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Purpose: Over the past 50 years, multiple pathology organizations worldwide have evolved in cancer histopathology reporting from subjective, narrative assessments to structured, synoptic formats using controlled vocabulary. These reporting protocols include the required data elements that represent the minimum set of evidence-based, clinically actionable parameters necessary to convey the diagnostic, prognostic, and predictive information essential for patient care. Despite these advances, the synoptic reporting protocols were not harmonized across the various pathology organizations. Cancer pathology continues to be widely reported and stored in free-text format, or without encoded data such that it is neither computable nor interoperable across organizations., Methods: In 2020, SNOMED International created the Cancer Synoptic Reporting Working Group (CSRWG). This resulted in international collaboration across multiple pathology organizations. CCRWG's mission was to use SNOMED Clinical Terms (CT) concepts to represent the required content within the College of American Pathologists (CAP) and International Collaboration on Cancer Reporting (ICCR) published pathology reporting protocols., Results: In late 2023, the CSRWG published over 1,300 new or revised SNOMED CT concepts to represent all required pathology cancer data elements for adult and pediatric solid tumors in both CAP and ICCR using the semantic principles of the SNOMED-CT concept model. Thus, computability and interoperability would be broadly established., Conclusion: This work brings to fruition the longstanding desire for an international, interoperable, human- and machine-readable cancer pathology report for use in patient care, health care quality improvement, population health, public health surveillance, and translational and clinical trial research. The following report describes the project, its methods, and applications in the stated use cases.

Competing Interests: The authors declare no conflict of interest.

Introduction: We describe the 5-year oncological and functional outcomes of transoral laser microsurgery, neck dissection (TLM + ND) and adjuvant radiotherapy (PORT) used to treat patients with oropharyngeal carcinoma. The effectiveness of external carotid artery (ECA) ligation in reducing post-operative bleeding, and fibrin glue following ND in reducing wound drainage and length of hospital stay is reported., Materials and Methods: This retrospective case review of consecutive patients undergoing TLM between 2006 and 2017 used the Kaplan-Meier Estimator and Log-Rank Test for univariate, time-to-event analyses, and Cox-Proportionate Hazard modelling for multivariate analysis., Results: 264 consecutive patients were included. Mean follow-up was 49.4 months. 219 (82.9%) patients received PORT. Five-year overall survival (OS), disease-free survival (DFS), and disease-specific survival (DSS) rates were 74.9%, 73.7%, and 86.2%, respectively. Five-year locoregional control was 89.4%. 65.5% of cases were Human papillomavirus associated (HPV+), for whom OS, DFS and DSS was 85.6%, 84.7% and 92.7%, respectively, and demonstrated significantly higher OS (hazard ratio (HR) 0.28, CI 0.16-0.49, p < 0.0001), DFS (HR 0.28, CI 0.17-0.47, p < 0.0001) and DSS (HR 0.2, CI 0.09-0.44, <0.001). Post-operative oropharyngeal bleeding occurred in 23 patients (8.7%), of which 5 were major/severe, in patients without ECA ligation. Fibrin glue significantly reduced neck drain output (p < 0.001), and length of hospital stay (p < 0.001). One-year gastrostomy dependence rate was 2.3%., Conclusions: TLM + ND + PORT results in favourable 5-year survival and locoregional control rates, and low feeding tube dependency rates. ECA ligation and fibrin glue appear to reduce major post-operative haemorrhage, wound drainage and length of hospital stay., Competing Interests: Declarations of competing interest None., (Copyright © 2020 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Genetic heterogeneity displayed by tumour cells (intratumoural heterogeneity, ITH) represents a diagnostic challenge when assessing tumour mutational profile. In oral squamous cell carcinoma (OSCC), ITH may be found both in tumour cells and in adjacent mucosa. Genetic heterogeneity of the adjacent mucosa can be interpreted as evidence of the field cancerization (field heterogeneity, FH). The aim of the study was to investigate the impact of intratumoural and intrafield heterogeneity on locoregional control. Ten OSCC patients (5 recurrent and 5 nonrecurrent) were studied. Multiple areas were sampled from the bulk of the tumour and the adjacent nonneoplastic mucosa. A panel of 10 tumour-specific OSCC driver genes was analysed for each sample and was used to calculate heterogeneity. Values were compared among recurrent and nonrecurrent OSCC. Mutational analysis highlighted that a single tumour sample has limited accuracy in assessing the genetic profiles of tumours. High values of ITH considering shared mutations between specimens were found in both recurrent and non-recurrent OSCC (p = 0.095). On the contrary, the intrafield genetic heterogeneity was significantly less frequently in the non-recurrent OSCC group (p = 0.032). Heterogeneity within each specimen calculated with variant allele frequency confirmed that there was better discrimination between recurrent and nonrecurrent groups using nonneoplastic adjacent mucosa than tumour tissue (p value 0.0006 and 0.0048 respectively). In agreement with the theory of field cancerization, intrafield genetic heterogeneity correlates with a higher risk of developing loco-regional recurrences and second primaries. In order to reduce the ITH effects, analysis of multiple tumour areas should be encouraged.

