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Prognoses and treatments are different for HL and between all the different forms of NHL, and also depend on the grade of tumour, referring to how quickly a cancer replicates. Paradoxically, high-grade lymphomas are more readily treated and have better prognoses: Burkitt lymphoma, for example, is a high-grade tumour known to double within days, and is highly responsive to treatment. Lymphomas may be curable if detected in early stages with modern treatment.
After a diagnosis and before treatment, a cancer is staged. This refers to determining if the cancer has spread, and if so, whether locally or to distant sites. Staging is reported as a grade between I (confined) and IV (spread). Staging is carried out because the stage of a cancer impacts its prognosis and treatment.
The Ann Arbor staging system is routinely used for staging of both HL and NHL. In this staging system, I represents a localized disease contained within a lymph node, II represents the presence of lymphoma in two or more lymph nodes, III represents spread of the lymphoma to both sides of the diaphragm, and IV indicates tissue outside a lymph node.
CT scan or PET scan imaging modalities are used to stage a cancer.
Age and poor performance status are established poor prognostic factors, as well.
Hodgkin's lymphoma must be distinguished from non-cancerous causes of lymph node swelling (such as various infections) and from other types of cancer. Definitive diagnosis is by lymph node biopsy (usually excisional biopsy with microscopic examination). Blood tests are also performed to assess function of major organs and to assess safety for chemotherapy. Positron emission tomography (PET) is used to detect small deposits that do not show on CT scanning. PET scans are also useful in functional imaging (by using a radiolabeled glucose to image tissues of high metabolism). In some cases a Gallium scan may be used instead of a PET scan.
Diagnosis usually occurs at an early stage of disease progression.
Treatment of Hodgkin's disease has been improving over the past few decades. Recent trials that have made use of new types of chemotherapy have indicated higher survival rates than have previously been seen. In one recent European trial, the 5-year survival rate for those patients with a favorable prognosis (FFP) was 98%, while that for patients with worse outlooks was at least 85%.
In 1998, an international effort identified seven prognostic factors that accurately predict the success rate of conventional treatment in patients with locally extensive or advanced stage Hodgkin's lymphoma. Freedom from progression (FFP) at 5 years was directly related to the number of factors present in a patient. The 5-year FFP for patients with zero factors is 84%. Each additional factor lowers the 5-year FFP rate by 7%, such that the 5-year FFP for a patient with 5 or more factors is 42%.
The adverse prognostic factors identified in the international study are:
- Age ≥ 45 years
- Stage IV disease
- Hemoglobin < 10.5 g/dl
- Lymphocyte count < 600/µl or < 8%
- Male
- Albumin < 4.0 g/dl
- White blood count ≥ 15,000/µl
Other studies have reported the following to be the most important adverse prognostic factors: mixed-cellularity or lymphocyte-depleted histologies, male sex, large number of involved nodal sites, advanced stage, age of 40 years or more, the presence of B symptoms, high erythrocyte sedimentation rate, and bulky disease (widening of the mediastinum by more than one third, or the presence of a nodal mass measuring more than 10 cm in any dimension.)
More recently, use of positron emission tomography (PET) early after commencing chemotherapy has demonstrated to have powerful prognostic ability. This enables assessment of an individual's response to chemotherapy as the PET activity switches off rapidly in patients who are responding. In this study, after two cycles of ABVD chemotherapy, 83% of patients were free of disease at 3 years if they had a negative PET versus only 28% in those with positive PET scans. This prognostic power exceeds conventional factors discussed above. Several trials are underway to see if PET-based risk adapted response can be used to improve patient outcomes by changing chemotherapy early in patients who are not responding.
Tumors generally located in the peripheral lymph nodes which can be detected via PET scan and CT scan.
The prognosis varies according with the type of ALCL. During treatment, relapses may occur but these typically remain sensitive to chemotherapy.
Those with ALK positivity have better prognosis than ALK negative ALCL. It has been suggested that ALK-negative anaplastic large-cell lymphomas derive from other T-cell lymphomas that are morphologic mimics of ALCL in a final common pathway of disease progression. Whereas ALK-positive ALCLs are molecularly characterized and can be readily diagnosed, specific immunophenotypic or genetic features to define ALK-negative ALCL are missing and their distinction from other T-cell non-Hodgkin lymphomas (T-NHLs) remains controversial, although promising diagnostic tools for their recognition have been developed and might be helpful to drive appropriate therapeutic protocols.
Systemic ALK+ ALCL 5-year survival: 70–80%.
Systemic ALK- ALCL 5-year survival: 15–45%.
Primary Cutaneous ALCL: Prognosis is good if there is not extensive involvement regardless of whether or not ALK is positive with an approximately 90% 5-year survival rate.
