Cancer of the oral cavity and oropharynx

Tumours in the oral cavity and oropharynx differ in presentation and prognosis and the detection of spread of tumour from one subsite to another is essential for the T-staging. This article reviews the anatomy and describes the pattern of spread of different cancers arising in the oral cavity and oropharynx; the imaging findings on computerized tomography and magnetic resonance imaging are also described. Brief mention is made on the role of newer imaging modalities such as [(18)F]fluorodeoxyglucose-positron emission tomography/computed tomography, perfusion studies and diffusion-weighted magnetic resonance imaging.

Pheochromocytoma in rats with multiple endocrine neoplasia (MENX) shares gene expression patterns with human pheochromocytoma

Pheochromocytomas are rare neoplasias of neural crest origin arising from chromaffin cells of the adrenal medulla and sympathetic ganglia (extra-adrenal pheochromocytoma). Pheochromocytoma that develop in rats homozygous for a loss-of-function mutation in p27Kip1 (MENX syndrome) show a clear progression from hyperplasia to tumor, offering the possibility to gain insight into tumor pathobiology. We compared the gene-expression signatures of both adrenomedullary hyperplasia and pheochromocytoma with normal rat adrenal medulla. Hyperplasia and tumor show very similar transcriptome profiles, indicating early determination of the tumorigenic signature. Overrepresentation of developmentally regulated neural genes was a feature of the rat lesions. Quantitative RT-PCR validated the up-regulation of 11 genes, including some involved in neural development: Cdkn2a, Cdkn2c, Neurod1, Gal, Bmp7, and Phox2a. Overexpression of these genes precedes histological changes in affected adrenal glands. Their presence at early stages of tumorigenesis indicates they are not acquired during progression and may be a result of the lack of functional p27Kip1. Adrenal and extra-adrenal pheochromocytoma development clearly follows diverged molecular pathways in MENX rats. To correlate these findings to human pheochromocytoma, we studied nine genes overexpressed in the rat lesions in 46 sporadic and familial human pheochromocytomas. The expression of GAL, DGKH, BMP7, PHOX2A, L1CAM, TCTE1, EBF3, SOX4, and HASH1 was up-regulated, although with different frequencies. Immunohistochemical staining detected high L1CAM expression selectively in 27 human pheochromocytomas but not in 140 nonchromaffin neuroendocrine tumors. These studies reveal clues to the molecular pathways involved in rat and human pheochromocytoma and identify previously unexplored biomarkers for clinical use.

Differential cell cycle and proliferation marker expression in ductal pancreatic adenocarcinoma and pancreatic intraepithelial neoplasia (PanIN)

Pancreatic cancer is an aggressive tumour following a multistep progression model through precursors called pancreatic intraepithelial neoplasia (PanIN). Identification of reliable prognostic markers would help in improving survival. The aim of this study was to investigate the role as well as the prognostic significance of different cell cycle and proliferation markers, namely p21, p27, p53 and Ki-67, in pancreatic carcinogenesis.

Risk profiles and penetrance estimations in multiple endocrine neoplasia type 2A caused by germline RET mutations located in exon 10

Multiple endocrine neoplasia type 2 is characterized by germline mutations in RET. For exon 10, comprehensive molecular and corresponding phenotypic data are scarce. The International RET Exon 10 Consortium, comprising 27 centers from 15 countries, analyzed patients with RET exon 10 mutations for clinical-risk profiles. Presentation, age-dependent penetrance, and stage at presentation of medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism were studied. A total of 340 subjects from 103 families, age 4-86, were registered. There were 21 distinct single nucleotide germline mutations located in codons 609 (45 subjects), 611 (50), 618 (94), and 620 (151). MTC was present in 263 registrants, pheochromocytoma in 54, and hyperparathyroidism in 8 subjects. Of the patients with MTC, 53% were detected when asymptomatic, and among those with pheochromocytoma, 54%. Penetrance for MTC was 4% by age 10, 25% by 25, and 80% by 50. Codon-associated penetrance by age 50 ranged from 60% (codon 611) to 86% (620). More advanced stage and increasing risk of metastases correlated with mutation in codon position (609?620) near the juxtamembrane domain. Our data provide rigorous bases for timing of premorbid diagnosis and personalized treatment/prophylactic procedure decisions depending on specific RET exon 10 codons affected.

