Hürthle cell carcinoma: diagnostic and therapeutic implications

BACKGROUND: Hürthle cell carcinoma is a variant of follicular cell carcinoma of thyroid. It may present as a low-grade tumour or as a more aggressive type. Prognosis depends upon the age of the patient, tumour size, extent of invasion and initial nodal or distant metastasis. PATIENT AND METHODS: The case of Hürthle cell carcinoma is reported in a 79-year-old man who presented with a rapidly increasing lump on the left side of his neck, having had a right hemithyroidectomy for colloid goitre 24-years-ago. Fine needle aspiration cytology confirmed the presence of Hürthle cells, raising the possibility of a Hürthle cell neoplasm. The patient underwent staging and surgery. Histology showed Hürthle cell carcinoma and the patient underwent adjuvant therapy. The literature on Hürthle cell neoplasms is reviewed. CONCLUSIONS: Fine needle aspiration cytology may recognise Hürthle cell lesion but final diagnosis of carcinoma depends upon histological confirmation of vascular or capsular invasion. Staging and surgery in Hürthle cell carcinoma are similar to follicular carcinoma of thyroid with favourable outcome despite the controversy regarding the histological classification and adjuvant therapy. Elderly patients with Hürthle cell carcinoma need to be made aware of their poorer prognosis and should be offered more radical treatment

Body Mass Index, Smoking, and Alcohol and Risks of Barrett’s Esophagus and Esophageal Adenocarcinoma: A UK Prospective Cohort Study

BACKGROUND: The timing of the risk factors cigarette smoking, alcohol and obesity in the development of Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) is unclear. AIMS: To investigate these exposures in the aetiology of BE and EAC in the same population. METHODS: The cohort included 24,068 men and women, aged 39–79 years, recruited between 1993 and 1997 into the prospective EPIC-Norfolk Study who provided information on anthropometry, smoking and alcohol intake. The cohort was monitored until December 2008 and incident cases identified. RESULTS: One hundred and four participants were diagnosed with BE and 66 with EAC. A body mass index (BMI) above 23 kg/m(2) was associated with a greater risk of BE [BMI ≥23 vs. 18.5 to <23, hazard ratio (HR) 3.73, 95 % CI 1.37–10.16], and within a normal BMI, the risk was greater in the higher category (HR 3.76, 95 % CI 1.30–10.85, BMI 23–25 vs. 18.5 to >23 kg/m(2)). Neither smoking nor alcohol intake were associated with risk for BE. For EAC, all BMI categories were associated with risk, although statistically significant for only the highest (BMI >35 vs. BMI 18.5 to <23, HR 4.95, 95 % CI 1.11–22.17). The risk was greater in the higher category of a normal BMI (HR 2.73, 95 % CI 0.93–8.00, p = 0.07, BMI 23–25 vs. 18.5 to >23 kg/m(2)). There was an inverse association with ≥7 units alcohol/week (HR 0.51, 95 % CI 0.29–0.88) and with wine (HR 0.49, 95 % CI 0.23–1.04, p = 0.06, drinkers vs. non-drinkers). CONCLUSIONS: Obesity may be involved early in carcinogenesis and the association with EAC and wine should be explored. The data have implications for aetiological investigations and prevention strategies

Eccrine Porocarcinoma of the Skin is Rising in Incidence in the East of England

[No abstract available

Eccrine Porocarcinoma of the Skin is Rising in Incidence in the East of England

[No abstract available

Carboxypeptidase-M is regulated by lipids and CSFs in macrophages and dendritic cells and expressed selectively in tissue granulomas and foam cells

Granulomatous inflammations, characterized by the presence of activated macrophages (MAs) forming epithelioid cell (EPC) clusters, are usually easy to recognize. However, in ambiguous cases the use of a MA marker that expresses selectively in EPCs may be needed. Here, we report that carboxypeptidase-M (CPM), a MA-differentiation marker, is preferentially induced in EPCs of all granuloma types studied, but not in resting MAs. As CPM is not expressed constitutively in MAs, this allows utilization of CPM-immunohistochemistry in diagnostics of minute granuloma detection when dense non-granulomatous MAs are also present. Despite this rule, hardly any detectable CPM was found in advanced/active tubercle caseous disease, albeit in early tuberculosis granuloma, MAs still expressed CPM. Indeed, in vitro both the CPM-protein and -mRNA became downregulated when MAs were infected with live mycobacteria. In vitro, MA-CPM transcript is neither induced remarkably by interferon-γ, known to cause classical MA activation, nor by IL-4, an alternative MA activator. Instead, CPM is selectively expressed in lipid-laden MAs, including the foam cells of atherosclerotic plaques, xanthomatous lesions and lipid pneumonias. By using serum, rich in lipids, and low-density lipoprotein (LDL) or VLDL, CPM upregulation could be reproduced in vitro in monocyte-derived MAs both at transcriptional and protein levels, and the increase is repressed under lipid-depleted conditions. The microarray analyses support the notion that CPM induction correlates with a robust progressive increase in CPM gene expression during monocyte to MA maturation and dendritic cell (DC) differentiation mediated by granulocyte–MA-colony-stimulating factor+IL-4. M-CSF alone also induced CPM. These results collectively indicate that CPM upregulation in MAs is preferentially associated with increased lipid uptake, and exposure to CSF, features of EPCs, also. Therefore, CPM-immunohistochemistry is useful for granuloma and foam MA detections in tissue sections. Furthermore, the present data offer CPM for the first time to be a novel marker and cellular player in lipid uptake and/or metabolism of MAs by promoting foam cell formation

