Spindle cell proliferations of the sigmoid colon, rectum and anus: a review with emphasis on perineurioma.

A wide range of spindle cell proliferations are found uncommonly in the sigmoid colon, rectum and anus. They usually present as polyps, and include reactive lesions and benign and malignant neoplasms which may be primary or metastatic. They are less frequently described in the literature compared to those in the upper gastrointestinal tract, and may be underdiagnosed. The widespread use of sigmoidoscopy in symptomatic patients and bowel cancer screening programmes means that histopathologists must be aware of, and adopt a logical approach to, diagnosing spindle cell proliferations in biopsy and polypectomy specimens. This is particularly relevant given the strong association of some mesenchymal polyps with hereditary cancer syndromes. This review article will focus on perineurioma and the recent debate in relation to its overlap with fibroblastic polyp. The clinical, endoscopic, histological and immunohistochemical features of spindle cell proliferations which should be considered in the differential diagnosis of perineurioma will be discussed. There is also a brief reference to malignant spindle cell tumours of diagnostic importance.

Histopathological Mimics of Inflammatory Bowel Disease.

This review article discusses the challenges of making a firm histopathological diagnosis of inflammatory bowel disease (IBD) on biopsy and resection material and the importance of its distinction from a range of other inflammatory and infective conditions that may closely mimic IBD. In many cases, the diagnosis of ulcerative colitis or Crohn's disease is straightforward, especially when patients have a typical presentation and characteristic histopathological features. Knowledge of the full clinical history is very important, particularly past and recent medical history, drug history, foreign travel, or known contact with individuals with specific infection. Discussion of all cases of suspected IBD within a multidisciplinary team meeting is required to ensure that clinical, radiological, and pathological features can be correlated. Mimics of IBD can be divided into 4 categories: 1) those due to specific infection, 2) those due to a specific localized inflammatory process, 3) those due to iatrogenic causes, and 4) other rarer causes. Accurate diagnosis of IBD and exclusion of these mimics are crucial for patient management. Once a diagnosis of IBD has been proffered by a pathologist, it is very difficult to "undiagnose" the condition when an alternative diagnosis or "mimic" has been subsequently identified. The histological diagnosis of each of these IBD mimics is discussed in detail, with guidance on how to avoid the pitfall of missing these sometimes very subtle and "difficult to diagnose" conditions.

Assessment of lymph node involvement in colorectal cancer.

Lymph node metastasis informs prognosis and is a key factor in deciding further management, particularly adjuvant chemotherapy. It is core to all contemporary staging systems, including the widely used tumor node metastasis staging system. Patients with node-negative disease have 5-year survival rates of 70%-80%, implying a significant minority of patients with occult lymph node metastases will succumb to disease recurrence. Enhanced staging techniques may help to identify this subset of patients, who might benefit from further treatment. Obtaining adequate numbers of lymph nodes is essential for accurate staging. Lymph node yields are affected by numerous factors, many inherent to the patient and the tumour, but others related to surgical and histopathological practice. Good lymph node recovery relies on close collaboration between surgeon and pathologist. The optimal extent of surgical resection remains a subject of debate. Extended lymphadenectomy, extra-mesenteric lymph node dissection, high arterial ligation and complete mesocolic excision are amongst the surgical techniques with plausible oncological bases, but which are not supported by the highest levels of evidence. With further development and refinement, intra-operative lymphatic mapping and sentinel lymph node biopsy may provide a guide to the optimum extent of lymphadenectomy, but in its present form, it is beset by false negatives, skip lesions and failures to identify a sentinel node. Once resected, histopathological assessment of the surgical specimen can be improved by thorough dissection techniques, step-sectioning of tissue blocks and immunohistochemistry. More recently, molecular methods have been employed. In this review, we consider the numerous factors that affect lymph node yields, including the impact of the surgical and histopathological techniques. Potential future strategies, including the use of evolving technologies, are also discussed.

A pathologist's survey on the reporting of sessile serrated adenomas/polyps.

