Extensive Vascular Invasion Research Articles

Invasive Fungal Rhinosinusitis: The First Histopathological Study in Vietnam.

Invasive fungal rhinosinusitis (IRFS) is a rare but highly fatal disease. The two primary groups of pathogens, Mucorales and Aspergillus, require different treatments and have distinct prognoses. This study aimed to analyze the histopathological features of IFRS. We conducted a retrospective study involving 57 IFRS cases. Demographic and comorbid characteristics were obtained from clinical records. Two pathologists independently examined the histopathological features using H&E, PAS, and GMS-stained slides. Fungal groups were identified with PCR under the guidance of histopathology. The mean age of IFRS was 58.9 ± 13.4. The male-to-female ratio was 1.4:1. 100% of cases had diabetes comorbidity. Mucorales, Aspergillus, and other fungi were found in 61.4%, 33.3%, and 5.3% of cases, respectively. No Aspergillus and Mucorales co-infections were detected. Histopathology and PCR results were strongly concordant in classifying pathogens (Cohen's kappa = 84.2%, 95% CI 60.1% - 100%, p < 0.001). Mucormycosis exhibited higher rates of extensive necrosis and vascular invasion, and lower rates of pigment and spore presence than the non-Mucormycosis group (p < 0.001, p = 0.01, p = 0.02, p = 0.03, respectively). Extensive necrosis and vascular invasion were statistically significantly correlative (OR = 13.03, 95% CI 2.62-64.75, p = 0.002). IFRS predominantly affects older adults and males. Histopathology is a reliable method for differentiating between Mucorales and Aspergillus. When extensive necrosis is detected, it is critical to investigate for vascular invasion carefully. The vascular invasion, degree of necrosis, pigments, and spores are valuable factors for distinguishing fungal agents of IFRS.

8172 Retrospective Analysis of mRNA Expression Based Signatures of Thyroid Tumor Invasion and Metastases

Abstract Disclosure: S. Ahmadi: None. E. Namiranian: None. M. Alshalalfa: Employee; Self; Veracyte, Inc.. Stock Owner; Self; Veracyte, Inc. R. Jiang: Employee; Self; Veracyte, Inc.. Stock Owner; Self; Veracyte, Inc. Y. Hao: Employee; Self; Veracyte, Inc.. Stock Owner; Self; Veracyte, Inc. J.P. Klopper: Employee; Self; Veracyte, Inc.. Stock Owner; Self; Veracyte, Inc. R.T. kloos: Employee; Self; Veracyte, Inc.. Stock Owner; Self; Veracyte, Inc.. E. Marqusee: None. The American Thyroid Association thyroid cancer risk stratification system is driven primarily by the extent of vascular and extrathyroidal extension, as well as lymph node metastases. Minimizing surgical intervention for thyroid tumors from indeterminate thyroid nodules (ITN - Bethesda III and IV cytology) is often preferred to mitigate surgical complications and lessen the need for thyroid hormone supplementation post-operatively if clinical outcomes are not worsened. By leveraging the whole transcriptome derived Afirma Genomic Sequencing Classifier (GSC) thyroid nodule molecular testing platform, mRNA expression-based signatures were developed to predict thyroid tumors with a low risk of clinically significant invasion and metastases with a &amp;gt; 95% negative predictive value as part of the Afirma Genomics Resource for Intelligent Discovery (GRID). The objective of this study was to analyze the performance of these signatures on a retrospective cohort of patients with ITN who had Afirma GSC suspicious findings and thyroid surgery. Two hundred three subjects were evaluated, and pathology reports were scored for the extent of thyroid tumor invasion or metastases. Tumors with extensive vascular invasion or extrathyroidal extension are labeled as high risk (and otherwise are low risk). Tumors with lymph node metastases that either have documented &amp;gt; 2mm tumor deposits, &amp;gt; 40% of central nodes involved, or lateral lymph node metastases are labeled as high risk (and otherwise are low risk). The Afirma GRID invasion and metastases signatures were applied to correlate with the pathology scoring. The cohort was comprised of 144 (70%) female and 59 (30%) male patients with median age of 54 [IQR 40-65]. The cohort was mostly Bethesda III (n= 152, 75%). Fifty three percent (n=109) of the samples were malignant upon histology review. Two samples were scored as high risk for lymph node metastases (LNM) and 4 samples were scored as high risk for invasion (INV) based on final pathology. The LNM signature ruled out 55% of samples with 100% NPV and 55% specificity. No samples with high risk LNM scores were erroneously ruled out by the LNM GRID signature. The rule out % was similar in female (58%) and males (46%) (chi-squared test p=0.1). For the invasion model, 57% of samples were ruled out with 99% NPV and 57% specificity. One sample with extra-thyroidal invasion had a false negative GRID INV signature. The INV rule out % was similar in female (57%) and males (54%) (chi-squared test p=0.19). In summary, the Afirma GRID INV and LNM signatures ruled out clinically significant thyroid tumor features in &amp;gt; 50% of the studied cohort with &amp;gt; 95% NPV. Prospective studies should be performed to confirm the potential for Afirma GRID tumor behavior signatures to optimize and individualize surgical decision-making, decreasing the burden of unnecessary extent of thyroid surgery while maintaining outstanding clinical outcomes. Presentation: 6/3/2024

