Skeletal Radiol DOI 10.1007/s00256-013-1779-0
CASE REPORT
Atypical growth on MRI in a case of Ewing’s sarcoma despite lower SUV on PET Zachary Sanford & Stanford Israelsen & Rajesh Sehgal & Felix H. Cheung
Received: 3 July 2013 / Revised: 23 October 2013 / Accepted: 6 November 2013 # ISS 2013
Abstract Ewing’s sarcoma is a rare primary bone malignancy of small round blue cells. Treatment typically consists of neoadjuvant chemotherapy, surgical resection, and adjuvant chemotherapy. The disease response to chemotherapy can be followed with fluorodeoxyglucose (FDG) positron emission tomography (PET), which measures the metabolic activity of the tumor, and by magnetic resonance imaging (MRI), which measures tumor size. We present a unique case in which the tumor grew in size following neoadjuvant chemotherapy but decreased in metabolic activity, making it difficult to judge efficacy of the chemotherapy. An atypical response to Z. Sanford Joan C. Edwards School of Medicine (JCESOM), Marshall University, Huntington, WV 25701, USA Z. Sanford (*) : S. Israelsen : F. H. Cheung Department of Orthopaedic Surgery, Joan C. Edwards School of Medicine JCESOM, Marshall University, 1600 Medical Center Drive, Suite G500, Huntington, WV 25701, USA e-mail: [email protected] S. Israelsen e-mail: [email protected] F. H. Cheung e-mail: [email protected] R. Sehgal Department of Medicine, Division of Oncology, JCESOM, Marshall University, Huntington, WV 25701, USA e-mail: [email protected] R. Sehgal Joan C. Edwards School of Medicine, Edwards Comprehensive Cancer Center, 1401 Hal Greer Blvd, Huntington, WV 25701, USA F. H. Cheung Department of Orthopaedic Surgery, Joan C. Edwards School of Medicine, Edwards Comprehensive Cancer Center, Marshall University, 1600 Medical Center Drive Suite G500, Huntington, WV 25701, USA
chemotherapy in this case caused tumor growth due to a fibrotic reaction while viable tumor cells were eradicated. This case highlights the ability of FDG-PET scan to identify the uncommon situation in which a tumor that increased in size may have had a favorable response to chemotherapy. This possibility should be considered in similar cases in which FDG-PET scan shows diminishing metabolic activity despite tumor growth. Keywords Ewing’s sarcoma . FDG-PET . Tumor . Growth . Fibrosis
Introduction Ewing’s sarcoma is a rare primary bone malignancy of small round blue cells preferentially affecting the femur, humerus, pelvis, ribs, and clavicle. The typical patient is a male in his second decade of life [1–3]. Most often, this disease is a result of a chromosomal translocation, placing the Ewing’s Sarcoma Breakpoint Region 1 (EWSR1) of chromosome 22 in direct contact with the Friend Leukemia Integration 1 transcription factor (FLI1) of chromosome 11 [4–6]. The resulting master regulator gene results in unregulated cellular growth at the epiphyseal plate [7]. Neoplastic growth is responsible for localized swelling, tenderness, and bone pain experienced by patients, although other more generalized symptoms such as fever are also experienced. Ewing’s sarcoma tests positive for overexpression of CD99, an O ‐glycosylated transmembrane protein of leukocyte and, specifically, thymocyte cell membranes that are pathognomonic and often detected by antibody assay in diagnosis of the disease by immunohistochemistry (IHC) techniques [8, 9]. Typical radiographic features include a layered “onion skinning”-type periosteal reaction with a radiolucent permeative lytic lesion in the
Skeletal Radiol
Haversian canal. Lesions usually present in the diaphysis of long bone, in which a wide zone of transition can often be visualized on plain film. Cortex can in many instances appear undamaged in early stages, however on expansion can present with radiolucencies [10–14]. Treatment for Ewing’s sarcoma often involves neoadjuvant chemotherapy. Response to this chemotherapy is often seen as a decrease in the size of the tumor volume as evident on MRI [15]. Positron emission tomography (PET) scan of fluorodeoxyglucose (FDG) is a minimally invasive procedure that reliably assesses disease progression as well as response to chemotherapy [16–20]. This case report involves a unique case of Ewing’s sarcoma in which tumor volume increased during neoadjuvant chemotherapy but PET scan activity decreased. Surgical pathology later revealed no viable tumor in the resected specimen, demonstrating good response to chemotherapy. This case illustrates the significance of PET scan in confirming response to chemotherapy in Ewing’s sarcoma despite worsening appearances on MRI.
