pielonefritis kronis

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ANGGA NUGRAHA - 0918011103 Pielonefritis kronis Tujuan Praktikum Mahasiswa mampu memahami dan menganalisa kasus pielonefritis khronis ditinjau dari ilmu patologi anatomi Petunjuk Praktikum 1. Mahasiswa diberikan ilustrasi kasus disertai beberapa gambar 2. Mahasiswa mempersiapkan mikroskop dan preparat sesuai skenario 3. Mahasiswa mengamati, mengevaluasi, dan menganalisa preparat sesuai skenario. 4. Mahasiswa mengambar hasil mikroskopis yang telah diamati 5. Mengerjakan tugas-tugas pertanyaan yang telah disediakan Dasar Teori Chronic pyelonephritis is renal injury induced by recurrent or persistent renal infection. It occurs almost exclusively in patients with major anatomic anomalies, including urinary tract obstruction, struvite calculi, renal dysplasia, or, most commonly, vesicoureteral reflux (VUR) in young children. Sometimes, this diagnosis is established based on radiologic evidence obtained during an evaluation for recurrent urinary tract infection (UTI) in young children. VUR is a congenital defect that results in incompetence of the ureterovesical valve due to a short intramural segment. The condition is present in 30-40% of young children with symptomatic UTIs and in almost all children with renal scars. VUR may also be acquired by patients with a flaccid bladder due to spinal cord injury. VUR is classified into 5 grades (I-V), according to the increasing degree of reflux. Pathophysiology Chronic pyelonephritis is associated with progressive renal scarring, which can lead to end-stage renal disease (ESRD), for example, reflux nephropathy. Intrarenal reflux of infected urine is suggested to induce renal injury, which heals with scar formation. In some cases, scars may form in utero in patients with renal dysplasia with perfusion defects. Infection without reflux is less likely to produce injury. Dysplasia may also be acquired from obstruction. Scars of high-pressure reflux can occur in persons of any age. In some cases, normal growth may lead to spontaneous cessation of reflux by age 6 years. Factors that may affect the pathogenesis of chronic pyelonephritis are as follows: (1) the sex of the patient and his or her sexual activity; (2) pregnancy, which may lead to progression of renal injury with loss of renal function; (3) genetic factors; (4) bacterial virulence factors; and (5) neurogenic bladder dysfunction. In cases with obstruction, the kidney may become filled with abscess cavities (see Pyonephrosis). Frequency VUR may be present in 30-45% of children with UTIs. The prevalence rate of VUR in siblings of patients with chronic pyelonephritis is approximately 35%. VUR and chronic pyelonephritis are less common in African American children than in white children. Mortality/Morbidity Conditions associated with mortality and morbidity related to chronic pyelonephritis include the following: (1) progressive renal scarring, (2) proteinuria, (3) hypertension, (4) end-stage renal disease, (5) focal glomerulosclerosis, and (6) xanthogranulomatous pyelonephritis (XPN). XPN occurs in 8.2% of patients and in 25% of patients with pyonephrosis. Race Chronic pyelonephritis is 3 times more common in white children than in African American children. Sex Chronic pyelonephritis is 2 times more common in females than in males. 1

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Page 1: Pielonefritis kronis

ANGGA NUGRAHA - 0918011103

Pielonefritis kronis

Tujuan PraktikumMahasiswa mampu memahami dan menganalisa kasus pielonefritis khronis ditinjau dari ilmu patologi anatomi

Petunjuk Praktikum1. Mahasiswa diberikan ilustrasi kasus disertai beberapa gambar2. Mahasiswa mempersiapkan mikroskop dan preparat sesuai skenario3. Mahasiswa mengamati, mengevaluasi, dan menganalisa preparat sesuai skenario.4. Mahasiswa mengambar hasil mikroskopis yang telah diamati5. Mengerjakan tugas-tugas pertanyaan yang telah disediakan

Dasar TeoriChronic pyelonephritis is renal injury induced by recurrent or persistent renal infection. It occurs almost exclusively in patients with major anatomic anomalies, including urinary tract obstruction, struvite calculi, renal dysplasia, or, most commonly, vesicoureteral reflux (VUR) in young children. Sometimes, this diagnosis is established based on radiologic evidence obtained during an evaluation for recurrent urinary tract infection (UTI) in young children. VUR is a congenital defect that results in incompetence of the ureterovesical valve due to a short intramural segment. The condition is present in 30-40% of young children with symptomatic UTIs and in almost all children with renal scars. VUR may also be acquired by patients with a flaccid bladder due to spinal cord injury. VUR is classified into 5 grades (I-V), according to the increasing degree of reflux.

