A Jungian Approach to Individual Neuropathological Specimens

I was reading The Undiscovered Self (1958) by Carl Jung today, and noted that Jung's description of individual patients could also be applied to individual tumors:

"The statistical method shows the facts in the light of the ideal average but does not give us a picture of their empirical reality.... The distinctive thing about real facts, however, is their individuality.... There is and can be no self-knowledge based on theoretical assumptions, for the object of this knowledge is an individual - a relative exception and an irregular phenomenon. Hence, it is not the universal and the regular that characterize the individual, but rather the unique. He is not to be understood as a recurrent unit but as something unique and singular which in the last analysis can be neither known nor compared with anything else."

Consider this the next time you sign out a "bread and butter" glioblastoma!

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.