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Parapharyngeal and skull base yolk sac tumor: A case report with lessons in diagnosis and management
International Journal of Pediatric Otorhinolaryngology 78 (2014) 2003–2006
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Case Report
Parapharyngeal and skull base yolk sac tumor: A case report with lessons in diagnosis and management Leah J. Hauser a,*, Tendy Chiang a, Vijay R. Ramakrishnan a, Mark A. Lovell b, Peggy E. Kelley a a b
Department of Otolaryngology-Head and Neck Surgery, University of Colorado, Aurora, CO, United States Department of Pathology, Children’s Hospital Colorado, Aurora, CO, United States
A R T I C L E I N F O
A B S T R A C T
Article history: Received 1 June 2014 Received in revised form 16 August 2014 Accepted 18 August 2014 Available online 28 August 2014
Yolk sac tumors are rare in the head and neck. A previously healthy 2-year-old female presented with a large parapharyngeal mass. Pathology was pathognomonic for yolk sac tumor, with glandular differentiation and focal mucin production, which has not been reported in a yolk sac tumor. She was treated aggressively with chemotherapy followed by endoscopic exploration with planned resection, but no viable tumor was encountered. Yolk sac tumors can be difficult to diagnose in the head and neck, but complete clinical response can be achieved. New endoscopic approaches to skull base tumors are applicable to the pediatric population with some technical modifications. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Yolk sac tumor Parapharyngeal tumor Skull base tumor Pediatric Endoscopic skull base surgery
1. Introduction Yolk sac tumor (YST) is a malignant neoplasm of germ cell origin, commonly found in gonadal sites (testis and ovary), though up to half can be located in extragonadal sites [1]. The most common extragonadal sites include the central nervous system, mediastinum, coccyx, and retroperitoneum, but they are very rare in the head and neck [1–4]. Case reports have documented primary lesions in the neck, pharynx, face, temporal bone, orbit, palate and oral cavity [3,5–9]. Diagnosis is made by characteristic pathologic findings, specifically Schiller–Duval bodies, and elevated alphafetoprotein. Management for gonadal and common extragonadal primary sites has been well documented with overall favorable outcomes [10–13]; however, treatment strategies and outcomes of head and neck YST vary widely given the rarity of the disease. 2. Case report A 2-year-old female with no significant past medical history presented to the emergency department of a tertiary care children’s hospital with 5 days of rhinorrhea, sore throat,
* Corresponding author at: Department of Otolaryngology-Head and Neck Surgery, University of Colorado, 12631 East 17th Avenue, B205, United States. Tel.: +1 303 724 1950; fax: +1 303 724 1961. E-mail addresses: [email protected], [email protected] (L.J. Hauser). http://dx.doi.org/10.1016/j.ijporl.2014.08.027 0165-5876/ß 2014 Elsevier Ireland Ltd. All rights reserved.
dysphagia, and 1 day of fever and noisy breathing. Exam was notable for stertor at rest, tender left neck lymphadenopathy, and fullness along the left palatal, peritonsillar, and parapharyngeal region. Cranial nerve and orbital exam were unremarkable. Given the clinical history, an initial concern for an infectious process led to pediatric otolaryngology consultation. Operative drainage was recommended, during which no purulence was found, but rather a large peritonsillar/parapharyngeal tumor which was biopsied and sent for further histopathologic analysis. CT and MRI imaging were then performed, which confirmed a large mass in the parapharyngeal space with skull base involvement and locoregional spread to level II lymph nodes (Fig. 1). Pediatric oncology consultation was obtained. Pathologic diagnosis was initially challenging given predominant glandular differentiation and focal mucin production, which suggested salivary gland origin. Subsequent lymph node biopsy showed positive staining for alpha-fetoprotein (AFP) and Schiller–Duval bodies, thus confirming a diagnosis of YST (Figs. 2 and 3). Serum AFP was significantly elevated at 11,600 ng/ml. She underwent treatment consisting of 4 cycles of Bleomycin, Etoposide and Cisplatin with good clinical and radiologic response. Serum AFP decreased to <1 ng/ml. Concern for residual mass versus treatment-related sclerosis was seen on follow up CT and MRI, prompting further operative exploration, which was approached through a transnasal endoscopic route. Given the age of the patient, working space in the nasal cavity was limited and the paranasal sinuses were poorly pneumatized.
