In accordance with the new classification of tumors of lymphoid tissue (WHO 2008), HIV-associated lymphomas are divided into a separate subgroup "Lymphoproliferative diseases associated with immunodeficiency". As a result of the study, it was found that the human immunodeficiency virus (HIV) significantly increases the risk of developing chronic lymphoproliferative diseases, such as non-Hodgkin's lymphomas (NHL) and Hodgkin's lymphoma. (LH). It has been epidemiologically proven that HIV-infected patients a 60–200-fold increase in the incidence of NHL is characteristic. The increase in the number of patients with NHL among HIV-infected is 5.6% per year, compared with 0.015% in the general population. The risk of NHL or primary central nervous system (CNS) lymphoma in HIV-infected individuals is strongly associated with CD4 count. One study found that NHL increased from 15.6 to 253.8 per 10,000 person-years and primary CNS lymphoma from 2 to 93.9 per 10,000 person-years in patients with a CD4 count >350 cells/µl compared to patients with<50 клеток/мкл CD4 соответственно .

In addition, it has been proven that patients with lower CD4 counts are most often diagnosed with primary CNS lymphoma and primary exudate lymphoma (PLE), while at the same time, HIV-infected patients with more high level CD4 cells reveal HL and Burkitt's lymphoma (BL).

Most HIV-associated lymphoid tumors, according to the ontogeny of lymphoid tissue cells, belong to diffuse large B-cell lymphoma (DLBCL), which also includes primary CNS lymphoma. BP in HIV-associated patients is 30-40%. PLE, plasmablastic lymphoma, and HL are much less commonly diagnosed. Other subtypes of lymphomas, such as follicular lymphoma and peripheral T-cell lymphoma, can also develop in this group, but are rare.

Pathogenesis of HIV-associated lymphomas

The pathogenesis of HIV-associated lymphoma involves a complex interplay of biological factors such as chronic antigen stimulation, co-infection with oncogenic viruses, genetic abnormalities, and cytokine dysregulation.

Chronic antigenic stimulation, which is associated with HIV infection, may initially lead to an increase in the number of polyclonal B cells and, probably, further contribute to the emergence of monoclonal B cells.

Recently, an increase in the number of circulating free light chains of immunoglobulin in patients with an increased risk of developing HIV-associated lymphoma has been noted, which may act as a marker of polyclonal B-cell activation. Current studies to identify free immunoglobulin light chains may be useful in determining whether HIV-infected individuals are at increased risk of developing lymphoma.

Most often, in approximately 40% of cases of HIV-associated lymphomas, the oncogenic Epstein-Barr virus (EBV) is detected. Almost all patients with primary CNS and HL lymphoma have EBV. In most cases of HIV-associated PLE, the association of 2 oncogenic viruses is noted: EBV and herpes virus type 8 (human herpesvirus - HHV-8), which is present in almost all patients. EBV is detected in 30–50% of HIV-associated LB and in 50% of cases of plasmablastic lymphoma (Table 1) . EBV-positive HIV-associated lymphomas often express latent membrane protein 1, which activates cell proliferation by activating the NF-kB pathway and inducing overexpression BCL2, thereby blocks apoptosis of tumor B-cells, promoting their survival.

Table 1. Association of oncogenic viruses in patients with HIV-lymphomas

Increased levels of cytokines such as IL-6, IL-10, tumor necrosis factor-β along with frequent aberrant hypermutations of somatic immunoglobulin genes indicate the role of immune stimulation in lymphoncogenesis in HIV-infected patients.

Polymorphism of chemokine pathways also affects the risk of developing HIV-associated lymphomas. For example, in HIV infection 3 ՛ A-variant factor 1 of stromal derivatives cells doubles, which 4 times increases the risk of NHL in heterozygotes and homozygotes, respectively.

Molecular genetic features of HIV-associated lymphomas

As a result of the research, whole line genetic abnormalities in HIV-associated lymphomas. A. Carbone (2003) proved that LB is associated with activation MYC gene. Interestingly, about 20% of HIV-infected patients with DLBCL also have MYC- translocation. In patients with HIV-associated lymphomas, BCL6 mutation occurs in 20% of cases with centroblast DLBCL and in 60% with PLE.

Genes associated with the germinal center B-cell like type (GCB) of DLBCL included germinal center differentiation markers such as CD10 and BCL6, while those associated with activated B-cell cell like type - ABC) DLBCL type contained IRF4/MUM1.

Several studies have found that the expression BCL2 gene was more than 4 times higher with ABC DLBCL than with DLBCL with GCB. These results suggest that the GCB and ABC DLBCL subtypes are derived from B cells at different stages differentiation. DLBCL with GCB originates from the germinal center of B cells, and DLBCL with ABC originates from the post-germ center of B cells at the stage of plasmatic differentiation of the lymphocyte.

Genetic analysis has shown that the pathogenetic mechanisms in ABC and GCB DLBCL are different. DLBCL with GCB is exclusively associated with t(14, 18) translocations involving BCL2 gene and gene of the heavy chain of immunoglobulins, as well as amplification of the c-rel locus on chromosome 2p. In addition, this lymphoma has an amplification of the oncogenic mir-17-92 microRNA cluster, a deletion of tumor suppressors PTEN and frequent anomaly BCL6 gene.

Oncogene amplification is often noted in ABC DLBCL SPIB, deletion of the tumor suppressor locus INK4a/ARF and trisomy 3, resulting in the expression of abnormal CARD11, BCL10 and A20, which activate IκB kinases and NF-kB pathways of tumor lymphogenesis.

In table. Figure 2 shows the histogenetic and molecular genetic features of lymphomas in HIV-infected patients depending on the histological origin of the tumor.

Table 2. Features of lymphomas associated with HIV infection

Notes: KSHV, Kaposi's sarcoma associated with herpes virus; MUM1 - multiple myeloma-1.

Diagnosis of HIV-associated lymphomas

The most important diagnostic test is the histological and immunohistochemical study of the material obtained from excisional biopsy.

In most cases, the histological picture of HIV-positive lymphomas is similar to those developing in HIV-negative patients.

Histological features of HIV-associated lymphomas

HIV-associated DLBCL is classified into 2 histological variants - centroblastic and immunoblastic. The centroblastic variant accounts for about 25% of HIV-associated lymphomas and is characterized by diffuse growth of large lymphoid cells with round or oval nuclei and prominent nucleoli. They often express follicle germinal center markers such as CD10 and BCL6, and generally all tumor cells are CD20 positive. The immunoblastic variant of DLBCL contains over 90% immunoblasts and often displays features of plasmacytoid differentiation. This variant of DLBCL accounts for about 10% of all HIV-associated lymphomas. This tumor is CD10 negative as it is a lymphoma from the post-fetal center of the lymph node follicle. Often, with DLBCL of the immunoblastic type, a positive expression is noted on MUM1/IRF4 and CD138/syndecan-1 markers. This tumor often has mitoses with high Ki-67/MIB-1 expression. In immunoblastic lymphoma, tumor cells may be CD20 negative due to EBV co-expression.

Activation-related markers such as CD30, CD38, CD71 are often expressed in the immunoblastic variant of DLBCL.

The tumor cell in PEL is a tumor of B-cell origin, but the tumor cells lack expression of B-cell antigens such as CD20 and CD79a. CD45, CD30, CD38, CD138 are commonly expressed and associated with KSHV/HHV-8 and EBV.

In plasmablastic lymphoma, as a rule, positive expression of CD38, CD138 and MUM1/IRF4 antigens and negative for CD20 and CD45.

HIV-associated BL is divided into 3 separate subtypes: classic, plasmacytoid, atypical. The classical type of BL is diagnosed in approximately 30% of all HIV-associated lymphomas, and morphologically it resembles the classical BL of HIV-negative patients. LP with plasmacytoid differentiation is characterized by an average cell size with abundant cytoplasm, which is much more often noted in conditions of severe immunodeficiency. In other cases, tumor cells have high nuclear pleomorphism, with a smaller but more prominent nucleus, in the past given type LB was called atypical LB. All 3 types have very high mitotic index scores with CD19, CD20, CD79a and CD10 expression and are negative for BCL2. Cases of EBV-positive LB range from 30% - with classical LB, and LB associated with plasmacytoid differentiation - 50-70%. Classical HL in HIV-infected patients is mainly represented by a mixed-cell variant, EBV is detected in almost all cases of HL. Interestingly, in the era of antiretroviral (ARV) therapy, there is a significant increase in the incidence of nodular sclerosis of HL due to a larger proportion of patients with high CD4 cell counts.

For the diagnosis of HIV-associated lymphomas, the study of gene expression is not used. But to establish the origin of DLBCL, an immunohistochemical study using CD10, BCL6, and MUM1 is necessary. According to the latest diagnostic and prognostic algorithm, additional GCET1 and FOXP1 markers need to be studied. Moreover, according to the current literature, MYC+ tumor cells in DLBCL can be used to predict the results of therapy. Proved that MYC- positive tumors respond poorly to therapy using the R-CHOP regimen. Therefore, it is reasonable to perform cytogenetic or FISH examination of the tumor to detect MYC translocations to determine the most effective treatment.

Clinical features of HIV-associated NHL

HIV-associated lymphomas are characterized by fast growth tumors. Most often in patients of this category, the presence of B-symptoms is detected (unexplained fever, night sweats, unexplained weight loss of more than 10% of normal). Bone marrow damage is diagnosed in 25-40% of patients, gastrointestinal tract - in 26%. Involvement of the CNS in the tumor process in HIV-infected patients is recorded in 12–57% of patients.

A complex of laboratory and instrumental examinations to establish the spread of the tumor process and determine the prognostic group in patients with HIV-associated lymphoma largely indistinguishable from those in HIV-negative patients.

The diagnostic and prognostic role of positron emission tomography with fluorodeoxyglucose (PET-FDG) has been proven in patients with HIV-negative aggressive lymphomas. At present, the role of PET-FDG in the diagnosis of HIV-associated lymphomas is not well understood. Previous experience with PET-FDG in patients with HIV-associated lymphomas is limited to a small retrospective analysis and requires further study. When performing PET in patients with HIV-associated lymphomas, it is also necessary to conduct a differential diagnosis of tumor lesions, nodular reactive hyperplasia, lipodystrophy, and infection.

