- Email: [email protected]
Small cell carcinoma of the maxilla
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 25 (2013) 179–182
Contents lists available at SciVerse ScienceDirect
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology journal homepage: www.elsevier.com/locate/jomsmp
Case report
Small cell carcinoma of the maxilla夽 Goro Kawasaki a,∗ , Souichi Yanamoto a , Izumi Yoshitomi a , Toshihiro Kawano a , Akio Mizuno a , Tomayoshi Hayashi b , Shuichi Fujita c , Tohru Ikeda c , Masahiro Umeda a a Department of Clinical Oral Oncology, Unit of Translational Medicine, Course of Medical and Dental Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan b Department of Pathology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan c Department of Oral Pathology and Bone Metabolism, Unit of Basic Medical Sciences, Course of Medical and Dental Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan
a r t i c l e
i n f o
Article history: Received 30 May 2011 Received in revised form 19 April 2012 Accepted 23 May 2012 Available online 29 June 2012 Keywords: Small cell carcinoma Maxillary gingiva
a b s t r a c t Small cell carcinoma (SmCC) in the oral and maxillofacial region is extremely rare high-grade malignant tumor. We report a case of a SmCC occurring in the maxillary gingiva. A 39-year-old man exhibited upper left gingival swelling that rapidly increased in size. Histopathological examination revealed proliferation of round cells with scant cytoplasm. Immunohistochemically, the tumor cells were positive for cytokeratin AE1/AE3, chromogranin A, synaptophysin, neuron-specific enorase (NSE), CD56, Leu 7, neurofilament and bcl-2, but negative for CD20, CD79a, S-100 and cyclin D1. Surgical resection and radical neck dissection were performed, and adjuvant chemotherapy combining CDDP and irinotecan (CPT11) was administered. Ten months after the operation, buccal lymph node metastasis and distant metastasis to the liver were found. Although irradiation therapy was performed, the liver lesion was unaffected by irradiation. Therefore, a further chemotherapy including etoposide was performed. The mass of the liver remained resistant to additional chemotherapy, and he subsequently died because of cachexia in spite of the partial hepatectomy. © 2012 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved.
1. Introduction
2. Case report
Small cell carcinoma (SmCC) is most frequent in the lung, and an extrapulmonary origin is uncommon [1]. Within the major salivary glands, SmCC constitutes less than 1% of all malignant tumors, with more than 80% arising in the parotid gland [2]. Primary SmCC in the oral cavity is extremely rare, and no standard treatment regimen has not been established. Histologically, SmCCs are characterized by the proliferation of small anaplastic cells with scant cytoplasm, fine nuclear chromatin, and inconspicuous nucleoli [1]. On the basis of ultrastructural features, SmCCs of salivary glands appear to be a heterogeneous group, encompassing neuroendocrine and ductal types [1], and neuroendocrine features of oral SmCC were not rare. We report herein an extremely rare case of small cell carcinoma arising in the maxillary gingiva.
A 39-year-old man was referred to our clinic because of swelling of the upper left gingiva. The patient noticed swelling two months prior to visiting our clinic. The patient’s medical and family histories were unremarkable. The facial appearance was asymmetrical, and slight swelling could be seen in the left submandibular region. Clinical oral examination revealed an elastic hard mass measuring 45 mm × 28 mm × 15 mm in the left palatal gingiva of the maxilla (Fig. 1). The surface mucosa covering the swelling was irregular and the margin was unclear. An ulcer was noted at the center of the lesion. The clinical diagnosis was a malignant tumor of the maxilla. Computed tomography and magnetic resonance imaging studies demonstrated a mass originating in the left palatal region with cortical bone resorption (Fig. 1). Metastasis to the lymph nodes was noted in the right submandibular region. Chest roentgenograms showed no signs of space-occupying lesions within the lungs and no findings suggestive of pulmonary neoplasia. A thoracic CT scan, abdominal CT scan, a technetium-99 whole bone scan and gallium scintigraphy revealed no evidence of distant metastasis. Biopsy was performed under local anesthesia. The pathological diagnosis was SmCC. A wide excision with a hemimaxillectomy and radical neck LN dissection on the left side was performed under general anesthesia.