AIM: The purpose of this survey was to ascertain reporting habits of pathologists towards sessile serrated adenomas/polyps (SSA/P). METHODS: A questionnaire designed to highlight diagnostic criteria, approach and clinical implications of SSA/P was circulated electronically to 45 pathologists in the UK and North America. RESULTS: Forty-three of 45 pathologists agreed to participate. The vast majority (88%) had a special interest in gastrointestinal (GI) pathology, had great exposure to GI polyps in general with 40% diagnosing SSA/P at least once a week if not more, abnormal architecture was thought by all participants to be histologically diagnostic, and 11% would make the diagnosis if a single diagnostic histological feature was present in one crypt only, while a further 19% would diagnose SSA/P in one crypt if more than one diagnostic feature was present. The vast majority agreed that deeper sections were useful and 88% did not feel proliferation markers were useful. More than one-third did not know whether, or did not feel that, their clinicians were aware of the implications of SSA/P. CONCLUSIONS: 98% of pathologists surveyed are aware that SSA/P is a precursor lesion to colorectal cancer, the majority agree on diagnostic criteria, and a significant number feel that there needs to be greater communication and awareness among pathologists and gastroenterologists about SSA/P.

In vivo optical coherence tomography (OCT) in periocular basal cell carcinoma: correlations between in vivo OCT images and postoperative histology.

AIM: To investigate in vivo optical coherence tomography (OCT) for imaging of periocular basal cell carcinoma (BCC). METHODS: Consecutive patients with periocular BCC were prospectively investigated with VivoSight OCT imaging prior to surgical excision. Histology sections were compared with OCT images with regard to lesion measurements (x, y and z dimensions) and histological features. RESULTS: A total of 15 patients with biopsy proven BCC were recruited. The OCT horizontal margins correlated positively with histology (r=0.8 and 0.66, x and y axes) and could be identified in 3/15 (x axis) and 6/15 (y axis) cases. The vertical margin correlation was r=0.43 and BCC depth could be measured in 9/15 cases. The following histological features of BCC could be identified on OCT images: (1) lobular pattern (100%); (2) dilated blood vessels (80%); (3) reflective margins of tumour lobules (100%); and (4) epidermal thinning overlying BCC lobules (100%). CONCLUSIONS: This study indicated a strong positive correlation between the margins of periocular BCCs measured using in vivo OCT and histology, and a weak positive correlation with depth of invasion. VivoSight OCT produced high resolution images of BCC morphology. The limitations in horizontal margin measurements could potentially be overcome by design modification of the scanning probe.

Investigation of basal cell carcinoma using dynamic focus optical coherence tomography.

Optical coherence tomography (OCT) is becoming a popular modality for skin tumor diagnosis and assessment of tumor size and margin status. We conducted a number of imaging experiments on periocular basal cell carcinoma (BCC) specimens using an OCT configuration. This configuration employs a dynamic focus (DF) procedure where the coherence gate moves synchronously with the peak of the confocal gate, which ensures better signal strength and preservation of transversal resolution from all depths. A DF-OCT configuration is used to illustrate morphological differences between the BCC and its surrounding healthy skin in OCT images. The OCT images are correlated with the corresponding histology images. To the best of our knowledge, this is the first paper to look at DF-OCT imaging in examining periocular BCC.

Quantitative evaluation of scattering in optical coherence tomography skin images using the extended Huygens-Fresnel theorem.

An optical properties extraction algorithm is developed based on enhanced Huygens-Fresnel light propagation theorem, to extract the scattering coefficient of a specific region in an optical coherence tomography (OCT) image. The aim is to quantitatively analyze the OCT images. The algorithm is evaluated using a set of phantoms with different concentrations of scatterers, designed based on Mie theory. The algorithm is then used to analyze basal cell carcinoma and healthy eyelid tissues, demonstrating distinguishable differences in the scattering coefficient between these tissues. In this study, we have taken advantage of the simplification introduced by the utilization of a dynamic focus OCT system. This eliminates the need to deconvolve the reflectivity profile with the confocal gate profile, as the sensitivity of the OCT system is constant throughout the axial range.

The routine use of histochemical stains in gastrointestinal pathology: a UK-wide survey.

AIMS: A survey was conducted into the routine use of special stains on gastrointestinal (GI) biopsy specimens in histopathology departments within the National Health Service. The aim was to compare the sole use of haematoxylin and eosin (H&E) staining with the use of H&E and special stains, according to the biopsy site. METHODS AND RESULTS: One hundred and sixty-seven histopathology departments in the UK were contacted using an e-mail questionnaire. Valid return rate was 55%. Sixty-eight percent of departments employ H&E only for oesophageal biopsy specimens. Gastric specimens are stained using only H&E in 47% of departments and 53% use H&E combined with special stains. Duodenal, small and large bowel biopsy specimens are mostly stained with H&E. CONCLUSIONS: The results show that the routine use of special stains in GI pathology in the UK is highly variable, especially for oesophageal and gastric biopsy specimens. The literature indicates that special stains in GI specimens can enhance sensitivity and specificity for the detection of pathological abnormalities, especially metaplasia and infections. The diversity of staining practice highlights the need to provide robust and evidence-based guidelines for the routine use of special stains to ensure universal best practice.

