Morphological Characteristics of the Lacrimal Apparatus in its Obstruction of Various Genesis

Purpose: morphological assessment of the lacrimal ducts at various anatomical levels in patients with primary (PANDO) and secondary (SALDO) obstruction after radioactive iodine therapy.Methods. The material was obtained during endoscopic dacryocystorinostomy with revision of Hasner's valve in patients with PANDO (n=7) in the distal segments of the nasolacrimal duct and in patients with SALDO (n=7) after radioactive iodine therapy. During the surgery, a biopsy of Hasner's valve, as well as a biopsy of the lacrimal sac wall were performed. The resulting material was stained with hemotoxylin and eosin, alcyan blue and by Masson method. Morphological and morphometric analyses were performed in semi-automatic mode. The results of histochemical staining of sections were translated into points taking into account the area and optical density (chromogenicity) in relative units: 1 – weak (0 – 0.3); 2 – moderate (0.3 – 0.6); 3 – significant (>0.6). The nonparametric Mann-Whitney criterion was used for statistical analysis. The differences were considered significant at p<0.05.Results. The comparative morphological study both confirmed the available information concerning the radiation nature of the obstruction and allowed to quantify the fibrosis level of the stromal component and other lacrimal ducts structures.Conclusion. It was shown that the nasolacrimal duct sclerosis is significantly lower (p=0.029) in patients with SALDO than in patients with PANDO while fibrosis in the lacrimal sac is the same in patients of the compared groups.

Effect of the prenatal action of fulvestrant on the ovaries of the offspring of laboratory mice

Relevance. Fulvestrant is used for the treatment of breast cancer in combination with other drugs. The aim of the study was to determine the effect of the prenatal action of fulvestrant on the ovaries of the offspring of laboratory mice. Materials and Methods. The experimental animals were divided into 4 groups: intact, control and 2 experimental, 5 animals in each group. Injections were administered to females after fertilization at the gestational stage E 11.5 once intramuscularly. In the control group (n=5), sterile castor oil was administered at a dose of 0.8 mcg/kg. In the first experimental group (n=5), an antiestrogen was introduced in the form of an oil solution of fulvestrant 0.08 ml 0.0005% at a dose of 20 mcg/kg. In the second group (n=5), an antiestrogen was introduced in the form of an oil solution of fulvestrant 0.4 ml 0.0005% at a dose of 100 mcg/kg. Results and Discussion . The study revealed that in the ovaries when the drug was administered at a dose of 20 mcg/kg (F-20), the number of primordial follicles was reduced. Accordingly, the number of follicles of subsequent generations decreased. With the introduction of the drug fulvestrant 100 mcg/kg (F-100) on the section of the ovary, sclerosis of the stromal component is observed, accompanied by a rearrangement of the vascular network with signs of atresia and cystic degeneration of the follicular epithelium in the secondary and tertiary follicles, formed cysts are observed in the ovarian parenchyma. Conclusion. The prenatal effect of the drug fulvestrant on the maternal body during pregnancy leads to persistent structural changes in the ovaries of the offspring, manifested in the late stages of ontogenesis, which, in turn, can lead to violations of reproductive function. The depth and scale of these changes are dose-dependent.

Morphological features and criteria of prognosis for stromal component of colorectal cancer ІІА-ІІІВ stages