PathophysiologyChronic pyelonephritis is associated with progressive renal scarring, which can lead to end-stage renal disease (ESRD), for example, reflux nephropathy. Intrarenal reflux of infected urine is suggested to induce renal injury, which heals with scar formation. In some cases, scars may form in utero in patients with renal dysplasia with perfusion defects. Infection without reflux is less likely to produce injury. Dysplasia may also be acquired from obstruction. Scars of high-pressure reflux can occur in persons of any age. In some cases, normal growth may lead to spontaneous cessation of reflux by age 6 years.Factors that may affect the pathogenesis of chronic pyelonephritis are as follows: (1) the sex of the patient and his or her sexual activity; (2) pregnancy, which may lead to progression of renal injury with loss of renal function; (3) genetic factors; (4) bacterial virulence factors; and (5) neurogenic bladder dysfunction. In cases with obstruction, the kidney may become filled with abscess cavities (see Pyonephrosis).FrequencyVUR may be present in 30-45% of children with UTIs. The prevalence rate of VUR in siblings of patients with chronic pyelonephritis is approximately 35%. VUR and chronic pyelonephritis are less common in African American children than in white children.Mortality/MorbidityConditions associated with mortality and morbidity related to chronic pyelonephritis include the following: (1) progressive renal scarring, (2) proteinuria, (3) hypertension, (4) end-stage renal disease, (5) focal glomerulosclerosis, and (6) xanthogranulomatous pyelonephritis (XPN). XPN occurs in 8.2% of patients and in 25% of patients with pyonephrosis.

RaceChronic pyelonephritis is 3 times more common in white children than in African American children. SexChronic pyelonephritis is 2 times more common in females than in males. AgeChronic pyelonephritis occurs more often in infants and young children (younger than 2 y) than in older children and adults.

ClinicalHistory

Many cases of VUR are suggested based on prenatal sonography findings. Patients with chronic pyelonephritis may report the following:

o Fevero Lethargyo Nausea and vomitingo Flank pain or dysuria

Some children may present with failure to thrive.Physical

The following may be noted:o Hypertensiono Failure to thrive in young childreno Flank tenderness

Causes Chronic pyelonephritis is renal injury induced by recurrent or persistent renal infection.

Skenario

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Seorang wanita berumur 48 tahun mengeluh nyeri pinggang kanan dan buang air kecil warna merah sejak 2 minggu yang lalu. dilakukan pemeriksaan IVP tampak ginjal kanan membesar; terdapat dilatasi pada kalik serta ditemukan batu. Hasil scanning tampak ginjal kanan membesar diserati identasi pada ginjal. Hasil pemeriksaan urin ditemukan banyak sel radang dan eritosit. Diputuskan nefrektomi, hasil operasi diperiksa histopatologi.

Gambar 1. Hasil rontgen IVP

Gambar 2. Hasil Scanning penderita pyelonefritis

MakroskopisJaringan ginjal berukuran 11x6x4 cm, , berat 100 gram, disertai ureter panjang 21 cm. Pada sayatan berwarna putih kecoklotan dengan konsistensi kenyal padat.

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Gambar3. Makroskopis pyelonefritis

MikroskopisJaringan ginjal menunjukan gambaran pada korteks tampak glamerulus dengan capsule bowman yang mengalami sclerosis. Tubulus proksimal dan tubulus distal sebagian besar mengalami degenerasi amiloid dan tampak deposit amiloid pada jaringan ikat diantara tubulus. Disekitarnya Tampak serbukan mosif sei radang limfosit. Pada pielum tampak ductus colligentes yang berdilatasi dan dalam lumen dengan eritrosit.

Gambar 4. Mikroskopis penderita pyelonefritis

KesimpulanPielonefritis kronis

Tugas1. Gambar atau buat foto mikroskopis, beri keterangan gambar yang telah dibuat!2. Jelaskan penyebob pyelonefritis khronis!3. Apakah terdapat kemungkinan terjadi keganasan? Jelaskan!

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Tumor Wilms

Tujuan PraktikumMahasiswa mampu memahami dan menganalisa kasus Tumor Wilms ditinjau dari ilmu patologi anatomi

Petunjuk Praktikum1. Mahasiswa diberikan ilustrasi kasus disertai beberapa gambar2. Mahasiswa mempersiapkan mikroskop dan preparat sesuai skenario3. Mahasiswa mengamati, mengevaluasi, dan menganalisa preparat sesuai skenario.4. Mahasiswa mengambar hasil mikroskopis yang telah diamati5. Mengerjakan tugas-tugas pertanyaan yang telah disediakan

Dasar TeoriWilms' tumorWilms' tumor or Wilms' tumour (see spelling differences) or nephroblastoma is cancer of the kidneys that typically occurs in children, rarely in adults. Its common name is an eponym, referring to Dr. Max Wilms, the German surgeon (1867–1918) who first described this kind of tumor. Approximately 500 cases are diagnosed in the U.S. annually. The majority (75%) occur in otherwise normal children; a minority (25%) is associated with other developmental abnormalities. It is highly responsive to treatment, with about 90% of patients surviving at least five years.

