Underwent Tissue Biopsy Research Articles

Clinical outcomes of screening and diagnostic mammography in a limited resource healthcare system

IntroductionBreast cancer is a significant public health concern in Jordan. It is the most common cancer among Jordanian women. Despite its high incidence and advanced stage at time of diagnosis, the uptake of breast cancer screening in Jordan is low. This study aims to compare clinical outcomes of both screening and diagnostic mammogram among women in Jordan.MethodsA retrospective cohort of 1005 women who underwent mammography in breast imaging unit in a tertiary hospital in Jordan. It aimed to investigate outcomes of screening and diagnostic mammography. recall rates, clinical manifestations and cancer rates were investigated.ResultsA total of 1005 participants were involved and divided into screening group (n = 634) and diagnostic group (n = 371). Women in the diagnostic group were more likely to be younger, premenopausal, smokers with higher BMI. Among the screening group, 22.3% were labeled with abnormal mammogram, 26% recalled for ultrasound, 46 patients underwent tissue biopsy and a total of 12 patients had a diagnosis of breast carcinoma. Among the diagnostic group, the most commonly reported symptoms were a feeling of breast mass, mastalgia and nipple discharge. Abnormal mammogram was reported in 50.4% of women, a complementary ultrasound was performed for 205 patients. A diagnostic Tru-cut biopsy for 144 patients and diagnostic excisional biopsy for 17 patients were performed. A total of 131 had a diagnosis of carcinoma.ConclusionWith the high possibility of identifying a carcinoma in mammography among symptomatic women and low uptake of screening mammogram, efforts to increase awareness and improve access to screening services are crucial in reducing the burden of breast cancer in Jordan.

Tissue or liquid rebiopsy? A prospective study for simultaneous tissue and liquid NGS after first-line EGFR inhibitor resistance in lung cancer.

According to current International Association for the Study of Lung Cancer guideline, physicians may first use plasma cell-free DNA (cfDNA) methods to identify epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI)-resistant mechanisms (liquid rebiopsy) for lung cancer. Tissue rebiopsy is recommended if the plasma result is negative. However, this approach has not been evaluated prospectively using next-generation sequencing (NGS). We prospectively enrolled patients with lung cancer with first-line EGFR-TKI resistance who underwent tissue rebiopsy. The rebiopsied tissues and cfDNA were sequenced using targeted NGS, ACTDrug®+, and ACTMonitor®Lung simultaneously. The clinicopathological characteristics and treatment outcomes were analyzed. Totally, 86 patients were enrolled. Twenty-six (30%) underwent tissue biopsy but the specimens were inadequate for NGS. Among the 60 patients with paired tissue and liquid rebiopsies, two-thirds (40/60) may still be targetable. T790M mutations were found in 29, including 14 (48%) only from tissue and 5 (17%) only from cfDNA. Twenty-four of them were treated with osimertinib, and progression-free survival was longer in patients without detectableT790M in cfDNA than in patients with detectableT790M in cfDNA (p = 0.02). For the 31 T790M-negative patients, there were six with mesenchymal-epithelial transition factor (MET) amplifications, four with ERBB2 amplifications, and one with CCDC6-RET fusion. One with MET amplification and one with ERBB2 amplification responded to subsequent MET and ERBB2 targeting agents respectively. NGS after EGFR-TKI resistance may detect targetable drivers besides T790M. To do either liquid or tissue NGS only could miss patients with T790M. To do tissue and liquid NGS in parallel after EGFR-TKI resistance may find more patients with targetable cancers.

Risk of malignancy in incidental oropharyngeal lesions exhibiting fluorodeoxyglucose uptake which proceed to tissue biopsy.

Utilization of positron emission tomography/computed tomography (PET/CT) with fluorodeoxyglucose is increasing in use for a variety of indications, including surveillance of cancer patients. There is a paucity of evidence pertaining to the significance of incidental PET-avid oropharyngeal lesions. This study aims to examine the clinical and radiological features of these incidental oropharyngeal lesions in patients undergoing PET for indications other than head and neck cancer. Retrospective cohort study of three Australian tertiary hospitals, from 2015 to 2021, on adult patients undergoing biopsy of incidental PET-avid oropharyngeal lesions. Primary outcome of interest was the incidence of malignancy. Patients with a previous history of, or undergoing investigations for, head and neck cancer were excluded. Thirty-one patients were included, wherein 21 patients had tonsillar uptake, and 13 patients had base of tongue uptake. Tonsillar disease was mostly asymmetrical (n = 15/21), bilateral (n = 11/21), and had median SUVmax 9.35 (n = 12, IQR 7.4-11.15). Base of tongue was mostly asymmetrical (n = 7/13, 54%), bilateral (n = 8/13, 62%), and had median SUVmax 8.2 (n = 10, IQR 6.9-12.65). Seven patients had malignancy confirmed on tissue biopsy: five biopsies confirmed the tissue diagnosis of suspected lymphoma, and two incidental findings of unexpected malignancies: one p16 positive tonsillar squamous cell carcinoma, and one metastatic breast cancer. In 31 patients undergoing tissue biopsy for incidental PET-avid oropharyngeal lesions, there were two unexpected malignancies. Our study results indicate that although unexpected malignancies are uncommon, a malignant diagnosis cannot be excluded from clinical features alone.

