Octreoscan Versus FDG-PET for Neuroendocrine Tumor Staging: A Biological Approach.

BACKGROUND: Clinicians may order Octreoscan or positron emission tomography (PET) scan for staging patients with neuroendocrine tumors (NETs). (111)In-Octreoscan (Octreoscan) identifies tumors by radiolabeled targeting of somatostatin receptors, while 18F-fluorodeoxyglucose-positron emission tomography ((18)FDG-PET) measures differential tissue glucose transport. We assessed the sensitivity of both nuclear imaging modalities with pathologic correlation to define the best initial choice for NET staging after standard cross-sectional imaging. METHODS: We identified all patients diagnosed with NETs of gastrointestinal or pancreatic origin who underwent nuclear imaging staging by Octreoscan and/or PET from 2000 to 2013. Imaging results were correlated with tumor differentiation and grade of pathology specimens. RESULTS: Imaging and pathology results were identified for 153 patients. Of these, 131 underwent Octreoscan, 43 underwent PET, and 21 patients had both performed. Overall sensitivity of Octreoscan and PET for NET detection was similar (77 vs. 72 %; p = not significant). For well-differentiated NETs, Octreoscan (n = 124) demonstrated sensitivity of 80 vs. 60 % (p = 0.28) for PET (n = 30). For poorly-differentiated NETs, Octreoscan (n = 7) proved significantly less sensitive than PET (n = 13) (57 vs. 100 %; p = 0.02). The sensitivity of Octreoscan versus PET varied similarly when analyzed by WHO tumor grade: Grade 1 (79 vs. 52 %; p = 0.16), Grade 2 (85 vs. 86 %; p = not significant), and Grade 3 (57 vs. 100 %; p = 0.02). CONCLUSIONS: Tumor differentiation can be used to guide selection of nuclear imaging modalities for staging gastrointestinal and pancreatic NETs. Octreoscan appears more sensitive than (18)FDG-PET for well-differentiated NETs, whereas (18)FDG-PET demonstrates superior sensitivity for poorly-differentiated NETs.

Polymorphous low-grade adenocarcinoma located in the maxillary sinus.

Polymorphous low-grade adenocarcinoma is a malignant epithelial tumour with low metastatic rate and infiltrative growth pattern. The palate is the most common site. Paranasal sinuses are uncommon venues for polymorphous low-grade adenocarcinoma. Here, we report a polymorphous low-grade adenocarcinoma case of the maxillary sinus, a very rare location. Although it is a low grade malignancy, progression may develop after a long time. Therefore, polymorphous low-grade adenocarcinoma should be kept in mind in the differential diagnosis even in rare sites in the head and neck.

[Clear cell mucoepidermoid carcinoma of the parotid gland: a case report]. / Parotis Bezinin Berrak Hücreli Mukoepidermoid Karsinomu: Olgu Sunumu.

Clear cell variant of mucoepidermoid carcinoma of the salivary glands is rare. A 55-year-old male patient with recently growing left parotid mass underwent superficial parotidectomy. Although the dominant component of the tumor was composed of clear cells, mucin containing cells were also present. Histochemically, alcian blue stain supported intracellular mucin positivity. Immunohistochemically, p63 was positive. Based on the morphological, histochemical and immunohistochemical findings, the case was diagnosed as mucoepidermoid carcinoma, clear cell variant.

An analysis of salivary gland neoplasms: a 12-year, single-institution experience in Turkey.

The epidemiology of salivary gland tumors worldwide is not very well defined. Although many studies on this subject have been undertaken, the data are generally focused on specific topics such as parotid gland neoplasms or tumors of the major salivary glands. We conducted a study to establish the prevalence and distribution of benign and malignant neoplasms of both the major and minor salivary glands at a single institution. We reviewed 244,204 cases that had come through our pathology department from January 1994 through December 2005 and found 235 cases of a salivary gland neoplasm (0.09%). The female-to-male ratio was 1.04:1, and the mean age of the patients was 47 years. Of the 235 neoplasms, 159 (67.66%) were located in the parotid gland, 34 (14.47%) in the submandibular gland, and 42 (17.87%) in the minor salivary glands. A total of 146 tumors (62.13%) were benign and 89 (37.87%) were malignant. Pleomorphic adenoma was the most common neoplasm, occurring in 98 cases (41.70%). The most common malignancy was mucoepidermoid carcinoma, with 27 cases (11.49%). Our data demonstrate that the characteristics of salivary gland tumors in a Turkish population at a single institution are similar to those reported in the literature worldwide.

