Diagnostic Surgical Pathology Research Articles

Digital Pathology in the Detection of Infectious Microorganisms: An Evaluation of Its Strengths and Weaknesses Across a Panel of Immunohistochemical and Histochemical Stains Routinely Used in Diagnostic Surgical Pathology.

The diagnosis of some infectious diseases requires their identification in tissue specimens. As institutions adopt digital pathology for primary diagnosis, the limits of microorganism detection from digital images must be delineated. To assess the reliability of microorganism detection from digitized images of histochemical and immunohistochemical stains commonly used in pathology. Original glass slides from 620 surgical pathology cases evaluated for the presence of infectious microorganisms were digitized. Immunohistochemical stains included those for herpes simplex virus (n = 100), cytomegalovirus (n = 100), Helicobacter pylori (n = 100), and spirochetes (n = 80). Histochemical stains included mucicarmine for Cryptococcus spp (n = 20), Grocott methenamine silver for fungi (n = 100), Giemsa for H pylori (n = 100), and Ziehl-Neelsen for acid-fast bacilli (n = 20). The original diagnosis based on the glass slides was regarded as the reference standard. Six pathologists reviewed the digital images. Digital review was generally associated with high (ie, ≥90%) specificity and positive predictive value owing to a low percentage of false positive reads, whereas a high percentage of false negatives contributed to low sensitivity and negative predictive value for many stains. Fleiss κ showed substantial interobserver agreement in the interpretation of Grocott methenamine silver and immunostains for herpes simplex virus, H pylori, and cytomegalovirus; moderate agreement for spirochete, Ziehl-Neelsen, and mucicarmine; and poor agreement for Giemsa. Digital immunohistochemistry generally outperforms histochemical stains for microorganism detection. Digital interpretation of Ziehl-Neelsen and mucicarmine stains is associated with low scores for interrater reliability, accuracy, sensitivity, and negative predictive value such that it should not substitute for conventional review of glass slides.

Medical Student’s Perception of Diagnostic Surgical Pathology Course: Necessities, Difficulties and Solutions

Background: Students’ perceptions and feedback have a significant impact on academic progress. The aim of this study was to determine the perceptions of medical students regarding the surgical pathology course taken by medical students at Northern Border University.
 Material and methods: In this cross-sectional study, a questionnaire was given to medical students taking this course. The questionnaire comprised several items on students’ attitudes toward surgical pathology. And a five-point Likert scale was used. Data were analysed using Statistical Package for the Social Science (SPSS) v 20 software. Results: One hundred and fifty three questionnaires received from the students were analysed. 
 Discussion and Conclusions: The answers to the questionnaire showed that ‘one size fits all’ approach cannot be employed for educating the students. A combination of different strategies and methods helped improve student satisfaction, particularly in regard with case presentation studies and practical’s. New strategies were adopted not just for improving academic performance but keeping in mind future clinical practice, enhancing students’ understanding and knowledge retention abilities.
 Key words: medical student’s, perception , diagnostic surgical pathology course: necessities, difficulties and solutions.

PRAME Expression in Cancer. A Systematic Immunohistochemical Study of >5800 Epithelial and Nonepithelial Tumors.

Preferentially expressed antigen in melanoma (PRAME) is considered a useful marker in the differential diagnosis between malignant melanoma and its melanocytic mimics. Recently PRAME expression was documented in nonmelanocytic tumors, but much of the data are based on mRNA studies. This investigation evaluated PRAME expression in the spectrum of normal tissues and >5800 human tumors using immunohistochemistry and EP461 monoclonal antibody. In normal tissues, PRAME was expressed in the testis and proliferative endometrium. In tumors, PRAME was variably expressed in malignancies of different lineages. Among epithelial tumors, >50% of PRAME-positive lesions were found among endometrial carcinomas (82%), uterine serous carcinomas (82%), uterine carcinosarcomas (60%), ovarian clear cell carcinomas (90%), ovarian serous carcinomas (63%), adenoid cystic carcinomas (81%), seminomas (78%), thymic carcinomas (75%), and basal cell carcinomas (62%). In mesenchymal and neuroectodermal malignancies, PRAME was frequently expressed in synovial sarcoma (71%), myxoid liposarcoma (76%), neuroblastoma (61%) and metastatic melanoma (87%). Also, PRAME was consistently expressed in 4 melanomas that lacked all melanoma markers including S100 protein and SOX10 but harbored typical for melanoma BRAF or NRAS driver mutations. However, strong and diffuse PRAME immunoreactivity was seen in many types of nonmelanocytic poorly differentiated carcinomas and sarcomas. Based on this study, PRAME is a relatively unspecific immunohistochemical marker, which limits its use in diagnostic surgical pathology. However, immunohistochemistry is a reliable and unexpensive method useful in detecting PRAME-positive malignancies for potential immunotherapy.

