Small cell carcinoma

As the spindle morphology, reminiscent of the histologic features of neuroendocrine carcinomas are commonly found in patients with high grade TCC, especially as it evolves over time. At present, there is no exact consensus on diagnostic criteria for declaring a "small cell" or a subset of "neuroendocrine". Some authorities put more emphasis on the histomorphology and others in the expression of neuroendocrine markers. In the MD Anderson Cancer Center, has been our understanding that the morphology is more predictive of clinical outcome of a particular pattern of immunohistochemical markers, and so still prefer the term "small cell carcinoma" and do not require immunohistochemistry "confirmation" to apply the term. As can be deduced from clinical observation, LOH studies of the coexistence of small and TCC cells suggest descent from a common precursor, as has been shown that sarcomatoid carcinoma. In part because of the lack of well defined diagnostic criteria, incidence of small cell carcinoma is very difficult to estimate. To record the MD Anderson (which obviously reflects the referral bias), we find small cell carcinoma has an incidence of 3% (115 of 3833). Other researchers have suggested 0.5 to 0.7%.

One occasionally encounters patients with small cell carcinoma found in the prostate and it is unclear whether this is interpreted as prostate or urothelial origin. In general, there is no urothelial dysplasia in the prostatic urethra (in favor of a urothelial origin), or signs of dysplasia in the prostatic acini (in favor of a prostatic origin.)Indeed, the distinction hardly matters, as the cornerstone of therapy for either primary site is the early exposure to systemic chemotherapy (eg, etoposide and cisplatin) followed by local concentration (which would be radical surgery in our center).

As is well established for other sites, small cell carcinoma of the urothelium is an aggressive cancer characterized by early development of micrometastases, a high incidence of liver disease, and significantly, for the brain as a "sanctuary" site metastasis. The rapid growth within the bladder is also typical. Indeed, it is not uncommon for patients with large tumors that had been "completely excised" only 2 to 3 weeks earlier. This may be the basis of the relatively poor results (detailed below) with the surgical treatment of this variant.

Once a small cell component has been identified, it is important to free up a little rehearsal studios. Even for patients with minimal invasion into the bladder, the possibility of metastasis is important, and therefore all patients should have a computed tomography (CT) scan of abdomen and pelvis in search of lymph node and liver. It is also very important to maintain surveillance for the development of brain metastases at any point in the clinical course of the disease. As more effective systemic therapy is available, the issue of prophylactic cranial irradiation (as is done for some patients with small cell carcinoma of the lung) will probably have to be studied. We have recently seen two patients treated with neoadjuvant chemotherapy and surgery who later succumbed to brain metastases without any evidence of other sites of involvement. It has long been recognized that cystectomy, in this context is associated with a cure rate much lower than obtained with conventional TCC. , existing clinic has been the rule, with a maximum of 76% of patients with small cell tumors metastatic to cystectomy.

In a recent study by MD Anderson Cancer Center in experience found that pathological stage was higher than expected in 56% of patients treated with initial cystectomy. Furthermore, 20% of patients in whom cystectomy is planned initial found that surgically unresectable during surgery, despite an average of 24 days from diagnosis to surgery. In light of this experience, many institutions have reported the addition of multimodal systemic therapy approaches with radiation and / or surgery. In a review of the literature since 1995, Abbas said that the best disease-free survival was observed when cystectomy was followed by adjuvant chemotherapy with a median survival of 21.1 months.

Of the 19 patients studied by Grignon, 12 four of the five survivors were treated with adjuvant chemotherapy after cystectomy. The University of Southern California-Norris Cancer Center reported an improvement in overall survival and relapse free for patients receiving multimodal therapy, most of whom received adjuvant chemotherapy.

However, the median survival in these patients was only 13 months with a 5-year survival of 10%. Initial chemotherapy (ie, neoadjuvant systemic therapy) has also been investigated, and with more promising results. Walther reported that five of the seven patients were alive and free of the disease in more than 36 months after combined modality treatment, and indeed, the five who were alive were treated with preoperative chemotherapy. A retrospective analysis of our own experience10 in 46 patients, who were the two candidates for surgery and had potentially resectable disease, found a statistically improved survival of patients treated with preoperative chemotherapy. Patients treated with initial cystectomy had median cancer-specific survival (CSS) of 23 months, and 36% CSS at 5 years (see Figure 2). By contrast, for those treated with preoperative chemotherapy median CSS has not been reached, and 5 years was 78% of CSS. There were only four cancer-related deaths among 21 patients treated with initial chemotherapy, and none in the subset, a lower stage "for pT2N0M0 or less. It is interesting note that 7 of 25 patients treated with initial cystectomy received adjuvant chemotherapy, however, survival was no better than those treated with cystectomy alone. Given these results, the view that all patients with small cell component should be treated first (and promptly), with three or four cycles of chemotherapy incorporating etoposide and cisplatin. After chemotherapy, we favor surgical consolidation. This is based on observations that most of these patients have generalized dysplasia often show glandular elements after chemotherapy. Therefore, we can infer that a significant fraction of patients do not have a good long-term control in the bladder through the radio-therapy. Limited data from case series suggest that this radiation is indeed the case.

