There is no proven or standard first-line chemotherapy that works for the majority of AITL patients. There are several clinical trials that offer treatment options that can fight the disease. Stem cell transplantation is the treatment of choice, with the allogeneic one being the preference because AITL tends to recur after autologous transplants.

mTOR inhibitors :

- Everolimus

- Temsirolimus

mTOR is a kinase enzyme inside the cell that regulates cell growth, proliferation, and survival. mTOR inhibitors lead to cell cycle arrest in the G1 phase and also inhibits tumor angiogenesis by reducing synthesis of VEGF.

A Phase II trial of Evorolimus on relapsed DLBCL patients showed a 30% Overall Response Rate (ORR).

Apoptosis is one of the major mechanisms of cell death targeted by cancer therapies. Reduced susceptibility to apoptosis increases the resistance of cancer cells to radiation and cytotoxic agents. B-cell lymphoma-2 (Bcl-2) family members create a balance between pro and anti-apoptotic proteins. Pro-apoptotic proteins include Bax and Bak. Anti-apoptotic proteins include Bcl-2, Bcl-X, Bcl-w, Mcl-1. When anti-apoptotic family members are overexpressed, apoptotic cell death becomes less likely.

- Oblimersen sodium (G3139, Genasense) targets BCL-2 mRNA

- ABT-737 (oral form navitoclax, ABT-263). A small molecule that targets anti-apoptotic Bcl-2 family proteins (Bcl-2, Bcl-X and Bcl-w). ABT-737 binds anti-apoptotic Bcl-2 proteins with an affinity two or three orders of magnitude more potent than previously reported compounds. High basal levels of Mcl-1 expression are associated with resistance to ABT-737. Combining ABT-737 with second agents that inactivate Mcl-1 may reduce this effect. ABT-737 has demonstrated single-agent efficacy against cell lines from lymphoid malignancies known to express high levels of Bcl-2, including DLBCL. It has also been found to be synergistic with proteasome inhibitors.

- Fenretinide. A synthetic retinoid that induces apoptosis of cancer cells and acts synergistically with chemotherapeutic drugs by triggering the activation of 12-Lox (12-lipoxygenase) leading to oxidative stress and apoptosis via the induction of the transcription factor Gadd153 and the Bcl-2-family member protein Bak.

Most histiocytomas will regress within two or three months. Surgical removal may be necessary if the tumor does not regress or if it is growing rapidly to a large size. Histiocytomas should never be treated with an intralesional injection of a corticosteroid, as remission relies on recognition of the tumour by the body's immune system which is suppressed by steroids.

Treatment with chemotherapy has been used with some success, particularly using lomustine, prednisone, doxorubicin, and cyclophosphamide. Because of the rapid progression of this aggressive disease, the prognosis is very poor.

One such development is in the delivery of doxorubicin. While it is an effective inducer of apoptosis, doxorubicin is quickly filtered out of the body. By loading a PEG-liposome with doxorubicin the circulation time and localization to tumors greatly increases. Cancerous tumors characteristically have extensive angiogenesis and leaky vasculatures, which causes the PEG-liposomes to naturally accumulate in the tumor. This also allows for patients to receive lower and fewer doses of the drug and experience fewer side effects. This is also being attempted with nanoparticles but has not been tested on FDCS. In 2008 COP plus (PEG)-liposomal doxorubicin went into a clinical trial for an FDCS patient to replace the CHOP regimen, and after 5 years the patient remains in CR.

In a large number of phase I and phase II studies, autologous and allogeneic CIK cells displayed a high cytotoxic potential against a broad range of varying tumor entities, whereas side effects were only minor. In many cases, CIK cell treatment led to complete remissions of tumor burden, prolonged survival durations and improved quality of life, even in advanced disease stages.

Currently, the utilization of CIK cell treatment is restricted to clinical studies, but this therapeutic approach might also benefit patients as first-line treatment modality in the future.

Guidelines for management of patients up to 18 years with Langerhans cell histiocytosis has been suggested. Treatment is guided by extent of disease. Solitary bone lesion may be amenable through excision or limited radiation, dosage of 5-10 Gys for children, 24-30 Gys for adults. However systemic diseases often require chemotherapy. Use of systemic steroid is common, singly or adjunct to chemotherapy. Local steroid cream is applied to skin lesions. Endocrine deficiency often require lifelong supplement e.g. desmopressin for diabetes insipidus which can be applied as nasal drop. Chemotherapeutic agents such as alkylating agents, antimetabolites, vinca alkaloids either singly or in combination can lead to complete remission in diffuse disease.