Can molecular markers stratify the diagnostic value of high-grade prostatic intraepithelial neoplasia?

The diagnostic performance of isolated high-grade prostatic intraepithelial neoplasia in prostatic biopsies has recently been questioned, and molecular analysis of high-grade prostatic intraepithelial neoplasia has been proposed for improved prediction of prostate cancer. Here, we retrospectively studied the value of isolated high-grade prostatic intraepithelial neoplasia and the immunohistochemical markers ?-methylacyl coenzyme A racemase, Bcl-2, annexin II, and Ki-67 for better risk stratification of high-grade prostatic intraepithelial neoplasia in our local Swiss population. From an initial 165 diagnoses of isolated high-grade prostatic intraepithelial neoplasia, we refuted 61 (37%) after consensus expert review. We used 30 reviewed high-grade prostatic intraepithelial neoplasia cases with simultaneous biopsy prostate cancer as positive controls. Rebiopsies were performed in 66 patients with isolated high-grade prostatic intraepithelial neoplasia, and the median time interval between initial and repeat biopsy was 3 months. Twenty (30%) of the rebiopsies were positive for prostate cancer, and 10 (15%) showed persistent isolated high-grade prostatic intraepithelial neoplasia. Another 2 (3%) of the 66 patients were diagnosed with prostate cancer in a second rebiopsy. Mean prostate-specific antigen serum levels did not significantly differ between the 22 patients with prostate cancer and the 44 without prostate cancer in rebiopsies, and the 30 positive control patients, respectively (median values, 8.1, 7.7, and 8.8 ng/mL). None of the immunohistochemical markers, including ?-methylacyl coenzyme A racemase, Bcl-2, annexin II, and Ki-67, revealed a statistically significant association with the risk of prostate cancer in repeat biopsies. Taken together, the 33% risk of being diagnosed with prostate cancer after a diagnosis of high-grade prostatic intraepithelial neoplasia justifies rebiopsy, at least in our not systematically prostate-specific antigen-screened population. There is not enough evidence that immunohistochemical markers can reproducibly stratify the risk of prostate cancer after a diagnosis of isolated high-grade prostatic intraepithelial neoplasia.

Functional Imaging of Pheochromocytoma with Ga-DOTATOC and C-HED in a Genetically Defined Rat Model of Multiple Endocrine Neoplasia

Rats affected by the MENX multitumor syndrome develop pheochromocytoma (100%). Pheochromocytomas are uncommon tumors and animal models are scarce, hence the interest in MENX rats to identify and preclinically evaluate novel targeted therapies. A prerequisite for such studies is a sensitive and noninvasive detection of MENXassociated pheochromocytoma. We performed positron emission tomography (PET) to determine whether rat pheochromocytomas are detected by tracers used in clinical practice, such as 68Ga-DOTATOC (somatostatin analogue) or (11)C-Hydroxyephedrine (HED), a norepinephrine analogue. We analyzed four affected and three unaffected rats. The PET scan findings were correlated to histopathology and immunophenotype of the tumors, their proliferative index, and the expression of genes coding for somatostatin receptors or the norepinephrine transporter. We observed that mean 68Ga-DOTATOC standard uptake value (SUV) in adrenals of affected animals was 23.3 ± 3.9, significantly higher than in control rats (15.4 ± 7.9; P = .03). The increase in mean tumor-to-liver ratio of (11)C-HED in the MENX-affected animals (1.6 ± 0.5) compared to controls (0.7 ± 0.1) was even more significant (P = .0016). In a unique animal model, functional imaging depicting two pathways important in pheochromocytoma biology discriminated affected animals from controls, thus providing the basis for future preclinical work with MENX rats.

