The association of pain and stiffness with fatigue in incident polymyalgia rheumatica: baseline results from the polymyalgia rheumatica cohort study.

We aimed to examine the association between pain, stiffness and fatigue in newly diagnosed polymyalgia rheumatica (PMR) patients using baseline data from a prospective cohort study. Fatigue is a known, but often ignored symptom of PMR. Newly diagnosed PMR patients were recruited from general practice and mailed a baseline questionnaire. This included a numerical rating scale for pain and stiffness severity, manikins identifying locations of pain and stiffness and the FACIT-Fatigue questionnaire. A total of 652 PMR patients responded (88.5%). The mean age of responders was 72.6 years (SD 9.0) and the majority were female (62.0%). Manikin data demonstrated that bilateral shoulder and hip pain and stiffness were common. The mean fatigue score (FACIT) was 33.9 (SD 12.4). Adjusted regression analysis demonstrated that a higher number of pain sites (23-44 sites) and higher pain and stiffness severity were associated with greater levels of fatigue. In newly diagnosed PMR patients, fatigue was associated with PMR symptom severity.

The real evidence for polymyalgia rheumatic as a paraneoplastic syndrome.

Not available.

Risk of fragility fracture among patients with late-onset psoriasis: a UK population-based study.

This study aimed to examine fracture risk in patients with late-onset psoriasis. A cohort study was conducted using primary care records from the Clinical Practice Research Datalink. Psoriasis patients had a 10% increased risk of fracture compared to matched controls (hazard ratio (HR) = 1.10; 95% confidence interval (CI) 1.04, 1.16). INTRODUCTION: This study aimed to examine fracture risk in patients with late-onset psoriasis and investigate the effect of methotrexate on fracture risk. METHODS: A cohort study was conducted using primary care records from the UK-based Clinical Practice Research Datalink. Individuals aged 40 years and over, with incident (new onset) diagnoses of psoriasis, were identified from 1990 to 2004 and followed up until 2015. For each exposed individual, up to four age-, gender-, and practice-matched controls were randomly selected. Incidence rates of fragility fracture (hip, vertebral, spine, radius or unspecified site) per 10,000 person-years were calculated and hazard rates were compared to the unexposed using Cox regression models. The risk of fracture was also estimated, within the exposed group for patients receiving/not receiving methotrexate. RESULTS: Twenty-four thousand two hundred nineteen patients with psoriasis and 94,820 controls were identified. The absolute rate of fracture in psoriasis patients was 58 per 10,000 person-years (95% CI 55, 61) and 53 per 10,000 person-years in the matched controls (CI 52, 54). Psoriasis patients had a 10% increased risk of fracture compared to their matched controls (HR = 1.10; 95% CI 1.04, 1.16). Methotrexate use was not associated with increased risk (HR = 0.91; 95% CI 0.72, 1.15). CONCLUSIONS: Identifying additional clinical factors associated with increased fracture risk is important in improving fracture risk stratification. Further work is needed to determine the relationship between age of onset of psoriasis and fracture risk, explore causative explanations, and identify if existing fracture risk stratification tools underestimate fracture risk in patients with psoriasis.

The real evidence for polymyalgia rheumatica as a paraneoplastic syndrome.

The aim of this study was to systematically consider the evidence for polymyalgia rheumatica (PMR) as a paraneoplastic disease. A systematic review of Medline and Embase was conducted from their inception to February 2017. Risk of bias was assessed using the Newcastle-Ottawa tool. Data were extracted regarding the PMR-cancer association, the types of cancer associated with PMR and the presentation of PMR patients subsequently diagnosed with cancer. Twenty-three full text articles were reviewed from the 1174 unique references identified in the search. Nine articles were included in the final review. There was some evidence of an association between PMR and cancer in the short-term (first 6 to 12 months after diagnosis), but no evidence of an association after this time. Limited evidence suggests that lymphoma, prostate and haematological cancers may be those cancers more commonly diagnosed in those with PMR. There was little evidence to suggest what presenting features may be associated with the development of cancer. There is little evidence of PMR as a true paraneoplastic disease. However, there is reason to be cautious when making the diagnosis of PMR. Clinicians should be aware of this potential association both prior to making a diagnosis and throughout the course of the condition.

Association between characteristics of pain and stiffness and the functional status of patients with incident polymyalgia rheumatica from primary care.

