OBJECTIVE:To determine the morphological features of IgG4-related lesions and to improve pathomorphological criteria for diagnosing various clinical variants of IgG4-related disease.MATERIAL AND METHODS:Biopsy and surgical materials from 100 patients with tumor-like lesions at various sites (63 cases of IgG4-related lesion and 37 cases of non-IgG4-related inflammatory processes) were studied. Histological and immunohistochemical studies were conducted to determine the absolute counts of CD138+ cells, IgG+ and IgG4+ in the inflammatory infiltrates, as well as IgG4/IgG and IgG4/CD138 cell ratios.RESULTS:When IgG4-related disease manifested, pancreatic, lacrimal, and salivary gland lesions prevailed. Brisk lymphoplasmacytic infiltration is characteristic for tissue damage in the eye, salivary glands, thyroid, pancreas, and skin. The formation of moiré fibrosis was specific to damages to the pancreas, liver and bile ducts, and eye tissues. Obliterative phlebitis is most often observed in pancreatic and salivary gland lesions. According to international criteria, the frequency of achieving the required level of IgG4+ plasma cells in each organ was high in lesions of the pancreas, bile ducts, and lymph nodes and that was low in lesions of the salivary and lacrimal glands and skin. The IgG4+/CD138+ and IgG4+/IgG+ cell ratios exceeded 40% in all cases.CONCLUSION:The morphologic diagnosis of IgG4-related disease is based on the detection of lymphoplasmacytic infiltration, moiré fibrosis, and obliterative phlebitis, as well as on the calculation of the absolute number of IgG4+ plasma cells in the inflammatory infiltrate and on the determination of IgG4+/IgG+ and IgG4+/CD138+ cell ratios. The number of IgG4+ plasma cells depends on the location of the lesion and on the phase of the process.

AIM:To determine the mitochondrial dysfunction in multiple sclerosis (MS).MATERIAL AND METHODS:Fourteen adult patients with MS and 23 healthy people were examined. Cytochemical analysis of lymphocytes in peripheral blood was carried out. The activity of the mitochondrial enzymes involved in metabolism of carbohydrates (lactate dehydrogenase, LDH), amino acids (glutamate dehydrogenase, GDH), fatty acids (alpha-glycerophosphate, α-GPDH) and II complex of the mitochondrial respiratory chain (succinate dehydrogenase, LDH), and the level of lactate in the blood were measured.RESULTS AND CONCLUSION:The activity of α-GPDH was reduced in 62.5% patients and increased in 37.5%. GDH activity in all patients was lowered. LDH activity was reduced in 71.4% patients and compensatory increased in 28.6%. In 66.7% patients, LDH activity was reduced and in 33.3% compensatory increased. Increased blood lactate was observed in 33.3% patients before meal and 44.4% after carbohydrate loading. After carbohydrate loading, in 33.3% patients lactate levels in the blood increased and in 11.1% increased above normal values. Therefore, the enzyme activity have decreased in most patients that suggests the decompensation of mitochondrial function. The results indicate the advisability of administering the energotrophic drugs carnicetin and coenzyme Q10 (idebenone) in patients with MS.

Parathyroid carcinoma (PTC) is a rare malignant tumor with the clinical manifestation of hyperparathyroidism, reliable morphological signs of invasive growth, and poor clinical prognosis. The differential diagnosis of PTC due to the rarity of this pathology, not always explicit morphological criteria, and the lack of a certain immunohistochemical panel is complex and needs further clarification. The paper summarizes an update on the clinical and morphological characteristics of PTC.

