See the corresponding article in this issue, pp 647–654.
J Neurosurg 120:645–646, 2014 ©AANS, 2014
Editorial
Gamma Knife radiosurgery and nonfunctioning pituitary adenomas Kalman Kovacs, M.D., Ph.D. Department of Laboratory Medicine, Division of Pathology, St. Michael’s Hospital, Toronto, Ontario, Canada
The publication of Lee et al. is a useful and well-written addition to the literature.1 They analyze, based on a review of previous studies and their own experience, the advantages and disadvantages of Gamma Knife radiosurgery (GKRS) in the treatment of patients with clinically nonfunctioning pituitary adenomas. The results of GKRS are also compared with those produced by conventional resection. Clinically nonfunctioning pituitary adenomas represent the most frequent pituitary adenoma type among pituitary tumors. Medical treatment is not available, and pituitary tumor irradiation has several significant disadvantages. Thus, the question is, Gamma Knife surgery or conventional resection? The authors conclude that in older patients (older than 70 years) and in patients with other comorbidities in whom surgical intervention is contraindicated, initial GKRS is an acceptable alternative. Obviously, as the authors emphasize, an experienced team is needed to decide which treatment to use and to undertake the GKRS. One great disadvantage of GKRS is that the tumor is not investigated by pathologists. Morphological investigation is of crucial importance. Several diseases can mimic pituitary adenomas: for example, other primary intrasellar neoplasms, metastatic tumors, inflammatory diseases, and others. We have seen several metastatic carcinomas arising from the lung, colon, and other organs, which were misdiagnosed as pituitary adenomas! Another reason morphological investigation is important is that it allows one to draw conclusions regarding the growth potential of tumor cells. We can assess the Ki 67 nuclear labeling index, a valuable method of revealing the cell proliferation rate. Maybe in the future new drugs will be developed, which will permit medical therapy. Advances in molecular/genetic methods may provide an alternative treatment option as well. Obviously, more studies are needed to decide whether one should use GKRS and in which patients. (http://thejns.org/doi/abs/10.3171/2013.10.JNS132248)
J Neurosurg / Volume 120 / March 2014
Disclosure The author reports no conflict of interest. Reference 1. Lee CC, Kano H, Yang HC, Xu Z, Yen CP, Chung WY, et al: Initial Gamma Knife radiosurgery for nonfunctioning pituitary adenomas. Clinical article. J Neurosurg [epub ahead of print January 3, 2014. DOI: 10.3171/2013.11.JNS131757]
Response Jason P. Sheehan, M.D., Ph.D.,1 Cheng-Chia Lee, M.D.,1 David Hung-Chi Pan, M.D.,3,4 and L. Dade Lunsford, M.D.2 Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia; 2Department of Neurosur gery, University of Pittsburgh, Pennsylvania; 3Department of Neuro surgery, Neurological Institute, Taipei Veterans General Hospital; and 4School of Medicine, National Yang-Ming University, Taipei, Taiwan 1
We appreciate and, for the most part, concur with the comments made by Dr. Kovacs. In general, we recommend resection for patients with progressive and symptomatic sellar tumors. As Dr. Kovacs notes, other entities can occasionally be mistaken for a nonfunctioning pituitary adenoma (NFA). Pathological entities of the sellar and juxtasellar region include abscess, aneurysm, arachnoid cyst, cephalocele, chordoma, colloid cyst, craniopharyngioma, dermoid, epidermoid, germinoma, hamartoma, histiocytosis, pituitary hyperplasia, hypophysitis, lipoma, lymphoma, meningioma, metastasis, glioma, parasitic cyst, osteocartilaginous tumor, Rathke cleft cyst, sarcoid, and esthesioneuroblastoma. Treatment with upfront radiosurgery should be considered when the diagnosis of NFA is fairly certain. A diagnosis of NFA without histology can be inferred based on the patient’s clinical history, physical examination, serial neuroimaging studies, and endocrine evaluation. In our study, none of the patients were found to have a pathological entity other than NFA; however, these were carefully selected patients who had a multidisciplinary assessment. Misdiagnosis remains a possibility for some tumors. However, the same argument about the essentialness of histopathological diagnosis has been made in the past regarding upfront radiosurgery in patients with presumptive acoustic neuroma, meningioma, and brain metasta645
