Extramammary Paget Disease. Part I. Epidemiology, Pathogenesis, Clinical Features, and Diagnosis.

Extramammary Paget disease (EMPD) is a rare skin cancer of apocrine-rich skin that mimics common inflammatory and infectious dermatoses, leading to delays in diagnosis and increased patient morbidity. Better clinical recognition of this entity, multidisciplinary patient assessment, and deeper understanding of the underlying pathophysiology are essential to improve patient care and disease outcomes. It is important to distinguish primary intraepithelial/micro-invasive EMPD from invasive EMPD or cases with adenocarcinoma arising within EMPD. This 2-part continuing medical education series provides a complete picture of EMPD. Part 1 of this continuing medical education series reviews the epidemiology, oncogenesis, clinical and histopathologic presentation, workup, and prognosis of this rare cancer.

Application of Aquaporins as Markers in Forensic Pathology: A Systematic Review of the Literature.

The study of aquaporins (AQPs) in various forensic fields has offered a promising horizon in response to the need to have reliable elements for the identification of the manner of death and for the individuation of forensic markers for the timing of lesions and vitality of injury. In the literature, various tissues have been studied; the most investigated are the lungs, brain, kidneys, skin, and blood vessels. A systematic literature review on PubMed following PRISMA 2020 guidelines enabled the identification of 96 articles. In all, 34 of these were enrolled to identify Aquaporin-like (AQP-like) forensic markers. The analysis of the literature demonstrated that the most significant markers among the AQPs are as follows: for the brain, AQP4, which is very important in brain trauma and hypoxic damage; AQP3 in the skin lesions caused by various mechanisms; and AQP5 in the diagnosis of drowning. Other applications are in organ damage due to drug abuse and thrombus dating. The focus of this review is to collect all the data present in the literature about the forensic application of AQPs as forensic markers in the most important fields of application. In the current use, the individuation, validation, and application of markers in forensic investigation are very useful in real forensic applications in cases evaluated in court.

[Molecular markers of M. tuberculosis virulence in lung tissue (experimental study)]. / Molekulyarnye markery virulentnosti M. tuberculosis v tkani legkikh (eksperimental'noe issledovanie).

More than a quarter of the world's population is infected with Mycobacterium tuberculosis. However, only about 10% of those infected develop active TB. This indicates a key role for innate immunity in limiting M. tuberculosis replication. Most often, bacteria can regulate the expression of host-specific molecules and weaken host immunity. OBJECTIVE: To use a biological model, in order to determine significant molecular immunohistochemical markers characterizing the virulence of the "Buryat" and "Omsk" subtypes of the M. tuberculosis Beijing genotype in lung tissue. MATERIAL AND METHODS: Lung samples of the C57BL/6 male mice were obtained during experimental infection with M. tuberculosis strains: the reference laboratory strain H37Rv, multidrug-resistant clinical strains 396 (highly lethal and hypervirulent «Buryat¼ genotype Beijing 14717-15) and 6691 (low-lethal and low-virulent "Omsk" genotype Beijing 1071-32) on days 14, 21, 60 and 120. They were studied by histological and immunohistochemical methods. The relative areas of expression of IL-6, IL-12A, iNOS, and TNF-α in the lung tissue of model animals were established. RESULTS: A study of strain 396 showed that both disease progression and damage to lung tissue are associated with a highly reactive immune response and increased synthesis of iNOS and strain characteristics that block the production of TNF-α. On the contrary, for strain 6691 a low reactivity of the immune response was revealed, with statistically significantly lower values of the relative area of expression of NOS and TNF-α during all observation periods (days 14-120). All animals that survived to day 120 showed a similar morphological picture with differences in cytokine levels, indicating a nonlinear relationship between proinflammatory factors and the damage substratum. CONCLUSION: The progression of the disease and damage of lung tissue were associated with a highly reactive immune response and increased synthesis of iNOS, strain properties that block the TNF-α production. Thus, iNOS and TNF-α can act as molecular markers characterizing the virulence of the "Buryat" and "Omsk" subtypes of M. tuberculosis in lung tissue.

Correlations between Immune Response and Etiopathogenic Factors of Medication-Related Osteonecrosis of the Jaw in Cancer Patients Treated with Zoledronic Acid.

