Lymphoma Diagnosis and Treatment

Diagnostic Tests

Excisional lymph node biopsy with immunohistochemistry analysis is the definitive diagnostic test to differentiate between Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL), as recommended by the American Society of Clinical Oncology and the National Comprehensive Cancer Network 1, 2, 3, 4, 5, 6
Histopathologic examination is essential for diagnosis, with HL characterized by the presence of Hodgkin and Reed-Sternberg (HRS) cells, and NHL lacking HRS cells and showing various patterns of lymphocyte proliferation 7
A complete blood count with differential, comprehensive metabolic panel, lactate dehydrogenase (LDH), and uric acid levels should be performed as part of the initial evaluation 2, 3, 8
Hepatitis B and C testing, as well as HIV screening, are essential for all patients with suspected non-Hodgkin's lymphoma 2, 3

HRS cells in HL are consistently positive for CD30 and CD15, and occasionally positive for CD20, but negative for CD45 7
Non-Hodgkin lymphoma markers vary by subtype, but are typically positive for CD20 and CD45, and negative for CD15 and CD30 7
Lymphocyte predominant (LP) cells in nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) express CD20 and CD45, but lack CD15 and CD30 expression 7

PET-CT scan is preferred for staging FDG-avid lymphomas, providing metabolic information and anatomic localization, and is more sensitive than CT alone for extranodal involvement 1, 3
Contrast-enhanced CT is used for non-FDG-avid lymphomas and for precise nodal measurements, but is less sensitive than PET-CT for bone marrow involvement 1

The Ann Arbor staging system is the standard for lymphoma staging, including designation of bulky disease, with the following stages:

Stage	Description
I	Involvement of a single lymphatic region or localized involvement of a single extralymphatic organ
II	Involvement of two or more lymphatic regions on the same side of the diaphragm
III	Involvement of lymphatic regions on both sides of the diaphragm
IV	Diffuse or disseminated involvement of one or more extralymphatic organs

Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are important prognostic markers, particularly for HL 7
Lactate dehydrogenase (LDH) is an important prognostic marker and should be measured 2, 3
The International Prognostic Index (IPI) is essential for risk stratification and should be calculated for all patients with non-Hodgkin's lymphoma, as recommended by the American College of Clinical Oncology and the National Comprehensive Cancer Network 13, 2

Obinutuzumab or rituximab combined with bendamustine or CHOP are preferred first-line therapy options, depending on the clinical course, as recommended by the European Society for Medical Oncology 4
Rituximab maintenance every 2 months for 2 years after immunochemotherapy is recommended, as suggested by the European Society for Medical Oncology 4
High-dose chemotherapy with autologous stem cell transplantation (ASCT) should be considered in patients with brief first remissions after rituximab-containing regimens, with a strength of evidence of II, B, according to the European Society for Medical Oncology 4
Lenalidomide plus rituximab may be considered for patients with short remissions after chemotherapy, with a strength of evidence of II, B, according to the European Society for Medical Oncology 4

After treatment, appropriate follow-up should include physical examination every 3 months for 2 years, then every 6 months for 3 years, then annually, as well as blood counts and LDH at 3, 6, 12, and 24 months, and appropriate imaging based on initial sites of disease, as recommended by the European Society for Medical Oncology and the National Comprehensive Cancer Network 5, 13, 2, 6
PET-CT is recommended after completion of induction chemotherapy for prognostic assessment, according to the European Society for Medical Oncology 4
Response evaluation should include imaging mid-treatment and after completion of chemotherapy, as suggested by the European Society for Medical Oncology 4

A watch-and-wait approach is the standard of care for asymptomatic patients, as recommended by the European Society for Medical Oncology and the National Comprehensive Cancer Network 4, 5, 6
Indications for treatment include B symptoms, hematopoietic impairment, bulky disease, vital organ compression, ascites, pleural effusion, or rapid lymphoma progression, as recommended by the European Society for Medical Oncology and the National Comprehensive Cancer Network 4, 5, 6
Confirmatory biopsy is strongly recommended at suspected relapse, according to the European Society for Medical Oncology 4
Fertility preservation should be discussed before starting treatment, as recommended by the National Comprehensive Cancer Network 14
Tumor lysis syndrome precautions should be taken in patients with high tumor burden, according to the European Society for Medical Oncology 15
CNS prophylaxis should be considered for high-risk patients, according to the European Society for Medical Oncology 15
Hepatitis B reactivation should be tested for in all patients before anti-CD20 therapy, and prophylaxis may be needed, according to the National Comprehensive Cancer Network 3