Frequency of Thyroid Microcarcinoma in Patients Who Underwent Total Thyroidectomy with Benign Indication-A 5-Year Retrospective Review.

Background and Objectives: Incidental thyroid cancers (ITCs) are often microcarcinomas. The most frequent histologic type is a papillary microcarcinoma. Papillary thyroid microcarcinomas are defined as papillary thyroid tumours measuring less than 10 mm at their greatest diameter. They are clinically occult and frequently diagnosed incidentally in histopathology reports after a thyroidectomy. The aim of this study is to evaluate the rate of papillary thyroid microcarcinomas (PTMC) in patients who were thyroidectomised with indications of benign disease. Materials and Methods: We retrospectively evaluated the histological incidence of PTMC in 431 consecutive patients who, in a 5 year period, underwent a thyroidectomy with benign indications. Patients with benign histology and with known or suspected malignancy were excluded. Results: Histopathology reports from 540 patients who underwent a total thyroidectomy in our department between 2016 and 2021 were reviewed. A total of 431 patients were thyroidectomised for presumed benign thyroid disease. A total of 395 patients had confirmed benign thyroid disease in the final histopathology, while 36 patients had incidental malignant lesions (33 PTMC-7.67%, one multifocal PTC without microcarcinomas-0.23%, two follicular thyroid carcinoma-0.46%). Out of the PTMC patients, 29 were female and four were male (7.2:1 female-male ratio). The mean age was 54.2 years old. A total of 24 out of 33 patients had multifocal lesions, 11 of which co-existed with macro PTC. Nine patients had unifocal lesions. A total of 21 of these patients were initially operated on for multinodular goitre (64%), while 13 were operated on for Hashimoto/Lymphocytic thyroiditis (36%). Conclusions: PTMC-often multifocal-is not an uncommon, incidental finding after thyroidectomy for benign thyroid lesions (7.67% in our series) and often co-exists with other incidental malignant lesions (8.35% in our series). The possibility of an underlying papillary microcarcinoma should be taken into account in the management of patients with benign-especially nodular-thyroid disease, and total thyroidectomy should be considered.

Ten-year clinical outcome, toxicity and compliance of dose-dense sequential adjuvant administration of cyclophosphamide & epirubicin followed by docetaxel in patients with early breast cancer: A hellenic cooperative oncology group observational study (HE 10/10) with concurrent investigation of significance of tumor infiltrating lymphocytes.

BACKGROUND: Dose-dense sequential (dds) chemotherapy has changed the clinical outcome of patients with early breast cancer (BC). To investigate the impact of dose intensity (DI) in the adjuvant setting of BC, this observational trial (HE 10/10) was conducted assessing the long-term survival outcome, safety and toxicity of a currently widely used chemotherapeutic regimen. In addition, the prognostic significance of tumor infiltrating lymphocytes (TILs) and infiltrating CD8+ lymphocytes were also evaluated in the same cohort. PATIENTS AND METHODS: Totally, 1054 patients were prospectively enrolled in the current study with 1024 patients being eligible, while adequate tissue was available for 596 of them. TILs, CD8+ lymphocytes in intratumoral areas in contact with malignant cells (iCD8), CD8+ lymphocytes in tumor stroma (sCD8) as well as the total number of CD8+ lymphocytes within the tumor area (total CD8) were assessed by immunohistochemistry. RESULTS: Within a median follow-up of 125.18 months, a total of 200 disease-free survival (DFS) events (19.5%) were reported. Importantly, the 10-year DFS and OS rates were 78.4% (95% CI 75.0-81.5) and 81.7% (95% CI 79.0-84.1), respectively. Interestingly, higher CD8+ T cells as well as TILs in the tumor microenvironment were associated with an improved long-term survival outcome. CONCLUSIONS: In conclusion, this study confirms the significance of dds adjuvant chemotherapeutic regimen in terms of long-term survival outcome, safety and toxicity as well as the prognostic significance of TILs and infiltrating CD8+ lymphocytes in BC patients with early-stage disease.