Editorial sis. Over the past 2 decades, careful patient selection and improvements in neuroimaging have led to the judicious use of radiosurgery without a histological diagnosis.2–4,8 In radiotherapy and radiosurgery series, misdiagnosis on the basis of imaging, clinical history, and patient examination is rare, likely occurring in 2%–11% of cases.2,6,7 More sophisticated neuroimaging, including MR perfusion, MR spectroscopy, and MRI- or CT-based positron emission tomography, are routinely used in lieu of histopathology to guide the treatment of patients with intracranial lesions.1,5 An epidemic of misdiagnosed intracranial pathology treated with radiosurgery has not occurred and seems unlikely. Further studies will be required to validate this approach. However, initial management of selected NFAs with radiosurgery probably has a place in contemporary treatment paradigms. References 1. Brandão LA, Castillo M: Adult brain tumors: clinical applications of magnetic resonance spectroscopy. Neuroimaging Clin N Am 23:527–555, 2013 2. Flickinger JC, Kondziolka D, Maitz AH, Lunsford LD: Gamma knife radiosurgery of imaging-diagnosed intracranial meningioma. Int J Radiat Oncol Biol Phys 56:801–806, 2003
646
3. Hasegawa T, Kida Y, Kato T, Iizuka H, Kuramitsu S, Yamamoto T: Long-term safety and efficacy of stereotactic radiosurgery for vestibular schwannomas: evaluation of 440 patients more than 10 years after treatment with Gamma Knife surgery. Clinical article. J Neurosurg 118:557–565, 2013 4. Kondziolka D, Kano H, Harrison GL, Yang HC, Liew DN, Niranjan A, et al: Stereotactic radiosurgery as primary and salvage treatment for brain metastases from breast cancer. Clinical article. J Neurosurg 114:792–800, 2011 5. Law M, Hamburger M, Johnson G, Inglese M, Londono A, Golfinos J, et al: Differentiating surgical from non-surgical lesions using perfusion MR imaging and proton MR spectroscopic imaging. Technol Cancer Res Treat 3:557–565, 2004 6. Mintz AH, Kestle J, Rathbone MP, Gaspar L, Hugenholtz H, Fisher B, et al: A randomized trial to assess the efficacy of surgery in addition to radiotherapy in patients with a single cerebral metastasis. Cancer 78:1470–1476, 1996 7. Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Kryscio RJ, et al: A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 322: 494–500, 1990 8. Starke RM, Williams BJ, Hiles C, Nguyen JH, Elsharkawy MY, Sheehan JP: Gamma Knife surgery for skull base meningiomas. Clinical article. J Neurosurg 116:588–597, 2012 Please include this information when citing this paper: published online January 3, 2014; DOI: 10.3171/2013.10.JNS132248.
J Neurosurg / Volume 120 / March 2014
J Neurosurg 120:645–646, 2014 ©AANS, 2014
Editorial
Gamma Knife radiosurgery and nonfunctioning pituitary adenomas Kalman Kovacs, M.D., Ph.D. Department of Laboratory Medicine, Division of Pathology, St. Michael’s Hospital, Toronto, Ontario, Canada
The publication of Lee et al. is a useful and well-written addition to the literature.1 They analyze, based on a review of previous studies and their own experience, the advantages and disadvantages of Gamma Knife radiosurgery (GKRS) in the treatment of patients with clinically nonfunctioning pituitary adenomas. The results of GKRS are also compared with those produced by conventional resection. Clinically nonfunctioning pituitary adenomas represent the most frequent pituitary adenoma type among pituitary tumors. Medical treatment is not available, and pituitary tumor irradiation has several significant disadvantages. Thus, the question is, Gamma Knife surgery or conventional resection? The authors conclude that in older patients (older than 70 years) and in patients with other comorbidities in whom surgical intervention is contraindicated, initial GKRS is an acceptable alternative. Obviously, as the authors emphasize, an experienced team is needed to decide which treatment to use and to undertake the GKRS. One great disadvantage of GKRS is that the tumor is not investigated by pathologists. Morphological investigation is of crucial importance. Several diseases can mimic pituitary adenomas: for example, other primary intrasellar neoplasms, metastatic tumors, inflammatory diseases, and others. We have seen several metastatic carcinomas arising from the lung, colon, and other organs, which were misdiagnosed as pituitary adenomas! Another reason morphological investigation is important is that it allows one to draw conclusions regarding the growth potential of tumor cells. We can assess the Ki 67 nuclear labeling index, a valuable method of revealing the cell proliferation rate. Maybe in the future new drugs will be developed, which will permit medical therapy. Advances in molecular/genetic methods may provide an alternative treatment option as well. Obviously, more studies are needed to decide whether one should use GKRS and in which patients. (http://thejns.org/doi/abs/10.3171/2013.10.JNS132248)
J Neurosurg / Volume 120 / March 2014