Impairment of the immune response in MRONJ (medication-related osteonecrosis of the jaws) is one of the still unclear etiopathogenic mechanisms of this condition encountered in cancer patients treated with bisphosphonates, with negative effects on the patient's quality of life. The aim of the present study was to correlate the immune response with etiopathogenic factors via immunohistochemical evaluation of the maxillary tissues in zoledronic acid osteonecrosis. The retrospective study included a group of 51 patients with various types of cancers, diagnosed with stage 2 or 3 MRONJ at zoledronic acid and treated surgically. Immunohistochemical expressions of αSMA, CD3, CD4, CD8, CD20, CD79α, CD68, CD204, and tryptase were evaluated. Immunohistochemical markers expressions were statistically analyzed according to the duration of the treatment, the trigger factor, the location of the MRONJ, and the healing status. Analysis of the immune response included T lymphocytes, B lymphocytes, plasma cells, macrophages, and mast cells. The duration of treatment significantly influenced the immunohistochemical expression of most markers (p < 0.05). For an increasing trend in treatment duration, a decreasing trend in marker score was observed, suggesting an inverse correlation. The expression of the markers was different depending on the trigger factor, on MRONJ localization (maxilla/mandible), and the healing status, being more intense in patients cured per primam compared to those who had relapses. The patient's immune response was negatively influenced by the duration of the treatment, the trigger factor, the location of the lesion in the mandible, and the recurrence of MRONJ.

Oxidative Stress Markers in Human Brain and Placenta May Reveal the Timing of Hypoxic-Ischemic Injury: Evidence from an Immunohistochemical Study.

During pregnancy, reactive oxygen species (ROS) serve as crucial signaling molecules for fetoplacental circulatory physiology. Oxidative stress is thought to sustain the pathogenesis and progression of hypoxic-ischemic encephalopathy (HIE). A retrospective study was performed on the brains and placentas of fetuses and newborns between 36-42 weeks of gestation (Group_1: Fetal intrauterine deaths, Group_2: Intrapartum deaths, Group_3: Post-partum deaths, Control group sudden neonatal death); all groups were further divided into two subgroups (Subgroup_B [brain] and Subgroup_P [placenta]), and the study was conducted through the immunohistochemical investigations of markers of oxidative stress (NOX2, 8-OHdG, NT, iNOS), IL-6, and only on the brain samples, AQP4. The results for the brain samples suggest that NOX2, 8-OHdG, NT, iNOS, and IL-6 were statistically significantly expressed above the controls. iNOS was more expressed in the fetal intrauterine death (Group_1) and less expressed in post-partum death (Group_3), while in intrapartum death (Group_2), the immunoreactivity was very low. IL-6 showed the highest expression in the brain cortex of the fetal intrauterine death (Group_1), while intrapartum death (Group_2) and post-partum death (Group_3) showed weak immunoreactivity. Post-partum death (Group_3) placentas showed the highest immunoreactivity to NOX2, which was almost double that of the fetal intrauterine death (Group_1) and intrapartum death (Group_2) placentas. Placental tissues of fetal intrauterine death (Group_1) and intrapartum death (Group_2) showed higher expression of iNOS than post-partum death (Group_3), while the IL-6 expression was higher in the fetal intrauterine death (Group_1) than the post-partum death (Group_3). The AQP4 was discarded as a possible marker because the immunohistochemical reaction in the three groups of cases and the control group was negative. The goal of this study, from the point of view of forensic pathology, is to provide scientific evidence in cases of medical liability in the Obstetric field to support the clinical data of the timing of HIE.

SLUG and SNAIL as Potential Immunohistochemical Biomarkers for Renal Cancer Staging and Survival.

