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Primary cerebral lymphoma in HIV infection. HIV-associated non-Hodgkin's lymphomas. Forecast at different stages and forms

The term "malignant lymphoma" was proposed by Theodor Billroth. Currently, this term is used for tumors originating from lymphoid tissue. Among the malignant forms of lesions of the lymphoid tissue, lymphogranulomatosis (Hodgkin's disease) and non-Hodgkin's lymphomas (lymphosarcomas) are distinguished. In patients with HIV infection, there are 3 main types of lymphomas: immunoblastic lymphomas, Burkitt's lymphoma, and primary brain lymphoma.

About 90% of all lymphomas are lymphomas that originate from B cells. Immunoblastic lymphomas account for about 60% of all cases of lymphomas in AIDS patients. Burkitt's lymphoma accounts for about 20% of all cases of lymphomas in AIDS patients. It occurs in persons aged 10-19 years, is characterized by a malignant course and rapid generalization. Primary brain lymphoma accounts for 20% of all lymphomas in AIDS patients.

The risk of developing lymphoma in AIDS patients is 100 times higher than in healthy people. It is known that lymphomas are evidence of late manifestations of HIV infection, as AIDS progresses, the risk of developing lymphomas increases. Co-factors for the rapid progression of lymphomas include:

• — The number of CD4 + cells is less than 100 in 1 µl
• – Age over 35 years old
• - History of an injection drug addict
• - Stage 3 or 4 HIV infection

In almost 80% of patients with lymphomas, the disease is characterized by symptoms that are characteristic of B-lymphomas: fever, weight loss, weakness, sweating at night. The main localization of the lesion is the central nervous system.

Primary cerebral lymphoma.

It occurs in 15% of HIV/AIDS patients and accounts for 20% of all lymphomas in AIDS patients. Primary brain lymphoma is associated with the Epstein-Barr virus. Clinically, primary cerebral lymphoma is manifested by local neurological defects, most often by lesions of the cranial nerves (CNN) and poor prognostic signs. The average life expectancy is 2-3 months. The second most common localization of lymphomas is the gastrointestinal tract. If the lymphoma is located in the stomach or intestines, then its clinic simulates cancer or peptic ulcer. The lungs and liver are affected somewhat less frequently, in 9% and 12% of cases, respectively.

Burkitt's lymphoma is B-cell non-Hodgkin's lymphoma.

This lymphoma in HIV-infected people is registered 1000 times more often than in healthy individuals. In Burkitt's lymphoma, the role of the provoking factor is assigned to the Epstein-Barr virus, whose DNA can often be found in tumor cells. LB is a small cell tumor, which includes single or multiple foci of malignant neoplasms, which are localized in the bones of the upper jaw, less often in the kidneys and ovaries.

In almost 50% of patients, lymphadenopathy is detected at the onset of the disease, but the process itself develops outside the lymphatic system, and later symptoms of intoxication, fever, and weight loss develop.

Classification of Burkitt's lymphoma according to the prevalence of the pathological process:

• 1 stage. Localization of the process within one organ, most often a single tumor of the jaw.
• 2 stage. The process is localized within two or more organs, numerous tumors of the jaws, or a tumor of the jaw with a tumor of another localization, with the exception of organs that are affected in stages 3 and 4.
• 3 stage. There is damage to the lymph nodes located in the middle of the chest or retroperitoneal, damage to the bones.
• 4 stage. Generalization of the process - the tumor spreads to the central nervous system and/or bone marrow,

The diagnosis is made on the basis of a histological examination of the tumor (picture of the "starry sky"). The average life expectancy of patients with lymphomas in persons with AIDS does not exceed 4-6 months - with sufficiently intensive treatment.

Cervical cancer in the stage of AIDS.

One of the main factors in the mortality of women. Intraepithelial tumor of the cervix and invasive cervical cancer are classified as AIDS-associated tumors. Etiologically, this type of tumor is associated with the human papillomavirus (HPV). Types of the HPV virus 16,18,31,33 in most cases are found in cells of invasive carcinomas, and the DNA of the virus is integrated into the DNA of tumor cells. It has been established that such HPVs, which are the cause of cervical cancer, form viral proteins E6 and E7, which play a major role in the malignant transformation of cells.

Co-factors in the development of cervical carcinoma caused by HPV are early onset of sexual activity, a large number of sexual partners, smoking, and immunosuppression. An important diagnostic test is cytological examination of smears from the cervical canal and colposcopy with biopsy.

