creation date: 2025-09-15 16:26
tags: Pathologies
Hodgkin Lymphoma
Background
Definitions
Hodgkin lymphoma (HL) is a rare monoclonal lymphoid neoplasm. There is two distinct categories:
Classical Hodgkin lymphoma (cHL): accounts for 95% of HL and further subdivided into subgroups based on histologic and clinical differences:
- Nodular sclerosis (NSHL)
- Lymphocyte-rich (LRHL)
- Mixed cellularity (MCHL)
- Lymphocyte-depleted (LDHL)
Nodular lymphocyte-predominant Hodgkin lymphoma (NLP-HL) which varies from CHL by their presence of lymphocyte-predominant cells. This category accounts for the remaining 5% of HL and is discussed as a footnote in each section.
Etiology & Risk Factors
The exact etiology is unknown but there is an associated increased in risk of Hodgkin lymphoma with:
- Epstein-Barr virus infections
- HIV infections
- Autoimmune diseases
- Immunosuppression
- Family predisposition
Pathogenesis
Classical Hodgkin lymphoma is characterized by the presence of Hodgkin and Reed-Sternberg cells which are neoplastic cells that are mononucleated or multinucleated, respectively. These cells are on a background of non-neoplastic inflammatory cells and often surrounded by T-lymphocytes.
Hodgkin/Reed-Sternberg (HRS) cells arise from germinal centre B lymphocytes. However, HRS cells:
- Lose/down-regulate expression of B cell-specific genes
- Exhibit aberrant autocrine and paracrine signalling resulting in attraction of immune cells
- Evade immune surveillance through disturbance of MHC, inhibition of cytotoxic T cells, and recruitment of immunosuppresive regulatory T cells
- Avoid apoptosis
NLP-HL is characterized by a lack of RS cells but has lymphocytic and histiocytic cells. THese are larger cells with folded multilobulated nuclei (aka. “popcorn cells”).
Clinical Presentation
Signs & Symptoms
The typical presentation (40%) is:
- Asymptomatic lymphadenopathy
- Mass on chest imaging
- Constitutional “B” symptoms (ie. fever, night sweats, and/or unintended weight loss)
Less common presentations include:
- Alcohol-associated pain
- Liver disease
- Intra-abdominal disease
- Skin lesions
- Bone/bone marrow involvement symptoms
- Neurologic findings
- Nephrotic syndrome
- Laboratory abnormalities (eg. anemia, lymphopenia, leukocytosis, hypoalbuminemia, hypercalcemia)
History & Physical Exam
History should evaluate the presence, duration, and extent of signs and symptoms. Personal or family history of malignancies should also be evaluated.
Physical exam should consist of at least a lymph node exam and evaluate for hepatomegaly and splenomegaly.
Diagnosis
Criteria
Diagnosis of cHL is done by tissue biopsy and determination of histologic subtype. The site and type of biopsy is informed by clinical presentation but excisional or incisional biopsy is preferred.
Staging for cHL is based on the Lugano classification (based on the Ann Arbor staging system):
- Stage I: single lymph node regions (I) or of a single extralymphatic organ or site (IE) without nodal involvement. A region can include one node or a group of adjacent nodes
- Stage II: involvement of two or more lymph node regions on the same side of the diaphragm alone (II) or involvement of a limited, contiguous extralymphatic organ or tissue (IIE)
- Stage III: involvement of lymph node regions or lymphoid structures on both sides of the diaphragm
- Stage IV: additional noncontiguous extralymphatic involvement
Each stage is also further notated based on:
- Presence (“B”) or absence (“A”) of B symptoms
- Size of bulky disease
- Extranodal involvement (using subscript “E)
Work-up
Initial workup consist of:
- CBC with differential
- ESR/CRP
- Electrolytes, creatinine/eGFR
- LFTs and albumin
Consider HIV testing in at-risk populations. Imaging may be necessary preceding biopsy. Tuberculosis screening is also recommended prior to treatment with immunosuppressants.
Following diagnosis, additional workup include evaluation of extranodal involvement via PET-CT and/or MRI.
Diagnosis is made with biopsy. Findings vary based on the subtype:
Nodular sclerosis (NSHL)
- Most common in developed countries
- Histology: nodular architecture, broad bands of collagen fibrosis, lacunar variant RS cells
- Mediastinal involvement
Lymphocyte-rich (LRHL) - Histology: background rich in small lymphocytes with few RS cells
- Clinical features similar to NSHL
Mixed cellularity (MCHL) - Histology: heterogeneous inflammatory background (eg. eosinophils, plasma cells, histiocytes), classic RS cells
- Associated with immunocompromised state
Lymphocyte-depleted (LDHL) - Rare
- Histology: paucity of lymphocytes, numerous RS cells, extensive fibrosis or necrosis
Differential
A number of causes can result in lymphadenopathy with fever, sweats, weight loss etc. These include:
- Reactive processes such as infections, autoimmune, or inflammation
- EPV-positive mucocutaneous ulcer - beneign course and extranodal presentation
Red Flags / Complications
The prognosis of HL is generally favourable with a 5 year survival of stage 1 or 2a at approximately 90% and stage 4 at approximately 60%.
Complications arise from the treatment (eg. radiotherapy or chemotherapy).
Management
Pharmacological / Interventional
Early (stage I-II)
Therapy is response guided in which treatment is modified according to the results of PET after two cycles of chemotherapy (ABVD). This consist of:
- Doxorubicin hydrochloride (Adriamycin)
- Bleomycin sulfate
- Vinblastine sulfate
- Dacarbazine
Further treatment ranges from additional chemotherapy only (if complete response) to combined modality therapy consisting of ABVD, and radiotherapy (ISRT).
Treatment may also be modified based on prognosis. Favourable prognosis generally refers to limited number of nodal sites involved and no extranodal disease but other prognostic models exist.
Advanced (stage III-IV)
Initial treatment is generally Nivolumab plus AVD followed by monitoring. Chemotherapy is generally the standard of care and radiotherapy is generally not beneficial over chemotherapy and thus not routine.