Renal cell carcinoma (RCC) is the deadliest urological neoplasm. Up to date, no validated biomarkers are included in clinical guidelines for the screening and follow up of patients suffering from RCC. Slug (Snail2) and Snail (Snail1) belong to the Snail superfamily of zinc finger transcriptional factors that take part in the epithelial-mesenchymal transition, a process important during embryogenesis but also involved in tumor progression. We examined Slug and Snail immunohistochemical expression in patients with different stages of renal cell carcinomas with the aim to investigate their potential role as staging and prognostic factors. A total of 166 samples of malignant renal cell neoplasms were analyzed using tissue microarray and immunohistochemistry. Slug and Snail expressions were evaluated qualitatively (presence or absence), in nuclear and cytoplasmic cell compartments and compared in relation to clinical parameters. The Kaplan-Meier survival analysis showed the impact of the sarcomatoid component and Slug expression on the survival longevity. Cox regression analysis separated Slug as the only independent prognostic factor (p = 0.046). The expression of Snail was associated with higher stages of the disease (p = 0.004), especially observing nuclear Snail expression (p < 0.001). All of the tumors that had metastasized showed nuclear immunoreactivity (p < 0.001). In clear cell RCC, we showed a significant relationship between a high nuclear grade and nuclear Snail expression (p = 0.039). Our results suggest that Slug and Snail could be useful immunohistochemical markers for staging and prognosis in patients suffering from various RCCs, representing potential targets for further therapy strategies of renal cancer.

The Correlation between Proliferative Immunohistochemical Markers and Papillary Thyroid Carcinoma Aggressiveness.

Background and Objectives: Papillary thyroid carcinoma (PTC) is one of the most common malignancies of the endocrine system. In order to improve the ability to predict tumor behavior, several studies have been conducted to search for surrogate prognostic immunohistochemical tumor markers. Objective: To evaluate the correlation between the intensity of different immunohistochemical marker staining in PTC and the risk for extrathyroidal extension and metastases. Materials and Methods: The study comprised patients who underwent hemi- or total thyroidectomy. Thyroid tissues were immunohistochemically stained for different tumor proliferative markers: Minichromosome maintenance proteins 2 (MCM2), Ki-67 labeling index, E-Cadherin, Neuropilin-1 and Metallothionein. The correlation between the intensity of each marker staining and the final diagnosis (benign neoplasm and PTC) and the correlation between the intensity of each staining and tumor extrathyroidal extension and metastases were evaluated. Results: The study included 66 patients. Staining for Metallothionein, E-Cadherin and MCM2 significantly differed between benign neoplasm (n = 22) and thyroid-confined PTC (n = 21) (p = 0.002, 0.004 and 0.005, respectively), between benign neoplasm and PTC with extrathyroidal extension (n = 11) (p = 0.001, 0.006 and 0.01, respectively), and between benign neoplasm and PTC with metastases (n = 12) (p = 0.01, <0.001 and 0.037, respectively). No staining correlated with extrathyroidal extension. The intensity of E-Cadherin staining was significantly lower in PTC with metastases than thyroid confined PTC and PTC with extrathyroidal extension (p = 0.028 and 0.021, respectively). Conclusions: Immunohistochemical staining for Metallothionein, E-Cadherin and MCM2 significantly distinguished between benign thyroid tumor and PTC. E-Cadherin staining significantly and inversely correlated with the presence of metastases.

STUDY OF THE INFLUENCE OF LINDANE AND SODIUM BICHROMATE ON THE MYOCARDIUM.

OBJECTIVE: Aim: The aim of the research is to study the immunohistochemical markers of the endothelium of blood vessels and myocardial ventricles under chronic exposure to sodium bichromate and lindane, as well as in conjunction with damaging biochemical agents contained in the blood. PATIENTS AND METHODS: Materials and Methods: The object of the experiment was outbred white mice (males). The study was carried out in 3 groups: 1st group - control, 2nd group - exposure to sodium bichromate 5 mg/kg, 3rd group - exposure to organochlorine pesticide lindane 100 mg/kg. In this experiment authors used the next methods: immunohistochemical method., biochemical research, statistical analysis. RESULTS: Results: The data obtained from an experimental study show that the level of cardiomarkers in blood plasma is characterized by different changes when exposed to these two compounds. Basically, the predominance of the effect of sodium bichromate on the LDH level is noted as compared to the effect of lindane; on the CK-MB level, their effects were the same, i.e., there is an increase in their level in blood plasma. CONCLUSION: Conclusions: Thus, long-term exposure to sodium bichromate leads to the activation of angiogenesis, destruction of the integrity of the endothelium, and this, in turn, leads to reparative changes located around in the myocardial cells.

DIAGNOSTIC UTILITY OF IMMUNOHISTOCHEMICAL EXPRESSION OF KI!67, P63 AND AMACR IN PROSTATE INTRAEPITHELIAL NEOPLASIA.

