Overall Risk Of Malignancy Research Articles

Incidence of Malignancies and the Association with Biological Disease-Modifying Antirheumatic Drugs in Japanese Patients with Rheumatoid Arthritis: A Time-Dependent Analysis from the IORRA Patient Registry.

Patients with rheumatoid arthritis (RA) may have an increased malignancy risk versus the general population, potentially elevated by biological disease-modifying antirheumatic drug (bDMARD) use. Using patient registry data, we determined malignancy risk, stratified by bDMARD use, among Japanese patients with RA versus the Japanese general population and investigated whether bDMARD use is a time-dependent risk factor for the development of malignancy. Patients aged ≥ 18years with ≥ 2 data entries of RA in the IORRA (Institute of Rheumatology, Rheumatoid Arthritis) patient registry, enrolled from January 2013-December 2018, were identified ('All RA' cohort). Patients were stratified into bDMARD (≥ 1bDMARD received) or non-bDMARD (no history of bDMARDs) sub-cohorts. Malignancy incidence rates and standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) versus the Japanese general population were calculated. Risk of RA medication use was analyzed using a time-dependent Cox proportional hazards model, after adjusting for covariates. A total of 8020 patients were identified for the All RA cohort; 2187 and 5833 for the bDMARD and non-bDMARD sub-cohorts, respectively. For all three cohorts, incidence of overall malignancies was similar versus the Japanese general population. Incidence of specific malignancies was also similar, but incidence of lymphoma was higher for all three cohorts (SIRs[95% CIs] 3.72 [2.71-4.93], 5.97 [3.34-9.59], and 2.79 [1.82-4.02], respectively). In the bDMARD sub-cohort, no increase in SIRs was observed for other site-specific malignancies. Inthe All RA cohort, use of methotrexate, tacrolimus, glucocorticoids, non-steroidal anti-inflammatory drugs, and bDMARDs were not associated with the risk of overall malignancy; the hazard ratio (95% CI) was 1.36(0.96-1.93) for bDMARD use. Increased disease activity was a time-dependent risk factor of overall malignancy with a hazard ratio (95% CI) of 1.35 (1.15-1.59). The use of bDMARDs was not a time-dependent risk factor for malignancy.

Cancer incidence following bariatric surgery in renal transplant recipients: a retrospective multi-center analysis

BackgroundObesity, a known independent risk factor for developing malignancy. Additionally, renal transplant recipients (RTR) confer a 2- to 4-fold increased risk of overall malignancies with an excess absolute risk of .7% per year. While transplant recipients are at risk for obesity and malignancy, the effect of bariatric surgery (BS) in the posttransplantation setting is not well known. ObjectivesOur study primarily evaluated the impact of BS on cancer incidence in RTR with severe obesity in the posttransplantation setting. Weight loss outcomes were analyzed secondarily. SettingUniversity Hospital. MethodsA retrospective study using TriNetX database was developed to analyze cancer outcomes in RTR with posttransplantation BS versus RTR without BS from 2000 to 2023. After the exclusion process and propensity matching, both cohorts consisted of 153 patients. ResultsRTR-BS had a significantly lower incidence of overall cancer and transplant-related cancers (P < .05). No significant difference was identified in cutaneous, gastrointestinal, and reproductive cancers. Percent Excess Weight Loss (%EWL) was significantly lower in RTR-only cohort (11.4%) versus RTR-BS cohort (57.8%) at 5 years. Sleeve gastrectomy (SG) patients (73.19%) had significantly higher %EWL than Roux en-Y gastric bypass (RYGB) patients (49.33%) at 3 years. No difference in cancer incidence was noted between SG and RYGB patients. ConclusionPostrenal transplantation BS had a diminishing effect on overall and transplant-related cancer incidence in RTR with severe obesity. Significant weight loss was also demonstrated with post-renal transplantation BS.

Diagnostic significance of clay-like materials aspirated from thyroid nodules.

