Histopathological Diagnostic Criteria Research Articles

Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP): what do we need to know?

Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) is a recently defined thyroid nodule category characterized by follicular architecture with papillary nuclear features but lacking classical papillary carcinoma features like papillae or psammoma bodies. The diagnosis of NIFTP is based on histological examination and excludes cases with high-risk mutations like BRAFV600E. NIFTP carries a low risk of recurrence and distant metastasis, prompting a more conservative surgical approach compared to classical papillary thyroid carcinoma. The management of NIFTP typically involves lobectomy with postoperative monitoring of thyroglobulin levels and performing neck ultrasounds. While the identification of NIFTP represents a significant advancement in thyroid cancer diagnosis, challenges remain in refining preoperative diagnostic tools and establishing optimal long-term follow-up strategies. The objective of this review is to provide a comprehensive overview of NIFTP, including its histopathological characteristics, molecular profile, clinical presentation, diagnostic criteria, management strategies, and future research directions.

Antral mucosa healing at long-term follow-up in patients with corpus atrophic gastritis and concomitant antral gastritis may mimic autoimmune gastritis

Background and aimCorpus atrophic gastritis (CAG) is defined as autoimmune when the antrum is spared, representing this element a crucial diagnostic criterium of autoimmune gastritis. In contrast, CAG with concomitant antral gastritis (AG), atrophic or non-atrophic, is generally attributed to H. pylori infection. During the natural history of CAG, possible antrum healing has been supposed. The current study aimed to assess the antral mucosa histopathological changes at long-term follow-up (FU) with respect to baseline in patients with CAG and concomitant atrophic or non-atrophic gastritis AG. MethodsRetrospective study on 130 patients with histologically diagnosed CAG with atrophic or non-atrophic AG. Mean FU gastroscopy was at 40.6 (range 4–192) months. Patients with confirmed CAG (n = 117; median age 66, range 20–87 years; 67.5 % F) were finally included. At baseline, 47 (40.2 %) had non-atrophic and 70 (59.8 %) atrophic AG. Helicobacter pylori (Hp) infection was present at histology in 27.3 % of patients, all treated. ResultsAt FU, 30/117(25.6 %) patients showed a complete antral healing; 11/29(37.9 %) were Hp positive at baseline, cured in all but one. Atrophic AG regressed in 16/70(22.8 %) patients. Both, antral healing and regression of antral AG, were found to be similar in Hp-cured and not-cured/ naïve-negatives patients (p > 0.05). ConclusionIn a subset of CAG patients, AG may regress at long-term FU irrespective of Hp cure, thus mimicking autoimmune atrophic gastritis and raising concerns about its current histopathological diagnostic criteria.

Expression of Programmed Death Ligand 1 and Indoleamine 2,3-Dioxygenase in Oral Lichen Planus and Oral Lichenoid Lesions.

Oral lichen planus (OLP) and oral lichenoid lesions (OLL) are inflammatory T-cell mediated disorders of the oral mucosa (OM). Both are associated with an increased risk of oral squamous cell carcinoma, with OLL possibly having a higher rate of malignant transformation than OLP. Programmed death ligand 1 (PD-L1) and indoleamine 2,3-dioxygenase (IDO) are immunosuppressive molecules possessing inhibitory effect on T-cells and have been implicated in carcinogenesis. The aim of this study was to examine the expression of PD-L1 and IDO in OLP and OLL. Sixty-eight formalin-fixed, paraffin-embedded tissue samples diagnosed as OLP, compatible with OLP, or OLL were divided into OLP (n = 39) or OLL (n = 29) groups based on both clinical and histopathological diagnostic criteria. Samples of healthy OM (n = 9) served as controls. Samples were immunohistochemically stained for PD-L1 and IDO, and staining distribution and intensity were evaluated. Immunohistochemical expression of PD-L1 was increased in the basal and intermediate layers of epithelium in OLP and in lamina propria in both OLP and OLL compared to controls. OLP and OLL showed increased expression of IDO in epithelium and lamina propria compared to controls. PD-L1 staining intensity in the basal epithelial layer, and IDO staining intensity in lamina propria were increased in OLP compared to OLL. The results indicate that the expression of PD-L1 and IDO increases in OLP and OLL, suggesting that these molecules may play a role in the pathogenesis of both disorders.