2004
L.J. Hauser et al. / International Journal of Pediatric Otorhinolaryngology 78 (2014) 2003–2006
Fig. 1. T1 coronal (left) and T2 axial (middle and right) post-contrast MRI images show enhancing lesion centered in the pterygoid plates with involvement of the palate, nasal cavity, paranasal sinuses, pterygopalatine fossa, and infratemporal fossa with extension into the inferior orbital fissure and middle cranial fossa.
Endoscopic transmaxillary transpterygoid access to the middle cranial fossa was achieved after the working space was enlarged by partial resection of the ipsilateral inferior and middle turbinates; the paranasal sinuses were widely opened, bone was removed from the inferomedial maxilla, maxillary and sphenoidal portions of the palatine bone, and pterygoid process of the sphenoid, and the obstructing maxillary tooth bud was removed (Fig. 4). Findings at the time of surgery included dense scar tissue in the rudimentary sphenoid, pterygopalatine fossa, and pterygoid regions. Bony trabeculae within the pterygoid process were encountered at the center of the corresponding lesion as confirmed with image guidance, but there was no evidence of tumor, either grossly or on frozen section examination (Fig. 4). Pathologic analysis showed dense fibrous connective tissue and bone without any evidence of viable tumor, confirming complete response to chemotherapy. Clinical, radiologic and laboratory follow up one year after completion of therapy continues to show no evidence of disease.
Fig. 2. Lymph node biopsy demonstrating glandular morphology. A Schiller–Duval body is seen in the inset (hematoxylin and eosin, 100, inset 200).
3. Discussion Yolk sac tumor, also known as endodermal sinus tumor, is a malignant neoplasm derived from germ cells, the precursors of gametes. Malignant germ cell tumors are rare and represent only about 3% of all pediatric malignancies [1,2]. This group includes teratoma (both mature and immature), germinoma, embryonal carcinoma, and choriocarcinoma [14]. Extragonadal primary tumors occur about 50% of the time, but are extremely rare in the head and neck [2,3]. Diagnosis is made by characteristic pathologic findings and elevated AFP. Histopathologically, YST resemble the yolk sac, the early fetal circulation system that obliterates during the first trimester of development. It was initially thought that these tumors arose from cells that were abnormally retained, however, it is now more commonly accepted that totipotent germ cells abnormally migrate and differentiate into tumor cells that form structures reminiscent of the fetal yolk sac [14]. The histopathology of YST can vary widely and at least eleven different patterns have been described [4]. The most common and well-recognized pattern is the reticularmicrocystic, but others include vascular, glandular, hepatoid, macrocystic, myxomatous, papillary, parietal, polyvesicular, sarcomatoid, and solid types [4]. In general, these different types represent various stages of evolution of the yolk sac during human fetal development. This wide variation can make the histopathologic diagnosis of yolk sac tumors challenging. About 20% of YST
Fig. 3. Initial biopsy showing mucin positive glands. (Mucicarmine stain, 400).
L.J. Hauser et al. / International Journal of Pediatric Otorhinolaryngology 78 (2014) 2003–2006
2005
Fig. 4. Intraoperative endoscopic photograph utilizing image guidance with fused CT and post-contrast MRI. The maxillary sinus was minimally pneumatized; however, endoscopic transpterygoid access to the middle cranial fossa was feasible after removal of a tooth bud, the inferomedial wall of the maxilla, and more extensive resection of the pterygoid process (arrow). The navigating instrument is located in the center of the enhancing lesion on MRI, consistent with bony trabeculae of the pterygoid process and absence of tumor.