OBJECTIVE: The aim: To determine malignant transformation and progression ability of high grade and low grade prostate intraepithelial neoplasia with the help of immunohistochemical method. PATIENTS AND METHODS: Materials and methods: The results of examination of 93 patients with PIN (50 patients with high grade PIN and 43 patients with low grade PIN) were assessed comparatively using immunohistochemical markers. Semiquantitative method was used to evaluate !"-67, #63 and AMACR tissue expression with four grades from "+" to "++++" or from 1 to 4 points: '+' - low reaction, '++' - poor reaction, '+++' - moderate reaction and '++++" - intense reaction. RESULTS: Results: There were statistically significant differences in immunohistochemical expression rates between HGPIN and LGPIN. Patients with HGPIN had higher Ki-67 and AMACR expression rate and lower p63 expression rate than patients with LGPIN. Intense and moderate Ki-67 expression was detected in HGPIN more often, in 24 % and 11 % respectively. Low and moderate AMACR expression was determined in HGPIN more often, in 28 % and 5 % respectively. Low and not evident p63 expression was observed in HGPIN more often, in 36 % and 8 % respectively. CONCLUSION: Conclusions: HGPIN has common morphological peculiarities with prostate adenocarcinoma. Immunohistochemical detection of Ki-67, p63 and AMACR is aimed to differentiate among patients with PIN a group of high malignant transformation risk.

Significance of immunohistochemical markers in women with breast cancer.

Background and Aims: This study aimed to investigate the importance of immunohistochemical (IHC) markers and other prognostic variables in the definition of breast cancer. Patients and Methods: Two hundred female patients who underwent breast cancer surgery were classified into two groups according to age: young women (≤45 years; n = 104) and older women (≥65 years; n = 96). Molecular subtypes and local stages were determined. The Kaplan-Meier method was used to estimate the survival curves. The relationships among categorical variables were analyzed using the Chi-square test. Results: The difference between the tumor diameter and distribution of Ki-67 levels was significant (P = 0.001, P < 0.05). T stage, local stage, histological grade, estrogen receptor status, lymphovascular invasion status, axillary nodal state, human epidermal growth factor receptor 2 status, and distribution of molecular subtypes were correlated (P < 0.05). The mean disease-free survival rates (DFS) at 1, 2, and 5 years were found 92.9%, 86.5%, and 70.1%, respectively, in the young female group. The DFS rates of older patients were 96.7%, 95.4%, and 84.6%, respectively. Conclusion: This study showed that young age was associated with poor prognostic features at the IHC marker level.

Accuracy evaluation of combining gastroscopy, multi-slice spiral CT, Her-2, and tumor markers in gastric cancer staging diagnosis.

BACKGROUND: To evaluate the diagnostic accuracy of single gastroscopy, multi-slice spiral CT, HER-2 or tumor markers, and their combination in the diagnosis of gastric cancer. METHODS: A total of 98 patients with gastric cancer were selected as the research subjects. All patients underwent preoperative gastroscopy, MSCT, and the expression levels of HER-2, CEA, CA199, CA724, and CA242 were detected. A control group of 98 normal adults was selected to compare the risk factors for gastric cancer and to analyze the data. RESULTS: There was statistical significance in the expression of the 5 markers in tumor size (P < 0.05), but no statistical significance in other clinical data (P > 0.05). The tumor marker CEA in gastric mucosal tissue of patients with gastric cancer had the highest positive detection rate for gastric cancer, and the difference was statistically significant (P < 0.05) compared with gastroscopy, MSCT and other markers. The combined diagnosis had higher sensitivity, specificity and accuracy compared with the single diagnosis of gastric cancer staging, and the difference was statistically significant (P < 0.05). Compared with normal adults, patients with gastric cancer had statistically significant differences in diet, body mass index, and family genetic history (P < 0.05), while there was no statistically significant difference in whether they had type A blood (P > 0.05). CONCLUSION: The combined diagnosis of gastroscopy, MSCT, immunohistochemical marker Her-2, and tumor markers CEA, CA199, CA724, and CA242 can more accurately determine the clinical staging and lesion invasion depth of patients with gastric cancer and can significantly improve the sensitivity of diagnosis.

Alveolar soft part sarcoma: A case report and review of the literature.

