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Management of Locally Advanced Esthesioneuroblastoma in a Pregnant Woman

Management of Locally Advanced Esthesioneuroblastoma in a Pregnant Woman Hindawi Case Reports in Oncological Medicine Volume 2019, Article ID 3789317, 5 pages https://doi.org/10.1155/2019/3789317 Case Report Management of Locally Advanced Esthesioneuroblastoma in a Pregnant Woman 1 1 2 3 4 Inês Maria Guerreiro , Cláudia Vieira, André Soares, António Braga, Manuel Jácome, and José Dinis Medical Oncology Department, Instituto Português de Oncologia do Porto Francisco Gentil (IPO-PORTO), Porto, Portugal Radiation Oncology Department, Instituto Português de Oncologia do Porto Francisco Gentil (IPO-PORTO), Porto, Portugal Department of Obstetrics and Gynecology, Centro Hospitalar do Porto, Porto, Portugal Pathology Department, Instituto Português de Oncologia do Porto Francisco Gentil (IPO-PORTO), Porto, Portugal Correspondence should be addressed to Inês Maria Guerreiro; ines.m.guerreiro@gmail.com Received 5 February 2019; Revised 17 June 2019; Accepted 7 July 2019; Published 19 August 2019 Academic Editor: Jeanine M. Buchanich Copyright © 2019 Inês Maria Guerreiro et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Esthesioneuroblastoma (ENB) is a rare malignant tumor that commonly develops in the upper nasal cavity. Standard treatment is not established, especially in locally advanced disease which portends the worse prognosis. Hereby, we report a case of a 27-year- old, 23-week pregnant woman, with a 2-month history of progressively growing right cervical lymphadenopathy, nasal obstruction, anosmia, frequent episodes of epistaxis, and right frontal headache. Imagiological evaluation revealed a lesion with 7×5,2×3,2 cm in the nasal fossae with extension to the ethmoidal complex and right olfactive fend and invasion of the endocranial compartment associated with lymphadenopathy. The biopsy revealed a high-grade EBN. Neoadjuvant chemotherapy with cisplatin and etoposide was administrated during pregnancy and continued after delivery up to 6 cycles of treatment with partial response. Radiotherapy followed, with complete response. This case report is intended to highlight that a high grade of suspicion should be kept in the presence of nonspecific symptoms of nasal obstruction, anosmia, facial pain, and/or headache and focus that chemotherapy is an important component of a combined-treatment modality for locally advanced ENB that can be used during pregnancy in a lifesaving situation. 1. Background tion in the second and sixth decade of life [1, 2]. The best treatment options in advanced stages are not well defined Esthesioneuroblastoma (ENB), also referred to as olfactory due to the rarity of the disease. The most frequent staging neuroblastoma (ONB), is a malignant neuroectodermal system is the Kadish staging modified by Morita and col- tumor thought to originate from the olfactory membrane of leagues [4]. A cervical lymph node or distant metastases represent the most advanced stage of the disease—stage D. the sinonasal tract [1]. ENB is a rare tumor and most com- monly develops in the upper nasal cavity in the region of The grading system developed by Hyams et al. [5] classifies the cribriform plate [1]. Consequently, the most common tumors in 4 groups based on mitotic activity, nuclear pleo- symptom is nasal obstruction that can be associated with epi- morphism, rosette formation, necrosis, and the characteris- staxis and pain [1–3]. Manifestations of locally advanced dis- tics of the fibrillary matrix. Both extent of disease and grading appear to have a prognostic significance [6, 7]. We ease include anosmia, proptosis, facial pain, or frontal headache due to invasion of adjacent structures [2]. There report the case of a pregnant woman with a locally advanced is a slight male predominance and a bimodal age presenta- esthesioneuroblastoma (Figure 1). 2 Case Reports in Oncological Medicine Pregnant female, 27y Diagnosis and interventions Follow-up and outcomes Complete response Esthesioneuroblastoma, stage D (Kadish), grade III/IV (Hayms) th 12 months of Fup: Allergic rhinitis ChT before delivery Delivery (i) Healthy baby with normal development Atopic eczema ChT aer deli ft very Sequential RT Present 2 2 (ii) Cisplatin 75 mg/m D1 Cisplatin 100 mg/m D1 VMAT at a dose of 70 Gy Patient clinically well 2 2 Treatment sequels: visual acuity in the Etoposide 75 mg/m D1-3 Etoposide 100 mg/m D1-3 right eye G1; xerostomia G1; cervical Past history every 28 days, 2 cycles every 21 days, 4 cycles fibrosis G1 Symptoms: Physical examination: (i) Right nasal obstruction (i) Voluminous right cervical lymphadenopathy (ii) Right cervical lymphadenopathy (ii) Cutaneous erythema (iii) Pain in the right superior dental arcade (iii) Right ocular oedema (iv) Vegetant non-ulcerated lesion on the nasopharynx Figure 1: Timeline. 