Prognostic criteria for HIV-associated lymphomas

The International Predictive Index (IPI) is the standard prognostic criterion in HIV-negative patients with DLBCL. However, the use of MPI in patients with HIV-associated DLBCL is a controversial issue. Several studies have shown that PFS and overall survival cannot be predicted when MPI is used in patients with HIV-associated lymphomas.

Prognostic value in HIV-infected patients is the number of CD4-positive lymphocytes. It has been shown that patients with CD4<100 клеток/мкл подвержены повышенному риску развития серьезных оппортунистических инфекций и летального исхода. Кроме того, как отмечалось ранее, у больных с тяжелой иммуносупрессией более часто диагностируют иммунобластный подтип ДВККЛ, большинство из которых являются ABC, они имеют плохие результаты по сравнению с пациентами с сохраненным иммунитетом, где подтип GCB более распространенный . В последнее время опубликованы исследования, в результате которых не установлена связь между происхождением опухолевых клеток и исходом ВИЧ-ассоциированных ДВККЛ .

CNS involvement, which is increased in HIV-associated aggressive B-cell lymphomas, also carries a poor prognosis.

Treatment for HIV-associated NHL

Treatment for HIV-associated lymphomas can be divided into 2 stages: before the use of ARV therapy and after the widespread use of specific complex ARV therapy.

Treatment outcomes for HIV-associated lymphomas prior to the era of ARV therapy were poor, with median patient survival averaging 5–6 months and determined primarily by CD4 cell count. These results were associated with the development of both hematological and non-hematological complications during chemotherapy. In one study, L.D. Kaplan et al noted that high doses of cyclophosphamide correlated with poor patient survival. In an attempt to improve treatment outcomes and reduce the risk of infectious complications, a multicenter, randomized trial was conducted that compared the results of mBACOD therapy at standard doses and at dose reduction in 192 patients with HIV-associated lymphomas.

As can be seen from Table. 3, the number of complete responses, median survival in the comparison groups were not statistically different, but hematological toxicity in the group of patients using low doses in the mBACOD regimen was statistically lower. The authors concluded that lower doses of chemotherapy are preferable in patients with HIV-associated lymphomas. However, the study included patients with a low number of CD4-positive lymphocytes. In the era of widespread use of ARV therapy, the number of patients with a large number of CD4 cells has increased, which ultimately makes it possible to increase the effectiveness of therapy and reduce the infectious risk when using standard doses of chemotherapy (see Table 3) .

Table 3 Results of therapy for HIV-associated lymphomas according to clinical trials

Notes: m-BACOD - methotrexate, bleomycin, doxorubicin, cyclophosphamide, vincristine, dexamethasone; GM-CSF colony stimulating factor; CDE - cyclophosphamide, doxorubicin, etoposide; R - rituximab; CHOP - cyclophosphamide, vincristine, doxorubicin, prednisolone; VS - vincristine, prednisolone; ACVBP - doxorubicin, cyclophosphamide, vincristine, bleomycin, prednisolone; EPOCH - etoposide, prednisolone, vincristine, doxorubicin, cyclophosphamide; SC - short course; DA is the corrected dose.

The introduction of ARV therapy about 15 years ago had a significant impact on the outcome of treatment in HIV-associated lymphomas with an increase in median survival, which is explained by the beneficial effect of ARV therapy on the immune system. Patients with HIV-associated lymphomas who have preserved immune function have a lower risk of developing infectious complications, which allows them to receive optimally effective chemotherapy in full. One study showed that in patients with HIV-associated lymphoma, overall survival and progression-free survival were largely dependent on ARV therapy, rather than the intensity of doses of cytotoxic therapy.

In table. 3 presents the results of randomized trials of various regimens of cytostatic therapy in patients with HIV-associated lymphomas.

In table. 4 shows the main schemes for the treatment of HIV-associated lymphomas, the effectiveness of which is presented in table. 3.

Table 4 The main schemes of cytostatic and maintenance therapy of HIV-associated lymphomas

Considering the risk of infections during and after completion of chemotherapy, especially in patients with CD4 counts<100 клеток/мм 3 , является важным проведение профилактических мер. Все пациенты с ВИЧ-ассоциированной лимфомой, независимо от числа лимфоцитов CD4 на момент установления диагноза и проведения химиотерапии, должны получать профилактику против Pneumocystis jiroveci pneumonia, preferably with trimethoprim/sulfamethoxazole (1 tablet 2 times a day 3 times a week during therapy and until recovery of the CD4 count >200 cells/mm3). Patients with CD4 count<50–100 клеток/мм 3 также требуют назначения азитромицина 1200 мг/нед в качестве профилактики развития Mycobacterium avium. The appointment of valaciclovir for the prevention of reactivation of the herpes simplex virus is indicated only for patients who have a history of clinical manifestations of labial and anogenital herpes. Patients with HIV-associated lymphoma who have been diagnosed with hepatitis B viremia require antiviral therapy. However, monotherapy with, for example, zidovudine will increase the likelihood of a specific HIV mutation, M184V, which may contribute to the development of resistance to ARV drugs and increase the hematological toxicity of chemotherapy. Patients with mucosal infections caused by Candida should not receive azoles concomitantly with chemotherapy.

The role of ARV therapy in chemotherapy in patients with HIV-associated lymphoma

Opinions about the risks and benefits of continuing ARV therapy during chemotherapy for aggressive lymphomas are controversial. Many researchers are rightly concerned that the uncontrolled replication of HIV during chemotherapy will lead to a deterioration in immune function, and the continuation of ARV therapy during chemotherapy and restoration of immunity can prevent the development of infectious complications, especially in patients with low CD4 counts. However, clinicians should be alert to potential pharmacokinetic interactions between ARVs and chemotherapy drugs, especially in first-generation ARV drugs (zidovudine, stavudine, didanosine, protease inhibitors).

Based on the results of studying the interaction of first-generation ARV drugs and cytotoxic drugs, a number of authors recommend suspending ARV therapy during chemotherapy. Some researchers are especially concerned about their pharmacokinetic and pharmacodynamic interactions, which can lead to a decrease in the required concentration of cytostatics, increase the toxicity of chemotherapy treatment. W.H. Wilson et al., B.N. Phenix in their work showed, for example, that some classes of first-generation ARV drugs inhibit apoptosis of lymphoid cells and increase the risk of developing new HIV mutations.

Currently, new generation antiretroviral drugs such as tenofovir, emtricitabine, raltegravir are widely used, which are well tolerated, do not accumulate side effects of chemotherapeutic treatment of lymphomas and do not affect lymphocyte apoptosis. In addition, in the setting of acute opportunistic infections, a 4-week delay in initiating ARV therapy is associated with a significant increased risk of developing AIDS or death. Patients with HIV-associated lymphoma commonly have co-morbid opportunistic infections, and an average 7-week delay in ARV therapy during chemotherapy may have negative consequences overall. However, it should be remembered that patients with HIV-associated lymphoma require 4-6 cycles of chemotherapy, which can increase the duration of the interruption in ARV therapy and negatively affect patient survival in general. M.H. Bateganya and W.O. Mwanda, as a result of their studies, have proven a clear survival advantage for patients with HIV-associated lymphoma while simultaneously prescribing ARV therapy and chemotherapy.

Clinical case

Patient A., 43 years old, complained of general weakness, aching abdominal pain, heartburn, weight loss by 20 kg during the year.

Antibodies to HIV were first detected on September 7, 2012, when the patient was examined for clinical and epidemiological indications (weight loss, active chronic hepatitis C, history of injection drug user).

From the anamnesis: ill during the last year; in July 2011, a stomach ulcer was diagnosed; repeatedly carried out antiulcer therapy on an outpatient and inpatient basis, without improvement. 4 times performed fibrogastroduodenoscopy (FGDS) with biopsy. One study (February 2012) revealed esophageal candidiasis. However, vigilance about HIV infection, early diagnosis of stomach cancer was not noted.

On examination FGDS dated 08/31/2012: in the antrum along all walls there is a tumor-like formation that deforms the stomach, rigid, contact bleeding, in places with a coating of fibrin. These changes apply to the pylorus and duodenal bulb. The pylorus as such is not defined, representing a tuberous formation.

The results of histopathological examination No. 4327-40 dated 09/06/12: the material contains fragments of purulent-inflammatory granulation tissue and necrotic detritus. The picture allows us to reliably judge only the presence of an ulcerative process. Recommended control after antiulcer therapy, if possible - a second biopsy to obtain intact tissue.

On September 13, 2012, the patient applied to the AIDS Department of the clinic of the Institute of Epidemiology and Infectious Diseases named after V.I. L.V. Gromashevsky.

During additional examination: CD4 - 8.7%, which is 147 cells/µl; HIV viral load - 1325 RNA copies/ml.

A decision was made to re-examine the histological preparations obtained by biopsy dated 31.08.2012 in a specialized laboratory.

The result of histological and immunohistochemical examination No. 12CSD6049 dated 02.10.2012: smooth muscle tissue (muscle tissue of the stomach) with dense infiltration of large lymphocyte-like cells with a small number of small lymphocytes is determined in the preparations. The nucleus of tumor cells is vesicular, contains 2–3 basophilic nucleoli. There are many figures of mitosis and apoptosis in the tumor. The morphological picture is most consistent with large cell lymphoma. According to immunohistochemical analysis, tumor cells are positive for CD20, negative for CD3, CD30 and total cytokeratins. Also, tumor cells are positive for CD10, negative for bcl6, MUM-1, which indicates their origin from the germinal center. Conclusion: DLBCL of the stomach, centroblastic variant, with the phenotype of cells of the germinal (germ) center.

Further treatment and observation of the patient is carried out jointly with a hematologist. An investigation is underway.

According to the performed PET/CT: metabolically active and structural changes in the lower third of the stomach were noted, no bone-destructive changes were detected (Fig. 1).

Rice. one. The results of PET/CT in the diagnosis of gastric lymphoma in patient A.

Data analysis of biochemistry and peripheral blood are presented in table. 5, 6.

Table 5 The results of the analysis of peripheral blood of patient A.

Table 6 The results of a biochemical blood test of patient A.

