Definition and overview of lymphoma
Lymphoma is a type of cancer that originates from lymphocytes, a type of white blood cell involved in fighting infections. This cancer has the potential to affect various tissues such as lymph nodes, bone marrow, and extranodal sites.1
Lymphoma, although relatively less common compared to other malignancies, still holds significant importance in the realm of cancer. It accounts for approximately 5% of all diagnosed malignancies1. Despite its lower prevalence, lymphoma's impact should not be underestimated, as it presents unique challenges in terms of diagnosis, classification, and treatment strategies. Understanding and addressing the complexities of lymphoma are essential for providing optimal care to affected individuals.
In this article, we want to provide an overview of lymphomas and briefly present some of the most common types of lymphoma.
Lymphoma development is influenced by various factors, including environmental, infectious, genetic, and immunological factors. Occupational exposure to certain substances, such as herbicides and pesticides, has been linked to an increased risk of lymphoma. Infections caused by organisms like Helicobacter pylori, Borrelia burgdorferi, and hepatitis C virus have been associated with specific lymphoma subtypes. Epstein Barr virus and cytomegalovirus,2,3 as well as immunodeficiency conditions, such as HIV infection and genetic immunodeficiency disorders,4 also increase the risk of lymphoma. Certain medications, autoimmune diseases, and chronic stimulation of lymphoid tissue due to persistent infections further contribute to the development of lymphoma.
Importance of understanding lymphoma types
Understanding the different types of lymphoma is really important for several reasons. Firstly, accurate classification and subtyping of lymphoma enable healthcare professionals to make precise diagnoses, which in turn guide appropriate treatment strategies. Each lymphoma subtype possesses unique clinical, pathological, and genetic characteristics that influence prognosis and treatment response.5 Furthermore, advancements in molecular research have revealed distinct subtypes within lymphoma, leading to the identification of specific genetic alterations, signalling pathways, and biomarkers that can serve as targets for novel therapies.6 Lastly, understanding lymphoma types aids in conducting meaningful research, facilitating clinical trials, and sharing knowledge among healthcare professionals, ultimately contributing to advancements in the field.7
Definition and characteristics of hodgkin lymphoma
Hodgkin lymphoma is a type of cancer characterized by the presence of abnormal cells called Hodgkin Reed-Sternberg (HRS) cells. These cells usually originate from B-cells and are found in the context of different tissue backgrounds. Classical Hodgkin lymphoma is divided into four main types: nodular sclerosing, mixed cellularity, lymphocyte-rich, and lymphocyte-depleted. There is also a non-classical type called nodular lymphocyte-predominant Hodgkin lymphoma.
This lymphoma can occur at two different age peaks, one in the early 20s and another in the mid-60s.
Clinical features, diagnosis, and staging of hodgkin lymphoma
The distinguishing feature of the classic forms of Hodgkin lymphoma is the presence of cells called Reed-Sternberg, which are large multinucleated cells with two mirror-image nuclei that resemble owl eyes. Nodular lymphocyte-predominant Hodgkin lymphoma does not exhibit the typical Reed-Sternberg but is characterized by the presence of lymphocytic and histiocytic cells. These cells are larger and have folded multilobulated nuclei, often referred to as "popcorn cells", and display nuclei with multiple basophilic nucleoli that are smaller compared to those observed in Reed-Sternberg cells.
To confirm a diagnosis of Hodgkin lymphoma, a biopsy of a lymph node or suspected organ is necessary. Laboratory tests, including a complete blood count; and imaging scans such as chest x-ray, CT, and PET/CT scans play a crucial role in determining the stage of the disease, which is important because the type of treatment is dependent on its stage.