PathologyMost nephroblastomas are unilateral, being bilateral in less than 5% of cases. They tend to be encapsulated and vascularized tumors that do not cross the midline of the abdomen. In cases of metastasis it is usually to the lung. A rupture of Wilms' tumor puts the patient at risk of hemorrhage and peritoneal dissemination of the tumor. In such cases, surgical intervention by a surgeon who is experienced in the removal of such a fragile tumor is imperative.Pathologically, a triphasic nephroblastoma comprises three elements:

blastema mesenchyme epithelium

Wilms' tumor is a malignant tumor containing metanephric blastema, stromal and epithelial derivatives. Characteristic is the presence of abortive tubules and glomeruli surrounded by a spindled cell stroma. The stroma may include striated muscle, cartilage, bone, fat tissue, fibrous tissue. The tumor is compressing the normal kidney parenchyma.The mesenchymal component may include cells showing rhabdomyoid differentiation. The rhabdomyoid component may itself show features of malignancy (rhabdomyosarcomatous Wilms).Wilms' tumors may be separated into 2 prognostic groups based on pathologic characteristics:

Favorable - Contains well developed components mentioned above Anaplastic - Contains diffuse anaplasia (poorly developed cells)

PrognosisTumor-specific loss-of-heterozygosity (LOH) for chromosomes 1p and 16q identifies a subset of Wilms' tumor patients who have a significantly increased risk of relapse and death. LOH for these chromosomal regions can now be used as an independent prognostic factor together with disease stage to target intensity of treatment to risk of treatment failure. Genome-wide copy number and LOH status can be assessed with virtual karyotyping of tumor cells (fresh or paraffin-embedded). The overall prognosis with surgical removal is positive. Early removal tends to promote positive outcomes.

Molecular biologyMutations of the WT1 gene on chromosome 11 p 13 are observed in approximately 20% of Wilms' tumors. At least half of the Wilms' tumors with mutations in WT1 also carry mutations in CTNNB1, the gene encoding the proto-oncogene beta-catenin.

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A gene on the X chromosome, WTX, is inactivated in up to 30% of Wilms' tumor cases, according to research published in 2007. Most cases do not have mutations in any of these genes.

Staging and treatmentStaging is determined by combination of imaging studies and pathology findings if the tumor is operable (adapted from www.cancer.gov). Treatment strategy is determined by the stage:Stage I (43% of patients)For stage I Wilms' tumor, 1 or more of the following criteria must be met:

Tumor is limited to the kidney and is completely excised. The surface of the renal capsule is intact. The tumor is not ruptured or biopsied (open or needle) prior to removal. No involvement of renal sinus vessels. No residual tumor apparent beyond the margins of excision.

Treatment: Nephrectomy +/- 18 weeks of chemotherapy depending on age of patient and weight of tumor. EG: less than 2 years old and less than 550g only requires Nephrectomy with observationOutcome: 98% 4-year survival; 85% 4-year survival if anaplasticStage II (23% of patients)For Stage II Wilms' tumor, 1 or more of the following criteria must be met:

Tumor extends beyond the kidney but is completely excised. No residual tumor apparent at or beyond the margins of excision. Any of the following conditions may also exist:

o Tumor involvement of the blood vessels of the renal sinus and/or outside the renal parenchyma.o The tumor has been biopsied prior to removal or there is local spillage of tumor during surgery, confined to the

flank.Treatment: Nephrectomy + abdominal radiation + 24 weeks of chemotherapyOutcome: 96% 4-year survival; 70% 4-year survival if anaplasticStage III (23% of patients)For Stage III Wilms' tumor, 1 or more of the following criteria must be met:

Unresectable primary tumor. Lymph node metastasis. Positive surgical margins. Tumor spillage involving peritoneal surfaces either before or during surgery, or transected tumor thrombus.

Treatment: Abdominal radiation + 24 weeks of chemotherapy + nephrectomy after tumor shrinkageOutcome: 95% 4-year survival; 56% 4-year survival if anaplasticStage IV (10% of patients)Stage IV Wilms' tumor is defined as the presence of hematogenous metastases (lung, liver, bone, or brain), or lymph node metastases outside the abdomenopelvic region.Treatment: Nephrectomy + abdominal radiation + 24 weeks of chemotherapy + radiation of metastatic site as appropriateOutcome: 90% 4-year survival; 17% 4-year survival if anaplasticStage V (5% of patients)Stage V Wilms’ tumor is defined as bilateral renal involvement at the time of initial diagnosis. Note: For patients with bilateral involvement, an attempt should be made to stage each side according to the above criteria (stage I to III) on the basis of extent of disease prior to biopsy. The 4-year survival was 94% for those patients whose most advanced lesion was stage I or stage II; 76% for those whose most advanced lesion was stage III.Treatment: Individualized therapy based on tumor burdenStage I-IV AnaplasiaChildren with stage I anaplastic tumors have an excellent prognosis (80-90% five-year survival). They can be managed with the same regimen given to stage I favorable histology patients.Children with stage II through stage IV diffuse anaplasia, however, represent a higher-risk group. These tumors are more resistant to the chemotherapy traditionally used in children with Wilms’ tumor (favorable histology), and require more aggressive regimens.

TreatmentOnce a kidney tumor is found, a surgical biopsy is done. A sample of tissue from the tumor is sent to a pathologist, who looks at it under a microscope to check for signs of cancer. If the tumor is only in the kidney (typical), it can be removed along with the whole kidney (a nephrectomy). If there are tumors in both kidneys or if the tumor has spread outside the kidney, a piece of the tumor will be removed. Children 16 years old or older have higher mortality rates within their stages. This is due to them being treated less aggressively and consistently. Adjuvant chemotherapy is sometimes used. Risk FactorsPeople of African descent have the highest rates of Wilms' tumor. Females are also more likely than males to develop the tumors. Most instances of cancer occur among children under the age of 5.

