A rare case of clear cell sarcoma of the foot with a cascade of pathological misdiagnosis-the importance of expert sarcoma pathology

Abstract

Sarcoma pathology discrepancy is well known owing to the extremely heterogenous and rare nature of this tumour. Through this case, we want to highlight the difficulty that a patient has to undergo in a case of misdiagnosis. A 20-year-old male presented with swelling in the right foot for 4 months, which was initially diagnosed as alveolar rhabdomyosarcoma, subsequently as synovial sarcoma and finally as Ewing's sarcoma (based upon positive Ewing Sarcoma Breakpoint Region 1 (EWSR1) by fluorescence in situ hybridisation and he underwent neoadjuvant chemotherapy and surgical excision with grafting before he presented to our institute, where the pathologists reviewed the biopsy slides, which were positive for HMB45 and negative for Melan-A suggestive of clear cell sarcoma. The next-generation sequencing suggested EWSR1-ATF1 fusion, which again reinforced the diagnosis. This case throws light on the importance of expert pathology and interpreting molecular results in the right context.

Keywords: EWSR1; clear cell sarcoma; diagnostic discrepancy; misdiagnosis; sarcoma.

Figure 1.. Photograph of the swelling on the plantar aspect of right foot, taken before chemotherapy, 3 months after the onset.

Figure 2.. MRI image of right foot (T1W post contrast). Lobulated soft tissue mass with poorly defined margins in the lateral plantar aspect of right foot measuring approx. 4.5 × 7.5 × 3.8 cm (CC × AP × TR). Non- enhancing regions likely representing cystic/necrotic changes. Insinuating between the 4th and 5th metatarsals and involving the intrinsic muscles and abutting the lateral aspect of flexor digitorum longus/brevis muscles and tendons. Also involving the subcutaneous tissue on the plantar aspect of the foot. No definite evidence of signal abnormality or destructive changes in the bones.

Figure 3.. Cell showing two green-orange (fusion) signals indicating negative for SYT gene rearrangement. Test method: FISH. Probe description: Vysis LSI EWSR1 (22q12) Break Apart Rearrangement Probe (CE).

Figure 4.. Cell showing one green-orange (yellow) fusion, one orange signal and one green signal, indicating positive for rearrangement of the EWSR1 gene. Test method: FISH. Probe description: Vysis LSI EWSR1 (22q12) Break Apart Rearrangement Probe (CE).

Figure 5.. Histopathology photomicrograph of the tumour showing oval to spindle shaped cells arranged in nests as well as syncytial pattern. The tumour cells showed moderate pleomorphism with vesicular chromatin and prominent nucleoli with moderate to abundant cytoplasm with epithelioid morphology at places. (H&E 200×).

Figure 6.. Immunohistochemistry for HMB45 showing diffuse cytoplasmic positivity in the tumour cells.