ABSTRACT
Familial endocrine tumor syndromes are continuously expanding owing to the growing role of genetic testing in routine clinical practice. Pathologists are usually the first on the clinical team to encounter these syndromes at their initial presentation; thus, recognizing them is becoming more pivotal in routine pathology practice to help in properly planning management and further family testing. Our increasing knowledge about them is reflected in the newer syndromes included in the new World Health Organization classification and in the evolving discovery of new endocrine tumors and new familial associations. In many of these syndromes, the clinical features and co-occurrence of multiple neoplasia are the only clues (multiple endocrine neoplasia syndromes). In other syndromes, specific morphologic findings (pituitary blastoma and DICER1 syndrome, cribriform morular thyroid carcinoma, and AFP syndrome) and available ancillary studies (SDHB in SDH-deficient tumor syndromes) can aid pathologists. The aim of this review is to provide a primer on recent updates on familial endocrine tumor syndromes and related tumors, focusing on recent classification changes or tumor syndromes where a clearer role for pathologists is at play.
Subject(s)
Multiple Endocrine Neoplasia , Neoplastic Syndromes, Hereditary , Humans , Neoplastic Syndromes, Hereditary/diagnosis , Neoplastic Syndromes, Hereditary/genetics , Neoplastic Syndromes, Hereditary/pathology , Multiple Endocrine Neoplasia/genetics , Ribonuclease III , DEAD-box RNA HelicasesABSTRACT
Poorly differentiated malignant neoplasms involving the gynecologic tract routinely include a poorly differentiated endometrial carcinoma (EC) in the differential diagnosis. Some nuclear lineage/site-specific immunohistochemical markers are utilized in this diagnostic setting including SATB2, cyclin D1, SALL4, and BCOR, but their specificity and use in small samples are not clear across the spectrum of ECs. Cases of undifferentiated/dedifferentiated endometrial carcinomas (UEC/DDEC), clear cell carcinoma (CCC), uterine serous carcinoma (USC), FIGO grade 3 endometrial endometrioid carcinoma (EEC), and uterine carcinosarcoma (UCS) were identified and diagnoses confirmed. Whole-section immunohistochemical stains for SATB2, cyclin D1, SALL4, BCOR, and PAX8 were performed. A total of 113 cases were utilized: 15 CCC, 26 EEC, 19 UCS, 22 USC, and 31 UEC/DDEC. Cases were distributed across both low (49%) and high (51%) FIGO clinical stages. SATB2 was expressed by UCS (8/19, 42%), EEC (10/26, 38%), UEC/DDEC (11/30, 37%), and USC (6/22, 27%). Cyclin D1 was expressed by EEC (24/26, 92%), USC (17/22, 77%), UEC/DDEC (15/20 EEC component, 75%; 22/30 UEC, 73%), UCS (10/16 carcinoma, 63%; 11/19 sarcoma, 58%), and CCC (8/15, 53%). SALL4 was expressed most frequently by UEC/DDEC (12/30, 40%), but also USC (7/22, 32%), EEC (5/26, 19%), and UCS (4/16 carcinoma, 25%; 3/19 sarcoma, 16%). BCOR was expressed at low levels in 2 USC, 2 UEC/DDEC, and 2 UCS. PAX8 was generally positive but showed lower expression in UEC/DDEC (17/30, 57%) and in the sarcomatous portions of UCS (6/19, 32%). SATB2, cyclin D1, SALL4, and BCOR stain variable numbers of poorly-differentiated EC and must be carefully interpreted within morphologic and clinical context.