Alveolar soft part sarcoma (ASPS) is a rarely diagnosed tumour of deep soft tissue origin. This tumour is more common in adolescents and young adults and has a slowly progressive clinical course, which often leads to delayed diagnosis and treatment. It is highly vascular, can be confused with other entities like haemangiomas and arteriovenous malformations clinically and radiologically and is thus challenging to report on fine needle aspiration cytology (FNAC). Diagnosing the tumour is difficult on cytology, so knowledge of this entity and the differentials with its morphological mimics on cytology is required for timely diagnosis and early management of the patient. We report a case of ASPS in a young female who presented with a large, painless swelling in the thigh, diagnosed on cytology combined with ancillary testing with immunohistochemical markers.

A prediction model based on clinical and histological features for predicting recurrence in patients with stage I-II endometrial cancer after surgical treatment.

OBJECTIVE: The study aimed to develop a prediction model combining clinical and histological features to predict recurrence in patients with stage I-II endometrial cancer (EC) after surgical treatment. METHODS: A total of 746 stage I-II EC patients who had received primary surgical treatment at Taizhou People's Hospital between 2014 and 2018 were included and randomly divided as a Training cohort (n = 520) and a Validation cohort (n = 226) at a 7:3 ratio. Clinical features including age, body mass index, comorbidities, lymphadenectomy, and adjuvant treatment, and histological features including histologic type, myometrial invasion, cervical stromal invasion, and expression levels of Ki67, estrogen receptor (ER), progesterone receptor (PR), whey acidic protein 4-disulphide core domain 2 (WFDC2), and p53 were used to develop a prediction model for EC recurrence in the Training cohort using a multivariable Cox regression model. Model discrimination and calibration were further evaluated in the Validation cohort. RESULTS: EC recurrence was observed in 60 (11.54%) patients in the Training cohort with a median length of follow-up of 39 months. Age, adjuvant treatment, histologic type, cervical stromal invasion, and expression levels of Ki67, ER, PR, and WFDC2 were factors significantly associated with EC recurrence based on univariable Cox regression analysis. After a model selection by AIC in a stepwise algorithm, the final model incorporated the above predictors showed a C-index of 0.85 and fair calibration in the Training cohort. In the Validation cohort, the model still showed good discrimination power (C-index 0.80) but moderate calibration. CONCLUSIONS: The developed prediction model combining clinical and histological features can help to predict the EC recurrence in patients with stage I-II EC after surgical treatment.

Retrospective study of the clinicopathological characteristics and prognostic factors of gastrointestinal stromal tumors in Chinese patients.

The purpose of this study was to investigate the clinicopathological characteristics and prognostic factors of patients with gastrointestinal stromal tumors (GISTs) in mainland China. We retrospectively analyzed the clinicopathological characteristics and survival data of 149 patients with GISTs admitted to Shengjing Hospital of China Medical University from July 2011 to October 2017. The following details were collected from all patients: sex, age, symptoms, preoperative examination, pathology, surgical procedures, and follow-up data. Recurrence-free survival (RFS) and overall survival (OS) were used to assess survival outcomes. The Kaplan-Meier method was performed to draw survival curves and calculate the survival rate. The log-rank test was performed for univariate analysis, and the significant factors were included in multivariate analysis using a Cox proportional hazards model to determine prognostic factors. The 5-year RFS rate was 78.5 % and 5-year OS rate was 83.2 %. The univariate analysis showed that the following prognostic factors could significantly predict 5-year RFS and OS: tumor size, initial status, modified NIH classification, mitotic index, CD117 expression, Ki67 index, and surgical procedure (P < 0.05). The multivariate analysis showed that mitotic index, CD117, and Ki67 index were independent prognostic factors associated with 5-year RFS and 5-year OS. This study provides a reference for the clinicopathological characteristics and prognostic factors of patients with GISTs in mainland China, and the results suggest that focusing on immunohistochemical markers in clinical practice may be more reliable for the prediction of clinical outcomes.

Towards the Search for Potential Biomarkers in Osteosarcoma: State-of-the-Art and Translational Expectations.

