Live PathCast Tomorrow: Rodriguez on Meningomas

Tuesday, April 30th - 8 AM EST Topic: Meningiomas Presented by Fausto Rodriguez, M.D., Associate Professor of Pathology, JHUSOM

This seminar can be accessed live through the following links at 8 AM on Tuesdsay: Facebook: https://www.facebook.com/events/355454475302665/ YouTube: https://www.youtube.com/channel/UCVxosS9hPP3ikMQXAE9Pamw/videos Website: http://pathologycast.com/

Sclerosing orbital lesions: broadening the differential diagnosis of "idiopathic sclerosing pseudotumor"

Sclerosing orbital lesion
(the biopsy revealed it to be Erdheim-Chester disease)

Sclerosing lesions of the orbit can present a diagnostic conundrum. Often submitted with a differential diagnosis that includes idiopathic sclerosing pseudotumor, it is incumbent upon the pathologist to rule out other diagnostic possibilities before designating the lesion as idiopathic. In order to survey the range of diagnoses for such specimens, we searched over a 10-year period for specimens submitted to the University of Colorado pathology department which either clinically or pathologically raised the possibility of idiopathic sclerosing pseudotumor. We found 31 specimens (from 27 patients) that met criteria for review. The diagnosis for each of the 27 patients was confirmed after review of medical records. For 11 patients, a final clinicopathologic diagnosis of idiopathic sclerosing pseudotumor was rendered. The remaining diagnoses included: Wegener's granulomatosis (3), IgG4-related disease (2), reactive change to a prior procedure (2), schwannoma (2), sclerosed vascular malformation (2), Erdheim-Chester disease (1), non-Langerhans cell histiocytosis NOS (1), sarcoidosis (1), fibromyxoma (1), and thyroid eye disease (1).  Based on this institutional review, the differential diagnosis of fibrosing lesions of the orbit is broad, encompassing autoimmune, reactive, neoplastic, malformative, and endocrine disease. However, the most common final diagnosis remains idiopathic sclerosing pseudotumor.

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.

PML in a patient with idiopathic CD4 lymphopenia

My last post prompted the inimitable Dr. Murat Gokden to write to me about an interesting case he published in 2015 of a 33-year-old man who with idiopathic CD4 lymphopenia (ICL) who was ultimately diagnosed with progressive multifocal leukoencephalopathy (PML).

Image from Dr. Gikden's paper: A and B are MRI FLAIR images showing hyperintense areas with gyral swelling and sulcal effacement (curved arrows). Image C depicts MR spectroscopy with abnormally elevated choline peak. Image D shows multifocal punctate enhancement in white matter.

Murat Gokden, MD

Progressive Multifocal Leukoencephalopathy in patients without obvious immunosuppression

I recently received a case in consultation which turned out to be progressive multifocal leukoencephalopathy (PML). Reading the clinical history, it was not entirely clear what predisposed the patient to PML. It wasn't clear, that is, until my mentor (the illustrious BK DeMasters) referred me to a nine-year-old paper by Sarah Gheuens, Gerald Pierone, Patrick Peeters, and Igor J. Koralnik entitled Progressive Multifocal Leukoencephalopathy in individuals with minimal or occult immunosuppression (J Neurol Neurosurg Psychiatry 2010;81:247-254). In this series, hepatic cirrhosis -- which was what my patient had -- was among the more common conditions in PML patients with minimal immunosuppression. Other conditions that can be associated with PML in the minimally immunosuppressed are those with renal failure and idiopathic CD4+ lymphopenia,

The authors discuss the possible mechanisms for the development of PML in patients with hepatic cirrhosis:

"[H]epatic cirrhosis can lead to portal hypertension and hypersplenism, with subsequent leucopenia as white blood cells are sequestrated in the enlarged spleen. Furthermore, cirrhosis also leads to hypogammaglobulinemia... It is well known that cirrhotic patients have a higher risk of developing bacterial infections, and 30–50% of deaths among cirrhotic patients are directly caused by infections. Immune dysfunction in hepatic disease may be caused by altered cytokine production, impaired cellular immune response and vascular disturbances, which lead together to increased susceptibility to infections."

Psychiatrist Hand-Knits an Anatomically Correct Textile Sculpture of the Human Brain

A psychiatrist from the National Bureau of Economic Research in Cambridge, MA, Dr. Karen Norberg spent an entire year knitting detailed replica of the central organ. 

Miller selected as division director of neuropathology at University of Alabama

C. Ryan Miller, MD, PhD

The University of Alabama at Birmingham Department of Pathology has recently named C. Ryan Miller, MD, PhD as director of the neuropathology division. He starts in that position on April 1.

Miller was most recently a professor in the Department of Pathology and Laboratory Medicine at the University of North Carolina-Chapel Hill. Miller also served as faculty director of the UNC Translational Pathology Laboratory in conjunction with the Lineberger Comprehensive Cancer Center

“We are excited to have Dr. Miller back at UAB in the Department of Pathology, where his experience in research on tumors of the brain and work with proteomics will enhance the Neuropathology Division’s portfolio for future growth in this important area,” said department chair George Netto, MD.

In 1999, prior to medical school, Miller completed a Ph.D. in the department’s Cellular and Molecular Pathology Graduate Program. He earned his medical degree from the UAB School of Medicine in 2002 and completed a postdoctoral fellowship in the UAB Brain Treatment and Research Program. Miller then moved to Washington University School of Medicine, where he completed a residency in anatomic pathology in 2004 and a fellowship in neuropathology in 2006.

Polymer coating embolism from intravascular medical devices

The deaths of at least three people who had hospital procedures in Vancouver were caused by coatings that sloughed off medical devices like catheters and scattered through blood vessels to major organs, a recent study has found. Here's a link to the relevant news article.

Rupal I. Mehta, MD

Thanks to Dr. Rupal I. Mehta of the University of Rochester for alerting me to this article. Dr. Mehta herself has published on this increasing recognized phenomenon. Here's a link to her update on the topic.

Dr. Harry Vinters had this to say about the new study coming out of Canada: “Their study is especially intriguing in that it utilizes what could be considered old technology — careful tissue analysis of autopsy specimens — to derive extremely important new information that has a direct impact on outcomes in a select group of patients. Indeed, the autopsy is about the only way this data could have been derived, and Dr. Maguire and his colleagues are to be congratulated for the care with which the study was performed and the data analyzed.” Dr. Vinters has published on this topic as well. Here is a link to his review.

Glial cytoplasmic inclusions filling putaminal pencillary fibers in a case of multiple system atrophy (striatonigral type)

Putamen (alpha-synuclein immunohistochemistry)

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.

Donahue does it again: a case of type 2 myotonic dystrophy from Providence, Rhode Island

A case from Dr. John Donahue, inimitable neuropathologist and neuropathology fellowship program director at Brown University:

"This is a fast myosin immunostain on a gluteus maximus biopsy from a 45-year-old woman who went on to have genetically-proven myotonic dystrophy, type 2 (DM2; proximal myotonic myopathy; PROMM).  The type 2 muscle fibers are EXTREMELY atrophic."