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Melanotic neuroectodermal tumor of infancy in the skull: case report and review of the literature
Surgical Neurology 63 (2005) 275 – 280 www.surgicalneurology-online.com
Melanotic neuroectodermal tumor of infancy in the skull: case report and review of the literature Masato Matsumoto, MD*, Jun Sakuma, MD, Kyouichi Suzuki, MD, Masahisa Kawakami, MD, Tatsuya Sasaki, MD, Namio Kodama, MD Department of Neurosurgery, Fukushima Medical University, Fukushima 960-1295, Japan Received 31 December 2003; accepted 12 February 2004
Abstract
Background: Melanotic neuroectodermal tumor of infancy (MNTI) is a rare neoplasm that develops during the first year of life and grows rapidly. Early diagnosis and radical surgery are critical for a long-term cure. We report a rare case of MNTI in the skull and discuss the importance of the radical surgery and the long-term follow-up results. Case Presentation: We describe a case of a 4-month-old girl with an MNTI in the skull who underwent the operation 11 years ago. The mass in the frontotemporosphenoid region grew rapidly after birth. The patient underwent a craniotomy. By referring to the histological findings of frozen section during surgery, a total excision of the tumor including its adjacent hypertrophic bone was performed. The patient has remained well without evidence of recurrence or neurological abnormality for 11 years. Conclusion: Radical surgery for MNTI provides complete cure. According to the literature including our case, there should be follow-up for at least 2 years after surgery. Especially in cases in which tumors recur, follow-up should be for longer periods because of the possibility of its malignant change. D 2005 Elsevier Inc. All rights reserved.
Keywords:
Infant; Melanotic neuroectodermal tumor; Skull; Surgery
1. Introduction Melanotic neuroectodermal tumor of infancy (MNTI) is a rare neoplasm that often occurs during the first year of life. Since the first description of an MNTI in 1918 by Krompecher [22], a variety of terms [1-3,7,19,23] have been used, such as melanotic adamantinoma, melanotic progonoma, retinal angle tumor, and melanotic carcinoma, because of the obscure origin of the tumor cell and its histogenesis [4,20]. By recent ultrastructural, immunocytochemical, and electron microscopic studies [9,11,31,34], the concept that the tumor cell originated from the neural crest has been widely accepted.
* Corresponding author. Tel.: +81 24 547 1267; fax: +81 24 548 1803. E-mail address: [email protected] (M. Matsumoto). 0090-3019/$ – see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.surneu.2004.02.032
The tumor commonly occurs in the maxilla [12,14,25,26], followed by the skull [1,5,7,11,16,17,19-21,30-33,35], mandible [28,38], and brain [8,37]. The tumor in the skull arises at the suture [31], with the most common site being the anterior fontanelle [4,7,16,17,30,32,33], followed by the temporoparietal [19] and frontotemporosphenoid [3,13,21] regions. Although MNTI is believed to be benign, it grows rapidly, and the recurrence and malignancy rates have been reported to be 10% to 15% and 1.9% to 6.6%, respectively [17,26,29]. In spite of the high recurrent rate, some patients have acquired good outcome and long-term cure after radical surgery [3,4,7,10,11,16,17,32]. We report an 11-year-old girl who underwent radical excision of MNTI arising from the skull at the age of 4 months. To date, there is no evidence of tumor recurrence. We also present a review of the literature and stress the importance of radical surgery for achieving favorable outcomes.
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2. Case report At the age of 3 months, this 11-year-old patient was brought to the pediatric department of our hospital because her mother noticed a lump in the right temporal region. The mass was 15 15 mm in size. At birth, there had been no abnormal skull deformities. One month later, she was referred to our department because the mass grew rapidly (Fig. 1). The tumor was firm, immobile, nontender, and fixed to the underlying skull with well-defined margins. The skin overlying the tumor was intact and freely movable, which measured 35 30 mm. Neurological and laboratory examinations revealed no abnormal findings. Urinary examination did not show the excretion of vanillylmandelic acid and cathecholamine. Plain radiographs showed a welldemarcated radiolucency in the right temporal bone, with apparent destruction of the superolateral orbital wall (Fig. 2). Computer tomography scans demonstrated a slightly high density mass that was homogenously enhanced, with highdensity area and associated reactive sclerosis and hyperostosis of the adjacent bone (Fig. 3). When the skin over the tumor was resected, the mass did not adhere to its surrounding tissue (Fig. 4A). The tumor was firm and bled minimally. We removed it piece by piece. Macroscopically, the tumor consisted of a grayish portion in the center surrounded by a white portion (Fig. 4B). The epidural tumor and its surrounding thickened and abnormal bone, including the superolateral wall of the right orbital, were completely removed. The tumor was not adhered to the
Fig. 2. A skull film showing a right radiolucent area with thickening of the adjacent temporal bone.
