Treatment and Prognosis Wilms Tumor ADULT kidney tumors

The prognosis of adults with WT is poor compared with children who have a 85% chance of cure. This success in pediatric WT represents a paradigm shift to multimodal treatment. Historically in the 1980's, most series of adult cases had reported long-term survival of about 25%. Before the report of Arrigo et al. of 27 patients reported to NWTSG 1979-87 with an overall survival at 3 years of 67%, it was believed that this high cure rate can not be achieved in adults. What is Wilms Tumor? you can read in Wilms Tumor ADULT kidney tumors

This series includes six stages I, five stage II, four stage III, eleven stage IV, one patient with stage V-four patients with anaplastic histology. In this series, 26 patients underwent nephrectomy, 25 received chemotherapy and 20 received radiation treatment. This led to recommendations that patients with stage I disease and favorable histology should be treated with surgery followed by 6 months of postoperative chemotherapy with actinomycin-D and vincristine without postoperative radiotherapy, and for stage II, III and IV / FH vincristine, actinomycin-D and doxorubicin for 15 months with 2000 cGy radiation to the tumor bed, from 1200 to 1500 cGy to the lungs, liver 2000 cGy and 3,000 cGy to other sites where appropriate in patients with metastatic at diagnosis. Kattan et al. reported the French experience in 22 adult patients 1973-92.

His series included four stage I, eight stage II, three stage III and seven patients with stage IV. All patients underwent nephrectomy followed by adjuvant treatment modality in only seven patients (radiotherapy and chemotherapy in one in six) and combined modality in 15 patients. The chemotherapeutic agents most often used actinomycin-D, vincristine and doxorubicin. Two of the seven (29%) and 07/15 (47%) patients were free of disease after first-line treatment. salvage chemotherapy had to be given in 13 patients. After a mean of 100 months, 12/22 patients (55%) were alive, including ten who were free of disease (45%). We recommend aggressive treatment, including the three-drug regimen (actinomycin-D + vincristine + doxorubicin), regardless of the stage, and irradiation starting phase II. Terenziani et al. reviewed the Italian experience with 17 adult patients between 1983-2001 who were treated with an Italian protocol and were followed for an average of 131 months.

This included eight patients with stage II, four patients with stage III and five patients with stage IV and included a patient with anaplasia. Sixteen patients undergoing nephrectomy patients, fifteen received chemotherapy (ten with both drugs and five with three drugs) and seven patients received radiation. The 5-year survival free of disease was 45% with an overall survival of 62%. Reinhard et al. reviewed the German experience, which included 30 adult patients in the SIOP 93-01 study. Ten patients (33%) had metastatic disease at presentation. There was a predominance of the upper stage (Stage I, 8 stage II, 7, stage III, 15 patients), histology revealed an intermediate risk in 23 high-risk patients and in 2 patients. Twenty-six patients underwent radical nephrectomy and primary of the other four patients received neoadjuvant chemotherapy before surgery. Nineteen patients received chemotherapy and 11 intermediate risk patients received chemotherapy with high risk according to the protocol. Intermediate-risk chemotherapy includes vincristine, doxorubicin, actinomycin-D ± 18 to 27 weeks, and high-risk scheme etoposide, carboplatin, ifosfamide and doxorubicin for 34 weeks. Four-teen patients received radiotherapy 15 to 35 Gy and three patients received radiation to sites of metastasis. Complete remission was obtained in 24 patients (80%) with event-free survival of 57% and overall survival of 83% with an average observation time of 4 years.

These four modern contemporary series have tended to rest the skepticism with regard to multimodal treatment of PT in adults. Multimodal approach tailored risk similar treatment to pediatric protocols WEIGHT is the current standard of care. In contrast to the pediatric population, where opinion differs as to whether the nephrectomy should be done primarily or after neoadjuvant therapy, there is a consensus view that primary surgery is recommended for adult WT because of the difficulty to establish this rare diagnosis before the operation. Only in cases of primarily inoperable patients the diagnosis is established by biopsy and neoadjuvant therapy in place to try to tumor regression and improve operations. In the absence of bilateral disease, which is rare in adults, primary surgery should include a radical nephrectomy with lymph node sampling.

