Background

Mediastinal lymphoma is a type of cancer that develops in the lymphatic system, specifically within the mediastinum. Mediastinum contains vital structures like lymph nodes, thymus gland, blood vessels & heart. Lymphomas arising in this region can affect various structures, leading to a range of symptoms and complications.

These lymphomas primarily involve abnormal growth and proliferation of lymphocytes, a type of white blood cell crucial for the body’s immune response. Mediastinal lymphomas are often categorized as a subtype of non-Hodgkin lymphoma (NHL), though in some cases, they may also manifest as Hodgkin lymphoma.

Epidemiology

Incidence and Prevalence:

Approximately 2% to 4% of all non-Hodgkin lymphomas (NHLs) and 10% of all big B-cell lymphomas are caused by PMBCL. Female predominance (female/male ratio, 2:1) and median age of approximately 35 years are the main age groups affected by it.

Mediastinal lymphomas are relatively rare and account for a small percentage of all lymphomas diagnosed.

They are more commonly diagnosed in younger individuals compared to other types of lymphomas. Hodgkin lymphoma is often associated with mediastinal involvement in younger patients, particularly in their 20s and 30s.

Non-Hodgkin lymphomas, such as primary mediastinal large B-cell lymphoma (PMBCL), are also more prevalent in younger adults, predominantly affecting individuals in their late teens to early thirties.

Risk Factors:

Specific risk factors for mediastinal lymphoma are not well-defined. However, certain associations have been observed, such as:

Gender: PMBCL is more frequently diagnosed in females compared to males.

Prior history of autoimmune diseases or immune system disorders may slightly elevate the risk.

Anatomy

Pathophysiology

Abnormal lymphocyte growth: Lymphomas are cancers that originate in lymphocytes. In mediastinal lymphoma, there’s uncontrolled proliferation of abnormal lymphocytes in the lymph nodes and lymphoid tissues of the mediastinum.

Lymph node involvement: The cancerous lymphocytes accumulate and form tumors in the lymph nodes within the mediastinum. This leads to the enlargement of these lymph nodes, often causing pressure effects on adjacent structures in the chest.

Cellular characteristics: The cancerous lymphocytes in mediastinal lymphoma may be of B-cell or T-cell origin, depending on the specific subtype of lymphoma. Each subtype may have distinct clinical features and treatment implications.

Etiology

Genetic Factors: Certain genetic predispositions or abnormalities might increase the risk of developing lymphoma. Individuals with a family history of lymphoma or certain genetic mutations may have a higher susceptibility.

Immune System Dysfunction: Dysregulation or dysfunction of the immune system might contribute to the development of lymphoma.

Viral Infections: There is evidence linking certain viruses to a higher risk of lymphoma. For instance, Epstein-Barr virus (EBV), which causes infectious mononucleosis, has been associated with certain types of lymphoma, including mediastinal large B-cell lymphoma.

Environmental Factors: It’s possible that exposure to specific chemicals or environmental pollutants causes lymphoma. However, the direct causal relationship between specific environmental factors and mediastinal lymphoma is not well-defined.

Age and Gender: Lymphomas, including mediastinal lymphoma, often occur more frequently in certain age groups. Young adults, particularly women, are more commonly affected by mediastinal large B-cell lymphoma.

Genetics

Prognostic Factors

Age: Younger age at diagnosis has been associated with better outcomes in some studies. However, this may vary depending on other factors and the specific subtype of mediastinal lymphoma.

Treatment Approach: The type of treatment received, including chemotherapy regimens, radiation therapy, and targeted therapies, can significantly influence prognosis.

Presence of B symptoms: B symptoms include fever, night sweats, and unexplained weight loss. Their presence can sometimes indicate a more aggressive disease and may affect prognosis.

Tumor Size and Bulk: The size of the tumor mass and its bulk within the mediastinum can impact prognosis. Larger masses may indicate more aggressive disease and can affect the treatment approach and overall prognosis.

Clinical History

Age group

Mediastinal lymphomas can occur in individuals of various age groups, but they are most diagnosed in young adults, particularly in individuals between the ages of 20 and 40 years old. However, they can also occur in children and older adults, though less frequently. Overall, the age range for individuals diagnosed with mediastinal lymphoma can vary widely.