dura mater. The operation was terminated after intraoperative histological confirmation that the frozen section did not contain any evidence of tumor cells at the surgical margin of the removed bone. The tumor consisted of nests of hyperchromatic cells with hypercellularity surrounded by abundant dense fibrous stroma (Fig. 5A). The nests involved 2 distinct cell types. The first type consisted of small cells with a dark-staining hyperchromatic nucleus with scanty cytoplasm; the second was hypochromatic cuboidal cells. Some cells of both types contained granular melanin pigments (Fig. 5B). Electron microscopic examination demonstrated an oval nucleus with premelanosomes and melanosomes at various stages of maturation (Fig. 5C). 2.1. Postoperative course The postoperative course was uneventful. Magnetic resonance images showed neither residual tumor nor recurrence 8 months after the operation (Fig. 6). For the next 11 years, the patient was regularly followed up at the pediatric department. At present, her mental and physical development is normal with no evidence of tumor recurrence.
3. Discussion
Fig. 1. Photograph showing right temporal swelling.
Of the more than 200 cases of MNTI reported in the literature [17], 95% developed during infancy under 1 year of age [4,9]. According to a review of the literature, approxi-
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Fig. 3. A: Computer tomography scans demonstrating a slightly high density mass with a high-density area in the center. B: The area of the slightly high density area was homogenously enhanced.
mately 40 cases of MNTI in the skull have been reported [1,4,5,7,8,10,11,16,17,19-21,30-33,35]. Only 4 cases of MNTI arising from the frontotemporosphenoid area have been reported, including the present case [3,13,21]. The tumor is characterized by rapid growth within a few months [4,17]. In our case, the tumor more than doubled within 1 month. Although MNTI has been considered to be benign [20], a relatively high mortality rate (25%) for patients has been described [33]. Jones et al [19] found that 6 of 29 cases of MNTI in the skull had died during surgery or in the immediate postoperative period. Hoshino et al [17]
speculated that the rapid fall in secretion of catecholamine levels after surgery might play a role in the high mortality of patients with MNTI associated with high serum levels of catecholamine. Alternatively, extensive intraoperative bleeding of midline tumors due to their adherence to the sinuses [20,35], recurrence, or a malignant course may account for the high mortality rate [11,26,35,36]. Favorable outcomes have been achieved by radical surgery alone [11,30], and even in a patient with malignant MNTI, the patient produced a good outcome with no evidence of recurrence during 5 years after extensive resection [10].
Fig. 4. Intraoperative photograph showing the tumor (A) beneath the skin and its cut surface, revealing a central grayish portion surrounded by a white portion (B).
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Fig. 5. Photomicrographs of the tumor specimens. A: Small hyperchromatic cell nests were surrounded by abundant dense fibrous tissue stroma. Note the characteristic alveolar-like pattern (hematoxylin-eosin, original magnification 100). B: Some of the cuboidal and small dark cells surrounded by dense fibrous stroma contain abundant pigment granules (hematoxylin-eosin, original magnification 400). C: Electron micrograph demonstrating oval-shaped nuclei and premelanosomes (short arrow) and maturing melanosome (long arrows) in the cytoplasm (original magnification 12 000).