Despite a complete resection of all viable tumor is the effort desirable surgical can endanger vital organs is not advisable, since the local control can be achieved by adjuvant treatment. Because of the rarity of the disease, there is no established treatment guideline in WT adult. The treatment should preferably be conducted in a tertiary hospital with expertise in this disease. On the basis of the recommendations in the literature, including the series of four cases cited above, current and previous experience NWTSG trial in the pediatric population suggest the following:

1. Based on test data and previous multinational experience NWTSG, radiotherapy can be avoided in patients with stage I and stage II patients with favorable histology, when treated with a combination chemotherapy regimen such as vincristine and actinomycin-D. Radiation should be used in the adjuvant treatment of stage III and IV after surgery. Radiation probably also be given to sites of metastasis.
2. Chemotherapy should be used in the adjuvant treatment at all stages in patients with adequate organ function and functional status. Stage I can be treated with a regimen of two drugs for 18 weeks. Chemotherapy for Stage II must be adapted to the risk based on histology and can vary from two to four drug regimens in 18 to 24 weeks. Chemotherapy for Stage III and IV also has to be adapted to the risk based on histology and requires three or four-drug regimens 18 to 24 weeks. The chemotherapy regimens used should be based on existing pediatric experience. In the recently closed NWTS-5 study, the two-drug regimen was vincristine and actinomycin-D for 18 weeks, the three-drug regimen was vincristine, actinomycin-D and doxorubicin for 24 weeks, and was the four-drug regimen doxorubicin vincristine, cyclophosphamide and etoposide for 24 weeks.
3. Patients with bilateral tumors (stage V) should be given primary chemotherapy for about 6-8 weeks, followed by bilateral partial nephrectomy nephrons in an attempt to preserve normal kidney tissue. Additional chemotherapy and radiotherapy may be needed after surgery. In an earlier series of Byrd et al. , Was observed that adults are at risk of relapse over a longer period of time compared with children. This has not been supported by more recent series. Recurrent disease in children has been successfully treated with radiation, multiagent salvage chemotherapy regimens (etoposide, carboplatin and ifosfamide), 129 or high-dose chemotherapy with stem cell support 130 which leads to long-term remissions (30-60%).

Wilms Tumor ADULT kidney tumors

WT (Wilms Tumor) is the most common renal tumor in children. It affects about 1 in 8,000 children with no significant sex predilection, and about 450 new cases reported each year in the United States. Ninety-eight percent of cases occur in children under 10 years and less than 300 cases of TW adults have been reported in the literature. It tends to occur with almost the same incidence throughout the world, suggesting the absence of an environmental factor. However, the incidence in the United States is highest among African Americans and lowest in Asians, suggesting a possible genetic redisposition.

Its true incidence in adults is difficult to determine since it is included with renal cell carcinoma in the epidemiological reports, and varying diagnostic criteria used in case reports. Currently, most experts use the following criteria to define adult WT (I) primary renal neoplasm, (ii) blastematous primitive spindle or round cell component, (iii) formation of the tubular structure or glomeruloid abortion or embryonic, (iv) any area of the tumor diagnosis of CRC, (v) a graphic confirmation of the histology, and (vi) age> 15 years. Approximately 1.2% of pediatric weights have a family background; however, this has not been reported in adults.

Pathology
In contrast to childhood turbines, which are often multicentric and bilateral, most adult cases are unincentric WEIGHT with multicentric and bilateral disease in 7 and 5% of patients, respectively. Horseshoe kidneys are associated with twice the incidence of WT. The macroscopic and microscopic appearance of WT adult it tends to resemble a pediatric weight. WT gross appearance is variable and reflects the proportion of stromal components and nonstromal. WT generally is pale gray or cream and has a soft, however, the predominant stromal tumors can be white and firm. cyst formation may be important in certain cases.

WEIGHT contains variable proportions of undifferentiated blast cells and differentiated cells of epithelial and stromal lineage. Blast cells are undifferentiated, small, active mitosis, rounded or oval, and densely populated, with little cytoplasm. Can occur in several distinctive growth patterns within individual tumors, including diffuse, nodular, serpentine, and basaloid. WT epithelial component may appear as rosette-shaped primitive tubules and occasional glomeruloid structures.

heterologous epithelial differentiation squamous epithelial components, mucinous, or hair can be detected. The stromal component may have great diversity, but is usually composed of spindle cells with a myxoid background. heterologous elements including skeletal muscle, cartilage, bone, fat and neural tissue may be present. WT histological diversity is a hallmark. Characteristically, it has a triphasic pattern with components called blast, epithelial and stromal. Chemotherapy can alter the morphology by inducing the maturation of the elements blast, epithelial and stromal that leads to a disproportionate reduction of actively proliferating cells compared with the sample prechemotherapy. WEIGHT Metastatic may comprise a single element or a combination of what is present in the primary tumor. WT-1 antigen is usually identified in the blast and epithelial elements, but not in differentiated epithelial and stromal components.

nuclear anaplasia associated with an adverse outcome has been recognized in 5% of pediatric cases and the increase in prevalence with age and in certain populations (eg African Americans). Anaplasia requires the presence of multipolar mitotic figures, marked nuclear enlargement (three times higher than that of anaplastic nuclei) and nuclear hyperchromasia. The prognostic significance is deeper in the diffuse anaplasia compared with focal anaplasia. Large blast cells have also been identified as an adverse prognostic factor.

