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Adenocarcinoma ex pleomorphic adenoma of the head and neck: Report of five cases
Auris Nasus Larynx 33 (2006) 43–46 www.elsevier.com/locate/anl
Adenocarcinoma ex pleomorphic adenoma of the head and neck: Report of five cases Shin Kariya a,*, Michiya Kosaka a, Yorihisa Orita a, Hirofumi Akagi b, Kazunori Nishizaki a a
Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-Cho, Okayama 700-8558, Japan b Department of Otolaryngology, National Hospital Organization Minami-Okayama Medical Center, Japan Received 17 March 2005; accepted 22 July 2005 Available online 15 September 2005
Abstract Objective: Adenocarcinoma ex pleomorphic adenoma is a rare tumor, and thus the management of the tumor has not been established. Methods: The retrospective review of the clinical records at Okayama University was performed. Results: We present five cases of adenocarcinoma ex pleomorphic adenoma of the head and neck, including a rare case with nasopharyngeal adenocarcinoma ex pleomorphic adenoma. There was no response to chemotherapy with nedaplatin and 5-FU, but the nasopharyngeal adenocarcinoma ex pleomorphic adenoma showed a remarkable regression after the administration of docetaxel. Conclusion: The combination therapy that includes docetaxel may be a promising treatment for adenocarcinoma ex pleomorphic adenoma of the head and neck. # 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Adonocarcinoma; Pleomorphic adenoma; Nasopharynx; Docetaxel; Chemotherapy
1. Introduction
2. Subjects and methods
Pleomorphic adenoma is a common neoplasm arising from the major salivary glands, especially the parotid gland. The incidence of malignant transformation in a pleomorphic adenoma is 1–7% [1]. Pleomorphic adenoma is frequently reported to occur in the parapharyngeal space, however, the nasopharynx is an uncommon site. Carcinoma ex pleomorphic adenoma is a rare, aggressive malignancy that accounts for 3.6% (range 0.9–14%) of all salivary neoplasms [2]. Carcinoma ex pleomorphic adenoma presenting in the nasopharynx is extremely rare [3]. We present five cases of adenocarcinoma ex pleomorphic adenoma of the head and neck treated in our institute, including a rare case of adenocarcinoma ex pleomorphic adenoma arising from the posterior wall of the nasopharynx.
The clinical records of all patients treated for head and neck tumors at Okayama University, Okayama, Japan, from 1990 to 2003 were retrospectively reviewed. One thousand two hundred and thirty-six cases presenting with head and neck tumors were identified, of which 128 cases had parotid tumors and 88 cases had pleomorphic adenomas.
* Corresponding author. Tel.: +81 86 235 7307; fax: +81 86 235 7308. E-mail address: [email protected] (S. Kariya).
3. Results Five cases of adenocarcinoma ex pleomorphic adenoma of the head and neck were identified, and the clinical records are summarized in Table 1. Staging criteria of the American Joint Committee on Cancer, 1992 were used [4]. Of the five cases of adenocarcinoma ex pleomorphic adenoma, two were male and three were female, and their age ranged from 52 to 87 years at the time of their first admission.
0385-8146/$ – see front matter # 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.anl.2005.07.001
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S. Kariya et al. / Auris Nasus Larynx 33 (2006) 43–46
Table 1 Clinical records of five patients with adenocarcinoma ex pleomorphic adenoma
In three cases, the parotid grand was the primary site. One case (case 3) had a past history of an operation for a parotid tumor. The tumor had recurred locally 5 years after the operation, but had been stable for 25 years. She was seen at our hospital due to increased right parotid swelling. Two cases (cases 1 and 5) had no past history of a parotid tumor. Of the three parotid cases, two cases died of distant metastases, and in one of these cases the clinical course was quite short. In the two cases without parotid involvement, the primary tumors were located in the palate and nasopharynx. One patient with palatal adenocarcinoma ex pleomorphic adenoma had a past history of a palatal tumor resection in his youth, though the histology was unknown. This patient had a gradual enlargement of the palatal tumor over 5 years and underwent a radical operation with reconstructive surgery. This patient had no local or distant recurrence.
