Run Yu

Ki-67 proliferative index predicts progression-free survival of patients with well-differentiated ileal neuroendocrine tumors

Ki-67 proliferative index (Ki-67 index) is suggested to be an important prognostic variable and is included as one of the grading parameters for neuroendocrine tumors. The present study was undertaken to determine the usefulness of the Ki-67 index and the corresponding tumor grade in predicting progression-free survival (PFS) of patients with ileal well-differentiated neuroendocrine tumors (wNETs). Tumors from 57 patients with ileal wNETs were studied. Immunohistochemical staining for Ki-67 was performed on the primary as well as selected metastatic tumors and quantitated by computer-assisted image analysis using the Ariol system. The tumors were graded based on mitotic activity and Ki-67 index. Clinical and pathological variables affecting the PFS were analyzed. There were 29 women and 28 men, with a mean age of 59 years. At the time of initial presentation, 8 patients (14%) had localized disease (stages I and II), 29 patients (51%) had regional (nodal/mesenteric) spread (stage III), and 20 patients (35%) had distant metastasis (stage IV). Twelve patients experienced disease progression during subsequent follow-up. Patients with initial stage IV disease were more likely to experience disease progression (P = .005). Additionally, higher histological grade (as determined by Ki-67 index >2%) was associated with a decreased PFS (P = .001). Ki-67 index greater than 2% at either the primary site or the metastatic site was found to be the only significant predictor of PFS after consideration of all other variables in an adjusted analysis. In conclusion, the Ki-67 index predicts PFS of patients with ileal wNETs.

Mixed acinar-endocrine carcinoma of the pancreas: new clinical and pathological features in a contemporary series.

Objective The objective of this study was to characterize the novel clinical and pathological features of mixed acinar-endocrine carcinoma of the pancreas. Methods This was a retrospective review of medical records and surgical pathology specimens of patients with a diagnosis of mixed acinar-endocrine carcinoma of the pancreas at Cedars-Sinai Medical Center between 2005 and 2011. Additional immunohistochemistry was performed on the specimens of some patients. Results Five patients were identified. The median age at presentation was 74 years (range, 59–89 years), and all patients were male. The presenting symptoms were all related to tumor mass effects. The median size of the tumor was 10 cm (range, 3.9–16 cm). Preoperative clinical diagnosis aided by fine-needle aspiration biopsy was incorrect in all 5 cases. Most tumors (3/5) exhibited predominantly endocrine differentiation without hormonal production. Only 10% to 30% of cells were truly amphicrine, whereas most were differentiated into either endocrine or acinar phenotype. The clinical behavior ranged from moderate to aggressive with postoperative survival from 2.5 months to more than 3 years. Four patients received neoadjuvant or adjuvant chemotherapy with variable responses. Conclusions Mixed acinar-endocrine carcinoma of the pancreas appears to be not uncommon in men, may harbor predominantly endocrine component, is often misdiagnosed by cytology, and exhibits variable clinical behavior. Mixed acinar-endocrine carcinoma of the pancreas should be considered in older patients with sizable pancreatic mass and may warrant aggressive surgical resection and chemotherapy.

FDG PET/CT as a prognostic test after 90Y radioembolization in patients with metastatic hepatic disease.

Abstract The purpose of this study was to determine FDG PET/CT utility in predicting patient outcome undergoing 90Y RE for metastatic liver tumors. Thirty-one patients with metastatic tumors to the liver underwent 90Y RE between March 15, 2007, and May 5, 2011, at our institution. FDG PET/CT imaging was performed on each patient within 3 months before and after undergoing 90Y RE. Pretreatment and posttreatment FDG PET/CT were evaluated for SUV, number of liver lesions, and presence of disease outside the liver. The Kaplan-Meier method and Cox proportional hazard modeling was used to evaluate if SUV was a predictor of overall survival. Of the 31 patients, 12 were alive at the end of the study; median survival was 9 months (95% confidence interval, 7–18 months). The 24-month survival rate was 0.28 (95% confidence interval, 0.12–0.48). Kaplan-Meier analysis of preprocedure FDG PET/CT imaging showed no difference in rates of survival by number of lesions observed in the liver (P = 0.114) or presence of disease observed outside the liver (P = 0.719). Cases with new lesions outside the liver after treatment had significantly shorter survival times than cases without new lesions outside the liver (P = 0.002). Cox proportional hazard model showed that SUV levels before and after treatment were not significant predictors of overall survival. The appearance of new lesions outside the liver on FDG PET/CT within 3 months after 90Y RE was the only statistically significant variable in predicting poor outcome. Absence of new lesions outside the liver on postprocedure FDG PET/CT imaging helps identify patients achieving long-term survival.