2. Case Presentation A 27-year-old 8-week pregnant woman, with a history of allergic rhinitis and atopic eczema, presented to a general hospital with right nasal obstruction, right cervical lymph- adenopathy, and pain in the right superior dental arcade. A nonsteroidal anti-inflammatory drug was started with reso- lution of the dental pain after one week of treatment. Two months later, while maintaining a progressively growing right cervical lymphadenopathy and right nasal obstruction, the patient developed anosmia, frequent episodes of epi- staxis, and right frontal headache. A fine needle biopsy of the lymphadenopathy was performed with an inconclusive result, revealing only the presence of inflammatory cells. A Figure 2 core biopsy was then performed which revealed lymph node metastasis from a poorly differentiated malignant neoplasm. At the 23rd week of pregnancy, the patient was referred to our hospital. On physical examination, the patient had a voluminous right cervical lymphadenopathy with 15 cm from levels Ib to V associated with cutaneous erythema as well as right ocular oedema (Figure 2). A vegetant nonulcer- ated lesion was detected on the nasopharynx occupying the right nasal vestibulum. A biopsy of the lesion was performed. Pathology’s result revealed respiratory epithelium with focal involvement by small round blue cells, neuron-specific eno- lase (NSE) positive, synaptophysin positive, PS 100 positive, and AE1/AE3 and CD99 negative. The cranial and cervical magnetic resonance images (MRI) revealed a lesion with 7×5,2×3,2 cm in the nasal fossae, ethmoidal complex, and right olfactive fend with invasion of the endocranial com- partment and the orbit and deviation of the internal rectum muscle as well as extension to the nasopharynx lumen and invasion of the sphenoidal sinus associated with lymphade- nopathy in the retropharyngeal area and right II, III, IV, and V levels (Figures 3 and 4). The patient was diagnosed with a right esthesioneuroblastoma stage D in the modified Figure 3 Kadish grading system [4] and grade III/IV in the Hyams grading system [5]. setron 8 mg. Additional treatment with daily folic acid, oral The case was evaluated by a multidisciplinary team of iron, iodine supplementation, and prophylactic enoxaparin head and neck surgeons, medical oncologists, and radiation was made as recommended by the obstetrician. oncologists. The multidisciplinary tumor board determined After the first cycle of treatment, a clinical reduction of that there was no indication to perform surgery due to local the lesion was noted (Figure 5). Concerning the baby devel- extent of the disease. The patient was proposed to do sys- opment, routine amniotic fluid assessment made by foetal temic treatment with chemotherapy followed by reevaluation echography after the 2nd cycle of chemotherapy showed an by the multidisciplinary tumor board. Treatment with cis- increase in systolic velocity in the Doppler midfoetal cerebral 2 2 platin 75 mg/m on day 1 and etoposide 75 mg/m on days artery (systolic peak > 1 5 MoMs for gestational age). This finding was in favour with an established foetal anemia 1 to 3, cycles every 28 days, was started after an appropriate discussion with the patient’s obstetrician. The following pre- and interpreted as a side effect of chemotherapy. Once medication before each treatment cycle was prescribed: the foetus was stable (normal foetal biophysical profile), hydrocortisone 100 mg, metoclopramide 10 mg, and ondan- a foetal lung maturation cycle with betamethasone was Case Reports in Oncological Medicine 3 Fourteen days after the delivery, chemotherapy was resumed at a full dose with cisplatin 100 mg/m on day 1 and etoposide 100 mg/m on days 1 to 3, cycles every 21 days. After 4 cycles of treatment, a positron emission tomography- computed tomography (PET-CT) and MRI were performed, revealing a partial response. The patient completed 6 cycles of treatment with good tolerance. The main toxicities reported during treatment were grade 1 anemia, grade 1 nau- sea, and emesis treated with oral iron, folic acid, and metoclo- pramide as needed. The case was again discussed in a multidisciplinary tumor board, and treatment with radiotherapy (RT) was pro- posed. The patient performed 33 fractions of treatment with volumetric modulated arc therapy (VMAT) at a dose of 70 Gy to the neoplastic lesion, right retropharyngeal area, and right cervical Ib to V levels and 50 Gy to the left retro- pharyngeal area, left cervical Ib to V levels, and left perinasal area. The treatment had a duration of 45 days with good tol- erance. The main toxicities were grade 2 dysphagia, grade 2 odynophagia, grade 2 xerostomia, grade 2 oral mucositis, and grade 2 cervical dermatitis. A period of clinical vigilance was started, and 12 weeks after the last treatment of radiotherapy, a PET-CT was per- formed revealing no radiopharmaceutical uptake. At the Figure 4 12th month of follow-up, the baby is healthy and presents a normal development. The patient is clinically well present- ing as treatment sequels a grade 1 diminution of visual acu- ity in the right eye, xerostomia grade 1, and cervical fibrosis grade 1. 3. Conclusions This clinical case demonstrates the challenge of diagnosis and management of a rare and aggressive type of esthesioneuro- blastoma in a pregnant woman. ENB is an uncommon tumor that frequently presents with nonspecific symptoms such as nasal obstruction and facial pain. The diagnosis is a challenge for the clinicians due to the rarity and unspecificity of this entity. Moreover, while the histologic diagnosis of a well- differentiated tumor is quite evident, a less differentiated form can be more laborious requiring additional markers for the differential diagnosis among the group of small round cell malignant neoplasms that can affect the sinonasal tract. Olfactory neuroblastomas frequently express NSE and synaptophysin and are negative for the expression of leuco- cyte common antigen and CD99 [1]. The entities to be consid- ered in differential diagnosis are neuroendocrine carcinomas, Figure 5 melanoma, rhabdomyosarcoma, sinonasal undifferentiated carcinoma, squamous cell carcinoma (including NUT carci- performed according to protocol, and a decision to terminate noma), lymphoma, Ewing sarcoma, and metastatic tumors [1, 8]. Both the nonspecific presentation and the rare histolog- the pregnancy in an elective