報告者： Intern E組 呂兆煜 吳迪峰 陳鈺文 陳韻婷 指導醫師：陳玉昆主任 林立民教授 暨口腔病理科全體醫師 Case Report 報告者： Intern E組 呂兆煜 吳迪峰 陳鈺文 陳韻婷 指導醫師：陳玉昆主任 林立民教授 暨口腔病理科全體醫師

General Data Name : O O O Sex : Female Age: 36y/o Native: 高雄 Marital status: 單身 Attending staff: O O O醫師 First visit : 2015/11/25

Chief Complaint Mass over upper anterior labial side for 20 days 2015/12/02

Present Illness This 36 y/o female patient found a mass and felt pain over upper anterior labial side for 20 days . She went to Tatung ear-nose-throat department for help and was given dexaltin and antibiotics. The mass has alleviated and pain relieved. She came to our OPD for further examination and treatment

Past History Past Medical History Systemic disease: denied Hospitalization (+) Surgery under GA (+) Drug and food allergy: denied Past Dental History General routine dental treatment Attitude to dental treatment: co-operative 5

Personal Habits Risk factors related to malignancy Alcohol (+), quit, socially Betel quid (-) Cigarette (+), for 20 years, 0.5 pack/day Denied any other dental oral habits

OMF Examination MMO: 57mm Site: Upper right lip Size: 2.0 cm Color: whitish-yellow surrounded with pink Induration (+) Pain (+) Tenderness (+) Surface: smooth Base: sessile Shape: dome Mobility: fixed Consistency: firm Fluctuation (-) Skin adhesion (-) LAP (-) 2015/12/02

Panorex (2015/12/02) 8

RATIONALE FOR DIFFERENTIAL DIAGNOSIS

Benign or malignant? Cyst or neoplasm? Inflammation? Working diagnosis

Inflammation, cyst, or neoplasm？ Our case Inflammation Cyst Neoplasm Color Pink to red Red Normal Variable Fever - + Consistency Firm Rubbery Soft Shape Irregular Regular Discharge +/- Pain Ulceration Mobility Fixed Fluctuation Duration 20 days Days Years Months Neoplasm瘤

Benign or Malignant ? Our case Benign Malignant Border Clear Unclear Surface Smooth Rough, smooth Ulceration - +/- Induration + Pain Metastasis Mobility Fixed Movable/fixed Duration 20 days Years/Months Months

Intrabony or peripheral？ Our case Intrabony Peripheral Bone expansion - + Bony destruction Consistency firm Hard Soft, firm, rubbery… → Our case is a peripheral malignant neoplasm

WORKING DIAGNOSIS Malignant minor salivary gland tumor - Mucoepidermoid carcinoma - Adenoid cystic carcinoma Most possible Malignant mesenchymal tumor - Fibrosarcoma Least possible

Differential Diagnosis

Mucoepidermoid carcinoma Our case Mucoepidermoid carcinoma 符合 Gender Female Equal or Slight female predominance V Age 36 y/o 15~86 y/o (wide range) Site Labial mucosa Parotid gland(common) Minor salivary gland(Palate) S/S Swelling, painless Usually asymptomatic, swelling or pain if high-grade Size 2X2 cm in diameter Variable Duration 20 days Slow Clinical features Pain (-) Tenderness (+) Induration (+)

Adenoid cystic carcinoma Our case Adenoid cystic carcinoma 符合 Gender Female Slight female predominance V Age 36 y/o Middle age adult Site Labial mucosa Minor salivary gland, palate S/S Swelling, painless Swelling, pain (common)  Slow growing, but aggressive Size 2X2 cm in diameter Not mention Duration 20 days slow Clinical features Pain (-) Tenderness (+) Induration (+) Pain (+)

fibrosarcoma Our case Fibrosarcoma 符合 Gender Female Male > female 36 y/o 30-55 y/o V S/S Swelling, pain Size 2X2cm in diameter <2 cm v

Clinical impression Mucoepidermoid carcinoma over right upper lip

Treatment course

Treatment course 2015/11/25 Incisional biopsy HP report Oral cavity, upper lip, middle right, incision, adenoid cystic carcinoma 2015/12/02 Arrange CT, bone scan, chest PA, abdominal eccho, endoscope, CEA, TPA, SCC marker, panorex Arrange operation under general anesthia on 2015/12/31. Gross Examination: The specimen submitted consists of 1 soft tissue fragment in 1 bottle, measuring 0.4 x 0.4 x 0.3 cm in size, fixed in formalin. Grossly, it is white in color and elastic in consistency. All for section. Jar 0. Microscopic Examination: The slide contains two identical groups of irregular-shaped soft tissue specimens. Microscopically, it is characterized by clusters of diffuse small basophilic bizarre appearance neoplasic cells with many abnormal mitosis arranged in cribriform-like pattern underlying the intact parakeratinized stratified squamous epithelium. These neoplastic cells show strong positive staining for CK and focal weak positive staining for CD-117; negative staining for S-100. The positive labelling index of Ki-67 for the neoplastic cells is about 20-30%. IMMUNOHISTOCHEMICAL RESULTS Gross Examination: The specimen submitted includes 5 bland slides labeled as " KMUOP-15-2210 " from department of oral pathology. The following immunohistochemical stains are performed according to the doctor's request. Microscopic Examination: ● The immunohistochemical stain study demonstrates: CK (+), S100 ( focal + ), CD117 (-), Ki-67 labeling index: around 15%. Please correlate the histopathological features and clinical context. 21

Chest PA(2015/12/03) Impression： No imaging evidence of active cardiopulmonary disease.