Positron emission tomography in the quantification of cellular and biochemical responses to intrapulmonary particulates.

Inhaled mineral dusts and fibres can cause chronic pulmonary inflammation, often leading to permanent scarring with loss of function, but the mechanisms involved remain obscure. There are currently no good methods for monitoring inflammatory processes in situ. Positron emission tomography (PET) of suitable intravenously injected radiolabelled markers provides non-invasive and repeatable methods of quantifying biochemical and cellular responses. We have developed animal models of fibrotic and non-fibrotic pulmonary response to particulate instillation and characterised these by histology. Different components of the inflammatory response have been investigated by PET: (1) [(18)F]-labelled fluoro-deoxyglucose, a positron emitting glucose analogue, accumulates in cells in proportion to their glucose uptake; ex vivo microautoradiography indicates that neutrophils are the cells responsible for an increased signal during pulmonary inflammation; a persistently high uptake is associated with lung scarring. (2) The radioligand [(11)C]-R-PK11195 binds to benzodiazepine-like receptors abundant in macrophages; following particulate instillation, the [(11)C]-R-PK11195 PET signal tracks with lung macrophage accumulation and also localises to regions consistent with macrophage clearance; poor macrophage clearance is associated with fibrosis. (3) [(18)F]-fluoroproline is likely a substrate for extracellular matrix production, especially proline-rich collagen; during active scarring, the rate of lung uptake of fluoroproline is elevated. Localisation of radioactivity in the lung has been validated ex vivo by microautoradiography of tritium analogues of each of the positron emitting tracers. The use of PET to monitor different inflammatory processes by repeated scanning of the same animal or individual is helping to identify key events in the fibrotic process.

Ophthalmic presentation of the Muir Torre syndrome.

The Muir Torre syndrome (MTS) is a rare autosomal dominant condition characterized by the association of certain skin tumors and systemic malignancies. We report the ophthalmic presentation of this syndrome in two cases.

Kinetics of lung macrophages monitored in vivo following particulate challenge in rabbits.

The ligand PK11195 binds specifically in macrophages. We have assessed the use of positron emission tomography (PET) of [(11)C]R-PK11195 to monitor macrophage disposition following particulate challenge to the lung. Repeated PET scanning was performed over 4 weeks following iv [(11)C]R-PK11195 in rabbits treated with 5-microm particles of either amorphous (aSiO(2)) or microcrystalline (xSiO(2)) silica instilled into right upper pulmonary lobes. aSiO(2) resulted in increased macrophages, few neutrophils, and no fibrosis, while xSiO(2) increased macrophages and neutrophils and caused fibrosis. After both stimuli, (11)C localized to the challenged area and correlated with macrophage numbers. Radioactive counts in challenged/control lung regions peaked at 4 days for aSiO(2) (2.88, n = 2) and 6 days for xSiO(2) (4.62, n = 2). The signal remained elevated throughout the study (aSiO(2), 2.33 +/- 0.77 SD, n = 14; xSiO(2), 3.99 +/- 1.29 SD, n = 9), as did macrophage accumulation. (11)C also localized to regions consistent with macrophage traffic through lymph ducts 6 days after aSiO(2) challenge, but not until 4 weeks after xSiO(2). Specific binding of R-PK11195 in macrophages was demonstrated by microautoradiography in lavage fluid from an inflamed rabbit knee-joint model. These data suggest that PET scanning after [(11)C]PK11195 provides a new noninvasive approach for the study of macrophage kinetics in the lung.

Primary biliary cirrhosis and idiopathic retroperitoneal fibrosis: a rare association.

Primary biliary cirrhosis has rarely been reported to be associated with idiopathic retroperitoneal fibrosis. We describe the case of a 57-year-old man who was confirmed to have both conditions, reflecting the likely autoimmune aetiopathogenesis common to both disorders.