manner was made, thus avoiding the worsening of the condition with a new cycle of chemo- ical diagnosis contribute to a delay for the final diagnosis therapy. In addition, after 30 weeks of gestation, clinical sus- which justifies that the majority of the ENB are found picion of foetal anemia is an indication for termination of in an advanced stage [9] as was the case in the clinical pregnancy, avoiding invasive foetal studies. Thus, 21 days case described. The standard treatment for ENB has not been estab- after the second cycle of treatment and at 31 weeks of preg- nancy, the patient delivered by caesarean a healthy baby lished. The lack of prospective data due to its rarity and the uneventfully. While hospitalized, the new-born presented a absence of molecular therapeutic targets are contributing normal development and no health problems were detected. factors [10, 11]. Surgery followed by RT has been the most 4 Case Reports in Oncological Medicine roids can be used at the lowest effective dose and for the frequent treatment strategy and is associated with improved overall survival compared with surgery or RT alone [12, 13]. shortest duration of time. Patients with cervical lymph node metastasis at presentation There were no complications during the neonatal period have a worse prognosis despite combined-treatment modal- and the 12th month period of follow-up for both the baby ity [13], and the optimal management of these patients is and the mother, although a longer period of follow-up is nec- uncertain. This clinical case describes a 23-week pregnant essary to ascertain this good outcome. Due to the aggressive woman with a stage D ENB with cervical lymph node metas- nature of the esthesioneuroblastoma, clinical evaluation is tasis from levels Ib to V. The aggressive phenotype of the dis- made on a monthly basis. ease characterized by a painful and rapidly growing locally This case highlights that chemotherapy is an important advanced tumor with lymph node metastasis and local inva- component of the multimodal treatment strategy of locally sion of the orbit and endocranial compartment motivated the advanced esthesioneuroblastoma and shows that in a lifesav- decision to do treatment with neoadjuvant chemotherapy ing situation, chemotherapy with cisplatin and etoposide can followed by radiotherapy. In fact, there is some published be administered in the 2nd and 3rd trimesters of pregnancy. data that suggests that EBN is chemosensitive, and the addi- Moreover, a prompt diagnosis is critical to achieve complete tion of induction chemotherapy to a combined-treatment remission of the disease especially in the case of a biologically modality in patients with advanced ENB may improve treat- aggressive neoplasm. Prognosis of patients diagnosed with ment outcomes [10, 13]. The objective response to chemo- cancer during pregnancy is usually comparable with non- therapy varied between 68% and 82% [10, 13–15], with a pregnant patients [17]; however, since recurrence of this type of tumor may develop 10 or more years following initial 5-year overall survival rate achieving 78% [13]. Various chemotherapy agents have been used, being cisplatin- treatment [23, 24], a prolonged surveillance is mandatory. based regimens (notably cisplatin and etoposide) frequently This clinical case should be looked as a contribution to chosen with encouraging responses [16]. In what concerns future similar cases as it is a unique illustration of a rare the treatment strategy, the 23-week pregnancy of the and aggressive esthesioneuroblastoma in a pregnant woman. patient posed an increasing challenge since the diagnosis of cancer during pregnancy is uncommon [17], and data Abbreviations about chemotherapy in esthesioneuroblastoma during preg- nancy is missing. ENB: Esthesioneuroblastoma Exposure to some chemotherapeutic agents during the MRI: Magnetic resonance image second and third trimesters has not been associated with NSE: Neuron-specific enolase increased risk of foetal malformations or major problems in OBN: Olfactory neuroblastoma the short and long terms [17–19], contrarily to administra- PET-CT: Positron emission tomography-computed tion of chemotherapy during the first trimester of gestation tomography which is associated with an increased risk of foetal congenital RT: Radiotherapy defects [17]. Cisplatin is usually safe for the foetus in the sec- 2 VMAT: Volumetric modulated arc therapy. ond and third trimesters [20] for doses up to 75 mg/m every 3 weeks [17]. There is evidence [21] that the rate of malfor- mations after exposure to cisplatin in the first trimester is Ethical Approval about 20% but is reduced to 1% in the second and third tri- mesters of pregnancy. Regarding etoposide, the data is more All procedures performed were in accordance with the limited reporting 3% of major malformations during the sec- ethical standards of the institutional and national research ond and third trimesters of pregnancy and a foetal growth committees and with the 1964 Helsinki Declaration and its restriction in 24% of cases [21]. later amendments or comparable ethical standards. Considering that it was a lifesaving situation for both the pregnant patient and her baby, the decision was to start treat- ment with chemotherapy with a regimen of cisplatin and eto- Consent poside that was administered during the 24th to 31st week of Informed consent was obtained from the participant pregnancy. Furthermore, due to the high emetogenic poten- included in the study. tial of cisplatin-based regimens, it was essential to decide the pretreatment associated with each cycle of chemotherapy for prevention of