Aim: Combined clinical and morphological analysis of the pancreatic neuroendocrine tumor (pNET) spectrum according to the new World Health Organization classification: patient distribution, hormonal status, morphological grading, somatostatin receptor 2 (SSR2) and 5 (SSR5) expression, the choice of tissue-specific markers for the differential diagnosis of primary NET in the pancreas based on metastases with unknown primary tumor. Materials and methods: The study was performed with 472 tissue samples from pNETs taken from patients. Morphological analysis consisted of histological and immunohistochemical examination with a panel of antibodies to chromogranin A, synaptophysin, CD56, insulin, glucagon, somatostatin, gastrin, calcitonin, adrenocorticotropic hormone (ACTH), serotonin, pancreatic polypeptide, cytokeratins (CK) of a wide spectrum, CK7 and CK19, p53, Ki-67, SSR 2 and SSR5, PDX-1, Isl-1, and NESP-55. Results: In women, the prevalence of pNETS was 2.3 higher than in men (2.3:1). We were able to identify 299 (63.3%) insulinomas, 134 (28.4%) non-functioning NETs, 28 (5.9%) gastrinomas and 1.8% rare tumors (somatostatinomas, “calcitoninomas” and ACTH-producing). Metastatic tumors were found in 16.5% of the cases. Multiple endocrine neoplasia syndrome type 1 was confirmed in 11.9% of the pNET patients, and in 30.8% of those aged below 30 years. Multiple tumors (2 to 10) were found in 32 patients by the time of the diagnosis or occurred at 7 to 18 years after initial surgery. 28.3% of the tumors were CK19-positive, with 54.4% of them being metastatic. Insulinomas were least prone to metastasizing (5.7% of the cases), with 41.2% of them being CK19-positive. Metastases were found in 70.4, 66.7, 100, and 100% of gastrinomas, “calcitoninomas”, ACTH-producing, and somatostatinomas, respectively, with CK19-positivity found in 85.2, 66.7, 66.7, and 100% of these tumors. SSR2 expression was observed in all gastrinomas and “calcitoninomas”, in 90.5% of “glucagonomas”, 85.7% of PPomas, and 66.7% of somatostatinomas. SSR5 expression was significantly less frequent. 86.3% of the studied tumors were PDX-1-positive: all somatostatinomas, 97.4% of insulinomas, 92.3% of gastrinomas, 83.3% of PPomas, 80% of the non-functioning NETs. PDX-1-negativity was identified in all “calcitoninomas” and in 57.1% of the non-functioning “glucagonomas”. 83.3% and 90.9% of the pNETs were Isl-1 and NESP-55-positive, respectively. Conclusion: Combined morphological and immunohistochemical examination of pNETs allows for the correct diagnosis, assessment of their prognosis and choice of the most effective treatment. The malignancy grade of pNETs depends on the cell immunophenotype and is higher in the cases with co-expression of the markers of neuroendocrine and ductal differentiation (CK19), as well as with ectopic hormonal production.

The most prevalent skin cancer in the transplant organ recipients is squamous cell cancer, followed by basal cell cancer. The skin cancer incidence and related mortality in the transplant organ recipient are significantly higher than those in the general population, which is to be linked with prolonged pharmaceutical immunosuppression. Multiple tumors are also typical for this patient group. The article describes two rare combinations of skin carcinomas with different histological characteristics in patients with cadaver renal allograft (CRA). Clinical case 1: A 43-year old female patient. In 2011, she was transplanted with a CRA due to end-stage renal failure caused by congenital cystic dysplasia (multicystic kidney disease), with subsequent removal of the allograft at 1.5 months after the transplantation. In 2014, she had her second CRA transplanted and until now is on immunosuppressive therapy. In 2013, the patient noticed two slowly growing masses in her right and left supraclavicular areas; they were clinically assessed as basal cell cancer and surgically resected. Histological examination of the resected skin fragments showed squamous cell carcinoma focuses in situ (Bowen's disease), with alternating superficial basalioma focuses; proliferating keratinizing squamous cell cancer with polymorphous structure, with prevailing acantholytic type, morphoeic basal cell carcinoma and basal squamous cell carcinoma were found throughout the dermal layer, up to the subcutaneous tissue. Clinical case 2: A 63-year old male patient was transplanted with CRA in 2007, due to end-stage renal failure caused by nephrolithiasis and chronic pyelonephritis. During the examination performed in 2013, a mushroom-like tumor (with a 3 cm diameter and a stipe of 1 cm in diameter, with erythematous tuberous surface) was found on the anterior neck surface, near the suprasternal notch. The tumor was surgically resected within the normal skin. Histological and immunochemical examinations showed that the mass consisted of two different tumors closely adjacent one to the other and separated by a narrow dermal layer, namely, neuroendocrine Merkel cell skin carcinoma and porocarcinoma with some signs of squamous cell and sebaceous cell differentiation.Conclusion: The descriptions of the rare cases confirm that transplantation-related skin cancers are highly relevant. Due to continuous renewal of the tissue components that is intrinsic to this organ, and due to deterioration of the immune control over proliferation and differentiation, they are characterized by a multiplicity of histological types and an unfavorable prognosis.

