Catherine Campbell

Prevalence of eosinophilic esophagitis in adults with food bolus obstruction of the esophagus.

Background and Goals Acute food bolus impaction is a common emergency in gastrointestinal practice. Management previously used the endoscope with an overtube to allow retrieval of the bolus per os. The push technique using air insufflation and gentle pressure on the bolus provides an alternative approach. Esophageal mucosal biopsy at the time of the initial endoscopy has not been a part of traditional practice. In view of the increasing recognition of eosinophilic esophagitis (EE) as a cause of dysphagia and food bolus obstruction in adults the etiology needs to be reassessed. Study Forty-three consecutive adults presenting with acute dysphagia secondary to food bolus obstruction of the esophagus were studied. The bolus was advanced into the stomach with the push technique or removed per os with a retrieval net. Protocol biopsies from the proximal and distal esophagus were obtained in 29 patients. Biopsies were contraindicated or not obtained in the remainder. Results Forty-one patients were successfully treated at endoscopy. Two subjects with a food bolus impacted at the crico-pharyngeal region required general anesthesia with endotracheal intubation for safe removal. Of 29 patients biopsied, 15 had peptic esophageal stricture as the cause. Fourteen patients (all males, mean age 32 y, range 19 to 62 y) had EE identified histologically. This represents 50% of those biopsied. Patients with EE had typical endoscopic features of linear furrows, mucosal rings, or narrow bore esophagus. Most had prior episodes of food bolus obstruction. Conclusions Food bolus obstruction can be safely managed by the push technique. EE is an important cause of food bolus obstruction that can be suspected on history and endoscopic appearance and confirmed on histology.

Novel markers for poor prognosis in head and neck cancer.

Head and neck cancer (HNSCC) is one of the most distressing human cancers, causing pain and affecting the basic survival functions of breathing and swallowing. Mortality rates have not changed despite recent advances in radiotherapy and surgical treatment. We have compared the expression of over 13,000 unique genes in 7 cases of matched HNSCC and normal oral mucosa. Of the 1,260 genes that showed statistically significant differences in expression between normal and tumor tissue at the mRNA level, the three top ranking of the top 5% were selected for further analysis by immunohistochemistry on paraffin sections, along with the tumor suppressor genes p16 and p53, in a total of 62 patients including 55 for whom >4‐year clinical data was available. Using univariate and multivariate survival analysis, we identified SPARC/osteonectin as a powerful independent prognostic marker for short disease‐free interval (DFI) (p < 0.002) and poor overall survival (OS) (p = 0.018) of HNSCC patients. In combination with other ECM proteins found in our analysis, PAI‐1 and uPA, the association with DFI and OS became even more significant (p < 0.001). Our study represents the first instance of SPARC as an independent prognostic marker in HNSCC.

Alpha B-crystallin, a new independent marker for poor prognosis in head and neck cancer

Objectives: Gene expression profiling has provided many insights into tumor progression but translation to clinical practice has been limited. We have previously identified a list of potential markers by the differences of expression profiling of seven matched head and neck cancer (HNSCC) tumors with autologous normal oral mucosa (NOM). Alpha B‐crystallin (CRYAB) was in the top 5% of genes identified with statistically significant differences in expression between tumor and NOM at the mRNA level. The objective was to confirm this in routine paraffin sections at the protein level.

Juvenile nasopharyngeal angiofibroma: an immunohistochemical characterisation of the stromal cell

Aims: Juvenile nasopharyngeal angiofibroma (JNA) is a rare tumour occurring almost exclusively in young adult males. Although histologically benign, it can be locally aggressive with a significant recurrence rate. The finding of activating beta‐catenin gene mutations in the stromal cells indicates these are the neoplastic cells and supports the association of JNA and familial adenomatous polyposis (FAP). Previous immunohistochemical studies have demonstrated a null or focal myoepithelial immunophenotype in the stromal cells. Recently, expression of several growth factors and oncoproteins including CD117 (c‐kit) in the stromal cells has been demonstrated. Our objective is to evaluate the immunohistochemical phenotype of the stromal cell of JNA, particularly within the proliferative zone of the tumour, by application of antibodies against MNF116, CAM5.2, S‐100, CD31, CD34, CD99, CD68, vimentin, EMA, SMA, desmin, calponin, Bcl‐2 and (CD117) c‐kit in a series of 54 cases. Methods: A routine immunohistochemical protocol was applied to representative paraffin sections of 54 JNAs collected from the Port Moresby General Hospital, Papua New Guinea, and Princess Alexandra and Royal Brisbane Hospitals, Queensland, Australia. Immunoexpression of each antigen was assessed in the stromal cells and the vessels. Results: The majority of stromal cells in more than half of the cases demonstrated no staining with any of the 14 antibodies other than vimentin. Of 54 cases, 22 contained a microvascular component (usually peripherally located and indicating the active growth front of the tumour) in which the stromal cells demonstrated a hybrid immunophenotype with both smooth muscle and endothelial differentiation. c‐kit was negative in all cases. Conclusions: The majority of stromal cells have an undifferentiated immunophenotype with no evidence of epithelial, myoid, endothelial or other lineage specific differentiation. In the microvascular component the stromal cells appear able to show smooth muscle or endothelial differentiation. No c‐kit expression was identified.

Leiomyoma of the Nipple

Abstract:  Leiomyoma is a rare, benign neoplasm of the nipple. We report the case of a patient with a leiomyoma arising from her left nipple who presented with persistent nipple pain and tenderness which led to the eventual complete excision of her left nipple and areola complex. The clinical characteristics, gross and microscopic pathologic findings, and management of this lesion are discussed. Surgical management should be tailored primarily to the control of symptoms. Clinicians should be aware that this is a rare, but potential cause of chronic persistent pain and swelling in the region of the nipple‐areola complex of the breast.