Newer cases are also starting to be treated by taxotere and gemcitabine. Taxotere is similar to Oncovin used in CHOP; it irreversibly binds beta tubulin halting formation of microtubules. Taxotere has an added benefit though; it also phosphorylates bcl-2 to halt the anti-apoptotic pathway. The dual effect of taxotere on integral cancer pathways makes it a more potent drug than Oncovin. Gemcitabene is a nucleoside analog and when incorporated into DNA during replication leads to apoptosis; the fluorine on the 2’ carbon atom stops other nucleosides from attaching. The most important part of this combination therapy, however, is the synergism between the drugs. While researchers are not entirely sure of the mechanism, there is evidence of synergistic effects of taxotere and gemcitabine when used in combination. This allows for decreased dosages of each single agent with an increased apoptotic response.

The high cure rates and long survival of many patients with Hodgkin's lymphoma has led to a high concern with late adverse effects of treatment, including cardiovascular disease and second malignancies such as acute leukemias, lymphomas, and solid tumors within the radiation therapy field. Most patients with early-stage disease are now treated with abbreviated chemotherapy and involved-field radiation therapy rather than with radiation therapy alone. Clinical research strategies are exploring reduction of the duration of chemotherapy and dose and volume of radiation therapy in an attempt to reduce late morbidity and mortality of treatment while maintaining high cure rates. Hospitals are also treating those who respond quickly to chemotherapy with no radiation.

In childhood cases of Hodgkin's lymphoma, long-term endocrine adverse effects are a major concern, mainly gonadal dysfunction and growth retardation. Gonadal dysfunction seems to be the most severe endocrine long-term effect, especially after treatment with alkylating agents or pelvic radiotherapy.

Patients with early stage disease (IA or IIA) are effectively treated with radiation therapy or chemotherapy. The choice of treatment depends on the age, sex, bulk and the histological subtype of the disease. Adding localised radiation therapy after the chemotherapy regimen may provide a longer progression-free survival compared with chemotherapy treatment alone. Patients with later disease (III, IVA, or IVB) are treated with combination chemotherapy alone. Patients of any stage with a large mass in the chest are usually treated with combined chemotherapy and radiation therapy.

It should be noted that the common non-Hodgkin's treatment, rituximab (which is a monoclonal antibody against CD20) is not routinely used to treat Hodgkin's lymphoma due to the lack of CD20 surface antigens in most cases. The use of rituximab in Hodgkin's lymphoma, including the lymphocyte predominant subtype has been recently reviewed.

Although increased age is an adverse risk factor for Hodgkin's lymphoma, in general elderly patients without major comorbidities are sufficiently fit to tolerate standard therapy, and have a treatment outcome comparable to that of younger patients. However, the disease is a different entity in older patients and different considerations enter into treatment decisions.

For Hodgkin's lymphomas, radiation oncologists typically use external beam radiation therapy (sometimes shortened to EBRT or XRT). Radiation oncologists deliver external beam radiation therapy to the lymphoma from a machine called linear accelerator which produces high energy X Rays and Electrons. Patients usually describe treatments as painless and similar to getting an X-ray. Treatments last less than 30 minutes each.

For lymphomas, there are a few different ways radiation oncologists target the cancer cells. Involved field radiation is when the radiation oncologists give radiation only to those parts of the patient's body known to have the cancer. Very often, this is combined with chemotherapy. Radiation therapy directed above the diaphragm to the neck, chest or underarms is called mantle field radiation. Radiation to below the diaphragm to the abdomen, spleen or pelvis is called inverted-Y field radiation. Total nodal irradiation is when the therapist gives radiation to all the lymph nodes in the body to destroy cells that may have spread.

CIK cells, along with the administration of IL-2 have been experimentally used to treat cancer in mice and humans with low toxicity.

Excellent for single-focus disease. With multi-focal disease 60% have a chronic course, 30% achieve remission and mortality is up to 10%.

