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Aims: To evaluate aspects of the current practice of sentinel lymph node (SLN) pathology in breast cancer via a questionnaire based survey, to recognise major issues that the European guidelines for mammography screening should address in the next revision. Methods: A questionnaire was circulated by mail or electronically by the authors in their respective countries. Replies from pathology units dealing with SLN specimens were evaluated further. Results: Of the 382 respondents, 240 European pathology units were dealing with SLN specimens. Sixty per cent of these units carried out intraoperative assessment, most commonly consisting of frozen sections. Most units slice larger SLNs into pieces and only 12% assess these slices on a single haematoxylin and eosin (HE) stained slide. Seventy one per cent of the units routinely use immunohistochemistry in all cases negative by HE. The terms micrometastasis, submicrometastasis, and isolated tumour cells (ITCs) are used in 93%, 22%, and 71% of units, respectively, but have a rather heterogeneous interpretation. Molecular SLN staging was reported by only 10 units (4%). Most institutions have their own guidelines for SLN processing, but some countries also have well recognised national guidelines. Conclusions: Pathological examination of SLNs throughout Europe varies considerably and is not standardised. The European guidelines should focus on standardising examination. They should recommend techniques that identify metastases . 2 mm as a minimum standard. Uniform reporting of additional findings may also be important, because micrometastases and ITCs may in the future be shown to have clinical relevance.

To assess the variability of oestrogen receptor (ER) testing using immunocytochemistry, centrally stained and unstained slides from breast cancers were circulated to the members of the European Working Group for Breast Screening Pathology, who were asked to report on both slides. The results showed that there was almost complete concordance among readers (kappa=0.95) in ER-negative tumours on the stained slide and excellent concordance among readers (kappa=0.82) on the slides stained in each individual laboratory. Tumours showing strong positivity were reasonably well assessed (kappa=0.57 and 0.4, respectively), but there was less concordance in tumours with moderate and low levels of ER, especially when these were heterogeneous in their staining. Because of the variation, the Working Group recommends that laboratories performing these stains should take part in a external quality assurance scheme for immunocytochemistry, should include a tumour with low ER levels as a weak positive control and should audit the percentage positive tumours in their laboratory against the accepted norms annually. The Quick score method of receptor assessment may also have too many categories for good concordance, and grouping of these into fewer categories may remove some of the variation among laboratories.

Cell omics such as single-cell genomics, proteomics and microbiomics allow the characterisation of tissue and microbial community composition, which can be compared between conditions to identify biological drivers. This strategy has been critical to unveiling markers of disease progression such as cancer and pathogen infection. For cell omic data, no method for differential variability analysis exists, and methods for differential composition analysis only take a few fundamental data properties into account. Here we introduce sccomp, a generalised method for differential composition and variability analyses able to jointly model data count distribution, compositionality, group-specific variability and proportion mean-variability association, with awareness against outliers. Sccomp is an extensive analysis framework that allows realistic data simulation and cross-study knowledge transfer. Here, we demonstrate that mean-variability association is ubiquitous across technologies showing the inadequacy of the very popular Dirichlet-multinomial modelling and provide mandatory principles for differential variability analysis. We show that sccomp accurately fits experimental data, with a 50% incremental improvement over state-of-the-art algorithms. Using sccomp, we identified novel differential constraints and composition in the microenvironment of primary breast cancer.Significance statementDetermining the composition of cell populations is made possible by technologies like single-cell transcriptomics, CyTOF and microbiome sequencing. Such analyses are now widespread across fields (~800 publications/month, Scopus). However, existing methods for differential abundance do not model all data features, and cell-type/taxa specific differential variability is not yet possible. Increase in the variability of tissue composition and microbial communities is a well-known indicator of loss of homeostasis and disease. A suitable statistical method would enable new types of analyses to identify component-specific loss of homeostasis for the first time. This and other innovations are now possible through our discovery of the mean-variability association for compositional data. Based on this fundamental observation, we have developed a new statistical model, sccomp, that enables differential variability analysis for composition data, improved differential abundance analyses, with cross-sample information borrowing, outlier identification and exclusion, realistic data simulation, based on experimental datasets, cross-study knowledge transfer.

We report a case of granular‐cell tumor (GCT) in the esophagus. This is a rare location for this tumor and only 80 cases have been described. The tumor was diagnosed in a 24‐yr‐old woman with epigastralgia. Endoscopic examination revealed a submucosal ulcerated lesion. The smears derived from esophageal brushings contained clusters of granular cells. Histologic examination of the endoscopic biopsy provided diagnostic confirmation of GCT. To our knowledge, this is the first reported case of esophageal GCT in which the characteristic tumor cells were seen in the endoscopic brushing material. This case demonstrates that a cytologic diagnosis of GCT is possible if the lesion is ulcerated and/or brushing is subsequent to taking the biopsy. Although rare in the esophagus, GCT should be considered in the differential diagnosis of esophageal neoplasms. Diagn. Cytopathol. 1998;19:455–457. © 1998 Wiley‐Liss, Inc.