A case of spontaneous ovarian malignant neoplasm rupture and life-threatening massive intra-abdominal bleeding

Although ovarian cancer is the second most common gynecological cancer, it is the most common gynecological malignancy that causes death. Approximately 75% of the patients are diagnosed at an advanced stage, and high-grade serous-type ovarian cancer is detected in most of these patients. The final pathology result in our case was high-grade serous ovarian carcinoma. Our patient, 39 years old, applied to our emergency department with complaints of inability to urinate for three days and new onset abdominal pain. We were consulted because of detection of an 11 cm solid mass and globe vesicle in the pelvic region detected on the computed tomography (CT) taken in the emergency department. The patient's initial hemoglobin value was 11.2 g/dL and the beta-human chorionic gonadotropin (ß-HCG) value was negative. During the follow-up, the patient’s hemoglobin values were 9.2 and then decreased to 8.6, 8.1, and 6.5 g/dL after which hypotensive shock developed in the patient. The patient was taken for an emergency laparotomy. Intra-operatively, 1500 mL of intra-abdominal hemorrhagic fluid and diffuse tumor fragments were observed. In the right adnexal area, approximately 11 cm of ruptured tumor tissue, which may originate from the ovary or uterus, was observed. It was observed that the Douglas pouch and uterine, internal iliac , and some parts of the external iliac arteries were extensively invaded by the tumor and active bleeding occurred. Total Abdominal Hysterectomy + Bilateral Salpingo-Oopherectomy (TAH+BSO) was performed on the patient. Additional surgical intervention could not be performed because the patient had extensive vascular tumor invasion, heavy bleeding, and was in hypotensive shock. Six anti-bleeding sponges were placed on intra-abdominal bleeding areas. In addition, packing was applied to the patient by placing four sterile compresses and soft drains inside the abdomen. Tranexamic acid was administered to the patient, and six units of red blood cell suspension and four units of fresh frozen plasma were transfused. The patient was transferred by ambulance to a higher institution, which is a gynecological oncology center, for follow-up, treatment, and complementary surgery. In this case, we aimed to draw attention to a rare case of ovarian malignancy rupture and hypotensive shock.

Transcriptomic Analysis of Cirrhosis-Like Hepatocellular Carcinoma Reveals Distinct Molecular Characteristics and Pathologic Staging Implications.

Cirrhosis-like hepatocellular carcinoma (CL-HCC) is a rare hepatocellular malignancy characterized by multiple tumor nodules that clinically, radiologically, macroscopically, and microscopically mimic cirrhosis. We aimed to elucidate the molecular biology of CL-HCC and determine tumor nodule clonality. We performed RNA sequencing on formalin-fixed, paraffin-embedded tissue from confirmed CL-HCC cases (n = 6), along with corresponding nonneoplastic hepatic tissue (n = 4) when available. Transcriptomes from our previous work on steatohepatitic hepatocellular carcinoma and The Cancer Genome Atlas (TCGA) were used for comparison purposes. Histologically, CL-HCC displayed innumerable nodules and extensive vascular invasion. Intratumoral nodule comparison indicated that the multiple nodules were all clonally related, not independent primaries. The unique histomorphologic appearance corresponded with a distinct transcriptome compared with other HCCs, including fibrolamellar HCC (n = 6), steatohepatitic HCC (n = 8), and conventional HCC in TCGA (n = 424). Tumor-normal gene expression analysis revealed consistent overexpression of several genes involved in degradation of tissue matrix. No recurrent translocations or point mutations were identified. CL-HCC showed a gene expression profile indicative of zone 2 hepatocytes. CL-HCC's distinctive clinicopathologic features correspond to a unique gene expression profile, increased expression of invasive markers, features of zone 2 hepatocytes, and features suggestive of intratumoral nodule monoclonality.