SkenarioSeorang anak laki-laki berusia 3 tahun, sejak 1 tahun yang lalu perut makin membucit, buang air kecil ada kalanya kemerahan. Pada pemeriksaan teraba massa tumor pada rongga perut kiri sebesar tinju orang dewasa. Rontgen foto abdomen tampak bayangan radiopoque menempati daerah ginjal kiri yang menekan kolon, diputuskan operasi dan massa tumor ginjal kiri di angkat untuk pemeriksaan patologi.

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Gambar 5. Scanning abdomen penderita tumor Wilms

MakroskopisMassa tumor ukuron 10 x 8 x 8 cm, warna putih bentuk benjol, permukaan putih konsistensi kenyal, padat. Pada irisan penampang kopsel tidak jelas, putih abu, homhogen padat dengan bercak-bercak perdarahan, tidak tampak struktur ginjal normal.

Gambar 6. Gross hasil operasi ginjal penderita tumor Wilms

MikroskopisSediaan massa tumor terdiri dari 3 bentuk sel. Pertama : komponen blostomatous terdiri dari sel bulat kecil, inti bulat hiper kromatis, sitoplasma tipis. Kedua : komponen mesenkim terdiri dari sel spindle seperti fibroblast, inti lonjong. Ketiga: komponen epitel terdiri dari sel kuboid yang menyusun dengan lumen dikelilingi sel tumor seperti sel basal. Pada setiap daerah perbandingan selularitas 3 komponen berfariasi.

Gambar 7. Mikroskopis penderita tumor Wilms Gambar 8. Mikroskopis tumor Wilms

KesimpulanTumor Wilm's

Tugas1. Gambar atau buat foto mikroskopis, beri keterangan gambar yang telah dibuat!2. Gambaran khas tumor Wilm's?3. Jelaskan penyebab tumor Wilm's?

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Karsinoma sel renal

Tujuan PraktikumMahasiswa mampu memahami dan menganalisa kasus karsinoma sel renal ditinjau dari ilmu patologi anatomi

Petunjuk Praktikum1. Mahasiswa diberikan ilustrasi kasus disertai beberapa gambar2. Mahasiswa mempersiapkan mikroskop dan preparat sesuai skenario3. Mahasiswa mengamati, mengevaluasi, dan menganalisa preparat sesuai skenario.4. Mahasiswa mengambar hasil mikroskopis yang telah diamati5. Mengerjakan tugas-tugas pertanyaan yang telah disediakan

Dasar TeoriRenal cell carcinomaRenal cell carcinoma (RCC, also known as hypernephroma) is a kidney cancer that originates in the lining of the proximal convoluted tubule, the very small tubes in the kidney that filter the blood and remove waste products. RCC is the most common type of kidney cancer in adults, responsible for approximately 80% of cases. It is also known to be the most lethal of all the genitourinary tumors. Initial treatment is most commonly a radical or partial nephrectomy and remains the mainstay of curative treatment.[2] Where the tumour is confined to the renal parenchyma, the 5-year survival rate is 60-70%, but this is lowered considerably where metastases have spread. It is resistant to radiation therapy and chemotherapy, although some cases respond to immunotherapy. Targeted cancer therapies such as sunitinib, temsirolimus, bevacizumab, interferon-alpha, and possibly sorafenib have improved the outlook for RCC (progression-free survival), although they have not yet demonstrated improved survival.Signs and symptomsA wide range of symptoms can be present with renal carcinoma depending on which areas of the body have been affected. The classic triad is hematuria (blood in the urine), flank pain and an abdominal mass. This triad only occurs in 10-15% of cases, and is generally indicative of more advanced disease. Today, the majority of renal tumors are asymptomatic and are detected incidentally on imaging, usually for an unrelated cause.Signs may include:

Abnormal urine color (dark, rusty, or brown) due to blood in the urine (found in 60% of cases) Loin pain (found in 40% of cases) Abdominal mass (25% of cases) Malaise, weight loss or anorexia (30% of cases) Polycythemia (5% of cases) Anaemia resulting from depression of erythropoietin (30% of cases) Also, there may be erythrocytosis (increased

production of red blood cells) due to increased erythropoietin secretion. The presenting symptom may be due to metastatic disease, such as a pathologic fracture of the hip due to a metastasis to

the bone Varicocele, the enlargement of one testicle, usually on the left (2% of cases). This is due to blockage of the left testicular

vein by tumor invasion of the left renal vein; this typically does not occur on the right as the right gonadal vein drains directly into the inferior vena cava.