Nephrogenic rests are abnormally persistent foci of embryonic kidney tissue are capable of becoming WT. The presence of diffuse or multifocal nephrogenic rests is
defined as nephroblastomatosis. There are two variants of nephrogenic rests perilobular called nephrogenic rests (PLNR) and intralobar nephrogenic rests (ILNR). Can be seen in 25-45% of WT were pediatric and adult patients seen in WT as well as in several ectopic sites outside the kidney.

Pediatric weight has been associated with a number of known syndromes and genetic mutations. WAGR (Wilms tumor, aniridia, genitourinary anomalies, mental retardation) and Denys-Drash syndrome (gonadal dysgenesis, nephropathy early onset) syndromes associated with deletion or mutations of the WT1 gene (11p13), a gene critical for development renal and gonadal. The Beckwith-Wiedemann syndrome (hemihypertrophy, macroglossia, omphalocele, and organomegaly) is associated with loss of imprinting of WT2 (11p15). Due to lack of enough cases, genetics and syndromic associations have not been well elucidated in adults.

Clinical Presentation
The most common clinical presentation of an adult WT flank pain, hematuria, abdominal mass or constitutional symptoms. Hypertension, which commonly occurs in pediatric WT has not been commonly reported in WT adult. While Kilton had described the 42% of patients have symptoms for more than a year before diagnosis, which has not been seen in other adult series. The tumors are often quite large on initial presentation. The varicocele may indicate an obstruction of the spermatic vein tumor thrombus secondary to renal vein or inferior vena cava. Acquired von Willebrand disease has been associated with pediatric WT proof is justified in adult patients with clinical bleeding tendency. CT scan of the chest and abdomen should be done before surgery to evaluate the metastasis and extrarenal WT. intravascular extension involving the renal vein and inferior vena cava can be seen. The most common sites of metastasis of WT are lung, lymph nodes and liver. The bone metastasis is rare and a bone scan or skeletal survey is warranted only in the presence of symptoms.

The classification system used by the Children's Oncology Group (COG), Société International d'Oncology Paeditrique / International Society of Pediatric Oncology (SIOP) and the National Wilms Tumor Study Group (NWTSG) has been accepted by most WEIGHT authorities’ adults in the staging of WT. The staging is based on both radiological and surgical pathology. WT's forecast is worse in adults than children, possibly due to a constellation of factors, including frequent advanced stage disease at presentation, increased incidence of nuclear anaplasia, increased incidence of recurrence, poorer tolerance of aggressive treatment, and poorer response to treatment.
to be continued in Treatment and Prognosis Wilms Tumor ADULT kidney tumors

Metanephric neoplasms in kidney tumors

These tumors were first described in 1980 by Pag`es Granier and French literature. Several reports of similar lesions described in a variety of names then arose and was confirmed as a distinct entity. Include metanephric adenoma (predominantly epithelial), metanephric adenofibroma and metanephric stromal tumor (gastrointestinal stromal tumor) which is a pediatric tumor identical to the stromal component of metanephric adenofibroma.

Most clinical and pathological features of metanephric adenoma outlined around mid-1990 in two large series. metanephric adenofibroma was identified then as a biphasic tumor with epithelial and stromal elements and occurs mainly in children and young adults. metanephric tumors as a group are highly cellular benign epithelial tumors, with a close relationship with the PT and conceptualized by some as the benign end, as opposed to a spectrum of tumors that also includes WT and its malignant counterpart.

Pathology

These tumors vary in diameter from 3-15 cm. They are usually single-center, clearly circumscribed without a capsule. The cut surface is gray to yellow with focal hemorrhage, cystic changes, and necroses are uncommon. Histologically composed of well-packed small, round acini. Half of the tumors containing papillary structures that resemble primitive glomeruli. Psammoma bodies are frequently present. No blast elements are present. The stroma may be discrete or edematous. The cells are generally cubic-like monotone, scant cytoplasm and small nuclei, uniform with inconspicuous nucleoli. metanephric adenofibroma is composed of nests of epithelial elements similar to metanephric adenoma included in the bands and sheets of fibroblast-like spindle cells.

The proportion of spindle cells and epithelial components in these tumors varies. metanephric stromal tumors, as its name implies, is very similar to the stromal component of metanephric adenofibroma. The immunohistochemical profile includes positive WT1 and CD56 and epithelial membrane antigen and CK7 negative. The differential diagnosis usually includes papillary renal cell carcinoma (PRCC) and epithelial predominant WT. PRCC is more common in men, tends to be multifocal, with a pseudocapsule, and a different immunohistochemical profile (WT-1 negative, EMA, and CK7 positive.)Epithelial predominant WT is usually seen in younger patients, with a pseudocapsule, and more atypical cells with abundant mitotic activity. Immunohistochemistry, metanephric tumors and WT share resemblance - both are positive for WT-1 antigen and negative for EMA and CK7. However, CD56 is positive in metanephric tumors and negative in WT.

