腭小唾液腺腫瘤之臨床病理研究

Abstract

背景: 腭是口內小唾液腺腫瘤最好發的位置。本研究的主要目的探討一系列 133 個良性及惡性腭小唾液腺腫瘤的臨床及病理特徵。 <br> 方法: 本研究的 133 個良性及惡性腭小唾液腺腫瘤，收集自國立台灣大學附屬醫院病理部門，從 1993 年 1 月到 2009 年 12 月期間的病例。此 133 個腭小唾液腺腫瘤的臨床病理特徵與相互關係被分析且報告。<br> 結果: 本研究共包涵 78 個良性 (58.6%) 與 55 個惡性 (41.4%) 腭小唾液腺腫瘤。其中多形性腺瘤 (pleomorphic adenoma) 佔 74 例，黏液表皮樣癌 (mucoepidermoid carcinoma) 佔 26 例，腺樣囊狀癌 (adenoid cystic carcinoma) 佔18 例 ，此三者包括所有腫瘤的 89%。多形性腺瘤明顯好發於女性患者 (女男比為 2: 1) 且平均年齡為 47 歲。74 例多形性腺瘤中，古典型有 47 例，細胞型有27 例；12 例有完整被膜 (capsule)，40 例有部分被膜，22 例無被膜。漿細胞樣肌上皮細胞、亮細胞、鱗狀上皮細胞巢、角質珠、透明基質、骨基質樣區域、軟骨樣區域各可發現於 50, 19, 29, 19, 49, 8 及 6 個病例。黏液表皮樣癌患者同樣明顯好發於女性患者 (女男比為 2.7: 1) 且其平均年齡為 43 歲。大多數的黏液表皮 樣癌患者 (69%)其腫瘤大小是 T1 或 T2 且分級上屬 stage 1 或 stage 2。於 26 個黏液表皮樣癌患者中，只有一個病例有局部淋巴結轉移，一個病例出現遠處轉移，及一個病例在治療後發生局部復發。更甚者，其中一個黏液表皮樣癌患者在治療一年後死亡。因此，黏液表皮樣癌患者的 2 年、5 年與 10 年的存活率都是 96%。組織學上，13 個黏液表皮樣癌為低惡性度 (low-grade)，4 黏液表皮樣癌是中惡性度 (intermediate-grade)，而 9 個黏液表皮樣癌是高惡性度 (high-grade) 腫瘤。神經周侵犯在 2 個黏液表皮樣癌中發現。高惡性度黏液表皮樣癌通常發生在 較年長的病人 (> 50 歲)，而低惡性度黏液表皮樣癌通常發生在較年輕的患者 (≦ 50 歲, P = 0.046)。反之，腺樣囊狀癌稍微好發於男性患者 (男女比為 1:0.8)， 且 平均年齡為 54 歲。三分之二的腺樣囊狀癌患者於最初發現時已為 T4 和 stage 4。再者，7 個腺樣囊狀癌患者有遠處轉移，但只有 2 個腺樣囊狀癌患者有局部淋巴結轉移。經過治療後，有 6 個病例發現局部復發。對於腺樣囊狀癌患者，其 2 年、5 年與 10 年的存活率分別為 100%，72%和 56%。於 18 個腺樣囊狀癌病例中，11 個被診斷為篩狀 (cribriform)，3 個為管狀 (tubular) 而 4 個為實心狀 (solid)腫瘤。13 個腺樣囊狀癌有神經周侵犯。統計分析顯示，當腫瘤為管狀或實心狀時，其腫瘤大小常為 T3 或 T4 (P = 0.057)，分級上常為 stage 3 或 stage 4 (P = 0.057)，其腫瘤較易局部復發 (P = 0.023)，且整體存活率較差 (P = 0.013)。而腺樣囊狀癌一旦伴隨神經周侵犯，其腫瘤大小常為 T3 或 T4 (P = 0.022)，且分類為stage 3 或 stage 4 的腫瘤 (P = 0.022)。而對於大小為 T3 或 T4 (P = 0.038) 且分級 上常為 stage 3 或 stage 4 (P = 0.038)。且 T3 或 T4 及 stage 3 或 stage 4 腺樣囊狀癌較常有遠處轉移。較大的腺樣囊狀癌 (T3 和 T4, P = 0.054) 和後期的腺樣囊狀癌(stage 3 和 stage 4, P = 0.054)，在治療後，較常有局部復發。除此之外，較年長 的腺樣囊狀癌患者 (> 50 歲, P = 0.025) 通常也有較差的整體存活率。<br> 結論：本研究發現，多形性腺瘤為最常見的良性腭小唾液腺腫瘤，而黏液表皮樣 癌和腺樣囊狀癌則是兩個最常見之惡性腭小唾液腺腫瘤。多形性腺瘤和黏液表皮 樣癌都有明顯好發於女性的傾向；相反的，腺樣囊狀癌則稍微好發於男性患者。 腺樣囊狀癌的患者平均年齡，相較於多形性腺瘤和黏液表皮樣癌的患者較為年 長。對腭黏液表皮樣癌的患者，其預後較腭腺樣囊狀癌的患者為佳。三分之二的 腺樣囊狀癌病例，在一開始就顯示出大小為 T4 和分級為 stage 4 的腫瘤。本研究 中，腺樣囊狀癌有較多遠處轉移，較少局部淋巴結轉移。腺樣囊狀癌常表現神經 周侵犯。除此之外，當患者的腺樣囊狀癌為管狀或實心狀，常更有機會發展成較 大的腫瘤，較高的分級，較多的局部復發，及較差的整體存活率。