夽 AsianAOMS: Asian Association of Oral and Maxillofacial Surgeons; ASOMP: Asian Society of Oral and Maxillofacial Pathology; JSOP: Japanese Society of Oral Pathology; JSOMS: Japanese Society of Oral and Maxillofacial Surgeons; JSOM: Japanese Society of Oral Medicine; JAMI: Japanese Academy of Maxillofacial Implants. ∗ Corresponding author. E-mail address: [email protected] (G. Kawasaki).
2212-5558/$ – see front matter © 2012 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ajoms.2012.05.006
180
G. Kawasaki et al. / Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 25 (2013) 179–182
Fig. 1. (A) Intraoral examination shows an elastic hard mass at the left palatal lesion. (B) Axial MRI of the patient showing the enhanced lesion in the palatal region.
After the operation, adjuvant chemotherapy combining CDDP and irinotecan (CPT11) was administered. It consisted of CDDP 110 mg on day 1 and CPT-11 110 mg on days 1, 8 and 15, beginning on January 16, 2008, both given intravenously. We administered three courses of this regimen during his admission. Ten months after the operation, buccal lymph node metastasis and distant metastasis to the liver were found. Irradiation therapy of 25 Gy for the lymph node was performed, and the lesion disappeared. The liver lesion was unaffected by irradiation, therefore, a further chemotherapy including etoposide was performed. The mass of the liver remained resistant to additional chemotherapy, and he subsequently died because of cachexia in spite of the partial hepatectomy. Histopathological and immunohistochemical findings (Figs. 2 and 3). The biopsy specimens of the oral upper gingival and hard palate lesion showed proliferation of round cells with scant cytoplasm. The nuclei contained fine, chromatin and inconspicuous nucleoli. The tumor cells arranged in small round nests and trabecular structures as well as diffuse proliferation. Nuclear molding pattern was noticed among the tumor cells. Results of immunohistochemical reactivity were as follows; AE1/AE3 (+), chromogranin A (+), synaptophysin (+), NSE (+), CD56 (+), Leu7 (+), neurofilament (+), CD20 (−), CD79a (−), CD3 (−), S-100 (−), bcl-2 (+) and cyclin D1 (−). The cytokeratin AE1/AE3 showed focal perinuclear expression. Positive reaction for chromogranin A, synaptophysin, NSE and CD56 suggested neuroendocrine feature. Based on these findings, we diagnosed this tumor as SmCC. Surgical material of hemimaxillectomy revealed same histological features as the biopsy. Maxillary primary tumor infiltrated from the gingivo-palatal mucosa into the maxillary bone, and lymph node metastasis was found in 2 superior internal jugular nodes. The
Fig. 2. Biopsy specimen stained with hematoxylin and eosin. (A) The gingivo-palatal mucosa protrusion with submucosal tumor. There is no continuity between the epithelium and the tumor (×2.5). (B) Diffuse proliferation of round anaplastic cells with scant cytoplasm (×20). (C) Small round nests of the tumor beneath the mucosal epithelium (×20). (D) Trabecular arrangements between the collagen bundles. Nuclear molding pattern is evident (×20).
G. Kawasaki et al. / Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 25 (2013) 179–182
181
Fig. 3. Immunohistochemical staining for cytokeratin AE1/AE3, chromogranin A, synaptophysin, NSE and CD56 of the biopsy material of the biopsy material. (A) cytokeratin AE1/AE3. Tumor cells show strong cytoplasmic reaction (×40). (B) cytokeratin AE1/AE3. Almost all tumor cells demonstrate paranuclear dot-like pattern (×120). (C) chromogranin A (×40). (D) synaptophysin (×40). (E) NSE (×40). (F) CD56 (×40). Tumor cells are positive for the neuroendocrine markers (×40 for all).
specimens of the partial hepatectomy showed nodular metastatic focus approximately 4 cm in diameter (Fig. 4).
