BLEOMYCIN.html


    
        
            
                
                    

                

            

            
                Bleomycin toxicity post injection into cranio-pharyngioma

                Ivan L Norval, MB ChB
            

            Jennifer R Tynan, MD, FRCP (C)
        

        Department of Medical Imaging, Royal University Hospital, University of Saskatchewan, Saskatoon, Canada

        Evan M Frangou, MD
    

    Department of Neurosurgery, Royal University Hospital

    
        Corresponding author: I Norval (ivan.norval@gmail.com)

        
        

        
            Abstract

            Craniopharyngioma
            is a common suprasellar mass that is frequently encountered in
            radiology. These tumours are difficult to treat, with a combination of
            resection and radiation therapy having been the gold standard. Our case
            highlights a complication of a newer approach to treatment in which
            bleomycin is administered into the tumour via a catheter, usually an
            Ommaya reservoir that is surgically placed.

        

        
        

        Presentation

        A 41-year-old woman was diagnosed with
        craniopharyngioma in 2002. Three separate surgical resections were
        performed in the course of 2002 and 2003. The patient subsequently
        developed panhypopituitarism, diabetes insipidus and total blindness.
        Following radiation therapy, she regained vision in her right eye. She
        also developed hydrocephalus post radiotherapy, for which a VP shunt
        was placed. An Ommaya reservoir was also placed.

        In July 2010, she was started on intra-tumoural
        bleomycin injections. A total of only 5 doses were administered. Doses
        of 5 mg bleomycin were administered 3 times a week on an outpatient
        basis. After the second dose, the patient developed transient
        headaches, and the third dose was omitted. Three further doses were
        administered as scheduled. After the fifth dose, she presented with
        worsening confusion, headache and agitation, and was admitted to
        hospital for further care; no further bleomycin was injected.

        Magnetic resonance imaging (MRI) was performed 12
        days after the final injection. This showed extensive vasogenic oedema
        in the basal ganglia and midbrain surrounding the tumour. A diagnosis
        of bleomycin toxicity post intra-tumoural injection into her
        craniopharyngioma was subsequently made on the basis of the imaging
        findings and exclusion of other aetiologies. The oedema progressed on a
        subsequent MRI performed a week later.

        On 4-month follow-up, the patient’s condition
        had improved, and repeat MRI revealed a significant decrease in the
        amount of oedema.

        Discussion

        Craniopharyngiomas are suprasellar tumours that are believed to arise from craniopharyngeal duct remnants.1 
        These tumours are common and represent 50% of all suprasellar tumours
        in childhood, with a peak incidence between the ages of 8 and 12 years
        and a second, smaller, peak in middle-aged adults.2  The tumours are typically lobulated, cystic masses with a mural nodule.2  The cystic component is often the predominant portion and occurs in over 90% of cases.3  The fluid content of the tumour is usually thick and yellow, and can be reminiscent of engine oil on gross pathology.2
    

    Typical features on computed tomography (CT)
    include a cystic component with attenuation slightly higher than CSF,
    and calcification, which may be thin and peripheral or coarse within
    the solid portion.2  Calcification is seen in about 50% of adult patients and in as much as 90% of paediatric patients.1  Contrast enhancement of the cyst walls and other solid components is present in more than 90% of cases.2


The MR appearance of the cystic component is
varied, but commonly the content is hypo-intense on T1 and hyperintense
on T2. The solid components usually enhance heterogeneously.2


Symptoms relate to mass effect on suprasellar structures, as well as local invasion,3  and often include headache, endocrine deficiencies and visual disturbances.4


Although these tumours show benign histology, their
location, as well as their intimate relationship with delicate sellar
structures, complicates management. Management generally consists of
either aggressive surgery or a combination of limited surgical
resection and radiation therapy.5 
Newer treatment options now include placement of an Ommaya catheter
into the cystic portion with instillation of bleomycin into the tumour.
Less commonly, other sclerosing agents or isotopes have also been used.
The Ommaya catheter is usually placed and tested postoperatively by
means of instillation of X-ray contrast, followed by non-enhanced CT to
assess for leakage.3


In the case of bleomycin, there is variability in
the schedule of administration, but a dose of 3 mg is typically given 3
times weekly for 5 weeks, followed by once weekly for 10 weeks.5  Doses can be temporarily discontinued or stopped if the patient becomes symptomatic, as in our case.