Invasive cervical cancer in women with HIV has a severe course, they develop metastases faster, on average, such patients do not live more than 3 months. Recently, not only the number of HIV-infected patients with various tumors has increased, but also the spectrum of tumors. The number of anal carcinomas, Hodgkin's disease, myeloma, seminomas, testicular cancer, oropharyngeal carcinomas has increased.

Lymphomas are rare malignant lymphoproliferative diseases. In patients with HIV infection, non-Hodgkin's lymphomas (NHL) are mainly detected, which are recorded 200-600 times more often than in the general population, and are classified as secondary diseases. According to histological characteristics, 5 types of NHL are distinguished: diffuse large B-cell lymphoma, primary exudative lymphoma, primary CNS B-cell lymphoma, Burkitt's lymphoma and Hodgkin's disease. In the vast majority of cases, immunoblastic lymphoma is detected in patients with HIV infection with a CD4+ T-lymphocyte count of less than 100 cells/µl, with a frequency of 3%. In pathogenesis, immunosuppression and the presence of the Epstein-Barr virus, which is detected in 50-80% of patients, are important. The main symptom of lymphomas is enlarged, compacted, inactive and painless lymph nodes. Most patients present with fever, weakness, weight loss, and night sweats. Depending on the localization of the process, there may be symptoms of organ damage (gastrointestinal tract, central nervous system, liver, lungs, bones, etc.). As a rule, the diagnosis is established at a late stage of lymphoma. The main diagnostic criterion is a histological examination of a bone marrow or lymph node biopsy. The most common differential diagnosis is with atypical tuberculosis. The oncological process in patients with HIV infection progresses rapidly. Specific highly active antiretroviral therapy (HAART) in combination with chemotherapy in the early stages of the disease can have some positive effect. The development of primary lymphoma in patients who did not receive HAART indicates the most unfavorable prognosis for this pathology among all AIDS-defining diseases.

In Novokuznetsk, the incidence of HIV infection is 216.3 per 100,000 population, the incidence rate is 1,881 per 100,000 population (according to official data for 2016). Every year, more than 400 adult patients with HIV infection are hospitalized in infectious diseases departments, mainly in the late stages of the disease. However, we observed only 4 cases of NHL.

Observation 1. Patient D., 41 years old (Fig. 1). She was admitted to the Infectious Diseases Department on April 7, 2015 with complaints of weakness, fever up to 39 °C, pain in the throat and neck. She fell ill on 03/25/15: fever, sore throat. On April 2, she went to the clinic, was examined by a general practitioner and an ENT doctor, and was referred for hospitalization with a diagnosis of lacunar tonsillitis, severe course. Upon admission, she denied chronic diseases, drug use, HIV status, noted tonsillitis 1-2 times a year. Moderate severity, clear consciousness, active position. T - 38.2 ° C. The skin is pale pink, warm. The mucous membranes of the pharynx are brightly hyperemic, on the left the tonsil is significantly enlarged in volume, almost completely covered with pus. Enlarged submandibular lymph nodes. The cervical lymph nodes on the left are enlarged up to 2 cm in diameter, painful. The tongue is coated, wet. In the lungs and heart without severe pathology, blood pressure 110/70 mm Hg. Art., pulse 74 bpm, respiratory rate 18/min. The abdomen is soft, painless, the liver is along the edge of the costal arch, the spleen is not enlarged. In the hemogram dated 08.04 ESR 80 mm/h, leukocytes 7.7 × 10 9 , P 11, C 59, L 9, M 21, Tr 304 × 10 9 , Er 2.8 × 10 12 , hemoglobin 80 g/l. In a biochemical blood test, bilirubin 11.0 µmol/l, AST 58 U/l, ALT 54 U/l, amylase 21 U/l, total protein 58 g/l, urea 5.7 mmol/l. Culture isolated from pharynx Klebsiella pneumoniae And Streptococcus viridans. ECG: sinus tachycardia, without changes in the myocardium. Diagnostic search included examination for diphtheria, tularemia, tuberculosis. Treatment: infusion therapy - 1250.0 ml / day, antibiotic therapy: Ampisid 3.0 × 3 times / day in / in drops, symptomatic therapy, local treatment. From April 10, increased antibiotic therapy with gentamicin 80.0 × 3 times/day IM and doxycycline 1.0 × 2 times/day.