Osteosarcoma represents a rare cause of cancer in the general population, accounting for <1% of malignant neoplasms globally. Nonetheless, it represents the main cause of malignant bone neoplasm in children, adolescents and young adults under 20 years of age. It also presents another peak of incidence in people over 50 years of age and is associated with rheumatic diseases. Numerous environmental risk factors, such as bone diseases, genetics and a history of previous neoplasms, have been widely described in the literature, which allows monitoring a certain group of patients. Diagnosis requires numerous imaging tests that make it possible to stratify both the local involvement of the disease and its distant spread, which ominously determines the prognosis. Thanks to various clinical trials, the usefulness of different chemotherapy regimens, radiotherapy and surgical techniques with radical intent has now been demonstrated; these represent improvements in both prognosis and therapeutic approaches. Osteosarcoma patients should be evaluated in reference centres by multidisciplinary committees with extensive experience in proper management. Although numerous genetic and rheumatological diseases and risk factors have been described, the use of serological, genetic or other biomarkers has been limited in clinical practice compared to other neoplasms. This limits both the initial follow-up of these patients and screening in populations at risk. In addition, we cannot forget that the diagnosis is mainly based on the direct biopsy of the lesion and imaging tests, which illustrates the need to study new diagnostic alternatives. Therefore, the purpose of this study is to review the natural history of the disease and describe the main biomarkers, explaining their clinical uses, prognosis and limitations.

Cutaneous Melanomas: A Single Center Experience on the Usage of Immunohistochemistry Applied for the Diagnosis.

Cutaneous melanoma (cM) is the deadliest of all primary skin cancers. Its prognosis is strongly influenced by the stage at diagnosis, with early stages having a good prognosis and being potentially treatable with surgery alone; advanced stages display a much worse prognosis, with a high rate of recurrence and metastasis. For this reason, the accurate and early diagnosis of cM is crucial-misdiagnosis may have extremely dangerous consequences for the patient and drastically reduce their chances of survival. Although the histological exam remains the "gold standard" for the diagnosis of cM, a continuously increasing number of immunohistochemical markers that could help in diagnosis, prognostic characterization, and appropriate therapeutical choices are identified every day, with some of them becoming part of routine practice. This review aims to discuss and summarize all the data related to the immunohistochemical analyses that are potentially useful for the diagnosis of cM, thus rendering it easier to appropriately applicate to routine practice. We will discuss these topics, as well as the role of these molecules in the biology of cM and potential impact on diagnosis and treatment, integrating the literature data with the experience of our surgical pathology department.

Immunoexpression of Bmi-1, CK15, Bcl-2 in different types of basal cell carcinomas.

Introduction: Basal cell carcinoma (BCC) occurs in aggressive and non-aggressive forms. The expression of immunohistochemical markers varies in different types of BCC. Aim: Immunohistochemical analysis of selected proteins in BCCs. Material and methods: The immunohistochemical method was used to examine the immunoexpression of Bmi-1, CK15 and Bcl-2 in 56 cases of BCC divided into four groups. Results: Positive Bmi-1 staining 3-4+ level (nodular type) was seen in 91.3% of samples, 4+ (infiltrative) in 92.3%, 4+ (nodular/infiltrative) - 69.2%, 3+ - 30.8%, in BSC 3+ - 42.8%, and 28.6% each for 2+ and 4+. Low grade positivity (0-1+) in CK15 staining was present in 52.1% of nodular BCC, 46.2% - nodular/infiltrative, 92.3% - infiltrative, and 100% - BSC, but levels 2-3+ in nodular BCC in 47.8%, nodular/infiltrative BCC - 53.8%, infiltrative - 7.7%. Bcl-2 positivity (3-4+) was revealed in nodular BCC in 95.6%, (1-2+) in 100% of BSC, infiltrative and infiltrative/nodular BCC, but the lowest (0-1+) in 76.9% of nodular/infiltrative BCC, 71.4% of BSC, and in 38.4% of infiltrative BCC. Conclusions: Positive Bmi-1 staining was the highest in the aggressive infiltrative subtype of BCCs, whereas the lowest in basosquamous cell carcinomas (BSC). Infiltrative BCC was characterized by a lower level of CK15 expression than nodular BCC and nodular/infiltrative BCC. Differentiation of Bcl-2 expression depended on the type of tumour; the highest level was found in nodular BCC, low grade in nodular/infiltrative and infiltrative BCCs, and BSC.

Shear-Wave Elastography-Guided Core Needle Biopsy for the Determination of Breast Cancer Molecular Subtype.