Clinical Presentation

Metanephric adenoma can occur in children and adults, however, is predominant in the fifth and sixth decades of life, with a distinct female preponderance (ratio between women and men 2: 1). metanephric adenofibroma is usually seen in children and young adults aged 5 months to 36 years with a male preponderance. Metanephric stromal tumors are seen mainly in children, if adults rarely reported. These tumors as a group comprise less than 1% of renal cell neoplasms. Most of these cases are discovered incidentally during imaging studies and differential diagnosis of incidental hematuria.

Radiographically, the metanephric adenoma appears as a hypovascular tumor protruding extrarenally.When symptomatic, can cause abdominal pain and hematuria. Erythrocytosis has been reported in patients at presentation.

Treatment and Prognosis

These tumors are benign, with the exception of a few case reports in question. If the metanephric adenoma is suspected on clinical findings, it is important to obtain an intraoperative diagnosis in order to avoid excessive resection. Erythrocytosis associated with these tumors resolved after complete resection. No local recurrence or distant metastasis has been reported metanephric stromal tumors. WT has been reported to have emerged in metanephric adenofibroma and metanephric stromal tumor, indicating a possible common origin of these entities. Renal angiodysplasia associated with these injuries may cause morbidity secondary to vascular complications. Resection without adjuvant chemotherapy is the preferred modality of treatment.

Renal Sarcomas in kidney tumors

Primary renal sarcoma in adults are rare, representing approximately 1% of all primary tumors of the kidney. Sarcomatoid components can be seen in approximately 5% of RCC, including clear cell, papillary, chromophobe, and CDCs. It should not be confused with primary renal sarcomas, as the two entities have entirely different biology, pathology, and clinical features.

Pathology
Any sarcomas that arise in other parts of the body can occur in the kidney, including leiomyosarcoma, osteosarcoma, malignant fibrous histiocytoma (MFH), angiosarcoma, rhabdomyosarcoma, and synovial sarcoma. As in other parts of the body, the diagnosis, and classification are traditionally based on H&E histology and immunohistochemistry. However, molecular studies have been increasingly used in the classification of sarcomas. For example, synovial sarcoma of the kidney, has a characteristic chromosomal translocation t (X;18) between the SYT gene on chromosome 18 and a member of the SSX family gene on chromosome X. Leiomyosarcoma constitutes the majority of primary renal sarcomas, and fewer than 50 cases of renal MFH have been described. Tumor grade, which is recognized as an important prognostic factor in soft tissue sarcomas, is also believed to be prognostic in primary renal sarcomas.

Clinical Presentation
Pain and a palpable mass are the most common presenting complaints. They can spread along tissue spaces and attain a large size before they are symptomatic, similar to retroperitoneal sarcomas. Gross hematuria may be present. Systemic symptoms are less commonly reported. The prevalence of primary renal sarcomas increases with age. Metastasis is generally hematogenous to involve the lungs, liver, and bone. CT and MRI scans are used in the evaluation of these tumors to define the local extent, vascular relations, and involvement of adjacent organs. Preoperative radiographic imaging of the chest should also be performed since this is one of the most common sites of metastatic disease.

Treatment and Prognosis
Complete surgical excision is the mainstay of treatment of soft tissue sarcomas at any location. Adjuvant radiation therapy, although used in locally extensive disease, has not been proven to prevent local recurrence or increase survival. The use of adjuvant chemotherapy in sarcomas other than extremity sarcomas is still experimental. Because of the rarity of this disease in the kidney, the role of either chemotherapy or radiation should be considered investigational. On the basis of case reports, complete surgical extirpation of the organ-confined tumor appears to offer patients the only reasonable chance for prolonged survival. The best outcome is seen with small tumors (<5cm) of low histological grade that are confined to the kidneys. Surgical resection of locally recurrent or oligo-metastatic disease may be beneficial in select patients.

Lymphoma in kidney tumors

Lymphomatous involvement of the kidney is produced in three different clinical scenarios. The most common is the advanced stage lymphoma affects the kidney in second place. Posttrans plantation lymphoproliferative disease (PTLD) may also involve the kidney secondary to iatrogenic immunosuppression. Primary renal lymphoma (PRL) is the least common. The incidence of PTLD arising in kidney transplants has increased over the past two decades due to the increasing frequency of transplants. Secondary renal involvement tends to be bilateral and is seen with a high incidence (37-47%) in advanced disease. If there really PRL remains a controversial issue because of its rarity, about 60 cases have been reported, and only about 30 cases really useful for filling the diagnostic criteria as PRL.

Pathology of Lymphoma in kidney tumors
PRL nephrectomy specimens can have a company uniform, pale appearance with occasional thrombus or renal vein involvement. The most common pattern of involvement is a diffuse involvement with lymphoma cells that permeates from the nephrons, the "interstitial pattern." However, the involvement of discrete nodular masses with intravascular lymphoma has also been described. diffuse large B cell is the most common histologic type, although Burkitt, lymphoblastic lymphoma, and other histologies have been described. The origin of these tumors remains controversial, since the renal parenchyma does not contain lymphoid tissue. PTLD in kidney transplants are related to the degree of immunosuppression and infection with EBV (Epstein Barr Virus) and can present the process as monoclonal or polyclonal.