Vision abnormalities Pallor or plethora Hirsutism - Excessive hair growth (females) Constipation Hypertension (high blood pressure) resulting from secretion of renin by the tumour (30% of cases) Elevated calcium levels (Hypercalcemia) Stauffer syndrome - paraneoplastic, non-metastatic liver disease Night Sweats Severe Weight Loss

Patients may also experience the following symptoms:

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Recurrent fevers which occur in 9% of the patients Cold intolerance Back pain Chronic fatigue Leg and ankle swelling Loss of appetite

ClassificationMicrograph of chromophobe renal cell carcinoma oncocytic variant. H&E stain.Recent genetic studies have altered the approaches used in classifying renal cell carcinoma. The following system can be used to classify these tumors:

Clear cell renal cell carcinoma (VHL and others on chromosome 3) Papillary renal cell carcinoma (MET, PRCC) Chromophobe renal cell carcinoma Collecting duct carcinoma

Renal epithelial neoplasms have characteristic cytogenetic aberrations that can aid in classification. [13] See also Atlas of Genetics and Cytogenetics in Oncology and Haematology.

Clear cell carcinoma: loss of 3p Papillary carcinoma: trisomy 7, 16, 17 Chromophobe carcinoma: hypodiploid with loss of chromosomes 1, 2, 6, 10, 13, 17, 21

Array-based karyotyping can be used to identify characteristic chromosomal aberrations in renal tumors with challenging morphology. Array-based karyotyping performs well on paraffin embedded tumors and is amenable to routine clinical use. See also Virtual Karyotype for CLIA certified laboratories offering array-based karyotyping of solid tumors.Other associated genes include TRC8, OGG1, HNF1A, HNF1B, TFE3, RCCP3, and RCC17.

EpidemiologyThe incidence of renal cell cancer has been rising steadily. Nearly 51190 new diagnoses and 12890 deaths reported in the United States in 2007. It is more common in men than women: the male-to-female ratio is 1.6:1 and has been decreasing over the last decade. Blacks have a slightly higher rate of renal cell cancer than whites. The reasons for this are not clear. [17] Note: in epidemiology, RCC is registered together with renal pelvis carcinoma, which is predominantly transitional cell type.In Europe the incidence of RCC has doubled in the period from 1975 to 2005. RCC accounted for 3777 deaths in the UK in 2006; male 2372, female 1820.

Risk factorsCigarette smoking and obesity are the strongest known risk factors. Hypertension and a family history of the disease are also risk factors. Dialysis patients with acquired cystic disease of the kidney showed a 30 times greater risk than in the general population for developing RCC. Exposure to asbestos, polycyclic aromatic hydrocarbons, gasoline has not been shown to be consistently associated with RCC risk. Patients with certain inherited disorders such as von Hippel-Lindau disease, hereditary papillary renal cancer, a hereditary leiomyoma RCC syndrome and Birt-Hogg-Dubé syndrome, show an enhanced risk of RCC. Also, patients with sickle cell trait are predisposed to developing Renal medullary carcinoma.Hysterectomy is associated with an approximately doubled risk. Hormonal factors or injury of the ureter during surgery were considered as possible causes. DiagnosisAn accurate diagnose may be difficult to establish given that the early stages of renal cancer are asymptomatic.The first steps taken in order to diagnose this condition are observing any of the signs and symptoms, and an anamnesis (the detailed medical review of past health state) to evaluate any risk factors. Upon physical examination, palpation of the abdomen may reveal the presence of a mass or an organ enlargement. However, the main diagnostic tool for detecting renal cell carcinoma is ultrasound of the kidneys. If the ultrasound shows a mass or cyst, a subsequent abdominal CT is the optimal test for diagnosis and staging. RadiologyThe characteristic appearance of renal cell carcinoma (RCC) is a solid renal lesion which disturbs the renal contour. It will frequently have an irregular or lobulated margin. Traditionally 85 to 90%% of solid renal masses will turn out to be RCC but this number may be decreasing as renal masses are being found at smaller and smaller sizes with larger numbers of benign lesions. 10% of RCC will contain calcifications, and some contain macroscopic fat (likely due to invasion and encasement of the perirenal fat).Renal cell carcinoma may also be cystic. As there are several benign cystic renal lesions (simple renal cyst, hemorrhagic renal cyst, multilocular cystic nephroma, polycystic kidney disease), it may occasionally be difficult for the radiologist to differentiate a benign cystic lesion from a malignant one. A classification system for cystic renal lesions that classifies them based specific imaging features into groups that are benign and those that need surgical resection is available. Percutaneous biopsy can be performed by a radiologist using ultrasound or computed tomography to guide sampling of the tumor for the purpose of diagnosis by pathology. However this is not routinely performed because when the typical imaging features of renal cell carcinoma are present, the possibility of an incorrectly negative result together with the risk of a medical complication to the patient make it unfavorable from a risk-benefit perspective. This is not completely accurate, there are new experimental treatments.

Staging

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The staging of renal cell carcinoma is the most important factor in predicting its prognosis. [33] Staging can follow the TNM staging system, where the size and extent of the tumour (T), involvement of lymph nodes (N) and metastases (M) are classified separately. Also, it can use overall stage grouping into stage I-IV, with the 1997 revision of AJCC described below:

Stage ITumor of a diameter of 7 cm (approx. 2 3/4 inches) or smaller, and limited to the kidney. No lymph node involvement or metastases to distant organs.

Stage II Tumor larger than 7.0 cm but still limited to the kidney. No lymph node involvement or metastases to distant organs.

