2021 Update on Meningeal Solitary Fibrous Tumor

Meningeal Solitary Fibrous Tumor (SFT) is an uncommon tumor, accounting for less than 1% of CNS tumors. It is a fibroblastic neoplasm with a genomic inversion at the 12q13 locus, leading to NAB2-STAT6 gene fusion and surrogate nuclear STAT6 immunohistochemical expression. SFT generally affects adults in the fifth to seventh decades. It is dural-based and typically supratentorial, but 10% have a spinal location. SFT has a high propensity for recurrence and metstasis, at times occuring decades after initial diagnosis. Imaging often prompts a pre-operative assumption of meningioma as the diagnosis. Histologically, the tumor has a spindle cell appearance and variably cellular with abundant stromal keloid-type collagen. Some examples are very cellular tumors with densely packed round-to ovoid cells and little intervening stroma. Mitoses and necrosis can be present. Can a true SFT be STAT6 negative on immunohsitochemical examination? Yes, but it is just as likely that the pathologist is looking at something else on the differential diagnosis, including other unusual mesechymal tumors. In such cases, molecular testing for STAT6 fusion is required to render a confident diagnosis. Grading of SFT has changes since the last iteration of the WHO Classification in 2016. The 2016 criteria depended on the histologic hemangiopericytoma phenotype as a factor in raising this tumor from a grade I up to a grade II tumor. Now, in the soon-to-be-released 2021 WHO Classification, this phenotype is not considered important -- with emphasis instead on mitotic count as a means of creating grading cut-offs. Specifically, SFTs with fewer than 5 mitoses per ten high-power fields are considered grade 1, while a mitotic count of 5 or greater justifies a grade 2 designation. If, in addition to this elevated mitotic count, necrosis is present, then a grade 3 designation is assigned. There have been reported some rare pattern in SFT, including lipomatous, pappillary, giant cell, and myxoid; but these do not affect prognosis. If STAT6 is negative, the pathologist shoud think about other entities in the differential diagnosis, including fibrous meningioma, a variety of mesenchymal tumors (such as phosphaturic mesenchymal tumor), malignant peripheral nerve sheath tumor, and primary non-pigmented melanocytic tumors of the CNS. To reiterate, three grade of SFT will be recognized in the 2021 WHO classification of CNS tumors: Grade 1 - SFT with less than five mitotic figures per ten high power fields; Grade 2 - SFT with five or greater mitotic figures per ten high power fields; Grade 3 - SFT with five or greater mitotic figures per ten high power fields and necrosis. This information is taken from an excellent lecture on this SFTs delivered by Dr. Caterina Giannini at this year's annual USCAP meeting (see photo of her below delivering her lecture remotely). Thanks Dr. Gianinni for distilling this topic down to a concoction suitable for us blue-collar neuropathologists to imbibe!

Today is Glioblastoma Awareness Day

Last month, a resolution recognizing today, July 17, as Glioblastoma Awareness Day was passed with unanimous consent in the U.S. Senate – a date on which we honor GBM patients, families, and caregivers, as well as recognize the tireless work of researchers and medical providers. Find out more at "Glioblastoma Awareness Day" 

Best Post of January 2019: Radiologically suspected meningioma turns out to be WHO grade II Pleomorphic Xanthoastrocytoma

The next in our "Best of the Month" series comes from January 18, 2019:

Rosethal fiber in oval. Eosinophilic granular body in rectangle

Rosenthal fibers can be seen in non-neoplastic "compressed" brain tissue. For example, I once saw Rosenthal fibers in the spinal cord adjacent to an epidural abscess.

cIMPACT-NOW Update 4: diffuse gliomas characterized by MYB, MYBL1, or FGFR1 alterations or BRAFV600E mutation

This cIMPACT-NOW update was published this month:

Summary:
cIMPACT (Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy) has reviewed the status of WHO grade II IDH-wt/H3-wt diffuse gliomas, focusing on those with a BRAFV600E mutation, FGFR1 alteration, or a MYB or MYBL1 rearrangement, and recommends the use of an integrated diagnosis to combine their histologic and genetic features. 

