Multiple-instance-learning-based detection of coeliac disease in histological whole-slide images.

We present a multiple-instance-learning-based scheme for detecting coeliac disease, an autoimmune disorder affecting the intestine, in histological whole-slide images (WSIs) of duodenal biopsies. We train our model to detect 2 distinct classes, normal tissue and coeliac disease, on the patch-level, and in turn leverage slide-level classifications. Using 5-fold cross-validation in a training set of 1841 (1163 normal; 680 coeliac disease) WSIs, our model classifies slides as normal with accuracy (96.7±0.6)%, precision (98.0±1.7)%, and recall (96.8±2.5)%, and as coeliac disease with accuracy (96.7±0.5)%, precision (94.9±3.7)%, and recall (96.5±2.9)% where the error bars are the cross-validation standard deviation. We apply our model to 2 test sets: one containing 191 WSIs (126 normal; 65 coeliac) from the same sources as the training data, and another from a completely independent source, containing 34 WSIs (17 normal; 17 coeliac), obtained with a scanner model not represented in the training data. Using the same-source test data, our model classifies slides as normal with accuracy 96.5%, precision 98.4% and recall 96.1%, and positive for coeliac disease with accuracy 96.5%, precision 93.5%, and recall 97.3%. Using the different-source test data the model classifies slides as normal with accuracy 94.1% (32/34), precision 89.5%, and recall 100%, and as positive for coeliac disease with accuracy 94.1%, precision 100%, and recall 88.2%. We discuss generalising our approach to screen for a range of pathologies.

The clinical significance of a pathologically positive lymph node at the circumferential resection margin in rectal cancer.

BACKGROUND: This study aimed to determine if the nature of circumferential resection margin (CRM) involvement, either by tumour or lymph nodes, had an impact upon local recurrence and survival in rectal cancer. METHODS: A retrospective analysis of a prospectively collected database was performed. Consecutive patients with stage I-III rectal cancer having curative surgery were included. All specimens were analysed by a single histopathologist. Statistical analysis was performed using chi-squared test and Kaplan-Meier. RESULTS: Of 265 patients, 29 (11%) had a positive CRM. Compared to patients with a negative CRM, a positive margin due to tumour was associated with a higher 5-year cumulative incidence of local recurrence (43.7% versus 8.8%, p = 0.001) and distant metastases (62% versus 13.6%, p = 0.001) with poorer 5-year cancer-specific survival (32% versus 87.8%, p = 0.001). Although patients with margin positivity due to lymph nodes had a higher rate of distant metastases (41.3% versus 13.6%, p = 0.004) and poorer 5-year cancer-specific survival (59.3% versus 87.8%, p = 0.038), the rate of local recurrence was comparable to that of patients with negative margins (8.3% versus 8.8%, p = 0.694). CONCLUSIONS: Our findings suggest that the nature of CRM involvement may be important in determining prognosis in rectal cancer. Local recurrence is higher only when there is tumour present at the margin. Lymph node involvement of the margin confers similar risk of local recurrence to patients with CRM-negative, node-positive disease. These results need further evaluation in multicentre, prospective studies.

A diagnostic challenge.

A 74 year-old woman presented with a 9 month history of a slowly enlarging exophytic lesion over her left nasal alar. Examination revealed a firm, cystic mass fixed to underlying skin. It was pedunculated with occasional superficial telangiectasia and a violaceous hue. A differential diagnosis of dermoid or sebaceous cyst, dermatofibroma, and neurofibroma was considered. Histopathological examination confirmed the rare diagnosis of chondroid syringoma (CS), which has a reported incidence of 0.01- 0.098% of excised skin tumors. It is unusual for CS to present in an elderly woman, as these benign primary skin tumors normally present in adult males. Dermoscopy does not reveal any specific features and the diagnosis is difficult to make based on clinical examination alone.

Misdiagnosis of cutaneous leishmaniasis and recurrence after surgical excision.