Immunohistochemical Evidence Linking Interleukin-22 Tissue Expression Levels to FOXP3+ Cells and Neutrophil Densities in the Mycosis Fungoides Microenvironment.

BACKGROUND: Emerging data indicate that the cellular microenvironment and interleukins (IL) play a crucial role in mycosis fungoides (MF). We aimed to explore the potential association between the composition of the cellular microenvironment and the expression of IL-22 and IL-17A in MF skin lesions. METHODS: The study encompassed 16 cases of MF of different stages, for which sufficient skin tissue for immunohistochemistry and frozen tissue for reverse transcription-polymerase chain reaction, both taken from the same lesion, were available. Histological evaluation of eosinophils, neutrophils, CD20+, CD4+, CD8+, FOXP3+, CD56+, and CD1a+ cells was conducted. Additionally, mRNA expression levels of IL-22 and IL-17 mRNA were quantified using reverse transcription-quantitative polymerase chain reaction. SPSS version 28 (IBM Corp., Armonk, NY) was utilized for statistical analysis. RESULTS: Among the cases examined, three were in the patch stage, eight in the plaque stage, and five in the transformation to high-grade large cell lymphoma (t-LCL). B-lymphocytes, neutrophils, and eosinophils were primarily observed in t-LCL cases. IL-22 levels displayed a significant association with IL-17A levels (Pearson's r = 0.961, p < 0.001), FOXP3+ cells (Pearson's r = 0.851, p < 0.001), and neutrophil density (Pearson's r = 0.586, p = 0.014). No correlation was detected between IL-17A levels and the evaluated subtypes of microenvironmental cells. CONCLUSION: The microenvironment of MF lesions with t-LCL is noticeably different from early MF in terms of cellular composition. Histopathological identification of the cellular microenvironment may serve as an indicator of IL-22 tissue levels. These results implicate certain types of cells in IL-22 expression in the MF microenvironment and may contribute to advancing our knowledge on the pathogenesis and progression of the disease.

N-Glycosylation of the Ig Receptors Shapes the Antigen Reactivity in Chronic Lymphocytic Leukemia Subset #201.

Subset #201 is a clinically indolent subgroup of patients with chronic lymphocytic leukemia defined by the expression of stereotyped, mutated IGHV4-34/IGLV1-44 BCR Ig. Subset #201 is characterized by recurrent somatic hypermutations (SHMs) that frequently lead to the creation and/or disruption of N-glycosylation sites within the Ig H and L chain variable domains. To understand the relevance of this observation, using next-generation sequencing, we studied how SHM shapes the subclonal architecture of the BCR Ig repertoire in subset #201, particularly focusing on changes in N-glycosylation sites. Moreover, we profiled the Ag reactivity of the clonotypic BCR Ig expressed as rmAbs. We found that almost all analyzed cases from subset #201 carry SHMs potentially affecting N-glycosylation at the clonal and/or subclonal level and obtained evidence for N-glycan occupancy in SHM-induced novel N-glycosylation sites. These particular SHMs impact (auto)antigen recognition, as indicated by differences in Ag reactivity between the authentic rmAbs and germline revertants of SHMs introducing novel N-glycosylation sites in experiments entailing 1) flow cytometry for binding to viable cells, 2) immunohistochemistry against various human tissues, 3) ELISA against microbial Ags, and 4) protein microarrays testing reactivity against multiple autoantigens. On these grounds, N-glycosylation appears as relevant for the natural history of at least a fraction of Ig-mutated chronic lymphocytic leukemia. Moreover, subset #201 emerges as a paradigmatic case for the role of affinity maturation in the evolution of Ag reactivity of the clonotypic BCR Ig.

Orchidopexy for congenital cryptorchidism in childhood and adolescence and testicular cancer in adults: an updated systematic review and meta-analysis of observational studies.