The consortium recommends the use of an integrated diagnosis to combine their histologic and genetic features, as suggested in the following:

• Diffuse glioma, MYB-altered
• Diffuse glioma, MYBL1-altered
• Diffuse glioma, FGFR1 TKD-duplicated
• Diffuse glioma, FGFR1-mutant
• Diffuse glioma, BRAFV600E-mutant (but without CDKN2A/B deletion)
• Diffuse glioma, other MAPK pathway alteration

The full for cIMPACT Update 4 can be found at:

Ellison DW, Hawkins C, Jones DTW, Onar-Thomas A, Pfister SM, Reifenberger G, Louis DN.  cIMPACT-NOW update 4: diffuse gliomas characterized byMYB, MYBL1, or FGFR1 alterations or BRAF^V600E mutation. Acta Neuropathol. https://doi.org/10.1007/s00401-019-01987-0.  PMID: 30848347

"Although our cIMPACT committee sees the utility of distinguishing these diffuse gliomas in diagnostic practice, it also acknowledges that the overlap between their morphologic and genetic features and those of other neuroepithelial tumors could occasionally compromise an accurate diagnosis. These other tumors, including pilocytic astrocytoma, PXA, and DNT, could themselves benefit from a classification based upon their combined histologic and genetic features; indeed, it seems likely that such tumors will be the subject of future cIMPACT recommendations on their classification."

The full cIMPACT Steering Committee comprises Drs. Ken Aldape, Dan Brat, David Capper, David W. Ellison, Dominique Figarella-Branger, Cynthia Hawkins, Takashi Komori, David N. Louis, Catriona McLean, Werner Paulus, Arie Perry, Guido Reifenberger, Andreas von Deimling, and Pieter Wesseling.

Best Post of December 2018: Giant cell GBM masquerading as an anaplastic PXA

The next in our "Best of the Month" series is from December 4, 2018:

At first glance, this tumor with pleomorphic cells and prominent perivascular lymphocytic cuffing strikes one as a pleomorphic xanthoastrocytoma (PXA).

The relative circumscription, as demonstrated by the stark difference in tumor burden in adjacent gyri depicted above also suggests the possibility of  PXA.

The presence of mitotic figures (center of picture above) and a small amount of necrosis and microvascular proliferation (not pictured) suggests the possibility of anaplastic PXA.

However, perivascular lymphocytes and relative circumscription can be seen in giant cell glioblastoma (GC-GBM). Pointing away from anaplastic PXA is the fact that there was no evidence of Rosenthal fibers and eosinophilic granular bodies. Additionally, there was strong p53 immunohistochemical positivity. The final diagnosis was Glioblastoma, IDH-wildtype, WHO grade IV, giant cell variant.

Radiologically suspected meningioma turns out to be WHO grade II Pleomorphic Xanthoastrocytoma

Rosethal fiber in oval. Eosinophilic granular body in rectangle

Rosenthal fibers can be seen in non-neoplastic "compressed" brain tissue. For example, I once saw Rosenthal fibers in the spinal cord adjacent to an epidural abscess.

Best Post of November 2018: The exquisite cellular uniformity of the central neurocytoma

The next in our "Best of the Month" series is from November 20, 2018:

Intraoperative ThinPrep smear demonstrates the striking cellular uniformity

Permanent section of the same tumor

Giant cell GBM masquerading as an anaplastic PXA

At first glance, this tumor with pleomorphic cells and prominent perivascular lymphocytic cuffing strikes one as a pleomorphic xanthoastrocytoma (PXA).

The relative circumscription, as demonstrated by the stark difference in tumor burden in adjacent gyri depicted above also suggests the possibility of  PXA.

The presence of mitotic figures (center of picture above) and a small amount of necrosis and microvascular proliferation (not pictured) suggests the possibility of anaplastic PXA.

However, perivascular lymphocytes and relative circumscription can be seen in giant cell glioblastoma (GC-GBM). Pointing away from anaplastic PXA is the fact that there was no evidence of Rosenthal fibers and eosinophilic granular bodies. Additionally, there was strong p53 immunohistochemical positivity. The final diagnosis was Glioblastoma, IDH-wildtype, WHO grade IV, giant cell variant.

The exquisite cellular uniformity of the central neurocytoma

Intraoperative ThinPrep smear demonstrates the striking cellular uniformity

Permanent section of the same tumor

True rosette situated within an Embryonal Tumor with Multilayered Rosettes, C19MC-altered, WHO grade IV

This aggressive tumor was located in the frontoparietal lobe of a young child. It had alterations in the C19MC locus at 19q13.42.

Xanthic cell in a pleomorphic xanthastrocytoma

Crooke cell change in a normal pituitary of a patient with ectopic ACTH producing tumor

CK20 immunohistochemistry highlights Crooke cells

Multinodular and vacuolating neuronal tumor,WHO grade I

The patient is a middle-aged male with a temporal lobe mass. Histopathology shows a low-grade ganglion cell tumor with clustered ganglion cells with a vacuolated neuropil background. The fragmented nature of the specimen precludes identification of a nodular architecture. The diagnosis is multinodular and vacuolating neuronal tumor, WHO grade I. This entity is a cousin of gangliocytoma.

