Critical diagnoses in paediatric gastrointestinal diseases.

Gastrointestinal biopsies represent an increasing proportion of the paediatric pathologist's workload, an increase fundamentally due to an expansion of the understanding of the basic clinical, molecular, genetic, and histopathological features of paediatric gastrointestinal disorders. The histological interpretation of endoscopically retrieved gastrointestinal biopsies in children requires a unique set of diagnostic expertise and detailed knowledge of various gastrointestinal disorders that have a predilection for the paediatric population. This article's major role is to highlight the unique problems inherent to paediatric gastrointestinal disorders that require immediate communication with the paediatric surgeon or the gastroenterologist. For this, we tried to cover the most important diseases that a paediatric pathologist might encounter in daily practice. Some of these diseases are relatively rare, such as microvillous inclusion disease and tufting enteropathy, but some are more common such as eosinophilic disorders and inflammatory bowel disease. Awareness of the histopathological features of these diseases, particularly those that are relatively uncommon, is crucial to spare the patient a lengthy and costly evaluation. We made a particular effort to abundantly reference this article should the reader wish to expand on the content of any section.

"Collecting duct carcinoma of the kidney: diagnosis and implications for management".

Collecting duct carcinoma of the kidney is a rare and aggressive subtype of renal cell carcinoma (RCC) arising from the distal convoluted tubules. At the time of diagnosis, patients are more frequently symptomatic, with advanced locoregional stage, and have metastatic disease. The 2016 WHO Classification of Tumours of the Urinary System defined diagnostic criteria for this entity. However, the diagnostic features continue to evolve, with typical, but not entirely specific, histologic and immunophenotypic characteristics. In addition, the lack of consistent molecular alterations makes collecting duct carcinoma a diagnosis of exclusion, with historical cases being re-classified as fumarate hydratase deficient RCC, ALK rearranged RCC, renal medullary carcinoma or high-grade urothelial carcinoma. The rarity and poor prognosis of the tumor makes it difficult to reach consensus guidelines to guide therapy. In this manuscript we review the clinicopathologic features of collecting duct carcinoma including pathologic diagnostic criteria, molecular characteristics and differential diagnosis, and their possible implications for management.

Utility of GATA-3 and Cytokeratin 5/6 Immunostains in Separating Condyloma Acuminatum Arising in the Urinary Tract From Non-Invasive Papillary Urothelial Carcinoma.

Background Condyloma acuminatum is a squamous epithelial lesion which uncommonly involves the urinary tract. In this location, non-invasive papillary urothelial carcinoma constitutes one of the main differential diagnoses with significant prognostic and therapeutic implications. To date, no ancillary immunohistochemical stain has been described to differentiate these two entities. We assess the utility of cytokeratin 5/6 (CK5/6) and GATA-3 immunohistochemistry in distinguishing condyloma acuminatum from non-invasive papillary urothelial carcinoma. Design We reviewed 9 condylomata acuminata involving the urinary tract, 12 low-grade and 8 high-grade non-invasive papillary urothelial carcinomas. CK5/6 immunostaining was performed in all cases. GATA-3 immunostaining and low-risk human papilloma virus (HPV) chromogenic in situ hybridization was performed in all condyloma cases and 2 urothelial carcinomas with squamous differentiation. Results 8/9 condylomata acuminata were positive for low-risk HPV. All condylomata acuminata exhibited strong full-thickness cytoplasmic staining for CK5/6. In 10 of 12 low-grade non-invasive papillary urothelial carcinomas, CK5/6 expression was continuous and limited to the basal cell layer, while it was patchy and limited to the basal cell layer in all 8 high-grade non-invasive papillary urothelial carcinomas. Two low-grade non-invasive papillary urothelial carcinomas showed focal full-thickness CK5/6 expression in the areas of squamous differentiation. These 2 cases were negative for low-risk HPV. GATA-3 immunostaining was positive in all condylomata acuminata. Conclusions CK5/6 immunostaining is a useful and simple tool that can help separate low-grade and high-grade non-invasive papillary urothelial carcinomas from condyloma acuminatum involving the urothelium-lined organs. GATA-3 has no discriminatory role between condyloma acuminatum and papillary urothelial carcinomas.

Novel fusion genes in spindle cell rhabdomyosarcoma: The spectrum broadens.

Rhabdomyosarcoma (RMS) encompasses a heterogeneous group of tumors with striated muscle differentiation. RMSs are classified as alveolar, embryonal, spindle cell/sclerosing, and pleomorphic types and molecular analysis of these tumors has identified aberrations that are useful in their further subclassification. Spindle cell rhabdomyosarcoma (SpRMS) is uncommon and has been described with VGLL2 fusions, EWSR1/FUS-TFCP2 rearrangements, and myoD1 mutations-the mutations are associated with significantly different prognoses. In addition, the NCOA2-MEIS1 fusion gene was recently described in two primary intraosseous RMS that contained spindle cell components. Herein, we report three cases of SpRMS harboring different novel fusion genes, one possessing EP300-VGLL3, a second with NCOA2-MEIS1 and CAV1-MET, and the third case had HMGA2-NEGR1 and multiple amplified genes.

