J Neurosurg Pediatrics 12:328–333, 2013 ©AANS, 2013
Giant ecchordosis physaliphora in an adolescent girl Case report Khaled M. Krisht, M.D.,1 Cheryl A. Palmer, M.D., 2 Anne G. Osborn, M.D., 3 and William T. Couldwell, M.D., Ph.D.1 1 3
Department of Neurosurgery, Clinical Neurosciences Center; and Departments of 2Pathology and Radiology, University of Utah, Salt Lake City, Utah
The authors describe a rare case of giant ecchordosis physaliphora (EP) in a 16-year-old female patient who presented with diplopia. Magnetic resonance imaging of the brain with Gd contrast revealed a 3.0 × 1.7 × 1.8–cm nonenhancing, extraaxial epidural mass along the dorsal aspect of the clivus that was T2 hyperintense and T1 isointense with intermediate signal on diffusion sequences. Resection via a transnasal transsphenoidal approach to the ventral clival wall resulted in a stable tumor size with no evidence of interval growth after 30 months. Although this case features a strictly extradural EP, this tumor more commonly occurs in the subdural space and requires differentiation from intradural chordoma. Unlike EP, intradural chordoma may enhance with Gd contrast, is more likely to be associated with cranial nerve palsies and brainstem symptoms, and will occasionally have an elevated MIB-1 index. In this paper the authors highlight the different possible midline locations for both EP and chordoma, the difficulty in distinguishing between intradural giant EP and intradural chordoma, and the potential occurrence of these lesions in young people despite their typically slow rate of growth, while also underscoring the need for further investigation into the tumors’ cytogenetic behavior. (http://thejns.org/doi/abs/10.3171/2013.5.PEDS1395)
Key Words • ecchordosis physaliphora • cerebrospinal fluid fistula • intradural chordoma • transsphenoidal • notochord • clivus • MIB-1 index • oncology
E
cchordosis physaliphora is a congenital hamartomatous growth of gelatinous tissue that is derived from ectopic vestigial notochord. It usually occurs in the midline along the dorsum of the clivus and, more rarely, the sacrum. Unlike clival chordomas, which usually occur in an extradural intraosseous location, EP is usually found intradurally.2,14,16,36 While cranial chordomas have a propensity for aggressive growth and recurrence causing bony destruction of the skull base and CN deficits, EP has a more indolent course and is often found incidentally in asymptomatic patients or in patients presenting with unrelated symptoms.3,8,22,26,30 At autopsy, its reported incidence is 0.5%–5%.18,30 Ecchordosis physaliphora begins as a notochord extradurally, perforates through the dorsal wall of the clivus and dura mater, ending in the intradural subarachnoid space, and may remain
Abbreviations used in this paper: CN = cranial nerve; EP = ec chordosis physaliphora.
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attached to the clivus by a thin bony stalk.4,14,17,28,29,36 The prepontine subarachnoid space is the textbook location for EP. In some instances, however, it may be isolated intradurally or present in the epidural space or is limited to the extradural space as in our case. To date, ours is the first reported case of a giant EP occurring strictly in the epidural space. Luschka first described the observation of notochord cells along the posterior clivus in 1856.31 The first microscopic description is credited to Virchow, who named the lesion “ecchondrosis physaliphora,” based on his theory that it is derived from the sphenooccipital synchondrosis.4,14,31 In 1858, Muller was the first to suggest a notochordal origin, which was confirmed in 1894 by Ribbert, who coined the term “ecchordosis physaliphora,” which remains in use today.11,22,36 Because of their typically slow rate of growth, EPs This article contains some figures that are displayed in color online but in black-and-white in the print edition.
J Neurosurg: Pediatrics / Volume 12 / October 2013
Giant ecchordosis physaliphora in an adolescent girl are generally small lesions. Unlike chordomas, which are radically resected and then treated with proton beam radiation given their destructive and invasive behavior, EPs can be managed expectantly with serial MRI follow-up since they have a low propensity for growth.28,32 Giant symptomatic EPs, however, may require resection. To date, 3 reported cases of giant EPs in adults have been reported, but no case has occurred in a pediatric patient and never one restricted to the epidural space.
Case Report History and Examination. A previously healthy 16-year-old girl presented with a 2-month history of headaches and worsening double vision. On clinical evaluation, she was noted to have bilateral CN VI palsies with no other neurological findings. A 1-mm, thin-sliced CT scan of the head demonstrated a low-density mass lesion at the dorsal margin of the clivus causing mild bony remodeling and irregularity with a small area of calcified bone stalk consistent with a notochord remnant (Fig. 1). Magnetic resonance imaging of the brain with Gd contrast revealed a 3.0 × 1.7 × 1.8–cm nonenhancing, extraaxial epidural mass along the dorsal aspect of the clivus that was T2 hyperintense and T1 isointense with intermediate signal on diffusion sequences. There was evident mass effect causing indentation of the ventral pons and displacement of the basilar artery to the left of midline (Fig. 2). The preoperative differential diagnosis was either a large epidural EP or a chordoma.
Fig. 2. Sagittal T2-weighted MR image (A) of the brain demonstrating the extradural location of the tumor as evidenced by tenting of the clival dura (arrow). Axial T2-weighted MR image (B) showing slight leftward displacement of the basilar trunk (arrow) by the mass. Sagittal (C) and axial (D) T1-weighted MR images with Gd revealing a 3.0 × 1.7 × 1.8–cm nonenhancing, extraaxial epidural mass along the dorsal aspect of the clivus (C, asterisk).
