1.題目: 下顎骨齒源性透明細胞癌-病例報告
2.簡題: Clear cell odontogenic carcinoma of mandible – case report
3.作者姓名: 簡杏宜(最高學位:國立陽明大學學士)
4.服務單位及職位:中國醫學大學附設醫院口腔顎面外科第一年住院醫師
5.稿件負責人:簡杏宜 (Hani Surianti).
Tel: 0952629572
, .E-mail: [email protected]
ADD:台中市北區育德路 2 號 牙醫部口腔顎面外科
共同作者: 陳百立
1,4.(Pai-Li Chen ), 薛水上
3(Hsue Shui-Sang),張加明
1.(Chiaming
Chang), 張佩穎
1.(Ina Peiying Chang), 陳遠謙
1,2.( Michael Yuanchien Chen).
通訊作者: 陳遠謙(Michael Yuanchien Chen).
Department of Oral and Maxillofacial Sugery, Taichung China Medical
University Hospital, No.2, Yu-der Rd., Taichung, Taiwan, R.O.C. e-mail:
[email protected].
機構名稱: 1. Department of Oral and Maxillofacial Surgery China Medical University
Hospital.
2. School of Dentistry, China Medical University.
3. School of Dentistry, Taipei Medical University
4. Tri-Heart Dental Hospital
Clear cell odontogenic carcinoma (CCOC) is a rare jaw neoplasm. It was originally defined as a benign but locally invasive epithelial neoplasm of odontogenic origin by Hansen et al in 1985. However,
additional cases, which was published later showed that the tumor has an aggressive behavior, predilection for local recurrence, evidence of distant metastasis, and even related to mortality . In the WHO classification of 2005, it was subsequently revised to be denoted as a malignant tumor. CCOC has a remarkable female predilection that is discovered most frequently in mandible of older adults. Wide age distribution between 14 to 89 years old had been published, with an average of 54 years. Due to its malignant property, radical surgery with margins free of tumor is the therapy of choice. .We would like to present a case of 70 year old woman who had enucleation of ameloblastoma at left mandibular body 5 years earlier in other hospital. Swelling at the same location occurred, therefore she came to our
department for further management. Panorex showed ill-defined radiolucent lesion at the left mandibular parasymphysis and right mandibular body with expansion of the lower border was also noticed. Report of incision biopsy showed a malignant jaw bone tumor, therefore composite resection including partial mandibulectomy, left neck supraomohyoid lymph node dissection, and immediate reconstruction with ALT flap were performed. Histopathologic report of the whole surgical specimen proved to be CCOC. Adjuvant radiotherapy was also arranged. Post-operative surveillance for more than one year showed no recurrence or distant metastasis.
Keywords: clear cell odontogenic carcinoma
中文摘要
年Hansen 等學者發表此乃良性但較具有局部侵犯性的腫瘤。但是後續文獻中指出該型腫瘤具有侵 襲特性，術後易於復發或轉移，甚至致死的案例。因此於2005 年經世界衛生組織(WHO)修訂將其 歸類於惡性腫瘤。CCOC 好發於女性，常見於老年人的下顎骨內。文獻中指出發病年齡從 17 歲至 59 歲，平均為 54 歲。由於該腫瘤惡性的特徵，治療以廣泛性全切除為主。本病例報告為一位 70 歲 女性，五年前在外院曾因左下顎造釉細胞瘤而於全身麻醉下接受刨除術。後因相同部位腫脹不適至 本院求診。環口X 光片顯示左下副聯合體及右下顎骨體有邊緣界線不明之放射線透過性影像，下 顎骨下緣有膨大之情形。經組織切片確定為惡行病灶，遂接受灶區廣泛性切除合併下顎骨部分截骨 術，以及頸部淋巴闊清術，同時使用大腿前外側游離皮瓣進行重建。術後病理檢查報告確認為齒源 性透明細胞癌，術後安排輔助性放射線治療。目前追蹤超過一年並無局部復發或遠端轉移現象。 關鍵詞: 齒源性透明細胞癌。 Introduction
Clear cell odontogenic carcinoma (CCOC) is a rare jaw bone tumor that was originally described in 1985 by Hansen et al. 1 as a benign but locally invasive neoplasm. However, cases reported by Bang2 and Branck3.
revealed a relatively high rate of recurrence and distant metastasis. Therefore, the World Health Organization reclassified it in 2005 as a malignant tumor of odontogenic origin. 4. Wide range of age
distribution between 17 to 89 years old had been published, with average of 54 years. Due to is malignant property, radical surgery with margins free of tumor is the therapy of choice. 5 Only 68 well-documented
cases have been reported in English literature, therefore our knowledge is based on limited case reports. 6
The purpose of this article was to present an additional case to the literature , thereby reinforced a better understanding and awareness to improve recognition of the rare tumor. .