Immunohistochemical Profile of Parathyroid Tumours: A Comprehensive Review

Immunohistochemistry remains an indispensable tool in diagnostic surgical pathology. In parathyroid tumours, it has four main applications: to detect (1) loss of parafibromin; (2) other manifestations of an aberrant immunophenotype hinting towards carcinoma; (3) histogenesis of a neck mass and (4) pathogenetic events, including features of tumour microenvironment and immune landscape. Parafibromin stain is mandatory to identify the new entity of parafibromin-deficient parathyroid neoplasm, defined in the WHO classification (2022). Loss of parafibromin indicates a greater probability of malignant course and should trigger the search for inherited or somatic CDC73 mutations. Aberrant immunophenotype is characterised by a set of markers that are lost (parafibromin), down-regulated (e.g., APC protein, p27 protein, calcium-sensing receptor) or up-regulated (e.g., proliferation activity by Ki-67 exceeding 5%) in parathyroid carcinoma compared to benign parathyroid disease. Aberrant immunophenotype is not the final proof of malignancy but should prompt the search for the definitive criteria for carcinoma. Histogenetic studies can be necessary for differential diagnosis between thyroid vs. parathyroid origin of cervical or intrathyroidal mass; detection of parathyroid hormone (PTH), chromogranin A, TTF-1, calcitonin or CD56 can be helpful. Finally, immunohistochemistry is useful in pathogenetic studies due to its ability to highlight both the presence and the tissue location of certain proteins. The main markers and challenges (technological variations, heterogeneity) are discussed here in the light of the current WHO classification (2022) of parathyroid tumours.

PD15-01 EVALUATING 99M TC-SESTAMIBI SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY/COMPUTED TOMOGRAPHY CONCORDANCE WITH SURGICAL PATHOLOGY FOR RENAL MASSES

You have accessJournal of UrologyCME1 May 2022PD15-01 EVALUATING 99M TC-SESTAMIBI SINGLE PHOTON EMISSION COMPUTED TOMOGRAPHY/COMPUTED TOMOGRAPHY CONCORDANCE WITH SURGICAL PATHOLOGY FOR RENAL MASSES Shilpa Argade, Carrie Ronstrom, Joel Vetter, Brijesh Patel, Mark Biebel, Joyce Mhlanga, and Robert Figenshau Shilpa ArgadeShilpa Argade More articles by this author , Carrie RonstromCarrie Ronstrom More articles by this author , Joel VetterJoel Vetter More articles by this author , Brijesh PatelBrijesh Patel More articles by this author , Mark BiebelMark Biebel More articles by this author , Joyce MhlangaJoyce Mhlanga More articles by this author , and Robert FigenshauRobert Figenshau More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002547.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Benign renal masses are challenging to differentiate from malignant renal masses using noninvasive techniques. 99m Tc-sestamibi scan single photon emission computed tomography/computed tomography (sestamibi scan) has emerged as a potential diagnostic tool. Already widely utilized in the diagnosis of hyperparathyroidism, sestamibi scans differentiate renal masses on the basis of differences in mitochondrial content between malignant renal masses and oncocytomas. This study sets out to evaluate the concordance between renal mass sestamibi scan interpretation and surgical pathology. METHODS: We retrospectively identified patients undergoing sestamibi scan and renal mass biopsy or excision between September 2016 and May 2021 at our institution. The sestamibi scan final diagnostic report and surgical pathology results were compared. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated. RESULTS: We identified 26 patients with 31 tumors. The average age of patients was 65.7 years. Sestamibi scan identified 7 oncocytomas, 20 renal cell carcinomas, and 4 mixed tumors with average size 4.8 cm, 3.2 cm, and 4.9 cm, respectively. Surgical pathology from 12 renal mass biopsies and 19 renal mass excisions showed 8 oncocytomas, 22 renal cell carcinomas, and 1 angiomyolipoma. Sestamibi scan overall accuracy was 61.3% with sensitivity 70.8%, specificity 28.6%, positive predictive value 77.3%, and negative predictive value 22.2% (Table 1). CONCLUSIONS: Previous studies have shown that as many as 20-30% of excised renal masses are benign, calling attention to the need for improved diagnostic techniques. While the overall accuracy of sestamibi scans was moderate, positive predictive value was the highest at 77.3%. This study demonstrates that sestamibi scans can be a useful noninvasive adjunct to differentiate between benign and malignant renal masses. Source of Funding: None © 2022 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 207Issue Supplement 5May 2022Page: e262 Advertisement Copyright & Permissions© 2022 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shilpa Argade More articles by this author Carrie Ronstrom More articles by this author Joel Vetter More articles by this author Brijesh Patel More articles by this author Mark Biebel More articles by this author Joyce Mhlanga More articles by this author Robert Figenshau More articles by this author Expand All Advertisement PDF DownloadLoading ...