Subject(s)
Endometrial Neoplasms , Matrix Attachment Region Binding Proteins , Uterine Neoplasms , Female , Humans , Carcinoma, Endometrioid/genetics , Carcinoma, Endometrioid/pathology , Cyclin D1 , Endometrial Neoplasms/genetics , Endometrial Neoplasms/pathology , Proto-Oncogene Proteins , Repressor Proteins , Sarcoma , Transcription Factors/metabolism , Uterine Neoplasms/genetics , Uterine Neoplasms/pathologySubject(s)
Common Variable Immunodeficiency , Fever , Liver Diseases , Liver , Splenomegaly , Aged , Humans , Male , Anti-Bacterial Agents/therapeutic use , Bacterial Infections/diagnosis , Bacterial Infections/drug therapy , Bacterial Infections/etiology , Bone Marrow/pathology , Common Variable Immunodeficiency/complications , Common Variable Immunodeficiency/diagnosis , Common Variable Immunodeficiency/therapy , Diagnosis, Differential , Digestive System Diseases/diagnosis , Digestive System Diseases/diagnostic imaging , Digestive System Diseases/drug therapy , Digestive System Diseases/etiology , Disease Progression , Fever/etiology , Granuloma/diagnostic imaging , Granuloma/drug therapy , Granuloma/etiology , Liver/pathology , Liver/diagnostic imaging , Liver Diseases/diagnostic imaging , Liver Diseases/drug therapy , Liver Diseases/etiology , Liver Neoplasms/pathology , Magnetic Resonance Imaging , Multiple Pulmonary Nodules/diagnostic imaging , Multiple Pulmonary Nodules/drug therapy , Multiple Pulmonary Nodules/etiology , Recurrence , Relapsing Fever/diagnosis , Relapsing Fever/drug therapy , Relapsing Fever/etiology , Splenomegaly/diagnostic imaging , Splenomegaly/drug therapy , Splenomegaly/etiology , Tomography, X-Ray ComputedABSTRACT
Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus with >90% of the adult population worldwide harbouring latent infection. A small subset of those infected develop EBV-associated neoplasms, including a range of lymphoproliferative disorders (LPD). The diagnostic distinction of these entities appears increasingly relevant as our understanding of EBV-host interactions and mechanisms of EBV-driven lymphomagenesis improves. EBV may lower the mutational threshold for malignant transformation, create potential vulnerabilities related to viral alteration of cell metabolism and allow for improved immune targeting. However, these tumours may escape immune surveillance by affecting their immune microenvironment, limiting viral gene expression or potential loss of the viral episome. Methods to manipulate the latency state of the virus to enhance immunogenicity are emerging as well as the potential to detect so-called 'hit and run' cases where EBV has been lost. Finally, measurement of EBV DNA remains an important biomarker for screening and monitoring of LPD. Methods to distinguish EBV DNA derived from virions during lytic activation from latent, methylated EBV DNA present in EBV-associated neoplasms may broaden the utility of this testing, particularly in patients with compromised immune function. We highlight some of these emerging areas relevant to the diagnosis and treatment of EBV-associated LPD with potential applicability to other EBV-associated neoplasms.
Subject(s)
Epstein-Barr Virus Infections/complications , Lymphoproliferative Disorders/virology , Humans , Lymphoproliferative Disorders/diagnosis , Lymphoproliferative Disorders/therapyABSTRACT
ABSTRACT: Mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase pathway activation has recently been found to be associated with almost all Langerhans cell histiocytosis cases. In BRAF V600E mutation-positive cases, this activation is seen as a downstream activation. In addition, cyclin D1 is a downstream target of the MAPK pathway. Recent studies have argued in favor of using cyclin D1 as a potential neoplastic marker to differentiate Langerhans cell histiocytosis from other reactive Langerhans cell proliferations in the skin and lymph nodes. Therefore, we chose to study the immunohistochemical expression of cyclin D1 in cutaneous xanthogranuloma (XG) cases. Fifteen XG cases were retrieved and stained for cyclin D1, BRAF (v-raf murine sarcoma viral oncogene homolog B1), CD1a, and langerin (CD207). Twelve cases showed strong and diffuse nuclear positivity for cyclin D1, both in the XG cells and in the multinucleated osteoclast-like giant cells. Three cases showed focal weak nuclear staining for cyclin D1. All 15 cases showed negative immunoreactivity for BRAF, CD1a, and CD207. Although limited by small sample size, we conclude that most cases of cutaneous XG should show at least weak nuclear staining with cyclin D1. The histogenesis of XG is still largely unknown, and the finding of cyclin D1 positivity in a majority of cases may indicate a role for the MAPK/extracellular signal-regulated kinase pathway in cutaneous XG.