Our survey indicated 11 cases, including our present case, with available information on the follow-up periods of MNTI in the skull (Table 1). In 2 [4,11] of 10 cases, the
Fig. 6. Gadolinium diethylenetriaminepentaacetic acid–enhanced T1weighted magnetic resonance image obtained 8 months after surgery demonstrating no tumor recurrence.
tumor recurred after resection because the invaded venous sinuses were not excised. Both patients underwent aggressive resection of the recurrent tumor and invaded venous sinuses, which carried excellent outcome without recurrence. In another 9 patients, radical resection produced favorable outcomes. The recurrences occur in a bimodal time pattern [20]. Some occur within 30 days after treatment, and others are delayed for long periods. There has been no detailed description regarding the optimal follow-up period. According to the literature, to our knowledge, the longest period between treatment and recurrence was 18 months [26], suggesting that it should be followed up for at least 2 years after resection. Likewise, cases in which tumor recurs should be followed up for long periods because of the possible rare malignant change in the tumor [20]. We intraoperatively confirmed the absence of tumor cells at the resected margin of the bone. Histological examination of frozen sections provides useful information for determining the extent of removal required for radical resection [12]. At present, there is no convincing evidence that supports the effectiveness of chemotherapy or radiation [10,11]. Therefore, we should endeavor to perform radical surgery even in the critical structures [4,10,11,17]. Consistent with previously reported ultrastructural studies, the tumor specimen contained premelanosomes and melanosomes at various stages of maturation [9,34].
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Table 1 Reports of MNTI in the skull that have available information on surgery, recurrence, and follow-up period Author and year
Age (mo) and gender
Location
First operation
Recurrence
Second operation
Follow-up (y)
Clarke et al, 1951 [7]
9, male
Anterior fontanelle
No
Not performed
1.2
Anagnostopoulos and Everrard, 1972 [3] Gilmor and Mealey, 1972 [16]
7, male
Temporosphenoid
No
Not performed
0.5
3, male
Anterior fontanelle
No
Not performed
1.7
Pascalis et al, 1977 [32]
6, female
Anterior fontanelle
No
Not performed
4
Atkinson et al, 1989 [4]
2, female
Anterior fontanelle
Resection of tumor, adjacent bone, and SSS Resection of tumor and adjacent bone Resection of tumor and cauterization of the dura Resection of tumor and SSS Resection of tumor without invaded dura
+
1
Kacker et al, 1993 [20]
3, male
Resection of tumor
No
0.5
Hoshino et al, 1994 [17]
5, male
Squamous and occipital Retromastoid
Resection of tumor and invaded sinuses Not performed
No
Not performed
0.7
Dammann et al, 1995 [10]
2, male
Temporal (malignant)
No
Not performed
5
Dashti et al, 1999 [11]
2, male
Retromastoid
Resection of tumor and adjacent bone Resection of tumor and adjacent bone Resection of tumor and curetting of the invaded dura
+
2
Nishio et al, 1999 [30]
4, female
Anterior fontanelle
No
Present report
4, female
Temporosphenoid
Resection of tumor and adjacent bone Resection of tumor and adjacent bone
Resection of tumor and invaded sinuses Not performed
No
Not performed
0.5 11
SSS indicates superior sagittal sinus.
Cutler et al [9] reported that MNTI has 2 distinct types of melanin-producing cell. The first type has an irregularly shaped nucleus cell, and the cytoplasm contained numerous premelanosomes and mature melanosomes. The second type has a large oval nucleus, and the cytoplasm contained a few melanin granules. Pettinato et al [34] described that melanin-producing cells, such as ovoid with cytoplasm, contained numerous premelanosomes in a laminar matrix and dense mature melanosomes. Ours resembled the findings of Pettinato et al. Thus, the findings of ultrastructural studies that tumor cells may show several patterns of pigmented granular formation indicate a relative diversity of differentiation within the neoplasm [9]. Biochemical and DNA studies strongly suggest that the MNTI is of neural crest origin [17,31]. Early diagnosis and radical excision of the tumor can lead to excellent long-term outcome. Delayed diagnosis may cause difficulty in radical resection because the tumor invades the adjacent critical structures, such as venous sinuses and skull base. If we encounter a mass in the skull of an infant, we have to include several kinds of skull disorders in the differential diagnosis [6,18,24,27]. Although neuroradiological studies [15,17,30] are helpful for the differential diagnoses, the characteristic feature of the MNTI, which is a rapid-growing tumor in an infant, allows us to easily reach the diagnosis. Although the second operation is necessary, we should perform it and excise as much as possible, because it carries a favorable outcome and a long-term cure.