Case Report
A 70 year old woman with hypertension under regular medical control complained of a swelling mass over left side of the mandible on 2004. Enucleation was performed at another hospital with a pathologic diagnosis of “ameloblastoma”, however and paresthesia over left lower lip occured subsequently. After that, she didn’t follow the scheduled recall until June 19 2009 when she was referred to our hospital from a private practicing dentist for management for a swelling mass at the left mandible accidentally found during dental examination. (Fig. 1). Oral examination revealed a nontender firm mass at the edentulous ridge compatible with the position of the left mandibular canine and premolar with intact overlying mucosa. There were a few palpable lymph nodes at the left submandibular area. Panoramic radiograph showed two ill-defined radiolucent images, one at left mandibular body to parasymphysis area while the other at right mandibular body.(Fig.2)
Incision biopsy at the edentulous ridge of the left mandibular body was performed on June 25,2009, and biopsy report showed “a picture of carcinoma composed of a sheet anasplastic squamous intermediate cell admixing some clear cell accompanied by mucin like productive cell.” (Fig.3). Due to the malignant findings, further systemic work-up was arranged. Computed tomography (CT) demonstrated a heterogenous enhancing mass over left mandibular body measured up to 2.5x2.5x2.5 cm in greatest dimension with
bucco-lingual cortical expansion, focal perforation, and erosion. Two remarkable lymph nodes, less than 3 cm in dimension were found at level I and II of left neck. (Fig. 4,5,6). Bone scan showed increased tracer uptake at the mental region of mandible. Chest X-ray displayed no evidence of metastasis disease. On July 15,2009, the patient underwent segmental mandibulectomy leading to a continuity defect from angle to angle, left supraomohyoid neck dissection, reconstruction with ALT flap and reconstruction plate under general anesthesia. Subsequent postoperative course was smooth and the patient discharged under stable condition on July 29,2009.
Post-operative histopathologic report proved to be clear cell odontogenic carcinoma which was composed of islands of malignant odontogenic epithelial cells revealing clear to faintly eosinophilic cytoplasm, well-demarcated cell membranes, and irregular dark-staining nuclei and scattered palisaded peripheral cells in the fibrous tumor stroma involving bone and adjacent soft tissue with moderate
peritumoral desmoplasia.(Fig.6). No malignancy findings at the left side lymph nodes. Unfortunately, the margin was not free at the soft tissue of the left mandibular angle. No definite lymphovascular permeation or perineural invasion was identified. Immunohistochemical findings for the tumor cells were as follows : DPAS (negative, non-expression), mucincarmine (negative, non-expression), CK8 (positive, moderate to focally strong membranous staining in about 70% tumor cells), CK14 (positive, focally strong membranous staining in about 20% tumor cells), HMB45 (negative, non-expression), EMA (positive, scattered moderate membranous staining in less than 10% tumor cells), vimentin (negative, non-expression) (Fig 7). These findings are compatible with the immunoprofiles of clear cell odontogenic carcinoma. (Table 1)
Due to the positive surgical margin, post-operative adjuvant radiotherapy was conducted with a total dose of 5940 cGy divided by 33 fractions. The patient had been under regular follow up for more than 1 year
after completion of adjuvant radiotherapy and showed no signs of recurrence by now. (Figure 8,9)
Discussion
Clear cell odontogenic carcinoma is a rare odontogenic neoplasm with a marked female predilection. The tumor appears to be of odontogenic origin, but its histogenesis and pathogenesis is still unknown. Wide distribution from 14 to 89 years of age has been described. More than 80% of lesions develop in the
mandible. 7. Clinical manifestations include pain or discomfort, jaw enlargement, tooth mobility or
displacement, and destruction of cortical plates. 8. Approximately 60% of patients will have evidence of soft
tissue involvement. Radiographically, CCOC presents as ill-defined radiolucent lesion with dental root resorption, alveolar bone loss, perforation of the cortical bone, and invasion of adjacent soft tissues. 9. In
some of the literatures reviewed, the final diagnosis of CCOCs were revised from ameloblastoma,
