Left dural‐based mass in a 62‐year‐old female

1. CLINICAL PRESENTATION AND IMAGING

A 62‐year‐old woman with history of chronic migraine presented with a recent syncopal episode with brief loss of consciousness. A brain MRI showed an avidly enhancing extra‐axial mass anterior to the left temporal lobe (Figure 1, arrow) and resection of the lesion was performed (Box 1).

FIGURE 1.

Axial T1 weighted brain MRI post‐ contrast shows a homogeneously enhancing, dural‐based mass in the left anterior temporal lobe (arrow).

BOX 1. Virtual glass slide.

Access at https://isn‐slidearchive.org/?col=ISN&fol=Archive&file=BPA‐22‐07‐181.svs

2. FINDINGS

Examination of the hematoxylin and eosin‐stained sections revealed a meningothelial neoplasm predominantly formed of cells with oval, vesicular nuclei and abundant eosinophilic cytoplasm with scattered whorl formation (Figure 2A) and psammoma bodies. Within these areas, mitotic activity was elevated (up to 8 mitoses per 10 high power fields). There was another distinct component, composed of cohesive epithelioid cells with large, atypical nuclei, prominent nucleoli and eosinophilic to clear cytoplasm embedded in a densely hyalinized stroma resembling a poorly differentiated carcinoma (Figure 2B,C). By immunohistochemistry, the meningiomatous component was diffusely positive for SSTR2 (Figure 2D), and focally positive for EMA and progesterone receptor (not shown). The carcinomatous component was negative for SSTR2 but diffusely positive for keratins such as CK7 (Figure 2E), CAM 5.2 and OSCAR (not shown). GFAP, CD56, synaptophysin, CK20, GATA3, CDX2, and PAX8 were negative in both components (not shown).

FIGURE 2.

Histologically, the tumor demonstrated areas with evident meningothelial differentiation showing oval vesicular nuclei and cellular whorling (panel A). This component showed transition into another component with different morphology (meningiomatous component upper left corner and carcinomatous component lower right corner, panel B). The other was composed of cells with abundant cytoplasm, markedly pleomorphic nuclei and prominent nucleoli, reminiscent of poorly differentiated carcinoma (panel C). SSTR2 was positive in the meningothelial component (panel D) and CK7 was positive in the carcinomatous component (panel E). Chromosomal microarray analysis showed loss of chromosomes 1, 10, 14, 18, and 22 (including NF2), and gain of 12q13.12q24.33 in both the meningiomatous and carcinomatous components of the tumor (panel F). Next generation sequencing showed identical NF2 and KMT2D mutations in both the tumor components as well (panel G).

Chromosomal microarray analysis was performed to assess copy number alterations within the two morphologically distinct regions of the tumor, representing the well‐differentiated meningioma and the carcinomatous components. Both components revealed nearly identical copy number changes, including loss of chromosomes 1, 10, 14, 18, and 22 (including NF2), and gain of chromosome 12 (Figure 2F). Similarly, next‐generation sequencing showed an identical mutational profile with pathogenic frameshift mutations in NF2 (c263del, p.Lys88Argfs*35) and KMT2D (c2450del, p.Pro817Leufs*113) genes (Figure 2G).

3. FINAL DIAGNOSIS

Anaplastic meningioma with carcinomatous differentiation (CNS WHO grade 3).

4. DISCUSSION

The presence of areas with overt carcinomatous differentiation in a meningioma raises the possibility of anaplastic meningioma with heterologous differentiation versus metastatic carcinoma involving a meningioma. Metastasis to meningioma is a well‐known occurrence, with breast and lung as the most frequent primary sites followed by kidney, prostate, and GI tract. In over one‐third of cases, the tumor‐to‐meningioma metastasis can be the initial presentation of a previously undiagnosed occult cancer [1]. Therefore, the lack of history of malignancy, such as in this case, does not exclude a tumor‐to‐meningioma metastasis.

Malignant meningiomas encompass diverse morphologies and can show carcinomatous or sarcomatous differentiation. Sarcomatous differentiation is a more frequent occurrence and tumors usually show heterologous elements that can either be found adjacent to areas with typical meningoma morphology or can represent the entire tumor without evidence of residual conventional meningioma [2]. These tumors usually express lineage specific immunohistochemical (IHC) markers related to the heterologous elements that are present, with weak or negative expression of meningioma markers [2]. On the other hand, aside from few limited reports, the pathology and IHC profile of carcinoma‐like areas in anaplastic meningiomas has not been evaluated in detail.

While the IHC findings were markedly different between the conventional meningiomatous foci and the carcinomatous component, their molecular profile was nearly identical, which is typical of what has been previously reported. Chromosomal microarray showed loss of chromosome 22, which is the most frequent alteration occurring in meningiomas of all histologic grades [3]. Losses of chromosomes 1p and 14q were also detected, which are frequent cytogenic abnormalities affecting approximately 50% of grade 2 and nearly all grade 3 meningiomas [3].

Next‐generation sequencing was also useful in confirming the diagnosis through detection of NF2 gene alterations which is a very common finding in meningiomas occurring in 40%–60% of cases [3]. NF2 gene alterations are usually secondary to either copy loss of 22q or inactivating mutations (the most frequent is frameshift mutations such as the mutation present in this case). KMT2D is also one of the mutations reported in meningiomas of various morphological subtypes and grades.

In conclusion, even though IHC had limited utility to reliably distinguish between metastatic carcinoma to a meningioma and meningioma with heterologous differentiation in this case, the nearly identical copy number results and identical mutational profile supported the diagnosis of anaplastic meningioma with heterologous carcinomatous differentiation. Molecular evaluation of distinct tumor regions in similar cases can provide valuable information for the diagnosis of these challenging neoplasms.

AUTHOR CONTRIBUTIONS

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Rofyda E. Elhalaby, Christina A. Kavran, Rachael A. Vaubel, and M. Adelita Vizcaino. The first draft of the manuscript was written by Rofyda E. Elhalaby and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

CONFLICT OF INTEREST

The authors declare no conflict of interest.

Elhalaby RE, Kavran CA, Vaubel RA, Vizcaino Villalobos MA. Left dural‐based mass in a 62‐year‐old female. Brain Pathology. 2023;33(4):e13145. 10.1111/bpa.13145

DATA AVAILABILITY STATEMENT

The data that support the findings of this study are available from the corresponding author upon reasonable request.