Reflectance confocal microscopy for plaque psoriasis therapeutic follow-up during an anti-interleukin-17A monoclonal antibody: an observational study

Interleukin-17A therapeutic inhibitors are among the most effective treatment methods for moderate-to-severe plaque psoriasis (PP). Reflectance confocal microscopy is a non-invasive imaging technique already documented to be beneficial in evaluating the follow-up of PP under treatment with topical actives and phototherapy. This study aimed to assess the epidermal and dermal changes associated with psoriasis and its treatment with RCM during systemic secukinumab treatment in patients with moderate-to-severe PP. A pilot study was conducted to evaluate RCM as a non-invasive tool for monitoring secukinumab treatment in patients with PP. For patients receiving secukinumab treatment, lesional skin was selected for RCM imaging, which were recorded at all scheduled times. The RCM evaluation criteria were established based on the histopathological diagnostic criteria for psoriasis. The clinical severity of psoriasis was assessed utilizing the psoriasis area severity index. A total of 23 patients with PP were included in the study. Each patient received 300 mg of subcutaneous secukinumab as induction therapy at baseline and weeks 1–4, followed by maintenance therapy every four weeks. Microscopic confocal changes were observed during the treatment. The results identified early microscopic evidence of the anti-inflammatory activity of secukinumab, which was not detected during the clinical examination. RCM findings correlating with the PASI were used to observe the patient’s response to treatment and were identified as follows: acanthosis and parakeratosis, presence of epidermal and dermal inflammatory cells, presence of non-edge dermal papillae, and vascularization in the papillary dermis. This study is the first to demonstrate the use of RCM as an effective tool for non-invasive monitoring of secukinumab therapeutic response at a cellular level in a clinical or research setting. Early detection of RCM parameters associated with secukinumab activity may facilitate the identification of an early treatment response. RCM appears to be capable of providing practical and helpful information regarding follow-up in patients with PP undergoing secukinumab treatment. RCM may also provide novel perspectives on the subclinical evaluation of PP’s response to biological therapy.

Atypical meningioma: Histopathological, genetic, and epigenetic features to predict recurrence risk.

Grading assessed according to World Health Organization (WHO) criteria is a major prognostic factor for determining the risk of recurrence in patients with meningiomas and establishing the most appropriate therapeutic strategy after surgery. However, the main issue is to predict the recurrence risk of WHO grade 2 meningioma and, more specifically, of the atypical subtype. Indeed, owing to a reported recurrence rate of 50%, either radiotherapy or observation is currently considered an option after gross total surgical resection of atypical meningiomas. These heterogeneous clinical outcomes are likely related to the broad histopathological diagnostic criteria for this subtype, and whether meningiomas only present as brain invasion should be classified as atypical remains controversial. Over the last few years, several studies have shown that DNA methylation profiling, next-generation sequencing, and transcriptomics can better stratify meningiomas for their recurrence risk than histology. The main limitations to the widespread use of these approaches to classify meningiomas are their high cost and the need for sophisticated technologies. However, all studies concurred that atypical meningiomas without chromosome 1p deletion display a low recurrence risk, suggesting that the assessment of this cytogenetic alteration could represent an easy and quick method to determine which patients could benefit from adjuvant treatment after surgery. In addition, prognostically unfavorable molecular groups can be distinguished using specific immunostainings, although further validation is required.

Peripheral neuroblastic tumors in childhood

Peripheral neuroblastic tumors represent the fourth-largest group of malignant tumors in childhood. The majority of these tumors are neuroblastomas, which can be classified into undifferentiated, poorly differentiated, and differentiating subtypes. In addition, peripheral neuroblastic tumors include ganglioneuroblastoma, acomposite tumor composed of Schwannian cell stroma and neuroblasts as well as benign ganglioneuroma. In this overview, histopathological diagnostic criteria and grading systems, as well as common molecular alterations that are of prognostic and therapeutic significance, are discussed.

Diagnostic value of Kaiser score combined with breast vascular assessment from breast MRI for the characterization of breast lesions.