On April 10, it was revealed that the patient was HIV-infected, the diagnosis was established in 2010, in March 2015, the CD4+ level was 10 cells. The prescribed HAART is not accepted. By April 13, oropharyngeal candidiasis and cheilitis developed, which required the appointment of fluconazole. The condition remained stable. Fever, lymphadenopathy, changes in the pharynx, moderate diarrhea persisted. On 15.04 the patient's condition worsened, vomiting started up to 5 times. A sharp decrease in PTI was recorded - 17.1%, an increase in fibrinolysis (360 min), a decrease in total protein (47 g/l) and albumin (16 g/l) with normal ALT values ​​(30.5 U/l) and a slight increase in AST (50.3 U/l). Hyponatremia (127.8), indicators of acid-base composition within the normal range (pH 7.43; PCO 2 36.1; BE 0.1; SBC 24.1). In the future, despite the treatment (fresh frozen plasma transfusion, detoxification therapy, ceftriaxone 2.0 × 2 times/day IV), the severity of the condition worsened, multiple organ failure, ascites, and anemia increased. With a safe state of consciousness on 21.04 at 23.25 there was a cardiac arrest, death was ascertained.

During his lifetime, a survey was also carried out: a chest x-ray (X-ray) of 15.04 without pathology. Ultrasound of the abdominal organs (ABP) dated April 16: liver +3 cm; ascites, no increase in abdominal l/nodes was detected. Gallbladder, pancreas, spleen, kidneys unchanged. Blood for sterility repeatedly - negative. Cytological examination of a smear from the tonsils dated April 17: a large amount of bacillary flora, squamous epithelial cells with nuclear degeneration; atypical cells were not found in the preparation. Sputum for pneumocystis from 16.04 negative. In the general blood test on April 20 and April 21, hyperleukocytosis (22.6 × 10 9, 21.7 × 10 9), progressive anemia (Er 2.l × 10 12), a shift in the leukoformula to promyelocytes and atypical cells, thrombocytopenia (l33 × 10 9 ), a decrease in hematocrit to 0.19. Biochemical analysis of blood from 20.04 without pathology. Prothrombin according to Quick 324.8, euglobulin fibrinolysis 360 min.

Post-mortem diagnosis: HIV infection, stage of secondary diseases IVB, progression phase. severe sepsis. Multiple organ failure. Fungal infection of the gastrointestinal tract. Anemia of complex origin. Nephropathy. Lymphadenopathy. Tuberculosis of the lymph nodes? Edema, swelling of the brain. Pulmonary edema.

Pathological anatomical examination revealed diffuse damage to internal organs (lungs, liver, spleen, heart, adrenal glands, kidneys) by lymphoblast-type cells, lymphocyte-like with a large number of mitoses, including pathological ones. Bacteriological examination of blood from the heart and spleen culture KIebsiella pneumoniae, which is regarded as evidence of the development of sepsis. The immediate cause of death was cerebral edema. pathological diagnosis. Primary: HIV-associated diffuse lymphoma affecting the lungs, liver, spleen, heart, adrenal glands, kidneys. HIV-associated sepsis. Complications: hepatosplenomegaly. Severe dystrophic changes in all internal organs. Cerebral edema.

This example testifies to the difficulties of intravital diagnosis of lymphoma in HIV infection, the malignancy of the lymphoproliferative process with rapid progression in combination with sepsis and an unfavorable outcome.

Observation 2. Patient S., 32 years old, was admitted to the infectious diseases hospital on June 20, 2017 with complaints of weakness, facial asymmetry, visual impairment. Acutely ill on June 7: a dark spot appeared in front of the right eye, examined by an ophthalmologist, diagnosis: retinitis? After 3 days - numbness of the lower lip, right half of the body, swelling of the right half of the face. On June 9, 2017, magnetic resonance imaging of the brain revealed hyper- and isointense foci in the frontal and parietal lobes, subcortical nuclei of presumably vascular origin, neck lymphadenopathy. From 15.06 subfebrile condition to 37.7 °C. 19.06 increased asymmetry of the face. History of life: drug addiction, chronic hepatitis C and HIV infection since 2012, has been taking HAART since 06/15/2017. CD4 31 cells.