Clinical Presentation of Lymphoma in kidney tumors
Patients may present with back pain / abdominal pain, fever, cachexia, renal failure or hematuria. Acute renal failure is a common complication. The TAC is the most sensitive diagnostic modality and effective renal lymphoma. In a review of Urban et al., Typical patterns of participation of the masses are simple and multiple invasion of renal disease, retroperitoneal, perirenal disease, and diffuse renal infiltration. PRL patients are usually treated by nephrectomy, because PRL is considered clinically as a renal epithelial tumor. Once the renal involvement of lymphoma is confirmed, a thorough search for extrarenal disease and staging studies such as CT scan and bone marrow biopsy, are warranted to rule out a secondary lymphoma, since it is much more common (30 times more common). Stallone et al. have proposed that the diagnosis of PRL is done only when the following conditions: 1) renal lymphomatous infiltration, 2) the expansion of non-obstructive kidney and 3) without extrarenal location at the time of diagnosis.

Treatment and Prognosis of Lymphoma in kidney tumors
Although there have been reports of modest disease-free survival after nephrectomy for PRL, the prognosis is generally poor, due to the spread of secondary sites. Early detection and systemic combination chemotherapy can reverse kidney failure and improve survival by preventing the spread. Secondary renal lymphomas are usually seen in the context of advanced lymphoma have a poor prognosis. PTLD is treated by reducing immunosuppression, if possible, although recent reports with anti-CD20 monoclonal antibody rituximab have been encouraging and is used as first-line therapy in appropriate settings.

Carcinoid tumors in the kidney

Primary renal carcinoid is extremely rare, well-differentiated neuroendocrine tumor of unknown etiology. The origin of this tumor is still unclear as neuroendocrine cells are not normally present in the renal parenchyma. There have been 50 cases reported in the literature, with a strong partnership with the horseshoe kidney in approximately 20% of cases. The relative risk for a person with horseshoe kidney to develop this tumor is estimated at 82 times the general population. Was first reported by Resnick in 1966 in a patient with carcinoid syndrome, however, most organ-confined tumors do not produce carcinoid syndrome, which resembles carcinoids in other organ systems.

Pathology

Macroscopically, it presents as a solitary well-circumscribed, moderately firm tumor with a lumpy appearance. The color is variable; the appearance is consistent with variable focal hemorrhage and calcification. The histopathologic features appear similar to carcinoid tumors in other organ systems. The cells are uniform in size and arranged in a trabecular pattern. Have small nuclei with "salt and pepper" chromatin and eosinophilic cytoplasm. Immunohistochemical staining is positive for chromogranin, neuron-specific enolase, and keratin. Variable positivity for serotonin, pancreatic polypeptide, prostatic acid phosphatase, and vasoactive intestinal polypeptide have been reported.

Clinical Presentation

Most patients present with an asymptomatic mass, however, can also present with abdominal pain, mass, or hematuria. Alternative source differential diagnosis is indicated when a lesion is found in the kidney, due to the rarity of primary renal carcinoid. carcinoid symptoms are present in less than 10% of patients at presentation.

The median age at diagnosis is 50 years, without sex predilection. The TC is presented as a circumscribed solid mass with occasional calcification or cystic changes. Some authorities have suggested that an octreotide scan can contribute to accurate staging
diagnosis.

Treatment and Prognosis

Because of the rarity of the disease, clinical outcome is difficult to predict. This is also complicated by the fact that a significant proportion of patients with metastatic disease have prolonged survival. Complete excision of localized disease in the kidney seems to have good long-term results, with reports available are limited. Carcinoid tumors arising in horseshoe kidneys tend to have a more indolent course.

Carcinoid crisis secondary to the release of vasoactive substances may occur with the biopsy or surgical resection of the tumor and can be managed with somatostatin. In patients with a solitary metastasis, especially in the liver, it would be appropriate to consider resection of primary tumor with metastasis, due to the lack of effective systemic treatment options. Radiation is effective for short-term relief. The scant information on therapy for metastatic renal carcinoid is available. In patients with carcinoid syndrome, control of symptoms with somatostatin or octreotide analogs as possible.

For people with metastatic disease, systemic treatment options are based on clinical trials in patients with gastrointestinal carcinoid tumors. Interferon produces tumor regression (15%) and biochemical responses in patients with metastatic disease. Combination chemotherapy is of limited value. In a cooperative oncology group of the East (ECOG) trial, 118 patients with metastatic carcinoid tumor were randomized to treatment with streptozotocin in combination with cyclophosphamide or 5-fluorouracil (5-FU). Objective response rates among evaluable patients treated with the combination of 5-FU was 33% and the combination of cyclophosphamide 26%, with substantial toxicity in both regimens.

