Blood changes in malignant tumors

Laboratory monitoring of patients with tumors

When monitoring patients receiving systemic anti-tumor therapy (e.g., for unresectable or recurrent renal cell carcinoma), regular blood testing is of critical importance. The main goals of such monitoring are to evaluate treatment efficacy, detect disease progression, and timely diagnose adverse events (drug toxicity).

The routine protocol includes a complete blood count, general blood biochemistry, and a urinalysis. These tests are performed before starting therapy and during its course.

Following surgical intervention (radical nephrectomy or partial nephrectomy), the standard algorithm requires laboratory diagnostics and imaging at 3, 6, and 12 months in the first year, and annually for five years thereafter. However, for high-risk groups (presence of a sarcomatoid component, G3–G4 anaplasia grade, or positive surgical margins), the follow-up schedule is intensified: every 3 months in the first year and every 6 months in the second and third years, with an extended overall duration of monitoring.

Mechanisms of lymphocyte malignant transformation

In a healthy organism, malignant processes associated with B-cell proliferation occur significantly more often than T-cell tumors. The situation changes drastically in the presence of immunosuppression. Whether due to hereditary immunodeficiencies or the effects of immunosuppressants (radiation, chemotherapy), T lymphocytes are much more frequently subjected to malignant transformation under these conditions.

The general mechanism of lymphoma development is closely linked to the formation of chromosomal translocations. Proto-oncogenes relocate to chromosome regions containing genes for antigen-recognizing receptors (BCR in B cells and TCR in T cells). Since recombination (rearrangement) processes normally occur actively in these regions, viruses and mutagenic factors exploit their heightened readiness for structural rearrangements. As a consequence, malignant lymphoproliferation proves to be directly linked to the physiological activation of lymphocytes in response to antigens.

Virus-associated hemoblastoses

Infection with specific viruses is a key, albeit not the sole, condition for genetic rearrangements. Triggering the tumor process often requires the synergism of the virus with cofactors.

• Epstein–Barr virus (EBV): In combination with other factors, it is capable of causing Hodgkin's lymphoma and endemic nasopharyngeal carcinoma. Infectious mononucleosis serves as a benign model of lymphocyte activation driven by this virus.
• HTLV-1 virus: This lymphotropic virus is the primary cause of adult T-cell leukemia. Similar to HIV, it exhibits a marked tropism for CD4+ T lymphocytes, but its effect is fundamentally different—it causes tumor transformation rather than cell destruction. Endemic cofactors are also necessary for the development of the disease.

Genetic instability and tumor markers

A striking example of the link between genetic defects and blood tumors is ataxia-telangiectasia, a disease combining immunodeficiency with chromosome instability. In this syndrome, a fragment containing the TCL1 gene (an analogue of BCL2) on chromosome 14 relocates to the localization sites of T-cell receptor polypeptide chain genes. Most frequently, the target is the TCRA gene, encoding the $\alpha/\delta$ chains of the TCR, and less commonly the TCRB gene. This type of translocation leads to the development of T-cell leukemia without a proven association with a viral infection.

Malignant lymphocytes may partially retain their functions. This is well studied using the example of plasma cell malignancy—multiple myeloma. In this disease, cells synthesize immunoglobulins, which is detected during serum protein electrophoresis as a specific homogeneous peak termed the M-protein.

Class and exam questions

What else to study on this topic

• Rationale for the timing of instrumental imaging (CT, MRI, ultrasound) across various tumor recurrence risk groups.
• The role of the sarcomatoid component and G3–G4 anaplasia grades as predictors of an aggressive clinical course in neoplasms.
• Endemic cofactors required for the induction of T-cell leukemia by the HTLV-1 virus and nasopharyngeal carcinoma by the Epstein–Barr virus.
• Infectious mononucleosis as a benign clinical model of the lymphoproliferative process.

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.