Upon admission, the state of moderate severity, in the mind, adynamic. The symptoms of intoxication are determined. Hematomas on the skin, moderate hyperemia in the pharynx, coated tongue. BP 140/100 mmHg Art., heart rate 109. No pathology was detected in the internal organs; doubtful meningeal symptoms, paresis of the upper and lower branches of the facial nerve on the right. HIV-associated encephalitis is suspected. In the hemogram, thrombocytopenia (47 × 10 9), anemia (Er 3.0 × 10 12, Hb 74). Liquor: C - 783 cells, N - 93%, b - 1.65 g / l, Pandi 3+. From 27.06 the condition worsened, hemorrhagic syndrome, tachycardia joined. Control lumbar puncture, CSF: C — 1898, H — 94%, b — 0.66 g/l. On September 28, repeated magnetic resonance imaging of the brain was performed: an isointense formation was additionally detected in the right Meckel space, with spread along the cerebellum tenon, up to 10 mm thick, pathologically accumulating contrast agent, the 7th pair of cranial nerves on the right was thickened up to 5 mm. Conclusion: Differentiate between lymphoma and meningioma. On June 29, the patient developed urge to vomit; the stomach is swollen, the chair is "melena". Esophagogastroduodenoscopy revealed Mallory-Weiss syndrome, bleeding, acute stomach ulcers, erosive bulbitis and duodenitis. Ultrasound of OBP: hepatosplenomegaly, portal hypertension. Chest X-ray shows pneumonia on the left. In the hemogram Er 1.47 × 10 12 , Nv 49, Tr 20 × 10 9 . On the evening of June 29, shortness of breath up to 42/min appeared, signs of acute renal failure: oliguria, an increase in nitrogenous wastes. 30.06 terminal condition, at 19.30 death was ascertained.

CSF analysis: polymerase chain reaction for CMV, EBV, herpes negative, tank. sowing on m / vial, mushrooms - negative. A study on AFB of sputum, urine, feces - negative. ELISA blood test for toxoplasmosis (IgG+, IgM-), CMV (IgG+, IgM-), fungi (IgM-), syphilis - negative. Blood for sterility and blood culture - negative.

Postmortem diagnosis: HIV infection, stage of secondary diseases 1VB. HIV-associated meningitis of unspecified etiology. Lymphoma of the brain? A brain tumor? Complications: multiple organ failure.

Pathological anatomical diagnosis: HIV-associated generalized small cell lymphoma with lesions of the brain, lungs, lymph nodes of the mediastinum, liver, kidneys, adrenal glands, spleen. Complications: tumor intoxication. Deep dystrophic changes in internal organs.

The case demonstrates the difficulties of intravital differential diagnosis of lymphoma with other CNS lesions in HIV infection, the rapid progression of the disease with generalization of the process, CNS involvement and an unfavorable ending.

Observation 3. Patient R., 45 years old (Fig. 2). She was in the infectious diseases department from 10/23 to 11/26/2017 (34 days). Complaints at admission: weakness, fever up to 38.5-40 °C, coughing. HIV infection was detected in 2014, according to the immunogram, CD4 = 70 cells/µl (April 2017). HAART received irregularly. Deterioration of health, fever notes within 2 months. Chest X-ray revealed a mass in the upper mediastinum, and the patient was referred to the hospital. She has a history of drug addiction for many years, chronic hepatitis C, nodular goiter.

During the initial examination, the state of moderate severity, in the mind, the position of the active. Reduced nutrition. The skin is pale pink, there are dense infiltrates of 4-5 cm on the legs, there is no fluctuation. Peripheral lymph nodes are not enlarged. In the lungs, the heart is without pathology, the liver is up to +3 cm below the costal arch. In dynamics, there were periodic rises in temperature up to 38.5-38.7 °C, enlargement of the liver and spleen. Changes in spiral computed tomography on October 27, 2017: in the upper floor of the anterior mediastinum from the level of the chest aperture, an additional pathological volumetric formation of homogeneous density, with a relatively clear contour, 47.4 × 54.3 mm, was detected, displacing the trachea to the left. The group of paratracheal, paravascular, prevascular, hilar lymph nodes was enlarged on both sides up to 16 mm along a short radius. Pneumofibrosis. Conclusion: mass formation of the anterior mediastinum. Differentiate with lymphoma, thyroid goiter, lipoma.

From 07.11 deterioration, abdominal pain, swelling of the lower extremities, anterior abdominal wall, an increase in the volume of the abdomen, a decrease in diuresis. In a biochemical blood test, an increase in creatinine (246.7-334.3 μmol / l) and urea (25.4 mmol / l), metabolic acidosis, according to ultrasound of the OBP - hepatosplenomegaly, ascites (07.11.2017), hydronephrosis on the right (11.11. 2017). Chronic virus-associated glomerulonephritis and chronic renal failure were suggested. In the future, gradual negative dynamics: an increase in edema spreading to the face and hands, progression of renal failure (blood urea 30.18 mmol/l, creatinine 376.6 µmol/l), from 23.11 the addition of respiratory failure, which led to death on 26.11.