Angiomyolipoma in kidney tumors part 1

Renal angiomyolipoma is a benign mesenchymal initially described by Grawitz et al. in 1900. Represent approximately 1% of renal tumors surgically removed. That was also described by Bourneville and Brissaud as part of tuberous sclerosis complex (TSC) at the same time. Hartwick et al. reported in 1989 an epithelioid angiomyolipoma with unusual histologic patterns mimicking malignancy after further investigation has revealed malignant characteristics in some cases. Has recently been classified as a variant of angiomyolipoma with malignant potential.

Pathology
Grossly, renal angiomyolipoma are large lesions, the mass of yellow-gray, well demarcated from the kidney, but not truly encapsulated. They are usually solitary, but if present in multiple numbers, the image is of a dominant tumor associated with minor injuries. As they grow, they cause a mass effect rather than infiltrating the surrounding tissue. They consist of a variable proportion of thick-walled blood vessels, poorly organized smooth muscle bundles and mature adipose tissue, and the variable proportion of each component accounts for the appearance of the lesion. Smooth muscle cells are often spindle-shaped epithelioid and occasionally rounded. regional lymph nodes are considered to represent multicentric involvement site of metastasis. Rarely, direct extension of tumor to the inferior vena cava and renal venous system in the absence of distant metastasis has been described.

The higher prevalence of angiomyolipoma in women has increased speculation that there may be a sex enhancement of growth hormone angiomyolipoma. Progesterone and estrogen receptors have been detected in these tumors, together with reports of rapid growth during pregnancy.

The immunohistochemical profile is characterized by co-expression of melanocytic (for example, HMB-45) and smooth muscle (smooth muscle actin, for example) markers. It can also be positive for CD68, neuron specific enolase, S-100, desmin, and hormone receptors, whereas epithelial markers were always negative.

Two genes are known to cause tuberous sclerosis, a gene TSC (TSC1) on chromosome 9q34, encoding hamartin, and TSC2 on chromosome 16p13, which produces tuberin, a protein active GTPase. The biology of these genes has been elucidated extensively in recent years. Angiomyolipoma frequently have a loss of heterozygosity one of the two TSC loci in both sporadic tumors associated with tuberous sclerosis.

Epithelioid angiomyolipoma is a potentially malignant mesenchymal neoplasm closely related to classic angiomyolipoma. There is a higher association (> 50%) with tuberous sclerosis. Patients are usually symptomatic, both sexes are equally affected, and the mean age of onset (38 years) is generally younger compared to classic angiomyolipoma. The lack of fat makes it more difficult radiological diagnosis. About a third of cases of epithelioid angiomyolipoma metastasize to lymph nodes, liver, lungs, or spine.

Microscopically there are layers of epithelioid cells with abundant eosinophilic granular cytoplasm, enlarged vesicular nuclei and prominent nucleoli. Classic angiomyolipoma areas can be found interspersed focal. Tumors with necrosis, increased mitotic activity, nuclear atypia, and infiltration into surrounding tissues should be considered potentially malignant. The immunohistochemical profile positive for melanocytic markers as HMB-45, but not always positive for smooth muscle markers such as actin. Although rare angiomyolipoma, epithelioid should be kept in perspective, when the diagnosis of angiomyolipoma was made.
to be continued to part 2

ONCOCYTOMA in kidney tumors

Attention first oncocytomas as benign kidney tumors after a series of cases reported by Klein and Valensi in 1976. They constitute about 3-5% of renal tumors in most large series. However, the tumor was similar to oncocytoma described above, Zippel et al. The term means oncocyte "Swollen cells" because of numerous cytoplasmic mitochondria. similar tumors may occur in the salivary glands, thyroid, parathyroid, adrenal and sites.

Pathology
Oncocytomas are well circumscribed, unencapsulated tumors with a characteristic central stellate scar, seen in 33%, most commonly in large tumors. The average size is about 5 cm, however, may be as large as 20 cm. The color is classically mahogany-brown, but can be brown to pale yellow. The bleeding may be seen in 20%. They are composed of solid nests and sheets with abundant eosinophilic cytoplasm oncocyte granular, residing in a stro edematous, mucopolysaccharide-rich extracellular evil of the matrix. Believed to be derived from collecting duct intercalated cells. The cores usually do not show pleomorphism, with a uniform dispersion of chromatin, central discrete nucleoli and mitotic activity are rare to absent. Features such as the perirenal fat, and lymphovascular invasion can be seen and seems to confer a worse prognosis.

However, "atypical" as the gross involvement of the renal vein, extensive papillary architecture, foci of clear cell sarcomatoid dedifferentiation, prominent necrosis and frequent or atypical mitosis have a different connotation and are incompatible with a diagnosis oncocytoma.