Synovial sarcoma − towards a simplified approach to prognosis

Background:  Synovial sarcoma is a high grade sarcoma that usually occurs in adults. Numerous studies have attempted to identify prognostic factors that might allow more effective treatment for particular subgroups of patients.

Subclassification of hepatocellular adenomas: practical considerations in the implementation of the Bordeaux criteria

Hepatocellular adenomas are benign liver lesions with a risk of rupture and malignant transformation. Various molecular subgroups have been identified which appear to have characteristic morphological and immunohistochemical features. We examined the morphology and immunohistochemical profile of a series of 121 HCA from 97 patients to identify the HCA subtypes present and determine the number at risk for malignant transformation according to the World Health Organization (WHO) criteria for hepatocellular adenomas. There were 34 HNF1α inactivated HCA (28%), 61 inflammatory HCA (50%), 15 β-catenin activated HCA (12%) and 11 unclassified adenomas (9%). This proportion of cases was similar to that seen in other series utilising molecular classification. The morphological features of the adenomas were suggestive but not definite indicators of the subtypes present. Morphological features that showed overlap between the subtypes included steatosis within the lesion, a ductular reaction and focal atypia, so that immunohistochemical typing was required for accurate classification. In conclusion, immunohistochemistry is a clinically useful surrogate for identifying underlying molecular changes in the HCA subtypes.

A Case of an Unsuspected Cause of Budd–Chiari Syndrome

C 22-year-old woman presented with a 12-month history of pruritus, nocturnal sweats, and increasing abdominal irth. She otherwise enjoyed good health, and her only mediation was the oral contraceptive pill. An abdominal computed tomography scan showed ascites nd hepatomegaly, with a hypertrophied caudate lobe and comression of the inferior vena cava (IVC) (Figure A, arrow). A omputed tomography– guided liver biopsy showed disrupted rchitecture, with central sclerosis obliterating the central veins nd surrounding liver parenchyma with encroachment on the ortal tracts. The sclerotic areas contained vacuolated cells with ccentrically placed nuclei that were thought to be hepatocytes ith fat (Figure B, arrow). Hepatic venography revealed comlete occlusion of the main left hepatic vein and branches of ight and middle hepatic veins. There was extrinsic narrowing f intrahepatic segment of the IVC. She was diagnosed with hronic Budd–Chiari syndrome (BCS), commenced on diuretcs, and the oral contraceptive was ceased. Four years later, she as referred to a hepatologist because of worsening ascites. She as found to have hepatosplenomegaly, ascites, multiple spider evi, and prominent veins on the anterior abdominal wall and umbar region suggestive of portosystemic collaterals and IVC bstruction. Investigations revealed elevation of her alkaline hosphatase at 356 U/L and -glutamyltransferase at 169 U/L. creening for procoagulants revealed an elevated serum homoysteine 16.5 mol/L (normal, 4 –14 mol/L) and heterozygosty for the prothrombin gene mutation guanine to adenine at osition 20210. Upper endoscopy revealed small esophageal arices. Because of resistant ascites, increasing fatigue, and decrease n her muscle bulk, she proceeded to orthotopic liver transplanation. The explant liver showed almost complete replacement f the hepatic parenchyma by multiple pale brown nodules urrounded by severe congestion. There was no thrombosis of he hepatic veins. Histology revealed the nodules consisted of brotic stroma containing single cells and cells arranged in ords. There were plump epithelioid cells with eosinophilic ytoplasm and atypical nuclei with prominent nucleoli and ntracytoplasmic lumina containing red blood cells. No mitoses ere evident. There was extensive involvement of the hepatic inusoids, terminal hepatic veins, and some portal veins, with lling and obliteration of some vessel lumina but no involveent of the portal vein at the hilum. Immunoperoxidase stains howed the epithelioid cells were positive for the endothelial ell markers CD31 and CD34. The morphology and immunohenotype of the lesion were those of an epithelioid hemanioendothelioma (EHE). Staining of the original biopsies for D34 showed positivity of the atypical vacuolated cells, sugesting these cells were of endothelial origin (Figure C, brown ositive stain, arrow). Seven years after transplant, she remains ell and gave birth to a healthy baby in 2008. Hepatic EHE is a rare, low-grade malignant neoplasm of ascular origin and most commonly presents with nonspecific ymptoms, but presentation with BCS has been previously eported.1 This case displayed clinical features of BCS from

Re: Synovial sarcoma ‐ towards a simplified approach to prognosis

BACKGROUND Synovial sarcoma is a high grade sarcoma that usually occurs in adults. Numerous studies have attempted to identify prognostic factors that might allow more effective treatment for particular subgroups of patients. METHODS We studied 25 histologically confirmed cases of synovial sarcoma in an attempt to identify particular patient, tumour or treatment characteristics that might have a prognostic significance using Cox proportional hazards regression modelling to identify differences in survival rates. All patients received their definitive surgical treatment from a single orthopaedic surgeon reducing the likelihood of bias related to variations in surgical technique. RESULTS Statistically significant higher survival rates were seen in female patients (P = 0.040) and in patients aged <50 years (P = 0.028). There was also a tendency towards higher survival rates in those cases with upper limb tumours, tumours less than 50 mm in size, and tumours that histologically showed low grade tumour nuclei. Differences in survival were not seen with the percentage of epithelioid, spindled or poorly differentiated areas present, the number of mitoses, or the presence of necrosis. No treatment characteristics were associated with differences in survival. CONCLUSIONS The present study has confirmed that male sex and older age are unfavourable prognostic features in synovial sarcoma. Additionally, the histological grade of synovial sarcomas might be more accurately and simply determined based on an assessment of nuclear grade alone.