Cutaneous Leishmaniasis (CL) occurs in British troops deployed to Belize, Afghanistan, Iraq and elsewhere. From 1998 to 2009, 156 (45%) of 343 confirmed cases seen in the UK were in military personnel. CL is a rare disease and requires specialist clinical management because numerous pitfalls exist during diagnosis and treatment. A 19-year-old soldier developed CL on his neck 6 weeks after taking part in jungle warfare training in Belize. However, this was not suspected and the diagnosis was not made from either a skin biopsy or following surgical excision. The travel history and the patient's own photograph prompted retrospective investigations that confirmed this was CL due to Leishmania mexicana. Three months after surgery, the disease recurred locally and was treated appropriately with a good outcome. British military personnel with suspected CL should be referred to the UK Role 4 Military Infectious Diseases & Tropical Medicine Service.

An unexpected abdominal tumour in an elderly woman.

We report the case of a 73-year-old woman who presented with pain and an abdominal mass and was found to have an abdominal tumour of unexpected origin.

Same Surgeon: Different Centre Equals Differing Lymph Node Harvest following Colorectal Cancer Resection.

Introduction. The aim of this study was to examine the effect of surgeon relocation on lymph node (LN) retrieval in colorectal cancer (CRC) resection. Methods. The study population was 213 consecutive patients undergoing CRC resection by a single surgeon, at two units: unit one 110 operations (2002-2005) and unit two 103 (2005-2009). LN yields and case mix were compared. Results. Median LN harvests were significantly different between the two centres: unit 1: 13 nodes/patient and unit 2: 22 nodes/patient (P < .001). In unit one 42% of cases were LN positive and in unit two 48% (P = .398). There was no difference in case mix. Multivariate analysis identified unit (P < .001) and pathologist (P = .007) as independent predictors of harvest. Conclusions. A surgeon moving units can experience significantly different LN yield following CRC resection. Both units comply with national standards, but the "surgeon's results" at the two units appear to be pathologist dependent. This has implications for nodal harvest as a surrogate marker of surgical quality.

Primary localised pleural neurofibroma: expanding the spectrum of spindle cell tumours of the pleura.

AIMS: Primary localised pleural neoplasms are a rare group of thoracic tumours, with solitary fibrous tumour representing the most frequently encountered entity. Two cases of localised pleural neurofibromas involving the pleura are described. METHODS AND RESULTS: The patients were both female: 78 and 29 years of age. In the former a pleural-based lesion was identified on a chest radiograph after she presented with shoulder pain. The second patient was known to have neurofibromatosis type I, and the pleural lesion was found incidentally during excision of a metastatic malignant peripheral nerve sheath tumour of the lung. Both tumours were localised and composed histologically of bland neoplastic spindle cells embedded in a loose collagenous matrix. There was variable immunoreactivity for S100 and CD34, while ultrastructure examination in the two cases showed a mixture of nerve sheath cell types. CONCLUSION: To the best of the authors' knowledge, localised neurofibromas have not been previously reported within the pleura. The presence of a bland spindle cell pleural neoplasm immunoreactive for CD34 may potentially be mistaken for a solitary fibrous tumour. While distinction is usually achieved on close attention to the histological features, staining with S100 protein, especially in small biopsies, should be considered to exclude a neurofibroma.

Balloon-related complications and technical failures in kyphoplasty for vertebral fractures.

BACKGROUND AND PURPOSE: Our aim was to describe the immediate or early complications and technical failures occurring during balloon kyphoplasty (BKP) procedures and attributable to balloon inflation. MATERIALS AND METHODS: We performed a retrospective review of all consecutive kyphoplasty procedures performed in our institution from May 2005 to October 2006. Fifty-one patients were treated by BKP at 75 spinal levels, and 137 vertebroplasties were performed as well. RESULTS: Several recurrent complications or procedural failures were observed during BKP: cortical or endplate fracture by balloon expansion (4 vertebrae), partial vertebral re-collapse after deflation (4 vertebrae), balloon rupture during inflation (5 vertebrae), and transient hyperalgia after the procedure (11 patients, 27.5%). CONCLUSIONS: Several symptomatic or asymptomatic complications and technical failures can occur during BKP. Some modifications of the usual kyphoplasty technique may decrease the frequency of these complications.

Interobserver variation in the classification of thymic tumours--a multicentre study using the WHO classification system.