chemotherapy-induced nausea and vomit- Conflicts of Interest ing in a pregnant patient. Both the dopamine D2 antagonist metoclopramide and the serotonin 5-hydroxytryptamine The authors declare that they have no conflict of interest. type (5-HT3) receptor antagonist ondansetron can be used during pregnancy as there is no report of an increased risk of pregnancy-related events [22]. In relation to corticoste- Authors’ Contributions roids, there is an association between oral clefts and use of systemic steroids during the first trimester of pregnancy, so The first author wrote the article; CV and JD wrote and its use should be cautious before 10 weeks of gestation [22]. reviewed the article. All authors read and approved the final Outside the first trimester of pregnancy, systemic corticoste- manuscript. Case Reports in Oncological Medicine 5 diagnosis, treatment and follow-up,” Annals of Oncology, References vol. 24, Supplement 6, pp. vi160–vi170, 2013. [1] L. Barnes, J. W. Eveson, P. Reichart, and D. Sidransky, “Olfac- [18] T. Vandenbroucke, M. Verheecke, M. Fumagalli, C. Lok, and tory neuroblastoma,” in Pathology and Genetics of Head and F. Amant, “Effects of cancer treatment during pregnancy on Neck Tumours, IARC Press, Lyon, France, 2005. fetal and child development,” The Lancet Child & Adolescent Health, vol. 1, no. 4, pp. 302–310, 2017. [2] A. S. Abdelmeguid, “Olfactory neuroblastoma,” Current Oncology Reports, vol. 20, no. 1, p. 7, 2018. [19] F. Amant, T. Vandenbroucke, M. Verheecke et al., “Pediatric [3] J. P. Marinelli, J. R. Janus, J. J. Van Gompel et al., “Esthesio- outcome after maternal cancer diagnosed during pregnancy,” The New England Journal of Medicine, vol. 373, no. 19, neuroblastoma with distant metastases: systematic review & meta-analysis,” Head & Neck, vol. 40, no. 10, pp. 2295–2303, pp. 1824–1834, 2015. [20] A. McCormick and E. Peterson, “Cancer in pregnancy,” [4] A. Morita, M. J. Ebersold, K. D. Olsen, R. L. Foote, J. E. Lewis, Obstetrics and Gynecology Clinics of North America, vol. 45, and L. M. Quast, “Esthesioneuroblastoma: prognosis and man- no. 2, pp. 187–200, 2018. agement,” Neurosurgery, vol. 32, no. 5, pp. 706–715, 1993. [21] National Toxicology Program, NTP Monograph on Develop- [5] V. Hyams, J. Batsakis, and L. Michaels, Tumors of the Upper mental Effects and Pregnancy Outcomes Associated with Can- Respiratory Tract and Ear. Armed Forces Institute of Pathology cer Chemotherapy Use during Pregnancy, U.S. Department of Fascicles, 2nd Series, American Registry of Pathology Press, health and Human services, 2013. Washington, DC, USA, 1988. [22] M. Erick, J. T. Cox, and K. M. Mogensen, “ACOG practice [6] N. Konuthula, A. M. Iloreta, B. Miles et al., “Prognostic signif- bulletin 189: nausea and vomiting of pregnancy,” Obstetrics icance of Kadish staging in esthesioneuroblastoma: an analysis and Gynecology, vol. 131, no. 5, p. 935, 2018. of the National Cancer Database,” Head & Neck, vol. 39, [23] P. D. Ward, J. A. Heth, B. G. Thompson, and L. J. Marentette, no. 10, pp. 1962–1968, 2017. “Esthesioneuroblastoma: results and outcomes of a single [7] B. A. Tajudeen, A. Arshi, J. D. Suh, M. St John, and M. B. institution’s experience,” Skull Base, vol. 19, no. 2, pp. 133– Wang, “Importance of tumor grade in esthesioneuroblastoma 140, 2009. survival: a population-based analysis,” JAMA Otolaryngology. [24] E. M. Diaz Jr., R. H. Johnigan III, C. Pero et al., “Olfactory Head & Neck Surgery, vol. 140, no. 12, pp. 1124–1129, 2014. neuroblastoma: the 22-year experience at one comprehensive [8] L. D. R. Thompson, “Small round blue cell tumors of the sino- cancer center,” Head & Neck, vol. 27, no. 2, pp. 138–149, nasal tract: a differential diagnosis approach,” Modern Pathol- 2005. ogy, vol. 30, Supplement 1, pp. S1–S26, 2017. [9] R. Kumar, S. Ghoshal, D. Khosla et al., “Survival and failure outcomes in locally advanced esthesioneuroblastoma: a single centre experience of 15 patients,” European Archives of Oto- Rhino-Laryngology, vol. 270, no. 6, pp. 1897–1901, 2013. [10] A. Modesto, P. Blanchard, Y. G. Tao et al., “Multimodal treat- ment and long-term outcome of patients with esthesioneuro- blastoma,” Oral Oncology, vol. 49, no. 8, pp. 830–834, 2013. [11] P. Czapiewski, M. Kunc, and J. Haybaeck, “Genetic and molec- ular alterations in olfactory neuroblastoma: implications for pathogenesis, prognosis and treatment,” Oncotarget, vol. 7, no. 32, pp. 52584–52596, 2016. [12] P. Dulguerov, A. S. Allal, and T. C. Calcaterra, “Esthesioneur- oblastoma: a meta-analysis and review,” The Lancet Oncology, vol. 2, no. 11, pp. 683–690, 2001. [13] S. Y. Su, D. Bell, R. Ferrarotto et al., “Outcomes for olfactory neuroblastoma treated with induction chemotherapy,” Head & Neck, vol. 39, no. 8, pp. 1671–1679, 2017. [14] D. W. Kim, Y. H. Jo, J. H. Kim et al., “Neoadjuvant etoposide, ifosfamide, and cisplatin for the treatment of olfactory neuro- blastoma,” Cancer, vol. 101, no. 10, pp. 2257–2260, 2004. [15] Y. Mishima, E. Nagasaki, Y. Terui et al., “Combination chemo- therapy (cyclophosphamide, doxorubicin, and vincristine with continuous-infusion cisplatin and etoposide) and radiother- apy with stem cell support can be beneficial for adolescents and adults with estheisoneuroblastoma,” Cancer, vol. 101, no. 6, pp. 1437–1444, 2004. [16] V. A. Resto, D. W. Eisele, A. Forastiere, M. Zahurak, D. J. Lee, and W. H. Westra, “Esthesioneuroblastoma: the Johns Hopkins experience,” Head & Neck, vol. 22, no. 6, pp. 550–558, 2000. [17] F. A. Peccatori, H. A. Azim, R. 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Management of Locally Advanced Esthesioneuroblastoma in a Pregnant Woman

