Pathological findings directing immunotherapy in renal cell carcinomas.

Tweetable abstract Immunotherapy options in RCC treatment are increasing day by day. In pursuit of this objective, we have explored the role of pathology throughout the process, from the development to the implementation of immunotherapy in this paper.

Toxic Skin Reactions Should Be Differentiated from Allergic Reactions to Chemotherapeutic Drugs in Children: A Case Series and Review of the Literature.

Background: Chemotherapeutic drugs can lead to a wide spectrum of cutaneous findings, ranging from nonimmune toxic reactions to severe immune-mediated hypersensitivity reactions. The aim of this study was to evaluate the clinical, histopathological features, and prognosis of toxic skin reactions to chemotherapeutic drugs and to compare them with characteristics of immune-mediated reactions in children with malignancies. Methods: The medical records of all children with cancer who experienced skin reactions after chemotherapy administration and diagnosed as a toxic skin reaction between 2010 and 2022 were retrospectively analyzed. The diagnosis was re-evaluated and differentiated from other similar disorders by using clinical manifestations, photodocumentation, and histopathological findings. Results: A total of 17 children aged 2-17 years were involved: toxic erythema of chemotherapy (TEC) in 14 children, methotrexate-induced epidermal necrosis in 2 children, and toxic epidermal necrolysis (TEN)-like TEC in 1 child. The most commonly implicated drug was methotrexate. Most patients recovered rapidly after drug cessation and supportive measures. In 10 of the 17 patients, reintroduction of the culprit chemotherapeutic drug at reduced doses or increased dosage intervals was possible without any recurrence. Six patients could not receive further doses since they deceased due to sepsis and other complications. Conclusions: Cutaneous toxic eruptions to chemotherapeutic drugs may present with a severe phenotype resembling Stevens-Johnson syndrome/TEN. An accurate diagnosis prevents potentially harmful therapeutic interventions, withholding of chemotherapy, and erroneous assignment of drug allergies.

Mineralogy, geochemistry, and micromorphology of human kidney stones (urolithiasis) from Mersin, the southern Turkey.

This study describes the primary characteristics of the selected kidney stones surgically removed from the patients at the Mersin University Hospital in the southern Turkey and interprets their formation via petrographic, geochemical, XRD, SEM-EDX, and ICP-MS/OES analyses. The analytical results revealed that the kidney stones are composed of the minerals whewellite, struvite, hydroxyapatite, and uric acid alone or in different combinations. The samples occur in staghorn, bean-shaped composite, and individual rounded particle shapes, which are controlled by the shape of the nucleus and the site of stone formation. The cross-section of the samples shows concentric growth layers due to variations in saturation, characterizing the metastable phase. Kidney stone formation includes two main stages: (i) nucleation and (ii) aggregation and/or growth. Nucleation was either Randall plaque of hydroxyapatite in tissue on the surface of the papilla or a coating of whewellite on the plaque, or crystallization as free particles in the urine. Subsequently, aggregation or growth occurs by precipitation of stone-forming materials around the plaque or coating carried into the urine, or around the nucleus formed in situ in the urine. Urinary supersaturation is the main driving force of crystallization processes; and is controlled by many factors including bacterially induced supersaturation.

Okadaic Acid-Induced Alzheimer's in Rat Brain: Phytochemical Cucurbitacin E Contributes to Memory Gain by Reducing TAU Protein Accumulation.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive memory loss and cognitive decline, with hallmark pathologies related to amyloid beta (Aß) and TAU. Natural phytochemicals show promise for drug discovery to fill the current therapeutic innovation gap in AD. This study investigated the effect of cucurbitacin E (CuE), one of the bioactive components of Ecballium elaterium, on TAU fibril formation in okadaic acid-induced AD in rats. In a randomized design, we assigned 30 female Sprague Dawley rats to one of five experimental groups: (1) control, (2) stereotaxic surgery, (3) stereotaxic surgery + artificial cerebrospinal fluid, (4) stereotaxic surgery + okadaic acid (AD model), and (5) stereotaxic surgery + okadaic acid + CuE treatment. For experimental groups 4 and 5, rats were administered OKA-ICV (200 ng/kg) followed by CuE (4 mg/[kg·day], intraperitoneally) for 20 days. Expression of the MAPK1/3 and MAPK14 genes associated with TAU metabolism, hippocampal protein levels of these genes, cognitive functions of the rats, and histological accumulation of TAU in the brain were evaluated. Our findings in this preclinical model collectively suggest that phytochemical CuE contributes to memory gain by reducing TAU protein accumulation, which warrants further evaluation in future in vitro and in vivo studies.

Deep learning as a new tool in the diagnosis of mycosis fungoides.