Unfortunately, given the rapid progression and metastatic potential of bladder cancer early small cells, many patients have surgically unresectable or metastatic disease at presentation. The most common sites are lymph nodes, liver, bone, lung and brain. With chemotherapy, the median survival ranges from 7.5 months to 15 months. There are few long-term survivors, but about 20% are alive at 3 years, which is more than 2 years longer than untreated natural history of disease. Despite the disappointing outcome in the long term, small cell urothelial tumors are highly sensitive to systemic chemotherapy, and most patients experience marked objective response is associated with rewarding (albeit temporary) palliation of symptoms

Sarcomatoid Carcinoma

The clinical course of advanced urothelial cancer is generally characterized by a more aggressive biological behavior over time. This is typically accompanied by phenotypic evolution patterns is readily recognized to reflect the more aggressive biological behavior. In this context, recognition of areas with spindled histomorphology is fairly common. When this pattern becomes dominant, cancers are often described as sarcomatoid carcinomas. These cases have long recognized, and many series of cases and fixes are available.

There remain several reports of sporadic cases each year. Almost always, recognizable as Highgrade nonspindled TCC areas are also present, suggesting that this pattern of results of evolution from a common ancestor. Indeed, by immunohistochemistry, the spindle areas are generally positive for keratin, epithelial membrane antigen and vimentin. (When the epithelial markers are lost in a significant fraction of tumor cells, the term carcinosarcoma is adequate, but the literature makes no systematic distinction between these two terms.) Clonality analysis based on loss of heterozygosity (LOH) of microsatellite markers5, 6 provides strong evidence that despite the various components can and should evolve independently once they diverge, they do, in fact, derive from a common precursor.

While it is clear that we can define a subset of sarcomatoid appearance, which is more important to know what such an important biological morphology portends. Although there appear to be particular risk factors or clinically distinctive features at initial presentation, a recurrent theme in the clinical experience with sarcomatoid urothelial cancer is having an aggressive natural history and poor outcome in relation to the classics of TCC . This is confirmed by the registration of MD Anderson in both locally advanced and metastatic settings. In view of this, we believe that the presence of a sarcomatoid component in bladder cancer minimally invasive otherwise be a strong indicator of early cystectomy. We know of no data to recommend a specific therapeutic approach of systemic therapy. Although we have investigated more intensive chemotherapy in this subgroup, who have no sense that this is justified by better results and does not endorse this approach in the absence of a clinical trial. It is very important to realize that not everything that appears spindle is dangerous.

In particular, the post-resection of sarcomatous nodules and inflammatory pseudotumor should not be confused with aggressive cancers that have some resemblance. In addition to the clinical context, it is reported that the presence of necrosis at the interface of muscle and nuclear atypia are the most useful features that distinguish true sarcomas or sarcomatoid carcinomas of these benign conditions. Although extremely rare, true sarcomas without an epithelial component occur in the bladder, and listed in the section of "sarcoma".

Rare cancers of the bladder

Found rare tumors that arise in the bladder fall naturally into two groups: rare histologies and tumor urothelial origin nonurothelial. Our discussion follows these lines, and took the unusual urothelial cancer in the first place, since these are by far the most common and clinically important. Most of what is called transitional cell carcinoma, about 80%, in fact, low histological grade and reflects mainly hyperplastic process. This process typically results in the papillary architecture of the mass thickness of cell proliferation, but not invasive. These injuries, known as "Ta", tend to recur and may progress to dysplasia and invasion in 15 to 20% of patients. However, for the most part, these tumors are more similar to polyps’ true carcinomas. An averlapping but definite pattern can be recognized in the remaining 20% of cases. In this group, high histological grade dysplasia and invasion are hallmarks.