Physical Examination

General Signs of Illness: Patients might present with signs of systemic illness such as fever, unintentional weight loss, fatigue, night sweats, and generalized weakness.

Abdominal Examination: Sometimes, abdominal lymph nodes might also be palpable, leading to findings on abdominal examination. This might include enlarged organs like the liver or spleen.

Neurological Examination: In rare cases where the lymphoma affects the nervous system, neurological signs or symptoms might be evident, such as weakness, sensory deficits, or changes in mental status.

Lymphadenopathy: Enlarged lymph nodes in the neck, supraclavicular area, and sometimes axillary or inguinal regions might be palpable. In mediastinal lymphoma, there may be enlarged lymph nodes detected on chest examination.

Age group

Associated comorbidity

Comorbidities:

Autoimmune Diseases: Patients with a history of autoimmune disorders like rheumatoid arthritis, lupus, or Sjogren’s syndrome might have an increased risk of developing lymphomas, including mediastinal lymphoma.

Immunodeficiency: Conditions that compromise the immune system, such as HIV/AIDS or primary immunodeficiency disorders, can increase the risk of lymphoma development, including mediastinal lymphoma.

Epstein-Barr Virus (EBV) Infection: EBV, a common virus, has been associated with the development of certain lymphomas, including PMBCL. However, not all cases of mediastinal lymphoma are linked to EBV.

Activities or Factors:

Gender: PMBCL is more commonly diagnosed in young women, often in their second or third decades of life. The reasons for this gender predilection are not entirely understood.

Smoking: While the exact relationship between smoking and mediastinal lymphoma isn’t fully established, some studies suggest a potential association between smoking and an increased risk of certain types of lymphomas, though not specifically PMBCL.

Genetic Factors: There might be genetic predispositions or familial factors that contribute to the development of lymphomas, including mediastinal lymphoma.

Associated activity

Acuity of presentation

Symptoms: Patients may present with various symptoms, such as chest pain, shortness of breath, cough, fever, night sweats, weight loss, and fatigue. The acuity can range from insidious onset with mild symptoms to acute presentation with severe respiratory distress or other urgent issues.

Diagnostic Imaging: Imaging studies such as chest X-rays, CT scans, or MRI scans may reveal a mediastinal mass or enlargement of lymph nodes. The acuity might be higher if there is rapid growth or compression of nearby structures leading to urgent complications.

Biopsy and Histology: Diagnosis usually involves a biopsy of the affected tissue or lymph nodes to identify the specific type of lymphoma. The acuity may vary based on how quickly the diagnosis is made, as some types of lymphomas can progress rapidly.

Histopathological Features: The histological subtype of the lymphoma (e.g., Hodgkin lymphoma, primary mediastinal large B-cell lymphoma) and its aggressiveness influence the acuity. For instance, some types may have a more aggressive clinical course, while others progress more slowly.

Staging: Staging determines the extent and spread of the disease. Higher stages may indicate a more acute or aggressive presentation, potentially involving distant organs or widespread involvement of lymph nodes.

Treatment Response: The response to treatment can also impact the acuity of presentation. Some mediastinal lymphomas might respond well to chemotherapy or radiation therapy, leading to a rapid improvement in symptoms, while others may require more aggressive interventions.

Complications: In advanced cases, mediastinal lymphomas leads to airway compression, or cardiac compression, which can present acutely and require immediate medical attention.

Differential Diagnoses

Thymoma: Tumors originating from the thymus gland can appear like mediastinal lymphomas on imaging. Thymomas are typically slow-growing tumors that develop in the thymus.

Germ cell tumors: These tumors can arise in the mediastinum and may present with similar imaging characteristics. Germ cell tumors include teratomas, seminomas, and non-seminomatous germ cell tumors.

Sarcoidosis: This inflammatory disease can cause the formation of granulomas in various organs, including the mediastinal lymph nodes, leading to lymphadenopathy, and mimicking lymphoma.

Hodgkin lymphoma: It’s important to differentiate between Hodgkin and non-Hodgkin lymphoma, as both can present with mediastinal involvement. Hodgkin lymphoma typically presents with Reed-Sternberg cells.

