Some patients have no symptoms, spontaneous remission, or a relapsing/remitting course, making it difficult to decide whether therapy is needed. In 2002, authors from Sapienza University of Rome stated on the basis of a comprehensive literature review that "clinical observation without treatment is advisable when possible."

Therapeutic options include surgery, radiation therapy, and chemotherapy. Surgery is used to remove single lymph nodes, central nervous system lesions, or localized cutaneous disease. In 2014, Dalia and colleagues wrote that for patients with extensive or systemic Rosai–Dorfman disease, "a standard of care has not been established" concerning radiotherapy and chemotherapy.

Immunotherapy with immune checkpoint inhibitors is being investigated in head and neck cancers.

Specific treatment depends on the location, type, and stage of the tumour. Treatment may involve surgery, radiotherapy, or chemotherapy, alone or in combination. This is a specialised area which requires the coordinated expertise of ear, nose and throat (ENT) surgeons (Otorhinolaryngologists) and Oncologists. A severely affected patient may require a laryngectomy, the complete or partial removal of the vocal cords.

Survival advantages provided by new treatment modalities have been undermined by the significant percentage of people cured of head and neck squamous cell carcinoma (HNSCC) who subsequently develop second primary tumors. The incidence of second primary tumors ranges in studies from 9%

to 23%

at 20 years. Second primary tumors are the major threat to long-term survival after successful therapy of early-stage HNSCC. Their high incidence results from the same carcinogenic exposure responsible for the initial primary process, called field cancerization.

A new model of pathogenesis (lymph node changes are not “benign tumors” that secrete cytokines, but reactive changes due to excessive cytokine release from an as-yet unknown cause) and a new classification system for MCD (based on HHV-8 status) have ensued. CDCN has launched a platform for online discussion among physicians and researchers, developed a global research agenda, and launched a global patient community in partnership with EURODIS and NORD. Current strategic priorities include: 1) establishing a global patient registry, 2) empowering the global patient community to support one another and join the fight against CD, and 3) distributing high-impact research grants.

Smoking is the most important risk factor for laryngeal cancer. Death from laryngeal cancer is 20 times more likely for heaviest smokers than for nonsmokers. Heavy chronic consumption of alcohol, particularly alcoholic spirits, is also significant. When combined, these two factors appear to have a synergistic effect.

Some other quoted risk factors are likely, in part, to be related to prolonged alcohol and tobacco consumption. These include low socioeconomic status, male sex, and age greater than 55 years.

People with a history of head and neck cancer are known to be at higher risk (about 25%) of developing a second cancer of the head, neck, or lung. This is mainly because in a significant proportion of these patients, the aerodigestive tract and lung epithelium have been exposed chronically to the carcinogenic effects of alcohol and tobacco. In this situation, a field change effect may occur, where the epithelial tissues start to become diffusely dysplastic with a reduced threshold for malignant change. This risk may be reduced by quitting alcohol and tobacco.

Due to the high risk of recurrence and ensuing problems, close monitoring of dogs undergoing chemotherapy is important. The same is true for dogs that have entered remission and ceased treatment. Monitoring for disease and remission/recurrence is usually performed by palpation of peripheral lymph nodes. This procedure detects gross changes in peripheral lymph nodes. Some of the blood tests used in diagnosing lymphoma also offer greater objectivity and provide an earlier warning of an animal coming out of remission.

Complete cure is rare with lymphoma and treatment tends to be palliative, but long remission times are possible with chemotherapy. With effective protocols, average first remission times are 6 to 8 months. Second remissions are shorter and harder to accomplish. Average survival is 9 to 12 months. The most common treatment is a combination of cyclophosphamide, vincristine, prednisone, L-asparaginase, and doxorubicin. Other chemotherapy drugs such as chlorambucil, lomustine (CCNU), cytosine arabinoside, and mitoxantrone are sometimes used in the treatment of lymphoma by themselves or in substitution for other drugs. In most cases, appropriate treatment protocols cause few side effects, but white blood cell counts must be monitored.

