancement. The imaging findings of the patient in the study suggest the
differential diagnoses of hemangioma, arteriovenous malformation (AVM),
hemangiopericytoma, and angiosarcoma. The authors were able to
distinguish from hemangioman by the presence of flow voids and central
necrotic area of ASPS, and from AVM by noteworthy soft tissue
component and slow washout of contrast medium of ASPS. Ultrasound
displayed a mixed echotexture or hypoechoic mass. CT had an attenuation
less than or equal to that of skeletal muscle and well defined to infiltrating
margins. MRI on T1w has equal to or higher SI than skeletal muscle, lower
than subcutaneous fat; heterogeneous on T2w.
In summation, ASPS shows high signal intensity on T1w and T2w
compared with surrounding structures and has strong enhancement on
contrast-enhanced CT and MRI. Frequently, vascular signal voids and
central necrosis are seen. These reliable findings are well correlated with
the high vascularity of the tumor. The signal intensity of ASPS is not as
intense on T1w and T2w as those seen with benign vascular tumors
including hemangioma. The imaging devices by themselves were lacking
in important information signaling the presence of ASPS. Combining the
modalities however, enabled the ability to pinpoint ASPS characteristics,
leading to proper diagnosis as well as a better idea on how to treat it.
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The consequences of a belated or erroneous diagnosis and of an
inadequate treatment are very relevant for the patient in terms of survival
and functionality. Soft-tissue tumors are common in clinical practice, but
there are several diagnostic problems that lead to an inappropriate initial
surgical treatment. In conclusion, the best way to image a sarcoma as
resilient and clandestine as Alveolar Soft Part Sarcoma is a systematic use
of the following mechanisms: clinical history, ultra-sonographic findings, CT
evaluation, and usage of MRI to guide the diagnosis of this disease.

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