Reverse clinical pathology conference

Today I went to my first reverse clinical pathology conference. It's reverse because rather than starting with the patient's presentation and moving forward in time, you start with the pathology slides and try to reconstruct the symptoms and diagnosis based on what you see under the microscope.

There are pathology rooms with multi-headed microscopes: 8-10 viewing stations connected to a single slide mount so everyone is viewing the same slide simultaneously. A pathologist usually "drives" and physician and fellows (and me!) sit around the other viewers. The pathologist loaded in stained, prepared slides of the brainstem, cerebellum, and cortex for examination.

Slide #1 cerebellum. The cerebellar cortex is made up of three layers: the molecular layer, granule layer, and Purkinje layer. In our slide there was no surface granule layer, indicating the cells had already completed their migration and the patient must have been at least 12 months of age. The Purkinje cells were dying, a classic hypoxia sign. We also saw evidence of infection in the meninges (membranes covering the brain) and the parenchyma (brain tissue) such as macrophages and perivascular cuffing.

In the parenchyma we noted neuronophagia: dying neurons surrounded by microglial cells. This pointed us towards considering a viral diagnosis. Bacteria can stay in the meninges surrounding the brain, but viruses are obligate cellular parasites and thus more likely to appear in the neural tissue itself. We examined the neurons for inclusion bodies, which are accumlations (not exclusive to viral infections) within either the cytoplasm (ex rabies) or nucleus (ex. herpes). Not all viral infections have inclusion bodies, but their presence, absence and type can help to identify the specific pathogen. In this patient there were no inclusion bodies.

Slide #2: pons (brainstem). We noted extensive liquefactive necrosis, leaving the tissue with a spongelike appearance. Basically, the neurons are dying and pockets of fluid-filled space are left where there used to be brain tissue (necrosis = abnormal cell death). The extent of the damage in this patient was severe, indicating a rampant infection and acute, considering the cell types present.

Slide #3: midbrain (brainstem). The substantia nigra in the midbrain was noted to be unpigmented. This area usually develops pigment between 3-5 years of age (and can be lost again in old age as part of a neurodegenerative process). This placed the patient's age between 12 months and 3 years.

Slide #4: spinal cord. Most infections have a regional preference within the nervous system; they don't invade all areas equally. Thus, looking at which regions are affected can narrow down the pathogens under consideration. In our patient, the anterior horn of the spinal cord was disproportionately infected, which led us to consider the enteroviruses (ex polio, Hep A).

Conclusion: The patient turned out to be 25 months old and died of a massive Coxsackie viral infection. Coxsackie virus (type B pictured to the right) is probably best described as a non-paralytic polio and it can affect other organ systems besides the central nervous system, most notably the heart and eyes.

Note: this case has been previously published so the details have not been altered. All photos used are from searching google images and are not the slides from the actual conference.