Dynamic real-time optical microscopy of oral mucosal lesions using confocal laser endomicroscopy.

Confocal laser endomicroscopy (CLE) is a novel non-invasive point-of-care optical biopsy technology that enables real-time in vivo microscopic visualisation of cellular and tissue architecture. In this study, we assessed the diagnostic accuracy of a hand-held fluorescence single-fibre distal-scanning CLE (fsdCLE) platform for diagnosing oral epithelial dysplasia (OED) and oral squamous cell carcinoma (OSCC). Forty-seven patients presenting with 63 distinct oral mucosal lesions were subjected to optical biopsy using a miniaturised fsdCLE system (ViewnVivo®, Optiscan Imaging Ltd) and topical exogenous acriflavine hydrochloride contrast agent before undergoing tissue biopsy and histopathological consensus review by four pathologists. CLE images were captured in vivo in real-time during clinical examination and assessed on-the-fly for the presence of cellular and architectural features of OED/OSCC offering an instantaneous diagnosis. Predicted optical diagnoses were compared to definitive consensus tissue histopathology. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were calculated for the presence/absence of dysplasia/malignancy on optical biopsy. Percentage agreement, Fleiss' kappa, and intraclass correlation coefficient (ICC) were calculated for each assessment stage during the consensus histopathology process. Diagnostic accuracy was extremely high at 88.9%. Other metrics were sensitivity 86.8%, specificity 92%, PPV 94.3% and NPV 82.1%. One hundred percent of carcinoma cases were detected accurately using CLE in the clinic. fsdCLE is a highly accurate, easy-to-use, rapid and slide-free point-of-care in vivo optical technology for diagnosing OED/OSCC and discriminating between dysplastic and non-dysplastic pathology. It demonstrates near-perfect agreement with traditional consensus histopathology without the need for physical tissue biopsy.

What Is the Prevalence of Clinically Important Findings Among Incidentally Found Osseous Lesions?

Patients with incidentally found musculoskeletal lesions are regularly referred to orthopaedic oncology. Most orthopaedic oncologists understand that many incidental findings are nonaggressive and can be managed nonoperatively. However, the prevalence of clinically important lesions (defined as those indicated for biopsy or treatment, and those found to be malignant) remains unknown. Missing clinically important lesions can result in harm to patients, but needless surveillance may exacerbate patient anxiety about their diagnosis and accrue low-value costs to the payor. (1) What percentage of patients with incidentally discovered osseous lesions referred to orthopaedic oncology had lesions that were clinically important, defined as those receiving biopsy or treatment or those found to be malignant? (2) Using standardized Medicare reimbursements as a surrogate for payor expense, what is the value of reimbursements accruing to the hospital system for the imaging of incidentally found osseous lesions performed during the initial workup period and during the surveillance period, if indicated? This was a retrospective study of patients referred to orthopaedic oncology for incidentally found osseous lesions at two large academic hospital systems. Medical records were queried for the word "incidental," and matches were confirmed by manual review. Patients evaluated at Indiana University Health between January 1, 2014, and December 31, 2020, and those evaluated at University Hospitals between January 1, 2017, and December 31, 2020, were included. All patients were evaluated and treated by the two senior authors of this study and no others were included. Our search identified 625 patients. Sixteen percent (97 of 625) of patients were excluded because their lesions were not incidentally found, and 12% (78 of 625) were excluded because the incidental findings were not bone lesions. Another 4% (24 of 625) were excluded because they had received workup or treatment by an outside orthopaedic oncologist, and 2% (10 of 625) were excluded for missing information. A total of 416 patients were available for preliminary analysis. Among these patients, 33% (136 of 416) were indicated for surveillance. The primary indication for surveillance included lesions with a benign appearance on imaging and low clinical suspicion of malignancy or fracture. A total of 33% (45 of 136) of these patients had less than 12 months of follow-up and were excluded from further analysis. No minimum follow-up criteria were applied to patients not indicated for surveillance because this would artificially inflate our estimated rate of clinically important findings. A total of 371 patients were included in the final study group. Notes from all clinical encounters with orthopaedic and nonorthopaedic providers were screened for our endpoints (biopsy, treatment, or malignancy). Indications for biopsy included lesions with aggressive features, lesions with nonspecific imaging characteristics and a clinical picture concerning for malignancy, and lesion changes seen on imaging during the surveillance period. Indications for treatment included lesions with increased risk of fracture or deformity, certain malignancies, and pathologic fracture. Diagnoses were determined using biopsy results if available or the documented opinion of the consulting orthopaedic oncologist. Imaging reimbursements were obtained from the Medicare Physician Fee Schedule for 2022. Because imaging charges vary across institutions and reimbursements vary across payors, this method was chosen to enhance the comparability of our findings across multiple health systems and studies. Seven percent (26 of 371) of incidental findings were determined to be clinically important, as previously defined. Five percent (20 of 371) of lesions underwent tissue biopsy, and 2% (eight of 371) received surgical intervention. Fewer than 2% (six of 371) of lesions were malignant. Serial imaging changed the treatment of 1% (two of 136) of the patients, corresponding to a rate of one in 47 person-years. Median reimbursements to work up the incidental findings analyzed was USD 219 (interquartile range USD 0 to 404), with a range of USD 0 to 890. Among patients indicated for surveillance, the median annual reimbursement was USD 78 (IQR USD 0 to 389), with a range of USD 0 to 2706. The prevalence of clinically important findings among patients referred to orthopaedic oncology for incidentally found osseous lesions is modest. The likelihood of surveillance resulting in a change of management was low, but the median reimbursements associated with following these lesions was also low. We conclude that after appropriate risk stratification by orthopaedic oncology, incidental lesions are rarely clinically important, and judicious follow-up with serial imaging can be performed without incurring high costs. Level III, therapeutic study.