Complete blood count from 11/02/2017: ESR 60, Hb 80 g/l, Er 2.6 U/l, L 4.5 U/l, e 1%, u 1%, n 17%, s 66%, lim 12%, mn 3%, mp 114.0 U/L, hematocrit 0.23; from November 24, 2017, a decrease in tr - 21.0 units / l. Multiple blood test for sterility, fungi - negative, sputum test (10/24/2017 - pneumococcus 10 5 CFU / ml), urine, feces for VC negative. In the immunogram dated October 25, 2017, CD4 = 7 cells/µl. Echocardiography without pathology. The patient underwent antibacterial, hormonal, antifungal, diuretic therapy, transfusions of fresh frozen plasma, erythromass, HAART.

Postmortem diagnosis: HIV infection, IVB stage. HIV-associated sepsis. Mediastinal lymphoma cannot be ruled out. Complications: multiple organ failure (hepatocellular, renal, respiratory, cytopenia). Congestive pneumonia. Pulmonary edema. Encephalopathy of complex origin. Cerebral edema. Chronic viral hepatitis C. Nephropathy. Anemia, thrombocytopenia.

pathological diagnosis. Primary: HIV-associated diffuse large cell lymphoma affecting the mediastinum, intrathoracic para-aortic lymph nodes, spleen, kidneys, pleura, peritoneum. Complications: pulmonary edema. Cerebral edema. Severe dystrophic changes in internal organs. Concomitant: chronic viral hepatitis C. Conclusion: a pathoanatomical examination of a patient suffering from HIV infection revealed a diffuse lesion of internal organs (spleen, kidneys, intrathoracic and para-aortic lymph nodes, pleura, peritoneum, mediastinum) with large lymphocyte-like cells with a large number mitoses, including pathological ones.

In this case, a mediastinal mass (presumably lymphoma) was detected 1 month before the patient's death. The diagnosis of diffuse lymphoma, specific lesions of other organs and systems were established only during post-mortem examination.

Observation 4. Patient S., 30 years old (Fig. 3). He was hospitalized in the infectious diseases department on September 28, 2017 due to HIV infection stage IVB, progression phase, bilateral polysegmental pneumonia, with complaints of fever, shortness of breath, cough, weakness. From 09/24/2017 fever, shortness of breath. According to X-ray data of the OGK on September 28, 2017, bilateral polysegmental pneumonia. Progression of the underlying disease? Accession of an opportunistic infection (pneumocystosis, tuberculosis)? From the anamnesis it is known that HIV infection was detected in 2016, and he is receiving HAART. DM4 = 400 cells (examined in September 2017). Drug addiction for many years, last used drugs in June 2017. Chronic hepatitis C without biochemical activity was diagnosed. Since April 2017, enlarged neck lymph nodes appeared on the right, fever up to 39.6 °C. Examined in the oncological dispensary, according to the results of histological examination, a diagnosis of large B-cell lymphoma of the 3rd stage with lesions of peripheral lymph nodes was established, 3 courses of chemotherapy (doxorubicin, vincristine, rituximab) were performed.

