An Unusual Case of Lethal Strongyloides stercoralis-Associated Chronic Fulminant Colitis in an Immunocompetent Patient.

A 70-year-old immunocompetent Lebanese male presented with 3-month history of watery diarrhoea and abdominal pain after recently arriving to Australia from Lebanon. He had a colectomy for an iatrogenic bowel perforation associated with a colonoscopy in Lebanon several months prior. His computed tomography (CT) scan demonstrated pancolitis. Stool culture and polymerase chain reaction (PCR) were positive for Strongyloides stercoralis. Despite Strongyloides treatment and total parenteral nutrition, his pancolitis unexpectedly persisted despite negative stool cultures, and the patient failed to progress over several weeks with worsening abdominal pain. A colectomy was considered. However, due to his recent myocardial infarct requiring cardiac stenting, his anticoagulant and antiplatelets could not be ceased for at least 3 months without significant cardiac risk. After hospitalisation for several weeks in Australia, he was discharged against medical advice and flew back to Lebanon, where he presented with worsening pain and underwent a subtotal colectomy. Unfortunately, he developed multiorgan failure and died 3 weeks following his colectomy. Strongyloides-related pancolitis is a rare condition in immunocompetent adults that has the potential to persist and be lethal, despite microbiological antiparasitic eradication.

A First Case Report of Cytomegalovirus Infection Presenting With Perianal Fistula and Abscess Formation in a Kidney Transplant Recipient.

Cytomegalovirus infection after transplant has been dramatically reduced in the modern era with improved understanding of immunosuppression and perioperative transplant care. However, cytomegalovirus syndrome with or without tissue invasive disease can still lead to significant morbidity and mortality. Several organs can be involved: most commonly, the gastrointestinal tract, liver, pancreas, lung, and the transplanted renal allograft. Postoperative cytomegalovirus colitis after renal transplant is well recognized and described, with symptoms including abdominal pain, nausea, and diarrhea. Biochemistry can demonstrate pancytopenia with a leukopenia with or without histopathology confirmation. A high index of suspicion is required for a timely diagnosis. This is the first published case report of a patient with cytomegalovirus tissue invasion presenting with a perianal fistula and abscess formation.The diagnosis and management ofthis case with a literature review is discussed.

The Importance of Kidney Medullary Tissue for the Accurate Diagnosis of BK Virus Allograft Nephropathy.

BACKGROUND AND OBJECTIVES: The published tissue adequacy requirement of kidney medulla for BK virus allograft nephropathy diagnosis lacks systematic verification and competes against potential increased procedural risks from deeper sampling. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We evaluated whether the presence of kidney medulla improved the diagnostic rate of BK nephropathy in 2244 consecutive biopsy samples from 856 kidney transplants with detailed histologic and virologic results. RESULTS: Medulla was present in 821 samples (37%) and correlated with maximal core length (r=0.35; P<0.001). BK virus allograft nephropathy occurred in 74 (3% overall) but increased to 5% (42 of 821) with medulla compared with 2% (32 of 1423) for cortical samples (P<0.001). Biopsy medulla was associated with infection after comprehensive multivariable adjustment of confounders, including core length, glomerular number, and number of cores (adjusted odds ratio, 1.81; 95% confidence interval, 1.02 to 3.21; P=0.04). In viremic cases (n=275), medulla was associated with BK virus nephropathy diagnosis (39% versus 19% for cortex; P<0.001) and tissue polyomavirus load (Banff polyomavirus score 0.64±0.96 versus 0.33±1.00; P=0.006). Biopsy medulla was associated with BK virus allograft nephropathy using generalized estimating equation (odds ratio, 2.04; 95% confidence interval, 1.05 to 3.96; n=275) and propensity matched score comparison (odds ratio, 2.24; 95% confidence interval, 1.11 to 4.54; P=0.03 for 156 balanced pairs). Morphometric evaluation of Simian virus 40 large T immunohistochemistry found maximal infected tubules within the inner cortex and medullary regions (P<0.001 versus outer cortex). CONCLUSIONS: Active BK virus replication concentrated around the corticomedullary junction can explain the higher detection rates for BK virus allograft nephropathy with deep sampling. The current adequacy requirement specifying targeting medulla can be justified to minimize a missed diagnosis from undersampling.

The Pathophysiology and Impact of Inflammation in Nonscarred Renal Interstitium: The Banff i Lesion.

BACKGROUND: Interstitial inflammation (i-INT) is the driver of T-cell-mediated rejection. Its causes, pathophysiology, kinetics, and outcomes are poorly documented. METHODS: The role of i-INT was evaluated in 2055 biopsies from 775 renal transplant recipients. RESULTS: i-INT was present in 374 (18.2% prevalence) from acute and subclinical rejection (67.4%); interstitial fibrosis and tubular atrophy (14.4%); BK virus nephropathy (BKVAN) 9.9%; and acute tubular necrosis (ATN with i-INT) in 5.9% of cases. i-INT was predicted by prior T-cell-mediated rejection and BKVAN, human leukocyte antigen mismatch, cyclosporine therapy, and indication biopsy for dysfunction. It correlated with tubulitis, arteritis, and antibody markers within concurrent histology (P < 0.001). After treatment, renal functional recovery was best with histological ATN, milder i-INT, and early posttransplant biopsy times. The initial histological improvement of inflammation depended on baseline i-INT severity. Complete resolution to Banff i0 was predicted by early biopsy time, antilymphocyte therapy, recipient age, and medication compliance (all P < 0.001). Clearance i-INT was followed by delayed resolution of tubulitis (P < 0.001). i-INT was associated with histological ATN, renal dysfunction, and increased incident fibrosis on sequential pathology. Progressive fibrosis following related-rejection i-INT was dependent on tubulitis using multivariable analysis. In contrast, fibrogenesis after BKVAN or ATN was unrelated to inflammation. i-INT cases were followed by recurrent rejection in 35.3%, increased graft loss, and greater patient mortality. Multiple complementary outcome analyses determined the optimal lower diagnostic threshold for inflammation was Banff i1 score. CONCLUSIONS: i-INT is a heterogeneous pathological phenotype that results in adverse functional and structural outcomes, for which active and robust therapy should be considered.