Extracardiac Biopsy Sensitivity in Transthyretin Amyloidosis Cardiomyopathy Patients With Positive 99 mTc-Labeled Pyrophosphate Scintigraphy Findings.

The accurate sensitivity of amyloid deposition in extracardiac tissue (subcutaneous tissue and gastrointestinal tract) has not been evaluated in transthyretin amyloidosis cardiomyopathy (ATTR-CM) patients. This study aimed to evaluate the sensitivity of amyloid deposition in obtained endomyocardial and extracardiac biopsies.Methods and Results: This study retrospectively evaluated 175 consecutive ATTR-CM patients (wild-type [ATTRwt]: 134, hereditary [ATTRv]: 41) who had positive findings on 99 mTc-labeled pyrophosphate (99 mTc-PYP) scintigraphy and underwent tissue biopsy of at least one organ (subcutaneous tissue, gastrointestinal tract, and endomyocardium). Amyloid deposition was observed in the subcutaneous tissue of 57/150 patients (38%), gastrointestinal tract of 80/131 patients (61%), and endomyocardium of 108/109 patients (99%). Compared to patients with ATTRv, ATTRwt had significantly lower sensitivity in subcutaneous tissue (73% vs. 25%, P<0.01) and tended to be lower in the gastrointestinal tract (74% vs. 57%, P=0.08) biopsies. Among 124 patients who underwent both subcutaneous tissue and gastrointestinal tract biopsies, amyloid was detected in at least 1 specimen in 91 (73%) patients. The sensitivity of the combination of extracardiac biopsies was 66% and 94% in ATTRwt-CM and ATTRv-CM, respectively. Multivariate analysis reveals that ATTRv was the only significant predictor of amyloid deposition in the subcutaneous tissue. Subcutaneous tissue and gastrointestinal tract biopsy sensitivity are inadequate, especially in patients with ATTRwt; however, the combination of these extracardiac biopsies contributes to increased sensitivity in patients with positive 99 mTc-PYP scintigraphy findings.

The Role of Tissue and Liquid Biopsy in the Clinical Management of Adult Lung Cancer Patients in King Abdul-Aziz Medical City in Riyadh, Saudi Arabia.

BackgroundLung cancer is the most fatal malignancy worldwide, characterized by uncontrolled growth in the tissue of the lung(s). The diagnosis of lung cancer depends on the medical history of the patient, along with the physical examination, and various imaging studies. Furthermore, sputum cytology, thoracentesis, or a tissue and liquid biopsy can be examined. The TNM (tumor size, lymph nodes, and metastasis) system is used for staging and grading lung cancer. This study aimed to evaluate the role of tissue vs liquid biopsy in the clinical management of adenocarcinoma, at King Abdulaziz Medical City, Riyadh.MethodsIn this cross-sectional study, all adenocarcinoma patients treated between January 2016 to December 2018 were included using consecutive sampling. The participants were ≥ 18 years old patients with histologically confirmed adenocarcinoma (stage IIIb/IV) regardless of the mutation status. This data was collected through chart review. Data analysis was performed using the IBM Statistical Software for Social Sciences (SPSS) software, version 22 (IBM SPSS Statistics for Windows, Armonk, NY). ResultsA total of 58 participants were included in the analysis. All of them had undergone a tissue biopsy, while only 16 patients underwent liquid biopsy. Out of all patients, 26% of patients had tissue biopsy-related complications (TBRC), with pneumothorax being the most common complication. Single gene testing for epidermal growth factor receptor (EGFR) for patients who underwent tissue biopsy showed a 35% mutation rate. For the anaplastic lymphoma kinase (ALK) gene, 13% were found to be mutated; for the ROS proto-oncogene 1 (ROS1) gene, only 7% were seen to be mutated. For a panel of 12 genes, 25% had the tumor protein 53 (TP53) gene mutation and 39% had the gene Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. For patients who underwent a liquid biopsy, 20% had the TP53 mutation, 43% had the EGFR mutations on a single gene test and 42% on a panel test, and 10% had the KRAS mutation.ConclusionWe found that tissue and liquid biopsy showed genetic mutations, particularly with EGFR, TP53, and KRAS genes, among adenocarcinoma patients. Identifying genetic changes in adenocarcinoma patients is essential for charting a targeted therapy. Primary EGFR mutations and rearrangements of ALK or ROS1 are the only gene mutations that can be done with specific tyrosine kinase inhibitors available for clinical practice. Therefore, we recommend further studies to evaluate the role of tissue and liquid biopsy in clinical practice.