The staging system commonly used for Hodgkin lymphoma classifies the disease into four stages:
- Stage I: the lymphoma affects a single lymph node region or lymphoid structure
- Stage II: the lymphoma involves two or more lymph node regions on the same side of the diaphragm
- Stage III: the lymphoma affects lymph nodes or structures on both sides of the diaphragm
- Stage IV: the lymphoma extends to extranodal sites
Treatment options for hodgkin lymphoma
The treatment approach for Hodgkin lymphoma depends on various factors, including histologic characteristics, disease stage, and prognostic factors. The primary goal of treatment is to achieve a cure while minimizing both short-term and long-term complications. For patients with early-stage disease and favourable prognostic features, a shorter duration of chemotherapy followed by restricted radiation therapy to the affected area is typically administered. In cases of limited-stage disease with unfavourable features, a longer course of chemotherapy (4 to 6 cycles) is followed by a higher dose of involved-field radiation therapy. For patients with advanced-stage disease different chemotherapy regimens are chosen according to the severity of the disease.8
Non hodgkin lymphoma (NHL)
Definition and characteristics of non hodgkin lymphoma
Non-Hodgkin lymphoma is a type of cancer that originates from different types of lymphoid tissues, including B cells and T cells at various stages of maturation. It can be categorized into two groups based on prognosis: indolent (slow-growing) and aggressive (fast-growing). Common types of Non-Hodgkin lymphoma include follicular lymphoma, Burkitt lymphoma, diffuse large B cell lymphoma, mantle cell lymphoma, marginal zone lymphoma, primary CNS lymphoma, adult T cell lymphoma, and mycosis fungoides.9 Indolent lymphomas often present with fluctuating lymph node enlargement over many years, while aggressive lymphomas cause specific symptoms like weight loss, night sweats, and fever, and can lead to rapid deterioration if not treated. Peripheral lymphadenopathy is a common symptom, although other manifestations such as skin rashes, increased sensitivity to insect bites, fatigue, itching, unexplained fever, ascites, and fluid accumulation can also occur. Non-Hodgkin lymphoma is more prevalent in individuals aged 65 to 74, with a median age of diagnosis around 67 years.10
Clinical features, diagnosis, and staging of NHL
The diagnosis of Non-Hodgkin Lymphoma includes several steps. A complete blood count is performed to assess for abnormalities such as anaemia, low platelet count, and abnormal white blood cell counts. Serum chemistry tests help evaluate for tumour lysis syndrome and liver involvement. Imaging, such as CT scans or PET scans, is conducted to determine the extent of the disease. Lymph node and tissue biopsy are crucial for diagnosis, with excisional biopsy being the preferred method.11 Lumbar puncture may be performed in high-risk cases to assess for central nervous system involvement. Immunophenotypic analysis of lymph nodes, peripheral blood, and bone marrow aids in characterizing the lymphoma subtype. Bone marrow aspiration and biopsy may be necessary for staging purposes, although their use is declining due to the availability of PET scans.
The current staging system used for Non-Hodgkin Lymphoma is the Lugano classification. As well as for Hodgkin's lymphoma, four stages are recognized:
- Stage I: indicates involvement of a single lymph node region or a single extranodal site without nodal involvement
- Stage II: refers to the involvement of two or more lymph node regions on one side of the diaphragm or localized involvement of an extranodal site
- Stage III: indicates lymph node involvement on both sides of the diaphragm
- Stage IV: indicates widespread involvement of one or more extranodal organs, with or without associated lymph node involvement
Treatment options for NHL
The treatment of Non-Hodgkin lymphoma depends on factors such as the specific type, stage, histopathological features, and symptoms. Common treatment options include chemotherapy, radiotherapy, immunotherapy, stem cell transplant, and occasionally surgery. A commonly used approach is chemoimmunotherapy, which combines chemotherapy with immunotherapy drugs like rituximab. Radiation therapy is primarily used for early-stage lymphoma (Stage I, II). For more advanced stages a combination of chemotherapy, immunotherapy, targeted therapy, and sometimes radiation therapy is employed.12
Primary central nervous system lymphoma (PCNSL)
Definition and characteristics of PCNSL
Primary central nervous system lymphoma (PCNSL) is an aggressive type of non-Hodgkin lymphoma that specifically affects the central nervous system (CNS), including the brain, spine, cerebrospinal fluid (CSF), and eyes. Unlike many other brain tumours, PCNSL generally responds well to chemotherapy and radiation therapy. However, when PCNSL does not respond to initial treatment, the overall prognosis is typically worse.13
Clinical features, diagnosis, and staging of PCNSL
Patients with PCNSL experience neurological symptoms over a period of weeks. These symptoms can include focal neurological deficits (such as weakness or numbness in specific body parts), changes in mental status and behaviour, symptoms related to increased pressure in the brain (such as headaches, nausea, vomiting, swelling of the optic nerve), and seizures.14 The specific symptoms depend on which parts of the central nervous system are affected.
