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Background and Objective: Nodular fasciitis (NF) is a self-limiting, transient neoplasm composed of fibroblasts and myofibroblasts. Since it regresses spontaneously, diagnosis by fine needle aspiration (FNA) cytology plays a major role in its management. Methods: We present a series of 8 cases with either FNA or biopsy diagnosis of NF, and study the major cytological features with a review of literature on diagnostic criteria and its pitfalls. Results and Conclusion: The 8 cases occurred in patients between the age of 14 ton72 years, with equal sex distribution. FNA diagnosis concurred in 4 cases. Causes of wrong diagnosis included lack of clinical information and paucicellular smear. FNA cytology is an important tool in the diagnosis of nodular fasciitis, in appropriate clinico-radiological setting.

Background: The association of human papillomavirus (HPV) with head and neck squamous cell carcinoma (HNSCC) was first described in 1982–1983 by the authors of this review. Prompted by this discovery 35 years ago, an entirely new field of HPV research has emerged, resulting in a paradigm shift from smoking and alcohol as the only etiological factors to confirmation of HNSCC as an important group of HPV-related human malignancies. Summary: In this review, the authors first describe the scope (i.e., HNSCC) by the anatomic sites of the tumors. Their important site-specific differences in epidemiology are emphasized, and the misconceptions caused by the adopted practice of pooling all tumors from these divergent anatomic sites as a single entity (HNSCC) are pinpointed. The convincing evidence of the established risk factors (smoking and alcohol) is briefly addressed, before entering in the discussion on the causal role of HPV in HNSCC pathogenesis. The global HPV prevalence in different subsets of HNSCC is summarized using the data extracted from all meta-analyses published since 2010. Of all HNSCC subsets, oropharyngeal SCC has an HPV profile distinct form all the other subsets, and the possible mechanisms explaining this intimate association with HPV are discussed. Key Messages: Recent global trends show a constant increase in HNSCC rates particularly among younger age groups. The evidence on cigarette smoking and alcohol consumption as the prime risk factors of HNSCC is overwhelming. During the past 35 years, however, increasing evidence has accumulated implicating an important causal role of HPV in HNSCC. These data have important clinical implications, HPV detection and tailored treatment strategies for HPV-positive HNSCCs currently being an integral part of the oncological management practices of HNSCC.

It is currently recognized that in addition to the major impact of human papillomavirus (HPV) infection in females, HPV causes considerable disease in men at the genitals, anal canal, and oropharynx. Specifically, genital HPV infections may progress to genital warts and penile carcinoma. Although studies concerning the natural history of HPV infections and associated neoplasias have mainly focused on women, during the last 2 decades considerable attention has been given in further understanding these infections in men. The HIM (HPV infection in men) Study, the only prospective multicenter study of male HPV natural history, consisted of a large prospective international cohort study in which men from Brazil, the United States, and Mexico were enrolled. The design and protocols of this study allowed unraveling crucial information regarding the relationship between HPV infection and clinical consequences in men, and associated risk factors at each of the anatomic sites where HPV is known to cause cancer in men.

Introduction: The recently described anaplasmosis infection is widespread but concerns to the insufficiently known group of diseases. The aim of our research is the development of uniform biological model for reproducing of artificial immunodeficient state by experimental anaplasmosis. Materials and methods: Algorithm of experimental anaplasmosis reproducing, consisted of such consecutive stages: 1) artificial forming of the immunodeficient state at nonlinear white mise (Mus musculus L.); 2) preparation of the tested biological material samples; 3) inoculation by prepared samples of the laboratory animals with the artificially formed immunodeficient state; 4) sampling from the dead or slaughtered (by the method of chloroformed anesthesia) experimental animals of sectional material (organs and targets tissues); 5) verification of aetiology by express detection of causative agents by the method of PCR in the selected samples of sectional material. Results: Biological model of experimental anaplasmosis have been created suitable for realization of both diagnostic and epidemiological, epizootic, ecobiological and other researches of different origin biological material samples, including samples of solid and liquid consistency material. Formed model realised in premature death of experimental animals in 17.4 % cases; resulted in an onset of disease clinical signs without death during the term of supervision in 43.8 % cases; coursed in the absence of the expressed symptoms of infection in 31.3 % cases. Conclusions: Developed biological model of experimental anaplasmosis consists in that as laboratory animals with the increased sensitiveness to the infection and accumulation of causative agent are used white nonlinear mice with the artificially formed immunodeficient state.

Objective: We aimed to assess the risk of malignancy (ROM) and predictive values in prior breast cytology studies as a basis for the new International Academy of Cytology (IAC) Yokohama system for reporting breast fine-needle aspiration biopsy (FNAB) cytology, which classifies cytologic diagnoses into 5 categories: (1) insufficient material, (2) benign, (3) atypical, (4) suspicious of malignancy, and (5) malignant. Study Design: Publications between January 1, 1997, and December 31, 2017, that studied the performance characteristics of FNAB from palpable and nonpalpable breast masses were identified through the PubMed database. Data for number of total cases and cases within each diagnostic category, if available, were collected. Performance characteristics, including absolute sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and ROM for each category were recorded or, when possible, calculated. Results: The literature review resulted in a case cohort of 33,341 breast FNABs, drawn from 27 studies. Pooling these cases together, the ROM for insufficient material, benign, atypical, suspicious, and malignant were 30.3, 4.7, 51.5, 85.4, and 98.7%, respectively. The complete sensitivity and specificity were 96.3 and 98.8%, correspondingly. The PPV and NPV were 98.7 and 95.3%, correspondingly. The false-negative and false-positive rates were 3.7 and 1.0%, respectively. Conclusions: This meta-analysis demonstrates that the diagnostic categories of the new IAC Yokohama System each carry an implied ROM, which increases from the benign to malignant categories. This study also shows the high sensitivity and specificity of FNAB for breast lesions.

Background: AgNOR pleomorphism has been widely used for its diagnostic importance in differentiating premalignant and malignant lesions of different human neoplasms. However, an evaluation of its potential for discriminating cases of high-risk squamous intraepithelial lesions of the cervix (SIL) has been rarely attempted. Aim: The tumor marker potential of AgNOR pleomorphism counts was assessed by correlating high and low mean counts in low-grade SIL (LSIL) cases with persistence or regression of the lesion and HPV positivity. Materials and Methods: The 115 LSIL cases selected for the study were registered from the ongoing cervical cancer screening of the rural population of Lucknow West. Silver nitrate staining for AgNOR counts and HPV DNA testing were done in all 115 cases. Results: The AgNOR counts in the 115 LSIL cases revealed low counts in 92 and high counts in 23 cases. Follow-up, available in 107 cases, revealed persistence of the lesion in 21 of the 23 cases with high counts and in 4 of the 84 cases with low counts. HPV positivity showed a strong correlation with high counts. Persistence of LSIL was also more frequent with high AgNOR counts and in HPV-positive cases. Conclusions: The study showed a correlation of high mean AgNOR counts with HPV positivity and persistence of LSIL.

Liquid biopsy represents the analysis of tumor-derived material in the blood and other body fluids of cancer patients. This portrays a minimally invasive detection tool for molecular biomarkers. Liquid biopsy has emerged as a complementary or alternative method to surgical biopsy. This non-invasive detection tool overcomes the recurrent problems in the clinical assessment of tumors that stem from the lack of accessibility to the tumor tissue and its clonal heterogeneity. Moreover, body fluid-derived components have shown to reflect the genetic profile of both primary and metastatic lesions and provide a real-time monitoring of tumor dynamics, representing a great promise for personalized medicine. This review will highlight the latest breakthroughs and the current applications of several tumor-derived biomarkers that can be found in body fluids. The authors will focus on tumor-derived exosomes, tumor-educated platelets, and circulating tumor miRNAs and mRNAs, and how these can be used for tumor detection.