Abstract Background: The palate is the most common site for intraoral minor salivary gland tumors. This study was aimed to present the clinicopathological features of a series of 133 benign and malignant palatal minor salivary gland tumors.

Methods: In this study, 133 benign and malignant palatal minor salivary gland tumors were retrieved from the files of Department of Pathology, National Taiwan University Hospital from January, 1993 to December, 2009. The clinicopathological features and their correlations of these 133 palatal minor salivary gland tumors were analyzed and reported.

Results: There were 78 (58.6%) benign and 55 (41.4%) malignant minor salivary gland tumors in the palate. Pleomorphic adenoma (PA, 74 cases), mucoepidermoid carcinoma (MEC, 26 cases), and adenoid cystic carcinoma (ACC, 18 cases) constituted 89% of all tumors. PA patients showed a marked female predominance (2:1) and a mean age of 47 years. Histopathologically, there were 47 classic and 27 cellular PAs. Of the 74 PAs, 12 were completely-encapsulated, 40 partially-encapsulated, and 22 non-encapsulated. Plasmacytoid myoepithelial cell, clear cell, squamous epithelial nest, keratin pearl, hyalinized stroma, osteoid area, and chondroid area were found in 50, 19, 29, 19, 49, 8, and 6 PAs, respectively. MEC patients also demonstrated a significant female predilection (2.7:1) and a mean age of 43 years. The majority of MEC patients had T1 or T2 (69%) and stage 1 or stage 2 tumors (69%) at the initial presentation. Of the 26 MEC patients, only one had regional lymph node metastasis, one distant metastasis, and one recurrence of the tumor after treatment. Moreover, only one MEC patient died 1 year after treatment. Thus, the 2-year, 5-year and 10-year survival rates were all 96% for MEC patients. Histologically, 13 MECs were classified as low-grade, 4 intermediate-grade, and 9 high-grade tumors. Perineural invasion was noted in 2 MECs. High-grade MECs occurred commonly in older patients (> 50 years old) and low-grade MECs frequently affected younger patients (≦ 50 years old, P = 0.046). The ACC patients, however, revealed a slight male predominance (1:0.8) and a mean age of 54 years. Two-thirds of ACC patients showed T4 and stage 4 tumors. Moreover, 7 ACC patients had distant metastases, but only 2 had regional lymph node metastases. Local recurrence was noted in 6 ACCs after treatment. The 2-year, 5-year and 10-year survival rates were 100%, 72% and 56% for ACC patients, respectively. Of the 18 ACCs, 11 were classified as cribriform type, 3 tubular type, and 4 solid type. Perineural invasion was present in 13 ACCs. Statistical analyses showed that patients with tubular or solid ACCs were more likely to have T3 or T4 tumors (P = 0.057), stage 3 or stage 4 disease (P = 0.057), local recurrence of the tumor (P = 0.023), and poorer overall survival (P = 0.013). ACCs with perineural invasion were prone to present as T3 or T4 (P = 0.022) and stage 3 or stage 4 tumors (P = 0.022). Moreover, T3 or T4 (P = 0.038) and stage 3 or stage 4 (P = 0.038) ACCs more frequently showed distant metastases. Larger ACCs (T3 and T4, P = 0.054) and advanced stage ACCs (stage 3 and stage 4, P = 0.054) were prone to have local recurrence after treatment. In addition, older ACC patients (> 50 years, P = 0.025) were more frequent to have poorer overall survival.

Conclusion: We conclude that PA is the most common benign and MEC and ACC are the two most frequent malignant palatal minor salivary gland tumors. Both PA and MEC patients have a prominent female predilection, but ACC patients have a slight male preponderance. The mean age of ACC patients is much older than that of PA or MEC patients. The prognosis of palatal MEC patients is better than that of palatal ACC patients. Two-thirds of ACC patients show T4 and stage 4 tumors at the initial presentation. ACCs are prone to have distant metastases rather than regional lymph node metastasis. Perineural invasion is frequently present in ACCs. In addition, patients with tubular or solid ACCs are more likely to have larger tumors, advanced stages, local recurrence, and poorer overall survival.