will form the classic Schiller–Duval bodies, which are tubulopapillary structures with vascular cores surrounded by endodermal epithelium resembling the human fetal yolk sac [4]. These structures are specific for YST, but absence of these does not preclude the diagnosis of YST. Additionally, AFP, a protein produced by yolk sac tumor cells, can assist in making the diagnosis. Though it can be produced both other organs, including the liver, AFP immunohistochemistry staining is considered the gold standard for diagnosing YSTs [4] and serum AFP levels can also be markedly elevated [14]. The primary histologic pattern of the tumor in our case was glandular, making diagnosis especially challenging given the high density of glandular tissue in the head and neck. Additionally, we demonstrated mucin production, which to our knowledge, has never been previously reported with YST (Fig. 3). Initial differential diagnosis included rhabdomyosarcoma (given the clinical presentation) and adenocarcinoma or malignant salivary gland tumors based on the initial glandular histopathologic findings. A final diagnosis was not able to be made until a locoregional lymph node was excised and examined, demonstrating Schiller–Duval bodies. Serum and tissue AFP were then sampled and were both significantly elevated, thus confirming the diagnosis of YST. Staging and prognosis for YST depends on the primary location and extent of disease [14], but all extragonadal primary tumors are considered high-stage or poor risk [12]. In general, complete surgical excision is advocated when possible [14]. Given the involvement of the palate, nasal cavity, paranasal sinuses, pterygopalatine fossa, and infratemporal fossa with extension into the orbit and middle cranial fossa, complete resection was not feasible in our case. In such scenarios, aggressive combination multidrug chemotherapy regimens of etoposide, bleomycin, and either cisplatin or carboplatin have been widely used to treat malignant germ cell tumors since the 1980s [11,12,15]. Prior to the adoption of this platinum-based treatment, prognosis for high
stage germ cell tumors was dismal and the disease was nearly uniformly fatal [1,12]. Now, using platinum-based therapies, 5-year event-free survival has been shown to be between 76% and 85% for extragonadal primary tumor sites [10–13]. However, none of these studies included head and neck primary sites given the paucity of cases, therefore, the true prognosis is unknown for these rare tumors. Due to the favorable outcomes in other anatomic locations, this chemotherapy regimen has been adopted for head and neck primary YST, as was with our case. Our patient showed a good response to this chemotherapy regimen with marked reduction in AFP levels, but nonspecific diffuse enhancement was present at the skull base on MRI (Fig. 4). For YST, surgical resection or continued chemotherapy is recommended for residual disease after standard platinum-based therapy [14]. Surgical approach to resection of this tumor was challenging given the location and diffuse involvement of the skull base. Modern techniques allow for visualization and access of this space through endoscopic transnasal transpterygoid approach. These approaches traverse the maxillary sinus and are well established in adults [16,17]. There have been many published reports and reviews of endoscopic approaches to the midline skull base in the pediatric population [18–20] and after evaluating multiple CT scans, Tatreau et al. concluded that endoscopic approaches to the skull base may be limited by inadequate paranasal sinus development only in the very young population, less than 3–4 years of age [21]. However, these studies focused solely on pyriform aperture width and sphenoid sinus anatomy for approaches to the sella, clivus, cribriform, or planum. These advancements do suggest, however, that other advanced endoscopic techniques may also be possible in this population. Studies evaluating development of the paranasal sinuses in the pediatric population have documented that the maxillary sinuses are not completely developed in the young pediatric population [22,23]. However, the clinical implication of this underdevelopment
2006
L.J. Hauser et al. / International Journal of Pediatric Otorhinolaryngology 78 (2014) 2003–2006
