Bacillus Calmette-Guérin pneumonitis after intravesical instillation: Report of two cases and a review of the literature.

OBJECTIVE: Intravesical administration of bacillus Calmette-Guérin is standard adjuvant treatment of non-muscle invasive bladder cancer. In spite of the fact that this immunotherapy is locoregional, there are still risk of some complications. METHODS: We describe two cases of systemic BCG infection after intravesical administration of BCG vaccine in patients with early stage of bladder cancer. RESULTS: Both patients suffered from systemic BCG infection manifesting as BCG pneumonitis. After standard therapy with antituberculotic agents, both of them fully recovered. CONCLUSION: BCG infection can occur as a rare but potentially serious complication of this treatment procedure. Gravity of this side effect and its specific therapy require prompt and right diagnosis.

Expansive intracardiac leiomyosarcoma - a combined therapeutic approach resulting in survival with complete remission. A literature review and case report.

Primary cardiac sarcomas are extremely rare and often with dismal prognosis. Only a few case series and retrospective studies regarding its biological characteristics, diagnostics, and treatment were reported. The multi-modality therapeutic strategy has been discussed in the published literature, but often with contradictory results. There is thus, no consensus on the optimal therapeutic approach to date. We present the case report of the 66-year old female endangered by a large primary leiomyosarcoma expanding in the right-sided heart chambers with imminent risk of acute obstruction of blood flow. The patient was managed by urgent surgical resection. After the histological confirmation of incomplete R1 resection, the treatment was supplemented by adjuvant CT-targeted radiotherapy, resulting in extraordinary survival with complete remission over a 24-month follow-up period. Our case report aims to demonstrate a favorable result of an individually suited complex surgical and oncological treatment to support the multidisciplinary therapeutic approach to these patients. The article is supplemented by a detailed literature review providing a theoretical background and an overview of the acquired knowledge and possible strategies.

Inhibition of Aryl Hydrocarbon Receptor (AhR) Expression Disrupts Cell Proliferation and Alters Energy Metabolism and Fatty Acid Synthesis in Colon Cancer Cells.

The aryl hydrocarbon receptor (AhR) plays a wide range of physiological roles in cellular processes such as proliferation, migration or control of immune responses. Several studies have also indicated that AhR might contribute to the regulation of energy balance or cellular metabolism. We observed that the AhR is upregulated in tumor epithelial cells derived from colon cancer patients. Using wild-type and the corresponding AhR knockout (AhR KO) variants of human colon cancer cell lines HCT116 and HT-29, we analyzed possible role(s) of the AhR in cell proliferation and metabolism, with a focus on regulation of the synthesis of fatty acids (FAs). We observed a decreased proliferation rate in the AhR KO cells, which was accompanied with altered cell cycle progression, as well as a decreased ATP production. We also found reduced mRNA levels of key enzymes of the FA biosynthetic pathway in AhR KO colon cancer cells, in particular of stearoyl-CoA desaturase 1 (SCD1). The loss of AhR was also associated with reduced expression and/or activity of components of the PI3K/Akt pathway, which controls lipid metabolism, and other lipogenic transcriptional regulators, such as sterol regulatory element binding transcription factor 1 (SREBP1). Together, our data indicate that disruption of AhR activity in colon tumor cells may, likely in a cell-specific manner, limit their proliferation, which could be linked with a suppressive effect on their endogenous FA metabolism. More attention should be paid to potential mechanistic links between overexpressed AhR and colon tumor cell metabolism.

Transcriptomic Profiling Revealed Lnc-GOLGA6A-1 as a Novel Prognostic Biomarker of Meningioma Recurrence.