Colorectal cancer (CRC) is the second leading cause of mortality among cancers after tumors of the respiratory system. One of the most significant prognostic criteria of CRC are the features of stromal component, which are not implemented in clinical practice. The aim was to study the main morphological features of the stroma of CRC T3N0-2M0 and to search for prognostic criteria of their recurrence and death. Group I included primary CRC without recurrences. Group II – primary CRC with recurrences; IIA – with recurrences that did not lead to death; ІІВ – with recurrences and fatal outcome from generalization of tumor process during 5 years from lethal outcome from the moment when the tumor was removed. The microslides of CRC were made by using the standard methods with G + E staining; immunohistochemical (IHC) reaction was performed by using monoclonal antibodies to smooth muscle actin alpha and vimentin. CRC with a stromal-parenchymal ratio (SPR)>50% were in 43.3% (26/60) of cases. SPR>50% is a prognostic criterion for recurrence (p<0.05), shorter disease free survival (p<0.001) and metastasis to regional lymph nodes (p<0.001). Immature stroma type of CRC IIA-IIIB stages is associated with the presence of tumor budding (p<0.001), G3 differentiation (p<0.01), shorter disease-free survival (p<0.001), metastatic activity (p<0.05); among recurrent CRC, the immature type of stroma is associated with the death of patients (p<0.05). A diffuse presence of tumor-activated fibroblasts is one of the criteria for immature CRC stroma (p<0.003), however, as an independent prognostic feature, it has limited prognostic value. SPR>50% and immature type of stroma are prognostic features for recurrence, metastasis and term of recurrence for CRC pT3N0-2M0; the presence of an immature type of stroma was associated with patient death.

Imaging findings of uterine adenosarcoma with sarcomatous overgrowth: two case reports, emphasizing restricted diffusion on diffusion weighted imaging

Background Adenosarcoma is classified as a mixed epithelial and mesenchymal tumor composed of a benign epithelial component and a malignant stromal component. The stromal component in adenosarcoma is usually low grade, and consequently the prognosis is relatively favorable. While, adenosarcoma with sarcomatous overgrowth (SO) is defined as an adenosarcoma in which the sarcomatous component constitutes more than 25% of the tumor. The stromal component is also high-grade sarcoma showing greater nuclear pleomorphism and mitotic activity, thus, it is associated with worse prognosis. MRI findings of adenosarcoma without SO have been described in previous literatures but the imaging findings in adenosarcoma with SO may be poorly defined. Therefore we present two cases of uterine adenosarcoma with SO. Case presentation Patient 1 was a 76-year-old woman referred to our hospital with complaint of abdominal distension and postmenopausal bleeding. Patient 2 was a 57-year-old woman with complaint of lower abdominal pain and abnormal uterine bleeding. On magnetic resonance imaging (MRI), T2 weighted imaging showed a large, heterogeneous high-intensity mass with hyperintense tiny cysts that expanded the uterine cavity and extended into the cervical canal for both patients. On diffusion-weighted imaging (DWI), both masses appeared as high signal intensity. Patient 2 also had a right ovarian adult granulosa cell tumor that may have contributed to development of the adenosarcoma. Patient 1 recurred with peritoneal sarcomatosis 6 months after surgery and died of the disease. Patient 2 also recurred with a left upper lung metastasis 3 months after surgery. Conclusions DWI may depict pathological changes produced by SO of adenosarcoma as high signal intensity, even though SO does not seem to change MRI findings of adenosarcoma on other sequences. Therefore, DWI could potentially predict SO in presumptive adenosarcoma on MRI and the patient’s prognosis. It is also important for pathologists to know if SO can arise in adenosarcoma because they need to examine the tumor thoroughly to determine the percentage of SO component in the tumor volume when SO is present.

Dynamic transcriptome analysis reveals signatures of paradoxical effect of vemurafenib on human dermal fibroblasts

