INTERESTING IMAGE
In Vivo and In Vitro Evidence of Somatostatin Receptors Expression in a Dedifferentiated Retroperitoneal Liposarcoma Alessio Imperiale, MD,*Þ Marie-Pierre Chenard, MD,þ Serge Rohr, MD,§ Anne Barlier, MD, PhD,¶ and Bernard Goichot, MD, PhD|| Abstract: A 62-year-old patient presented with mildly elevated catecholamines and an abdominal painless mass. Abdominal CT revealed an 18 12 cm tumor in the right retroperitoneum with intense contrast enhancement. Somatostatin receptor scintigraphy (SRS) showed pathologic uptake by the lesion. Given the suspicion of paraganglioma, the patient was referred to surgery for tumor removal. Surprisingly, the histopathological examination revealed a dedifferentiated liposarcoma. Somatostatin receptors of type 2 were identified and quantified by reverse transcription polymerase chain reaction. The unexpected presentation of our patient draws clinicians’ attention when performing diagnostic procedure for retroperitoneal lesions, even though hormone secretion and positive SRS strongly suggest paraganglioma. Key Words: sarcoma, liposarcoma, somatostatin receptors, somatostatin receptors scintigraphy, RT-PCR, paraganglioma (Clin Nucl Med 2014;39: 892Y893)
Received for publication June 18, 2013; and revision accepted December 28, 2013. From the *Department of Biophysics and Nuclear Medicine, Strasbourg University Hospitals, Strasbourg; †ICube, University of Strasbourg/CNRS (UMR 7357) and Fe´de´ration de Me´decine Translationnelle de Strasbourg, Faculty of Medicine, Strasbourg; ‡Departments of Pathology and §General Surgery, Strasbourg University Hospitals, Strasbourg; ¶Molecular Biology Laboratory, Conception University Hospital, Marseille; and ||Department of Internal Medicine, Strasbourg University Hospitals, Strasbourg, France. Conflicts of interest and sources of funding: none declared. Reprints: Alessio Imperiale, MD, Department of Biophysics and Nuclear Medicine, Strasbourg University Hospitals Hautepierre University HospitalV1, Avenue Molie`re, 67098 Strasbourg Cedex, France. E-mail: [email protected]. Copyright * 2014 by Lippincott Williams & Wilkins ISSN: 0363-9762/14/3910Y0892
892
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ACKNOWLEDGMENTS The authors would like to thank Jeremy Godefroy, MD for bibliographic research. REFERENCES 1. Guillou L, Coindre JM, Bonichon F, et al. Comparative study of the National Cancer Institute and French Federation of Cancer Centers Sarcoma Group grading systems in a population of 410 patients with soft tissue sarcoma. J Clin Oncol. 1997;15:350Y362. 2. Liu D, Quinonez G, Latosinsky S. Dedifferentiated liposarcoma with a paraganglioma-like histologic pattern: a case report and review of the literature. Arch Pathol Lab Med. 2004;128:788Y791. 3. Plachcinska A, Mikolajczak R, Maecke H, et al. Clinical usefulness of 99mTcEDDA/HYNIC-TOC scintigraphy in oncological diagnostics: a pilot study. Canc Biother Radiopharm. 2004;19:261Y270. 4. Florio T, Montella L, Corsaro A, et al. In vitro and in vivo expression of somatostatin receptors in intermediate and malignant soft tissue tumors. Anticancer Res. 2003;23:2465Y2471. 5. Reubi JC, Waser B, Laissue JA, et al. Somatostatin and vasoactive intestinal peptide receptors in human mesenchymal tumors: in vitro identification. Cancer Res. 1996;56:1922Y1931. 6. O’Toole D, Saveanu A, Couvelard A, et al. The analysis of quantitative expression of somatostatin and dopamine receptors in gastro-entero-pancreatic tumors opens new therapeutic strategies. Eur J Endocrinol. 2006;155:849Y857. 7. Trimeche Ajmi S, Marmouch H, Trabelsi A, et al. Retroperitonial liposarcoma mimicking pheochromocytoma. Pathologica. 2008;100:470Y472. 8. Bonvalot S, Raut CP, Pollock RE, et al. Technical considerations in surgery for retroperitoneal sarcomas: position paper from E-Surge, a master class in sarcoma surgery, and EORTC-STBSG. Ann Surg Oncol. 2012;19:2981Y2991. 9. Pelosi G, Volante M, Papotti M, et al. Peptide receptors in neuroendocrine tumors of the lung as potential tools for radionuclide diagnosis and therapy. Q J Nucl Med Mol Imaging. 2006;50:272Y287.