is not well understood when considering endoscopic skull base surgery. It has been suggested previously that the transmaxillary transpterygoid endoscopic approach may not be feasible in the pediatric population until the teenage years [18]. However, we were pleased to find that this advanced endoscopic approach to the skull base was relatively easily adaptable to the pediatric population. In this case, the endoscopic approach allowed for resection of the lesion with frozen section pathologic analysis that spared the child a large open approach for what turned out to be a complete response to chemotherapy. Given the small working space in the 2-year old nasal cavity, a portion of the middle turbinate and inferior turbinate were resected to allow for appropriate instrumentation and visualization. To work in the pterygopalatine fossa, additional maneuvers were required that are not traditionally utilized in adults, given the lack of pneumatization of the sinuses. The tooth bud was removed, the inferomedial wall of the maxilla was removed, and more extensive resection of the pterygoid process was required. In the more pneumatized sinus and larger working space of the adult, these low-morbidity maneuvers would not be necessary. Fortunately, all biopsies in this area were negative for residual tumor and complete resection was not pursued. As such, we found that advanced endoscopic skull base techniques were possible in the pediatric population with some modification, similar to what has been documented for the midline skull base. 4. Conclusions In summary, this rare case of a parapharyngeal yolk sac tumor highlights many important clinical concerns. Yolk sac tumors are rare in the head and neck and can be difficult to diagnose, particularly those with a glandular morphology. Many histopathologic patterns are possible, but mucin production has not previously been described in yolk sac tumor. Accurate diagnosis is paramount, as complete clinical response can be achieved with standard treatment that has been widely accepted for other extragonadal primary tumor sites. New endoscopic approaches to skull base tumors are applicable to the pediatric population with some technical modifications, but further exploration is warranted. Funding source None declared. References [1] U. Gobel, D.T. Schneider, G. Calaminus, R.J. Haas, P. Schmidt, D. Harms, Germ-cell tumors in childhood and adolescence, Ann. Oncol. 11 (2000) 263–271.
[2] D.T. Schneider, G. Calaminus, S. Koch, C. Teske, P. Schmidt, R.J. Haas, et al., Epidemiologic analysis of 1,442 children and adolescents registered in the German germ cell tumor protocols, Pediatr. Blood Cancer 42 (2004) 169–175. [3] B. Bernbeck, D.T. Schneider, B. Bernbeck, S. Koch, C. Teske, J. Ledtrodt, et al., Germ cell tumors of the head and neck: report from the MAKEI study group, Pediatr. Blood Cancer 52 (2009) 223–226. [4] F.F. Nogales, O. Preda, A. Nicolae, Yolk sac tumours revisited. A review of their many faces and names, Histopathology 60 (2012) 1023–1033. [5] S. Pasricha, A. Gupta, M. Shah, H. Vadodaria, Extragonadal yolk sac tumor of face in a female infant: a case report, Indian J. Pathol. Microbiol. 53 (3) (2010) 598–599. [6] P. Kusumakumari, N. Geetha, V.G. Chellam, M.K. Nair, Endodermal sinus tumors in the head and neck region, Med. Pediatr. Oncol. 29 (1997) 303–307. [7] B.C.A. Filho, J.B. McHugh, R.L. Carrau, A.B. Kassam, Yolk sac tumor in the nasal cavity, Am. J. Otolaryngol. – Head Neck Med. Surg. 29 (2008) 250–254. [8] A. Kutluhan, S. Ugras, E. Akman, Endodermal sinus (yolk sac) tumor of oral cavity originating from the gingiva, Auris Nasus Larynx 25 (1998) 459–462. [9] N.A. Rozbahany, M. Hasanzadazar, H. Latifi, A. Mohammadi, B. Ilkhanizadeb, M. Ghasemi-Rad, Yolk-sac tumor of the postauricular region: case report and review of the literature, J. Oral Maxillofac. Surg. 70 (2012) 1891–1895. [10] U. Gobel, D.T. Schneicher, G. Calaminus, et al., Multimodal treatment of malignant sacrococcygeal germ cell tumors: a prospective analysis of 66 patients of the German cooperative protocols MAKEI 83/86 and 89, J. Clin. Oncol. 19 (7) (2001) 1943–1950. [11] J.R. Mann, F. Raafat, K. Robinson, et al., The United Kingdom Children’s Cancer Study Group’s Second Germ Cell Tumor Study: carboplatin, etoposide, and bleomycin are effective treatment for children with malignant extracranial germ cell tumors, with acceptable toxicity, J. Clin. Oncol. 