Objective: Recently the International Academy of Cytology (IAC) proposed a new reporting system for breast fine needle aspiration biopsy (FNAB) cytology. We aimed to categorize our samples according to this classification and to assess the risk of malignancy (ROM) for each category as well as the diagnostic yield of breast FNAB. Study Design: Breast FNAB specimens obtained between January 2007 and December 2017 were reclassified according to the newly proposed IAC Yokohama reporting system. The ROM for each category was determined. Diagnostic yield was evaluated based on a three-category approach, benign versus malignant. Results: The samples were distributed as follows: insufficient material 5.77%, benign 73.38%, atypical 13.74%, suspicious for malignancy 1.57%, and malignant 5.54%. Of the 3,625 cases collected, 776 (21.4%) had corresponding histology. The respective ROM for each category was 4.8% for category 1 (insufficient material), 1.4% for category 2 (benign), 13% for category 3 (atypical), 97.1% for category 4 (suspicious for malignancy), and 100% for category 5 (malignant). When only malignant cases were considered positive tests, the sensitivity, specificity, and diagnostic accuracy were 97.56, 100, and 99.11%, respectively. Conclusions: Our study is the first to categorize breast FNAB cytology samples according to the proposed IAC reporting system and to evaluate patient outcomes based on this categorization.

Objective: The exfoliative cell analyzer, LC-1000 (Sysmex Corporation, Japan), is a medical device that presents the cell proliferation index and 23 research parameters as indicators of cellular proliferative potential. The objective was to evaluate the clinical usability of qualitative assessment by LC-1000 compared with cytology, the human papillomavirus (HPV) test, and histology as gold standard. Study Design: Women that visited 3 sites between July 2015 and March 2017 were registered. The primary endpoint in this study was the comparison between LC-1000 measurement and HPV test for sensitivity and specificity for cervical intraepithelial neoplasia 2+ (CIN2+). A tree model algorithm was newly constructed by a statistical method and its relationship with histological results was evaluated. Results: The sensitivity and specificity of LC-1000 were 78.3 and 74.1%, while those of the HPV test were 94.7 and 85.4%, respectively. A tree model comprising five categories was constructed. The proportion of advanced lesions was higher with the change in the rank classification results from 1 to 5. The positive predictive values of CIN2+ in the categories 4 and 5 were high. Despite the small number of subjects, cancer was undetected in categories 1 and 2. In addition, the comparison with follow-up results in 19 women assessed as CIN1 showed that the rate of progression in the categories 3–5 was 50% (7/14); progression in the categories 1 and 2 was 0% (0/5). Conclusions: LC-1000 may be useful for cervical cancer screening as an index to qualitatively evaluate CIN and cancer based on the changes in characteristics of cells.

Objective: Evidence shows that the switch/sucrose nonfermenting chromatin remodeling complex plays a critical role in DNA repair, cancer progression and dedifferentiation. BRG1 is one of its key catalytic subunits. While the loss of BRG1 expression by immunocytochemistry has been identified in a subset of malignancies arising in various sites with undifferentiated/rhabdoid morphology and poor prognosis, the underlying basis for its loss is unclear. Methods: A retrospective search was conducted in our cytopathology archive for undifferentiated malignant tumors with rhabdoid phenotype and BRG1 loss. Clinical information was obtained from electronic medical records. Next-generation sequencing was performed following macro-dissection of paraffin-embedded cellblock tissue. Results: Three cases were identified; all presented with widely metastatic disease with no previously diagnosed primary malignancy, and subsequently died within 6 months of initial presentation. Cytologically, the aspirates showed dyshesive and undifferentiated cells with rhabdoid features. Extensive immunocytochemical workup demonstrated immunoreactivity with vimentin only and could not establish a specific lineage. BRG1 expression was absent, while INI1 expression was retained. Two cases harbored deleterious mutations in BRG1/SMARCA4. Pathogenic mutations in TP53 were identified in all tumors. Conclusions: BRG1 deficiency reflects underlying mutation in SMARCA4 gene in some but not all cases, suggesting that additional mechanisms may be causing BRG1 silencing. Pathogenic mutations in TP53 in all tumors are consistent with their highly aggressive nature. Recognizing the cytomorphology of this group of neoplasms and confirming their BRG1-deficient status by immunocytochemistry not only has prognostic implications, but may also impart potentially therapeutic value in the near future.

HPV is the most common sexually transmitted biological agent and is the cause of many conditions in men and women, including precancer lesions and cancer. Three prophylactic HPV vaccines targeting high-risk HPV types are available in many countries worldwide: 2-, 4- and 9-valent vaccines. All the 3 vaccines use recombinant DNA technology and are prepared from the purified L1 protein that self-assembles to form HPV type-specific empty shells. This non-systematic review aims to summarize the HPV epidemiology and the vaccine development to review the landmark trials of HPV vaccine, to present to most remarkable results from clinical trials and the real world, and to stress the challenges and the barriers for HPV vaccine implementation.

Objective Introduction: Herpes zoster (HZ), or shingles, is localized disease characterized by unilateral radicular pain and a vesicular rash limited to the area of skin innervated by a single dorsal root or cranial sensory ganglion. Whereas varicella, or chickenpox, results from primary exogenous varicella-zoster virus (VZV) infection, HZ is caused by reactivation of endogenous VZV that has persisted in latent form within sensory ganglia following an earlier episode of chickenpox. The aim: To explore the clinical features, diagnosis, and treatment of CNS injury caused by VZV infection in a prospective single center study from January 2014 to January 2018. Patients and methods Materials and methods: 117 adult patients, among which young women predominated with confirmed VZV infection were analyzed in the study. CSF and blood contents, antibody for herpes zoster M and G classes, and MRI scans have been studied, but the crucial diagnostic sign was the presence of specific viral DNA in the CSF or blood. The main clinical manifestations of the disease were ganglionitis and ganglioradiculoneuritis. Another brain lesion like uveitis, encephalitis and vasculitis were observed also. A clinical case of an unusual course of VZV-infection is given. Results Results and conclusions: The most common clinical variants of HZ were ganglionitis (69.7%). Cranial localization was observed in 31% of patients, spinal one - in 38.7%, injury to the meninges was found in 16.3% of patients.

Objective: Differentiation between gynecomastia, a common cause of male breast enlargement, and breast cancer is crucial for appropriate management. Fine-needle aspiration biopsy has been shown to be sensitive and specific in assessing female breast lesions, comparable to core needle biopsy. Few such studies have been conducted in men. We assessed its diagnostic value in a male patient cohort. Study Design: Men who underwent fine-needle aspiration (FNA) for palpable breast lesions at Massachusetts General Hospital from January 2007 to December 2016 were evaluated. Clinical data, radiographic findings, and cytologic diagnoses of 74 breast FNA from 71 men were reviewed. Breast aspirates were classified as nondiagnostic, benign, atypical, suspicious for malignancy, or malignant. Histology was obtained in 37 cases, and clinical and radiological data were used as follow-up in 37 patients. Results: Most FNA biopsies (73%) were performed by cytopathologists, and 93.2% of the breast FNA in men were adequate; 58% showed benign processes, mostly gynecomastia (n = 22), and 28.4% (n = 21) were malignant, most often ductal carcinoma. No false-positive cytologies were obtained, and there was 1 false-negative cytology. In our study, FNA of palpable male breast lesions was 95.8% sensitive and 100% specific. Conclusions: FNA allows sensitive, specific, and safe evaluation and diagnosis of palpable male breast lesions.