Breast implant-associated ALCL has an excellent prognosis when the lymphoma is confined to the fluid or to the capsule surrounding the breast implant. This tumor can be recurrent and grow as a mass around the implant capsule or can extend to regional lymph nodes if not properly treated.
Diagnosis generally requires stained slides of a surgically removed part of a lymph node. Other methods are also commonly used, including cytogenetics and fluorescence in situ hybridization (FISH). Polymerase chain reaction (PCR) and CER3 clonotypic primers are additional methods, but are less often used.
The immunophenotype profile consists of CD5+ (in about 80%), CD10-/+, and it is usually CD5+ and CD10-. CD20+, CD23-/+ (though plus in rare cases). Generally, cyclin D1 is expressed but it may not be required. The workup for Mantle cell lymphoma is similar to the workup for many indolent lymphomas and certain aggressive lymphomas.
Mantle cell lymphoma is a systemic disease with frequent involvement of the bone marrow and gastrointestinal tract (generally showing polyposis in the lining). There is also a not-uncommon leukemic phase, marked by presence in the blood. For this reason, both the peripheral blood and bone marrow are evaluated for the presence of malignant cells. Chest, abdominal, and pelvic CT scans are routinely performed.
Since mantle cell lymphoma may present a lymphomatous polyposis coli and colon involvement is common, colonoscopy is now considered a routine part of the evaluation. Upper endoscopy and neck CT scan may be helpful in selected cases. In some patients with the blastic variant, lumbar puncture is done to evaluate the spinal fluid for involvement.
CT scan - Computerized tomography scan yields images of part or whole body. Gives a large number of slices on X-ray image.
PET scan - Generally of the whole body, shows a three-dimensional image of where previously injected radioactive glucose is metabolized at a rapid rate. Faster-than-average metabolism indicates that cancer is likely present. Metabolism of radioactive glucose may give a false positive, particularly if the patient has exercised before the test.
PET scans are much more effective when the information from them is integrated with that from a CT scan to show more precisely where the cancer activity is located and to more accurately measure the size of tumors.
Biopsy of affected lymph nodes or organs confirms the diagnosis, although a needle aspiration of an affected lymph node can increase suspicion of the disease. X-rays, ultrasound and bone marrow biopsy reveal other locations of the cancer. There are now a range of blood tests that can be utilised to aid in the diagnosis of lymphoma. Flow cytometry detects antibodies linked to tumour cell surface antigens in fluid samples or cell suspensions. Polymerase chain reaction (PCR) for antigen receptor rearrangements (PARR) identifies circulating tumour cells based on unique genetic sequences. The canine Lymphoma Blood Test (cLBT) measures multiple circulating biomarkers and utilises a complex algorithm to diagnose lymphoma. This test utilises the acute phase proteins (C-Reactive Protein and Haptoglobin). In combination with basic clinical symptoms, it gives in differential diagnosis the sensitivity 83.5% and specificity 77%. The TK canine cancer panel is an indicator of general neoplastic disease. The stage of the disease is important to treatment and prognosis. Certain blood tests have also been shown to be prognostic.
The stage of the disease is important to treatment and prognosis.
- Stage I - only one lymph node or lymphoid tissue in one organ involved.
- Stage II - lymph nodes in only one area of the body involved.
- Stage III - generalized lymph node involvement.
- Stage IV - any of the above with liver or spleen involvement.
- Stage V - any of the above with blood or bone marrow involvement.
Each stage is divided into either "substage a", those without systemic symptoms; or "substage b", those with systemic symptoms such as fever, loss of appetite, weight loss, and fatigue.
As the appearance of the hallmark cells, pattern of growth (nesting within lymph nodes) and positivity for EMA may mimic metastatic carcinoma, it is important to include markers for cytokeratin in any diagnostic panel (these will be negative in the case of anaplastic lymphoma). Other mimics include CD30 positive B-cell lymphomas with anaplastic cells (including Hodgkin lymphomas). These are identified by their positivity for markers of B-cell lineage and frequent presence of markers of EBV. Primary cutaneous T-cell lymphomas may also be positive for CD30; these are excluded by their anatomic distribution. ALK positivity may also be seen in some large-cell B-cell lymphomas and occasionally in rhabdomyosarcomas.
The overall 5-year survival rate for MCL is generally 50% (advanced stage MCL) to 70% (for limited-stage MCL).
Prognosis for individuals with MCL is problematic and indexes do not work as well due to patients presenting with advanced stage disease. Staging is used but is not very informative, since the malignant B-cells can travel freely though the lymphatic system and therefore most patients are at stage III or IV at diagnosis. Prognosis is not strongly affected by staging in MCL and the concept of metastasis does not really apply.