Diffuse interstitial fibrosis assessed by cardiac magnetic resonance is associated with dispersion of ventricular repolarization in patients with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is characterized by myocyte hypertrophy, disarray, fibrosis, and increased risk for ventricular arrhythmias. Increased QT dispersion has been reported in patients with HCM, but the underlying mechanisms have not been completely elucidated. In this study, we examined the relationship between diffuse interstitial fibrosis, replacement fibrosis, QTc dispersion and ventricular arrhythmias in patients with HCM. We hypothesized that fibrosis would slow impulse propagation and increase dispersion of ventricular repolarization, resulting in increased QTc dispersion on surface electrocardiogram (ECG) and ventricular arrhythmias. METHODS: ECG and cardiac magnetic resonance (CMR) image analyses were performed retrospectively in 112 patients with a clinical diagnosis of HCM. Replacement fibrosis was assessed by measuring late gadolinium (Gd) enhancement (LGE), using a semi-automated threshold technique. Diffuse interstitial fibrosis was assessed by measuring T1 relaxation times after Gd administration, using the Look-Locker sequence. QTc dispersion was measured digitally in the septal/anterior (V1-V4), inferior (II, III, and aVF), and lateral (I, aVL, V5, and V6) lead groups on surface ECG. RESULTS: All patients had evidence of asymmetric septal hypertrophy. LGE was evident in 70 (63%) patients; the median T1 relaxation time was 411±38 ms. An inverse correlation was observed between T1 relaxation time and QTc dispersion in leads V1-V4 (p<0.001). Patients with HCM who developed sustained ventricular tachycardia had slightly higher probability of increased QTc dispersion in leads V1-V4 (odds ratio, 1.011 [1.004-1.0178, p=0.003). We found no correlation between presence and percentage of LGE and QTc dispersion. CONCLUSION: Diffuse interstitial fibrosis is associated with increased dispersion of ventricular repolarization in leads, reflecting electrical activity in the hypertrophied septum. Interstitial fibrosis combined with ion channel/gap junction remodeling in the septum could lead to inhomogeneity of ventricular refractoriness, resulting in increased QTc dispersion in leads V1-V4.

Prostate biopsy and radical prostatectomy Gleason score correlation in heterogenous tumors: proposal for a composite Gleason score.

When prostate biopsy cores are separately identified in multiple containers, current recommendations are to grade each specimen individually. For treatment algorithms, the highest Gleason score (HGS) is typically used as the overall score, even if a lower score predominates. This practice has the potential to misrepresent the overall cancer in the entire gland for some patients and place them in a higher-grade group. We compare a novel composite Gleason score (CGS), integrating grade patterns from contiguous positive biopsy sites, with HGS to determine correlation with the radical prostatectomy (RP) Gleason score (GS). One hundred needle biopsy cases from 2008 to 2012 with >2 GSs in a biopsy set (eg, 3+3=6, 3+4=7, and 4+3=7) or more than a 1-step difference in GS (eg, 3+4=7 and 4+4=8 without 4+3=7) were analyzed. Grades were assigned using both methods (HGS and CGS) and compared with RPGS. Grade groups I to V were used to define downgrade and upgrade. Comparing HGS with RPGS, 31% remained the same and 69% had a change in GS (87% downgraded and 13% upgraded). Comparing CGS with RPGS, 59% remained the same and 41% had a change in GS (10% downgraded and 90% upgraded). Of the 2 methods, the CGS showed better overall correlation with RP (P<0.001) and was less likely to be downgraded compared with HGS. CGS correlates better with RPGS than HGS when >2 grades are present in a biopsy set. CGS has a significantly lower rate of downgrade and predicts the RPGS more accurately than HGS.

Does discontinuous involvement of a prostatic needle biopsy core by adenocarcinoma correlate with a large tumor focus at radical prostatectomy?

When prostate needle biopsies are involved discontinuously by tumor, no consensus remains on the optimal method of tumor quantification. We investigated whether discontinuous biopsy involvement usually results from a large tumor focus or multiple small foci. Prostate needle biopsies with discontinuous tumor and corresponding whole-mounted radical prostatectomies from 2008 to 2013 were analyzed. Linear length and percentage of biopsy involvement were measured both including and subtracting the benign intervening tissue. The corresponding region of the prostatectomy specimen was evaluated for tumor size and multifocality. From over 800 biopsy sets and 400 prostatectomies performed annually, 40 patients met inclusion criteria. Excluding benign tissue, length and percentage of biopsy involvement ranged from 1 to 7 mm and 5% to 66% (median 2.5 mm, 20%), whereas including intervening tissue yielded 4 to 15.5 mm and 25% to 100%, (median 7 mm, 70%), respectively. Benign intervening tissue measured from 2 to 10.5 mm (median 3.5 mm). In 31 patients (78%), a single tumor focus was present in the corresponding region of the prostate (the dominant tumor in 25/31). In 9 patients, multiple small foci were present. Eleven patients could have been excluded from active surveillance eligibility by measuring tumor from end to end (>50% involvement), of whom only 1 met criteria for clinically insignificant cancer at prostatectomy. Discontinuous tumor in a prostate biopsy often results from a single tumor focus in the corresponding region of the prostate (78%). Therefore, we recommend that an end-to-end measurement be provided, with accompanying diagnostic comment that this often correlates with the size of a single tumor focus.