- Email: [email protected]
Human papillomavirus-related carcinoma with adenoid cystic-like features of the inferior turbinate: A case report
Auris Nasus Larynx 42 (2015) 53–55
Contents lists available at ScienceDirect
Auris Nasus Larynx journal homepage: www.elsevier.com/locate/anl
Human papillomavirus-related carcinoma with adenoid cystic-like features of the inferior turbinate: A case report Sun Jin Hwang a, Sohea Ok a, Heung-Man Lee a, Eunjung Lee b, Il-Ho Park a,* a b
Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, Republic of Korea Department of Pathology, Korea University College of Medicine, Seoul, Republic of Korea
A R T I C L E I N F O
A B S T R A C T
Article history: Received 31 March 2014 Accepted 5 July 2014 Available online 8 September 2014
Sinonasal malignancies are uncommon, but are of many different histologic types. Recently, Human papillomavirus (HPV)-related carcinoma with adenoid cystic features was reported as a new histologic form. Although this histologic type resembles an adenoid cystic carcinoma, it differs from adenoid cystic carcinomas with regard to its association with HPV. Here, we present a case of HPV-related carcinoma with adenoid cystic features in the nasal cavity. We also review the histological characters of the tumor. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Sinonasal malignancy HPV Adenoid cystic carcinoma
1. Introduction Malignant neoplasms of the sinonasal tract are uncommon, accounting for 1% of all malignant tumors [1,2] and approximately 5% of head and neck malignancies [3,4]. These tumors are diverse, and include squamous cell carcinomas (SCC), adenocarcinomas, adenoid cystic carcinomas (ACC), melanomas, sarcomas, and lymphomas. Although the causative factors of sinonasal tract cancer are not clearly defined [5], a few factors are known to be associated with specific histologic types. The association of wood dust exposure with adenocarcinoma is one such example. Human papillomavirus (HPV) is considered a causative agent of carcinoma of the sinonasal tract [6], although this has not been conclusively established. According to a recent report by Bishop et al. [7], HPV is detected in 21% of sinonasal carcinomas and is associated with SCC and carcinoma with adenoid cystic-like features. HPV-related carcinoma with adenoid cystic-like features is an unfamiliar disease that is not still included in the World Health Organization classification. In spite of significant morphologic resemblance to ACC, HPV-related carcinoma with adenoid cysticlike features is quite distinct from ACC in several respects including an association with surface squamous dysplasia that cannot be observed in ACC and an association with HPV, particularly type
* Corresponding author at: Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, 80 Guro-dong, Guro-gu, Seoul 152703, South Korea. Tel.: +82 2 2626 1298; fax: +82 2 868 0475. E-mail address: [email protected] (I.-H. Park). http://dx.doi.org/10.1016/j.anl.2014.07.005 0385-8146/ß 2014 Elsevier Ireland Ltd. All rights reserved.