Subject(s)
Cyclin D1/metabolism , Skin Diseases/pathology , Xanthogranuloma, Juvenile/pathology , Adult , Aged , Aged, 80 and over , Biomarkers/analysis , Biomarkers/metabolism , Cyclin D1/analysis , Female , Humans , Immunohistochemistry , Male , Middle AgedABSTRACT
CDC73 alterations are associated with three main parathyroid lesions according to the World Health Organization (WHO) classification of tumors of the endocrine system. These include hyperparathyroidism-jaw tumor (HPT-JT) syndrome-associated adenomas, atypical parathyroid tumors (APTs), and parathyroid carcinomas (PCs). The loss of nuclear parafibromin expression, which serves as a surrogate marker for the underlying CDC73 alteration, encompasses these tumors under the term parafibromin-deficient parathyroid tumors. They have distinct morphologic features of more abundant eosinophilic cytoplasm with perinuclear clearing surrounding a large nucleus as well as prominent dilated branching "hemangiopericytoma-like" vasculature and a thick capsule as well as variably sized cystic spaces. These tumors include cases that show unequivocal histologic features fulfilling the criteria for PCs with growing data indicating a higher rate of recurrence or metastasis compared with parafibromin intact PCs. More importantly, the loss of parafibromin expression can be used in clinical practice to recognize APTs that fall short of a conclusive diagnosis of PCs, but clinically behave akin to them. Moreover, recognizing these tumors can lead to an underlying germline mutation and a diagnosis of HPT-JT, which impacts long-term treatment and surveillance for patients and close family.
Subject(s)
Hyperparathyroidism , Jaw Neoplasms , Neoplastic Syndromes, Hereditary , Parathyroid Neoplasms , Humans , Parathyroid Neoplasms/diagnosis , Parathyroid Neoplasms/genetics , Parathyroid Neoplasms/pathology , Tumor Suppressor Proteins/genetics , Tumor Suppressor Proteins/metabolism , Hyperparathyroidism/pathology , Jaw Neoplasms/diagnosis , Jaw Neoplasms/genetics , Neoplastic Syndromes, Hereditary/complications , Transcription FactorsABSTRACT
Background: Since the noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTPs) was introduced in 2016, most retrospective studies have included cases diagnosed as encapsulated follicular variant of papillary thyroid carcinoma. We investigate a cohort diagnosed with NIFTP at resection. Methods: Retrospective institutional cohort of NIFTP from 2016 to 2022, including clinical, cytological, and molecular data for 319 cases (6.6% of thyroid surgeries, 183 cases as NIFTP-only). Results: The patient cohort had unifocal or multifocal thyroid nodules. Female:male ratio was 2.7:1, mean age was 52 years and median NIFTP size was 2.1 cm. NIFTP was associated with multiple nodules in 23% patients (n = 73) and 12% of NIFTP were multifocal (n = 39). Fine needle aspiration (FNA) of NIFTP (n = 255) were designated as nondiagnostic = 5%, benign = 13%, atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) = 49%, follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) = 17%, suspicious for malignancy = 12%, or malignant = 4%. Molecular alterations were identified in 93% (n = 114), RAS or RAS-like. Thyroid Imaging Reporting and Data System (TI-RADS) score 4 was recorded in 50% of NIFTP, followed by scores 3 and 5 (26% and 20%, respectively). We also investigated the factors associated with extent of surgery. In our NIFTP-only group (n = 183), 66% were identified after hemithyroidectomy (HT) and 34% after total thyroidectomy (TT). On univariate analysis, TT patients demonstrated higher Bethesda category by FNA, more often had aberrant preoperative thyroid function, and/or underwent an FNA of additional nodule(s). With multivariable regression, Bethesda V NIFTP, in the presence of other nodules being evaluated by FNA and aberrant preoperative thyroid function, independently predicts TT. Bethesda II NIFTP correlated significantly with HT. Fifty-two patients (28%) with NIFTP-only had at least one postoperative surveillance ultrasound. In the NIFTP-only cohort, no HT patients had completion thyroidectomy or received postoperative radioactive iodine. No recurrence or metastases were recorded with median follow-up of 35 months (6-76 months; n = 120). Conclusions: Given this large cohort of NIFTP, including a large subset of isolated NIFTP-only, some with >6 years of follow-up and no tumor recurrences, consensus practical guidelines are needed for adequate postoperative management. Given the American Thyroid Association (ATA) provides guidelines for management of low-risk malignancies, guidance regarding that for borderline/biologically uncertain tumors, including NIFTP, is a reasonable next step.