Stage IIIany of the following

Tumor of any size with involvement of a nearby lymph node but no metastases to distant organs. Tumor of this stage may be with or without spread to fatty tissue around the kidney, with or without spread into the large veins leading from the kidney to the heart.Tumor with spread to fatty tissue around the kidney and/or spread into the large veins leading from the kidney to the heart, but without spread to any lymph nodes or other organs.

Stage IVany of the following

Tumor that has spread directly through the fatty tissue and the fascia ligament-like tissue that surrounds the kidney.Involvement of more than one lymph node near the kidneyInvolvement of any lymph node not near the kidneyDistant metastases, such as in the lungs, bone, or brain.

At diagnosis, 30% of renal cell carcinomas have spread to the ipsilateral renal vein, and 5-10% has continued on into the inferior vena cava.

HistopathologyThe gross and microscopic appearance of renal cell carcinomas is highly variable. The following describes a typical clear cell carcinoma, which is the most common type.The renal cell carcinoma may present reddened areas where blood vessels have bled, and cysts containing watery fluids. The body of the tumor shows large blood vessels that have walls composed of cancerous cells.Gross examination often shows a yellowish, multilobulated tumor in the renal cortex, which frequently contains zones of necrosis, hemorrhage and scarring.Light microscopy shows tumor cells forming cords, papillae, tubules or nests, and are atypical, polygonal and large. Also, the cells that make up a renal carcinoma may be clear, granular, mixed clear and granular or sarcomatoid or spindle type. Recent studies have brought to attention that the type of cancerous cells and the aggressiveness of the condition are closely related.Because these cells accumulate glycogen and lipids, their cytoplasm appear "clear", the nuclei remain in the middle of the cells, and the cellular membrane is evident. Some cells may be smaller, with eosinophilic cytoplasm, resembling normal tubular cells. The stroma is reduced, but well vascularized. The tumor compresses the surrounding parenchyma, producing a pseudocapsule. The clear cells are thought to be the least likely to spread and usually respond more favorably to treatment. [37] However, most of the tumors contain a mixture of cells. The most aggressive stage of renal cancer is believed to be the one in which the tumor is mixed, containing both clear and granular cells.

PrognosisA study in Turkey that used the 1997 AJCC staging system estimated the five year survival rate to be 90% for stage I, 51% for stage II, 22% for stage III and 4.6% for stage IV. The same study estimated the median survival time to be 7.7 years for stage I, 5.0 years for stage II, 3.1 years for stage III and 1.1 years for stage IV. For those that have tumor recurrence after surgery, the prognosis is generally poor. Renal cell carcinoma does not generally respond to chemotherapy or radiation. Immunotherapy, which attempts to induce the body to attack the remaining cancer cells, has shown promise. Recent trials are testing newer agents, though the current complete remission rate with these approaches are still low, around 12-20% in most series. Most recently, treatment with tyrosine kinase inhibitors including nexavar, pazopanib, and rapamycin have shown promise in improving the prognosis for advanced RCC since 2004.TreatmentIf it is only in the kidneys, which is about 40% of cases, it can be cured roughly 90% of the time with surgery. If it has spread outside of the kidneys, often into the lymph nodes or the main vein of the kidney, then it must be treated with adjunctive therapy, including cytoreductive surgery. RCC is resistant to chemotherapy and radiotherapy in most cases, but does respond well to immunotherapy with interleukin-2 or interferon-alpha, biologic, or targeted therapy. In early stage cases, cryotherapy and surgery are the preferred options.

Watchful waitingSmall renal tumors (< 4 cm) are treated increasingly by way of partial nephrectomy when possible.[39][40][41] Most of these small renal masses manifest indolent biological behavior with excellent prognosis. More centers of excellence are incorporating needle biopsy to confirm the presence of malignant histology prior to recommending definitive surgical extirpation. In the elderly, patients with co-morbidities and in poor surgical candidates, small renal tumors may be monitored carefully with serial imaging. Most clinicians conservatively follow tumors up to a size threshold between 3–5 cm, beyond which the risk of distant spread (metastases) is about 5%.

SurgerySurgical removal of all or part of the kidney (nephrectomy) is recommended. This may include removal of the adrenal gland, retroperitoneal lymph nodes, and possibly tissues involved by direct extension (invasion) of the tumor into the surrounding tissues. In cases where the tumor has spread into the renal vein, inferior vena cava, and possibly the right atrium, this portion of the tumor can be surgically removed, as well. In cases of known metastases, surgical resection of the kidney ("cytoreductive nephrectomy") may improve survival,[43] as well as resection of a solitary metastatic lesion. Kidneys are sometimes embolized prior to surgery to minimize blood loss.

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Surgery is increasingly performed via laparoscopic techniques. These have the advantage of being less of a burden for the patient and the disease-free survival is comparable to that of open surgery. For small exophytic lesions that do not extensively involve the major vessels or urinary collecting system, a partial nephrectomy (also referred to as "nephron sparing surgery") can be performed. This may involve temporarily stopping blood flow to the kidney while the mass is removed as well as renal cooling with an ice slush. Mannitol can also be administered to help limit damage to the kidney. This is usually done through an open incision although smaller lesions can be done laparoscopically with or without robotic assistance.Laparoscopic cryotherapy can also be done on smaller lesions. Typically a biopsy is taken at the time of treatment. Intraoperative ultrasound may be used to help guide placement of the freezing probes. Two freeze/thaw cycles are then performed to kill the tumor cells. As the tumor is not removed followup is more complicated (see below) and overall disease free rates are not as good as those obtained with surgical removal.