OBJECTIVE: To investigate whether shear-wave elastography (SWE) guidance during core-needle biopsy can improve diagnostic accuracy and accurate determination of the molecular subtypes of breast cancer. METHODS: This controlled, randomized prospective cohort study included 58 patients (mean age: 56.9 ± 16.2) who were referred for image-guided core-needle biopsy between May 2018 and April 2019 for lesions larger than 1 cm. In Group 1, 30 lesions were biopsied without SWE guidance and recorded as Biopsy A. In Group 2, 30 lesions were examined with SWE before biopsy, and then two different parts of the lesions were biopsied; biopsies from the relatively rigid areas of the lesions were recorded as Biopsy B, and biopsies from the less rigid areas of the lesions were recorded as Biopsy C. The histopathological and immunohistochemical results of biopsies were compared with the surgical results. RESULTS: The sensitivity of Biopsy A, B and C were 96.7%, 100% and 100%, respectively. The benign-malignant concordance rates were 94.7%, 100%, and 90% and the diagnostic concordance rates were 89.5%, 100%, and 90% in Biopsies A, B, and C, respectively. When the 10% differences in the estrogen receptor (ER), progesterone receptor (PR), and Ki67 rates were considered significant, the concordance rate of ER was highest in Biopsy B (77.8%; p = 0.040). The concordance rate of immunohistochemical subtyping was 100% in Biopsy B and 71.4% in Biopsies A and C (p = 0.086). CONCLUSION: SWE-guided core-needle biopsy of breast lesions increased the sensitivity, diagnostic accuracy, and accuracy of immunohistochemical subtyping to 100%.

The combined ratio of estrogen, progesterone, Ki-67, and P53 to predict the recurrence of endometrial cancer.

BACKGROUND AND OBJECTIVES: We aimed to explore the capacity of the combined ratio of biomarkers to predict the recurrence of Stage I-III endometrial cancer (EC). METHODS: A total of 473 patients were enrolled after screening. The cut-off value of the ratio was calculated by the receiver operating characteristic curve (ROC). The univariate and multivariate Cox regression analysis was used to assess the correlation between the combined ratio and the recurrence of EC. The differences of clinicopathological parameters between the two groups divided based on the threshold were compared. RESULT: The ROC curve showed that 0.92 was the optimal cut-off value of the ratio ([ER + PR]/[P53 + Ki67]). The multivariate analysis demonstrated that only International Federation of Gynecology and Obstetrics stage (p = .031) and the combined ratio (p = .004) were independent risk factors of recurrence. The 3-year recurrence-free survival (RFS) and overall survival of patients in the low-ratio group were 54.1% and 66.8%, respectively; while in the high-ratio group were 94.9% and 97.9%, respectively (p < .001). The 3-year RFS of 194 patients, who did not receive the adjuvant therapy, was 54.7% and 97.2% between two groups (p < .001). CONCLUSIONS: The optimal cut-off value (0.92) of the combined ratio was demonstrated to be better to predict the recurrence of EC than a single immunohistochemical marker.

Factors associated with use of immunohistochemical markers in the histopathological diagnosis of cutaneous melanocytic lesions.

BACKGROUND: Melanocytic tumors are often challenging and constitute almost one in four skin biopsies. Immunohistochemical (IHC) studies may assist diagnosis; however, indications for their use are not standardized. METHODS: A test set of 240 skin biopsies of melanocytic tumors was examined by 187 pathologists from 10 US states, interpreting 48 cases in Phase I and either 36 or 48 cases in Phase II. Participant and diagnosis characteristics were compared between those who reported they would have ordered, or who would have not ordered IHC on individual cases. Intraobserver analysis examined consistency in the intent to order when pathologists interpreted the same cases on two occasions. RESULTS: Of 187 participants interpreting 48 cases each, 21 (11%) did not request IHC tests for any case, 85 (45%) requested testing for 1 to 6 cases, and 81 (43%) requested testing for ≥6 cases. Of 240 cases, 229 had at least one participant requesting testing. Only 2 out of 240 cases had more than 50% of participants requesting testing. Increased utilization of testing was associated with younger age of pathologist, board-certification in dermatopathology, low confidence in diagnosis, and lesions in intermediate MPATH-Dx classes 2 to 4. The median intraobserver concordance for requesting tests among 72 participants interpreting the same 48 cases in Phases I and II was 81% (IQR 73%-90%) and the median Kappa statistic was 0.20 (IQR 0.00, 0.39). CONCLUSION: Substantial variability exists among pathologists in utilizing IHC.