Mycosis Fungoides (MF) makes up the most of the cutaneous lymphomas. As a malignant disease, the greatest diagnostical challenge is to timely differentiate MF from inflammatory diseases. Contemporary computational methods successfully identify cell nuclei in histological specimens. Deep learning methods are especially favored for such tasks. A deep learning model was used to detect nuclei Hematoxylin-Eosin(H-E) stained micrographs. Nuclear properties are extracted after detection. A multi-layer perceptron classifier is used to detect lymphocytes specifically among the detected nuclei. The comparisons for each property between MF and non-MF were carried out using statistical tests the results are compared with the findings in the literature to provide a descriptive analysis as well. Random forest classifier method is used to build a model to classify MF and non-MF lymphocytes. 10 nuclear properties were statistically significantly different between MF and non-MF specimens. MF nuclei were smaller, darker and more heterogenous. Lymphocyte detection algorithm had an average 90.5% prediction power and MF detection algorithm had an average 94.2% prediction power. This project aims to fill the gap between computational advancement and medical practice. The models could make MF diagnoses easier, more accurate and earlier. The results also challenge the manually examined and defined nuclear properties of MF with the help of data abundance and computer objectivity.

The role of CD1a expression in the diagnosis of cutaneous leishmaniasis, its relationship with leishmania species and clinicopathological features.

Cutaneous leishmaniasis is caused by a flagellated protozoan transmitted by the bite of a female sandfly. The clinical and demographic details of this disease, predominantly affecting immunocompetent individuals, are recognized by the WHO as a Neglected Tropical Disease. We sought to determine the usability of CD1a immunohistochemical staining to detect amastigotes especially in cases where leishmaniasis is suspected but evident amastigotes could not observed. We also evaluated the relationship between CD1a expression and leishmania subtypes. A total of 84 cases diagnosed with leishmaniasis or suspected leishmania on histo-morphological evaluation of skin biopsies were included in the study. Amastigotes were easily detected in hematoxylin eosin in 18 of 84 cases. In 23 cases, amastigotes could not detect in hematoxylin eosin sections. The immunostains for CD1a are demonstrated amastigotes in 60 of 84 cases. However, a small number of amastigotes became visible by positive staining with CD1a in 43.4% of the cases in that amastigotes could not detected in hematoxylin eosin. A statistically significant correlation was found between amastigote amount in hematoxylin eosin and CD1a expression. In addition, a significant correlation was observed between CD1a expression, age and clinical pre-diagnosis of the cases. It was observed that amastigotes were easily detected in hematoxylin eosin in Leishmania Infantum / donovani positive cases in polymerase chain reaction (PCR), and at the same time, it was found that CD1a expression was significantly higher. Using histopathology examination with CD1a staining and/or PCR methods, a diagnosis of leishmaniasis can be established and early treatment initiated. This contributes to reduce transmission and prevalence.

The role of COL6A1and PD-1 expressions in renal cell carcinoma.

OBJECTIVE: The COL6A1 is a gene encoding the alpha 1 polypeptide subunit of collagen 6 (COL6A1), an extracellular matrix protein subunit. Programmed cell death receptor-1 (PD-1) and its ligand, programmed cell death receptor ligand-1 (PD-L1) have been shown to have a prognostic significance in clear cell renal cell carcinomas (RCCs). In this study, we evaluated the expressions of COL6A1 and PD-1 in four different RCC subtypes. MATERIALS AND METHODS: A total of 161 radical nephrectomy and nephron-sparing surgery cases with RCCs from five different health care centers were included in this study. Clinical data of the cases were taken from electronic records of the institutions. The pathological data were collected by an expert uropathologist and re-evaluated with slides obtained from paraffin blocks of the cases. The correlation of COL6A1 and PD-1 expression with sex, age, tumor type, lymphovascular invasion (LVI), World Health Organization/International Society of Urological Pathology (WHO/ISUP) grade, and tumor stage (pT) was analyzed with the Pearson chi-squared test. RESULTS: Patients with sarcomatoid RCC and clear cell RCC had significantly higher COL6A1 scores and intensities than in other types of RCC (p=0.004 and p=0.002, respectively). WHO/ISUP grade and, COL6A1 and PD-1 staining scores also showed positive correlation (r=0.230, p=0.004 and r=0.277, p=0.001, respectively for COL6A1 and r=0.191, p=0.018 and r=0.166, p=0.041, respectively for PD-1). The staining scores and intensities of COL6A1 and PD-1 were not different between the patients with positive and negative LVI (p>0.05). CONCLUSION: In high-grade RCCs, we found the relationship between immunohistochemical staining scores of COL6A1 and PD-1 proteins and clinical, demographic, and histopathological parameters. Our results proved that COL6A1 and PD-1 are really promising proteins as prognostic parameters and for targeted immunotherapy.