Disclosure The author reports no conflict of interest. Reference 1. Lee CC, Kano H, Yang HC, Xu Z, Yen CP, Chung WY, et al: Initial Gamma Knife radiosurgery for nonfunctioning pituitary adenomas. Clinical article. J Neurosurg [epub ahead of print January 3, 2014. DOI: 10.3171/2013.11.JNS131757]
Response Jason P. Sheehan, M.D., Ph.D.,1 Cheng-Chia Lee, M.D.,1 David Hung-Chi Pan, M.D.,3,4 and L. Dade Lunsford, M.D.2 Department of Neurological Surgery, University of Virginia Health System, Charlottesville, Virginia; 2Department of Neurosur gery, University of Pittsburgh, Pennsylvania; 3Department of Neuro surgery, Neurological Institute, Taipei Veterans General Hospital; and 4School of Medicine, National Yang-Ming University, Taipei, Taiwan 1
We appreciate and, for the most part, concur with the comments made by Dr. Kovacs. In general, we recommend resection for patients with progressive and symptomatic sellar tumors. As Dr. Kovacs notes, other entities can occasionally be mistaken for a nonfunctioning pituitary adenoma (NFA). Pathological entities of the sellar and juxtasellar region include abscess, aneurysm, arachnoid cyst, cephalocele, chordoma, colloid cyst, craniopharyngioma, dermoid, epidermoid, germinoma, hamartoma, histiocytosis, pituitary hyperplasia, hypophysitis, lipoma, lymphoma, meningioma, metastasis, glioma, parasitic cyst, osteocartilaginous tumor, Rathke cleft cyst, sarcoid, and esthesioneuroblastoma. Treatment with upfront radiosurgery should be considered when the diagnosis of NFA is fairly certain. A diagnosis of NFA without histology can be inferred based on the patient’s clinical history, physical examination, serial neuroimaging studies, and endocrine evaluation. In our study, none of the patients were found to have a pathological entity other than NFA; however, these were carefully selected patients who had a multidisciplinary assessment. Misdiagnosis remains a possibility for some tumors. However, the same argument about the essentialness of histopathological diagnosis has been made in the past regarding upfront radiosurgery in patients with presumptive acoustic neuroma, meningioma, and brain metasta645
Editorial sis. Over the past 2 decades, careful patient selection and improvements in neuroimaging have led to the judicious use of radiosurgery without a histological diagnosis.2–4,8 In radiotherapy and radiosurgery series, misdiagnosis on the basis of imaging, clinical history, and patient examination is rare, likely occurring in 2%–11% of cases.2,6,7 More sophisticated neuroimaging, including MR perfusion, MR spectroscopy, and MRI- or CT-based positron emission tomography, are routinely used in lieu of histopathology to guide the treatment of patients with intracranial lesions.1,5 An epidemic of misdiagnosed intracranial pathology treated with radiosurgery has not occurred and seems unlikely. Further studies will be required to validate this approach. However, initial management of selected NFAs with radiosurgery probably has a place in contemporary treatment paradigms. References 1. Brandão LA, Castillo M: Adult brain tumors: clinical applications of magnetic resonance spectroscopy. Neuroimaging Clin N Am 23:527–555, 2013 2. Flickinger JC, Kondziolka D, Maitz AH, Lunsford LD: Gamma knife radiosurgery of imaging-diagnosed intracranial meningioma. Int J Radiat Oncol Biol Phys 56:801–806, 2003
646
3. Hasegawa T, Kida Y, Kato T, Iizuka H, Kuramitsu S, Yamamoto T: Long-term safety and efficacy of stereotactic radiosurgery for vestibular schwannomas: evaluation of 440 patients more than 10 years after treatment with Gamma Knife surgery. Clinical article. J Neurosurg 118:557–565, 2013 4. Kondziolka D, Kano H, Harrison GL, Yang HC, Liew DN, Niranjan A, et al: Stereotactic radiosurgery as primary and salvage treatment for brain metastases from breast cancer. Clinical article. J Neurosurg 114:792–800, 2011 5. Law M, Hamburger M, Johnson G, Inglese M, Londono A, Golfinos J, et al: Differentiating surgical from non-surgical lesions using perfusion MR imaging and proton MR spectroscopic imaging. Technol Cancer Res Treat 3:557–565, 2004 6. Mintz AH, Kestle J, Rathbone MP, Gaspar L, Hugenholtz H, Fisher B, et al: A randomized trial to assess the efficacy of surgery in addition to radiotherapy in patients with a single cerebral metastasis. Cancer 78:1470–1476, 1996 7. Patchell RA, Tibbs PA, Walsh JW, Dempsey RJ, Maruyama Y, Kryscio RJ, et al: A randomized trial of surgery in the treatment of single metastases to the brain. N Engl J Med 322: 494–500, 1990 8. Starke RM, Williams BJ, Hiles C, Nguyen JH, Elsharkawy MY, Sheehan JP: Gamma Knife surgery for skull base meningiomas. Clinical article. J Neurosurg 116:588–597, 2012 Please include this information when citing this paper: published online January 3, 2014; DOI: 10.3171/2013.10.JNS132248.
J Neurosurg / Volume 120 / March 2014