The simplest way to determine the adequacy of aspirated materials is the on-site gross visual assessment of aspirated materials. However, few studies have examined the gross findings of thyroid aspirates. This study aimed to clarify the diagnostic significance of clay-like material aspirated from thyroid nodules. We reviewed 69,848 thyroid nodules that underwent aspiration cytology at Kuma Hospital between January 2007 and August 2021. Among them, 355 (0.5%) nodules with aspirated materials described as clay-like materials were retrospectively examined. Among 355 nodules, 322 (90.7%) were categorized as cystic fluid or benign. The aspirated materials were mainly composed of non-epithelial components, including colloid or proteinaceous materials, foamy histiocytes, and degenerative red blood cells. In original ultrasound reports, the incidence of intermediate and high suspicion was 11.0%. Malignant cells were observed in 21 nodules (5.9%), one-third of which were papillary thyroid carcinomas. The materials aspirated from papillary and follicular thyroid carcinomas exhibited necrotic carcinoma cells derived from infarcted areas. The overall risk of malignancy was 3.9%. The risk of malignancy in nodules interpreted as highly suspicious on ultrasound examination was 37.5%. As clay-like materials aspirated from thyroid nodules were considered sufficient specimens, the recognition contributes to avoiding unnecessary second punctures. The presence of clay-like materials was indicative of the colloid and/or blood components of benign cystic lesions, or, more rarely, of infarcted carcinoma. The ultrasound examination results tended to overestimate nodules. We should reaffirm that on-site gross visual assessment of aspirated materials is a fast and reasonably accurate predictor of the on-site adequacy of the samples.

Basal Cell Carcinoma in a Case of Systemic Lupus Erythematosus – A Case Report

Systemic lupus erythematosus (SLE) is a chronic, systemic autoimmune with autoantibody production, complementactivation, and immune complex deposition. SLE patients have higher mortality rates as compared to the general populationEven though there have been improvements in finding and treating diseases, cancer is still a major reason for death in this group.The most common type of cancer is Basal cell carcinoma, and it is widespread. The risk of malignancy in SLE is of considerableinterest because the immune and genetic pathways underlying the pathogenesis of SLE and the immunosuppressant drugs (ISDs)used in its management may mediate this altered risk. Here, we present a case of long-standing SLE in an elderly female who wason treatment for the same. She presented with a chronic ulcer over her scalp. She got checked, and a biopsy showed she hadBasal Cell Carcinoma on her scalp. Doctors removed it with surgery and covered the open area with skin from another part ofher body. At her first checkup, everything looked good, and the new skin was healing well. Even though skin cancers are knownto happen in people with certain skin conditions, getting Basal Cell Carcinoma with lupus is very uncommon. In various cohortstudies of adults with SLE and overall risk of malignancy, ranging from 1992 to 2017, it was found that though cutaneousmalignancies did occur, not a single study reported Basal Cell Carcinoma.

Added value of the EUSOBI diffusion levels in breast MRI

ObjectivesTo investigate whether using the diffusion levels (DLs) proposed by the European Society of Breast Imaging (EUSOBI) improves the diagnostic accuracy of breast MRI.Materials and methodsThis retrospective study included 145 women who, between September 2019 and June 2020, underwent breast 1.5-T MRI with DWI. Reader 1 and reader 2 (R1-R2) independently assessed breast lesions using the BI-RADS on dynamic contrast-enhanced imaging and T2-weighted imaging. DWI was subsequently disclosed, allowing readers able to measure lesions ADC and subjectively express the overall risk of malignancy on a 1–5 Likert scale. ADCs were interpreted as a range of values corresponding to the EUSOBI DLs. The analysis evaluated the inter-reader agreement in measuring ADC and DLs, the per-DL malignancy rate, and accuracy for malignancy using ROC analysis against histological examination or a 3-year follow-up.ResultsLesions were malignant and showed non-mass enhancement in 67.7% and 76.1% of cases, respectively. ADC was measurable in 63.2%/66.7% of lesions (R1/R2), with a minimal discrepancy on Bland–Altman analysis and 0.948 (95%CI 0.925–0.965)/0.989 (95%CI 0.988–0.991) intraclass correlation coefficient in measuring ADC/DLs. The malignancy rate (R1/R2) increased from 0.5/0.5% (“very high” DL) to 96.0/96.8% (“very low” DL), as expected. Likert categorization showed larger areas under the curve than the BI-RADS for both R1 (0.91 versus 0.87; p = 0.0208) and R2 (0.91 versus 0.89; p = 0.1171), with improved specificity (81.5% versus 78.5% for R1 and 84.4% versus 81.2% for R2).ConclusionThough ADC was not measurable in about one-third of lesions, DLs were categorized with excellent inter-reader agreement, improving the specificity for malignancy.Clinical relevance statementDLs proposed by the EUSOBI are a reproducible tool to interpret the ADC of breast lesions and, in turn, to improve the specificity of breast MRI and reduce unnecessary breast biopsies.Key Points• The European Society of Breast Imaging proposed diffusion levels for the interpretation of the apparent diffusion coefficient in diffusion-weighted imaging of the breast.• Adding diffusion levels to the interpretation of magnetic resonance imaging improved the diagnostic accuracy for breast cancer, especially in terms of specificity.• Diffusion levels can favor a more widespread and standardized use of diffusion-weighted imaging of the breast.