Topical Application of High-Dose Mesna Prevents Adhesion Formation: An Experimental Animal Study.

BACKGROUND: Adhesion formation is a common complication of abdominal surgeries. Mesna is a drug with fibrinolytic properties which has been used in surgical field to facilitate tissue dissection. The aim of this experimental animal study was to investigate the effect of mesna on prevention of intra-abdominal adhesion in rats. MATERIALS AND METHODS: Twenty-eight Wistar albino rats were used in the study. To create abdominal adhesion, cecum was abraded in all rats. No additional surgical procedure was performed other than adhesion in group 1 (only adhesion). In the other groups, rats were treated topically by administering 0.9% saline (group 2), 40 mg/kg mesna (group 3), and 400 mg/kg mesna (group 4). All rats were sacrificed on postoperative 21st day. Histopathological and macroscopic evaluations of adhesion formation were performed. RESULTS: Quantity of adhesion scores (P = 0.022), severity of adhesion scores (P = 0.041), total adhesion scores (P = 0.023), and histopathological adhesion grading scores (P < 0.001) were reduced by 400 mg/kg mesna. CONCLUSIONS: This is the first study for mesna on prevention of abdominal adhesion formation in rats. We concluded that dose-dependent reduction of adhesion was achieved by mesna. With future studies, topical administration of mesna during open abdominal surgeries may be used to prevent adhesion formation.

What does the Data of 354,725 Patients from Turkey Tell Us About Cervical Smear Epithelial Cell Abnormalities? - The Epithelial Cell Abnormality Rate is Increasing - Quality Control Studies and Corrective Activity are Musts.

OBJECTIVE: There is no other screening program close to the success rate of PAP test. Cervical cytology constitutes a large workload so that quality control in cervical cytology is important for the quality assurance of pathology laboratories. MATERIAL AND METHOD: In this study, we collected the cervical cytology results from all over Turkey and discussed the parameters influencing the quality of the PAP test. The study was conducted with Turkish gynaecopathology working group and 38 centers (totally 45 hospitals) agreed to contribute from 24 different cities. The study was designed to cover the cervical cytology results during 2013. The results were evaluated from the data based on an online questionnaire. RESULTS: The total number of Epithelial Cell Abnormality was 18,020 and the global Epithelial Cell Abnormality rate was 5.08% in the total 354,725 smears and ranging between 0.3% to 16.64% among centers. The Atypical squamous cells /Squamous intraepithelial lesion ratios changed within the range of 0.21-13.94 with an average of 2.61. When the centers were asked whether they performed quality assurance studies, only 14 out of 28 centers, which shared the information, had such a control study and some quality parameters were better in these centers. CONCLUSION: There is an increase in the global Epithelial Cell Abnormality rate and there are great differences among centers. Quality control studies including the Atypical squamous cells/Squamous intraepithelial lesion ratio are important. Corrective and preventive action according to quality control parameters is a must. A cervical cytology subspecialist in every center can be utopic but a dedicated pathologist in the center is certainly needed.

The histopathological evaluation of healing effects of vitamin C administered before methotrexate therapy on testicular injury induced by methotrexate.

OBJECTIVE: Methotrexate (MTX) leads to acute toxic side effects in tissues or organs containing rapidly dividing cells such as seminiferous tubules. In this study, we investigated the protective effects of vitamin C against MTX-induced injury in rat testis. MATERIAL AND METHODS: A total of 31 rats were divided into 4 groups, including the control group. The study was completed within 4 weeks and the rats received daily doses of 2 mL/kg SF, 100 mg/kg vitamin C and 10 mg/kg/day MTX i.p according to their groups. The mean seminiferous tubular diameter, germinal epithelial cell thickness, and mean testicular biopsy score were determined by histologic examination of each group. RESULTS: The vitamin C + MTX group showed more similarity with the control group. Statistically significant results were achieved between groups as for mean seminiferous tubular diameter, germinal epithelial cell thickness, and mean testicular biopsy score. When compared with the group which received vitamin C after MTX therapy, values for mean seminiferous tubular diameter, germinal epithelial cell thickness, and mean testicular biopsy score were significantly higher in the group which received vitamin C before initiation of MTX therapy. CONCLUSION: Vitamin C decreased MTX-induced testicular histological injuries, especially when used before MTX therapy.

Cholesteatoma in ectopic kidney.