Hürthle–Cell Carcinoma with Extensive Vascular Invasion Has a Higher Risk of Recurrence than Follicular–Cell Carcinoma

Hürthle–Cell Carcinoma with Extensive Vascular Invasion Has a Higher Risk of Recurrence than Follicular–Cell Carcinoma

Clinical Predictors of Unresectable Disease at Laparotomy in Patients With Pancreatic Ductal Adenocarcinoma Planning to Undergo Surgical Resection.

Computed tomography and positron emission tomography cannot detect all minute distant metastases and fully evaluate extensive vascular invasion in patients with pancreatic ductal adenocarcinoma (PDAC). The aim of this study was to investigate predictors of laparotomy only and palliative surgery in PDAC patients planning surgical resection. We reviewed 239 PDAC patients planning surgical resection. Patients were divided into two groups based on resection status. Multivariate analyses were performed to identify predictors of unresectable disease at laparotomy. Twenty-five patients had unresectable disease at laparotomy. Multivariate analysis revealed that anatomical borderline resectable status (yes/no) (HR=5.458, p=0.012), pretreatment CA19-9 (>260/≤260 ng/ml) (HR=4.907, p=0.041), and tumor size (>25/≤25 mm) (HR=21.42, p=0.004) were associated with unresectable disease at laparotomy. Borderline resectable status, pretreatment CA19-9, and tumor size were closely associated with unresectable disease at laparotomy in PDAC patients planning surgical resection.

Are all Bismuth type IV Klatskin tumors unresectable? Impact of surgery on survival outcomes and radiologic parameters of resectability for Bismuth type IV Klatskin tumor

The Bismuth-Corlette type IV Klatskin tumor has been considered as unresectable. This study was to demonstrate survival improvement of type IV Klatksin tumor when resected, and suggest possible radiological features for R0 resectability. Data on type IV Klatskin tumor diagnosed from 2008 to 2019 were retrospectively reviewed. Patients with poor general condition/liver function, distant metastasis, concomitant other cancers at the initial state, and extensive vascular invasion were excluded. Survival outcomes and radiologic parameters of bile duct tumor were compared between curative-intended resection (R0, 1 resection) and non-resection groups. Demographic findings of patient with curative-intended resection (n = 48) and with non-resection (n = 111) were comparable. Both were potentially resectable at the initial state. The most common surgical procedure was the right-sided hepatectomy (60.4%). The postoperative morbidity was 22.9% and the 90-days mortality 4.2%. There was a significant difference in median survival month among the curative-intended resection, palliative treatment, and supportive care (35, 16, and 12 months respectively; p < 0.001). In right-sided hepatectomy, shorter length of the left bile duct tumor (17.89 ± 6.42, 23.74 ± 7.48; p < 0.001) and longer length of left tumor end to the umbilical point (25.59 ± 7.69, 14.52 ± 9.40; p < 0.001) and in left-sided hepatectomy, shorter length of the right anterior bile duct tumor (17.22 ± 6.07, 21.50 ± 7.46; p = 0.001) were observed in the curative-intended resection compared to the non-resection group. In patients without extensive tumor extension into adjacent tissues including major vessels, aggressive surgical resection should be considered because it warrants markedly better survival than any other treatment.

Use of the ligamentum teres hepatis for outflow reconstruction during ex vivo liver resection and autotransplantation in patients with hepatic alveolar echinococcosis: A case series of 24 patients

BackgroundPatients with extensive hepatic alveolar echinococcosis might require ex vivo liver resection and autotransplantation to remove the lesion. Patients with extensive vascular invasion will need reconstruction, but the selection of the proper graft is complicated. This study aimed to investigate the effectiveness and adverse events of using the ligamentum teres hepatis as a vascular replacement graft in ex vivo liver resection and autotransplantation. MethodsThis was a retrospective case series of patients with hepatic alveolar echinococcosis who underwent ex vivo liver resection and autotransplantation between August 2010 and October 2018 and in whom the ligamentum teres hepatis was used to repair the remnant liver. The operative outcomes, recurrence, and survival were examined. ResultsTwenty-four patients were included (10 men, 14 women). The anhepatic period was 290 to 672 minutes (median of 450 minutes). The ratio of the remnant liver volume to the standard liver volume was 0.43 to 0.97 (median of 0.71). The blood loss was 1,000 (500–5,000) mL. The postoperative hospital stay was 23 (1–85) days. Of the 24 patients, 3 died after the operation, but those deaths were unrelated to liver vascular complications. ConclusionThe ligamentum teres hepatis could be used as a vascular replacement graft in ex vivo liver resection and autotransplantation. It has the advantages of convenient specimen extraction, no donor site injury, and no immunological rejection, which has promising clinical application prospects.

