3. Discussion and conclusions
We describe a case of acute cerebellar hemorrhage secondary to
CLIPPERS, with PET/CT suggesting
increased metabolism in both cerebellar. In a recent review of the
published cases, Buttmann et al(Buttmann, et al.,2013) have reported a
case of subacute bleeding in the right cerebellar. Blaabjerg et
al(Blaabjerg, et al.,2016) presented a patient that responded to steroid
treatment but then had a fatal brainstem hemorrhage. Additionally, In
the case report presented by Vivek Sudhakar, susceptibility-weighted
angiography (SWAN) imaging demonstrated a hemorrhagic component of the
right occipital lobe lesion in the patient(Sudhakar, et al.,2021). Since
cerebrovascular events in CLIPPERS patients are rare, the mechanism by
which CLIPPERS leads to cerebrovascular manifestations has not been
established yet.
There are usually a large number of lymphocytes or lymphoid tissue
infiltration around the blood vessels of CLIPPERS lesions, and the
affected lymphocytes are mainly CD3+ and
CD4+(Axelerad, et al.,2021). Different from previous
case reports showing CD4+T cell infiltration around CLIPPERS related
intracerebral hemorrhage lesions, our patient’s cerebellar biopsy showed
diffuse CD3+T cell infiltration around blood vessels, which indicated
significant inflammation around blood vessels(Buttmann, et al.,2013;
Blaabjerg, et al.,2016; Sudhakar, et al.,2021). Similar to most
CLIPPERS, there is perivascular infiltration of inflammatory cells
pathologically in our case, but no characteristic histological features
of vasculitis such as fibrinoid necrosis(Axelerad, et al.,2021).
However, transmural lymphocytic infiltrates and inflammatory vessel
occlusion have been shown to be present in biopsy samples in patients
with CLIPPERS(Taieb, et al.,2016; Axelerad, et al.,2021), suggesting the
direct destruction of immune cells around the blood
vessel wall may be the main cause of bleeding. Interestingly, most
CLIPPERS secondary to cerebral hemorrhage are characterized by a long
course or recurrent disease. The patients reported in our report had
cerebral hemorrhage during hormone therapy due to multiple relapses of
the disease. We can speculate that the long course of disease and
repeated intensive treatment may easily cause cerebral hemorrhage.
It is worth mentioning that Primary central nervous system lymphomas
(PCNSL) is easily confused with CLIPPERS clinically. In addition to
similar clinical symptoms, PCNSL can also show CLIPPERS like image
appearance, and lesions can show high metabolism on PET/CT(Lin, et
al.,2014). The pathology of PCNSL is not specific and therefore cannot
be completely distinguished from CLIPPERS(Axelerad, et al.,2021).
However, PCNSL is not sensitive to hormone therapy, and the condition
cannot be effectively improved(Schaff and Grommes,2021). Recently, one
case reported that patients with intracerebral hemorrhage secondary to
CLIPPERS showed hypermetabolism at the focal site on PET/CT(Sudhakar, et
al.,2021), and our patient also showed hypermetabolism at the focal
site, which was confined to the brain. In addition, our patient was
responding to glucocorticoid therapy and were more radiologically and
pathologically prone to CLIPPERS. Although there is no more evidence,
this led us to wonder if hypermetabolic lesions were associated with
bleeding.
Intracranial hemorrhage is an unfamiliar
complication of CLIPPERS, and physicians should be reminded to pay
attention to the possibility of intracranial hemorrhage, especially in
patients with acute neurological deterioration. In addition,
intracranial hemorrhage may be associated with a long course of disease
and repeated treatment. To our knowledge, this is the first report of
cerebellar hemorrhage and PET shows hypermetabolism in a Chinese
CLIPPERS patient. The possibility of this complication should also be
considered when finding hypermetabolic lesions in CLIPPERS patients.