Clinical Nuclear Medicine
& Volume 39, Number 10, October 2014
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Clinical Nuclear Medicine
& Volume 39, Number 10, October 2014
Somatostatin Receptors Expression in a Liposarcoma
FIGURE 1. Somatostatin receptor scintigraphy (SRS) anterior and posterior planar whole-body images (A) and SPECT/CT axial (B) and coronal (C) slices obtained respectively 4 and 24 hours after the i.v. injection of 163 MBq of 111In-pentetreotide, showing a pathologic peripheral radiotracer uptake in a heterogeneous and extra adrenal right retroperitoneal mass. After surgery, the histopathological examination revealed a dedifferentiated liposarcoma of grade 3 according to Federation Nationale des Centres de Lutte Contre le Cancer grading system.1 The periphery of the tumor was a well-differentiated liposarcoma (D) while the center showed the typical features of dedifferentiation (E) as spindle-shape, epithelioid, and plurinuclear giant cells, and large necrotic areas.2 Immunohistologically, tumor cells expressed CD4 and MDM2, but did not express NSE, synaptophysin, nor chromogranin A. Intense MDM2 amplification was confirmed by fluorescent in situ hybridization. The mitotic index established on H&E-stained slides was equal to 5. In the reported case, both pathological findings and SRS results suggest a possible correlation between the degree of tumoral differentiation and the intensity of 111In-pentetreotide uptake, which was more pronounced in the exterior well-differentiated area. Unfortunately, the presence of central necrosis, which represented more than 60% of total tumoral volume, prevents definitive conclusions. To the best of our knowledge, in vivo somatostatin receptors (sstr) expression in liposarcoma has been reported in only 1 patient with liposarcoma of the lung.3 In vitro expression of sstr was found by Florio et al4 in 5 out of 7 well-differentiated liposarcoma of the limbs. Conversely, none of the 4 liposarcomas studied by Reubi et al5 had in vitro sstr expression. For the first time here, the mRNA of sstr of a liposarcoma was assessed and quantified by reverse transcription polymerase chain reaction. The only expressed receptor was sstr2, consistent with SRS positivity. Although significant (82 10j3 copy/copy A-Gus), the level of sstr2 mRNA was smaller in the liposarcoma compared with those observed in pituitary somatotroph adenomas and gastroenteropancreatic neuroendocrine tumors (NET).6 The low sstr2 expression potentially contrasts with the intense radiotracer uptake showed at SRS. Tumor heterogeneity and size may contribute to explain these results. As previously established in NET with positive SRS, the sstr2 mRNA levels are significantly lower in big tumors than in small ones. However, in voluminous lesions, low sstr2 expression is sufficient to obtain a clearly positive SRS. Tumor size represents a bias in SRS results,6 so 111 In-pentetreotide uptake intensity is not directly proportional to sstr2 expression. In our patient, the tumor involvement in catecholamines secretion remains doubtful. Hormone secretion has been reported in only 1 patient with well-differentiated liposarcoma and concomitant adrenal hyperplasia.7 In patients with catecholamine secretion and imaging findings consistent with paraganglioma, surgical removal of the mass after conditioning is the standard. Even if tumoral biopsy is contraindicated by fear of hormone release, it should be discussed in a multidisciplinary board familiar with retroperitoneal tumor managing.8 Finally, given the availability of radiolabeled somatostatin analogues for peptide-receptor radiotherapy, the sstr2 expression could allow potential therapeutic option in chemoresistant and poor-prognosis tumors.9 * 2014 Lippincott Williams & Wilkins
www.nuclearmed.com
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
893