Malignancy Risk in 18F-FDG-Avid Thyroid Incidentalomas: Controversies and Limitations

Introduction: The prevalence of malignancy in thyroid incidentalomas (TI) discovered on 18F-FDG-PET or PET/CT varies between 0% and 63.6%. The pooled malignancy rate according to three systematic reviews is 33-35%. The 2015 American Thyroid Association (ATA) guidelines recommend that such nodules, when one centimeter or larger in size, should undergo further investigation with thyroid ultrasound (US) and fine-needle aspiration (FNA) cytology. Objectives: The objective of our study was to determine the rate of malignancy amongst TI discovered incidentally on 18F-FDG-PET or PET/CT, examine their clinicopathologic characteristics, and assess the usefulness of maximum standardized uptake values (SUVmax) in differentiating benign and malignant lesions. Methods: We performed an electronic medical record search looking at all 18F-FDG-PET or PET/CT reports during the study period of 12/01/2015 to 05/31/2019 that included the keyword ‘thyroid’ in the impression. Exclusion criteria included a history of thyroid disease or malignancy, known lesion(s) detected on previous clinical or radiological examinations and diffuse radiotracer uptake. Of the 476 reports reviewed, 136 cases were included in the study. Results: Common indications included initial staging or restaging of lymphoma (diffuse large B-cell, mantle-cell, T-cell types) (27.9%), lung adenocarcinoma (18.4%), head and neck cancer (16.9%) and breast cancer (11%). Fifty-eight (42.6%) patients had metabolically inactive lesions; five (8.6%) underwent further investigation with thyroid US and 3 subsequently with FNA (5%). All 3 had benign cytology. Seventy-seven (56.6%) patients had metabolically active lesions and 25 (32.5%) underwent imaging with thyroid US. Twelve (15.6%) had FNA; eight (66.7%) had benign cytology, two (16.7%) revealed atypia of undetermined significance and two (16.7%) were malignant. Biopsy for the two patients with malignant cytology showed follicular cell neoplasm of oncocytic hurtle cell type, and invasive follicular carcinoma with focal insular and papillary features and extensive capsular and vascular invasion. The mean SUVmax in malignant vs benign lesions was 9.05 and 6.41 respectively. Conclusion: The malignancy rate was 2.6% amongst all patients with 18F-FDG-avid TI and 8% amongst patients with metabolically active lesions who were investigated with thyroid US+/- FNA. This is significantly lower than malignancy rates previously reported in the literature. The evident inhomogeneity in the literature is likely multifactorial and may be explained in part by a dissimilarity among studies, and an informed decision by some to avoid invasive testing in the context of poor prognosis from underlying non-thyroidal cancer. Research is needed to determine the cohort of patients who could potentially benefit from further evaluation and treatment.

Wnt (canonical and non canonical) pathways in breast carcinoma with extensive vascular invasion and inflammatory breast carcinoma

BackgroundBreast carcinoma with extensive peritumoral vascular invasion (ePVI-BC) is a cancer with massive vascular invasion (>10) detected in more than one slide. This neoplasm shows clinic-pathological affinity with inflammatory breast carcinoma (IBC). In this paper we evaluate their biological relationship through the study of surrogate markers (β-catenin and NFAT5) of Canonical (cWnt) and non-canonical (nWnt) Wnt pathways activation. MethodsBy immunoistochemistry, we investigate β-catenin and NFAT5 in 39 IBC, 74 ePVI-BC and 84 control cases (CG-BC). ResultscWnt was activated in 100 % of ePVI-BC, in 64 % of IBC and 10 % of CG-BC. nWnt was activated in 20 % of ePVI-BC, 50 % of IBC and 1% of CG-BC. The prognosis of carcinomas with nWnt activated was poor similar to IBC. The statistical analysis evidences as both the pathways are synergistic in malignant progression and survival time. β-catenin show an important association with prognostic factors and NFAT5 shows a relevant prognostic role on OS (p = 1.5*10−6) and DFS (P = 1,2*10-4). nWnt is associated with a worse prognosis independently of cWnt. cWnt is associated with adverse prognosis (DFS p = 0.0469; OS p = 0.004891) but its prognostic role is indifferent in carcinoma with nWnt activated. ConclusionsCanonical Wnt pathway is involved in malignant progression with dominant role for vascular invasion whereas non canonical Wnt pathway plays an important role on survival time including the capacity to identify carcinomas with IBC-like prognosis. Furthermore ePVI may represent a “prodromal form of IBC” as demonstrated by its clinicopathological and biological similarity with IBC.