The most common differential diagnosis oncocytomas and chromophobe RCC are clear cell RCC with eosinophilic cells. The distinction between these tumors by aspiration cytology specimen can be difficult. Hale's colloidal iron, parvalbumin, and vimentin were negative (although luminal focal) compared with diffuse cytoplasmic iron, colloidal can be seen in oncocytomas and mitochondrial antibody was positive in oncocytoma and can help in the differential diagnosis. The electron microscope, characterized by the accounts of numerous mitochondria of normal appearance of cytoplasmic granularity, which leads to the use of the term "mitochondrioma" by some authors. Microvesicles seen in chromophobe RCC oncocytoma are absent.

Oncocytosis is a condition in which the kidneys contain oncocytomatous multifocal nodules with oncocytic changes in the renal tubules and cysts in the surrounding regions of the kidneys. Multifocality and bilaterality can occur in 5-13% of oncocytomas resected. It behaves similarly to solitary tumors. Sometimes an injury can contain both components oncocytomatous and chromophobe RCC, a condition known as "hybrid oncocytic tumor (tumor HOT)." Therefore, it is crucial to examine thoroughly and properly shows a lesion grossly resembles a oncocytoma. The coexistence of chromophobe RCC and oncocytoma with morphological similarities have sparked a debate about whether these two entities represent two ends of the spectrum, with a common origin of collecting duct intercalated cells. Recent molecular evidence suggests that renal oncocytoma and chromophobe RCC share some similarities not only morphological, but also the first cytogenetic abnormalities, including loss of chromosomes Y, 1, and 14

The Birt-Hogg-Dube syndrome is a family where the gene autosomaldominant, FSH has been located on the short arm of chromosome 17. This is characterized by skin papules domed in the facial area, renal tumors (27% of patients), lung cysts and spontaneous pneumothorax. The most common renal tumor is a hybrid of chromophobe RCC and oncocytoma with multiple tumors in the majority. The possibility of this familial syndrome should be entertained in a diagnosis of renal oncocytosis.

Clinical Presentation
Oncocytoma may occur anywhere between the ages of 14-90 years, without gender predilection. Mainly detected as an incidental finding on routine radiographic studies. Occasionally, patients may have hematuria, flank pain or a palpable mass. On CT, the lesion is usually hypodense, well-defined, peripheral location and a central scar. It has a "pattern of spokes of the wheel" on angiography.

Treatment and Prognosis
Current literature supports the benign nature of the disease, curative surgery to be. metachronous lesions were reported as late as 9 years after initial diagnosis. If the clinical data or information confirms preoperative oncocytoma can be safely treated by partial nephrectomy. Therefore, the preoperative diagnosis can prevent overtreatment. However, most patients undergo nephrectomy due to the inability of current diagnostic methods for reliably distinguish renal cell carcinoma, and occasional coexistence of RCC chromophobe and clear cell RCC with oncocytoma .

Renal Medullary Carcinoma in kidney tumors

Renal medullary carcinoma was first described by Davis et al. as a sickle cell nephropathy and termed so because of its predominantly medullary location. Prior to this report, many of these tumors were probably mistakenly classified as CDCs due to their histological resemblance to the latter. In a literature review of renal medullary carcinoma by Dimashkieh et al.,hemoglobinopathy was found in 53 of the 55 cases (50 patients had hemoglobin AS, two patients had hemoglobin SC, and one patient had hemoglobin SS disease).

Pathology
Renal medullary carcinoma is a centrally located tumor with an infiltrative growth pattern similar to that of CDC. It is believed to arise from the epithelium of the distal portion of the collecting duct. The right kidney is involved three times more commonly than the left kidney, and the mean tumor size ranges from 4–12 cm (mean of 7 cm).

Renal medullary carcinomas are widely infiltrative, and have variable areas of hemorrhage and necrosis. Histologically, a variety of growth patterns have been described with reticular growth pattern and compact adenoid cystic morphology being the common features. Most renal medullary carcinomas have areas of poorly differentiated cells with solid sheets of tumor cells. The tumor cells contain vesicular or clear nuclei with prominent nucleoli and amphophilic cytoplasm, which can have a squamoid or rhabdoid quality. The tumor cells are usually high grade and as with CDC, there is often marked desmoplasia and inflammation.

The immunohistochemical profile is similar to CDC but can be helpful in distinguishing renal medullary carcinoma from other poorly differentiated kidney tumors. The clinical scenario is the key to diagnosing this rare neoplasm.

Clinical Presentation
Renal medullary carcinoma is a highly aggressive tumor that occurs almost exclusively in young people (mean age 22 years), predominantly males (male to female ratio 2 : 1) with sickle cell disease or trait. The common presenting symptoms are gross hematuria, abdominal/flank pain, or weight loss. Metastatic disease in the lymph nodes or distant organs such as the brain can also be the initial evidence of the tumor. Of the patients with adequate staging information available from the two largest case series, 18% had stage III disease and 82% had stage IV disease on presentation.