33. It is supposed that relation to HPV in sinonasal carcinoma has clinical significance as shown in oropharyngeal carcinoma. In oropharyngeal carcinoma, detection of HPV is a powerful indicator of improved clinical outcome. Here, we report our experience in managing what we believe to be the first case of HPV-related carcinoma with adenoid cystic-like features occurring in the inferior turbinate. 2. Case report A 75-year-old female patient presented with a chief complaint of recurrent epistaxis for 3 months. Nasal endoscopy revealed a nasal mass in the left nasal cavity, but the origin of the mass was undefined (Fig. 1). The mass had a smooth surface and bled easily on contact. Computed tomography (CT) imaging revealed a mass-like hyperdense lesion between the left inferior turbinate and the nasal septum (Fig. 2). Magnetic resonance imaging showed a lesion with an isointense-signal on a T1-weighted image and heterogeneous signal intensity on a T2-weighted image (Fig. 2). The images showed a markedly enhanced mass with an indistinct margin in the left inferior turbinate. A punch biopsy was performed. Histopathology of the biopsy specimen showed a suspicious, malignant small round cell tumor, consistent with Ewing sarcoma/primitive neuroectodermal tumor (PNET). No metastases were observed on positron emission tomography-CT of the torso. The initial operative plan for a left inferior medial maxillectomy was changed after we identified the origin of the mass to be the inferior turbinate through a stalk during endoscopic examination in the operating room. The operative plan was changed to wide excision including inferior
54
S.J. Hwang et al. / Auris Nasus Larynx 42 (2015) 53–55
turbinectomy and was performed endoscopically. Histology revealed proliferation of basaloid cells that were compacted into nests and a cribriform structure that is similar to ACC. However, squamous dysplasia of the overlying surface epithelium was also observed. The specimen was positive for p16 (marker for HPV infection) on immunohistochemistry and HPV DNA positive on in situ hybridization (Fig. 3). In HPV in situ hybridization and HPVspecific PCR, tumor tissue was positive with the high-risk prove cocktail and negative with the probe for HPV type 6, 11, 16, and 18. The resection margins were free of tumor cells, and no perineural invasion was noted. On the basis of these findings, the postoperative histopathological diagnosis was HPV-related carcinoma with adenoid cystic-like features. No further treatment was provided. No complications and no recurrences were observed at the 12month follow-up examination postoperatively. 3. Discussion
Fig. 1. Endoscopic findings: an ovoid, smooth contoured mass between the septum (S) and the inferior turbinate (IT) of the left nasal cavity.
HPV-related carcinoma with adenoid cystic-like features is a recently proposed disease that is characterized by its resemblance with ACC in morphology, immunohistochemistry, origin in the sinonasal tract, and association with HPV 33 [7]. Morphologically, because of the presence of solid and cribriform patterns and highly cellular lesions composed of basaloid cells and some ductal cells, it is difficult to differentiate it from ACC or basaloid SCC and can be especially challenging for inexperienced pathologists. However, the treatment and prognosis of HPV-related carcinoma with
Fig. 2. (A and B) Axial and coronal view computed tomography images; (C and D) axial and coronal view T1-weighted enhanced magnetic resonance images: an approximately 1.3 cm 2.5 cm enhancing mass-like lesion (arrow) between the nasal septum and the left inferior turbinate.
S.J. Hwang et al. / Auris Nasus Larynx 42 (2015) 53–55
55
Fig. 3. (A) Scan view of whole tumor. Lesions with adenoid cystic like feature (black box), (B) cribriform structure (100), (C) squamous dysplasia of the surface epithelium (200), (D) P16 positivity (100), and (E) HPV positivity (100).
adenoid cystic-like features differ from those of other sinonasal carcinomas; therefore, an accurate diagnosis is important. HPV-related carcinomas are mainly identified as mucosal lesions exposed to the external environment including the cervix, anus, penis, vulva, vagina, and oropharynx [8]. Therefore, it is not surprising that carcinomas of the sinonasal tract are also associated with HPV. The characteristics of HPV-related carcinoma are different and depend on the type of lesion. In cases of uterine cervical cancer, best known for their HPV association, HPV is detected in more than 90% of cases, and most of the cases are associated with type 16 and type 18 [9]. HPV-positive cervical cancer is associated with a relatively favorable prognosis. The rates of relapse and distant metastasis associated with HPV-positive cervical cancers are lower than HPVnegative cancers, and the disease-free survival rate is also higher in HPV-positive cases [10]. Oropharyngeal squamous cell carcinoma is another example of a tumor closely associated with HPV, particularly HPV 16 [8]. It often shows features of a small primary tumor and extensive nodal involvement [11]. Despite the extensive nodal involvement, treatment outcomes and survival are better than those associated with HPV-negative cancers [12]. However, in vulvar cancer, the association with HPV does not affect the clinical features and prognosis, unlike with the other previously described cancer cases [13]. Little is known about the clinical features of HPV-related carcinoma with adenoid cystic-like features in the sinonasal tract. There is only one previously published report that describes the characteristics of this carcinoma. In this case series [7], regional and distant metastasis was not identified, irrespective of the T stage. The main treatment strategy was surgery, with or without radiation therapy. Of the seven cases, local recurrence was reported in two cases. To further define this rare disease, more data on such cases need to be collected. Since initial diagnosis in our case, on the basis of the pathologic examination of a punch biopsy specimen, was Ewing sarcoma/ primitive neuroectodermal tumor (PNET), the initial surgical plan was an inferior medial maxillectomy. However, under endoscopic examination, the lesion was found to be connected with the inferior turbinate by a stalk, and this finding is not consistent with a malignant tumor. Therefore, only wide excision was performed, including inferior turbinectomy, under endoscopic guidance. No local recurrence or distant metastasis was observed at the 1-year follow-up examination. Here, we report, what is to our knowledge, the first case of HPVrelated carcinoma with adenoid cystic-like features originating from the inferior turbinate, which was managed successfully with surgery only.