Treatment. A frameless stereotactic-guided, microscope-assisted transnasal transsphenoidal approach to the ventral clival wall was undertaken. The inferior posterior wall of the sphenoid sinus forming the ventral cortical wall of the clivus was carefully drilled with a 4-mm diamond drill all the way to and through the posterior cortex. The tumor was noted to be lying in the epidural space and was gelatinous and avascular in consistency. Several specimens were carefully resected and sent to pathology for both frozen and permanent sections. Frozen section revealed a probable EP, and we decided to decompress the lesion to remove pressure on the abducent nerves bilaterally, but a wide excision was not performed. No fat
Histopathology. Microsections of a yellow-tan, irregular soft tissue specimen revealed scattered physaliphorous cell nests with a lobular growth pattern. Cells contained a vacuolated eosinophilic cytoplasm with a mucin-filled matrix (Fig. 3 left). No mitotic activity or cellular pleomorphism was noted. Immunohistochemical staining with proliferation marker MIB-1 showed a relatively low proliferation index (Fig. 3 right). A final diagnosis of a clival chondroid lesion most consistent with EP was made.
Fig. 1. Sagittal (left) and axial (right) 1-mm, thin-sliced CT scans of the head demonstrating a low-density mass lesion at the dorsal margin of the clivus causing mild bony remodeling and irregularity with a small area of calcified bone stalk (arrows).
Fig. 3. Left: Photomicrograph showing hypocellular physaliphorous cells with a lobular growth pattern. These cells were eosinophilic with large prominent intracytoplasmic vacuoles and myxomatous matrices. No mitosis or cellular pleomorphism was noted. Right: Immunohistochemical staining for MIB-1 marker indicative of a low proliferation index. H & E (left), original magnifications ×200.
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or fascia graft was necessary because there was no CSF leak.
Postoperative Course. The patient had a short and
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K. M. Krisht et al. uneventful postoperative course. A postoperative CT scan of her head demonstrated interval reduction in the tumor size and improvement in the mass effect. She was discharged home on postoperative Day 1. Since undergoing her procedure, she has been seen in the clinic for the 2-, 4-, and 30-month clinical and MRI follow-ups. She has experienced complete and persistent resolution of her diplopia and demonstrated a stable residual lesion with no evidence of interval growth.
Discussion
Phylogenetically, the notochord represents the primitive skeleton of vertebrates. It forms during the 3rd week of gestation and eventually becomes the nucleus pulposus of the intervertebral disk. Heterotopic cells may be found outside the nucleus pulposus anywhere along the axial skeleton.17,24,30,32 The complex course of the notochord within the clivus and sacrum makes those regions more susceptible to harboring vestigial notochord cells that can result in EP. Although these cells usually have an intraosseous location, they occasionally perforate through the dorsal wall of the clivus into the subdural and subarachnoid spaces, which may explain the pathogenesis of EP at the prepontine region.4,18,28,29,36 With EP, there is often a bony stalk that connects it with the clivus, emphasizing its clival origin.17,24,32 This potential continuum of cells from the clivus to the intradural space explains the occurrence of lesions anywhere along this path, such as was seen in our case in which the lesion was isolated in the epidural spaces. Histological examination reveals striking similarities among EP, primitive notochord, and chordoma. They all exhibit physaliphorous cells with an abundance of intracytoplasmic vacuoles and extracellular mucin.2,6,21,23,24,26,27,37 These histological qualities lend to their iso- to hypointensity on T1-weighted MRI and hyperintensity on T2weighted MRI.6,22,23,34,35 However, EP demonstrates no contrast enhancement, unlike chordomas, which usually enhance and are more often located extradurally.3,21,35 These are helpful features in making the distinction between the two lesions. When radiographically evaluating these lesions, we recommend thin-section transverse T2weighted images of the skull base.22 Because of the small size of the lesion and the possible artifacts in the posterior fossa, CT scanning seems to have limited utility unless magnified, thin-sliced bone windows through the skull base are obtained. Chordomas tend to be faster growing and more aggressive, often causing CN deficits and bony infiltration. The increased propensity of chordoma cells to multiply and grow is underscored by the relatively higher proliferation index of their MIB-1 proliferation marker, which is another helpful distinguishing feature.9,12,13,17,19,22,25 Ecchordosis physaliphora, instead, is usually slow growing and therefore rarely causes direct symptoms. It is often discovered incidentally as part of an evaluation for unrelated symptoms. Many of these lesions go undetected throughout a person’s lifetime and are only found later at autopsy (Fig. 4). Among the 18 in-hospital cases described in the literature, 2 instances of EP were discovered at au330
Fig. 4. A representative photograph of an intradural EP found at autopsy (arrow). Note the gelatinous tan-looking appearance of the tumor. Used with permission from Amirsys, Inc.