Internal Jugular Vein and Sternocleidomastoid Muscle Invasion by Papillary Carcinoma Thyroid.

Thyroid cancer has a good prognosis among all cancers, the disease being confined to the thyroid gland for a long time. Thyroid cancer with the direct invasion of internal jugular vein and SCM muscle is a rare condition. In carcinoma thyroid, extensive vascular invasion is considered as a risk factor for distant metastasis and early relapse. We report a case of carcinoma thyroid with internal jugular vein tumor thrombosis and sternocleidomastoid muscle invasion with review of literature.

Prognostic Significance of Extent of Invasion in Poorly Differentiated Thyroid Carcinoma.

Background: The 2017 World Health Organization (WHO) Classification of Tumors of Endocrine Organs defines poorly differentiated thyroid carcinoma (PDTC) as a tumor with conventional criteria of malignancy (capsular penetration or vascular invasion) with solid, insular, or trabecular growth, a lack of nuclear features of papillary thyroid carcinoma, and increased mitotic activity, tumor necrosis, or convoluted nuclei. The extent of invasion has been shown to be prognostic in follicular thyroid carcinoma and Hürthle cell carcinoma. Our aim was to evaluate how extent of invasion impacts clinical outcome for PDTC. Methods: We retrospectively identified 47 consecutively diagnosed cases of PDTC that were resected between 2005 and 2018. All cases were reviewed to confirm that the tumors met the 2017 Endocrine WHO criteria of PDTC. In addition, tumors were categorized as follows: encapsulated with capsular penetration only, encapsulated with focal vascular invasion (fewer than four foci), encapsulated with extensive vascular invasion (four or more foci), or widely invasive. Histopathologic characteristics and clinical outcome data were recorded. Results: A total of 47 cases of PDTC, including 15 oncocytic tumors, were identified from 28 (60%) women and 19 (40%) men (mean age of 57 years at diagnosis). The mean tumor size was 4.3 cm. Mitoses numbered 8 per 10 high-power fields (HPF) on average (range: 1-34), and necrosis was present in 21 (45%) cases. Eight (17%) cases were encapsulated with capsular penetration only, 5 (11%) were encapsulated with focal vascular invasion, 18 (38%) were encapsulated with extensive vascular invasion, and 16 (34%) were widely invasive. Of the 42 (89%) patients with follow-up data, 7 (17%) died of disease (with a mean survival time of 6.4 years), 11 (26%) have distant metastatic disease, and 24 (57%) have no evidence of disease (mean follow-up 5.6 years). Eight (19%) patients presented with M1 disease at diagnosis. The 5-year disease-free survival (DFS) for patients with M0 disease at diagnosis was 100% for patients with tumors with capsular invasion only or focal vascular invasion (n = 7), 73% for patients with encapsulated tumors with extensive vascular invasion (n = 11), and 17% for patients with widely invasive PDTCs (n = 6). DFS estimates by Kaplan-Meier analysis were significantly different between these groups (p = 0.0016). Conclusions: Extent of invasion appears to be an important parameter that affects clinical outcome for patients with PDTC. In our cohort, patients with encapsulated PDTC with capsular invasion only or focal vascular invasion had an excellent outcome.

