Renal Cell Carcinoma
(RCC) accounts for the majority of renal tumors. The proportion of these tumors
in all kidney tumors is approximately 85% to 90%. Also, Renal Cell Carcinoma (RCC)
is a large cancer title which is divided into many subtypes, and the most
common seen subtype is clear cell carcinoma (ccRCC).
Although the most commonly diagnosed renal tumors are medullary renal tumors, approximately 10-15% of the kidney masses are rare renal tumors, which are tumors derived from the cortex. 
Renal cortical tumors are very rare renal tumors with sporadic and familial types and only a few of them have recently been fully identified. Many of these tumors are still not fully understood and are unclassified.
In this section, the most recent and detailed information about these rare renal tumors will be shared with you.
Renal Medullary Carcinomas (RMC) are extremely rare kidney tumors that form less than 0.5% of Renal Cell Carcinomas (RCC). These tumors are predominantly seen in young adults. The mean age of diagnosis is 28 years. They are known to be more common in patients with sickle cell disease, also including the sickle cell trait.
Renal medullary carcinoma is the most aggressive subtype of Renal Cell Carcinoma (RCC) with the most aggressive clinical progression. [2, 3] At the time of diagnosis, approximately 67% of patients had metastasized to distant organs. Besides, macrometastases develop in a very short time even in patients who are thought to have a localized disease. The mean duration of metastasis in patients diagnosed with localized disease is a few weeks.[2, 4]
Despite all necessary interventions and correct treatments, the median survival of patients with Renal Medullary Carcinoma (RMC) is approximately 13 months. In recent case series studies, it is said that its infiltrative and medullary epicenter feature cause such survival time.
radical nephrectomy is mostly used as treatment in these patients, partial
nephrectomy may be preferred in some patients according to tumor size. However,
partial nephrectomy is superior to radical nephrectomy in many patients, in also
early stages, because of the aggressive progression of the tumor.
has such an aggressive progression, the reason for choosing a surgical
treatment is that retrospective studies have shown that radical nephrectomy
alone provides a longer survival time than systemic chemotherapy.
The mean life expectancy of patients treated with radical nephrectomy is 16.4 months, whereas the mean survival of patients treated with systemic chemotherapy alone is approximately 7 months. 
contribution of distant metastatectomy or nephrectomy to the treatment of
metastasis has not yet been established.
The use of palliative radiation therapy in treatment is controversial. Because palliative radiation therapy has been shown to prevent progression in targeted areas. However, it is still unable to prevent progression outside the targeted areas and cannot exactly cure the disease.[5, 6]
Renal Medullary Carcinoma (RMC) is also a tumor resistant to monotherapy with both tyrosine kinase inhibitors (TKIs) and mammalian target of rapamycin (mTOR) inhibitors, which are the targeted anti-angiogenic preparations.[2, 7, 8]
The mainstay treatment currently used in Renal Medullary Carcinoma (RMC) is cytotoxic combination regimens that provide partial or complete response in approximately 29% of patients. 
Although there is no retrospective study comparing the effectiveness and contribution to survival of different chemotherapy preparations, the most recently used case series are combinations of platinum agents, taxanes, gemcitabine, and / or anthracyclines. [2, 3]
In addition to these agents, methotrexate, vinblastine, doxorubicin and cisplatin (MVAC) combination has been shown to be effective against Renal Medullary Carcinoma (RMC).
Another agent that has been widely studied recently, single-agent anti-PD-1 (monoclonal antibodies against programmed death-1), has also been shown to be effective in several case reports. This preparation is also known as immune checkpoint therapy. However, there is still insufficient data to determine the response rate of this agent in Renal Medullary Carcinoma (RMC).[5, 6]
conditions are appropriate, patients who fail to respond to cytotoxic
chemotherapy preparations as initial therapy should be encouraged to enroll in
the clinical trials of new therapeutic approaches.
features of end stage renal diseases (ESRD) are cystic degenerative diseases (acquired
cystic kidney disease [ACKD]) characterized by cysts in the kidney and the higher
incidence of Renal Cell Carcinoma (RCC). Renal cancers are seen in
approximately 4% of native end-stage renal disease patients. The risk of
developing Renal Cell Carcinoma (RCC) is approximately 10 times higher in
end-stage renal disease than in the general population.