Removal of the mast cell tumor through surgery is the treatment of choice. Antihistamines, such as diphenhydramine, are given prior to surgery to protect against the effects of histamine released from the tumor. Wide margins (two to three centimeters) are required because of the tendency for the tumor cells to be spread out around the tumor. If complete removal is not possible due to the size or location, additional treatment, such as radiation therapy or chemotherapy, may be necessary. Prednisone is often used to shrink the remaining tumor portion. H2 blockers, such as cimetidine, protect against stomach damage from histamine. Vinblastine and CCNU are common chemotherapy agents used to treat mast cell tumors.

Toceranib and masitinib, examples of receptor tyrosine kinase inhibitors, are used in the treatment of canine mast cell tumors. Both were recently approved by the U.S. Food and Drug Administration (FDA) as dog-specific anticancer drugs.

Grade I or II mast cell tumors that can be completely removed have a good prognosis. One study showed about 23 percent of incompletely removed grade II tumors recurred locally. Any mast cell tumor found in the gastrointestinal tract, paw, or on the muzzle has a guarded prognosis. Previous beliefs that tumors in the groin or perineum carried a worse prognosis have been discounted. Tumors that have spread to the lymph nodes or other parts of the body have a poor prognosis. Any dog showing symptoms of mastocytosis or with a grade III tumor has a poor prognosis. Dogs of the Boxer breed have a better than average prognosis because of the relatively benign behavior of their mast cell tumors. Multiple tumors that are treated similarly to solitary tumors do not seem to have a worse prognosis.

Mast cell tumors do not necessarily follow the histological prognosis. Further prognostic information can be provided by AgNOR stain of histological or cytological specimen. Even then, there is a risk of unpredictable behavior.

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.

Interdigitating dendritic cell sarcoma is a form of malignant histiocytosis affecting dendritic cells.

It can present in the spleen. It can also present in the duodenum.

Langhans cells are often found in transbronchial lung biopsies or lymph node biopsies in patients suffering from sarcoidosis.

General treatment regimens have not changed much in the past 30 years, in part due to the lack of randomized clinical trials. Surgery is the treatment of choice if the tumor is determined to be resectable. Curettage is a commonly used technique. The situation is complicated in a patient with a pathological fracture. It may be best to immobilize the affected limb and wait for the fracture to heal before performing surgery.

Patients with tumors that are not amenable to surgery are treated with radiation therapy. However caution is employed since a majority of recurrent tumors with transformations to the malignant sarcoma phenotype have been in patients receiving radiotherapy for their primary benign lesion. Pharmacotherapy for GCTOB, includes bisphosphonates such as Zoledronate, which are thought to induce apoptosis in the MNGC fraction, preventing tumor-induced osteolysis. Indeed, "in vitro" studies have shown zolidronate to be effective in killing osteoclast-like cells. More recently, humanized monoclonal antibodies such as Denosumab targeting the RANK ligand have been employed in treatment of GCTOB in a phase II study. This is based on the notion that increased expression of RANK-ligands by stromal cells plays a role in tumor pathogenesis.

Langhans giant cells (also known as Pirogov-Langhans cells) are large cells found in granulomatous conditions.

They are formed by the fusion of epithelioid cells (macrophages), and contain nuclei arranged in a horseshoe-shaped pattern in the cell periphery.

Although traditionally their presence was associated with tuberculosis, they are not specific for tuberculosis or even for mycobacterial disease. In fact, they are found in nearly every form of granulomatous disease, regardless of etiology.

Malignant histiocytosis (also known as "Histiocytic medullary reticulosis") is a rare hereditary disease found in the Bernese Mountain Dog and humans, characterized by histiocytic infiltration of the lungs and lymph nodes. The liver, spleen, and central nervous system can also be affected. Histiocytes are a component of the immune system that proliferate abnormally in this disease. In addition to its importance in veterinary medicine, the condition is also important in human pathology.

A histiocytoma in the dog is a benign tumor. It is an abnormal growth in the skin of histiocytes (histiocytosis), a cell that is part of the immune system. A similar disease in humans, Hashimoto-Pritzker disease, is also a Langerhans cell histiocytosis. Dog breeds that may be more at risk for this tumor include Bulldogs, American Pit Bull Terriers, American Staffordshire Terriers, Scottish Terriers, Greyhounds, Boxers, and Boston Terriers. They also rarely occur in goats and cattle.

