What is lymphoma?
Lymphomas are a group of diseases caused by malignant lymphocytes that accumulate in lymph nodes leading to lymphadenopathy. The major subdivision of lymphomas is into Hodgkin lymphoma and non-Hodgkin lymphoma.
What is Hodgkin Lymphoma?
Hodgkin lymphoma is distinguished from non-Hodgkin lymphoma by two main features. The first is the presence of Reed-Sternberg cells. The second is a strong tendency for Hodgkin lymphoma to arise within a single lymph node group and spread from one lymph node group to the next. Thus, staging has a greater influence on the treatment of Hodgkin lymphoma than on non-Hodgkin lymphomas.
What are Reed-Sternberg cells?
Reed-Sternberg cells are large, abnormal white blood cells that are found in the lymph nodes of people with Hodgkin lymphoma. They are the hallmark of this type of cancer. Reed-Sternberg cells are thought to be derived from B cells, a type of white blood cell that produces antibodies. This B cell has a ‘crippled’ immunoglobulin gene caused by the acquisition of mutations that prevent synthesis of full-length immunoglobulin. They have lost many of the characteristics of B cells and have become cancerous.
Reed-Sternberg cells are typically large and have multiple nuclei. They may also contain eosinophilic inclusion bodies, which are structures that stain pink with eosin, a type of dye used in histology.
Reed-Sternberg cells can produce a variety of cytokines, which are proteins that communicate with other cells. These cytokines can help to promote the growth and survival of Reed-Sternberg cells and can also suppress the immune system.
What are the different subtypes of Hodgkin lymphoma?
The World Health Organization (WHO) divides Hodgkin lymphoma into two main subtypes. They are the Classical Hodgkin lymphoma and Nodular lymphocyte-predominant Hodgkin lymphoma. Classical HL is the more common subtype, accounting for about 90% of cases. Nodular lymphocyte-predominant HL is a less common subtype, accounting for about 10% of cases.
Classical Hodgkin lymphoma has four subtypes.
- Nodular sclerosis is the most common form of HL in young adults. It is characterized by two pathologic findings.
- The presence of lacunar cells which are variant RS cells. Their ample cytoplasm tends to retract during formalin fixation so that they are surrounded by empty space.
- The presence of large bands of collagen that are deposited by reactive fibroblasts. This subtype is rarely associated with Epstein-Barr virus.
- Mixed cellularity HL. This subtype is most common in older males where the lymph nodes are composed of a mixture of inflammatory cells and numerous RS cells with intermediate numbers of lymphocytes. About 70% of cases are associated with EBV.
- Lymphocyte-rich HL. This is not a common subtype with predominantly small lymphocytes. About 40% of cases are associated with EBV.
- Lymphocyte-depleted subtype. This is a rare subtype except in HIV positive patients. There is a dominance of RS cells with a sparse number of lymphocytes. It is almost always associated with EBV.
Nodular lymphocyte-predominant Hodgkin lymphoma is characterized by the presence of lymphocyte-predominant cells, sometimes termed “popcorn cells,” which are a variant of Reed-Sternberg cells. It is uncommon and found primarily in young to middle-aged males within axillary or cervical lymph nodes. Classic RS cells are rare or absent.
It is important to know the subtype since it plays a large part in determining the type of treatment the patient will receive.
What are the clinical signs of Hodgkin lymphoma?
Hodgkin lymphoma (HL) is a type of cancer that starts in the lymphatic system. The lymphatic system is a network of vessels and nodes throughout the body that helps to fight infection. HL is a relatively rare type of cancer, accounting for about 1% of all cancers.
The most common clinical sign of HL is a painless, asymmetrical enlargement of the lymph nodes in the neck, underarms, or groin. The most common lymph node involvement is the cervical nodes followed by the axillary nodes and then the inguinal nodes. The lymph nodes may be firm, discrete and rubbery to the touch. Clinical splenomegaly occurs during the course of the disease in 50% of patients and is seldom massive.
- Fever
- Night sweats
- Pruritus / itching
- Alcohol-induced pain in the areas where disease is present
- Hypermetabolism symptoms
- Weight loss
- Night sweating
- Anorexia
- Cachexia
Less common clinical signs of HL may include:
- Bone pain
- Headache
- Skin rash
- Jaundice (yellowing of the skin and eyes)
- Peripheral neuropathy (numbness and tingling in the hands and feet)
How is Hodgkin lymphoma diagnosed?
Staging is performed by thorough clinical examination together with chest X-ray and CT scan to detect intrathoracic, intra-abdominal or pelvic disease. MRI scanning may be needed for particular sites while PET scan may be useful for staging and when combined with CT may detect small foci of residual disease following treatment.