Cholesteatoma in the urinary system is a rarely seen benign condition. Rosina firstly defined this condition in the year 1953. Histopathologically it is characterized with keratinization, and squamous metaplasia of urothelial epithelium associated with desquamation of keratinized layers. Flank pain is the most common symptom that is caused by elimination of keratinous material. In our case we will discuss cholesteatoma developed in an ectopic kidney which has not been described in the literature before.

Intranodal palisaded myofibroblastoma - a rare case report and literature review.

Intranodal palisaded myofibroblastoma (IPM) is a benign mesenchymal neoplasm originating from smooth muscle cells and myofibroblasts. The inguinal region is the most common site of this rare tumor. As there are only about 89 such cases reported in the literature, the precise etiology and pathogenesis have yet to be explained adequately. It is characterized by spindle cells, amianthoid fibers, and by the proliferation of hemosiderin-containing histiocytes in the lymph node. A nodular lesion was excised from the inguinal region of a 47-year-old female patient with the clinical diagnosis of lymphoma and/or metastase. Macroscopic examination of a section of the lesion demonstrated a solid appearance. Microscopic examination revealed spindle-cell proliferation, amianthoid fibers, hemosiderin pigment, and extravasated erythrocytes. Nuclei of the spindle cells displayed a palisaded appearance. Compressed lymphoid tissue was observed around the lesion. Neoplastic cells were identified by the presence of vimentin, SMA, Cyclin D1, and beta-catenin. The Ki67 index was less than 1%. Histological examination confirmed the diagnosis of IPM. Although IPM is benign, it is frequently confused with metastatic lesions and lymphomas.

Three different clinical faces of the same histopathological entity: hair follicle nevus, trichofolliculoma and accessory tragus.

BACKGROUND: Hair follicle nevus is a rare, congenital hamartoma with follicular differentiation characterized histologically by numerous, tiny, mature hair follicles. Trichofolliculoma, the histopathological features of which are quite similar to those of hair follicle nevus, is also a hamartoma that differs from hair follicle. Accessory tragus is a relatively common, benign congenital abnormality of the external ear with an incidence rate of 1 to 10 per 1,000 live births. OBJECTIVE: This study seeks to assess the discriminatory value of currently available, histological criteria in the differential diagnosis of hair follicle nevus, accessory tragi and trichofolliculoma. METHODS: Twenty-one patients comprising 9 cases of hair follicle nevus, 8 accessory tragi patients and 4 trichofolliculoma cases, were recruited to perform the study. RESULTS: There were 10 males and 11 females in the study group. No significant difference was observed between the three study groups in terms of age, gender or histopathological parameters such as density of hair follicles, subcutaneous fat score and presence of connective tissue framework. Cartilaginous component was seen in 8 cases that were diagnosed as accessory tragi, while central cyst and radiating hair follicles were seen in 4 cases which were diagnosed as trichofolliculoma. CONCLUSION: The results of our study showed that diagnostic discrimination of these diseases could be made only with the clinicopathologic correlation because of their clinical and histopathological similarities.

Three different clinical faces of the same histopathological entity: hair follicle nevus, trichofolliculoma and accessory tragus

AbstractBACKGROUND:Hair follicle nevus is a rare, congenital hamartoma with follicular differentiation characterized histologically by numerous, tiny, mature hair follicles. Trichofolliculoma, the histopathological features of which are quite similar to those of hair follicle nevus, is also a hamartoma that differs from hair follicle. Accessory tragus is a relatively common, benign congenital abnormality of the external ear with an incidence rate of 1 to 10 per 1,000 live births.OBJECTIVE:This study seeks to assess the discriminatory value of currently available, histological criteria in the differential diagnosis of hair follicle nevus, accessory tragi and trichofolliculoma.METHODS:Twenty-one patients comprising 9 cases of hair follicle nevus, 8 accessory tragi patients and 4 trichofolliculoma cases, were recruited to perform the study.RESULTS:There were 10 males and 11 females in the study group. No significant difference was observed between the three study groups in terms of age, gender or histopathological parameters such as density of hair follicles, subcutaneous fat score and presence of connective tissue framework. Cartilaginous component was seen in 8 cases that were diagnosed as accessory tragi, while central cyst and radiating hair follicles were seen in 4 cases which were diagnosed as trichofolliculoma.CONCLUSION:The results of our study showed that diagnostic discrimination of these diseases could be made only with the clinicopathologic correlation because of their clinical and histopathological similarities.

A rare cause of dysphagia in children: lymphangiomatous polyp of the palatine tonsil.

Oropharyngeal and tonsillar masses are a very rare cause of dysphagia in children. In this article, we describe a rare cause of dysphagia in children, a lymphangiomatous lesion of the palatine tonsil, and discuss the clinical and histopathologic features of these lesions.