Flow cytometry is a diagnostic tool in order to count/visualize the amount of lymphatic cells in the body. T cells, B cells and NK cells are nearly impossible to distinguish under a microscope, therefore one must use a flow cytometer to distinguish them.

Diagnosing ALL begins with a thorough medical history, physical examination, complete blood count, and blood smears. While many symptoms of ALL can be found in common illnesses, persistent or unexplained symptoms raise suspicion of cancer. Because many features on the medical history and exam are not specific to ALL, further testing is often needed. A large number of white blood cells and lymphoblasts in the circulating blood can be suspicious for ALL because they indicate a rapid production of lymphoid cells in the marrow. The higher these numbers typically points to a worse prognosis. While white blood cell counts at initial presentation can vary significantly, circulating lymphoblast cells are seen on peripheral blood smears in the majority of cases.

A bone marrow biopsy provides conclusive proof of ALL, typically with >20% of all cells being leukemic lymphoblasts. A lumbar puncture (also known as a spinal tap) can determine whether the spinal column and brain have been invaded. Brain and spinal column involvement can be diagnosed either through confirmation of leukemic cells in the lumbar puncture or through clinical signs of CNS leukemia as described above. Laboratory tests that might show abnormalities include blood count, kidney function, electrolyte, and liver enzyme tests.

Pathological examination, cytogenetics (in particular the presence of Philadelphia chromosome), and immunophenotyping establish whether the leukemic cells are myeloblastic (neutrophils, eosinophils, or basophils) or lymphoblastic (B lymphocytes or T lymphocytes). Cytogenetic testing on the marrow samples can help classify disease and predict how aggressive the disease course will be. Different mutations have been associated with shorter or longer survival. Immunohistochemical testing may reveal TdT or CALLA antigens on the surface of leukemic cells. TdT is a protein expressed early in the development of pre-T and pre-B cells, whereas CALLA is an antigen found in 80% of ALL cases and also in the "blast crisis" of CML.

Medical imaging (such as ultrasound or CT scanning) can find invasion of other organs commonly the lung, liver, spleen, lymph nodes, brain, kidneys, and reproductive organs.

Cytogenetic analysis has shown different proportions and frequencies of genetic abnormalities in cases of ALL from different age groups. This information is particularly valuable for classification and can in part explain different prognosis of these groups. In regards to genetic analysis, cases can be stratified according to ploidy, number of sets of chromosomes in the cell, and specific genetic abnormalities, such as translocations. Hyperdiploid cells are defined as cells with more than 50 chromosomes, while hypodiploid is defined as cells with less than 44 choromosomes. Hyperdiploid cases tend to carry good prognosis while hypodiploid cases do not. For example, the most common specific abnormality in childhood B-ALL is the t(12;21) "ETV6"-"RUNX1" translocation, in which the "RUNX1" gene, encoding a protein involved in transcriptional control of hemopoiesis, has been translocated and repressed by the "ETV6"-"RUNX1" fusion protein.

Below is a table with the frequencies of some cytogenetic translocations and molecular genetic abnormalities in ALL.

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.

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

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.

While it is generally considered incurable, CLL progresses slowly in most cases. Many people with CLL lead normal and active lives for many years—in some cases for decades. Because of its slow onset, early-stage CLL is, in general, not treated since it is believed that early CLL intervention does not improve survival time or quality of life. Instead, the condition is monitored over time to detect any change in the disease pattern.

The decision to start CLL treatment is taken when the patient's clinical symptoms or blood counts indicate that the disease has progressed to a point where it may affect the patient's quality of life.

Clinical "staging systems" such as the Rai four-stage system and the Binet classification can help to determine when and how to treat the patient.

Determining when to start treatment and by what means is often difficult; no survival advantage is seen in treating the disease very early. The National Cancer Institute Working Group has issued guidelines for treatment, with specific markers that should be met before it is initiated.

Lymphoma Association (UK)

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Staging, determining the extent of the disease, is done with the Rai staging system or the Binet classification (see details) and is based primarily on the presence of a low platelet or red cell count. Early-stage disease does not need to be treated. CLL and SLL are considered the same underlying disease, just with different appearances.

