This pattern is composed of whorls and small sheets of syncytial, polygonal cells with smooth eosinophilic cytoplasm, regularly contoured oval nuclei, minute nucleoli, and pale, finely granular chromatin (Figures 9-3 and 9-4). Scattered nuclei contain pseudoinclusions, or cytoplasmic intrusions, similar to those seen in papillary thyroid carcinoma. Present in most patterns of meningioma, pseudoinclusions are sharply circumscribed, devoid of contents, and compress the surrounding chromatin against the nuclear envelope. The whorls in this pattern are often vague and lobular, their edges blending with the surrounding tumor cells (Figure 9-5). Collagen deposition is minor, but fibrous septa and perivascular collagen can be present.

Fibrous meningiomas share few of the morphologic characteristics of their meningothelial siblings and can be mistaken for other
entities, specifically schwannoma (when in the cerebellopontine angle) and solitary fibrous tumor. The architecture ranges from fascicular to storiform (Figures 9-6 and 9-7), with few whorls or psammoma bodies and abundant collagen deposition. Collagen is deposited both in thick bands along blood vessels and as a dense, diffuse background matrix admixed with tumor cells. Dense bands of acellular collagen can replace the vast majority of the tumor, leaving only traces of the tumor’s cells. These cases
are sometimes called “sclerotic” meningiomas (Figure 9-8). The typical nuclear features of oval shape with regular outlines and pale chromatin are distorted into elongate nuclei with irregular outlines.

This pattern, transitional between meningothelial and fibrous, comprises the largest fraction of meningiomas and is the archetype of meningioma (Figure 9-9). The centers of the cellular whorls often hyalinize over time, leaving bubble-gum–colored spheres of protein, which,
after more time, transform into psammoma bodies. Psammoma bodies are common in several patterns of meningioma and can provide a helpful diagnostic cue when other features are lacking.

This striking pattern is an ordinary meningioma that has numerous whorls that have mineralized and formed lamellated spheres of calcium, or psammoma bodies (Figure 9-10). As might be inferred from the heavy calcification, these lesions are generally slow-growing (if at all),
lack atypical features, and have a low MIB1 index. In extreme cases, it may be difficult to identify the residual meningioma cells among the extensive calcifications. Most psammomatous meningiomas occur in the spinal canal in women older than 40 years. Even among intracranial examples, there remains a strong predilection for women (26).

This pattern overlaps with microcystic meningioma, with vacuolated cells and cobweb cytoplasm in many cases, but requires 50% or greater area of blood vessels to tumor tissue for inclusion, as put forward in one large series examining these lesions pathologically (27). The authors of this series recognized two patterns of angiomatous meningioma, macrovascular and microvascular, the macrovascular comprising a little more than half of the total cases. The macrovascular pattern displayed mostly large blood vessels with prominent hyalinization and intervening areas of usual meningioma, with syncytial whorls and short fascicles. The microvascular pattern was composed of small blood vessels with delicate walls in a background of microcystic meningioma in almost all cases, at least focally (27) (Figure 9-11). The vast majority of angiomatous meningiomas are grade I. Like secretory meningiomas, angiomatous ones are also associated with exaggerated peritumoral edema (28).

Theoretically, in the rare instance of an angiomatous meningioma in the posterior fossa, one could mistake a microvascular angiomatous meningioma with microcystic change for a hemangioblastoma. A dural-based location on imaging would heavily favor the former, as would positive immunostaining for somatostatin receptor 2A (SSTR2A), EMA, or progesterone receptors, and no inhibin immunostaining.

Microcystic meningioma is most notable for not resembling the other members of the meningioma group. Although microcystic change is common focally in meningiomas of other patterns, some cases express it diffusely, creating diagnostic confusion for the pathologist expecting whorls and regular oval nuclei. In contrast to other subtypes, microcystic meningioma has large cells with clear cytoplasm formed from large vacuoles separated by cobweb-like strands (Figure 9-12). The cytoplasmic vacuoles in this lesion
vary greatly in size, lacking the regularity of those usually seen in renal clear cell carcinoma or hemangioblastoma, with single large vacuoles sometimes occupying the entire cytoplasm. Nuclei in microcystic meningioma are prone to degenerative atypia, becoming hyperchromatic, irregular, and variable in size, ranging from small to gigantic (Figure 9-13). Some of the meningioma characteristics that microcystic lesions retain are hyalinized blood vessels and thick collagen bands, either of which can be diagnostically helpful. Nuclear pseudoinclusions are also retained. Although the cytoplasm of microcystic meningioma is clear, or nearly so, this generally indolent grade I pattern should not be mistaken for the grade II clear cell meningioma. Microcystic meningioma can occur as a purely intraosseous lesion and can be mistaken clinically for metastasis (29).