The Kaiser scoring system for breast magnetic resonance imaging is a clinical decision-making tool for diagnosing breast lesions. However, the Kaiser score (KS) did not include the evaluation of breast vascularity. Therefore, this study aimed to use KS combined with breast vascular assessment, defined as KS*, and investigate the effectiveness of KS* in differentiating benign from malignant breast lesions. This retrospective study included 223 patients with suspicious breast lesions and pathologically verified results. The histopathological diagnostic criteria were according to the fifth edition of the WHO classification of breast tumors. The KS* was obtained after a joint evaluation combining the original KS and breast vasculature assessment. The receiver operating characteristic (ROC) curve was used for comparing differences in the diagnostic performance between KS* and KS, and the area under the receiver operating characteristic (AUC) was compared. There were 119 (53.4%) benign and 104 (46.6%) malignant lesions in total. The overall sensitivity, specificity, and accuracy of increased ipsilateral breast vascularity were 69.2%, 76.5%, and 73.1%, respectively. The overall sensitivity, specificity, and accuracy of AVS were 82.7%, 76.5%, and 79.4%, respectively. For all lesions included the AUC of KS* was greater than that of KS (0.877 vs. 0.858, P = 0.016). The largest difference in AUC was observed in the non-mass subgroup (0.793 vs. 0.725, P = 0.029). Ipsilaterally increased breast vascularity and a positive AVS sign were significantly associated with malignancy. KS combined with breast vascular assessment can effectively improve the diagnostic ability of KS for breast lesions, especially for non-mass lesions.

Comparative evaluation of podoplanin in odontogenic cysts and tumours to determine their proliferative potential-An immunohistochemical study.

Odontogenic cysts and tumours are a wide array of complex pathological entities ranging from mild indolent to aggressive detrimental in nature, which occur as a result of anomalous alterations in normal odontogenesis. Hence, these odontogenic lesions need to be evaluated extensively by using potential immunohistochemical markers. To evaluate and compare the expression of podoplanin, a lymphoendothelial IHC marker in odontogenic cysts and odontogenic tumours to determine their proliferative potential. All the study samples were retrieved from the archives of the Department of Oral Pathology and Microbiology, PIDS&RC, Hyderabad. The study samples were selected as per the standard histopathological diagnostic criteria and subjected for IHC analysis using podoplanin. Seventy paraffin-embedded tissue specimens of OKC, OOC, dentigerous cyst (DC) and ameloblastoma (AM) include study sample, which were stained with podoplanin IHC marker and staining properties were evaluated. All the cases were categorized as high, moderate, weak or negatively reactive on the basis of the composite scoring. Statistical analysis was done using SPSS version 14, and then results were compared by ANOVA post hoc test and Kruskal Wallis Test. In the comparison of composite scores of OKCs and AM, there was no significant statistical difference. The present study contributes to the significant association of podoplanin expression with cellular proliferation, cystic expansion and local invasiveness of odontogenic cysts and tumours through cytoskeletal reorganization and cell migration.

Mass Spectrometry Proteomic Analysis of Four p53 Patterns in Differentiated Vulvar Intraepithelial Neoplasia.

The histopathologic diagnostic criteria of differentiated vulvar intraepithelial neoplasia (dVIN), the precursor of human papillomavirus-independent squamous cell carcinoma, are basal atypia, a negative or non-block-positive p16, and a supportive p53 immunohistochemistry (IHC). Several different patterns of supportive p53 IHC have been described. This study aims to determine the relationship between p53 IHC patterns and mass spectrometry analysis of cellular proteins in dVIN. Four patterns of p53 IHC were studied: overexpression, cytoplasmic, wild type, and intermediate expression between wild type and overexpression. For each pattern, tissue samples of 4 examples were subjected to mass spectrometry. The protein profile within each p53 IHC pattern shared common features. Each of the 4 p53 patterns had a distinguishable protein profile when compared with the other 3 patterns. The distinguishable protein profiles in different p53 IHC patterns suggest diverse mechanisms of TP53 dysfunction. Subtyping dVIN by p53 IHC is worthy of further study because varied protein expression profiles may translate into different clinical behavior.