Background: The cause of late diagnosis of renal cancer lies in its durable, almost asymptomatic course. Due to the use of antiangiogenic therapies much progress has been made in its treatment in recent years. Yet, many questions concerning the diagnosis, prognosis and prediction of the efficiency of targeted therapy remain unsolved. Therefore, exploration of new renal cancer molecular markers, especially those related to its angiogenic and invasive activities, are still on the agenda. Such markers include the family of matrix metalloproteinases (MMPs) that degrade the majority of extracellular matrix components and are involved at all stages of tumor progression. Aim: Comparative evaluation of MMP2, 7, 8, 9 and type 1 tissue inhibitor (TIMP-1) levels in serum of healthy individuals and patients with renal cancer or benign renal tumors, analysis of their associations with the main clinical and pathologic characteristics of the disease. Materials and methods: We examined 99 renal cancer patients (of those 94 with primary tumor and 5 at progression) and 10 patients with benign renal tumors. The control group included 97 healthy individuals. Levels of the proteins studied were measured using respective direct ELISA kits (Quantikine®, R&D Systems, USA). Results: MMP-7, MMP-8 and TIMP-1 levels in the sera of renal cancer patients were significantly higher than in the control group and in benign renal tumor patients. MMP-2 and MMP-9 levels did not differ significantly between the study and control groups. At MMP-7 cut-off level of 3.0 ng/mL, its diagnostic sensitivity for primary renal cancer was 84%, specificity in relation to “healthy” control – 87.5%, in relation to the pathologic control (healthy donors+benign renal tumor patients) – 73%. The best sensitivity: specificity ratio for TIMP-1 was 67 and 65% at the cut-off level of 315 ng/ml. No cut-off value with acceptable sensitivity: specificity ratio was found for MMP-8. Serum levels of all these 3 markers were positively associated with disease stage and TNM indices; MMP-7 and TIMP-1 levels also increased with lower differentiation grade. In 5 patients evaluated at disease progression the levels of all the markers studied were markedly higher than in the primary patients, and exceeded the estimated cut-off values. Conclusion: MMP-7 should be regarded as the most promising serological renal cancer marker; its serum levels exceed the cut-off value even in 84% stage I patients. TIMP-1 has acceptable sensitivity (70% and above) only from stage II renal cancer onwards, while MMP-8 levels are increased only at stage III–IV of the disease.

The progress in treatment of kidney cancer is related to application of anti-angiogenic medications. Therefore, investigation and searching for new molecular markers characterizing its angiogenic activity is actual still. The purpose of study is to compare VEGF, VEGFR1 and VEGFR2 in blood serum of healthy people, patients with cancer and benign tumors of kidney and to analyze their relationship with main clinical morphological characteristics of neoplasms. The study sampling consisted of 94 patients with cancer and 10 patients with benign tumors of kidney. The control group included 80 individuals. The concentration of analyzed proteins was determined using QuantikineТ (R&D Systems, USA), a reagents' kit for direct immune enzyme analysis. The content of VEGF, VEGFR1 and VEGFR2 in blood serum of patients with cancer of kidney was reliably higher than in control group. The level of VEGF also was increased in patients with benign tumors. Under threshold level of VEGF of 365 pg/ml the diagnostic sensitivity of detection of primary cancer of kidney amounted to 67% and specificity - 70%. The stage of disease and T and N indices were correlated only with VEGFR1 level. The relationship between level of markers and histological structure and degree of differentiation of cancer of kidney was not established. Therefore, VEGF and its receptors have a limited diagnostic value under cancer of kidney but they can be applied for monitoring and prognosis of efficiency of anti-angiogenic therapy.

Pleuropulmonary blastoma is a rare primary malignant tumor originating from lungs and/or pleura. It is more frequent in young children and differs from other lung neoplasms by a number of histopathological particulars. We present a clinical case of such tumor in a 3-year-old child. Initially, the disease was diagnosed as pleuropneumonia, however, computed tomography revealed a tumor originating from mediastinum. Current data indicates that diagnostics of pleuropulmonary blastoms is difficult even with the use of a full range of radiation assessment methods and participation of qualified specialists.

