A 10 year old girl presents with a tibial mass. Histopathological examination reveals a small round cell tumor. Which of the following molecular findings is most likely to be present? (AIPG 2011)
|A||11, 22 translocati|
11, 22 translocation
The t(11;22)(q24;q12) translocation is present in over 90% of Ewing’s sarcoma cases. The resulting EWS-FLI1 fusion gene has been demonstrated to have oncogenic potential.Other associated genetic abnormalities are; t(21;22) t(17;22) t(7;22) Trisomy 8 Trisomy 12 Del 1p36
Ewing’s Sarcoma and PNET
a. Ewing’s sarcoma is part of a family of peripheral neuroectodermal tumors (PNET) that share a common cytogenetic translocation of chromosomes 11 and 22 t (11 : 22), differing only in their degree of neural differentiation.
b. Ewing’s sarcoma is poorly differentiated whereas PNET exhibits definite neural differentiation.
Ewing’s sarcoma is very primitive tumor and lacks differentiation along any specific mesenchymal lineage; whereas PNET has signs of neural differentiation (S-100, Neuron specific enolase staining, rosettes, and neural elements by electron microscopy).
Both may involve soft tissue or bone and their treatment approches are same.
a. Arising in medullary cavity usually invade the cortex, & periosteum producing a soft tissue mass.
i. Composed of sheets of uniform, small round cells (that are slightly larger than lymphocytes), with pale clear appearing cytoplasm due to presence of glycogen.
ii. Cytoplasm is PAS positive and diastase digestible. Presence of Homer- wright rosettes (tumor cells are arranged in circle around a central fibrillary space) and pseudo rosette is indicative of neural differentiation (i.e. PNET)
iii. Both Ewings Sarcoma and PNET cells express the MIC 2 gene in very high amount, which distinguish them from other round cell tumors.
Most definitive test for Ewing’s SA / PNET is demonstration of chromosomal translocation by karyotyping or reverse transcriptase- polymerase chain reaction (RT - PCR) detection of t (11 : 22). 80- 95% patients have a translocation mostly t (11: 22)> t (21 :22) and rarely t (7: 22), trisomy 8.
a. Mostly in males between 10-20 years of age (5-30 yrs range)
May appear in any bone or occasionally soft tissue but most present in diaphysis of femur. Systemic symptoms such as fever, generalized weakness, weight loss, and lab anomalies as anemia, leukocytosis, ↑LDH & raised ESR are hallmark of fulminating course, advanced disease or metastasis.
b. Poor prognostic factors are — large tumor volume, size >8cm, elevated LDH, age > 12 years and presence of metastasis.
c. 50% of all metastases occurs to lung& 25% to bone & bone marrow
Mottled rarefaction of spongiosa with permeation of overlying cortex, reflecting rapid bone destruction is the principal finding
Lamellated (layered) periosteal new bone formation - onion- peel appearance
Soft tissue masse, indicating neoplasm has perforated cortex
Mostly diaphyseal but may extend into metaphysis.
a. Highly radiosensitive (melts on RT)but overall survival is not much enhanced
b. Chemotherapy is much more effective & include vincristine, actinomycin D, cyclophosphamide, bleomycin, adriamycin, ifosfamide & etoposide.
c. Best results are achieved by
Preoperative chemotherapy; then wide excision (or amputation) if tumor is in favourable site and further chemotherapy for 1 years.
d. Radiotherapy followed by local excision if it is in less accessible site & then further chemotherapy for 1 year.