In Europe and North America, KSHV is transmitted through saliva. Thus, kissing is a theoretical risk factor for transmission. Higher rates of transmission among gay and bisexual men have been attributed to "deep kissing" sexual partners with KSHV. Another alternative theory suggests that use of saliva as a sexual lubricant might be a major mode for transmission. Prudent advice is to use commercial lubricants when needed and avoid deep kissing with partners with KSHV infection or whose status is unknown.

KSHV is also transmissible via organ transplantation and blood transfusion. Testing for the virus before these procedures is likely to effectively limit iatrogenic transmission.

Kaposi's sarcoma-associated herpesvirus (KSHV), also called HHV-8 is present in almost 100% of Kaposi sarcoma lesions, whether HIV-related, classic, endemic, or iatrogenic.

The Center for Disease Control and Prevention (CDC) included certain types of non-Hodgkin's lymphoma as AIDS-defining cancers in 1987. Immune suppression rather than HIV itself is implicated in the pathogenesis of this malignancy, with a clear correlation between the degree of immune suppression and the risk of developing NHL. Additionally, other retroviruses such as HTLV may be spread by the same mechanisms that spread HIV, leading to an increased rate of co-infection. The natural history of HIV infection has been greatly changed over time. As a consequence, rates of non-Hodgkin's lymphoma (NHL) in people infected with HIV has significantly declined in recent years.

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

Staging attempts to distinguish patients with localized from those with metastatic disease. Most commonly, metastases occur in the chest, bone and/or bone marrow. Less common sites include the central nervous system and lymph nodes.

Five-year survival for localized disease is 70% to 80% when treated with chemotherapy. Prior to the use of multi-drug chemotherapy, long-term survival was less than 10%. The development of multi-disciplinary therapy with chemotherapy, irradiation, and surgery has increased current long-term survival rates in most clinical centers to greater than 50%. However, some sources state it is 25–30%.

Retrospective research in patients led by Idriss M. Bennani-Baiti (Cancer Epigenetics Society) showed that two chemokine receptors, CXCR4 and CXCR7, can be used as molecular prognosis factors. Patients who express low levels of both chemokine receptors have the highest odds of long-term survival with >90% survival at 5 years post-diagnosis versus <30% survival at 5 years for patients with very high expression levels of both receptors.

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.

Unlike some other lymphomas, whose incidence increases with age, Hodgkin's lymphoma has a bimodal incidence curve; that is, it occurs most frequently in two separate age groups, the first being young adulthood (age 15–35) and the second being in those over 55 years old although these peaks may vary slightly with nationality. Overall, it is more common in males, except for the nodular sclerosis variant, which is slightly more common in females. The annual incidence of Hodgkin's lymphoma is 2.7 per 100,000 per persons per year, and the disease accounts for slightly less than 1% of all cancers worldwide.

In 2010, globally it resulted in about 18,000 deaths down from 19,000 in 1990.

The incidence of Hodgkin's lymphoma is increased in patients with HIV infection. In contrast to many other lymphomas associated with HIV infection it occurs most commonly in patients with higher CD4 T cell counts.

Chemotherapy is the mainstay of treatment for lymphoma in cats. Most of the drugs used in dogs are used in cats, but the most common protocol uses cyclophosphamide, vincristine, and prednisone. Gastrointestinal lymphoma has also commonly been treated with a combination of prednisolone and high dose pulse chlorambucil with success. The white blood cell count must be monitored. Remission and survival times are comparable to dogs. Lower stage lymphoma has a better prognosis. Multicentric lymphoma has a better response to treatment than the gastrointestinal form, but infection with FeLV worsens the prognosis.

About 75% of cats treated with chemotherapy for lymphoma go into remission. Unfortunately, after an initial remission, most cats experience a relapse, after which they have a median survival of 6 months. However, about one-third of cats treated with chemotherapy will survive more than 2 years after diagnosis; a small number of these cats may be cured of their disease. Untreated, most cats with lymphoma die within 4–6 weeks. Most cats tolerate their chemotherapy well, and fewer than 5% have severe side effects. Cats do not lose their fur from chemotherapy, though loss of whiskers is possible. Other side effects include low white blood cell count, vomiting, loss of appetite, diarrhea, or fatigue. These can typically be controlled well, and most cats have a good quality of life during treatment. If a cat relapses after attaining remission, the cat can be treated with different chemotherapy drugs to try for a second remission. The chances of a second remission are much lower than the chances of obtaining a first, and the second remission is often shorter than the first.

The lymphoma is more common in the young and in males.