Percutaneous therapiesPercutaneous, image-guided therapies, usually managed by radiologists, are being offered to patients with localized tumor, but who are not good candidates for a surgical procedure. This sort of procedure involves placing a probe through the skin and into the tumor using real-time imaging of both the probe tip and the tumor by computed tomography, ultrasound, or even magnetic resonance imaging guidance, and then destroying the tumor with heat (radiofrequency ablation) or cold (cryotherapy). These modalities are at a disadvantage compared to traditional surgery in that pathologic confirmation of complete tumor destruction is not possible. Therefore, long-term follow-up is crucial to assess completeness of tumour ablation.

Medications for advanced or metastatic casesRCC "elicits an immune response, which occasionally results in dramatic spontaneous remissions." This has encouraged a strategy of using immunomodulating therapies, such as cancer vaccines and interleukin-2 (IL-2), to reproduce this response. IL-2 has produced "durable remissions" in a small number of patients, but with substantial toxicity. Another strategy is to restore the function of the VHL gene, which is to destroy proteins that promote inappropriate vascularization. Bevacizumab, an antibody to VEGF, has significantly prolonged time to progression, but As of 2008 phase 3 trials have not been published. Sunitinib (Sutent), sorafenib (Nexavar), and temsirolimus, which are small-molecule inhibitors of proteins, have been approved by the U.S. F.D.A. Treatment with tyrosine kinase inhibitors including Nexavar, pazopanib, and rapamycin have shown promise in improving the prognosis for advanced RCC since 2004.Sorafenib (Nexavar), a protein kinase inhibitor, was FDA approved in December 2005 for treatment of advanced renal cell cancer.A month later, Sunitinib (Sutent) was approved as well. Sunitinib (an oral, small-molecule, multi-targeted (RTK) inhibitor) and sorafenib both interfere with tumor growth by inhibiting angiogenesis as well as tumor cell proliferation. Sunitinib appears to offer greater potency against advanced RCC, perhaps because it inhibits more receptors than sorafenib.

ChemotherapyMost of the currently available cytostatics are ineffective for the treatment of RCC. Their use can not be recommended for the treatment of patients with metastasized RCC,as response rates are very low,often just 5-15%,and most responses are short lived. The use of Tyrosine Kinase (TK) inhibitors, such as Sunitinib and Sorafenib, and Temsirolimus are described in a different section

VaccineCancer vaccines, such as TroVax, have shown promising results in phase 2 trials for treatment of renal cell carcinoma. However, issues of tumor immunosuppression and lack of identified tumor-associated antigens must be addressed before vaccine therapy can be applied successfully in advanced renal cell cancer.

Metastatic renal cell carcinomaThis section has multiple issues. Please help improve it or discuss these issues on the talk page.

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The metastatic stage of the renal cell carcinoma occurs when the disease invades and spreads to other organs. It is most likely to spread to neighboring lymph nodes, the lungs, the liver, the bones, or the brain. Metastatic renal cell carcinoma presents a special challenge to oncologists, as about 70% of patients with renal cell carcinoma develop metastases during the course of their disease, and 5 year survival for patients with metastatic renal cell carcinoma is between 5-15%,though it is much improved if metastatectomy and nephrectomy to remove all visible disease is performed. even if metastases are not removed,cytoreductive nephrectomy is sometimes used in the treatment of metastatic renal cell carcinoma,and at least 1 study has supported the use of cytoreductive nephrectomy in "some cases" of metastatic renal cell carcinoma,citing improved response rates to interleukin-2 immunotherapy and modestly prolonged survival.Radiotherapy and chemotherapy have less of a role in therapy of renal cell carcinoma then in other malignancies; but they are still sometimes used in treatment of metastatic renal cell carcinoma. Radiotherapy is used in bone metastases from renal cell carcinoma to reduce pain and lower the risk of pathologic fracture, in patients with brain metastases, and to palliate symptoms of metastatic disease to the liver, adrenals, or lungs from renal cell carcinoma. Interleukin-2, has been the standard of care since the 1990s in metastatic renal cell carcinoma, as although response rates are low [7-16%], about half of patients that respond have long term disease free survival, and some of these patients may be cured of their disease. However,the side effects of interleukin-2 are very severe, including decreased neutrophil function, increased risk of dissemenated infection, including central venous catheter infections, septicaemia, and bacterial endocarditis, capillary leak syndrome, which can result in myocardial infarction, renal failure, angina, hypotension, reduced organ perfusion, altered mental status, pulmonary failure requiring intubation, cardiac arrhythmias, edema, and gastrointestinal bleeding. Proleukin also can result in lethargy and somnolence; if interleukin-2 therapy is not discontinued lethargy