Conflict of interest None. Funding None. Acknowledgement This study was supported by a Korea University grant (K1326201). References [1] Tufano RP, Mokadam NA, Montone KT, Weinstein GS, Chalian AA, Wolf PF, et al. Malignant tumors of the nose and paranasal sinuses: hospital of the University of Pennsylvania experience 1990–1997. Am J Rhinol 1999;13:117–23. [2] Rinaldo A, Ferlito A, Shaha AR, Wei WI. Is elective neck treatment indicated in patients with squamous cell carcinoma of the maxillary sinus? Acta Otolaryngol 2002;122:443–7. [3] Le QT, Fu KK, Kaplan M, Terris DJ, Fee WE, Goffinet DR. Treatment of maxillary sinus carcinoma: a comparison of the 1997 and 1977 American Joint Committee on cancer staging systems. Cancer 1999;86:1700–11. [4] Tiwari R, Hardillo JA, Mehta D, Slotman B, Tobi H, Croonenburg E, et al. Squamous cell carcinoma of maxillary sinus. Head Neck 2000;22:164–9. [5] Barnes L, Tse LLY, Hunt JL, Brandwein-Gensler M, Curtin HD, Boffetta P. Tumours of the nasal cavity and paranasal sinuses: introduction. In: Barnes L, Eveson JW, Reichart P, Sidransky D, editors. World Health Organization classification of tumours: pathology and genetics of head and neck tumours. Lyon, France: IARC Press; 2005. p. 12–5. [6] Bishop JA, Guo TW, Smith DF, Wang H, Ogawa T, Pai SI, et al. Human papillomavirus related carcinomas of the sinonasal tract. Am J Surg Pathol 2013;37:185–92. [7] Bishop JA, Ogawa T, Stelow EB, Moskaluk CA, Koch WM, Pai SI, et al. Human papillomavirus related carcinoma with adenoid cystic like features: a peculiar variant of head and neck cancer restricted to the sinonasal tract. Am J Surg Pathol 2013;37:836–44. [8] Pytynia KB, Dahlstrom KR, Sturgis EM. Epidemiology of HPV-associated oropharyngeal cancer. Oral Oncol 2014 [Epub ahead of print]. ˜ oz N, Sherman M, Jansen AM, Peto J, et al. Preva[9] Bosch FX, Manos MM, Mun lence of human papillomavirus in cervical cancer: a worldwide perspective. J Natl Cancer Inst 1995;87:796–802. [10] Riou G, Favre M, Jeannel D, Bourhis J, Le Doussal V, Orth G. Association between poor prognosis in early-stage invasive cervical carcinomas and non-detection of HPV DNA. Lancet 1990;335:1171–4. [11] O’Sullivan B, Huang SH, Perez-Ordonez B, Massey C, Siu LL, Weinreb I, et al. Outcomes of HPV-related oropharyngeal cancer patients treated by radiotherapy alone using altered fractionation. Radiother Oncol 2012;103:49–56. [12] Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Taˆn PF, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 2010;363:24–35. [13] Hørding U, Kringsholm B, Andreasson B, Visfeldt J, Daugaard S, Bock JE. Human papillomavirus in vulvar squamous-cell carcinoma and in normal vulvar tissues: a search for a possible impact of HPV on vulvar cancer prognosis. Int J Cancer 1993;55:394–6.