Tumor-infiltrating neutrophils in pancreatic neoplasia.

The interaction between tumor cells and inflammatory cells has an important role in cancer initiation and progression; however, this interaction has not been systematically investigated in pancreatic neoplasia. In this study, the presence of tumor-infiltrating neutrophils within and/or adjacent to neoplastic cells was investigated in pancreatic neoplasms. Areas with >10 tumor-infiltrating neutrophils/100 epithelial cells were arbitrarily classified as positive. Those with 11-15 tumor-infiltrating neutrophils were considered 'borderline' while those with >15 tumor-infiltrating neutrophils were considered 'significant'. Among 363 invasive ductal carcinomas, 15 showed significant tumor-infiltrating neutrophils (8 were micropapillary carcinomas and 7 were undifferentiated carcinomas). Of 19 mucinous cystic neoplasms with a carcinomatous high-grade papillary component, 11 showed significant tumor-infiltrating neutrophils (mean, 25; range, 14-63 tumor-infiltrating neutrophils). Among intraductal papillary mucinous neoplasms, significant tumor-infiltrating neutrophils were identified in 4/16 pancreatobiliary type, but were uncommon in other types (1/11 oncocytic and 1/23 intestinal types had borderline tumor-infiltrating neutrophils, and 0/10 gastric type had tumor-infiltrating neutrophils). Non-carcinomatous (low-grade and non-papillary) components of these neoplasms did not have tumor-infiltrating neutrophils. Tumor-infiltrating neutrophils were not striking in neuroendocrine tumors (40), serous cystadenomas (18), acinar cell carcinomas (9) or solid-pseudopapillary neoplasms (8). In conclusion, significant tumor-infiltrating neutrophils are uncommon in pancreatic ductal adenocarcinoma, and when they occur it is typically in the micropapillary and undifferentiated types with a known poor prognosis. Among pre-invasive neoplasia, tumor-infiltrating neutrophils show a predilection for papillary in-situ carcinomas of mucinous cystic neoplasms, or less commonly, pancreatobiliary-type intraductal papillary mucinous neoplasms (both of which express cell surface-associated mucin 1 (MUC1)). MUC1 expression by these tumors may have biologic implications, considering its recently established relationship with inflammatory cells in carcinogenesis, and the differential expression of mucins in pancreatic neoplasia. Larger studies are needed to investigate the association between tumor-infiltrating neutrophils and pancreatic neoplasms and their role in their clinical behavior.

Quantifying the expression of VEGF using qRT-PCR, evaluation of MVD and their correlation with clinicopathological factors in laryngeal squamous cell carcinoma.

OBJECTIVES: In this study we quantified the expression of vascular endothelial growth factor (VEGF) using quantitative real-time polymerase chain reaction in laryngeal squamous cell carcinoma (LSCC) tissues and evaluated the correlation between the level of VEGF and microvessel density (MVD), and clinicopathological factors. PATIENTS AND METHODS: Twenty-seven patients with LSCC undergoing total or partial laryngectomy at the Ear, Nose, and Throat and Head and Neck Surgery Department of the Izmir Tepecik Training and Research Hospital between September 2006 and July 2008. There was no VEGF expression in two patients that were excluded from the study. Twenty-five patients (24 males, 1 female; mean age 61 years; range 43 to 82 years) were included in this study, but MVD levels of 10 patients could not be determined. RESULTS: As defined by the 2003 American Joint Committee on Cancer (AJCC) TNM classification, seven patients (28%) were stage 1, six patients (24%) were stage 2, four patients (16%) were stage 3, and eight patients (32%) were stage 4. Thirteen patients (52%) had well-differentiated (G1) tumors, and twelve had moderately differentiated tumors. Among the 15 patients for whom the MVD was determined, the median value was 48, with a (range 13-78; vessels / 3.76 mm2). Among the 25 patients for whom the VEGF level was determined, the median value was 0.035 vessels / 3.76 mm2 (range 0.010-0.127). CONCLUSION: We could not find a statistical correlation between clinicopathological factors and either VEGF or MVD. Our study demonstrates that VEGF is expressed by LSCC.