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Copyright © 2019 Inês Maria Guerreiro et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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10.1155/2019/3789317
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Abstract

Hindawi Case Reports in Oncological Medicine Volume 2019, Article ID 3789317, 5 pages https://doi.org/10.1155/2019/3789317 Case Report Management of Locally Advanced Esthesioneuroblastoma in a Pregnant Woman 1 1 2 3 4 Inês Maria Guerreiro , Cláudia Vieira, André Soares, António Braga, Manuel Jácome, and José Dinis Medical Oncology Department, Instituto Português de Oncologia do Porto Francisco Gentil (IPO-PORTO), Porto, Portugal Radiation Oncology Department, Instituto Português de Oncologia do Porto Francisco Gentil (IPO-PORTO), Porto, Portugal Department of Obstetrics and Gynecology, Centro Hospitalar do Porto, Porto, Portugal Pathology Department, Instituto Português de Oncologia do Porto Francisco Gentil (IPO-PORTO), Porto, Portugal Correspondence should be addressed to Inês Maria Guerreiro; ines.m.guerreiro@gmail.com Received 5 February 2019; Revised 17 June 2019; Accepted 7 July 2019; Published 19 August 2019 Academic Editor: Jeanine M. Buchanich Copyright © 2019 Inês Maria Guerreiro et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Esthesioneuroblastoma (ENB) is a rare malignant tumor that commonly develops in the upper nasal cavity. Standard treatment is not established, especially in locally advanced disease which portends the worse prognosis. Hereby, we report a case of a 27-year- old, 23-week pregnant woman, with a 2-month history of progressively growing right cervical lymphadenopathy, nasal obstruction, anosmia, frequent episodes of epistaxis, and right frontal headache. Imagiological evaluation revealed a lesion with 7×5,2×3,2 cm in the nasal fossae with extension to the ethmoidal complex and right olfactive fend and invasion of the endocranial compartment associated with lymphadenopathy. The biopsy revealed a high-grade EBN. Neoadjuvant chemotherapy with cisplatin and etoposide was administrated during pregnancy and continued after delivery up to 6 cycles of treatment with partial response. Radiotherapy followed, with complete response. This case report is intended to highlight that a high grade of suspicion should be kept in the presence of nonspecific symptoms of nasal obstruction, anosmia, facial pain, and/or headache and focus that chemotherapy is an important component of a combined-treatment modality for locally advanced ENB that can be used during pregnancy in a lifesaving situation. 1. Background tion in the second and sixth decade of life [1, 2]. The best treatment options in advanced stages are not well defined Esthesioneuroblastoma (ENB), also referred to as olfactory due to the rarity of the disease. The most frequent staging neuroblastoma (ONB), is a malignant neuroectodermal system is the Kadish staging modified by Morita and col- tumor thought to originate from the olfactory membrane of leagues [4]. A cervical lymph node or distant metastases represent the most advanced stage of the disease—stage D. the sinonasal tract [1]. ENB is a rare tumor and most com- monly develops in the upper nasal cavity in the region of The grading system developed by Hyams et al. [5] classifies the cribriform plate [1]. Consequently, the most common tumors in 4 groups based on mitotic activity, nuclear pleo- symptom is nasal obstruction that can be associated with epi- morphism, rosette formation, necrosis, and the characteris- staxis and pain [1–3]. Manifestations of locally advanced dis- tics of the fibrillary matrix. Both extent of disease and grading appear to have a prognostic significance [6, 7]. We ease include anosmia, proptosis, facial pain, or frontal headache due to invasion of adjacent structures [2]. There report the case of a pregnant woman with a locally advanced is a slight male predominance and a bimodal age presenta- esthesioneuroblastoma (Figure 1). 2 Case Reports in Oncological Medicine Pregnant female, 27y Diagnosis and interventions Follow-up and outcomes Complete response Esthesioneuroblastoma, stage D (Kadish), grade III/IV (Hayms) th 12 months of Fup: Allergic rhinitis ChT before delivery Delivery (i) Healthy baby with normal development Atopic eczema ChT aer deli ft very Sequential RT Present 2 2 (ii) Cisplatin 75 mg/m D1 Cisplatin 100 mg/m D1 VMAT at a dose of 70 Gy Patient clinically well 2 2 Treatment sequels: visual acuity in the Etoposide 75 mg/m D1-3 Etoposide 100 mg/m D1-3 right eye G1; xerostomia G1; cervical Past history every 28 days, 2 cycles every 21 days, 4 cycles fibrosis G1 Symptoms: Physical examination: (i) Right nasal obstruction (i) Voluminous right cervical lymphadenopathy (ii) Right cervical lymphadenopathy (ii) Cutaneous erythema (iii) Pain in the right superior dental arcade (iii) Right ocular oedema (iv) Vegetant non-ulcerated lesion on the nasopharynx Figure 1: Timeline. 