Subject(s)
Adenocarcinoma, Follicular , Thyroid Neoplasms , Humans , Male , Female , Middle Aged , Thyroid Neoplasms/diagnosis , Thyroid Neoplasms/surgery , Thyroid Neoplasms/pathology , Adenocarcinoma, Follicular/diagnosis , Adenocarcinoma, Follicular/surgery , Adenocarcinoma, Follicular/pathology , Retrospective Studies , Iodine Radioisotopes , Neoplasm Recurrence, LocalABSTRACT
Importance: Lip, oral, and pharyngeal cancers are important contributors to cancer burden worldwide, and a comprehensive evaluation of their burden globally, regionally, and nationally is crucial for effective policy planning. Objective: To analyze the total and risk-attributable burden of lip and oral cavity cancer (LOC) and other pharyngeal cancer (OPC) for 204 countries and territories and by Socio-demographic Index (SDI) using 2019 Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study estimates. Evidence Review: The incidence, mortality, and disability-adjusted life years (DALYs) due to LOC and OPC from 1990 to 2019 were estimated using GBD 2019 methods. The GBD 2019 comparative risk assessment framework was used to estimate the proportion of deaths and DALYs for LOC and OPC attributable to smoking, tobacco, and alcohol consumption in 2019. Findings: In 2019, 370â¯000 (95% uncertainty interval [UI], 338â¯000-401â¯000) cases and 199â¯000 (95% UI, 181â¯000-217â¯000) deaths for LOC and 167â¯000 (95% UI, 153â¯000-180â¯000) cases and 114â¯000 (95% UI, 103â¯000-126â¯000) deaths for OPC were estimated to occur globally, contributing 5.5 million (95% UI, 5.0-6.0 million) and 3.2 million (95% UI, 2.9-3.6 million) DALYs, respectively. From 1990 to 2019, low-middle and low SDI regions consistently showed the highest age-standardized mortality rates due to LOC and OPC, while the high SDI strata exhibited age-standardized incidence rates decreasing for LOC and increasing for OPC. Globally in 2019, smoking had the greatest contribution to risk-attributable OPC deaths for both sexes (55.8% [95% UI, 49.2%-62.0%] of all OPC deaths in male individuals and 17.4% [95% UI, 13.8%-21.2%] of all OPC deaths in female individuals). Smoking and alcohol both contributed to substantial LOC deaths globally among male individuals (42.3% [95% UI, 35.2%-48.6%] and 40.2% [95% UI, 33.3%-46.8%] of all risk-attributable cancer deaths, respectively), while chewing tobacco contributed to the greatest attributable LOC deaths among female individuals (27.6% [95% UI, 21.5%-33.8%]), driven by high risk-attributable burden in South and Southeast Asia. Conclusions and Relevance: In this systematic analysis, disparities in LOC and OPC burden existed across the SDI spectrum, and a considerable percentage of burden was attributable to tobacco and alcohol use. These estimates can contribute to an understanding of the distribution and disparities in LOC and OPC burden globally and support cancer control planning efforts.