topsy (Table 1). In 1 patient, a fatal subarachnoid hemorrhage from a ruptured EP was believed to be the direct cause of death.12 In the second patient, the discovered EP had no relation to the cause of death, which was a fatal heart infarction.1 Among the remaining 16 cases (not including our case), 10 were reported as incidental. Among the 6 symptomatic cases, 2 patients presented with CSF rhinorrhea due to a skull base CSF fistula, 1 patient presented with facial pain, and a fourth patient presented with diplopia.2,4,18,26 In these cases, the symptomatology was consistent with the potential effects of the lesion given its proximity to the clivus and pons. In the remaining 2 cases, the reported symptoms were headaches, dizziness, or confusion, which might have been caused by the EP but were very likely coincidental.3,25 The difficulty in diagnosis arises when attempting to differentiate intradural EP from intradural chordomas. The latter have a slower growth pattern compared with the classic intraosseous infiltrating chordomas and may be very difficult to distinguish from intradural EP. Just like EP, intradural chordomas may have a low MIB-1 index, making it difficult to discern the two based on immunohistochemical means as well.15,21,25,36 The MRI and CT characteristics may be helpful in distinguishing between the two. Intradural chordomas almost never have an associated stalk, and, unlike EP, they usually enhance with Gd administration.5,10,15,16,20,22,24,38 However, there are cases of isolated intradural EP without a stalk, and in some rare cases, an intradural chordoma may not demonstrate enhancement. Another important consideration is the clinical presentation. Patients with intradural chordoma are more likely to present with compressive symptoms such as CN deficits. The lack of a clear-cut distinction between intradurally located EP and chordoma has led some to believe that they signify the same spectrum of disease and that intradural chordoma may represent a J Neurosurg: Pediatrics / Volume 12 / October 2013
Giant ecchordosis physaliphora in an adolescent girl TABLE 1: Literature summary of in-hospital cases of EP* Authors & Year
Age (yrs), Sex
Max Tumor Diameter (cm)
Macdonald et al., 1990 Watanabe et al., 1994 Akimoto et al., 1996 Toda et al., 1998 Rodríguez et al., 1999 Cha et al., 2002 Mehnert et al., 2004
66, F 48, M 51, F 56, F 54, F 49, M 71, M 38, M 74, M 55, F 10, M 47, F 45, M 52, F 48, F 31, F 22, M 78, M 17, F
NA NA NA 1.5 3 1.5 1.3 0.5 0.6 0.5 0.3 NA 3 1.3 3.2 NA NA 0.6 3
Rotondo et al., 2007 Ling et al., 2007 Alli et al., 2008 Fracasso et al., 2008 Srinivasan et al., 2008 Alkan et al., 2009 Adamek et al., 2011 present case
Presenting Symptoms CSF rhinorrhea incidental headache, diplopia incidental dizziness incidental incidental incidental incidental incidental incidental headache, facial pain incidental CSF rhinorrhea autopsy incidental headache, confusion autopsy headache, diplopia
* NA = not available.
symptomatic form of EP (Table 2).7,26,33 Rodríguez et al.25 have proposed this notion and have recommended that instances of intradural chordoma be classified as giant or symptomatic EP. In our case, the patient’s 3-cm lesion was symptomatic, showed no contrast enhancement, was noted to have a bony stalk connecting through the clivus, lacked bony infiltration and destruction, revealed a low MIB-1 index level, and demonstrated no interval growth 30 months after resection—all factors consistent with a diagnosis of a symptomatic giant EP. In the literature, only 3 other cases of giant EPs measuring at least 3 cm in their widest diameter have been reported. Unlike our case, however, those cases were all discovered in adults and were located in the prepontine subdural space (Table 1). Rodríguez et al.25 described the case of a 54-year-old woman with a 3-cm EP who had presented with a 1.5-year history of dizzi-
ness. Ling et al.17 documented the case of a 45-year-old man who presented with left-sided hearing loss and tinnitus, which led to an MR image of the brain demonstrating an incidental 30 × 30 × 14–mm EP. Finally, Fracasso et al.12 reported an unusual case of a fatal subarachnoid hemorrhage due to a ruptured giant EP measuring 3.2 cm that was discovered at autopsy. To our knowledge, ours is the first instance of a giant symptomatic EP in an adolescent. The majority of reported cases have fallen in the age group of 21–60 years (13 of 19 patients), with a mean age of 48 years and a female/male ratio of 1.1:1. Given the slow-growing, asymptomatic nature of EP, the present case is a unique presentation in a pediatric patient. The only other case of EP in a young patient was provided by Mehnert et al.,22 who described a small, 3-mm lesion in a 10-year-old boy identified during a review of 300 consecutive 1.5-T MRI studies in asymptomatic subjects.
TABLE 2: Distinguishing features of intra- and extradurally located EP and chordoma Pathology
Intradural Location
Extradural Location
chordoma
small size low MIB-1 index contrast enhancing no bony stalk may have CN involvement small size low MIB-1 index rarely contrast enhances may have bony stalk rarely has CN involvement
larger size invasive w/ increased MIB-1 index contrast enhancing no bony stalk CN involvement usually small size low MIB-1 index rarely contrast enhances may have bony stalk may have CN involvement
EP
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K. M. Krisht et al. Conclusions