Commentary on why implementing and standardizing histologic diagnosis of myocarditis is crucial for the clinical setting and patient care

Histological examination of endomyocardial biopsy or myocardium at autopsy is key to the diagnosis of myocarditis. Among pathologists there is currently extensive variability in routine practice and criteria used to define, diagnose, and report myocarditis as well as to achieve consensus on cases. Two manuscripts emphasizing the need to standardize and implement histopathological diagnostic criteria for myocarditis are reviewed.

Results of a worldwide survey on the currently used histopathological diagnostic criteria for invasive lobular breast cancer

Invasive lobular carcinoma (ILC) represents the second most common subtype of breast cancer (BC), accounting for up to 15% of all invasive BC. Loss of cell adhesion due to functional inactivation of E-cadherin is the hallmark of ILC. Although the current world health organization (WHO) classification for diagnosing ILC requires the recognition of the dispersed or linear non-cohesive growth pattern, it is not mandatory to demonstrate E-cadherin loss by immunohistochemistry (IHC). Recent results of central pathology review of two large randomized clinical trials have demonstrated relative overdiagnosis of ILC, as only ~60% of the locally diagnosed ILCs were confirmed by central pathology. To understand the possible underlying reasons of this discrepancy, we undertook a worldwide survey on the current practice of diagnosing BC as ILC. A survey was drafted by a panel of pathologists and researchers from the European lobular breast cancer consortium (ELBCC) using the online tool SurveyMonkey®. Various parameters such as indications for IHC staining, IHC clones, and IHC staining procedures were questioned. Finally, systematic reporting of non-classical ILC variants were also interrogated. This survey was sent out to pathologists worldwide and circulated from December 14, 2020 until July, 1 2021. The results demonstrate that approximately half of the institutions use E-cadherin expression loss by IHC as an ancillary test to diagnose ILC and that there is a great variability in immunostaining protocols. This might cause different staining results and discordant interpretations. As ILC-specific therapeutic and diagnostic avenues are currently explored in the context of clinical trials, it is of importance to improve standardization of histopathologic diagnosis of ILC diagnosis.

Etiopathogenesis, Diagnosis, and Treatment Strategies for Lymphomatoid Papulosis with Particular Emphasis on the Role of the Immune System.

Lymphomatoid papulosis (LyP) is a very rare disease that belongs to the group of CD30+ lymphoproliferative skin diseases. LyP is localized or generalized and usually presents as isolated or clustered red/brown-red lesions in the form of nodules and/or papules. The course of the disease is in most cases mild; however, depending on concomitant risk factors and history, it may progress to lymphoma, significantly reducing the survival rate and prognosis. Importantly, the clinical picture of the disease remains somewhat ambiguous, leading to a large number of misdiagnoses that result in inappropriate treatment, which is usually insufficient to alleviate symptoms. In addition to clinical manifestations, the histological characteristics vary widely and usually overlap with other conditions, especially those belonging to the group of lymphoproliferative disorders. Although diagnosis remains a challenge, several recommendations and guidelines have been introduced to standardize and facilitate the diagnostic process. This article reviews the available literature on the most important aspects of etiopathogenesis, clinical and histopathological features, diagnostic criteria, and possible treatment strategies for LyP, with particular emphasis on the role of the immune system.

Comparative study of histopathological diagnostic criteria in cutaneous lesions of lichen planus and discoid lupus erythematosus