18 (2000) 3809–3818. [12] B. Cushing, R. Giller, J.W. Cullen, et al., Randomized comparison of combination chemotherapy with etoposide, bleomycin, and either high-dose or standard-dose cisplatin in children and adolescents with high-risk malignant germ cell tumors: a pediatric intergroup study-pediatric oncology Group 9049 and Children’s Cancer Group 8882, J. Clin. Oncol. 22 (2004) 2691–2700. [13] A. DeBacker, G.C. Madem, R. Pieters, P. Haentjens, F.G.A.J. Hakvoort-Cammel, J.W. Oosterhuis, et al., Influence of tumor site and histology on long-term survival in 193 children with extracranial germ cell tumors, Eur. J. Pediatr. Surg. 18 (2008) 1–6. [14] Lanzkowsky P:, Germ cell tumors, in: P. Lanzkowsky (Ed.), Manual of Pediatric Hematology and Oncology, Elsevier, Boston, 2011. [15] C.R. Pinkerton, J. Pritchard, L. Spitz, High complete response rate in children with advanced germ cell tumors using cisplatin-containing combination chemotherapy, J. Clin. Oncol. 4 (2) (1986) 194–199. [16] F.S. Fortes, L.U. Sennes, R.L. Carrau, et al., Endoscopic anatomy of the pterygopalatine fossa and the transpterygoid approach: development of a surgical instruction model, Laryngoscope 118 (1) (2008) 44–49. [17] A.B. Kassam, P. Gardner, C. Snyderman, A. Mintz, R. Carrau, Expanded endonasal approach: fully endoscopic, completely transnasal approach to the middle third of the clivus, petrous bone, middle cranial fossa, and infratemporal fossa, Neurosurg. Focus 19 (1) (2005) E6. [18] S.C. Manning, D.C. Bloom, J.A. Perkins, J.S. Gruss, A. Inglis, Diagnostic and surgical challenges in the pediatric skull base, Otolaryngol. Clin. N. Am. 38 (2005) 773–794. [19] P. Castelnuovo, B. Marurizio, A. Pistochini, et al., Endoscopic endonasal management of encephaloceles in children: an eight-year experience, Int. J. Pediatr. Otorhinolaryngol. 73 (2009) 1132–1136. [20] D. Locatelli, F. Rampa, I. Acchiardi, M. Bignami, A. Postochini, Endoscopic endonasal approaches to anterior skull base defects in pediatric patients, Childs Nerv. Syst. 22 (2006) 1411–1418. [21] J.R. Tatreau, M.R. Patel, R.N. Shah, et al., Anatomical considerations for endoscopic endonasal skull base surgery in pediatric patients, Laryngoscope 120 (2010) 1730–1737. [22] R.K. Shah, J.K. Dhingra, B.L. Carter, E.E. Rebeiz, Paranasal sinus development: a radiographic study, Laryngoscope 113 (2003) 205–209. [23] Z.H. Adibelli, M. Songu, H. Adibelli, Paranasal sinus development in children: a magnetic resonance imaging analysis, Am. J. Rhinol. Allergy 25 (2011) 30–35.
Contents lists available at ScienceDirect
International Journal of Pediatric Otorhinolaryngology journal homepage: www.elsevier.com/locate/ijporl
Case Report
Parapharyngeal and skull base yolk sac tumor: A case report with lessons in diagnosis and management Leah J. Hauser a,*, Tendy Chiang a, Vijay R. Ramakrishnan a, Mark A. Lovell b, Peggy E. Kelley a a b
Department of Otolaryngology-Head and Neck Surgery, University of Colorado, Aurora, CO, United States Department of Pathology, Children’s Hospital Colorado, Aurora, CO, United States
A R T I C L E I N F O
A B S T R A C T
Article history: Received 1 June 2014 Received in revised form 16 August 2014 Accepted 18 August 2014 Available online 28 August 2014
Yolk sac tumors are rare in the head and neck. A previously healthy 2-year-old female presented with a large parapharyngeal mass. Pathology was pathognomonic for yolk sac tumor, with glandular differentiation and focal mucin production, which has not been reported in a yolk sac tumor. She was treated aggressively with chemotherapy followed by endoscopic exploration with planned resection, but no viable tumor was encountered. Yolk sac tumors can be difficult to diagnose in the head and neck, but complete clinical response can be achieved. New endoscopic approaches to skull base tumors are applicable to the pediatric population with some technical modifications. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Yolk sac tumor Parapharyngeal tumor Skull base tumor Pediatric Endoscopic skull base surgery