Ecchordosis physaliphora and intradural chordoma are phylogenetically, histologically, and clinically closely related lesions that may represent the same spectrum of disease. In some instances, such as in our case, the distinction can be easily made; in other cases, it may be very difficult to differentiate between the two. Contrast enhancement, elevated MIB-1 levels, and brainstem/CN involvement remain important features that help to distinguish intradural chordoma from EP. While EP has an indolent growth and rarely causes symptoms throughout a person’s lifetime, our case demonstrates that these tumors can, in fact, be large and cause compressive symptoms early in life. In such cases, surgery may be necessary. The strictly extradural location of this particular EP indicates that EP, like chordoma, can be isolated to the epidural space and that both disease entities can occupy any space extending from the clivus to the prepontine cistern, with EP having a greater propensity for the subdural space and chordoma for the extradural space. Although difficult given the rarity of EP, further investigation into its cytogenetics is needed for more accurate diagnosis and prognostication. Disclosure Dr. Osborn has direct stock ownership in Amirsys Inc. and Amirsys Publishing Inc. Author contributions to the study and manuscript preparation include the following. Conception and design: Couldwell. Acquisition of data: Krisht. Analysis and interpretation of data: Krisht, Palmer. Drafting the article: Krisht. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Couldwell. Administrative/technical/material support: Osborn. References 1. Adamek D, Malec M, Grabska N, Krygowska-Wajs A, Gałą zka K: Ecchordosis physaliphora—a case report and a review of notochord-derived lesions. Neurol Neurochir Pol 45: 169–173, 2011 2. Akimoto J, Takeda H, Hashimoto T, Haraoka J, Ito H: [A surgical case of ecchordosis physaliphora.] No Shinkei Geka 24: 1021–1025, 1996 (Jpn) 3. Alkan O, Yildirim T, Kizilkiliç O, Tan M, Cekinmez M: A case of ecchordosis physaliphora presenting with an intratumoral hemorrhage. Turk Neurosurg 19:293–296, 2009 4. Alli A, Clark M, Mansell NJ: Cerebrospinal fluid rhinorrhea secondary to ecchordosis physaliphora. Skull Base 18:395– 399, 2008 5. Burger P, Scheithauer BW, Vogel F: Surgical Pathology of the Nervous System and Its Coverings. New York: Churchill Livingstone, 2002 6. Cha ST, Jarrahy R, Yong WH, Eby T, Shahinian HK: A rare symptomatic presentation of ecchordosis physaliphora and unique endoscope-assisted surgical management. Minim Invasive Neurosurg 45:36–40, 2002 7. Ciarpaglini R, Pasquini E, Mazzatenta D, Ambrosini-Spaltro A, Sciarretta V, Frank G: Intradural clival chordoma and ecchordosis physaliphora: a challenging differential diagnosis: case report. Neurosurgery 64:E387–E388, 2009 8. Congdon CC: Benign and malignant chordomas; a clinicoanatomical study of twenty-two cases. Am J Pathol 28:793– 821, 1952
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9. Dow GR, Robson DK, Jaspan T, Punt JA: Intradural cerebellar chordoma in a child: a case report and review of the literature. Childs Nerv Syst 19:188–191, 2003 10. Erdem E, Angtuaco EC, Van Hemert R, Park JS, Al-Mefty O: Comprehensive review of intracranial chordoma. Radiographics 23:995–1009, 2003 11. Fasanotti A: [Benign chordoma of the clivus; spheno-occipital physaliphorous ecchondrosis; ecchordosis physaliphora.] Riv Anat Patol Oncol 10 (Suppl 1):1–115, 1955–1956 (Ital) 12. Fracasso T, Brinkmann B, Paulus W: Sudden death due to subarachnoid bleeding from ecchordosis physaliphora. Int J Legal Med 122:225–227, 2008 13. Gonzalez-Martinez JA, Guthikonda M, Vellutini E, Zamorano L, Li Q, Kupski W, et al: Intradural invasion of chordoma: two case reports. Skull Base 12:155–161, 2002 14. Ho KL: Ecchordosis physaliphora and chordoma: a comparative ultrastructural study. Clin Neuropathol 4:77–86, 1985 15. Katayama Y, Tsubokawa T, Hirasawa T, Takahata T, Nemoto N: Intradural extraosseous chordoma in the foramen magnum region. Case report. J Neurosurg 75:976–979, 1991 16. Lantos PL, Louis DN, Rosenblum MK, Kleihues P: Tumours of the nervous system, in Graham DI, Lantos PL (eds): Greenfield’s Neuropathology, ed 7. London: Arnold, 2002, Vol 2, pp 767–1052 17. Ling SS, Sader C, Robbins P, Rajan GP: A case of giant ecchordosis physaliphora: a case report and literature review. Otol Neurotol 28:931–933, 2007 18. Macdonald RL, Cusimano MD, Deck JH, Gullane PJ, Dolan EJ: Cerebrospinal fluid fistula secondary to ecchordosis physaliphora. Neurosurgery 26:515–519, 1990 19. Macdonald RL, Deck JH: Immunohistochemistry of ecchordosis physaliphora and chordoma. Can J Neurol Sci 17:420– 423, 1990 20. Mapstone TB, Kaufman B, Ratcheson RA: Intradural chordoma without bone involvement: nuclear magnetic resonance (NMR) appearance. Case report. J Neurosurg 59:535–537, 1983 21. Matsuno A, Sasaki T, Nagashima T, Matsuura R, Tanaka H, Hirakawa M, et al: Immunohistochemical examination of proliferative potentials and the expression of cell cycle-related proteins of intracranial chordomas. Hum Pathol 28:714–719, 1997 22. Mehnert F, Beschorner R, Küker W, Hahn U, Nägele T: Retroclival ecchordosis physaliphora: MR imaging and review of the literature. AJNR Am J Neuroradiol 25:1851–1855, 2004 23. Ng SH, Ko SF, Wan YL, Tang LM, Ho YS: Cervical ecchordosis physaliphora: CT and MR features. Br J Radiol 71:329– 331, 1998 24. Nishigaya K, Kaneko M, Ohashi Y, Nukui H: Intradural retroclival chordoma without bone involvement: no tumor regrowth 5 years after operation. Case report. J Neurosurg 88: 764–768, 1998 25. Rodríguez L, Colina J, López J, Molina O, Cardozo J: Intradural prepontine growth: giant ecchordosis physaliphora or extraosseous chordoma? Neuropathology 19:336–340, 1999 26. Rotondo M, Natale M, Mirone G, Cirillo M, Conforti R, Scuotto A: A rare symptomatic presentation of ecchordosis physaliphora: neuroradiological and surgical management. J Neurol Neurosurg Psychiatry 78:647–649, 2007 27. Sarasa JL, Fortes J: Ecchordosis physaliphora: an immunohistochemical study of two cases. Histopathology 18:273–275, 1991 28. Sassin JF: Intracranial chordoma, in Vinkin PJ, Bruyn GW (eds): Handbook of Clinical Neurology: Tumours of the Brain and Skull, Part III. New York: Elsevier, 1975, pp 151– 164 29. Srinivasan A, Goyal M, Kingstone M: Case 133: Ecchordosis physaliphora. Radiology 247:585–588, 2008