SUN-LB102 Uncommon Pathology of Neck Mass

Poorly differentiated thyroid carcinoma (PDTC) is an uncommon form of thyroid cancer, accounting for less than 5 % of all cases. It tends to be more clinically aggressive than differentiated thyroid cancers. While thyroidectomy is the mainstay of treatment, radioactive iodine plays an adjunctive role as well as TSH suppression with thyroid hormone. Some patients with advanced disease, may benefit from external beam radiation and/or systemic therapy. Case Description: A 94-year-old man presents with a left neck mass. His past medical history is significant for controlled hypertension. He notices a slowly growing mass while shaving over few months. He has no dysphagia, hoarseness, or shortness of breath. He has no history of radiation exposure and no family history of thyroid disease. A CT of the neck with contrast shows multiple pathologic appearing lymph nodes on the left side of the neck. The largest measures 5.4 x 4 x 3.9 cm, displacing the carotid space, and indenting the left internal jugular vein. The left lobe of the thyroid is heterogeneously enlarged compared to the right lobe with multiple irregular hypo-enhancing nodules. A fine-needle aspiration of the left cervical lymph node is positive for malignant large cells in sheets and clusters. Some clusters have a vague papillary/trabecular type arrangement. A total thyroidectomy and left level II-IV neck dissection is performed. Pathology shows multifocal poorly differentiated papillary thyroid carcinoma measuring 2.2 cm in greatest dimension with extensive necrosis. There is a background of lymphocytic thyroiditis. There is extensive vascular invasion (>4 foci) and extra-thyroidal extension invading only the strap muscles. There is metastasis to 7 of 12 examined lymph nodes. The largest metastatic deposit at level III measures 2.8 cm with extra-nodal extension. Tumor is negative for BRAF-V600, NRAS and TERT. His postoperative labs are as follows: TSH 346 (post-rhTSH) uiu/ml (0.5-5.0), free T4 0.87 ng/dl (0.6-1.15),Tg 1.0 ng/ml and anti-Tg <0.9 iu/ml. Adjuvant therapy with 125 mCi of I-131 is performed as well as thyroid replacement with levothyroxine 100 mcg daily. A whole-body scan shows residual uptake in the thyroid bed and increased uptake to the left of the thyroid bed. FDG PET scan shows 2 left parapharyngeal nodes with SUV of 6.94 (0.8 cm), SUV of 3.73 (1.8 cm). There is a focus of increased activity at lateral left thyroid bed SUV of 4.59. There is a right mediastinal paratracheal lymph node with SUV of 9.79 measures 1.5 x 1.2 cm. Considering patient age, external beam radiation is deferred with patient agreement as the risk outweighs the benefit. Patient will be followed by imaging closely. Conclusion: PDTC is an uncommon form of thyroid cancer. These tumors generally do not produce thyroglobulin and close monitoring with imaging is essential to detect early metastatic disease. Unless otherwise noted, all abstracts presented at ENDO are embargoed until the date and time of presentation. For oral presentations, the abstracts are embargoed until the session begins. s presented at a news conference are embargoed until the date and time of the news conference. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO.

Renal Cell Carcinoma Embolization for the Treatment of Budd–Chiari Syndrome

AbstractRenal cell carcinoma (RCC) is the eighth most common malignancy, accounting for 3% of all newly diagnosed neoplasms. RCC venous invasion occurs in 4 to 10% of cases. We report a case of RCC with extensive vascular invasion and new-onset liver dysfunction. The etiology of the liver dysfunction was attributed to hepatic vein obstruction; herein we describe the first reported case of transcatheter embolization of RCC for Budd–Chiari syndrome.

Anti-thyroglobulin antibodies do not significantly increase the risk of finding iodine avid metastases on post-radioactive iodine ablation scan in low-risk thyroid cancer patients.

Post-operative thyroglobulin (Tg) levels can predict the likelihood of residual cancer, including distant metastases, thereby influencing postsurgical treatment strategies even in patients with low-risk disease. Circulating anti-thyroglobulin antibodies (anti-Tg Abs) interfere with Tg measurement preventing this clinical use. It is not known if the presence of anti-Tg Abs predicts metastatic disease on post-therapy scan in patients with low-risk disease or if they should influence the use or dose of I-131 therapy. In the present study, we compare post-therapy scans in low-risk patients with and without anti-Tg Abs. This is a single-institution retrospective study. The study population (Group A) included all patients with low-risk differentiated thyroid cancer (DTC) who underwent total thyroidectomy and RAI between 1/1/2006 to 9/11/2015 with intrathyroidal T1-T2, Nx, N0 or N1a (≤5 nodes all measuring, when reported, <2mm) that had anti-thyroglobulin antibodies. Patients were excluded if they had known distant metastases and/or extensive vascular invasion. A second group of patients (Group B) treated during the same period but without anti-Tg antibodies was selected to match group A by propensity core matching with a logistic regression model. Each group included 37 patients. In group A: Median age was 40years, 86% female and 76% PTC. Median tumor size was 2cm (0.2-3.8), 32% had multifocal disease, 16% were N1a and 4% had vascular invasion. Parameters in group B were not statistically different from Group A, as expected based on the selection criteria, except being less likely to have Hashimoto's thyroiditis on pathology (p<0.001). Post-therapy scan results were compared by Chi-square test with 86% negative post therapy scan frequency in group A and 92% in group B without evidence of a difference (p=0.45). In patients with low-risk DTC, anti-Tg Abs did not significantly predict metastatic disease on post-therapy scan. If confirmed, these data suggest that the presence of anti-Tg Abs alone should not influence initial therapy in patients with low-risk DTC.

Serum HE4 is correlated to prognostic factors and survival in patients with endometrial cancer.