References [1] Adeloye A, Morgan SP, Aghadiuno P, Bohrer S. Melanotic ameloblastoma (retinal anlage tumour) of the skull in a Nigerian child. Surg Neurol 1977;7:42 - 4. [2] Allen Jr MS, Harrison W, Jahrdoerfer RA. bRetinal anlageQ tumors. Melanotic progonoma, melanotic adamantinoma, pigmented epulis, melanotic neuroectodermal tumor of infancy, benign melanotic tumor of infancy. Am J Clin Pathol 1969;51:309 - 14. [3] Anagnostopoulos DI, Everrard JH. Melanotic progonoma of the skull. J Neurol Neurosurg Psychiat 1972;35:88 - 91. [4] Atkinson GO, Davis PC, Patrick LE, Winn KJ, Ball TI, Wyly JB. Melanotic neuroectodermal tumor of infancy. MR findings and a review of the literature. Pediatr Radiol 1989;20:20 - 2. [5] Best PV. Pigmented tumor arising in the skull of an infant. J Pathol 1972;107:69 - 72. [6] Brat DJ, Giannini C, Scheithauer BW, Burger PC. Primary melanotic neoplasms of the central nervous system. Am J Surg Pathol 1999;23:745 - 54. [7] Clarke BE, Parsons H. An embryological tumor of retinal angle involving the skull. Cancer 1951;1:78 - 85. [8] Cohen BH, Handler MS, De Vivo DC, Garvin Jr JH, Haya AP, Caramel P. Central nervous system melanotic neuroectodermal tumor of infancy: value of chemotherapy in management. Neurology 1988;38:163 - 4. [9] Cutler LS, Chauder AP, Topazian R. Melanotic neuroectodermal tumor of infancy. An ultrastructural study, literature review, and reevaluation. Cancer 1981;48:257 - 70. [10] Dammann O, Hagel C, Allers B, Grubel G, Schulte FJ. Malignant melanotic neuroectodermal tumor of infancy. Child’s Nerv Syst 1995;11:186 - 8. [11] Dashti SR, Cohen ML, Cohen AR. Role of radical surgery for intracranial melanotic neuroectodermal tumor of infancy: case report. Neurosurgery 1999;45:175 - 8. [12] Dehner LP, Sibley RK, Sauk JJ, Vicers RT, Nesbit ME, Leonard AS, Waite DE, Neeley JE, Ophoven J. Malignant melanotic
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M. Matsumoto et al. / Surgical Neurology 63 (2005) 275–280 neuroectodermal tumor of infancy: a clinical, pathologic, ultrastructural and tissue culture study. Cancer 1979;43:1389 - 410. Dooling EC, Chi JG, Gilles FH. Melanotic neuroectodermal tumor of infancy. Cancer 1977;39:1535 - 41. El-Sagan A, Bang G, Olofsson J. Melanotic neuroectodermal tumor of infancy arising in the maxilla. J Laryngol Otol 1998;112:61 - 4. George JC, Edwards MK, Jakacki RI, Kho-Duffin J. Melanotic neuroectodermal tumor of infancy. AJNR Am J Neuroradiol 1991;12: 689 - 97. Gilmor RL, Mealey J. Melanotic neuroectodermal tumor involving the cranium in infancy. J Neurosurg 1972;36:507 - 11. Hoshino S, Takahashi H, Shimura T, Nakazawa S, Naito Z, Asano G. Melanotic neuroectodermal tumor of infancy in the skull associated with high serum levels of catecholamine. J Neurosurg 1994;80:919 - 24. Isozumi T, Tsuji A, Nakasu S, Matsuda M, Handa J. Congenital dermoid cyst over the anterior fontanelle. No Shikei Geka 1995;23: 423 - 7. Jones HH, Parker BR, Ballerio CG, Silverman FN, Kempson RL. Case report 617. Melanotic neuroectodermal tumor of infancy (melanotic progonoma) involving the calvaria. Skeletal Radiol 1990;19:527 - 30. Kacker A, Bahadur S, Singh M. Melanotic neuroectodermal tumor of infancy arising from the squamous and occipital bone. J Laryngol Otol 1993;107:843 - 4. Koudstaal J, Oldhoff J, Panders AK, Hardonk MJ. Melanotic neuroectodermal tumor of infancy. Cancer 1968;22:151 - 61. Krompecher E. Zur Histogenese und Morphologie der Adamntinoma and Sowstiger Keifergesschwulste. Beiter Pathol Anat 1918;64:165 - 7. Lurie HI. Congenital melanocarcinoma, melanotic adamantinoma, retinal anlage tumor, progonoma, and pigmented epulis of infancy. Summary and review of the literature and report of the first case in adult. Cancer 1961;14:1090 - 108. Mahapatra AK, Suri A. Anterior encephalocele: a study of 92 cases. Pedir Neurosurg 2002;36:113 - 8. Mast BA, Kapadia SB, Yunis E, Bentz M. Subtotal maxillectomy for melanotic neuroectodermal tumor of infancy. Plast Reconstr Surg 1999;103:1961 - 3.
