[The morphological characteristics of HIV-associated tuberculosis in relation to blood CD4+ lymphocyte counts].

OBJECTIVE: To investigate the morphological features of HIV-associated tuberculosis with different peripheral blood CD4 lymphocyte counts. MATERIAL AND METHODS: Intraoperative and biopsy specimens from 148 patients with HIV-associated tuberculosis were examined. Group 1 included 16 (10.8%) patients having a CD4+ lymphocyte count above 350 cells/µl; Group 2 comprised 38 (25.7%) patients having 200 to 349 cells/µl; Group 3 consisted of 94 (63.5%) patients with a CD4+ lymphocyte count below 200 cells/µl. Histological and immunohistochemical studies and a polymerase chain reaction assay were used. RESULTS: According to the predominant inflammatory phase, all analyzed cases were divided into 4 patterns of tissue responses: 1) typical productive granulomatous tuberculous inflammation; 2) obscure productive granulomatous inflammation; 3) a predominant alterative phase with the formation of pyonecrotic foci; 4) a predominant exudative tissue response with the development of amorphofunctional pattern typical of nonspecific inflammation. A relationship was found between the count of CD4+ lymphocytes and the predominant pattern of a tissue inflammatory response. A productive component of inflammation prevailed in Group 1; a mild productive response with the significantly obscure features of a granulomatous process was dominant in Group 2; alterative phenomena were noted in Group 3. Most patients (n=132, 89.2%) were stated to have an obscure granulomatous response (n=61, 41.2%), and a preponderance of an alternative (n=48, 32.4%) and vascular (n=23, 15.6%) components of inflammation. CONCLUSION: The magnitude of alterative and exudative components in the foci of tuberculous inflammation suggested that there was a change-over from a delayed hypersensitivity reaction that was typical of tuberculosis to an immediate hypersensitivity reaction and reflected severe immune system dysfunction.

[Basic principles in the formulation of a postmortem diagnosis in HIV-associated infections].

If a patient dies from HIV-associated disease, after the heading "Underlying disease" the postmortem diagnosis should contain the heading "Secondary diseases" wherein HIV-associated infection is given with the form, site, extent, and activity of the process being indicated. While comparing clinical and postmortem diagnoses in HIV infection, the discrepancy should be specified in view of a secondary disease. If there are a few HIV-associated infections, they all are indicated in the heading "Secondary diseases", one of them, the complications of which are of crucial importance in tanatogenesis, is better chosen to be encoded in the medical death certificate. In some situations, HIV infection can be mixed, competitive, background, or concomitant regardless of its stage.

[Acute toxic dystrophy of the liver during antituberculosis therapy].

The paper considers a case of acute toxic dystrophy of the liver developing as a manifestation of an idiosyncratic dose-independent unpredictable reaction during standard antituberculosis therapy. The process of liver damage was fulminant with massive diffuse centrilobular necroses, lymphoid-eosinophilic infiltration in the portal tracts, and the development of liver failure.

[Analysis of lethal outcomes in patients with newly-diagnosed tuberculosis of the respiratory organs in combination with HIV-infection].

AIM: To analyse lethal outcomes in patients with newly-diagnosed respiratory tuberculosis comorbid with HIV-infection depending on initial count of CD4+ lymphocytes. MATERIAL AND METHODS: Of 304 HIV patients with newly-diagnosed tuberculosis treated in Moscow Tubercusis Hospital N 7 in 2006-2010, 40 (13.2%) patients died. Tuberculosis diagnosis was made after detection of M. tuberculosis (MT) by different tests, MT DNA in different biological material, histological verification or by effectiveness of specific antituberculous therapy. Postmortem examinations were made according to the protocol. RESULTS: Significant differences were detected in patients with initial count of CD4+ lymphocytes less than 50 in 1 mcl. Specific CNS affection was found in patients with initial lymphocyte count CD4+ less than 100 in 1 mcl. Most of autopsy examinations registered generalized acutely progressive tuberculosis with multiple lesions of internal organs and lymph nodes (LN). Microscopy revealed obscure morphological picture of specific inflammation with prevalence of alternative-exudative tissue reactions in the absence of a productive inflammation component. Cases with submiliary dissemination which was invisible in macroscopic examination due to a bright picture of exudative tissue reaction (rare plethora of the lungs, alveolar and interstitial edema, perifocal inflammatory reaction of nonspecific reactive nature) and small size of the lesions. The comparison of clinical and autopsy diagnoses revealed that involvement of intrathoracic LN and miliary dissemination, according to autopsy, occurred much more frequently than shown by antemortem standard x-ray examination of the chest. CONCLUSION: It is strongly recommended to perform computed tomography of the chest in all HIV-infected patients with long-term fever but without visible alterations on chest x-ray.