1. Introduction Yolk sac tumor (YST) is a malignant neoplasm of germ cell origin, commonly found in gonadal sites (testis and ovary), though up to half can be located in extragonadal sites [1]. The most common extragonadal sites include the central nervous system, mediastinum, coccyx, and retroperitoneum, but they are very rare in the head and neck [1–4]. Case reports have documented primary lesions in the neck, pharynx, face, temporal bone, orbit, palate and oral cavity [3,5–9]. Diagnosis is made by characteristic pathologic findings, specifically Schiller–Duval bodies, and elevated alphafetoprotein. Management for gonadal and common extragonadal primary sites has been well documented with overall favorable outcomes [10–13]; however, treatment strategies and outcomes of head and neck YST vary widely given the rarity of the disease. 2. Case report A 2-year-old female with no significant past medical history presented to the emergency department of a tertiary care children’s hospital with 5 days of rhinorrhea, sore throat,
* Corresponding author at: Department of Otolaryngology-Head and Neck Surgery, University of Colorado, 12631 East 17th Avenue, B205, United States. Tel.: +1 303 724 1950; fax: +1 303 724 1961. E-mail addresses: [email protected], [email protected] (L.J. Hauser). http://dx.doi.org/10.1016/j.ijporl.2014.08.027 0165-5876/ß 2014 Elsevier Ireland Ltd. All rights reserved.
dysphagia, and 1 day of fever and noisy breathing. Exam was notable for stertor at rest, tender left neck lymphadenopathy, and fullness along the left palatal, peritonsillar, and parapharyngeal region. Cranial nerve and orbital exam were unremarkable. Given the clinical history, an initial concern for an infectious process led to pediatric otolaryngology consultation. Operative drainage was recommended, during which no purulence was found, but rather a large peritonsillar/parapharyngeal tumor which was biopsied and sent for further histopathologic analysis. CT and MRI imaging were then performed, which confirmed a large mass in the parapharyngeal space with skull base involvement and locoregional spread to level II lymph nodes (Fig. 1). Pediatric oncology consultation was obtained. Pathologic diagnosis was initially challenging given predominant glandular differentiation and focal mucin production, which suggested salivary gland origin. Subsequent lymph node biopsy showed positive staining for alpha-fetoprotein (AFP) and Schiller–Duval bodies, thus confirming a diagnosis of YST (Figs. 2 and 3). Serum AFP was significantly elevated at 11,600 ng/ml. She underwent treatment consisting of 4 cycles of Bleomycin, Etoposide and Cisplatin with good clinical and radiologic response. Serum AFP decreased to <1 ng/ml. Concern for residual mass versus treatment-related sclerosis was seen on follow up CT and MRI, prompting further operative exploration, which was approached through a transnasal endoscopic route. Given the age of the patient, working space in the nasal cavity was limited and the paranasal sinuses were poorly pneumatized.
2004
L.J. Hauser et al. / International Journal of Pediatric Otorhinolaryngology 78 (2014) 2003–2006
Fig. 1. T1 coronal (left) and T2 axial (middle and right) post-contrast MRI images show enhancing lesion centered in the pterygoid plates with involvement of the palate, nasal cavity, paranasal sinuses, pterygopalatine fossa, and infratemporal fossa with extension into the inferior orbital fissure and middle cranial fossa.
Endoscopic transmaxillary transpterygoid access to the middle cranial fossa was achieved after the working space was enlarged by partial resection of the ipsilateral inferior and middle turbinates; the paranasal sinuses were widely opened, bone was removed from the inferomedial maxilla, maxillary and sphenoidal portions of the palatine bone, and pterygoid process of the sphenoid, and the obstructing maxillary tooth bud was removed (Fig. 4). Findings at the time of surgery included dense scar tissue in the rudimentary sphenoid, pterygopalatine fossa, and pterygoid regions. Bony trabeculae within the pterygoid process were encountered at the center of the corresponding lesion as confirmed with image guidance, but there was no evidence of tumor, either grossly or on frozen section examination (Fig. 4). Pathologic analysis showed dense fibrous connective tissue and bone without any evidence of viable tumor, confirming complete response to chemotherapy. Clinical, radiologic and laboratory follow up one year after completion of therapy continues to show no evidence of disease.