CLINICAL USE AND UTILITY OF METAIODOBENZYLGUANIDINE SCINTIGRAPHY IN PHEOCHROMOCYTOMA DIAGNOSIS

OBJECTIVEnTo examine the indications for metaiodobenzylguanidine (MIBG) scintigraphy and to assess its performance in localizing pheochromocytoma in the post-computed tomography and magnetic resonance imaging era.nnnMETHODSnIn this retrospective study, electronic and paper medical records of patients who underwent MIBG scintigraphy at a large academic hospital in Los Angeles, California, between January 1995 and July 2009 were reviewed for indications for MIBG scintigraphy, clinical history, biochemical test results, findings from imaging studies, and pathologic diagnoses. MIBG score was defined as follows: 3 (or intensive uptake) meant MIBG uptake of adrenal gland or other locus was higher than that of the liver; 2 (or moderate uptake) meant uptake was similar to that of the liver; 1 (or borderline uptake) meant uptake was lower than that of liver; and 0 (or negative uptake) meant background signal.nnnRESULTSnNinety-eight patients underwent MIBG scintigraphy during the study period; the indication was suspected pheochromocytoma in 75 cases. Pheochromocytoma diagnosis was excluded in 48 and confirmed in 15. The remaining 12 patients had insufficient information in the medical records to render a diagnosis. Among the 63 patients, 47 received 131I-MIBG and 16 received 123I-MIBG. Sensitivity was 73% and specificity was 69% if any adrenal uptake was considered positive, but increased to 90% if borderline uptake was considered negative. False results were more common in younger patients, but not correlated with biochemical test results. In patients with pheochromocytoma either excluded or confirmed, the MIBG scintigraphy results were confirmatory in 63%, but misleading in 37%. MIBG scintigraphy results did not provide additional diagnostic value to any case and contributed to pheochromocytoma overdiagnosis and even unnecessary adrenalectomy.nnnCONCLUSIONSnMIBG scintigraphy results are either confirmatory or misleading, and this imaging modality is not necessary for most patients in modern practice.

Metabolic and receptor imaging in patients with neuroendocrine tumors: Comparison of fludeoxyglucose-positron emission tomography and computed tomography with indium in 111 pentetreotide

OBJECTIVEnTo determine whether positron emission tomography/computed tomography (PET/CT) and indium In 111 pentetreotide, individually or collectively, predict the outcome of patients with neuroendocrine tumors (NETs).nnnMETHODSnBetween July 31, 2002, and May 4, 2007, 29 patients with previously diagnosed NETs underwent both PET/CT and indium In 111 pentetreotide imaging at our institution. The images were evaluated for the presence of abnormalities. Clinical outcomes were classified as survival without major morbidities, survival with severe complications of disease, or death. Time to outcome was measured in months from the imaging date to outcome. Kaplan-Meier survival curves were calculated in which patient outcome was compared with results on PET/CT and indium In 111 pentetreotide imaging.nnnRESULTSnOf the 29 patients, 9 had abnormalities on both PET/CT and indium In 111 pentetreotide imaging. Two patients had abnormal findings on PET/CT but normal findings on pentetreotide imaging. In 5 patients, findings were normal on PET/CT but abnormal on pentetreotide imaging. In 13 patients, normal findings were noted on both PET/CT and pentetreotide imaging. Kaplan-Meier analysis demonstrated a significant survival advantage for patients who had normal findings on PET/CT in comparison with abnormal PET/CT findings (P = .01). Patients with normal findings on indium In 111 pentetreotide imaging had a higher but insignificant survival advantage over those with abnormal results on pentetreotide imaging (P = .08).nnnCONCLUSIONnFor evaluation of NETs, PET/CT and indium In 111 pentetreotide are complementary. Increased metabolic activity in tumor cells is reflected by abnormalities on PET/CT. Patients who had abnormal PET/CT findings had a generally poorer prognosis and a more rapid clinical deterioration than those with normal PET/CT findings.

Radioembolization for treatment of liver metastases from neuroendocrine tumors: correlation with imaging and biomarkers.