Background: The contemporary treatment of oropharyngeal squamous cell carcinoma (SCC) is an area of debate. We report outcomes of a minimally invasive approach involving transoral laser microsurgery (TLM)., Methods: A consecutive series of patients (n = 153) undergoing primary TLM for oropharyngeal SCC from 2006 to 2013 was studied. Human papillomavirus (HPV) status was determined by p16 immunohistochemistry and high-risk HPV DNA in situ hybridization. Survival analyses were evaluated using Kaplan-Meier statistics., Results: Tumor subsites included tonsil (n = 94; 61.5%), tongue base (n = 38; 24.8%), and soft palate (n = 21; 13.7%), with the majority being American Joint Committee on Cancer (AJCC) stage III/IVa (n = 124; 81.0%) and HPV-positive (n = 101; 66.0%). Three-year overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were 84.5%, 91.7%, and 78.2%, respectively. HPV-positivity portended favorable oncologic outcomes. One-year gastrostomy tube (G-tube) dependency was 1.3%., Conclusion: To the best of our knowledge, this is the largest single-center TLM oropharyngeal SCC series to date. Our data suggest that TLM +/- postoperative radiotherapy (PORT) results in at least as good oncologic outcomes as chemoradiotherapy (CRT), while conferring swallowing function advantages. © 2016 Wiley Periodicals, Inc. Head Neck , 2016 © 2016 Wiley Periodicals, Inc. Head Neck 38:1263-1270, 2016., (© 2016 Wiley Periodicals, Inc.)

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. It introduces the current best practice in histopathology and cytopathology as it pertains to head and neck and thyroid cancers. Recommendations • Accurate diagnosis of the type of malignancy is a key component of effective management. (R) • Surgeons and oncologists should understand the scope and limitations of cellular pathology in order to inform multidisciplinary discussions. (R) • A clinically suspected diagnosis of malignancy should be confirmed by biopsy or cytology before operation. (R) • Cytopathological diagnoses should be discussed with surgeons and radiologists to maximise the information gained from each modality of investigation. (R) • Pathological investigations are the basis for accurate cancer staging and stratification of clinical outcomes. (R).

This review covers the histopathology and pathogenesis of non-infectious inflammatory diseases of the sinonasal tract, in particular, sarcoidosis, granulomatous vasculitides Wegener, Churg-Strauss), relapsing polychondritis, eosinophilic angiocentric fibrosis, chronic rhinosinusitis and nasal perforations. Molecular associations and mechanisms are emphasised to assist pathologists to put their observations into the context of clinical, genetic and environmental influences on patients' diseases.

Among the high bone mass disorders, the osteopetroses reflect osteoclast failure that prevents skeletal resorption and turnover, leading to reduced bone growth and modeling and characteristic histopathological and radiographic findings. We report an 11-year-old boy with a new syndrome that radiographically mimics osteopetrosis (OPT), but features rapid skeletal turnover. He presented at age 21 months with a parasellar, osteoclast-rich giant cell granuloma. Radiographs showed a dense skull, generalized osteosclerosis and cortical thickening, medullary cavity narrowing, and diminished modeling of tubular bones. His serum alkaline phosphatase was >5000 IU/L (normal <850 IU/L). After partial resection, the granuloma re-grew but then regressed and stabilized during 3 years of uncomplicated pamidronate treatment. His hyperphosphatasemia transiently diminished, but all bone turnover markers, especially those of apposition, remained elevated. Two years after pamidronate therapy stopped, bone mineral density (BMD) Z-scores reached +9.1 and +5.8 in the lumbar spine and hip, respectively, and iliac crest histopathology confirmed rapid bone remodeling. Serum multiplex biomarker profiling was striking for low sclerostin. Mutation analysis was negative for activation of lipoprotein receptor-related protein 4 (LRP4), LRP5, or TGFβ1, and for defective sclerostin (SOST), osteoprotegerin (OPG), RANKL, RANK, SQSTM1, or sFRP1. Microarray showed no notable copy number variation. Studies of his nonconsanguineous parents were unremarkable. The etiology and pathogenesis of this unique syndrome are unknown., (© 2014 American Society for Bone and Mineral Research.)