Comparison of proliferating cell nuclear antigen, thyroid transcription factor-1, Ki-67, p63, p53 and high-molecular weight cytokeratin expressions in papillary thyroid carcinoma, follicular carcinoma, and follicular adenoma.

The searching of the reliable and repeatable immunohistochemical markers in the differential diagnosis of the thyroid's differentiated follicular epithelial neoplasms has been continuing. Recently, the studies have majored on immunohistochemical markers such as high-molecular weight cytokeratin (HMW-CK), galectin-3, cytokeratin 19, and p27. We aimed to evaluate the differences of the expressions of the proliferating cell nuclear antigen (PCNA), thyroid transcription factor-1 (TTF-1), Ki-67, p63, p53, and HMW-CK among the papillary thyroid carcinomas (PTCs), follicular carcinomas (FCs), and follicular adenomas (FAs). Thirty-nine patients with the diagnoses of the PTC, FC, and FA in the archives of the Izmir Tepecik Training and Research Hospital Pathology Laboratory registries in between 2004 and 2009 were included in the study. Immunohistochemical stains for PCNA, TTF-1, Ki-67, p63, p53, and HMW-CK were applied. The results were analyzed statistically by using Statistical Package for the Social Sciences (SPSS) for Windows 16.0 program (SPSS Inc., IBM, Somers, New York, USA). In all 3 groups, all tumors showed PCNA and TTF-1 positivity. Ki-67 proliferation index varied in a wide range in all groups. Although it was not statistically significant, 19 of 39 tumors (7 PTCs, 2 FCs, and 10 FAs) were stained with p63. The results of the immunoreactivity seen in PTCs with p53 (41.2%) and HMW-CK (52.9%) were statistically significant. The tumors in the other 2 groups (FC and FA) showed no reactivity with HMW-CK. Although the differential diagnosis of the thyroid follicular neoplasms are based on the histologic and cytomorphological criteria, p53 and HMW-CK positivity might be undertaken in favor of the diagnosis of the PTC.

Sarcomatoid carcinoma of the upper aerodigestive tract: an immunohistochemical analysis demonstrating latent Epstein-Barr virus in a subset of eight cases.

BACKGROUND: Sarcomatoid or spindle cell carcinomas are rare malignancies which are considered as a poorly differentiated variant of squamous cell carcinoma. Epstein-Barr virus (EBV) is associated with a wide variety of malignancies. MATERIALS AND METHODS: We examined the expression of EBV latent membrane protein-1 (LMP-1) and EBV EBNA-2 as well as the immunohistochemical profile of AE-1/AE-3, vimentin, desmin, CK 5-6, smooth muscle actin (SMA), p63, S-100, p53 and CD-117 with the clinicopathological correlation of eight patients of sarcomatoid carcinoma (SC) in the upper aerodigestive tract. RESULTS: Four cases showed EBV LMP-1 positivity (50%) and there was no EBV EBNA-2 positivity. However, the EBV LMP-1 results of our series could be considered only as a coincidental finding in the SCs of the upper aerodigestive tract. CONCLUSIONS: This finding supports the idea that further studies based on larger series might be helpful enlighting the role played by EBV in carcinogenesis of SC.

Ureteritis cystica presenting with atrophic kidney: report of a case.