Background Vemurafenib (PLX4032) is one of the most frequently used treatments for late-stage melanoma patients with the BRAFV600E mutation; however, acquired resistance to the drug poses as a major challenge. It remains to be determined whether off-target effects of vemurafenib on normal stroma components could reshape the tumor microenvironment in a way that contributes to cancer progression and drug resistance. Methods By using temporally-resolved RNA- and ATAC-seq, we studied the early molecular changes induced by vemurafenib in human dermal fibroblast (HDF), a main stromal component in melanoma and other tumors with high prevalence of BRAFV600 mutations. Results Transcriptomics analyses revealed a stepwise up-regulation of proliferation signatures, together with a down-regulation of autophagy and proteolytic processes. The gene expression changes in HDF strongly correlated in an inverse way with those in BRAFV600E mutant malignant melanoma (MaMel) cell lines, consistent with the observation of a paradoxical effect of vemurafenib, leading to hyperphosphorylation of MEK1/2 and ERK1/2. The transcriptional changes in HDF were not strongly determined by alterations in chromatin accessibility; rather, an already permissive chromatin landscape seemed to facilitate the early accessibility to MAPK/ERK-regulated transcription factor binding sites. Combinatorial treatment with the MEK inhibitor trametinib did not preclude the paradoxical activation of MAPK/ERK signaling in HDF. When administered together, vemurafenib partially compensated for the reduction of cell viability and proliferation induced by trametinib. These paradoxical changes were restrained by using the third generation BRAF inhibitor PLX8394, a so-called paradox breaker compound. However, the advantageous effects on HDF during combination therapies were also lost. Conclusions Vemurafenib induces paradoxical changes in HDF, enabled by a permissive chromatin landscape. These changes might provide an advantage during combination therapies, by compensating for the toxicity induced in stromal cells by less specific MAPK/ERK inhibitors. Our results highlight the relevance of evaluating the effects of the drugs on non-transformed stromal components, carefully considering the implications of their administration either as mono- or combination therapies.

Deep Learning-Based Microscopic Diagnosis of Odontogenic Keratocysts and Non-Keratocysts in Haematoxylin and Eosin-Stained Incisional Biopsies

Background: The goal of the study was to create a histopathology image classification automation system that could identify odontogenic keratocysts in hematoxylin and eosin-stained jaw cyst sections. Methods: From 54 odontogenic keratocysts, 23 dentigerous cysts, and 20 radicular cysts, about 2657 microscopic pictures with 400× magnification were obtained. The images were annotated by a pathologist and categorized into epithelium, cystic lumen, and stroma of keratocysts and non-keratocysts. Preprocessing was performed in two steps; the first is data augmentation, as the Deep Learning techniques (DLT) improve their performance with increased data size. Secondly, the epithelial region was selected as the region of interest. Results: Four experiments were conducted using the DLT. In the first, a pre-trained VGG16 was employed to classify after-image augmentation. In the second, DenseNet-169 was implemented for image classification on the augmented images. In the third, DenseNet-169 was trained on the two-step preprocessed images. In the last experiment, two and three results were averaged to obtain an accuracy of 93% on OKC and non-OKC images. Conclusions: The proposed algorithm may fit into the automation system of OKC and non-OKC diagnosis. Utmost care was taken in the manual process of image acquisition (minimum 28–30 images/slide at 40× magnification covering the entire stretch of epithelium and stromal component). Further, there is scope to improve the accuracy rate and make it human bias free by using a whole slide imaging scanner for image acquisition from slides.

Papillary Thyroid Carcinoma with Desmoid-Type Fibromatosis: Review of Published Cases

Desmoid-type fibromatosis (DTF) is a very rare variant of papillary thyroid carcinoma (PTC). It is essentially a dual tumor with a component of classical PTC with malignant epithelial proliferation (BRAF-mutated) and another component of mesenchymal proliferation (CTNNB1-mutated). We conducted a literature review on PTC-DTF. In total, 31 articles were identified, that together reported on 54 patients. The mean age was 47 years, with a 2.2:1 female predominance. No ultrasound features were found to be helpful in differentiating PTC-DTF from other PTC variants. Of the 43 cases that reported histological details, 60% had locally infiltrative disease (T3b or T4). Around 48% had cervical lymph node metastases, but none had distant metastases. While PTC-DTF may be locally more aggressive than classic PTC, its overall behavior is similar and can include extrathyroidal extension and lymph node metastases, which may contain a stromal component and show extranodal invasion. The mainstay of treatment for PTC-DTF is surgery, and the DTF component is not expected to be sensitive to radioactive iodine. External radiotherapy, non-steroidal anti-inflammatory drugs, tyrosine kinase inhibitors and chemotherapy have also been used in selected cases. Due to the rarity of these tumors and the lack of specific treatment guidelines, management should be discussed in a multidisciplinary team.