Malignancy outcomes in patients with rheumatoid arthritis treated with abatacept and other disease-modifying antirheumatic drugs: Results from a 10-year international post-marketing study

ObjectiveTo evaluate the risk of malignancy (overall, breast, lung, and lymphoma) in patients with rheumatoid arthritis treated with abatacept, conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs), and other biologic/targeted synthetic (b/ts)DMARDs in clinical practice. MethodsFour international observational data sources were included: ARTIS (Sweden), RABBIT (Germany), FORWARD (USA), and BC (Canada). Crude incidence rates (IRs) per 1000 patient-years of exposure with 95% confidence intervals (CIs) for a malignancy event were calculated; rate ratios (RRs) were estimated and adjusted for demographics, comorbidities, and other potential confounders. RRs were then pooled in a random-effects model. ResultsAcross data sources, mean follow-up for patients treated with abatacept (n = 5182), csDMARDs (n = 73,755), and other b/tsDMARDs (n = 37,195) was 3.0–3.7, 2.9–6.2, and 3.1–4.7 years, respectively. IRs per 1000 patient-years for overall malignancy ranged from 7.6–11.4 (abatacept), 8.6–13.2 (csDMARDs), and 5.0–11.8 (other b/tsDMARDs). IRs ranged from: 0–4.4, 0–3.3, and 0–2.5 (breast cancer); 0.1–2.8, 0–3.7, and 0.2–2.9 (lung cancer); and 0–1.1, 0–0.9, and 0–0.6 (lymphoma), respectively, for the three treatment groups. The numbers of individual cancers (breast, lung, and lymphoma) in some registries were low; RRs were not available. There were a few cases of lymphoma in some of the registries; ARTIS observed an RR of 2.8 (95% CI 1.1–6.8) with abatacept versus csDMARDs. The pooled RRs (95% CIs) for overall malignancy with abatacept were 1.1 (0.8–1.5) versus csDMARDs and 1.0 (0.8–1.3) versus b/tsDMARDs. ConclusionsThis international, post-marketing observational safety study did not find any statistically significant increase in the risk of overall malignancies in pooled data in patients treated with abatacept compared with csDMARDs or with other b/tsDMARDs. Assessment of larger populations is needed to further evaluate the risks for individual cancers, especially lymphoma.

Imaging and pathologic correlation of composite pheochromocytoma-ganglioneuroma.

A 50-year-old man consulted our institution for headaches and uncontrolled high blood pressure. Laboratory work-up and endocrine evaluation were consistent with pheochromocytoma with elevated plasma free metanephrine, free normetanephrine, plasma epinephrine, norepinephrine, total catecholamines, and 24-hour urine fractionated metanephrines, normetanephrines and total metanephrines levels. CT showed a contrast-enhancing 11.5 × 12.4 × 8.8 cm right adrenal complex cystic mass (Fig. 1A). Subsequent 68Ga-DOTATATE PET/CT confirmed the large right adrenal lesion with prominent tracer avidity (Fig. 1B). Surgical resection and pathology (Figs. 1C and 2) reached the diagnosis of composite pheochromocytoma-ganglioneuroma (CPG). The patient’s symptoms resolved after surgery. Genetic testing was normal. CPG, a rare tumor of mostly third-to-fifth decade of life with no gender preference, contains both pheochromocytoma (PC) and ganglioneuroma (GN) neoplastic components. CPG features symptoms of catecholamine overproduction: headache, palpitations, hypertension, and diaphoresis, and abdominal pain and watery diarrhea from excess VIP production by ganglioneuroma cells. CPG is indistinguishable from PC by clinical presentation, imaging features and biomarkers. Most CPG patients present with elevated catecholamines (1,2). CPG appears on CT as a well-circumscribed, heterogeneous or cystic adrenal mass with contrast enhancement. 68Ga-DOTATATE PET/CT may be an effective functional imaging modality for the detection and post-surgical monitoring of CPG based on its PC component (2). Diagnosis is histological with the identification of admixed regions of usually dominant PC and GN. PC cells stain positively for synaptophysin, GN cells with NeuN and Schwann cells with S-100. BRAF and HRAS mutations are frequently associated with CPG (3). CPG resection proceeds like PC surgery with preoperative adrenergic blockade, increased oral hydration and salt supplementation. The overall risk of malignancy associated with CPG is notably lower than with pure PC. Symptoms usually resolved upon CPG surgical resection, as seen in our case. One-out-of-eight treated patients may develop recurrence within 15 months (1).

