Pathogenesis features and cell properties
Lymphoid cells represent an extremely heterogeneous population that varies in immunophenotypic and functional characteristics. The capacity for tumor transformation persists at virtually all stages of cellular differentiation. This is precisely what accounts for the tremendous variety of forms of lymphoproliferative disorders.
Properties of malignant lymphoid cells include:
- Presence of normal counterparts: in most cases, tumor cells clearly correspond to a specific stage of maturation of normal lymphocytes.
- Monoclonality: the basis of tumor growth.
- Genetic reorganization: during the differentiation of T and B lymphocytes, a regular reorganization of the genes encoding their receptors occurs. These changes are preserved in the tumor clone as well.
Differential diagnosis: clonality
Normally, each lymphocyte acquires its own unique antigen receptor. During tumor progression, this specific receptor is replicated many times across all daughter cells. As a result, a monoclonal population is formed.
Detecting monoclonality is of decisive diagnostic importance. This feature allows the pathologist to reliably distinguish a true tumor from reactive states or polyclonal leukemoid reactions.
Primary localization and biological unity
According to the primary site of origin, tumors are divided into two large groups:
- Lymphoid leukemias — transformation primarily occurs in the bone marrow.
- Lymphomas (lymphosarcomas) — primarily have an extra-medullary localization (lymph nodes, spleen, skin, lymphoid tissue of the gastric mucosa).
Modern medicine recognizes the concept of biological unity. It proves the affinity of leukemias and lymphomas of the same lineage regardless of where they originated (in the bone marrow or an extranodal site).
For example, acute lymphoblastic leukemia and lymphoblastic lymphoma share histogenetic similarity and common genetic aberrations, although they are not completely clinically identical. The same applies to the pair "chronic B-cell lymphocytic leukemia — small lymphocytic B-cell lymphoma." The boundary between them is blurred in the leukemic phase, when the lymphoma infiltrates the bone marrow and enters the blood.
General characteristics and classification of lymphomas
Lymphomas are malignant monoclonal tumors originating from malignant cells at various levels of differentiation (before or after contact with the thymus, lymph nodes, or spleen). They can affect any organ containing lymphoid tissue.
The disease often starts in the lymph nodes, progressing to involve new groups, the spleen, the liver, and the bone marrow. Clinically, this manifests as prominent lymphadenopathy and splenomegaly. Without treatment, tumors tend to disseminate and metastasize, with an unfavorable prognosis.
According to cytogenesis, the following are distinguished:
- B-cell neoplasms.
- T- and NK-cell neoplasms (e.g., angioimmunoblastic T-cell lymphoma, anaplastic large cell lymphoma).
- Lymphogranulomatosis (Hodgkin disease).
To verify the diagnosis according to the WHO classification, it is necessary to establish the lineage, degree of differentiation, stage of dissemination, and molecular genetic alterations.
Variants of Hodgkin disease
Hodgkin disease (lymphogranulomatosis) is classified into several morphological variants:
- Nodular lymphocyte-predominant variant.
- Classical variants: lymphocyte-rich, nodular sclerosis, mixed cellularity, and lymphocyte-depleted.
Briefly: answers to topical questions
What genetic translocations are characteristic of follicular lymphoma?
Follicular lymphoma is characterized by the chromosomal translocation t(14;18). In this mutation, a region of chromosome 18 containing the proto-oncogene bcl-2 is translocated to chromosome 14 adjacent to the immunoglobulin heavy chain locus (IGH). This leads to overexpression of the BCL2 protein, which protects tumor cells from apoptosis and sustains malignant growth.
What cells serve as the morphological substrate of Hodgkin lymphoma?
The morphological substrate of Hodgkin lymphoma consists of specific tumor cells originating from germinal center B lymphocytes. The cellular composition of the tumor population includes:
- Reed-Sternberg cells (Reed-Sternberg cell) — large binucleated blast cells.
- Hodgkin cells — mononuclear counterparts of Reed-Sternberg cells.
- Lacunar cells — a variant of tumor cells.
- Mummified cells — a variant of tumor cells.
- LP cells — lymphocytic-histiocytic cells.
These elements constitute a minority in the affected lymph node, whereas the bulk is formed by a reactive polymorphic cellular microenvironment.
What are the Ann Arbor staging stages for the extent of lymphomas?
According to the Ann Arbor classification, four stages of lymphoma dissemination are distinguished based on the number of affected regions and their location relative to the diaphragm:
- Stage I (localized) — involvement of a single lymph node region or 2 contiguous regions on the same side of the diaphragm.
- Stage II (regional) — involvement of 2 or more contiguous regions or 2 non-contiguous regions on the same side of the diaphragm.
- Stage III (generalized) — lymph node involvement on both sides of the diaphragm, but the process is limited to the lymphatic system.
- Stage IV (disseminated) — extranodal involvement extending beyond the lymphatic system with involvement of internal organs.
What clusters of differentiation (CD) are characteristic of B-cell lymphomas?
For B-cell tumors, sources indicate the following markers:
- CD19 and CD20 — for follicular lymphoma, Burkitt lymphoma, and diffuse lymphomas.
- CD19, CD20, CD23, and CD5 — for chronic B-cell lymphocytic leukemia.
- CD138 — for plasma cell tumors, including multiple myeloma.
- CD21 — a specific B-cell marker.
What types of T-cell lymphomas exist?
Nodal and extranodal (primary cutaneous) types of T-cell lymphomas are distinguished. These include:
- Angioimmunoblastic T-cell lymphoma — a nodal form.
- Anaplastic large cell lymphoma — a T/null-cell tumor with primary systemic involvement.
- Mycosis fungoides (Mycosis fungoides) is a primary epidermotropic cutaneous T-cell lymphoma.
- Sézary syndrome is a T-cell lymphoma of mature CD4+ T cells.
Class and exam questions
How to differentiate a neoplastic process in lymphoid tissue from a reactive state?
The main criterion is clonality. The tumor population is always monoclonal (cells carry the identical receptor), whereas reactive leukemoid reactions involve the proliferation of polyclonal cells.
What is the fundamental difference between leukemia and lymphoma?
The site of primary origin. Leukemias originate in the bone marrow, whereas lymphomas start in extranodal tissues (lymph nodes, spleen, skin, mucosa).
What is the leukemization of lymphoma?
This is a process of lymphoma progression in which tumor cells from the primary extranodal site begin to infiltrate the bone marrow and massively enter the peripheral blood.
What criteria are required for WHO diagnosis?
The pathologist must determine the cell lineage, their degree of differentiation, the disease stage, and specific molecular genetic alterations.
What else to study on this topic
- Immunophenotypic characteristics and clusters of differentiation (CD)
- Mechanisms of genetic rearrangement of T- and B-lymphocyte receptors
- Morphological differences of classical Hodgkin lymphoma variants
- Features of angioimmunoblastic and anaplastic large cell T-cell lymphomas
- Pathogenesis of dissemination and metastasis in non-Hodgkin lymphomas
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