Plasmacytoid dendritic cells (pDCs) are innate immune cells that circulate in the blood and are found in peripheral lymphoid organs. They develop from bone marrow hematopoietic stem cells and constitute < 0.4% of peripheral blood mononuclear cells (PBMC).

In humans they exhibit plasma cell morphology and express CD4, HLA-DR, CD123, blood-derived dendritic cell antigen-2 (BDCA-2), Toll-like receptor (TLR) 7 and TLR9 within endosomal compartments, but do not express high levels of CD11c or CD14, which distinguishes them from conventional dendritic cells or monocytes, respectively. Mouse pDC express CD11c, B220, BST-2/Tetherin (mPDCA) and Siglec-H and are negative for CD11b.

As components of the innate immune system, these cells express intracellular Toll-like receptors 7 and 9 which detect ssRNA and unmethylated CpG DNA sequences, respectively. Upon stimulation and subsequent activation, these cells produce large amounts (up to 1,000 times more than other cell type) of type I interferon (mainly IFN-α (alpha) and IFN-β (beta)), which are critical pleiotropic anti-viral compounds mediating a wide range of effects.

The number of circulating pDCs are found to be decreased during chronic HIV infection as well as HCV infection.

Langerhans cells are dendritic cells (antigen-presenting immune cells) of the skin and mucosa, and contain organelles called Birbeck granules. They are present in all layers of the epidermis and are most prominent in the stratum spinosum. They also occur in the papillary dermis, particularly around blood vessels, as well as in the mucosa of the mouth, foreskin, and vagina. They can be found in other tissues, such as lymph nodes, particularly in association with the condition Langerhans cell histiocytosis (LCH).

Research into AM functionality has been on the rise since AMs are one of the first lines of a defense against invasive pathogens. One of the most prominent fields is investigating liposomes as deliverers of antibiotics for treatment of respiratory intracellular infections. Intracellular parasites, such as M. tuberculosis, C. pneumoniae, L. monocytogenes, L. pneumophila, and F. tularensis, (to name a few) are taken up by AMs via phagocytosis, but are resistant to the biocidal mechanisms of AMs and can survive intracellularly, thus inducing severe respiratory infections. Pulmonary tuberculosis is caused by M. tuberculosis, and is now a major infectious disease worldwide and its incidence is increasing, especially in association with the AIDS pandemic. For sterilization of intracellular parasites in AMs, antibiotics are normally given orally or intravenously, but much of the antibiotics disperse to many different tissues, diminishing its effectiveness. Pulmonary administration of mannosylated liposomes is a much more direct, efficient route in targeting AMs; it enhances antimicrobial effect, reduces the dosage needed, and avoids unnecessary distribution to the blood. Since mannose receptors are exclusively expressed on the surface of AM, mannosylation of liposomes is an appealing approach to cell-selective targeting to AM. The efficacy of pulmonary administration of ciprofloxacin (CPFX) incorporated into mannosylated liposomes (mannosylated CPFX-lipososomes) was examined in rats, and determined to be an efficient means to target AMs.

Systemic corticosteroids such as (prednisone) can produce rapid improvement and are the “gold standard” for treatment. The temperature, white blood cell count, and eruption improve within 72 hours. The skin lesions clear within 3 to 9 days. Abnormal laboratory values rapidly return to normal. There are, however, frequent recurrences. Corticosteroids are tapered within 2 to 6 weeks to zero.

Resolution of the eruption is occasionally followed by milia and scarring. The disease clears spontaneously in some patients. Topical and/or intralesional corticosteroids may be effective as either monotherapy or adjuvant therapy.

Oral potassium iodide or colchicine may induce rapid resolution.

Patients who have a potential systemic infection or in whom corticosteroids are contraindicated can use these agents as a first-line therapy.

In one study, indomethacin, 150 mg per day, was given for the first week, and 100 mg per day was given for 2 additional weeks. Seventeen of 18 patients had a good initial response; fever and arthralgias were markedly attenuated within 48 hours, and eruptions cleared between 7 and 14 days.

Patients whose cutaneous lesions continued to develop were successfully treated with prednisone (1 mg/kg per day). No patient had a relapse after discontinuation of indomethacin.

Other alternatives to corticosteroid treatment include dapsone, doxycycline, clofazimine, and cyclosporine. All of these drugs influence migration and other functions of neutrophils.