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

Diagnosis and Staging: Accurate diagnosis and staging are crucial. This often involves a biopsy of the affected lymph nodes in the mediastinum (the central chest area). Additional imaging tests like CT scans, PET scans, and bone marrow biopsies may be performed to determine the extent of the disease.

Chemotherapy: The mainstay of treatment for mediastinal lymphoma is chemotherapy. Regimens like R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone) are commonly used for diffuse large B-cell lymphoma, which is a frequent type of mediastinal lymphoma. Other chemotherapy combinations might be utilized based on the specific subtype and stage of the disease.

Radiation Therapy: Radiation therapy may be used following chemotherapy to target residual disease or used concurrently in specific cases. It helps to eradicate cancer cells that might remain after chemotherapy or to shrink tumors for symptomatic relief.

Surgery: Surgery is not typically the primary treatment for mediastinal lymphoma but may be considered in certain situations. For instance, if there’s a single localized mass or if a biopsy is needed for diagnosis.

Stem Cell Transplant: In cases of relapsed or refractory disease, a stem cell transplant (autologous or allogeneic) might be considered as a consolidation therapy, especially in younger and fit patients.

Targeted Therapies and Immunotherapy: Depending on the subtype of lymphoma and individual patient characteristics, targeted therapies like monoclonal antibodies (e.g., rituximab) and newer immunotherapy drugs may be used either alone or in combination with chemotherapy.

Supportive Care: Supportive care is essential throughout treatment. This includes managing side effects, preventing infections, providing nutritional support, and addressing any psychological or emotional needs of the patient.

Follow-up Care: After completing the initial treatment, Patients usually have follow-up appointments on a regular basis to check for treatment side effects or any indications of recurrence. Follow-up includes physical exams, imaging tests, and blood work.

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

lifestyle-modifications-in-treating-mediastinal-lymphoma

Clean Air Environment: Ensure good air quality by reducing exposure to pollutants, smoke, and allergens. Use air purifiers or filters to maintain clean air indoors, especially in the patient’s living and resting areas. 

Reducing Infection Risks: Immunocompromised individuals with lymphoma are more susceptible to infections. Practice strict hygiene, encourage frequent handwashing, and limit contact with individuals who may have infections. Avoid crowded places and consider using face masks when necessary. 

Emotional Support: Foster a positive and stress-free environment by providing emotional support, encouragement, and understanding. This could include creating spaces for relaxation, engaging in activities that the patient enjoys, and promoting a supportive social network. 

Temperature Control: Ensure a comfortable temperature in the home environment. Extreme temperatures (both hot and cold) might be challenging for someone undergoing treatment. Use heating or cooling systems to maintain a suitable temperature. 

Reducing Stressors: Minimize stress triggers by organizing the environment to be calm and soothing. This might involve reducing noise levels, creating peaceful spaces, and establishing a predictable routine. 

Access to Medical Supplies: Ensure easy access to necessary medical supplies, medications, and emergency contacts. Organize these in a way that is easily accessible in case of need. 

Regular Medical Checkups: Schedule regular checkups and follow-ups with healthcare providers to monitor the patient’s condition and make necessary adjustments to their environment or treatment plan. 

Support Services: Consider utilizing support services such as counseling, support groups, or other resources that can assist both the patient and their caregivers in coping with the challenges of mediastinal lymphoma. 

Effectiveness of DA-EPOCH (<a class="wpil_keyword_link" href="https://medtigo.com/drug/etoposide/" title="etoposide" data-wpil-keyword-link="linked">etoposide</a>, prednisone, vincristine, (Oncovin), cyclophosphamide, doxorubicin in combination with rituximab in treating PMBCL

In 56 patients with newly diagnosed PMBCL, Morgenstern et al. conducted retrospective research and discovered that the rates of progression-free survival, overall survival, and complete response were comparable for DA-EPOCH-R and R-CHOP/R-ICE. 

Similar high overall survival and complete response rates were obtained with DA-EPOCH-R in a retrospective analysis by Elhagracy et al. with 41 patients; these authors favour R-CHOP over DA-EPOCH-R for low-risk patients with non-bulky illness. 