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Giant ecchordosis physaliphora in an adolescent girl 30. Stam FC, Kamphorst W: Ecchordosis physaliphora as a cause of fatal pontine hemorrhage. Eur Neurol 21:90–93, 1982 31. Stewart MJ, Burrow J le F: Ecchordosis physaliphora sphenooccipitalis. J Neurol Psychopathol 4:218–220, 1923 32. Takeyama J, Hayashi T, Shirane R: Notochordal remnant-derived mass: ecchordosis physaliphora or chordoma? Pathology 38:599–600, 2006 33. Tashiro T, Fukuda T, Inoue Y, Nemoto Y, Shakudo M, Katsuyama J, et al: Intradural chordoma: case report and review of the literature. Neuroradiology 36:313–315, 1994 34. Toda H, Kondo A, Iwasaki K: Neuroradiological characteristics of ecchordosis physaliphora. Case report and review of the literature. J Neurosurg 89:830–834, 1998 35. Watanabe A, Yanagita M, Ishii R, Shirabe T: Magnetic resonance imaging of ecchordosis physaliphora—case report. Neurol Med Chir (Tokyo) 34:448–450, 1994 36. Wolfe JT III, Scheithauer BW: “Intradural chordoma” or “gi-
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ant ecchordosis physaliphora”? Report of two cases. Clin Neuropathol 6:98–103, 1987 37. Wyatt RB, Schochet SS Jr, McCormick WF: Ecchordosis physaliphora. An electron microscopic study. J Neurosurg 34:672–677, 1971 38. Yuhi F, Asakura T, Tomosugi T, Kusumoto K, Awa H, Uetsuhara K: [A case of clival chordoma without bone destruction.] No Shinkei Geka 14:547–552, 1986 (Jpn) Manuscript submitted February 27, 2013. Accepted May 23, 2013. Please include this information when citing this paper: published online August 2, 2013; DOI: 10.3171/2013.5.PEDS1395. Address correspondence to: William T. Couldwell, M.D., Ph.D., Department of Neurosurgery, University of Utah, 175 N. Medical Dr. East, Salt Lake City, UT 84132. email: [email protected].
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Giant ecchordosis physaliphora in an adolescent girl Case report Khaled M. Krisht, M.D.,1 Cheryl A. Palmer, M.D., 2 Anne G. Osborn, M.D., 3 and William T. Couldwell, M.D., Ph.D.1 1 3
Department of Neurosurgery, Clinical Neurosciences Center; and Departments of 2Pathology and Radiology, University of Utah, Salt Lake City, Utah
The authors describe a rare case of giant ecchordosis physaliphora (EP) in a 16-year-old female patient who presented with diplopia. Magnetic resonance imaging of the brain with Gd contrast revealed a 3.0 × 1.7 × 1.8–cm nonenhancing, extraaxial epidural mass along the dorsal aspect of the clivus that was T2 hyperintense and T1 isointense with intermediate signal on diffusion sequences. Resection via a transnasal transsphenoidal approach to the ventral clival wall resulted in a stable tumor size with no evidence of interval growth after 30 months. Although this case features a strictly extradural EP, this tumor more commonly occurs in the subdural space and requires differentiation from intradural chordoma. Unlike EP, intradural chordoma may enhance with Gd contrast, is more likely to be associated with cranial nerve palsies and brainstem symptoms, and will occasionally have an elevated MIB-1 index. In this paper the authors highlight the different possible midline locations for both EP and chordoma, the difficulty in distinguishing between intradural giant EP and intradural chordoma, and the potential occurrence of these lesions in young people despite their typically slow rate of growth, while also underscoring the need for further investigation into the tumors’ cytogenetic behavior. (http://thejns.org/doi/abs/10.3171/2013.5.PEDS1395)
Key Words • ecchordosis physaliphora • cerebrospinal fluid fistula • intradural chordoma • transsphenoidal • notochord • clivus • MIB-1 index • oncology
E
cchordosis physaliphora is a congenital hamartomatous growth of gelatinous tissue that is derived from ectopic vestigial notochord. It usually occurs in the midline along the dorsum of the clivus and, more rarely, the sacrum. Unlike clival chordomas, which usually occur in an extradural intraosseous location, EP is usually found intradurally.2,14,16,36 While cranial chordomas have a propensity for aggressive growth and recurrence causing bony destruction of the skull base and CN deficits, EP has a more indolent course and is often found incidentally in asymptomatic patients or in patients presenting with unrelated symptoms.3,8,22,26,30 At autopsy, its reported incidence is 0.5%–5%.18,30 Ecchordosis physaliphora begins as a notochord extradurally, perforates through the dorsal wall of the clivus and dura mater, ending in the intradural subarachnoid space, and may remain
Abbreviations used in this paper: CN = cranial nerve; EP = ec chordosis physaliphora.
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attached to the clivus by a thin bony stalk.4,14,17,28,29,36 The prepontine subarachnoid space is the textbook location for EP. In some instances, however, it may be isolated intradurally or present in the epidural space or is limited to the extradural space as in our case. To date, ours is the first reported case of a giant EP occurring strictly in the epidural space. Luschka first described the observation of notochord cells along the posterior clivus in 1856.31 The first microscopic description is credited to Virchow, who named the lesion “ecchondrosis physaliphora,” based on his theory that it is derived from the sphenooccipital synchondrosis.4,14,31 In 1858, Muller was the first to suggest a notochordal origin, which was confirmed in 1894 by Ribbert, who coined the term “ecchordosis physaliphora,” which remains in use today.11,22,36 Because of their typically slow rate of growth, EPs This article contains some figures that are displayed in color online but in black-and-white in the print edition.