Fluorodeoxyglucose positron emission tomography/CT for primary malignant intraosseous neoplasms of the mandible.

Primary intraosseous malignant neoplasm of the mandible is a very rare entity. There are few publications regarding fluorodeoxyglucose (FDG) positron emission tomography (PET)/CT for primary intraosseous neoplasms of the mandible. FDG PET/CT scans from 10 patients with primary malignant neoplasm of the mandible were retrieved from the Picture Archiving and Communication System database, and image findings were analyzed with correlation to contrast-enhanced diagnostic CT and surgical pathology. Accuracy of the FDG PET/CT findings was evaluated with respect to uptake intensity, lesion extension to adjacent soft tissue, lymph node and distant metastasis. All untreated primary mandible neoplasms demonstrated high FDG avidity on PET imaging. Most mandible lesions extended beyond the bones and involved perimandibular soft tissue. FDG PET/CT imaging showed improved sensitivity and specificity compared with that for CT for lymph node staging in 3 cases, with discordant findings between diagnostic CT and PET/CT. FDG PET/CT identified 4 distant metastases, which were not documented prior to PET/CT. The results suggested that FDG PET/CT was a valuable image modality to demonstrate all primary and metastatic lesions of primary malignant neoplasm of the mandible, to define perimandibular soft tissue involvement, and more accurately stage/restage the disease than diagnostic CT.

Histomorphological Assessment of Formalin versus Nonformalin Fixatives in Diagnostic Surgical Pathology

Introduction Fixation is the critical step in the preservation of tissues in diagnostic pathology. The formalin is an economical and excellent fixative with the inherent property of adequate fixation. The well-established side effects of formalin include mucosal irritation, upper respiratory diseases, and corrosive injury to the gastrointestinal tract. In addition, substantial evidence exists regarding the potential role of formaldehyde as a human carcinogen. The carcinogenic and toxic effects of formalin encourage searching for alternative fixatives for tissue fixation. However, “the formalin dogma” has severely hampered the search for alternative fixatives for many years. Material and Methods Ninety tissues of liver and skeletal muscle obtained during autopsies were immersed in adequate amounts of the following fixatives: formalin (10%), methyl alcohol (70%), and acetone (100%). The comparison among the three was made based on time for fixation, preservation of tissue architecture, cell borders, cytoplasm, nuclear contours, chromatin texture, and uniformity of staining. Results The tissue preserved in formalin undergoes rapid fixation compared with alcohol and acetone. The tissue architecture, cell border characteristics of alcohol and acetone was found satisfactory compared with formalin. The cytoplasm and nuclear contour were superior with the formalin. The chromatin texture and uniformity of staining were similar with all the three fixatives. Conclusion The formalin is considered superior to most of the parameters, whereas both methyl alcohol and acetone showed nearly equivalent scores. Hence, owing to the potential human health hazards and carcinogenicity of formalin, no rational reasons hamper the complete substitution of formalin with alternative fixatives such as alcohol and acetone in diagnostic pathology and medical research.

The Utility of Myoepithelial Cell Layer Identification in Adnexal Carcinomas.