Recurrent Giant Malignant Phyllodes Tumor of the Breast

Phyllodes tumors (PTs) are rare fibroepithelial neoplasms of the breast. They have a proliferating stromal component that can be graded as benign, borderline, and malignant. In addition, they are associated with an increased risk of local recurrence and distant metastasis. The authors hereby present a case report of a 34-year-old woman with recurrent malignant PT with an increasing aggressiveness. There were two recurrences of giant tumors that consumed the entire right breast, which developed over a three-year period. The final surgical treatment was a total extirpation of the tumor with subsequent plastic reconstruction using a cutaneous flap from the region of the latissimus dorsi muscle. The patient died three months after the last recurrence due to multiorgan failure.

Stromal and Tumor Glioma-Derived Cells with Similar Characteristics have Differences in α-Smooth Muscle Actin Expression and Localization

Gliomas are solid brain tumors composed of tumor cells and recruited heterogenic stromal component. The study of the interactions between the perivascular niche and its surrounding cells is of great value in unraveling mechanisms of drug resistance in malignant gliomas. In this study, we isolated the stromal diploid cell population from oligodendroglioma and a mixed population of tumor aneuploid and stromal diploid cells from astrocytoma specimens. The stromal cells expressed neural stem/progenitor and mesenchymal markers showing the same discordant phenotype that is typical for glioma cells. Moreover, some of the stromal cells expressed CD133. For the first time, we demonstrated that this type of stromal cells had the typical myofibroblastic phenotype as the α-SMA+ cells formed α-SMA fibers and exhibited the specific function to deposit extracellular matrix (ECM) proteins at least in vitro. Immunofluorescent analysis showed diffuse or focal α-SMA staining in the cytoplasm of the astrocytoma-derived, A172, T98G, and U251MG glioma cells. We could suggest that α-SMA may be one of the main molecules, bearing protective functions. Possible mechanisms and consequences of α-SMA disruptions in gliomas are discussed.

Prostate state under varicosis of the pelvis (experimental study)

BACKGROUND: Chronic pelvic pain syndrome / chronic abacterial prostatitis is one of the most common diseases in urological practice. Despite its frequency the pathogenesis of the disease remains poorly understood. It is known that the morphological manifestation of chronic inflammation is sclerosis, in the development of which the venous congestion of the prostate is also important. AIM: To evaluate the effect of chronic venous congestion of the pelvis on the prostate in a chronic experiment. MATERIALS AND METHODS: An original model of persistent chronic varicose of the pelvis has been created. The experiment was carried out on 35 mature rabbits weighing 2.63.2 kg. Animals were divided into 3 groups. Control (n = 5) study of the normal anatomy of animals. In group 2 (n = 15), the creation of a model: ligation of the v. sacralis mediana, in combination with administration of progesterone solution. In group 3 (n = 15), false surgery and progesterone administration. Duplex scanning of the pelvic veins was performed at 1, 3 and 6 months, the diameter of the veins and the reflux after manual compression was assessed. After removing the animals from the experiment histological examination and morphometry of the prostate tissue were carried out. In prostate samples the concentration of hydroxyproline was investigated as a marker of connective tissue development. RESULTS: Venous congestion of the pelvic organs in animals in the second group negatively affected the structure of the prostate gland. Histological examination of the samples showed infiltration of the prostate tissue, edema of the stroma, a sharp expansion of the veins at the beginning of the experiment, later noted the proliferation of connective tissue, compression of the acini and a decrease in the secretory activity of the prostate gland. The results of morphometry showed an increase in the area of the stromal component to a greater extent due to an increase in the volume of connective tissue. There was a tendency to an increase in the concentration of hydroxyproline in the prostate tissue in animals of the 2nd group with the achievement of maximum values by the 6th month of the experiment. In animals of the 3rd group no significant changes in the structure of the prostate gland were revealed. CONCLUSIONS: The morphological manifestation of chronic venous hyperemia is infiltration of the prostate stroma and sclerogenesis.