3. Discussion Extrapulmonary SmCC is rare, but a few cases have been reported in the head and neck region occurring mainly in the major salivary glands [1–4]. Only about 60 cases of major salivary gland SCC have been reported [1]. Most tumors involved the parotid gland, but a few cases have been described involving the submandibular and minor salivary glands [5–9]. Since the present case arose from the upper gingival or palatal mucosa, we speculate the origin of this tumor to be the minor salivary gland. Small cell carcinoma of the oral cavity, which is thought to originate from the minor salivary gland, is extremely rare, with only 10 cases including the present patient being reported [7,10–12].
A review of the literature on lesions in the head and neck region revealed distant metastasis in more than 50% of patients with SmCC after the initial diagnosis [13]. Even though the incidence of cervical lymph node involvement is high, it may be exceeded by that of hematogenous metastasis. Several investigators have subclassified SmCCs into 2 major types (neuroendocrine and ductal types) according to the presence or absence of dense-core neuroendocrine granules [1,6,8,14] and it has been suggested that about one fourth of SmCC were suggested to be the neuroendocrine type [14]. In 11 cases of SmCC studied by Gnepp and Wick [15], neurosecretory granules were found in only 4 cases, but all 11 cases showed positive immunostaining for at least 1 of 3 neuroendocrine markers. Neuroendocrine features of oral SCC were not rare. There are some controversy regarding to the correlation of these pathological types with prognosis. Nagao et al. [1] concluded that tumors with a greater number of immunopositive neuroendocrine markers showed a better prognosis. However, some investigators
182
G. Kawasaki et al. / Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 25 (2013) 179–182
et al. [18] suggested that treatment programs should emphasize the use of multi-drug regimens, including CDDP, active in SmCC of the lung, with or without radiation therapy for the primary lesion, and they also included a case report which described that 3 courses of a regimen lacking CDDP led to an unfavorable response. Our case was thought to be operable because the tumor was mainly in the upper gingiva and hard palate, so we selected surgical treatment initially, and used a combination of CDDP and CPT 11 for the adjuvant chemotherapy. Recurrence in the oral cavity was not detected in the present case, but buccal lymph node and distant metastases were noted after surgery and chemotherapy. Radiation therapy is effective, and is now routinely used for limited disease; however, since the radiation therapy is a local control therapy, radiation alone in not an appropriate choice as a first treatment [15]. In the present case, irradiation therapy was effective for the buccal lymph node. We conclude that SmCC of minor salivary gland origin which is 4 cm or larger is very aggressive, and it is almost impossible to achieve complete healing. We suggest to employ a multi-drug chemotherapy initially, and then combination therapy with surgical resection and radiation for such aggressive cases. Acknowledgment We thank the staff of the Department of Surgery and the Department of Radiology and Cancer Biology, Nagasaki University Graduate School of Biomedical Sciences. References
Fig. 4. Metastasis in the liver. (A) Partially excised liver. The nodular metastatic focus with hemorrhage and necrosis. (B) The same histological features as primary lesion (HE, ×10).