Objectives: To review the performance and utility of the International Academy of Cytology (IAC) Yokohama System for Reporting Breast Fine Needle Aspiration Biopsy (FNAB) Cytology five category stratification and evaluate the impact of rapid onsite evaluation (ROSE). Method: A retrospective analysis of breast FNAB cytology cases with matched histopathological results at a single institution over a 32 months period using a structured reporting system with 5 diagnostic categories (“inadequate/insufficient,” “benign,” “atypical,” “suspicious of malignancy” and “malignant”) closely paralleling the proposed IAC System. Results: Of 2,696 breast FNAB cases, there were 579 with matched histopathology and 456 of these had ROSE. ROSE decreased the number in the “insufficient” category (17.1% without ROSE to 4.0% with ROSE) and increased the number in the “malignant” (17.9 to 39.0%) with a lesser impact on the “atypical,” “benign” and “suspicious of malignancy” categories. The performance data showed a positive predictive value of 96.4%, negative predictive value of 97.6%, and a risk of malignancy of a FNAB categorized as “insufficient” to be 2.6%, “benign” 1.7%, “atypical” 15.7%, “suspicious of malignancy” 84.6%, and “malignant” 99.5%. Conclusion: Breast FNAB is an accurate test enabling effective diagnosis of breast lesions. ROSE improved the performance by decreasing the proportion of “insufficient” and “atypical” and increasing the “suspicious of malignancy” and “malignant” diagnoses and enabling immediate triage for further biopsy where necessary.

Whilst cytological smears are still the basis of cytodiagnosis, there is an increasing role for ancillary testing. Specimens obtained are not always optimal, often with limited material for ancillary studies. Several reports have described the utility of scraping material from cytological smears to manufacture cell blocks to provide material for ancillary studies. Our objective was a retrospective review of the PathWest (QE2) experience with manufactured cell blocks (mCB) over the last 10 years. A total of 178 fine-needle aspiration cases with mCB were extracted from the PathWest database. Data were subdivided into: lymph node (89), breast (31), thyroid (23), soft tissue (13), liver (11), and other sites (11) and were analysed. All available material was reviewed. Diagnostic material was identified in 163 mCB (91.6%). Immunohistochemistry (IHC) was performed on 149 cases. Positive IHC staining was seen in 139 cases (93.3%) and advanced the diagnosis in 119 cases (79.9%). Molecular studies were performed on 38 mCB with adequate DNA obtained in 37 cases (97.3%). Our review has demonstrated that cellular material scraped from air-dried or prefixed smears can be made into cell blocks. Antigen preservation is adequate to provide diagnostically useful results with IHC whilst DNA integrity is preserved to allow molecular analysis.

Background: Current automated cervical cytology screening systems still heavily depend on manipulation of glass slides. We developed a new system called CytoProcessorTM (DATEXIM, Caen, France), which increases sensitivity and takes advantage of virtual slide technology to simplify the workflow and save worker time. We used an approach based on artificial intelligence to identify abnormal cells among the tens of thousands in a cervical preparation. Objectives: We set out to compare the diagnostic sensitivity and specificity of CytoProcessorTM and the ThinPrep Imaging System (HOLOGIC, Marlborough, MA, USA). Methods: A representative population of 1,352 cases was selected from the routine workflow in a private laboratory. Diagnoses were established using the ThinPrep Imaging System and CytoProcessorTM. All discordances were resolved by a consensus committee. Results: Compared to the ThinPrep Imaging System, CytoProcessorTM significantly improves diagnostic sensitivity without compromising specificity. The sensitivity of detection of “atypical squamous cells of undetermined significance (ASC-US) and more severe” and “low-grade squamous intraepithelial lesion and more severe” was significantly higher using CytoProcessorTM. Considering that cases with a truth diagnosis of ASC-US or more severe required clinical follow-up, 1.5% of the cases (21/1,360) would have been missed if the CytoProcessorTM diagnosis had been used for clinical decision-making. In contrast, 4% of the cases (54/1,360) were missed when the ThinPrep Imaging System diagnosis was used for clinical decision-making. There were 2.6 times fewer false negatives using CytoProcessorTM. The CytoProcessorTM workflow was 1.5 times faster in terms of worker time. Conclusions: CytoProcessorTM is the first of a new generation of automated screening systems, demonstrating improved sensitivity and yielding significant gains in processing time. In addition, the fully digital nature of slide presentation in CytoProcessorTM allows the remote diagnosis of Papanicolaou tests for the first time.

Background: Atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS) criterion in thyroid fine-needle aspirates (FNAs) has been a heterogeneous entity with much inter-observer variation. Sub-categorisation of AUS/FLUS has been observed to play an effective role in risk stratification. We aimed to validate AUS/FLUS sub-categorisation in correlation with the spectrum of malignancy. Study Design: Subjects included patients with AUS/FLUS diagnosed between January 2015 and December 2016. AUS/FLUS cases were sub-categorised into those exhibiting (1) architectural atypia, (2) cytological atypia, (3) architectural and cytological atypia, (4) AUS with Hürthle cells, and (5) AUS not otherwise specified (AUS-NOS). Each sub-category was correlated with their corresponding incidence of malignancy in surgical resections. Result: The overall incidence of AUS/FLUS in our centre was 13% (132/1,018). On retrospective review of 117 patients with AUS/FLUS, smears with cytological atypia showed a higher incidence of malignancy (78.3%) than those with architectural atypia (75.3%). AUS/FLUS cases with both cytological and architectural atypia had a malignancy rate of 71.4%. Conclusion: AUS/FLUS cases with cytological atypia had a higher risk of malignancy than those with architectural atypia. The sub-categorisation of AUS/FLUS is diagnostically important for the proper risk stratification of patients.

SMARCB1 (INI-1)-deficient sinonasal carcinoma is a rare entity within the subgroup of poorly differentiated sinonasal tract carcinomas. As there are only two papers describing the cytologic features of this entity, herein we describe the unique cytomorphologic features of a pulmonary metastasis of this tumor and include the differential diagnosis based on tumor location. The patient was a 53-year-old male who initially presented with sinus congestion and vision changes including left-eye proptosis and diplopia. The initial biopsy of the ethmoid-centered sinonasal mass was non-keratinizing squamous cell carcinoma based on strong immunoreactivity with p40 and absence of immunoreactivity for chromogranin, synaptophysin, p16, and EBER. However, the final diagnosis of the surgical resection was amended to SMARCB1 (INI-1)-deficient sinonasal carcinoma after additional immunohistochemical stains were performed. Post-primary resection, follow-up computed tomography imaging revealed significant interval progression of a solitary, initially indeterminate 1-cm lung nodule in the left upper lobe. Endobronchial ultrasound-guided fine-needle aspiration with concomitant core-needle biopsy was performed. Rapid on site evaluation of cytologic smears revealed a hypercellular specimen consisting of sheets of epithelioid cells with very scant to absent cytoplasm, ill-defined cell borders, enlarged fragile nuclei, and areas of nuclear molding. Mitotic figures were present. Other areas showed tumor cells with spindled to elongated nuclei and scant to ill-defined wispy cytoplasm. Both cytology cell block and core-needle biopsy histopathologic material showed the tumor cells to be negative for INI-1 nuclear staining as well as CK5/6, CAM5.2, p40, p63, CK7, AE1/3, and TTF-1. SMARCB1 (INI-1)-deficient sinonasal carcinoma can have a spectrum of morphologies and may mimic “small-round-blue-cell” and spindle-cell tumors on cytology preparations. Given the pulmonary location of the aspirate, familiarity with the cytomorphologic spectrum of SMARCB1 (INI-1)-deficient sinonasal carcinoma, inclusion of this entity within the differential diagnosis, and performance of immunohistochemistry will aid in arriving at the correct diagnosis.