Genotyping for carriage of the HLA-B*5701 allele was carried out.

Based on the results of the study, the diagnosis was made:

HIV infection. Clinical stage IV. HIV-associated non-Hodgkin gastric DLBCL IIE from the germinal center, T2N0M0. Candidiasis of the oral mucosa, esophagus. Chronic viral hepatitis C, replicative form, HCV+ RNA, genotype 3a, 1.2×10 6 copies.

Before starting chemotherapy, the patient was prescribed ARV therapy: ABC/3TC+LPV/rit (abacavir/lamivudine combination + lopinavir/ritonavir combination)

Conducted 1 course of polychemotherapy R-CHOP-21 and two courses of CHOP-21 in standard doses against the backdrop of symptomatic therapy. Rituximab was discontinued because the CD4 count decreased to 90 cells/mcL after rituximab administration and severe neutropenia developed.

After each course of chemotherapy on the 7th day, filgrastim was administered at a dose of 5 mg/kg until the absolute number of neutrophils increased by 1x10 9 /l or more. For prevention Pneumocystis jiroveci pneumonia prescribed trimethoprim/sulfamethoxol 960 mg 3 times a week continuously. In order to prevent bacterial infections, the patient took moxifloxacin 400 mg once a day for 10 days after each course of chemotherapy. Given the development of candidal stomatitis during chemotherapy, the patient was prescribed fluconazole 200-400 mg daily continuously, on average 10 days.

After completing the 3rd course of chemotherapy, the patient was diagnosed with complete remission, which was confirmed by the results of a PET-CT study on December 20, 2012 (after 3 courses of chemotherapy). When compared with the previous PET-CT dated October 11, 2012, a decrease in the thickness of the stomach walls to 0.75 cm along the lesser and greater curvature was noted. In the lower third of the stomach, the wall thickness decreased to 0.85 cm. No increase in metabolic activity was detected. Conclusion: B-cell lymphoma of the stomach, condition after 3 courses of polychemotherapy. PET-CT picture of complete metabolic regression and partially morphological (Fig. 2).

However, the patient developed rotten egg belching, vomiting of undigested food, spastic pain in the epigastric region after completion of chemotherapy. According to the X-ray examination of the stomach (December 21, 2012), decompensated stenosis of the gastric outlet was established. During FGDS (08.01.2013) the esophagus was passable, the mucosa was pale pink, edematous, there were multiple linear non-confluent erosions up to 10 mm in size. The stomach does not expand well with air, on an empty stomach the amount of cloudy secretory fluid, mucus, and bile is significantly increased. Peristalsis is preserved. The folds are preserved, elastic. Cardiac fold II degree. Diffuse erythema of the mucosa throughout the stomach. In the antrum, there is a bright spotted erythema and a mosaic pattern of the mucous membrane. The folds are rough, thickened, twisted, with an uneven surface. The pylorus is stenotic, it is impossible to pass an apparatus with a diameter of 9 mm into the duodenum. Conclusion: reflux esophagitis, stenosis of the gastric outlet (Fig. 3).

Rice. 3. X-ray of the stomach of patient A.

Taking into account cicatricial deformity of the lower third of the stomach with decompensated pyloric stenosis, alimentary cachexia and ascites, a decision was made on the advisability of surgical palliative intervention. After adequate preoperative preparation (correction of water-protein-electrolyte metabolism, establishment of a nutrient nasointestinal probe), an operation was performed in the amount of bypass anterior transverse colonic gastroenteroanastomosis with a Brownian fistula (according to Velfer-Shalimov), drainage of the abdominal cavity. The postoperative period was relatively satisfactory, without complications. Positive dynamics in the evacuation of gastric contents against the background of adequate support therapy was noted from the 10th day, which made it possible to add the introduction of oral fractional infant nutritional supplements to parenteral and enteral nutrition. Nasogastric decompression tube together with interrupted skin sutures were removed on the 14th day of the postoperative period. The patient was discharged from the hospital on the 15th day.

Thus, by the time an HIV diagnosis is made, many patients may develop lymphoma. In order to exclude a diagnostic error, the histological material should be sent for examination only to a specialized histopathological laboratory. Features of the clinical picture and treatment of HIV-associated lymphomas, as well as a high risk of developing both infectious and non-infectious complications during chemotherapy, require further study to improve the prognosis of the disease in general. Although aggressive polychemotherapy is possible in many patients with immunodeficiency, it is accompanied by severe side effects and requires well-coordinated interaction between a hematologist-oncologist and a specialist in the treatment of HIV infection, often involving specialists of a different profile in the treatment process.

List of used literature

1. Diagnostic oncohematology (2011) / Ed. D.F. Gluzman. Kyiv: DIA, 256 p.

2. Alizadeh A.A, Eisen M.B., Davis R.E. et al. (2000) Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature, 403(6769): 503–511.

3. Ambinder R.F. (2001) Epstein-Barr virus associated lymphoproliferations in the AIDS setting. Eur. J. Cancer, 37(10): 1209–16.

4. Bateganya M.H., Stanaway J., Brentlinger P.E. et al. (2011) Predictors of Survival After a Diagnosis of Non-Hodgkin Lymphoma in a Resource-Limited Setting: A Retrospective Study on the Impact of HIV Infection and Its Treatment. J. of Acquired Immune Deficiency Syndromes, 56(4): 312–319.

5. Besson C., Goubar A., ​​Gabarre J. et al. (2001) Changes in AIDS-related lymphoma since the era of highly active antiretroviral therapy. Blood, 98(8): 2339–44.

6. Biggar R.J., Jaffe E.S., Goedert J.J. et al. (2006) Hodgkin lymphoma and immunodeficiency in persons with HIV/AIDS. Blood, 108(12): 3786–91.

7. Boue F., Gabarre J., Gisselbrecht C. et al. (2006) Phase II trial of CHOP plus rituximab in patients with HIV-associated non-Hodgkin's lymphoma. J.Clin. Oncol., 24(25): 4123–28.

8. Boulanger E., Gerard L., Gabarre J. et al. (2005) Prognostic factors and outcome of human herpesvirus 8-associated primary effusion lymphoma in patients with AIDS. J.Clin. Oncol., 23(19): 4372–80.

9. Carbone A. (2003) Emerging pathways in the development of AIDS-related lymphomas. Lancet Oncol., 4(1): 22–29.

10. Carbone A., Gloghini A. (2005) AIDS-related lymphomas: from pathogenesis to pathology. Br. J. Haematol., 130(5): 662–670.

11. Castillo J.J., Winer E.S., Stachurski D. et al. (2010) Clinical and pathological differences between human immunodeficiency virus-positive and human immunodeficiency virus-negative patients with plasmablastic lymphoma. Leuk. Lymphoma, 51(11): 2047–53.

12. Chadburn A., Chiu A., Lee J.Y. et al. (2009) Immunophenotypic analysis of AIDS-related diffuse large B-cell lymphoma and clinical implications in patients from AIDS Malignancies Consortium clinical trials 010 and 034. J. Clin. Oncol., 27(30): 5039–48.

13. Choi W.W., Weisenburger D.D., Greiner T.C. et al. (2009) A new immunostain algorithm classifies diffuse large B-cell lymphoma into molecular subtypes with high accuracy. Clin. cancer. Res., 15(17): 5494–02.

14. Colomo L., Loong F., Rives S. et al. (2004) Diffuse large B-cell lymphomas with plasmablastic differentiation represent a heterogeneous group of disease entities. Am. J. Surg. Pathol., 28(6): 736-747.

15. Dalla-Favera R., Migliazza A., Chang C.C. et al. (1999) Molecular pathogenesis of B cell malignancy: the role of BCL-6. Curr. top. microbiol. Immunol., 246: 257–263.

16 . Dave S.S., Fu K., Wright G.W. et al. (2006) Molecular diagnosis of Burkitt's lymphoma. N. Engl. J. Med., 354(23): 2431–42.

17. Davis R.E., Brown K.D., Siebenlist U. et al. (2001) Constitutive nuclear factor kappaB activity is required for survival of activated B cell-like diffuse large B cell lymphoma cells. J. Exp. Med., 194(12): 1861–74.

18. Davis R.E., Ngo V.N., Lenz G. et al. (2010) Chronic active B-cell-receptor signaling in diffuse large B-cell lymphoma. Nature, 463(7277): 88–92.

19. Dunleavy K., Little R.F., Pittaluga S. et al. (2010) The role of tumor histogenesis, FDG-PET, and short-course EPOCH with dose-dense rituximab (SC-EPOCH-RR) in HIV-associated diffuse large B-cell lymphoma. Blood., 115(15): 3017–24.

20. Dunleavy K., Wilson W.H. (2010) Role of molecular subtype in predicting outcome of AIDS-related diffuse large B-cell lymphoma. J.Clin. Oncol., 8(16): e260–e262.

21. Dunleavy K., Mikhaeel G., Sehn L.H. et al. (2010) The value of positron emission tomography in prognosis and response assessment in non-Hodgkin lymphoma. Leuk. Lymphoma., 51 suppl 1: 28–33.

22. Fan W., Bubman D., Chadburn A. et al. (2005) Distinct subsets of primary effusion lymphoma can be identified based on their cellular gene expression profile and viral association. J. Virol., 79(2): 1244–51.

23. Gaidano G., Capello D., Carbone A. (2000) The molecular basis of acquired immunodeficiency syndrome-related lymphomagenesis. Semin. Oncol., 27(4): 431–441.

24. Gaidano G., Capello D., Cilia A.M. et al. (1999) Genetic characterization of HHV-8/KSHV-positive primary effusion lymphoma reveals frequent mutations of BCL6: implications for disease pathogenesis and histogenesis. Genes Chromosomes Cancer., 24(1): 16–23.

25. Gaidano G., Carbone A., Pastore C. et al. (1997) Frequent mutation of the 5' noncoding region of the BCL-6 gene in acquired immunodeficiency syndrome-related non-Hodgkin's lymphomas. Blood., 89(10): 3755-62.

26. Hans C.P., Weisenburger D.D., Greiner T.C. et al. (2004) Confirmation of the molecular classification of diffuse large B-cell lymphoma by immunohistochemistry using a tissue microarray. Blood, 103(1): 275–282.