Risk of malignancy following exposure to Epstein-Barr Virus associated infectious mononucleosis: A nationwide population-based cohort study.

Epstein-Barr virus (EBV) infection has been shown to contribute to oncogenesis and often causes acute clinical manifestation of Infectious mononucleosis (IM). It is unknown whether IM could increase the risk of subsequent malignancies. We aimed to evaluate the association of IM caused by EBV (EBV-IM) with overall and subtypes of malignancy in a large population-based cohort study. This study included 1,419,407 individuals born in Denmark between 1973 and 2016 identified from national registers and 23,057 individuals had IM. The 5,394 of them had confirmed EBV-IM and they were birth date- and sex- matched (1:63) to 1,396,350 non-IM individuals. Cox regression was used to examine the associations of EBV-IM with malignancy. Individuals with a history of confirmed EBV-IM had an 88% increased overall risk of malignancy (hazard ratio [HR]:1·88, 95% confidence interval [CI]: 1·42-2·49) and a five-fold risk of hematologic malignancies (HR 5·04, 95% CI: 3·07-8·25), compared to those without IM. Similar estimates were observed in the sibling analysis. The overall risk of malignancy was greater for EBV-IM with complications (HR 8·93, 95% CI: 3·35-23·81) than that for EBV-IM without complications (HR 1·35, 95% CI: 1·20-1·53). EBV-IM duration was related to increased risk of malignancy in a dose-response way. Notably, the significant elevated risk of overall malignancy was observed in the first two years after EBV-IM onset (rate ratio [RR] 4·44, 95% CI: 2·75-7·17) and attenuated thereafter. EBV-IM was associated with an increased risk in malignancy, particularly hematologic malignancies and in the first two years following IM exposure. Our findings suggest an important time-window for early screening of the EBV-attributed malignancy.

The impact of thyroid imaging reporting and data system on the management of Bethesda III thyroid nodules

ObjectivesAtypia of undetermined significance (AUS) or follicular lesion of undetermined significance (FLUS) is a heterogeneous category of fine needle aspiration cytology (FNAC); the management of this condition remains controversial. The clinical significance of such patients relies on the exclusion of malignancy. In this study, we aimed to determine the validity of the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) (2017) for predicting malignancy in this specific category of patients. MethodsIn this study, we analysed a cohort of patients from our previous retrospective study. This four-year retrospective cohort study included all cases undergoing surgery with a cytological diagnosis of AUS/FLUS. We enrolled 110 cases with documented final histopathological diagnoses and ultrasound examinations. ResultsThe study included 83 females (75.5%) and 27 males (24.5%). The overall risk of malignancy (ROM) for AUS/FLUS thyroid nodules was 47.3%. The ROMs of TI-RADS 3 (TR3), TI-RADS 4 (TR4), and TI-RADS 5 (TR5) were 43.5%, 49.4% and 40%, respectively. There was no significant association between TI-RADS and final pathological analysis. ConclusionsRepeated FNAC with initial AUS/FLUS nodules is crucial. Our findings showed that ACR TI-RADS did not contribute to the cancer risk stratification of AUS/FLUS nodules. A large prospective multi-institutional study is now required to determine the validity of ACR TI-RADS and whether other adjunct clinical, cytological, molecular, or biochemical tools could facilitate the management of patients with these heterogeneous nodules.

267 (PB-091) Poster - Assessment and management of lesions of uncertain malignant potential of the breast at Trieste Breast Unit: a single center experience

Background: Breast lesions of uncertain malignant potential (B3 lesions) represent a heterogeneous group of abnormalities with an overall risk for malignancy of 9.9%–35.1% after total resection. Given their different risk of upgrade to malignancy the management of B3 lesions with the goal of finding the balance between open surgical excision, vacuum guided percutaneous excision and surveillance is still an issue for breast centers.