Curvularia dacryoadenitis and panophthalmitis: case report

Purpose: To examine the clinical course of dacryoadenitis and panophthalmitis from Curvularia infection. Methods: Retrospective case review. The authors reported a case of 36-year-old female who presented with dacryoadenitis and panophthalmitis. Clinical features, investigations and management were described. Results: A 36-year-old female with history of controlled bilateral pars planitis presented with dacryoadenitis and panophthalmitis in the right eye. Her medication at presentation was prednisolone 5 mg/d and mycophenolate mofetil 250 mg/d.&nbsp; She underwent tissue biopsy. The culture yielded Curvularia spp. Topical and systemic anti-fungal medications were given with a good response. Conclusion: Curvularia can be the cause of dacryoadenitis with panophthalmitis in immunocompromised hosts. Keywords: Curvularia, dacryoadenitis, panophthalmitis, fungus

Circulating miRNAs as Novel Non-Invasive Biomarkers to Aid the Early Diagnosis of Suspicious Breast Lesions for Which Biopsy Is Recommended.

Simple SummaryIn population-based screens, tissue biopsy remains the standard practice for women with imaging that suggests breast cancer. We examined circulating microRNAs as minimally invasive diagnostic biomarkers to discriminate malignant from benign breast lesions. A retrospective cohort of plasma samples divided into training and testing sets and a prospective cohort of women with suspicious imaging findings who underwent tissue biopsy were investigated through a global microRNA profile by OpenArray. Seven signatures, involving 5 specific miRNAs (miR-625, miR-423-5p, miR-370-3p, miR-181c, and miR-301b), were identified and validated in the testing set. Among the 7 signatures, the discriminatory performances of 5 of them were confirmed in the prospective cohort.In population-based screens, tissue biopsy remains the standard practice for women with imaging that suggests breast cancer. We examined circulating microRNAs as minimally invasive diagnostic biomarkers to discriminate malignant from benign breast lesions. miRNAs were analyzed by OpenArray in a retrospective cohort of plasma samples including 100 patients with malignant (T), 89 benign disease (B), and 99 healthy donors (HD) divided into training and testing sets and a prospective cohort (BABE) of 289 women with suspicious imaging findings who underwent tissue biopsy. miRNAs associated with disease status were identified by univariate analysis and then combined into signatures by multivariate logistic regression models. By combining 16 miRNAs differentially expressed in the T vs. HD comparison, 26 signatures were also able to significantly discriminate T from B disease. Seven of them, involving 5 specific miRNAs (miR-625, miR-423-5p, miR-370-3p, miR-181c, and miR-301b), were statistically validated in the testing set. Among the 7 signatures, the discriminatory performances of 5 were confirmed in the prospective BABE Cohort. This study identified 5 circulating miRNAs that, properly combined, distinguish malignant from benign breast disease in women with a high likelihood of malignancy.

Abstract PD9-10: Investigating the clinical utility of tumor mutational burden in predicting rapid progression and death in patients with metastatic breast cancer