[Destructive changes of lung in HIV-associated infections: differential diagnosis].

HIV-associated infections have progressing and generalized character and most of all affect the lung caused destructive lung disorders. The morphology of opportunistic infections is unclear because of inadequate immune response to severe immunodeficiency. For the right differential diagnosis of the destructive lung changes in HIV-associated infections it's necessary to use complete bacteriological, cytological, histological, histobacteriological and molecular-genetic researches.

[The clinical and morphological features of the course of tuberculosis in HIV infection].

The development of an acutely progressing process of varying extent to the point of total damage to both lungs is typical of a patient with tuberculosis concurrent with HIV infection due to progressive immunodeficiency. There is an apparent need for dividing patients with comorbidity into 2 groups: (1) HIV/TB, in patients HIV infection is a primary disease; (2) TB/HIV, in whom tuberculosis is accordingly primary. These groups differ in clinical manifestations, forms of tuberculosis, and pathomorphological changes. Group 1 patients are mostly typified by the primary forms of tuberculosis with involvement of lymph nodes of all groups and by miliary processes at the sites of multiple organs (the lung, abdomen, and central nervous system). Most patients from Group 1 are observed to have fever, progressive intoxication, and morphologically necrotic foci without signs of differentiation and in the absence of typical granulomas. Multiple drug resistance is noted in more than 20% of the patients; in these patients, the efficiency of an intensive therapy phase in arresting bacterial discharge is 26.9%. In Group 2 patients, comorbidity takes a less acute course, pulmonary symptoms are less marked; there is a preponderance of infiltrative, disseminated, firocavernous pulmonary tuberculosis, and caseous pneumonia. In this group, the signs of a prior tuberculous process with phenomena of a slight or moderate productive reaction and with resolution elements are morphologically detectable. In late-stage HIV infection--AIDS, the patients from both groups develop a generalized tuerculous process. Both patient groups are typified by the severe progressive course with identical clinical and pathomorphological manifestations, which results in death.

[Efficiency of partial pneumonectomies in patients with multidrug-resistant tuberculosis].

The immediate results of partial resections were analyzed in 120 patients with drug-resistant pulmonary tuberculosis, among whom 70 patients had multidrug resistance. A complete clinical effect (abacillation and no decay cavities) was achieved in 117 (97.5%) patients, including in 67 (95.7%) patients with multidrug resistance who showed improvement in 3 (2.5%) cases, fatal outcomes being absent.

[Lung pathology in HIV-associated infections].

The lung and intrathoracic lymph nodes taken from 153 persons who had taken from HIV infection at the age of 20 to 32 years, with the development of various infectious diseases were examined. Secondary diseases were of generalized progressive pattern. Among these diseases accompanied by pulmonary lesions tuberculosis, as well as bacterial pneumonias, cytomegalovirus infection, pneumocystic pneumonia, cryptococcosis, and non-tuberculous mycobacterial diseases were most common. Lung tissue reactions at terminal stages of HIV infection were polymorphic, which had been caused by severe immunodeficiency, a change in the course of diseases, obliteration of typical morphological signs, and a mixed lung lesion. This makes the differential diagnosis of diseases difficult and requires a comprehensive study of specimens in each specific case, by widely employing additional methods and stains to detect different pathogens.

[Pathomorphological changes in the lung in tuberculosis patients died from HIV infection at the stage of AIDS].