Objective This study aimed to investigate the diagnostic utility of immunohistochemistry (IHC) analysis (FNA) and Epstein-Barr virus- (EBV) encoded small RNAs (EBERs) in situ hybridisation analyses of cell block (CB) sections obtained using fine needle aspiration in nasopharyngeal carcinoma (NPC) with lymph node metastasis. Methods A total of 38 FNA biopsies were collected using a Youyi aspirator. The cytomorphology, CB-based histomorphology, IHC, and EBERs in situ hybridisation were observed and the sensitivity/final diagnostic rates were compared with those of simple smears and a combination of smears and CBs. Results The 38 cases of metastatic lymph nodes from NPC displayed the morphological characteristics of non-keratinising carcinoma in cell smears and CB sections. The tumour cells showed high expression of CK5/6, P63, Ki-67, and EBERs (94.7%, 36/38 cases) in the CB sections. The sensitivity and the final diagnostic rates were lowest with the simple cell smears (86.8%, 33/38 and 71.1%, 27/38 cases), moderate with the smears combined with CB sections (92.1%, 35/38 cases and 81.6%, 31/38 cases), and the highest with IHC and EBERs in situ hybridisation (94.7%, 36/38 and 94.7%, 36/38 cases). Conclusions FNA has great value in the diagnosis of NPC with lymph node metastases, and using cell smears combined with IHC and EBERs in situ hybridisation of CB sections could help clinical doctors promptly identify the primary lesions.

Granular cell tumors (GCT) are mesenchymal neoplasms of Schwann cell/neural origin. Malignant granular cell tumors (MGCTs) represent1-2% of all GCT and defined as tumors demonstrating metastases or destructive local growth. Other clinical parameters suggestive of malignancy include rapid growth, size4 cm and necrosis. An apparently inconsistent set of histological features have been described in MGCT. Although the histologic parameters of a GCT are not always predictive of biologic behavior, the presence of atypical features may be indicative of an aggressive clinical behavior (recurrence and metastases). A preoperative estimate of features suggestive of malignancy is important for treatment and prognostication. Diagnosis and prognostication from preoperative fine needle aspiration (FNA) cytology is hampered by the fact that only a few case reports on cytologic features of malignant GCT have been published. We report a case of metastatic MGCT to breast and compare cytologic features to that of primary breast GCT and apocrine/histiocytoid variants of breast carcinoma.

Objective: Regarding cytological findings of squamous dysplasia, a comparison was made between a three-tiered classification – low-grade squamous intraepithelial lesion (LSIL), high-grade SIL/cervical intraepithelial neoplasia 2 (HSIL/CIN2), and HSIL/CIN3 – and a two-tiered classification – LSIL and HSIL. The respective risk for CIN2+ and CIN3+ was calculated to make decisions regarding management. Methods: A total of 2,949 women with first-time cytologic findings of squamous dysplasia (LSIL, HSIL/CIN2, or HSIL/CIN3) between January 2013 and June 2016 were enrolled. Subsequent cytological findings and histological diagnoses were evaluated until August 2018. For each category of findings, the risk for CIN2+ and CIN3+ was determined by Kaplan-Meier estimates. The differences in risk between the cytological categories were checked for significance using the log-rank test. Results: For the categories LSIL, HSIL/CIN2, and HSIL/CIN3, the risk for CIN2+ after 12, 24, and 60 months was 3.4, 9.4, and 23.3%; 35.2, 44.8, and 59.8%; and 95.5, 97.8, and 98.9%, respectively. For CIN3+ the risk was 2.0, 5.5, and 13.5%; 28.6, 35.6, and 48.3%; 91.3, 95.6, and 97.9%, respectively. The differences in risk between the categories are highly significant, respectively (p < 0.001). Conclusion: A three-tiered classification of squamous dysplasia such as the Munich Nomenclature III for cytology is suitable for risk-adapted clinical management, especially to avoid overdiagnosis and overtreatment.

Nucleolar organiser regions (NORs) are loops of DNA which are responsible for ribosomal RNA (rRNA) transcription in the nucleus of cells. NORs can be selectively stained by silver methods. The NORs agyrophilia is due to a group of nucleolar proteins, which have affinity for silver (Agyrophilic Nucleolar Organizer Regions, AgNOR proteins). The aim of the present study is to assess proliferative index in different grades of invasive ductal carcinoma (IDC) by using AgNOR as a marker. A total of 18 formalin fixed paraffin-embedded breast tissue blocks were retrieved from the archives of the histopathology department of the Komfo Anokye Teaching Hospital, Ghana. The tissue blocks included 17 IDC, (with 8 as grade 2 IDC, 9 as grade 3 IDC) and 1 normal breast tissues. Tissue sections were diagnosed and graded following haematoxylin and eosin (H&E) staining. Silver staining was used to demonstrate the presence of AgNOR. The AgNOR dots were manually counted in 50 and 100 cells. The mean AgNOR count (mAgNOR) and proliferative index, (pAgNOR, percentage of cells with ≥5 AgNOR dots per nucleus), significantly increased with increasing grade of IDC. The mAgNOR and pAgNOR were low in normal breast, (at p-value less than 0.05). There was no significant difference in the mAgNOR and pAgNOR score for counting 50 and 100 cells (at a p-value of 0.01). mAgNOR and pAgOR increases with increase in grade of IDC and hence can be used to assess proliferative index of IDC. Keywords: Nucleolar organiser regions (NORs), Agyrophilic Nuclear Organizer Region (AgNOR), Proliferative activity, Breast Cancer

The disease induced by Bibersteinia trehalosi usually occurs in lambs. It is triggered by certain stress factors and often emerges in the form of severe outbreaks. In adult sheep, only sporadic cases have been reported so far. This paper reports a B. trehalosi-induced high-mortality case occurring only in adult sheep. Seventy out of 628 adult sheep (11%) died in the affected pen during the six days of the outbreak. None of the 146 lambs kept in the neighbouring pen showed any clinical signs during that period. Several preceding events (shearing, vaccination and antiparasitic treatment) can be regarded as factors predisposing to the disease. Five adult sheep (4 females and 1 male) were sent for laboratory examination. Clinical, gross pathological, histological and bacteriological examinations revealed results corresponding to those reported previously in lambs that had died of a B. trehalosi-induced septicaemia.

Summary Introduction Eosinophilic pneumonia (EP) is a rare but serious adverse drug reaction (ADR) induced by non-steroidal anti-inflammatory drugs (NSAIDs). Methods We describe the second published case of EP induced by oral diclofenac. We also reviewed the literature as well as French pharmacovigilance database. Case presentation A 63 year-old woman with polyarthralgia had taken diclofenac for three days for analgesic purposes. Progressively, the patient presented weakness, dyspnea and fever. Computed tomography (CT) scan revealed bilateral interstitial infiltration. Broncho-alveolar lavage (BAL) showed an elevated level of eosinophils. After ruling out all other possible etiologies, drug-induced EP was diagnosed and treatment by corticosteroid was initiated. The patient recovered in three months. Results In the French pharmacovigilance database, six cases of EP were recorded (3 with naproxen, 2 with ibuprofen, 1 with piroxicam). In the literature, twenty-six cases of EP with NSAIDs were published. The most commonly involved drug was naproxen (n = 8), followed by fenbufen (n = 4), ibuprofen (n = 3) and diclofenac (n = 2). A high level of eosinophils was systematically observed in the blood cell count or BAL. Corticosteroid therapy was started in eleven cases. All patients recovered. Conclusion Complete history taking and examination should be done to rule out other etiological diagnoses. BAL is sufficient to diagnose EP. Corticosteroid therapy should be indicated for more severe or refractory cases. This adverse drug reaction is underestimated, healthcare professionals should be informed.

Cadmium is a known environmental and industrial pollutant with an enormous tissue disrupting potential. Mimosa pudica ( M. pudica ) is a creeping annual or perennial herb known to possess anti asthmatic, anti-epileptic, anti-tumour, anti-fertility, aphrodisiac, analgesic, anti-depressant, sedative, emetic properties and a strong radical scavenging activity. This research was aimed at investigating the ameliorative effects of M. pudica on cadmium-induced testicular damage in adult male Sprague Dawley rats. Twenty adult Sprague Dawley rats were employed in the study. They were divided into 4 groups (A–D) of 5 rats each, and toxicity was induced by administering 0.4 mg/ml cadmium chloride through drinking water to groups B–D for 21days. M. pudica extract was administered orally at 250 and 500 mg/kg to groups C and D. Animals in Groups C and D showed remarkable histological improvements in testicular tissue and markedly reduced damages when compared with group B.The active sperm motility of group B (6.00 ± 1.00%) was significantly ( p = 0.0001) decreased compared to that of the groups A (15.00 ± 0.00%)) and C (13.00 ± 1.22%). Sperm count analysis of group B (1.36 ± 0.28 × 10 6 /cc), C (4.18 ± 0.81 × 10 6 /cc) and D (2.54 ± 1.13 × 10 6 /cc) were significantly lower (p = 6 /cc), respectively. Sperm morphology of group A (70.00 ± 3.16%), B (66.00 ± 2.50), C (74.00 ± 2.45%) and D (64.00 ± 2.45%) recorded no significant difference. This study demonstrates that M. pudica has potential protective and restorative properties on the histoarchitecture of the testes of cadmium-treated rats.