The Mantle Cell Lymphoma International Prognostic Index (MIPI) was derived from a data set of 455 advanced stage MCL patients treated in series of clinical trials in Germany/Europe. Of the evaluable population, approximately 18% were treated with high-dose therapy and stem cell transplantation in first remission. The MIPI is able to classify patients into three risk groups: low risk (median survival not reached after median 32 months follow-up and 5-year OS rate of 60%), intermediate risk (median survival 51 months) and high risk (median survival 29 months). In addition to the 4 independent prognostic factors included in the model, the cell proliferation index (Ki-67) was also shown to have additional prognostic relevance. When the Ki67 is available, a biologic MIPI can be calculated.
MCL is one of the few NHLs that can cross the boundary into the brain, yet it can be treated in that event.
There are a number of prognostic indicators that have been studied. There is not universal agreement on their importance or usefulness in prognosis.
Ki-67 is an indicator of how fast cells mature and is expressed in a range from about 10% to 90%. The lower the percentage, the lower the speed of maturity, and the more indolent the disease. Katzenberger et al. Blood 2006;107:3407 graphs survival versus time for subsets of patients with varying Ki-67 indices. He shows median survival times of about one year for 61-90% Ki-67 and nearly 4 years for 5-20% Ki-67 index.
MCL cell types can aid in prognosis in a subjective way. Blastic is a larger cell type. Diffuse is spread through the node. Nodular are small groups of collected cells spread through the node. Diffuse and nodular are similar in behavior. Blastic is faster growing and it is harder to get long remissions. Some thought is that given a long time, some non-blastic MCL transforms to blastic. Although survival of most blastic patients is shorter, some data shows that 25% of blastic MCL patients survive to 5 years. That is longer than diffuse type and almost as long as nodular (almost 7 yrs).
Beta-2 microglobulin is another risk factor in MCL used primarily for transplant patients. Values less than 3 have yielded 95% overall survival to 6 yrs for auto SCT where over 3 yields a median of 44 most overall survival for auto SCT (Khouri 03). This is not yet fully validated.
Testing for high levels of LDH in NHL patients is useful because LDH is released when body tissues break down for "any" reason. While it cannot be used as a sole means of diagnosing NHL, it is a surrogate for tracking tumor burden in those diagnosed by other means. The normal range is approximately 100-190.
Nevertheless, the Working Formulation and the NHL category continue to be used by many. To this day, lymphoma statistics are compiled as Hodgkin's versus non-Hodgkin lymphomas by major cancer agencies, including the US National Cancer Institute in its SEER program, the Canadian Cancer Society and the IARC.
The most common chemotherapy used for non-Hodgkin lymphoma is R-CHOP.
Lymphoma is common in ferrets and is the most common cancer in young ferrets. There is some evidence that a retrovirus may play a role in the development of lymphoma like in cats. The most commonly affected tissues are the lymph nodes, spleen, liver, intestine, mediastinum, bone marrow, lung, and kidney.
In young ferrets, the disease progresses rapidly. The most common symptom is difficulty breathing caused by enlargement of the thymus. Other symptoms include loss of appetite, weight loss, weakness, depression, and coughing. It can also masquerade as a chronic disease such as an upper respiratory infection or gastrointestinal disease. In older ferrets, lymphoma is usually chronic and can exhibit no symptoms for years. Symptoms seen are the same as in young ferrets, plus splenomegaly, abdominal masses, and peripheral lymph node enlargement.
Diagnosis is through biopsy and x-rays. There may also be an increased lymphocyte count. Treatment includes surgery for solitary tumors, splenectomy (when the spleen is very large), and chemotherapy. The most common protocol uses prednisone, vincristine, and cyclophosphamide. Doxorubicin is used in some cases. Chemotherapy in relatively healthy ferrets is tolerated very well, but possible side effects include loss of appetite, depression, weakness, vomiting, and loss of whiskers. The white blood cell count must be monitored. Prednisone used alone can work very well for weeks to months, but it may cause resistance to other chemotherapy agents. Alternative treatments include vitamin C and Pau d'Arco (a bark extract).
The prognosis for lymphoma in ferrets depends on their health and the location of the cancer. Lymphoma in the mediastinum, spleen, skin, and peripheral lymph nodes has the best prognosis, while lymphoma in the intestine, liver, abdominal lymph nodes, and bone marrow has the worst.
Treatment with conventional immunochemotherapy is usually indicated; in younger patients, allogeneic bone marrow transplantation may be curative.
Castleman disease is diagnosed when a lymph node biopsy reveals regression of germinal centers, abnormal vascularity, and a range of hyaline vascular changes and/or polytypic plasma cell proliferation. These features can also be seen in other disorders involving excessive cytokine release, so they must be excluded before a Castleman disease diagnosis should be made.