[26] Nagase M, Ueda K, Fukushima M, Nakajima T. Recurrent melanotic neuroectodermal tumor of infancy. Case report and survey of 16 cases. J Maxillofac Surg 1983;11:131 - 6. [27] Nakasu Y, Nakasu S, Minouchi K. Multiple sinus pericranii with systemic angioma. Surg Neurol 1993;39:41 - 5. [28] Navas Papacios JJ. Malignant melanotic neuroectodermal tumor. Light and electron microscopic study. Cancer 1980;46:529 - 36. [29] Nikai H, Ijuhnin N, Yamasaki A, Niitani K, Imai K. Ultrastructural evidence for neural crest origin of the melanotic neuroectodermal tumor of infancy. J Oral Pathol 1977;6:221 - 32. [30] Nishio S, Morioka T, Murakami N, Fukui M, Inamitsu T, Ishihara S. Melanotic neuroectodermal tumour of infancy at the anterior fontanelle. Neuroradiol 1999;41:202 - 4. [31] Nitta T, Endo T, Tsunoda AY, Matsumoto T, Sato K. Melanotic neuroectodermal tumor of infancy: a molecular approach to diagnosis. J Neurosurg 1995;83:145 - 8. [32] Pascalis CD, Mastroiacovo P, Mastrangelo R. A melanotic neuroectodermal tumor of infancy arising from the anterior fontanel. Tumori 1977;63:373 - 80. [33] Paueksakon P, Parker JR, Fan X, Miles FG, Ruiz H, Wushensky C, Johnson MD. Melanotic neuroectodermal tumor of infancy discovered after head trauma. Pediatr Neurosurg 2002;36:33 - 6. [34] Pettinato G, Manivel JC, d’ Amore ESG, Jaszcz W, Gorlin R. Melanotic neuroectodermal tumor of infancy. A reexamination of a histogenetic problem based on immunohistochemical, flow cytometric and ultrastructural study of 10 cases. Am J Surg Path 1991;15:233 - 45. [35] Pierre-Kahn A, Cinalli G, Lellouch-Tubiana A, Villarejo FJ, SanteRose C, Pfister A, Couly G. Melanotic neuroectodermal tumor of the skull and meninges in infancy. Pediatr Neurosurg 1992;18:6 - 15. [36] Salomao JF, Duarte F. Progonoma melanotico craniano. Tumor neuroectodermico melanotico da infancia. Arq Bras Neurochir 1989;8:47 - 52. [37] Shuangshoti S. Melanotic mucin-producing neuroepithelial neoplasm of mesencephalon with consideration of similar tumours in different locations. J Neurol Neurosurg Psychiatry 1980;43:810 - 7. [38] Stirling RW, Powell G, Fletcher CDM. Pigmented neuroectodermal tumor of infancy: an immunohistological study. Histopathology 1980;12:425 - 35.
