Verification and Validation of Digital Pathology (Whole Slide Imaging) for Primary Histopathological Diagnosis: All Wales Experience.

AIMS: The study is aimed to verify Aperio AT2 scanner for reporting on the digital pathology platform (DP) and to validate the cohort of pathologists in the interpretation of DP for routine diagnostic histopathological services in Wales, United Kingdom. MATERIALS METHODS AND RESULTS: This was a large multicenter study involving seven hospitals across Wales and unique with 22 (largest number) pathologists participating. 7491 slides from 3001 cases were scanned on Leica Aperio AT2 scanner and reported on digital workstations with Leica software of e-slide manager. A senior pathology fellow compared DP reports with authorized reports on glass slide (GS). A panel of expert pathologists reviewed the discrepant cases under multiheader microscope to establish ground truth. 2745 out of 3001 (91%) cases showed complete concordance between DP and GS reports. Two hundred and fifty-six cases showed discrepancies in diagnosis, of which 170 (5.6%) were deemed of no clinical significance by the review panel. There were 86 (2.9%) clinically significant discrepancies in the diagnosis between DP and GS. The concordance was raised to 97.1% after discounting clinically insignificant discrepancies. Ground truth lay with DP in 28 out of 86 clinically significant discrepancies and with GS in 58 cases. Sensitivity of DP was 98.07% (confidence interval [CI] 97.57-98.56%); for GS was 99.07% (CI 98.72-99.41%). CONCLUSIONS: We concluded that Leica Aperio AT2 scanner produces adequate quality of images for routine histopathologic diagnosis. Pathologists were able to diagnose in DP with good concordance as with GS. STRENGTHS AND LIMITATIONS OF THIS STUDY: Strengths of this study - This was a prospective blind study. Different pathologists reported digital and glass arms at different times giving an ambience of real-time reporting. There was standardized use of software and hardware across Wales. A strong managerial support from efficiency through the technology group was a key factor for the implementation of the study. LIMITATIONS: This study did not include Cytopathology and in situ hybridization slides. Difficulty in achieving surgical pathology practise standardization across the whole country contributed to intra-observer variations.

The diagnostic challenge of pulmonary Kaposi's sarcoma with pulmonary tuberculosis in a renal transplant recipient: a case report.

We report a case of a 39-year-old, HIV-negative, post renal transplant patient who developed mucocutaneous Kaposi's sarcoma with lung parenchymal involvement and concurrently culture proven pulmonary tuberculosis. To the best of our knowledge, this is the first case report of this combination, which presented with cavitating lung nodules and responded well to withdrawal of immunosuppressive drugs beside antituberculous treatment.

Acanthoma fissuratum.

Acanthoma fissuratum secondary to the use of spectacles is a rare clinical finding associated with an ill-fitting frame. An interesting case is presented to highlight such a problem. Surgical excision of such lesions is recommended with advice to the patient regarding the suitable fitting of spectacles.

Acute tubular necrosis due to captopril.

Angiotensin-converting enzyme (ACE) inhibitors are standard therapy for congestive cardiac failure. ACE inhibitors have been used worldwide and are usually safe and have relatively few side effects. Hypotension can develop with the first dose of captopril and can lead to symptomatic renal hypoperfusion with subsequent acute renal failure (ARF). The case of a 65-year-old patient with congestive heart failure who developed acute renal failure following the first dose of captopril is described. He required hemodialysis for 8 weeks for the improvement of his renal function and urinary output. The renal biopsy confirmed the presence of acute tubular necrosis. The reversibility of captopril-induced ARF is confirmed and the patient made an uneventful recovery. An immunoallergic mechanism is not thought to have been responsible for this adverse effect. It is advised that caution should be exerted in giving ACE inhibitors to elderly patients with congestive heart failure, particularly if they are on diuretics. Routine biochemical monitoring is suggested before and during captopril therapy.

Unilateral papillary necrosis complicating renal artery stenosis--evidence of activation of the intrarenal renin-angiotensin system?

We report an association between renal artery stenosis and papillary necrosis. We studied three kidneys with renal artery stenosis, two of which showed ipsilateral acute papillary necrosis. In all three cases there had been a sudden fall in perfusion of the ischaemic kidney. In the case with intact papillae, immunostainable renin was normal in amount and distribution, whereas both kidneys with papillary necrosis showed hyperplasia of renin-containing cells, and these were mainly in the JGAs of the juxtamedullary cortex. Since the contralateral kidneys were spared, we suggest that in an ischaemic kidney with hyperplasia of renin-secreting cells in the deep cortex, local activation of the renin-angiotensin system could cause acute papillary necrosis due to vasoconstriction.