J Neurosurg: Pediatrics / Volume 12 / October 2013
Giant ecchordosis physaliphora in an adolescent girl are generally small lesions. Unlike chordomas, which are radically resected and then treated with proton beam radiation given their destructive and invasive behavior, EPs can be managed expectantly with serial MRI follow-up since they have a low propensity for growth.28,32 Giant symptomatic EPs, however, may require resection. To date, 3 reported cases of giant EPs in adults have been reported, but no case has occurred in a pediatric patient and never one restricted to the epidural space.
Case Report History and Examination. A previously healthy 16-year-old girl presented with a 2-month history of headaches and worsening double vision. On clinical evaluation, she was noted to have bilateral CN VI palsies with no other neurological findings. A 1-mm, thin-sliced CT scan of the head demonstrated a low-density mass lesion at the dorsal margin of the clivus causing mild bony remodeling and irregularity with a small area of calcified bone stalk consistent with a notochord remnant (Fig. 1). Magnetic resonance imaging of the brain with Gd contrast revealed a 3.0 × 1.7 × 1.8–cm nonenhancing, extraaxial epidural mass along the dorsal aspect of the clivus that was T2 hyperintense and T1 isointense with intermediate signal on diffusion sequences. There was evident mass effect causing indentation of the ventral pons and displacement of the basilar artery to the left of midline (Fig. 2). The preoperative differential diagnosis was either a large epidural EP or a chordoma.
Fig. 2. Sagittal T2-weighted MR image (A) of the brain demonstrating the extradural location of the tumor as evidenced by tenting of the clival dura (arrow). Axial T2-weighted MR image (B) showing slight leftward displacement of the basilar trunk (arrow) by the mass. Sagittal (C) and axial (D) T1-weighted MR images with Gd revealing a 3.0 × 1.7 × 1.8–cm nonenhancing, extraaxial epidural mass along the dorsal aspect of the clivus (C, asterisk).
Treatment. A frameless stereotactic-guided, microscope-assisted transnasal transsphenoidal approach to the ventral clival wall was undertaken. The inferior posterior wall of the sphenoid sinus forming the ventral cortical wall of the clivus was carefully drilled with a 4-mm diamond drill all the way to and through the posterior cortex. The tumor was noted to be lying in the epidural space and was gelatinous and avascular in consistency. Several specimens were carefully resected and sent to pathology for both frozen and permanent sections. Frozen section revealed a probable EP, and we decided to decompress the lesion to remove pressure on the abducent nerves bilaterally, but a wide excision was not performed. No fat
Histopathology. Microsections of a yellow-tan, irregular soft tissue specimen revealed scattered physaliphorous cell nests with a lobular growth pattern. Cells contained a vacuolated eosinophilic cytoplasm with a mucin-filled matrix (Fig. 3 left). No mitotic activity or cellular pleomorphism was noted. Immunohistochemical staining with proliferation marker MIB-1 showed a relatively low proliferation index (Fig. 3 right). A final diagnosis of a clival chondroid lesion most consistent with EP was made.
Fig. 1. Sagittal (left) and axial (right) 1-mm, thin-sliced CT scans of the head demonstrating a low-density mass lesion at the dorsal margin of the clivus causing mild bony remodeling and irregularity with a small area of calcified bone stalk (arrows).
Fig. 3. Left: Photomicrograph showing hypocellular physaliphorous cells with a lobular growth pattern. These cells were eosinophilic with large prominent intracytoplasmic vacuoles and myxomatous matrices. No mitosis or cellular pleomorphism was noted. Right: Immunohistochemical staining for MIB-1 marker indicative of a low proliferation index. H & E (left), original magnifications ×200.
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or fascia graft was necessary because there was no CSF leak.
Postoperative Course. The patient had a short and
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K. M. Krisht et al. uneventful postoperative course. A postoperative CT scan of her head demonstrated interval reduction in the tumor size and improvement in the mass effect. She was discharged home on postoperative Day 1. Since undergoing her procedure, she has been seen in the clinic for the 2-, 4-, and 30-month clinical and MRI follow-ups. She has experienced complete and persistent resolution of her diplopia and demonstrated a stable residual lesion with no evidence of interval growth.
Discussion
Phylogenetically, the notochord represents the primitive skeleton of vertebrates. It forms during the 3rd week of gestation and eventually becomes the nucleus pulposus of the intervertebral disk. Heterotopic cells may be found outside the nucleus pulposus anywhere along the axial skeleton.17,24,30,32 The complex course of the notochord within the clivus and sacrum makes those regions more susceptible to harboring vestigial notochord cells that can result in EP. Although these cells usually have an intraosseous location, they occasionally perforate through the dorsal wall of the clivus into the subdural and subarachnoid spaces, which may explain the pathogenesis of EP at the prepontine region.4,18,28,29,36 With EP, there is often a bony stalk that connects it with the clivus, emphasizing its clival origin.17,24,32 This potential continuum of cells from the clivus to the intradural space explains the occurrence of lesions anywhere along this path, such as was seen in our case in which the lesion was isolated in the epidural spaces. Histological examination reveals striking similarities among EP, primitive notochord, and chordoma. They all exhibit physaliphorous cells with an abundance of intracytoplasmic vacuoles and extracellular mucin.2,6,21,23,24,26,27,37 These histological qualities lend to their iso- to hypointensity on T1-weighted MRI and hyperintensity on T2weighted MRI.6,22,23,34,35 However, EP demonstrates no contrast enhancement, unlike chordomas, which usually enhance and are more often located extradurally.3,21,35 These are helpful features in making the distinction between the two lesions. When radiographically evaluating these lesions, we recommend thin-section transverse T2weighted images of the skull base.22 Because of the small size of the lesion and the possible artifacts in the posterior fossa, CT scanning seems to have limited utility unless magnified, thin-sliced bone windows through the skull base are obtained. Chordomas tend to be faster growing and more aggressive, often causing CN deficits and bony infiltration. The increased propensity of chordoma cells to multiply and grow is underscored by the relatively higher proliferation index of their MIB-1 proliferation marker, which is another helpful distinguishing feature.9,12,13,17,19,22,25 Ecchordosis physaliphora, instead, is usually slow growing and therefore rarely causes direct symptoms. It is often discovered incidentally as part of an evaluation for unrelated symptoms. Many of these lesions go undetected throughout a person’s lifetime and are only found later at autopsy (Fig. 4). Among the 18 in-hospital cases described in the literature, 2 instances of EP were discovered at au330
Fig. 4. A representative photograph of an intradural EP found at autopsy (arrow). Note the gelatinous tan-looking appearance of the tumor. Used with permission from Amirsys, Inc.