27. Hummel M., Bentink S., Berger H. et al. (2006) A biologic definition of Burkitt's lymphoma from transcriptional and genetic profiling. N. Engl. J. Med., 354(23): 2419–30.

28. Kaplan L.D., Lee J.Y., Ambinder R.F. et al. (2005) Rituximab does not improve clinical outcome in a randomized phase 3 trial of CHOP with or without rituximab in patients with HIV-associated non-Hodgkin lymphoma: AIDS-Malignancies Consortium Trial 010. Blood, 106(5): 1538–43.

29. Kaplan L.D., Straus D.J., Testa M.A. et al. (1997) Low-dose compared with standard-dose m-BACOD chemotherapy for non-Hodgkin's lymphoma associated with human immunodeficiency virus infection: National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group. N. Engl. J. Med., 336(23): 1641-48.

30. Klein U., Gloghini A., Gaidano G. et al. (2003) Gene expression profile analysis of AIDS-related primary effusion lymphoma (PEL) suggests a plasmablastic derivation and identifies PEL-specific transcripts. Blood, 101(10): 4115–21.

31. Landgren O., Goedert J.J., Rabkin C.S. et al. (2010) Circulating serum free light chains as predictive markers of AIDS-related lymphoma. J.Clin. Oncol., 28(5): 773–779.

32. Little R.F., Wilson W.H. (2003) Update on the pathogenesis, diagnosis, and therapy of AIDS-related lymphoma. Curr .Infect. Dis. Rep., 5(2): 176–184.

33. Lenz G., Staudt L.M. (2010) Aggressive lymphomas. N. Engl. J. Med., 362(15): 1417–29.

34. Lenz G., Wright G.W., Emre N.C. et al. (2008) Molecular subtypes of diffuse large B-cell lymphoma arise by distinct genetic pathways. Proc. Natl. Acad. sci. U S A., 105(36): 13520–25.

35. Lenz G., Davis R.E., Ngo V.N. et al. (2008) Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science, 319(5870): 1676–79.

36. Little R.F., Pittaluga S., Grant N. et al. (2003) Highly effective treatment of acquired immunodeficiency syndrome-related lymphoma with dose-adjusted EPOCH: impact of antiretroviral therapy suspension and tumor biology. Blood, 101(12): 4653–59.

37. Mounier N., Spina M., Gabarre J. et al. (2006) AIDS-related non-Hodgkin lymphoma: final analysis of 485 patients treated with risk-adapted intensive chemotherapy. Blood, 107(10): 3832–40.

38. Mwanda W. O., Orem J., Fu P. et al. (2009) Dose-Modified Oral Chemotherapy in the Treatment of AIDS-Related Non-Hodgkin's Lymphoma in East Africa. J.Clin. Oncol., 27 (21): 3480–88;.

39. Ngo V.N., Davis R.E., Lamy L. et al. (2006) A loss-of-function RNA interference screen for molecular targets in cancer. Nature, 441(7089): 106–110.

40. Parekh S., Polo J.M., Shaknovich R. et al. (2007) BCL6 programs lymphoma cells for survival and differentiation through distinct biochemical mechanisms. Blood, 110(6): 2067–74.

41. Phenix B.N., Cooper C., Owen C. et al. (2002) Modulation of apoptosis by HIV protease inhibitors. Apoptosis, 7(4): 295–312.

42. Phenix B.N., Lum J.J., Nie Z. et al. (2001) Antiapoptotic mechanism of HIV protease inhibitors: preventing mitochondrial transmembrane potential loss. Blood, 98(4): 1078–85.

43. Rabkin C.S., Yang Q., Goedert J.J. et al. (1999) Chemokine and chemokine receptor gene variants and risk of non-Hodgkin's lymphoma in human immunodeficiency virus-1-infected individuals. Blood, 93: 1838.

44. Ratner L., Lee J., Tang S. et al. (2001) Chemotherapy for human immunodeficiency virus-associated non-Hodgkin's lymphoma in combination with highly active antiretroviral therapy. J.Clin. Oncol., 19(8): 2171–78.

45. Ribera J.M., Oriol A., Morgades M. et al. (2008) Safety and efficacy of cyclophosphamide, adriamycin, vincristine, prednisone and rituximab in patients with human immunodeficiency virus-associated diffuse large B-cell lymphoma: results of a phase II trial. Br. J. Haematol., 140(4): 411-419.

46. Rothe M., Sarma V., Dixit V.M. et al. (1995) TRAF2-mediated activation of NF-kappa B by TNF receptor 2 and CD40. Science., 269(5229): 1424–27.

47. Sparano J.A., Lee J.Y., Kaplan L.D. et al. (2010) Rituximab plus concurrent infusional EPOCH chemotherapy is highly effective in HIV-associated B-cell non-Hodgkin lymphoma. Blood, 115(15): 3008–16.

48. Sparano J.A., Lee S., Chen M.G. et al. (2004) Phase II trial of infusional cyclophosphamide, doxorubicin, and etoposide in patients with HIV-associated non-Hodgkin's lymphoma: an Eastern Cooperative Oncology Group Trial (E1494). J.Clin. Oncol., 22(8): 1491-1500.

49. Spina M., Jaeger U., Sparano J.A. et al. (2005) Rituximab plus infusional cyclophosphamide, doxorubicin, and etoposide in HIV-associated non-Hodgkin lymphoma: pooled results from 3 phase 2 trials. Blood, 105(5): 1891–97.

50. Swerdlow S.H., Campo E., Harris N.L. et al. (2008) WHO Classification of Tumors of Haematopoietic and Lymphoid Tissues. Lyon, France: IARC.

51. Thompson L.D., Fisher S.I., Chu W.S. et al. (2004) HIV-associated Hodgkin lymphoma: a clinicopathologic and immunophenotypic study of 45 cases. Am. J.Clin. Pathol., 121(5): 727-738.

52. Tulpule A., Sherrod A., Dharmapala D. et al. (2002) Multidrug resistance (MDR-1) expression in AIDS-related lymphomas. Leuk. Res., 26(2): 121-127.

53 . Vega F., Chang C.C., Medeiros L.J. et al. (2005) Plasmablastic lymphomas and plasmablastic plasma cell myelomas have nearly identical immunophenotypic profiles. Mod. Pathol., 18(6): 806–815.

54. Zolopa A.R., Andersen J., Komarow L. et al. (2009) Early Antiretroviral Therapy Reduces AIDS Progression/Death in Individuals with Acute Opportunistic Infections: A Multicenter Randomized Strategy Trial. PLOS. One, 4(5): e5575.

55. DeVitaV.T., Lawrence T.S., Rosenberg S.A. (2012) Cancer: Principles & Practice of Oncology, 9e

VIL-associated non-Hodgkin's lymphoma

O.A. Karnabeda 1, L.I. Getman 2 , S.M. Antonyak 2 , T.V. Roslyakova 3 , O.V. Shuliga-Nedaykhlibova 3

1 National Medical University named after O.O. Bogomolets
2 Institute of Epidemiology and Infectious Diseases named after L.V. Gromashevsky
3 Medical clinic "Innovation"

Summary. The article presents the features of the clinical picture, diagnosis and treatment of VIL-associated non-Hodgkin's lymphomas. The majority of VIL-associated lymphomas is consistent with the WHO 2008 classification of diffuse B-large-cell lymphomas. For VIL-associated lymphomas, a typical swelling growth is characteristic, often in these patients, the presence of B-symptoms is indicated. Lesions of the cystic cerebellum are diagnosed in 25–40% of patients, and those of the intestinal tract in 26%. Radiation in the swelling process of the CNS in HIV-infected patients is recorded in 12–57% of patients. Patients with VIL-associated lymphomas, in whom the immune function is preserved, may have a greater low risk of developing infectious conditions, which allows them to recognize optimally effective chemotherapy in the general condition.

Keywords:ВІL-associated lymphoma, lіkuvannya, diagnostics.

HIV-associated non-Hodgkin lymphoma

O.A. Karnabeda 1 , L.I. Getman 2, S.N. Antoniak 2, T.V. Roslyakova 3 , O.V. Shuliga-Nedaykhlibova 3

1 National Medical University named after O.O. Bogomolets
2 Institute of Epidemiology and Infectious Disease named after L.V. Gromashevsky
3 "INNOVACIA" Cancer Center

summary. In this article the clinical features, diagnosis, and treatment of HIV-associated non-Hodgkin's lymphoma. Most HIV-associated lymphoid tumors, according to the WHO classification, 2008 are diffuse large cell lymphoma. For HIV-of associated lymphomas characterized by rapid growth of the tumor and the most common in these patients is determined by the presence of B-symptoms. Bone marrow is diagnosed in 25–40% of patients, gastrointestinal tract in 26%. During the process of attraction in the CNS tumor in HIV-infected is determined in 12–57% of patients. Patients with HIV-associated lymphomas, which immune function is preserved, have a lower risk of infection, so you can prescribe them to an optimally-effective chemotherapy in full.

key words: HIV-associated lymphoma, treatment, diagnosis.

Cerebral lymphoma is a rare but extremely dangerous disease. Elderly people and those with weakened immune systems are prone to its appearance. Unfortunately, to date, this type of medicine has not been invented for oncology, and patients can only count on delaying the inevitable death.

Causes of Lymphoma

The reasons why lymphoma develops are conventionally divided into two categories. This is the influence of external factors and internal processes in the body. The environment plays an important role in the development of brain oncology.

Living or working in an area with high radiation in 97% of cases provokes the development of cancer. A prerequisite for the appearance of the disease is also the influence of such toxic substances as vinyl chloride, a gas that is used in many industries, asparkam, used as a sugar substitute.

There is a version that electromagnetic radiation from mobile phones and power lines can lead to lymphoma. Although this theory has not received scientific confirmation.

Internal factors that become the impetus for the development of lymphoma are:

• undergoing radiation therapy to treat any disease;
• weakened immunity as a result of HIV infection;
• immunodeficiency after prevention of rejection of implanted donor organs.

Genetic predisposition plays an important role in the development of brain cancer. Medicine knows cases when lymphoma affected relatives of the first order. In such patients, multiple tumors of a benign nature appear in adolescence, but without proper treatment they can transform into cancer cells. Of parents diagnosed with HIV, more than 10% of children are born with brain lymphoma.