BACKGROUND: Meningioma is the most common primary central nervous system neoplasm, accounting for about a third of all brain tumors. Because their growth rates and prognosis cannot be accurately estimated, biomarkers that enable prediction of their biological behavior would be clinically beneficial. OBJECTIVE: To identify coding and noncoding RNAs crucial in meningioma prognostication and pathogenesis. METHODS: Total RNA was purified from formalin-fixed and paraffin-embedded tumor samples of 64 patients with meningioma with distinct clinical characteristics (16 recurrent, 30 nonrecurrent with follow-up of >5 years, and 18 with follow-up of <5 years without recurrence). Transcriptomic sequencing was performed using the HiSeq 2500 platform (Illumina), and biological and functional differences between meningiomas of different types were evaluated by analyzing differentially expression of messenger RNA (mRNA) and long noncoding RNA (IncRNA). The prognostic value of 11 differentially expressed RNAs was then validated in an independent cohort of 90 patients using reverse transcription quantitative (real-time) polymerase chain reaction. RESULTS: In total, 69 mRNAs and 108 lncRNAs exhibited significant differential expression between recurrent and nonrecurrent meningiomas. Differential expression was also observed with respect to sex (12 mRNAs and 59 lncRNAs), World Health Organization grade (58 mRNAs and 98 lncRNAs), and tumor histogenesis (79 mRNAs and 76 lncRNAs). Lnc-GOLGA6A-1, ISLR2, and AMH showed high prognostic power for predicting meningioma recurrence, while lnc-GOLGA6A-1 was the most significant factor for recurrence risk estimation (1/hazard ratio = 1.31; P = .002). CONCLUSION: Transcriptomic sequencing revealed specific gene expression signatures of various clinical subtypes of meningioma. Expression of the lnc-GOLGA61-1 transcript was found to be the most reliable predictor of meningioma recurrence.

Targeting the Aryl Hydrocarbon Receptor with Microbial Metabolite Mimics Alleviates Experimental Colitis in Mice.

Targeting the aryl hydrocarbon receptor (AhR) is an emerging therapeutic strategy for multiple diseases (e.g., inflammatory bowel disease). Thermosporothrix hazakensis microbial metabolite 2-(1'H-indole-3'-carbonyl)-thiazole-4-carboxylic acid methyl ester (ITE) is a putative AhR endogenous ligand. To improve the chemical stability, we synthesized a series of ITE chemical mimics. Using a series of in vitro assays, we identified 2-(1H-indole-3-carbonyl)-N-methyl thiazole-4-carboxamide (ITE-CONHCH3) as a highly potent (EC50 = 1.6 nM) AhR agonist with high affinity (Ki = 88 nM). ITE-CONHCH3 triggered AhR nuclear translocation and dimerization of AhR-ARNT, enhanced AhR binding in the CYP1A1 promoter, and induced AhR-regulated genes in an AhR-dependent manner. The metabolic stability of ITE-CONHCH3 in a cell culture was 10 times higher than that of ITE. Finally, we observed protective effects of ITE-CONHCH3 in mice with DSS-induced colitis. Overall, we demonstrate and validate a concept of microbial metabolite mimicry in the therapeutic targeting of AhR.

IDH1/2 Mutations in Patients With Diffuse Gliomas: A Single Centre Retrospective Massively Parallel Sequencing Analysis.

Patients below 55 years were genetically studied because the prevalence of isocitrate dehydrogenase 1 (IDH1) decreases in older patients and on grounds of cost-effectiveness, as suggested by the World Health Organization (WHO) in 2016. The aim of our study was to use novel massively parallel sequencing (MPS) approaches to examine rare variants of IDH1/2 in Czech diffuse astrocytic and oligodendroglial tumors (gliomas) patients below 55 years of age who had been immunohistochemically (IHC) diagnosed as IDH1 R132H negative. The IHC IDH1 status (wild type or mutant) of 275 tissue samples was analyzed using antibodies against the IDH1 R132H protein. Sixty-three samples of 55 years old patients with IHC IDH1 WT status were genotyped using two different MPS technologies to detect rare IDH1 and IDH2 variants. The tiered IHC (60 positive) and molecular (10 positive) approach thus revealed that 70 of the 275 samples (25%) bore IDH1/IDH2 mutations. The combined molecular and IHC approach thus revealed that 70 of the 275 samples (25%) considered in the study bore IDH1/IDH2 mutations. IHC detection of the IDH1 R132H variant should be routinely complemented with MPS to detect rare IDH1/2 variants in glioma patients below 55 years of age with negative IHC result of IDH R132H variant.

Lewy body disease or diseases with Lewy bodies?