Congenital cryptorchidism is a well-established risk factor of testicular malignancies. However, there is still remarkable variability in the measures of associations between of these two clinical entities. The current meta-analysis investigates the up-to-date risk of testicular cancer in adults with a history of surgically corrected congenital cryptorchidism until adolescence. The meta-analysis was conducted with strict criteria for the identification of the congenital cryptorchidism cases that underwent surgery before adulthood. The study was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search of the PubMed and the Scopus databases was conducted, using a defined strategy, from inception to February 2023. Two independent authors screened the literature and extracted the data, using inclusion and exclusion criteria. Of the 2176 articles identified, 93 articles were fully retrieved, and 6 articles met all the inclusion criteria. The Newcastle-Ottawa scale was applied for the studies' quality assessment. The random-effects model in RevMan 5.4 program was used for the meta-analysis. Three case-control studies and three cohort studies were selected. They included 371,681 patients and 1786 incidents of testicular cancer. The pooled odds ratio (OR) was 3.99 (95% confidence intervals (CI): 2.80-5.71). The heterogeneity was moderate and estimated at 51% with the I-squared statistic. A forest plot and a funnel plot were produced to evaluate the ORs and the probable publication bias, respectively. The mean Newcastle-Ottawa score was 8/9 for all the included reports.  Conclusion: This systematic review and meta-analysis verifies, with an updated estimate, the increased risk of testicular cancer in adults with an orchidopexy history. New evidence on the maldescent laterality supports that the cancer risk remains increased and for the contralateral, unaffected testicle, although to a lesser extent. The orchidopexy in the first year of life prevents the testicular damage and decreases the overall cancer risk. What is Known: • Congenital cryptorchidism is the commonest genitourinary abnormality and a risk factor for testicular cancer. • The most recent meta-analysis reporting this association was in 2013. What is New: • After reviewing literature until February 2023, the association of congenital cryptorchidism with testicular cancer risk in adulthood was verified: odds ratio=3.99 [2.80-5.71], 95% CI. • The meta-analysis highlights the protective role of early orchidopexy and the controversial data about maldescent and testicular cancer laterality.

Association between CD8+ Tumor Infiltrating Lymphocytes and the Clinical Outcome of Patients with Operable Breast Cancer Treated with Adjuvant Dose-Dense Chemotherapy-A 10 Year Follow-Up Report of a Hellenic Cooperative Oncology Group Observational Study.

Tumor-infiltrating lymphocytes (TILs) contribute to breast cancer (BC) prognosis. We investigated the prognostic impact of CD8+ TILs in patients with early breast cancer treated with adjuvant chemotherapy in a large observational clinical trial. Along with a 10 year follow-up, considering the efficacy and safety, we report the results of the translational part of our study. We examined the patients' tumors for total (t), stromal (s), and intratumoral (i) CD8 lymphocyte density (counts/mm2) on tissue-microarray cores. The impact of CD8+ TILs counts on DFS and OS, and its correlation with breast cancer subtypes and standard clinicopathological parameters, were investigated, along with efficacy and safety data. Among the 928 eligible patients, 627 had available CD8+ data. Of which, 24.9% had a high expression of sCD8, iCD8, and total CD8, which were correlated with higher Ki67, TILs density, ER/PgR negativity, and higher histological grade. The 5year DFS and OS rates were 86.1% and 91.4%, respectively. Patients with high iCD8 and tCD8 had longer DFS and OS compared to those with low counts/mm2 (DFS: HR = 0.58, p = 0.011 and HR = 0.65, p = 0.034 and OS: HR = 0.63, p = 0.043 and HR = 0.58, p = 0.020, respectively). Upon adjustment for clinicopathological parameters, iCD8 and tCD8 retained their favorable prognostic significance for DFS and OS, whereas high sCD8 was only prognostic for DFS. Menopausal status, tumor size, and nodal status retained their prognostic significance in all examined multivariate models. CD8+ TILs, and especially their intratumoral subset, represent a potential favorable prognostic factor in early BC.