Unlike classic Renal Cell Carcinomas (RCC), Renal Cell Carcinomas (RCC) associated with end-stage renal disease (ESRD) are usually multicentric and bilateral, also are often seen in young male adults. Besides, these cancers have a less aggressive progression.[10, 11]
This indolent clinical course of kidney cancer in end-stage renal diseases (ESRD) is thought to be related to the mode of diagnosis and to a specific ACKD-related molecular pathway, which is still unclear and to be studied.
histologic, pathological and morphologic features of kidney tumors in end-stage
renal disease (ESRD) are similar to sporadic Renal Cell Carcinoma (RCC),
predominant subtype is papillary cell carcinoma (pRCC). Most of the tumors
outside of them are clear cell cell carcinoma (ccRCC).
Acquired Cystic Disease-associated Renal Cell Carcinoma (ACD-RCC) is a specific subtype in Renal Cell Carcinoma (RCC) classification and is seen only in people with end-stage renal disease (ESRD).
This usually has an indolent progression and can be diagnosed early in routine checkups of people with end-stage renal disease (ESRD).
3. Papillary Adenoma
These tumors have a papillary or tubular structure as indicated by their name. Papillary adenomas have low nuclear grades and also may be 15mm or smaller in diameter.
All these features of papillary adenomas and their involvement in renal cancer classification have been reported in the 2016 World Health Organization (WHO) Classification.
4. Hereditary Renal Tumors
5% to 8% of Renal Cell Carcinomas (RCC) are hereditary cancers. To date, ten
hereditary Renal Cell Carcinoma (RCC) syndromes and their specific germline
mutations, histology and comorbidities have been described.
kidney cancers are usually associated with a family history. The time of
diagnosis, presence of other lesions and typical respective syndromes of
individuals in the family history are largely similar in each other.
Approximately 70% of hereditary kidney cancers occur before the age of 46. This mean diagnosis time is the lowest decile in all Renal Cell Carcinoma (RCC) tumors. The average age for hereditary Renal Cell Carcinoma (RCC) is 37 years. 
The entities with hereditary kidney cancers are listed below: [12, 14, 16, 17]
Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC)
Non-Polyposis Colorectal Cancer Syndrome
Germline Succinate Dehydrogenase (SDH) Mutation
Medullary Carcinoma (RMC) may also be included in this list because it is
associated with hereditary hemoglobinopathies such as sickle cell anemia.
Treatment of patients with hereditary rare renal tumors usually requires multiple surgical interventions. Nephron-sparing approaches are recommended for almost all hereditary Renal Cell Carcinomas (RCC).[18, 19]
Hereditary Leiomyomatosis and Renal Cell Carcinoma (HLRCC) and Germline
Succinate Dehydrogenase (SDH) Mutation syndromes, the situation is different.
Because the tumors seen in these syndromes have a very aggressive progression,
the recommended treatment is immediate surgical intervention.
In other hereditary cancers such as von Hippel Lindau syndrome, active follow up recommended until the largest solid mass is reaches the diameter of 3cm, to reduce the interventions. 
monitoring in von Hippel Lindau (VHL), Birt-Hogg-Dubé (BDH) and Hereditary
Papillary Renal Carcinoma (HPRCC) syndromes should include monitoring of
changes in growth kinetics, size and location of the tumor which are specific
to each individual, rather than a standardized and fixed follow-up interval.
In regular screenings for both renal and extra-renal masses, it is recommended to follow separately published international guideline for each of these syndromes. A multidisciplinary approach and a coordinated care should be provided to patients with this syndromes whenever appropriate. 
Although not hereditary, somatic fusion translocations of TFE3 and TFEB genes are seen in approximately 15% of Renal Cell Carcinoma (RCC) patients younger than 45 years. This rate may reach up to 20% or even 45% in children and young adults with Renal Cell Carcinoma (RCC). 