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Melanotic neuroectodermal tumor of infancy in the skull: case report and review of the literature Masato Matsumoto, MD*, Jun Sakuma, MD, Kyouichi Suzuki, MD, Masahisa Kawakami, MD, Tatsuya Sasaki, MD, Namio Kodama, MD Department of Neurosurgery, Fukushima Medical University, Fukushima 960-1295, Japan Received 31 December 2003; accepted 12 February 2004
Abstract
Background: Melanotic neuroectodermal tumor of infancy (MNTI) is a rare neoplasm that develops during the first year of life and grows rapidly. Early diagnosis and radical surgery are critical for a long-term cure. We report a rare case of MNTI in the skull and discuss the importance of the radical surgery and the long-term follow-up results. Case Presentation: We describe a case of a 4-month-old girl with an MNTI in the skull who underwent the operation 11 years ago. The mass in the frontotemporosphenoid region grew rapidly after birth. The patient underwent a craniotomy. By referring to the histological findings of frozen section during surgery, a total excision of the tumor including its adjacent hypertrophic bone was performed. The patient has remained well without evidence of recurrence or neurological abnormality for 11 years. Conclusion: Radical surgery for MNTI provides complete cure. According to the literature including our case, there should be follow-up for at least 2 years after surgery. Especially in cases in which tumors recur, follow-up should be for longer periods because of the possibility of its malignant change. D 2005 Elsevier Inc. All rights reserved.
Keywords:
Infant; Melanotic neuroectodermal tumor; Skull; Surgery
1. Introduction Melanotic neuroectodermal tumor of infancy (MNTI) is a rare neoplasm that often occurs during the first year of life. Since the first description of an MNTI in 1918 by Krompecher [22], a variety of terms [1-3,7,19,23] have been used, such as melanotic adamantinoma, melanotic progonoma, retinal angle tumor, and melanotic carcinoma, because of the obscure origin of the tumor cell and its histogenesis [4,20]. By recent ultrastructural, immunocytochemical, and electron microscopic studies [9,11,31,34], the concept that the tumor cell originated from the neural crest has been widely accepted.
* Corresponding author. Tel.: +81 24 547 1267; fax: +81 24 548 1803. E-mail address: [email protected] (M. Matsumoto). 0090-3019/$ – see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.surneu.2004.02.032
The tumor commonly occurs in the maxilla [12,14,25,26], followed by the skull [1,5,7,11,16,17,19-21,30-33,35], mandible [28,38], and brain [8,37]. The tumor in the skull arises at the suture [31], with the most common site being the anterior fontanelle [4,7,16,17,30,32,33], followed by the temporoparietal [19] and frontotemporosphenoid [3,13,21] regions. Although MNTI is believed to be benign, it grows rapidly, and the recurrence and malignancy rates have been reported to be 10% to 15% and 1.9% to 6.6%, respectively [17,26,29]. In spite of the high recurrent rate, some patients have acquired good outcome and long-term cure after radical surgery [3,4,7,10,11,16,17,32]. We report an 11-year-old girl who underwent radical excision of MNTI arising from the skull at the age of 4 months. To date, there is no evidence of tumor recurrence. We also present a review of the literature and stress the importance of radical surgery for achieving favorable outcomes.
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2. Case report At the age of 3 months, this 11-year-old patient was brought to the pediatric department of our hospital because her mother noticed a lump in the right temporal region. The mass was 15 15 mm in size. At birth, there had been no abnormal skull deformities. One month later, she was referred to our department because the mass grew rapidly (Fig. 1). The tumor was firm, immobile, nontender, and fixed to the underlying skull with well-defined margins. The skin overlying the tumor was intact and freely movable, which measured 35 30 mm. Neurological and laboratory examinations revealed no abnormal findings. Urinary examination did not show the excretion of vanillylmandelic acid and cathecholamine. Plain radiographs showed a welldemarcated radiolucency in the right temporal bone, with apparent destruction of the superolateral orbital wall (Fig. 2). Computer tomography scans demonstrated a slightly high density mass that was homogenously enhanced, with highdensity area and associated reactive sclerosis and hyperostosis of the adjacent bone (Fig. 3). When the skin over the tumor was resected, the mass did not adhere to its surrounding tissue (Fig. 4A). The tumor was firm and bled minimally. We removed it piece by piece. Macroscopically, the tumor consisted of a grayish portion in the center surrounded by a white portion (Fig. 4B). The epidural tumor and its surrounding thickened and abnormal bone, including the superolateral wall of the right orbital, were completely removed. The tumor was not adhered to the
Fig. 2. A skull film showing a right radiolucent area with thickening of the adjacent temporal bone.
