■ Identify the most commonly affected organs in IgG4-related disease. ■ Describe characteristic imaging findings of pancreatic and extrapancreatic IgG4-related disease. ■ Discuss the differential diagnosis in each affected organ.
Background: Contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) and quantitative-elastography endoscopic ultrasound (QE-EUS) are considered useful tools for the evaluation of solid pancreatic tumors (SPT). The aim of our study was to evaluate the diagnostic accuracy of CEH-EUS, QE-EUS, and the combination of both for the differential diagnosis of SPT. Methods: Sixty-two consecutive patients (mean age 64.3 years, range 32-89 years, 44 male) who underwent EUS for the evaluation of SPT were prospectively included. EUS was performed with a linear Pentax-EUS and a Hitachi-Preirus processor. The mass (area A) and a reference area B were selected during QE-EUS, and results expressed as B/A (strain ratio). A strain histogram of the mass was also evaluated. Microvascularization of the tumor was evaluated over 2 min during CEH-EUS after intravenous injection of 4.8 mL SonoVue. Final diagnosis was based on histopathology of surgical specimens or EUS-guided tissue acquisition and clinical follow-up in non-operated cases. Diagnostic accuracy of CEH-EUS, QE-EUS, and their combination was calculated. Results: Median size of the masses was 32 mm (range 12-111). Final diagnosis was pancreatic adenocarcinoma (n ¼ 45), neuroendocrine tumor (n ¼ 3), inflammatory mass (n ¼ 10), pancreatic metastasis (n ¼ 2), autoimmune pancreatitis (n ¼ 1), and a mucinous cystadenocarcinoma (n ¼ 1). Overall accuracies for determination of malignancy using QE-EUS, CEH-EUS, their combination, and EUS-guided tissue acquisition were 98.4% (95% confidence interval (CI): 91.4-99.7), 85.5% (95% CI: 74.7-92.2), 91.9% (95% CI: 82.5-96.5), and 91.5% (95% CI: 83.6-99.5), respectively. Conclusion: The combination of QE-EUS and CEH-EUS is a useful tool for the differential diagnosis of SPT, giving complementary information. However, this combination does not significantly increase the diagnostic accuracy of either of the techniques performed alone.
Duplication cysts are rare gastrointestinal congenital abnormalities. They can occur anywhere throughout the gastrointestinal tract, and gastric duplication cysts are most uncommon, representing only 4-8% of all gastrointestinal duplication cysts. Nowadays several theories try to explain the pathogenic mechanisms involved. These cysts are usually diagnosed during early childhood, and very rarely are detected in adults, mostly incidentally due to a lack of symptoms. Close to 50% of gastric cysts are associated with other abnormalities. It is extremely important that a meticulous differential diagnosis is performed regarding other diseases, mainly malignancies with a cystic component. Although extremely uncommon, a malignant transformation of these lesions has been reported, which highlights the importance of a correct diagnosis. Herein we report the case of a duplication cyst in an adult, which was detected by endoscopic ultrasound-guided fine-needle aspiration, recently proposed as the most accurate technique for the identification of these lesions.
Anaplastic thyroid carcinoma (ATC) and poorly differentiated thyroid carcinoma (PDTC) have limited treatment options, and immune profiling may help select patients for immunotherapy. The prevalence and relevance of programmed death-1 ligand (PD-L1) expression and the presence of immune cells in ATC and PDTC has not yet been well established. The present study investigated PD-L1 expression (clone 22C3) and cells in the tumor microenvironment (TME), including tumor-infiltrating lymphocytes (TILs), tumor-associated macrophages (TAMs) and dendritic cells, in whole tissue sections of 15 cases of ATC and 13 cases of PDTC. Immunohistochemical PD-L1 expression using a tumor proportion score (TPS) with a 1% cut-off was detected in 9/15 (60%) of ATC cases and 1/13 (7.7%) of PDTC cases (P=0.006). PD-L1 expression in TILs was limited to the ATC group (73.3 vs. 0% in ATC and PDTC, respectively). In the ATC group, the TPS for tumor positive PD-L1 expression revealed a non-significant trend towards worse survival, but no difference was observed when investigating PD-L1 expression in TILs and TAMs. In addition to increased PD-L1 expression, all ATC cases exhibited significantly increased CD3 + and CD8 + T cells, CD68 + and CD163 + macrophages, and S100 + dendritic cells compared with the PDTC cases. Loss of mutL homolog 1 and PMS1 homolog 2 expression was observed in one ATC case with the highest PD-L1 expression, as well as in the only PDTC case positive for PD-L1. Notably, the latter was the only PDTC case exhibiting positivity for p53 and a cellular microenvironment similar to ATC. The current results indicated that PD-L1 expression was frequent in ATC, but rare in PDTC. In addition to PD-L1, the present study suggested that microsatellite instability may serve a role in both the TME and the identification of immunotherapy candidates among patients with PDTC.