4. Clinical presentation (case 4) The patient was a 59-year-old female complaining of right nasal obstruction of 3 months duration. She had no epistaxis, pain, or rhinorrhea. Her past history was unremarkable. Endoscopic examination revealed a massive tumor occupying the nasopharyngeal space. The pharyngeal ostium of the Eustachian tube on the right side was obstructed due to the mass (Fig. 1). Though the tumor touched the nasal septum, direct invasion into the nasal septum was not detected. A computed tomographic scan of the pharynx showed a large mass in the nasopharynx with heterogeneous enhancement (Fig. 2). The tumor was partly gadolinium-enhanced on T1 weighted magnetic resonance imaging and showed homogeneously intermediate signal intensity on the T2 image. An endoscopic transnasal biopsy was performed, and the histopathological examination
S. Kariya et al. / Auris Nasus Larynx 33 (2006) 43–46
45
Fig. 1. Endoscopic view showing a massive tumor in the nasopharynx (case 4). INC, inferior nasal concha; T, tumor; NS, nasal septum.
Fig. 3. Endoscopic view showing the small remaining tumor (*) in the posterior wall of nasopharynx after four cycles of the chemotherapy with docetaxel (case 4).
revealed an adenocarcinoma of the nasopharynx. On palpation, the cervical lymph nodes were not palpable, and no distant metastases were detected. Neoadjuvant chemotherapy with nedaplatin (80 mg/(m2 day 1)) and 5-FU (700 mg/(m2 days 1–5)) was administered, but the tumor showed no response. Therefore, the patient was given a different neoadjuvant chemotherapy protocol using docetaxel (60 mg/(m2 day 1)). After four cycles of the
chemotherapy with docetaxel, the tumor showed a remarkable remission (Fig. 3). Resection of the small remaining tumor via a transmaxillary approach was performed followed by postoperative irradiation of 74.4 Gy (hyperfractionation: 1.2 Gy b.i.d. on days 1–31). The pathological findings from the extirpated tumor were consistent with adenocarcinoma ex pleomorphic adenoma (Fig. 4). Two years later the patient was clinically disease free in the nasopharyngeal area, and no metastases were detected.
5. Discussion Pleomorphic adenoma is one of the most common benign tumors arising in the head and neck, and is especially
Fig. 2. Axial CT scan of case 4 with iopamidol enhancement. The arrow shows the adenocarcinoma ex pleomorphic adenoma in the nasopharynx.
Fig. 4. Photomicroscopy of case 4 showing adenocarcinoma ex pleomorphic adenoma (H&E; original magnification 200).
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S. Kariya et al. / Auris Nasus Larynx 33 (2006) 43–46
frequent in the parotid grand. Carcinoma ex pleomorphic adenoma arises from either long-standing or recurrent pleomorphic adenoma, and is classified into several subtypes: adenocarcinoma, salivary duct carcinoma, adenosquamous carcinoma, undifferentiated carcinoma, adenoid cystic carcinoma, myoepithelial carcinoma, epithelialmyoepithelial carcinoma, and sarcomatoid carcinoma [5]. Adenocarcinoma ex pleomorphic adenoma accounts for 44% of carcinoma ex pleomorphic adenoma [5]. In this study, the parotid gland was the primary site in three of five cases. Though one case (case 3) had a long history of parotid swelling, adenocarcinoma ex pleomorphic adenoma should also be considered in patients with a primary parotid tumor that have a short clinical course (case 1). The solid portion of the carcinoma ex pleomorphic adenoma exhibits intermediate signal intensity on conventional T2 weighted magnetic resonance imaging, and it is composed of papilliform epithelial cells with abnormal nuclei including large nucleoli [6]. Laminin and collagen IV are considered to be the factors responsible for both malignant transformation and biological progression in a pleomorphic adenoma [7]. Saleh et al. [8] reported that the expression of the neural cell adhesion molecule (N-CAM) was decreased in carcinoma ex pleomorphic adenoma compared to benign pleomorphic adenoma, and that N-CAM might be used as an auxiliary tool in the diagnosis of early pleomorphic adenoma malignancy. Lewis et al. [5] showed that mutation of p53 was an early event in the malignant transformation of a pleomorphic adenoma. Olsen and Lewis [2] reported 73 cases with carcinoma ex pleomorphic adenoma in the major salivary glands, and showed an overall survival of 39% at 3 years and 30% at 5 years. Surgical excision is the usual treatment, with postoperative radiation therapy being given due to the high-grade malignancy of carcinoma ex pleomorphic adenoma located in the major salivary glands [2]. Though minor salivary gland tumors are histologically identical to those of the major glands [3], the management of carcinoma ex pleomorphic adenoma in the minor salivary glands has not been established. The therapeutic strategy to the carcinoma ex pleomorphic adenoma in head and neck in our institute is the surgical operation with wide margin. The indication for postoperative radiation therapy or chemotherapy depends on the sufficiency of the surgical margin. All cases in this study showed no local recurrence.
