biology

Primary central nervous system lymphoma

Primary central nervous system lymphoma is a biology topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Primary central nervous system lymphoma rather than just read about it. In short: Primary central nervous system lymphoma (PCNSL), also termed primary diffuse large B-cell lymphoma of the central nervous system (DLBCL-CNS), is a primary intracranial tumor appearing mostly in patients with severe immunodeficiency (typically patients with AIDS). It is a subtype and one of the most aggressive of the diffuse large B-cell lymphomas.

Key takeaways

Primary central nervous system lymphoma belongs to biology; place it in that map before memorising details.
Learn the definition first, then one example that makes the definition concrete.
Connect Primary central nervous system lymphoma to a quantity you can measure, compute or draw — that is where exam questions come from.
Reproduce the core statement of Primary central nervous system lymphoma from memory before moving on to harder problems.

Reference excerpt

Primary central nervous system lymphoma (PCNSL), also termed primary diffuse large B-cell lymphoma of the central nervous system (DLBCL-CNS), is a primary intracranial tumor appearing mostly in patients with severe immunodeficiency (typically patients with AIDS). It is a subtype and one of the most aggressive of the diffuse large B-cell lymphomas. PCNSLs represent around 20% of all cases of lymphomas in HIV infections. (Other types are Burkitt's lymphomas and immunoblastic lymphomas). Primary CNS lymphoma is highly associated with Epstein-Barr virus (EBV) infection (> 90%) in immunodeficient patients (such as those with AIDS and those immunosuppressed), and does not have a predilection for any particular age group. Mean CD4+ count at time of diagnosis is ~50/μL. In immunocompromised patients, prognosis is usually poor. In immunocompetent patients (that is, patients who do not have AIDS or some other acquired or secondary immunodeficiency), there is rarely an association with EBV infection or other DNA viruses. In the immunocompetent population, PCNSLs typically appear in older patients in their 50s and 60s. Importantly, the incidence of PCNSL in the immunocompetent population has been reported to have increased more than 10-fold from 2.5 cases to 30 cases per 10 million population. The cause for the increase in incidence of this disease in the immunocompetent population is unknown.

Signs and symptoms A primary CNS lymphoma usually presents with seizure, headache, cranial nerve findings, altered mental status, or other focal neurological deficits typical of a mass effect. Systemic symptoms may include fever, night sweats, or weight loss. Other symptoms include

diplopia dysphagia vertigo monocular vision loss progressive dementia or stupor in patients with a nonfocal neurologic exam and minimal abnormalities on MRI (more common in AIDS patients) facial hypoesthesia

Diagnosis

The current standard for diagnosis typically includes positive CSF cytology, vitreous biopsy, or brain/leptomeningeal biopsy. Histopathological confirmation is essential for definitive diagnosis. MRI or contrast enhanced CT classically shows multiple ring-enhancing lesions in the deep white matter. The major differential diagnosis (based on imaging) is cerebral toxoplasmosis, which is also prevalent in AIDS patients and also presents with a ring-enhanced lesion, although toxoplasmosis generally presents with more lesions and the contrast enhancement is typically more pronounced. Imaging techniques cannot distinguish the two conditions with certainty, and cannot exclude other diagnoses. Thus, patients undergo a brain biopsy or vitreous biopsy, if there is intraocular involvement. Another diagnostic challenge is distinguishing PCNSLs from high-grade gliomas. On MRI, PCNSLs typically show a more homogenous contrast enhancement whereas high-grade gliomas have a more heterogeneous contrast enhancement with necrotic area. However, a brain biopsy can be needed to distinguish between these two brain tumours.

Classification Most PCNSLs are diffuse large B cell non-Hodgkin lymphomas.