have reported that the presence or absence of neurosecretory granules has no prognostic significance in SmCC of the salivary gland [5,6]. Although few reports mentioned the clinicopathologic prognostic factors of salivary gland SmCC, Hui et al. [6] suggested that the tumor size is the most important prognostic factor in major salivary gland SmCC, and neoplasms 4 cm or larger have a particularly poor prognosis. Our case indicates that the SmCC of the minor salivary gland may also present some prognostic behavior on the tumor size, and is a highly aggressive tumor. There are still some controversy regarding the surgical management for the SmCC of the lung [15]. After the 1969 report of the British Medical Research Council, surgical treatment was abandoned. However, in recent years, it has become clear that a favorable surgical outcome after induction therapy can be expected in a selected group of patients with limited disease [16]. Several cases of SmCC of the esophagus with limited disease, treated by various adjuvant therapies with surgical resection and achieving a longer survival time, were recently reported [16,17]. In our series, within 8 cases of SmCC reportedly arising from the minor salivary gland, 5 underwent surgery as the first treatment [7,10,11]. As only one case was alive, we suggest to be treated with multi-drug chemotherapy and operation for longer survival. In recent reports of SmCC of the esophagus, regimens involving CDDP seemed to yield a more favorable response [16]. Takiyama
[1] Nagao T, Gaffey TA, Olsen KD, Serizawa H, Lewis JE. Small cell carcinoma of the major salivary glands. Clinicopathologic study with emphasis on cytokeratin 20 immunoreactivity and clinical outcome. Am J Surg Pathol 2004;28:762– 70. [2] Walters DM, Little SC, Hessler RB, Gourin CG. Small cell carcinoma of the mandibular gland: a rare small round blue cell tumor. Am J Otolaryngol 2007;28:118–21. [3] Toyosawa S, Ohnishi A, Ito R, Ogawa Y, Kishino M, Yasui Y, et al. Small cell carcinoma undifferentiated carcinoma of the submandibular gland: immunohistochemical evidence of myoepithelial, basal and luminal cell features. Pathol Int 1999;49:887–92. [4] Lin YC, Wu HP, Tzeng JE. Small-cell undifferentiated carcinoma of the submandibular gland: an extremely rare extrapulmonary site. Am J Otolaryngol 2005;26:60–3. [5] Gnepp DR, Corio RL, Brannon RB. Small cell carcinoma of the major salivary glands. Cancer 1986;58:705–14. ˜ [6] Hui KK, Luna MA, Bastakis JG, Ordónez NG, Weber R. Undifferentiated carcinomas of the major salivary glands. Oral Surg Oral Med Oral Pathol 1990;69:76–83. [7] Koss LG, Spiro RH, Haidu S. Small cell carcinoma of minor salivary gland origin. Cancer 1972;30:737–41. [8] Kraemer BB, Mackay B, Batsakis JG. Small cell carcinoma of the parotid gland: a clinicopathologic study of three cases. Cancer 1983;52:2115–21. [9] Nagao K, Matsuzaki O, Saiga H, Sugano I, Shigematsu H, Kaneko T, et al. Histopathologic studies of undifferentiated carcinoma of the parotid gland. Cancer 1982;50:1572–9. [10] Benning TL, Volmer RT, Crain BJ, Shelburne JD. Neuroendocrine carcinoma of the oral cavity. Modern Pathol 1990;3:631–4. [11] Morikawa H, Nakanoboh M, Hyodoh Y, Kihara K, Kitahara S. A case of a small cell carcinoma in the oral cavity. Pract Otol 1998;91:369–72. [12] Nishihara K, Nozoe E, Hirayama Y, Miyawaki A, Semba I, Nakamura N. A case of small cell carcinoma in the buccal region. Int J Oral Maxillofac Surg 2009;38:1000–3. [13] Pierce ST, Cibull ML, Metcalfe MS, Sloan D. Bone marrow metastases from small cell carcinoma of the head and neck. Head Neck 1994;16:266–71. [14] Huntrakoon M. Neuroendocrine carcinoma of the parotid gland: a report of two cases with ultrastructural and immunohistochemical studies. Human Pathol 1987;18:1212–7. [15] Gnepp DR, Wick MR. Small cell carcinoma of the major salivary glands: an immunohistochemical study. Cancer 1990;66:185–92. [16] Ohmura Y, Takiyama W, Mandai K, Doi T, Nishikawa Y. Small cell carcinoma of the esophagus: a case report. Jpn J Clin Oncol 1997;27:95–100. [17] Mori M, Matsukuma A, Adachi Y, Miyagahara T, Matsuda H, Kuwano H, et al. Small cell carcinoma of the esophagus. Cancer 1989;63:564–73. [18] Takiyama W, Fujii M, Moriwaki S. Small cell carcinoma of the esophagus: report of a case treated with chemotherapy. Jpn J Surg 1988;18:330–5.
