Neuropathology

preservation of axons. There was a long temporal gap between the two fields of study, so much so that MS was frequently considered to be degenerative rather than inflammatory. The status of "activity" remained speculative. Lesions that contained lipid-filled macrophages ("gitter cells") were thought to be active, forgetting that macrophages can persist for many months, even years. Other lesions were only loose mesh works of astrocytic fibers and were truly old. Mild, focal, perivascular lymphocytic cuffs were also considered "active" but rarely did neuropathologists encounter a really active lesion: a small focus at the circumference where microglia in various stages of phagocytosing and digesting myelin (Fig. 3.2) could be seen as evidence of some process beginning only a few days before death. Neuropathologists did not expect a biopsy of an MS lesion until modern scans began to reveal "solitary" expanding lesions that required a biopsy to differentiate a neoplasm (glioma, lymphoma or metastatic carcinoma) from an abscess or granuloma. MS was just not on the list of differential diagnoses in those days.

When the authors saw their first case of MS at biopsy (Fig. 3.3), their first impression was anaplastic astrocytoma with pleomorphic nuclei (later shown to be both microglia and astrocytes in various stages of evolution), the astrocytes being especially pleomorphic with chromatin patterns that were suggestive of mitoses but which are now recognized as micronuclei. There was only mild perivascular lymphocytic cuffing. The evolving macrophages were not obvious on H&E (hematoxylin & eosin)-stained sections and, indeed, the authors were not sensitized enough even to be looking for macrophages. Only when they saw the CT scan showing what looked like a head full of marbles did they realize that not only were they wrong in their diagnosis of glioma but also that the clinicians were wrong in diagnosing metastatic cancer. The diagnosis had to be MS even though the primary complaint had been an epileptic seizure! Fortunately, although the concept of pleomorphic xantho-astrocytoma (PXA) was not yet popularized in those days, the foamy and spongy stroma of the tissue raised their suspicion of MS. Subsequent special stains revealed that the lesion was packed with foamy macrophages and had a sharply defined loss of myelin and preservation of axons.

They thus learned the hard way that demyeli-nating disease must be added to their list of differential diagnoses. However, it can still be quite confusing because the edge is not always sharp and the preservation of axons far from perfect. They know of several cases of litigation against pathologists because of the misdiagnosis of neoplasm.

Abscess and Granuloma vs Tumor Hypercellu-larity is one of the characteristics of most neoplasms but it is not specific. The number of cells increases even more markedly in many inflammatory processes but the types of cells are quite different and should cause only temporary difficulty in differential diagnosis. The granulation tissue in the wall of an organizing abscess or granuloma with abundant, actively proliferating, immature fibroblasts may look quite wild and mimic pleomorphic astro-cytomas, especially if the adjacent reactive glio-sis is included in the specimen and the more central inflammatory exudate is not. Macrophages are usually present in the granulation tissue and these contribute to the pleomophism as the microglia evolve into macrophages. On the other hand, acute and chronic inflammatory exudates may be seen focally in glioblastomas, probably in response to necrosis. This can cause a differential nightmare when the specimen is small and does not show representative areas of the glioblastoma. Since the treatment for glioblastoma and abscess is so different, re-biopsy has to be requested if the problem cannot be solved.

Vascular Diseases

Hemorrhages, old and recent, usually pose no problem for diagnosis except that the gliosis adjacent to an old hemorrhage can be so disorganized as to raise a question of glioma. Foci of vascular malformation in gliomas, both low and high grade, are not uncommon and oligo-dendrogliomas are notorious for spontaneously bleeding as their first sign. When a large arteri-ovenous malformation (AVM) is present adjacent to a glioma, it is difficult to tell whether the AVM is a focal change in the glioma or two independent lesions that just happen to occur in the same location.

Congophilic angiopathy should be considered and the amyloid-containing blood vessels

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