June 27, 2017
The diagnosis of inflammatory brain diseases often requires a tissue diagnosis.
Neuroinflammatory diseases such as neurosarcoidosis and chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) can be difficult to differentiate from neoplastic or infectious conditions on clinical or radiologic grounds alone. Although hemispheric biopsy is commonly performed, the yield and safety of posterior fossa biopsies haven't been clearly defined.
Cerebellar and brainstem parenchymal biopsy for diagnosis of tumor and inflammatory conditions
A. MRI of a 68-year-old patient who presented with progressive ataxia over two months. Cerebral spinal fluid was normal, and malignancy was considered the most likely diagnosis. She was referred to Mayo Clinic, where stereotactic biopsy of the right cerebellar peduncle was performed, resulting in a diagnosis of demyelinating disease. An appropriate treatment plan was instituted within two weeks of the patient's referral appointment at Mayo Clinic. B. MRI of a 26-year-old man with Hodgkin lymphoma and tingling around his face. Intracranial lymphoma was considered the most likely diagnosis. Left stereotactic biopsy of the cerebellum was performed at Mayo Clinic without complications. Pathology revealed a granulomatous disorder, dramatically altering the patient's treatment plan. C and D. MRIs of a 75-year-old man with progressive speech disturbance, ataxia and swallowing difficulty over five months. Preoperative diagnosis was chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Biopsy was performed at Mayo Clinic to exclude malignancy. Pathology confirmed the absence of malignancy, and appropriate immunotherapy was begun. The patient's symptoms improved.
At Mayo Clinic in Rochester, Minnesota, cerebellar and brainstem parenchymal biopsy for diagnosis of tumor and inflammatory conditions is performed in carefully selected patients. The diagnostic yield and safety of the procedures at Mayo Clinic are similar to yield and safety of hemispheric biopsy.
"Physicians typically shy away from performing biopsies in the eloquent area of the posterior fossa, particularly the brainstem. The risk of complications is thought to be high, and there is the possibility of death if bleeding occurs within the confined space available. But that's not what we've found at Mayo Clinic," says W. Oliver Tobin, M.B., B.Ch., BAO, Ph.D., a consultant in Neurology at Mayo Clinic's campus in Minnesota." In carefully selected patients, it is appropriate to biopsy."
A study of posterior fossa biopsies performed at Mayo Clinic from 1996 to 2009 found that the diagnostic yield in patients with diverse pathologies was 80 percent. Transient complications were seen in 11 percent of cases. Only three patients sustained permanent, nonfatal complications; two deaths were attributable to biopsy. The study, published in the December 2015 issue of World Neurosurgery, reviewed 137 posterior fossa biopsies performed in 136 patients.
"These biopsies actually look pretty safe," Dr. Tobin says. "That's attributable to our careful selection of patients for this procedure. But we also believe that the level of experience our neurosurgeons have with this procedure is improving our outcomes."
Fredric B. Meyer, M.D., enterprise chair of Neurosurgery at Mayo Clinic, performs these biopsies. "Coming to a place like Mayo Clinic is important when patients are suffering from neurological deterioration and no answer has been identified," he says. "There's a chance that we can get an answer and, we hope, find a treatable disease.
"This is a team endeavor," he adds. "The neurologist is key in conducting exhaustive evaluations to make sure a diagnosis can't be provided without undertaking this type of biopsy. It's also important to have good neuroradiology, so you can be sure you've identified everything before the procedure. Then you need an expert pathologist who can look at small bits of tissue and figure out what's going on. That's an art and a science."
Mayo Clinic neurologists see many patients with posterior fossa conditions, due to the center's expertise in neoplastic and inflammatory brainstem lesions as well as in atypical demyelinating conditions. Patients referred to Mayo Clinic with these conditions often have not responded to immunotherapy and other treatments.
"In these cases the clinical scenario is clouded by the fact that the patients may have been on treatment. It can be challenging to get an accurate diagnosis without biopsy," Dr. Tobin says. Among patients with suspected posterior fossa neoplasm who undergo biopsy, about 85 percent have neoplasm confirmed by the procedure. "That's 15 percent who don't, and that is very useful clinical information," Dr. Tobin says.
Among patients with suspected neuroinflammatory disease who undergo biopsy, about 45 percent receive a definitive tissue diagnosis. "Additionally, we're able to confirm, for most of the additional patients in that group, that they don't have cancer," Dr. Tobin says. "That allows us to treat the condition with more confidence, either with immunotherapy or clinical monitoring."
Among patients referred with suspected CLIPPERS — an atypical demyelinating condition identified at Mayo Clinic in 2010 — about half are diagnosed with the disease. "In patients with suspected CLIPPERS, brain biopsy should be considered if at all possible because we don't have a specific biomarker for that disease as yet," Dr. Tobin says. "CLIPPERS can be misdiagnosed as tumor, lymphoma, vasculitis or sarcoidosis, which requires different treatment paradigms."
Patients with widespread systemic malignancy and other significant comorbidities are generally poor candidates for posterior fossa biopsy. However, patients with suspected focal lesion or neuroinflammatory disease — even patients experiencing severe symptoms such as dysarthria, ataxia and swallowing problems — can often tolerate posterior fossa biopsy well.
"At Mayo Clinic we have a large number of providers with expertise in neuro-oncology and in inflammatory brainstem disorders," Dr. Tobin says. "As a result, we have a large volume of patients with unusual presentations, who may benefit from a posterior fossa brain biopsy. That experience helps us provide the best possible outcome for patients."
For more information
Tobin WO, et al. Diagnostic yield and safety of cerebellar and brainstem parenchymal biopsy. World Neurosurgery. 2015;84:1973.
Pittock SJ, et al. Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Brain. 2010;133:2626.