To the Editor: In their article ‘‘Long-Term Clinical and Imaging Follow-up of Nonoperated Branch Duct Form of Intraductal Papillary Mucinous Neoplasms of the Pancreas’’, Arlix et al. state that branch duct IPMNs with no signs of malignancy should be managed conservatively. In their 10-year prospective study, none of the patients developed malignancy (n = 49 patients). In contrast, predominantly main duct or mixed forms of IPMNs should be reviewed for surgery due to its high risk of neoplastic transformation. We would like to point out that even in high volume centers and by the use of modern abdominal imaging, it remains difficult to reliably differentiate between IPMNs of the main duct and branch duct type. Furthermore, there exist an increasing number of reports indicating that also in small BD-IPMNs there is a significant risk of malignancy. In our own series, in a large proportion of small (‘‘Sendai negative’’) BD-IPMNs, high-grade dysplasia or frank invasive carcinoma was diagnosed on final histological examination (incidence 25%). With regard to the data of Arlix et al., an increase in cyst size or main pancreatic duct dilation was observed in 18/47 patients which led to surgical resection in 5 patients. It is conceivable that in some of the remaining 13 patients with cyst size progression over time, neoplastic changes could be found histologically. Indeed, Arlix et al. found borderline lesions in 4/5 patients who underwent surgery. It is also possible that some of the lesions observed in this study were rather pseudocysts due to acute or chronic pancreatitis than mucinous cystic neoplasms. Particularly, as the authors report that IPMNs frequently occur in patients with acute pancreatitis. In our opinion, all IPMNs (including the branch duct type) have to be considered as potential precursors to invasive adenocarcinoma. Thus, close follow-up or surgical pancreatic resection are warranted in most cases. ACKNOWLEDGMENT The authors declare no conflict of interest.

Humoral hypercalcemia of malignancy caused by parathyroid hormone-related peptide-secreting neuroendocrine tumors. Report of six cases.

We report the clinical characteristics and management of six patients with metastatic gastroentero-pancreatic neuroendocrine tumor (NET) presenting with severe hypercalcemia due to elevation of parathyroid hormone-related protein (PTHrP). All patients had histological confirmation of NET, five well-differentiated and one poorly differentiated. In 5 patients, hypercalcemia developed after years after the initial diagnosis of NET. One patient presented with concomitant elevation of PTHrP and intact parathyroid hormone (PTH) in the setting of multiple endocrine neoplasia 1 (MEN1). In all the other cases, PTH levels were low or undetectable. Management of malignant hypercalcemia due to PTHrP-producing NET is challenging, and optimal therapy depends on the extent of metastatic disease and the grade of malignancy. Aggressive tumor cytoreduction in addition to the systemic treatment modalities is frequently used to control disease progression and endocrine symptoms. To our knowledge, this is the largest series to date of hypercalcemia mediated by PTHrP-secreting NET.

Small Pheochromocytomas: Significance, Diagnosis, and Outcome

J Clin Hypertens (Greenwich). 2012; 14:307–315. ©2012 Wiley Periodicals, Inc.

Clinical utility of FDG-PET for diagnosis of adrenal mass: a large single-center experience.

OBJECTIVETo examine the clinical utility of 18F-fluorodeoxyglucose-positron emission tomography (FDG-PET) for diagnosing whether an adrenal mass is malignant, in contemporary clinical practice.DESIGNRetrospective medical record review of patients from 2 databases at a large hospital. The first database consisted of patients who underwent FDG-PET between the years 2009 to 2011 while the second database included patients who had histological diagnosis of adrenal mass between the years 1997 to 2011.RESULTS3.4% of 2921 patients had adrenal FDG uptake. Approximately 43% of them did not exhibit corresponding adrenal mass. FDG-PET performance parameters were better if a cutoff of SUV (standardized uptake value) ≥3 was used to define positivity. The imaging characteristics of malignant adrenal masses and pheochromocytoma were similar but differed remarkably compared to those of benign tumors. Serial imaging revealed that the malignant adrenal masses consistently exhibited high CT attenuation, while more than half of them initially exhibited SUV<3 and in some cases FDG uptake indistinguishable from the background. The FDG-PET results were confirmatory in 87% of patients, contributory in 11%, but definitely misleading in 2%.CONCLUSIONSFDG-PET is not required for adrenal mass diagnosis in most patients in contemporary practice but may help clinical decision making in specific situations.

Sellar Atypical Teratoid/Rhabdoid Tumor: Any Preoperative Diagnostic Clues?

ABSTRACT Objective: Our objectives were to describe a rare adult-onset sellar atypical teratoid/rhabdoid tumor (AT/RT) and to identify preoperative diagnostic clues for this aggressive tumor. Methods: A case report and review of the relevant literature. Results: A 36-year-old female presented with headache for 1 month and blurry vision for 6 days. Imaging identified a large sellar mass with suprasellar extension that was indistinguishable from a pituitary adenoma. Hormonal studies revealed hypopituitarism and hyperprolactinemia. A presumptive diagnosis of pituitary macroadenoma was made, but the histologic, immunohistochemical, electron microscopic, and cytogenetic studies of the tumor supported a diagnosis of AT/RT. Despite multiple surgical resections, radiation, and chemotherapy, the tumor recurred and regrew relentlessly. The patient died 2.5 years after presentation. Conclusion: This case highlights the importance of suspecting aggressive sellar masses in management planning and prognosis counseling....