Clinical Utility of Urinary Cytology to Detect BK Viral Nephropathy.

BACKGROUND: Reactivation of BK polyoma virus can result in destructive viral allograft nephropathy (BKVAN) with limited treatment options. Screening programs using surrogate markers of viral replication are important preventive strategies, guiding immunosuppression reduction. METHODS: We prospectively evaluated the diagnostic test performance of urinary decoy cells and urinary SV40T immunochemistry of exfoliated cells, to screen for BKVAN, (defined by reference histology with SV40 immunohistochemistry, n = 704 samples), compared with quantitative viremia, from 211 kidney and 141 kidney-pancreas transplant recipients. RESULTS: The disease prevalence of BKVAN was 2.6%. Decoy cells occurred in 95 of 704 (13.5%) samples, with a sensitivity of 66.7%, specificity of 88.6%, positive predictive value (PPV) of 11.7%, and negative predictive value of 98.5% to predict histologically proven BKVAN. Quantification of decoy cells improved the PPV to 32.1% (10 ≥ cells threshold). Immunohistochemical staining of urinary exfoliated cells for SV40T improved sensitivity to 85.7%, detecting atypical or degenerate infected cells (specificity of 92.3% and PPV of 33.3%), but was hampered by technical failures. Viremia occurred in 90 of 704 (12.8%) with sensitivity of 96.3%, specificity of 90.3%, PPV of 31.5%, and negative predictive value of 99.8%. The receiver-operator curve performance of quantitative viremia surpassed decoy cells (area under the curve of 0.95 and 0.79, respectively, P = 0.0018 for differences). Combining decoy cell and BK viremia in a diagnostic matrix improved prediction of BKVAN and diagnostic risk stratification, especially for high-level positive results. CONCLUSIONS: Although quantified decoy cells are acceptable surrogate markers of BK viral replication with unexceptional test performances, quantitative viremia displayed superior test characteristics and is suggested as the screening test of choice.

Intraoperative sentinel lymph node assessment in breast cancer: a comparison of rapid diagnostic method based on CK19 mRNA expression and imprint cytology.

BACKGROUND: Sentinel lymph node biopsy in breast cancer is a routine technique for staging the axilla. The two most common methods of intraoperative histopathological assessment, imprint cytology and frozen section, are hampered by poor sensitivity and lack standardized methodology. The one-step nuclei acid amplification (OSNA) assay is a rapid quantification of cytokeratin 19 mRNA. This prospective study compared an existing intraoperative imprint cytology protocol with the OSNA system. METHODS: Of the 110 prospectively recruited patients, 98 met the inclusion criteria with a total of 170 lymph nodes. Intraoperative sentinel nodes were serially sectioned and imprints made of each cut surface for cytological assessment. Alternate slices were submitted for OSNA while the remaining slices were for final histopathological evaluation with six hematoxylin and eosin levels and one AE1/AE3 immunoperoxidase stain of each slice. RESULTS: On histopathological analysis, 24.5% of patients (16.5% of nodes) had sentinel node metastases and 3.1% (2.4%) had isolated tumour cells. With isolated tumour cells cases taken as negative, the sensitivity of imprint cytology and OSNA compared with histopathology were 66.7% on patient basis (71.4% on per-node basis) and 95.8% (89.3%), respectively. One of 22 patients with macrometastases and two of three micrometastases were designated negative while five false-positive nodes were identified with OSNA, likely due to tissue allocation bias. CONCLUSION: The OSNA assay is highly sensitive in comparison with imprint cytology and may be used effectively in the intraoperative setting. Clinical follow-up studies are warranted to further assess its use in routine practice.

Detection of MYC rearrangement in high grade B cell lymphomas: correlation of MYC immunohistochemistry and FISH analysis.

The aim of this study was to analyse sensitivity, specificity and predictive values of recently available MYC immunohistochemistry (IHC) against the currently standard diagnostic method, fluorescence in situ hybridisation (FISH) analysis. MYC IHC and FISH analyses were performed on 30 cases of diffuse large B cell lymphoma (DLBCL) with 80% or more Ki-67 index, one case of DLBCL transformed from follicular lymphoma, three cases of B cell lymphoma intermediate between DLBCL and Burkitt lymphoma (IM), six cases of Burkitt lymphoma (BL) and one case of reactive lymph node. The inclusion criteria of high Ki-67 index, more than 80%, was imposed to exclude dependence of MYC positivity on Ki-67 positivity. The indices of specificity and positive predictive value (PPV) were low and varied widely with different thresholds of IHC positivity in percentage. At the threshold of 40% IHC positivity, specificity index was 0.45 and PPV was 0.37. At the threshold of 50% and 70% IHC positivity, specificity indices were 0.61 and 0.84, and PPVs were 0.45 and 0.67, respectively. Good sensitivity and negative predictive value (NPV) were maintained at all different thresholds. A heterogenous staining pattern of IHC was also noted. The heterogeneous IHC staining pattern observed warranted caution in interpretation and counting of IHC positive cells. MYC protein expression detected by IHC was more common than MYC translocation detected by FISH analysis. As a result, low specificity and PPV of MYC IHC, in relation to FISH analysis, were observed despite good sensitivity and NPV.