The authors characterize a rare variant of Langerhans cell histiocytosis in a child of early age. Multiple-system form including liver damage is characterized by a particularly severe course, especially in early childhood. The authors report clinical, morphological and immunohistochemical data of the patient aged 1 year and 11 months. It is shown that timely diagnosis of this disease should be carried out in close cooperation of surgeons and morphologists.Представлена характеристика редкого варианта гистиоцитоза из клеток Лангерганса у ребенка раннего возраста. Мультисистемная форма, включающая поражение печени, отличается наиболее тяжелым течением, в особенности у детей первых лет жизни. Приведено собственное наблюдение пациента в возрасте 1 года 11 месяцев, которому установлен соответствующий диагноз на основании клинической, морфологической и иммуногистохимической картины. Показано, что своевременная дифференциальная диагностика формы данного заболевания должна проводиться при тесном сотрудничестве хирургов и патоморфологов с использованием комплекса высокотехнологичных методов.

Peripheral primitive neuroendodermal tumors (PNETs) and Ewing's sarcoma belong to the Ewing family of tumors and are small round-cell malignancies originating from spinal cord cells. These tumors account for 5% of all small round-cell malignant neoplasms. PNETs that arise from the lung parenchyma without pleural or chest wall involvement are very rare. We report a case of an adult female with a large pulmonary PNET who had given birth just 1 month prior to the diagnosis. She had cough and expectoration for 6 months, and the preoperative examination showed no metastases. Thus, we performed radical pneumonectomy and lymph node dissection. The patient recovered well without surgical complications and was discharged 7 days after the surgery. Postoperative pathology confirmed that the tumor was a small round-cell malignancy, and the tumor cells were positive for CD99, Friend leukemia virus integration 1 (FLI-1), and neuron-specific enolase (NSE), which was consistent with the diagnosis of a PNET. For primary large pulmonary PNETs, radical pneumonectomy may be a safe surgical method, worthy of further application in clinical practice.

Primary breast angiosarcoma (PBA) is a rare malignant tumor. PBA usually undergoes hematogenous metastasis; lymph node metastasis is very rare in such patients, and metastasis of PBA to the supraclavicular lymph nodes has not previously been reported. Here, we describe a rare case of PBA manifested by a diffuse enlargement of the left breast, with metastasis to the left axillary and bilateral supraclavicular lymph nodes. Contrast-enhanced ultrasound and positron emission tomography findings indicated a malignant lesion, whereas magnetic resonance imaging suggested a benign lesion. Core needle biopsy identified the lesion as a lymphangioma, and the histological characteristics suggested a high-grade angiosarcoma. Multimodal imaging and perfusion patterns obtained using various contrast agents can thus help to diagnose PBA.

KEY POINTS • A broad differential should be maintained in the returning traveller with fever, and a detailed travel, social and exposure history elicited to help guide appropriate diagnostics. • Spirochetes seen in routine peripheral blood or malaria smears are pathognomonic for tick-borne or louse-borne relapsing fever caused by Borrelia species. • In North America, tick-borne relapsing fever is endemic to British Columbia and the western United States, and is transmitted by Ornithodoros soft ticks. • Patients should be closely monitored for the Jarisch– Herxheimer reaction after initiation of effective therapy for all forms of relapsing fever.

Objective The role of tumor-infiltrating lymphocytes (TILs) has not yet been characterized in sarcomas. The aim of this bioinformatics study was to explore the effect of TILs on sarcoma survival and genome alterations. Methods Whole-exome sequencing, transcriptome sequencing, and survival data of sarcoma were obtained from The Cancer Genome Atlas. Immune infiltration scores were calculated using the Tumor Immune Estimation Resource. Potential associations between abundance of infiltrating TILs and survival or genome alterations were examined. Results Levels of CD4+ T cell infiltration were associated with overall survival of patients with pan-sarcomas, and higher CD4+ T cell infiltration levels were associated with better survival. Somatic copy number alterations, rather than mutations, were found to correlate with CD4+ T cell infiltration levels. Conclusions This data mining study indicated that CD4+ T cell infiltration levels predicted from RNA sequencing could predict sarcoma prognosis, and higher levels of CD4+ T cells infiltration indicated a better chance of survival.

The worldwide health crisis due to SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) has affected all healthcare systems. Low- and middle-income countries have needed to establish health strategies to combat the pandemic, many of which have collaterally affected the diagnosis and treatment of other illnesses. One of these other illnesses is cancer, which in Peru represents the primary cause of mortality. In recent decades, interventional cytopathology with fine-needle biopsy techniques has emerged as a minimally invasive, rapid, economical and effective procedure for diagnosing and staging cancer. However, in the current health context, it is confronted by the challenge of continuing to function in spite of the pandemic. This article reviews the existing literature on interventional cytopathology, the risk of infection from SARS-CoV-2 and biosafety and provides recommendations for carrying out said procedures for the benefit of the patient and the safety of healthcare staff.

Background, Previous studies have shown the value in studying lineage tracing in slices of human tumors. However, a tumor is not a two-dimensional structure and to better understand how a tumor, and its corresponding metastasis grow, a three-dimensional (3-D) view is necessary., Results, Using somatic mitochondrial mutations as a marker for lineage tracing, it is possible to identify and follow tumor specific cell lineages. Using cycling temperature capillary electrophoresis (CTCE) a total of 8 tissues from 5 patients (4 primary tumors and 4 metastasis) containing clear mitochondrial markers of tumor lineages were selected. From these 8 tissues over 9,500 laser capture microdisection (LCM) samples were taken and analyzed, in a way that allows 3-D rendering of the observations., Conclusion, Using CTCE combined with LCM makes it possible to study the 3-D patterns formed by tumors and metastasis as they grow. These results clearly show that the majority of the volume occupied by a tumor is not composed of tumor derived cells. These cells are most likely recruited from the neighboring tissue.

Objective To study the clinicopathological features and differential diagnosis of gastrofibromatosis-like undifferentiated carcinoma (GFLUC). Methods Three patients with GFLUC underwent histological and immunophenotypic analyses and fluorescence in situ hybridization to detect human epidermal growth factor receptor ( HER2) gene amplification. Results Among the three patients (2 male [36 and 44 years old], 1 female [58 years old]), two had lesions in the gastric body and one had lesions in the gastric antrum. Histological analysis revealed mixtures of aggressive fibromatosis and undifferentiated carcinoma in all three cases. Highly invasive fibromatous tissue, consisting of fibroblasts, proliferating myofibroblasts, and collagenous fibrous tissues, accounted for >90% of the tumor, with undifferentiated cancerous tissue accounting for Conclusions Unlike other gastric carcinomas, GFLUC shows specific histological, biological, and immunophenotypic characteristics.