Background and aims: Lichen planus (LP) and discoid lupus erythematosus (DLE) are two relatively common mucocutaneous lesions whose clinical and histopathological features overlap in some cases. The present study aimed to distinguish between these two lesions histopathologically in order to treat them more accurately. Methods: In a cross-sectional descriptive-analytical study, 29 and 48 microscopic slides of skin samples of DLE and LP, respectively, were examined in the pathology archive of Al-Zahra hospital of Isfahan from 2008 to 2018. The slides prepared by hematoxylin-eosin staining were examined simultaneously and blindly by three pathologists with a light microscope and compared according to certain histopathological criteria. Then obtained data were analyzed by SPSS version 24 using chi-square, Fisher’s exact, Mann-Whitney, and t tests (P<0.05). Results: Based on the findings, the presence of hyperparakeratosis with superficial hyperorthokeratosis, epithelial atrophy, deep perivascular infiltration, presence of edema in the papillary dermis, presence of plasma cells with lymphohistiocytes in inflammatory infiltration, and presence of mucin in the dermis were significantly higher in DLE than in LP (P<0.05). On the other hand, the intensity of lichenoid infiltration, presence of saw tooth hyperplasia of rete ridges, presence of cleft between the epithelium and connective tissue, spongiosis, hyperorthokeratosis alone, and wedge-shaped hypergranulosis were significantly higher in LP than in DLE (P<0.05). Conclusion: Perieccrine and perifollicular inflammation, presence of Civatte bodies (CBs), abundance of fibrosis, presence of pale keratinocytes, and presence of pseudoepitheliomatous hyperplasia were not the criteria for differential diagnosis of LP and DLE.

Breast cancers originating from the major lactiferous ducts and the process of neoductgenesis: Ductal Adenocarcinoma of the Breast, DAB

PurposeTo call attention to a highly fatal breast cancer subtype arising from the major lactiferous ducts that is currently underdiagnosed as ductal carcinoma in situ (DCIS) with or without microinvasion. MethodAll breast cancers diagnosed at the Department of Mammography, Falun Central Hospital, Sweden, since 1977 have been classified according to their mammographic tumour features (imaging biomarkers) and followed up at regular intervals for the past four decades. The imaging biomarkers characteristic of breast cancers apparently arising from the major lactiferous ducts have been correlated with large format thin and thick section histopathology and long-term patient outcome. ResultsBreast cancers arising within the major lactiferous ducts propagate intraductally and produce continuously branching neoducts through epithelial-mesenchymal transformation (EMT), an invasive process termed neoductgenesis, which eventually forms a massive tumour burden. The high fatality of this breast cancer subtype indicates its truly invasive nature, although it is conventionally termed ductal carcinoma in situ, DCIS, terminology which is at odds with its poor long-term patient outcome. The neoducts are filled with multiple layers of malignant cells, have no attached lobules, and propagate by forming multiple invasive side branches. These newly formed duct-like structures are surrounded by a desmoplastic reaction (cancer associated fibroblasts, CAFs) and periductal lymphocytic infiltration. The neoducts are tightly packed together in irregular formations bearing no resemblance to the paniculate branching structure of normal lactiferous ducts. Cancers originating from the major ducts have six imaging biomarkers which can be easily recognized at breast imaging. These are described in detail in an accompanying article. ConclusionsNeoductgenesis in the breast, DAB, is similar in appearance and prognosis to ductal adenocarcinoma of the prostate, DAP. We propose the term ductal adenocarcinoma of the breast, DAB, to facilitate its recognition as a distinct invasive breast cancer subtype. The high fatality rates associated with neoductgenesis reflect the failure of current histopathologic diagnostic criteria to effectively guide therapeutic practice. When the neoducts are associated with small stellate/spiculated or spherical/oval-shaped invasive cancers arising from the terminal ductal lobular units (TDLUs), the prognosis and management are erroneously estimated according to the smaller invasive tumour(s), giving a false sense of security often resulting in undertreatment. Recognition that neoductgenesis is an invasive malignancy is a prerequisite for preventing treatment failure.

Acute rejection and post lung transplant surveillance.

PurposeThe purpose of this review is to summarize the current evidence on the evaluation and treatment of acute rejection after lung transplantation.ResultsDespite significant progress in the field of transplant immunology, acute rejection remains a frequent complication after transplantation. Almost 30% of lung transplant recipients experience at least one episode of acute cellular rejection (ACR) during the first year after transplant. Acute cellular rejection, lymphocytic bronchiolitis, and antibody-mediated rejection (AMR) are all risk factors for the subsequent development of chronic lung allograft dysfunction (CLAD). Acute cellular rejection and lymphocytic bronchiolitis have well-defined histopathologic diagnostic criteria and grading. The diagnosis of antibody-mediated rejection after lung transplantation requires a multidisciplinary approach. Antibody-mediated rejection may cause acute allograft failure.ConclusionsAcute rejection is a risk factor for development of chronic rejection. Further investigations are required to better define risk factors, surveillance strategies, and optimal management strategies for acute allograft rejection.

