威爾姆氏腫瘤(Wilms Tumor)在19世紀初由一位德國外科醫師首先描述(Dr. Max Wilms, the German surgeon, first described this kind of tumor)，又稱腎芽細胞瘤或腎母細胞瘤(nephroblastoma)，是最常見的兒童惡性腎臟腫瘤，佔兒童腎臟腫瘤85%~ 90%。根據統計，每年約有10人被診斷為Wilms Tumor。最常發生在3~3.5歲，且非洲兒童更好發(People of African descent have the highest rates of Wilms tumor. Most instances of cancer occur among children between 3 to 3.5 years old)。15%患兒合併先天性異常，包括：隱睪症(Cryptorchidism)、尿道下裂(Hypospadias)、馬蹄腎(Horseshoe Kidney)、腎臟發育不全(Renal Dysplasia)、無虹彩症(1%)、半側肢體肥大、肋骨及肢體和髖關節異常，或合併各種症候群，如Denys-Drash syndrome、Beckwith-Wiedemann syndrome。
(註1)Denys-Drash syndrome (DDS) is a rare disorder consisting of the triad of congenital nephropathy, Wilms tumor, and intersex disorders resulting from mutations in the Wilms tumor suppressor (WT1) gene。
(註2)之前我們曾經談過Beckwith wiedemann syndrome，它與基因印記(imprinting)有關，是第11對染色體上基因11p15突變(Mutations of the WT1 gene on chromosome 11 p 15)，造成過度生長、大舌頭、臍膨出、內臟腫大、半邊肥大、新生兒低血糖、耳摺痕及後凹等表現(Beckwith wiedemann syndrome,An overgrowth syndrome, whose clinical manifestations typically include macrosomia, macroglossia, omphalocele (exomphalos), organomegaly, hemihypertrophy, neonatal hypoglycemia, and ear creases and ear pits)。根據研究指出，少數Wilms Tumor兒童是因第11對染色體上基因突變所致(Most cases do not have mutations in any of these genes)，其中20%是Wilms Tumor I型基因異常(Mutations of the WT1 gene on chromosome 11 p 13 are observed in 20% of Wilms tumors)，常伴有生殖泌尿系統異常。另外，至少有一半以上患者還伴隨CTNNB1基因突變(At least half of the Wilms tumors with mutations in WT1 also carry mutations in CTNNB1, the gene encoding the proto-oncogene beta-catenin)。
大多沒有疼痛不適感，偶在體檢時發現腹部腫塊。症狀輕微者會出現以下的表現：
- 腹部膨脹(an abnormally large abdomen)、腹痛(abdominal pain)、噁心、嘔吐(nausea and vomiting)、便秘(constipation)
- 發熱(fever)
- 精神倦怠、食慾差、體重減輕
- 血尿(blood in the urine (in about 20% of cases))
- 高血壓(high blood pressure in some cases)
診斷過程，應詳細了解病史、母親懷孕史、家族史、癌症史，以及詳細的身體評估，檢查是否有先天性異常部位，尤其是生殖泌尿系統的異常。血液和尿液的檢查不可少。影像學的檢查可用來確定腫瘤的位置，如超音波(Ultrasound)、CT、MRI、X-ray、IVP(用以檢查腎實質、膀胱、輸尿管形狀及排泄功能)；此外，還要進一步評估是否腫瘤有遠處轉移。
治療方式是手術+化學治療或放射線治療，但須依據腫瘤的分期及病理來決定(Treatment strategy is determined by the stage；Staging is determined by combination of imaging studies and pathology findings if the tumor is operable)。放射線治療針對生長分裂迅速的癌細胞加以摧毀，通常是術後幾天開始執行。
|
腫瘤 |
部位 |
|---|---|
|
Stage I (43% of patients) |
腫瘤局限在腎臟內(Tumor is limited to the kidney and is completely excised) |
|
Stage II (23% of patients) |
腎臟周圍的組織及結構(如脂肪及血管)受到侵犯 |