Acute side-effects include transient mild fever,
nausea, vomiting and headaches. These occur in up to 70% of patients
within the first 24 hours after each administration, and are usually
self-limiting.3  More severe
delayed side-effects are highly varied, but much more rare, and
occurred in only 2 out of 17 cases in a Canadian series.4 
Intravenous corticosteroid administration is often used for treatment
of peri-tumoural oedema and seems effective, although it is not well
researched as to whether supportive therapy alone would have a much
different outcome.5


MRI – in particular, FLAIR – is the modality of choice for diagnosing bleomycin toxicity.5  Findings usually consist of varying degrees of peri-tumoural vasogenic oedema in the midbrain and basal ganglia,6 
which is thought to be the result of local bleomycin effect in
combination with a small amount of peri-tumoural leakage, and are
predominantly reversible.5


This treatment option is used in combination with
traditional modalities, and can be of significant value if surgery can
be deferred as long as possible, because the intra-tumoural
instillation of bleomycin has a decreased morbidity for the patient
compared with surgery.4


Conclusion

Intralesional bleomycin injection is becoming an
increasingly more popular treatment option for cystic
craniopharyngioma. Although this procedure is less invasive compared to
open resection and is relatively safe, there are still significant
risks involved with this form of treatment. It is of the utmost
importance that radiologists are aware of possible complications and
are able to identify them early to ensure prompt management.




1.	Barkovich J. Pediatric Neuroimaging. 4th ed. Philadelphia: Lippincot Williams & Wilkins, 2005:580-584.

1.	Barkovich J. Pediatric Neuroimaging. 4th ed. Philadelphia: Lippincot Williams & Wilkins, 2005:580-584.

2.	Osborn A. Diagnostic Neuroradiology. St. Louis: Mosby, 1994:654-656.

2.	Osborn A. Diagnostic Neuroradiology. St. Louis: Mosby, 1994:654-656.

3.	Steinbok P, Hukin J. Inracystic treatments for craniopharyngioma. Neurosurg Focus 2010;28(4):1-5.

3.	Steinbok P, Hukin J. Inracystic treatments for craniopharyngioma. Neurosurg Focus 2010;28(4):1-5.

4. Hukin J, Steinbok P, Lafay-Cousin L, et al. Intracystic bleomycin
therapy for craniopharyngioma in children. Cancer 2007;109:2124-2131.

4. Hukin J, Steinbok P, Lafay-Cousin L, et al. Intracystic bleomycin
therapy for craniopharyngioma in children. Cancer 2007;109:2124-2131.

5. Lafay-Cousin L, Bartels U, Raybaud C, et al. Neuroradiological
findings of bleomycin leakage in cystic craniopharyngioma. J Neurosurg
2007;107:318-323.

5. Lafay-Cousin L, Bartels U, Raybaud C, et al. Neuroradiological
findings of bleomycin leakage in cystic craniopharyngioma. J Neurosurg
2007;107:318-323.

6. Kim S, Park J, Park J, et al. Radiological findings following
postsurgical intra tumoural bleomycin injection for cystic
craniopharyngioma. Clin Neurol Neurosurg 2007;109:236-241.

6. Kim S, Park J, Park J, et al. Radiological findings following
postsurgical intra tumoural bleomycin injection for cystic
craniopharyngioma. Clin Neurol Neurosurg 2007;109:236-241.




    




    
        
    

    
        Fig. 1. Axial FLAIR image through the level of the midbrain pre bleomycin administration.

        
        

    




    
        
    

    
        Fig. 2. Axial FLAIR image through the level of the
        midbrain 3 weeks post bleomycin administration, which shows significant
        peri-tumoural vasogenic oedema.

        
        

    




    
        

    




    
        
    

    
        Fig. 3. Axial CT image shows an Ommaya catheter in
        place with contrast instilled into the tumoural cavity to check for any
        leakage of contrast pre bleomycin instillation.