The distinction of metastatic carcinomas to the skin (MCS) from cutaneous adnexal carcinomas can pose a significant diagnostic challenge. The differentiation between (MCS) from a primary cutaneous adnexal tumor is one of the most difficult tasks in the field of dermatopathology, and immunohistochemistry has only been partially helpful in solving this problem. In routine diagnostic surgical pathology, it is essential to identify the myoepithelial cell layer by immunohistochemistry to distinguish between an in situ and invasive breast carcinomas and when establishing the presence of microinvasion. The purpose of this study was to evaluate the role of myoepithelial cell layer expression in difficult cases of cutaneous adnexal carcinomas in which histologically it was challenging to separate them from MCS. We studied 38 adnexal carcinomas and evaluated them for myoepithelial markers to confirm the primary nature of the neoplasm. The used markers to search for myoepithelial cell layer retention included calponin, p63, and smooth muscle actin. Of the 38 cases, we found that 13 cases showed myoepithelial layer retention, confirming the primary cutaneous origin of the neoplastic process. The results of our study suggest that the presence of an identifiable retention of the myoepithelial cell layer in adnexal carcinomas could be a useful adjunct observation in the diagnosis of primary adnexal carcinomas, especially in the clinical setting of a questionable primary adnexal versus metastatic neoplasm.

A firm mass of the maxillary gingiva

A firm mass of the maxillary gingiva

Clear cell carcinoma of the hard palate – A case report

Salivary gland neoplasia is a challenging area of diagnostic surgical pathology due to significant histomorphologic overlap between benign and malignant entities with the resultant risk of misdiagnosis and inappropriate treatment. Clear cell carcinoma is a rare infiltrative, low grade salivary gland neoplasm with an indolent clinical course, little metastatic potential and a propensity for local recurrence. This case reports a 32-year-old woman who presented with a 1-year history of a mass on her hard palate. The clinical history, histomorphologic, immunophenotypic and molecular features are described and discussed with emphasis on diagnostic pitfalls.

Polymerase chain reaction (PCR) – A review with its pertinency to dentistry

Advances in molecular technologies over recent years have a profound impact on diagnostic pathology. These techniques utilize DNA, RNA and enzymes that interact with nucleic acids to understand biology at a molecular level. They will also provide a complementary approach to traditional methods of histopathological analysis in the future. Various molecular techniques are now being widely used throughout the world including polymerase chain reaction (PCR), hybridization methods, flow cytometry, tissue microarray and laser capture microdissection (LCM). Among these PCR is one of the most common diagnostic modality with high specificity, sensitivity and variety of applications. It will significantly impact three major areas: specific diagnosis, prognosis determination and prediction of response to therapy. Therefore, it has a great potential to become a standard procedure in diagnostic surgical pathology. The application of PCR in the context of dentistry is also presented here, along with the basics of PCR and its fundamental aspects. Keywords: Applications, Dentistry, Inhibitors, Oral cancer, Polymerase Chain reaction, Tumor biology.

Precise Identification of Cell and Tissue Features Important for Histopathologic Diagnosis by a Whole Slide Imaging System

Background: Previous studies have demonstrated the noninferiority of pathologists’ interpretation of whole slide images (WSIs) compared to microscopic slides in diagnostic surgical pathology; however, to our knowledge, no published studies have tested analytical precision of an entire WSI system. Methods: In this study, five pathologists at three locations tested intra-system, inter-system/site, and intra- and inter-pathologist precision of the Aperio AT2 DX System (Leica Biosystems, Vista, CA, USA). Sixty-nine microscopic slides containing 23 different morphologic features suggested by the Digital Pathology Association as important to diagnostic pathology were identified and scanned. Each of 202 unique fields of view (FOVs) had 1-3 defined morphologic features, and each feature was represented in three different tissues. For intra-system precision, each site scanned 23 slides at three different times and one pathologist interpreted all FOVs. For inter-system/site precision, all 69 slides were scanned once at each of three sites, and FOVs from each site were read by one pathologist. To test intra- and inter-pathologist precision, all 69 slides were scanned at one site, FOVs were saved in three different orientations, and the FOVs were transferred to a different site. Three different pathologists then interpreted FOVs from all 69 slides. Wildcard (unscored) slides and washout intervals were included in each study. Agreement estimates with 95% confidence intervals were calculated. Results: Combined precision from all three studies, representing 606 FOVs in each of the three studies, showed overall intra-system agreement of 97.9%; inter-system/site agreement was 96%, intra-pathologist agreement was 95%, and inter-pathologist agreement was 94.2%. Conclusions: Pathologists using the Aperio AT2 DX System identified histopathological features with high precision, providing increased confidence in using WSI for primary diagnosis in surgical pathology.

Vulval squamous cell carcinoma and its precursors.