A 2008 study found an increased risk of ALCL of the breast in women with silicone breast implants (protheses), although the overall risk remained exceedingly low due to the rare occurrence of the tumor.

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

In women, chemotherapy may damage the ovaries and cause infertility. To avail future pregnancies, the woman may preserve oocytes or ovarian tissue by oocyte cryopreservation or ovarian tissue cryopreservation prior to starting chemotherapy. However, the latter may reseed the cancer upon reinsertion of the ovarian tissue. If it is performed, the ovarian tissue should be examined for traces of malignancy at both the pathological and molecular levels prior to the grafting of the cryopreserved tissue.

Histologic transformation to diffuse large B-cell lymphoma (DLBCL) can occur in up to 12% of cases. After transformation, neoplastic cells carry monoclonal immunoglobulin gene rearrangements. Histological transformation may lead to poor prognosis and therefore repeat biopsy is required at relapse.

One study found a transformation rate of 7.6%, and suggested that prior exposure to chemotherapy and a presentation with splenic involvement were associated with increased risks of transformation.

Untreated dogs have an average survival time of 60 days. Lymphoma with a histologic high grade generally respond better to treatment but have shorter survival times than dogs with low grade lymphoma. Dogs with B-lymphocyte tumors have a longer survival time than T-lymphocyte tumors. Mediastinal lymphoma has a poorer prognosis than other types, especially those with hypercalcemia. Clinical stage and substage have some prognostic value, with poorer prognosis associated with Stage V disease, and with substage b (clinical illness at time of presentation).

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.

Most soft-tissue sarcomas are not associated with any known risk factors or identifiable cause. There are some exceptions:

- Studies suggest that workers who are exposed to chlorophenols in wood preservatives and phenoxy herbicides may have an increased risk of developing soft-tissue sarcomas. An unusual percentage of patients with a rare blood vessel tumor, angiosarcoma of the liver, have been exposed to vinyl chloride in their work. This substance is used in the manufacture of certain plastics, notably PVC.

- In the early 1900s, when scientists were just discovering the potential uses of radiation to treat disease, little was known about safe dosage levels and precise methods of delivery. At that time, radiation was used to treat a variety of noncancerous medical problems, including enlargement of the tonsils, adenoids, and thymus gland. Later, researchers found that high doses of radiation caused soft-tissue sarcomas in some patients. Because of this risk, radiation treatment for cancer is now planned to ensure that the maximum dosage of radiation is delivered to diseased tissue while surrounding healthy tissue is protected as much as possible.

- Kaposi's sarcoma, a rare cancer of the cells that line blood vessels in the skin and mucus membranes, is caused by Human herpesvirus 8. Kaposi's sarcoma often occurs in patients with AIDS (acquired immune deficiency syndrome). Kaposi's sarcoma, however, has different characteristics than typical soft-tissue sarcomas and is treated differently.

- In a very small fraction of cases, sarcoma may be related to a rare inherited genetic alteration of the p53 gene and is known as Li-Fraumeni syndrome. Certain other inherited diseases are associated with an increased risk of developing soft-tissue sarcomas. For example, people with neurofibromatosis type I (also called von Recklinghausen's disease, associated with alterations in the NF1 gene) are at an increased risk of developing soft-tissue sarcomas known as malignant peripheral nerve sheath tumors. Patients with inherited retinoblastoma have alterations in the RB1 gene, a tumor suppressor gene, and are likely to develop soft-tissue sarcomas as they mature into adulthood.

Prognosis depends on the primary tumor grade (appearance under the microscope as judged by a pathologist), size, resectability (whether it can be completely removed surgically), and presence of metastases. The five-year survival is 80%.

Soft-tissue sarcomas are relatively uncommon cancers. They account for less than 1% of all new cancer cases each year. This may be because cells in soft tissue, in contrast to tissues that more commonly give rise to malignancies, are not continuously dividing cells.

In 2006, about 9,500 new cases were diagnosed in the United States. Soft-tissue sarcomas are more commonly found in older patients (>50 years old) although in children and adolescents under age 20, certain histologies are common (rhabdomyosarcoma, synovial sarcoma).

Around 3,300 people were diagnosed with soft tissue sarcoma in the UK 2011.

Undifferentiated pleomorphic sarcoma is regarded as the most common soft tissue sarcoma of late adult life. It rarely occurs in children. It occurs more often in Caucasians than in those of African or Asian descent and is a male-predominant disease, afflicting two males for every female.

The prognosis for DSRCT remains poor. Prognosis depends upon the stage of the cancer. Because the disease can be misdiagnosed or remain undetected, tumors frequently grow large within the abdomen and metastasize or seed to other parts of the body.