The authors revealed the typical morphological changes of lung tuberculous lesion in HIV infection at the stage of AIDS: these included alterative changes without typical tuberculosis granulomas; a well-defined exsudative inflammatory component with a predominance of leukocytic infiltration and a drastically decrease of and, occasionally, a complete disappearance of macrophages and lymphocytes; formation of pyonecrotic foci; the focal monomorphic pattern illustrating the loss of the signs of process indulation. These signs suggest the specific features of immunity and the course of specific inflammation as immediate hypersensitivity with the acutest progression of tuberculosis.

[On the morphological diagnosis of drug-resistant pulmonary tuberculosis].

The intraoperative samples taken from 15 patients with acutely progressive drug-resistant fibrocavernous pulmonary tuberculosis were studied. There were typical signs of granulomatosis inflammation, a predominance of an exudative tissue reaction, and an extensive vascular bed lesion. Two types of perifocal cellular infiltrates were identified. Mononuclear infiltrates with epithelioid cellular transformation along the periphery were defined as specified. Nonspecific infiltrates were composed of foam macrophages-lipophages and they reflected lipid metabolic disturbances. In addition, the severity of the process was determined by an extensive specific bronchial lesion of all generations. A morphological study of the samples could reveal the tissue and cellular features of respiratory organs in drug-resistant tuberculosis and identify the diagnostically significant signs of specific and nonspecific inflammation.

[Impact of phthisiosurgery on the development of morphological studies of the lung].

The paper describes the most important developmental stages of phthisiomorphology in chronological order, by using as an example the work of the Pathomorphology Laboratory, Central Tuberculosis Research Institute, since its organization. It also shows the stages of phthisiosurgery with the inestimable scientific and practical contribution of the works by L. K. Bogush and his followers from the formation of lung surgery to today's achievements. The authors give examples of the long-term working partnership of surgeons and morphologists in the development of these two disciplines, which was fruitful in deciding many issues of phthisiology.

[The tissue and cellular reactions of the lung in drug-resistant tuberculosis]. / Tkanevye i kletochnye reaksii legkikh pri lekarstvenno-ustoichivom tuberkuleze.

The material obtained from 52 patients with drug-resistant fibrocavernous pulmonary tuberculosis was studied. Morphological studies established the progression of a process in 94.2% of the cases. There was a prevalence of an alternatively exudative tissue reaction, a generalization of the process with specific and non-specific changes in the lung, lesion to the vascular bed with a predominance of an exudative reaction, generalized nonspecific and specific bronchitis with impaired elimination of the intraalveolar contents and with the preserved extensive cellular infiltrates in the lung. Healing elements as the signs of the encapsulation of caseous necrosis, the proliferation of lymphoid elements, and a macrophageal response were simultaneously revealed, which provides evidence for that different modalities of pathogenetic therapy should be used.

[Clinical and morphological characteristics of migrating erythema in patients with Ixodes tick-borne Lyme disease]. / Kliniko-morfologicheskie osobennosti proiavlenii migriruiushchei éritemy u bol'nykh iksodovym kleshchevym borreliozom.

Patients with erythematous Ixodes tick-borne relapsing fever were examined and their skin biopsy specimens were morphologically studied to reveal clinical, immunological and morphological features of erythematous Ixodes tick-borne relapsing fever. Two types of development of erythema migrans were identified. These include 1) a typical type that appears as an area of homogenous hyperemia or that of annular shape and 2) an atypical one that presents as minor vesicles. There were elevated serum immunoglobulins A levels at the height of the disease. Morphologically, at the early stage of the disease, the center of erythema shows disturbances characterized by epidermal dystrophic processes, koilocytosis, subhorny and epidermal vesicles. The dermis displays solid perivascular lymphocytic infiltrates admixed with fibroblasts, fibrocytes, macrophages, plasmocytes, eosinophils, degranulated labrocytes. The interstitium exhibits scanty infiltrates. These changes are less pronounced at the periphery. Electron microscopy shows the structures morphologically similar to those of Borrelia. The late stage (days 15-23) of the disease is marked by insignificant dystrophy and perivascular fibrosis. There were no interstitial infiltrates. By and large, the pattern of clinical and immunological manifestations in patients with erythema migrans correlates with dermal morphological changes.