Reducing workload in malignant melanoma sentinel node examination: a national study of pathology reports from 507 melanoma patients.

AIMS: Even though extensive melanoma sentinel node (SN) pathology protocols increase metastasis detection, there is a need for balancing high detection rates with reasonable workload. A newly tested Danish protocol recommended examining nodes at six levels 150 µm apart (six-level model) and using SOX10 and Melan-A immunohistochemistry (IHC). We explored if a protocol examining 3 levels 300 µm apart (three-level model) combined with IHC would compromise metastasis detection. The study aim was to optimise the protocol to reduce workload without compromising detection rate. METHODS: 8 months after protocol implementation, we reviewed the pathology reports of SNs from 507 melanoma patients nationwide, including 117 SN-positive patients. Each report was reviewed to determine histopathological features, including detection of metastasis, exact levels with metastasis, exact levels with metastasis >1 mm in diameter and IHC results. RESULTS: The six-level model detected metastases in 23% of patients, whereas the three-level model would have detected metastases in 22% of patients. The three-level model would have missed a few small metastases (n=4), measuring <0.1 mm, 0.1 mm, 0.4 mm and 0.1 mm, respectively. The six-level model detected metastases >1 mm in 7% of patients. One of these metastases (measuring 1.1 mm) would have been detected by the three-level model, but not as >1 mm. SOX10 and Melan-A had equal sensitivity. CONCLUSIONS: Reducing the number of levels examined to three levels 300 µm apart combined with IHC does not have significant impact on metastasis detection rate, and we will therefore recommend that the future melanoma SN guideline takes this into consideration to reduce overall workload.

Intravenous Pyogenic Granuloma in the Inguinal Canal Mimicking Lymph Node Metastasis on PSMA PET/CT.

ABSTRACT: We present a 68-year-old man with newly diagnosed high-risk prostate cancer who was referred for PSMA PET/CT after the initial CT showed a contrast-enhanced structure resembling a lymph node in the left inguinal canal. No other findings suggesting metastatic disease were seen on CT or bone scintigraphy. PSMA PET/CT showed moderate PSMA uptake in the inguinal tissue, substantiating an unexpected location of lymph node metastasis. The uncommon location warranted an excision biopsy, and an IV pyogenic granuloma was diagnosed on histological examination, emphasizing the importance of biopsy of unexpected findings.

Thrombotic Microangiopathy in Inverted Formin 2-Mediated Renal Disease.

The demonstration of impaired C regulation in the thrombotic microangiopathy (TMA) atypical hemolytic uremic syndrome (aHUS) resulted in the successful introduction of the C inhibitor eculizumab into clinical practice. C abnormalities account for approximately 50% of aHUS cases; however, mutations in the non-C gene diacylglycerol kinase-ε have been described recently in individuals not responsive to eculizumab. We report here a family in which the proposita presented with aHUS but did not respond to eculizumab. Her mother had previously presented with a post-renal transplant TMA. Both the proposita and her mother also had Charcot-Marie-Tooth disease. Using whole-exome sequencing, we identified a mutation in the inverted formin 2 gene (INF2) in the mutational hotspot for FSGS. Subsequent analysis of the Newcastle aHUS cohort identified another family with a functionally-significant mutation in INF2 In this family, renal transplantation was associated with post-transplant TMA. All individuals with INF2 mutations presenting with a TMA also had aHUS risk haplotypes, potentially accounting for the genetic pleiotropy. Identifying individuals with TMAs who may not respond to eculizumab will avoid prolonged exposure of such individuals to the infectious complications of terminal pathway C blockade.

Use of eculizumab in crescentic IgA nephropathy: proof of principle and conundrum?

IgA nephropathy (IgAN) is characterized by a variable clinical course and multifaceted pathophysiology. There is substantial evidence to suggest that complement activation plays a pivotal role in the pathogenesis of the disease. Therefore, complement inhibition using the humanized anti-C5 monoclonal antibody eculizumab could be a rational treatment. We report here a 16-year-old male with the vasculitic form of IgAN who failed to respond to aggressive conventional therapy including high-dose steroids, cyclophosphamide and plasma exchange and who was treated with four weekly doses of 900 mg eculizumab followed by a single dose of 1200 mg. He responded rapidly to this treatment and has had a stable creatinine around 150 µmol/L (1.67 mg/dL) for >6 months. However, proteinuria was unabated on maximal conventional anti-proteinuric treatment, and a repeat renal biopsy 11 months after presentation revealed severe chronic changes. We believe this case provides proof of principle that complement inhibition may be beneficial in IgAN but also that development of chronicity may be independent of complement.

