Pre-operative incisional biopsy of oral squamous cell carcinoma: high podoplanin expression is related to perineural invasion and may be a useful predictor of disease progression.

OBJECTIVE: Immunohistochemical analysis of podoplanin expression as a pre-operative molecular marker for perineural invasion (PNI) may represent an attractive strategy for surgical management of oral squamous cell cancer (OSCC). We evaluated the relationship between podoplanin expression and PNI in pre-operative incisional biopsies of OSCC. STUDY DESIGN: After performing pathological staging and histologic and immunohistochemical evaluation of 83 surgical specimens, we performed multivariable logistic regression analysis to examine the relationship between PNI and independent variables. To evaluate the utility of podoplanin immunopositivity for discrimination of PNI status pre-operatively, we calculated the sensitivity, specificity, positive predictive value, and negative predictive value. We performed receiver operating characteristic curve analysis to evaluate the diagnostic accuracy of podoplanin immunopositivity for predicting PNI alone and in combination with age, T stage, N stage, and index site. RESULTS: We observed podoplanin expression in 42 (50.6%) of all the 83 pre-operative incisional biopsies and 29 of the pre-operative biopsies of the 31 (93.5%) postoperative specimens with PNI. The rate of podoplanin expression was significantly higher in patients with pT3 to pT4 stage and pN+ stage disease. Podoplanin positivity in the pre-operative biopsy showed high sensitivity in predicting PNI in the surgical specimen. CONCLUSION: Podoplanin expression appears to be an independent pre-operative variable significantly related to PNI and a possibly valuable prognostic marker for therapeutical planning and surgical treatment of OSCC.

Papulo-purpuric dermatitis of childhood: a distinct PLEVA-like eruption associated to SARS-CoV-2 infection. Clinical, histopathological and immunohistochemical study of 10 cases.

We observed ten children with a papular eruption with purpuric features during the SARS-CoV-2 pandemic in Northern Italy (May-December 2020). Histological examination showed signs of SARS-CoV-2-related dermatosis. Evidence of nucleocapsid viral proteins using SARS-CoV-2 (2019-nCoV) nucleocapsid antibody revealed cuticular staining of the deep portion of the eccrine glands in all cases.

Similarities in Cutaneous Histopathological Patterns between COVID-19-positive and COVID-19 High-risk Patients with Skin Dermatosis.

Only recently histopathological studies of patients with dermatosis and concomitant SARS-Cov-2 viral infection were published. Seven months into the COVID-19 pandemic, more skin biopsies of COVID-19 positive patients are taking place. We examined the histological features of 30 skin biopsies from two groups of patients: Ten specimens of patients tested positive for COVID-19 with an active systemic infection and associated dermatosis. Twenty specimens were from patients not considered COVID-positive (due to PCR swab negativity or not tested at all) with cutaneous lesions either showing viral infection symptoms (fever, cough, ageusia and severe immunocompromised condition due to HIV infection and malignancies), or presented a high risk of being infected (such as cohabitation with COVID-19 positive parents and siblings with simultaneous chilblains). This study analyses the histological and immunohistochemical (SARS-CoV-2 2019-nCoV nucleocapsid antibody) characteristics of the two groups and identifies 4 histopathological patterns. The histopathological features of the two groups present similar features that may help to identify an ongoing COVID-19 infection even in asymptomatic carriers with dermatosis.

Anal Fibroepithelial Polyp With Epithelial Vascular Pseudoinvasion.

In this article, we report a case of anal fibroepithelial polyp with benign squamous cell vascular pseudoinvasion. The patient was a 38-year-old Caucasian man, who presented at our institution for recurrent episodes of anal discomfort. Clinical evaluation revealed the presence of 2 pedunculated anal polyps that were resected and submitted for histological evaluation. On microscopic evaluation, one of the polyps shows epithelial endovascular displacement associated with morphological signs of traumatism. The differential diagnosis and possible pathogenetic mechanisms explaining the presence of such findings are discussed. To the best of our knowledge, this is the first case reported of an anal fibroepithelial polyp with epithelial vascular pseudoinvasion.

First-in-Man Study Evaluating the Emblok Embolic Protection System During Transcatheter Aortic Valve Replacement.