The extent of surgery and the decision for adjuvant treatment in patients with endometrial cancer (EC) depend on the presence of risk factors for lymph node metastases and disease recurrence. Postoperative markers such as myometrial infiltration and specific mutations can select patients for adjuvant treatment but will not influence surgical planning. A biomarker stratifying patients into low-risk and high-risk groups before surgery could identify patients who benefit from more extensive surgery. Therefore, we evaluated the correlation of serum biomarker HE4 with clinical and recently identified prognostic pathological variables and survival. Patients treated for endometrial cancer between 1994 and 2014 were included. Serum HE4 concentration was measured in preoperatively obtained samples. A total of 88 patients were eligible for analysis. The majority (64%) was diagnosed with endometrioid-type adenocarcinoma. Serum HE4 concentration is significantly associated with stage of disease (p=0.001), deep myometrial invasion (p<0.001), exact depth of myometrial invasion (≥4mm) (p=0.01), tumour-free distance to serosa (≤7mm) (p<0.001), extensive lymph vascular space invasion (p=0.04) and cervical involvement (p=0.001). HE4 concentration and nodal involvement were correlated, although not significant (p=0.17). Serum HE4 is an independent prognostic factor for recurrence-free survival (HR 5.12 per 10-fold increase in HE4, 95% CI 1.54-17.1) and overall survival (HR 7.48 per 10-fold increase in HE4, 95% CI 1.76-31.7). HE4 is a prognostic marker in endometrial cancer and is helpful in addition to other variables for the preoperative risk stratification of patients with endometrial cancer.

Primary Thyroid Carcinoma with Low-Risk Histology and Distant Metastases: Clinicopathologic and Molecular Characteristics.

Distant metastases (DM) are a rare occurrence in well-differentiated thyroid carcinoma. The aim of this study was to analyze the clinical, pathologic, and molecular features of primary thyroid carcinoma with low-risk histology that develop DM. A detailed clinicopathologic review and targeted next-generation sequencing were performed on a cohort of well-differentiated thyroid carcinoma lacking gross extrathyroidal extension, extensive vascular invasion, or significant lymph node metastases but exhibiting DM. Primary well-differentiated thyroid carcinoma with low-risk histologic features and DM was a rare occurrence, accounting for only 3% of metastatic non-anaplastic thyroid carcinoma. All 15 cases meeting the inclusion criteria harbored DM at presentation. The majority (11/15) of these tumors were follicular variant of papillary thyroid carcinoma (PTC), especially the encapsulated form (n = 8). The remaining patients harbored encapsulated Hürthle cell carcinoma (n = 2), encapsulated follicular carcinoma (n = 1), and an encapsulated papillary carcinoma classical variant (n = 1). Of the 12 encapsulated carcinomas, 10 had capsular invasion only and no vascular invasion. Ninety-two percent of the tumors exhibited extensive intra-tumoral fibrosis. Among the eight tumors that were subjected to next-generation sequencing analysis, a RAS mutation was the main driver (5/8), and TERT promoter mutation was highly prevalent (6/8). In four cases, TERT promoter mutations were associated with RAS or BRAF mutations. BRAF-mutated classical variant of papillary carcinoma also presented with DM but was less common (1/8). In 11/15 cases, the clinician was able to diagnose distant disease based on the clinical presentation. In 3/4 incidental cases that were genotyped, TERT promoter mutations were found. When DM occur in primary thyroid carcinoma with low-risk histology, they are almost always found at presentation. The majority are encapsulated follicular variant of PTC with capsular invasion only. TERT promoter mutations occur at a higher rate than that seen in PTC in general and may help explain the aggressive behavior of these histologically deceptive primary carcinomas.

Imaging features of hepatic sarcomatous carcinoma on computed tomography and gadoxetic acid-enhanced magnetic resonance imaging.

To determine the imaging features of hepatic sarcomatous carcinoma including sarcomatous intrahepatic cholangiocarcinoma (S-ICC) and sarcomatous hepatocellular carcinoma (S-HCC) on computed tomography (CT) and gadoxetic acid-enhanced magnetic resonance imaging (MRI). Twenty-four patients with pathologically confirmed S-ICCs (n=13), S-HCCs (n=7), sarcomatous carcinoma (n=2), carcinosarcoma (n=1), and sarcomatous combined HCC-CC (n=1) (size range 2.1-23 cm, mean 8.3 cm) underwent gadoxetic acid-enhanced MRI (n=20) and/or dynamic CT (N=24). Underlying chronic hepatitis or cirrhosis was found in 17 patients. Two reviewers evaluated morphology, signal intensity, and enhancement features of tumors based on a consensus. Lobulated contour was observed in 15 tumors (62.5%); the rest were round or oval masses. During dynamic imaging, S-ICCs showed poor enhancement (n=10 on CT; n=7 on MRI) or initial thin-rim enhancement with/without progressive enhancement (n=3 on CT; n=6 on MRI). S-HCCs and the other four tumors showed a thin or thick enhancement pattern on both CT and MRI. T2 bright signal intensity similar to fluid was found in 10 tumors. Target appearance on hepatobiliary phase and diffusion-weighted imaging was seen in two S-ICCs and two S-HCCs. Of 18 surgically resected tumors, 17 showed vascular invasion and/or thrombosis in histology and 12 in CT and MRI. Ten tumors were accompanied by intrahepatic metastasis or tumor seeding and 19 patients had recurrence or progression of tumors during follow-up. Hepatic sarcomatous carcinoma including S-HCC and S-ICC generally presents minimal rim-like arterial enhancement or extreme hypovascularity on CT and gadoxetic acid-enhanced MRI with a high frequency of T2 bright area due to extensive necrosis and vascular invasion.