Mucinous adenocarcinoma arising from a tailgut cyst: A case report.

BACKGROUND: Retrorectal hamartomas or tailgut cysts (TCs) are rare. In most cases, they are asymptomatic and benign; however, rarely, they undergo malignant transformation, mainly in the form of adenocarcinoma. CASE SUMMARY: A 55-year-old woman presented to our hospital with lower back pain. On magnetic resonance imaging, a large pelvic mass was found, which was located on the right of the ischiorectal fossa, extending to the minor pelvis. The patient underwent extensive surgical resection of the lesion through the right buttock. Histological examination confirmed the diagnosis of a retrorectal mucinous adenocarcinoma originating from a TC. Surgical resection of the tumour was complete, and the patient recovered without complications. The pilonidal sinus was then excised. One year later, semi-annual positron emission tomography-computed tomography and magnetic resonance imaging scans did not reveal any evidence of local recurrence or metastatic disease. CONCLUSION: Preoperative recognition, histological diagnosis, and treatment of TCs pose significant challenges. In addition, the possibility of developing invasive mucinous adenocarcinoma, although rare, should be considered.

IgIDivA: immunoglobulin intraclonal diversification analysis.

Intraclonal diversification (ID) within the immunoglobulin (IG) genes expressed by B cell clones arises due to ongoing somatic hypermutation (SHM) in a context of continuous interactions with antigen(s). Defining the nature and order of appearance of SHMs in the IG genes can assist in improved understanding of the ID process, shedding light into the ontogeny and evolution of B cell clones in health and disease. Such endeavor is empowered thanks to the introduction of high-throughput sequencing in the study of IG gene repertoires. However, few existing tools allow the identification, quantification and characterization of SHMs related to ID, all of which have limitations in their analysis, highlighting the need for developing a purpose-built tool for the comprehensive analysis of the ID process. In this work, we present the immunoglobulin intraclonal diversification analysis (IgIDivA) tool, a novel methodology for the in-depth qualitative and quantitative analysis of the ID process from high-throughput sequencing data. IgIDivA identifies and characterizes SHMs that occur within the variable domain of the rearranged IG genes and studies in detail the connections between identified SHMs, establishing mutational pathways. Moreover, it combines established and new graph-based metrics for the objective determination of ID level, combined with statistical analysis for the comparison of ID level features for different groups of samples. Of importance, IgIDivA also provides detailed visualizations of ID through the generation of purpose-built graph networks. Beyond the method design, IgIDivA has been also implemented as an R Shiny web application. IgIDivA is freely available at https://bio.tools/igidiva.

A Rare Case of Multiple Gastrointestinal Stromal Tumors Coexisting with a Rectal Adenocarcinoma in a Patient with Attenuated Familial Adenomatous Polyposis Syndrome and a Mini Review of the Literature.

BACKGROUND: Multiple gastrointestinal stromal tumors (GISTs) are extremely rare entities that exist either as spontaneous GISTs or as part of various syndromes, such as Carney's triad and type I neurofibromatosis (NF1). Attenuated familial adenomatous polyposis (AFAP) is a variant of familial adenomatous polyposis (FAP) with a milder clinical presentation. Both GISTs and AFAP have been reported to coexist with colorectal cancer, but the coexistence of GISTs and AFAP has never been reported in the literature before. CASE REPORT: A 45-year-old male patient with known AFAP arrived scheduled for a total colectomy and ileo-rectal anastomosis due to the malignancy of one of the previously biopsied polyps of the upper rectum. Intraoperatively, multiple nodular tumors were found at the jejunum within a length of 45 cm, for which an enterectomy and enteroanastomosis were performed. A histopathological examination of the whole colectomy specimen confirmed the presence of multiple polyps in the large intestine along with a rectal invasive adenocarcinoma. At the same time, in the examined part of the small intestine, 15 GISTs sized from 0.5 to 2.0 cm of prognostic group I, were identified. The patient's postoperative course was uncomplicated. CONCLUSION: Multiple GISTs may present as an asymptomatic disease, and the same thing is true for colorectal cancer. Therefore, the appropriate screening is crucial for entities such as AFAP, since the surgery was performed because of the malignant transformation in one of the polyps and revealed multiple GISTs, as well.