topsy (Table 1). In 1 patient, a fatal subarachnoid hemorrhage from a ruptured EP was believed to be the direct cause of death.12 In the second patient, the discovered EP had no relation to the cause of death, which was a fatal heart infarction.1 Among the remaining 16 cases (not including our case), 10 were reported as incidental. Among the 6 symptomatic cases, 2 patients presented with CSF rhinorrhea due to a skull base CSF fistula, 1 patient presented with facial pain, and a fourth patient presented with diplopia.2,4,18,26 In these cases, the symptomatology was consistent with the potential effects of the lesion given its proximity to the clivus and pons. In the remaining 2 cases, the reported symptoms were headaches, dizziness, or confusion, which might have been caused by the EP but were very likely coincidental.3,25 The difficulty in diagnosis arises when attempting to differentiate intradural EP from intradural chordomas. The latter have a slower growth pattern compared with the classic intraosseous infiltrating chordomas and may be very difficult to distinguish from intradural EP. Just like EP, intradural chordomas may have a low MIB-1 index, making it difficult to discern the two based on immunohistochemical means as well.15,21,25,36 The MRI and CT characteristics may be helpful in distinguishing between the two. Intradural chordomas almost never have an associated stalk, and, unlike EP, they usually enhance with Gd administration.5,10,15,16,20,22,24,38 However, there are cases of isolated intradural EP without a stalk, and in some rare cases, an intradural chordoma may not demonstrate enhancement. Another important consideration is the clinical presentation. Patients with intradural chordoma are more likely to present with compressive symptoms such as CN deficits. The lack of a clear-cut distinction between intradurally located EP and chordoma has led some to believe that they signify the same spectrum of disease and that intradural chordoma may represent a J Neurosurg: Pediatrics / Volume 12 / October 2013
Giant ecchordosis physaliphora in an adolescent girl TABLE 1: Literature summary of in-hospital cases of EP* Authors & Year
Age (yrs), Sex
Max Tumor Diameter (cm)
Macdonald et al., 1990 Watanabe et al., 1994 Akimoto et al., 1996 Toda et al., 1998 Rodríguez et al., 1999 Cha et al., 2002 Mehnert et al., 2004
66, F 48, M 51, F 56, F 54, F 49, M 71, M 38, M 74, M 55, F 10, M 47, F 45, M 52, F 48, F 31, F 22, M 78, M 17, F
NA NA NA 1.5 3 1.5 1.3 0.5 0.6 0.5 0.3 NA 3 1.3 3.2 NA NA 0.6 3
Rotondo et al., 2007 Ling et al., 2007 Alli et al., 2008 Fracasso et al., 2008 Srinivasan et al., 2008 Alkan et al., 2009 Adamek et al., 2011 present case
Presenting Symptoms CSF rhinorrhea incidental headache, diplopia incidental dizziness incidental incidental incidental incidental incidental incidental headache, facial pain incidental CSF rhinorrhea autopsy incidental headache, confusion autopsy headache, diplopia
* NA = not available.
symptomatic form of EP (Table 2).7,26,33 Rodríguez et al.25 have proposed this notion and have recommended that instances of intradural chordoma be classified as giant or symptomatic EP. In our case, the patient’s 3-cm lesion was symptomatic, showed no contrast enhancement, was noted to have a bony stalk connecting through the clivus, lacked bony infiltration and destruction, revealed a low MIB-1 index level, and demonstrated no interval growth 30 months after resection—all factors consistent with a diagnosis of a symptomatic giant EP. In the literature, only 3 other cases of giant EPs measuring at least 3 cm in their widest diameter have been reported. Unlike our case, however, those cases were all discovered in adults and were located in the prepontine subdural space (Table 1). Rodríguez et al.25 described the case of a 54-year-old woman with a 3-cm EP who had presented with a 1.5-year history of dizzi-
ness. Ling et al.17 documented the case of a 45-year-old man who presented with left-sided hearing loss and tinnitus, which led to an MR image of the brain demonstrating an incidental 30 × 30 × 14–mm EP. Finally, Fracasso et al.12 reported an unusual case of a fatal subarachnoid hemorrhage due to a ruptured giant EP measuring 3.2 cm that was discovered at autopsy. To our knowledge, ours is the first instance of a giant symptomatic EP in an adolescent. The majority of reported cases have fallen in the age group of 21–60 years (13 of 19 patients), with a mean age of 48 years and a female/male ratio of 1.1:1. Given the slow-growing, asymptomatic nature of EP, the present case is a unique presentation in a pediatric patient. The only other case of EP in a young patient was provided by Mehnert et al.,22 who described a small, 3-mm lesion in a 10-year-old boy identified during a review of 300 consecutive 1.5-T MRI studies in asymptomatic subjects.