A WHO grade IV diagnosis in the face of a low-grade histophenotype: a difficult situation for the surgical neuropathologist

This midbrain mass in a 33-year-old patient has low-grade histology (minimal mitoses, low MIB-1 cell cycling index, and a single Rosenthal fiber), yet it harbors the H3 K27M mutation. Perivascular lymphocytes were present, but ganglioglioma was ruled out. So, the following diagnosis was rendered: diffuse midline glioma, H3 K27M mutant, WHO grade IV.  Other molecular changes included loss of p16 (CDKN2a) and loss of PTEN and 10 centromere, consistent with monosomy for chromosome 10. The discordance between histopathology and molecular findings can make the diagnostician squeamish about rendering a high-grade diagnosis. But, sometimes, this is where we find ourselves.

Circadian Rhythm Gene May Serve as Target for Glioblastoma Therapies

Scientists from the Virginia Tech Carilion Research Institute say a gene involved in the body's circadian rhythms is a potential target for therapies for glioblastoma.

Their discovery (“Casein Kinase 1 Epsilon Regulates Glioblastoma Cell Survival”), published in Scientific Reports, points to a subtype of a particular gene that apparently is enabling the survival of cancer cells, although it is more commonly associated with circadian rhythms.

“In our previous work, we identified casein kinase 1 ε (CK1ε, also known as CSNK1E) as a potential survival factor in glioblastoma. However, how CK1ε controls cell survival remains elusive and whether targeting CK1ε is a possible treatment for glioblastoma requires further investigation. Here we report that CK1ε was expressed at the highest level among six CK1 isoforms in glioblastoma and enriched in high-grade glioma, but not glia cells. Depletion of CK1ε remarkably inhibited the growth of glioblastoma cells and suppressed self-renewal of glioblastoma stem cells, while having limited effect on astrocytes,” write the investigators.

(Source: Genetic Engineering and Biotechnology News)

A gaggle of Rosenthal fibers forming at the pushing border of an ependymoma

Ependymoma (left) pushing on adjacent brain induces numerous Rosenthal fibers,
particularly around a blood vessel

Tumours of the CNS Dataset is now published to the ICCR website

The International Collaboration on Cancer Reporting has published the Tumours of the CNS Dataset.

According to the published document, the "dataset has been developed for the histological assessment of benign and malignant tumours of the central nervous system (CNS) and its coverings, as well as tumours from those aspects of the peripheral nervous system immediately adjacent to the CNS. This dataset applies to both biopsy and resection specimens. Haematological lesions that may originate in the brain are included. Tumours of the anterior pituitary gland are included as the majority of these tumours are reported by neuropathologists worldwide (a separate dataset specifically for pituitary tumours may be considered when the 5th series of the World Health Organisation (WHO) Classification of Tumours is being developed). It is intended that this dataset should be used in conjunction with the ‘Molecular information for CNS specimens’ and the ‘Final integrated report/diagnosis for CNS specimens’ datasets. A full diagnosis of CNS tumours should ideally conform to the final integrated diagnoses in the 2016 World Health Organisation (WHO) Classification of Tumours of the CNS (2016 CNS WHO), which requires integration of elements from histological and ancillary analyses. Nonetheless, it is realized that some diagnoses may not fit precisely within existing diagnostic categories."

Best Post of May 2018: Moving beyond histologic grading of IDH-wildtype diffuse astrocytic gliomas

The next in our "Best of the Month" series comes from May, 30, 2018:

Despite the fact that the most recent update of the World Health Organization (WHO) classification of central nervous system tumors was published only two years ago, the data is already showing that we are moving beyond that classification system when if comes to IDH-wildtype diffuse astrocytomas. The concept of an "integrated diagnosis" in the setting of IDH-wildtype histologic grade II and III tumors has already been eclipsed in the literature by the primacy of the genetic signature over histologic appearance in predicting outcome. In the near future, diffuse IDH-wildtype astrocytic gliomas with (1) combined whole chromosome gain of 7 and loss of 10, and/or (2) EGFR amplification will be designated as equivalent to WHO grade IV gliomas. Histologic grades for such tumors will be stricken from the top diagnostic line so as to avoid unfounded reassurance that these tumors will behave in any way other than very aggressively.

Atypical teratoid/rhabdoid tumor (AT/RT) in an infant

Rhabdoid cells (such as those circled above) frequently are seen in AT/RTs

Malignant astroblastoma in a 23-year-old female

Headaches prompted imaging which showed a large right parieto-occipital tumor. Astroblastic pseudorossettes are prominent, with cells that are fairly monotonous. GFAP was only focally positive, not unusual for this diagnosis. Mitotic rate ranged up to 8 per 10 HPF, with a MIB1 cell cycling index reaching 40%.