Mazabraud's syndrome: case report and literature review.

Mazabraud's syndrome is a rare disorder characterized by the association of single or multiple intramuscular myxomas with fibrous dysplasia. Here, we present the first case of Mazabraud's syndrome visualized on 18F-FDG PET/CT with histopathological confirmation of the myxoma. Our case demonstrates a slightly increased FDG uptake (SUVmax 2.1) within the myxomas and a moderately to highly increased tracer uptake (SUVmax 7.0) within the fibrous dysplastic lesions. The typical histological appearance of the intramuscular myxoma confirmed the radiological diagnosis. Further, we discuss the imaging findings and the histopathological features of this rare case with a review of the related literature.

Carotid artery atherosclerotic plaque: clinical and morphological-immunohistochemical correlation.

BACKGROUND: The purpose of the study was to: 1) investigate carotid atherosclerotic plaque morphology and immunohistochemistry (IHC) with respect to the localization sites of Chlamydia pneumoniae, 2) find correlations between plaque morphology and clinical sonographical characteristics, and 3) determine the correlation between abundance of C. pneumoniae and complexity of the plaque. MATERIAL/METHODS: 200 patients with asymptomatic (A=59) and symptomatic (S=141) courses of carotid stenosis admitted to the Neurology and Neurosurgery Clinic for TIA or acute ischemic stroke were studied. For IHC the atherosclerotic plaques were incubated with primarily monoclonal anti-Chlamydia pneumoniae antibody clone RP402, code no. M6600, diluted 1:50 (DAKO). Statistical evaluation was performed. RESULTS: 34 (17%) homogeneous (HO), or stable, and 166 (83%) heterogeneous (HE), or unstable, plaques were divided into 3 HO and 5 HE subtypes according to the number of histopathological signs and prevalence of inflammatory cell types, having different sonographical characteristics and plaque thickness. Complex plaques of both A and S patients have activation signs for chronic inflammation, phagocytosis, and atheromatosis: all three of these in HE plaque subtypes, and only for atheromatosis in HO plaques. CONCLUSIONS: 1) C. pneumoniae IHC signals were found in every kind of phagocyte (histiocytes, macrophages, foreign body macrophages, foam cells, PMNs) located in the fibrous cap, atheroma (necrotic core), and especially at the boundary of fibrous cap/atheroma; 2) complexities were found, so plaque instability signs strongly correlate with abundance of C. pneumoniae (p<0.001); 3) sufficient correlation between plaque thickness and disease symptomaticity (p<0.01) was found.

[Potential causes of antigenemia in the patients with an immune complex-mediated membranoproliferative glomerulonephritis in Lithuania]. / Galimos imunokompleksinio membranoproliferacinio glomerulonefrito antigenemijos priezastys Lietuvoje.

UNLABELLED: The pathogenesis of an immune complex-mediated membranoproliferative glomerulonephritis (IMPGN) involves persistent deposition of circulating immune complexes in the glomeruli caused by persistent antigenemia. We have previously reported relatively high incidence of IMPGN in Lithuania. The objective of our study was to evaluate potential causes of persistent antigenemia in the patients with IMPGN. MATERIAL AND METHODS: Forty-five patients with IMPGN diagnosed on renal biopsy during 2000-2002 were retrospectively evaluated for the presence of persistent bacterial or viral infections, autoimmune diseases and other associated medical conditions. Patients with established diagnosis of systemic lupus erythematosus (SLE) before the biopsy were not included in the study. RESULTS: A great majority (20; 44%) of the patients were found to have persistent bacterial infections of various localization. Four patients (9%) were infected with hepatitis B virus (HBV). Three (7%) patients were eventually diagnosed with SLE and another 3 (7%) had other associated pathology. In the remaining 15 (33%) patients, IMPGN remained idiopathic. Testing for hepatitis C virus (HCV) antibody was performed in 36 patients (12 of them with idiopathic IMPGN) and was negative in all patients. Testing for HCV RNA was not performed. Patients with bacterial infections were significantly younger compared to the group of idiopathic IMPGN (36.5+/-19.1 and 53.8+/-16.4, respectively, p=0.01). We conclude that persistent bacterial infection was a major potential source of antigenemia in our patients with IMPGN, particularly in the younger patients, while HBV and HCV infection was rarely detected.