Patients’ medulloblastoma-related features
Six patients (5 of them females) were diagnosed between 2007 and 2016
and met our inclusion criteria. They were a median 10 years old (range
6-26 years) at medulloblastoma diagnosis. All patients presented at
diagnosis with a clinical picture correlating with the tumor site (i.e.
cerebellar deficits, endocranial hypertension, strabismus). None of them
had had MRI before the suspect of brain tumor diagnosis for surveillance
purposes .
The original MRI findings could be retrieved for review in 5/6 cases.
Tumors were classified on the grounds of site, T2-weighted and DWI
signal intensity, and contrast enhancement in accordance with the
classification of WNT medulloblastoma proposed by Patay et al and
already above summarized12. All tumors were located in
the IV ventricle and characterized by uneven T2 hyperintensity, patchy
contrast enhancement, and low ADC levels on DWI. All. Two were subtype
A, and 3 were subtype B. Hydrocephalus was absent in 3 and present in 2
cases (Figure 1, case 5 not shown).
All patients underwent complete surgical excision of their tumors, which
were all attributed to classic histotype and WNT subtype since WNT is
deregulated where there is a germline APC pathogenetic mutation For all
patients Beta-catenin immunostaining was assessed in tumoral tissue.
Nuclear positivity at immunohistochemistry was found in 2/6 patients’
samples.
All patients were homogeneously treated irrespective of age under or
over 18 years, as already reported16. Importantly, all
patients received craniospinal irradiation (CSI) up to a total dose of
23.4 Gy, and a boost to the posterior fossa (in 3 patients) or tumor bed
(in the other 3) up to a total dose of 54 Gy, delivered in fractions of
1.8 Gy, without any interruption due to acute side-effects of
hematological toxicity (table 1).
In one patient (who was 26 years old at diagnosis), the post-operative
schedule including cisplatin, vincristine and lomustine was changed -
replacing cisplatin with carboplatin and omitting vincristine - due to
ototoxicity after the second course and severe peripheral neurotoxicity
with gait impairment .
All patients were in complete remission at 44-142 months after diagnosis
(median 65 months) and were in active follow-up at the time of this
report.
Late effects - Three patients had hypoacusia for acute tones,
three had hypothyroidism (accompanied by thyroid nodules in 2 cases),
two had growth hormone deficits, and five had vitamin D deficiency. One
patient was married and having fertility treatment.
Three patients were still in main stream school, with
special education program and
extra-help teacher in one case each (at MBL diagnosis 6 and 10 years
old, respectively), while the third one did not need education tailored
program or help (6 years old at diagnosis).
One patient, 13 years old at diagnosis, was
attending university; one, 12 years
old at diagnosis, was working after
completing a professional course and one, 26 years old at diagnosis, had
a university degree, was married and
stayed at home, fully independent. Full Intelligence Quotients (FIQ)
were available for 5 patients after 2-7 years from diagnosis (table 1).
Table 1 shows also each patient’s oncological history after treatment
for MBL. One patient developed a melanocytic tumor of uncertain
malignant potential (MELTUMP), one a melanoma, another a thyroid nodule
(classified as TIR3, i.e. uncertain malignancy, after needle biopsy) and
a pancreatoblastoma a mean 6 years after MBL.
Figure 2 shows patients subsequent oncological disease-free survival,
which was 50% at 5 years.