Vulval squamous cell carcinoma (VSCC) can arise through two distinct pathways [human papillomavirus (HPV)-associated and HPV-independent], and these VSCC variants are recognised as different disease entities on the basis of different aetiologies, morphological features, molecular events during oncogenesis, precursor lesions, prognosis, and response to treatment. The precursor of HPV-associated VSCC, variously referred to as high-grade squamous intraepithelial lesion (HSIL) [vulvar intraepithelial neoplasia (VIN) 2/3] or usual-type VIN, is morphologically identical to the more common HSIL (cervical intraepithelial neoplasia 2/3) of the cervix. The precursor lesions of HPV-independent VSCC include differentiated VIN, differentiated exophytic vulvar intraepithelial lesion, and vulvar acanthosis with altered differentiation; these have been under-recognised by pathologists in the past, leading to delays in treatment. This review will discuss the recent advances in diagnostic surgical pathology of VSCC and its precursors, and how these diagnoses can impact on patient management.

Identity determination in diagnostic surgical pathology.

From a technical perspective, specimen identity determination in surgical pathology over the last several decades has primarily focused on analysis of repetitive DNA sequences, specifically microsatellite repeats. However, a number of techniques have recently been developed that have similar, if not greater, utility in surgical pathology, most notably analysis of single nucleotide polymorphism (SNPs) and gene panels by next generation sequencing (NGS). For cases with an extremely limited sample or a degraded sample, sequence analysis of mitochondrial DNA continues to be the method of choice. From a diagnostic perspective, interest in identity determination in surgical pathology is usually centered on resolving issues of specimen provenance due to specimen labeling/accessioning deficiencies and possible contamination, but is also frequently performed in cases for which the patient's clinical course following definitive therapy is remarkably atypical, in cases of an unexpected diagnosis, and by patient request for "peace of mind". However, the methods used for identity determination have a much broader range of applications in surgical pathology beyond tissue provenance analysis. The methods can be used to provide ancillary information for cases in which the histomorphology is not definitively diagnostic, as for example for tumors that have a virtually identical microscopic appearance but for which the differential diagnosis includes synchronous/metachronous tumors versus a metastasis, and for the diagnosis of hydropic early gestations versus hydatidiform molar pregnancies. The methods also have utility in several other clinical settings, for example to rule out a donor-transmitted malignancy in a transplant recipient, to monitor bone marrow transplant engraftment, and to evaluate natural chimerism.

SUN-384 Aldosterone Secreting Adrenocortical Carcinoma and the Importance of Initial Imaging

Aldosterone secreting adrenocortical carcinomas are extremely rare and aggressive with a reported incidence of 1-2 cases per 1 million population (1). They are known to have poor prognosis often with resistance to adjuvant therapy and tumor recurrence. The assessment of the malignant potential of an adrenal mass is heavily dependent on the image phenotype. In the era of widespread use of CT and magnetic resonance imaging, unexpected adrenal masses are identified more frequently and it is critical to identify surgical candidates. We report a 54 year old man with history of poor follow-up presented in 2013 at another facility with hypertension and persistent hypokalemia. On chart review laboratory evaluation initially revealed an aldosterone 14.2 with a peak of 28 (supine/ambulant <10 ng/dL) and suppressed plasma renin activity 0.53 (.25-5.82 ng/ml per h) including an elevated PRA ratio 26.7. The urinary catecholamines and low-dose dexamethasone-suppression test were noted normal. The initial CT abdomen July 2013 revealed a heterogeneous left adrenal mass measuring 4.3 cm, 53 HU attenuation value with rapid washout of 70%. CT scan in April 2014 revealed growth of the adenoma to 5.4 cm, irregular contours, heterogenous tissue appearance with 74-89 HHU and a washout of 42%. Patient was then taken for open left adrenalectomy Nov 2014 due to significant growth of adenoma. A 7 cm necrotic mass was removed. Pathology report was consistent with a primary adrenocortical carcinoma with lymphovascular invasion and a ki-67 index <10%. The second CT abdomen surveillance completed November 2015 was suspicious for local recurrence with a newly discovered 1.4 cm x 1.4 cm nodule in left surgical bed. Subsequent findings included an enlarging lung nodule and a GE junction ulcerated mass requiring VATS biopsy/wedge resection 2017 and EUS biopsy October 2018 were consistent with metastatic adrenocortical carcinoma. The patient failed multiple therapies including: mitotane, cisplatin/etoposide, and abraxane/gemcitabine. In our case the appearance, density and size of adenoma were initially consistent with malignancy while the washout study favored benignity revealing a suboptimal clinical reliability to the washout study (3). The phenotypic characteristics such as tumor size > 4 cm, heterogenous enhancement, central intramural necrosis with irregular margins should have prompt surgical resection for the best chance of survival (2). Endocrinologist should be a proactive member in reading and confirming the presence of malignancy on imaging. 1. Mills S. (2010) Diagnostic Surgical Pathology, 5th Edition. Lippincott Williams and Wilkins, Baltimore. 2. Ng L, Libertino JM. Adrenocortical carcinoma: diagnosis, evaluation and treatment. J Urol 2003; 169:5-11. 3. Sangwaiya, M. August 2010. Incidental Adrenal Lesions: Accuracy of Characterization with contrast-enhances washout.Radiology Volume 256