Use of growth factors in treating Non-Hodgkin’s lymphoma

Peg-filgrastim 

As a supportive care treatment, pegfilgrastim with DA-R-EPOCH and filgrastim had similar safety and efficacy results in terms of dose intensity levels and incidence of bone pain, infections, and FN. 

Effectiveness of RICE (rituximab, ifosfamide, <a class="wpil_keyword_link" href="https://medtigo.com/drug/carboplatin" title="carboplatin" data-wpil-keyword-link="linked">carboplatin</a>, and etoposide) for refractory/relapsed disease

Patients who experience a relapse in their condition frequently have extranodal disease in addition to systemic involvement. It is advised that these patients have salvage systemic chemotherapy, which will be followed by stem cell harvesting and transplantation. A popular salvage strategy includes rituximab, ifosfamide, carboplatin, and etoposide (RICE), while alternative regimens are also appropriate. 

Use of humanized anti–PD-1 monoclonal antibody for PMBCL

Pembrolizumab 

 In the phase II KEYNOTE-170 and phase IB KEYNOTE-013 trials, pembrolizumab inhibits the interaction of PD-1 with its ligands, PD-L1 and PD-L2—showed a feasible safety profile, a higher response rate, and long-lasting activity in patients with refractory or relapsed PMBCL. 

Role of CAR-T Cell therapies in treating PMBCL

axicabtagene ciloleucel (Yescarta)  

Adults suffering from B-cell lymphomas, such as PMBCL, who have not responded to or have relapsed after at least two previous forms of treatment, may receive axicabtagene ciloleucel, according to approval from the US-FDA. 

role-of-surgery-in-treating-mediastinal-lymphoma

Mediastinal lymphadenectomy: A surgical operation called a mediastinal lymphadenectomy involves removing lymph nodes from the mediastinum. 

If surgery is deemed necessary, a mediastinal lymphadenectomy might be performed as part of a larger surgical procedure to remove affected lymph nodes in the mediastinum.

The extent of lymphadenectomy and the specific nodes removed can vary depending on the individual case and the goals of the surgery. 

role-of-management-in-treating-mediastinal-lymphoma

Diagnosis: 

Clinical Assessment: This involves a thorough medical history, physical examination, and assessment of symptoms like chest pain, cough, difficulty breathing, or swelling in the neck or face. 

Imaging Studies: Imaging techniques such as chest X-rays, CT scans, PET scans, and MRI help visualize the mediastinum and detect any abnormal lymph nodes or masses. 

Biopsy: A biopsy of the affected lymph nodes or tissue within the mediastinum is crucial for confirming the diagnosis and determining the specific type of lymphoma present. 

Staging: 

The stage of lymphoma is determined based on the extent of the disease, including location & size of the tumor and involvement of nearby organs. Staging helps guide treatment decisions. 

Treatment: 

Chemotherapy: It is often the primary treatment for mediastinal lymphoma. Depending on the type and stage of the disease, various chemotherapy regimens may be used. 

Radiation Therapy: Radiation therapy can sometimes be utilised to target the mediastinum’s afflicted area, either by itself or in conjunction with chemotherapy. 

Targeted Therapy: Certain medications target specific molecules or pathways involved in lymphoma growth and may be used in combination with chemotherapy. 

Stem Cell Transplant: For some cases, especially in relapsed or refractory lymphomas, after receiving high-dose chemotherapy, it may be possible to restore damaged bone marrow with healthy stem cells through a stem cell transplant. 

Follow-up Care: 

Monitoring and Surveillance: After completion of treatment, regular monitoring through follow-up appointments and imaging examinations is crucial to detect any potential signs of recurrence or complications. 

Supportive Care: This includes managing side effects of treatment, providing supportive therapies, and addressing any physical or emotional challenges the patient faces during and after treatment. 

Clinical Trials: 

For certain people, taking part in clinical trials could be an option, offering access to innovative treatments or novel therapies that are being studied for effectiveness in mediastinal lymphoma. 

Long-Term Management: 

Long-term management involves ongoing monitoring, addressing late effects of treatment, managing potential complications, and supporting the patient’s overall health and well-being.

Medication

Future Trends

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References

Primary mediastinal B-cell lymphoma: biology and evolving therapeutic strategies – PMC (nih.gov)