Abstract Background Up to 30% of breast cancer patients will eventually relapse with metastatic disease. With an increasing array of therapeutic options, there is an ongoing need for predictive biomarkers to help guide treatment strategies including sequencing of therapies in the metastatic setting. We sought to evaluate the prognostic and predictive potential of a panel-specific tumor mutational burden (TMB) in metastatic breast cancer patients. Methods METAMORPH is a prospective, longitudinal cohort study. Eligible patients (pts) had newly diagnosed or progressive metastatic breast cancer and enrolled prior to starting a new line of therapy (physician’s choice) at the University of Pennsylvania. Pts underwent tissue biopsy of a suspected metastatic site. Tumor samples were analyzed for mutations and copy number alterations (CNA’s) using our institution’s CLIA-certified Center for Personalized Diagnostics (CPD) targeted gene panel, which evolved over the course of the study from 20 genes to 152 genes. TMB-high (TMB-H) was defined as ≥3 mutations and/or copy-number gains (CNG) among 18 genes shared across all panel versions. Pts were followed for time to progression (TTP), progression-free survival (PFS), and overall survival (OS). The frequency of rapid progressors and rapid death (defined as having progressed or died within 3 months of enrollment, respectively) was assessed. Results Three hundred pts enrolled from 2013-2020, of whom 200 pts had CPD reports generated. Of these, 12 pts were excluded due to either no treatment change on enrollment (n=11) or different primary cancer on biopsy (n=1). Thus 188 pts were included in this analysis. The median age was 55 years (range 28-79). 77% of pts identified as white, 18% as Black or African American, and 3.2% as Asian. Pts had a median of 1 line (range 0-12) of prior systemic therapy in the metastatic setting. 46.8% had no prior therapies for MBC, while 31% had ≥3 prior lines of therapy. 74.4% were HR+, 22.8% TNBC, and 2.7% HR-/HER2+. 6.9% of the cohort were classified as TMB-H. The average mutation/CNG rate was 2.2/sample, and 22.5% had no mutations or CNA’s. The most common mutations were TP53 (35%) and PIK3CA (26%). While TMB-H patients showed a statistically non-significant trend towards shorter median TTP and PFS compared with TMB-L, they comprised a significantly greater proportion of rapid progressors (54.5% vs 24.1%, p=0.027), with an odds ratio for rapid progression of 3.8 (95% CI 1.08-13.2). In a multivariate logistic regression analysis, TMB-H remained independently associated with rapid progression when adjusted for receptor subtype and next line of therapy. Receptor subtype analysis revealed that ER- (including ER-/PR+) patients with TMB-H had a shorter median TTP compared to ER- TMB-L (147 vs 68 days, p=0.03). TMB-H was also associated with significantly shorter OS compared with TMB-L (587 vs 648 days, p=0.02; HR 2.2 [95% CI 1.11-4.41]). 44.4% of TMB-H pts died within 3 months of enrollment, as compared to 11.0% of TMB-L pts (p=0.005), with an odds ratio for rapid death, adjusted for number of previous lines of therapy and receptor subtype, of 6.7 (95% CI 1.5-31.0). Conclusion MBC pts who are TMB-H represent a population who are highly resistant to standard therapies, progress rapidly, and have significantly shorter overall survival with more rapid time to death. Our data support further studies investigating the utility of TMB as a predictive biomarker in directing patients away from standard treatment options and towards novel approaches e.g. immunotherapy. Citation Format: Igor Makhlin, Amy S Clark, Paul Wileyto, Noah Goodman, John Ndicu, Shannon DeLuca, Candace Clark, S. William Stavropoulos, Natalie Shih, Michael D Feldman, Susan M Domchek, Jennifer M Matro, Payal D Shah, Hayley M Knollman, Kevin R Fox, Kara N Maxwell, Lewis A Chodosh, Angela DeMichele. Investigating the clinical utility of tumor mutational burden in predicting rapid progression and death in patients with metastatic breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PD9-10.

Value of diffusion-weighted images in diagnosis of locoregionally recurrent rectal tumors

IntroductionTo assess the value of referring to Diffusion-weighted images in evaluation of T2-weighted images of patients clinically suspicious of locoregional rectal cancer recurrence. MethodsAfter ethics committee approval and informed consent were obtained, 37 consecutive patients (male/female of 22/15; mean age 56 ± 13.5 SD) clinically suspicious of recurrent rectal tumor were prospectively included in the study over a two-year period. T2-weighted images of the patients were reviewed and the results were recorded. Right after that, the corresponding DWI images were provided for the radiologist and new ratings were given to the patients after taking into account the DWI findings. Finally, the patients underwent tissue biopsy. Receiver Operating Characteristic (ROC) analysis was performed, and Area Under the Curve (AUC) of the “T2-weighted alone” and “T2-weighted + DWI” methods were calculated and compared. Results“T2-weighted alone” and “T2-weighted + DWI” methods had an AUC of 0.64 (95% CI 0.47 to 0.79) and 0.75 (95% CI 0.58 to 0.88), respectively. The Difference between the two AUCs was 0.11 (P = 0.16). In the subgroup of patients having equivocal ratings in T2-weighted images, DWI images correctly identified 81% (13/16) of patients with true tumor recurrence and 66% (8/12) of patients without recurrence. ConclusionOur results suggest that referring to DWI does not significantly change the overall diagnostic performance of T2-weighted images. However, DWI is of great value in evaluation of the subgroup of patients with equivocal findings in T2-weighted images. Studies with larger sample sizes are needed to confirm these findings. Implications for practiceWhen T2-weighted images are equivocal, DWI images may be helpful in evaluation of patients with suspected locoregional recurrence of rectal tumor.

Clinical and imaging findings suggestive of histopathological immunoglobulin G4-related disease: a single-center retrospective study.

