Lymphomas In The Kidney

Introduction

Definition and overview

Lymphomas in the kidney can be split into two categories: primary renal lymphomas and secondary renal lymphomas. Primary renal lymphoma is rare and involves the kidneys without any evidence of the disease elsewhere in the body. Secondary renal lymphoma, however, is where the presence of lymphoma is widespread i.e. there are signs of metastasis. Diagnosis can be difficult, though imaging techniques can be used. Following diagnosis, chemotherapy is a commonly used treatment.³

Prevalence and incidence rates

Renal lymphoma is most commonly observed in patients of middle to the advanced age of around 80-85 years. Of all extranodal lymphomas, primary renal lymphomas make up only 0.7%, with the majority being secondary renal lymphomas. Those who are at an increased risk of renal lymphoma include people who have undergone organ transplantation, experienced uncontrolled Epstein-Barr virus proliferation, and those with HIV.²⁴

Types of lymphomas affecting the kidney

Primary renal lymphoma (PRL)

Primary renal lymphoma (PRL) is categorized as non-Hodgkin’s lymphoma where development is within the lymph nodes, where it is isolated in the kidneys with the lack of nodal disease. It is a considerably rare condition as it makes up only 0.7% of all extranodal lymphomas. In PRL, there is malignancy within the kidneys without the involvement of other organs. Whilst the exact characteristics of this condition are yet to be described, there are several ideas about the source of PRL from the renal capsule into the kidney. The most common subtype of PRL is thought to be diffuse large B-cell lymphoma, with it accounting for 56.3% of cases.^1,2

Secondary renal lymphoma

Secondary renal lymphoma is described as the widespread nodal or extranodal lymphoma with renal involvement. The difference between secondary and primary renal lymphoma is that primary renal lymphoma involves only the kidneys in the disease, whereas secondary renal lymphoma is more widespread. Secondary renal lymphoma can cause acute renal failure or altered renal function in patients with the condition. Autopsies following a patient’s death have suggested that secondary renal failure could have an incidence of up to 60%, whilst secondary renal lymphoma is only shown in up to 3% when using imaging.³

Risk factors for kidney lymphomas

Immunodeficiency conditions

Non-Hodgkin lymphoma is more prevalent following organ transplantation. This is often associated with infection following immunosuppression and there are ongoing studies considering the duration of immunosuppression and how immunosuppressive drugs are used. Interestingly, when the immunosuppressive agents are stopped, there has been shown to be a reversal of non-Hodgkin lymphoma risk. This suggests that immunodeficiency and suppression should be considered when looking at lymphomas.⁴

Chronic kidney disease

Thought to be an important factor in lymphoma is renal involvement. Yet, the influence of chronic kidney disease is not fully detailed in lymphoma patients. Chronic kidney disease is categorized as a long-term condition where the kidneys do not function effectively. Often, there are no symptoms until a later stage in the disease. There is a clear association between chronic kidney disease and cancer, yet the relationship between chronic kidney disease and lymphoma is not as well understood.⁵

A recent study carried out by Ubukata et al. aimed to investigate the relationship between chronic kidney disease and lymphoma. They found that of 429 patients with lymphoma, 148 of them were chronic kidney disease patients. The research study confirmed the prevalence of chronic kidney disease in people with lymphoma, describing the prevalence to be 34.5%. The prevalence of chronic kidney disease in people with lymphoma is shown to be higher than that in the general population, indicating a relationship between the two. It is also suggested that lymphoma patients who also have chronic kidney disease could potentially be at higher risk for mortality than patients without kidney disease.⁵

Viral Infections (e.g., epstein-barr virus)

It is thought that viral infections are involved in around 15%-20% of all human cancer cases. There is a known link between Epstein-Barr virus and Burkitt lymphoma. There is also a known association between human T-lymphotropic virus 1 and adult T-cell leukemia/lymphoma. Furthermore, there is the idea that primary effusion lymphoma is associated with Kaposi sarcoma-associated herpes virus. There is a difference in opinion surrounding the idea that hepatitis C is related to non-Hodgkin lymphoma, but there is evidence supporting the link from cohort studies published in the last 20 years.⁷

A viral infection associated with lymphoma is the Epstein-Barr virus. The virus was first discovered following its link to Burkitt lymphoma and is now associated with a range of malignant lymphomas. This discovery was made by Epstein, Barr, and Achong in 1964. There are suggestions that the Epstein-Barr virus could stimulate B-cell growth transforming agent and potentially stimulate lymphomagenesis, which is a process involved in the growth and development of lymphoma. However, this is still poorly understood. Yet, it is thought that cells infected with the Epstein-Barr virus become involved in reactions, potentially during viral colonization of the cell, and genetic mistakes can occur from this process and go on to play a part in the pathogenesis of Epstein-Barr-associated lymphomas.⁶   