S2150 Triangle of Lymphocytic Colitis, Epstein-Barr Virus, and Lymphoma: Is There Any Association?

Introduction: Epstein–Barr virus (EBV), is linked to range of lymphoproliferative lesions and malignant lymphomas of B-, T- and NK-cell origin. EBV-positive diffuse large B cell lymphoma (DLBCL) not otherwise specified is a variant of DLBCL seen in patients without known immunodeficiency or prior lymphoma. In few reports EBV infection was more commonly detected in colonic mucosa of patients with Microscopic Colitis (MC), but it remains unclear if this translates to higher incidence of lymphoma in this subgroup of people. Here, we describe a case of DLBCL in patient with MC associated with EBV infection in context of recent findings. Case Description/Methods: 77-year-old female with history of COPD, diabetes underwent colonoscopy for chronic diarrhea of 4-month duration. She suffered from 3-4 loose stools/day, and had normal celiac panel, fecal elastase, and infectious workup. Colonoscopy was unremarkable except for 4 mm Paris Is polyp in sigmoid colon removed with cold snare. On pathology, the random colon biopsies were positive for lymphocytic colitis along and polyp showed DLBCL (non-germinal center phenotype) along with positive EBV infection (Figure). Discussion: It is widely believed that overall risk of malignancy is not increased in MC. However, theoretically MC should increase risk of lymphoma as it is more likely to be associated with oncogenic EBV than Ulcerative colitis or irritable bowel syndrome (90 % vs 66 % vs 0 % respectively). EBV increases the risk of lymphoma due to protein expression in transformed infected lymphocytes that results in immune evasion and suppression of apoptosis. Earlier studies have shown no evidence of higher risk of lymphoma in MC, however recently Bergman et al. (2021) analyzed data from Sweden´s pathology departments and from the Swedish Cancer Register and included 11758 patients with incident MC and found an increased risk of lymphoma (adjusted HR 1.43 [1.06–1.92]). Studies are needed to explore risk of lymphoma in subgroup of MC patients with EBV infection as inflammation cause by MC and concomitant EBV infection enhance the overall malignant potential. In conclusion, MC may not be as benign entity as it was once thought to be as it is more likely to harbor oncogenic EBV virus. Even diminutive polyps in MC can potentially harbor lymphoma and should be removed and submitted for analysis rather than being discarded.Figure 1.: Colonoscopy image showing small polyp (left) and schematic (right) of triangle between CMV, microscopic colitis and lymphoma error.

Risk of malignancy in rheumatoid arthritis patients initiating biologics: an historical propensity score matched cohort study within the French nationwide healthcare database

ObjectiveTo compare the risk of malignancy between patients with rheumatoid arthritis (RA) initiating their first biological disease-modifying antirheumatic drug (bDMARD) and those continuing conventional synthetic DMARDs (csDMARDs).MethodsNine-year historical Propensity Score...

Nondiagnostic salivary gland FNAs are associated with decreased risk of malignancy compared with "all-comer" patients: Analysis of the Milan System for Reporting Salivary Gland Cytopathology with a focus on Milan I: Nondiagnostic.

The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) reports a 25% rate of malignancy (ROM) for the Milan I: Nondiagnostic (ND) category. We clarify the ROM of ND salivary gland fine-needle aspirations (SGFNAs) based on our institutional experience and review of the literature. Overall risk of malignancy (OROM) and that for those with surgical/flow cytometric follow-up (FROM) for each category and "all-comers" were calculated for Emory SGFNAs from January 2010 through March 2021. From a literature review of 50 articles using MSRSGC, distribution of diagnoses, rates of follow-up, FROM, and OROM by category were calculated. FROMs and OROMs between ND FNAs and all-comers were compared. Milan I rate was compared with the ratio of Milan I OROM to all-comer OROM. Of 819 SGFNAs at Emory, 12.8% (n=105/819) were ND. Thirty-two had known follow-up, with 12 (37.5%) being malignant. Nonmucinous cyst contents accounted for 26.7% of ND SGFNAs (n=28/105); all 7 with surgical follow-up were benign. Of 50 MSRSGC studies, 18.2% (n=2384/13,129) of SGFNAs were classified as ND, 26.6% (n=635/2384) with known follow-up. Total FROM and OROM for ND FNAs (15.7% and 4.1%, respectively) were significantly lower than those for all-comers (24.9% and 11.4%, respectively) (p < .001). There was no relationship between rate of ND SGFNA and ND ROM. The ND category is associated with a lower ROM than that of all-comer SGFNA patients. The "true" ROM for ND SGFNAs is likely best estimated by the 4.1% OROM. SGFNAs showing nonmucinous cyst contents have a particularly low ROM. Rate of ND SGFNAs does not influence ND ROM.