To investigate the clinical and imaging features predicting the histopathological diagnosis of immunoglobulin G4 (IgG4)-related disease (IgG4RD) in patients with suspected IgG4RD on computed tomography (CT). We retrospectively reviewed the medical records of 178 patients with CT findings suspicious of IgG4RD from January 2015 to December 2017. Patients who underwent tissue biopsy were included to evaluate the association between patient characteristics and histopathological diagnosis of IgG4RD. The histopathological diagnosis was classified into IgG4RD and non-IgG4RD. Clinical, laboratory, and imaging features were compared between patients with IgG4RD and non-IgG4RD, and logistic regression analysis was performed to identify the predictors for histopathologically confirmed IgG4RD. Of the 103 patients with histopathologically proven diseases, 46 and 57 patients were classified as IgG4RD and non-IgG4RD, respectively. The median age was 64 years; 65% of patients were male. There were significant differences in sex (P = 0.035), fever (P = 0.039), serum IgG4 level (P < 0.001), renal involvement (P = 0.036), lacrimal or salivary glands involvement (P = 0.050), swelling pattern on CT (P = 0.001), and positron emission tomography (PET)-CT findings (P < 0.001) between patients with IgG4RD and non-IgG4RD. Multivariate analysis revealed elevated IgG4 level > 135 mg/dL (odds ratio [OR] = 5.418, P < 0.001), kidney involvement (OR = 6.170, P = 0.044), and the swelling feature on CT (OR = 4.301, P = 0.012) to be independent factors for histopathological diagnosis of IgG4RD. This study suggests that elevated IgG4 level, renal involvement, and swelling pattern on CT are associated with histopathological diagnosis of IgG4RD. The clinical and imaging features might help to decide further evaluation in patients with clinically suspected IgG4RD. Key Points • Computed tomography (CT) is not sufficient to discriminate between IgG4-related disease (IgG4RD) and non-IgG4RD conditions. • Histopathological diagnosis of IgG4RD is associated with elevated IgG4 level, renal involvement, and swelling pattern on CT. • Positron emission tomography-CT may be a useful diagnostic tool in patients with clinically suspected IgG4RD. >.

Outcomes of incidental pulmonary nodules in head-and-neck squamous cell cancer patients treated with curative intent

Introduction: Incidental pulmonary nodule(s) (IPNs) are a common finding during staging imaging for the head-and-neck squamous cell cancers (HNSCC) treated with curative intent. Currently, the incidence of metastasis or synchronous malignancies and outcomes for IPN in this population is unknown. Methods: All cases (n = 2489) reviewed at a tertiary Australian Institution's head and neck (H and N) multidisciplinary meeting, from January 2010 to December 2014, were included. Of these patients, 310 (12.5%) had an HNSCC with an IPN that had been detected during staging imaging. These patients were also to undergo treatment by curative intent. Clinicopathological characteristics, the incidence of malignancy, progression-free survival, and overall survival (OS) were collected retrospectively over 5 years. Results: The median age of patients with an IPN was 66 (range 25–95) years. Tissue diagnosis of IPN was attempted in 46 (14.8%) patients due to radiological suspicion of malignancy. Malignancy was confirmed in 33 (11.0%) patients. From these, 33 patients, 11 (30.3%) had histological diagnoses of nonsquamous cell lung cancers and hence are not due to metastatic spread from a primary HNSCC. Age, gender, previous malignancies, smoking status, p16 status, stage, or primary site did not predict for malignancy. The incidence of pulmonary metastasis in patients who did not undergo tissue biopsy due to low clinical and radiological suspicion of malignancy (n = 244) occurred in 10 patients (4.1%). At the time of analysis, 91 (29.4%) patients had died, and tumor recurrence had occurred in 82 (26.5%) patients. The mean OS was 48 months (95% confidence interval: 44–51). OS was significantly associated with greater age (hazards ratio [HR] 1.04, P < 0.001); immunosuppression (HR 2.15, P = 0.013); and biopsy being attempted (HR 1.78, P = 0.013). There was no biopsy related mortality. Discussion: Detection of an IPN in patients undergoing workup for H and N cancer is common. The risk of malignancy in these IPNs however, is low. We did not identify any clinicopathological parameters to predict malignancy in this setting. Advanced age, current smoking status, and history of immunosuppression predict for poor outcomes. Further work is being undertaken to analyze radiological features that may predict malignancy in an IPN found during the radiological staging of HNSCC.

P897Diagnostic utility of tissue biopsy in transthyretin cardiac amyloidosis diagnosed by non-invasive diagnostic criteria