2. Case Presentation A 27-year-old 8-week pregnant woman, with a history of allergic rhinitis and atopic eczema, presented to a general hospital with right nasal obstruction, right cervical lymph- adenopathy, and pain in the right superior dental arcade. A nonsteroidal anti-inflammatory drug was started with reso- lution of the dental pain after one week of treatment. Two months later, while maintaining a progressively growing right cervical lymphadenopathy and right nasal obstruction, the patient developed anosmia, frequent episodes of epi- staxis, and right frontal headache. A fine needle biopsy of the lymphadenopathy was performed with an inconclusive result, revealing only the presence of inflammatory cells. A Figure 2 core biopsy was then performed which revealed lymph node metastasis from a poorly differentiated malignant neoplasm. At the 23rd week of pregnancy, the patient was referred to our hospital. On physical examination, the patient had a voluminous right cervical lymphadenopathy with 15 cm from levels Ib to V associated with cutaneous erythema as well as right ocular oedema (Figure 2). A vegetant nonulcer- ated lesion was detected on the nasopharynx occupying the right nasal vestibulum. A biopsy of the lesion was performed. Pathology’s result revealed respiratory epithelium with focal involvement by small round blue cells, neuron-specific eno- lase (NSE) positive, synaptophysin positive, PS 100 positive, and AE1/AE3 and CD99 negative. The cranial and cervical magnetic resonance images (MRI) revealed a lesion with 7×5,2×3,2 cm in the nasal fossae, ethmoidal complex, and right olfactive fend with invasion of the endocranial com- partment and the orbit and deviation of the internal rectum muscle as well as extension to the nasopharynx lumen and invasion of the sphenoidal sinus associated with lymphade- nopathy in the retropharyngeal area and right II, III, IV, and V levels (Figures 3 and 4). The patient was diagnosed with a right esthesioneuroblastoma stage D in the modified Figure 3 Kadish grading system [4] and grade III/IV in the Hyams grading system [5]. setron 8 mg. Additional treatment with daily folic acid, oral The case was evaluated by a multidisciplinary team of iron, iodine supplementation, and prophylactic enoxaparin head and neck surgeons, medical oncologists, and radiation was made as recommended by the obstetrician. oncologists. The multidisciplinary tumor board determined After the first cycle of treatment, a clinical reduction of that there was no indication to perform surgery due to local the lesion was noted (Figure 5). Concerning the baby devel- extent of the disease. The patient was proposed to do sys- opment, routine amniotic fluid assessment made by foetal temic treatment with chemotherapy followed by reevaluation echography after the 2nd cycle of chemotherapy showed an by the multidisciplinary tumor board. Treatment with cis- increase in systolic velocity in the Doppler midfoetal cerebral 2 2 platin 75 mg/m on day 1 and etoposide 75 mg/m on days artery (systolic peak > 1 5 MoMs for gestational age). This finding was in favour with an established foetal anemia 1 to 3, cycles every 28 days, was started after an appropriate discussion with the patient’s obstetrician. The following pre- and interpreted as a side effect of chemotherapy. Once medication before each treatment cycle was prescribed: the foetus was stable (normal foetal biophysical profile), hydrocortisone 100 mg, metoclopramide 10 mg, and ondan- a foetal lung maturation cycle with betamethasone was Case Reports in Oncological Medicine 3 Fourteen days after the delivery, chemotherapy was resumed at a full dose with cisplatin 100 mg/m on day 1 and etoposide 100 mg/m on days 1 to 3, cycles every 21 days. After 4 cycles of treatment, a positron emission tomography- computed tomography (PET-CT) and MRI were performed, revealing a partial response. The patient completed 6 cycles of treatment with good tolerance. The main toxicities reported during treatment were grade 1 anemia, grade 1 nau- sea, and emesis treated with oral iron, folic acid, and metoclo- pramide as needed. The case was again discussed in a multidisciplinary tumor board, and treatment with radiotherapy (RT) was pro- posed. The patient performed 33 fractions of treatment with volumetric modulated arc therapy (VMAT) at a dose of 70 Gy to the neoplastic lesion, right retropharyngeal area, and right cervical Ib to V levels and 50 Gy to the left retro- pharyngeal area, left cervical Ib to V levels, and left perinasal area. The treatment had a duration of 45 days with good tol- erance. The main toxicities were grade 2 dysphagia, grade 2 odynophagia, grade 2 xerostomia, grade 2 oral mucositis, and grade 2 cervical dermatitis. A period of clinical vigilance was started, and 12 weeks after the last treatment of radiotherapy, a PET-CT was per- formed revealing no radiopharmaceutical uptake. At the Figure 4 12th month of follow-up, the baby is healthy and presents a normal development. The patient is clinically well present- ing as treatment sequels a grade 1 diminution of visual acu- ity in the right eye, xerostomia grade 1, and cervical fibrosis grade 1. 3. Conclusions This clinical case demonstrates the challenge of diagnosis and management of a rare and aggressive type of esthesioneuro- blastoma in a pregnant woman. ENB is an uncommon tumor that frequently presents with nonspecific symptoms such as nasal obstruction and facial pain. The diagnosis is a challenge for the clinicians due to the rarity and unspecificity of this entity. Moreover, while the histologic diagnosis of a well- differentiated tumor is quite evident, a less differentiated form can be more laborious requiring additional markers for the differential diagnosis among the group of small round cell malignant neoplasms that can affect the sinonasal tract. Olfactory neuroblastomas frequently express NSE and synaptophysin and are negative for the expression of leuco- cyte common antigen and CD99 [1]. The entities to be consid- ered in differential diagnosis are neuroendocrine carcinomas, Figure 5 melanoma, rhabdomyosarcoma, sinonasal undifferentiated carcinoma, squamous cell carcinoma (including NUT carci- performed according to protocol, and a decision to terminate noma), lymphoma, Ewing sarcoma, and metastatic tumors [1, 8]. Both