A 35-year-old female initially attributed night pain, swelling, and painful ambulation to a hyperextension injury to her right knee; however, after a week of continued symptoms, she presented to her local emergency department for evaluation. Radiographs revealed a large joint effusion in addition to mild patchy sclerosis of the proximal tibia. Follow-up examination by her primary care physician documented a knee effusion with physical exam features typical of a meniscus tear although repeat X-ray showed a mixed lytic and blastic lesion with periosteal reaction along the posterolateral proximal tibial metaphysis. Magnetic resonance imaging (MRI) without contrast later revealed a lesion consistent with primary bone sarcoma, having a large soft tissue component on the lateral and posterior aspect of the proximal tibia. Computed tomography (CT) scan and Xray radiography confirmed involvement of the distal femur and patella with osteolytic lesions and signs of perforation of the articular surface (Fig. 1). MRI with contrast showed a mass
PRE-TREATMENT
POST-TREATMENT
a
b
c
d
X-ray (Coronal) X-ray (Sagittal)
Fig. 1 Tumor assessment by Xray in comparable locations before and after chemotherapy. a Pre-treatment X-ray radiography (coronal); b Post-treatment X-ray radiography (coronal); c Pretreatment X-ray radiography (sagittal); d Post-treatment X-ray radiography (sagittal)
Case report
Skeletal Radiol
measuring 8.2 cm AP × 9.8 cm ML × 8.9 cm proximal to distal (tumor volume=536 ml) with some central areas of necrosis and soft tissue edema. The mass also surrounded the tibial nerve and posterior tibial vein (Fig. 2). Tumor metabolic activity as measured by FDG-PET utilization was observed at a maximum SUV of 16 with no evidence of distant metastatic disease (Fig. 3). Percutaneous
POST-TREATMENT
PRE-TREATMENT
b
c
d
e
f
g
h
T1 MRI (Coronal)
a
T1 MRI (Axial) T1 MRI + Contrast (Axial) T2 MRI (Axial)
Fig. 2 Pre-therapy and posttherapy MRI visualization of Ewing’s sarcoma in the right lower limb from comparable locations. MRI with contrast shows a mass measuring 8.2 cm AP × 9.8 cm ML × 8.9 cm proximal to distal (tumor volume=536 ml) with some central areas of necrosis and soft tissue edema. Post-treatment MRI with contrast shows distal extent of the tumor increasing approximately 3 cm from the previous measurement (tumor volume=717 ml). The final tumor size at time of amputation (not illustrated) measured 8.3 cm AP × 10.0 cm ML × 13.0 cm proximal to distal (tumor volume=809 ml). a Pre-treatment MRI (T1 signal, coronal); b Posttreatment MRI (T1 signal, coronal); c Pre-treatment MRI (T1 signal, axial); d Posttreatment MRI (T1 signal, axial). Note the growth of mass after chemotherapy; e Pre-treatment MRI with contrast (T1 signal, axial); f Post-treatment MRI with contrast (T1 signal, axial); g Pretreatment MRI (T2 signal, axial); h Post-treatment MRI (T2 signal, axial)
needle biopsy under general anesthetic with a 14-gauge TruCut needle revealed ample though necrotic small round blue cells in a monotonous fashion that did not appear osteogenic. Immunohistochemistry (IHC) was performed revealing tumor cells strongly positive for CD99 while negative for CD56 and leukocyte common antigen, consistent with Ewing’s sarcoma (Fig. 4). Fluorescence in situ hybridization (FISH) fusion
Skeletal Radiol Fig. 3 Tumor assessment by FDG-PET in comparable locations before and after chemotherapy. a Pre-treatment FDG-PET (axial); b Posttreatment FDG-PET (axial). Note the decrease in SUV intensity as measured by decrease in color intensity
a
b