Subject(s)
Global Burden of Disease , Pharyngeal Neoplasms , Adult , Female , Humans , Male , Global Health , Incidence , Lip , Pharyngeal Neoplasms/epidemiology , Quality-Adjusted Life Years , Risk Factors , Tobacco Use/epidemiologyABSTRACT
There is limited literature detailing the histology of pharyngeal papillomas. Herein, we report our experience with papillomas occurring in the oro-and nasopharynx that have both squamous and respiratory features akin to the sinonasal Schneiderian papilloma. We retrospectively reviewed pharyngeal papillomas that were composed of both squamous and respiratory epithelium received at our institution between 2010 and 2020. Cases of sinonasal papillomas directly extending into the pharynx were excluded. Immunohistochemistry for p16 as well as RNA in situ hybridization to evaluate for 6 low-risk and 18 high-risk HPV genotypes were performed on all cases. Thirteen cases were included. Mean age was 61 with 12 males and 1 female. While often incidentally found, presenting symptoms included globus sensation, hemoptysis, and hoarseness of voice. Histologically, all tumors consisted of squamous and respiratory epithelium with neutrophilic infiltrates arranged in an exophytic/papillary architecture that was reminiscent of the exophytic type of Schneiderian papilloma. Immunohistochemistry for p16 was negative in all papillomas. 85% were positive for low-risk human papillomavirus (HPV) subtypes and all were negative for high-risk HPV subtypes. A well-differentiated, invasive squamous cell carcinoma was associated with two of the cases. Papillomas with squamous and respiratory features similar to the sinonasal exophytic Schneiderian papilloma can arise in the oro- and nasopharynx and like their sinonasal counterparts show an association with HPV. While many in this series were benign, they can be harbingers for invasive squamous cell carcinoma.
Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Nasopharyngeal Neoplasms , Papilloma , Papillomavirus Infections , Carcinoma, Squamous Cell/pathology , Female , Head and Neck Neoplasms/complications , Humans , Male , Middle Aged , Nasopharyngeal Neoplasms/complications , Papilloma/pathology , Papillomaviridae/genetics , Pharynx/pathology , Retrospective StudiesABSTRACT
Non-bacterial thrombotic endocarditis (NBTE), also known as Libman-Sacks, marantic, thrombotic, or verrucous endocarditis, is a form of non-infective endocarditis that affects cardiac structures in patients who have predisposing underlying conditions.1 As it is rarely encountered in routine clinical practice, the condition may be overlooked or misdiagnosed. On the other hand, other similar clinical entities might be erroneously labeled as NBTE. Notwithstanding its ostensibly uncommon appearance in clinical practice, our understanding of NBTE has been expanding, especially with the advent of modern and advanced diagnostic tools that facilitate the evaluation process. Herein, we provide a comprehensive review of NBTE, with a focus on the contemporary diagnostic evaluation and management.
Subject(s)
Endocarditis, Non-Infective , Endocarditis , Thrombosis , Humans , Endocarditis, Non-Infective/diagnostic imaging , Endocarditis, Non-Infective/etiology , Endocarditis/diagnosis , Endocarditis/therapy , Thrombosis/diagnostic imaging , Thrombosis/etiologyABSTRACT
BACKGROUND: Investing in children's early years can have a lasting positive effect, such as better academic outcomes throughout their school careers. In Jordan, investments have been made in early childhood development and early childhood care and education to improve children's school readiness. School readiness comprises a range of abilities needed to succeed in school, including physical, emotional, social, and cognitive skills. To measure the impact of these investments on children's school readiness, Jordan has been implementing the Early Development Instrument (EDI), a population-level, teacher-completed checklist of children's school readiness, assessing children's development in five main areas, referred to as domains. METHODS: The goal of the current study was to examine the psychometric properties of the Arabic version of the EDI, using data collected in 2018 on a sample of 5952 children in Jordan. The EDI was translated from the original English version to Arabic and adapted for use in Jordan. We conducted a categorical confirmatory factor analysis (CFA) for each of the five domains of the EDI and examined the reliability of the domains and subdomains using Cronbach's alpha reliability coefficient. RESULTS: With few exceptions, the study results are in line with those of the analysis of the psychometric properties found with the original, Canadian English version of the EDI in a population of Canadian children. Results of CFAs demonstrated, for the most part, good model fits. Internal consistency indices of the domains ranged from 0.60 for physical health and well-being to 0.96 for social competence. For the subdomains, they ranged from 0.26 to 0.94. CONCLUSIONS: Our results provide empirical support for the adaptation of the EDI for population monitoring of school readiness in Jordan. Validation of the Arabic adaptation opens up the possibility of assessing school readiness of young children in Jordan in comparison to the many other countries that have successfully adapted and applied the EDI.
