Pathogenesis and Molecular Basis
The development of the disease is driven by the aberrant activation of the NF-κB transcription factor. Normally, this protein protects B lymphocytes from apoptosis and stimulates their proliferation, but in pathology, its activity becomes uncontrolled. Causes of this activation may include:
- Somatic mutations in cells.
- The influence of Epstein–Barr virus proteins in infected cells.
Impaired apoptosis regulation leading to uncontrolled proliferation of tumor cells.
Macroscopic picture
Lymph nodes in Hodgkin's lymphoma tend to form dense conglomerates. On cross-section, the tissue appears heterogeneous, with yellowish areas of necrosis. Over time, the nodes become drier and denser due to the development of fibrosis.
Special attention should be paid to the condition of the spleen, known as "porphyry spleen". The organ enlarges and becomes dense, and the cross-section reveals red tissue with characteristic white-yellow foci and streaks.
Clinical Stages
Staging of the disease relies on the number of involved lymph node groups, their location relative to the diaphragm, and the presence of extranodal lesions:
- Stage I: involvement of a single lymph node region or a single extranodal site.
- Stage II: involvement of two or more lymph node regions on the same side of the diaphragm.
- Stage III: involvement of lymph node regions on both sides of the diaphragm, potentially with splenic involvement.
- Stage IV: diffuse involvement of extranodal organs (liver, bone marrow).
Additionally, variants A (without systemic symptoms) and B (with fever, weight loss, or sweats) are distinguished.
Briefly: answers to topical questions
Which cells are the specific morphological substrate and diagnostic criterion for Hodgkin's lymphoma?
The specific morphological substrate and diagnostic criterion for Hodgkin's lymphoma are multinucleated Reed–Sternberg cells and their mononuclear precursors, Hodgkin cells. The tumor population is represented by the following cell types:
- Reed–Sternberg cells — large cells with two or more nuclei.
- Hodgkin cells — mononuclear forms.
- Lacunar cells — feature peripheral cytoplasmic vacuoles.
- L- and H-type cells — feature multilobated or spirally folded nuclei.
- Mummified cells.
- Polymorphic multinucleated cells.
What 5 pathohistological variants of Hodgkin's lymphoma does the WHO classification distinguish?
The WHO classification distinguishes 5 pathohistological types of Hodgkin's lymphoma, divided into two groups.
Independent form:
- Nodular lymphocyte-predominant Hodgkin lymphoma — differs in pathogenesis and immunophenotype.
Classic variants:
- Lymphocyte-rich (lymphocyte-rich) — mature lymphocytes predominate.
- Nodular sclerosis — fibrous bands divide the lymphoid tissue into nodules.
- Mixed cellularity — polymorphic cellular composition.
- Lymphocyte depletion — lymphocyte count is sharply reduced, fibrosis predominates.
What immunohistochemical markers (CD antigens) are characteristic of classic Hodgkin's lymphoma?
All variants of classic Hodgkin's lymphoma share a uniform immunophenotype with the expression of specific CD antigens.
| Expression type | CD markers |
|---|---|
| Positive | CD30, CD15 |
| Variable | CD20, CD19 |
| Negative | CD45, CD3 |
The primary diagnostic markers also include PAX-5 with weak nuclear expression. In the absence of CD30 expression, the diagnosis of classic Hodgkin's lymphoma is considered doubtful and requires further investigation.
To memorize the stages, use the diaphragm rule: I — one side, II — two groups on one side, III — both sides, IV — extension beyond the lymphatic system (organs).
Class and exam questions
What are B-symptoms and why are they important?
These are systemic manifestations: fever, night sweats, pruritus, and weight loss. Their presence (the "B" modifier) significantly impacts staging and treatment tactics.
What is considered an "extranodal" lesion?
This is the involvement of organs or tissues outside the lymphatic system, such as the liver, lungs, stomach, skin, or bone marrow.
Why do opportunistic infections occur in Hodgkin's lymphoma?
Due to cell-mediated immunity deficiency, which is often observed in patients, especially in the early stages of the disease.
What else to study on this topic
- Detailed analysis of the 5 pathohistological types according to the WHO classification.
- Mechanisms of fibrosis formation in lymph nodes.
- Differential diagnosis of the "porphyry spleen" with other diseases.
- The role of the Epstein–Barr virus in lymphoma oncogenesis.
- Criteria for the transition from localized stage to generalized stage.
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