Treatment and Prognosis
Renal medullary carcinomas are now widely regarded as a highly aggressive variant of RCC, with an almost uniformly fatal outcome. The mean survival after surgery has been about 4 months. Strouse et al. have reported that only one of the over 80 reported patients is alive at 2 years. This patient had a small tumor (<2 cm) confined to the kidney at the time of resection. Chemotherapy has been shown to increase survival beyond 4 months in anecdotal reports, but with no reported long-term survivors. In this review of chemotherapy, of the 15 patients assessable for response, there was one complete response, two partial responses, one minor response, one stable disease and ten patients had progressive disease.

The most common chemotherapy regimen used was MVAC. Radiation therapy in an adjuvant or palliative role was disappointing. Immunotherapy in a few patients also had disappointing results. In healthy patients
with systemic disease, treatment plans similar to those for urothelial cancers and CDC, with combination chemotherapy consisting of cisplatin-gemcitabine or the MVAC regimen) appears to be a reasonable choice, but is unsupported by specific data. We are unaware of any collaborative clinical trials addressing this issue.

Carcinoma of the Bellini collecting duct in kidney tumors

CDC is a rare tumor cells derived from renal collecting ducts of Bellini, and has less than 1% renal malignancies. Reported by Mancilla-Jimenez et al. in its report on papillary tumors, the examination renal tissue distant from the tumor to appear, in some cases, atypical hyperplastic changes of collecting tubules.

This raised the possibility that some papillary tumors arose from distal tubular pithelium. Fleming and Lewi ago describe the detailed features of the CDC as pathological entity based on several case reports.

Pathology
This tumor is characterized by a core location, with a size ranging from 2 to 12 cm, the appearance of firm white-gray and irregular infiltrative edge. Grows radially from the renal hilum to invade the renal cortex, renal cap Sule, and the renal sinus. Histologically, an irregular pattern of growth embedded in a desmoplastic tubulopapillary stroma. The tubules are lined with cells with eosinophilic cytoplasm nail scarce. The cells display high-grade nuclei with brisk mitotic activity, and prominent nucleoli. Sometimes sarcomatoid changes or mucin can be seen. Molecular events and cytogenetic changes that contribute are not well characterized, and a different pattern has yet emerged. The immunohistochemical profile is variable, with generally positive for phytoagglutinins and high molecular weight cytokeratin, with coexpression of vimentin and negative for CD10 and villi.


Clinical Presentation
It is a very aggressive tumor, usually presenting at an advanced stage, with gross hematuria, abdominal pain / back pain and a flank mass. At diagnosis, they often have metastatic disease in the lung, liver, lymph nodes, bone, or adrenal gland. It is more common in men (ratio of about 2: 1) with a wide range of age groups (13-83 years with an
average 55 years). Computed tomography (CT), this tumor appears as a central mass arising infiltrating the preservation of the renal contour and minimal contrast enhancement. Patients may have generalized inflammatory symptoms secondary to the release of cytokines of the tumor and the inflammatory reaction associated with the tumor.

Treatment and Prognosis
The diagnosis of CDC is usually done after the operation, and unlike other radiological RCC is difficult and there is a low preoperative suspicion in view of the rarity of the disease. The prognosis is generally very poor with most patients with distant metastases developing rapidly, with a median survival of 22 months.

The role of nephrectomy has been the subject of debate due to frequent metastasis to the presentation. Radical nephrectomy in the context of metastasis CDC appears to be useful only for palliation. Based on the pathological, immunohistochemical and cytogenetic
similarity with urothelial (CTP), compared with conventional carcinomas clear cell RCC, the preferred approach in treatment of metastatic disease with chemotherapy has been in place for immunotherapy.

In the largest series reported Dimopoulos et al. subsequently reported the MD Anderson Cancer Center experience involving 12 patients with CDC treated from 1980-90. Seven of eight patients with metastatic disease were treated with different combinations of chemotherapy with doxorubicin and cisplatin, methotrexate; vinblastine (MVAC) regimen is the most common. Only one patient achieved a minor response lasting 5 months. Six patients were treated with a combination of interleukin-2 and IFN-α with a response in a patient. Peyromaure et al. reported two complete responses with cisplatin and gemcitabine combination chemotherapy, which lasted 9 and 27 months.

Radiotherapy in this series appeared to have minimal benefit for local recurrence. Chao et al. a review noted that some patients with regional nodal disease without distant etastases have long-term disease-free survival with adjuvant therapy.

While the overall benefit of chemotherapy or immunotherapy appears to be minimal, there seems to be a select group of patients who will benefit of these approaches. Cisplatin-Gemcitabine has significant activity with a favorable toxicity profile in urothelial cancers and has caused some significant response in patients with CDC. Thus access to the system to some extent, since the preferred first-line chemotherapy simply because it is less toxic than MVAC regimen, and no other major series of chemotherapy for collecting duct tumors has apparently better results.