Fig. 2. Lymph node biopsy demonstrating glandular morphology. A Schiller–Duval body is seen in the inset (hematoxylin and eosin, 100, inset 200).
3. Discussion Yolk sac tumor, also known as endodermal sinus tumor, is a malignant neoplasm derived from germ cells, the precursors of gametes. Malignant germ cell tumors are rare and represent only about 3% of all pediatric malignancies [1,2]. This group includes teratoma (both mature and immature), germinoma, embryonal carcinoma, and choriocarcinoma [14]. Extragonadal primary tumors occur about 50% of the time, but are extremely rare in the head and neck [2,3]. Diagnosis is made by characteristic pathologic findings and elevated AFP. Histopathologically, YST resemble the yolk sac, the early fetal circulation system that obliterates during the first trimester of development. It was initially thought that these tumors arose from cells that were abnormally retained, however, it is now more commonly accepted that totipotent germ cells abnormally migrate and differentiate into tumor cells that form structures reminiscent of the fetal yolk sac [14]. The histopathology of YST can vary widely and at least eleven different patterns have been described [4]. The most common and well-recognized pattern is the reticularmicrocystic, but others include vascular, glandular, hepatoid, macrocystic, myxomatous, papillary, parietal, polyvesicular, sarcomatoid, and solid types [4]. In general, these different types represent various stages of evolution of the yolk sac during human fetal development. This wide variation can make the histopathologic diagnosis of yolk sac tumors challenging. About 20% of YST
Fig. 3. Initial biopsy showing mucin positive glands. (Mucicarmine stain, 400).
L.J. Hauser et al. / International Journal of Pediatric Otorhinolaryngology 78 (2014) 2003–2006
2005
Fig. 4. Intraoperative endoscopic photograph utilizing image guidance with fused CT and post-contrast MRI. The maxillary sinus was minimally pneumatized; however, endoscopic transpterygoid access to the middle cranial fossa was feasible after removal of a tooth bud, the inferomedial wall of the maxilla, and more extensive resection of the pterygoid process (arrow). The navigating instrument is located in the center of the enhancing lesion on MRI, consistent with bony trabeculae of the pterygoid process and absence of tumor.
will form the classic Schiller–Duval bodies, which are tubulopapillary structures with vascular cores surrounded by endodermal epithelium resembling the human fetal yolk sac [4]. These structures are specific for YST, but absence of these does not preclude the diagnosis of YST. Additionally, AFP, a protein produced by yolk sac tumor cells, can assist in making the diagnosis. Though it can be produced both other organs, including the liver, AFP immunohistochemistry staining is considered the gold standard for diagnosing YSTs [4] and serum AFP levels can also be markedly elevated [14]. The primary histologic pattern of the tumor in our case was glandular, making diagnosis especially challenging given the high density of glandular tissue in the head and neck. Additionally, we demonstrated mucin production, which to our knowledge, has never been previously reported with YST (Fig. 3). Initial differential diagnosis included rhabdomyosarcoma (given the clinical presentation) and adenocarcinoma or malignant salivary gland tumors based on the initial glandular histopathologic findings. A final diagnosis was not able to be made until a locoregional lymph node was excised and examined, demonstrating Schiller–Duval bodies. Serum and tissue AFP were then sampled and were both significantly elevated, thus confirming the diagnosis of YST. Staging and prognosis for YST depends on the primary location and extent of disease [14], but all extragonadal primary tumors are considered high-stage or poor risk [12]. In general, complete surgical excision is advocated when possible [14]. Given the involvement of the palate, nasal cavity, paranasal sinuses, pterygopalatine fossa, and infratemporal fossa with extension into the orbit and middle cranial fossa, complete resection was not feasible in our case. In such scenarios, aggressive combination multidrug chemotherapy regimens of etoposide, bleomycin, and either cisplatin or carboplatin have been widely used to treat malignant germ cell tumors since the 1980s [11,12,15]. Prior to the adoption of this platinum-based treatment, prognosis for high