There is evidence to suggest that docetaxel is a promising agent for the treatment of adenocarcinoma [9,10]. In particular, in case 4, although chemotherapy using nedaplatin and 5-FU was ineffective for the adenocarcinoma ex pleomorphic adenoma, with docetaxel treatment a notable improvement was seen. In fact, using docetaxel to shrink the tumor pre-operatively, as was done in case 4, may be useful, since it is difficult to excise a nasopharyngeal tumor with a large enough margin. Thus, the clinical course of case 4 demonstrates that docetaxel treatment may become a useful therapeutic approach in the management of adenocarcinoma ex pleomorphic adenoma of the minor salivary glands. In general, adenocarcinoma ex pleomorphic adenoma should be considered in all patients with a nasopharyngeal tumor.
References [1] Izzo L, Frati R, Cianfrone F, Sassayannis PG, Costi U, Galati G, et al. Parotid gland cancer: a case report of a primitive adenocarcinoma arising from a multirecurrent pleomorphic adenoma. J Exp Clin Cancer Res 2004;23:153–6. [2] Olsen KD, Lewis JE. Carcinoma ex pleomorphic adenoma: a clinicopathologic review. Head Neck 2001;23:705–12. [3] Furukawa M, Suzuki H, Matsuura K, Takahashi E, Suzuki H, Tezuka F. Carcinoma ex pleomorphic adenoma of the palatal minor salivary gland with extension into the nasopharynx. Auris Nasus Larynx 2001;28:279–81. [4] American Joint Committee on Cancer. 4th ed., Manual for staging of cancer, Philadelphia, PA: Lippincott, 1992. [5] Lewis JE, Olsen KD, Sebo TJ. Carcinoma ex pleomorphic adenoma: pathologic analysis of 73 cases. Hum Pathol 2001;32: 596–604. [6] Sakamoto M, Sasano T, Higano S, Takahashi S, Iikubo M, Kakehata S. Usefulness of heavily T2 weighted magnetic resonance images for the differential diagnosis of parotid tumours. Dentomaxillofac Radiol 2003;32:295–9. [7] Felix A, Rosa JC, Fonseca I, Cidadao A, Soares J. Laminin and collagen IV in pleomorphic adenoma and carcinoma ex-pleomorphic adenoma: an immunohistochemical study. Hum Pathol 1999;30:964– 9. [8] Saleh ER, Franca CM, Marques MM. Neural adhesion molecule (NCAM) in pleomorphic adenoma and carcinoma ex-pleomorphic adenoma. J Oral Pathol Med 2003;32:562–7. [9] Haller DG, Misset JL. Docetaxel in advanced gastric cancer. Anticancer Drugs 2002;13:451–60. [10] Jatoi A, Tirona MT, Cha SS, Alberts SR, Rowland KM, Morton RF, et al. A phase II trial of docetaxel and CPT-11 in patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction, and gastric cardia. Int J Gastrointest Cancer 2002;32:115–23.
