Traditionally, immunohistochemistry (IHC) is used by pathologists to localise specific proteins or peptides in tissue slides. In the era of personalised medicine, however, molecular tissue analysis becomes indispensable for correct diagnosis, prognosis and therapeutic decision, not only on the DNA or mRNA level but also on the protein level. Combining molecular information with imaging presents many advantages. Therefore, matrix-assisted laser desorption/ionisation imaging mass spectrometry (MALDI IMS) is a promising technique to be added to the armamentarium of the pathologist. Here, we focus on the workflow, advantages and drawbacks of both MALDI IMS and IHC. We also briefly discuss a few other protein imaging modalities and give examples of applications.

Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome (PVHH, OMIM 225790), also known as Fowler syndrome, is a rare autosomal recessive disorder of brain angiogenesis. PVHH has long been considered to be prenatally lethal. We evaluated the phenotypes of the first three siblings with survival into adulthood, performed a systematic review of the Fowler syndrome literature and delineated genotype-phenotype correlations using a scoring system to rate the severity of the disease. Thirty articles were included, describing 69 individual patients. To date, including our clinical reports, 72 patients have been described with Fowler syndrome. Only 6/72 (8%) survived beyond birth. Although our three patients carry the same mutations (c.327T>A-p.Asn109Lys and c.887C>T-p.Ser296Leu) in FLVCR2, only two of them presented with the same cerebral features, ventriculomegaly and cerebral calcifications, as affected fetuses. The third sibling has a surprisingly milder clinical and radiological phenotype, suggesting intrafamilial variability. Although no clear phenotype-genotype correlation exists, some variants appear to be associated with a less severe phenotype compatible with life. As such, it is important to consider Fowler syndrome in patients with gross ventriculomegaly, cortical malformations and/or cerebral calcifications on brain imaging.

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