To diagnose the disease, doctors recommend performing several tests. These include an MRI of the brain (and spine if spinal symptoms are present), evaluation by an eye specialist, and examination of the CSF. Additional tests such as a PET/CTS of the body and a bone marrow biopsy may be done to check for the involvement of non-central nervous system areas. To confirm the diagnosis of PCNSL, a stereotactic biopsy (a procedure that uses imaging guidance to obtain a tissue sample) is usually performed. In some cases, if there is evidence of eye or CSF involvement, a vitrectomy (removal of fluid from the eye) or CSF cytology (examination of CSF cells) may be sufficient for diagnosis.15
Treatment options for PCNSL
The treatment approach for PCNSL has undergone changes in recent years, but there is currently no universally agreed-upon consensus regarding the best treatment regimen. However, experts in the field concur that high-dose methotrexate (HD-MTX) plays a central role in multimodal therapy, which may involve the use of other chemotherapy drugs along with or without radiation. Several aspects of treatment remain controversial, including the role of surgery, the most effective initial chemotherapy regimen, the necessity of radiation therapy, and how to address the treatment of the cerebrospinal fluid space.
Definition and characteristics of cutaneous lymphoma
Cutaneous lymphomas are a diverse group of lymphoid neoplasms that primarily affect the skin. They can be classified into two main categories: primary cutaneous lymphomas, which originate in the skin, and secondary cutaneous lymphomas, which involve the skin as part of a systemic lymphoma.16 It is important to note that cutaneous lymphoma has different prognoses and treatment approaches compared to systemic lymphomas that share similar histological features.
Clinical features, diagnosis, and staging of cutaneous lymphoma
The clinical presentation of cutaneous lymphomas can vary widely and depends on the specific subtype. Common clinical features include skin lesions, such as erythematous patches, plaques, nodules, or tumours on the skin, that may be localized or widespread, pruritus, skin ulceration, and in aggressive forms, systemic symptoms such as fever, weight loss, and night sweats.17
The diagnosis of cutaneous lymphoma involves a combination of clinical, histopathological, immunophenotypic, and molecular studies. Key steps in the diagnostic process include skin biopsy, essential for establishing the diagnosis, on which histopathological examination is performed; immunohistochemistry or flow cytometry, used to determine the immunophenotype of the lymphoma cells; and molecular studies to detect specific genetic abnormalities associated with certain subtypes of cutaneous lymphoma.18
Treatment options for cutaneous lymphoma
Treatment options for cutaneous lymphoma are determined by factors like the subtype, stage, and individual patient characteristics. Common treatments include topical therapies, phototherapy, radiation therapy, and systemic therapies such as chemotherapy, immunotherapy, targeted therapies, and stem cell transplant.19 Decisions regarding treatment should involve a multidisciplinary team and consider the specific subtype and stage of the lymphoma, as well as the patient's overall health and preferences. Consulting healthcare professionals is essential for accurate diagnosis and treatment recommendations.
While we have attempted to provide a concise overview of lymphomas, it is important to acknowledge the complexity and diversity of this topic. Due to the numerous subtypes of lymphoma, their distinct characteristics, diagnostic methods, and treatment options, it is impossible to delve into each one in detail within this summary. It is crucial to consult with a medical specialist for accurate information and personalized advice. Our intention was to highlight the wide range of lymphoma subtypes and emphasize the significance of understanding their differences to determine the most suitable treatment approach.
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