Laboratory tests:
- Complete blood count (CBC) and peripheral blood smear: A CBC can show normochromic, normocytic anemia, lymphocytosis (an increased number of lymphocytes), or neutrophilia (an increased number of neutrophils) in some patients with HL. Eosinophilia is also frequent. Advanced disease is associated with lymphopaenia and loss of cell-mediated immunity.
- Serum protein electrophoresis (SPEP): A SPEP can show an elevated albumin level in patients with HL.
- Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP): Usually raised
- Serum lactodehydrogenase (LDH): Increased in 30 – 40% of cases.
- Immunofixation electrophoresis (IFE): An IFE can show an elevated monoclonal gammopathy (M protein) level in patients with HL.
Imaging studies
- X-rays: X-rays can show enlarged lymph nodes and other signs of HL.
- Computed tomography (CT) scans: CT scans can provide more detailed images of the lymph nodes and other organs in the body. CT scans can be used to look for enlarged lymph nodes and other signs of HL.
- Positron emission tomography (PET) scans: PET scans can show areas of increased metabolic activity in the body. PET scans can be used to look for enlarged lymph nodes and other signs of HL.
Diagnosis of HL
The diagnosis of HL is confirmed by the presence of Reed-Sternberg cells in a biopsy specimen of lymph node tissue. Reed-Sternberg cells are large, abnormal white blood cells that are characteristic of HL. The RS cells stain CD30 and CD15 positive but CD45- and for other B-cell markers. In contrast, nodular lymphocyte-predominant HL are uniformly positive for B-cell markers such as CD20 but CD15, CD30 and EBV negative.
Once a diagnosis of HL is confirmed, the doctor will need to determine the stage of the disease. The stage of HL is determined by the location of the cancer and the presence of certain clinical signs. The stage of HL is important for determining the prognosis for patients with HL and for guiding treatment decisions.
What are the stages of Hodgkin lympoma?
The Ann Arbor staging system is the most commonly used staging system for Hodgkin lymphoma (HL). The Ann Arbor staging system is based on the location of the cancer and the presence of certain clinical signs. The stage of HL is important for determining the prognosis for patients with HL and for guiding treatment decisions.
The Ann Arbor staging system for HL is as follows:
- Stage I: The cancer is limited to a single lymph node region or to a single organ outside of the lymphatic system.
- Stage II: The cancer is limited to two or more lymph node regions on the same side of the diaphragm, or to a single organ outside of the lymphatic system and to adjacent lymph node regions.
- Stage III: The cancer is located in lymph node regions on both sides of the diaphragm, or it is located in the spleen or bone marrow.
- Stage IV: The cancer is disseminated to multiple organs outside of the lymphatic system for example it refers to diffuse or disseminated disease in the bone marrow, liver and other extranodal sites.
In addition to the stage number, the letters A, B, E, or S may be used to further classify the stage of HL.
- Category A: The patient does not have B symptoms (unexplained fever above 38 °C, night sweats, or weight loss).
- Category B: The patient has B symptoms.
- Category E: The patient has HL cells in organs or tissues outside of the lymphatic system.
- Category X: Indication of bulky disease, a lymphoma that is greater than 10 cm (4 inches) wide
For example, a patient with HL that is localized to a single lymph node region in the neck and who does not have B symptoms would be classified as stage I, category A (I, A). A patient with HL that is located in lymph node regions on both sides of the diaphragm and who has B symptoms would be classified as stage III, category B (III, B).
The Ann Arbor staging system is a useful tool for determining the prognosis for patients with HL and for guiding treatment decisions. Patients with early-stage HL (stage I or II) generally have a good prognosis and can be cured with radiation therapy or chemotherapy. Patients with advanced-stage HL (stage III or IV) have a worse prognosis, but many patients can still be cured with more aggressive treatment regimens.
In recent years, there have been a number of advances in the treatment of HL. New drugs and treatment regimens have been developed that have improved the outcomes for patients with HL. As a result, the prognosis for patients with HL has improved significantly in recent years.
What is the current treatment for Hodgkin lymphoma?
The treatment for Hodgkin lymphoma (HL) depends on the stage of the disease and the patient’s age and health. The main goal of treatment is to achieve remission, which is a state in which there is no evidence of the disease.
Radiation therapy
Radiation therapy is a type of treatment that uses high-energy rays to kill cancer cells. Radiation therapy is often used to treat early-stage HL (stage I or II). Radiation therapy is typically given in short daily sessions over several weeks.
Chemotherapy
Chemotherapy is a type of treatment that uses drugs to kill cancer cells. Chemotherapy is typically given in cycles, with each cycle lasting several weeks. Cyclical chemotherapy is used for stage III or IV disease and also in stage I and II patients who have bulky disease, type B symptoms or have relapsed following initial radiotherapy. The combination of adriamycin, bleomycin, vinblastine and dacarbazine or ABVD is now most widely used.