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and accounts for about 5% of all malignant paediatric tumours. β-Catenin, a multifunctional nuclear transcription factor in the canonical Wnt signaling pathway, is active in myogenesis and embryonal somite patterning. Dysregulation of Wnt signaling facilitates tumour invasion and metastasis. This study characterizes Wnt/β-catenin signaling and functional activity in paediatric embryonal and alveolar RMS. Immunohistochemical assessment of paraffin-embedded tissues from 44 RMS showed β-catenin expression in 26 cases with cytoplasmic/membranous expression in 9/14 cases of alveolar RMS, and 15/30 cases of embryonal RMS, whereas nuclear expression was only seen in 2 cases of embryonal RMS. The potential functional significance of β-catenin expression was tested in four RMS cell lines, two derived from embryonal (RD and RD18) RMS and two from alveolar (Rh4 and Rh30) RMS. Western blot analysis demonstrated the expression of Wnt-associated proteins including β-catenin, glycogen synthase kinase-3β, disheveled, axin-1, naked, LRP-6 and cadherins in all cell lines. Cell fractionation and immunofluorescence studies of the cell lines (after stimulation by human recombinant Wnt3a) showed reduced phosphorylation of β-catenin, stabilization of the active cytosolic form and nuclear translocation of β-catenin. Reporter gene assay demonstrated a T-cell factor/lymphoid-enhancing factor-mediated transactivation in these cells. In response to human recombinant Wnt3a, the alveolar RMS cells showed a significant decrease in proliferation rate and induction of myogenic differentiation (myogenin, MyoD1 and myf5). These data indicate that the central regulatory components of canonical Wnt/β-catenin signaling are expressed and that this pathway is functionally active in a significant subset of RMS tumours and might represent a novel therapeutic target.

Purpose: Human papillomavirus-16 (HPV16) is the causative agent in a biologically distinct subset of oropharyngeal squamous cell carcinoma (OPSCC) with highly favorable prognosis. In clinical trials, HPV16 status is an essential inclusion or stratification parameter, highlighting the importance of accurate testing., Experimental Design: Fixed and fresh-frozen tissue from 108 OPSCC cases were subject to eight possible assay/assay combinations: p16 immunohistochemistry (p16 IHC); in situ hybridization for high-risk HPV (HR HPV ISH); quantitative PCR (qPCR) for both viral E6 RNA (RNA qPCR) and DNA (DNA qPCR); and combinations of the above., Results: HPV16-positive OPSCC presented in younger patients (mean 7.5 years younger, P = 0.003) who smoked less than HPV-negative patients (P = 0.007). The proportion of HPV16-positive cases increased from 15% to 57% (P = 0.001) between 1988 and 2009. A combination of p16 IHC/DNA qPCR showed acceptable sensitivity (97%) and specificity (94%) compared with the RNA qPCR "gold standard", as well as being the best discriminator of favorable outcome (overall survival P = 0.002). p16 IHC/HR HPV ISH also had acceptable specificity (90%) but the substantial reduction in its sensitivity (88%) impacted upon its prognostic value (P = 0.02). p16 IHC, HR HPV ISH, or DNA qPCR was not sufficiently specific to recommend in clinical trials when used in isolation., Conclusions: Caution must be exercised in applying HPV16 diagnostic tests because of significant disparities in accuracy and prognostic value in previously published techniques., (©2011 AACR)

We report a 58-year-old man who had a multi-lobulated pseudomyxomatous lesion in his ascending aorta 6 months after his root and ascending aorta was replaced by a Dacron graft., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Recent genetic studies have implicated p53 mutation as a significant risk factor for therapeutic failure in squamous cell carcinoma of the head and neck (SCCHN). However, in a recent meta-analysis in the literature of p53 from major anatomical subsites (larynx, oral cavity, oropharynx/hypopharynx), associations between patient survival and p53 status were ambiguous., Methods: The authors examined a cohort of SCCHNs using a previously developed biomarker combination that likely predicts p53 status based on p53/MDM2 expression levels determined by immunohistochemistry (IHC). In addition, the authors generated and validated an antibody to MTBP (an MDM2 binding protein that alters p53/MDM2 homeostasis and may contribute to metastatic suppression) and have incorporated data for MTBP expression into the current analyses., Results: Analysis of expression data for p53 and MDM2 in 198 SCCHN patient samples revealed that the biomarker combination p53 + ve/MDM2-low (likely indicative of p53 mutation) was significantly associated with reduced overall survival (log-rank P = .035) and was an independent prognostic factor (P = .013; HR, 1.705; 95% CI, 1.12-2.60); thus, these data were compatible with earlier genetic analyses. By using IHC for p53 and MDM2 to dichotomize patients, the authors found that loss of MTBP expression was significantly associated with reduced survival (log-rank P = .004) and was an independent prognostic factor (P = .004; HR, 2.78; 95% CI, 1.39-5.54) in p53 + ve/MDM2-low patients., Conclusions: These results represent the first examination of MTBP expression in human tissues and provide evidence for a p53 status-dependent role for MTBP in suppressing disease progression in SCCHN patients as well as confirming a role for p53 pathway function in delaying disease progression., (Copyright © 2011 American Cancer Society.)