Background: Neuroendocrine tumors of the lung (NETL) are a wide range of tumors with various malignancy grades and prognosis. Despite their prevalence being 20 to 25% of all lung cancers, many aspects that impact their clinical course and prognosis are not well understood. Aim – to identify morphological and immunophenotypic characteristics of various NETL types would that more accurately reflect their biological potential and allow for prediction of their unfavorable clinical outcomes. Materials and methods: We performed immunohistochemical assessment of the diagnostic biopsies and surgical specimens from 152 patients with NETL aged 53 ± 13 years and identified 49 typical carcinoids, 32 atypical carcinoids, 60 small cell neuroendocrine carcinomas and 11 large cell neuroendocrine carcinomas, which accounted for 32.2, 21.1, 39.5 and 7.2%, respectively. Markers of neuroendocrine differentiation, such as synaptophysin, chromogranin A and CD56, as well as cytokeratins 7 and 19, thyroid transcription factor-1 (TTF-1), and Ki67 were used. The results were analyzed with analysis of variance (ANOVA), chi-square test (χ²), and post-hoc comparisons with the Bonferroni correction. Results: Most often, the expression of cytokeratins 7 and 19 was found in large cell neuroendocrine carcinoma (72.7 and 90.9%, respectively), less frequently, in atypical carcinoids and small cell neuroendocrine carcinomas (50 and 53.3%; 41.7 and 64.6% of cases, respectively), whereas in typical carcinoids it was rare (5.9 and 15.9%, respectively). The rates of cytokeratin 7 and 19 expression were significantly lower in the typical carcinoids, compared to the atypical carcinoids, small cell neuroendocrine carcinomas and large cell neuroendocrine carcinomas (р < 0.05, χ²). The expression of cytokeratin 19 was significantly more common for large cell neuroendocrine carcinomas, than for small cell neuroendocrine carcinomas and atypical carcinoids (р < 0.01, χ²). The expression of TTF-1 was very rare in the typical carcinoid cells (6.5% of cases) and significantly more often in atypical carcinoids (61.5%) and in small cell neuroendocrine carcinomas and large cell neuroendocrine carcinomas (82.7 and 77.8% of cases, respectively). TTF-1 expression was significantly less frequent in typical than in atypical carcinoids, small cell neuroendocrine carcinomas and large cell neuroendocrine carcinomas (р < 0.01, χ²). The mean index of tumor cell proliferation (Ki67) was the lowest in typical carcinoids (2.6%), amounted to 12% in atypical carcinoids, to 44% in large cell neuroendocrine carcinomas and reached the maximum of 61% in small cell neuroendocrine carcinomas. There were significant differences in the mean Ki67 index in the NETL 4 groups (р < 0.001, ANOVA). Conclusion: Expression of TTF-1, cytokeratin 7 and 19 in the neuroendocrine tumors of the lung is characteristic for a less differentiated cell immunophenotype and allows for identification of the risk group with unfavorable clinical outcome among low-grade typical and atypical carcinoids.

The paper presents the data available in the literature on IgG4-related disease (IgG4-RD) concurrent with malignancies at different sites, as well as possible common pathogenetic mechanisms of their development and morphological diagnostic criteria for IgG4-RD. The authors give their own observation of gastric signet ring cell carcinoma concurrent with morphologically verified IgG4-RD.

Pleuropulmonary blastoma is a rare primary malignant tumor originating from lungs and/or pleura. It is more frequent in young children and differs from other lung neoplasms by a number of histopathological particulars. We present a clinical case of such tumor in a 3-year-old child. Initially, the disease was diagnosed as pleuropneumonia, however, computed tomography revealed a tumor originating from mediastinum. Current data indicates that diagnostics of pleuropulmonary blastoms is difficult even with the use of a full range of radiation assessment methods and participation of qualified specialists.

We present a clinical case of parathyroid cancer in a patient with relapsing secondary hyperparathyroidism at 4 years after subtotal parathyroidectomy. Its unique character is related to the combination of relapsing secondary hyperparathyroidism, parathyromatosis, ectopic of an adenomatous hyperplastic parathyroid gland into the thyroid gland, and parathyroid cancer. Several most complicated aspects of parathyroid surgery are disclosed, such as the choice of strategy for surgical intervention in secondary hyperparathyroidism, complexity of morphological and cytological diagnostics of this disorder.

OBJECTIVE:To analyze 60 cases of solid pseudopapillary tumors (SPTs) of the pancreas, to reveal their most characteristic clinical and morphological features, and to study their possible histogenesis.MATERIAL AND METHODS:Sixty cases of SPTs of the pancreas underwent clinical, morphological, and immunohistochemical (IHC) examinations; a comparison group consisted of 86 pancreatic tumors of other histogenesis.RESULTS:It has been shown for the first time that SPTs are characterized by the nuclear expression of claudin 3 and the cytoplasmic expression of claudin 7. It has been also ascertained that the aberrant perinuclear (dot-like) expression of CD99 is a unique feature of these tumors.CONCLUSION:SPTs of the pancreas are distinguished by a diversity of clinical manifestations and morphological features, but have a unique immunophenotype, which can differentiate them from other types of pancreatic tumors.

Introduction: The treatment of Huntington's chorea and hereditary myopathy is absent. We studied the efficacy of energotropic therapy.

It was examined the expression of somatostatin receptors 1, 2, 3 and 5 types in 56 pancreatic neuroendocrine tumors: 48 function (45 insulinomas and 3 gastrinomas) and 18 non-function tumors. Twenty of 56 tumors were malignant (6 insulinomas, 9 non-function tumors, 3 gastrinomas). In function tumors dominated expression of receptor of 3 type (48%), and in non-function tumors type 2 (63.2%). In tumors with metastases the number of cells expressing the receptor type 2 and 3 increased, and receptor type 1 decreased.