Цель. Осуществить иммуногистохимические исследования факторов клеточного иммунитета в биоптатах острых и хронических ран с учетом клинико-микробиологических характеристик раневой поверхности. Материалы и методы. Выполнен анализ относительного содержания (%) CD3+ (Т-лимфоциты), CD4+ (Т-хелперы) и CD8+ (Т-цитотоксические лимфоциты), CD20+ (В-лимфоциты), CD138+ (плазмоциты), CD68+ (макрофаги), CD15+ (нейтрофилы), CD34+ (эндотелий сосудов), CD57+ (натуральные киллеры), d2-40 (лимфатический эндотелий), Ki 67+ (маркер пролиферации), каспаза 3+ (маркер апоптоза), S100 (маркер воспаления), COX-2 (маркер воспаления) клеток по результатам иммуногистохимического исследования биоптатов грануляционной ткани пациентов с острыми ранами (ОР, n=30, срок раны от 5 до 21 суток) и хроническими ранами (ХР, n=120, срок раны более 3 недель). Оценивали также клинический статус раны на предмет наличия признаков воспаления и выполняли микробиологический посев раневого отделяемого. Результаты. Более высокие значения иммунорегуляторного индекса (отношение CD4+/CD8+) и маркера пролиферации Ki 67+ регистрировались в острых ранах сроком от 5 до 21 суток, более низкие – в хронических ранах сроком более 22 суток и существенно не изменялись в зависимости от клинико-микробиологического состояния ран. Дополнительным признаком локального иммунного ответа являлось количество нейтрофилов, преобладающее в хронических ранах. Воспалительный статус ран и присутствие микроорганизмов, переход от стадии колонизации к стадии критической колонизации и инфекции характеризовались увеличением относительного содержания в ранах Т-лимфоцитов и их основных субпопуляций (CD4+ и CD8+ клеток), В-лимфоцитов, нейтрофилов и макрофагов, более высокими значениями S100 и COX-2. При выделении из хронических ран монокультур S. aureus в биоптатах в меньшем количестве обнаруживались В-лимфоциты, натуральные киллеры и макрофаги по сравнению с их содержанием в ранах, в которых этиологическими факторами инфекционного процесса были P. aeruginosa и A. baumannii. Выводы. Определение клеточных факторов локального иммунитета является перспективным направлением для дифференциальной диагностики острой и хронической раны, а особенности их изменения позволяют установить стадию инфекционного процесса. Purpose. To analyze the results of immunohistochemical studies of biopsy specimens from acute and chronic wounds taking into account their clinical and microbiological characteristics. Materials and methods. The relative content (%) of CD3+ (T-lymphocytes), CD4+ (T-helpers) and CD8+ (T-cytotoxic lymphocytes), CD20+ (B-lymphocytes), CD138+ (plasmocytes), CD68+(macrophages), CD15+(neutrophils), CD34+(vascularendothelium), CD57+ (natural killer cells), d2-40 (lymphatic endothelium), Ki 67+ (proliferation marker), caspase 3+ (apoptosis marker), S100 (inflammatory marker), COX-2 (inflammatory marker) cells was analyzed according to the results of immunohistochemical study of granulation tissue biopsy specimens from patients with acute wounds (n=30, wound duration from 5 to 21 days) and chronic wounds (n=120, wound duration more than 3 weeks). The clinical status of the wound was also assessed for signs of inflammation, and microbiological culture of wound swabs was performed. Results. Higher values of the immunoregulatory index (the ratio of CD4+/CD8+ lymphocytes) and the proliferation marker Ki 67 were recorded in acute wounds for a period of 5 to 21 days, lower values – in chronic wounds for a period of more than 22 days, and did not significantly change depending on the clinical and microbiological state of wounds. An additional feature was the number of neutrophils predominating in chronic wounds. The inflammatory status of wounds and the presence of microorganisms, as well as switch from colonisation stage to critical colonisation and infection stage were characterised by an increase in T-lymphocytes relative content and their major subpopulations (CD4+ and CD8+ cells), B-lymphocytes, neutrophils and macrophages, higher values of S100 and COX-2 in wounds. When S. aureus monocultures were isolated from chronic wounds, B-lymphocytes, natural killer cells and macrophages were lower in biopsy specimens compared to their content in wounds in which P. aeruginosa and A. baumannii were etiologic factors of the infectious process. Conclusions. Immunohistochemical cell markers are promising objective criteria for differential diagnosis of acute and chronic wounds, allowing to establish the infectious process stage.