These "non-papillary" cancers are the cause of most mortality, and show a significant range of histomorphology. In the end, they are so different from transitional cell carcinoma (TCC) that called for an alternative taxonomy. Although very rare as "pure" variant, the fact remains that about one third of non-papillary bladder cancers exhibit at least focal areas of unusual histologies discussed below. Therefore, in practice, there is considerable uncertainty about which of the cases showing lesser degrees of histological variant is considered really outside the normal spectrum of TCC, and should be classified as distinct entities.

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 2

This is cotinued from Angiomyolipoma in kidney tumors part 1
Clinical Presentation
The prevalence of this tumor in the general population is low. A series of 8,501 autopsies in patients without TSC showed angiomyolipoma in 2 men and 25 women. A Japanese study of 12 970 men and 4971 women through population-based ultrasonography identified 13 men (0.1%) and 11 women (0.22%) with angiomyolipoma, respectively, as confirmed by CT or tissue diagnosis. Angiomyolipoma can occur sporadically (80%) or in association with TSC (20%). There is a female predominance (4: 1) in the sporadic form, but not in tumors associated with tuberous sclerosis. Tuberous sclerosis is an autosomal dominant with incomplete penetrance. Was first described by Bourneville in 1880 in a child with mental retardation, epilepsy and brain damage characteristics sclera (tubers). Bourneville and Brissaud later in 1900, noted the association of the syndrome with renal tumors. Vogt described the classic triad of seizures, mental retardation and sebaceous adenoma. This triad has been replaced by a constellation of findings that establish the diagnosis.

When patients with tuberous sclerosis are monitored, more than half of them are the development of angiomyolipoma. In a combined analysis of Nelson et al. , Suggest that angiomyolipoma associated with tuberous sclerosis, in contrast to sporadic cases is likely to be found in an earlier age (mean age 30 vs 52 years), with larger tumors (8.9 vs 5.4 cm) frequent multicentricity (97 vs 13%) and bleeding (44 vs 14%).

Steiner et al. found that tuberous sclerosis-associated tumors were more likely to grow (67 vs 21%) and require surgical intervention (50 vs 28%) within 4 years of follow-up. De Luca et al. reported on 51 patients with sporadic angiomyolipoma had immediate surgery, or were under observation. Ninety-two percent of patients observed (mean tumor size of 1.5 cm) showed no radiological angiomyolipoma growth during the 5 year period. Large tumors (> 4 cm) were more likely to grow (46 vs 27%) or require surgical intervention (54 vs 7%) than smaller tumors.

Angiomyolipoma was once considered a rare benign hamartoma. However, with increased use of imaging studies, is now recognized as relatively common injury. Can present with symptoms such as flank pain, a tender palpable mass, and gross hematuria or as an incidental finding in radiological studies. Morbidity secondary to angiomyolipoma are related to retroperitoneal hemorrhage (Wunderlich syndrome) and renal failure secondary to invasion of normal kidney tissue.

The radiologic diagnosis has improved in recent years with the advent of helical CT and cut thin section. Identification of fat in renal injury is the key to the radiological diagnosis. Some of the lesions contain a small amount of fat that can not be detected and may lead to nephrectomy. Fat has been reported in RCC tumors, secondary to the invasion and perirenal fat trap. MRI can help differentiate angiomyolipoma from RCC in selected cases and evaluation during pregnancy.

The incidental diagnosis of angiomyolipoma should also promote a series of analysis for tuberous sclerosis. Historically there was an association between renal cell carcinoma, angiomyolipoma and tuberous sclerosis. Renal cell carcinoma clear cell appear to develop at a higher rate in patients with tuberous sclerosis, in general. Eble et al. He also suggested that some tumors diagnosed historically as renal cell carcinoma in this group of patients may have been epithelioid angiomyolipoma, overestimating the association.

Treatment and Prognosis
Renal angiomyolipomas are usually slow-growing tumors, and its morbidity is secondary to its growth. With the lack of randomized trials, there is considerable controversy regarding the indication for the treatment of asymptomatic angiomyolipoma, and organ preservation with partial nephrectomy is a valid approach in this context. Asymptomatic, benign-looking small can be observed. minimal hematuria usually resolves with hydration and bed rest. In this approach, patients should be advised to avoid contact sports and should be followed closely to assess the growth pattern of the lesion. The main reasons for intervention must be a suspicion of malignancy in a lesion with low-fat, relief of symptoms secondary to spontaneous bleeding and the risk of rupture or other complications. European surveys indicate that 1% of people with tuberous sclerosis is on dialysis, emphasizing the importance of preserving renal function.