|
Stage III (23% of patients) |
腫瘤已侵犯腎外組織、淋巴結、腹膜(Unresectable primary tumor；Lymph node metastasis；Tumor is present at surgical margins；Tumor spillage involving peritoneal surfaces either before or during surgery, or transected tumor thrombus) |
|
Stage IV (10% of patients) |
腫瘤轉移到肺、肝、骨、腦等器官 |
|
Stage V (5% of patients) |
兩側腎腫瘤 |
|
腫瘤 |
治療 |
|---|---|
|
Stage I (43% of patients) |
單純腎切除手術(Simple nephrectomy)，只切除腎，不清掃淋巴及周圍組織；或全腎切除手術(Radical nephrectomy)，淋巴及周圍組織做病理。術後做化學治療18週 |
|
Stage II (23% of patients) |
全腎切除手術(Radical nephrectomy)以切除整個腎及周圍組織，附近淋巴結也須清掃，之後做化學治療24週(Nephrectomy + abdominal radiation + 24 weeks of chemotherapy) |
|
Stage III (23% of patients) |
放射治療及化學藥物治療後再做全腎切除手術(Radical nephrectomy)+ (Abdominal radiation + 24 weeks of chemotherapy + nephrectomy after tumor shrinkage) |
|
Stage IV (10% of patients) |
手術切除+放射線治療+化學治療，轉移處放射線治療(Nephrectomy + abdominal radiation + 24 weeks of chemotherapy + radiation of metastatic site as appropriate) |
|
Stage V (5% of patients) |
個體化治療(Individualized therapy based on tumor burden)。一般先做幾次化學治療，然後再將最嚴重的腎做全腎切除，但必須先確認另一側腎功能健全。一側腎切除後，另一側腎的病灶則視情況，做腫瘤切除或部份腎切除(Partial nephrectomy)。化學治療及放射線治療是必須的 |
|
腫瘤 |
結果 |
|---|---|
|
Stage I (43% of patients) |
(1)98% 4-year survival |
|
Stage II (23% of patients) |
(1)96% 4-year survival |
|
Stage III (23% of patients) |
(1)95% 4-year survival |
|
Stage IV (10% of patients) |
(1)90% 4-year survival |
|
Stage V (5% of patients) |
(1)The 4-year survival was 94%：advanced lesion was stage I or stage II |
(註)腎癌與Wilms瘤的比較
|
|
腎細胞癌 |
Wilms tumor |
|---|---|---|
|
好發年齡 |
>40歲 |
< 7歲的兒童 |
|
腫瘤起源 |
腎小管上皮細胞 |
後腎胚芽基組織 |
|
基因突變 |
Mutations of the VHL gene |
Mutations of the WT1 gene (chromosome 11 p 13) |
|
好發部位 |
腎上、下極，尤其是上極 |
腎上、下極 |
|
肉眼觀 |
|
|
|
病理特徵 |
70%~80%為透明細胞癌，其他有乳頭狀癌、厭色細胞癌、集合管癌、未分類腎癌等。常伴隨腫瘤旁症候群(paraneoplastic syndrome) |
|
|
症狀 |
血尿（90%）、腎區腫塊、腰痛 |
腹部包塊 |
|
轉移途徑 |
以血液轉移至肺、骨最多見，淋巴轉移少見 |
以血液轉移至肺最多見，淋巴轉移少見 |
<96-1-65> 下列有關腎細胞癌（renal cell carcinoma）之敘述，何者正確?
- 腎細胞癌源自腎臟之distal renal tubule 上皮
- 結節性硬化（tuberous sclerosis）與腎細胞癌有關
- 腎細胞癌常伴隨腫瘤旁症候群（paraneoplastic syndrome）
- 腎細胞癌對化學藥物治療之反應很
<97-1-53> 一位35歲男性被診斷為腎臟細胞癌，手術時發現肝及胰臟有囊腫存在，患者父親也有腎臟癌病史，腦部磁振照影發現小腦部位有一腫瘤，則患者最有可能是下列那一個基因發生突變?
- Rb
- p53
- VHL
- WT-1
<101-1-95>下列何者為威姆氏腫瘤（Wilms tumor）預後不佳之指標?
- 散發性（sporadic）案例
- 具三相式病理變化（Triphasic pattern），包括腎芽基（Blastema）、基質及上皮細胞等
- 退行分化（Anaplasia）程度高
- 2歲以下之病人