Water clear cell adenoma (WCCA) is one of the rarest forms of primary hyperparathyroidism associated solitary adenomas [1]. According to Boutzios et al. [2], the frequency of WCCA is less than 1% of all primary parathyroid hyperplasia. We herein report a case of primary hyperparathyroidism in a 64-year-old woman with adenoma of the upper left parathyroid gland. Preoperative biochemical analysis revealed serum calcium level of 3.0 mmol/l (reference range 2.15–2.50 mmol/l), serum phosphorus level of 0.64 mmol/l (reference range 0.81–1.45 mmol/l) and intact parathyroid hormone level­ of 117.4 pg/ml (reference range 15.0–65.0 pg/ml). Bone densitometry revealed osteopenia and loss of bone density. Surgical resection of parathyroid glands was performed. Grossly, the specimen was presented by pale gray nodule 30×21×25 mm in capsule weighing 5.34 g. Histopathological examination revealed “nest” pattern areas of large clear cells with foamy vacuolated cytoplasm (Figure, а) and in some areas with granular cytoplasm (Figure, b). Cell nuclei were dense with mild atypia and prominent nucleoli (Figure, c). It was resembled as paraganglioma and renal clear cell adenoma. For clarification of the diagnosis, immunohistochemical analysis was conducted for S100, PAX8, CD10 and vimentin. This analysis did not demonstrate an expression of PAX8, CD10 or vimentin, which excluded the possibility of renal clear cell carcinoma metastasis. An absence of S100 expression eliminated the diagnosis of paraganglioma. The diagnosis of WCCA of parathyroid gland was conducted based on the above data. After surgical resection of the neoplasm, the levels of serum calcium and intact parathyroid hormone level decreased. Figure. Nest pattern of growth of WCCA (a) (hematoxylin-eosin, original magnification × 40); granular cytoplasm of the WCCA cells (b) (hematoxylin-eosin, original magnification × 200); dense nucleus with mild atypia (c) (hematoxylin-eosin, original magnification × 400) In 1994, the first case of WCCA was described by Kovacs et al. [3]. Since then, over 20 cases of this tumor have been described (according to searches in Pubmed, Scopus and Google Scholar). This neoplasm has a low endocrine activity, making clinical manifestation only when the adenoma become large enough for causing high serum calcium levels [1]. In our study, we also observed high levels of serum calcium, but intact parathyroid hormone level also increased. The differential diagnosis of WCCA includes metastatic renal cell carcinoma in the parathyroid gland and paraganglioma.