Dysmotility in Eosinophilic Esophagitis.

Eosinophilic esophagitis (EoE) is an immune mediated chronic inflammatory disease resulting from antigen exposure and is characterized by mucosal inflammation with eosinophils. Diagnosis is based on the histological finding of at least 15 eosinophils per high power field in esophageal biopsy specimens from upper gastrointestinal endoscopies. These endoscopies are usually performed in the setting of esophageal dysfunction, however, EoE can occasionally be incidentally diagnosed during endoscopies performed for other indications like coeliac disease. The eosinophilia is in the absence of other causes of esophageal eosinophilia (e.g., parasitic infection, esophageal leiomyomatosis or Crohn's disease). Presentation can be wide ranging and often varies according to age. Infants and younger children can present with choking/gagging, feed refusal, failure to thrive, irritability and vomiting. Older children and adults commonly present with dysphagia, chest pain or food bolus obstruction. EoE was first described in the 1970s, but was only recognized as a distinct disease entity in the 1990s. It has been rising in incidence and prevalence, with reported prevalence ranging between 1 in 2,500 and 1 in 10,000. Although the diagnosis of EoE is dependent on clear histopathologic diagnostic criteria, there is a disconnect between the degree of esophageal eosinophilia and symptom severity especially that of reported dysphagia. Multiple anatomical changes can be seen in the spectrum of presentations of EoE which explain dysphagia, including isolated strictures, diffuse trachealisation, fixed rings, including Schatzki, as well as tissue remodeling and fibrotic changes. However, a majority of EoE patients do not have any of these findings and will still often report ongoing dysphagia. Some will report ongoing dysphagia despite histological remission. This suggests an underlying esophageal dysmotilty which cannot be assessed with endoscopy or correlated with histological changes seen in biopsies. This review will describe the types of motor disturbances seen and their prevalence, the pathophysiological basis of dysmotility seen in EoE, how best to investigate esophageal dysfunction in EoE and the role of manometry in the management of EoE.

Abstract P1-02-09: Results of a worldwide survey on the currently used histopathological diagnostic criteria for invasive lobular breast cancer (ILC)