Upon admission, the patient's condition was severe due to intoxication, he was conscious, he was in an active position. Satisfactory nutrition. Flesh-coloured skin. The face is asymmetric, enlargement and deformity of the neck on the right (photo), a tumor with a diameter of 12-15 cm (a conglomerate of lymph nodes, soft tissue edema). There are no edema. Respiration is hard, 24/min, dry rales in all lung fields, wet rales on the right. BP 100/60 mmHg Art., heart sounds are clear, rhythmic, heart rate 100/min. The abdomen is soft, painless, the liver is 3.5-4 cm below the costal arch, dense. Spleen at the edge of the ribs. In the hemogram ESR 52 mm/h, Er 3.5 × 10 12 , L 9.9 × 10 9 , basophils 2%, eosinophils 4%, blasts 26%, promyelocytes 2%, myelocytes 2%, young 4%, stab 4 %, segmented 2%, lymphocytes 42%, monocytes 14%, platelets 94.5 × 10 9 . In the biochemical blood test, an increase in liver enzymes (ALT / AST - 73.7 / 136.1 U / l), nitrogenous wastes (urea 14.08 mmol / l, creatinine 146.6 μmol / l), a decrease in glucose (2, 91 mmol/l). According to the results of the study of the acid-base state of venous blood - metabolic disorders: pH 7.394, PCO2 29.1↓, PO2 36↓↓, BEb -6.2, BEecf -7.3,% SO 2 c 69.9%. Spiral computed tomography of the OGK from 05.10.2017. Diffusely in all lung fields of both lungs, symmetrically, more in the basal zone, an alveolar lesion is detected in the form of a spotty seal like ground glass, with partial preservation of the subpleural areas of the lungs. Additionally, in both lungs, single hyperdense foci of various sizes, ranging in size from 3 to 12 mm, are determined. Lymph nodes are enlarged up to 12 mm. Conclusion: bilateral pneumocystis pneumonia. Focal lesion of the lungs to differentiate with metastatic lesion, septic embolism, focal tuberculosis. Tuberculosis is excluded by consultation with a phthisiatrician. Conducted detoxification, antibacterial (ceftriaxone, Hemomycin, Biseptol, co-trimoxazole), antifungal (fluconazole), symptomatic therapy. 02.10 epistaxis, subcutaneous hemorrhages on the forearms. Against the background of ongoing therapy, since 09.10 there has been a positive trend, manifested in a decrease in intoxication, normalization of temperature, disappearance of dyspnea, improvement of the physical picture in the lungs. However, from 12.10 again fever up to 38.1 °C, cough with mucous sputum intensified, multiple moist rales appeared in the lungs in all fields. On October 15, from 20:00, signs of respiratory failure began to increase; at 22:00, cardiac activity and respiration stopped. Resuscitation measures were not effective, death was pronounced.

Laboratory in dynamics in the hemogram revealed a decrease in hemoglobin and platelets, in biochemical analysis, along with the normalization of hepatic and renal parameters, an increase in LDH to 1938.7 U/l. Decrease in prothrombin according to Quick to 57.2%. Pneumocysts were found in the sputum on September 29, a culture was isolated candida albicans. Blood and urine cultures are negative.

Postmortem diagnosis. HIV infection IVB-C, progression phase. Pneumocystis pneumonia, severe. B-large cell lymphoma of the 3rd stage with lesions of peripheral lymph nodes. Complications: severe sepsis. Multiple organ failure. Endotoxic shock. Pulmonary edema. Encephalopathy of complex origin. Cerebral edema. Nephropathy. Anemia of complex origin. Chronic viral hepatitis. Background: addiction.

pathological diagnosis. Main: HIV-associated diffuse B-cell lymphoma with lesions of peripheral, intrathoracic, para-aortic lymph nodes, spleen, liver, kidneys, stomach wall. Complications: pulmonary edema. Cerebral edema. Severe dystrophic changes in internal organs. Concomitant disease: drug addiction.

In the above clinical case, the diagnosis of B-cell lymphoma was established during life, active chemotherapy was performed against the background of HAART. Nevertheless, the progression of the oncological process could not be stopped.

conclusions

1. B-cell lymphoma should be included in the differential diagnosis of opportunistic diseases in HIV infection.
2. B-cell lymphoma develops, as a rule, in the late stages of HIV infection, has a rapidly progressive course with a pronounced intoxication syndrome and involves various organs and systems, including the brain.
3. B-cell lymphoma in patients with HIV infection is often combined with other opportunistic diseases (in our case, with pneumocystis pneumonia, fungal infections) and comorbidities (chronic hepatitis C, drug addiction).
4. When B-cell lymphoma is detected at a late stage of HIV infection, even against the background of HAART and chemotherapy, the prognosis is poor.

