Delayed diagnosis of an Ewing sarcoma of the knee during pregnancy
A 37-year-old woman, gravida 6 para 3 abortion 2, was admitted to our maternity ward at a gestational age of 41 weeks for induction of labour. She had received antenatal care from an obstetrician in a University hospital clinic and from a midwife at home. She presented to the emergency department of the university hospital with an intense pain in the right knee and lower leg since 4 months.. A deep vein thrombosis, one of the most current pregnancy-related problems, was excluded by a negative Doppler examination and the patient was sent home. Over the last two weeks an increased loss of function occurred inducing difficulties with standing up and walking. She was referred again by her midwife to the same emergency ward but no further examinations were performed and she was sent home without a diagnosis. At admission to our maternity ward clinical examination of the painful area revealed a swollen knee, painful and warm at palpation. Because her delivery was imminent, only a blood analysis and an ultrasound of the knee and lower leg were performed. The ultrasound showed the presence of a necrotic/inflammatory collection at the superior part of the tibia with an irregular aspect of the periost and external cortical layer. Underlying bone pathology was therefore suspected, possibly related to osteomyelitis of the superior part of the tibia. Laboratory investigation showed signs of infection (CRP 44, white blood count 11300 cells/µL, neutrophilia 8803 cells/µL). Given the suspicion of osteomyelitis, an antibiotic treatment (Floxacilline) was started. Labour and delivery were uneventful and she gave birth to a healthy boy.\nThe next day an additional work up was performed. Clinical head-to-toe examination showed the already described findings regarding the right knee and leg, but additionally the astonishing presence of several lumps in both breasts, the largest being a mass of 4 centimetres in the right breast. Blood tests showed normal kidney function tests, slightly elevated hepatic tests, a normal CA 15.3 (14 IU/ml) but an elevated CA 125 (121 IU/ml). Further radiologic examinations, including X-Rays and an MRI of the knee and leg confirmed the presence of a massive destruction of the proximal part of the tibia seen as an infiltrating lesion of the metaphysis of the tibia with signs of resorption (). RX thorax revealed the presence of lung metastases in both pulmonary fields. Computer Tomography (CT) of thorax and abdomen confirmed the presence of lung metastases, but showed also peritoneal and multiple bone metastases. Mammography and ultrasound of both breasts not only confirmed the presence of two large lumps, but in addition it showed 12 neoplastic lesions in the right and 7 neoplastic lesions in the left breast. Finally, a whole bone scan and positron emission tomography (PET) scan confirmed all sites of neoplastic lesions ().\nIn view of these findings the differential diagnosis of a metastatic breast cancer or metastases of a primary bone tumour was withheld. The microscopic examination of a biopsy of one of the large breast nodules revealed the presence of a small blue round cell tumour, suggesting a primary bone tumour, which was confirmed by immunohistochemistry (CD99 expression) (). Additional FISH analysis revealed rearrangement of the EWS gene, and not of the WT1 gene, indicating the diagnosis of Ewing sarcoma (). Four days postpartum, chemotherapy was initiated. A 3-week alternating treatment of vincristine/adriamycin/cyclophosphamide (VAC) and etoposide/iphosphamide (IFO-VP16) was given, which was well tolerated apart from slight anaemia and constipation. After one cycle of chemotherapy the patient reported less pain and a reduction of the volume, redness and inflammation around the knee was observed.\nAfter five cycles of chemotherapy, subjective and objective response was excellent and the patient was able to stand up again and walk small distances after a long period of suffering from an intense pain and inability to walk. After the total of nine cycles, the PET-scan showed complete response ().\nSince the last studies on Ewing sarcoma showed that additional 5 cycles of chemotherapy increase the durability of the remission, her treatment was extended with 5 extra cycles. Unfortunately, three months after the total of 14 cycles, a solitary brain metastasis was discovered. While writing this case report she just completed one month of stereotactic radiotherapy with complete response.