Contents lists available at SciVerse ScienceDirect
Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology journal homepage: www.elsevier.com/locate/jomsmp
Case report
Small cell carcinoma of the maxilla夽 Goro Kawasaki a,∗ , Souichi Yanamoto a , Izumi Yoshitomi a , Toshihiro Kawano a , Akio Mizuno a , Tomayoshi Hayashi b , Shuichi Fujita c , Tohru Ikeda c , Masahiro Umeda a a Department of Clinical Oral Oncology, Unit of Translational Medicine, Course of Medical and Dental Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan b Department of Pathology, Nagasaki University Hospital, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan c Department of Oral Pathology and Bone Metabolism, Unit of Basic Medical Sciences, Course of Medical and Dental Sciences, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki 852-8588, Japan
a r t i c l e
i n f o
Article history: Received 30 May 2011 Received in revised form 19 April 2012 Accepted 23 May 2012 Available online 29 June 2012 Keywords: Small cell carcinoma Maxillary gingiva
a b s t r a c t Small cell carcinoma (SmCC) in the oral and maxillofacial region is extremely rare high-grade malignant tumor. We report a case of a SmCC occurring in the maxillary gingiva. A 39-year-old man exhibited upper left gingival swelling that rapidly increased in size. Histopathological examination revealed proliferation of round cells with scant cytoplasm. Immunohistochemically, the tumor cells were positive for cytokeratin AE1/AE3, chromogranin A, synaptophysin, neuron-specific enorase (NSE), CD56, Leu 7, neurofilament and bcl-2, but negative for CD20, CD79a, S-100 and cyclin D1. Surgical resection and radical neck dissection were performed, and adjuvant chemotherapy combining CDDP and irinotecan (CPT11) was administered. Ten months after the operation, buccal lymph node metastasis and distant metastasis to the liver were found. Although irradiation therapy was performed, the liver lesion was unaffected by irradiation. Therefore, a further chemotherapy including etoposide was performed. The mass of the liver remained resistant to additional chemotherapy, and he subsequently died because of cachexia in spite of the partial hepatectomy. © 2012 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved.
1. Introduction
2. Case report
Small cell carcinoma (SmCC) is most frequent in the lung, and an extrapulmonary origin is uncommon [1]. Within the major salivary glands, SmCC constitutes less than 1% of all malignant tumors, with more than 80% arising in the parotid gland [2]. Primary SmCC in the oral cavity is extremely rare, and no standard treatment regimen has not been established. Histologically, SmCCs are characterized by the proliferation of small anaplastic cells with scant cytoplasm, fine nuclear chromatin, and inconspicuous nucleoli [1]. On the basis of ultrastructural features, SmCCs of salivary glands appear to be a heterogeneous group, encompassing neuroendocrine and ductal types [1], and neuroendocrine features of oral SmCC were not rare. We report herein an extremely rare case of small cell carcinoma arising in the maxillary gingiva.
A 39-year-old man was referred to our clinic because of swelling of the upper left gingiva. The patient noticed swelling two months prior to visiting our clinic. The patient’s medical and family histories were unremarkable. The facial appearance was asymmetrical, and slight swelling could be seen in the left submandibular region. Clinical oral examination revealed an elastic hard mass measuring 45 mm × 28 mm × 15 mm in the left palatal gingiva of the maxilla (Fig. 1). The surface mucosa covering the swelling was irregular and the margin was unclear. An ulcer was noted at the center of the lesion. The clinical diagnosis was a malignant tumor of the maxilla. Computed tomography and magnetic resonance imaging studies demonstrated a mass originating in the left palatal region with cortical bone resorption (Fig. 1). Metastasis to the lymph nodes was noted in the right submandibular region. Chest roentgenograms showed no signs of space-occupying lesions within the lungs and no findings suggestive of pulmonary neoplasia. A thoracic CT scan, abdominal CT scan, a technetium-99 whole bone scan and gallium scintigraphy revealed no evidence of distant metastasis. Biopsy was performed under local anesthesia. The pathological diagnosis was SmCC. A wide excision with a hemimaxillectomy and radical neck LN dissection on the left side was performed under general anesthesia.