The current nosological concept of α-synucleinopathies characterized by the presence of Lewy bodies (LBs) includes Parkinson's disease (PD), Parkinson's disease dementia (PDD), and dementia with Lewy bodies (DLB), for which the term "Lewy body disease" (LBD) has recently been proposed due to their considerable clinical and pathological overlap. However, even this term does not seem to describe the true nature of this group of diseases. The subsequent discoveries of α-synuclein (αSyn), SNCA gene, and the introduction of new immunohistochemical methods have started intensive research into the molecular-biological aspects of these diseases. In light of today's knowledge, the role of LBs in the pathogenesis and classification of these nosological entities remains somewhat uncertain. An increasingly more important role is attributed to other factors as the presence of various LBs precursors, post-translational αSyn modifications, various αSyn strains, the deposition of other pathological proteins (particularly ß-amyloid), and the discovery of selective vulnerability of specific cells due to anatomical configuration or synaptic dysfunction. Resulting genetic inputs can undoubtedly be considered as the main essence of these factors. Molecular-genetic data indicate that not only in PD but also in DLB, a unique genetic architecture can be ascertained, predisposing to the development of specific disease phenotypes. The presence of LBs thus remains only a kind of link between these disorders, and the term "diseases with Lewy bodies" therefore results somewhat more accurate.

The short- and long-term outcomes of pancreaticoduodenectomy for distal cholangiocarcinoma.

BACKGROUND: The aim of the study was to calculate the short-term and long-term outcomes of curative-intent surgery in distal cholangiocarcinoma (DCC) patients to identify potential prognostic factors. PATIENTS AND METHODS: A retrospective cohort study of 32 consecutive DCC patients treated with pancreaticoduodenectomy between 2009-2017. The clinicopathological and histopathological data were evaluated for prognostic factors using the univariable Cox regression analysis. The Overall Survival (OS) was estimated using the Kaplan-Meier analysis. RESULTS: The study comprised a total of 32 patients, with a mean age of 65.8 (± 9.0) years at the time of surgery. R0 resection was achieved in 25 (86.2%) patients, 19 (65.5%) patients received adjuvant oncological therapy. The OS rates at 1, 3 and 5 years were 62.5%, 37.5% and 21.9%, respectively. The 90-day mortality was 3/32 (9.4%) accounting for one-fourth of the first-year mortality rate. The median OS was 28.5 months. The only statistically significant prognostic factor was vascular resection, which was associated with worse OS in the univariable analysis (HR: 3.644; 95%-CI: 1.179-11.216, P=0.025). An age less than 65 years, ASA grade I/II, hospital stay of fewer than 15 days, R0 resection, lymph node ratio less than 0.2 and adjuvant oncological therapy tended to be associated with better OS but without statistically significant relevance. CONCLUSION: The main factor directly influencing the survival of DCC patients is surgical complications. Surgical mortality comprises a significant group of patients, who die in the first year following pancreaticoduodenectomy. Vascular resection is the most important negative prognostic factor for long-term survival.

HELLP syndrome and HELLP-like syndrome in pregnancies with covid-19 - case reports.

OBJECTIVE: We present two case reports of severe course of covid-19 in pregnancy demonstrating similarity between covid-19 and HELLP syndrome. CASE REPORT: The first case report describes an asymptomatic course of covid-19 accompanied by elevation of liver enzymes and lactate dehydrogenase but low ratio of angiogenic bio-markers. No severe pregnancy complication occurred. All laboratory results had normalized after recovering from covid-19. The second case report describes a patient with elevated liver enzymes and lactate dehydrogenase which preceded a respiratory failure. Furthermore, one of the most feared complication of pregnancy occurred, namely hepatic rupture. After a delivery, the condition of the patient had been improving only slowly. It is not clear whether this condition represented a severe course of covid-19 or a concurrence of covid-19 and HELLP syndrome. CONCLUSION: A severe course of covid-19 in pregnancy may cause a dia-gnostic dilemma for its similarity between covid-19 and a specific complication of pregnancy - HELLP syndrome. This might lead to an unnecessary intervention and iatrogenic prematurity or underestimation of symptoms and delayed dia-gnosis of HELLP syndrome.

Case report: Gaucher disease in trepanobiopsy of 16yo woman examined for suspected myelodysplastic syndrome.

Gaucher disease is an autosomal recessive disease belonging to the so-called storage diseases. More than 300 mutations of the GBA1 gene encoding the β-glucocerebrosidase enzyme are known. It is a very rare disease in the Czech Republic. Currently 35 patients are treated. In our case report, we present the case of a 16 year old female patient attending the Clinic of Pediatric Medicine at the University Hospital in Ostrava. Since 2007, the patient has suffered prolonged thrombocytopenia, at the time with progression, and splenomegaly, which has not been further investigated. Trepanobiopsy was sent to the Department of Pathology with suspicion of myelodysplastic syndrome in May of 2018. In the biopsy examination, the individual bloodline did not show dysplastic features and the number of blasts was not increased. The marrow interstitium was 70% permeated with gaucher cells with intraplasmatic fibrous material. Cells were in the appearance of „crumpled paper“ and expressed CD68 in immunohistochemical stain and in histochemical examination of PAS and iron (Fe) staining. Based on a morphological finding, Gauchers disease was suspected. Repeated bone marrow aspirates were subsequently captured by gaucher cells, and a next biochemical examination showed a β-glucocerebrosidase enzyme decrease of activity. Gaucher disease is a progressive disease that requires early diagnosis with the onset of therapy.