Surgical excision or core needle biopsy with immunohistochemical staining should be considered when there is no diagnostic accuracy. Symptomatic angiomyolipoma can be managed by angio-embolization or surgical removal. When clinical risk factors such as childbearing age, large tumor, suspicion or difficulty TSC provided with periodic imaging are present, asymptomatic angiomyolipoma can be managed by observation or intervention, according to individual preferences.

Retrospective data show that patients who have symptoms or bleeding are more likely to have larger tumors. Oesterling et al. proposed a threshold of 4 cm to the risk of symptoms and intervention in asymptomatic patients.

Prospective data of De Luca et al. and others suggest that larger lesions may become symptomatic over time, especially in patients with TSC. These studies have also shown that there is no need to treat all asymptomatic lesions large as it can grow slowly without morbidity. Based on the available evidence suggests an intervention in an asymptomatic patient must be based on the overall evaluation of the clinical situation, including tumor size, tumor growth pattern, the presence of tuberous sclerosis patient comorbidity , renal function, pregnancy plans, and compliance.

Angiographic embolization has become a common modality for surgical management of these tumors. In a review of embolization by Nelson et al., Complications were reported in 10% of cases, including abscess (5%) and pleural effusion (3%). A death from respiratory failure in a patient with preexisting pulmonary disease were reported. recurrent or persistent bleeding symptoms need to repeat embolization and surgery in 14% and 16% of patients, respectively.
 

The advantages of selective embolization including the preservation of renal function, the recovery time of 2-5 days, and the ability to selectively embolize bleeding vessels without major surgery. The effect of embolization to reduce tumor size appears to be resistant to a median follow up of 23 months. Embolization seems to be appropriate for acute bleeding caused by rupture of the tumor, resulting in the stabilization and the elimination of the need for surgical treatment. elective embolization of the tumor may also be appropriate for symptomatic patients with multiple renal tumors in which the preservation of renal function is essential for the prevention of dialysis, and also for patients with limited reserve renal function or poor performance.

Surgery for angiomyolipoma is usually reserved for patients with symptoms unresponsive to conservative, with injury having renal vein or soft tissue invasion, or suspected malignancy in the images. Nelson et al. reported that 19% of patients underwent enucleation or partial nephrectomy, 35% underwent total nephrectomy, 6% underwent embolization, and 40% observation.

Conservative surgery is the preferred modality for the benign nature of tumor. Fazeli-Matin and Novick reported 27 patients with angiomyolipoma that underwent partial nephrectomy, of whom 21 had a contralateral solitary kidney or impaired.

All kidneys were operated after functional surgery, including seven with tumors larger than 12 cm. None of the patients required dialysis after surgery and none had recurrent symptoms angiomyolipoma in a median follow up of 39 months. total nephrectomy should be reserved for patients with a nonfunctioning kidney secondary to angiomyolipoma replacement, with strong evidence of malignancy on radiological or pathological examination, and in situations where other conservative measures have failed.

Angiomyolipoma with thrombus involving the renal vein, inferior vena cava and right atrium has been reported. This may be asymptomatic or may present with fatal thromboembolic consequences. Because of the risks of stroke, the traditional intervention included total nephrectomy with tumor thrombectomy, although there are several reports that angiomyolipoma has been treated with embolization followed by partial nephrectomy to preserve renal function.

Pregnancy can complicate the treatment of young women with angiomyolipoma. While the incidence of bleeding during pregnancy is low, the consequences can be catastrophic, with damage to the mother and fetus.

Hormonal link also suggest that these tumors can grow faster secondary to the changed environment, leading to rupture of the tumor. Optimal diagnostic methods may be limited by pregnancy, and may be difficult to distinguish tumor rupture or ruptured uterus placenta. This gives further credence to the belief that women with known angiomyolipoma larger than 4 cm, intending to conceive should be treated prophylactically to prevent the risk of rupture

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.

Papillary adenoma Tumors of the Kidney

Historically, the adenomas were recognized as lesions less than 3 cm based on the work of Bell. This was later modified identified in 1970 by Murphy and Mostofi who felt that the histological differentiation of Aden carcinomas adenomas was true possible. Renal papillary adenomas are small, discrete, and arise from renal tubular epithelium. In autopsy studies, increasing in frequency with age (7-40%).