In Vivo and In Vitro Evidence of Somatostatin Receptors Expression in a Dedifferentiated Retroperitoneal Liposarcoma Alessio Imperiale, MD,*Þ Marie-Pierre Chenard, MD,þ Serge Rohr, MD,§ Anne Barlier, MD, PhD,¶ and Bernard Goichot, MD, PhD|| Abstract: A 62-year-old patient presented with mildly elevated catecholamines and an abdominal painless mass. Abdominal CT revealed an 18 12 cm tumor in the right retroperitoneum with intense contrast enhancement. Somatostatin receptor scintigraphy (SRS) showed pathologic uptake by the lesion. Given the suspicion of paraganglioma, the patient was referred to surgery for tumor removal. Surprisingly, the histopathological examination revealed a dedifferentiated liposarcoma. Somatostatin receptors of type 2 were identified and quantified by reverse transcription polymerase chain reaction. The unexpected presentation of our patient draws clinicians’ attention when performing diagnostic procedure for retroperitoneal lesions, even though hormone secretion and positive SRS strongly suggest paraganglioma. Key Words: sarcoma, liposarcoma, somatostatin receptors, somatostatin receptors scintigraphy, RT-PCR, paraganglioma (Clin Nucl Med 2014;39: 892Y893)
Received for publication June 18, 2013; and revision accepted December 28, 2013. From the *Department of Biophysics and Nuclear Medicine, Strasbourg University Hospitals, Strasbourg; †ICube, University of Strasbourg/CNRS (UMR 7357) and Fe´de´ration de Me´decine Translationnelle de Strasbourg, Faculty of Medicine, Strasbourg; ‡Departments of Pathology and §General Surgery, Strasbourg University Hospitals, Strasbourg; ¶Molecular Biology Laboratory, Conception University Hospital, Marseille; and ||Department of Internal Medicine, Strasbourg University Hospitals, Strasbourg, France. Conflicts of interest and sources of funding: none declared. Reprints: Alessio Imperiale, MD, Department of Biophysics and Nuclear Medicine, Strasbourg University Hospitals Hautepierre University HospitalV1, Avenue Molie`re, 67098 Strasbourg Cedex, France. E-mail: [email protected]. Copyright * 2014 by Lippincott Williams & Wilkins ISSN: 0363-9762/14/3910Y0892
892
www.nuclearmed.com
ACKNOWLEDGMENTS The authors would like to thank Jeremy Godefroy, MD for bibliographic research. REFERENCES 1. Guillou L, Coindre JM, Bonichon F, et al. Comparative study of the National Cancer Institute and French Federation of Cancer Centers Sarcoma Group grading systems in a population of 410 patients with soft tissue sarcoma. J Clin Oncol. 1997;15:350Y362. 2. Liu D, Quinonez G, Latosinsky S. Dedifferentiated liposarcoma with a paraganglioma-like histologic pattern: a case report and review of the literature. Arch Pathol Lab Med. 2004;128:788Y791. 3. Plachcinska A, Mikolajczak R, Maecke H, et al. Clinical usefulness of 99mTcEDDA/HYNIC-TOC scintigraphy in oncological diagnostics: a pilot study. Canc Biother Radiopharm. 2004;19:261Y270. 4. Florio T, Montella L, Corsaro A, et al. In vitro and in vivo expression of somatostatin receptors in intermediate and malignant soft tissue tumors. Anticancer Res. 2003;23:2465Y2471. 5. Reubi JC, Waser B, Laissue JA, et al. Somatostatin and vasoactive intestinal peptide receptors in human mesenchymal tumors: in vitro identification. Cancer Res. 1996;56:1922Y1931. 6. O’Toole D, Saveanu A, Couvelard A, et al. The analysis of quantitative expression of somatostatin and dopamine receptors in gastro-entero-pancreatic tumors opens new therapeutic strategies. Eur J Endocrinol. 2006;155:849Y857. 7. Trimeche Ajmi S, Marmouch H, Trabelsi A, et al. Retroperitonial liposarcoma mimicking pheochromocytoma. Pathologica. 2008;100:470Y472. 8. Bonvalot S, Raut CP, Pollock RE, et al. Technical considerations in surgery for retroperitoneal sarcomas: position paper from E-Surge, a master class in sarcoma surgery, and EORTC-STBSG. Ann Surg Oncol. 2012;19:2981Y2991. 9. Pelosi G, Volante M, Papotti M, et al. Peptide receptors in neuroendocrine tumors of the lung as potential tools for radionuclide diagnosis and therapy. Q J Nucl Med Mol Imaging. 2006;50:272Y287.