Subject(s)
Child Development , Humans , Child , Child, Preschool , Psychometrics , Jordan , Reproducibility of Results , Canada , Surveys and QuestionnairesABSTRACT
Preformed donor-specific antibodies are associated with a higher risk of rejection and worse graft survival in organ transplantation. However, in heart transplantation, the risk and benefit balance between high mortality on the waiting list and graft survival may allow the acceptance of higher immunologic risk donors in broadly sensitized recipients. Transplanting donor-recipient pairs with a positive complement dependent cytotoxic (CDC) crossmatch carries the highest risk of hyperacute rejection and immediate graft loss and is usually avoided in kidney transplantation. Herein we report the first successful simultaneous heart-kidney transplant with a T- and B-cell CDC crossmatch positive donor using a combination of rituximab, intravenous immunoglobulin, plasmapheresis, bortezomib and rabbit anti-thymocyte globulin induction followed by eculizumab therapy for two months post-transplant. In the year following transplantation, both allografts maintained stable graft function (all echocardiographic left ventricular ejection fractions ≥ 65%, eGFR>60) and showed no histologic evidence of antibody-mediated rejection. In addition, the patient has not developed any severe infections including cytomegalovirus or BK virus infection. In conclusion, a multitarget immunosuppressive regimen can allow for combined heart/kidney transplantation across positive CDC crossmatches without evidence of antibody-mediated rejection or significant infection. Longer follow-up will be needed to further support this conclusion.
ABSTRACT
IMPORTANCE: The Global Burden of Diseases, Injuries, and Risk Factors Study 2019 (GBD 2019) provided systematic estimates of incidence, morbidity, and mortality to inform local and international efforts toward reducing cancer burden. OBJECTIVE: To estimate cancer burden and trends globally for 204 countries and territories and by Sociodemographic Index (SDI) quintiles from 2010 to 2019. EVIDENCE REVIEW: The GBD 2019 estimation methods were used to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life years (DALYs) in 2019 and over the past decade. Estimates are also provided by quintiles of the SDI, a composite measure of educational attainment, income per capita, and total fertility rate for those younger than 25 years. Estimates include 95% uncertainty intervals (UIs). FINDINGS: In 2019, there were an estimated 23.6 million (95% UI, 22.2-24.9 million) new cancer cases (17.2 million when excluding nonmelanoma skin cancer) and 10.0 million (95% UI, 9.36-10.6 million) cancer deaths globally, with an estimated 250 million (235-264 million) DALYs due to cancer. Since 2010, these represented a 26.3% (95% UI, 20.3%-32.3%) increase in new cases, a 20.9% (95% UI, 14.2%-27.6%) increase in deaths, and a 16.0% (95% UI, 9.3%-22.8%) increase in DALYs. Among 22 groups of diseases and injuries in the GBD 2019 study, cancer was second only to cardiovascular diseases for the number of deaths, years of life lost, and DALYs globally in 2019. Cancer burden differed across SDI quintiles. The proportion of years lived with disability that contributed to DALYs increased with SDI, ranging from 1.4% (1.1%-1.8%) in the low SDI quintile to 5.7% (4.2%-7.1%) in the high SDI quintile. While the high SDI quintile had the highest number of new cases in 2019, the middle SDI quintile had the highest number of cancer deaths and DALYs. From 2010 to 2019, the largest percentage increase in the numbers of cases and deaths occurred in the low and low-middle SDI quintiles. CONCLUSIONS AND RELEVANCE: The results of this systematic analysis suggest that the global burden of cancer is substantial and growing, with burden differing by SDI. These results provide comprehensive and comparable estimates that can potentially inform efforts toward equitable cancer control around the world.
Subject(s)
Global Burden of Disease , Neoplasms , Disability-Adjusted Life Years , Global Health , Humans , Incidence , Neoplasms/epidemiology , Prevalence , Quality-Adjusted Life Years , Risk FactorsABSTRACT
OBJECTIVES: Comparative assessments of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) molecular assays that have been operationalized through the US Food and Drug Administration's Emergency Use Authorization process are warranted to assess real-world performance. Characteristics such as sensitivity, specificity, and false-negative rate are important to inform clinical use. METHODS: We compared five SARS-CoV-2 assays using nasopharyngeal and nasal swab specimens submitted in transport media; we enriched this cohort for positive specimens, since we were particularly interested in the sensitivity and false-negative rate. Performance of each test was compared with a composite standard. RESULTS: The sensitivities and false-negative rates of the 239 specimens that met inclusion criteria were, respectively, as follows: Centers for Disease Control and Prevention 2019 nCoV Real-Time RT-PCR Diagnostic Panel, 100% and 0%; TIB MOLBIOL/Roche z 480 Assay, 96.5% and 3.5%; Xpert Xpress SARS-CoV-2 (Cepheid), 97.6% and 2.4%; Simplexa COVID-19 Direct Kit (DiaSorin), 88.1% and 11.9%; and ID Now COVID-19 (Abbott), 83.3% and 16.7%. CONCLUSIONS: The assays that included a nucleic acid extraction followed by reverse transcription polymerase chain reaction were more sensitive than assays that lacked a full extraction. Most false negatives were seen in patients with low viral loads, as extrapolated from crossing threshold values.
