Risk of malignancy in thyroid nodules with indeterminate (THY3f) cytology.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is an integral part of thyroid nodule assessment. Nodules with an indeterminate cytology (THY3a-f) require formal histological assessment to confirm benign or malignant pathology. This study aimed to provide data for an evidence-based approach for management of patients with THY3f nodules. METHODS: Retrospective review of patients who had a thyroid FNAC reported as suspicious of follicular neoplasm (THY3f) or showing atypia (THY3a) were identified, and clinical, operative and outcomes data were analysed. RESULTS: Between 2018 and 2020, 200 patients (167F:33M, median age 51 years (range:18-86 years)) had a THY3f cytology. Most presented with a palpable nodule (n=104; 68.4%). Overall, 152 (76.0%;130F:23M) underwent surgery and 31 (20.4%) were found to have a thyroid carcinoma (22 follicular carcinomas, 7 papillary carcinomas, 1 medullary thyroid carcinoma and 1 metastatic renal carcinoma). An additional incidental carcinoma (size: 0.7-13mm) was found in seven (4.6%). Among those with cancer, a completion thyroidectomy and radioactive iodine treatment was indicated in nine (<6% of the entire cohort). Previously suggested risk factors for malignancy, eg male gender, large tumour size (>4cm) or age, were not found to be associated with increased risk. During the same period, THY3a cytology was reported in 53 patients, of whom 29 underwent diagnostic surgery and 4 patients were found to have a thyroid cancer (follicular, n=3 and medullary, n=1). CONCLUSION: One in five patients with features suspicious of a follicular neoplasm (THY3f) has a thyroid carcinoma. This risk is much lower for THY3a. This study reinforces the current recommendation for thyroid surgery in all patients with a reliable THY3f cytology, as no further stratifying risk factors could be identified.

A pilot study to evaluate assisted freehand ultrasound elasticity imaging in the sizing of early breast cancer: a comparison of B-mode and AFUSON elasticity ultrasound with histopathology measurements.

OBJECTIVE: This pilot study investigates the role of assisted-freehand ultrasound (AFUSON) elasticity imaging of the breast in assessing the contour, size and area of 23 early breast cancers by making comparison of AFUSON with the equivalent B-mode ultrasound images and gold standard histopathology slides. METHODS: The B-mode, AFUSON and digitised histopathology slides of three early breast cancers were compared for contour, size and area with histopathology scans. AFUSON features that corresponded to areas of known malignant change on the histopathology slides were regarded as diagnostic. These diagnostic criteria were then applied to the B-mode and AFUSON elasticity images of all 23 breast cancers in the pilot study without having the availability of the histopathology scans for reference. Corresponding diameters were measured and the results were compared with the equivalent measurements on the scans of the histology slides. The results were tabulated in histogram form. Diagnostic confidence levels were evaluated. RESULTS: Size dimension accuracy increased from 66% using B-mode alone to 82% using combined B-mode and AFUSON elasticity images. Tumour area accuracy was also increased. A small number of cases had a striking visual similarity of shape on AFUSON elasticity scans and histopathology slides. CONCLUSION: In spite of the shortfalls in this study, AFUSON elasticity imaging was capable of acquiring some high-quality images that showed strong correlation between AFUSON elasticity and scans of histology slides. Further studies will be carried out to refine the technique and determine if it has a role in the diagnosis and management of breast cancer.

A mammographic dilemma: calcification or haemosiderin as a cause of opacities? Validation of a new digital diagnostic tool.

Core biopsies of an area of microcalcification demonstrated large collections of macrophages containing haemosiderin, with evidence of minimal microcalcification on H&E staining. Algorithms were developed that were capable of differentiating with high accuracy those signs due to calcification, using quantitative measurements such as the apparent volume composition of calcium. Using the linear attenuation coefficients of calcification and assuming an ellipsoid model for the 3-dimensional shape of calcification, we computed the relative calcification volume for each region of interest. The difference in the linear attenuation coefficients of iron and calcification allowed the two to be differentiated on a mammogram based on this measure of relative calcification volume.

Histopathological assessment of metastasis.

In spite of advances in the fields of immunohistochemistry and molecular biology, in clinical practice much of the assessment of metastases still relies on light microscopy using conventional histological stains. This is not so much a reflection of a reluctance by histopathologists to adopt new techniques, but more an indication that for most malignancies an enormous amount of useful prognostic data can be gained from relatively unsophisticated assessment of tissues, and that many of the strongest studies of prognostic factors in malignancy predate the era of molecular diagnostics. Although it is undoubtedly true that newer techniques have added prognostic information in the assessment of many tumors, and many, such as the measurement of estrogen receptor status in breast cancer, could be considered routine, a skilled assessment of the morphology of the tissues still provides the fundamental basis of assessing prognosis in the vast majority of cases.

Proliferating cell nuclear antigen expression grossly over-estimates cellular proliferation in cardiac myxomas.

AIMS: Myxomas are thought to be slowly growing benign neoplasms. Presentation is often due to embolic phenomena, though rapid increase in size is sometimes seen. Such an increase may be due to proliferation of cellular components, an increase in matrix due to synthesis or oedema, haemorrhage into the lesion, or the addition of surface thrombus. Routine microscopy suggests a low proliferation rate. The aim of this study was to investigate cellular proliferation, and to assess its contribution to tumour growth. METHODS: The antibodies JC1, Ki67, PC10, and MIB1 were used to make an immunohistochemical assessment of proliferation in five cases of cardiac myxoma. RESULTS: A significant difference was seen between number and type of cells stained with PC10 and the other markers. Whilst PC10 stained the nuclei of most (60 - 95%) endothelial and stromal cells in all cases, the other markers stained far fewer cells (up to 5%). All markers stained varying numbers of lymphoid cells. CONCLUSIONS: Proliferation in cardiac myxomas is unlikely to be rapid. The widespread positivity for PC10 suggests that PCNA is not a reliable marker in such tissues. Clinical cases in which myxomas have grown rapidly are probably due to changes in intercellular matrix rather than cellular proliferation.