dura mater. The operation was terminated after intraoperative histological confirmation that the frozen section did not contain any evidence of tumor cells at the surgical margin of the removed bone. The tumor consisted of nests of hyperchromatic cells with hypercellularity surrounded by abundant dense fibrous stroma (Fig. 5A). The nests involved 2 distinct cell types. The first type consisted of small cells with a dark-staining hyperchromatic nucleus with scanty cytoplasm; the second was hypochromatic cuboidal cells. Some cells of both types contained granular melanin pigments (Fig. 5B). Electron microscopic examination demonstrated an oval nucleus with premelanosomes and melanosomes at various stages of maturation (Fig. 5C). 2.1. Postoperative course The postoperative course was uneventful. Magnetic resonance images showed neither residual tumor nor recurrence 8 months after the operation (Fig. 6). For the next 11 years, the patient was regularly followed up at the pediatric department. At present, her mental and physical development is normal with no evidence of tumor recurrence.
3. Discussion
Fig. 1. Photograph showing right temporal swelling.
Of the more than 200 cases of MNTI reported in the literature [17], 95% developed during infancy under 1 year of age [4,9]. According to a review of the literature, approxi-
M. Matsumoto et al. / Surgical Neurology 63 (2005) 275–280
277
Fig. 3. A: Computer tomography scans demonstrating a slightly high density mass with a high-density area in the center. B: The area of the slightly high density area was homogenously enhanced.
mately 40 cases of MNTI in the skull have been reported [1,4,5,7,8,10,11,16,17,19-21,30-33,35]. Only 4 cases of MNTI arising from the frontotemporosphenoid area have been reported, including the present case [3,13,21]. The tumor is characterized by rapid growth within a few months [4,17]. In our case, the tumor more than doubled within 1 month. Although MNTI has been considered to be benign [20], a relatively high mortality rate (25%) for patients has been described [33]. Jones et al [19] found that 6 of 29 cases of MNTI in the skull had died during surgery or in the immediate postoperative period. Hoshino et al [17]
speculated that the rapid fall in secretion of catecholamine levels after surgery might play a role in the high mortality of patients with MNTI associated with high serum levels of catecholamine. Alternatively, extensive intraoperative bleeding of midline tumors due to their adherence to the sinuses [20,35], recurrence, or a malignant course may account for the high mortality rate [11,26,35,36]. Favorable outcomes have been achieved by radical surgery alone [11,30], and even in a patient with malignant MNTI, the patient produced a good outcome with no evidence of recurrence during 5 years after extensive resection [10].
Fig. 4. Intraoperative photograph showing the tumor (A) beneath the skin and its cut surface, revealing a central grayish portion surrounded by a white portion (B).
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M. Matsumoto et al. / Surgical Neurology 63 (2005) 275–280
Fig. 5. Photomicrographs of the tumor specimens. A: Small hyperchromatic cell nests were surrounded by abundant dense fibrous tissue stroma. Note the characteristic alveolar-like pattern (hematoxylin-eosin, original magnification 100). B: Some of the cuboidal and small dark cells surrounded by dense fibrous stroma contain abundant pigment granules (hematoxylin-eosin, original magnification 400). C: Electron micrograph demonstrating oval-shaped nuclei and premelanosomes (short arrow) and maturing melanosome (long arrows) in the cytoplasm (original magnification 12 000).
Our survey indicated 11 cases, including our present case, with available information on the follow-up periods of MNTI in the skull (Table 1). In 2 [4,11] of 10 cases, the
Fig. 6. Gadolinium diethylenetriaminepentaacetic acid–enhanced T1weighted magnetic resonance image obtained 8 months after surgery demonstrating no tumor recurrence.