Adenocarcinoma ex pleomorphic adenoma of the head and neck: Report of five cases Shin Kariya a,*, Michiya Kosaka a, Yorihisa Orita a, Hirofumi Akagi b, Kazunori Nishizaki a a
Department of Otolaryngology-Head & Neck Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikata-Cho, Okayama 700-8558, Japan b Department of Otolaryngology, National Hospital Organization Minami-Okayama Medical Center, Japan Received 17 March 2005; accepted 22 July 2005 Available online 15 September 2005
Abstract Objective: Adenocarcinoma ex pleomorphic adenoma is a rare tumor, and thus the management of the tumor has not been established. Methods: The retrospective review of the clinical records at Okayama University was performed. Results: We present five cases of adenocarcinoma ex pleomorphic adenoma of the head and neck, including a rare case with nasopharyngeal adenocarcinoma ex pleomorphic adenoma. There was no response to chemotherapy with nedaplatin and 5-FU, but the nasopharyngeal adenocarcinoma ex pleomorphic adenoma showed a remarkable regression after the administration of docetaxel. Conclusion: The combination therapy that includes docetaxel may be a promising treatment for adenocarcinoma ex pleomorphic adenoma of the head and neck. # 2005 Elsevier Ireland Ltd. All rights reserved. Keywords: Adonocarcinoma; Pleomorphic adenoma; Nasopharynx; Docetaxel; Chemotherapy
1. Introduction
2. Subjects and methods
Pleomorphic adenoma is a common neoplasm arising from the major salivary glands, especially the parotid gland. The incidence of malignant transformation in a pleomorphic adenoma is 1–7% [1]. Pleomorphic adenoma is frequently reported to occur in the parapharyngeal space, however, the nasopharynx is an uncommon site. Carcinoma ex pleomorphic adenoma is a rare, aggressive malignancy that accounts for 3.6% (range 0.9–14%) of all salivary neoplasms [2]. Carcinoma ex pleomorphic adenoma presenting in the nasopharynx is extremely rare [3]. We present five cases of adenocarcinoma ex pleomorphic adenoma of the head and neck treated in our institute, including a rare case of adenocarcinoma ex pleomorphic adenoma arising from the posterior wall of the nasopharynx.
The clinical records of all patients treated for head and neck tumors at Okayama University, Okayama, Japan, from 1990 to 2003 were retrospectively reviewed. One thousand two hundred and thirty-six cases presenting with head and neck tumors were identified, of which 128 cases had parotid tumors and 88 cases had pleomorphic adenomas.
* Corresponding author. Tel.: +81 86 235 7307; fax: +81 86 235 7308. E-mail address: [email protected] (S. Kariya).
3. Results Five cases of adenocarcinoma ex pleomorphic adenoma of the head and neck were identified, and the clinical records are summarized in Table 1. Staging criteria of the American Joint Committee on Cancer, 1992 were used [4]. Of the five cases of adenocarcinoma ex pleomorphic adenoma, two were male and three were female, and their age ranged from 52 to 87 years at the time of their first admission.
0385-8146/$ – see front matter # 2005 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.anl.2005.07.001
44
S. Kariya et al. / Auris Nasus Larynx 33 (2006) 43–46
Table 1 Clinical records of five patients with adenocarcinoma ex pleomorphic adenoma
In three cases, the parotid grand was the primary site. One case (case 3) had a past history of an operation for a parotid tumor. The tumor had recurred locally 5 years after the operation, but had been stable for 25 years. She was seen at our hospital due to increased right parotid swelling. Two cases (cases 1 and 5) had no past history of a parotid tumor. Of the three parotid cases, two cases died of distant metastases, and in one of these cases the clinical course was quite short. In the two cases without parotid involvement, the primary tumors were located in the palate and nasopharynx. One patient with palatal adenocarcinoma ex pleomorphic adenoma had a past history of a palatal tumor resection in his youth, though the histology was unknown. This patient had a gradual enlargement of the palatal tumor over 5 years and underwent a radical operation with reconstructive surgery. This patient had no local or distant recurrence.