Literature

1. HIV infection and AIDS: national guidelines / Ed. acad. RAMS V. V. Pokrovsky. Moscow: GEOTAR-Media. 2013. 608 p.
2. Barlett J., Gallant J., Pham P. Clinical aspects of HIV infection. 2012. M.: R. Valen. 2012. 528 p.
3. Pokrovsky V. V., Yurin O. G., Kravchenko A. V., Belyaeva V. V., Ermak T. N., Kanestri V. G., Shakhgildyan V. I., Kozyrina N. V., Buravtsova V. V., Narsia R. S., Khokhlova O. N., Pokrovskaya A. V., Efremova O. S., Konnov V. V., Kuimova U. A., Popova A. A. National recommendations for dispensary observation and treatment of patients with HIV infection. Clinical protocol // Epidemiology and infectious diseases. 2015. No. 6 (Appendix).
4. Pivnik A. V., Tumanova M. V., Seregin N. V., Parkhomenko Yu. G., Tishkevich O. A., Kovrigina A. M., Likunov E. B. Lymphomas in HIV-infected patients: a review of the literature // Clinical oncohematology. Reviews. 2014. V. 7. No. 3.
5. Pokrovsky V. I., Lobzin Yu. V., Volzhanin V. M., Belozerov E. S., Bulankov Yu. I. Infections of the nervous system with a progressive course. St. Petersburg: LLC "Publishing House Foliant", 2007. 264 p.
6. Goreiko T. V., Kalinina N. M., Drygina L. B. Modern ideas about the immunopathogenesis of infection caused by the Epstein-Barr virus // Infection and Immunity. 2011. V. 1. No. 2. S. 121-130.
7. Pagano J.S. Viruses and lymphomas // N. Eng. J. Med. 2002 Vol. 347. No. 2. P. 78-79.
8. Shakhgildyan V. I., Yadrikhinskaya M. S., Safonova A. P., Domonova E. A., Shipulina O. Yu., Alvarez-Figueroa M. V., Dolgova E. A., Tishkevich O. A. The structure of secondary diseases and modern approaches to their laboratory diagnosis in patients with HIV infection // Epidemiology and infectious diseases. Topical issues. 2015. No. 1. S. 24-30.
9. Yachie A., Kanegane H., Kasahara Y. Epstein-Barr virus-associated T-/natural killer cell lymphoproliferative diseases // Semin. Hematol. 2003 Vol. 40. No. 2. P. 124-132.

Z. A. Khokhlova* , 1 ,doctor of medical sciences, professor
R. A. Gileva*
T. V. Sereda*, Candidate of Medical Sciences
N. A. Nikolaeva*, Candidate of Medical Sciences
A. P. Tishkina**
L. Yu. Zolotukhina***
Yu. M. Kirillova***

* NGIUV - branch of FGBOU DPO RMANPO of the Ministry of Health of the Russian Federation, Novokuznetsk
** GBUZ KO NGKIB No. 8, Novokuznetsk
*** GBUZ KO NGKB No. 29, Novokuznetsk

Generalized lymphoma associated with HIV infection / Z. A. Khokhlova, R. A. Gileva, T. V. Sereda, N. A. Nikolaeva, A. P. Tishkina, L. Yu. Zolotukhina, Yu. M. Kirillova
For citation: Attending physician No. 8/2018; Page numbers in the issue: 64-68
Tags: malignant lymphoproliferative diseases, skin, viruses, poor prognosis

Primary cerebral lymphoma is a fairly rare disease caused by damage to the lymphoid tissue in the head section of the central nervous system. Pathology is also known under other names - reticulosarcoma, microglioma, diffuse histocytic lymphoma.

What it is

Cerebral lymphomas are non-Hodgkin B-cell tumors characterized by a high degree of malignancy. Neoplasms of this type grow directly from the tissues of the brain, the soft membranes of the brain (less often the eyeball). In most cases, the primary tumor remains within the CNS, rarely metastasizing.

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Like any oncological tumor, lymphoma develops gradually and rarely gives pronounced specific symptoms in the first stages. For this reason, the detection of lymphoma does not always occur at the stage when it is possible to effectively and quickly cure the disease.

In addition, the presence of the blood-brain barrier (a physiological barrier that protects the brain from toxins and other pathogenic factors) prevents the full use of typical treatment methods for lymphomas. For this reason, the therapy of this disease is difficult and often has an unfavorable prognosis.

Causes

Most often, lymphomas occur in people over 50-60 years of age with a weakened immune system.

The reasons for the weakening of the immune system and the development of lymphomas can be as follows:

• organ transplant (heart, kidney and liver);
• the presence of an immunodeficiency virus;
• the presence of the Epstein-Barr virus and mononucleosis caused by this virus;
• exposure to high doses of radiation;
• contact with carcinogens;
• predisposition to chromosomal mutations, inherited.

Brain lymphoma in HIV is a kind of complication caused by a malfunction of the lymphatic system. In such patients, the treatment of the disease is difficult due to the limited possibility of using strong drugs and is often fraught with death.

Recently, all over the world, physicians have noted a trend towards an increase in the number of malignant diseases associated with lesions of the lymphoid tissue. Perhaps the reason is the deterioration of the general environmental situation in large cities, as well as the nutritional habits of a modern person who consumes an increased amount of products with chemical additives - potential carcinogens.

In addition, the number of HIV-infected patients with brain lymphoma is increasing.