Also, oncology can appear against the background of mononucleosis, Epstein-Barr virus disease and chromosomal mutations. Recently, doctors have noted an increase in the number of patients with brain cancer. The reason for this was the deterioration of the general environmental situation in large cities and the nutritional habits of modern man. Increasingly, a large number of foods containing carcinogens began to be consumed in food.

Types of brain lymphomas

Brain cancer is classified into several types. Thus, it is easier to make a general picture of the disease and choose the right treatment.

1. Reticulosarcoma. Originates from reticulum cells. In practice, it is extremely rare, so it was not possible to find out the history of its origin until the end. The disease is easily confused with lymphosarcoma. The symptomatology of reticulosarcoma is multiple and depends on the place of its localization and stage of development. Initially appears in the lymph nodes. The disease is sensitive to radiation therapy. With early diagnosis and treatment, the patient has approximately 10 years of remission.


2. Microglioma. The most dangerous type of lymphoma, since the place of its localization does not always allow for a full treatment. Malignant cancer cells grow very quickly and are almost incurable. Benign neoplasms spread more slowly, may not manifest themselves for quite a long time. Microglioma is diagnosed in half of patients with brain tumors. The disease appears from glial tissues at the cellular level. It is the primary type of formations that do not penetrate into the bone cranial tissue and into the inner lining of the brain. It has the appearance of a dense clot of pinkish or reddish-gray color without clear boundaries. It can grow up to 15 cm in diameter. The disease can affect anyone, including children.
3. Diffuse histiocytic lymphoma. In the process of the course of the disease, the destruction of both individual brain cells and its tissues occurs. Metastases spread quite quickly, are diffuse in nature and, when germinating into healthy tissues, give new impulses to the central nervous system. The patient feels hot, sweats profusely and rapidly loses weight. But, despite the fact that this type of oncology has an aggressive form, it is quite treatable.

Depending on the site of manifestation of lymphoma, a single or multiple isolated lesion of the brain tissue is divided. In 10% of cases, the eyes are affected with involvement of the meninges, with spread to the spinal cord.

Symptoms of the manifestation of lymphoma

In brain lymphoma, the symptoms do not have any specific manifestations, which greatly complicates the diagnosis of the disease. Oncology can be suspected by the following signs:

• increased intracranial pressure, causing persistent headaches that do not go away after taking painkillers, increase in the morning, in a supine position, when bending over. May be accompanied by nausea or vomiting;
• turning off certain functions of the part of the brain that the tumor presses on. This may be a paralysis of the facial nerve, loss of speech, decreased vision, complete or partial loss of sensation on any side of the body, etc .;
• mental disorders. A sick person loses concentration, becomes distracted, practically does not answer questions. The feeling of drowsiness increases, which can develop into lethargy. In some cases, a person can become rude, jokes become flat, the feeling of self-criticism disappears, appetite increases up to voracity;
• epileptic seizures. Periodically there are convulsions with loss of consciousness or twitching of any muscle group. These symptoms occur with the following frequency: neurological deficit in 70% of cases, mental disorders in 43%, signs of intracranial hypertension in 33%, convulsions in 14%. In patients with HIV, epileptic seizures occur in 25% of cases, and encephalopathy often develops at the age of 30-40 years.

In the later stages of lymphoma, personality changes occur. A person becomes emotionally unstable, his reactions are unpredictable, memory lapses appear.

Diagnosis of brain lymphoma

Diagnosing brain cancer is not easy. Usually, a blood test does not show the presence of pathological changes in the body, and the symptoms are uninformative. If you suspect the presence of lymphoma, the doctor should conduct a complete examination of the patient. To begin with, a series of neurological tests are carried out to help identify violations in reflex function, coordination of movements, the functioning of muscles and sensory organs. A full diagnosis is possible only with a complete clinical picture, but in this case there is practically no chance of a surgical cure. For the early diagnosis of brain lymphoma, a number of instrumental and laboratory methods including the following activities:

• magnetic resonance therapy, which is carried out by introducing a contrast agent through a vein into the body. Brain lymphoma on MRI is visible on the computer due to the accumulation around the formation of this substance. that accumulates around the neoplasm;
• tomography will show the presence of a tumor in the body;
• trepanobiopsy - a study of biomaterial taken from brain tissue after opening the skull;
• stereotactic biopsy. This is a biopsy analysis, which is obtained by taking brain tissue through a hole made in the skull;
• electroencephalogram. It is used to detect the focus of violations of the brain biopotential, their criticality and influence on the activity of the central nervous system as a whole;
• x-ray allows you to consider the presence of secondary signs of lymphoma and hypertension inside the brain;
• for the examination of infants, the method of ultrasonography is used.

In addition to all of the above, the patient is prescribed a blood test and biochemistry. To determine the primary lymphoma of the brain, x-rays are performed, for the secondary - ultrasound.

Ways to treat brain cancer

Having diagnosed brain lymphoma, treatment is prescribed based on the stage of development of the disease, the location of the tumor and its size. It is not always possible to select the correct therapy due to the blood-brain barrier, which delays the medications entering the body and neutralizes some of their components. In total, there are three ways to stop the development of metastases at least temporarily: chemotherapy, radiation therapy and surgery.

Chemotherapy

Cerebral lymphoma responds well to treatment with chemotherapy. Depending on the type of tumor and its sensitivity to a different group of drugs, mono or polychemotherapy may be prescribed. The drugs are administered to the patient by spinal puncture, because. It is this approach that gives the maximum effectiveness of drugs.

The choice of certain medications is determined only by the attending physician. Usually, Methotrexate is prescribed for a course of monochemotherapy. If it is necessary to use a combination of agents, then Cytarabine, Temozolomide or Etoposide are preferred.

Despite the fact that chemotherapy has good prerequisites for achieving remission, it is not without negative consequences. This is due to the fact that drugs act not only on diseased cells, but also on healthy ones. Manifestation side effects depends on the chosen medicine and its dosage. This can be severe nausea and dizziness, hair loss, dry mouth, weight loss, malfunction of the gastrointestinal tract and a decrease in the protective functions of the body. If chemotherapy has given positive results, and there is no place for secondary infection, then the patient can expect remission in several years.

Radiation therapy

Treatment by radiation is a proven and effective method, but not always in the case of brain lymphoma. If it is used, then only in combination with "chemistry" or a bone marrow transplant operation. This decision is especially relevant for patients with a history of HIV.

Surgical intervention

Operations to remove a tumor in the head are practically not carried out, because. this can lead to disruption of mental and nervous activity. Any attempts at radical intervention led to injuries of brain structures at a deep level.

The only type of surgery that is possible in the case of brain cancer is a stem cell transplant. But this procedure is performed only for patients at a young age and does not guarantee a positive result.

Prognosis for lymphoma

With brain lymphoma, the prognosis for survival is not encouraging. According to statistics, only 75% of patients receive remission for up to 5 years, but on condition that the therapy was carried out on time. In old age, the figure decreases to 40%. Possible relapses increase the mortality among patients by almost two times. Good indicators can be obtained if radical therapy is carried out and the tumor is not allowed to grow in a short period of time. In such cases, the lifespan can be extended up to 10 years.

Source: www.oonkologii.ru

General concept of lymphomas of the central nervous system

The neoplasm is more often a secondary lesion in stage 4 of various types of non-Hodgkin's lymphomas. That is, initially, growth is noted in the lymph nodes, then dissemination occurs with the formation of extranodal (extranodal) foci.

Primary lymphoma of the central nervous system (PCNS) is a tumor originating from the lymphoid tissue that originated in the brain or spinal cord and does not go beyond them. To make such a diagnosis, a thorough examination and complete confidence in the absence of a lesion outside the nervous system is necessary.

Among the primary localizations, PLCNS ranks second after gastric lymphomas. It is quite rare (in the structure of primary brain tumors, its share is not more than 5%). Global incidence figures are 5-5.5 per 1 million population.

However, in recent decades there has been a significant increase in non-Hodgkin's lymphomas, including PLCNS. Therefore, when conducting a differential diagnosis of space-occupying formations of the central nervous system, this type of malignant formations should always be borne in mind.

Interest in this tumor is also due to the fact that it is extremely sensitive to chemotherapy and in 50% of cases it is possible to achieve complete remission.

Morphologically, PLCNS is represented in 90% by diffuse large B-cell lymphoma. This is a highly malignant form.

At-risk groups

The main one is patients with immunodeficiency. PLCNS is diagnosed in 6-10% of HIV-positive individuals. On average, this complication occurs 5 years after the initial diagnosis of HIV infection. In almost 100% of cases, the appearance of lymphoma in these patients is associated with the Epstein-Barr virus. The average age of patients is 30-40 years, 90% of them are men.

The second group in which PLCNS occurs much more often than the rest (according to some sources, 150 times) are those receiving immunosuppressive therapy in connection with organ transplantation. The average age of the patients is 55 years.

An increase in the incidence is also observed in people without immunodeficiency. However, in this group, the median age is higher - over 60 years. Men also get sick more often (3:2 against women). The reasons for the growth are not reliably clear, doctors adhere to the viral theory.

Classification of CNS lymphomas

There is no staged gradation of PLCNS. The presence of one or more foci, as well as damage to various parts of the central nervous system, does not affect the prognosis of the disease and the choice of treatment method.

Lymphomas are classified according to anatomical localization: single or multiple isolated lesion of the brain tissue, foci in the brain with involvement of the eye (in 10% of cases), with involvement of the meninges, with spread to the spinal cord, isolated lesion of the spinal cord, isolated lesion of the eye. In 85% of cases, primary cerebral lymphoma is located supratentorially, that is, in the hemispheres, and in 15% - infratentorially (cerebellum, ventricular region, brain stem). In the hemispheres, the frontal lobes are more often affected (20%).

What does CNS lymphoma look like?

By localization, the tumor can manifest itself as single foci, different in size, located in the hemispheres, in the basal ganglia, and in the corpus callosum. In 35% of cases, there are many foci (more often in people with immunodeficiency). Spinal cord lesions can occur initially (70% in the lumbar region) or spread from the brain through the medulla oblongata by direct infiltration (cervical and thoracic), as well as dissemination of tumor cells into the cerebrospinal fluid.