Subject(s)
COVID-19 Nucleic Acid Testing/methods , COVID-19/diagnosis , Adult , Aged , COVID-19 Nucleic Acid Testing/standards , Cohort Studies , False Negative Reactions , Female , Humans , Logistic Models , Male , Middle Aged , Sensitivity and SpecificityABSTRACT
Solitary fibrous tumor (SFT) is a mesenchymal tumor initially described in the pleura. When the tumor is located in the pleura and the classic histologic findings are present, the diagnosis of SFT can be straightforward. However, the cytologic diagnosis of perigastric SFT can be challenging due its rarity with only one cytology case report. Another confounding factor is its potential mimicry with other perigastric/gastric mesenchymal tumors. Herein, we report a case of perigastric SFT diagnosed on cytology in conjunction with immunohistochemical stains. The patient is a 79-year-old woman who presented with an enlarging perigastric mass on computerized tomography scan which was highly concerning for a saccular aneurysm. Endoscopic ultrasound (EUS) revealed a 6.6 cm hypoechoic lesion abutting the stomach. An EUS-guided fine needle aspiration was performed. The smears showed singly scattered to clusters of bland spindle cells with scant cytoplasm dispersed in a bloody background. The cell block showed similar spindle cells focally supported by a collagenized stroma. Immunohistochemical stains performed on the cell block showed the tumor cells were positive for CD34, BCL2, and STAT6 and negative for CD117, DOG1, CD31, ERG-ENDO, AE1/AE3, S-100, desmin, and synaptophysin, supporting the diagnosis of solitary fibrous tumor.
Subject(s)
Solitary Fibrous Tumors/diagnosis , Solitary Fibrous Tumors/pathology , Stomach Neoplasms/diagnosis , Stomach Neoplasms/pathology , Aged , Biomarkers, Tumor/metabolism , Biopsy, Fine-Needle/methods , Diagnosis, Differential , Female , Humans , Immunohistochemistry/methods , Solitary Fibrous Tumors/metabolism , Stomach Neoplasms/metabolismABSTRACT
BACKGROUND Immunoglobulin G4 (IgG4)-related disease is immune-mediated and was first proposed as a defined entity after studies on patients with autoimmune pancreatitis. Since then, it has been reported in many organs. Involvement of the ovaries is rare, and to our knowledge, only 2 cases have been reported in the literature. IgG4-related disease is associated with increased serum IgG4 levels. Organ involvement includes a lymphoplasmacytic infiltrate, fibrosis, and obliterative phlebitis, with immunohistochemistry showing IgG4-positive plasma cells. This report is of a case of IgG4-related disease involving the right ovary. CASE REPORT A 47-year-old woman presented with a right ovarian cyst. An ultrasound scan revealed a complex right ovarian cyst with multiple septations. The hormonal profile and tumor markers were unremarkable. Gross examination showed fragments of cyst wall. Histologic examination revealed a follicular cyst, surrounded by a dense lymphoplasmacytic infiltrate rich in eosinophils, partially obliterative phlebitis, and fibrosis. Immunohistochemically, IgG marked most of the plasma cells, of which 70% expressed IgG4, with a count >50 cells per high-power field. Subsequent testing of serum IgG4 showed that the level was elevated (330 mg/dL). A diagnosis of IgG4-related disease was made. CONCLUSIONS Ovarian involvement by IgG4-related disease is rarely described in the literature. Our patient is likely to be the third case. We believe that cumulative findings from our case along with the 2 already reported cases increase awareness and may establish a framework for building more objective criteria to define this entity in the ovaries, similar to what has been achieved in some other organs.