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may progress to coma. Interleukin-2 can also worsen pre-existing autoimmune diseases.exacerbation of scleroderma, diabetes mellitus, thyroiditis, inflammatory bowel disease, myesthinisa gravis, nephritis, and other autoimmune diseases have been reported. Neurological side effects can also occur, and include ataxia, cortical blindness, hallucinations, psychosis, speech problems, and coma. Other side effects include abdominal pain, rigors, fever, malaise, asthenia, acidosis, tachycardia, vasodialation, diarrhea, vomiting, mouth sores, loss of appetite, dermatitis, dyspnea, thrombocytopenia, and anaemia. Also, patients must be in good health with normal cardiovascular, hepatic, pulmanary,and neurological function to be treated with interleukin-2.Recently, targeted therapies including torisel, nexavar, sutent, and bevacizumab have been developed, and all are now approved for the treatment of metastatic renal cell carcinoma. Also, votrient [pazopanib] was approved for the treatment of metastatic renal cell carcinoma in October 2009. This is the sixth drug to be approved for metastatic renal cell carcinoma since 2005. The last 3–5 years have seen dramatic improvements in treatment for those with metastatic renal cell carcinoma, Richard Pazdur, MD, director of the office of oncology drugs at the U.S. Food and Drug Administration (FDA). However, despite these improvements in therapy, overall survival in metastatic renal cell carcinoma remains quite poor.Currently, tumor vaccines and chemotheraputic, biologic, and immunologic agents are being researched in the treatment of metastatic renal cell carcinoma, and some appear promising. It is not known whether or not detecting metastatic renal cell carcinoma earliar improves survival or response to treatment. Symptoms of metastatic renal cell carcinoma are often mistaken for other, less severe illness,and include: for bone metastases, pain, stiffness, bruit, and pathologic fracture; for liver metastases, abdominal pain, jaundice, elevations in AST and ALT, and vomiting, for lung metastases, cough, dyspnea, and abnormal chest radiograph. Brain metastases produce diplopia, personality changes, headache, ataxia, vertigo, and seizures. Systemic symptoms occur in some people with metastatic renal cell carcinoma, and include anorexia, fatigue, fever of unknown origin, weight loss, and malaise. Given that many diseases can cause these symptoms, extensive testing is typically required to diagnose metastatic renal cell carcinoma. Differential diagnoses include leukaemia, arthritis, any other neoplastic disease, locomotor ataxia, Lyme disease [in the case of unexplained malaise, fatigue, and bone pain], and other chronic infections.

Adjuvant therapy in renal cell carcinomaAdjuvent therapy is typically a secondary treatment that is administerted after all visible cancer has either been surgically excised, radiated or otherwise eliminated, in order to prevent any new (metastatic) cancer growths from re-appearing. The re-appearance of cancer typically occurs after micro-cancerous cells remain in the body after the primary cancer has been removed.There is currently no established adjuvant therapy for renal cell carcinoma, although there have been a number of clinical trials exploring the effectiveness of various potential treatments.The use of non-specific cytokines has so far been shown to be ineffective. Unlike most other cancers, renal cell carcinoma is resistant to most cytotoxic and cytostatic agents,which severely limits possible effective adjuvant therapy. Trials of "cancer vaccines", radiotherapy, chemotherapy, immunotherapy, or biologic therapies (i.e. nexavar, sutent) have been met with little success,and currently the standard of care for completely resected high-risk renal cell carcinoma is close observation with no other therapy. There does appear to be some evidence that if there cancer is incompletely resected (positive surgical margins,adrenal involvement,vena caval involvement) radiotherapy reduces the risk of invasive local disease,but data is lacking on that as well.There have also been a number of trials of Autolymphocyte therapy (ALT) which have shown varying degrees of efficacy. ALT is a form of outpatient adoptive immunotherapy utilizing autologous ex vivo activated T-cells accompanied by high dose cimetidine.

SkenarioSeorang laki-laki berumur 40 tahun mengeluh buang air kecil warna merah di sertai panas badan dan tekanan darah tinggi. Pada pemeriksaan arteriografi tampak pembuluh-pembuluh darah yang abnormal pada daerah ginjal.

MakroskopisTampak massa tumor yang menembus sel korteks ginjal. Massa tumor berwarna kuning keemasan.Pada pembelahan massa tumor, tampak daerah perdarahan, nekrosis dan disertai daerah-daerah yang mengeras.

Gambar. Gross ginjal penderita tumor Grawitz Gambar . gros ginjal penderita tumor Grawitz

MikroskopisPada pemeriksaan mikroskopis masih tampak perubahan dari ginjal menjodi massa tumor. Sel-sel tumor tampak cerah atau bergranuler dengan inti yang hiperkromatis. Tampak pula focus-focus perdarahan dan serbukan sel radang limfosit.

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Gambar. Mikroskopis penderita tumor Grawitz Gambar . mikroskopis penderita tumor grawitz

Gambar. Mikroskopis penderita tumor Grawitz

KesimpulanKarsinoma sel renal

Tugas1. Gambar atau buat foto mikroskopis, beri keterangan gambar yang telah dibuat!2. Karsinoma sel renal tersebut di atas berasal dari sel?3. Bedakan antara karsinoma sel renal dan transitional cell carcinoma?

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