Diagnostic procedures for kidney lymphomas

1. Imaging techniques (e.g., CT, MRI, PET)

Secondary renal lymphoma can present either unilaterally or bilaterally and as a single mass or as multiple masses when viewed using a CT scan. CT scans are the gold standard of imaging for diagnosing the presence of kidney lymphomas. Using a CT scan provides a high level of sensitivity when looking at renal lesions, tumor extension, and the spread to additional organs. To identify smaller lesions a contrast might be administrated. Make sure to check with your doctor on what contrast may be suitable for you. On CT scans, lymphomas look like solid masses.^3,8

MRI scans are an additional way of diagnosing the presence of lymphoma. They can highlight both renal and perirenal disease, but the use of MRI in diagnosis is less detailed in research. Using MRI, renal lymphomas appear as T1 hypointense and T2 hypointense relative to the renal cortex of the kidney.⁸

When a patient presents with renal insufficiency, an ultrasound is often carried out. Despite ultrasounds often being used first, CT scans and MRIs are better at diagnosing and detecting lesions such as lymphomas. A contrast-enhanced ultrasound can be good when characterizing lesions and has the ability to tell the difference between solid tumor masses and cysts. Yet, ultrasound is not capable of telling the difference between renal lymphomas and other malignant renal masses.⁸ 

2. Biopsy and histopathological examination

It can be difficult to diagnose kidney lymphomas as they can present subtly. Some masses can impersonate renal cell carcinomas, tumor metastasis, and abscesses. This means that there can be a delay in diagnosis for the patients and increasing risk of a poor outcome. A kidney biopsy can often show extensive destruction of the parenchyma.⁹

Definitive diagnosis relies heavily on histopathological evidence from a renal biopsy. A biopsy can enable the differentiation between secondary kidney involvement in a systematic disease and the rarer primary kidney lymphoma. This would mean that management and treatment for the patients is more specific, improving the outcome.^1,9

When lymphoma is shown on a kidney biopsy, it means that a diagnosis can be made between the kidney-limited form and the systematic lymphoproliferative condition surrounding the kidney. It is important for prognosis and therapy that a prompt diagnosis can be made.⁹

3. Blood tests and tumour markers

Tumor markers are used in disease diagnosis as they are easily measured in blood or urine. They are also minimally invasive for the patients and easy to use. However, there is not yet a perfect marker used in diagnosis. Various substances such as enzymes and hormones can be used as tumor markers and used in disease diagnosis.

For a good tumor marker, it should only be present when malignancy is present, to provide a definitive diagnosis. It should also be measured easily and associated with a stage of the disease. However, such markers are not yet categorized.¹⁰

Wild-type beta-2-microglobulin has a role in building a complex used in antigen presentation and it is found on the surface of all nucleated cells. It is also secreted in blood, synovial fluid, and urine. When serum levels are higher than expected, it suggests that there is an increased level of production, often found in lymphoproliferative diseases such as Hodgkin's disease and non-Hodgkin’s lymphoma.¹⁰

Treatment options for kidney lymphomas

• Chemotherapy

Currently, chemotherapy is the most commonly prescribed treatment for primary kidney lymphoma. Typically, a patient will go through 6 to 8 cycles of a regime on a regular basis. In a study looking at the treatments for primary renal lymphoma, out of 49 cases, chemotherapy was used in 21 cases and the average survival time of these patients was only 15.8 months. However, when patients are treated with both surgery and chemotherapy, the average survival time is higher at 49.4 months. Therefore, this suggests that perhaps chemotherapy used in combination with other treatments could be more effective in increasing survival time.¹¹ 

While primary renal lymphoma is often associated with a poor prognosis, recent studies have shown that early diagnosis and chemotherapy can improve renal function within 2 to 4 weeks of the start of therapy.¹² 

• Radiation therapy

Lymphomas have been found to be very radiosensitive, meaning radiotherapy could be a potential treatment option. Radiotherapy is thought to be the best therapy for the local control of lymphomas. However, this can only be an effective treatment if all lymphoma tissue can be included in the volume to be irradiated in the suggested dose. Therefore, radiation therapy is only used alone in the early stage of non-Hodgkin’s lymphoma. Often, radiation therapy can be used as an option following chemotherapy. Yet, its role in advanced aggressive non-Hodgkin’s lymphoma is still debated.¹³

• Immunotherapy

Immunotherapy is yet again another effective go-to route of treatment in cancer patients. Simply put this is a form of therapy that involves boosting the patient's own immune system in order to fight malignant cells. Immunotherapy drugs, also termed as checkpoint inhibitors, are administered intravenously. Typically chemicals known as cytokines are the first line of therapy for cancers, however, they can cause potential health risks and are hence only used in the advanced stages of the disease. In combination with other treatments, immunotherapy can prove to be extremely effective.

• Stem cell transplantation

In recent years, hematopoietic stem cell transplantation has become a key therapeutic option for hemato-oncological patients. It is a treatment that can be used to treat cancer and other diseases. It involves the donation of stem cells from a donor. This form of treatment is associated with a better outcome for patients, and increasing survival rates, and is currently being used as a tentative treatment for lymphoma.¹⁴

• Surgery

Whilst renal involvement in non-Hodgkin’s lymphoma is fairly common, primary renal lymphoma is a considerably rare disease. The patient’s prognosis is poor, but in some cases when surgery is used in combination with chemotherapy, there have been some cases of long-term survivors. In one study, 6 months after surgery, there were still signs of bone marrow infiltration, so chemotherapy was then prescribed. In this case, 67 months after surgery and 36 months after chemotherapy, there were no signs of disease.