the nonspecific presentation and the rare histolog- the pregnancy in an elective manner was made, thus avoiding the worsening of the condition with a new cycle of chemo- ical diagnosis contribute to a delay for the final diagnosis therapy. In addition, after 30 weeks of gestation, clinical sus- which justifies that the majority of the ENB are found picion of foetal anemia is an indication for termination of in an advanced stage [9] as was the case in the clinical pregnancy, avoiding invasive foetal studies. Thus, 21 days case described. The standard treatment for ENB has not been estab- after the second cycle of treatment and at 31 weeks of preg- nancy, the patient delivered by caesarean a healthy baby lished. The lack of prospective data due to its rarity and the uneventfully. While hospitalized, the new-born presented a absence of molecular therapeutic targets are contributing normal development and no health problems were detected. factors [10, 11]. Surgery followed by RT has been the most 4 Case Reports in Oncological Medicine roids can be used at the lowest effective dose and for the frequent treatment strategy and is associated with improved overall survival compared with surgery or RT alone [12, 13]. shortest duration of time. Patients with cervical lymph node metastasis at presentation There were no complications during the neonatal period have a worse prognosis despite combined-treatment modal- and the 12th month period of follow-up for both the baby ity [13], and the optimal management of these patients is and the mother, although a longer period of follow-up is nec- uncertain. This clinical case describes a 23-week pregnant essary to ascertain this good outcome. Due to the aggressive woman with a stage D ENB with cervical lymph node metas- nature of the esthesioneuroblastoma, clinical evaluation is tasis from levels Ib to V. The aggressive phenotype of the dis- made on a monthly basis. ease characterized by a painful and rapidly growing locally This case highlights that chemotherapy is an important advanced tumor with lymph node metastasis and local inva- component of the multimodal treatment strategy of locally sion of the orbit and endocranial compartment motivated the advanced esthesioneuroblastoma and shows that in a lifesav- decision to do treatment with neoadjuvant chemotherapy ing situation, chemotherapy with cisplatin and etoposide can followed by radiotherapy. In fact, there is some published be administered in the 2nd and 3rd trimesters of pregnancy. data that suggests that EBN is chemosensitive, and the addi- Moreover, a prompt diagnosis is critical to achieve complete tion of induction chemotherapy to a combined-treatment remission of the disease especially in the case of a biologically modality in patients with advanced ENB may improve treat- aggressive neoplasm. Prognosis of patients diagnosed with ment outcomes [10, 13]. The objective response to chemo- cancer during pregnancy is usually comparable with non- therapy varied between 68% and 82% [10, 13–15], with a pregnant patients [17]; however, since recurrence of this type of tumor may develop 10 or more years following initial 5-year overall survival rate achieving 78% [13]. Various chemotherapy agents have been used, being cisplatin- treatment [23, 24], a prolonged surveillance is mandatory. based regimens (notably cisplatin and etoposide) frequently This clinical case should be looked as a contribution to chosen with encouraging responses [16]. In what concerns future similar cases as it is a unique illustration of a rare the treatment strategy, the 23-week pregnancy of the and aggressive esthesioneuroblastoma in a pregnant woman. patient posed an increasing challenge since the diagnosis of cancer during pregnancy is uncommon [17], and data Abbreviations about chemotherapy in esthesioneuroblastoma during preg- nancy is missing. ENB: Esthesioneuroblastoma Exposure to some chemotherapeutic agents during the MRI: Magnetic resonance image second and third trimesters has not been associated with NSE: Neuron-specific enolase increased risk of foetal malformations or major problems in OBN: Olfactory neuroblastoma the short and long terms [17–19], contrarily to administra- PET-CT: Positron emission tomography-computed tion of chemotherapy during the first trimester of gestation tomography which is associated with an increased risk of foetal congenital RT: Radiotherapy defects [17]. Cisplatin is usually safe for the foetus in the sec- 2 VMAT: Volumetric modulated arc therapy. ond and third trimesters [20] for doses up to 75 mg/m every 3 weeks [17]. There is evidence [21] that the rate of malfor- mations after exposure to cisplatin in the first trimester is Ethical Approval about 20% but is reduced to 1% in the second and third tri- mesters of pregnancy. Regarding etoposide, the data is more All procedures performed were in accordance with the limited reporting 3% of major malformations during the sec- ethical standards of the institutional and national research ond and third trimesters of pregnancy and a foetal growth committees and with the 1964 Helsinki Declaration and its restriction in 24% of cases [21]. later amendments or comparable ethical standards. Considering that it was a lifesaving situation for both the pregnant patient and her baby, the decision was to start treat- ment with chemotherapy with a regimen of cisplatin and eto- Consent poside that was administered during the 24th to 31st week of Informed consent was obtained from the participant pregnancy. Furthermore, due to the high emetogenic poten- included in the study. tial of cisplatin-based regimens, it was essential to decide the