Contents lists available at ScienceDirect
Auris Nasus Larynx journal homepage: www.elsevier.com/locate/anl
Human papillomavirus-related carcinoma with adenoid cystic-like features of the inferior turbinate: A case report Sun Jin Hwang a, Sohea Ok a, Heung-Man Lee a, Eunjung Lee b, Il-Ho Park a,* a b
Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, Republic of Korea Department of Pathology, Korea University College of Medicine, Seoul, Republic of Korea
A R T I C L E I N F O
A B S T R A C T
Article history: Received 31 March 2014 Accepted 5 July 2014 Available online 8 September 2014
Sinonasal malignancies are uncommon, but are of many different histologic types. Recently, Human papillomavirus (HPV)-related carcinoma with adenoid cystic features was reported as a new histologic form. Although this histologic type resembles an adenoid cystic carcinoma, it differs from adenoid cystic carcinomas with regard to its association with HPV. Here, we present a case of HPV-related carcinoma with adenoid cystic features in the nasal cavity. We also review the histological characters of the tumor. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Sinonasal malignancy HPV Adenoid cystic carcinoma
1. Introduction Malignant neoplasms of the sinonasal tract are uncommon, accounting for 1% of all malignant tumors [1,2] and approximately 5% of head and neck malignancies [3,4]. These tumors are diverse, and include squamous cell carcinomas (SCC), adenocarcinomas, adenoid cystic carcinomas (ACC), melanomas, sarcomas, and lymphomas. Although the causative factors of sinonasal tract cancer are not clearly defined [5], a few factors are known to be associated with specific histologic types. The association of wood dust exposure with adenocarcinoma is one such example. Human papillomavirus (HPV) is considered a causative agent of carcinoma of the sinonasal tract [6], although this has not been conclusively established. According to a recent report by Bishop et al. [7], HPV is detected in 21% of sinonasal carcinomas and is associated with SCC and carcinoma with adenoid cystic-like features. HPV-related carcinoma with adenoid cystic-like features is an unfamiliar disease that is not still included in the World Health Organization classification. In spite of significant morphologic resemblance to ACC, HPV-related carcinoma with adenoid cysticlike features is quite distinct from ACC in several respects including an association with surface squamous dysplasia that cannot be observed in ACC and an association with HPV, particularly type
* Corresponding author at: Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, 80 Guro-dong, Guro-gu, Seoul 152703, South Korea. Tel.: +82 2 2626 1298; fax: +82 2 868 0475. E-mail address: [email protected] (I.-H. Park). http://dx.doi.org/10.1016/j.anl.2014.07.005 0385-8146/ß 2014 Elsevier Ireland Ltd. All rights reserved.
33. It is supposed that relation to HPV in sinonasal carcinoma has clinical significance as shown in oropharyngeal carcinoma. In oropharyngeal carcinoma, detection of HPV is a powerful indicator of improved clinical outcome. Here, we report our experience in managing what we believe to be the first case of HPV-related carcinoma with adenoid cystic-like features occurring in the inferior turbinate. 2. Case report A 75-year-old female patient presented with a chief complaint of recurrent epistaxis for 3 months. Nasal endoscopy revealed a nasal mass in the left nasal cavity, but the origin of the mass was undefined (Fig. 1). The mass had a smooth surface and bled easily on contact. Computed tomography (CT) imaging revealed a mass-like hyperdense lesion between the left inferior turbinate and the nasal septum (Fig. 2). Magnetic resonance imaging showed a lesion with an isointense-signal on a T1-weighted image and heterogeneous signal intensity on a T2-weighted image (Fig. 2). The images showed a markedly enhanced mass with an indistinct margin in the left inferior turbinate. A punch biopsy was performed. Histopathology of the biopsy specimen showed a suspicious, malignant small round cell tumor, consistent with Ewing sarcoma/primitive neuroectodermal tumor (PNET). No metastases were observed on positron emission tomography-CT of the torso. The initial operative plan for a left inferior medial maxillectomy was changed after we identified the origin of the mass to be the inferior turbinate through a stalk during endoscopic examination in the operating room. The operative plan was changed to wide excision including inferior
54
S.J. Hwang et al. / Auris Nasus Larynx 42 (2015) 53–55
turbinectomy and was performed endoscopically. Histology revealed proliferation of basaloid cells that were compacted into nests and a cribriform structure that is similar to ACC. However, squamous dysplasia of the overlying surface epithelium was also observed. The specimen was positive for p16 (marker for HPV infection) on immunohistochemistry and HPV DNA positive on in situ hybridization (Fig. 3). In HPV in situ hybridization and HPVspecific PCR, tumor tissue was positive with the high-risk prove cocktail and negative with the probe for HPV type 6, 11, 16, and 18. The resection margins were free of tumor cells, and no perineural invasion was noted. On the basis of these findings, the postoperative histopathological diagnosis was HPV-related carcinoma with adenoid cystic-like features. No further treatment was provided. No complications and no recurrences were observed at the 12month follow-up examination postoperatively. 3. Discussion
Fig. 1. Endoscopic findings: an ovoid, smooth contoured mass between the septum (S) and the inferior turbinate (IT) of the left nasal cavity.