Objective: Head and neck squamous cell carcinoma (HNSCC) patients with N3 neck disease at presentation are the minority. Prognosis for such patients is poor, but there is disagreement about which treatment policy is best adopted. The aim of this study was to identify which groups of patients are best offered radical treatment, examining factors of association, prognosis, and survival., Study Design: Prospective cohort study., Setting: Regional tertiary head and neck cancer unit., Subjects and Methods: Data were collected prospectively from patients treated for HNSCC with N3 nodal disease between 1975 and 2005. The data collected included age, sex, tumor TNM stage, histological grade, treatment, and survival. Odds ratio was used to calculate whether each parameter was statistically significant. Tumor-specific and observed survival curves were also calculated., Results: A total of 275 patients had N3 disease. Multivariate analysis confirmed that advanced disease at the primary site (odds ratio = 4.6, P = .0261) mitigated against curative treatment. Comparison of tumor-specific survival between curative and palliative treatment strategies suggests that aggressive treatment is associated with greatly improved survival (median survival = 1.45 years, 95% confidence interval [CI] = 1.23-1.67 years; 5-year survival = 26.6%, CI = 17.14%-36.06%) compared with those treated palliatively (median survival = 3.18 months, CI = 3.06-3.30 months; no 5-year survivors; P < .0001)., Conclusion: A major factor in determining treatment strategies for N3 disease HNSCC is the extent of disease at the primary site. These data suggest that aggressive treatment of the neck improves survival and should be considered in these patients.

Alkaptonuria (AKU) is a rare autosomal recessive condition caused by deficiency of the enzyme homogentisate 1,2 dioxygenase, resulting in widespread deposition of oxidised homogentisic acid (HGA) polymer, primarily in joint tissues but also in other connective tissues. Macroscopic pigmentation of connective tissues in AKU is well documented and is the end point of a process that is not understood. Deposition in less common regions may provide clues to the pigment formation process. This is the first report of detection of ochronotic pigment in acinar cells and lumina in the submandibular gland of a patient with AKU. Deposition was noted in the apical region of the cells. A lobar duct presented a large calculus with unusual deposits possibly associated with calcium salts. This report highlights the effect that local and intracellular factors may have on converting HGA into polymeric derivatives in the absence of an extracellular matrix.

Treatment of neck recurrence following radical neck dissection is extremely difficult. Retrospective review of 699 radical neck dissections was performed. Recurrence rates, host, tumor, treatment factors, and survival were analyzed. One hundred nineteen patients who had undergone radical neck dissections had recurrence, 69 were considered candidates for salvage surgery. Factors that increased the risk of neck recurrence were neck node (N) status and no adjuvant radiotherapy. Factors associated with radical salvage treatment were young age, good general condition, and low recurrent N classification. Five-year survival for salvage neck dissection was 31%. Young patients and low T and N classification did well. Low recurrent N classification and salvage surgery were associated with good prognosis for recurrence. In our study, radical neck dissection has a regional failure rate of 20%, a third of recurrence cases were offered curative treatment. Of these, 31% were cured with salvage surgery., ((c) 2008 Wiley Periodicals, Inc. Head Neck 2008.)

Alkaptonuria is a rare, inherited defect of homogentisic acid 1,2-dioxygenase that leads to the widespread deposition of polymeric homogentisic acid, and clinical symptoms from degeneration of joints and the aortic valve. Pathological descriptions are few and mainly those of late-stage changes related to joint or valve failure. In this review, the macroscopic and histopathological changes in the tissues in alkaptonuria are illustrated by the detailed autopsy study of a 74-year-old female who died from disseminated ovarian carcinoma. The pathology is discussed in the context of the literature and in relation to potential pathogenic mechanisms of tissue damage. This review highlights the heterogeneity of some of the manifestations. In symptomatic patients, degenerative changes in synovial and intervertebral joints are usually well advanced, while early changes include diffuse cartilage pigmentation and chondrocyte necrosis. The initial stage of pigment deposition in the cardiovascular system may be influenced by intravascular pressure and flow disturbances, whereas more intense pigmentation affects fibrolipid components of atheromatous plaques. Pigmentation of the aortic and mitral valve cusps and valve rings is a result of intracellular and extracellular pigment deposition and is associated with calcification and clinically significant aortic stenosis.

Cell cycle modulators are important in carcinogenesis and may be of prognostic and therapeutic relevance. This study has examined the influence of the proliferation index (Ki-67) and immunocytochemical expression of epidermal growth factor receptor (EGFR), cyclin D1, and retinoblastoma protein on recurrence rates at the primary site in 50 patients with T2N0 laryngeal carcinomas treated with radical irradiation. Pre-treatment biopsies were retrieved and sections scored for the four immunocytochemical markers. Statistical analysis for association, interaction and survival was performed. Five cases showed loss of expression of Rb protein. The median Ki-67 index was 50%, the median cyclin D1 index 21% and the median EGFR index 47% of cells. EGFR and cyclin D1 expression were positively correlated and, whilst local recurrence tended to occur with a Ki-67 labelling index of <50%, this was not statistically significant. When interactions were examined using Multiple Logistic Regression it was found that there was a direct relationship between EGFR and cyclin D1 expression. If the EGFR index was >20% and the cyclin D1 index >10%, then the odds ratio in favour of a primary site recurrence was very high (5.32 +/-0.41). This study demonstrates that the relationship between EGFR index and cyclin D1 index has a very strong association with primary site recurrence for T2 N0 laryngeal carcinomas treated by irradiation.

