Biomarkers of Type IV Collagen Turnover Reflect Disease Activity in Patients with Early-Stage Non-Alcoholic Fatty Liver (NAFL).

BACKGROUND: Identification of progressive liver disease necessitates the finding of novel non-invasive methods to identify and monitor patients in need of early intervention. Investigating patients with early-liver injury may help identify unique biomarkers. Early-liver injury is characterized by remodeling of the hepatocyte basement membrane (BM) of the extracellular matrix. Thus, we quantified biomarkers targeting two distinct neo-epitopes of the major BM collagen, type IV collagen (PRO-C4 and C4M), in patients spanning the non-alcoholic fatty liver disease (NAFLD) spectrum. METHODS: We evaluated PRO-C4 and C4M in a cross-sectional study with 97 patients with NAFLD confirmed on histology. Serological levels of PRO-C4 and C4M were quantified using validated competitive enzyme-linked immunosorbent assays (ELISA). Using the fatty liver inhibition of progression (FLIP) algorithm, we stratified patients into two groups: non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH). Biomarker levels were investigated in the two groups in patients stratified by the NAFLD activity score (NAS). In both groups, biomarker measurements were analyzed in relation to histological scorings of steatosis, inflammation, ballooning, and fibrosis. RESULTS: Patients had a body mass index (BMI) of 30.9 ± 5.6 kg/m2, age of 53 ± 13 years and a NAS range of 1-8. Upon stratification by FLIP, the NASH patients had higher platelets, ALT, and AST levels than the NAFL group. Both PRO-C4 (p = 0.0125) and C4M (p = 0.003) increased with increasing NAS solely within the NAFL group; however, a large variability was present in the NASH group. Furthermore, both markers were significantly associated with lobular inflammation (p = 0.020 and p = 0.048) and steatosis (p = 0.004 and p = 0.015) in patients with NAFL. CONCLUSIONS: This study found that type IV collagen turnover increased with the increase in NAS in patients with NAFL; however, this was not the case in patients with NASH. These findings support the assessments of the BM turnover using biomarkers in patients with early-disease development. These biomarkers may be used to track specific processes involved in the early pathobiology of NAFL.

Angiosarcoma arising in the capsule of a mammary silicone implant.

A 40-year-old woman with silicone implants inserted 21 years before presented with sudden onset of painful right breast swelling. Clinical examination revealed a firm swollen breast with appearance of old bruising. Ultrasound showed fluid around the implant. Cytology of the fluid showed cells with large pleomorphic nuclei with prominent nucleoli including elongated forms and very occasional vacuoles. The cell block also contained small fragments with atypical spindle cells around slit-like spaces that were positive for CD31 and CD34. MRI showed a 25 mm serpiginous area of enhancement on the inner aspect of the fibrous capsule with haematoma between the capsule and the implant. The capsule and adjacent area were excised. Histology showed angiosarcoma extending from the inner aspect of the capsule into the cavity around the implant. The location of the tumour on the inner aspect of the capsule is the same site that breast implant associated anaplastic large cell lymphomas arise and suggests a possible causal link between the implant and the angiosarcoma. This case emphasises the value of cytological assessment of fluid around breast implants and the role of cell blocks and immunohistochemistry.

Isolated appendiceal endometriosis resulting in intussusception.

An inverted (intussuscepted) appendix is a rare finding, often mistaken for a polyp as it presents with vague symptoms. This can result in misdiagnosis and inappropriate management. Diagnosis is usually made through surgery. Rarely, endometriosis has been found as the cause of the intussusception. A 42-year-old woman presented with frequent loose stools over 2 years, an elevated calprotectin over 400 µg/g faeces (normal <110) and a serum C-reactive protein of 40 mg/l (normal <5 mg/l). Endoscopy showed an inverted appendix. Histopathology results showed inflammation and ulceration. Laparoscopic appendicectomy was performed successfully, and endometriosis was found on the inverted appendix. This is the first case reported of an inverted appendix containing endometriosis, in which the intussusception of the appendix has been diagnosed on endoscopy. This case highlights how endometriosis can involve just the appendix, without any involvement of reproductive organs. We suggest considering inverted appendix as a differential diagnosis when investigating caecal lesions.

The impact of using defined criteria for adequacy of fine needle aspiration cytology of the thyroid in routine practice.

The fine needle aspiration cytology (FNAC) of the thyroid is the predominant method of preoperative tissue diagnosis of thyroid lesions. The routine use of FNAC has reduced the rate of unnecessary surgery for thyroid nodules. However, there are overlaps in the existing criteria for defining adequacy in thyroid aspirates. In this study, we aimed to explore the reasons for high percentage of inadequate thyroid FNAC samples and to reevaluate those samples by applying clearly defined criteria suggested in the literature to reduce the proportion of inadequate aspirates. The results of 550 smears reported as inadequate FNAC samples are presented over a period of 15 years extending from 1986 to 2000 (18.8%). For the purpose of the study, only those patients with subsequent histological or cytological analysis were included (279). The original FNA samples were reviewed by two cytopathologists, unaware of the subsequent repeat cytology or histology results. Specific criteria for adequacy of specimens were used which include the presence of six or more groups of follicular cells, each having more than 10 discernable viable cells or 60 isolated viable follicular cells. Out of 279, 82 (29%) FNAC samples originally reported as inadequate met our criteria and were considered adequate on review. Of these 82 cases, subsequent surgical excision showed malignancy in 5 cases (6%), adenoma in 7 (9%), and benign hyperplasia and thyroiditis in 70 cases (85%). In addition, 16 (5%) cases were classified as cysts. The slide preparation error was noticed in 26 (14%) and the sampling error was observed in 160 (86%) cases. The use of well-defined criteria for adequacy is helpful because it improves the diagnostic efficiency of thyroid FNA and avoids unnecessary surgery for benign nonneoplastic thyroid lesions. However, since application of these criteria has also resulted in an increase in the false-negative diagnoses, they should be applied in the multidisciplinary context.