The impact of frozen sections on final surgical margins in squamous cell carcinoma of the oral cavity and lips: a retrospective analysis over an 11 years period

Taking intraoperative frozen sections (FS) is a widely used procedure in oncologic surgery. However so far no evidence of an association of FS analysis and premalignant changes in the surgical margin exists. Therefore, the aim of this study was to evaluate the impact of FS on different categories of the final margins of squamous cell carcinoma (SCC) of the oral cavity and lips.

The unspoken disease: symptom experience in women with vulval neoplasia and surgical treatment: a qualitative study

Women with vulval neoplasia often experience severe post-surgical complications. This study focuses on symptom experience of women during the first 6 months following surgical treatment for vulval neoplasia considering their socio-cultural context. In this qualitative study using a critical hermeneutic approach, narrative interviews were conducted. A purposeful sample of 20 patients was recruited from one Swiss and two German university hospitals. Content analysis was employed to analyse the transcribed interviews considering women's experiences and social perceptions. Narratives showed eight interrelated themes: delayed diagnosis, disclosed disease, disturbed self-image, changed vulva care, experienced wound-related symptoms, evoked emotions, affected interpersonal interactions and feared illness progression. The women experienced a general lack of information pertaining to above themes and all described strategies used to handle their situation, which affected their distress. The communication, assessment and treatment of symptoms were hampered by the society's and the health system's tendency to overlook these symptoms and leave them in the realm of the unspeakable. Health professionals need new strategies to support these women to recognise, assess and evaluate the seriousness of symptoms, and to communicate their symptom experience so that timely medical treatment is sought. This support may minimise potentially preventable complications and symptom-related distress.

Incomplete ovariosalpingectomy and subsequent malignant granulosa cell tumor in a female green iguana (Iguana iguana)

Case Description-A 9-year-old spayed female green iguana (Iguana iguana) was evaluated because of a distended coelom and weight loss. History included a single episode of egg binding and subsequent bilateral ovariosalpingectomy.;Clinical Findings-Physical examination revealed a mass within the coelomic cavity. Ultrasonography revealed a large, irregular mass with hypoechoic regions and coelomic effusion. Clinicopathologic derangements included heterophilia, monocytosis, lymphopenia, basophilia, hypocholesterolemia, hypoproteinemia, and hypercalcemia. Results of cytologic evaluation of the mass were suggestive of malignant epithelial neoplasia, but neoplastic cells were not found in the effusion. An ovarian tumor was suspected on the basis of clinical signs, clinicopathologic findings, and results of cytologic evaluation of the mass.;Treatment and Outcome-Surgical exploration revealed a large left ovary, a normal-appearing contralateral ovary, and a mass in the fat body, all of which were removed and submitted for histologic examination. The histologic diagnosis was granulosa cell tumor with metastasis to the fat body. The patient died 11 months after evaluation, and disseminated granulosa cell tumor was confirmed at necropsy; histologic examination at that time also identified systemic mastocytosis.;Clinical Relevance-Granulosa cell tumors are uncommon in reptiles, and this was the first granulosa cell tumor described antemortem cytologically, histologically, and ultrastructurally in an iguana. Findings in this iguana underscored concerns associated with incomplete oophorectomy of iguanas; cytologic and histopathologic findings were similar to those observed in other domestic animals. Oophorectomy should be considered as an alternative to standard ovariosalpingectomy to avoid potential complications in pet reptiles, and use of microsurgical instruments and vascular clips is advised. (J Am Vet Med Assoc 2011239:237-242)

Outcome and patterns of failure after postoperative intensity modulated radiotherapy for locally advanced or high-risk oral cavity squamous cell carcinoma

