No abstract

Tumour associated macrophages (TAMs) are increasingly recognized as supporters of tumour growth. The present study was undertaken to examine benign pilocytic astrocytomas (PAs) for the presence of M2 macrophages. We have asked the question whether TAMs in PAs share the predominant CD163 immunophenotype with tumour-associated microglia/macrophages of malignant gliomas. In addition, we were interested in the question whether there is evidence that the macrophages in PAs derive from resident microglia in surrounding normal brain or whether cells expressing a macrophage phenotype may invade PAs from the vasculature. The latter question is of great interest with regard to so-called "bone marrow-derived microglia" (BMDM) which may provide a physiological route of entry into the CNS that could be used for novel cell-based treatments of brain cancer. In fact, we have found strong morphological evidence for such macrophage recruitment into PAs. We propose therefore that PAs may be used as a model for the study of macrophage recruitment into gliomas. Importantly, our results also confirm that microglia/macrophage infiltration per se is not associated with malignant glioma behaviour.

Background Although 10% formalin is a standard preservative in pancreatic FNAs, the effect of CytoLyt on pancreatic tissue preservation has not been systematically explored. Methods Smears and cell blocks from CytoLyt‐fixed (CF‐CBs) and formalin‐fixed (FF‐CBs) pancreatic FNAs were blindly reviewed without knowledge of the fixative used, and the presence of tissue/tumor autolysis was noted. Controls included FF‐CBs from pancreatic FNAs, CF‐CBs from nonpancreatic FNAs, and 4 pancreatic FNAs with matched CF‐CBs and FF‐CBs. Results We found that 62 of 85 (73%) pancreatic FNAs with CF‐CBs showed significant autolysis, which was most pronounced in acinar cells and/or tumor cells with benign acinar cells in the background, compared with 2 of 46 (4%) FF‐CBs (P < .0001) and 3 of 26 (12%) CF‐CBs from nonpancreatic FNAs (73% vs 12%; P < .0001). Of the 4 pancreatic FNAs with matched CF‐CBs and FF‐CBs, all 4 CF‐CBs showed marked autolysis versus none of the matched FF‐CBs. Of the 23 (27%) pancreatic FNAs with CF‐CBs that did not show autolysis, 10 had no acinar cells, and 7 had only minute tissue fragments on CB. Conclusion While CytoLyt is a useful fixative for nonpancreatic FNAs it is a suboptimal fixative for pancreatic FNAs and is associated with tissue/tumor autolysis in the majority of cases, influencing morphologic evaluation, and potentially immunocytochemical staining. Autolysis appears to be due to acinar enzymes whose effect is likely interrupted/inhibited by formalin fixation. Cytopathologists and cytotechnologists should be mindful of this pitfall and should avoid using CytoLyt as a fixative for pancreatic FNAs.

No abstract

We describe a woman with the known pathogenic germline variant CHEK2:c.1100delC and synchronous diagnoses of both pelvic genital type leiomyosarcoma (LMS) and metastatic invasive ductal breast carcinoma. CHEK2 (checkpoint kinase 2) is a tumor-suppressor gene encoding a serine/threonine-protein kinase (CHEK2) involved in double-strand DNA break repair and cell cycle arrest. The CHEK2:c.1100delC variant is a moderate penetrance allele resulting in an approximately twofold increase in breast cancer risk. Whole-genome and whole-transcriptome sequencing were performed on the leiomyosarcoma and matched blood-derived DNA. Despite the presence of several genomic hits within the double-strand DNA damage pathway (CHEK2 germline variant and multiple RAD51B somatic structural variants), tumor profiling did not show an obvious DNA repair deficiency signature. However, even though the LMS displayed clear malignant features, its genomic profiling revealed several characteristics classically associated with leiomyomas including a translocation, t(12;14), with one breakpoint disrupting RAD51B and the other breakpoint upstream of HMGA2 with very high expression of HMGA2 and PLAG1. This is the first report of LMS genomic profiling in a patient with the germline CHEK2:c.1100delC variant and an additional diagnosis of metastatic invasive ductal breast carcinoma. We also describe a possible mechanistic relationship between leiomyoma and LMS based on genomic and transcriptome data. Our findings suggest that RAD51B translocation and HMGA2 overexpression may play an important role in LMS oncogenesis.