OBJECTIVES: This study sought to evaluate the feasibility of complete cerebral protection during transcatheter aortic valve replacement (TAVR) with a novel embolic protection device. BACKGROUND: Evidences and data about new cerebral embolic protection devices are lacking and scarce. METHODS: A prospective, nonrandomized, multicenter, first-in-man pilot study designed to evaluate the efficacy and safety of cerebral embolic protection utilizing the Emblok embolic protection system (Innovative Cardiovascular Solutions, Grand Rapids, Michigan) during TAVR. The Emblok is a transfemoral aortic filter that provide full coverage of the epiaortic vessels. Brain diffusion-weighted magnetic resonance imaging (DW-MRI) was performed at baseline and 2 to 5 days after TAVR. Primary endpoints were technical success and immediate cerebral embolic burden after TAVR, defined as number and volume of new brain lesions detected with DW-MRI at days 2 to 5 post-TAVR compared with baseline. RESULTS: A total of 20 subjects were enrolled. The Emblok system was successfully positioned in all the cases. At 30-day follow-up, no major adverse cardiovascular and cerebrovascular events occurred. Nineteen (95%) patients had new ischemic defects at post-procedural DW-MRI. The median number of new lesions per patient was 10.00 (interquartile range [IQR]: 4.75 to 15.25). The total new lesion volume was 199.9 mm3 (IQR: 83.9 to 447.5 mm3) and the mean lesion volume per lesion was 42.5 mm3 (IQR: 21.5 to 75.6 mm3). Histopathologic analysis showed evidence of significant debris in 18 (90%) filters. CONCLUSIONS: The Emblok embolic protection system appears to be feasible and safe during TAVR. The device was successfully placed and retrieved in all cases and no neurological events were observed. Cerebral total new lesion volume was similar to other trials on cerebral protection during TAVR, thus warranting a larger study. (European Study Evaluating the Emblok Embolic Protection System During TAVR; NCT03130491).

Agreement on endoscopic ultrasonography-guided tissue specimens: Comparing a 20-G fine-needle biopsy to a 25-G fine-needle aspiration needle among academic and non-academic pathologists.

BACKGROUND AND AIM: A recently carried out randomized controlled trial showed the benefit of a novel 20-G fine-needle biopsy (FNB) over a 25-G fine-needle aspiration (FNA) needle. The current study evaluated the reproducibility of these findings among expert academic and non-academic pathologists. METHODS: This study was a side-study of the ASPRO (ASpiration versus PROcore) study. Five centers retrieved 74 (59%) consecutive FNB and 51 (41%) FNA samples from the ASPRO study according to randomization; 64 (51%) pancreatic and 61 (49%) lymph node specimens. Samples were re-reviewed by five expert academic and five non-academic pathologists and rated in terms of sample quality and diagnosis. Ratings were compared between needles, expert academic and non-academic pathologists, target lesions, and cytology versus histological specimens. RESULTS: Besides a higher diagnostic accuracy, FNB also provided for a better agreement on diagnosing malignancy (ĸ = 0.59 vs ĸ = 0.76, P < 0.001) and classification according to Bethesda (ĸ = 0.45 vs ĸ = 0.61, P < 0.001). This equally applied for expert academic and non-academic pathologists and for pancreatic and lymph node specimens. Sample quality was also rated higher for FNB, but agreement ranged from poor (ĸ = 0.04) to fair (ĸ = 0.55). Histology provided better agreement than cytology, but only when a core specimen was obtained with FNB (P = 0.004 vs P = 0.432). CONCLUSION: This study shows that the 20-G FNB outperforms the 25-G FNA needle in terms of diagnostic agreement, independent of the background and experience of the pathologist. This endorses use of the 20-G FNB needle in both expert and lower volume EUS centers.

Interobserver Variability in the Histopathologic Assessment of Extrathyroidal Extension of Well Differentiated Thyroid Carcinoma Supports the New American Joint Committee on Cancer Eighth Edition Criteria for Tumor Staging.