夽 AsianAOMS: Asian Association of Oral and Maxillofacial Surgeons; ASOMP: Asian Society of Oral and Maxillofacial Pathology; JSOP: Japanese Society of Oral Pathology; JSOMS: Japanese Society of Oral and Maxillofacial Surgeons; JSOM: Japanese Society of Oral Medicine; JAMI: Japanese Academy of Maxillofacial Implants. ∗ Corresponding author. E-mail address: [email protected] (G. Kawasaki).
2212-5558/$ – see front matter © 2012 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.ajoms.2012.05.006
180
G. Kawasaki et al. / Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 25 (2013) 179–182
Fig. 1. (A) Intraoral examination shows an elastic hard mass at the left palatal lesion. (B) Axial MRI of the patient showing the enhanced lesion in the palatal region.
After the operation, adjuvant chemotherapy combining CDDP and irinotecan (CPT11) was administered. It consisted of CDDP 110 mg on day 1 and CPT-11 110 mg on days 1, 8 and 15, beginning on January 16, 2008, both given intravenously. We administered three courses of this regimen during his admission. Ten months after the operation, buccal lymph node metastasis and distant metastasis to the liver were found. Irradiation therapy of 25 Gy for the lymph node was performed, and the lesion disappeared. The liver lesion was unaffected by irradiation, therefore, a further chemotherapy including etoposide was performed. The mass of the liver remained resistant to additional chemotherapy, and he subsequently died because of cachexia in spite of the partial hepatectomy. Histopathological and immunohistochemical findings (Figs. 2 and 3). The biopsy specimens of the oral upper gingival and hard palate lesion showed proliferation of round cells with scant cytoplasm. The nuclei contained fine, chromatin and inconspicuous nucleoli. The tumor cells arranged in small round nests and trabecular structures as well as diffuse proliferation. Nuclear molding pattern was noticed among the tumor cells. Results of immunohistochemical reactivity were as follows; AE1/AE3 (+), chromogranin A (+), synaptophysin (+), NSE (+), CD56 (+), Leu7 (+), neurofilament (+), CD20 (−), CD79a (−), CD3 (−), S-100 (−), bcl-2 (+) and cyclin D1 (−). The cytokeratin AE1/AE3 showed focal perinuclear expression. Positive reaction for chromogranin A, synaptophysin, NSE and CD56 suggested neuroendocrine feature. Based on these findings, we diagnosed this tumor as SmCC. Surgical material of hemimaxillectomy revealed same histological features as the biopsy. Maxillary primary tumor infiltrated from the gingivo-palatal mucosa into the maxillary bone, and lymph node metastasis was found in 2 superior internal jugular nodes. The
Fig. 2. Biopsy specimen stained with hematoxylin and eosin. (A) The gingivo-palatal mucosa protrusion with submucosal tumor. There is no continuity between the epithelium and the tumor (×2.5). (B) Diffuse proliferation of round anaplastic cells with scant cytoplasm (×20). (C) Small round nests of the tumor beneath the mucosal epithelium (×20). (D) Trabecular arrangements between the collagen bundles. Nuclear molding pattern is evident (×20).
G. Kawasaki et al. / Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 25 (2013) 179–182
181
Fig. 3. Immunohistochemical staining for cytokeratin AE1/AE3, chromogranin A, synaptophysin, NSE and CD56 of the biopsy material of the biopsy material. (A) cytokeratin AE1/AE3. Tumor cells show strong cytoplasmic reaction (×40). (B) cytokeratin AE1/AE3. Almost all tumor cells demonstrate paranuclear dot-like pattern (×120). (C) chromogranin A (×40). (D) synaptophysin (×40). (E) NSE (×40). (F) CD56 (×40). Tumor cells are positive for the neuroendocrine markers (×40 for all).
specimens of the partial hepatectomy showed nodular metastatic focus approximately 4 cm in diameter (Fig. 4).