Abstract Background In the recent past, transthyretin cardiac amyloidosis (TTR-CA) is recognized as an important cause of heart failure with preserved ejection fraction, and diagnostic utility of 99mTc-pyrophosphate (99mTc-PYP) scintigraphy in TTR-CA has been established. However, pathological evaluation is still the basis to confirm diagnosis. Subcutaneous tissue and gastrointestinal tract biopsy are useful examinations alternative to endomyocardial biopsy. Nevertheless, the positive ratio of amyloid deposition in these organs is not fully evaluated based on recent non-invasive diagnostic criteria. Purpose Our aim was to evaluate the diagnostic sensitivity of tissue biopsy in TTR-CA patients diagnosed by 99mTc-PYP scintigraphy. Methods We retrospectively evaluated 124 consecutive TTR-CA patients [wild-type (ATTRwt): 90, hereditary (hATTR): 34] who were diagnosed by positive findings of 99mTc-PYP scintigraphy (visual score 2 or 3) between June 2002 and January 2019 at our institute. Results A total of 114 patients underwent tissue biopsy at least one organ. Amyloid was detected on Congo red staining of subcutaneous tissue (43/97: 44%), gastrointestinal tract (52/78: 67%) and heart (78/79: 99%), respectively. Among 70 patients who underwent both subcutaneous tissue and gastrointestinal tract biopsy, amyloid was detected at least one specimen in 57/70 (81%). Compared to hATTR CA patients, ATTRwt CA patients had lower positive ratio of subcutaneous tissue (81% vs. 27%) and gastrointestinal tract (73% vs. 63%) biopsy. Conclusion Non-invasive diagnostic criteria of TTR-CA had excellent sensitivity of amyloid deposition in heart. The diagnostic sensitivity of subcutaneous tissue and gastrointestinal tract biopsy was lower in ATTRwt CA compared to hATTR CA. Combination of subcutaneous tissue and gastrointestinal tract biopsy was useful for pathological confirmation of amyloid deposition without endomyocardial biopsy.

Abstract 4920: A status of re-biopsy for non-small-cell lung cancer patients after first EGFR-TKI failure and incidence of T790M mutation

Abstract Background: Among patients with advanced non-small-cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutation, T790M mutation is the most common mechanism of drug resistance to first- or second-generation EGFR tyrosine kinase inhibitors (TKIs). However, the proportion of patients with T790M mutation at re-biopsy is varied by studies or biopsy methods. Methods: A total of 126 patients who were treated with first- or second-generation EGFR TKIs and had disease progression in our institution from January 2017 to September 2018 were eligible for this study. We retrospectively evaluated re-biopsy methods and the proportion of patients who harbor T790M mutation. Result: A total of 126 patients (male, 36.5% ; median age, 69 year ) were included. Among 126 patients, 118 patients (93.7%) underwent re-biopsy by any methods: tissue biopsy or cytology sampling in 68 patients and plasma sampling in 50 patients during a first re-biopsy, and 44 patients (37.3%) had T790M mutation. During the first biopsy, in the 68 patients who underwent tissue biopsy or cytology sampling, 32 patients (47%) were positive for T790M mutation, nevertheless there were no tumor samples in 4 patients and only atypical cells in 3 patients and 1 patient was identified transformation to SCLC. In the 50 patients who performed plasma sampling during a first re-biopsy, T790M mutation was detected in only 12 patients (24%). Second re-biopsy was conducted in 19 patients among 74 patients resulted in T790M-negative or unknown after the first re-biopsy, and 10 patients were positive for T790M mutation. Eventually, a total of 80 patients were performed tissue biopsy or cytology sampling, 74 patients (96.1%) were found to have any EGFR mutations and T790M mutation was detected in 39 patients (48.1%). On the other hand, 59 patients underwent plasma sampling and 31 patients (52.5%) were found to have any EGFR mutations and T790M mutation was detected in only 17 patients (28.8%). Totally 54 patients (42.9%) were detected T790M mutation, and 52 patients (41.3%) received Osimertinib subsequently. Conclusion: After progression of first- or second-generation EGFR-TKIs, about 95% of patients underwent re-biopsy, and T790M mutation was present in approximately half of patients who underwent re-biopsy and almost all patients who were positive for T790M mutation could receive Osimertinib. In patients who underwent tissue biopsy or cytology sampling, high frequency of detecting any EGFR mutations contributed to higher detection rate of T790M mutation compared to plasma sampling. To improve the sensitivity for T790M mutation detection, tissue biopsy or cytology sampling should be performed if possible. Citation Format: Tetsuya Sakai, Hibiki Udagawa, Yoshitaka Zenke, Keisuke Kirita, Shigeki Umemura, Shingo Matsumoto, Kiyotaka Yoh, Seiji Niho, Genichiro Ishii, Koichi Goto. A status of re-biopsy for non-small-cell lung cancer patients after first EGFR-TKI failure and incidence of T790M mutation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4920.

Provisional Guideline Recommendation for EGFR Gene Mutation Testing in Liquid Samples of Lung Cancer Patients: A Proposal by the Korean Cardiopulmonary Pathology Study Group.

Liquid biopsy for detection of mutation from circulating tumor DNA is a new technology which is attractive in that it is non-invasive. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) is an effective first line drug for advanced non-small cell lung cancer patients who harbor activating EGFR mutation. During the course of treatment, resistance against TKI arises which can be contributed to EGFR T790M mutation in about 50–60% of patients. Third generation TKI may overcome the resistance. In patients who cannot undergo tissue biopsy due to variable reasons, liquid biopsy is an excellent alternative for the detection of EGFR T790M mutation. However, this relatively novel method requires standardization and vigorous quality insurance. Thus, a standard set of guideline recommendations for liquid biopsy for EGFR mutation testing suitable for the Korean medical community is necessary. In this article, we propose a set of provisional guideline recommendations that was discussed and approved by the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists.