Allogeneic and autologous stem cell transplantations (as is commonly done in humans) have recently been shown to be a possible treatment option for dogs. Most of the basic research on transplantation biology was generated in dogs. Current cure rates using stem cell therapy in dogs approximates that achieved in humans, 40-50%.

When cost is a factor, prednisone used alone can improve the symptoms dramatically, but it does not significantly affect the survival rate. The average survival times of dogs treated with prednisone and untreated dogs are both one to two months. Using prednisone alone can cause the cancer to become resistant to other chemotherapy agents, so it should only be used if more aggressive treatment is not an option.

Isotretinoin can be used to treat cutaneous lymphoma.

The treatment for tonsil carcinoma includes the following methods:

Early radio-sensitive tumors are treated by radiotherapy along with irradiation of cervical nodes. The radiation uses high-energy X-rays, electron beams, or radioactive isotopes to destroy cancer cells.

As with the radiotherapy data, most of the available knowledge on the efficacy of chemotherapy derives from the treatment of advanced head and neck cancer rather than specific studies of HPV+OPC. Since 1976, many clinical studies have compared CRT to RT alone in the primary management of locally advanced head and neck cancers and have demonstrated an advantage to CRT in both survival and locoregional control. Cisplatin is considered the standard agent, and a survival advantage was seen for those patients who received radiation with concurrent cisplatin. Despite this no trials directly comparing cisplatin with other agents in this context have been conducted. The other agent that is widely used is Cetuximab, a monoclonal antibody directed at the epidermal growth factor receptor (EGFR). A 10% survival advantage at three years was noted when cetuximab was given concurrently with radiation (bioradiation). Cetuximab trials were completed prior to knowledge of HPV status. The main toxicity is an acneiform rash, but it has not been compared directly to cisplatin in HPV+OPC, although RTOG 1016 is addressing this question. Concurrent chemotherapy is also superior to chemotherapy alone (induction chemotherapy) followed by radiation. Cetuximab shows no advantage when added to cisplatin in combination with radiation. Although chemoradiation became a treatment standard based on clinical trials and in particular, meta-analyses, a subsequent population based study of patients with OPC, indicated no advantage to the addition of chemotherapy to radiation in either HPV+OPC or HPV-OPC, and significant concerns about added toxicity.

Chemotherapy also has a role, combined with radiation, in the postoperative setting (adjuvant therapy). Generally it is used where the pathology of the resected specimen indicates features associated with high risk of locoregional recurrence (e.g. extracapsular extension through involved lymph nodes or very close margins). It has shown improved disease-free survival and locoregional control in two very similar clinical trials in such high risk patients, EORTC 22931 (1994–2000) and RTOG 9501 (1995–2000). However, for HPV+OPC patients, such extracapsular spread does not appear to be an adverse factor and the addition of chemotherapy to radiation in this group provided no further advantage. Since the sample size to detect a survival advantage is large, given the small number of events in this group, these studies may have been underpowered and the question of the utility of adding chemotherapy is being addressed in a randomized clinical trial (ADEPT) with two year locoregional control and disease free survival as the endpoint. The addition of chemotherapy to radiation increases acute and late toxicity. In the GORTEC trial, chemotherapy with docetaxel provided improved survival and locoregional control in locally advanced OPC, but was associated with increased mucositis and need for feeding by gastrostomy. Chemotherapy and radiation are associated with a risk of death of 3–4% in this context. It is unclear whether the added toxicity of adding chemotherapy to radiation is offset by significant clinical benefit in disease control and survival.