rearrangement of interphase nuclei for Ewing’s Sarcoma Breakpoint Region 1 (EWSR1) gene rearrangement was positive. The patient underwent four, three-week cycles of neoadjuvant chemotherapy consisting of 2 mg of vincristine per square meter of body-surface area with a maximal dose of 2 mg per day, bolus infusion of doxorubicin at 75 mg per square meter per day, 1,200 mg of cyclophosphamide per square meter per day with mesna, 1,800 mg of ifosfamide per square meter per day also given with mesna, and 100 mg of etoposide per square meter per day. When a total doxorubicin dose of 375 mg per square meter was reached, dactinomycin at 1.25 mg per square meter per dose was substituted. The addition of ifosfamide and etoposide to traditional vincristine, doxorubicin, cyclophosphamide, and actinomycin D (VDCA) therapy was based on Intergroup Ewing’s Sarcoma Study‐III (IESS‐III), which was associated with significantly better 5-year relapse-free survival compared to VDCA alone [21]. The addition of mesna was intended to prevent possible hemorrhagic cystitis caused by cyclophosphamide toxicity. After four cycles of chemotherapy, the peak SUV value decreased from 16 to 5 as measured by FDG-PET scan and the
tumor no longer involved the femur and patella (Fig. 3), although the lesion showed a more obvious sunburst periosteal reaction. No distant sites of disease were found. Moderate to severe pain was present in the knee and radiated up and down the affected leg but was steadily improving. However, radiographic examination using X-ray and MRI without contrast during the fifth cycle of chemotherapy displayed aggressive destruction of the proximal tibia both anteriorly and posteriorly with the distal extent of the tumor increasing approximately 3 cm from the previous measurement (Figs. 1 and 2). Considerable aggressive progression of the disease was most notable in the radial extension through cortex and soft tissue in contrast to usual lamellar progression associated with Ewing’s sarcoma. Due to the large size of the mass and its proximity to the neurovascular bundle, the sarcoma team opted to continue chemotherapy for an additional 2 months in the hopes of reducing the size of the mass for possible limb salvage. MRI without contrast after 2 months showed no increase in the size. As the mass still involved the neurovascular bundle, it was deemed unresectable, and an above-the-knee amputation was performed. At the time of amputation, the leg was examined to reveal no areas of gross tumor and that the joint capsule was intact.
Fig. 4 Histological cross section of tissue samples pre (a, b) and post (c) chemotherapeutic treatment. a H&E preparation of tissue sample taken before initiation of chemotherapy, 100×. Original tumor shows round small blue cell tumor with necrosis represented as darkly staining purple in the figure. Molecular results proved positive for rearrangement of EWSR1 gene. b CD99 preparation of tissue sample taken before
initiation of chemotherapy, 100×. Tissue is positive with cytoplasmic and membranous staining patterns as indicated by intensity of stain uptake. c H&E preparation of tissue sample post-amputation, 100×. Of note is the replacement of viable tumor with fibrotic scar tissue, seen above as fibers arranged in parallel formations
Skeletal Radiol Table 1 Diagnostic parameters used for response assessment Morphological imaging
FDG-PET
SK
Vol1
Vol2
ΔVol
ST
CE
T2
SUV1
SUV2
ΔSUV
VI
Grade
R/NR
536
809
34 %
5
5
+
16
5
−69 %
R
III
R
Vol1 volume of primary tumor pre-treatment (ml); Vol2 volume of primary tumor post-treatment at time of amputation (ml), ΔVol change from Vol1 to Vol2 (%), T2 change of signal on T2-weighted images (“+” change, “−” no change); CE contrast enhancement score (Table 2), ST soft tissue component score (Table 2); SUV1 maximum standardized uptake value of primary tumor pre-treatment; SUV2 SUVmax of primary tumor post-treatment, ΔSUV reduction from SUV1 to SUV2 (%); VI visual interpretation, SK histological regression according to Salzer–Kuntschik [23]; R response; NR nonresponse. Methods based on Denecke et al. [15].