TABLE 2: Distinguishing features of intra- and extradurally located EP and chordoma Pathology
Intradural Location
Extradural Location
chordoma
small size low MIB-1 index contrast enhancing no bony stalk may have CN involvement small size low MIB-1 index rarely contrast enhances may have bony stalk rarely has CN involvement
larger size invasive w/ increased MIB-1 index contrast enhancing no bony stalk CN involvement usually small size low MIB-1 index rarely contrast enhances may have bony stalk may have CN involvement
EP
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K. M. Krisht et al. Conclusions
Ecchordosis physaliphora and intradural chordoma are phylogenetically, histologically, and clinically closely related lesions that may represent the same spectrum of disease. In some instances, such as in our case, the distinction can be easily made; in other cases, it may be very difficult to differentiate between the two. Contrast enhancement, elevated MIB-1 levels, and brainstem/CN involvement remain important features that help to distinguish intradural chordoma from EP. While EP has an indolent growth and rarely causes symptoms throughout a person’s lifetime, our case demonstrates that these tumors can, in fact, be large and cause compressive symptoms early in life. In such cases, surgery may be necessary. The strictly extradural location of this particular EP indicates that EP, like chordoma, can be isolated to the epidural space and that both disease entities can occupy any space extending from the clivus to the prepontine cistern, with EP having a greater propensity for the subdural space and chordoma for the extradural space. Although difficult given the rarity of EP, further investigation into its cytogenetics is needed for more accurate diagnosis and prognostication. Disclosure Dr. Osborn has direct stock ownership in Amirsys Inc. and Amirsys Publishing Inc. Author contributions to the study and manuscript preparation include the following. Conception and design: Couldwell. Acquisition of data: Krisht. Analysis and interpretation of data: Krisht, Palmer. Drafting the article: Krisht. Critically revising the article: all authors. Reviewed submitted version of manuscript: all authors. Approved the final version of the manuscript on behalf of all authors: Couldwell. Administrative/technical/material support: Osborn. References 1. Adamek D, Malec M, Grabska N, Krygowska-Wajs A, Gałą zka K: Ecchordosis physaliphora—a case report and a review of notochord-derived lesions. Neurol Neurochir Pol 45: 169–173, 2011 2. Akimoto J, Takeda H, Hashimoto T, Haraoka J, Ito H: [A surgical case of ecchordosis physaliphora.] No Shinkei Geka 24: 1021–1025, 1996 (Jpn) 3. Alkan O, Yildirim T, Kizilkiliç O, Tan M, Cekinmez M: A case of ecchordosis physaliphora presenting with an intratumoral hemorrhage. Turk Neurosurg 19:293–296, 2009 4. Alli A, Clark M, Mansell NJ: Cerebrospinal fluid rhinorrhea secondary to ecchordosis physaliphora. Skull Base 18:395– 399, 2008 5. Burger P, Scheithauer BW, Vogel F: Surgical Pathology of the Nervous System and Its Coverings. New York: Churchill Livingstone, 2002 6. Cha ST, Jarrahy R, Yong WH, Eby T, Shahinian HK: A rare symptomatic presentation of ecchordosis physaliphora and unique endoscope-assisted surgical management. Minim Invasive Neurosurg 45:36–40, 2002 7. Ciarpaglini R, Pasquini E, Mazzatenta D, Ambrosini-Spaltro A, Sciarretta V, Frank G: Intradural clival chordoma and ecchordosis physaliphora: a challenging differential diagnosis: case report. Neurosurgery 64:E387–E388, 2009 8. Congdon CC: Benign and malignant chordomas; a clinicoanatomical study of twenty-two cases. Am J Pathol 28:793– 821, 1952
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Giant ecchordosis physaliphora in an adolescent girl 30. Stam FC, Kamphorst W: Ecchordosis physaliphora as a cause of fatal pontine hemorrhage. Eur Neurol 21:90–93, 1982 31. Stewart MJ, Burrow J le F: Ecchordosis physaliphora sphenooccipitalis. J Neurol Psychopathol 4:218–220, 1923 32. Takeyama J, Hayashi T, Shirane R: Notochordal remnant-derived mass: ecchordosis physaliphora or chordoma? Pathology 38:599–600, 2006 33. Tashiro T, Fukuda T, Inoue Y, Nemoto Y, Shakudo M, Katsuyama J, et al: Intradural chordoma: case report and review of the literature. Neuroradiology 36:313–315, 1994 34. Toda H, Kondo A, Iwasaki K: Neuroradiological characteristics of ecchordosis physaliphora. Case report and review of the literature. J Neurosurg 89:830–834, 1998 35. Watanabe A, Yanagita M, Ishii R, Shirabe T: Magnetic resonance imaging of ecchordosis physaliphora—case report. Neurol Med Chir (Tokyo) 34:448–450, 1994 36. Wolfe JT III, Scheithauer BW: “Intradural chordoma” or “gi-
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ant ecchordosis physaliphora”? Report of two cases. Clin Neuropathol 6:98–103, 1987 37. Wyatt RB, Schochet SS Jr, McCormick WF: Ecchordosis physaliphora. An electron microscopic study. J Neurosurg 34:672–677, 1971 38. Yuhi F, Asakura T, Tomosugi T, Kusumoto K, Awa H, Uetsuhara K: [A case of clival chordoma without bone destruction.] No Shinkei Geka 14:547–552, 1986 (Jpn) Manuscript submitted February 27, 2013. Accepted May 23, 2013. Please include this information when citing this paper: published online August 2, 2013; DOI: 10.3171/2013.5.PEDS1395. Address correspondence to: William T. Couldwell, M.D., Ph.D., Department of Neurosurgery, University of Utah, 175 N. Medical Dr. East, Salt Lake City, UT 84132. email: [email protected].
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