Background To determine the outcome and patterns of failure in oral cavity cancer (OCC) patients after postoperative intensity modulated radiotherapy (IMRT) with concomitant systemic therapy. Methods All patients with locally advanced (AJCC stage III/IV) or high-risk OCC (AJCC stage II) who underwent postoperative IMRT at our institution between December 2006 and July 2010 were retrospectively analyzed. The primary endpoint was locoregional recurrence-free survival (LRRFS). Secondary endpoints included distant metastasis-free survival (DMFS), overall survival (OS), acute and late toxicities. Results Overall 53 patients were analyzed. Twenty-three patients (43%) underwent concomitant chemotherapy with cisplatin, two patients with carboplatin (4%) and four patients were treated with the monoclonal antibody cetuximab (8%). At a median follow-up of 2.3 (range, 1.1–4.6) years the 3-year LRRFS, DMFS and OS estimates were 79%, 90%, and 73% respectively. Twelve patients experienced a locoregional recurrence. Eight patients, 5 of which had both a flap reconstruction and extracapsular extension (ECE), showed an unusual multifocal pattern of recurrence. Ten locoregional recurrences occurred marginally or outside of the high-risk target volumes. Acute toxicity grades of 2 (27%) and 3 (66%) and late toxicity grades of 2 (34%) and 3 (11%) were observed. Conclusion LRRFS after postoperative IMRT is satisfying and toxicity is acceptable. The majority of locoregional recurrences occurred marginally or outside of the high-risk target volumes. Improvement of high-risk target volume definition especially in patients with flap reconstruction and ECE might transfer into better locoregional control.

Multiple small "imaging" branch-duct type intraductal papillary mucinous neoplasms (IPMNs) in familial pancreatic cancer: indicator for concomitant high grade pancreatic intraepithelial neoplasia?

Most screening programs for familial pancreatic cancer are currently based on endoscopic ultrasonography and/or magnetic resonance imaging (MRI). Cystic lesions, especially those suspicious for small intraductal pancreatic mucinous neoplasms (IPMNs) of the branch ducts, can be visualized in up to 40 % of individuals at risk, but their pathological importance in the setting of FPC is yet not well established. Individuals at risk from a prospective screening program for familial pancreatic cancer with small "imaging" IPMNs of the branch-duct type (BD-IPMN) who underwent pancreatic resection were analysed regarding clinico-pathological data and the locations of pancreatic lesions. Five of 125 individuals at risk who underwent screening had multiple small (size 2-10 mm) unicystic lesions and/or multicystic single lesions in the pancreatic body and tail suspicious for BD-IPMNs upon MRI imaging and decided to undergo surgical resection after interdisciplinary counselling, although none fulfilled the consensus criteria for IPMN resection. Histological examination revealed BD-IPMNs with low or moderate dysplasia of the gastric type in combination with multifocal PanIN2 and PanIN3 lesions in 4 individuals. The remaining patient had only tiny ductectasias in the pancreatic tail with multifocal PanIN 2 lesions in the entire gland and one PanIN3 lesion in the pancreatic head. Intriguingly, the location of the most dysplastic histological lesions (PanIN3) did not correspond to the preoperatively detected lesions and were not visible in preoperative imaging. In the setting of FPC, the presence of multiple small "imaging" BD-IPMNs may indicate the presence of high-grade PanIN lesions elsewhere in the pancreas.

Development of a postsurgical patient-reported outcome instrument for women with vulvar neoplasia

To (a) develop the Women With Vulvar Neoplasia-Patient-Reported Outcome (WOMAN-PRO) instrument as a measure of women's post-vulvar surgery symptom experience and informational needs, (b) examine its content validity, (c) describe modifications based on pilot testing, and (d) examine the content validity of the revised instrument.

Self-adjoint extensions for confined electrons: From a particle in a spherical cavity to the hydrogen atom in a sphere and on a cone

In a recent study of the self-adjoint extensions of the Hamiltonian of a particle confined to a finite region of space, in which we generalized the Heisenberg uncertainty relation to a finite volume, we encountered bound states localized at the wall of the cavity. In this paper, we study this situation in detail both for a free particle and for a hydrogen atom centered in a spherical cavity. For appropriate values of the self-adjoint extension parameter, the bound states localized at the wall resonate with the standard hydrogen bound states. We also examine the accidental symmetry generated by the Runge–Lenz vector, which is explicitly broken in a spherical cavity with general Robin boundary conditions. However, for specific radii of the confining sphere, a remnant of the accidental symmetry persists. The same is true for an electron moving on the surface of a finite circular cone, bound to its tip by a 1/r1/r potential.