It is thought that HPV+OPC patients benefit better from radiotherapy and concurrent cetuximab treatment than HPV-OPC patients receiving the same treatment, and that radiation and cisplatin induce an immune response against an antigenic tumour which enhances their effect on the cancer cells. Although the incidence of HPV positivity is low (10–20%), an advantage for HPV+OPC was seen in trials of both cetuximab and panitumumab, a similar anti-EGFR agent, but not a consistent interaction with treatment, although HPV+OPC appears not to benefit to the same extent as HPV-OPC to second line anti-EGFR therapy, possibly due to lower EGFR expression in HPV+OPC.

With the decrease in the death rate among people with HIV/AIDS receiving new treatments in the 1990s, the rates and severity of epidemic KS also decreased. However, the number of people living with HIV/AIDS is increasing in the United States, and it is possible that the number of people with AIDS-associated Kaposi sarcoma will again rise as these people live longer with HIV infection.

While less studies have been completed examining deintensification in this setting, than in primary radical radiation for this cancer (see below), it is an area of active investigation. In one single institution study, a decision was made to reduce the radiation dose in high risk patients with HPV+OPC from 66 to 60 Gy, corresponding to the actual evidence, and follow up has shown no decrease in cancer control. Current trials, both in North America and Europe (such as ECOG 3311 and PATHOS) use 50 Gy as the comparison arm. The comparator of 50 Gy was chosen on the grounds of (i) the exquisite sensitivity of HPV+OPC to radiation, both "in vitro" and "in vivo"; ECOG 1308 showing excellent disease control at 54 Gy; and data suggesting that 50 Gy in 1.43 Gy (iso-effective dose 43 Gy in 2.0 Gy was sufficient to electively treat the neck. Other studies are evaluating doses as low as 30 Gy in high risk cases.

Chemotherapy has been used concurrently with radiation in this setting, as in primary treatment with radical radiation, particularly where pathological features indicated a higher risk of cancer recurrence. a number of studies have suggested that this does not improve local control, although adding toxicity.

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.

Paget's disease of the breast is a type of cancer of the breast. Treatment usually involves a lumpectomy or mastectomy to surgically remove the tumour. Chemotherapy and/or radiotherapy may be necessary, but the specific treatment often depends on the characteristics of the underlying breast cancer.

Invasive cancer or extensive ductal carcinoma "in situ" is primarily treated with modified radical mastectomies. The procedure consists in the removal of the breast, the lining over the chest muscles and a part of the lymph nodes from under the arm. In cases of noninvasive cancers, simple mastectomies are performed in which only the breast with the lining over the chest muscles is removed.

Patients suffering from cancer that has not spread beyond the nipple and the surrounding area are often treated with breast-conserving surgery or lumpectomy. They usually undergo radiation therapy after the actual procedure to prevent recurrence. A breast-conserving surgery consists in the removal of the nipple, areola and the part of the breast that is affected by cancer.

In most cases, adjuvant treatment is part of the treatment schema. This type of treatment is normally given to patients with cancer to prevent a potential recurrence of the disease. Whether adjuvant therapy is needed depends upon the type of cancer and whether the cancer cells have spread to the lymph nodes. In Paget's disease, the most common type of adjuvant therapy is radiation following breast-conservative surgery.

Adjuvant therapy may also consist of anticancer drugs or hormone therapies. Hormonal therapy reduces the production of hormones within the body, or prevents the hormones from stimulating the cancer cells to grow, and it is commonly used in cases of invasive cancer by means of drugs such as tamoxifen and anastrozole.

Cervical lymphadenopathy refers to lymphadenopathy of the cervical lymph nodes (the glands in the neck). The term "lymphadenopathy" strictly speaking refers to disease of the lymph nodes, though it is often used to describe the enlargement of the lymph nodes. Similarly, the term "lymphadenitis" refers to inflammation of a lymph node, but often it is used as a synonym of lymphadenopathy.