Pathology revealed the tumor to be composed of small round blue cells in variable fibrotic to necrotic background with coagulative tumor necrosis consisting of 5 % of tumor mass while over 90 % of the mass consisted of dense fibrosis that was suspected to be replacing previously viable tumor. The final tumor size at time of amputation measured 8.3 cm AP × 10.0 cm ML × 13.0 cm proximal to distal. Margins were negative. Baseline imagery confirmed no residual/early recurrent disease 2 months postoperatively using PET CT and MRI. Figures 1, 2, and 3 summarize X-ray radiography, MRI, and FDG-PET analyses, respectively, of the mass both before and after chemotherapeutic treatment while Fig. 4 illustrates histopathologic findings as measured by hematoxylin and eosin (H&E) and CD99. Table 1 includes a summary of the data pertaining to this case of Ewing’s sarcoma. Volume was calculated by cylindrical approximation of the mass in accordance with the EURO E.W.I.N.G. protocols for therapy optimization [22]. Soft tissue component, contrast enhancement, and T2 signal intensity were reported based on the methods outlined in Denecke et al. [15] and are further elaborated in Table 2. Metabolic activity of the mass was quantified using SUV corrected for body weight and injected FDG activity. Response assessment was assessed based on FDG-PET measurements before (SUV1) and after (SUV2) chemotherapeutic treatment, percent change in SUV intensity between these two measurements (ΔSUV), and visual interpretation. Histological grade and response were assessed in accordance with methodologies summarized in Salzer–Kuntschik (SK) [23]. Patients with 50 %) Minimal reduction (50 %) Minimal reduction (
CASE REPORT
Atypical growth on MRI in a case of Ewing’s sarcoma despite lower SUV on PET Zachary Sanford & Stanford Israelsen & Rajesh Sehgal & Felix H. Cheung
Received: 3 July 2013 / Revised: 23 October 2013 / Accepted: 6 November 2013 # ISS 2013
Abstract Ewing’s sarcoma is a rare primary bone malignancy of small round blue cells. Treatment typically consists of neoadjuvant chemotherapy, surgical resection, and adjuvant chemotherapy. The disease response to chemotherapy can be followed with fluorodeoxyglucose (FDG) positron emission tomography (PET), which measures the metabolic activity of the tumor, and by magnetic resonance imaging (MRI), which measures tumor size. We present a unique case in which the tumor grew in size following neoadjuvant chemotherapy but decreased in metabolic activity, making it difficult to judge efficacy of the chemotherapy. An atypical response to Z. Sanford Joan C. Edwards School of Medicine (JCESOM), Marshall University, Huntington, WV 25701, USA Z. Sanford (*) : S. Israelsen : F. H. Cheung Department of Orthopaedic Surgery, Joan C. Edwards School of Medicine JCESOM, Marshall University, 1600 Medical Center Drive, Suite G500, Huntington, WV 25701, USA e-mail: [email protected] S. Israelsen e-mail: [email protected] F. H. Cheung e-mail: [email protected] R. Sehgal Department of Medicine, Division of Oncology, JCESOM, Marshall University, Huntington, WV 25701, USA e-mail: [email protected] R. Sehgal Joan C. Edwards School of Medicine, Edwards Comprehensive Cancer Center, 1401 Hal Greer Blvd, Huntington, WV 25701, USA F. H. Cheung Department of Orthopaedic Surgery, Joan C. Edwards School of Medicine, Edwards Comprehensive Cancer Center, Marshall University, 1600 Medical Center Drive Suite G500, Huntington, WV 25701, USA
chemotherapy in this case caused tumor growth due to a fibrotic reaction while viable tumor cells were eradicated. This case highlights the ability of FDG-PET scan to identify the uncommon situation in which a tumor that increased in size may have had a favorable response to chemotherapy. This possibility should be considered in similar cases in which FDG-PET scan shows diminishing metabolic activity despite tumor growth. Keywords Ewing’s sarcoma . FDG-PET . Tumor . Growth . Fibrosis