The defining feature of this meningioma pattern is the “pseudopsammoma body,” which is an intracellular, eosinophilic, spherical cytoplasmic inclusion that occurs in scattered cells within an otherwise usual meningioma (Figure 9-14). These structures are periodic acid-Schiff (PAS)-positive and immunoreactive for cytokeratins and carcinoembryonic antigen (CEA) (30). Secretory meningiomas usually also contain mast cell infiltrates. Although overwhelmingly benign, these lesions may have a higher rate of postoperative complication due to severe peritumoral edema. About 35% of patients with secretory meningiomas in one series had severe peritumoral edema that persisted after excision, and over a third of these patients required mechanical ventilation and intracranial pressure monitoring (31).

In a recent series, mutations in two genes, KLF4 and TRAF7, were both present in nearly all tested cases of secretory meningioma and were not found together in a large group of meningiomas of other patterns,
other brain tumors, metastatic tumors, or a small set of tumors from other organs, although isolated TRAF7 mutations were found in a few other meningiomas. KLF4 is more restricted to secretory meningiomas and has only shown one hotspot mutation in that context, K409Q. These mutations appear to be mutually exclusive with mutations in NF2, which are the most common genetic finding in meningiomas overall, suggesting that secretory meningiomas arise through a related but separate pathway from most others (32).

This rare class of meningiomas has not been studied in great numbers, the largest series being 19 cases, and remains controversial as a distinct pathologic entity (33). A dense, sometimes overwhelming, lymphoplasmacytic infiltrate crowds, and sometimes conceals, the native tumor cells (Figure 9-15). Plasma cells in these lesions frequently contain Russell bodies. Some patients with this lesion have had a polyclonal hypergammaglobulinemia (33,34,35). No evidence suggests that the lymphoplasmacytic infiltrate is neoplastic. An examination of 16 cases showed that plasma cells make up a minor component of the inflammation and generally don’t express IgG4. That work also found that the predominant inflammatory cell type was macrophages and recommended the term “inflammation-rich meningioma” as a more accurate term (36). Immunostaining for SSTR2A might sometimes be useful to demonstrate the meningothelial component of this lesion. EMA immunostaining would label both tumor cells and plasma cells. Dural lesions that could possibly be confused with this entity include low-grade lymphoma, sarcoidosis, Rosai–Dorfman disease, Castleman disease, Langerhans histiocytosis, idiopathic pachymeningitis, and “plasma cell granuloma.”

Mesenchymal tissue including bone and cartilage can develop within otherwise regular meningiomas. Although still generally considered a part of metaplastic meningiomas, evidence suggests that those with apparent adipose metaplasia (Figure 9-16) may result from lipidization of tumor cells (37,38). The term metaplastic has been applied to meningiomas with a prominent myxoid background into which tumor cells are singly dispersed, a description that overlaps significantly with that
of chordoid meningioma. Although the vast majority of metaplastic meningiomas are grade I, metaplasia has also been described rarely in malignant meningiomas (39).

WHO grade II meningiomas have an increased rate of recurrence and tumor-associated mortality compared with WHO grade I meningiomas. In addition to the chordoid and clear cell patterns that automatically earn grade II status, there are three other avenues by which this grade can be achieved: increased mitotic count, a total of three or more atypical histologic features, or brain invasion (17,18) (Table 9-1). Atypia of mitotic figures, pleomorphism, and nuclear atypia do not predict the behavior of meningiomas and are not components of their grading. About 15% to 20% of all meningiomas are grade II.

Atypical meningiomas, WHO grade II, may be diagnosed by two sets of histologic criteria: (1) mitotic rate; or (2) a combination of three or more histologic features of atypia. In meningiomas, an elevated mitotic count is defined as a rate of 4 or more mitoses in 10 contiguous 400× fields, in the area of greatest mitotic activity in the examined tissue. Twenty or more mitoses elevate the neoplasm to grade III. Although not part of the meningioma grading scheme itself, a MIB1 immunostain is helpful in finding the area of maximal proliferation. Examining contiguous fields within the area of greatest proliferation is not specifically suggested in the WHO manual but recapitulates the methodology used in the articles that established these criteria (17,18).

There are five histologic features that indicate increased aggressiveness of meningiomas, even when the mitotic rate is lower than that required for atypical status: necrosis, loss of architecture, hypercellularity, macronucleoli,
and high nucleus to cytoplasm ratio (small cell formation) (Figures 9-17 to 9-19). If three or more of these features are identified in a lesion, in any amount, the lesion meets criteria for “atypical meningioma, WHO grade II” according to the 2016 classification (40). Necrosis can be multifocal or geographic throughout a lesion and need not be in a particular pattern or amount. That is, any necrosis counts, as long as it is spontaneous. Widespread necrosis occasionally can be the result of presurgical embolization
of a meningioma, in which case it does not count as an atypical feature (Figure 9-20). Loss of architecture, or “sheetlike” growth pattern, means that the tumor cells lose their whorling or fascicular arrangement and grow in a homogeneous, patternless fashion. Hypercellularity has been quantified as 53 or more nuclei per high-power field (hpf) diameter (18) but can be evaluated subjectively in most cases. Small cell formation typically
occurs as multifocal aggregates of very small tumor cells with round nuclei and scant cytoplasm that resemble lymphocytes.