HPV-related carcinoma with adenoid cystic-like features is a recently proposed disease that is characterized by its resemblance with ACC in morphology, immunohistochemistry, origin in the sinonasal tract, and association with HPV 33 [7]. Morphologically, because of the presence of solid and cribriform patterns and highly cellular lesions composed of basaloid cells and some ductal cells, it is difficult to differentiate it from ACC or basaloid SCC and can be especially challenging for inexperienced pathologists. However, the treatment and prognosis of HPV-related carcinoma with
Fig. 2. (A and B) Axial and coronal view computed tomography images; (C and D) axial and coronal view T1-weighted enhanced magnetic resonance images: an approximately 1.3 cm 2.5 cm enhancing mass-like lesion (arrow) between the nasal septum and the left inferior turbinate.
S.J. Hwang et al. / Auris Nasus Larynx 42 (2015) 53–55
55
Fig. 3. (A) Scan view of whole tumor. Lesions with adenoid cystic like feature (black box), (B) cribriform structure (100), (C) squamous dysplasia of the surface epithelium (200), (D) P16 positivity (100), and (E) HPV positivity (100).
adenoid cystic-like features differ from those of other sinonasal carcinomas; therefore, an accurate diagnosis is important. HPV-related carcinomas are mainly identified as mucosal lesions exposed to the external environment including the cervix, anus, penis, vulva, vagina, and oropharynx [8]. Therefore, it is not surprising that carcinomas of the sinonasal tract are also associated with HPV. The characteristics of HPV-related carcinoma are different and depend on the type of lesion. In cases of uterine cervical cancer, best known for their HPV association, HPV is detected in more than 90% of cases, and most of the cases are associated with type 16 and type 18 [9]. HPV-positive cervical cancer is associated with a relatively favorable prognosis. The rates of relapse and distant metastasis associated with HPV-positive cervical cancers are lower than HPVnegative cancers, and the disease-free survival rate is also higher in HPV-positive cases [10]. Oropharyngeal squamous cell carcinoma is another example of a tumor closely associated with HPV, particularly HPV 16 [8]. It often shows features of a small primary tumor and extensive nodal involvement [11]. Despite the extensive nodal involvement, treatment outcomes and survival are better than those associated with HPV-negative cancers [12]. However, in vulvar cancer, the association with HPV does not affect the clinical features and prognosis, unlike with the other previously described cancer cases [13]. Little is known about the clinical features of HPV-related carcinoma with adenoid cystic-like features in the sinonasal tract. There is only one previously published report that describes the characteristics of this carcinoma. In this case series [7], regional and distant metastasis was not identified, irrespective of the T stage. The main treatment strategy was surgery, with or without radiation therapy. Of the seven cases, local recurrence was reported in two cases. To further define this rare disease, more data on such cases need to be collected. Since initial diagnosis in our case, on the basis of the pathologic examination of a punch biopsy specimen, was Ewing sarcoma/ primitive neuroectodermal tumor (PNET), the initial surgical plan was an inferior medial maxillectomy. However, under endoscopic examination, the lesion was found to be connected with the inferior turbinate by a stalk, and this finding is not consistent with a malignant tumor. Therefore, only wide excision was performed, including inferior turbinectomy, under endoscopic guidance. No local recurrence or distant metastasis was observed at the 1-year follow-up examination. Here, we report, what is to our knowledge, the first case of HPVrelated carcinoma with adenoid cystic-like features originating from the inferior turbinate, which was managed successfully with surgery only.