There is no known organ or area of origin. DSRCT can metastasize through lymph nodes or the blood stream. Sites of metastasis include the spleen, diaphragm, liver, large and small intestine, lungs, central nervous system, bones, uterus, bladder, genitals, abdominal cavity, and the brain.

A multi-modality approach of high-dose chemotherapy, aggressive surgical resection, radiation, and stem cell rescue improves survival for some patients. Reports have indicated that patients will initially respond to first line chemotherapy and treatment but that relapse is common.

Some patients in remission or with inoperable tumor seem to benefit from long term low dose chemotherapy, turning DSRCT into a chronic disease.

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.

Castleman disease (CD) is a lymphoproliferative disorder of unknown cause. CD is associated with an increased risk of B-cell lymphoma.

Human herpesvirus 8 (HHV-8), also known as Kaposi sarcoma-associated herpesvirus (KSHV) has been found in some cases of multicentric Castleman disease (MCD). The HHV8 can give rise to an increased number of plasmablast cells within the mantle zone of B-cell follicles. These plasmablasts express IgM-immunoglobulin light chains, most often of lambda subtype. These plasmablasts can give rise to a spectrum of abnormalities including progression to microlymphoma (microscopic clusters of plasmablast cells) or clinical lymphoma.

This type of lymphoma is predominantly seen in acquired immunodeficiencies, including acquired immunodeficiency syndrome (AIDS) but it can also occur in immunosuppression such as with organ transplantation or the elderly. The plasmablasts do not show rearranged immunoglobulin genes, and typically lack EBV infection.

The disease predominantly affects lymph nodes and the spleen, a pattern dissimilar to plasmablastic lymphoma of the oral cavity of AIDS which is not associated with HHV-8 infection. Despite traditional chemotherapy with CHOP (cyclophosphamide, doxorubicin, prednisone, vincristine), and the possible addition of antiviral therapy and inhibition of specific cellular targets including the use of rituximab, the prognosis in this lymphoma has been poor.

This lymphoma subtype has sometimes been confused with plasmablastic lymphoma in the literature, although that is a dissimilar specific entity. Similarly, this subtype is considered distinct from other lymphomas which have a plasmablastic immunophenotype such as primary effusion lymphoma, ALK+ large B-cell lymphoma, and extracavitary HHV–8-positive lymphoma.

HHV8 is also associated with Kaposi's sarcoma and with another subtype of lymphoma, primary effusion lymphoma, previously called body cavity-based lymphoma.

There are no known risk factors that have been identified specific to the disease. The tumor appears to arise from the primitive cells of childhood, and is considered a childhood cancer.

Research has indicated that there is a chimeric relationship between desmoplastic small-round-cell tumor (DSRCT) and Wilms' tumor and Ewing's sarcoma. Together with neuroblastoma and non-Hodgkin's lymphoma, they form the small cell tumors.

DSRCT is associated with a unique chromosomal translocation t(11;22)(p13:q12) resulting in an EWS/WT1 transcript that is diagnostic of this tumor. This transcript codes for a protein that acts as a transcriptional activator that fails to suppress tumor growth.

The EWS/WT1 translocation product targets ENT4. ENT4 is also known as PMAT.

It was previously a relatively common complication of the massive lymphedema of the arm which followed removal of axillary (arm pit) lymph nodes and lymphatic channels as part of the classical Halstedian radical mastectomy, as a treatment for breast cancer. The classical radical mastectomy was abandoned in most areas of the world in the late 1960s to early 1970s, being replaced by the much more conservative modified radical mastectomy and, more recently, by segmental breast tissue excision and radiation therapy. Because of this change in clinical practice lymphedema is now a rarity following breast cancer treatment—and post-mastectomy lymphangiosarcoma is now vanishingly rare. When it occurs following mastectomy it is known as Stewart-Treves syndrome (which can be both lymphangiosarcoma and hemangiosarcoma following mastectomy). The pathogenesis of lymphangiosarcoma has not been resolved, however several vague mechanisms have been proposed. Stewart and Treves, proposed that a cancer causing agent is present in lymphedematous limbs. Schreiber "et al." proposed that local immunodeficiency as a result of lymphedema results in a "immunologically privileged site" in which the sarcoma is able to develop.

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.

Large B-cell lymphoma arising in HHV8-associated multicentric Castleman's disease is a type of large B-cell lymphoma, recognized in the WHO 2008 classification. It is sometimes called the plasmablastic form of multicentric Castleman disease. It has sometimes been confused with plasmablastic lymphoma in the literature, although that is a dissimilar specific entity. It has variable CD20 expression and unmutated immunoglobulin variable region genes.