Angiomyolipoma (AML) is a benign mesenchymal tumor that may occur sporadically or as part of tuberous sclerosis syndrome.  Angiomyolipoma belongs to a family of tumors called PEComas (perivascular epithelioid cell tumours). This tumor family is characterized by proliferation of perivascular epitheloid cells. Some PEComas (perivascular epithelioid cell tumours) are known to have a very aggressive clinical course and even they may produce distant metastasis. However, classically, angiomyolipoma (AML) are completely benign tumors. [13, 14, 24]
Due to the
adipose tissue in PEComas, ultrasound, computered tomography (CT) or magnetic
resonance imaging (MRI) is very helpful in diagnosis. However, imaging studies
have no diagnostic effect on angiomyolipoma (AML) that are poor in fat tissue.
biopsy is rarely preferred because it is not helpful in diagnosis.
differential diagnoses include smooth muscle cell tumors and epithelial tumors,
and it is difficult to distinguish between angiomyolipoma (AML).
b. Metastasis potential
sclerosis syndrome, angiomyolipoma (AML) may be found in enlarged lymph nodes
(LNs), but this is considered multicentric spread rather than metastatic
rare cases, there may be a non-malignant thrombus extension to the renal vein
or inferior vena cava. This situation is related to angiotrophic-type growth of
Epithelioid angiomyolipoma is a very rare variant and they consist of at least 80% epithelioid cells. [14, 24] These rare renal tumors have the potential for malignancy with an aggressive clinical course with a very large degree of variability between cases. Criteria for predicting clinical behavior in epithelhoid angiomyolipoma are set out in a statement issued by the World Health Organization in 2016.[14, 24]
Because angiomyolipoma (AML) generally have a slow and stable growth rate, and also, they have minimal morbidity. 
d. Clinical manifestations
In some cases, large-sized angiolipomas can cause symptoms such as pain. In addition, the most serious complication associated with these tumors is life-threatening retroperitoneal bleeding or bleeding into the urinary collection system as a result of spontaneous rupture of the tumor. The main cause of this condition is the formation of irregular and aneurysmatic vessels in the angiogenic compartment within the anjiomyolipoma (AML).  Major risk factors for life-threatening bleeding complications include tumor size, grade of angiogenic compartment, and the presence of tuberous sclerosis syndrome. [26, 27]
recommendations for the treatment of Renal Cell Carcinoma (RCC) in international
guidelines should be followed in tumors that cannot be clearly identified as
benign, in diagnostic studies.
In many cases of angiomyolipoma, active surveillance is the most appropriate treatment option. [23, 25, 28]
the patient has detoriating conditions such as persistent pain, episodes of
acute or recurrent bleeding, intervention is necessary.
prophylactic resection of the tumor may be preferred for the tumor that larger
than 4-5cm in diameter, to prevent the spontaneous rupture and severe
hemorrhage. The risk of spontaneous rupture and bleeding increases in proportion to
the size of angiomyolipoma (AML).
sparing surgery is currently the mainstay treatment of angiomyolipoma (AML). However,
for the tumors that are not suitable for surgical treatment and are larger than
4-5 cm in diameter, transarterial selective catheter embolisation can be used as
an emergency approach in cases of acute hemorrhage.
angiomyolipoma (AML) with very large dimensions, selective arterial embolisation
is a highly effective treatment option prior to nephron-sparing surgery in
order to reduce the size of the tumor and to provide better preservation of
renal parenchyma function .
Selective arterial embolisation is effective only to reduce the volume of angiomyolipoma (AML) with devascularization, while its long-term therapeutic effects are very limited. [29, 30, 31]
In some patients, radiofrequency ablation can be used as a treatment option. [25, 26, 32]
In patients diagnosed with tuberous sclerosis, the reduction of bilateral angiomyolipomas (AML) is usually achieved by inhibiting the mTOR pathway with everolimus, which demonstrated in many randomized clinical trials (RCT). [33, 34]
6. Renal Oncocytoma
Oncocytomas are benign tumors representing 3% to 7% of all renal masses. Incidence of these rare kidney tumors can increase up to 18% when considering those have diameter less than 4cm. [13, 35]
Diagnostic values of imaging tests such as computerized tomography (CT) or magnetic resonance imaging (MRI) are extremely low in renal oncocytomas, although histopathology remains as the most valuable method. [13, 35]
standart treatment of renal oncystomas is partial or radical nephrectomy with histopathological
confirmation as in most other rare renal tumors. However, since advanced imaging
techniques are not sufficient to differentiate benign and malignant renal
masses, in the clinical approach, there is increasing interest in renal mass biopsy
(RMB) before surgical intervention.