Patient-specific cancer genes contribute to recurrently perturbed pathways and establish therapeutic vulnerabilities in esophageal adenocarcinoma

Abstract: The identification of cancer-promoting genetic alterations is challenging particularly in highly unstable and heterogeneous cancers, such as esophageal adenocarcinoma (EAC). Here we describe a machine learning algorithm to identify cancer genes in individual patients considering all types of damaging alterations simultaneously. Analysing 261 EACs from the OCCAMS Consortium, we discover helper genes that, alongside well-known drivers, promote cancer. We confirm the robustness of our approach in 107 additional EACs. Unlike recurrent alterations of known drivers, these cancer helper genes are rare or patient-specific. However, they converge towards perturbations of well-known cancer processes. Recurrence of the same process perturbations, rather than individual genes, divides EACs into six clusters differing in their molecular and clinical features. Experimentally mimicking the alterations of predicted helper genes in cancer and pre-cancer cells validates their contribution to disease progression, while reverting their alterations reveals EAC acquired dependencies that can be exploited in therapy

A multicentre review of the histology of 1012 periocular basal cell carcinomas

Aims: To evaluate primary periocular basal cell carcinomas (BCCs) in depth including comparing histological margins with subtype, location and surgical specialty after wide local excision.  Methods: A retrospective review was performed for all BCCs excised from three hospitals over 5 years, covering a population of just over 1 million. Tumours were classified according to histological subtype location. Incomplete excision rates and margins were analysed in detail and comparisons made.  Results: The most common subtype found was nodular followed by infiltrative. Lesions were most commonly located at the lower lid. Infiltrative BCCs were associated with perineural invasion and incomplete excision despite the largest peripheral margins. Superficial BCCs had the smallest mean peripheral margin but the largest mean deep margin. 2 mm histological margins gave an 83.7% complete excision rate, 6.4% incomplete excision rate and 7.1% where the clearance margin was 0.3 mm or less.  Conclusion: Distribution of eyelid BCCs based on subtype and periocular location mirrored the general consensus. Infiltrative BCCs should be excised with wider margins or referred for Mohs surgery, especially if the medial canthus is involved. Superficial BCCs should be excised with wider but shallower surgical margins. Ophthalmologists were more likely than dermatologists or plastic surgeons to incompletely excise a periocular BCC, which is reflective of their more difficult case mix

Giant Cell Arteritis – Incidence and Mortality

Background Giant cell arteritis is the most common vasculitis in the western world in those aged greater than 50yrs old and has significant morbidity from both its pathology and treatment. There are no recent (after 2001) estimates of the occurrence in the UK. Objectives The aim of this study was to estimate the occurrence of GCA in the UK and to record death from all cause mortality upto a period of ten years post diagnosis. Methods All histology reports for patients referred to a university hospital in Norwich, Norfolk for temporal artery biopsy between 1st January 2003 and December 2009 were reviewed. The population denominator was calculated from national census data to calculate incidence. All positive biopsy proven patients with GCA were followed until 7th January 2013. Patients were followed from time of diagnosis until either their death or 7th January, 2013. Results There were 325 temporal biopsies performed at the NNUH between the years 2003 to 2009. Subsequently 119 individuals were diagnosed with biopsy positive GCA (36.6%). The mean age at diagnosis was 75.6yrs. 85 were women (71.4%). The incidence rate per 100,000 was 6.8 (95% CI = 4.2 to 11.1) in people aged >50years. By 7th January, 2013, 25 patients (21.0%) with biopsy confirmed GCA had died with a median follow up of 66 months (44-86). One, 2 and 5 year survival rates were 96, 92, and 84%, respectively. There were no statistical significant survival gender effects (male vs female p=0.308). Conclusions The results reveal an estimate of 6.8 per 100,000 people aged >50yrs. This is much lower than the estimate from the General Practice Research Database (GPRD) study carried out in 2001. Within the GPRD study only three out of a selection of 45 cases that were reviewed had a positive temporal artery biopsy (6.7%) and 10 cases (22.2%) were diagnosed and managed in primary care alone. Assuming an incidence for our study is similar to that of the GPRD then in Norfolk perhaps as much as 50% of cases of GCA are managed in the community without undergoing biopsy. However death from all cause mortality does not appear to be too dissimilar compared to the general population. References Smeeth L, Cook C, Hall AJ. Incidence of diagnosed polymyalgia rheumatica and temporal arteritis in the United Kingdom, 1990-2001. Annals of the Rheumatic Diseases. 2006 Aug;65(8):1093-8. Disclosure of Interest None Declare