Introduction Ewing’s sarcoma is a rare primary bone malignancy of small round blue cells preferentially affecting the femur, humerus, pelvis, ribs, and clavicle. The typical patient is a male in his second decade of life [1–3]. Most often, this disease is a result of a chromosomal translocation, placing the Ewing’s Sarcoma Breakpoint Region 1 (EWSR1) of chromosome 22 in direct contact with the Friend Leukemia Integration 1 transcription factor (FLI1) of chromosome 11 [4–6]. The resulting master regulator gene results in unregulated cellular growth at the epiphyseal plate [7]. Neoplastic growth is responsible for localized swelling, tenderness, and bone pain experienced by patients, although other more generalized symptoms such as fever are also experienced. Ewing’s sarcoma tests positive for overexpression of CD99, an O ‐glycosylated transmembrane protein of leukocyte and, specifically, thymocyte cell membranes that are pathognomonic and often detected by antibody assay in diagnosis of the disease by immunohistochemistry (IHC) techniques [8, 9]. Typical radiographic features include a layered “onion skinning”-type periosteal reaction with a radiolucent permeative lytic lesion in the
Skeletal Radiol
Haversian canal. Lesions usually present in the diaphysis of long bone, in which a wide zone of transition can often be visualized on plain film. Cortex can in many instances appear undamaged in early stages, however on expansion can present with radiolucencies [10–14]. Treatment for Ewing’s sarcoma often involves neoadjuvant chemotherapy. Response to this chemotherapy is often seen as a decrease in the size of the tumor volume as evident on MRI [15]. Positron emission tomography (PET) scan of fluorodeoxyglucose (FDG) is a minimally invasive procedure that reliably assesses disease progression as well as response to chemotherapy [16–20]. This case report involves a unique case of Ewing’s sarcoma in which tumor volume increased during neoadjuvant chemotherapy but PET scan activity decreased. Surgical pathology later revealed no viable tumor in the resected specimen, demonstrating good response to chemotherapy. This case illustrates the significance of PET scan in confirming response to chemotherapy in Ewing’s sarcoma despite worsening appearances on MRI.
A 35-year-old female initially attributed night pain, swelling, and painful ambulation to a hyperextension injury to her right knee; however, after a week of continued symptoms, she presented to her local emergency department for evaluation. Radiographs revealed a large joint effusion in addition to mild patchy sclerosis of the proximal tibia. Follow-up examination by her primary care physician documented a knee effusion with physical exam features typical of a meniscus tear although repeat X-ray showed a mixed lytic and blastic lesion with periosteal reaction along the posterolateral proximal tibial metaphysis. Magnetic resonance imaging (MRI) without contrast later revealed a lesion consistent with primary bone sarcoma, having a large soft tissue component on the lateral and posterior aspect of the proximal tibia. Computed tomography (CT) scan and Xray radiography confirmed involvement of the distal femur and patella with osteolytic lesions and signs of perforation of the articular surface (Fig. 1). MRI with contrast showed a mass
PRE-TREATMENT
POST-TREATMENT
a
b
c
d
X-ray (Coronal) X-ray (Sagittal)
Fig. 1 Tumor assessment by Xray in comparable locations before and after chemotherapy. a Pre-treatment X-ray radiography (coronal); b Post-treatment X-ray radiography (coronal); c Pretreatment X-ray radiography (sagittal); d Post-treatment X-ray radiography (sagittal)
Case report
Skeletal Radiol
measuring 8.2 cm AP × 9.8 cm ML × 8.9 cm proximal to distal (tumor volume=536 ml) with some central areas of necrosis and soft tissue edema. The mass also surrounded the tibial nerve and posterior tibial vein (Fig. 2). Tumor metabolic activity as measured by FDG-PET utilization was observed at a maximum SUV of 16 with no evidence of distant metastatic disease (Fig. 3). Percutaneous
POST-TREATMENT
PRE-TREATMENT
b
c
d
e
f
g
h
T1 MRI (Coronal)
a
T1 MRI (Axial) T1 MRI + Contrast (Axial) T2 MRI (Axial)