Background Chronic refractory plasma cell mastitis (CRPCM) is an aseptic inflammation of the breast with a chronic course of the disease, extended treatment cycle (months to years), with a high recurrence rate. The objective of this study was to evaluate the efficacy of continuous postoperative negative pressure irrigation assisted mammaplasty (CPNPIAM) in treating CRPCM. Methods Between 2016 and 2018, 36 CRPCM patients receiving CPNPIAM were enrolled in this study. CPNPIAM mainly involved complete lesion removal, immediate breast mammaplasty, and continuous postoperative negative pressure irrigation. The age of the patients, local symptoms, history of treatment, the duration of the disease before surgery, hospitalization period, related risk factors, the success rate, the recurrence rate and patients' overall satisfaction ratings were analyzed in the article. Results Patients were aged between 22 and 53 years (mean 34.64 years). All patients had a history of conservative treatment or simple drainage. Local symptoms included inflammatory mass (n=36, 100%), abscess (n=33, 92%), nipple discharge (n=7, 19%), inflammatory plaque (n=34, 94%), and sinus tract formation (n=19, 53%). The lesion sizes ranged from 3 to 10 cm (mean 5.13 cm) in diameter. The mean hospitalization period was 8.42 days. The success rate was 100% (36/36) and the recurrence rate was 0% (0/36) at a 3-month follow-up. The patients' overall satisfaction ratings were "very good" (n=22, 61%), "good" (n=12, 33%), and "moderate" (n=2, 6%) with no poor or unsatisfactory ratings. Conclusions CPNPIAM is an effective way of treating CRPCM, and showed a high success rate, a low recurrence rate, and high patient satisfaction.

Aims: The aim of this study to determine the expression of MMP-28 in bladder urothelial carcinoma and to analyze the correlation between MMP-28 and the clinicopathological characteristics of human bladder carcinoma, and its relationship with patient prognosis. Methods: A total of 491 surgically resected bladder cancer samples and 80 normal tissue adjacent to the tumor were stained by immunohistochemistry. The expression of MMP-28 in these samples was quantitated, and the value of MMP-28 as a marker of bladder cancer and prognosis was assessed. Results: The expression of MMP-28 in urinary bladder carcinoma was higher than in normal bladder mucosa. The high level of MMP-28 was significantly correlated with tumor histology grade, lymphatic metastasis, lymph node infiltration, and distant metastasis (P < 0.05). The upregulation of MMP-28 was also closely related to the risk of cancer progression and the survival of patients. Further analysis documented that high expression of MMP-28 was associated with decreased overall survival in bladder cancer patients. Conclusions: The abnormal expression of MMP-28 may be related to the initiation and development of urothelial carcinoma. The upregulation of MMP-28 can be used as one of the effective indicators to diagnose bladder cancer and predict tumor progression.

Background This study evaluated the marginal adaptation, solubility and biocompatibility of TheraCal LC compared with mineral trioxide aggregate (MTA-Angelus) and Biodentine when used as a furcation perforation repair material. Methods The marginal adaptation was assessed by scanning electronic microscope and presence of any gap between the dentin surface and filling material in each quadrant of the sample was analyzed at 1000 X magnification. The solubility was measured after one week by the ISO standard method. Biocompatibility was evaluated by the inflammatory response and radiography after one month and three months of repair of experimental furcation perforations in dog's teeth. Results There were significant differences in the marginal adaptation, solubility and biocompatibility of the tested materials (P Conclusion Unlike Biodentine, TheraCal LC is incapable of alternating the MTA in furcation perforation repair due to its poor biocompatibility and poor marginal adaptation.

Sinonasal lymphoepithelial carcinoma (SLEC) is an extremely rare malignancy. We present a case of SLEC in a 77-year-old man who presented with nasal congestion and persistent sinusitis. Imaging revealed a large right nasal mass involving right paranasal sinuses along with bulky bilateral cervical lymphadenopathy. In addition, there was a fluorodeoxyglucose avid L1 vertebral lesion. Biopsy of nasal mass and cervical lymph nodes showed syncytial growth of tumor cells in a lymphoplasmacytic background. Immunohistochemical stains showed positivity for pankeratin, CK5/6, epithelial membrane antigen, p40 (focal), and p63 (focal). An Epstein-Barr virus-encoded RNA by in situ hybridization was strong and diffusely positive. Based on these pathologic findings and considering the location of tumor, diagnosis of SLEC was rendered. L1 vertebral body lesion was clinical and radiologically considered to be a metastasis. Correlation with radiology to determine the exact location of tumor is extremely important for correct diagnosis due to its histopathologic similarities with relatively more common undifferentiated type of nasopharyngeal carcinoma. No standard treatment protocol has been established for this tumor yet. To our knowledge, this is first ever report of SLEC presented with clinical stage IV disease.

ObjectivesThis study aimed to expand knowledge about soluble low-density lipoprotein receptor-related protein 1 (sLRP1) in juvenile idiopathic arthritis (JIA) by determining associations of sLRP1 levels in nonsystemic JIA patients with clinical and inflammatory biomarker indicators of disease activity.MethodsPlasma sLRP1 and 44 inflammation-related biomarkers were measured at enrollment and 6 months later in a cohort of 96 newly diagnosed Canadian patients with nonsystemic JIA. Relationships between sLRP1 levels and indicators of disease activity and biomarker levels were analyzed at both visits.ResultsAt enrollment, sLRP1 levels correlated negatively with age and active joint counts. Children showed significantly higher levels of sLRP1 than adolescents (mean ranks: 55.4 and 41.9, respectively; P = 0.02). Participants with 4 or fewer active joints, compared to those with 5 or more active joints, had significantly higher sLRP1 levels (mean ranks: 56.2 and 40.7, respectively; P = 0.006). At enrollment, considering the entire cohort, sLRP1 correlated negatively with the number of active joints (r = –0.235, P = 0.017). In the entire cohort, sLRP1 levels at enrollment and 6 months later correlated with 13 and 6 pro- and antiinflammatory biomarkers, respectively. In JIA categories, sLRP1 correlations with inflammatory markers were significant in rheumatoid factor–negative polyarticular JIA, oligoarticular JIA, enthesitis-related arthritis, and psoriatic arthritis at enrollment. Higher sLRP1 levels at enrollment increased the likelihood of absence of active joints 6 months later.ConclusionPlasma sLRP1 levels correlate with clinical and biomarker indicators of short-term improvement in JIA disease activity, supporting sLRP1 as an upstream biomarker of potential utility for assessing JIA disease activity and outcome prediction.

Coronaviruses (CoVs) are important human and animal pathogens. There have been several outbreaks of lung involvement by this category of viruses in the world, ie, severe acute respiratory syndrome (SARS-CoV-1) in 2002 and 2003, the Middle East respiratory syndrome (MERS-CoV) in 2012, and the new coronavirus (2019-nCoV) outbreak of pneumonia from Wuhan, China, since December 2019. There have been several studies about the clinical features and imaging features, but very few reports have been published about pathologic findings in lung tissue, which was partly because of the lack of tissue diagnosis secondary to suddenness of the outbreak. Overall, less than 30 reports have been published in the literature about histologic findings of lung in these viruses, so far. In this report, we will review the published reports about the histopathologic findings of lung tissue in the patients infected with SARS-CoV-2 in comparison with 2 other coronaviruses that have caused outbreaks, ie, SARS-CoV-1 and MERS-CoV.

It was shown that the human Angiotensin-converting enzyme 2 (ACE2) is the receptor of recent coronavirus SARS-CoV-2, and variation in this gene may affect the susceptibility of a population. Therefore, we have analysed the sequence data of ACE2 among 393 samples worldwide, focusing on South Asia. Genetically, South Asians are more related to West Eurasian populations rather than to East Eurasians. In the present analyses of ACE2, we observed that the majority of South Asian haplotypes are closer to East Eurasians rather than to West Eurasians. The phylogenetic analysis suggested that the South Asian haplotypes shared with East Eurasians involved two unique event polymorphisms (rs4646120 and rs2285666). In contrast with the European/American populations, both of the SNPs have largely similar frequencies for East Eurasians and South Asians, Therefore, it is likely that among the South Asians, host susceptibility to the novel coronavirus SARS-CoV-2 will be more similar to that of East Eurasians rather than to that of Europeans.