tumor recurred after resection because the invaded venous sinuses were not excised. Both patients underwent aggressive resection of the recurrent tumor and invaded venous sinuses, which carried excellent outcome without recurrence. In another 9 patients, radical resection produced favorable outcomes. The recurrences occur in a bimodal time pattern [20]. Some occur within 30 days after treatment, and others are delayed for long periods. There has been no detailed description regarding the optimal follow-up period. According to the literature, to our knowledge, the longest period between treatment and recurrence was 18 months [26], suggesting that it should be followed up for at least 2 years after resection. Likewise, cases in which tumor recurs should be followed up for long periods because of the possible rare malignant change in the tumor [20]. We intraoperatively confirmed the absence of tumor cells at the resected margin of the bone. Histological examination of frozen sections provides useful information for determining the extent of removal required for radical resection [12]. At present, there is no convincing evidence that supports the effectiveness of chemotherapy or radiation [10,11]. Therefore, we should endeavor to perform radical surgery even in the critical structures [4,10,11,17]. Consistent with previously reported ultrastructural studies, the tumor specimen contained premelanosomes and melanosomes at various stages of maturation [9,34].
M. Matsumoto et al. / Surgical Neurology 63 (2005) 275–280
279
Table 1 Reports of MNTI in the skull that have available information on surgery, recurrence, and follow-up period Author and year
Age (mo) and gender
Location
First operation
Recurrence
Second operation
Follow-up (y)
Clarke et al, 1951 [7]
9, male
Anterior fontanelle
No
Not performed
1.2
Anagnostopoulos and Everrard, 1972 [3] Gilmor and Mealey, 1972 [16]
7, male
Temporosphenoid
No
Not performed
0.5
3, male
Anterior fontanelle
No
Not performed
1.7
Pascalis et al, 1977 [32]
6, female
Anterior fontanelle
No
Not performed
4
Atkinson et al, 1989 [4]
2, female
Anterior fontanelle
Resection of tumor, adjacent bone, and SSS Resection of tumor and adjacent bone Resection of tumor and cauterization of the dura Resection of tumor and SSS Resection of tumor without invaded dura
+
1
Kacker et al, 1993 [20]
3, male
Resection of tumor
No
0.5
Hoshino et al, 1994 [17]
5, male
Squamous and occipital Retromastoid
Resection of tumor and invaded sinuses Not performed
No
Not performed
0.7
Dammann et al, 1995 [10]
2, male
Temporal (malignant)
No
Not performed
5
Dashti et al, 1999 [11]
2, male
Retromastoid
Resection of tumor and adjacent bone Resection of tumor and adjacent bone Resection of tumor and curetting of the invaded dura
+
2
Nishio et al, 1999 [30]
4, female
Anterior fontanelle
No
Present report
4, female
Temporosphenoid
Resection of tumor and adjacent bone Resection of tumor and adjacent bone
Resection of tumor and invaded sinuses Not performed
No
Not performed
0.5 11
SSS indicates superior sagittal sinus.
Cutler et al [9] reported that MNTI has 2 distinct types of melanin-producing cell. The first type has an irregularly shaped nucleus cell, and the cytoplasm contained numerous premelanosomes and mature melanosomes. The second type has a large oval nucleus, and the cytoplasm contained a few melanin granules. Pettinato et al [34] described that melanin-producing cells, such as ovoid with cytoplasm, contained numerous premelanosomes in a laminar matrix and dense mature melanosomes. Ours resembled the findings of Pettinato et al. Thus, the findings of ultrastructural studies that tumor cells may show several patterns of pigmented granular formation indicate a relative diversity of differentiation within the neoplasm [9]. Biochemical and DNA studies strongly suggest that the MNTI is of neural crest origin [17,31]. Early diagnosis and radical excision of the tumor can lead to excellent long-term outcome. Delayed diagnosis may cause difficulty in radical resection because the tumor invades the adjacent critical structures, such as venous sinuses and skull base. If we encounter a mass in the skull of an infant, we have to include several kinds of skull disorders in the differential diagnosis [6,18,24,27]. Although neuroradiological studies [15,17,30] are helpful for the differential diagnoses, the characteristic feature of the MNTI, which is a rapid-growing tumor in an infant, allows us to easily reach the diagnosis. Although the second operation is necessary, we should perform it and excise as much as possible, because it carries a favorable outcome and a long-term cure.
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Finish each day and be done with it. You have done what you could. Some blunders and absurdities no doubt crept in; forget them as soon as you can. Tomorrow is a new day; begin it well and serenely and with too high a spirit to be cumbered with your old nonsense. —Ralph Waldo Emerson http://www.quotationspage.com/quote/2760.html