Clinicopathologic Features of Fatal Non-Anaplastic Follicular Cell-Derived Thyroid Carcinomas.

The vast majority of thyroid cancers, in particular the non-anaplastic follicular cell-derived thyroid carcinomas (non-ANA FCDC), are considered indolent tumors with very low mortality. Hence, it is crucial to analyze the subgroup of these patients who die of disease (DOD) in order to identify clinicopathologic features predictive of disease-specific mortality. All non-ANA FCDC operated at a tertiary cancer center between 1985 and 2010 who were DOD were identified and submitted to a meticulous clinicopathologic analysis. Out of 3750 non-ANA FCDC, 58 (1.5%) DOD cases were identified. The DOD group was composed of 33 (57%) poorly differentiated carcinomas (PDTC), 14 (24%) tall-cell variant papillary thyroid carcinomas (TCVPTC), four (7%) Hürthle cell carcinomas, three (5%) papillary microcarcinomas, two (3%) classical variant PTC, and two (3%) follicular variant PTC. Twenty-seven (47%) patients presented with distant metastases (DM), 28 (48%) developed DM during follow-up, while the remaining three (5%) had locally advanced non-resectable recurrence. Gross extension beyond the thyroid (GET) was present in 36 (62%) and extensive vascular invasion (VI) in 21 (36%) of cases. All microcarcinomas had PDTC in their clinically apparent cervical lymph nodes at presentation. Encapsulated thyroid carcinomas were responsible for 17% of DOD cases, and all had extensive VI and/or DM at presentation. All patients had at least one of these high-risk features at diagnosis: DM at presentation, PDTC, GET, and/or extensive VI. The majority of patients died from DM (n = 51; 88%), three (5%) from locoregional disease, three (5%) from both, and one (2%) from unknown cause. PDTC and TCVPTC are responsible for the vast majority of deaths in differentiated thyroid carcinomas, while the few fatal classical, follicular variant PTC and microcarcinomas all harbor a PDTC component, DM, or GET. Encapsulated differentiated thyroid carcinoma with focal capsular and/or VI without DM at presentation does not seem to cause death. Lack of DM at presentation, PDTC, GET, and extensive VI identify thyroid carcinomas that are at almost no risk of DOD. The vast majority of patients die of DM rather than locoregional invasion, prompting the need for effective systemic treatment.

Prognostic Impact of Further Treatments on Distant Metastasis in Patients With Minimally Invasive Follicular Thyroid Carcinoma: Verification Using Inverse Probability of Treatment Weighting.

The aim of this study was to evaluate the prognostic impact of further treatments in minimally invasive follicular thyroid carcinoma (MIFTC) patients. The risk factors for distant metastases were analyzed, and the impact of surgical extent on distant metastasis was verified by using weighted logistic regression models with inverse-probability of treatment weighting (IPTW). 166 patients including 31 males (18.7%) and 135 females (81.3%), with the mean age of 41.5±13.5years, were enrolled for this study. The median follow-up period was 103.5months (range, 13-244months). Seven patients (4.2%) had distant metastases during follow-up period. The presence of vascular invasion (Hazard ratio [HR]=29.06; 95% Confidence Interval [CI]=3.06-209.08; p=0.015) and extensive vascular invasion≥4 foci (HR=40.57; 95% CI=2.09-789.13; p=0.014) were the independent risk factors for distant metastasis by multivariate analysis. Surgical extent did not influence distant metastasis. Logistic regression with IPTW also demonstrated that there were no statistically significant differences in the development of distant metastasis based on surgical extent (HR=1.28; 95% CI=0.15-10.87; p=0.823). The presence of extensive vascular invasion is the most powerful predictor of distant metastasis. However, it is noteworthy that further treatments do not demonstrate an advantageous effect on preventing distant metastasis during the follow-up period.