Subject(s)
Autoimmune Diseases , Immunoglobulin G4-Related Disease , Autoimmune Diseases/diagnosis , Female , Humans , Immunoglobulin G , Immunoglobulin G4-Related Disease/diagnosis , Middle Aged , Ovary , Plasma CellsABSTRACT
The classification of sinonasal adenocarcinoma (SNAC) is complex. The high-grade, non-intestinal SNAC group is particularly heterogeneous, with tumors showing widely variable morphology. SMARCB1 (INI-1)-deficient sinonasal carcinoma is a newly described, aggressive tumor that usually resembles sinonasal undifferentiated carcinoma (SNUC) or non-keratinizing squamous cell carcinoma; however, glandular differentiation has been rarely reported and this feature may be under-recognized. We present a dedicated series of 12 SMARCB1-deficient SNACs. All tumors had an oncocytoid/plasmacytoid cytomorphology with variable degrees of glandular differentiation consisting of tubules and cribriform structures with foci of intracellular or intraluminal mucin. Three of 12 tumors exhibited foci of yolk sac tumor-like histologic features. The tumors were uniformly high-grade, with nuclear pleomorphism, elevated mitotic rates and frequent necrosis. By immunohistochemistry, all tumors were entirely SMARCB1-deficient, and 10 of 12 were CK7-positive. Occasional expression of CDX2 (4 of 12), CK20 (3 of 12), and p40 (3 of 10) was seen. Expression of yolk sac markers was variably present in tumors that harbored yolk sac-like areas but also tumors that did not: glypican-3 (10 of 11), SALL4 (6 of 11), HepPar-1 (4 of 11), PLAP (1 of 10), and AFP (1 of 11). SMARCB1-deficient sinonasal carcinoma, particularly the oncocytoid/plasmacytoid form, can demonstrate variable degrees of glandular differentiation. This unexpected morphology combined with variable immunohistochemical results may lead to misdiagnoses of high-grade intestinal or non-intestinal SNAC, myoepithelial carcinoma, or even yolk sac tumor or metastatic hepatocellular carcinoma.
Subject(s)
Adenocarcinoma/pathology , Paranasal Sinus Neoplasms/pathology , SMARCB1 Protein/deficiency , Adult , Aged , Aged, 80 and over , Biomarkers, Tumor/analysis , Endodermal Sinus Tumor/pathology , Female , Humans , Male , Middle Aged , Paranasal Sinuses/pathology , Young AdultABSTRACT
BACKGROUND: Glioblastoma is a highly malignant brain tumour that usually leads to death. Several studies have reported a link between the distribution of ABO blood group antigens and a risk of developing specific types of cancer, although no consensus has been reached. This study aims to investigate the relationship between the distribution of ABO blood group antigens and the incidence of glioblastoma. MATERIALS AND METHODS: The study cohort consisted of 115 glioblastoma patients who were diagnosed at King Abdullah University Hospital, Jordan, between 2004 and 2015. Three different patient populations made up three control groups and these were selected from among patients at the same institution between 2014 and 2015 as follows: 3,847 healthy blood donors, 654 accidental trauma patients admitted to the Departments of Neurosurgery and Orthopaedics, and 230 age- and sex-matched control subjects recruited blindly from the Departments of Paediatrics and Internal Medicine. RESULTS: There was a significant association between the distribution of ABO blood group antigens and the incidence of glioblastoma. Post hoc residual analysis revealed that individuals with group A had a higher than expected chance of developing glioblastoma, while individuals with group O had a lower than expected chance. Furthermore, individuals with group A were found to be at a 1.62- to 2.28-fold increased risk of developing glioblastoma compared to individuals with group O. DISCUSSION: In the present study, we demonstrate that, in Jordan, individuals with group A have an increased risk of developing glioblastoma, while individuals with group O have a reduced risk. These findings suggest that the distribution of ABO blood group antigens is associated with a risk of brain tumours and may play an important role in their development. However, further clinical and experimental investigations are required to confirm this association.