Background: Inflammatory pseudotumor of the kidney or inflammatory myofibroblastic tumor (IMT) is composed of spindle cells admixed with variable amount of proliferating myofibroblasts, fibroblasts, extracellular collagen, lymphocytes and plasma cells. This mainly affects the urinary bladder or prostate. Renal involvement is rare., Case Presentation: A 56 year-old man was diagnosed with asymptomatic left sided hydronephrosis while being investigated for rheumatoid arthritis. CT scan imaging showed ill defined fascial plains around the kidney and thickening around the renal hilum suggestive of localized inflammatory change. Worsening intermittent left loin pain with increasing hydronephrosis, significant cortical thinning and marked deterioration of renal function necessitated nephrectomy. Macroscopy showed a hydronephrotic fibrotic kidney with microscopy and immunohistochemistry consistent with a histological diagnosis of IMT., Conclusion: We report a case of an inflammatory pseudotumor of the kidney. It is unique in that the patient presented with painless hydronephrosis followed two years later with progressive deterioration in renal function and worsening loin pain.

Unlabelled: OBJECTIVE, DESIGN AND PATIENTS: Hibernoma is an uncommon, slow-growing, benign soft-tissue tumour resembling brown adipose tissue. The histological appearances are well-documented, but there are relatively few descriptions of the magnetic resonance (MR) imaging features. We report a retrospective comparison of the histological and MR appearances of ten hibernomas of the extremities, classified histologically into lipoma-like [<70% multivacuolated adipocytes (MVAs)] and non-lipoma-like hibernomas (>70% MVAs)., Results: The lipoma-like hibernomas measured 4-27 cm in maximum size. All were well-defined on MR imaging and histology except for one subcutaneous lesion that blended in with surrounding fat histologically. All lesions were isointense with subcutaneous fat on T1- and T2-weighting apart from one lesion that was predominantly slightly hypointense on T1-weighting and predominantly slightly hyperintense on T2-weighting and STIR. Two slightly inhomogeneous lesions contained thin (<5 mm thickness) tortuous vessels. One patient received intravenous contrast, but the lesion did not enhance. The six non-lipoma-like hibernomas measured 2.5-15.5 cm in maximum size and all were unencapsulated. Three were well-defined and three partly ill-defined on MR imaging. There were no significant differences in the MR characteristics of the non-lipoma-like variants. On T1-weighting, the non-lipoma-like hibernomas that contained >90% MVAs were predominantly slightly hypointense to subcutaneous fat. One lesion was isointense with subcutaneous fat, but this lesion only contained from 80-90% MVAs. All non-lipoma-like lesions were slightly hyperintense on STIR but so too were two of the four lipoma-like lesions. Four of the six non-lipoma-like lesions showed marked or moderate inhomogeneity due to thick septa and prominent vessels. Of the two cases that received intravenous contrast, both showed enhancement corresponding to regions of >90% MVAs or prominent vessels within fibrous septa., Conclusions: MR imaging has shown some distinguishing features between lipoma-like and non-lipoma-like hibernomas. Lipoma-like hibernomas are usually isointense with subcutaneous fat on T1-weighting, are either homogeneous or slightly inhomogeneous and may contain thin tortuous vascular structures. Non-lipoma-like hibernomas are pre-dominantly slightly hypointense to subcutaneous fat on T1-weighting, often display marked or moderate inhomogeneity with prominent septa and vessels and enhancement is typical. The appearances of non-lipoma-like hibernomas are not diagnostic and may be mimicked by lipoma variants and by well-differentiated liposarcoma or atypical lipoma.

The accepted method of modelling and predicting failure/survival, Cox's proportional hazards model, is theoretically inferior to neural network derived models for analysing highly complex systems with large datasets. A blinded comparison of the neural network versus the Cox's model in predicting survival utilising data from 873 treated patients with laryngeal cancer. These were divided randomly and equally into a training set and a study set and Cox's and neural network models applied in turn. Data were then divided into seven sets of binary covariates and the analysis repeated. Overall survival was not significantly different on Kaplan-Meier plot, or with either test model. Although the network produced qualitatively similar results to Cox's model it was significantly more sensitive to differences in survival curves for age and N stage. We propose that neural networks are capable of prediction in systems involving complex interactions between variables and non-linearity.