Be(a)ware of Leukocytosis in Papillary Thyroid Cancer.

Leukocytosis can be present at any time during various malignancies. A 42-year-old male was admitted to our department for surgical management of his metastatic papillary thyroid cancer. Persistent white blood cell (WBC) elevation with left shift led to a thorough investigation. Having excluded other causes, leukocytosis was attributed to thyroid cancer itself. Positive immunostaining for IL-6 and CEA, as well as elevated serum levels, established this connection.

Association of stress induced hyperglycemia with angiographic findings and clinical outcomes in patients with ST-elevation myocardial infarction.

BACKGROUND: Stress induced hyperglycemia (SIH) is common among patients with ST-elevation myocardial infarction (STEMI), even in patients without diabetes mellitus. However, evidence regarding its role on the angiographic outcomes and the prognosis of patients presenting with STEMI is scarce. METHODS: This study included 309 consecutively enrolled STEMI patients undergoing primary percutaneous coronary intervention (pPCI). Patients were diagnosed with SIH if blood glucose on admission was > 140 mg/dl. Also, patients had to fast for at least 8 hours before blood sampling. The objective was to assess whether SIH was associated with major adverse cardiovascular and cerebrovascular (MACCE) events and explore its relationship with angiographic predictors of worse prognosis such as poor initial TIMI flow, intracoronary thrombus burden, distal embolization, and presence of residual thrombus after pPCI. RESULTS: SIH in diabetic and non-diabetic patients was associated with a higher incidence of LTB (aOR = 2.171, 95% CI 1.27-3.71), distal embolization (aOR = 2.71, 95% CI 1.51-4.86), and pre-procedural TIMI flow grade = 0 (aOR = 2.69, 95% CI 1.43-5.04) after adjusting for relevant clinical variables. Importantly, during a median follow-up of 1.7 years STEMI patients with SIH with or without diabetes experienced increased occurrence of MACCE both in univariate (HR = 1.92, 95% CI 1.19-3.01) and multivariate analysis (aHR = 1.802, 95% CI 1.01-3.21). CONCLUSIONS: SIH in STEMI patients with or without diabetes was independently associated with increased MACCE. This could be attributed to the fact that SIH was strongly correlated with poor pre-procedural TIMI flow, LTB, and distal embolization. Large clinical trials need to validate SIH as an independent predictor of adverse angiographic and clinical outcomes to provide optimal individualized care for patients with STEMI.

Neutrophil extracellular traps enriched with IL-1ß and IL-17A participate in the hepatic inflammatory process of patients with non-alcoholic steatohepatitis.

Neutrophil extracellular traps (NETs) are implicated in the pathogenesis of various non-infectious inflammatory and thrombotic diseases. We investigated the presence and possible associations of NETs with various histopathologic parameters in patients with non-alcoholic steatohepatitis (NASH). We retrospectively assessed 20 liver biopsy specimens from patients with non-alcoholic fatty liver disease (NAFLD), including 17 specimens with NASH, and 14 control specimens. NETs were identified with confocal microscopy as extracellular structures with co-localization of neutrophil elastase (NE) and citrullinated histone-3. Interleukin-1ß (IL-1ß) and IL-17A were assessed with the same methodology. Histologic features of NAFLD were semi-quantitatively evaluated, and correlated with presence of NETs, neutrophil density, and platelet density/aggregates (assessed by immunohistochemistry for NE and CD42b, respectively). NETs were identified in 94.1% (16/17) of the NASH biopsy specimens; they were absent from all other NAFLD and control specimens. The presence of NETs was strongly correlated with steatosis (p = 0.003), ballooning degeneration (p < 0.001), lobular inflammation (p < 0.001), portal inflammation (p < 0.001), NAS score (p = 0.001), stage (p = 0.001), and diagnosis of NASH (p < 0.001). NETs were decorated with IL-1ß and IL-17A. Platelet aggregates were much larger in NASH specimens, as compared to controls. In conclusion, NETs are implicated in the pathogenesis of NASH. Their associations with inflammation, ballooning degeneration (a hallmark of NASH), and stage emphasize their role in the disease process. In this setting, NETs provide a vehicle for IL-1ß and IL-17A. In addition, platelet aggregation in hepatic sinusoids implies a role for thromboinflammation in NASH, and may explain the low peripheral blood platelet counts reported in patients with NASH.