Pathology
In the most recent WHO classification, papillary adenomas are less than 5 mm in diameter with a low nuclear grade. They appear as pale yellow, gray, well circumscribed nodules, usually below the renal capsule in the renal cortex. They usually not encapsulated, however, some have thin pseudo capsule. In microscopic examination, which have tubular architecture, papillary or tubular-like papillary renal cell carcinoma. The cells have scant cytoplasm, round to oval nuclei and have high nuclear grade (Fuhrman nuclear grade 3 or 4). Cytogenetics Features include trisomy (chromosome 7 and 17) and the loss of similarity chromosome. The And in this tumor with papillary renal cell carcinoma has led to the view that it may represent a precursor lesion for CRC.

Clinical presentation and treatment
Most of these lesions are discovered accidentally. They tend to occur more frequently in patients with underlying kidney disease related to atherosclerosis, scarring, acquired renal cystic disease secondary to hemodialysis, and other malignancy prevailing conditions of the kidney.

With small tumors incidentally detected increasingly during radiological procedures, the current view is to consider them all as probable early cancer to a clear marker of benignity is discovered. Renal tumors with diameters of 0.5 to 2 cm often behave sluggish, although the biologic behavior is difficult to determine, so that tumors less than 2 cm

They are sometimes called "renal epithelial tumors of uncertain malignant potential, and observed for progression, while Larger tumors may require surgical removal, depending on the clinical scenario. There is no defined role for radiation therapy or chemotherapy in the treatment of renal papillomas.

MOLECULAR DIAGNOSTIC TECHNIQUES IN RENAL NEOPLASMS in Tumors of the Kidney

Tumors of the kidney account for about 3% of adult malignancies, with an incidence of approximately 36 000 new cases/year in the United States. The first classification of renal tumors was proposed by Konig in 1826. This classification was made on the basis of gross morphologic characteristics. Extensive study of renal neoplasms in the last couple of decades has led to a standardized nomenclature by the European and American authorities. 

The 2004 WHO classification, which includes nearly 50 distinct entities, is based on a combination of immunohistochemistry, histology, and clinical and genetic features that are widely accepted and relatively reproducible. Several large series have shown this classification to have prognostic significance and that it is
relevant to diagnosis by fine needle aspiration techniques. It is anticipated this current classification system will be reassessed in 5 years

MOLECULAR DIAGNOSTIC TECHNIQUES IN RENAL NEOPLASMS
 

The application of molecular and cytogenetic techniques has resulted in improved understanding of these tumors. Routine use of these techniques for diagnosis is cumber some, although they serve as useful adjuncts in selected cases. In the forefront among these technologies are comparative genomic hybridization (CGH), fluorescent in situ hybridization (FISH), allelic loss analysis, classical cytogenetics, and karyotyping. The von Hippel-Lindau tumor suppressor gene resides in the short arm of chromosome and is commonly inactivated by gene mutation or promoter hypermethylation in sporadic clear cell RCC.

It is also the causative gene for the von Hippel-Lindau syndrome.Papillary RCC, chromophobic RCC, carcinoma of the collecting ducts of Bellini, metanephric adenomas, and renal oncocytomas have also exhibited characteristic chromosomal anomalies.

Recently, RCC associated with chromosomal translocation involving TFE3 gene on Xp11.2 has been described as a distinct clinicopathological entity. Differentiating the various histological subtypes of renal tumors is crucial, since they differ in their prognosis and therapeutic response to treatment. Definitive diagnosis based on H&E morphology is possible in the majority of cases. In the minority circumstances where distinction becomes difficult, immunohistochemistry and other molecular techniques are being increasingly relied upon to make the distinction.

Renal cell carcinoma marker (RCC Ma) is a monoclonal antibody against the proximal tubular brush border antigen, which is relatively specific for renal neoplasms that originate from the proximal renal tubules including clear and papillary RCC, despite a rather low sensitivity.The anti body is positive in nearly 80% of clear cell and papillary RCC, is variably expressed in chromophobe RCC, and is absent in oncocytomas and CDCs. CD10 is another marker that helps in the differential diagnosis, by being expressed in clear cell and papillary RCC, and absent in chromophobe RCC and oncocytomas.

Vimentin is variably expressed in clear cell and papillary RCC and is absent in chromophobe RCC and oncocytomas. Cytokeratins represent a widely used diagnostic immunohistochemical marker in differentiating renal tumors. Cytokeratin 7 (CK7) is strongly positive in most chromophobe RCC, absent in clear cell RCC, and variably expressed in oncocytomas. Routine metaphase cytogenetics, performed on cultured tumor cells, has been used to identify cytogenetic changes associated with each RCC histological subtypes. Using specific probe sets, FISH can be used to identify those RCC with characteristic chromosomal alterations