Abstract Background. ILC represents the second most common histological type of breast cancer (BC), accounting for approximately 15% of all invasive BCs. Loss of cell-cell adhesion due to genomic alterations of CDH1,. the gene coding for E-cadherin, is the hallmark of ILC. So far, in the WHO guidelines, it is essential to recognize the dispersed or linear discohesive cells but it is not mandatory to demonstrate E-cadherin loss by immunohistochemistry (IHC) for diagnosing ILC. Recent central pathology revisions of clinical trials have demonstrated overdiagnosis of ILC in local pathological diagnosis, as only ~60% of the locally diagnosed ILCs were confirmed by central pathology. To understand the possible underlying reasons, we undertook a worldwide survey on the currently used histopathological diagnostic criteria for ILC. Materials and Methods. A survey was drafted using the online tool SurveyMonkey by a panel of pathologists and researchers from the European Lobular Breast Cancer Consortium (ELBCC). This survey was circulated to pathologists from December 14, 2020 until July, 1 2021. The main goals were to register the use of E-cadherin as a diagnostic marker for ILC and the systematic reporting of the ILC subtypes. Results. A total of 149 entries were recorded from 34 different countries from 6 continents. Pathologists declared working in a large tertiary (30%, 44/149) or university hospital (56%, 84/149), with an average yearly volume of BC samples >300 in 111/149 (74%) and >500 in 80/149 (54%) respondents. 117/149 (79%) are specialized in breast pathology. About half of the pathologists systematically perform IHC for ILC diagnosis (52%, 77/149), whilst others only perform staining in case of doubt (43%, 64/149) or for differentiating DCIS from LCIS (3%, 4/149). There was no association between the systematic use of IHC, the volume of BC samples, the type of institution (academic, large tertiary, private), and the number of pathologists in the institution. Concerning the use of IHC, 141/145(97%) participants use E-cadherin, 35/145 (24%) use β-catenin and 49/145 (34%) use p120-catenin. The majority (50%, 73/145) uses only E-cadherin, 13% (19/145) use E-cadherin in combination with β-catenin or 23% (33/145) use E-cadherin with p120-catenin, while 11% (16/145) use all 3 antibodies. For E-cadherin, 11 different clones were reported, of which the NCH-38 is the most frequently used (45%, 39/86), followed by Clone 36 (17%, 15/86) and EP700Y (16%, 14/86). Heterogeneity is reported regarding the used concentration per clone. The most frequently used modality of antigen retrieval is the heat induced one. Similar findings were observed for β-catenin and p120-catenin with each 4 different clones reported, again with variable concentrations. Only 4/104 (4%) respondents reported to perform DNA sequencing for CDH1 for diagnosing ILC. Most special lobular types are systematically reported by the vast majority of the pathologists: classic (149/149, 100%), pleomorphic (140/149, 94%), solid (108/149, 72%), histiocytoid/apocrine (90/149, 60%), alveolar (90/149, 60%), trabecular (54/149, 36%), mixed non-classic (54/149, 36%) and mucinous (51/149, 34%). Conclusions. We report the results of the first worldwide survey concerning diagnosis of ILC in pathological practice. The results demonstrate that ~half of the institutions systematically perform E-cadherin IHC to support the diagnosis of ILC. There is a great variability in E-cadherin antibody clones used as well as their concentrations, which might result in differences in staining results and their interpretation. As ILC-specific therapeutic avenues are currently being explored, some of which already in the context of clinical trials, it is of utmost importance to further improve the standardization of ILC diagnosis at the pathology level. Citation Format: Maxim De Schepper, Anne Vincent-Salomon, Matthias Christgen, Karen Van Baelen, Hitoshi Tsuda, Sasagu Kurozumi, Maria Jose Brito, Gabor Cserni, Stuart Schnitt, Denis Larsimont, Janina Kulka, Pedro Luis Fernandez, Paula Rodriguez, Ana Aula, Cristina Mendelez, Mieke Van Bockstal, Aniko Kovacs, Zsuzsanna Varga, Jelle Wesseling, Rohit Bhargava, Pia Boström, Camille Franchet, Blessing Zambuko, Gustavo Matute, Anca Berghian, Paul van Diest, Steffi Oesterreich, Patrick WB Derksen, Giuseppe Floris, Christine Desmedt. Results of a worldwide survey on the currently used histopathological diagnostic criteria for invasive lobular breast cancer (ILC) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P1-02-09.

Oral lichenoid contact lesions related to dental metal allergy may resolve after allergen removal

Background/ purposeDistinguishing oral lichenoid contact lesions (OLCLs) from oral lichen planus (OLP) is challenging. This study aimed to identify clinicopathological findings to distinguish OLCLs from OLP, and to evaluate the effectiveness of removing metal allergens in the treatment of OLCLs. Materials and methodsThis study retrospectively evaluated 30 patients diagnosed with OLCLs, and 30 age- and sex-matched OLP patients. We also evaluated the effectiveness of removing dental metal containing positive metal allergen, confirmed by skin patch test and metal component analysis in patients with OLCLs. ResultsPalladium and gold were the most common patch test-positive metals observed in the oral cavity of patients with OLCLs. The patients with OLCLs were more likely to present with white type lesions in the buccal mucosa and gingiva than were the patients with OLP (p = 0.030, 0.009, respectively). Overall, 50.0% of patients with OLCLs failed to meet the histopathological diagnostic criteria of OLP. Twenty-three of 24 (95.8%) patients with OLCLs showed a complete or partial improvement after the removal of dental metal. ConclusionThe present findings suggest the importance of a skin patch test and metal component analysis to confirm suspected OLCLs related to dental metal allergy, as these lesions may improve with the removal of the allergy-inducing metal.

Combining FORGE Score and Histopathological Diagnostic Criteria of Atypical Meningioma Enables Risk Stratification of Tumor Progression.

