Diagnosis usually occurs at an early stage of disease progression.

The two types of lymphoma research are clinical or translational research and basic research. Clinical/translational research focuses on studying the disease in a defined and generally immediately patient-applicable way, such as testing a new drug in patients. Studies may focus on effective means of treatment, better ways of treating the disease, improving the quality of life for patients, or appropriate care in remission or after cures. Hundreds of clinical trials are being planned or conducted at any given time.

Basic science research studies the disease process at a distance, such as seeing whether a suspected carcinogen can cause healthy cells to turn into lymphoma cells in the laboratory or how the DNA changes inside lymphoma cells as the disease progresses. The results from basic research studies are generally less immediately useful to patients with the disease, but can improve scientists' understanding of lymphoma and form the foundation for future, more effective treatments.

Tumors generally located in the peripheral lymph nodes which can be detected via PET scan and CT scan.

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.

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.

Treatment with dose-adjusted EPOCH with rituximab has shown promising initial results in a small series of patients (n=17), with a 100% response rate, and 100% overall survival and progression-free survival at 28 months (median follow-up).

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.

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.

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.

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 most typical symptom at the time of diagnosis is a mass that is rapidly enlarging and located in a part of the body with multiple lymph nodes.

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.

Treatment with conventional immunochemotherapy is usually indicated; in younger patients, allogeneic bone marrow transplantation may be curative.

Pralatrexate is one compound currently under investigations for the treatment of PTCL.

Of all cancers involving the same class of blood cell, 2.3% of cases are Burkitt lymphoma. Epstein-Barr virus infection is strongly correlated with this cancer.

The definitive diagnosis is arrived at from tissue, i.e. a biopsy, by a pathologist.

MRI or contrast enhanced CT classically shows multiple ring-enhancing lesions in the deep white matter. The major differential diagnosis (based on imaging) is cerebral toxoplasmosis, which is also prevalent in AIDS patients and also presents with a ring-enhanced lesion, although toxoplasmosis generally presents with more lesions and the contrast enhancement is typically more pronounced. Imaging techniques cannot distinguish the two conditions with certainty, and cannot exclude other diagnoses. Thus, patients undergo a brain biopsy.

With the apparent success of gene expression profiling in separating biologically distinct cases of DLBCL, NOS, some researchers examined whether a similar distinction could be made using immunohistochemical staining (IHC), a widely used method for characterizing tissue samples. This technique uses highly specific antibody-based stains to detect proteins on a microscope slide, and since microarrays are not widely available for routine clinical use, IHC is a desirable alternative. Many of these studies focused on stains against the products of prognostically significant genes which had been implicated in DLBCL gene expression studies. Examples of such genes include BCL2, BCL6, MUM1, LMO2, MYC, and p21. Several algorithms for separating DLBCL cases by IHC arose out of this research, categorizing tissue samples into groups most commonly known as GCB and non-GCB. The correlation between these GCB/non-GCB immunohistochemical groupings and the GCB/ABC groupings used in gene expression profiling studies is uncertain, as is their prognostic value. This uncertainty may arise in part due to poor inter-rater reliability in performing common immunohistochemical stains.

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.

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.

The most common chemotherapy used for non-Hodgkin lymphoma is R-CHOP.

Cutaneous T-cell lymphoma may be divided into the several subtypes. Mycosis fungoides is the most common form of CTCL and is responsible for half of all cases.A WHO-EORTC classification has been developed.

Multiagent chemotherapy is recommended, but the preferred regimen is controversial, as is consolidative radiotherapy.

Radiotherapy is the most effective treatment for local disease either as the sole treatment for low-grade lymphoma or in combination with chemotherapy for intermediate- and high-grade lymphoma. Radiotherapy dose in range of 30-45 Gy administered in fractions are advised in treating the local orbital lymphomas.

Patients with AIDS and PCNSL have a median survival of only 4 months with radiotherapy alone. Untreated, median survival is only 2.5 months, sometimes due to concurrent opportunistic infections rather than the lymphoma itself. Extended survival has been seen, however, in a subgroup of AIDS patients with CD4 counts of more than 200 and no concurrent opportunistic infections, who can tolerate aggressive therapy consisting of either methotrexate monotherapy or vincristine, procarbazine, or whole brain radiotherapy. These patients have a median survival of 10–18 months. Of course, highly active antiretroviral therapy (HAART) is critical for prolonged survival in any AIDS patient, so compliance with HAART may play a role in survival in patients with concurrent AIDS and PCNSL.

The typical patient with angioimmunoblastic T-cell lymphoma (AITL) is either middle-aged or elderly, and no gender preference for this disease has been observed. AITL comprises 15–20% of peripheral T-cell lymphomas and 1–2% of all non-Hodgkin lymphomas.