Topical immunotherapy treatment of alopecia areata with diphenylcyclopropenone: Regulatory T cells as biomarkers for treatment response.

Treatment of alopecia areata is often challenging, especially for patients with extended disease. Contact immunotherapy with diphenylcyclopropenone (DPCP) has been reported as an effective topical treatment but the exact immunologic mechanism of diverting the immune response is still unknown. We investigated the efficacy of topical immunotherapy with DPCD in acute, intermediate, and chronic lesions of AA and the response rate was associated with perifollicular infiltrate of T regulatory cells. Approximately two-thirds of our patients (67.5%) had a response rate > 50% after 6 months of DPCP therapy. Patients with acute and intermediate onset of the disease were more likely to respond to the therapy. Although responders demonstrated FOXP3+ positive lymphocytes in immunohistochemistry, this association could not be confirmed by statistical significance (p = 0.052). In patients with multiple lesions, that had different chronological onset, the lesions with more recent onset responded faster than lesions of longer duration.

Investigation of Autologous Fat Transfer in Capsule Formation around Silicone Implants in a Rat Model.

BACKGROUND: In this experimental study, the authors investigated whether fat placement in the pocket during implant insertion affects capsule formation. METHODS: Twenty albino Wistar rats, 400 g each, were used. The rats were divided into two groups, A and B, of 10 rats each. At the dorsum of each rat, four pockets (2 × 2 cm each) were dissected, two left and two right of the midline. In each pocket, a 1 × 1 × 1.5-cm silicone implant was inserted. In the two left pockets, only silicone implants were placed (control). In the two right pockets, 0.4 ml of fat was injected around the implant. Animals in group A were killed 2 months postoperatively, and those in group B were killed 4 months postoperatively. The implants were dissected with the capsule and sent for histopathologic examination. RESULTS: The data of the fat transfer group was compared with control in groups A and B. Capsule thickness, neovascularization, myofibroblast layer thickness, and mast cell population demonstrated no statistically significant difference in either group A (p = 0.385, p = 0.862, p = 0.874, and p = 0.210, respectively) or group B (p = 0.338, p = 1.000, p = 0.288, and p = 0.344, respectively). Inflammation was statistically significantly less (p = 0.07) at 4 months (group B) in the fat transfer group compared to the control group. Likewise, cellularity was statistically significantly less (p = 0.019) at 4 months for the fat transfer group compared with the control group. CONCLUSION: Fat injection in the pocket during implant placement may reduce inflammation and cellularity of capsules and predispose to faster capsule maturation. CLINICAL RELEVANCE STATEMENT: Fat transfer around implants may positively affect implant-based breast reconstruction and/or breast augmentation.

Tumor-Associated Macrophages in Hepatocellular Carcinoma Pathogenesis, Prognosis and Therapy.