More than 50% of atypical meningiomas regrow within 5 years after surgery. FORGE score is a newly created tool to estimate the MIB-1 index in cranial meningiomas. In this investigation, we aimed to assess the predictive value of the FORGE score in combination with major diagnostic criteria of atypical meningioma (brain invasion, mitotic count ≥ 4) regarding recurrence in atypical meningiomas. We included patients operated on primary atypical meningiomas in our center from 2011 to 2019. The study included 71 patients (58% women, median age 63 years). ROC curves revealed a superiority of FORGE score combined with histopathological diagnostic criteria of atypical meningioma (AT-FORGE) in the prediction of tumor progression compared to FORGE score only (AUC: 0.72; 95% CI: 0.54–0.91, cut-off: ≥5/<5, sensitivity: 75%, specificity: 78%). Patients with an AT-FORGE score ≥ 5 had a shorter time to tumor progression (32.8 vs. 71.4 months, p < 0.001) in the univariable analysis. Multivariable cox regression analysis revealed significant predictive value of Simpson grade > II, presence of multiple meningiomas and AT-FORGE score ≥ 5 for tumor progression. The combination of histopathological diagnostic criteria for atypical meningioma with FORGE score might facilitate an effective identification of patients with an atypical meningioma who have an increased risk of tumor progression.

Failure of placental detachment in accreta placentation is associated with excessive fibrinoid deposition at the utero-placental interface

The main histopathologic diagnostic criteria for the diagnosis of placenta accreta for more than 80 years has been the finding of a direct attachment of the villous tissue to the superficial myometrium or adjacent to myometrial fibers without interposing decidua. There have been very few detailed histopathologic studies in pregnancies complicated by placenta accreta spectrum disorders and our understanding of the pathophysiology of the condition remains limited. To prospectively evaluate the microscopic changes used in grading and to identify changes that might explain the abnormal placental tissue attachment. A total of 40 consecutive cesarean delivery hysterectomy specimens for placenta previa accreta at 32 to 37 weeks of gestation with at least 1 histologic slide showing deeply implanted villi were analyzed. Prenatal ultrasound examination included placental location, myometrial thickness, subplacental vascularity and lacunae. Macroscopic changes of the lower segment were recorded during surgery and areas of abnormal placental adherence were sampled for histology. In addition, 7 hysterectomy specimens with placenta in-situ from the Boyd Collection at 20.5 to 32.5 weeks were used as controls. All 40 patients had a history of at least 2 previous cesarean deliveries and presented with a mainly anterior placenta previa. Of note, 37 (92.5%) cases presented with increased subplacental vascularity, 31 (77.5%) cases with myometrial thinning and all with lacunae. Furthermore, 20 (50%) cases presented with subplacental hypervascularity, lacunae score of >3, and lacunae feeder vessels. Intraoperative findings included anterior lower segment wall increased vascularization in 36 (90.0%) cases and extended area of dehiscence in 18 (45.0%) cases. Immediate gross examination of hysterectomy specimens showed an abnormally attached areas involving up to 30% of the basal plate, starting at <2 cm from the dehiscence area in all cases. Histologic examination found deeply implanted villi in 86 (53.8%) samples with only 17 (10.6%) samples presenting with villous tissue reaching at least half the uterine wall thickness. There were no villi crossing the entire thickness of the uterine wall. There was microscopic evidence of myometrial scarification in all cases. Dense fibrinoid deposits, 0.5 to 2 mm thick, were found at the utero-placental interface in 119 (74.4%) of the 160 samples between the anchoring villi and the underlying uterine wall at the accreta areas and around all deeply implanted villi. In the control group, the Nitabuch stria and basal plate became discontinuous with advancing gestation and there was no evidence of fibrinoid deposition at these sites. Samples from accreta areas at delivery present with a thick fibrinoid deposition at the utero-placental interface on microscopic examination independently of deeply implanted villous tissue in the sample. These changes are associated with distortion of the Nitabuch membrane and might explain the loss of parts of the physiological site of detachment of the placenta from the uterine wall in placenta accreta spectrum. These findings indicate that accreta placentation is more than direct attachment of the villous tissue to the superficial myometrium and support the concept that accreta villous tissue is not truly invasive.