Multi-institutional validation of a modified scheme for subcategorizing salivary gland neoplasm of uncertain malignant potential (SUMP).

The salivary gland neoplasm of uncertain malignant potential (SUMP) category in the Milan System is diagnostically challenging. This study aims to validate a modified scheme for subcategorizing SUMP in a large multi-institutional cohort. Retrospective review of salivary gland fine-needle aspirations (FNAs) from 10 institutions were classified based on the Milan System. Cases diagnosed as SUMP with available cytology slides and surgical follow-up were retrieved for review and subcategorized based on a modified scheme as follows: basaloid SUMP (B1: absent/scant nonfibrillary matrix; B2: presence of nonfibrillary/mixed-type matrix), oncocytic/oncocytoid SUMP (O1: with mucinous background; O2: without mucinous background), and SUMP not otherwise specified (NOS). A total of 742 (7.5%) cases from 9938 consecutive salivary gland FNAs were classified as SUMP. Among them, 525 (70.8%) had surgical follow-up and 329 (62.7%) were available for review. The overall risk of malignancy (ROM) of SUMP was 40.4%. There were 156 cases (47.4%) subcategorized as basaloid SUMP with a ROM of 36.5%, 101 (30.7%) as oncocytic/oncocytoid SUMP with a ROM of 52.5%, and 72 (21.9%) as SUMP NOS with a ROM of 31.9%. The ROM of oncocytic/oncocytoid SUMP was significantly higher than basaloid SUMP (P=.0142) and SUMP NOS (P=.0084). No significant differences in ROM were noted between B1 and B2 (36.7% vs 36.4%, P=1.0000) and O1 and O2 (65.2% vs 48.7%, P=.2349). The ROM of oncocytic/oncocytoid SUMP was 52.5% and significantly higher than that of basaloid SUMP (36.5%, P=.0142) and SUMP NOS (31.9%, P=.0084), whereas no significant differences in ROM were noted for cases with different types of extracellular matrix or background material.

Carcinogenicity risk associated with tacrolimus use in kidney transplant recipients: a systematic review and meta-analysis.

BackgroundCurrently, tacrolimus is the preferred anti-rejection therapy for kidney transplant recipients due to its greater protection against acute rejections compared to cyclosporin A (CsA). Despite the advantages of kidney transplantation, it has been associated with an increased incidence of de novo malignancies. Furthermore, a systematic review in 2005 revealed no statistical difference in tumorigenicity between tacrolimus and CsA. This report provides an up to date systematic review and evaluation of all relevant studies in the literature to determine the risk of malignancy in kidney transplant recipients exposed to tacrolimus.MethodsA systematic literature search was performed using the Medline (PubMed and Ovid), Embase, Clinical Trials, and Cochrane databases (from creation to May 2021). We performed a meta-analysis of 11 studies with 36,985 kidney transplant recipients that compared the tacrolimus group with the control group. Outcomes of this study were incidence of malignancies and skin cancer risk. Risk of Bias was assessed in terms of whether there was random sequence generation, allocation concealment, blinding, completeness of results, selective reporting, etc. This meta-analysis was performed in accordance with PRISMA guidelines.ResultsOf the 11 included studies, 8 were high quality studies, 1 was assessed as medium quality, and 2 were low quality studies. The results showed a significantly increased risk of overall malignancy associated with tacrolimus exposure compared to non-tacrolimus therapy [risk ratio (RR) =1.59; 95% confidence interval (CI): 1.19–2.11; P=0.002], and especially with sirolimus (SRL) (RR =2.58; 95% CI: 1.62–4.09; P<0.0001). The incidence of skin cancer was consistent with the overall study (RR =2.03; 95% CI: 1.25–3.28; P=0.004). However, there was no significant difference in the incidence of tumors between tacrolimus and cyclosporine A treatment (RR =1.12; 95% CI: 0.80–1.56; P=0.52), even in studies with long follow-up periods of more than 3 years.DiscussionThe data demonstrated that patients treated with tacrolimus had a higher risk of carcinogenicity compared to patients treated with SRL. However, patients treated with tacrolimus had a similar incidence of carcinogenicity compared to patients treated with CsA. Further clinical studies are warranted to confirm these findings.