Pre-existing vascular disease in the radial artery and other coronary artery bypass conduits.

BACKGROUND: There is increasing interest in the radial artery (RA) as a coronary artery bypass graft (CABG). However, few studies have examined the prevalence of pre-existing disease in this vessel. METHODS: Histological specimens from 177 RA were compared with 168 of internal mammary artery (IMA) and 86 of long saphenous vein (LSV) from the same patients undergoing CABG. The degree of stenosis, active atheroma, intimal thickening, and medial hyaline sclerosis was assessed. - RESULTS: 99% of IMAs, 98% of RAs and 100% of SVs had less than 30% stenosis. 91% of IMAs, 42% of RAs and 70% of SVs had less than 5% stenosis. Medial sclerosis was present in 10% of IMAs, 36% of LSVs and 46% of RAs. Medial calcification was present in 9% of RAs, 1% of LSVs and not in IMAs. CONCLUSION: The majority of conduits did not have evidence of severe disease. There is an increased prevalence of mild intimal thickening, medial sclerosis and medial calcification in RAs compared with IMAs and LSVs. The implications for longer-term graft patency are uncertain.

Treated bacterial endocarditis as a histological mimic of fungal infection.

Histological assessment of cardiac valve tissue contributes to the diagnosis of infective endocarditis and is of particular importance in cases in which no organism is cultured. Antibiotic treatment of bacterial endocarditis may lead to abnormal bacterial morphology and staining characteristics. Although in many cases the presence of some residual bacteria of normal appearance makes the diagnosis straightforward, in some only abnormal bacteria may be seen. Unless the appearances of these are interpreted with caution, the presence of larger spherical organisms with the staining properties of a yeast may lead to an erroneous diagnosis of fungal infection.

Apparent deficiency of mucosal vascular collagen type IV associated with angiodysplasia of the colon.

AIMS: To investigate the presence and distribution of vascular collagen type IV in colonic tissue in cases of angiodysplasia and age and sex matched controls. METHODS: Sections of colon from seven cases of colonic angiodysplasia and eight age and sex matched controls were examined for the presence of collagen type IV in vessels of the mucosa and submucosa. Immunohistochemical staining was performed on paraffin wax embedded sections, and the degree of vascular staining for each marker compared between mucosa and submucosa and between cases and controls. Staining for endothelial markers P-selection and factor VIII was used to control for non-specific differences in immunostaining. RESULTS: In both the angiodysplastic tissues and approximately half the control tissues, staining for collagen type IV was considerably weaker in vessels in the mucosa than in the submucosa. In angiodysplasia, ectatic vessels in the mucosa appeared to contain less collagen type IV than similarly sized vessels in the submucosa, and perforating vessels appeared in many cases to lose staining at the level of the muscularis mucosae. No differences were found in staining intensity for the control endothelial markers between cases and controls. CONCLUSIONS: The apparent relative deficiency of collagen type IV in the mucosal vessels in angiodysplasia may be related to their susceptibility to ectasia and haemorrhage. The finding of a similar deficiency in half of the control cases may reflect a population at risk of this relatively common condition.

Bilateral ureteric obstruction secondary to the prolonged use of tiaprofenic acid.

There is increasing awareness that the long-term use of the non-steroidal anti-inflammatory agent tiaprofenic acid (Surgam) is associated with a severe form of cystitis. The condition is usually reversible with complete resolution of symptoms on stopping the drug. We present a case of tiaprofenic acid-induced cystitis resulting in bilateral hydronephrosis suggesting ureteric obstruction. The previous reported cases are reviewed and the risks of delay in withdrawal of the drug and of permanent ureteric damage are discussed.

Ulcerative colitis complicated by renal cell carcinoma: a series of three patients.

Three patients are described in whom renal cell carcinoma was diagnosed between seven months and 14 years after the onset of ulcerative colitis. All three had required treatment with corticosteroids and azathioprine, as well as maintenance therapy with 5-aminosalicylate derivatives, for chronic active colitis. One patient had coexisting polymyalgia rheumatica; one had primary biliary cirrhosis. It is uncertain whether this association, which has not previously been described, has pathogenetic importance or has arisen simply by chance. Genetic predisposition or the effect of drug treatment, particularly immunosuppression, may be pertinent to the co-occurrence of these diseases.

HIV associated cytomegalovirus colitis as a mimic of inflammatory bowel disease.

Cytomegalovirus (CMV) colitis may cause symptoms and signs identical to those of idiopathic inflammatory bowel disease. Although difficult to diagnose with certainty, the histological finding of cytomegalovirus inclusions in tissue from a case of suspected inflammatory bowel disease is strongly suggestive. CMV colitis is an entity almost entirely confined to cases of severe immunosuppression. The case of a 79 year old widower who was admitted to hospital with symptoms suggestive of inflammatory bowel disease is presented. Despite medical treatment his condition worsened and he developed toxic dilatation of the colon requiring colectomy. Histological examination showed a mild superficial pancolitis, with focal severe inflammation, deep fissuring ulceration, and pseudopolyposis. Abundant CMV inclusions were seen in cells associated with the ulcerating inflammatory tissue. A diagnosis of indeterminate colitis with CMV was made. The patient's condition worsened after surgery and he died a few days later despite intensive treatment, including antiviral chemotherapy directed against CMV. After death HIV serology was found to be positive. Regardless of the age and perceived lifestyle of the patient, a diagnosis of CMV colitis in someone not known to be immunosuppressed raises the possibility of HIV infection.