Complex Alterations of Fatty Acid Metabolism and Phospholipidome Uncovered in Isolated Colon Cancer Epithelial Cells.

The development of colon cancer, one of the most common malignancies, is accompanied with numerous lipid alterations. However, analyses of whole tumor samples may not always provide an accurate description of specific changes occurring directly in tumor epithelial cells. Here, we analyzed in detail the phospholipid (PL), lysophospholipid (lysoPL), and fatty acid (FA) profiles of purified EpCAM+ cells, isolated from tumor and adjacent non-tumor tissues of colon cancer patients. We found that a number of FAs increased significantly in isolated tumor cells, which also included a number of long polyunsaturated FAs. Higher levels of FAs were associated with increased expression of FA synthesis genes, as well as with altered expression of enzymes involved in FA elongation and desaturation, including particularly fatty acid synthase, stearoyl-CoA desaturase, fatty acid desaturase 2 and ELOVL5 fatty acid elongase 5 We identified significant changes in ratios of specific lysoPLs and corresponding PLs. A number of lysophosphatidylcholine and lysophosphatidylethanolamine species, containing long-chain and very-long chain FAs, often with high numbers of double bonds, were significantly upregulated in tumor cells. Increased de novo synthesis of very long-chain FAs, or, altered uptake or incorporation of these FAs into specific lysoPLs in tumor cells, may thus contribute to reprogramming of cellular phospholipidome and membrane alterations observed in colon cancer.

The Influence of Gene Aberrations on Survival in Resected IDH Wildtype Glioblastoma Patients: A Single-Institution Study.

This prospective population-based study on a group of 132 resected IDH-wildtype (IDH-wt) glioblastoma (GBM) patients assesses the prognostic and predictive value of selected genetic biomarkers and clinical factors for GBM as well as the dependence of these values on the applied therapeutic modalities. The patients were treated in our hospital between June 2006 and June 2015. Clinical data and tumor samples were analyzed to determine the frequencies of TP53, MDM2, EGFR, RB1, BCR, and CCND1 gene aberrations and the duplication/deletion statuses of the 9p21.3, 1p36.3, 19q13.32, and 10p11.1 chromosome regions. Cut-off values distinguishing low (LCN) and high (HCN) copy number status for each marker were defined. Additionally, MGMT promoter methylation and IDH1/2 mutation status were investigated retrospectively. Young age, female gender, Karnofsky scores (KS) above 80, chemoradiotherapy, TP53 HCN, and CCND1 HCN were identified as positive prognostic factors, and smoking was identified as a negative prognostic factor. Cox proportional regression models of the chemoradiotherapy patient group revealed TP53 HCN and CCND1 HCN to be positive prognostic factors for both progression-free survival and overall survival. These results confirmed the influence of key clinical factors (age, KS, adjuvant oncotherapy, and smoking) on survival in GBM IDH-wt patients and demonstrated the prognostic and/or predictive importance of CCND1, MDM2, and 22q12.2 aberrations.

Epithelial to mesenchymal transition and microRNA expression are associated with spindle and apocrine cell morphology in triple-negative breast cancer.