4. Clinical presentation (case 4) The patient was a 59-year-old female complaining of right nasal obstruction of 3 months duration. She had no epistaxis, pain, or rhinorrhea. Her past history was unremarkable. Endoscopic examination revealed a massive tumor occupying the nasopharyngeal space. The pharyngeal ostium of the Eustachian tube on the right side was obstructed due to the mass (Fig. 1). Though the tumor touched the nasal septum, direct invasion into the nasal septum was not detected. A computed tomographic scan of the pharynx showed a large mass in the nasopharynx with heterogeneous enhancement (Fig. 2). The tumor was partly gadolinium-enhanced on T1 weighted magnetic resonance imaging and showed homogeneously intermediate signal intensity on the T2 image. An endoscopic transnasal biopsy was performed, and the histopathological examination
S. Kariya et al. / Auris Nasus Larynx 33 (2006) 43–46
45
Fig. 1. Endoscopic view showing a massive tumor in the nasopharynx (case 4). INC, inferior nasal concha; T, tumor; NS, nasal septum.
Fig. 3. Endoscopic view showing the small remaining tumor (*) in the posterior wall of nasopharynx after four cycles of the chemotherapy with docetaxel (case 4).
revealed an adenocarcinoma of the nasopharynx. On palpation, the cervical lymph nodes were not palpable, and no distant metastases were detected. Neoadjuvant chemotherapy with nedaplatin (80 mg/(m2 day 1)) and 5-FU (700 mg/(m2 days 1–5)) was administered, but the tumor showed no response. Therefore, the patient was given a different neoadjuvant chemotherapy protocol using docetaxel (60 mg/(m2 day 1)). After four cycles of the
chemotherapy with docetaxel, the tumor showed a remarkable remission (Fig. 3). Resection of the small remaining tumor via a transmaxillary approach was performed followed by postoperative irradiation of 74.4 Gy (hyperfractionation: 1.2 Gy b.i.d. on days 1–31). The pathological findings from the extirpated tumor were consistent with adenocarcinoma ex pleomorphic adenoma (Fig. 4). Two years later the patient was clinically disease free in the nasopharyngeal area, and no metastases were detected.
5. Discussion Pleomorphic adenoma is one of the most common benign tumors arising in the head and neck, and is especially
Fig. 2. Axial CT scan of case 4 with iopamidol enhancement. The arrow shows the adenocarcinoma ex pleomorphic adenoma in the nasopharynx.
Fig. 4. Photomicroscopy of case 4 showing adenocarcinoma ex pleomorphic adenoma (H&E; original magnification 200).
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S. Kariya et al. / Auris Nasus Larynx 33 (2006) 43–46
frequent in the parotid grand. Carcinoma ex pleomorphic adenoma arises from either long-standing or recurrent pleomorphic adenoma, and is classified into several subtypes: adenocarcinoma, salivary duct carcinoma, adenosquamous carcinoma, undifferentiated carcinoma, adenoid cystic carcinoma, myoepithelial carcinoma, epithelialmyoepithelial carcinoma, and sarcomatoid carcinoma [5]. Adenocarcinoma ex pleomorphic adenoma accounts for 44% of carcinoma ex pleomorphic adenoma [5]. In this study, the parotid gland was the primary site in three of five cases. Though one case (case 3) had a long history of parotid swelling, adenocarcinoma ex pleomorphic adenoma should also be considered in patients with a primary parotid tumor that have a short clinical course (case 1). The solid portion of the carcinoma ex pleomorphic adenoma exhibits intermediate signal intensity on conventional T2 weighted magnetic resonance imaging, and it is composed of papilliform epithelial cells with abnormal nuclei including large nucleoli [6]. Laminin and collagen IV are considered to be the factors responsible for both malignant transformation and biological progression in a pleomorphic adenoma [7]. Saleh et al. [8] reported that the expression of the neural cell adhesion molecule (N-CAM) was decreased in carcinoma ex pleomorphic adenoma compared to benign pleomorphic adenoma, and that N-CAM might be used as an auxiliary tool in the diagnosis of early pleomorphic adenoma malignancy. Lewis et al. [5] showed that mutation of p53 was an early event in the malignant transformation of a pleomorphic adenoma. Olsen and Lewis [2] reported 73 cases with carcinoma ex pleomorphic adenoma in the major salivary glands, and showed an overall survival of 39% at 3 years and 30% at 5 years. Surgical excision is the usual treatment, with postoperative radiation therapy being given due to the high-grade malignancy of carcinoma ex pleomorphic adenoma located in the major salivary glands [2]. Though minor salivary gland tumors are histologically identical to those of the major glands [3], the management of carcinoma ex pleomorphic adenoma in the minor salivary glands has not been established. The therapeutic strategy to the carcinoma ex pleomorphic adenoma in head and neck in our institute is the surgical operation with wide margin. The indication for postoperative radiation therapy or chemotherapy depends on the sufficiency of the surgical margin. All cases in this study showed no local recurrence.