Fig. 2 Pre-therapy and posttherapy MRI visualization of Ewing’s sarcoma in the right lower limb from comparable locations. MRI with contrast shows a mass measuring 8.2 cm AP × 9.8 cm ML × 8.9 cm proximal to distal (tumor volume=536 ml) with some central areas of necrosis and soft tissue edema. Post-treatment MRI with contrast shows distal extent of the tumor increasing approximately 3 cm from the previous measurement (tumor volume=717 ml). The final tumor size at time of amputation (not illustrated) measured 8.3 cm AP × 10.0 cm ML × 13.0 cm proximal to distal (tumor volume=809 ml). a Pre-treatment MRI (T1 signal, coronal); b Posttreatment MRI (T1 signal, coronal); c Pre-treatment MRI (T1 signal, axial); d Posttreatment MRI (T1 signal, axial). Note the growth of mass after chemotherapy; e Pre-treatment MRI with contrast (T1 signal, axial); f Post-treatment MRI with contrast (T1 signal, axial); g Pretreatment MRI (T2 signal, axial); h Post-treatment MRI (T2 signal, axial)
needle biopsy under general anesthetic with a 14-gauge TruCut needle revealed ample though necrotic small round blue cells in a monotonous fashion that did not appear osteogenic. Immunohistochemistry (IHC) was performed revealing tumor cells strongly positive for CD99 while negative for CD56 and leukocyte common antigen, consistent with Ewing’s sarcoma (Fig. 4). Fluorescence in situ hybridization (FISH) fusion
Skeletal Radiol Fig. 3 Tumor assessment by FDG-PET in comparable locations before and after chemotherapy. a Pre-treatment FDG-PET (axial); b Posttreatment FDG-PET (axial). Note the decrease in SUV intensity as measured by decrease in color intensity
a
b
rearrangement of interphase nuclei for Ewing’s Sarcoma Breakpoint Region 1 (EWSR1) gene rearrangement was positive. The patient underwent four, three-week cycles of neoadjuvant chemotherapy consisting of 2 mg of vincristine per square meter of body-surface area with a maximal dose of 2 mg per day, bolus infusion of doxorubicin at 75 mg per square meter per day, 1,200 mg of cyclophosphamide per square meter per day with mesna, 1,800 mg of ifosfamide per square meter per day also given with mesna, and 100 mg of etoposide per square meter per day. When a total doxorubicin dose of 375 mg per square meter was reached, dactinomycin at 1.25 mg per square meter per dose was substituted. The addition of ifosfamide and etoposide to traditional vincristine, doxorubicin, cyclophosphamide, and actinomycin D (VDCA) therapy was based on Intergroup Ewing’s Sarcoma Study‐III (IESS‐III), which was associated with significantly better 5-year relapse-free survival compared to VDCA alone [21]. The addition of mesna was intended to prevent possible hemorrhagic cystitis caused by cyclophosphamide toxicity. After four cycles of chemotherapy, the peak SUV value decreased from 16 to 5 as measured by FDG-PET scan and the
tumor no longer involved the femur and patella (Fig. 3), although the lesion showed a more obvious sunburst periosteal reaction. No distant sites of disease were found. Moderate to severe pain was present in the knee and radiated up and down the affected leg but was steadily improving. However, radiographic examination using X-ray and MRI without contrast during the fifth cycle of chemotherapy displayed aggressive destruction of the proximal tibia both anteriorly and posteriorly with the distal extent of the tumor increasing approximately 3 cm from the previous measurement (Figs. 1 and 2). Considerable aggressive progression of the disease was most notable in the radial extension through cortex and soft tissue in contrast to usual lamellar progression associated with Ewing’s sarcoma. Due to the large size of the mass and its proximity to the neurovascular bundle, the sarcoma team opted to continue chemotherapy for an additional 2 months in the hopes of reducing the size of the mass for possible limb salvage. MRI without contrast after 2 months showed no increase in the size. As the mass still involved the neurovascular bundle, it was deemed unresectable, and an above-the-knee amputation was performed. At the time of amputation, the leg was examined to reveal no areas of gross tumor and that the joint capsule was intact.
