4 year old high ESR, leucocytosis, tibial lesion best investigation is (AIIMS May 2009)
a. The clinical presentation given can be there in osteomyelitis or ewings sarcoma as they have same presentation
b. If the question asks about next investigation then MRI would be the answer and if the questions asks about best investigation then we need to obtain biopsy and send the tissue for culture/sensitivity (for osteomyelitis)and biopsy(for ewings).
c. Ewing’s sarcoma is highly malignant, undifferentiated peripheral primitive neuro ectodermal tumor (PEN) occurring most commonly diaphysis of femur, fibula or other long bone in 10-20 years old male.
d. It is frequently associated with pain, cortical breech, soft tissue invasion & swelling; and systemic symptoms as fever, weight loss, ↑ESR, anemia.
e. On histopathology round neural cell contain glycogen and reticulin; are PAS positive and diastase digestible and mostly possess t (11;22) translocation (80 - 95%). X -ray reveal onion peel appearance.
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, Ewing’s sarcoma is poorly differentiated whereas PNET exhibits definite neural differentiation.
b. 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).
c. Both may involve soft tissue and or bone and their treatment approaches are same.
a. Arising in medullary cavity usually invade the cortex, &periosteum producing a soft tissue mass.
b. Composed of sheets of uniform, small round cells (that are slightly larger than lymphocytes), with pale clear appearing cytoplasm due to presence of glycogen.
c. Cytoplasm is PAS positive and diastase digestiable. Presence of Homer- wright rosetles (tumor cells are arranged in circle around a central fibrillary space) and pseudo resette is indicative of neural differentiation (i.e. PNET)
d. Both Ewings and PNET cells express the MIC 2 gene in very high amount, which distinguish them from other round cell tumors.
e. Hence monoclonal antibodies (HB-71 and 12 E7) to a cell surface glycoprotein (p30 /32 MIC 2) encoded by MIC 2 gene is a useful screening measure.
f. Most definitive test for Ewing’s / 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)
a. Mostly in males between 10-20 years of age (5-30 yrs range)
b. May appear in any bone or occasionally soft tissue but most present in diaphysis of femur.
c. Systemic symptoms such as fever, generalized weakness, weight loss, anemia, leukocytosis, ↑LDH & raised ESR are hallmark of fulminating course, advanced disease or metastasis.
d. 50% of all metastases occurs to lung & 25% to bone & bone marrow
a. Mottled rarefaction of spongiosa with permeation of overlying cortex, reflecting rapid bone destruction is the principal finding
b. Laminated (layered) periosteal new bone formation onion- peel appearance
c. Soft tissue masse, indicating neoplasm has perforated cortex
d. 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, cytoxan, adriamycin, ifosamide&etoposide
c. Best results are achieved by
i. Preoperative chemotherapy; then wide excision (or amputation) if tumor is in favourable site and further chemotherapy for 1 years.
ii. Radiotherapy followed by local excision if it is in less accessible site & then further chemotherapy for 1 year.