Adeola AwowaleBioe420

May 21, 2014

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 0.5–1% 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

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soft part sarcoma" for a rare soft-tissue tumor. This tumor normally

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ASPS, they did quote an unpublished letter from Dr.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 non‐chromaffin 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

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tumor grows slowly at first causing few symptoms long before a mass

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).

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Figure 1 Low‐power view of a typical alveolar soft‐part sarcoma, showing an organoid, pseudoalveolar proliferation of large, eosinophilic cells and a delicate capillary network.

ASPS differs little in its appearance from case to case, and is in

some respects remarkable among soft‐tissue 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

capillary‐sized 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)

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can also be used to show the vascularity of the tumor in selected cases

(Khameh 2007).

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,

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such as antiangiogenic approaches and tyrosine kinase inhibitors, include

the most encouraging new approaches for the treatment of ASPS, a

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

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cytoplasm, clustered in well-defined nests separated by delicate fibrous

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.

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There are a few reports describing the sonographic findings of

ASPS, which are as follows: well circumscribed hypo-echoic lesions with

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

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modalities however, enabled the ability to pinpoint ASPS characteristics,

leading to proper diagnosis as well as a better idea on how to treat it.

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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References

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4. Pappo AS1, Parham DM et al. Alveolar soft part sarcoma in children and adolescents: clinical features and outcome of 11 patients. Med Pediatr Oncol. 1996 Feb;26(2):81

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