Stem cell transplantation
Stem cell transplantation is a procedure in which healthy stem cells are transplanted into the patient’s body. Stem cells are the immature cells that develop into different types of blood cells. Stem cell transplantation can be used to treat patients with HL who have relapsed after initial treatment or who have not responded to initial treatment.
Immunotherapy
Immunotherapy is a type of treatment that uses the patient’s own immune system to fight cancer. Immunotherapy drugs can help to activate the immune system to kill cancer cells. Immunotherapy is a newer type of treatment for HL and is still under investigation.
Treatment for HL according to stage
The following is a general overview of the treatment for HL according to stage:
- Stage I: Radiation therapy is the most common treatment for stage I HL. Patients with stage I HL have a very good prognosis and can be cured with radiation therapy alone.
- Stage II: Radiation therapy is also the most common treatment for stage II HL. Patients with stage II HL may also need chemotherapy, depending on the specific characteristics of their cancer.
- Stage III: Patients with stage III HL typically receive chemotherapy. Patients with stage III HL who respond well to chemotherapy may also receive radiation therapy.
- Stage IV: Patients with stage IV HL typically receive chemotherapy. Patients with stage IV HL may also receive other treatments, such as radiation therapy or stem cell transplantation.
Prognosis for HL
The prognosis for HL is generally good. With treatment, most patients with HL can achieve remission. However, the prognosis for patients with HL depends on a number of factors, including the stage of the disease, the patient’s age and health, and the type of treatment received.
Patients with early-stage HL (stage I or II) have a very good prognosis and can be cured with radiation therapy or chemotherapy. Patients with advanced-stage HL (stage III or IV) have a worse prognosis, but many patients can still be cured with more aggressive treatment regimens.
Below is a synopsis on Hodgkin lymphoma.
Definition of Hodgkin lymphoma (HL)
A heterogeneous group of disorders caused by malignant lymphocytes that accumulate in lymph nodes presenting as lymphadenopathy. Hodgkin lymphoma is differentiated from non-Hodgkin lymphoma by presence of Reed-Sternberg (RS) cells and a strong predisposition to appear within one lymph node group and spread to the next.
Classification of Hodgkin lymphoma (HL)
| Classification | Characteristics | |||
| Classical Hodgkin Lymphoma | ||||
| Nodular Sclerosis | Most common in young adultsPresence of lacunar cellsPresence of large collagen bands deposited by reactive fibroblasts | |||
| Mixed Cellularity | Most common in older malesA combination of inflammatory and RS cells with lymphocytes~70% associated with Epstein-Barr virus (EBV) | |||
| Lymphocyte-rich | Predominantly small lymphocytes with scanty RS cells40% associated with EBV | |||
| Lymphocyte-depleted | Rare other than in HIV patientsPredominantly RS cells with scanty lymphocytesAlmost always associated with EBV | |||
| Nodular lymphocyte-predominant Hodgkin lymphomaUncommonPrimarily in young to middle-aged malesThe tumor cells have nuclei that are lobulated or popcorn-kernel likeClassic RS cells are rare or absent | ||||
Signs and symptoms of Hodgkin lymphoma (HL)
- Painless, asymmetrical, firm, discrete and rubbery lymphadenopathy
- Splenomegaly (~50% of cases) but seldom massive
- Fever
- Pruritus
- Alcohol-induced pain
- Hypermetabolism e.g. weight loss, cachexia, anorexia, night sweats
Laboratory investigations of Hodgkin lymphoma (HL)
- FBC & PBF: Normochromic normocytic anemia, neutrophilia, eosinophilia and lymphopenia
- Lymph node biopsy: Presence of RS cells
- ↑ ESR, CRP and serum LDH
- Immunophenotyping: CD15+, CD30+, CD45-
: CD20+, CD15-, CD30-, EBV- (nodular lymphocyte-predominant)
- Positive in situ hybridization (ISH) to EBV-encoded RNA (EBER) or detection of EBV-LMP1 (latent-membrane protein 1) by immunohistochemical staining.
Clinical staging of Hodgkin lymphoma (HL)
- Overall prognosis is excellent
- Chest X-ray and CT scan to detect intrathoracic, intra-abdominal or pelvic disease
- MRI scanning for particular sites
- Ann Arbor staging for treatment
- PET scan when combined with CT may detect small foci of residual disease following treatment
Treatment and management of Hodgkin lymphoma (HL)
- Radiotherapy and/or chemotherapy (combination of adriamycin, bleomycin, vinblastine and dacarbazine (ABVD))
- Allogeneic stem cell transplantation