pretreatment associated with each cycle of chemotherapy for prevention of chemotherapy-induced nausea and vomit- Conflicts of Interest ing in a pregnant patient. Both the dopamine D2 antagonist metoclopramide and the serotonin 5-hydroxytryptamine The authors declare that they have no conflict of interest. type (5-HT3) receptor antagonist ondansetron can be used during pregnancy as there is no report of an increased risk of pregnancy-related events [22]. In relation to corticoste- Authors’ Contributions roids, there is an association between oral clefts and use of systemic steroids during the first trimester of pregnancy, so The first author wrote the article; CV and JD wrote and its use should be cautious before 10 weeks of gestation [22]. reviewed the article. All authors read and approved the final Outside the first trimester of pregnancy, systemic corticoste- manuscript. Case Reports in Oncological Medicine 5 diagnosis, treatment and follow-up,” Annals of Oncology, References vol. 24, Supplement 6, pp. vi160–vi170, 2013. [1] L. Barnes, J. W. Eveson, P. Reichart, and D. Sidransky, “Olfac- [18] T. Vandenbroucke, M. Verheecke, M. Fumagalli, C. Lok, and tory neuroblastoma,” in Pathology and Genetics of Head and F. Amant, “Effects of cancer treatment during pregnancy on Neck Tumours, IARC Press, Lyon, France, 2005. fetal and child development,” The Lancet Child & Adolescent Health, vol. 1, no. 4, pp. 302–310, 2017. [2] A. S. Abdelmeguid, “Olfactory neuroblastoma,” Current Oncology Reports, vol. 20, no. 1, p. 7, 2018. [19] F. Amant, T. Vandenbroucke, M. Verheecke et al., “Pediatric [3] J. P. Marinelli, J. R. Janus, J. J. Van Gompel et al., “Esthesio- outcome after maternal cancer diagnosed during pregnancy,” The New England Journal of Medicine, vol. 373, no. 19, neuroblastoma with distant metastases: systematic review & meta-analysis,” Head & Neck, vol. 40, no. 10, pp. 2295–2303, pp. 1824–1834, 2015. [20] A. McCormick and E. Peterson, “Cancer in pregnancy,” [4] A. Morita, M. J. Ebersold, K. D. Olsen, R. L. Foote, J. E. Lewis, Obstetrics and Gynecology Clinics of North America, vol. 45, and L. M. Quast, “Esthesioneuroblastoma: prognosis and man- no. 2, pp. 187–200, 2018. agement,” Neurosurgery, vol. 32, no. 5, pp. 706–715, 1993. [21] National Toxicology Program, NTP Monograph on Develop- [5] V. Hyams, J. Batsakis, and L. Michaels, Tumors of the Upper mental Effects and Pregnancy Outcomes Associated with Can- Respiratory Tract and Ear. Armed Forces Institute of Pathology cer Chemotherapy Use during Pregnancy, U.S. Department of Fascicles, 2nd Series, American Registry of Pathology Press, health and Human services, 2013. Washington, DC, USA, 1988. [22] M. Erick, J. T. Cox, and K. M. Mogensen, “ACOG practice [6] N. Konuthula, A. M. Iloreta, B. Miles et al., “Prognostic signif- bulletin 189: nausea and vomiting of pregnancy,” Obstetrics icance of Kadish staging in esthesioneuroblastoma: an analysis and Gynecology, vol. 131, no. 5, p. 935, 2018. of the National Cancer Database,” Head & Neck, vol. 39, [23] P. D. Ward, J. A. Heth, B. G. Thompson, and L. J. Marentette, no. 10, pp. 1962–1968, 2017. “Esthesioneuroblastoma: results and outcomes of a single [7] B. A. Tajudeen, A. Arshi, J. D. Suh, M. St John, and M. B. institution’s experience,” Skull Base, vol. 19, no. 2, pp. 133– Wang, “Importance of tumor grade in esthesioneuroblastoma 140, 2009. survival: a population-based analysis,” JAMA Otolaryngology. [24] E. M. Diaz Jr., R. H. Johnigan III, C. Pero et al., “Olfactory Head & Neck Surgery, vol. 140, no. 12, pp. 1124–1129, 2014. neuroblastoma: the 22-year experience at one comprehensive [8] L. D. R. Thompson, “Small round blue cell tumors of the sino- cancer center,” Head & Neck, vol. 27, no. 2, pp. 138–149, nasal tract: a differential diagnosis approach,” Modern Pathol- 2005. ogy, vol. 30, Supplement 1, pp. S1–S26, 2017. [9] R. Kumar, S. Ghoshal, D. Khosla et al., “Survival and failure outcomes in locally advanced esthesioneuroblastoma: a single centre experience of 15 patients,” European Archives of Oto- Rhino-Laryngology, vol. 270, no. 6, pp. 1897–1901, 2013. [10] A. Modesto, P. Blanchard, Y. G. Tao et al., “Multimodal treat- ment and long-term outcome of patients with esthesioneuro- blastoma,” Oral Oncology, vol. 49, no. 8, pp. 830–834, 2013. [11] P. Czapiewski, M. Kunc, and J. Haybaeck, “Genetic and molec- ular alterations in olfactory neuroblastoma: implications for pathogenesis, prognosis and treatment,” Oncotarget, vol. 7, no. 32, pp. 52584–52596, 2016. [12] P. Dulguerov, A. S. Allal, and T. C. Calcaterra, “Esthesioneur- oblastoma: a meta-analysis and review,” The Lancet Oncology, vol. 2, no. 11, pp. 683–690, 2001. [13] S. Y. Su, D. Bell, R. Ferrarotto et al., “Outcomes for olfactory neuroblastoma treated with induction chemotherapy,” Head & Neck, vol. 39, no. 8, pp. 1671–1679, 2017. [14] D. W. Kim, Y. H. Jo, J. H. Kim et al., “Neoadjuvant etoposide, ifosfamide, and cisplatin for the treatment of olfactory neuro- blastoma,” Cancer, vol. 101, no. 10, pp. 2257–2260, 2004. [15] Y. Mishima, E. Nagasaki, Y. Terui et al., “Combination chemo- therapy (cyclophosphamide, doxorubicin, and vincristine with continuous-infusion cisplatin and etoposide) and radiother- apy with stem cell support can be beneficial for adolescents and adults with estheisoneuroblastoma,” Cancer, vol. 101, no. 6, pp. 1437–1444, 2004. [16] V. A. Resto, D. W. Eisele, A. Forastiere, M. Zahurak, D. J. Lee, and W. H. Westra, “Esthesioneuroblastoma: the Johns Hopkins experience,” Head & Neck, vol. 22, no. 6, pp. 550–558, 2000. [17] F. A. Peccatori, H. A. Azim, R. 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