Cervical lymphadenopathy is a sign or a symptom, not a diagnosis. The causes are varied, and may be inflammatory, degenerative, or neoplastic. In adults, healthy lymph nodes can be palpable (able to be felt), in the axilla, neck and groin. In children up to the age of 12 cervical nodes up to 1 cm in size may be palpable and this may not signify any disease. If nodes heal by resolution or scarring after being inflamed, they may remain palpable thereafter. In children, most palpable cervical lymphadenopathy is reactive or infective. In individuals over the age of 50, metastatic enlargement from cancers (most commonly squamous cell carcinomas) of the aerodigestive tract should be considered.

Most patients diagnosed with Paget's disease of the nipple are over age 50, but rare cases have been diagnosed in patients in their 20s. The average age at diagnosis is 62 for women and 69 for men. The disease is rare among both women and men.

For HHV-8-negative MCD (idiopathic MCD), the following treatments have been used: corticosteroids, rituximab, monoclonal antibodies against IL-6 such as tocilizumab and siltuximab, and the immunomodulator thalidomide.

Prior to 1996 MCD carried a poor prognosis of about 2 years, due to autoimmune hemolytic anemia and non-Hodgkin's lymphoma which may arise as a result of proliferation of infected cells. The timing of diagnosis, with particular attention to the difficulty of determining the cause of B symptoms without a CT scan and lymph node biopsy, may have a significant impact on the prognosis and risk of death. Left untreated, MCD usually gets worse and becomes increasingly difficult and unresponsive to current treatment regimens.

Siltuximab prevents it from binding to the IL-6 receptor, was approved by the U.S. Food and Drug Administration for the treatment of multicentric Castleman disease on April 23, 2014. Preliminary data suggest that treatment siltuximab may achieve tumour and symptomatic response in 34% of patients with MCD.

Other treatments for multicentric Castleman disease include the following:

- Corticosteroids

- Chemotherapy

- Thalidomide

Lymph nodes may become enlarged in malignant disease. This cervical lymphadenopathy may be reactive or metastatic. Alternatively, enlarged lymph nodes may represent a primary malignancy of the lymphatic system itself, such as lymphoma (both Hodgkin's and non-Hodgkin's), lymphocytic leukemia,

Metastatic lymph nodes are enlarged because tumor cells have detached from the primary tumor and started growing in the lymph node ("seeded"). Since cancer generally occurs more frequently in older people, this kind of lymphadenopathy is more common in older persons. Metastatic lymph nodes tend to feel hard and may be fixed to underlying tissues and may or may not be tender. Usually the lymph nodes that directly drain the area of the cancer are affected by the spread (e.g. Sometimes metastatic cervical lymph node is detected before the main cancer). In such cases, this discovery leads to a search for the primary malignancy, firstly in the nearby area with endoscopy, "blind" biopsies, and tonsillectomy on the side of the lymphadenopathy. If no tumor is found, then the rest of the body is examined, looking for lung cancer or other possible sites. If still no primary tumor is detected, the term "occult primary" is used.

In lymphoma, usually there are multiple enlarged nodes which feel rubbery to palpation.

- Rhabdomyosarcoma

- Neuroblastoma

Rosai–Dorfman disease, originally known as sinus histiocytosis with massive lymphadenopathy, is a rare disorder of unknown cause that is characterized by abundant histiocytes in the lymph nodes or other locations throughout the body.

Factors that contribute to the development of hypopharyngeal cancer include:

- Smoking

- Chewing tobacco

- Heavy alcohol use

- Poor diet

Smoking, like lung cancer, can cause hypopharyngeal cancer because it contains carcinogens that alter the DNA or RNA in a dividing cell. These alterations may change a normal DNA sequence to an oncogene, a gene that causes cancer after exposure to a carcinogen.

Squamous cells, a type of cell that lines hollow organs like the throat, mouth, lungs, and outer layer of skin, are particularly vulnerable when exposed to cigarette smoke.

