Lymphoma: A Comprehensive Guide for USMLE

Introduction

Lymphoma is a group of blood cancers that develop in the lymphatic system, a vital part of the body's immune system. It occurs when lymphocytes, a type of white blood cell, undergo abnormal growth and divide uncontrollably. Lymphoma can affect people of all ages, but is most commonly diagnosed in individuals between 15 and 35 years old, as well as those over 55. This guide aims to provide a thorough overview of lymphoma, its classification, clinical manifestations, diagnostic approaches, and treatment options.

Classification

Lymphomas are broadly categorized into two main types: Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). The key distinction lies in the presence of Reed-Sternberg cells, which are giant multinucleated cells found in HL. NHL is further divided into various subtypes, each with its own unique characteristics and prognosis. Familiarity with these classifications is essential for accurate diagnosis and appropriate management.

Hodgkin Lymphoma (HL)

HL is characterized by the presence of Reed-Sternberg cells within the lymph nodes. It accounts for approximately 10% of all lymphomas. HL is further classified into four subtypes: nodular sclerosis, mixed cellularity, lymphocyte-rich, and lymphocyte-depleted. It typically presents with painless lymphadenopathy, fever, night sweats, weight loss, and generalized pruritus.

Non-Hodgkin Lymphoma (NHL)

NHL refers to a heterogeneous group of lymphomas that lack Reed-Sternberg cells. It comprises various subtypes, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), mantle cell lymphoma (MCL), and many others. NHL can present with a wide range of symptoms, depending on the subtype and stage of the disease. Common symptoms include lymphadenopathy, fever, night sweats, fatigue, and unintended weight loss.

Clinical Manifestations

Lymphoma can present with a variety of clinical manifestations. The most common symptom is painless lymphadenopathy, involving cervical, axillary, or inguinal lymph nodes. Other general symptoms may include fever, night sweats, fatigue, unintended weight loss, and pruritus. In advanced stages, lymphoma can infiltrate various organs, leading to hepatomegaly, splenomegaly, and bone marrow involvement. Systemic symptoms, such as B symptoms (fever, night sweats, weight loss), are more commonly seen in HL than NHL.

Diagnostic Approaches

Accurate diagnosis of lymphoma involves a comprehensive approach, combining clinical evaluation, imaging studies, laboratory tests, and histopathological examination. The following diagnostic modalities are commonly employed:

1. Medical History and Physical Examination: A detailed medical history, including symptoms, risk factors, and family history, is obtained. physical examination focuses on lymph node evaluation, organomegaly assessment, and overall disease staging.
2. Imaging Studies: Imaging techniques, such as computed tomography (CT) scans, positron emission tomography (PET) scans, and magnetic resonance imaging (MRI), help identify the extent and location of lymphoma involvement.
3. Laboratory Tests: Blood tests, including complete blood count (CBC), liver function tests (LFTs), renal function tests (RFTs), lactate dehydrogenase (LDH), and beta-2 microglobulin levels, aid in assessing organ function and identifying disease-related abnormalities.
4. Lymph Node Biopsy: A definitive diagnosis of lymphoma requires histopathological examination of lymph node tissue. Excisional or incisional biopsy is performed, followed by immunohistochemistry and molecular studies to further characterize the lymphoma subtype.

Treatment Options

Lymphoma treatment depends on various factors, including the subtype, stage, patient age, and overall health status. The two main treatment modalities are chemotherapy and radiation therapy. Other therapeutic options include immunotherapy, targeted therapy, stem cell transplantation, and watchful waiting.

1. Chemotherapy: The cornerstone of lymphoma treatment, chemotherapy involves the use of cytotoxic drugs to kill cancer cells. Combination chemotherapy regimens, such as CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone), are commonly administered. Newer agents, such as rituximab and brentuximab vedotin, have shown improved outcomes in certain lymphoma subtypes.
2. Radiation Therapy: Often used in combination with chemotherapy, radiation therapy targets specific areas of lymphoma involvement. It is particularly effective in localized disease and in palliative settings to alleviate symptoms.
3. Immunotherapy: Monoclonal antibodies, such as rituximab, are used to enhance the