Apa maksud tumor suppressor gene lipoma

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Disease definition

Well-differentiated liposarcoma (WDLS), the most common type of liposarcoma (LS; see this term), is a slow growing, painless tumor usually located in the retroperitoneum or the limbs. It is composed of proliferating mature adipocytes.

Classification level: Subtype of disorder

Synonym(s):
- ALT
- Atypical lipoma
- Atypical lipomatous tumor
- WDLS
Prevalence: Unknown
Inheritance: Not applicable
Age of onset: Adult
ICD-10: C49.9
OMIM: -
UMLS: C1370889
MeSH: -
GARD: -
MedDRA: -

The incidence is approximately 1/200,000 per year and it accounts for 30-50% of all liposarcomas.

WDLS occurs in adulthood, most often between the ages of 50 to 60 years, and it is seen more frequently in males. A slow growing, painless mass presents most often in the retroperitoneum or the limbs but occasionally in the spermatic cord and the mediastinum. The mass can be soft and fleshy or firm. Symptoms of urinary or bowel obstruction may be experienced if the tumor is large and compresses these organs.

WDLS is characterized by extensive chromosomal aberrations, which in 90% of cases include amplification of the chromosomal region 12q13-15. This amplification causes the overexpression of three genes that promote cell growth: MDM2 (that blocks p53 tumor suppressor function), CDK4 (involved in cell cycle regulation) and HMGA2.

When a mass is detected, computed tomography (CT) or magnetic resonance imaging (MRI) is performed. Chest and abdominal lesions do not require pretreatment biopsy unless resection is likely to be incomplete or highly morbid. Extremity lesions are generally removed completely without prior biopsy. WDLS resembles large, cohesive groups of adipocytes of varying cell size. Fluorescent in situ hybridization (FISH) and immunohistochemistry show the overexpression of MDM2 and CDK4. The four morphological subtypes of WDLS are adipocytic (lipoma-like), sclerosing, inflammatory and spindle cell.

Differential diagnoses include benign lipomas and other types of sarcomas, inflammatory myofibroblastic tumor and Castleman disease (see these terms).

Surgery is the mainstay of treatment for WDLS. If tumor excision is complete, then no further therapy is recommended, although the patient should be monitored for recurrence. Complete excision is often curative if the tumor is located in an extremity. Lesions in the retroperitoneum and inguinal areas are more difficult to treat and are more likely to recur locally and transform into dedifferentiated liposarcoma (DDLS; see this term). If the tumor is unresectable (or if the excision was incomplete), systemic therapies and radiation can be proposed but have shown little efficacy. Clinical trials are ongoing to assess new therapies in patients with advanced unresectable disease (CDK4 and MDM2 inhibitor trials).

WDLS prognosis depends on the tumor location. Extremity WDLS usually has a good prognosis after the tumor has been removed, with low rates of recurrence and essentially no mortality. Retroperitoneal WDLS, however, has a 5-year probability of freedom from recurrence of only 54% and a 5-year disease-specific survival of 80 to 90%.

Expert reviewer(s): Dr Samuel SINGER - Last update: January 2013

Detailed information

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Page 2

Variable		ALT	Lipoma	Odds Ratio95% CI)a	P-value	Sensitivityb	Specificityb	PPVb	NPVb
Region	Lower limb/trunk	45	48	1.32 (1.12–1.54)	0.002	0.957	0.273	0.682	0.900
	Upper limb	2	18
Tumor size	> 130.0 mm	37	19	2.74 (1.82–4.11)	< 0.001	0.787	0.712	0.661	0.824
	≤ 130.0 mm	10	47
Septation	Thick (> 2 mm)	40	9	6.24 (3.36–11.59)	< 0.001	0.851	0.864	0.816	0.891
	Absent/thin (< 2 mm)	7	57
Contrast enhancement	Presence	42	20	2.95 (2.01–4.31)	< 0.001	0.894	0.697	0.677	0.902
Absence	5	46
Nodules	Presence	9	0	0.81 (0.70–0.92)	0.001	0.191	1.000	1.000	0.635
	Absence	38	66

aData given as odds ratio (95% confidence interval). bSensitivity, specificity, PPV and NPV given for the identification of ALT versus lipoma, respectively. PPV, positive predictive value; NPV, negative predictive value