Ureteritis cystica is a rare proliferative condition that is found predominantly in the bladder, renal pelvis, and upper ureter. It may occlude the ureteral lumen and should be considered in the reasons for an atrophic kidney. A 65-year-old-female with a 2-year history of right flank pain that increased in the last 2 months was presented. Abdominal ultrasonography revealed right-sided atrophic kidney. Nephroureterectomy was performed. On the gross examination, along the ureter wall, there were numerous polyps, 0.5 cm in maximum diameter, protruding into the lumen. On the histopathological evaluation, ureteritis cystica and chronic pyelonephritis was detected. In conclusion, ureteritis cystica is a benign and indolent lesion that needs to be kept in mind among the causes of renal atrophy.

Langerhans cell histiocytosis of the cervical spine in an adult: a case report.

We present a case of a 47-year-old-woman with a complaint of cervical pain with paresthetic appearance on her left arm. She was treated with analgetics. Further radiological evaluation because of the persistent pain revealed an osteolytic destruction of the fourth cervical vertebra. The patient underwent anterior cervical corpectomy with total excision of the tumor. Stabilization of the cervical spine was performed. Histology confirmed the diagnosis of Langerhans cell histiocytosis (LCH) of the cervical spine. This case report presents the histopathological evaluation, diagnostic work-up and the treatment procedures because of rarity of cervical spinal LCH cases in the literature.

Lipomatous pseudohypertrophy of the pancreas: a clinicopathologically distinct entity.

OBJECTIVES: Owing to the challenges in obtaining pancreatic biopsies, pancreatic resection for presumed malignancy is often performed without histological confirmation. As a result, benign lesions are sometimes surgically removed. One such condition, which is poorly defined in the literature, is referred to as lipomatous pseudohypertrophy (LPH) of the pancreas. METHODS: Five cases of LPH were analyzed. RESULTS: Four patients underwent surgical resection, 3 of which were diagnosed preoperatively by radiology as having ductal adenocarcinoma. The fourth case was correctly interpreted by magnetic resonance imaging as LPH, but the patient underwent resection because of the intractable pain due to pancreatitis. The fifth patient has been placed on watchful waiting.Two tumors were in the pancreatic head, one in the tail, one in the uncinate process, and one demonstrated diffuse involvement. Microscopically, they were characterized as having normal lipocytes without lipoblasts or inflammation. Within the adipose tissue, scattered microscopic foci of pancreatic parenchyma could be seen. CONCLUSION: Lipomatous pseudohypertrophy of the pancreas is a distinct entity characterized by localized/diffuse replacement of pancreatic parenchyma with mature adipose tissue. It forms a pseudotumor that may be difficult to distinguish clinically from pancreatic adenocarcinoma. This entity should be considered when evaluating patients with a new diagnosis of a hypodense pancreatic neoplasm on imaging.

Isolated solitary ducts (naked ducts) in adipose tissue: a specific but underappreciated finding of pancreatic adenocarcinoma and one of the potential reasons of understaging and high recurrence rate.

The distinction of ductal adenocarcinoma from chronic pancreatitis remains one of the most difficult challenges in surgical pathology. The glandular units of invasive carcinoma are often well formed with well-polarized cells, appearing deceptively benign. Conversely, the ducts of chronic pancreatitis may be atypical and pseudoinfiltrative as a result of acinar atrophy and fibrosis. We recently noted isolated solitary ductal units (ISDs) in adipose tissue to be a reliable indicator of adenocarcinoma. In this study, the frequency of ISDs was investigated in 105 pancreatic resections with ductal adenocarcinoma and 32 with chronic pancreatitis only. ISD was defined as a solitary gland lying individually in adipose tissue, either directly abutting adipocytes or separated from them by only a thin rim of fibromuscular tissue. ISD was detected in 50/105 (47.6%) of pancreatic resections for ductal adenocarcinoma, but not in any resections with chronic pancreatitis only (specificity 100%; sensitivity 47.6%). Most of the ISDs were very well differentiated and cytologically bland. A small subset of these units represented vascular invasion, in which the carcinoma cells epithelialized the vessel lining, transforming the vessel into a duct-like structure, virtually indistinguishable from normal ducts or PanINs. The vascular nature of these units was verified by Elastic-Van Gieson stain and muscular markers highlighting the elastic lamina and muscular wall, respectively. ISDs were often located in histologic sections taken for the evaluation of the retroperitoneal margin and pancreatic-free surfaces where adipose tissue is more abundant. In conclusion, ISD lying in adipose tissue unaccompanied by other elements, present in 47.6% of pancreatic resections when peripancreatic soft tissues away from the tumor are sampled, is a very specific finding for carcinoma that may be instrumental in the diagnosis and staging of carcinoma as well as margin evaluation.

