The term tumour budding denotes that at the invasion front of colorectal adenocarcinomas tumour cells, singly or in small aggregates, become detached from the neoplastic glands. This morphological feature is increasingly being recognized as a strong and robust adverse prognostic factor. Biologically, tumour budding is closely related to the epithelial-mesenchymal transition. In this review the morphological features of tumour budding are discussed, as observed by the surgical pathologist reporting colorectal carcinoma resection specimens. The morphological features are put into context with the rapidly expanding knowledge of the epithelial-mesenchymal transition in general, and the molecular pathology of colorectal carcinoma in particular. Finally, a systematic analysis of the relevant published clinicopathological studies emphasizes the potential of tumour budding as a prognostic factor for routine surgical pathology.

This study confirms the prognostic value of budding in a contemporary series of colorectal carcinomas that by TNM were low risk. Technically easy, rapid and robust to determine, budding quantified in pan-cytokeratin stains significantly aids in the identification of high-risk patients and is recommended for more general use in surgical pathology.

CD66a, also called biliary glycoprotein (BGP), is a member of the carcinoembryonic antigen (CEA) family and of the immunoglobulin superfamily. CD66a is the human homologue of Cell-CAM, a well-defined cell adhesion molecule of the rat. In the present study a monoclonal antibody specific for CD66a was used to locate CD66a in human tissues. CD66a is expressed in epithelia, in certain endothelia, and in cells of the myeloid lineage. Hepatocytes were stained along the bile canaliculi. A characteristic apical membranous staining was observed in enterocytes, superficial absorptive cells of the colon, in the epithelia of esophageal and Brunner's glands, bile ducts and gallbladder, pancreatic ducts, proximal tubules of the kidney, prostate, endometrium, and mammary ducts. Selective staining of endothelia was present in glomeruli and vasa recta of the kidney, small placental vessels, adrenal sinusoids, endometrium, the prostate. Among the cells of the myeloid lineage, granulocytes and myelocytes were positive. The expression of CD66a by human cells and tissues is well comparable with the expression reported for Cell-CAM, the rat counterpart of CD66a. The wide tissue distribution of CD66a indicates that CD66a is a prominent human adhesion molecule.

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The syndrome of paraganglioma (PGL), somatostatinoma (SOM), and early childhood polycythemia in patients with somatic mutations in the hypoxia-inducible factor 2 alpha (HIF2A) gene is described in only a few patients worldwide. The present study provides detailed information about the clinical aspects and course of 7 patients with this syndrome and brings these experiences into perspective with the pertinent literature. Six females and one male presented at a median age of 28 years (range 11–46). Two were found to have HIF2A somatic mosaicism. No relatives were affected. All patients were diagnosed with secondary polycythemia before age 8 and before PGL/SOM developed. PGLs were found at a median age of 17 years (range 8–38) and SOMs at 29 years (range 22–38). PGLs were multiple, recurrent, and metastatic in 100%, 100%, and 29% of all cases, and SOMs in 40%, 40%, and 60%, respectively. All PGLs were primarily norepinephrine producing. All patients had abnormal ophthalmologic findings and those with SOMs had gallbladder disease. Computed tomography (CT) and magnetic resonance imaging revealed cystic lesions at multiple sites and hemangiomas in 4 patients (57%), previously thought to be pathognomonic for von Hippel-Lindau disease. The most accurate radiopharmaceutical to detect PGL appeared to be [18F]-fluorodihydroxyphenylalanine ([18F]-FDOPA). Therefore, [18F]-FDOPA PET/CT, not [68Ga]-(DOTA)-[Tyr3]-octreotate ([68Ga]-DOTATATE) PET/CT is recommended for tumor localization and aftercare in this syndrome. The long-term prognosis of the syndrome is unknown. However, to date no deaths occurred after 6 years follow-up. Physicians should be aware of this unique syndrome and its diagnostic and therapeutic challenges.

In WHO grade II astrocytomas, IDH1/2 mutations mostly occur in tumors infiltrating the frontal lobe. Seizure as the initial symptom is associated with IDH1 or IDH2 mutation.