Primary renal lymphoma is so rare, that there is limited information available on the combination of chemotherapy, radiation therapy, and surgery. Yet, it has been found that those with lymphomatous who had their masses removed through surgery, showed a longer disease-free period and survival.¹⁵

Management and supportive care

• Palliative care

Such care is widely used and involves multiple disciplines to help support clinicians to benefit patients in the best way possible. It aims to meet the needs of those with the disease as well as their families. Typically, palliative care takes into account the physical and psychological symptoms of the disease.¹⁶ 

• Symptom management

Symptoms reported by those with primary renal lymphoma include fever, night sweats, nausea, weight loss, vomiting, proteinuria, and hydronephrosis. To better improve the quality of life for patients, treatment can aim to minimize the effects of these symptoms.¹⁷

• Psychological support

A factor that should be more routinely considered in prognosis and treatment is the mental state of patients, as it has been found that stress while dealing with cancer and suppressed emotions correlates with an unfavorable prognosis. It is thought that stress can decrease survival and contribute to poor quality of life. 

A study found that there is a high number of patients with renal cancer who suffer from increased psychological stress, highlighting the importance of good psychological support. Psychological help can aid a patient in coping with the disease and reduce psychological symptoms. There is the general idea that screening for distress will benefit the patients and improve the quality of care.¹⁸

• Follow-up and monitoring

Following treatment, patients are scheduled follow-up appointments to check for relapse. From this information, progression-free survival can be determined.¹⁹

Prognosis and survival rates

• Factors influencing prognosis

In terms of prognosis, advanced age was the key risk factor for overall survival. Those aged over 60 were at a three times higher risk of dying when compared to younger patients. However, this finding was contrasted by results from a different study where it was found that younger age was a poor prognosis factor. The use of rituximab has also been found to improve overall survival in those with aggressive lymphoma. However, its role in other forms of lymphoma is yet to be determined.²⁰

• Survival rates for different stages

Whilst there is no definitive answer as to how long a patient will survive after diagnosis, estimates can be made based on the stage of kidney cancer. 

Stage one: it is expected that more than 85% of people will live for 5 or more years

Stage two: it is expected that more than 75% of people will live for 5 or more years 

Stage three: it is expected that around 75% of people will live for 5 or more years

Stage four: it is expected that more than 10% of people will live for 5 or more years 

• Long-term outcomes and recurrence

Currently, the prognosis of primary renal lymphoma is largely undocumented. The one-year death rate of primary renal lymphoma can be up to 75%. Median survival time is from 8 months to 3 years. Additionally, 5-year survival is at 40% to 50%.¹¹

Prevention and lifestyle factors

• Maintaining a healthy immune system

From laboratory studies, it has been shown that certain bioactive nutrients are effective in protecting the body from various diseases. Whilst it is well known that smoking and genetics play a role in a person’s immune system, so does diet. There is a considerable amount of evidence supporting the idea that dietary nutrients play a role in the inflammatory response and pro-tumorigenic responses in cells of the immune system.²²

The immune system is vital in protecting the body from neoplastic cells and bioactive agents. For example, tryptophan is an amino acid, needed by the body in a very small amount to maintain healthy nutrition. It has a role in neurotransmission, modulation, and immune responses. It is knowingly associated with the innate and adaptive immune response and is found in foods such as sunflower seeds, peanuts, and chicken.²²

Furthermore, Vitamin C can act as a pro-oxidant or antioxidant depending on whether there are catalytic metals. When patients with cancer were given high doses of Vitamin C alongside normal treatment, there was a significant decrease in pro-inflammatory cytokines observed. Vitamin C can be found in citrus fruits, broccoli, and bell peppers.²²  

Screening and early detection

Screening for early stages of a disease can be done before a patient has any symptoms. Screening is often offered to those with a high risk of developing kidney cancer. For example, if it runs in the family. 

Summary

Kidney lymphomas fall into two main categories: Primary Renal Lymphoma (PRL), a rare form that solely affects the kidneys, and the more prevalent Secondary Renal Lymphoma, which has a broader reach in the body. Typically found in older individuals around the ages of 80-85, risk factors encompass organ transplants and specific viral infections, notably the Epstein-Barr virus. Diagnosis primarily employs imaging techniques like CT and MRI scans, but biopsies and blood tests play an essential supplementary role. The cornerstone of treatment is chemotherapy, with potential supplementary treatments like radiation, immunotherapy, and surgery.

Comprehensive patient care involves both palliative and psychological support. The prognosis varies, with factors such as age, treatment type, and disease stage playing significant roles. Emphasizing the importance of immune health, maintaining a robust immune system via a nutrient-rich diet is vital for prevention. Regular post-treatment check-ups are pivotal, and early detection through screening is beneficial, especially for high-risk demographics.