Celiac disease in Arabs.

A systematic study of celiac disease in a defined population of Arab children has not been previously reported. We therefore performed a prospective study to determine the incidence and clinical presentation of celiac disease in Jordanian children. A total of 34 (12 boys and 22 girls) cases were diagnosed over a period of 36 months. Nine cases were clustered in three families. The incidence was calculated to be 1:2,800 live births. The mean age at presentation was 4.6 years (range 0.3-13), but it was 8.4 years at the time of diagnosis. Diarrhea was the main initial symptom in 15 (44%) patients. Other signs and symptoms included recurrent abdominal pain in five patients (14%), short stature in four (12%), abdominal distension in three (9%), constipation in three (9%), pallor and recurrent mouth ulcers in two patients each. At the time of diagnosis, 24 (71%) had hypochromic microcytic anemia, and nine (26%) had rickets. The relatively high incidence of celiac disease may be related to the large wheat consumption in this population (135 kg/head/year), and the late onset could be related to the widespread prevalence of prolonged breast-feeding in Jordan (12 months) and late introduction of cereals (6.2 months) in children with late presentation. The delay in diagnosis might be due to the presence of other diseases clinically resembling celiac disease in our community.

Abnormalities of intrahepatic bile ducts in extrahepatic biliary atresia.

The infantile cholangiopathies are a group of conditions associated with neonatal jaundice, which include extrahepatic biliary atresia, paucity of intra-hepatic bile ducts and disorders associated with persistence of fetal biliary structures, the so-called ductal plate malformations. Although previously regarded as distinct entities, it has recently been suggested that they may represent parts of a disease spectrum in which the principal process is one of bile duct destruction, the morphological manifestations in individual cases being influenced by the stage of intra-uterine development at which such injury occurs and by the site within the biliary system at which there is maximum damage. To further examine this concept, we have studied liver biopsy specimens from 37 neonates with extrahepatic biliary atresia, with particular reference to abnormalities of the intrahepatic bile ducts. Paucity of intrahepatic ducts, defined as a bile duct: portal tract ratio of less than 0.9, was identified in six cases (16.2%). In eight cases (21.6%) we found concentric tubular ductal structures similar to those observed in ductal plate malformations. In one case, both abnormalities could be demonstrated. Our findings support the concept that there is overlap between the various types of infantile cholangiopathy.

Pyostomatitis vegetans in childhood.

UNLABELLED: Pyostomatitis vegetans is an oral eruption, characterized by small pustules, ulcers and erythematous vegetations of the labial and buccal mucosae as well as labial-attached gingivae. Its importance lies in its high correlation with inflammatory bowel disease. It is commonly associated with skin and inflammatory bowel disease and is rare in children. We here report a sister and brother with onset of the disease at the age of 5 and 7 years, respectively. It is the first report of familial pyostomatitis vegetans occurring in the youngest patients hitherto reported. CONCLUSION: The observation of two sibs with pyostomatitis, vegetans pyoderma gangrenosum and inflammatory bowel disease suggest a hereditary disposition to this rare triad.

Distribution of renin-containing cells in the developing human kidney: an immunocytochemical study.

OBJECTIVE: To characterize the pattern of renin containing cells (RCC) within the human kidney between 20 weeks of gestation and 6 months of postnatal life. DESIGN: Descriptive study using paraffin-embedded blocks of kidney stored following postmortem examination. METHODS: Sections of kidney were stained immunocytochemically using an antibody to human renin; the proportion of RCC within each of three zones (superficial, middle and deep) of the cortex, and their anatomical relation to individual glomeruli were determined. The cases were divided into five groups for analysis to gestational or postnatal age. RESULTS: Fetal RCC were usually at the vascular pole of the most mature glomeruli within the deeper areas of the cortex and were occasionally located within glomeruli. This distribution persisted until birth, even when the kidney was histologically mature. By contrast there were fewer RCC in neonatal and infant kidneys and, as in adult kidneys, these were located predominantly in the superficial cortex. CONCLUSION: The change in RCC distribution around the time of normal birth may relate to the transition to independent renal function. The location and density of RCC during fetal life may influence renal perfusion and amniotic fluid production.