Microscopically, lymphoma is a perivascular (around the vessels) accumulation of immunoblasts or centroblasts with infiltration of brain tissue.

Symptoms

Brain

There is no specific symptom complex in this tumor. Clinically, it is possible to suspect a volumetric formation of the brain on the following grounds:

1. Increased intracranial pressure. It manifests itself as a bursting headache, which is not relieved by conventional painkillers, increases in the morning, in the supine position, when bending over, accompanied by nausea or vomiting.

2. Neurological deficit. This is the loss of certain functions due to the shutdown of the part of the brain that the tumor presses on.

• Violation of the movement of the limbs (with damage to the left frontal lobe - on the right, with right-sided localization - on the left). Movements are either completely absent (paralysis) or severely limited (paresis).
• Aphasia is a speech disorder.
• Double vision or loss of visual fields, a sharp decrease in vision.
• Swallowing disorders (choking).
• Change in the sensitivity of the right or left half of the body.
• Paralysis of the facial nerve.
• Hearing loss.
• Dizziness, unsteadiness when walking with damage to the cerebellum.

3. Mental deviations. Attention and concentration noticeably worsen, the patients are inhibited, it is difficult to answer questions. May develop drowsiness up to lethargy. Signs of the frontal psyche: patients are sloppy, criticism decreases, a tendency to flat jokes, rude, voracious, sexually disinhibited.

4. Seizures. Generalized convulsions with loss of consciousness or periodic twitching of any muscle group. These symptoms of cerebral lymphoma occur with the following frequency: neurological deficit in 70% of cases, mental disorders in 43%, signs of intracranial hypertension in 33%, convulsions in 14%. In people with HIV infection, epileptic seizures are more common (in 25%), and the development of encephalopathy at a young age (30-40 years) is also a common sign in them.

Spinal cord

The defeat of this department of the central nervous system is manifested by signs of compression: impaired movement, sensitivity, loss of reflexes, urinary and fecal incontinence.

Diagnostics

Main

Finding lymphoma is not easy. Although it is conditional and refers to hematological diseases, there are usually no changes in the blood test. If the above symptoms are detected, the neurologist prescribes:

• Examination by an ophthalmologist.
• Electroencephalography.
• CT or MRI of the brain or spinal cord with and without contrast.

Lymphoma has certain signs that make it possible to suspect it already at the stage of neuroimaging. On MRI - single or multiple foci, which are either lower in density or do not differ from the surrounding brain tissue, usually homogeneous, sometimes annular. With the introduction of contrast, they accumulate it intensively. Perifocal edema, calcifications, hemorrhages, and displacement of median structures are less common than in other primary CNS tumors.

The diagnosis must be confirmed histologically. Stereotactic biopsy (STB) is the standard for suspected primary brain lymphoma. Before the procedure, it is not recommended to prescribe steroids, because due to their cytolytic effect, they can significantly change the size and histological structure of the tumor. An open biopsy is performed only in cases where STP cannot be performed (for example, if localized in the brainstem). In spinal lymphoma, a laminectomy is performed to take a biopsy.

The obtained material is examined histologically, and immunohistochemical identification is also carried out (determination of the CD45 antigen).

Clarifying diagnostics

With a confirmed diagnosis of lymphoma, the patient is examined further to:

• Search for an extraneural lymphoma focus.
• Exclusion or confirmation of immunodeficiency (HIV).
• General status assessments to determine prognosis and upcoming treatment.

Appointed:

• An extended blood test.
• Biochemical analysis with the determination of lactate dehydrogenase (LDH), creatinine clearance, albumin, urea, transaminases.
• Spinal puncture with general clinical and cytological examination of cerebrospinal fluid.
• Determination of antibodies to HIV.
• Test for antibodies to the Epstein-Barr virus, herpes, toxoplasmosis, syphilis, viral hepatitis.
• CT scan of the chest.
• Ultrasound of the lymph nodes.
• MRI of the abdomen, small pelvis.
• Fibrogastroscopy.
• Puncture of the bone marrow.
• In men, ultrasound of the testicles.
• If necessary, PET, spirometry, echocardiography. The general condition of the cancer patient is assessed according to the Karnofsky scale (0-100%) or the ECOG scale (0-4 points).

Treatment

Surgical treatment for primary CNS lymphomas is usually not used. An exception is a significant compression of the brain structures or the spinal cord.

The main method of treatment of such tumors is systemic chemotherapy and subsequent irradiation of the remaining foci.

The most effective drug for PLCNS is methotrexate. It is used alone or in combination with other cytostatics, more often with cytarabine. Clinical studies with rituximab also show good results.

For a full therapeutic effect, sufficiently high doses of methotrexate (up to 10 g / m2) are required. But this drug is very toxic, it causes oppression of hematopoiesis, dysfunction of the kidneys and liver, and neuropathy. Therefore, it is important to choose a regimen that the patient can tolerate - curative doses with high toxicity or palliative doses with low toxicity.

Methotrexate is administered by intravenous infusion only in a hospital setting. To reduce toxicity, it is necessary to additionally use calcium folinate (leucovorin) and inject large volumes of fluid. The course is from 4 to 8 cycles every 2 weeks.

After completing the course of chemotherapy, radiation therapy is performed on the brain, including the eyes. The total dose is usually 30-36 Gy, the regimen is 2 Gy per session 5 times a week. If after chemotherapy, according to MRI, tumor foci persist, then additional local radiation exposure is prescribed.

In patients with primary spinal lymphoma, RT is considered as the main method after surgical removal of spinal cord compression. However, due to the very rare occurrence of this localization of PLCNS, data are still insufficient.

Forecast

The life expectancy of a patient with PLCNS without therapy is no more than 2 months. Timely diagnostics and the initiated adequate complex effect allow to cure 70% of patients completely. The prognosis for brain lymphoma is individual and depends on many factors. For PLCNS, there is a special international prognostic index IELGS. Based on it, taking into account the patient's risk factors, it is possible to predict the overall 2-year survival rate.

Risk factors

1. Age over 60 years.
2. The patient's condition on the ECOG scale is more than 2 points (Karnovsky index> 50%).
3. Increased plasma LDH.
4. Increasing the concentration of protein in the cerebrospinal fluid.
5. Damage to the deep structures of the brain.

The prognosis of 2-year survival in the presence of 1 factor is 80%, 2-3 - 48%, and the definition of 4-5 factors reduces this figure to 15%.

Main conclusions

Primary CNS lymphoma is a rare tumor. But it has its own characteristics that distinguish it from other malignant tumors of the nervous system.

Main characteristics of PLCNS:

It occurs more often in immunocompromised individuals.

If lymphoma is suspected, steroids should not be given until a biopsy is obtained.

Unlike other brain tumors, it cannot be operated on.

Responds well to chemoradiation treatment.

Source: RosOnco.ru

The reasons

There are two types of factors that provoke the development of pathology:

1. External negative influence;
2. Internal processes leading to the development of lymphoma.

Doctors recommend paying more attention to the influence of environmental factors on the brain. When a person lives in places with high levels of radiation, in 97 out of 100% problems in the head of an oncological nature are found. The basis for the development of cancer is a substance - gas. Vinyl chloride is used in factories that make asparkame and a sugar substitute for diabetics.

There are statements that the development of a malignant tumor in the head comes from electromagnetic radiation, as well as from the harmful effects of telephones or high-voltage power lines. True, science has not yet been able to confirm the veracity of the assumptions.

When the reason appearance established, you should carefully consider what is capable of provoking the development of a tumor in the brain from the inside:

• Irradiation during the period of radiation therapy.
• With HIV disease, the protective functions of the body are significantly reduced. He is unable to fight the developing pathology.
• After an organ transplant operation. In this situation, the patient develops immunodeficiency.

Doctors do not exclude that heredity is one of the reasons for the appearance of degenerated brain cells. If relatives in the first line became the source of the disease, then the child still has youth observed clinical picture. However, at the first stage, neoplasms are benign. When there is no treatment, the risk of cell transition from healthy to cancerous increases.

Mononucleosis also causes an oncological tumor to develop inside the skull. Additional reasons:

• Epstein-Barr virus disease;
• Mutations in pairs of chromosomes.

Every day, it is recorded that the number of patients with a fatal disease is growing. A surge in diseases is often recorded in large metropolitan areas. You should also pay attention to food. In large retail outlets and on the market, a product grown naturally and ripened thanks to the sun, rather than a carcinogenic composition, is less common.

Symptoms

The danger of the disease lies in the absence special features ailments. Diagnosis is difficult because the patient does not complain of deterioration.

To determine possible problems within the body, doctors recommend paying attention to each symptom described below.

Increased intracranial pressure

Intense headaches are provoked. The syndrome does not recede even after taking painkillers. In the morning, the headache becomes more intense. Lying down and when bending over, the pain intensifies. Often, additional symptoms are a gag reflex and nausea.

Loss of function

The patient loses certain functions controlled by the part of the head organ where the neoplasm is located. As a result, an increase in the size of the tumor leads to pressure on the areas, the patient loses skills.

Mental health disorders

The patient cannot concentrate, is often distracted, and cannot answer simple questions. The patient tends to sleep, capable of turning into lethargic.

In other cases, a person is active, but when talking, he can be rude. He tries to joke, but these are flat, meaningless jokes. The patient ceases to criticize himself. There is an appetite, reaching gluttony.

epileptic seizures

The patient notes the appearance of convulsive phenomena, fainting, twitching of a finger or hand is not excluded.

The frequency of manifestation of symptoms of this group: 70% - neurological deficit, 43% - mental disorders, 33% - intracranial pressure, 14% - convulsive phenomena. From HIV infection the patient's immunity decreases and then epileptic attacks are observed in 25% of patients. Encephalopathy affects more than 50% of patients from 30 to 40 years old.

The last stages of lymphoma lead to the fact that the patient's personality changes. There is instability in mood, emotions. It is impossible to predict a person's actions and reactions. The patient develops memory problems when there are no periods of memories.

Classification

Oncology of the head organ is divided into three types. In order for the treatment to take place with the result, it is necessary to clearly determine the degree of damage. human body and source of abnormal cells.