Feasibility of Prostate PAXgene Fixation for Molecular Research and Diagnostic Surgical Pathology

Advances in prostate cancer biology and diagnostics are dependent upon high-fidelity integration of clinical, histomorphologic, and molecular phenotypic findings. In this study, we compared fresh frozen, formalin-fixed paraffin-embedded (FFPE), and PAXgene-fixed paraffin-embedded (PFPE) tissue preparation methods in radical prostatectomy prostate tissue from 36 patients and performed a preliminary test of feasibility of using PFPE tissue in routine prostate surgical pathology diagnostic assessment. In addition to comparing histology, immunohistochemistry, and general measures of DNA and RNA integrity in each fixation method, we performed functional tests of DNA and RNA quality, including targeted Miseq RNA and DNA sequencing, and implemented methods to relate DNA and RNA yield and quality to quantified DNA and RNA picogram nuclear content in each tissue volume studied. Our results suggest that it is feasible to use PFPE tissue for routine robot-assisted laparoscopic prostatectomy surgical pathology diagnostics and immunohistochemistry, with the benefit of significantly improvedDNA and RNA quality and RNA picogram yield per nucleus as compared with FFPE tissue. For fresh frozen, FFPE, and PFPE tissues, respectively, the average Genomic Quality Numbers were 7.9, 3.2, and 6.2, average RNA Quality Numbers were 8.7, 2.6, and 6.3, average DNA picogram yields per nucleus were 0.41, 0.69, and 0.78, and average RNA picogram yields per nucleus were 1.40, 0.94, and 2.24. These findings suggest that where DNA and/or RNA analysis of tissue is required, and when tissue size is small, PFPE may provide important advantages over FFPE. The results also suggest several interesting nuances including potential avenues to improve RNA quality in FFPE tissues and confirm recent suggestions that some DNA sequence artifacts associated with FFPE can be avoided.

Emerging paradigm of virtual-microscopy for histopathology diagnosis: survey of US and Canadian oral pathology trainees

Objectives/Aims:The application of virtual microscopy (VM) to research, pre-doctoral medical and dental educational training, and diagnostic surgical and anatomic pathology is well-documented but its application to the field of oral and maxillofacial pathology has not been explored. This is the first study to evaluate the enthusiasm and readiness of US-/Canada-based oral and maxillofacial pathology (OMFP) residents toward employing VM use over conventional microscopy (CM) for diagnostic purposes.Materials and Methods:All 46 current US-/Canada-based OMFP residents were invited to participate in an anonymous electronic survey via ‘Survey Monkey’ in 2015. The survey comprised sixteen multiple choice questions and two ‘free text’ questions.Results:14% of respondents of the 22 (48%) respondents who completed the survey indicated a willingness to substitute CM with VM in <5 years, and 33% within 10 years. 52% reported they would never substitute CM with VM. Approximately 10 and 57% of respondents thought VM will become an acceptable sole diagnostic tool in most centers within 5 and 10 years, respectively. These findings are irrespective of the fact that overall, 90% of respondents reported being familiar with VM use.Discussion:VM technology is unlikely to substitute CM in diagnostic oral and maxillofacial histopathology practice among future OMFP practitioners in the foreseeable future.