ObjectivesEvaluation of rituximab and glucocorticoids as therapy to induce remission after relapse in ANCA-associated vasculitis (AAV) in a prospective observational cohort of patients enrolled into the induction phase of the RITAZAREM trial.MethodsPatients relapsing with granulomatosis with polyangiitis or microscopic polyangiitis were prospectively enrolled and received remission-induction therapy with rituximab (4×375 mg/m2) and a higher or lower dose glucocorticoid regimen, depending on physician choice: reducing from either 1 mg/kg/day or 0.5 mg/kg/day to 10 mg/day by 4 months. Patients in this cohort achieving remission were subsequently randomised to receive one of two regimens to prevent relapse.Results188 patients were studied: 95/188 (51%) men, median age 59 years (range 19–89), prior disease duration 5.0 years (range 0.4–34.5). 149/188 (79%) had previously received cyclophosphamide and 67/188 (36%) rituximab. 119/188 (63%) of relapses had at least one major disease activity item, and 54/188 (29%) received the higher dose glucocorticoid regimen. 171/188 (90%) patients achieved remission by 4 months. Only six patients (3.2% of the study population) did not achieve disease control at month 4. Four patients died in the induction phase due to pneumonia (2), cerebrovascular accident (1), and active vasculitis (1). 41 severe adverse events occurred in 27 patients, including 13 severe infections.ConclusionsThis large prospective cohort of patients with relapsing AAV treated with rituximab in conjunction with glucocorticoids demonstrated a high level of efficacy for the reinduction of remission in patients with AAV who have relapsed, with a similar safety profile to previous studies.

Objectives: Peritoneal fluid cytology is done routinely in cases with serous carcinoma of ovary. However, morphologic features of borderline serous tumors (BSTs) of ovary in ascitic fluid have been rarely described. The aim of our study was to evaluate the morphologic features of BST with and without ascitic fluid involvement (BST+ and BST-, respectively) and compare with those of serous carcinomas, both in conventional and liquid-based cytology (LBC) smears. Material and Methods: Out of 30 BST cases reported in 3 years, seven cases had BST+. We compared the cytomorphology of seven cases of BST+, seven cases of BST-, and seven cases of serous adenocarcinoma with positive ascitic fluid cytology. Both conventional and LBC smears were studied in all cases and compared. Histopathology of omentum in these cases was also studied. Results: Most cases with BST+ had regular papillary fragment borders with nuclei showing mild-to-moderate pleomorphism, fine nuclear chromatin with small nucleoli as compared with serous carcinomas all of which had irregular borders with moderate-to-severe nuclear pleomorphism, coarse chromatin, and macronucleoli. Conclusion: A combination of cytoarchitectural and nuclear features can help in suspecting BST in ascitic fluid. Ascitic fluid cytology together with tissue histology can increase the rate of the detection of peritoneal implants.

Introduction: Ozone is a potent antioxidant that acts as a precursor of various radicals, being indicated as a powerful therapy, assisting in the process of tissue healing. Objectives: The proposal of this study was to analyze material and structural properties via mechanical testing in tibias after application of ozone in bone defects produced surgically. Methods: Ten male 40-day old albino Wistar rats have been used, divided in two groups: control group and ozone group, this last one being treated with ozonized water in 25 µg/mL of concentration until the day of euthanasia. Trichotomy and longitudinal incision was conducted in the animals’ leg skin, exposing the tibia’s diaphysis of both antimers, and with help of a high rotation pen a flaw has been produced on the bone. After 60 days of surgery the animals were euthanized, and tibias were collected for biomechanical analysis. Results: The results of the biomechanical properties – structural and material – evidenced significant interactions through exposure to ozone, showing a diminished bone resistance in animals from the control group, observed by the decrease of the maximum force (N) needed to rupture the bone when compared to the value needed to break the bones of the animals from the ozone group, and the analysis of the morphometrical properties did not show any difference between both experimental groups. Conclusion: The use of ozone did not alter the morphological structures of the tibias, and the group which used ozone presented more resistance during mechanical testings, because the maximum force for the rupture of tibia was greater in this group. Introducción: El ozono es un potente oxidante que actúa como precursor de varios radicales, siendo indicado con potente terapéutico con auxiliar en el proceso de reparación de tejidos. Objetivos: El propósito de este estudio fue analizar las propiedades materiales y estructurales mediante ensayos mecánicos en tibias después de la aplicación del ozono en la insuficiencia ósea producida quirúrgicamente. Metodología: Se utilizaron diez ratas wistar albinas macho con 40 días de vida, divididas en dos grupos: grupo de control y grupo de ozono, que fue tratado con agua ozonizada a una concentración de 25 g/ml hasta la fecha de la eutanasia. En la pierna de los animales, se realizó tricotomía e incisión longitudinal en la piel, exponiendo la diáfisis de la tibia de ambos antimémeros y con la ayuda de una pluma de alta rotación, produciendo una falla ósea. Después de 60 días de cirugía, los animales fueron eutanasiados, y las tibias fueron recolectadas para análisis biomecánicos. Resultados: las propiedades biomecánicas (estructurales y materiales) mostraron interacciones significativas a través de la exposición al ozono, evidenciando una disminución en la resistencia ósea de los animales del grupo de control, observadas por la disminución de la fuerza máxima (N) necesaria para romper el hueso en comparación con los valores necesarios para romper los huesos de los animales del grupo de ozono y los análisis de propiedades morfométricas no revelaron diferencias entre los grupos experimentales. Conclusión: El uso del ozono no alteró las propiedades morfológicas de las tibias y que el grupo que utilizó ozono exhibiera más resistencia en el ensayo mecánico, porque la fuerza máxima para la ruptura tibial fue mayor en este grupo. Introdução: O ozônio é um oxidante potente que age como precursor diversos radicais, sendo indicado com terapêutico potente com auxiliar no processo de reparação tecidual. Objetivos: A proposta do presente estudo foi analisar as propriedades materiais e estruturais por meio de ensaio mecânico em tíbias após aplicação de ozônio em falha óssea produzidas cirurgicamente. Metodologia: Foram utilizados 10 ratos albinos Wistar, machos, com 40 dias de vida, divididos em dois grupos: grupo controle e grupo ozônio, sendo este tratado com água ozonizada na concentração de 25 μg/ml até a data da eutanásia. Na perna dos animais foi realizada tricotomia e incisão longitudinal na pele, expondo a da diáfise da tíbia de ambos antimeros e com auxílio de uma caneta de alta-rotação, produzindo uma falha óssea. Após 60 dias da cirurgia os animais foram eutanesiados, as tibias foram coletadas para análise biomecânica. Resultados: as propriedades biomecânicas (estruturais e materiais) evidenciaram interações significativas mediante a exposição ao ozônio, evidenciando uma diminuição na resistência óssea dos animais do grupo controle, observado por meio da diminuição na força máxima (N) necessária para romper o osso quando comparado aos valores necessários para quebrar os ossos dos animais do grupo ozônio e as análises das propriedades morfométricas não revelaram diferenças entre os grupos experimentais. Conclusão: O uso do ozônio não alterou as propriedades morfológicas das tíbias e que o grupo que usou ozônio exibiu mais resistência no ensaio mecânico, pois a força máxima para ruptura da tíbia foi maior neste grupo.

