Download Solid Tumour Section Soft tissue tumors: Alveolar soft part sarcoma

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Solid Tumour Section
Mini Review
Soft tissue tumors: Alveolar soft part sarcoma
Jean-Loup Huret
Genetics, Dept Medical Information, University of Poitiers, CHU Poitiers Hospital, F-86021 Poitiers, France
Published in Atlas Database: Update -July 2007
Online updated version: http://AtlasGeneticsOncology.org/Tumors/AlveolSoftPartSID5125.html
DOI: 10.4267/2042/38534
This article is an update of: Huret JL. Soft tissue tumors: Alveolar soft part sarcoma. Atlas Genet Cytogenet Oncol
Haematol.2001;5(4):296-297.
This work is licensed under a Creative Commons Attribution-Non-commercial-No Derivative Works 2.0 France Licence.
© 2008 Atlas of Genetics and Cytogenetics in Oncology and Haematology
Pathology
Identity
Well circumscribed tumours with a multinodular
pattern, haemorrhagic and necrotic.
Microcopically, exhibits an alveolar structure, the
center of the alveolar space being formed by
detachment of necrotic cells, and with surronding
capillaries (there is a more solid pattern in children).
Cells are large, with abundant cytoplasm. Mitoses are
rare.
Secretory process with the formation of cytoplasmic
membrane-bound crystals (PAS+, diastase resistant)
can often be seen with electron microscopy, a feature of
great diagnostic value (they are pathognomic). These
granules contain monocarboxylate transporter 1
(MCT1) - CD147 complexes.
Immunochemistry: in general, alveolar soft part
sarcomas are negative for neuroendocrin and epithelial
markers, and often positive for vimentin, musclespecific actin, and desmin. The strong nuclear staining
of an anti C-term TFE3 can be used for diagnosis
(although cytogenetics and/or molecular genetics are
the most relevant tools for diagnosis).
To be noted is that a subset of renal cell carcinomas,
the primary renal ASPSCR1-TFE3 tumour, share some
morphological features with the alveolar soft part
sarcoma (it may be a differential diagnosis); they also
share a common genetic substratum.
Other
names:
Malignant
nonchromaffin
paraganglioma; Malignant organoid granular cell
myoblastoma
Clinics and pathology
Embryonic origin
The histogenesis of this tumour is still unknown,
despite immunohistochemistry studies and electron
microscopy. It may have a myogenic origin, and might
be a variant of rhabdomyosarcoma.
Epidemiology
Rare tumour: represents less than 1% of soft tissues
sarcomas of adults and 1-2% of soft tissues sarcomas in
children.
Occurs most often in the young adult, less frequently in
children.
Median age is 20 years in female patients, and 30 years
in male patients. More frequently, patients are females
(ratio M/F is 2/3).
Clinics
Involve the muscles and soft tissues, in particular those
of the lower extremities (buttocks, thighs and legs).
This represents more than half cases in the adults. It
may also arise in the upper extremities, in the head and
neck regions, especially in the child, but it can also
have extra muscular localizations, such as the female
genital tract, the trunk, the mediastinum, or the
retroperitoneum.
Metastases are frequent. They occur mainly in lungs,
bones, and brain.
Symptoms at diagnosis may be pain and/or swelling.
Diagnosis is often retarded.
Atlas Genet Cytogenet Oncol Haematol. 2008;12(3)
Treatment
Primary tumours: large surgical excision (a complete
resection is of great importance) and radiation.
Metastases: chemotherapy, with or without radiation or
surgery, depending on the number of metastases.
Evolution
Slow growing tumour, but highly angiogenic, which
favours metastases dissemination.
250
Soft tissue tumors: Alveolar soft part sarcoma
Huret JL
Metastases appear in more than half of the patients who
presented without metastases at diagnosis (up to 70% in
one study); however, there is a long disease-free
interval before appearence of metastases (median 6
years) in these patients.
Protein
Transcription factor; member of the basic helix-loophelix family (b-HLH) of transcription factors primarily
found to bind to the immunoglobulin enchancer muE3
motif.
Prognosis
ASPSCR1
Relatively indolent clinical course. In one study,
overall survival of adult patients without metastases
reached 87% at 5 years, but that of adult patients with
metastases at diagnosis was only 20% at 5 years, with a
median survival of 40 mths. Pediatric cases had a better
prognosis, with a 5 years survival of 80% for all cases
included, reaching 91% in cases without metastases.
Median survival in patients without metastases at
diagnosis was noted above 10 years in a large -but old
(period 1923-1986)- study, and it may be expected that
progress has been made. Due to the rarity of the disease
and its long course, survival data are outdated.
Location: 17q25
Protein
Contains an UBX domain, ASPSCR1 binds SLC2A4
(solute carrier family 2 (facilitated glucose transporter),
member 4, also called GLUT4) endocytosed from the
plasma membrane into vesicles. SLC2A4 is retained in
the cell by ASPSCR1 in the absence of insulin. Insulin
stimulates the release of retained SLC2A4 to
exocytosis, allowing the rapid mobilization of glucose
transporters to the cell surface.
Cytogenetics
Result of the chromosomal
anomaly
Cytogenetics morphological
Hybride Gene
t(X;17)(p11;q25) is found in all alveolar soft part
sarcomas so far studied, but also in primary renal
ASPSCR1-TFE3 tumours. In the case of alveolar soft
part sarcoma, the chromosome rearrangement is found
in an unbalanced form, as a der(17)t(X;17)(p11;q25), in
80% of cases;
the unbalanced form implicates:
1- the formation of a hybrid gene at the breakpoint, but
also,
2- gain in Xp11-pter sequences, and loss of
heterozygocity in
17q25-qter,
with
possible
implications, although no clinical (including
prognostic) nor pathological differences have so far
been noted between balanced and unbalanced cases...
but, again, the disease is rare, and cases with
cytogenetic studies even rarer (about 25 cases).
Note: the t(X;17)(p11;q25) in primary renal
ASPSCR1-TFE3 tumours is balanced in all known
cases.
Description
5' ASPSCR1 - 3' TFE3; the reciprocal 5' TFE3 - 3'
ASPSCR1 is most often absent. ASPSCR1 is fused in
frame either to TFE3 exon 3 or to exon 4 (type 1 and
type 2 fusions respectively).
Fusion protein
Description
234 NH2 term amino acids from ASPSCR1, fused to
the 280 or 315 C term amino acids from TFE3,
including the activation domain, the helix-loop-helix,
and the leucine zipper from TFE3.
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This article should be referenced as such:
Huret JL. Soft tissue tumors: Alveolar soft part sarcoma. Atlas
Genet Cytogenet Oncol Haematol.2008;12(3):250-252.
van Ruth S, van Coevorden F, Peterse JL, Kroon BB. Alveolar
soft part sarcoma. a report of 15 cases. Eur J Cancer
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