Fig. 4 Histological cross section of tissue samples pre (a, b) and post (c) chemotherapeutic treatment. a H&E preparation of tissue sample taken before initiation of chemotherapy, 100×. Original tumor shows round small blue cell tumor with necrosis represented as darkly staining purple in the figure. Molecular results proved positive for rearrangement of EWSR1 gene. b CD99 preparation of tissue sample taken before
initiation of chemotherapy, 100×. Tissue is positive with cytoplasmic and membranous staining patterns as indicated by intensity of stain uptake. c H&E preparation of tissue sample post-amputation, 100×. Of note is the replacement of viable tumor with fibrotic scar tissue, seen above as fibers arranged in parallel formations
Skeletal Radiol Table 1 Diagnostic parameters used for response assessment Morphological imaging
FDG-PET
SK
Vol1
Vol2
ΔVol
ST
CE
T2
SUV1
SUV2
ΔSUV
VI
Grade
R/NR
536
809
34 %
5
5
+
16
5
−69 %
R
III
R
Vol1 volume of primary tumor pre-treatment (ml); Vol2 volume of primary tumor post-treatment at time of amputation (ml), ΔVol change from Vol1 to Vol2 (%), T2 change of signal on T2-weighted images (“+” change, “−” no change); CE contrast enhancement score (Table 2), ST soft tissue component score (Table 2); SUV1 maximum standardized uptake value of primary tumor pre-treatment; SUV2 SUVmax of primary tumor post-treatment, ΔSUV reduction from SUV1 to SUV2 (%); VI visual interpretation, SK histological regression according to Salzer–Kuntschik [23]; R response; NR nonresponse. Methods based on Denecke et al. [15].
Pathology revealed the tumor to be composed of small round blue cells in variable fibrotic to necrotic background with coagulative tumor necrosis consisting of 5 % of tumor mass while over 90 % of the mass consisted of dense fibrosis that was suspected to be replacing previously viable tumor. The final tumor size at time of amputation measured 8.3 cm AP × 10.0 cm ML × 13.0 cm proximal to distal. Margins were negative. Baseline imagery confirmed no residual/early recurrent disease 2 months postoperatively using PET CT and MRI. Figures 1, 2, and 3 summarize X-ray radiography, MRI, and FDG-PET analyses, respectively, of the mass both before and after chemotherapeutic treatment while Fig. 4 illustrates histopathologic findings as measured by hematoxylin and eosin (H&E) and CD99. Table 1 includes a summary of the data pertaining to this case of Ewing’s sarcoma. Volume was calculated by cylindrical approximation of the mass in accordance with the EURO E.W.I.N.G. protocols for therapy optimization [22]. Soft tissue component, contrast enhancement, and T2 signal intensity were reported based on the methods outlined in Denecke et al. [15] and are further elaborated in Table 2. Metabolic activity of the mass was quantified using SUV corrected for body weight and injected FDG activity. Response assessment was assessed based on FDG-PET measurements before (SUV1) and after (SUV2) chemotherapeutic treatment, percent change in SUV intensity between these two measurements (ΔSUV), and visual interpretation. Histological grade and response were assessed in accordance with methodologies summarized in Salzer–Kuntschik (SK) [23]. Patients with 50 %) Minimal reduction (50 %) Minimal reduction (