3. Discussion Extrapulmonary SmCC is rare, but a few cases have been reported in the head and neck region occurring mainly in the major salivary glands [1–4]. Only about 60 cases of major salivary gland SCC have been reported [1]. Most tumors involved the parotid gland, but a few cases have been described involving the submandibular and minor salivary glands [5–9]. Since the present case arose from the upper gingival or palatal mucosa, we speculate the origin of this tumor to be the minor salivary gland. Small cell carcinoma of the oral cavity, which is thought to originate from the minor salivary gland, is extremely rare, with only 10 cases including the present patient being reported [7,10–12].
A review of the literature on lesions in the head and neck region revealed distant metastasis in more than 50% of patients with SmCC after the initial diagnosis [13]. Even though the incidence of cervical lymph node involvement is high, it may be exceeded by that of hematogenous metastasis. Several investigators have subclassified SmCCs into 2 major types (neuroendocrine and ductal types) according to the presence or absence of dense-core neuroendocrine granules [1,6,8,14] and it has been suggested that about one fourth of SmCC were suggested to be the neuroendocrine type [14]. In 11 cases of SmCC studied by Gnepp and Wick [15], neurosecretory granules were found in only 4 cases, but all 11 cases showed positive immunostaining for at least 1 of 3 neuroendocrine markers. Neuroendocrine features of oral SCC were not rare. There are some controversy regarding to the correlation of these pathological types with prognosis. Nagao et al. [1] concluded that tumors with a greater number of immunopositive neuroendocrine markers showed a better prognosis. However, some investigators
182
G. Kawasaki et al. / Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology 25 (2013) 179–182
et al. [18] suggested that treatment programs should emphasize the use of multi-drug regimens, including CDDP, active in SmCC of the lung, with or without radiation therapy for the primary lesion, and they also included a case report which described that 3 courses of a regimen lacking CDDP led to an unfavorable response. Our case was thought to be operable because the tumor was mainly in the upper gingiva and hard palate, so we selected surgical treatment initially, and used a combination of CDDP and CPT 11 for the adjuvant chemotherapy. Recurrence in the oral cavity was not detected in the present case, but buccal lymph node and distant metastases were noted after surgery and chemotherapy. Radiation therapy is effective, and is now routinely used for limited disease; however, since the radiation therapy is a local control therapy, radiation alone in not an appropriate choice as a first treatment [15]. In the present case, irradiation therapy was effective for the buccal lymph node. We conclude that SmCC of minor salivary gland origin which is 4 cm or larger is very aggressive, and it is almost impossible to achieve complete healing. We suggest to employ a multi-drug chemotherapy initially, and then combination therapy with surgical resection and radiation for such aggressive cases. Acknowledgment We thank the staff of the Department of Surgery and the Department of Radiology and Cancer Biology, Nagasaki University Graduate School of Biomedical Sciences. References
Fig. 4. Metastasis in the liver. (A) Partially excised liver. The nodular metastatic focus with hemorrhage and necrosis. (B) The same histological features as primary lesion (HE, ×10).