stage germ cell tumors was dismal and the disease was nearly uniformly fatal [1,12]. Now, using platinum-based therapies, 5-year event-free survival has been shown to be between 76% and 85% for extragonadal primary tumor sites [10–13]. However, none of these studies included head and neck primary sites given the paucity of cases, therefore, the true prognosis is unknown for these rare tumors. Due to the favorable outcomes in other anatomic locations, this chemotherapy regimen has been adopted for head and neck primary YST, as was with our case. Our patient showed a good response to this chemotherapy regimen with marked reduction in AFP levels, but nonspecific diffuse enhancement was present at the skull base on MRI (Fig. 4). For YST, surgical resection or continued chemotherapy is recommended for residual disease after standard platinum-based therapy [14]. Surgical approach to resection of this tumor was challenging given the location and diffuse involvement of the skull base. Modern techniques allow for visualization and access of this space through endoscopic transnasal transpterygoid approach. These approaches traverse the maxillary sinus and are well established in adults [16,17]. There have been many published reports and reviews of endoscopic approaches to the midline skull base in the pediatric population [18–20] and after evaluating multiple CT scans, Tatreau et al. concluded that endoscopic approaches to the skull base may be limited by inadequate paranasal sinus development only in the very young population, less than 3–4 years of age [21]. However, these studies focused solely on pyriform aperture width and sphenoid sinus anatomy for approaches to the sella, clivus, cribriform, or planum. These advancements do suggest, however, that other advanced endoscopic techniques may also be possible in this population. Studies evaluating development of the paranasal sinuses in the pediatric population have documented that the maxillary sinuses are not completely developed in the young pediatric population [22,23]. However, the clinical implication of this underdevelopment
2006
L.J. Hauser et al. / International Journal of Pediatric Otorhinolaryngology 78 (2014) 2003–2006
is not well understood when considering endoscopic skull base surgery. It has been suggested previously that the transmaxillary transpterygoid endoscopic approach may not be feasible in the pediatric population until the teenage years [18]. However, we were pleased to find that this advanced endoscopic approach to the skull base was relatively easily adaptable to the pediatric population. In this case, the endoscopic approach allowed for resection of the lesion with frozen section pathologic analysis that spared the child a large open approach for what turned out to be a complete response to chemotherapy. Given the small working space in the 2-year old nasal cavity, a portion of the middle turbinate and inferior turbinate were resected to allow for appropriate instrumentation and visualization. To work in the pterygopalatine fossa, additional maneuvers were required that are not traditionally utilized in adults, given the lack of pneumatization of the sinuses. The tooth bud was removed, the inferomedial wall of the maxilla was removed, and more extensive resection of the pterygoid process was required. In the more pneumatized sinus and larger working space of the adult, these low-morbidity maneuvers would not be necessary. Fortunately, all biopsies in this area were negative for residual tumor and complete resection was not pursued. As such, we found that advanced endoscopic skull base techniques were possible in the pediatric population with some modification, similar to what has been documented for the midline skull base. 4. Conclusions In summary, this rare case of a parapharyngeal yolk sac tumor highlights many important clinical concerns. Yolk sac tumors are rare in the head and neck and can be difficult to diagnose, particularly those with a glandular morphology. Many histopathologic patterns are possible, but mucin production has not previously been described in yolk sac tumor. Accurate diagnosis is paramount, as complete clinical response can be achieved with standard treatment that has been widely accepted for other extragonadal primary tumor sites. New endoscopic approaches to skull base tumors are applicable to the pediatric population with some technical modifications, but further exploration is warranted. Funding source None declared. References [1] U. Gobel, D.T. Schneider, G. Calaminus, R.J. Haas, P. Schmidt, D. Harms, Germ-cell tumors in childhood and adolescence, Ann. Oncol. 11 (2000) 263–271.
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