Consider the types of brain damage.

Reticulosarcoma

The cells of the connective tissue of the hematopoietic organs for certain reasons become malignant. Doctors rarely encounter this disease. Therefore, the pathology remains unexplored to the end. The clinical picture of the disease is similar to lymphosarcoma. These are always multiple foci of the development of pathology, depending on the location and degree of development of the disease.

microglioma

Lymphoma attributed to dangerous species pathology. The tumor is located where it is impossible to carry out therapy in full. Diseased cells grow rapidly, the volume of the affected tissue increases. Does not respond to treatment. If a benign tumor has penetrated the brain, then the growth of the pathology is slow, without external manifestations.

Microglioma is found in 50% of patients with a neoplasm in the brain. Glial tissues serve as the basis for growth. The tumor does not grow and does not affect the layers of the organ, does not grow into the bone tissue. A dense clot with fuzzy edges is visible on the screen. Cases were recorded when the size of the tumor reached 15 centimeters. Microglioma develops in adults and children.

Diffuse histiocytic lymphoma

The disease destroys the brain from within. First, individual cells are subject to destruction, then tissues suffer. The development and spread of the tumor is rapid. Metastases spread throughout the body, affecting healthy tissues. Central nervous system receives new impulses from already damaged tissues. The patient's body temperature rises, sweating increases, body weight decreases. This type of oncological disease, rapidly spreading throughout the body, is sensitive to ongoing treatment.

Lymphoma of the central nervous system and GM is capable of forming a single focus of development of pathology and a plurality of foci. In 10 out of 100 patients suffering from this type of cancer, the eyes, the membranes of the organ in the skull are affected, and the spinal cord is affected.

In the vast majority of cases of lymphoma, the neoplasm spreads within the cerebral hemispheres (85%). Cerebellar involvement can occur in 15% of cases. The same number of patients have a tumor in the ventricles of the brain and in the trunk.

Diagnostics

It has already been said that the diagnosis of the disease is carried out only in the case of a visit to the doctor due to another disease. A blood test is not considered a reliable source for determining a tumor, so a comprehensive examination prescribed by a doctor is needed.

The following medical equipment is used for the procedure:

• MRI. The patient is first injected with a contrast agent. On an MRI, a lymphoma will immediately appear, streamlined from all sides with a contrast agent.
• Tomography. Here, the study will confirm that there is a tumor and warn of the need for treatment.
• Trepanobiopsy. This is a study of a part of the biological material taken from the site of the lesion after opening the skull.
• Stereotactic biopsy. Here, the resulting biomaterial comes through a hole in the bones of the skull.
• Electroencephalogram. This method can be used when the source of the pathology is clarified. The influence and criticality of the situation with the Central nervous system is measured.
• X-ray. The photo shows a secondary sign of oncology and intracranial pressure.
• The study in children is performed using ultrasonography.

Treatment

The doctor, having received research data confirming the diagnosis of lymphoma, prescribes treatment on an individual basis. Three ways to fight:

• Therapy with chemicals;
• radiation exposure;
• Operation.

Chemotherapy

An effective way to fight cancer. The oncologist individually selects medicines, calculates the dose. The use of several medicines at the same time gives a greater result.

Often there is a combination of chemotherapy and radiation. Preparations containing chemicals:

• Cytarabine;
• Etoposide;
• Methotrexate;
• Cyclophosphamide;
• Chlorambucil etc.

For treatment, medicines with monoclonal antibodies are used. The downside of using chemicals to try to heal is that it destroys diseased and healthy cells at the same time.

Side effects after a course of chemotherapy:

• Anemia develops, leading to weakness in the body and muscles.
• Gagging, nausea.
• Disorder of the digestive system.
• Hair loss.
• Constant feeling of dryness. At the same time, small sores and wounds on the mucous membrane appear in the oral cavity.
• Body weight is rapidly decreasing.
• The protective shell of the body does not work. This means that third-party infections freely enter the body.

If you need to anesthetize, take Celebrex.

Radiation exposure

Since chemotherapy does not always give positive results in the treatment of oncology, radiation exposure becomes an additional means that enhances the effect of the first. Radiation exposure reaches metastases, destroying the source of excretion. It is not used as independent way fight against oncology.

Lymphoma of the brain is called rare disease affecting lymphoid tissue. The disease is malignant in nature and is concentrated mainly in the meninges. The danger of pathology is that it manifests itself in the last stages, which aggravates the treatment. The situation is complicated by the fact that the blood-brain barrier does not allow the use of methods for the treatment of the disease that successfully cope with lymphomas in other parts of the body.

Differentiate between non-Hodgkin's lymphoma and Hodgkin's disease. In the first case, the tumor develops in the case of a mutation of one lymphocyte cell. When the entire lymphatic system is affected, Hodgkin's disease begins.

Non-Hodgkin's lymphomas of the brain are either primary or secondary. Mostly men are affected by this disease. The primary tumor rarely appears in the brain. More often it is formed due to metastasis, and is secondary.

There are the following types of tumors in B-cells:

1. Diffuse large cell lymphoma. It is diagnosed in 30% of cases, mainly among the elderly. It is easily treatable, and most patients live longer than 5 years after the disease is discovered.
2. Small cell lymphocytic lymphoma. The tumor grows slowly, but is highly malignant. This type of lymphoma occurs in 7% of patients. This tumor can degenerate into a tumor with rapid growth.
3. Follicular lymphoma. A fairly common tumor, diagnosed in 22% of cases. It grows slowly and has a low malignancy. At risk are people over 60 years of age. The disease is treated easily, 60% of patients live longer than 5 years.
4. Lymphoma from the cells of the mantle zone. Such a tumor grows slowly, but its treatment prognosis is unfavorable, since only 20% of patients survive. Such lymphoma occurs in 6% of cases.
5. Burkitt's lymphoma. The disease is diagnosed in people over 30 years old, mainly among men. It occurs very rarely, only in 2% of the case. The success of treatment depends on the stage at which the pathology is detected. Timely chemotherapy increases the chances of recovery.

T-tumors are classified as follows:

1. T-lymphoblastic malignant lymphoma. It affects young people in their 20s. It was diagnosed in 75% of cases. The chances of survival increase if the disease is diagnosed early. If the tumor has affected the spinal cord, recovery is unlikely and is observed in only 20% of patients.
2. Anaplastic large cell lymphoma. Pathology occurs in young people. Recovery is possible if treatment is started early.
3. Extranodal T-cell lymphoma. Pathologies susceptible to people of any age can occur in different ages outcome depends on the stage of the disease.

Reticulosarcoma

Reticulosarcoma is a malignant proliferation of cells of the reticular lymphoid tissue. She doesn't show up for a long time. Only in the later stages, when metastases appear, the patient's liver, spleen increase, and jaundice may begin.

Primary reticulosarcoma is localized in the lymph nodes. At this stage, the lymph nodes are very dense and do not hurt. Over time, the tumor grows into nearby tissues, as a result of which blood circulation and lymph flow are disturbed. When spreading to the lymph nodes of the mediastinum, the neoplasm compresses the esophagus and trachea. Metastases in the abdominal cavity lead to excessive accumulation of fluid in the lower abdomen, and if the vessels passing in the chest cavity are damaged, a compression syndrome occurs. Growth in the intestine leads to its obstruction.

microglioma

Refers to primary malignant lymphomas. The neoplasm consists of atypical microglial cells.

Diffuse histiocytic lymphoma

A malignant form of the disease characterized by large cells lymphomas with abundant cytoplasm and polymorphic nuclei. such cells are capable of phagocytosis, absorbing mainly erythrocytes. Very rarely diagnosed.

Bone marrow lymphoma

The bone marrow stores the stem cells of erythrocytes, platelets, and leukocytes. Increased division of lymphocytes leads to the displacement of blood cells. Thus, hematopoiesis is disrupted. This pathology is called bone marrow lymphoma. It does not show any signs for a long time, and is found only at stages 3-4.

The disease is difficult to treat, the effectiveness of therapy is influenced by internal and external factors.

The reasons

The exact causes of brain lymphoma are unknown. In the course of medical research, it has been established that brain lymphoma develops with a weakened immune system. Pathologies favor:

• HIV infection;
• radiation exposure;
• genetic predisposition;
• systematic influence of carcinogens, which include heavy metals and various chemicals;
• Epstein-Barr virus;
• Infectious mononucleosis;
• environmental conditions;
• organ transplant;
• blood transfusion;
• age after 60 years.

The described factors, under certain conditions, provoke the development of the disease, especially with a complex effect.

External factors

There are external factors that can cause brain lymphoma. Among them:

• radiation exposure;
• vinyl chloride gas, which is used in the manufacture of plastics;
• aspartame is a sugar substitute.

The causes of the development of the disease have not been precisely established. Most doctors believe that electromagnetic fields and high-voltage transmission lines contribute to the appearance of lymphoma.

Weak immune system

People with impaired work are at risk of developing primary cerebral lymphoma immune system. The causes of lymphoma in immunodeficiency are:

1. Organ transplantation.
2. hereditary predisposition.
3. Contact with a carcinogen.

If a healthy person develops lymphoma, it usually develops in the lymph nodes. In patients with the immunodeficiency virus, the disease progresses in the spinal cord or brain.

genetic predisposition

The reason for the development of cancer is a genetic predisposition. Members of the same family are faced with the occurrence of benign tumors, but if treatment is ignored, they can develop into cancer. Children with HIV are often born with brain lymphoma.

Neurofibromatous diseases cause the development of tumors of the spinal cord. The disease is inherited by relatives of the first order.

Symptoms

People with lymphoma in the brain experience the following symptoms to varying degrees:

• speech disorder;
• dropsy;
• visual impairment;
• nerve damage without inflammation;
• numbness of the hands;
• hallucinations;
• mental disorders;
• impaired coordination of movements;
• fever;
• headache;
• dizziness;
• drastic weight loss.

The symptomatology of lymphoma is exacerbated by the fact that the pathology can lead to ischemic stroke and hemorrhage. Hematomas that appear disrupt brain activity and provoke the development of encephalopathy.