It is essential for the biopsy sample to be tested for HHV-8 with latent associated nuclear antigen (LANA) by immunohistochemistry or PCR for HHV-8 in the blood.
In the unicentric form of the disease, surgical resection is often curative, and the prognosis is excellent.
Historically, hematological malignancies have been most commonly divided by whether the malignancy is mainly located in the blood (leukemia) or in lymph nodes (lymphomas).
However, the influential WHO Classification (published in 2001) placed a greater emphasis on cell lineage.
Relative proportions of hematological malignancies in the United States
For the analysis of a suspected "hematological malignancy", a complete blood count and blood film are essential, as malignant cells can show in characteristic ways on light microscopy. When there is lymphadenopathy, a biopsy from a lymph node is generally undertaken surgically. In general, a bone marrow biopsy is part of the "work up" for the analysis of these diseases. All specimens are examined microscopically to determine the nature of the malignancy. A number of these diseases can now be classified by cytogenetics (AML, CML) or immunophenotyping (lymphoma, myeloma, CLL) of the malignant cells.
The prognosis is generally poor. The "RS score" (Richter syndrome score), which is an estimate of the patient's prognosis, is based on the patient's performance status, LDH, platelet count, the size of the lymphoma tumors, and the number of prior therapies already received. Overall, the median survival is between five and eight months. Untreated, RS is invariably fatal.
The Hodgkin's lymphoma variant of Richter's carries a better prognosis than the predominant diffuse large B-cell lymphoma type, but a worse prognosis than a "de novo" case of Hodgkin's.
There are numerous kinds of lymphomas involving B cells. The most commonly used classification system is the WHO classification, a convergence of more than one, older classification systems.
Additionally, some researchers separate out lymphomas that appear to result from other immune system disorders, such as AIDS-related lymphoma.
Classic Hodgkin's lymphoma and nodular lymphocyte predominant Hodgkin's lymphoma are now considered forms of B-cell lymphoma.
Current medical treatments result in survival of some longer than 10 years; in part this is because better diagnostic testing means early diagnosis and treatments. Older diagnosis and treatments resulted in published reports of median survival of approximately 5 years from time of diagnosis. Currently, median survival is 6.5 years. In rare instances, WM progresses to multiple myeloma.
The International Prognostic Scoring System for Waldenström’s Macroglobulinemia (IPSSWM) is a predictive model to characterise long-term outcomes. According to the model, factors predicting reduced survival are:
- Age > 65 years
- Hemoglobin ≤ 11.5 g/dL
- Platelet count ≤ 100×10/L
- B2-microglobulin > 3 mg/L
- Serum monoclonal protein concentration > 70 g/L
The risk categories are:
- Low: ≤ 1 adverse variable except age
- Intermediate: 2 adverse characteristics or age > 65 years
- High: > 2 adverse characteristics
Five-year survival rates for these categories are 87%, 68% and 36%, respectively. The corresponding median survival rates are 12, 8, and 3.5 years.
The IPSSWM has been shown to be reliable. It is also applicable to patients on a rituximab-based treatment regimen. An additional predictive factor is elevated serum lactate dehydrogenase (LDH).
In the absence of symptoms, many clinicians will recommend simply monitoring the patient; Waldenström himself stated "let well do" for such patients. These asymptomatic cases are now classified as two successively more pre-malignant phases, IgM monoclonal gammopathy of undetermined significance (i.e. IgM MGUS) and smoldering Waldenström's macroglobulinemia.
But on occasion, the disease can be fatal, as it was to the French president Georges Pompidou, who died in office in 1974. Mohammad Reza Shah Pahlavi, the Shah of Iran, also suffered from Waldenström's macroglobulinemia, which resulted in his ill-fated trip to the United States for therapy in 1979, leading to the Iran hostage crisis.
Diagnosis is usually based on repeated complete blood counts and a bone marrow examination following observations of the symptoms. Sometimes, blood tests may not show that a person has leukemia, especially in the early stages of the disease or during remission. A lymph node biopsy can be performed to diagnose certain types of leukemia in certain situations.
Following diagnosis, blood chemistry tests can be used to determine the degree of liver and kidney damage or the effects of chemotherapy on the patient. When concerns arise about other damage due to leukemia, doctors may use an X-ray, MRI, or ultrasound. These can potentially show leukemia's effects on such body parts as bones (X-ray), the brain (MRI), or the kidneys, spleen, and liver (ultrasound). CT scans can be used to check lymph nodes in the chest, though this is uncommon.
Despite the use of these methods to diagnose whether or not a patient has leukemia, many people have not been diagnosed because many of the symptoms are vague, non-specific, and can refer to other diseases. For this reason, the American Cancer Society estimates that at least one-fifth of the people with leukemia have not yet been diagnosed.