The long Tramp from Cellular Pathology to Molecular Pathology

Background: The Charite is a well known and one of the biggest University Hospital in Germany. Its Institute of Pathology was founded in 1831, and took part in all changes and modifications of diagnostic surgical pathology. Herein, it forms the basis to describe the history and development of molecular pathology from its early beginning. The appearance of biological structures at microscopic levels forms its fundament, similar to additional tissue theories which have been derived from cellular pathology. Theories of pathology: Theories of pathology frequently describe reaction patterns, and try to explain the relationship between disease and its visible manifestation. They have entered pathology in the 20th century. To name some of them: theory of inflammation [Heinrich Schade 1924, [1], pathology of relations [Gustav Ricker (1924), [2], intercellular pathology [Tivadar Huzella (1937), [3].Derivatives: The observation of principal identity of biological meaningful elements can be agglutinated to a ‘general theory of live’ and its manifestation. All of the investigated elements posses the same regularities, which are altered, destroyed or newly built by external influences such as disease, physical and psychological forces. Not all magnification levels that display with these elements are of the same significance. Already Virchow suggested that ‘smaller elements (molecules) might be responsible for changes that are visible ‘in larger elements’ (at cellular level). The reflection on these ideas can be associated with the implementation of molecular techniques which has been developed in the 20th century and are still ongoing today. Perspectives: Thus, cellular and molecular pathology can be integrated under one umbrella. This umbrella will lead to newly man-formed structures, such as artificial DNA and gene components or functional chip implantations.

GATA3 immunohistochemistry in urothelial carcinoma of the upper urinary tract as a urothelial marker and a prognosticator

Immunohistochemistry of a transcription factor, GATA3, has been widely used as a promising urothelial marker in diagnostic surgical pathology practice. However, the expression status of GATA3 in upper urinary tract urothelial carcinomas (UUTUCs) and its prognostic significance have not been fully investigated. We immunohistochemically stained for GATA3 in 99 UUTUC samples and paired nonneoplastic urothelial tissues. GATA3 was positive in 51 (51.5%; 32 [32.3%] weak, 11 [11.1%] moderate, 8 [8.1%] strong) of 99 UUTUCs, which was significantly lower than in benign urothelium (79 [96.3%] of 82; 33 [40.2%] weak, 35 [42.7%] moderate, 11 [13.4%] strong; P<.001). However, there were no statistically significant associations between GATA3 expression and tumor grade, pT stage, lymph node involvement, or distant metastasis. Meanwhile, the rate of GATA3 positivity was significantly higher (P=.004) in ureteral tumors (66.0%) than in renal pelvic tumors (35.6%). Kaplan-Meier and log-rank tests revealed that GATA3 negativity was significantly associated with lower recurrence-free survival (P=.037 for all cases, P=.026 for muscle-invasive tumors) and cancer-specific survival (P=.007 for all cases, P=.012 for muscle-invasive tumors, P=.035 for cases with adjuvant chemotherapy) rates. Multivariate analysis further identified strong correlations of GATA3 expression with tumor progression (all cases: hazard ratio [HR], 0.479 [95% confidence interval {CI},0.229-1.003; P=.051]; muscle-invasive tumors: HR, 0.387 [95% CI, 0.166-0.903; P=.028) or cancer-specific mortality (all cases: HR, 0.354 [95% CI, 0.135-0.925; P=.034]; muscle-invasive tumors: HR, 0.402 [95% CI, 0.149-1.086; P=.072]). Thus, compared with nonneoplastic urothelium, a significant decrease in the expression of GATA3 in UUTUC was seen. Moreover, loss of GATA3 expression was found to be an independent predictor of poor patient outcomes. Of note was that only roughly half of high-grade and/or muscle-invasive UUTUCs were immunoreactive for GATA3.

The changing landscape of gynaecological cancer diagnosis: implications for histopathological practice in the 21st century.

The era of molecular medicine has led to dramatically improved understanding of the genetic events that give rise to different types of cancers. In the case of gynaecological malignancies, this has resulted in distinct shifts in how these tumours are diagnosed in routine surgical pathology practice, with an increased emphasis on accurate subtype diagnosis. This has happened across all sites in the gynaecological tract and for most cell types, but in ways that are site-specific and may appear to be subtle, as in most instances the diagnostic terminology has not changed. For example, the diagnosis of clear cell carcinoma of the ovary is still in use, but the diagnostic criteria and clinical implications are different in 2017 from what they were in 2000. As a result, there can be a failure to appreciate how important these changes are and the resulting necessity of incorporating them into our daily practice. In this review we will describe changes in diagnostic surgical pathology occasioned by improved understanding of molecular events during pathogenesis, for cancers of ovary/tube, endometrium, cervix and vulva, and highlight how current practice differs from that of only a few years ago.