Given the high incidence and excellent prognosis of many papillary thyroid microcarcinomas, the Porto proposal uses the designation papillary microtumor (PMT) for papillary microcarcinomas (PMCs) without risk factors to minimize overtreatment and patients’ stress. To validate Porto proposal criteria, we examined a series of 190 PMC series, also studying sex hormone receptors and BRAF V600E mutation. Our updated Porto proposal (uPp) reclassifies as PMT incidental PMCs found at thyroidectomy lacking the following criteria: (a) detected under the age of 19 years; (b) with multiple tumors measuring >1 cm adding up all diameters; and (c) with aggressive morphologic features (extrathyroidal extension, angioinvasion, tall, and/or hobnail cells). PMCs not fulfilling uPp criteria were considered “true” PMCs. A total of 102 PMCs were subclassified as PMT, 88 as PMC, with no age or sex differences between subgroups. Total thyroidectomy and iodine-131 therapy were significantly more common in PMC. After a median follow-up of 9.6 years, lymph node metastases, distant metastases, and mortality were only found in the PMC subgroup. No subgroup differences were found in calcifications or desmoplasia. Expression of estrogen receptor-α and estrogen receptor-β, progesterone receptor, and androgen receptor was higher in PMC than in nontumorous thyroid tissue. BRAF mutations were detected in 44.7% of PMC, with no differences between subgroups. In surgical specimens, the uPp is a safe pathology tool to identify those PMC with extremely low malignant potential. This terminology could reduce psychological stress associated with cancer diagnosis, avoid overtreatment, and be incorporated into daily pathologic practice.
AIMTo evaluate factors that influence the diagnostic accuracy of endoscopic ultrasound (EUS)-guided tissue acquisition for lymph node enlargement in the absence of an on-site pathologist.METHODSA retrospective analysis of patients who underwent EUS-guided tissue acquisition for the pathological diagnosis of lymph node enlargement between April 2012 and June 2015 is reported. Tissue acquisition was performed with both cytology and biopsy needles of different calibers. The variables evaluated were lymph node location and size, number of passes and type of needle used. Final diagnosis was based on surgical histopathology or, in non-operated cases, on EUS-guided tissue acquisition and imaging assessment with a minimum clinical follow-up of 6 mo.RESULTSDuring the study period, 168 lymph nodes with a median size of 20.3 mm (range 12.5-27) were sampled from 152 patients. Ninety lymph nodes (53.6%) were located at mediastinum, and 105 (62.5%) were acquired with biopsy needles. The final diagnosis was benign/reactive origin in 87 cases (51.8%), malignant in 65 cases (38.7%), and lymphoma in 16 cases (9.5%). The sensitivity, specificity, positive predictive value and negative predictive value for the detection of malignancy were 74.1%, 100%, 100% and 80.6%, respectively. The overall accuracy was 87.5% (95%CI: 81.7-91.7). No variables were independently associated with a correct final diagnosis according to the multivariate analysis.CONCLUSIONEUS-guided tissue acquisition is a highly accurate technique for assessing lymph node enlargement. None of the variables evaluated were associated with diagnostic accuracy.
The hobnail variant (HV) of papillary thyroid carcinoma (PTC) is an unusual entity recently proposed as an aggressive variant of PTC. We describe the pathologic and molecular features of 2 cases of HV of PTC. Both tumors presented in stage III (pT3 pN1a M0). The first case was diagnosed in a 62-year-old man, whereas the second was in a 53-year-old woman. Both patients were treated with total thyroidectomy and radioactive iodine. The primary tumors showed a hobnail/micropapillary pattern in ≥50% of the neoplasm, and positivity for TTF-1, TTF-2, thyroglobulin (TG), cyclin D1, and p53. The Ki-67 index was 4.6% and 5%, respectively. In case 1, the tumor disclosed BRAFV600E and TERT C228T (124:G>A) promoter gene mutation, negativity for NRAS, HRAS, and KRAS mutations, and negativity for RET/PTC1, RET/PTC3, and PAX8/PPARγ rearrangements. After 11 years the patient died with cervical lymph node, bone, and liver metastases. In the liver metastasis, the tumor displayed columnar cell PTC areas (positive for TTF-1, TG, and BRAFV600E) merging with undifferentiated carcinoma (UC) areas (positive for TTF-1 and BRAFV600E; negative for TG). In case 2, the patient died 6 years after treatment with local recurrence and disseminated metastases to the lung, pleura, bone, and liver. The tumor recurrence showed a UC component (positive for cyclin D1 and p53; negative for TTF-1 and TG) with a residual HV of PTC (positive for cyclin D1, p53, TTF-1, and TG). No BRAF, TERT, NRAS, HRAS, nor KRAS mutations were detected in the primary tumor or recurrence in case 2. Our findings suggest that p53-positive HV is a very aggressive form of PTC prone to progression to UC.
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