Symptoms of brain lymphoma

In the case of brain lymphoma of non-Hodgkin's type, neoplasms may originate from the lymphoid tissue of originally non-lymphoid organs. In addition, the disease can be secondary - in this case, the brain is involved in a process that began elsewhere in the body. Secondary cancerous foci (metastases) are single or multiple tumor nodes.

There are also the following forms of brain lymphoma:

• diffuse meningeal infiltration (the so-called leptomeningeal form, affecting primarily the meninges);
• ocular lymphoma (orbital) - a neoplasm that affects the vitreous body of the organ of vision or the retina;
• spinal form, affecting not only the brain, but also the spinal cord.

The clinical symptoms of cerebral lymphoma resemble other CNS cancers.

The list of manifestations includes:

• headache;
• drowsiness;
• focal neurological symptoms (the features of this group of signs depend on the location of the primary focus and its size);
• epileptic seizures;
• emotional disturbances;
• neuropathy;
• hydrocephalus (accumulation of excess CSF in the subarachnoid space and ventricles of the brain);
• speech disorders;
• visual disturbances;
• hallucinations;
• loss of coordination of movements;
• weakness and numbness in the hands.

At later stages, as the malignant process progresses and the tumor grows, there may be signs of personality changes, inadequacy of emotional reactions, memory lapses. These disorders are especially characteristic of lesions of the frontal and temporal lobes.

Diagnostics

If a primary brain lymphoma is suspected, magnetic resonance imaging (MRI) is prescribed. This imaging method allows you to study in detail the state of the brain, membranes and internal cavities inside the skull. If necessary (to check the condition of the vessels), tomography with a contrast agent is prescribed.

Clarification of the diagnosis may require additional studies:

• lumbar puncture and further examination of the cerebrospinal fluid for the presence of specific cells (cancer markers);
• stereotaxic biopsy: a sample of tumor tissue - a biopsy - is taken through a small hole in the skull, and then examined in the laboratory (this method allows you to identify the degree of malignancy of the neoplasm, the stage of its development and prescribe adequate therapy);
• trepanobiopsy - taking a sample by the method of full opening of the skull;
• blood analysis.

If a secondary nature of brain lymphoma is suspected, additional studies of the body are prescribed - ultrasound, CT, x-rays.

Sometimes a bone marrow biopsy may be needed (if the primary focus is in the bone marrow). This variant of the development of the disease is represented by infiltration of the brain parenchyma with leukocytes.

Secondary brain lesions cause similar symptoms with a predominance of pain symptoms. Patients are haunted by an excruciating bursting headache, nausea and vomiting, swelling of the optic nerves, blurred vision, hearing.

In a number of clinical cases, secondary brain lesions cause sudden hemorrhages, ischemic cerebral infarctions. Subdural (epidural and intracerebral) hematomas disrupt brain activity and lead to progressive encephalopathy.

You can find out the cost of lymphoma treatment in Moscow.

Treatment

Over the past decades, brain radiotherapy has remained a priority in the treatment of lymphomas. This technique is indeed quite effective, but the positive dynamics after exposure to radiation is temporary.

More stable results are achieved when systemic chemotherapy is used in conjunction with radiation. Patients with an adequate immune status (doctors call such patients "immunocompetent") respond well to complex treatment: the remission period is extended to several years.

Immunotherapy and targeted therapy can be used as experimental methods, however, long-acting drugs against lymphomas have not yet been created.

Symptomatic therapy is also used - treatment of concomitant disorders:

• hypertension;
• pain syndrome;
• neuropathy;
• hypercalcemia.

Palliative treatment at the last stage of malignant cerebral lymphomas involves the relief of intense pain symptoms with narcotic analgesics. Often this is the only help that doctors can provide to patients. Surgical removal of brain lymphomas is impossible in almost 100% of cases, since the risk of disturbing the nervous and mental activity of the patient is too great.

In the past, attempts at radical treatment of brain tumors were made, and repeatedly, but in most such therapy ended in damage to the deep structures of the brain. The difficulty lies also in the inability to define clear boundaries of lymphomas.

Video: About brain tumors

Forecast

If cerebral lymphomas occur in AIDS patients, the prognosis is unfavorable. The life expectancy of patients does not exceed several months. Primary lymphomas in people with normal immunity who are exposed to radiation therapy may stop growing and develop for some time, but this period does not exceed 12-18 months.

The use of complex therapy improves the prognosis. The impact of chemotherapy drugs increases the life expectancy of patients by several years. However, complete cure of brain lymphoma is extremely rare.