Triple negative breast cancers (TNBC) are a morphologically and genetically heterogeneous group of breast cancers with uncertain prediction of biological behavior and response to therapy. Epithelial to mesenchymal transition (EMT) is a dynamic process characterized by loss of typical epithelial phenotype and acquisition of mesenchymal characteristics. Aberrant activation of EMT can aggravate the prognosis of patients with cancer, however, the mechanisms of EMT and role of microRNAs (miRNAs) in EMT activation is still unclear. The aim of our study was to analyze miRNA expression within areas of TNBCs with cellular morphology that may be related to the EMT process and discuss possible associations. Out of all 3953 re-examined breast cancers, 460 breast cancers were diagnosed as TNBC (11.64%). With regard to complete tumor morphology preservation, the tissue samples obtained from core-cut biopsies and influenced by previous neoadjuvant therapy were excluded. We assembled a set of selected 25 cases to determine miRNA expression levels in relation to present focal spindle cell and apocrine cell morphology within individual TNBCs. We used descriptive (histological typing and morphology), morphometric, molecular (microdissection of tumor and non-tumor morphologies, RNA isolation and purification, microchip analysis) and bioinformatic analysis (including pathway analysis). The results were verified by quantitative real-time PCR (RT-qPCR) on an extended set of 70 TNBCs. The majority of TNBCs were represented by high-grade invasive carcinomas of no special type (NST) with medullary features characterized by well-circumscribed tumors with central necrosis or fibrosis and frequent tendency to spindle-cell and/or apocrine cell transformation. Apocrine and spindle cell transformation showed a specific miRNA expression profile in comparison to other tumor parts, in situ carcinoma or non-tumor structures, particularly down-regulated expression of hsa-miRNA-143-3p and hsa-miRNA-205-5p and up-regulated expression of hsa-miR-22-3p, hsa-miRNA-185-5p, and hsa-miR-4443. Apocrine cell tumor morphology further revealed decreased expression of hsa-miR-145-5p and increased expression of additional 14 miRNAs (e.g. hsa-miR-182-5p, hsa-miR-3135b and hsa-miR-4417). Pathway analysis for target genes of these miRNAs revealed several shared biological processes (i.e. Wnt signaling, ErbB signaling, MAPK signaling, endocytosis and axon guidance), which may in part contribute to the EMT and tumor progression. We provide the first miRNA expression profiling of specific tissue morphologies in TNBC. Our results demonstrate a specific miRNA expression profile of apocrine and spindle cell morphology which can exhibit a certain similarity with the EMT process and may also be relevant for prognosis and therapy resistance of TNBC.

Targeted Sequencing of Pancreatic Adenocarcinomas from Patients with Metachronous Pulmonary Metastases.

Mutation spectra of 250 cancer driver, druggable, and actionable genes were analyzed in surgically resected pancreatic ductal adenocarcinoma (PDAC) patients who developed metachronous pulmonary metastases. Targeted sequencing was performed in DNA from blood and archival samples of 15 primary tumors and three paired metastases. Results were complemented with the determination of G12V mutation in KRAS by droplet digital PCR. The median number of protein-changing mutations was 52 per patient. KRAS and TP53 were significantly enriched in fractions of mutations in hotspots. Individual gene mutation frequencies or mutational loads accounting separately for drivers, druggable, or clinically actionable genes, did not significantly associate with patients' survival. LRP1B was markedly mutated in primaries of patients who generalized (71%) compared to those developing solitary pulmonary metastases (0%). FLG2 was mutated exclusively in primary tumors compared to paired metastases. In conclusion, signatures of prognostically differing subgroups of PDAC patients were generated for further utilization in precision medicine.

Alcohol-related liver diseases (ALD).

The main aim of this educational article ( narrative review ) is to reflect clinical practice guidelines of the European Association for the Study of the Liver (EASL) published in J Hepatol 2018, contrasting with the 2012 guidelines especialy in the new terminology of alcohol-related liver diseases (ALD). The strong emphasis on prevention of alcohol use disorders (AUD) may be exert at all stages of public health care. Another aim of the article are ALD history, epidemiology, metabolism of alcohol and clinical pictures of ALD.

Identification of Meningioma Patients at High Risk of Tumor Recurrence Using MicroRNA Profiling.

BACKGROUND: Meningioma growth rates are highly variable, even within benign subgroups, with some remaining stable, whereas others grow rapidly. OBJECTIVE: To identify molecular-genetic markers for more accurate prediction of meningioma recurrence and better-targeted therapy. METHODS: Microarrays identified microRNA (miRNA) expression in primary and recurrent meningiomas of all World Health Organization (WHO) grades. Those found to be deregulated were further validated by quantitative real-time polymerase chain reaction in a cohort of 172 patients. Statistical analysis of the resulting dataset revealed predictors of meningioma recurrence. RESULTS: Adjusted and nonadjusted models of time to relapse identified the most significant prognosticators to be miR-15a-5p, miR-146a-5p, and miR-331-3p. The final validation phase proved the crucial significance of miR-146a-5p and miR-331-3p, and clinical factors such as type of resection (total or partial) and WHO grade in some selected models. Following stepwise selection in a multivariate model on an expanded cohort, the most predictive model was identified to be that which included lower miR-331-3p expression (hazard ratio [HR] 1.44; P < .001) and partial tumor resection (HR 3.90; P < .001). Moreover, in the subgroup of total resections, both miRNAs remained prognosticators in univariate models adjusted to the clinical factors. CONCLUSION: The proposed models might enable more accurate prediction of time to meningioma recurrence and thus determine optimal postoperative management. Moreover, combining this model with current knowledge of molecular processes underpinning recurrence could permit the identification of distinct meningioma subtypes and enable better-targeted therapies.