Tumor involvement of the brachial plexus is uncommon. The most common intrinsic neoplasms involving the brachial plexus are benign neurilemmomas and neurofibromas that are usually associated with neurofibromatosis-1 (NF-1). Solitary neurofibromas unassociated with NF-1 are very uncommon. Malignant peripheral nerve-sheath tumors (MPNST) are rare at this site, arising spontaneously or in the context of NF-1. This presentation discusses the clinical presentation, pathology, and management of these tumors, which usually occur in young adults. MPNST are intermediate or high-grade sarcomas with a high risk of local and distant spread. Approximately 50% of MPNST arise in patients with NF-1, and therefore these patients should be thoroughly investigated for any new symptoms or masses. MPNST of the brachial plexus should be treated with an adequate wide local excision, with adjuvant high-dose radiotherapy pre- or postoperatively. The role of chemotherapy in the treatment of MPNST is not clearly defined, but it may have some benefit in salvaging treatment failures.

Introduction/methods: After the recognition of contaminating algae on histopathological sections stained by periodic acid Schiff (PAS) and Grocott methods, a detailed audit was undertaken to assess the extent of contamination and its possible source., Results: The contaminating organism was a member of the staurastrum genus of Chlorophyta, star shaped organisms commonly found in fresh water marshes. The organisms were seen on sections stained by the diastase-PAS, PAS, or Grocott methods and on cytological preparations between July 2003 and May 2004. It is unlikely that contamination of water baths or concentrated staining solutions was to blame, and a more general contamination of the laboratory water supply is the most likely source., Conclusions: Contaminating organisms may appear on histological and cytological material and their nature and source should be investigated. Although in this instance, confusion with pathologically important organisms was minimal, algae may occasionally cause significant disease.

We defined the immunocytochemical expression of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in benign soft tissue neoplasms, fibromatoses, and sarcomas, together with the activity of gelatinase MMPs and TIMPs measured by zymography and reverse zymography in a subset of cases. The most strongly expressed MMP in all tumors was MMP-1, with weaker expression of MMP-10, MMP-11, and MMP-14 in most tumors. Nuclear expression of MMP-1, MMP-8, and MMP-13 was an unusual feature. TIMP-2 was expressed in all tumors, with stronger expression in fibromatoses than in sarcomas. Fibromatoses and high-grade sarcomas showed greater MMP-1 expression than other groups, and endothelial MMP-2 expression was more extensive in sarcomas. Differences in MMP and TIMP expression might be linked to the biologic behavior of soft tissue neoplasms. The activation of endothelial MMP-2 linked to widespread MMP-14 expression provides a mechanism for sarcomas to modulate their matrix and facilitate angiogenesis.

Few comprehensive epidemiological studies of the prevalence of muscle diseases have been undertaken, and none has been carried out in our locality. The present cross-sectional study was conducted in Assiut Governorate (Upper Egypt) to estimate the prevalence of different types of primary muscular disorder in 1997. The study involved 52,203 subjects, 15,617 (30%) from the rural community and 36,586 (70%) from the urban community. Patients were identified from a door-to-door survey, and all were subjected to a full clinical examination, with confirmation of the diagnosis through electrophysiological, and biochemical investigations. Histopathological studies were performed for the classification of muscular dystrophies. Forty patients with muscular disorders were identified, with a point prevalence of 76.6 per 100,000 in the total community with no significant differences between the rural and urban communities. The creatine kinase level was abnormally high (>225 IU/l) in 80% of the cases, increased in all patients with muscular dystrophy or myositis, in 88.8% of patients with systemic myopathy and 66.6% of patients with myotonia. None of the cases of myasthenia showed an increase in the creatine kinase level. The lifetime prevalence per 100,000 was 26.8 for muscular dystrophy, 11.49 for myotonia, 11.49 for myositis, 17.24 for systemic myopathy and 9.57 for myasthenia., (Copyright (c) 2005 S. Karger AG, Basel.)

This best practice article reviews the published evidence on the pathology and patterns of spread of carcinomas of the hypopharynx, and the relevance of pathological features to prognosis. Medline (1966-2001) was searched using a combination of head and neck neoplasms and prognosis, focusing on hypopharynx and pathology. Other relevant publications were identified from the bibliographies of these papers, and from those obtained opportunistically. There is relatively little pathological literature devoted specifically to squamous carcinomas of the hypopharynx and most information comes from large series of patients with head and neck cancers at a range at sites. Lack of consistency in reporting and shifts in terminology make comparisons between series difficult. The most important features determining prognosis are size and extent of local spread of the primary carcinoma and extent of involvement of regional lymph nodes. There is evidence to support the use of the minimum dataset criteria for head and neck carcinomas at this site. Within the hypopharynx, subsite related differences in aetiology and biology may become important.