Hepatocellular carcinoma (HCC) constitutes a major health burden globally, and it is caused by intrinsic genetic mutations acting in concert with a multitude of epigenetic and extrinsic risk factors. Cancer induces myelopoiesis in the bone marrow, as well as the mobilization of hematopoietic stem and progenitor cells, which reside in the spleen. Monocytes produced in the bone marrow and the spleen further infiltrate tumors, where they differentiate into tumor-associated macrophages (TAMs). The relationship between chronic inflammation and hepatocarcinogenesis has been thoroughly investigated over the past decade; however, several aspects of the role of TAMs in HCC development are yet to be determined. In response to certain stimuli and signaling, monocytes differentiate into macrophages with antitumor properties, which are classified as M1-like. On the other hand, under different stimuli and signaling, the polarization of macrophages shifts towards an M2-like phenotype with a tumor promoting capacity. M2-like macrophages drive tumor growth both directly and indirectly, via the suppression of cytotoxic cell populations, including CD8+ T cells and NK cells. The tumor microenvironment affects the response to immunotherapies. Therefore, an enhanced understanding of its immunobiology is essential for the development of next-generation immunotherapies. The utilization of various monocyte-centered anticancer treatment modalities has been under clinical investigation, selectively targeting and modulating the processes of monocyte recruitment, activation and migration. This review summarizes the current evidence on the role of TAMs in HCC pathogenesis and progression, as well as in their potential involvement in tumor therapy, shedding light on emerging anticancer treatment methods targeting monocytes.

Dysregulation of Plasma miR-146a and miR-155 Expression Profile in Mycosis Fungoides Is Associated with rs2910164 and rs767649 Polymorphisms.

Diagnosis of Mycosis Fungoides (MF) may be challenging, due to its polymorphic nature. The use of miRNAs as biomarkers to assist in diagnosis has been investigated, mainly in skin lesion biopsies. The purpose of this study is to evaluate the plasma levels of miR-146a and miR-155 in MF patients and to investigate their association with SNPs of their genes. Plasma miRNAs were quantified by RT-qPCR. Genomic DNA was used for SNPs' genotyping by Sanger sequencing. Plasma levels of miR-146a and miR-155 were significantly higher in patients vs. controls, in early MF patients vs. controls, and in advanced vs. early MF patients. Both miRNAs' levels were significantly higher in stage IIB vs. early-stage patients. miR-155 plasma levels were significantly higher in patients with skin tumors or erythroderma. CC genotype (rs2910164 C>G) was significantly more frequent in healthy controls and associated with lower MF risk and lower miR-146a levels. The AA genotype (rs767649 T>A) was significantly more frequent in patients and correlated with increased MF risk and increased miR-155 levels. The combination of GG+AA was only detected in patients and was correlated with higher MF susceptibility. Increased mir-146a and mir-155 plasma levels in MF is an important finding to establish putative noninvasive biomarkers. The presence of SNPs is closely associated with miRs' expression, and possibly with disease susceptibility.

Diagnosing a Patient with Erdheim-Chester Disease during the COVID-19 Pandemic.

Background: Erdheim-Chester disease (ECD) is a rare hematopoietic neoplasm of histiocytic origin characterized by an insidious course. The coronavirus disease 2019 (COVID-19) pandemic has put an enormous strain on healthcare systems worldwide both directly and indirectly, resulting in the disruption of healthcare services to prevent, diagnose and manage non-COVID-19 disease. Case Presentation: We describe the case of a 58-year-old male patient with sporadic episodes of self-resolving mild fever and anemia of chronic disease with onset two years before the current presentation. Positron emission/computed tomography scan revealed the presence of moderately hypermetabolic perirenal tissue masses. In order to achieve diagnosis, repeated perirenal tissue biopsies were performed, and the diagnostic evaluation was complicated by the strain put on the healthcare system by the COVID-19 pandemic. The patient contracted SARS-CoV-2 and required hospitalization, but recovered fully. No further ECD target organ involvement was documented. Treatment options were presented, but the patient chose to defer treatment for ECD. Conclusion: A high index of suspicion and multidisciplinary team collaboration is paramount to achieve diagnosis in rare conditions such as ECD. Disruptions in healthcare services in the pandemic milieu may disproportionately affect people with rare diseases and further study and effort is required to better meet their needs in the pandemic setting.