Acute onset of autoimmune hepatitis in children and adolescents.

BACKGROUND: Autoimmune hepatitis (AIH) is a rare progressive liver disease, which manifests as acute hepatitis in 40%-50% of pediatric cases. This refers predominantly to spontaneous exacerbations of previously unrecognized subclinical AIH with laboratory and histological signs of chronic hepatitis, or to acute exacerbations of known chronic disease. Only a few of these patients fulfill criteria for acute liver failure (ALF). METHODS: Forty children diagnosed with AIH in our center between 2000 and 2018 were included in this study. All of them fulfilled revised diagnostic criteria of the International Autoimmune Hepatitis Group (IAIHG) for probable or confirmed AIH, and other etiologies of liver diseases were excluded. Patients were divided into two groups: acute AIH (A-AIH) or chronic AIH (C-AIH). RESULTS: Acute onset of AIH occurred in 19/40 children (48%). Six of them fulfilled the criteria of ALF with coagulopathy and encephalopathy. Five of 6 children with ALF suffered from exacerbation of previously undiagnosed chronic AIH, among which 4 children were histologically confirmed as micronodular cirrhosis. The remaining one patient had fulminant AIH with centrilobular necrosis, but no histological signs of previous chronic liver damage. We observed significantly lower levels of albumin, higher levels of aminotransferases, bilirubin, INR, IgG, higher IAIHG score and more severe histological findings in A-AIH than in C-AIH. No differences in patient age and presence of autoantibodies were observed between A-AIH and C-AIH. All children, including those with ALF and cirrhosis, were treated with corticosteroids, and are alive and achieved AIH remission. Liver transplant was not indicated in any patient. CONCLUSION: Rapid and accurate diagnosis of A-AIH may be difficult. However, timely start of immunosuppressive therapy improves prognosis and decreases number of indicated liver transplantations in children with AIH.

Tumor-Infiltrating Lymphocytes/Plasmocytes in Chemotherapeutically Non-Influenced Triple-Negative Breast Cancers - Correlation with Morphological and Clinico-Pathological Parameters.

BACKGROUND: Triple-negative breast cancers (TNBCs) are considered a morphologically heterogeneous group of breast carcinomas characterized by the absence or low protein expression of hormone receptors and HER2/neu/ERBB2 with a specific biological behavior and therapeutic response. This study aimed to evaluate correlations of the density of tumor-infiltrating lymphocytes/plasmocytes (TILs) in the tumor parenchyma, stroma, and invasive margins with tumor morphology, the proliferation rate, Bcl-2 expression, and selected clinical and pathological parameters in early breast cancer patients prior to mastectomy who had not received initial chemotherapy. MATERIALS AND METHODS: Samples of 3,544 breast cancer patients investigated in our department between 2007 and 2017 were re-examined. In total, 413 (11.65%) patients were diagnosed with TNBC. Only 61 cases did not undergo neoadjuvant therapy prior to mastectomy. Correlations between the density of TILs and tumor morphology, Bcl-2 expression, proliferative activity measured by Ki-67, patient age at diagnosis, tumor grade, and metastases were investigated. RESULTS: The samples were predominantly relatively well-localized invasive carcinomas of no special type with medullary features (80.32%) that measured on average 13.4mm (range 5-20mm, median 15mm) and exhibited central necrosis or fibrosis, a tendency to undergo spindle cell and/or apocrine-like differentiation, and intensive infiltration of TILs. There were significant positive correlations between TILs and premenopausal status (p=0.003), Ki-67 expression (p=0.015), and tumor grade (p=0.002), a marginal positive correlation between TILs and tumor size (p=0.065), and a significant negative correlation between TILs and Bcl-2 expression (p=0.035). In younger patients (< 50 years) with tumor size less than or equal to 20 mm (pT1a-pT1c) we recorded a lower number of women with metastatic lymph node involvement (p=0.001). CONCLUSION: The density and location of TILs in non-therapeutically influenced TNBCs, evaluated in the context of morphological changes and other clinicopathological parameters, may have prognostic significance and assist effective therapy planning.