Ischaemic preconditioning is a process by which exposure of a tissue to a short period of non-damaging ischaemic stress leads to resistance to the deleterious effects of a subsequent prolonged ischaemic stress. It has been extensively described in the heart, but few studies have examined the possibility that it can occur in skeletal muscle. We have used a rat model of ischaemia of one limb to examine this possibility. Exposure of the hind limb to a period of ischaemia of five minutes and reperfusion for five minutes significantly protected the tibialis anterior muscle against the structural damage induced by a subsequent period of limb ischaemia for four hours and reperfusion for one hour. This protection was evident on examination of the muscle by both light and electron microscopy. Longer or shorter times of prior ischaemia had no effect.

Aim: Ten percent of soft tissue sarcomas (STS) arise in the retroperitoneal tissues. The prognosis for patients with retroperitoneal sarcoma is poor with a 5-year survival rate between 12% and 70%. Stage at presentation, high histological grade, unresectable primary tumour and incomplete resection are associated with a less favourable outcome., Methods: Complete follow-up data were available on 22 patients who underwent surgery for retroperitoneal STS in our institution between 1990 and 2000. Patient, tumour and treatment variables were analysed including use of adjuvant therapy and survival status., Results: Eighteen patients underwent surgery for primary disease, four patients were treated for recurrent disease or metastases. Ten patients presented with pain, seven with an abdominal mass, other presentation included weight loss and haematuria. Thirteen patients presented with tumours larger than 10 cm. The tumours were seven liposarcomas, six leiomyosarcomas, three malignant fibrous histiocytomas, two rhabdomyosarcomas, two malignant schwannomas and two undifferentiated sarcomas. Six primary tumours were completely excised, five patients received radiotherapy and five received chemotherapy. Local recurrence rate was 45% and recurrence-free interval for 10 patients with recurrence was 11 months. Five patients received radiotherapy and five received chemotherapy. The median survival for patients with primary tumours was 36 months, and 5-year survival was 44%. Adjuvant therapy was not associated with higher survival rates., Conclusion: This study re-emphasizes the poor outcome of patients with retroperitoneal STS. Adjuvant radiotherapy and chemotherapy do not appear to be any proven benefit and the single most important prognostic factor is aggressive successful en bloc resection of the primary tumour. Our resection rate and 5-year survival rates are comparable with previous reported UK series although lower than large reports from North American centres. This might partly be explained by difficulty in data collection in a retrospective analysis, but may reflect inadequate subspecialization in UK centres., (Copyright Harcourt Publishers Limited.)

The prognosis for patients with squamous carcinomas of the head and neck region is strongly influenced by the presence or absence of cervical lymph node metastases. Biological markers that indicated a high risk of metastasis would have a major role in determining the optimal therapeutic strategy for these patients. This editorial discusses recent studies of molecular and genetic markers of squamous carcinomas in relation to metastatic potential and highlights some of the issues that limit current progress in this field of study., (Copyright 2001 John Wiley & Sons, Ltd.)

A 15-year-old male presented with an 18-month history of increasing swelling on the radial aspect of his left forearm. Radiographs and MR images showed a partly calcified mass on the lateral border of the radius with erosion of the underlying cortex. Following a CT-guided needle biopsy, the mass was excised by segmental resection of the radial shaft with replacement by a vascularised fibular graft. Histological examination of the resected specimen showed many features typical of a bizarre parosteal osteochondromatous proliferation (BPOP) but with destruction of the underlying cortical bone by cellular spindle cell tissue. Although there were no cytological signs of malignancy, we believe that this unusual disease should be regarded as a particularly aggressive form of BPOP and treated by wide excision. Clinical follow-up of our patient at 2 years shows no sign of local recurrence or metastasis.

The relationship between basic fibroblast growth factor (bFGF), receptors for bFGF and neoangiogenesis was investigated in 51 patients with squamous cell carcinoma of the tongue, 26 of whom had metastatic disease in cervical lymph nodes. Vessels were demonstrated by immunocytochemical labelling for CD34 and expressed as raw counts and volume-weighted counts. bFGF protein and its receptors FGFR1(flg) and FGFR2(bek), were demonstrated using immunocytochemical labelling. In situ hybridisation for bFGF mRNA was performed using a 250-bp digoxigenin-labelled RNA probe. In normal epithelium, the expression of bFGF protein and mRNA was more intense in the basal layer, while receptors for bFGF were expressed more strongly in the superficial parts. In carcinomas, expression of bFGF was greater in the more poorly-differentiated cells, but showed no relation to the overall tumour differentiation. There was strong bFGF expression in tumour-infiltrating lymphocytes. The expression of bFGF receptors was variable, with FGFR2 being particularly high in areas of keratinisation. There were no consistent changes in bFGF or receptor expression between primary carcinomas and their lymph node metastases, and there was no correlation with measures of vascularity or tumour growth pattern. bFGF is synthesised by all squamous carcinomas and has the potential to modulate angiogenesis. However, these data suggest that changes in the expression of bFGF and its receptors are not related to the intensity of neoangiogenesis in lingual carcinomas or their nodal metastases.