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OBJECTIVES/HYPOTHESIS Ultrasound-guided fine-needle aspiration cytology (US-FNAC) is a well-established procedure performed to establish the diagnosis of Kikuchi-Fujimoto disease (KFD). Ultrasound-guided core needle biopsy (US-CNB) is an alternative diagnostic tool for KFD. However, the efficacy of US-CNB is not well evaluated. This study aimed to evaluate the efficacy of US-CNB and compare it with that of US-FNAC in the diagnosis of KFD. STUDY DESIGN Retrospective cohort study. METHODS We analyzed 170 patients who were diagnosed with KFD between January 2009 and May 2019. US-FNAC, US-CNB, and excisional biopsy were performed in 47, 114, and 9 patients, respectively. Diagnostic accuracies of US-FNAC and US-CNB were analyzed and compared. RESULTS Of the 170 patients, 45 and 125 were men and women, respectively. The mean age was 26.9 ± 9.1 years. The most common symptom was cervical lymphadenopathy, followed by fever, headache, and myalgia. The diagnosis of KFD was established primarily by US-FNAC in 21 (44.7%) of the 47 patients, by US-CNB in 109 (95.6%) of the 114 patients, and by excisional biopsy in all 9 patients. There was no specific major complication related to US-FNAC and US-CNB. CONCLUSION US-CNB can be considered safe and effective and used as the primary modality for the pathological diagnosis of KFD. LEVEL OF EVIDENCE 4. Laryngoscope, 131:E1519-E1523, 2021.

Renal cell carcinoma (RCC) represents 3% of human malignant tumors and approximately 90% of malignant renal neoplasms. Despite great therapeutic advances in the last decade, metastatic RCC (mRCC) is still considered an incurable disease. In this study, we examined the potential of essential elements as biomarkers of mRCC using an orthotropic metastatic mouse model. Frozen lung and plasma samples from healthy and mRCC-induced mice were lyophilized, digested, and analyzed using inductively coupled plasma mass spectrometry. In metastatic lungs, a significant increase in Ca concentration (268%) was observed, whereas a significant decrease in Cu (23.2%), Fe (17.4%), Mn (38.8%), and Na (11.7%) was observed. The plasma of mRCC-induced mice showed decreased concentrations of Mn (53%), Na (19.7%) and Zn (49,50%) and increased levels of Ca (53%), Cu (39.5%), Our findings revealed marked differences in the concentrations of essential elements in the lung and plasma of the metastatic mouse model. The circulating levels of Ca, Cu, Mn, Na, and Zn could be utilized as diagnostic and therapeutic response biomarkers.

Resumo Este trabalho problematiza os pressupostos ontológicos assumidos no debate bioético sobre a seleção e edição do genoma humano. Com vistas ao manejo de desordens genéticas, diferentes terapêuticas têm sido empregadas clínica e experimentalmente, desde a década de 1990. Entre as estratégias de tratamento destacam-se a seleção de embriões (mediante diagnóstico genético pré-implantação) e a terapia gênica (mediante edição genética). O desenvolvimento destas técnicas suscita discussões acerca de suas implicações éticas. O presente artigo postula que distintas concepções de humanidade podem ser identificadas nas discussões, as quais fundamentam posicionamentos acerca de intervenções sobre o genoma da espécie. O artigo busca analisar essas concepções, percorrendo três passos. Primeiramente, apresenta-se o contexto biomédico de aplicação da seleção e edição do genoma humano. Em seguida, são evidenciadas discussões sobre os aspectos éticos de tais intervenções. Por fim, explicitam-se diferentes concepções de humanidade que fundamentam as referidas discussões, de maneira a problematizá-las, tendo em vista a noção de justiça distributiva. Abstract This study discusses the ontological assumptions assumed in the bioethical debate about human genetic selection and gene editing. With a view to managing genetic disorders, different therapies have been employed clinically and experimentally, since the 1990s. Among the treatment strategies, we find embryo selection (by means of pre-implantation genetic diagnosis) and gene therapy (by means of gene editing). The development of these techniques raises discussions about their ethical implications. This article postulates that different conceptions of humanity can be identified in these discussions, grounding ethical positions regarding genome interventions. The article seeks to analyze these conceptions, following three steps. First, the biomedical context of genetic selection and gene editing is presented. Then, discussions on the ethical aspects of these interventions are highlighted. Finally, different conceptions of humanity grounding these discussions are identified and analyzed, considering the notion of distributive justice.

ObjectivesSince neuropathologic diagnosis in the developing world is hampered by limitations in technical infrastructure, trained laboratory personnel, and subspecialty-trained pathologists, the use of telepathology for diagnostic support, second-opinion consultations, and ongoing training holds promise as a means of addressing these challenges. This study aims to assess the utility of static teleneuropathology in improving neuropathologic diagnoses in low- and middle-income countries.MethodsConsecutive neurosurgical biopsy and resection specimens obtained at Muhimbili National Hospital in Tanzania between July 1, 2018, and June 30, 2019, were selected for retrospective, blinded static-image neuropathologic review followed by on-site review by an expert neuropathologist.ResultsA total of 75 neuropathologic cases were reviewed. The agreement of static images and on-site glass diagnosis was 71% with strict criteria and 88% with less stringent criteria. This represents an overall improvement in diagnostic accuracy from 36% by general pathologists to 71% by a neuropathologist using static telepathology (or from 76% to 88% with less stringent criteria).ConclusionsTelepathology offers a promising means of providing diagnostic support, second-opinion consultations, and ongoing training to pathologists practicing in resource-limited countries. Moreover, static digital teleneuropathology is an uncomplicated, cost-effective, and reliable way to achieve these goals.

Introduction: The main risk factor for the development of cervical cancer (CC) is persistent infection by human papillomavirus (HPV) oncogenic types. In order to persist, HPV exhibits a plethora of immune evasion mechanisms. PI3/Elafin (Peptidase Inhibitor 3) is an endogenous serine protease inhibitor involved in epithelial protection against pathogens. PI3/Elafin’s role in CC is still poorly understood. Materials and Methods: In the present study, we addressed PI3/Elafin protein detection in 123 CC samples by immunohistochemistry and mRNA expression in several datasets available at Gene Expression Omnibus and The Cancer Genome Atlas platforms. Results: We observed that PI3/Elafin is consistently downregulated in CC samples when compared to normal tissue. Most of PI3/Elafin-positive samples exhibited this protein at the plasma membrane. Besides, high PI3/Elafin expression at the cellular membrane was more frequent in in situ stages I + II than in invasive cervical tumor stages III + IV. This indicates that PI3/Elafin expression is gradually lost during the CC progression. Of note, advanced stages of CC were more frequently associated with a more intense PI3/Elafin reaction in the nuclei and cytoplasm. Conclusion: Our results suggest that PI3/Elafin levels and subcellular localization may be used as a biomarker for CC severity.

Context.— Breast cancer biomarker assessment is critical in determining treatment and prognosis. In Tanzania, immunohistochemistry (IHC) is limited to surgical specimens and core biopsies. However, performing IHC on fine-needle aspiration biopsy cell blocks would offer numerous advantages. Objective.— To compare the performance between estrogen receptor (ER) IHC performed at Muhimbili National Hospital (MNH) in Tanzania and ER IHC performed at University of California, San Francisco (UCSF), to demonstrate feasibility of performing IHC using cell blocks in Tanzania. Design.— Patients with breast masses were recruited prospectively from the fine-needle aspiration biopsy clinic at MNH. Estrogen receptor IHC results on cell blocks, performed at both MNH and UCSF, and corresponding tissue blocks, performed at MNH, were compared to determine concordance. Results.— Eighty-six cell blocks were evaluated by ER IHC at MNH, with 41 of 86 (47.7%) positive and 45 of 86 (52.3%) negative. Among 65 UCSF and MNH cell block pairs, overall ER IHC concordance was 93.8% (61 of 65) and positive concordance was 93.5% (29 of 31) (κ = 0.88, P > .99). Among 43 paired UCSF cell blocks and MNH tissue blocks, overall ER IHC concordance was 88.3% (38 of 43) and positive concordance was 90.5% (19 of 21) (κ = 0.77, P > .99). We compared 62 MNH cell block and tissue block pairs. Overall ER IHC concordance was 90.3% and positive concordance was 87.9% (κ = 0.81, P = .69). Conclusions.— Pairwise comparisons between ER IHC at MNH, on cell blocks and tissue blocks, with ER IHC at UCSF on cell blocks showed excellent concordance. We demonstrate that ER IHC on fine-needle aspiration biopsy specimens can be implemented in resource-constrained settings.