have reported that the presence or absence of neurosecretory granules has no prognostic significance in SmCC of the salivary gland [5,6]. Although few reports mentioned the clinicopathologic prognostic factors of salivary gland SmCC, Hui et al. [6] suggested that the tumor size is the most important prognostic factor in major salivary gland SmCC, and neoplasms 4 cm or larger have a particularly poor prognosis. Our case indicates that the SmCC of the minor salivary gland may also present some prognostic behavior on the tumor size, and is a highly aggressive tumor. There are still some controversy regarding the surgical management for the SmCC of the lung [15]. After the 1969 report of the British Medical Research Council, surgical treatment was abandoned. However, in recent years, it has become clear that a favorable surgical outcome after induction therapy can be expected in a selected group of patients with limited disease [16]. Several cases of SmCC of the esophagus with limited disease, treated by various adjuvant therapies with surgical resection and achieving a longer survival time, were recently reported [16,17]. In our series, within 8 cases of SmCC reportedly arising from the minor salivary gland, 5 underwent surgery as the first treatment [7,10,11]. As only one case was alive, we suggest to be treated with multi-drug chemotherapy and operation for longer survival. In recent reports of SmCC of the esophagus, regimens involving CDDP seemed to yield a more favorable response [16]. Takiyama
[1] Nagao T, Gaffey TA, Olsen KD, Serizawa H, Lewis JE. Small cell carcinoma of the major salivary glands. Clinicopathologic study with emphasis on cytokeratin 20 immunoreactivity and clinical outcome. Am J Surg Pathol 2004;28:762– 70. [2] Walters DM, Little SC, Hessler RB, Gourin CG. Small cell carcinoma of the mandibular gland: a rare small round blue cell tumor. Am J Otolaryngol 2007;28:118–21. [3] Toyosawa S, Ohnishi A, Ito R, Ogawa Y, Kishino M, Yasui Y, et al. Small cell carcinoma undifferentiated carcinoma of the submandibular gland: immunohistochemical evidence of myoepithelial, basal and luminal cell features. Pathol Int 1999;49:887–92. [4] Lin YC, Wu HP, Tzeng JE. Small-cell undifferentiated carcinoma of the submandibular gland: an extremely rare extrapulmonary site. Am J Otolaryngol 2005;26:60–3. [5] Gnepp DR, Corio RL, Brannon RB. Small cell carcinoma of the major salivary glands. Cancer 1986;58:705–14. ˜ [6] Hui KK, Luna MA, Bastakis JG, Ordónez NG, Weber R. Undifferentiated carcinomas of the major salivary glands. Oral Surg Oral Med Oral Pathol 1990;69:76–83. [7] Koss LG, Spiro RH, Haidu S. Small cell carcinoma of minor salivary gland origin. Cancer 1972;30:737–41. [8] Kraemer BB, Mackay B, Batsakis JG. Small cell carcinoma of the parotid gland: a clinicopathologic study of three cases. Cancer 1983;52:2115–21. [9] Nagao K, Matsuzaki O, Saiga H, Sugano I, Shigematsu H, Kaneko T, et al. Histopathologic studies of undifferentiated carcinoma of the parotid gland. Cancer 1982;50:1572–9. [10] Benning TL, Volmer RT, Crain BJ, Shelburne JD. Neuroendocrine carcinoma of the oral cavity. Modern Pathol 1990;3:631–4. [11] Morikawa H, Nakanoboh M, Hyodoh Y, Kihara K, Kitahara S. A case of a small cell carcinoma in the oral cavity. Pract Otol 1998;91:369–72. [12] Nishihara K, Nozoe E, Hirayama Y, Miyawaki A, Semba I, Nakamura N. A case of small cell carcinoma in the buccal region. Int J Oral Maxillofac Surg 2009;38:1000–3. [13] Pierce ST, Cibull ML, Metcalfe MS, Sloan D. Bone marrow metastases from small cell carcinoma of the head and neck. Head Neck 1994;16:266–71. [14] Huntrakoon M. Neuroendocrine carcinoma of the parotid gland: a report of two cases with ultrastructural and immunohistochemical studies. Human Pathol 1987;18:1212–7. [15] Gnepp DR, Wick MR. Small cell carcinoma of the major salivary glands: an immunohistochemical study. Cancer 1990;66:185–92. [16] Ohmura Y, Takiyama W, Mandai K, Doi T, Nishikawa Y. Small cell carcinoma of the esophagus: a case report. Jpn J Clin Oncol 1997;27:95–100. [17] Mori M, Matsukuma A, Adachi Y, Miyagahara T, Matsuda H, Kuwano H, et al. Small cell carcinoma of the esophagus. Cancer 1989;63:564–73. [18] Takiyama W, Fujii M, Moriwaki S. Small cell carcinoma of the esophagus: report of a case treated with chemotherapy. Jpn J Surg 1988;18:330–5.