Sinonasal Rhabdomyosarcoma Case Report 邱暄晉 王瀛標 呂宜興 台北馬偕紀念醫院 耳鼻喉科 各位師長同儕大家好，我是馬偕醫院耳鼻喉科第一年住院醫師邱暄晉，我今天要報告一個sinonasal rhabdomyosarcoma的病例報告

Case Information 31 y/o woman Alcohol/betel nuts/cigarette usage: nil Past history: Hypertension Type II diabetes mellitus Polycystic ovary syndrome 患者是31歲女性，平時沒有使用菸酒檳榔，過去有高血壓、糖尿病以及多囊性卵巢症候群的病史

Case Information 31 y/o woman Alcohol/betel nuts/cigarette usage: nil Past history: Hypertension Type II diabetes mellitus Polycystic ovary syndrome Headache and nasal obstruction with blood-tinged discharge for 1 month. 此次求診的主訴是近一個月有左側頭痛以及左側鼻塞合併帶有血絲的分泌物

Brief History 2018/08/09 OPD 2018/08/18 OPD Treated as rhinosinusitis with Augmentin for 1 week →Unresponsive 2018/08/18 OPD Lt level II neck mass Sinoscopy: Lt nasal cavity mucopus & nasal tumor →Biopsy 患者在今年八月九日來到門診求診，最初認為是鼻竇炎，因此給予一週的Augmentin治療，但使用後沒有改善。因此在八月十八日回診接受再次評估，做了鼻竇內視鏡後發現左側鼻腔有膿狀鼻涕及一個腫瘤樣病灶，因此在當日進行了biopsy

病理切片在顯微鏡下可見這種Small blue round cells

Myogenin (+) CD56 (+/-) MyoD1 (+) Chromogranin (+/-) Myogenin及myoD1免疫染色為陽性。CD56及chromogranin為weak positive。 CK(-) p63(- for SqCC) Mild expression of CD56(for lymphoma) and CGA(for neuroendocrine tumor) S100(- for melanoma) CD99(- for Ewing sarcoma family of tumors) Strong expression of myogenin and Myo-D1 Cytokeratin AE1/AE3: (-) for epithelial tumors MyoD1 (+) Chromogranin (+/-)

Myogenin (+) CD56 (+) MyoD1 (+) Chromogranin (+/-) 代表epithelial tumor的cytokeratin AE1/AE3、squamous cell carcinoma的p63、melanoma的S-100及ewing sarcoma的CD99則皆為陰性 CK(-) p63(- for SqCC) Mild expression of CD56(for lymphoma) and CGA(for neuroendocrine tumor) S100(- for melanoma) CD99(- for Ewing sarcoma family of tumors) Strong expression of myogenin and Myo-D1 Cytokeratin AE1/AE3: (-) for epithelial tumors MyoD1 (+) Chromogranin (+/-)

Rhabdomyosarcoma, favor embryonal type Myogenin (+) CD56 (+) 因此病理診斷為rhabdomyosarcoma，favor embryonal type CK(-) p63(- for SqCC) Mild expression of CD56(for lymphoma) and CGA(for neuroendocrine tumor) S100(- for melanoma) CD99(- for Ewing sarcoma family of tumors) Strong expression of myogenin and Myo-D1 Cytokeratin AE1/AE3: (-) for epithelial tumors MyoD1 (+) Chromogranin (+/-)

MRI 2018/08/29 Tumor in Bil. E+S sinuses, septum, and nasal cavity Staging MRI顯示腫瘤侵犯雙側鼻腔、鼻中膈、篩竇及蝶竇，其中左側的腫瘤體積較大。同時還有在額葉處顱底侵犯顱內，在左側level二到三及雙側retropharyngeal space都可能有淋巴結轉移 Tumor in Bil. E+S sinuses, septum, and nasal cavity Lt > Rt Intracranial invasion Lt lvl. II-III LAPs

PET/CT 2018/08/30 PET/CT除了在前述病灶有顯影外，並沒有找到遠端轉移的證據

Tentative Diagnosis Sinonasal rhabdomyosarcoma, T2aN1M0 stage 3 Tumor involvement Bil nasal cavity, nasal septum, ethmoid and sphenoid sinuses Intracranial invasion at frontal region Lt cervical lvl. II-III LAPs Hypertension Type II diabetes mellitus Polycystic ovary syndrome 因此tentative diagnosis為sinonasal rhabdomyosarcoma，T2aN1M0 stage 3

Left neck level II-III excision Treatment Plan Tumor involvement: Bil nasal cavity, nasal septum, ethmoid and sphenoid sinuses Intracranial invasion at frontal region Lt cervical lvl. II-III LAPs Transnasal endoscopic resection + frontal base dural repair Left neck level II-III excision 在治療計畫上，我們針對鼻腔及顱內的腫瘤侵犯安排了經鼻內視鏡腫瘤切除手術加上括肌膜張肌硬腦膜修補術。針對左側level二至三的淋巴結轉移則安排了手術切除。雙側retropharyngeal LAPs則因為手術切除可能會產生較嚴重morbidity之故，並未安排手術切除。術後則會安排放射及化學治療。 Adjuvant R/T C/T

