Primary CNS lymphoma: a tumor that preys on the immunosuppressed

Here’s another primary CNS tumor that arises in the brain parenchyma: primary CNS lymphoma.

Definition

Just to clarify the word “primary” here – these are lymphomas that arise right in the brain itself. You can also have a lymphoma that arises elsewhere in the body that secondarily spreads to the brain parenchyma. This is exceedingly rare (usually, if lymphoma spreads to the CNS, it just involves the CSF or very superficial areas of the brain). Weird: lymphoma arising in brain parenchyma rarely spreads elsewhere, and lymphoma arising elsewhere rarely spreads to the brain parenchyma.

Most primary CNS lymphomas are B-cell in nature; diffuse large B-cell lymphoma is the most common type. In patients who are immunosuppressed, as you might expect, the tumor cells are usually are positive for Epstein-Barr virus.

Incidence

This is a rare tumor, overall: it accounts for 2% of all extra-nodal lymphomas, and only 1% of intracranial tumors. However, in immunosuppressed patients (like patients with AIDS, or patients who have had a transplant), it is the most common tumor of the CNS.

Gross appearance

Grossly, primary CNS lymphoma is usually multifocal within the brain; it can involve both deep gray matter and white matter. There’s often a lot of necrosis.

Morphology

Here’s a weird thing: the tumor cells tend to accumulate around blood vessels, like this:

Here’s another weird thing: if you stain a section of tumor with reticulin, you’ll often see little reticulin fibers forming “hoops” in between the tumor cells:

Prognosis

This is not a nicely-behaving tumor. Compared to regular lymphoma, primary CNS lymphoma is more aggressive, with a worse response to chemotherapy.

Neuroma vs. neurofibroma

Q. What is the difference between a neurofibroma and a neuroma?

A. A neuroma is a general term that applies to any of a number of different things (neoplastic or non-neoplastic) that make a nerve or nerve bundle swell. Usually, another word is attached to give more specific meaning.

Neoplastic neuromas are tumors of any part of a nerve (including the surrounding myelin); sometimes the term is used more broadly to refer to any tumor of neural tissue. An example of a neoplastic neuroma is acoustic neuroma, a benign tumor surrounding the 8th cranial nerve (you can also call this tumor a schwannoma, since it is a neoplasm derived from the Schwann cells surrounding the nerve, not the nerve itself).

The main non-neoplastic neuromas are traumatic neuroma (a non-neoplastic reaction of a nerve to some sort of damage) and Morton’s neuroma (which is not even a neuroma, but just an accumulation of fibrous tissue around a nerve, usually in the foot).

Neurofibromas are benign neoplasms derived from the myelin sheath of peripheral nerves (just as a reminder: the myelin surrounding peripheral nerves is supplied by Schwann cells; the myelin surrounding central nerves is supplied by oligodendrocytes). They often occur in the context of neurofibromatosis, a hereditary condition characterized by multiple cutaneous neurofibromas, pigmented skin lesions, skeletal abnormalities, macrocephaly, epilepsy, and a bunch of other findings. In the photo above, the patient has multiple neurofibromas scattered over his entire body.

Neurofibromas are like schwannomas, in that they are derived from schwann cells. However, a schwannoma has mostly just schwann cells in it, whereas a neurofibroma has a bunch of other cell types, like fibroblasts, endothelial cells, and mast cells.

What is the prognosis in multiple sclerosis?

MS

Q. My 28 year old friend was just diagnosed with multiple sclerosis. What can he expect regarding prognosis?

A. MS is a demyelinating disease that is thought to be autoimmune in nature. It is not easy to predict an exact prognosis for an individual patient, but I think you can boil it down to the fact that while a small number of people with MS become unable to write, speak, or walk, the vast majority of patients are mildly affected by their disease. Let’s look at this in a little more detail.

Subtypes

There are several subtypes of MS, each with different symptoms and prognoses. Note that the frequencies of the different subtypes listed in different sources may not be comparable, because some sources refer to the frequency at diagnosis, while others refer to an overall frequency. It would be useful to know which subtype your friend fits into, because that may help determine his prognosis.

1. Benign MS
People with this type of MS have only rare attacks, and are minimally disabled 10 years after their diagnosis (therefore, you can’t make this diagnosis until 10 years have elapsed!).

2. Relapsing-Remitting
People with this type of MS attacks followed by partial or complete recovery periods free of disease progression. This is the most common type at diagnosis – but some patients move into one of the other types later on.

2. Primary-Progressive
People with this type of MS experience a slow but nearly continuous worsening of their disease from the onset, with no distinct relapses or remissions. This is an uncommon subtype.

3. Secondary-Progressive
People with this type of MS experience an initial period of relapsing-remitting MS, followed by a steadily worsening disease course. Many people with relapsing-remitting MS developed this form later on – but that was before new drugs for MS were introduced. This subtype may be less frequent now.

4. Progressive-Relapsing
People with this type of MS experience a steadily worsening disease from the onset but also have relapses, with or without recovery. In contrast to relapsing-remitting MS, the periods between relapses are characterized by continuing disease progression. This is an uncommon subtype.

Factors influencing prognosis

1. Factors associated with a better prognosis:

  • female gender
  • age of disease onset earlier than 40 years
  • a first attack consisting of optic neuritis or other sensory symptoms
  • lack of significant disability 5 years after onset
  • minor abnormalities on brain MRI scan at the time of diagnosis.

2. Factors associated with a less favorable prognosis:

  • male gender
  • age of onset at age 40 or later
  • a first attack consisting only of motor symptoms
  • difficulty walking or sustained impairment in coordination after resolution of first attack
  • large number of MRI lesions

All that being said.

It’s going to be hard to tell with a lot of certainty at this point what your friend’s prognosis is, because the diagnosis is new. Once he has had the disease a few years, then it will be important to see how it has progressed (or not progressed), because one of the more important predictors of one’s future MS course is one’s past MS course.

Here are some good web resources for learning more about MS:

1. The NIH
http://www.ninds.nih.gov/disorders/multiple_sclerosis/multiple_sclerosis.htm

2. The National Multiple Sclerosis Society
http://www.nationalmssociety.org/index.aspx

3. The University of California – San Francisco Multiple Sclerosis Center
http://www.ucsf.edu/msc/faq.htm#beyond

4. The Multiple Sclerosis International Federation
http://www.msif.org/en/about_ms/types_of_ms.html

The illustration above is from Joseph Babinski’s 1885 thesis, “Etude anatomique et clinique de la sclérose en plaques.”