AIMS: To test the reproducibility of the current World Health Organization (WHO) classification of thymic epithelial tumours and to determine the level of interobserver variation within a group of pathologists, all with experience and expertise in thoracic pathology. METHODS AND RESULTS: Ninety-five thymic tumours were circulated to a group of 17 pathologists in the UK and The Netherlands over a 1-year period. Participants were asked to classify them according to WHO criteria. The diagnoses were subjected to statistical analysis and kappa values calculated. The overall level of agreement was moderate (kappa 0.45). When the categories were reduced in number by creating two groups, (A + AB + B1 + B2 and B3 + C), the level of agreement increased to 0.62. An alternative grouping (A + AB + B1 and B2 + B3 + C) increased it slightly further. The best agreement was in tumour types A and AB. Difficulties arose in distinguishing B1 tumours from B2 tumours and B2 tumours from B3 tumours. CONCLUSIONS: Although the WHO system describes a number of well-defined tumour types with clear diagnostic criteria, the overall level of agreement was moderate and improved if some groups were amalgamated.

Focal nodular hyperplasia with calcification and ossification.

We describe a 33-year-old woman with Crohn's disease, who presented with recurrent episodes of small bowel obstruction. A solitary liver lesion was discovered incidentally by abdominal ultrasound. Pathological examination of the resected specimen revealed features typical of focal nodular hyperplasia together with uncommon findings including calcification, ossification and fibrous obliteration of blood-filled "cysts", changes more commonly associated with regression in hepatic haemangiomas. This report strengthens the favoured hypothesis that a vascular malformation underlies the pathogenesis of focal nodular hyperplasia.

Absence of the ductus venosus with direct connection between the umbilical vein and right atrium.

Abnormalities of the ductus venosus are rare. We present the case of a dichorionic, diamniotic twin pregnancy in which complete absence of the ductus venosus, with direct communication between the umbilical vein and right atrium, was detected in one infant on antenatal ultrasonography. Autopsy confirmed the aberrant course of the umbilical vein, which also had an abnormal histological structure. Associated congenital anomalies included an ostium secundum type atrial septal defect, absent inferior vena cava, single left pulmonary vein, stenosed right pulmonary artery, proliferation of the hepatic arterioles with reduction of portal venules, and a duplex ureter. The literature is reviewed and pathogenesis relevant to this case is discussed.

Role of non-alcoholic steatohepatitis in methotrexate-induced liver injury.

BACKGROUND AND AIMS: Hepatotoxicity, especially liver fibrosis, is the major concern with long-term, 'low-dose' oral methotrexate (MTX) therapy for psoriasis. The histological features are non-specific and resemble those of non-alcoholic steatohepatitis (NASH). Moreover, most of the risk factors of MTX-induced liver injury are also associated with NASH. In this study, we investigate whether NASH contributes to the prevalence and progression of MTX-induced liver injury in patients receiving MTX for psoriasis. METHODS: Clinical details, including MTX dosage schedules and risk factors for liver injury, was documented for 24 patients on long-term MTX therapy for psoriasis. Serial liver biopsies were graded according to the Roenigk classification scale and a recently proposed grading and staging system for NASH. RESULTS: Thirteen of the 17 patients who had a NASH-like pattern of liver injury also had the risk factors for NASH obesity and/or diabetes, and all had progressive liver injury. The other four patients had no risk factors, but a mean cumulative dose of 6.5 g. Seven patients, who did not have a NASH-like pattern of injury, had a mean cumulative dose of 3.8 g. There was a positive correlation between the cumulative dose, risk factors and progression when the biopsies were scored by the modified grading and staging classification for NASH, but not with the Roenigk system. CONCLUSIONS: Non-steatohepatitis, probably aggravated by MTX, is an important cause of liver injury in patients on long-term, 'low-dose' MTX treatment for psoriasis. In addition, MTX alone can cause a NASH-like pattern of injury that is at least, in part, caused by a higher cumulative dose.

Angiocentric T-cell lymphoma: an extensive lesion involving the posterior tongue, hypopharynx and supraglottis.

Angiocentric T-cell lymphoma, which in the past has been grouped with a variety of granulomatous diseases, occur uncommonly as a destructive condition of the posterior nasal space and midface. We report on a patient with a chronic granular ulcerative lesion involving the posterior tongue, hypopharynx and supraglottis.