EKG(2015/12/03) EKG Diagnosis: ■Low voltage (chest ) 不完全右束枝傳導阻塞(Incomplete RBBB) 23

EGD(2015/12/08) Assessment : . Reflux esophagitis, Grade A . Superficial gastritis at antrum . ECA survey : WL(-), NBI(-), no LVL, group A 　 　 　 　 　 24

Abdomen echo(2015/12/07) DIAGNOSIS：No liver metastasis 　 　 　 　 　 25

Treatment Plan WE+ Terudermis (12/31) 2015/12/02

DISCUSSION

Adenoid Cystic Carcinoma(ACC) 3rd most common salivary malignancies Commonly in head and neck Other sites: trachea, lacrimal gland, breast, skin, and vulva Distinctive histologic appearance Metastasis rate is high: bone and lung after mucoepidermoid carcinoma (mixed tumor) and polymorphous low grade adenocarcinoma Minor salivary gland, equal distribution in parotid and submandibular gland histologic appearance: swiss cheese Metastasis rate is high ->影響之後survival rate(為什要照chest PA) Oral and Maxillofacial Pathology 3rd edition, p.495-497

Clinical and Radiographic Features Sex predilection:♀≥♂ (3:2) Age predilection: middle-aged, rare younger than 20 y/o Site : 50-60% in minor salivary glands, palate Features: Pain, Slow growing mass Facial nerve paralysis if in parotid gland Bone destruction showed in radiograph if in palate or maxillary sinus Site: 小唾液腺腫瘤最常見就是ACC, 最好發位置是 palate 痛是重要的特徵, 通常比腫瘤swelling還早發生, surface有可能是(smooth or ulcerated) Oral and Maxillofacial Pathology 3rd edition, p.495-497

Histopathologic Features Mixture of myoepithelial and ductal cell Three major patterns, usually combination Cribriform, Swiss cheese Tubular Soild 1. glandular (cribiform) - classic, swiss cheese 2. tubular - well formed ducts lined by 2-3 cells 3. solid - solid epithelial islance Oral and Maxillofacial Pathology 3rd edition, p.495-497

Treatment and Prognosis Recurrence and metastasis → Surgical excision, adjunct RT may improve survival rate in some cases Survival rate 5-year : 70% 10-year : 50% 20-year : 25% 長久survival 影響來自於Recurrence and metastasis 還有tumor type(solid) 跟接受治療的方式 所以我們想討論影響survial rate的因素有哪些 What affects survival rate?

是一篇來自歐洲ENT的journal文章

總共取樣25人(年齡大ㄝ約從40-80歲) 大部分落在T3-4 只有兩個人是T2(沒有T1) 分別根據他的histology type有無接RT 等來去探討survial rate

TNM stage at diagnosis (P=0.03), Histological subtype (P=0.023), A:表示腫瘤分期 根據腫瘤分期越大的 survial rate越不好 B:表示histology type 由高至低 為 tubular -> mixed -> cribriform -> solid C:有無接受RT 有RT的明顯高出許多 TNM stage at diagnosis (P=0.03), Histological subtype (P=0.023), Combined surgery and radiotherapy (P=0.03), were significant factors of improved 5-year overall survival.

“ 使用人工真皮(Terudermis)真的有比較好嗎？” 醫學倫理討論 “ 使用人工真皮(Terudermis)真的有比較好嗎？”

Tom Beauchamp & James Childress 六大原則 - 1979 生命的神聖性(Sanctity of life) 行善原則(Beneficence)： 醫師要盡其所能延長病人之生命且減輕病人之痛苦。 誠信原則(Veractity)：醫師對其病人有「以誠信相對待」的義務。 自主原則(Autonomy)： 病患對其己身之診療決定的自主權必須得到醫師的尊重。 不傷害原則(Nonmaleficence)： 醫師要盡其所能避免病人承受不必要的身心傷害。 保密原則(Confidentiality)： 醫師對病人的病情負有保密的責任。 公義原則(Justice)： 醫師在面對有限的醫療資源時，應以社會公平、正義的考量來協助合理 分配此醫療資源給真正最需要它的人。

Jonson架構 醫療現況 (Medical indication for intervention) 病人選擇 (Patient’s preference) 生命品質 (Quality of life) 社會脈絡 (Contextual issues) Jonsen, Siegler and Winslade; Clinical Ethics: A Practical Approach to Ethical Decisions in Clinical Medicine (3rd edition McGraw-Hill 1992 )

生命的神聖性(Sanctity of life) 強調尊重自己和他人的生命 尊重生命的價值

行善原則(Beneficence) 做了wide excision後是否有盡可能減輕患者的不適與疼痛感？ A:術前預先告知病人術後可能會有的疼痛感，若有需要則搭配藥物的使用，並提醒病人相關的術後照護方式

誠信原則(Veractity) 手術前是否有詳細告知病人，使用人工真皮的優點與缺點？ A:自體植皮手術和人工真皮的差別

自主原則(Autonomy) 在詳細解釋治療計劃以及風險後，是否有讓病患完全自主的選擇治療計劃？ A:除了清楚闡述相關治療計劃的優缺點和比較之外，應避免使用主觀的用詞，來影響或左右病人之選擇

不傷害原則(Nonmaleficence)

保密原則(Confidentiality) 告知的對象 本人為原則 病人未明示反對時，亦得告知其配偶與親屬 病人為未成年人時，亦須告知其法定代理人 若病人意識不清或無決定能力, 應須告知其法定代理人 、配偶、親屬或關係人 病人得以書面敘明僅向特定之人告知或對特定對象不 予告知

公義原則(Justice) 以病人的情況來說，是不是真的需要使用 到人工真皮？ A :若傷口涵蓋的範圍較大，或病人不適合使用自體皮移植手術時，在評估病人的條件適合後，建議使用