The number of lymph nodes identified in a simple pancreatoduodenectomy specimen: comparison of conventional vs orange-peeling approach in pathologic assessment.

Lymph node status is one of the most important predictors of survival in resectable pancreatic ductal adenocarcinoma; therefore, thorough lymph node evaluation is a critical assessment in pancreatoduodenectomy specimens. There is considerable variability in pancreatoduodenectomy specimens processed histologically. This study compares two approaches of lymph node dissection and evaluation (standard vs orange peeling) of pancreatoduodenectomy specimens. A different approach to dissection of pancreatoduodenectomy specimens was designed to optimize lymph node harvesting: All peripancreatic soft tissues were removed in an orange-peeling manner before further dissection of the pancreatic head. This approach was applied to 52 consecutive pancreatoduodenectomy specimens performed for ductal adenocarcinoma at two institutions. Specimen dissection was otherwise performed routinely. Overall number of lymph nodes harvested, number of positive lymph nodes, and their anatomic distribution were analyzed and compared with cases that had been dissected by the conventional approach. The mean number of lymph nodes identified by the orange-peeling approach was 14.1 (by institution, 13.8 and 14.4), as opposed to 6.1 (by institution, 7 and 5.3) in cases processed by conventional approach (P=0.0001). The number of lymph node-positive cases also increased substantially from 50% (by institution, 54 and 46%) in the conventional method to 73% (by institution, 88 and 58%) in the orange-peeling method (P=0.02). The orange-peeling method of lymph node harvest in pancreatoduodenectomy specimens for ductal adenocarcinoma enhances overall and positive lymph node yield and optimizes ductal adenocarcinoma staging. Therefore, lymph node harvest by the orange-peeling method should be performed routinely before specimen sectioning in assessment of pancreatoduodenectomy for ductal adenocarcinoma.

Is serous cystadenoma of the pancreas a model of clear-cell-associated angiogenesis and tumorigenesis?

BACKGROUND: Similar to the other von Hippel-Lindau (VHL)-related tumors such as renal cell carcinomas and capillary hemangioblastomas, serous cystadenomas (SCAs) of the pancreas are also characterized by clear cells. Over the years, we have also noticed that the tumor epithelium shows a prominent capillary network. METHODS: Eighteen cases of SCA were reviewed histologically, and immunohistochemical analysis was performed for CD31 and vascular endothelial growth factor (VEGF) as well as the molecules implicated in clear-cell tumorigenesis: GLUT-1, hypoxia-inducible factor-1 (HIF-1alpha), and carbonic anhydrase IX (CA IX). RESULTS: There was an extensively rich capillary network that appears almost intraepithelially in all cases of SCA, which was confirmed by CD31 stain that showed, on average, 26 capillaries per every 100 epithelial cells. VEGF expression was identified in 10/18 cases. Among the clear-cell tumorigenesis markers, CA IX was detected in all cases, GLUT-1 and HIF-1alpha in most cases. CONCLUSION: As in other VHL-related clear-cell tumors, there is a prominent capillary network immediately adjacent to the epithelium of SCA, confirming that the clear-cell- angiogenesis association is also valid for this tumor type. Molecules implicated in clear-cell tumorigenesis are also consistently expressed in SCA. This may have biologic and therapeutic implications, especially considering the rapidly evolving drugs against these pathways. More importantly, SCA may also serve as a model of clear-cell-associated angiogenesis and tumorigenesis, and the information gained from this tumor type may also be applicable to other clear-cell tumors.