This paper aims to examine the relationship between different characteristics of pain and stiffness and the functional status of patients with newly diagnosed polymyalgia rheumatica (PMR). Baseline analysis of an inception cohort study was conducted. Patients aged ≥18 years, with a new diagnosis of PMR were recruited from 382 English general practices. Participants were mailed a baseline questionnaire, including separate pain and stiffness manikins and numerical rating scales (NRS), a question on their ability to raise their arms above their head and the modified Health Assessment Questionnaire (mHAQ) to examine participants' functional status. Linear regression analysis, reported as regression co-efficients (95% confidence intervals (95% CI)), was used to assess the association of pain and stiffness with function, initially unadjusted and then adjusted for age, gender, deprivation status, smoking status, BMI, anxiety and depression. Six hundred fifty two patients responded to the baseline survey (88.5%). The majority (88.2%) reported no, or mild impairment in their functional status. Adjusted linear regression analysis demonstrated that high (NRS ≥8) pain (0.20 (95% CI 0.10-0.28)) or stiffness (0.18 (0.09-0.26)) ratings, an increasing number of sites of pain (0.18 (0.06-0.29)) or stiffness (0.19 (0.08-0.31)) and shoulder pain (0.18 (0.05-0.31)), stiffness (0.10 (0.01-0.20)) and difficulty raising arms above one's head (0.19 (0.10-0.28)) were all associated with increased functional impairment. The majority of newly diagnosed PMR patients reported no or minimal functional difficulty. However, those who experience severe or widespread pain or stiffness often have significant functional limitation in performing their daily activities and may be a subset worthy of additional focus in primary care.

Pathological aspects of the assessment of head and neck cancers: United Kingdom National Multidisciplinary Guidelines.

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).

Calculi and intracellular ochronosis in the submandibular tissues from a patient with alkaptonuria.

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.

Tracheopathia chondro-osteoplastica--an unusual cause of stridor.

OBJECTIVES: A case of tracheopathia chondro-osteoplastica causing sub-glottic stenosis is described. STUDY DESIGN: Case report and literature review. MATERIALS AND METHODS: A 37-year-old man presented with a 15-year history of gradually worsening dyspnoea and stridor due to sub-glottic stenosis. His medical and radiographic records were reviewed. This patient's presentation, histopathological findings and radiology images are presented and discussed. RESULTS: Histopathological evaluation of microlaryngoscopy biopsy specimens, taken during laser debulking of the stenosis, confirmed the presence of tracheopathia chondro-osteoplastica. CONCLUSIONS: This is the first reported case of sub-glottic stenosis caused by tracheopathia chondro-osteoplastica which required an urgent tracheostomy.

Expression of cell cycle associated proteins influences radiocurability of T2N0 squamous cell carcinoma of the larynx.

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.

Alkaptonuria--a review of surgical and autopsy pathology.

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.

Ultrasound-guided fine needle aspiration cytology in the diagnosis and management of thyroid nodules.

OBJECTIVE: To examine the accuracy of fine needle aspiration cytology (FNAC) in the diagnosis of thyroid nodules and compare the inadequacy rates for ultrasound-guided and freehand FNAC. METHODS: A retrospective study of 434 patients with thyroid nodules who underwent diagnostic FNAC over a 2-year period. Cytological diagnoses have been compared with the histological assessment of resection specimens in 69 cases. RESULTS: The inadequacy rate was significantly lower from ultrasound guided FNAC (24/373 cases, 6.4%) than from freehand FNAC (8/61 cases, 13.1%) (P = 0.043). Seventy-six percentage of patients had a non-neoplastic cytological diagnosis and, after multidisciplinary review, the patients were reassured and assigned to clinical follow-up. Sixty-seven patients had a resection for cytological appearances consistent with non-neoplastic disease (n = 34), suspicious of follicular neoplasia (n = 23), or suspicious of malignancy (n = 10), and two patients had resections following inadequate cytology with ultrasound appearances suspicious of a neoplasm. The overall accuracy of FNAC analysis for malignancy was 97.0%, with sensitivity 83.3%, specificity 98.0%, positive predictive value 71.4% and negative predictive value 98.4%. The overall accuracy of FNAC analysis for the prediction of neoplasia was 97.5%, with sensitivity 80.5%, specificity 97.8%, positive predictive value 89.2% and negative predictive value 95.9%. Difficulties in cytological diagnosis were associated with lymphoid infiltrates and with degenerative changes in follicular adenomas. CONCLUSION: Ultrasound-guided FNAC has a significantly lower yield of inadequate aspirates than palpable FNAC. The ability of FNAC to predict neoplasia in 89% patients and to exclude neoplasia in 95.9% patients makes an important contribution to the multidisciplinary assessment of patients.

Hibernoma--correlation of histopathology and magnetic-resonance-imaging features in 10 cases.

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.

Marsh stars in Liverpool.

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.

acp Best Practice No 169. Evidence based pathology: squamous carcinoma of the hypopharynx.

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.

The spectrum of pathology in central core disease.

Central core disease is a congenital myopathy with muscle weakness defined pathologically by the presence of extensive areas in muscle fibres that are devoid of oxidative enzyme activity. The gene responsible has been shown to be the ryanodine receptor 1 on chromosome 19q13 and mutations have now been identified in several patients. Some cases with the morphological defect remain molecularly undefined, particularly those studied before molecular studies were available. We have studied three families with congenital onset, each with a dominantly inherited mutation in a C-terminal exon of the ryanodine receptor 1. They illustrate the spectrum of pathology that can be observed in patients with the myopathic features of central core disease. We show that extensive fibrosis and fat may be present, type 1 fibre uniformity may occur in the absence of cores; cores may be central or peripheral, single or multiple; and that an appearance of multiple focal minicores might cause a diagnostic pathological dilemma. In addition, we show the value of immunocytochemistry in identifying cores, in particular the use of antibodies to desmin and gamma-filamin.