The risk of malignancy in patients with IgG4-related disease: a systematic review and meta-analysis

BackgroundThe relationship between IgG4-related disease (IgG4-RD) and the risk of malignancy is still controversial. This article focused on assessing the risk of cancer in patients with IgG4-RD by meta-analysis.MethodsWe conducted a systematic review of the literature and meta-analysis characterizing the associated risk of overall malignancy and four site-specific malignancies (pancreas, lung, gastric and lymphoma) in patients with IgG4-RD. A search from 2003 to 2020 was performed using specified terms from PubMed, Embase, Web of Science and SinoMed. Random-effects model analysis was used to pool standardized incidence ratios (SIRs) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were conducted to clarify the heterogeneity of the included studies. Begg’s funnel plot and Egger’s linear regression test were used to evaluate the bias of the meta-analysis. A P value < 0.05 indicated the existence of publication bias.ResultsA total of 10 studies were included in the article. The overall SIR estimates suggested an increased risk of overall cancer in IgG4-RD patients (SIR 2.57 95% CI 1.72–3.84) compared with the general population. The specific SIRs for pancreas and lymphoma were higher than those of the general population in IgG4-RD patients (SIR 4.07 95% CI 1.04–15.92, SIR 69.17 95% CI 3.91–1223.04, respectively). No significant associations were revealed in respiratory and gastric cancer (SIR 2.14 95% CI 0.97–4.75, SIR 0.95 95% CI 0.24–3.95, respectively). Four studies were found to be the major sources of heterogeneity by sensitivity analysis. There was no evidence of publication bias via Egger’s test.ConclusionCompared with the general population, patients with IgG4-RD appear to have a higher risk of overall cancer, especially pancreatic and lymphoma. The risk of lung and gastric cancer was not different between IgG4-RD patients and the general population.

Is Milan for kids?: The Milan System for Reporting Salivary Gland Cytology in pediatric patients at an academic children's hospital with cytologic-histologic correlation.

The Milan System for Reporting Salivary Gland Cytopathology (MSRSGC) provides a useful framework for the diagnosis of salivary gland fine-needle aspiration (FNA) biopsies. In this study, the MSRSGC was applied to salivary gland FNAs in pediatric patients to assess its usefulness and look at pitfalls. The laboratory information system was queried over a 15-year period for all salivary gland FNAs in patients 18 years old or younger. Patient demographics, FNA diagnosis categorized according to the MSRSGC, and follow-up surgical pathology diagnoses were examined and correlated. Thirty-two cases were identified, with an average age of 12 years (range, 0.6-18 years). A majority of the cases (84.4%) were from the parotid region. Twenty of 32 cases (62.5%) had follow-up resection. MSRSGC recategorization diagnoses of the 32 FNA cases were 34% benign neoplasm, 31% nonneoplastic, 16% nondiagnostic, 9% atypia of undetermined significance, 3% salivary neoplasm of uncertain malignant potential, 3% suspicious for malignancy, and 3% malignant. Overall, the sensitivity and specificity were 100% and 80%, respectively. On follow-up resection, 55% were neoplastic: pleomorphic adenomas (n = 6; 55%), pilomatricoma (n = 3; 28%), mucoepidermoid carcinoma (n = 1; 9%), schwannoma (n = 1; 9%), and myofibroma (n = 1; 9%). The MSRSGC performed fairly well in the pediatric population with a low overall risk of malignancy (6%) and high sensitivity. Although the majority of pediatric salivary gland FNAs were benign, 55% of resected cases were positive for a neoplasm, with benign neoplasms outnumbering malignancy. Challenging entities included inflammatory conditions, like immunoglobulin G4-related sialadenitis, and skin and soft tissue lesions near the salivary gland.

TNF-alpha immunosuppressive use and future malignancy risk.