Chewing tobacco can have the same effects as smoking and is also linked to hypopharyngeal cancer. The chewing tobacco is placed into the mouth, leaving it exposed to enzymes, like amylase, which partly digests the carcinogenic material. Saliva is swallowed, along with the cancer-promoting material, which passes through the hypopharynx on its way to the esophagus.

Heavy alcohol use is linked to Hypopharyngeal Cancer as well. Alcohol damages the lining of the hypopharynx, increasing the amount of chemicals that are allowed to seep into the underlying membranes. Heavy alcohol use is also associated with nutritional deficiencies.

A disease called Plummer-Vinson syndrome, a genetic disorder that causes a long-term iron deficiency, may also lead to Hypopharyngeal Cancer. Other factors like a deficiency in certain vitamins also appear to contribute to this type of cancer.

Nasopharyngeal carcinoma can be treated by surgery, by chemotherapy, or by radiotherapy. The expression of EBV latent proteins within undifferentiated nasopharyngeal carcinoma can be potentially exploited for immune-based therapies.

Most people with cancer of unknown primary origin have widely disseminated and incurable disease, although a few can be cured through treatment. With treatment, typical survival with CUP ranges from 6 to 16 months. Survival rates are lower in cases with visceral metastatic disease, ranging from 6 to 9 months. Survival rates are higher when the cancer is more limited to lymph nodes, pleura, or peritoneal metastasis, which ranges from 14 to 16 months. Long-term prognosis is somewhat better if a particular source of cancer is strongly suggested by clinical evidence.

People with HPV-mediated oropharyngeal cancer tend to have higher survival rates. The prognosis for people with oropharyngeal cancer depends on the age and health of the person and the stage of the disease. It is important for people with oropharyngeal cancer to have follow-up exams for the rest of their lives, as cancer can occur in nearby areas. In addition, it is important to eliminate risk factors such as smoking and drinking alcohol, which increase the risk for second cancers.

While sarcoids may spontaneously regress regardless of treatment in some instances, course and duration of disease is highly unpredictable and should be considered on a case-by-case basis taking into account cost of the treatment and severity of clinical signs. Surgical removal alone is not effective, with recurrence occurring in 50 to 64% of cases, but removal is often done in conjunction with other treatments. Topical treatment with products containing bloodroot extract (from the plant "Sanguinaria canadensis") for 7 to 10 days has been reported to be effective in removing small sarcoids, but the salve's caustic nature may cause pain and the sarcoid must be in an area where a bandage can be applied. Freezing sarcoids with liquid nitrogen (cryotherapy) is another affordable method, but may result in scarring or depigmentation. Topical application of the anti-metabolite 5-fluorouracil has also obtained favorable results, but it usually takes 30 to 90 days of repeated application before any effect can be realized. Injection of small sarcoids (usually around the eyes) with the chemotherapeutic agent cisplatin and the immunomodulator BCG have also achieved some success. In one trial, BCG was 69% effective in treating nodular and small fibroblastic sarcoids around the eye when repeatedly injected into the lesion and injection with cisplatin was 33% effective overall (mostly in horses with nodular sarcoids). However, BCG treatment carries a risk of allergic reaction in some horses and cisplatin has a tendency to leak out of sarcoids during repeated dosing. External beam radiation can also be used on small sarcoids, but is often impractical. Cisplatin electrochemotherapy (the application of an electrical field to the sarcoid after the injection of cisplatin, with the horse under general anesthesia), when used with or without prior surgery to remove the sarcoid, had a non-recurrence rate after four years of 97.9% in one retrospective study. There is a chance of sarcoid recurrence for all modalities even after apparently successful treatment. While sarcoids are not fatal, large aggressive tumors that destroy surrounding tissue can cause discomfort and loss of function and be resistant to treatment, making euthanasia justifiable in some instances. Sarcoids may be the most common skin-related reason for euthanasia.

CUP sometimes runs in families. It has been associated with familial lung, kidney, and colorectal cancers, which suggests that these sites may often be the origin of unidentifiable CUP cancers.