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14 March 2019 - Case of the Week #477

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Thanks to Dr. Rawia Mubarak Mohamed and Dr. Najla Saleh Ben Gashir, Sheikh Khalifa Medical City, Abu Dhabi (UAE) for contributing this case and Dr. Maria Martinez-Lage, Massachusetts General Hospital, Boston, Massachusetts (USA) for editing the discussion. To contribute a Case of the Week, first make sure that we are currently accepting cases, then follow the guidelines on our main Case of the Week page.





Pathologist

POWELL, OHIO (USA). Discovery Life Sciences is a trusted provider of bioanalytic and biospecimen services to hundreds of customers across the U.S. and around the world. The contracting Pathologist will provide (non-clinical) pathology review of FFPE H&E slides (as well as other special stains on occasion) in order to confirm alignment of original clinical pathology records and add other data points of research interest (i.e. % tumor, identification of certain tissue types or cellular structures). This review involves the hand marking of the slides per a specific protocol using super fine permanent markers and the use of company software in which to record the findings. Discovery Life Sciences will provide training in all areas of specific protocols to follow that are unique to DLS. Contractor may be asked to participate in special projects according to their areas of specialization.

Qualifications:
• Board Certification (U.S.) in Pathology (please present copy of certification)
• Participation in Continuing Certification (CC) programs encouraged
• Must reside in Central Ohio / Columbus Metro area
• Strong IHC experience preferred

Hours and Location:
• Flexible work scheduling Mon-Fri. - between 8am and 6pm preferred
• Minimum 12 hours/week preferred, (i.e. 3 x 4 hours shifts), up to 30 hours
• Powell, OH office location
• Work station, microscope, computer and office supplies will be provided

Pay rate: $75/hour

For more information or to apply please contact:
Heather Allison
Sr. Human Resources Generalist
Direct Telephone: (256) 327-0618
Main Telephone: (866) 838-2798
Mobile Telephone: (256) 425-5105
Fax: (256) 327-0527
Email: heather.allison@dls.com

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Case of the Week #477

Clinical history:
A 5 year old girl presented with headache and vomiting for one week. MRI showed a large, round, relatively well circumscribed tumor measuring 6 x 5 x 4.5 cm in the right thalamic region. The lesion displayed heterogeneous signal intensity and showed enhancement of its superomedial aspect, which also contained an irregular area of necrosis. A biopsy was obtained.

Radiology image:


Histopathology images:



What is your diagnosis?

































Diagnosis:
Diffuse midline glioma, H3 K27M mutant

Test question (answer at the end):

Which statement about diffuse midline glioma, H3 K27M mutant is true?

A. Despite its name, it is typically NOT found in the midline.
B. It often lacks high grade histologic features but is still considered grade IV.
C. This diagnosis includes midline gliomas that are diffusely infiltrating but have not been tested for the H3 K27M mutation.
D. The prognosis varies based on the histologic features.

Stains:

Olig2

H3K27M



Discussion:

The entity called "diffuse midline glioma, H3 K27M mutant" was added to the World Health Organization (WHO) Classification of Tumours of the Central Nervous System (Acta Neuropathol 2016;131:803) in 2016, and constitutes most of the diffuse gliomas in the brainstem. They are considered WHO grade IV despite the lack of high grade histological features and have a dismal prognosis. They typically occur in the pons (comprising most tumors previously called "diffuse pontine infiltrating gliomas") and thalamus (Brain Pathol 2016;26:569) but can be seen anywhere in the midline.

The clinical features vary by tumor location but commonly include headache, ataxia and sensory disturbance. MRI typically shows T2 hyperintensity and a heterogeneously enhancing infiltrative mass with T1 hypointensity (J Med Case Rep 2009;3:87). Many tumors show high grade morphology but may also have lower grade histology and mimic pilocytic astrocytoma and ganglioglioma (Acta Neuropathol Commun 2016;4:84). By definition, this diagnosis requires that the tumor be a diffusely infiltrating, midline, glioma with the H3 K27M mutation (Acta Neuropathol 2018;135:639). In pediatric patients (but potentially not adult patients), this mutation is associated with a poorer prognosis (J Cancer Res Clin Oncol 2019 Jan 4 [Epub ahead of print]).

Test question answer:
B.
This tumor is considered grade IV regardless of the histologic features and all of these tumors are considered to have a dismal prognosis. Most of these tumors appear in the midline. Molecular or IHC testing to confirm the mutation is required for this diagnosis.