A 14-year-old boy presented with a 3-year history of a skin rash typical of juvenile dermatomyositis, and a 2-month history of mild proximal weakness, myalgia, and weight loss. A quadriceps biopsy showed perifascicular fibre atrophy, focal necrosis and regeneration, immunohistochemical labelling for HLA-1 on the surface of the fibres, and focal C5-9 deposition in capillaries. Macrophages with diastase-resistant, PAS-positive cytoplasm were present. Ultrastructural studies showed electron dense and membranous debris. The patient's symptoms responded to intravenous immunoglobulin and oral prednisolone. Four months after discontinuing prednisolone, the patient developed cardiac failure, ventricular tachycardia, and a recurrence of his rash. The 16S ribosomal RNA specific for Tropheryma whippelii was identified by polymerase chain reaction (PCR) analysis in skeletal and cardiac muscle. The myalgia and skin rash responded to prednisolone and oral co-trimoxazole, and the tachycardia is controlled by oral verapamil. This patient appears to have a novel association of juvenile dermatomyositis and Whipple's disease.

The relationship between neoangiogenesis and prognosis was investigated in 51 patients with surgically resected squamous carcinomas of the tongue. Twenty-six patients had lymph node metastases treated by radical neck dissection. Potential methodological sources of variation in vascular counts were examined. Vessels were immunolabeled for CD34, and the vessel counts (VC)--as well as the vessel counts adjusted for tumor area (VV)--were obtained in the most vascular parts of the carcinomas. Vascular hot spots were distributed throughout the carcinomas. The VC per hot spot increased with increasing size of carcinoma, and was higher in the resected carcinoma than in the diagnostic biopsy in four of eight cases. VC was not related to the growth pattern of the carcinoma or to metastasis, but patients with nodal metastases tended to have a lower VV than those with no metastases (p = 0.049). The tumor-specific survival of the whole group was 59%, and patients with nodal metastases had a shorter survival than those without metastases (p = 0.008). Cox's proportional hazards model demonstrated that carcinomas with a low VC tended to have a good prognosis (p = 0.023). The results from this relatively small series of cases support the hypothesis that some measures of neoangiogenesis are independent predictors of the spread and prognosis of lingual carcinomas. The variations in methodology among different studies currently preclude an accurate assessment of the prognostic significance of neoangiogenesis.

Muscle wasting and weakness are common features of patients with critical illnesses, and may impair their recovery. This study examines whether cytoskeletal and contractile proteins are damaged, and which proteolytic mechanisms might be involved, in the muscle fibre atrophy or necrosis associated with the acute myopathy of critically ill patients. Ninety-eight muscle biopsies were obtained by the conchotome method from 57 critically ill patients and examined morphometrically and by immunohistochemical labelling. Sequential biopsies showed a mean reduction in fibre cross-sectional areas of 3-4% per day. More intense immunolabelling for desmin was seen in the smaller fibres of 52% of the biopsies, while immunolabelling for dystrophin, actin and myosin heavy chains was maintained. Myosin ATPase activity was weak in the smaller fibres in some biopsies, and electron microscopy showed the loss of myosin filaments in atrophic fibres. These changes suggest that loss of the filamentous structure of myosin, without degradation of the immunolabelled epitopes, leads to the collapse of the intermyofibrillar desmin network. Fibres with abnormal desmin labelling showed increased cathepsin B, lysozyme and ubiquitin immunolabelling. Nine cases showed increased immunolabelling for heat shock protein 72. The changes in desmin immunolabelling were more prevalent in patients with higher APACHE II scores on admission, but were not related to other clinical features. The results indicate that fibre atrophy is associated with myosin filament depolymerization and the presence of several proteolytic enzymes. In our study, these changes occurred in patients who were critically ill but who did not receive large doses of steroids or neuromuscular blocking agents.

1. Duchenne and Becker muscular dystrophies are X-linked disorders caused by defects in muscle dystrophin. The mdx mouse is an animal model for Duchenne muscular dystrophy which has a point mutation in the dystrophin gene, resulting in little (<3%) or no expression of dystrophin in muscle. Mdx mice show a characteristic pattern of muscle necrosis and regeneration. Muscles are normal until the third postnatal week when widespread necrosis commences. This is followed by muscle regeneration, with the persistence of centrally nucleated fibres. 2. This work has examined the hypothesis that the onset of this muscle necrosis is associated with postnatal maturation of the thyroid endocrine system and that pharmacological inhibition of thyroid hormone synthesis delays the onset of muscle necrosis. 3. Serum T4 and T3 concentrations of mice were found to rise immediately before the onset of muscle necrosis in the mdx mouse, and induction of hypothyroidism by treatment of animals with propylthiouracil was found to delay the onset of muscle necrosis. 4. The results provide the first demonstration of experimental delay of muscle necrosis by manipulation of the endocrine system in muscle lacking dystrophin, and provide a novel insight into the way in which a lack of dystrophin interacts with postnatal development to precipitate muscle necrosis in the mdx mouse.