Rai staging system

- "Stage 0": characterized by absolute lymphocytosis (>15,000/mm) without adenopathy, hepatosplenomegaly, anemia, or thrombocytopenia

- "Stage I": characterized by absolute lymphocytosis with lymphadenopathy without hepatosplenomegaly, anemia, or thrombocytopenia

- "Stage II:" characterized by absolute lymphocytosis with either hepatomegaly or splenomegaly with or without lymphadenopathy

- "Stage III": characterized by absolute lymphocytosis and anemia (hemoglobin <11 g/dL) with or without lymphadenopathy, hepatomegaly, or splenomegaly

- "Stage IV": characterized by absolute lymphocytosis and thrombocytopenia (<100,000/mm) with or without lymphadenopathy, hepatomegaly, splenomegaly, or anemia

Binet classification

- "Clinical stage A": characterized by no anemia or thrombocytopenia and fewer than three areas of lymphoid involvement (Rai stages 0, I, and II)

- "Clinical stage B": characterized by no anemia or thrombocytopenia with three or more areas of lymphoid involvement (Rai stages I and II)

- "Clinical stage C": characterized by anemia and/or thrombocytopenia regardless of the number of areas of lymphoid enlargement (Rai stages III and IV)

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).

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.

Splenic MZL is difficult to diagnose and can look similar to other types of lymphoma. Tests include a physical examination, blood tests to determine overall health and detect infections (ex. hepatitis C), a bone marrow biopsy, CT scan, and a PET scan. Sometimes a splenectomy is necessary during the diagnosis process in order to determine the exact type of lymphoma. If the spleen is removed, you will be at a larger risk of infection.

One study has suggested improved overall survival in response to chemotherapy for African Americans.

In order to diagnose MALT, a biopsy is needed from the affected tissue. If the abnormal tissue is suspected to be in the stomach or bowel, an endoscopy is done in order to get the biopsy. This requires either a gastroscopy or colonoscopy. If the lymphoma is thought to have spread to other areas in this region, an ultrasound scan is often done at the same time. If the abnormal tissue is thought to be in the lungs, a bronchoscopy is ordered.

In order to determine the correct type of lymphoma and stage it accurately, the physician will also need to do a physical exam, blood tests to determine blood cell counts, a CT scan, an MRI and/or a PET scan. A PET scan is the most important in planning a course of treatment.

A bone marrow biopsy may be ordered to test for lymph node involvement. If the lymphoma is in the stomach, the physician will test for H.pylori infection through a stool sample. This infection would be necessary to treat in conjunction to treating the cancer.

ANKL is treated similarly to most B-cell lymphomas. Anthracycline-containing chemotherapy regimens are commonly offered as the initial therapy. Some patients may receive a stem cell transplant.

Most patients will die 2 years after diagnosis.

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.

While the bone marrow is commonly involved, the detection of the neoplastic infiltrate may be difficult due to diffuse, interstitial pattern. Immunohistochemistry can aid in the detection of this lymphoma.

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.

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.

Following observation of the symptoms, the patients need to get complete blood counts and a bone marrow examination. If the patient has leukemia, the morphology and immunophenotype check is needed to make sure the type of leukemia.

The morphology of the blast in BAL is not certain. The cells could display both myeloid lineage and lymphoid or undifferentiated morphology. Therefore, the diagnosis cannot based on the morphology result. The immunophenotype check is the most important basis of the diagnosis of BAL.

Before 2008, the diagnosis of BAL was based on a score system proposed by the European Group for the Immunological Classification of Leukemias (EGIL) which could differentiate from other kinds of acute leukemia. The table shows this method.

If the score of only one lineage is higher than 2, the acute leukemia could be acute myeloid leukemia (AML) or acute lymphoblastic leukemia (ALL). According to the original EGIL scoring system BAL is defined when scores are over two points for both myeloid and T- or B- lymphoid lineages.

In 2008, WHO established a new and strict criteria standard for diagnosis of BAL. The presence of specific T-lymphoid antigens, cytoplasmic CD3 (cCD3), MPO and CD 19 became the most important standard for recognizing the lineage. Other B-lineage markers (CD22, CD79a, CD 10) and monocytic markers are also needed. Table 2 shows the method.

Compared with the EGIL scoring system, the current 2008 WHO criteria applied less but more specific markers to define the lineage of the blasts, and incorporated the intensity of markers expression into the diagnostic algorithm.

The diagnosis of BAL is so difficult that sometimes is misdiagnosed with AML or ALL because the morphology thus the therapy would not have a good effect.

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.

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.

Of all cancers involving the same class of blood cell, 8% of cases are MALT lymphomas.

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.

Chemotherapy with CHOP, infusional EPOCH, hyperCVAD, and CODOX-M/IVAC is often used. The prognosis is generally poor, for example 6 to 7 months and 14 months.