Background: Extrathyroidal extension (ETE) by papillary and follicular thyroid carcinoma can be associated with increased risk of tumor recurrence and mortality. In the seventh edition of its Cancer Staging Manual, the American Joint Committee on Cancer (AJCC) defined minimal ETE as the involvement of skeletal muscle (i.e., strap muscles) or perithyroidal soft tissue. The eighth edition of the AJCC Cancer Staging Manual has changed the criteria so that only grossly evident (macroscopic) ETE involving strap muscles (not microscopic ETE involving perithyroidal soft tissue) affects tumor staging. Summary: Concordance of identifying microscopic ETE (as well as extranodal extension by carcinoma metastatic to lymph nodes) was previously evaluated among 11 expert endocrine pathologists. The overall agreement rate was slight when rendering a diagnosis of ETE. Concordance was highest when pathologists assessed the spatial relationship of carcinoma to skeletal muscle. This article discusses the significance of these findings. It also reviews relevant anatomic and developmental considerations related to the boundaries of the thyroid. Conclusions: The results of the concordance study provide additional rationale supporting stringent criteria for diagnosing ETE, as proposed by the eighth edition of the AJCC Cancer Staging Manual. It is expected that these rigid morphologic criteria will potentially reduce interobserver variability and enhance consistency in the diagnosis and staging of thyroid carcinoma.

An infrastructure for precision medicine through analysis of big data.

BACKGROUND: Nowadays, the increasing availability of omics data, due to both the advancements in the acquisition of molecular biology results and in systems biology simulation technologies, provides the bases for precision medicine. Success in precision medicine depends on the access to healthcare and biomedical data. To this end, the digitization of all clinical exams and medical records is becoming a standard in hospitals. The digitization is essential to collect, share, and aggregate large volumes of heterogeneous data to support the discovery of hidden patterns with the aim to define predictive models for biomedical purposes. Patients' data sharing is a critical process. In fact, it raises ethical, social, legal, and technological issues that must be properly addressed. RESULTS: In this work, we present an infrastructure devised to deal with the integration of large volumes of heterogeneous biological data. The infrastructure was applied to the data collected between 2010-2016 in one of the major diagnostic analysis laboratories in Italy. Data from three different platforms were collected (i.e., laboratory exams, pathological anatomy exams, biopsy exams). The infrastructure has been designed to allow the extraction and aggregation of both unstructured and semi-structured data. Data are properly treated to ensure data security and privacy. Specialized algorithms have also been implemented to process the aggregated information with the aim to obtain a precise historical analysis of the clinical activities of one or more patients. Moreover, three Bayesian classifiers have been developed to analyze examinations reported as free text. Experimental results show that the classifiers exhibit a good accuracy when used to analyze sentences related to the sample location, diseases presence and status of the illnesses. CONCLUSIONS: The infrastructure allows the integration of multiple and heterogeneous sources of anonymized data from the different clinical platforms. Both unstructured and semi-structured data are processed to obtain a precise historical analysis of the clinical activities of one or more patients. Data aggregation allows to perform a series of statistical assessments required to answer complex questions that can be used in a variety of fields, such as predictive and precision medicine. In particular, studying the clinical history of patients that have developed similar pathologies can help to predict or individuate markers able to allow an early diagnosis of possible illnesses.

Inter-Observer Variation in the Pathologic Identification of Extranodal Extension in Nodal Metastasis from Papillary Thyroid Carcinoma.

BACKGROUND: Extranodal extension (ENE) in lymph node metastases has been shown to worsen the prognosis of papillary thyroid cancer (PTC). Despite the clinical significance of ENE, there are no stringent criteria for its microscopic diagnosis, and its identification is subject to inter-observer variability. The objective of this study was to determine the level of agreement among expert pathologists in the identification of ENE in PTC cases. METHODS: Eleven expert pathologists from the United States, Italy, and Canada were asked to review 61 scanned slides of representative permanent sections of PTC specimens from Mount Sinai Beth Israel Medical Center in New York. Each slide was evaluated for the presence of ENE. The pathologists were also asked to report the criteria they use to identify ENE. RESULTS: The overall strength of agreement in identifying ENE was only fair (κ = 0.35), and the proportion of observed agreement was 0.68. The proportions of observed agreement for the identification of perinodal structures (fat, nerve, skeletal, and thick-walled vessel involvement) ranged from 0.61 to 0.997. CONCLUSIONS: Overall agreement for the identification of ENE is poor. The lack of agreement results from both variation in pathologists' identification of features and disagreement on the histologic criteria for ENE. This lack of concordance may help explain some of the discordant information regarding prognosis in clinical studies when this feature is identified.