10558 Background: Tumor Necrosis Factor Alpha (TNF-a) inhibitors suppress the immune system in patients with systemic inflammatory conditions. Long term data assessing future cancer risk for these patients is not known. We assessed long term risk of malignancy in patients with Rheumatoid Arthritis [RA], Inflammatory Bowel Disease [IBD], Psoriasis [PS], and Ankylosing Spondylitis [AS], who were or were not exposed to a TNF-a inhibitor. Methods: This was a retrospective, cohort study conducted using electronic medical record data for patients with complete demographic and treatment data at Northwestern Medicine from years 1998 to 2020 (RA: n = 10763; IBD: n = 12106; PS: n = 1920; AS: n = 5103). Inverse Probability of Treatment Weighting (IPTW) was used to balance the distributions of age, race, gender, smoking status, and follow-up time across exposure groups within each inflammatory condition type. Relative risk (RR) of malignancy based on TNF-a exposure was assessed using logistic regression. Results: 2583 (24.0%) of RA, 2185 (18.0%) of IBD, 1811 (94.3%) of PS, 572 (11.2%) of AS patients had TNF-a exposure. Median follow-up for patients was 43 months. The RR for any cancer was higher for patients exposed to a TNF-a agent with rheumatoid arthritis (RR 1.121 (95% CI 1.02-1.23, p = 0.015) and psoriasis (RR 1.763 (95% CI 1.32-2.37, p &lt; 0.001). The relative risk of any cancer was lower in patients exposed to a TNF-a agent with IBD (RR 0.858 (95% CI 0.78-0.94, p = 0.001). No significant difference in relative risk associated with TNF-a exposure was detected with ankylosing spondylitis (RR 0.929 (95% CI 0.8-1.08, p = 0.344). Conclusions: Patients with RA or PS and TNF-a exposure had higher RR of overall malignancy. Patients with IBD and TNF-a exposure had lower risk of overall malignancy. TNF-a immunosuppression may alter cancer risk differently based on the disease states for which it is being used. This information is critical when counseling patients on long term risk and screening strategies when considering TNF-a inhibition.

Comorbidities (excluding lymphoma) in Sjögren's syndrome.

The information about comorbidities (excluding lymphoma) in primary Sjögren's syndrome (pSS) is relatively scarce. Cardiovascular disease, infections, musculoskeletal conditions or malignancy are likely the most relevant comorbid conditions in pSS. Different infections (particularly oral candidal infections) and fibromyalgia are extremely frequent in the daily clinical practice. On the other hand, the incidence of cardiovascular events and cancer in pSS is low, so information about them comes from large epidemiological studies or meta-analysis. For this reason, preclinical vascular disease is investigated by different techniques, demonstrating the presence of early atherosclerosis in pSS patients. Coronary events could be slightly more frequent in pSS than in the general population. The overall risk of malignancy in pSS patients seems to be slightly increased, likely due to excess occurrence of lymphoma. An association between pSS and thyroid cancer might exist, although it should be confirmed by further investigations.

Patient outcomes following surgical management of thyroid nodules classified as Bethesda category III (AUS/FLUS).

The Bethesda classification system for reporting thyroid cytopathology is the standard for interpreting fine needle aspirate (FNA). Because of its heterogeneity and inconsistent reporting, atypia of undetermined significance or follicular lesion of undetermined significance (AUS/FLUS), known as Bethesda category III, is the most controversial category. Thyroid nodules that fall within Bethesda categories III-IV have an overall risk of malignancy of between 15 and 40%. The aim of this study was to determine the malignancy rate in Bethesda III nodules. A retrospective study was performed for 1166 patients who underwent thyroid surgery for multinodular goitre (MNG) or solitary nodular goitre (SNG) in our institution between June 2010 and May 2020. Data retrieved included demographic characteristics of the patients, FNB cytology, thyroid function test results, type of thyroidectomy, and final histology results. During the study period, 29.5% (344/1166) of patients with an FNA categorized as AUS/FLUS underwent thyroid surgery. Of these 344 patients, 190 were diagnosed with MNG and 154 with SNG. Incidental malignancy was found in 35 of 190 cases of MNG (18.42%) and 31 of 154 cases of SNG (20.13%). The most common malignant tumour type in either category was the follicular variant of papillary thyroid carcinoma. The current study demonstrates that patients with a FNA categorized as AUS/FLUS may have a higher risk of malignancy than traditionally believed. Reconsideration may be necessary to guidelines that recommend observation or repeat FNA in this category of patients.