There is evidence to suggest that docetaxel is a promising agent for the treatment of adenocarcinoma [9,10]. In particular, in case 4, although chemotherapy using nedaplatin and 5-FU was ineffective for the adenocarcinoma ex pleomorphic adenoma, with docetaxel treatment a notable improvement was seen. In fact, using docetaxel to shrink the tumor pre-operatively, as was done in case 4, may be useful, since it is difficult to excise a nasopharyngeal tumor with a large enough margin. Thus, the clinical course of case 4 demonstrates that docetaxel treatment may become a useful therapeutic approach in the management of adenocarcinoma ex pleomorphic adenoma of the minor salivary glands. In general, adenocarcinoma ex pleomorphic adenoma should be considered in all patients with a nasopharyngeal tumor.
References [1] Izzo L, Frati R, Cianfrone F, Sassayannis PG, Costi U, Galati G, et al. Parotid gland cancer: a case report of a primitive adenocarcinoma arising from a multirecurrent pleomorphic adenoma. J Exp Clin Cancer Res 2004;23:153–6. [2] Olsen KD, Lewis JE. Carcinoma ex pleomorphic adenoma: a clinicopathologic review. Head Neck 2001;23:705–12. [3] Furukawa M, Suzuki H, Matsuura K, Takahashi E, Suzuki H, Tezuka F. Carcinoma ex pleomorphic adenoma of the palatal minor salivary gland with extension into the nasopharynx. Auris Nasus Larynx 2001;28:279–81. [4] American Joint Committee on Cancer. 4th ed., Manual for staging of cancer, Philadelphia, PA: Lippincott, 1992. [5] Lewis JE, Olsen KD, Sebo TJ. Carcinoma ex pleomorphic adenoma: pathologic analysis of 73 cases. Hum Pathol 2001;32: 596–604. [6] Sakamoto M, Sasano T, Higano S, Takahashi S, Iikubo M, Kakehata S. Usefulness of heavily T2 weighted magnetic resonance images for the differential diagnosis of parotid tumours. Dentomaxillofac Radiol 2003;32:295–9. [7] Felix A, Rosa JC, Fonseca I, Cidadao A, Soares J. Laminin and collagen IV in pleomorphic adenoma and carcinoma ex-pleomorphic adenoma: an immunohistochemical study. Hum Pathol 1999;30:964– 9. [8] Saleh ER, Franca CM, Marques MM. Neural adhesion molecule (NCAM) in pleomorphic adenoma and carcinoma ex-pleomorphic adenoma. J Oral Pathol Med 2003;32:562–7. [9] Haller DG, Misset JL. Docetaxel in advanced gastric cancer. Anticancer Drugs 2002;13:451–60. [10] Jatoi A, Tirona MT, Cha SS, Alberts SR, Rowland KM, Morton RF, et al. A phase II trial of docetaxel and CPT-11 in patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction, and gastric cardia. Int J Gastrointest Cancer 2002;32:115–23.