Inter-Observer Variation in the Pathologic Identification of Minimal Extrathyroidal Extension in Papillary Thyroid Carcinoma.

BACKGROUND: Extrathyroidal extension (ETE) is a significant prognostic factor in papillary thyroid carcinoma (PTC). Minimal extrathyroidal extension (mETE) is characterized by involvement of the sternothyroid muscle or perithyroid soft tissue, and is generally identified by light microscope examination. Patients with mETE, identified pathologically, are automatically upstaged to pT3. However, the prognostic implications of mETE have been a source of controversy in the literature. Moreover, there is also controversy surrounding the identification of mETE on pathological specimens. The objective of this study was to determine the level of agreement among expert pathologists in the identification of mETE in PTC cases. METHODS: Eleven expert pathologists from the United States, Italy, and Canada were asked to perform a review of 69 scanned slides of representative permanent sections of PTC specimens. Each slide was evaluated for the presence of mETE. The pathologists were also asked to list the criteria they use to identify mETE. RESULTS: The overall strength of agreement for identifying mETE was slight (κ = 0.14). Inter-pathologist agreement was best for perithyroidal skeletal muscle involvement (κ = 0.46, moderate agreement) and worst for invasion around thick-walled vascular structures (κ = 0.02, slight agreement). In addition, there was disagreement over the constellation of histologic features that are diagnostic for mETE, which affected overall agreement for diagnosing mETE. CONCLUSIONS: Overall agreement for the identification of mETE is poor. Disagreement is a result of both variation in individual pathologists' interpretations of specimens and disagreement on the histologic criteria for mETE. Thus, the utility of mETE in staging and treatment of PTC is brought into question. The lack of concordance may explain the apparent lack of agreement regarding the prognostic significance of this pathologic feature.

Gain of hTERC: a genetic marker of malignancy in oral potentially malignant lesions.

Oral squamous cell carcinoma (OSCC) is the most common oral cancer, and major efforts is being made to identify molecular markers capable to differentiate oral potentially malignant lesions (OPMLs) with indolent course from lesions with aggressive behavior. We undertook a study to evaluate if gain of the human telomerase RNA component (hTERC) gene in OPMLs could indicate lesions at high risk of developing OSCC. The study was performed on 30 OPMLs with long-term follow-up using a dual-color interphase fluorescence in situ hybridization (FISH) for hTERC status. Progression to malignancy was observed in 9 of 10 cases harboring hTERC gain and in 1 of 20 cases retaining a normal copy number of hTERC (P < .0001). Combining morphological grading and FISH analysis, all the cases with high-grade squamous intraepithelial lesion or carcinoma in situ harboring hTERC amplification progressed to OSCC, whereas none of the low-grade squamous intraepithelial lesions without hTERC gain progressed. Intermediate situations occurred. The data suggest that precise morphological evaluation together with FISH assessment for hTERC gain might pave the way to stratify OPMLs into high-risk and low-risk categories and could be helpful in selecting the most appropriate treatment.

Recurrent apocrine carcinoma of the scrotum: a case report.

Apocrine carcinoma is a rare tumor of the skin that typically arises in areas rich in apocrine glands, such as axilla and perineum. The main differential diagnosis is a metastasis from a primary apocrine carcinoma of the breast. Several authors have attempted to define morphological and immunohistochemical parameters to differentiate metastasis from primary apocrine carcinoma of the skin, but none of these had been demonstrated to be reliable markers. Here, we report a case of primary apocrine carcinoma of the scrotum that relapsed three times within a few years, without any clinical or radiological evidence of any other tumor of breast or other sites.

Multifocal fibrosing thyroiditis: report of 55 cases of a poorly recognized entity.