odontogenic fibroma, and squamous cell carcinoma. In one histologic section even showed findings of a
clear cell odontogenic carcinoma in proximity to a squamous cell carcinoma. . Therefore a discussion of
whether CCOC might develop out of ameloblastoma or other entities such as squamous cell carcinoma would naturally arise, because CCOC and squamous cell carcinoma could appear simultaneously. 10
There are three different histologic patterns of CCOC. The first pattern is the biphasic pattern which consists of varying-sized nests of epithelial cells with faintly eosinophilic admixed with more eosinophilic polygonal epithelial cells. The second pattern the monophasic pattern which was characterized only by clear cells that are arranged in nests and cords. The third pattern has a resemblance to ameloblastoma in that the peripheral cells of the clear cell islands may infrequently demonstrate palisading. The cells oftenly do not exhibit significant pleomorphism. Furthermore, mitoses and necrosis are generally sparse.. 7. In this
with intercellular bridges were noticed. Histopathologic findings of the operative specimen were consistent with the biopsy result.
Clear cells are believed to be a result of intracellular accumulation of nonstaining compounds, such as glycogen, lipid, mucin, etc. Clear cells can originate from various sources, including salivary gland tumor, metastatic renal cell carcinoma, melanocytic tumors, and other odontogenic tumors. Therefore,
immunohistochemical staining may be helpful in confirming the epithelial nature of the tumor cells and identification of CCOC. . Immunohistochemical findings of the specimen were compared with the
immunohistochemical features of various origin of clear cell tumors and the final diagnosis of CCOC was reached. (Table 1) 11 Abundant glycogen storage could display PAS positivity. However, in our case, there
may be a few accumulation of glycogen storage that would display negative PAS stain.
It has been postulated that the clear cells of CCOC are derived from the dental lamina. Some authors regard CCOC and clear cell ameloblastoma (CCAM) as a spectrum of a single pathological entity. Clear cell ameloblastoma exhibits typical ameloblastomatous microscopic features, such as central stellate reticulum, peripheral palisading, reverse polarity. When metastases occurred, it is termed as “clear cell ameloblastic carcinoma.(CCACa). The relationship between CCOC and CCACa is still controversial. Due to limited number of cases, it is difficult to separate these two lesions. The comparison between these two entities showed that both should be considered as low-grade malignancies that could well represent a
clinicopathologic continuum of a single disease entity rather than two separate lesions. 12
Out of the reported 68 cases, 59 patients’ follow up data was available. The overall recurrence rate for these tumors are 41.2% (28/68). Of the 15 patients who were treated by enucleation or curettage, 13 (86.7%) had local and / or regional recurrences, 3 out of 4 (75%) patients died from tumor developed metastatic
disease. Local and/or regional recurrences occurred in 14 (14/27, 29.8%) patients who underwent surgical resection. In conclusion, the recurrence rate after initial treatment by resection was remarkably lower than conservative therapy. Adjuvant radiotherapy should be considered in locally-regionally advanced and/or positive margin resection cases. Carcinoma doses should be used , ie. total dose of 6600 cGy at 200 cGy per fraction delivered once a day or a total dose of 7440cGy at 120 cGy per fraction delivered twice daily. Chemotherapy should be reserved for palliation because there is a paucity of evidence for its efficacy in definitive treatment of CCOC. 13.
Conclusion
Due to the rarity of the tumor, d iagnosis and treatment of CCOC are challenging for surgeons. A thorough and careful analysis of the tumor must be done in order to conclude a correct diagnosis.
Immunostaining pattern and cellular distribution may help to develop the final diagnosis. Furthermore, its aggressive clinical behavior, metastatic spread and lower survival rate, calls for a wide surgical resection margins, loco-regional control by lymph node dissection, and adjuvant radiation therapy in situations such as extensive soft tissue invasion, perineural spread, lymph node metastasis with extranodal involvement or in cases where tumor-free margins are not possible. 14. Most importantly, long term follow up is mandatory.
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