Utility of minimally invasive thoracoscopy for assessment of residual mediastinal lymphoma

BackgroundPatients with primary mediastinal lymphomas frequently present with a residual mass after completion of first-line therapy. Although a positron emission tomography scan is usually recommended, it fails to distinguish between persistent lymphoma and inflammation. Although percutaneous biopsy may have a high diagnostic yield for the initial diagnosis of mediastinal lymphomas, this biopsy has poor accuracy for detecting persistent disease in a residual mass given the heterogeneity of these residual masses. Because persistent disease has important therapeutic implications, we evaluated the role of operative biopsy in detecting lymphoma in the residual mass. MethodsBetween 2009 and 2015, consecutive patients (n = 77) undergoing tissue biopsy for initial diagnosis as well as for a positron emission tomography-positive residual mass were included. Tissue biopsy for a residual mass was repeated until frozen section was diagnostic or at least the mass on the ipsilateral hemi-mediastinum was resected. ResultsOf the initial 77 patients, 34 underwent operative restaging for a residual mass after chemotherapy, while 43 had a complete response. In these 34 patients, operative biopsy revealed the presence of lymphoma in 53%, predominantly Hodgkin's disease and diffuse large B-cell lymphoma. There was no significant difference in tumor volume (51% versus 39%) and a decrease in the positron emission tomography-standardized uptake valuemax (68% vs 60%) in patients with or those without persistent lymphoma. There were no surgical complications and the duration of stay for all patients undergoing thoracoscopy was <24 hours. Residual lymphoma was treated with second-line therapy guided by the pathologic analysis. ConclusionA large proportion of patients with residual positron emission tomography-avidity after first-line chemotherapy of mediastinal lymphomas have residual disease that can be detected safely using minimally invasive thoracoscopy.

Expression of vascular endothelial growth factor receptor 2 and clinical response to lenvatinib in patients with anaplastic thyroid cancer.

Angiogenesis plays a crucial role in the development, growth, and metastasis of carcinomas, and studies have reported conflicting evidence regarding the VEGFR expression in anaplastic thyroid cancer. We investigated the expression of VEGFR2 in patients with anaplastic thyroid cancer (ATC) and analyzed the clinical response to the VEGFR inhibitor lenvatinib. This cross-sectional study included primary tumor samples obtained from 12 patients with ATC, including 5 males and 7 females (age range 63-89years) who underwent surgery or core needle biopsy for a thyroid tumor in the Department of Breast and Endocrine Surgery at Kanagawa Cancer Center in Kanagawa, Japan. VEGFR2 protein expression in the ATC samples was analyzed by immunohistochemistry in all patients, and the therapeutic effect of lenvatinib was evaluated in seven patients who underwent tissue biopsy and lesion evaluation. VEGFR expression was not detected in any of the samples from the 12 patients. Four of the 12 patients treated with lenvatinib had partial response, the three patients achieved stable disease, and the five patients were not examined. There was no correlation between the expression of VEGFR2 in tumor tissue and the clinical response to lenvatinib among patients with ATC. Further studies are necessary to elucidate the mechanism underlying the response to lenvatinib.

Endogenous Fluorescence Lifetime Imaging (FLIM) Endoscopy For Early Detection Of Oral Cancer And Dysplasia.

We have performed a pilot clinical study, in which multispectral endogenous fluorescence (or autofluorescence) lifetime imaging (FLIM) was performed on clinically suspicious oral lesions of 73 patients undergoing tissue biopsy for oral dysplasia and cancer diagnosis. The results from this pilot study indicated that mild-dysplasia and early stage oral cancer could be detected from benign lesions using a computed aided diagnosis system developed based on biochemical and metabolic biomarkers derived from the endogenous FLIM images. The diagnostic performance of this novel FLIM clinical tool was estimated using a leave-onepatient-out cross-validation approach, which reported levels of sensitivity >90%, specificity >85%, and Area Under the Receiving Operating Curve (ROC-AUC) >0.9.

Relative Gene Expression Analysis from Urine Samples of Patients with Prostate Disease

Conventional screening and diagnostic procedures in prostate complaints rely on PSA (Prostate Specific Antigen) concentration which is not specific for prostate cancer and frequently leads to unnecessary invasive procedures in order to exclude malignant disease. It is estimated that approximately 50% of persons who underwent tissue biopsy did so based on false positive PSA value. Therefore a proper and timely differential diagnosis of malignant disease using non-invasive techniques remains one of the biggest challenges in medicine. Urine is the invaluable source of biological information contained in small molecules i.e. RNA that is easily accessible and detectable using molecular genetics techniques. We describe economical and fast method for relative expression analysis applicable to any target gene using urine as a sample. Efficient non-invasive method for identification of malignant or high risk cases prove useful in reduction of patient distress during the diagnostic procedure and significantly reduce healthcare costs.