During the course of our consultation activity, we have recognized a peculiar form of thyroiditis in which multiple foci of fibrosis, most of which were associated with reactive atypia of the surrounding follicles, are present. We have referred to this condition, both in our consultation reports and in the third series of A.F.I.P. Fascicle on Tumors of the Thyroid Gland, as "multifocal fibrosing thyroiditis" or (less frequently) "multifocal sclerosing thyroiditis," which are descriptive terms that highlight the benign/inflammatory nature of the process, its multiplicity, and its unknown pathogenesis. The aim of this study is to better define the morphologic features of this process and correlate it with some clinical data. With this purpose, the consultation files of one of the authors (J.R.) were searched for cases coded as multifocal fibrosing thyroiditis or multifocal sclerosing thyroiditis in a 20-year period ranging from January 1989 to December 2009. A total of 55 cases were identified that displayed the above-listed features. There were 51 (93%) female and 4 (7%) male patients (F/M=12.75), with ages ranging between 15 and 71 years (mean age, 47.03 y; median age, 44.5 y). Microscopically, multiple foci of fibrosis were identified in all cases, their number ranging from 2 to 51 per case (mean number, 16), with a mean diameter of 3 mm (range: 0.36 to 15.1 mm). Although heterogenous in shape and size, the individual foci were rather similar to each other in composition, being characterized by a fibrotic poorly cellular center that merged with a cellular peripheral zone. Some of the follicular structures present at the periphery of the scar and-to a lesser extent-those entrapped inside it underwent complex reactive and regenerative (atypical) changes that simulated malignancy. We discuss the differential diagnosis with other benign and malignant thyroid conditions and speculate about its pathogenesis and possible relationship with papillary thyroid microcarcinoma.

A prospective assessment defining the limitations of thyroid nodule pathologic evaluation.

BACKGROUND: Clinical management of thyroid neoplasms is based on light microscopic diagnosis, but its accuracy and precision are poorly defined. OBJECTIVE: To assess inter- and intraobserver variability of preoperative cytopathologic and postoperative histopathologic thyroid diagnoses. DESIGN: Samples were collected in a prospective, multicenter trial validating a gene expression classifier between June 2009 and December 2010. SETTING: 14 academic and 35 community clinical sites. PATIENTS: 653 patients with 776 surgically resected thyroid nodules of 1 cm or greater. MEASUREMENTS: Intraobserver concordance among 2 or more central histopathologists who independently read histopathology slides was calculated. Interobserver concordance between the diagnoses made by the central histopathologists and those made by local pathologists were calculated. Intra- and interobserver concordance for cytopathology was similarly calculated by comparing diagnoses made by local pathologists with those made by a central panel of 3 cytopathologists. RESULTS: Concordance on the histopathologic distinction between benign and malignant diagnoses was 91% comparing local with central histopathologists and 90% comparing 2 central histopathologists. Using the 6-category Bethesda System, 64.0% of diagnoses made by local and central cytopathologists and 74.7% of intraobserver diagnoses were concordant. Central cytopathologists made fewer indeterminate diagnoses than local pathologists (41.2% vs. 55.0%). LIMITATIONS: Many local pathologists did not use the Bethesda System, so their reports were translated to allow comparison. The study required histopathology, and the study population and specimens did not encompass all newly evaluated patients with a thyroid nodule. CONCLUSION: Substantial inter- and intraobserver variability exists in the cytopathologic and histopathologic evaluation of thyroid nodules, confirming an inherent limitation of visual microscopic diagnosis. PRIMARY FUNDING SOURCE: Veracyte.

Multifocal capillary hemangioma-like vascular proliferation of the kidney associated with clear cell renal cell carcinoma: a case report and review of the literature.

We report the case of a 69-year-old man who underwent a radical left nephrectomy for a renal mass. Microscopically, the features were those of a clear cell-type renal cell carcinoma associated with 2 foci of capillary hemangioma-like vascular proliferation in the adjacent renal parenchyma. The main differential diagnosis and the possible pathogenesis of this vascular lesion are discussed.

Eccrine porocarcinoma with carcinomatous lymphangitis in a patient with history of arsenic exposure: a case report.

Eccrine porocarcinoma is a potentially fatal form of sweat gland carcinoma, due to its propensity to metastasize through lymph vessels. The authors report the case of a 69-year-old female who presented with swelling of the right leg and an ulcerated lesion of the right great toe. The initial histologic diagnosis was invasive squamous cell carcinoma. On follow-up, the patient developed lymphangitic tumor spread in the right leg, associated with right inguinal lymphadenopathy and lesions in vulva and flank. Reevaluation of the toe lesion led to a revised diagnosis of eccrine porocarcinoma. The patient also had 2 basal cell carcinomas of the multicentric/superficial type in the skin overlying the left breast. Past history included chronic ingestion of liquore arsenic (Fowler's solution) in early adulthood as treatment for dermatitis herpetiformis.