Background. The group of plasma cell neoplasms includes benign and malignant diseases. Sometimes there are difficulties in making a diagnosis. The study of the diagnostic and prognostic significance of immunohistochemical (IHC) markers is of current interest.Aim. To study the significance of IHC markers and histological features of the bone marrow in primary diagnosis in patients with multiple myeloma (MM) and monoclonal gammopathy of undetermined significance (MGUS).Materials and methods. The study included 287 patients with plasma cell neoplasms: MGUS (n = 148), MM (n = 139). The observation period was 50 months. All patients have performed an aspiration biopsy and histological examination of the bone marrow with IHC analysis of CD138+, CD56+, CD34+, κ- and λ-chains expression.Results. During the observation period the progression of MGUS to MM was recorded in 8.8 % (n = 13) of cases, the progression of MM was determined in 38.1 % (n = 53) of cases.In patients with MGUS and MM the determined percentage of plasma cells at aspiration biopsy was somewhat lower than at histological examination (p >0.001). Statistically significant differences were determined between the groups MGUS and MM by the type of infiltration (р <0.001). With an increase in the percentage of bone marrow lesions by IHC (<20 % vs. 20–50 % and 20–50 % vs. >50 %), in our study interstitial and diffuse type of lesion with large accumulations was more common compared to the nodular type (p = 0.001).The CD138+ expression (IHC) more than 10 % was associated with a decrease of progression-free survival in patients with MGUS.In MM patients with an interstitial type of bone marrow infiltration and CD138+ over 10 % osteodestructive syndrome was detected by X-ray methods in 82.9 % of cases.Determination of CD56+ and immunoglobulin light chains expression in patients with MM and MGUS indicated an unfavorable prognosis.Resistance to chemotherapy or disease progression in MM patients most often occurred with a combination of IgG and immunoglobulin light chains secretion, with CD138+ plasma cells more than 50 % according to IHC, with a diffuse type of bone marrow lesion with accumulations of plasma cells. MGUS patients progressed more frequently with more than 20 % CD138+ plasma cells according to IHC, interstitial type and diffuse plasma cells accumulation type of bone marrow lesion, secretion of IgG or two immunoglobulins.Conclusion. The significance of the IHC study in the diagnosis of plasma cell neoplasms was confirmed. Markers associated with the disease progression and chemotherapy resistance in patients with MGUS and MM were identified.

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Background:The number or size of focal lesions (FL) on whole-body magnetic resonance imaging (MRI) or positron emission tomography integrated with computed tomography (PET-CT) was shown to be associated with poor prognosis in multiple myeloma (MM) patients. However, it is complicated to determine the number or amount of FL on MRI or PET-CT imaging and patients cannot always undergo such medical imaging examination at diagnosis for many reasons. Therefore, developing simple method to estimate the amount of tumor burden from imaging data may be useful to predict prognosis of MM patients under various conditions. Aims: The aim of this study was to assess whether the number of involved bone regions at diagnosis could become a predictive marker of disease progression and survival in newly diagnosed MM patients. Methods: Clinical and imaging data of patients newly diagnosed with MM and immediately treated with chemotherapy from January 2013 to August 2018 at the institution were evaluated retrospectively. All imaging data had been interpretated by experienced radiologists. Each bone lesion was sorted according to 8 anatomical regions: skull, rib including clavicula, scapula, sternum, spine, ilium, upper limb, and lower limb. Factors associated with progression-free survival (PFS) or overall survival (OS) were statistically analyzed using log-rank test and Cox regression model. Results: Eighty-three evaluated patients had a median age of 69 years old (yo) (range: 45-92). 9% of them were classified as revised International Staging System (R-ISS) stage 3. As imaging tools for evaluation of bone disease, CT and additional skeletal x-ray were conducted in all cases, MRI (of not the whole-body, usually of the spine) in 80%, PET-CT in 45% and bone scintigraphy in 16%. Median number of involved bone regions was 2 (range: 0-8). 9% of patients had no bone disease and 46% had bone lesions in at least 3 different regions. The most involved region was spine (77%) following rib (46%), ilium (38%), lower limb (27%), sternum (26%), skull (24%), upper limb (21%), and scapula (13%). Only 3 patients had extramedullary disease (EMD). 95% of patients were initially treated with therapeutic regimen containing bortezomib or lenalidomide, 34% combined with radiation, and 6% followed by surgery. Autologous transplantation was performed in only 11 patients (13%). With a median follow-up of 26 months (range: 0-72 months), 2-year PFS and OS for all patients were 48% and 78%, respectively. The presence of bone lesions in at least 3 regions (PFS; P = .