The majority of oncocytomas progress extremely slowly in size. On average, annual growth rates are below 14 mm. [36, 37]
to preliminary data, active follow-up treatment may also be a safe way to treat
renal oncocytoma in correctly selected patients.
c. Differential diagnosis
be kept in mind that only 66.4% of the tumors that were diagnosed as renal oncocytoma
by renal mass biopsy (RMB) procedure were diagnosed as also renal oncocytoma
after surgery. Therefore, biopsies and the management of advanced
or progressing oncoytomas need to be evaluated within this context.
Tumors outside the 66.4% slice are indicated as follows; [13, 38]
Chromophobe Renal Cell Carcinoma (chRCC) – 12.4%
Hybrid Oncocytic/Chromophobe Tumors – 6.3%
Other Renal Cell Carcinoma Subtypes – 12.5%
Other Benign Lesions – %4.2
7. Cystic Renal Tumors
Cystic renal tumors are also other rare renal tumors that currently classified according to Bosniak classification.
and II cysts are benign cysts that do not even require active surveillance.
cysts, on the other hand, are very likely malignant cysts with only
Bosniak IIF and III classification are still uncertain for clinicians. Computed
tomography (CT), magnetic resonance imaging (MRI) and contrast enhanced
ultrasound (CEUS) are used in the differential diagnosis of benign and
malignant cysts in this category.
Contrast enhanced ultrasound (CEUS) has the highest sensitivity and 97% specificity with 100%, followed by magnetic resonance imaging (MRI) with 71% sensitivity and 91% specificity and after them, computed tomography (CT) with a poor sensitivity of 36% and specificity of 91%. 
to the information obtained from the surgical and radiological cohort studies,
the prevalence of malignancy is 0.51 in Bosniak III cysts and 0.89 in Bosniak IV
In a scientific research in the medical literature, less than 1% of cysts in the Bosniak IIF class showed malignancy in clinical follow-up. It was also reported that 12% of cysts in this class were re-classified as Bosniak III/IV during radiological follow-up and showed a malignancy rate of 85%. 
The most common histological types for Bosniak III cysts can be listed as follows; [41, 42]
Clear Cell Renal Cell Carcinoma (ccRCC) with low malignancy potential and pseudocystic changes
Papillary Renal Cell Carcinoma (pRCC) Type I with very low malignancy potential
Benign Group of Renal Epithelial and Stromal Tumors (REST)
Multilocular Cystic Renal Neoplasm of Low Malignant Potential (MCRNLMP)
Benign Multilocular Cyst
The choice of surgical management in the treatment of 49% of Bosniac III cysts is overtreatment because these tumors have extremely low malignancy potential. Since these patients often have an extremely good prognosis, active surveillance may be the best treatment option in well-selected patients. [40, 43, 44]
Summary of Rare Renal Tumors
Sarcomatoid variants of Renal Cell Carcinoma
Sign of high-grade transformation without being a distinct histological entity.
Surgery.Nivolumab and ipilimumab. Sunitinib, gemcitabine plus doxorubicin is also an option
Multilocular cystic renal neoplasm of low malignant potential
Formerly multilocular cystic RCC
Surgery, nephron-sparing surgery (NSS).
Carcinoma of the collecting ducts of Bellini
Rare, often presenting at an advanced stage (N+ 44% and M1, 33% at diagnosis). The hazard ratio (HR) CSS in comparison with ccRCC is 4.49
High, very aggressive. Median survival30 months
Surgery. Response to targeted therapies is poor
Renal medullary carcinoma
Very rare. Mainly young black men with sickle cell trait.
High, very aggressive, median survival is five months
Surgery. Different chemotherapy regimes, radiosensitive.
Translocation Renal Cell Carcinoma (TRCC) Xp11.2
Rare, mainly younger patients < 40, more common in females. It constitutes with TRCC 6p21 MiT translocation RCCs