Clinical Nuclear Medicine
& Volume 39, Number 10, October 2014
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
Clinical Nuclear Medicine
& Volume 39, Number 10, October 2014
Somatostatin Receptors Expression in a Liposarcoma
FIGURE 1. Somatostatin receptor scintigraphy (SRS) anterior and posterior planar whole-body images (A) and SPECT/CT axial (B) and coronal (C) slices obtained respectively 4 and 24 hours after the i.v. injection of 163 MBq of 111In-pentetreotide, showing a pathologic peripheral radiotracer uptake in a heterogeneous and extra adrenal right retroperitoneal mass. After surgery, the histopathological examination revealed a dedifferentiated liposarcoma of grade 3 according to Federation Nationale des Centres de Lutte Contre le Cancer grading system.1 The periphery of the tumor was a well-differentiated liposarcoma (D) while the center showed the typical features of dedifferentiation (E) as spindle-shape, epithelioid, and plurinuclear giant cells, and large necrotic areas.2 Immunohistologically, tumor cells expressed CD4 and MDM2, but did not express NSE, synaptophysin, nor chromogranin A. Intense MDM2 amplification was confirmed by fluorescent in situ hybridization. The mitotic index established on H&E-stained slides was equal to 5. In the reported case, both pathological findings and SRS results suggest a possible correlation between the degree of tumoral differentiation and the intensity of 111In-pentetreotide uptake, which was more pronounced in the exterior well-differentiated area. Unfortunately, the presence of central necrosis, which represented more than 60% of total tumoral volume, prevents definitive conclusions. To the best of our knowledge, in vivo somatostatin receptors (sstr) expression in liposarcoma has been reported in only 1 patient with liposarcoma of the lung.3 In vitro expression of sstr was found by Florio et al4 in 5 out of 7 well-differentiated liposarcoma of the limbs. Conversely, none of the 4 liposarcomas studied by Reubi et al5 had in vitro sstr expression. For the first time here, the mRNA of sstr of a liposarcoma was assessed and quantified by reverse transcription polymerase chain reaction. The only expressed receptor was sstr2, consistent with SRS positivity. Although significant (82 10j3 copy/copy A-Gus), the level of sstr2 mRNA was smaller in the liposarcoma compared with those observed in pituitary somatotroph adenomas and gastroenteropancreatic neuroendocrine tumors (NET).6 The low sstr2 expression potentially contrasts with the intense radiotracer uptake showed at SRS. Tumor heterogeneity and size may contribute to explain these results. As previously established in NET with positive SRS, the sstr2 mRNA levels are significantly lower in big tumors than in small ones. However, in voluminous lesions, low sstr2 expression is sufficient to obtain a clearly positive SRS. Tumor size represents a bias in SRS results,6 so 111 In-pentetreotide uptake intensity is not directly proportional to sstr2 expression. In our patient, the tumor involvement in catecholamines secretion remains doubtful. Hormone secretion has been reported in only 1 patient with well-differentiated liposarcoma and concomitant adrenal hyperplasia.7 In patients with catecholamine secretion and imaging findings consistent with paraganglioma, surgical removal of the mass after conditioning is the standard. Even if tumoral biopsy is contraindicated by fear of hormone release, it should be discussed in a multidisciplinary board familiar with retroperitoneal tumor managing.8 Finally, given the availability of radiolabeled somatostatin analogues for peptide-receptor radiotherapy, the sstr2 expression could allow potential therapeutic option in chemoresistant and poor-prognosis tumors.9 * 2014 Lippincott Williams & Wilkins
www.nuclearmed.com
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
893