Conflict of interest None. Funding None. Acknowledgement This study was supported by a Korea University grant (K1326201). References [1] Tufano RP, Mokadam NA, Montone KT, Weinstein GS, Chalian AA, Wolf PF, et al. Malignant tumors of the nose and paranasal sinuses: hospital of the University of Pennsylvania experience 1990–1997. Am J Rhinol 1999;13:117–23. [2] Rinaldo A, Ferlito A, Shaha AR, Wei WI. Is elective neck treatment indicated in patients with squamous cell carcinoma of the maxillary sinus? Acta Otolaryngol 2002;122:443–7. [3] Le QT, Fu KK, Kaplan M, Terris DJ, Fee WE, Goffinet DR. Treatment of maxillary sinus carcinoma: a comparison of the 1997 and 1977 American Joint Committee on cancer staging systems. Cancer 1999;86:1700–11. [4] Tiwari R, Hardillo JA, Mehta D, Slotman B, Tobi H, Croonenburg E, et al. Squamous cell carcinoma of maxillary sinus. Head Neck 2000;22:164–9. [5] Barnes L, Tse LLY, Hunt JL, Brandwein-Gensler M, Curtin HD, Boffetta P. Tumours of the nasal cavity and paranasal sinuses: introduction. In: Barnes L, Eveson JW, Reichart P, Sidransky D, editors. World Health Organization classification of tumours: pathology and genetics of head and neck tumours. Lyon, France: IARC Press; 2005. p. 12–5. [6] Bishop JA, Guo TW, Smith DF, Wang H, Ogawa T, Pai SI, et al. Human papillomavirus related carcinomas of the sinonasal tract. Am J Surg Pathol 2013;37:185–92. [7] Bishop JA, Ogawa T, Stelow EB, Moskaluk CA, Koch WM, Pai SI, et al. Human papillomavirus related carcinoma with adenoid cystic like features: a peculiar variant of head and neck cancer restricted to the sinonasal tract. Am J Surg Pathol 2013;37:836–44. [8] Pytynia KB, Dahlstrom KR, Sturgis EM. Epidemiology of HPV-associated oropharyngeal cancer. Oral Oncol 2014 [Epub ahead of print]. ˜ oz N, Sherman M, Jansen AM, Peto J, et al. Preva[9] Bosch FX, Manos MM, Mun lence of human papillomavirus in cervical cancer: a worldwide perspective. J Natl Cancer Inst 1995;87:796–802. [10] Riou G, Favre M, Jeannel D, Bourhis J, Le Doussal V, Orth G. Association between poor prognosis in early-stage invasive cervical carcinomas and non-detection of HPV DNA. Lancet 1990;335:1171–4. [11] O’Sullivan B, Huang SH, Perez-Ordonez B, Massey C, Siu LL, Weinreb I, et al. Outcomes of HPV-related oropharyngeal cancer patients treated by radiotherapy alone using altered fractionation. Radiother Oncol 2012;103:49–56. [12] Ang KK, Harris J, Wheeler R, Weber R, Rosenthal DI, Nguyen-Taˆn PF, et al. Human papillomavirus and survival of patients with oropharyngeal cancer. N Engl J Med 2010;363:24–35. [13] Hørding U, Kringsholm B, Andreasson B, Visfeldt J, Daugaard S, Bock JE. Human papillomavirus in vulvar squamous-cell carcinoma and in normal vulvar tissues: a search for a possible impact of HPV on vulvar cancer prognosis. Int J Cancer 1993;55:394–6.