This issue contains papers that illustrate the scope of twenty-first century pathology. Some are classical descriptive anatomical papers, as pathological anatomy even in this molecular era continues to contribute essential basic data. Most papers, however, have a molecular focus between diagnostics and discovery. An example of a diagnostic molecular paper is the study by Aldecoa et al. (DOI 10.1007/s00428–016–1990-1). The question the group asked is whether molecular detection of the presence of epithelial (cancer) cells in lymph nodes in a colectomy specimen in a case of colon cancer might be a more accurate approach to detection of lymph node metastases. They took the negative lymph nodes from stages I–II (pN0) colorectal cancer patients and determined per lymph node the amount of tumor cytokeratin 19 mRNA with a quantitative molecular assay. A substantial number of cases turned out to be positive in this test. To determine whether this was clinically significant, they determined for each positive patient a total tumor load by adding up quantitative data from positive lymph nodes. Total tumor load was related to pT stage, tumor size, and tumor grade, classical high-risk factors for stage III colon cancer patients. This suggests that “molecular total lymph node tumor load” might be a quantitative and objective measure of lymph node involvement. Clinical application in terms of improved staging of early colon cancer patients, however, will need quite a bit of additional validation.
Telomerase has generated considerable interest in the cancer field for over two decades already, and recently, somatic activating mutations in the promoter of the telomerase reverse transcriptase (TERT) gene were found in a variety of cancer types. Nguyen et al. (DOI 10.1007/s00428–016–2001-2) looked for TERT promoter mutations, well known in urothelial carcinoma in the urinary tract, in the much rarer microcropapillary variant and included urothelial carcinoma with focal micropapillary features. They found TERT promoter mutations in pure micropapillary carcinomas but also in urothelial carcinomas with micropapillary foci. The authors conclude that conventional urothelial carcinoma and its micropapillary variant have a common oncogenesis. As yet, this finding does not seem to be “en route” towards daily diagnostics.
In the wave of molecular studies, much attention has been and still is dedicated to frequent cancer types. Bell et al. (DOI 10.1007/s00428–016-1985-y) decided to scrutinize relatively rare chordomas by whole-transcriptome shotgun sequencing, one of the state-of-the-art methods for expression profiling. This hunt resulted in more than 200 cancer-related transcripts, either up- or downregulated and containing expressed genes as well as non-coding RNA. Some of the chordoma defining transcripts, among which a series of developmental genes, merit to be further explored as potential biomarker or target for therapy. This dream figures frequently in the final phrase of an exploratory molecular paper, but the route between initial discovery and validated clinical application is characteristically long and sinuous. The cover image is from this paper and illustrates the network of genes discovered and defining chordoma.
With the paper of Brodsky et al. (DOI 10.1007/s00428–016-1994-x), we shift gears completely. The paper presents classical anatomical data in their simplest form: organ weight. The study was motivated by the shift in body weight that reflects the (almost) global obesity epidemic. The authors reasoned that standard reference tables for organ weights provide little or no information on individuals with a pathologically increased body mass index. They set out to produce reference tables for organ weight based on more than 800 autopsies, more than half cases of death due to natural causes. In the tables, a distinction is made between naturally deceased and non-naturally deceased individuals, degree of overweight but also gender, age, and race. A striking finding in the paper is the higher variation in organ weight between individuals who died of natural causes than in those with a non-natural cause of death. As explanation, the existence of comorbidity in natural death cases is proposed, specifics of comorbidity bearing on the weight of specific organs. For those of us still concerned with autopsies, important data. For those of us no longer concerned with autopsies, an evidence based confrontation with the consequences of obesity: food for thought!