There are two main types of lymphoma cancer known as:

• Non-Hodgkin’s Lymphoma (NHL): there are several subtypes, the most frequent are diffuse large B-cell lymphoma (DLB-CL) and follicular lymphoma (FL).
• Hodgkin’s Lymphoma (HL)

Non-Hodgkin’s Lymphoma is by far more common than Hodgkin’s Lymphoma. Overall, lymphoma cancer is the most frequent type of hematological malignancy.

STAFF

At the IEO lymphoma cancer is treated by a multidisciplinary team consisting of specialists in:

• Clinical Haemato-Oncology
• Haematopathology
• New Drugs and Early Drug Development for Innovative Therapies
• Department of Pathology and Laboratory Medicine
• Department of Medical Imaging and Radiation Sciences

Hodgkin lymphoma risk factors are:

• Previous infection with Epstein-Barr virus (EBV) infection or mononucleosis
• Weakened immune system
• Age: between ages 15-40, especially in the 20s or after age 55
• Family history

Non-Hodgkin lymphoma risk factors include:

• Age: after age 60
• Exposure to cancer-causing agents , such as benzene and herbicides and insecticides
• Previous chemotherapy or radiation therapy
• Radiation exposure
• Immune system deficiency and HIV infection
• Infection with HIV, HTLV-1, HHV8, or Epstein-Barr virus
• Chronic infection with HCV or Helicobacter pylori

The most common presentation of the lymphoma cancer is a swollen lymph node in one or more sites of the body, such as in the neck, armpit, groin, as well as in the thorax and abdomen. Patients may also have fever, weight loss or wake up at night with profuse sweats that soak their clothes.

Lymph node biopsy and histological diagnosis: excision of the swollen lymph node for microscopic examination is the most critical step in the diagnosis of lymphoma cancer.

Due to the multiple subtypes of NHL and HL, the histological examination is fundamental for the appropriate management and treatment of all patients with a lymphoma cancer. With this in mind, the IEO has set up a dedicated unit for the histological diagnosis of hematological neoplasms, with particular focus on Lymphoma. The Unit is directed by Prof. Stefano Pileri, who is a highly renowned expert in the field of pathological diagnosis of lymphoma cancer. Indeed, due to his high reputation, Prof. Pileri is one of the eight editors of the 2008 WHO Classification of Tumors of Hematopoietic and Lymphoid Tissues.

Imaging techniques: CT scan, PET scan and ultrasound are the common imaging procedures employed to evaluate the extent of the lymphoma cancer in the body (staging procedure).

Bone marrow biopsy is usually needed in order to investigate possible bone marrow involvement by the lymphoma cancer.

The treatment plan for lymphoma cancer is quite variable, depending on several factors, namely: 

1. Histological type/subtype of the lymphoma; 
2. extent of lymphoma cancer dissemination; 
3. patient age; 
4. patient characteristics and comorbidities.

In general, slowly growing forms of lymphoma cancer with no symptoms may not need any treatment or mild treatment schedules, while fast growing lymphomas necessitate immediate and often intensive therapy.

The main treatment options currently available for lymphoma cancer are, in summary:

• Chemotherapy: a number of regimens, i.e. combinations of chemotherapeutic agents, have been developed and validated for the treatment of the fast growing lymphoma cancers. These regimens are regularly administered in repeated courses and they still represent the main treatment options for several lymphoma cancers.
• Immunotherapy with humanized Monoclonal Antibody: Humanized Monoclonal antibodies were introduced in the clinical practice and had produced an unprecedented advancement in the management of most lymphoma cancers. By far, the most representative and highly effective is the anti-CD20 Rituximab Monoclonal Antibody, which has been widely employed, either alone or in combination with chemotherapy, over the last 15 years in the management of virtually all B-cell lymphomas, including the most frequent DLBCL and FL forms. The availability of Rituximab has resulted in significant improvements in cure rate and in the overall life expectancy for most B-cell lymphoma. Several novel antibodies targeting various tumor-associated antigens have been developed over the last 15 years and studies are still ongoing aimed at optimizing the therapeutic use of monoclonal antibodies and other immunotherapeutic drugs.
• Radiation therapy: this is an additional treatment option in the management of lymphoma cancer. It is generally used to kill remaining lymphoma cells at end of chemotherapy courses or as an alternative option in cases of lymphoma cancer recurrence and reduced tolerability to systemic treatments.
• Bone marrow transplantation: this type of transplant is performed using the bone marrow cells of the same person. The bone marrow cells that generate the blood elements are collected. The patient then receives a more intensive chemotherapy regimen that aims to kill all blood cancers but it also kills the bone marrow cells. So, after the intensive chemotherapy, the collected bone marrow cells are put back into the patient body to support them during the period needed for recovery from the chemotherapy effect
• Novel targeted drugs: In the last decade, impressive advancements have been obtained in the understanding of normal and pathological lymphocyte generation, with major contributions by some eminent research groups, including the group directed by Riccardo Dalla Favera at Columbia University in New York. This has led to the identification of several molecular checkpoints that are crucial for the proliferation of lymphoma cancers. As a consequence, novel lymphoma subtypes have been recognized and the WHO Classification is the unique reference text (see the front-page reported in Figure 8) for the correct pathological diagnosis of any lymphoma entity that can be now identified on the basis of specific cellular and molecular markers. As mentioned, Prof. Stefano Pileri, Director of the Hematophatology Unit at IEO, is among the eight Editors of the WHO Classification. The recently identified molecular markers have been viewed as potential therapeutic targets. Thus, novel drugs have been developed and others are under development to target molecular checkpoints that might be specifically altered in each lymphoma subtype. The present challenge is to define the ideal place of these new drugs, in combination with other effective treatment already available for lymphoma cancer. The accurate and detailed histological diagnosis for any new patient is now mandatory to optimally exploit the novel molecularly-directed drugs.