Transnasal Endoscopic Resection + Frontal Base Dural Repair +Left Neck Level II-III Excision 2018/09/03 首先我們進行左側的頸部淋巴結切除 Lt level II-III mass /p excision

Transnasal Endoscopic Resection + Frontal Base Dural Repair +Left Neck Level II-III Excision 2018/09/03 接著進行內視鏡腫瘤切除，往顱內切除直至可見正常腦組織為止

Transnasal Endoscopic Resection + Frontal Base Dural Repair +Left Neck Level II-III Excision 2018/09/03 之後取左側擴筋膜張肌筋膜進行硬腦膜修補，並以tissel及dura seal封上並以nasopore填塞

Surgical Pathology Rhabdomyosarcoma involvement of: Frontal base dura Nasal septum Lt paranasal sinuses Nasal floor Lt neck LN (4/6) Rt paranasal sinuses: chronic inflammation 術後病理報告顯示在frontal base dura, nasal septum, 左側鼻竇、nasal floor及左側的淋巴結皆有腫瘤侵犯。右側的鼻竇則僅有慢性發炎。

Final Diagnosis and Plan Sinonasal rhabdomyosarcoma, favor embryonal type, left, T2aN1M0 stage 3, IRSG clinical group III /p transnasal endoscopic resection + frontal base dural repair + left neck level II-III excision 2018/09/03 Hypertension Type II diabetes mellitus Polycystic ovary syndrome Plan sequential CCRT(weekly CDDP) followed by adjuvant C/T(adriamycin/Ifosfomide) 因此術後的final diagnosis為sinonasal rhabdomyosarcoma, favor embryonal tuype, T2aN1M0 stage 4, IRSG clinical group III經內視鏡手術切除及頸部level II-III淋巴結切除。在團隊會議後，決定為其安排adjuvant CCRT (每週施打cisplatin)，CCRT後追加adriamycin/ifosfomide化療 患者在接受內視鏡手術一週後即出院，術後沒有發生手術腦脊髓液鼻漏或顱內感染等相關併發症

Postoperative Follow UP 2018/10/05 然而，術後約一個月，病人發生左側鼻血及hoarseness，內視鏡發現左側自鼻咽處突出之腫瘤，以及左側的聲帶麻痹 因此我們將R/T頻率增加為BID，病人現仍住院治療中 Left vocal cord palsy + local tumor progression →Hyperfraction R/T BID

Rhabdomyosarcoma Predominantly a disease of children. Presentation depends on the location of the tumor Children Adult Embryonal, alveolar Predominantly occurs in head & neck Only 15% present with metastatic diseases 5y survival= 49~84% Pleomorphic Predominantly occurs in extremities >60% present with regional an distant metastasis 5y survival= 8% 橫紋肌肉瘤較常發生在孩童，疾病的symptom/sign大多與其生長的位址有關 孩童患者較常出現的細胞型為embryonal及alveolar，相對地，成人較常出現的為pleomorphic(其預後通常較為不佳) 在兒童身上較常出現於頭頸部，在成人則是四肢為多，而且較多人在診斷時已經有淋巴或遠端轉移 因此兒童的survival也顯著地比大人為佳 El Sanharawia et al. Paranasal sinus rhabdomyosarcoma: A rare tumor of poor prognosis. European Annals of Otorhinolaryngology, Head and Neck Diseases, Volume 130, Issue 1, 2013, Pages 26-29, Brockstein et al. Head and neck sarcomas. Uptodate, Jan 23 2018

H&N Rhabdomyosarcoma in Adults Location Orbit Parameningeal area Paranasal sinuses Nasopharynx Nasal cavity Middle ear/mastoid Infratemporal fossa Non-orbital non-parameningeal sites Scalp Parotid gland Oral cavity Pharynx Thyroid and parathyroid glands Neck Histologic types Alveolar Embryonal Botryoid Spindle cell Pleomorphic Treatment Limited experience for adults Surgery + R/T + multi-agent C/T Vincristine-dactinomycin-cyclophosphamide (VAC) 頭頸部的橫紋肌肉瘤在分類上可依其發生的位置及組織型態進行分類 在頭頸部可分為三種：orbital、parameningeal、及其他 其治療主要已手術+R/T及多種藥物CT為主，經典的處方為vincristine-dactinomycin-cyclophosphamide El Sanharawia et al. Paranasal sinus rhabdomyosarcoma: A rare tumor of poor prognosis. European Annals of Otorhinolaryngology, Head and Neck Diseases, Volume 130, Issue 1, 2013, Pages 26-29,

Conclusion Sinonasal rhabdomyosarcoma is a rare tumor of poor prognosis in adults Adult patients often present with advanced disease Combined surgery, R/T, and C/T are required for its treatment