Treatment Surgical resection is usually ineffective because of the depth of the tumour. Treatment with irradiation and corticosteroids often only produces a partial response and tumour recurs in more than 90% of patients. Median survival is 10 to 18 months in immunocompetent patients, and less in those with AIDS. The addition of IV methotrexate and folinic acid (leucovorin) may extend survival to a median of 3.5 years. If radiation is added to methotrexate, median survival time may increase beyond 4 years. However, radiation is not recommended in conjunction with methotrexate because of an increased risk of leukoencephalopathy and dementia in patients older than 60. In AIDS patients, perhaps the most important factor with respect to treatment is the use of highly active anti-retroviral therapy (HAART), which affects the CD4+ lymphocyte population and the level of immunosuppression. The optimal treatment plan for patients with PCNSL has not been determined. Combination chemotherapy and radiotherapy at least doubles survival time, but causes dementia and leukoencephalopathy in at least 50% of patients who undergo it. The most studied chemotherapeutic agent in PCNSL is methotrexate (a folate analogue that interferes with DNA repair). Methotrexate therapy in patients with PCNSL typically requires hospitalization for close monitoring and intravenous fluids. Leucovorin is often given for the duration of the therapy. Standard chemotherapeutic regimens for lymphoma such as CHOP are ineffective in PCNSL, probably due to poor penetration of the agents through the blood brain barrier. Newer treatments, such as high dose chemotherapy combined with autologous stem cell transplant are proving to increase survival by years. New research to increase permeability of the blood brain barrier with NGR-hTNF followed by CHOP, produced responses in 75% cases. A phase 1 clinical trial of ibrutinib – an inhibitor of Bruton's tyrosine kinase – in 13 patients reported responses in 10 (77%). Five of the responses were complete.

Prognosis

In immunocompetent patients The initial response to radiotherapy is often excellent, and may result in a complete remission. However, the duration of response with radiotherapy alone remains short, with median survival after treatment with radiotherapy just 18 months. Methotrexate based chemotherapy markedly improves survival, with some studies showing median survival after methotrexate chemotherapy reaching 48 months.

In AIDS patients Patients with AIDS and PCNSL have a median survival of only 4 months with radiotherapy alone. Untreated, median survival is only 2.5 months, sometimes due to concurrent opportunistic infections rather than the lymphoma itself. Extended survival has been seen, however, in a subgroup of AIDS patients with CD4 counts of more than 200 and no concurrent opportunistic infections, who can tolerate aggressive therapy consisting of either methotrexate monotherapy or vincristine, procarbazine, or whole brain radiotherapy. These patients have a median survival of 10–18 months. Of course, highly active antiretroviral therapy (HAART) is critical for prolonged survival in any AIDS patient, so compliance with HAART may play a role in survival in patients with concurrent AIDS and PCNSL.

References

External links

MedPix Teaching File MR Scans of Primary Brain Lymphoma

Illustrations

Worked examples

Example 1 — a first encounter with Primary central nervous system lymphoma

Start with the simplest possible case. Write down what Primary central nervous system lymphoma claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In biology, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Primary central nervous system lymphoma before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Primary central nervous system lymphoma ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Primary central nervous system lymphoma

In research: Primary central nervous system lymphoma appears in biology research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry: Engineering practice reuses Primary central nervous system lymphoma in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom: Primary central nervous system lymphoma is common in secondary-school and first-year university syllabi. It links to neighbouring topics Brain tumor, Epstein–Barr virus–associated diseases, HIV/AIDS, so understanding it makes those chapters shorter.
In everyday life: Look for Primary central nervous system lymphoma outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.

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How to study Primary central nervous system lymphoma in 20 minutes

Read the reference excerpt below once, without taking notes.
Close the page and write down what Primary central nervous system lymphoma means in your own words.
Compare your version with the excerpt and mark what you missed.
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Frequently asked questions

What is Primary central nervous system lymphoma in simple terms?

Why does Primary central nervous system lymphoma matter?

Because it connects several biology ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Primary central nervous system lymphoma?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Primary central nervous system lymphoma.