Diagnostics

A number of laboratory methods are used to accurately diagnose lymphoma. Among them:

1. CT scan.
2. Spinal puncture for the study of cerebrospinal fluid.
3. X-ray examination of the chest to examine the state of the lymphatic system.
4. Trepanobiopsy - examination of brain tissue for the presence of lymphoma by opening the skull.
5. Magnetic resonance imaging of the brain.
6. Stereotactic biopsy for histological examination.
7. General blood analysis.

If there is not enough information to study the material, it is possible to use an ultrasound examination or a bone marrow biopsy, which can detect the disease at an early stage of development.

Therapy

Is it possible to cure brain lymphoma with chemotherapy, there is no consensus among physicians. In most cases, complex treatment of brain lymphoma is practiced. During chemotherapy, the patient's condition improves if large doses of drugs are used in the treatment. Medications are selected individually, taking into account the sensitivity of lymphoma to certain substances. It is advisable to use chemotherapy in conjunction with a course of radiation therapy, which increases the life span of the patient. This is especially true for HIV-infected patients.

To eliminate the symptoms of the disease, narcotic drugs are used that can reduce pain. Surgery is not recommended because there is a risk of neurological damage due to accidental damage to the tissues surrounding the lymphoma. The operation is also difficult because of the difficulty to establish clear boundaries of the tumor.

Desensitization begins with a group of non-steroidal anti-inflammatory drugs (non-narcotic analgesics), such as ketanes, nise or aertal. These are weak painkillers and the effect may not be enough even at the initial stage. Of the drugs that can be sold in a pharmacy without a prescription, it is better to ask for Celebrex. To purchase narcotic drugs, you will need a prescription form 107-1 / y-NP. The pink form is obtained from the therapist.

The disease in a neglected form is treated with the help of palliative medicine, the essence of which is to provide emotional support to the patient and improve overall well-being. Headaches at this stage are so severe that they cannot be removed with narcotic analgesics.

Forecast

In the absence of treatment, the life of the patient is several months. Chemotherapy may increase survival up to two years. After a course of radiation therapy, HIV-infected and AIDS patients can live for about 10 months.

Malignant lesions are reduced with the use of stem cell transplantation. Primary brain lymphoma is difficult to treat. Young people have a better survival prognosis than older people. It must be remembered that in the treatment of chemotherapy, side effects are possible. These include low levels of white blood cells, tissue death, and impaired consciousness.

Irradiation also leads to negative consequences. Patients have mainly neurological disorders, sometimes years after the procedure.

Lymphoma is a pathological malignant neoplasm consisting of atypical lymphocytes, actively multiplying, which form a tumor. Such a formation affects the lymphoid tissue, it can occur in different organs. Primary cerebral lymphoma is a fairly rare disease, diagnosed in five people per million population. Among all the primary formations of the brain, 1-3% of all cases fall on the shares of lymphoma.

Classification

There is non-Hodgkin's lymphoma and Hodgkin's disease. The first variant is characterized by the appearance of a tumor due to a mutation of one lymphocyte cell and can affect the brain. Hodgkin's lymphoma affects the entire lymphatic system, named after the scientist who first described the pathology.

Non-Hodgkin's formations can be primary or secondary, affecting men more often. Primary neoplasms in the brain are extremely rare, more often the tumor occurs due to metastasis from a different location and is called secondary.

According to the WHO classification, the following types of B-tumors are distinguished:

T-tumors include:

mediastinal lymphomas

Mediastinal cancer occurs mainly in adults aged 20-40 years. The frequency of occurrence is 3-7% of all types of neoplasms with different localization and malignancy. For the most part, not cancer occurs in the mediastinum, but benign tumors, in a ratio of 80 to 20. Regarding lymphomas, they form in the lymphatic system of the mediastinum. The main signs to look out for are an increase in lymphatic
nodes in the neck or axillary sinuses. They can be non-painful at first, later there is discomfort, pain and redness in the affected area of ​​the mediastinum. Also, mediastinal cancer has such a feature as breathing complications, the occurrence of dysphagia or shortness of breath. Wheezing or coughing may occur. All this is due to the growth of lymphoma in the mediastinal cavity and the relief of the normal functioning of the respiratory system.

As a rule, there is no point in using the surgical method, since atypical cells are carried with the lymph flow to different organs, this is a particular difficulty in the treatment of lymphomas. As in the case of the brain, the main method remains a course of radiation and chemotherapy. Often, the formation of lymphoma in the mediastinum becomes the cause of the secondary occurrence of a tumor in the brain, as a result of metastasis.

To additional methods include bone marrow transplantation, the method is innovative, but expensive and specific. As well as immunotherapy to improve the overall resistance of the body, suppressed disease and a course of chemotherapy.

Causes

Cancer has no exact cause. But at the same time, malignant lymphoma is more often formed against the background of weakened immunity, to the main factors possible occurrence include:

• the presence of HIV infection;
• exposure to radiation exposure;
• genetic predisposition;
• systematic interaction with carcinogens, especially with chemicals and heavy metals;
• Infectious mononucleosis;
• organ transplants and blood transfusions;
• age after 60 years.

Burkitt's lymphoma in most cases develops as a result of infection with the Epstein-Barr virus and this is a proven fact. Apart from this case, the rest of the list is only possible factors that can increase the risk of provoking the disease under certain conditions, but are not considered proven causes.

Clinical picture

Lymphoma has symptoms, usually manifested by squeezing the brain tissue. These include:

• headaches and dizziness;
• visual, auditory and olfactory hallucinations;
• mental disorders;
• impaired coordination or loss of sensation in a particular part of the body;
• convulsions and sudden epileptic seizures;
• auditory and visual disturbances;
• swelling of regional lymph nodes;
• sudden hemorrhages;
• vomit.

Together with these signs, when the cancer is not at the initial stage, general symptoms characteristic of oncology of any localization appear:

• loss of appetite;
• weakness;
• disability;
• sudden weight loss;
• temperature rise;
• fever.

In some cases, there are no such manifestations, so you should be attentive to your body. Focal signs occur in 73% of patients, personality and mental changes in almost 50% of patients. A third of patients experience vomiting and headaches. Epileptic seizures occur in 15% of patients, and visual disturbances in only a few percent. Some patients note the absence of symptoms at an early stage of cancer or their slight manifestation. In the case when malignant lymphoma develops secondarily, against the background of metastasis from another organ, specific signs of the primary tumor may be inherent. In some cases, metastasis is detected faster than the main neoplasm. Sometimes in the early stages, cancer does not show any signs.

Diagnostic Measures

Non-Hodgkin's lymphoma is best identified by magnetic resonance imaging. For greater information content of the method, the patient is injected with a contrast agent that detects cancer cells and accumulates in them, which allows you to get a more detailed picture of what is happening.

If cancer is suspected, of any localization, a biopsy is an obligatory research method that allows obtaining damaged tissues for histological examination. Further analysis determines the type and structure of the tumor, as well as the degree of its malignancy. In addition to taking tissue samples from the tumor itself, a puncture is also made from spinal cord cells.

A chest x-ray is performed to view the state of the lymphatic system of the mediastinum and thymus gland.

In addition to instrumental studies, laboratory blood tests are systematically required to monitor the body's response to a neoplasm.

Therapy

Non-Hodgkin's lymphoma in the brain is difficult to treat because the organ has a blood-brain barrier that protects it from damage. Because of this, most methods are simply not able to radically affect the neoplasm.

Burkitt's lymphoma and its other varieties are better
are generally treatable with a course of chemotherapy. A course of mono or polychemotherapy may be prescribed. Depending on the type of lymphoma and its sensitivity to a particular group of drugs. Medicines are administered, as a rule, through a lumbar puncture, since it is this approach that makes it possible to achieve the maximum effect from the drugs. For a mono-course of chemotherapy, Methotrexate is most often prescribed. If necessary, the combined use of funds, preference is given to Cytarabine, Temozolomide or Etoposide. The choice of medicines remains only with the attending physician. A course of chemotherapy has many side effects and can often provoke a deterioration in the patient's well-being, but the risk of overgrowth of the neoplasm justifies the expediency of its use. Side effects occur as a result of damage to healthy cells, since, unfortunately, chemotherapy cannot only kill cancer cells without affecting healthy ones. The frequency and intensity of certain manifestations depends on the dose and type of selected drug. Common side effects of chemotherapy include:

• nausea and vomiting;
• general weakness, malaise caused by anemia;
• hair loss;
• suppression of the immune functions of the body, as a result of a greater susceptibility to infections;
• dry mouth and the formation of ulcers and wounds in its cavity;
• disorder in the gastrointestinal tract.

Radiation therapy

radiation exposure as independent method is rarely used, more often it is combined with a course of chemotherapy or surgery. At a late stage of the disease, radiation therapy is used as a palliative method to alleviate the patient's condition by shrinking the tumor and squeezing its healthy tissues. Side effects from radiation therapy can be of a different nature, depending on the place of radiation. Regarding the effects of radiation on the brain, negative manifestations may occur after a few years. They are expressed, as a rule, in the form of neurological disorders. With the complex effect of a course of chemotherapy and radiation exposure, the negative consequences of the first may be aggravated.

Burkitt's lymphoma is virtually incurable with surgery. The reason for this is the specific location and type of growth of the formation. Follicular lymphoma and many of its other types capture different brain cells, for example, the location of the main tumor can be in the cerebellum, and microscopic atypical cells can be scattered throughout the organ. In this regard, a radical type of operation is almost impossible to perform. They resort to surgical intervention in order to remove the maximum part of the formation in order to reduce the growth of the tumor and take the material for a biopsy, and then they use a course of chemotherapy or radiation exposure to destroy the remaining atypical cells.

If brain cancer is at an early stage and the size of the neoplasm is not impressive, and the place of its localization allows for surgery, we can talk about the success of the method and a positive outcome after surgery. But in any case, in order to make sure that all cancer cells are destroyed, despite the initial stage of the disease, the patient is recommended to undergo a course of chemotherapy to consolidate the result.

The prognosis depends on the stage, type of lymphoma and its location. Young patients, cancer endure a little easier and have a better survival rate than older patients. Without urgently started treatment, cancer with localization in the mediastinum or brain very quickly affects their work and leads to death in a few months. With properly selected, timely therapy, 40% of patients can overcome the five-year milestone.

Reading strengthens neural connections: