Freiburg Neuropathology Case Conference

Primary central nervous system lymphomas (PCNSL) are relatively rare (accounting for only 4% of all intracranial neoplasms) with a peak incidence at about 60 years [1, 2]. The World Health Organization (WHO) classification of tumors has defined a number of subtypes according to the presumed ethology and genesis [3].

In contrast to the imaging presented in this case report, lymphomas typically present as a hyperdense mass on NCCT with vivid and homogeneous enhancement after contrast administration and restricted diffusion on DWI [4]. While a solitary manifestation can be observed in the majority of cases, PCNSL may present as multiple intra-axial lesions in about 30–40% of patients [4]; however, just as in the case presented PCNLS have a predilection for the periventricular white matter and may show no or irregular enhancement mimicking primary angiitis of the CNS [5]. The frequency of simultaneous diagnosis of PCNSL and primary vasculitis of the CNS observed, suggests an immunologic paraneoplastic mechanism [6].

Primary vasculitis of the CNS (PVCNS) is an extremely rare disorder with an estimated average annual incidence of 2.4 cases per 1 million of the population [7]. While it may affect patients of all ages and both genders, the highest risk is found among males around 50 years of age [8]. The clinical and radiological diagnosis remains challenging as symptoms and imaging may show a variety of nonspecific findings.

Ischemic manifestations as observed in the left hemisphere of the patient presented in this case report are the most common [7]; however, they usually affect multiple vascular territories in both hemispheres [7]. In the majority of cases PVCNS also cause intracranial haemorrhage, parenchymal, subarachnoid or both [7]. A tumor-like presentation is found in about 1 of 10 patients [7]. While the most characteristic enhancement pattern presents with very small partial rims on axial sections, some patients may show variable patterns including filiform perivascular enhancement similarly to the one seen in Figs. 1 and 2b–d [7]. PVCNs usually also leads to the steno-occlusive vascular lesions involving proximal or distal segments of at least two cerebral arteries [7]. There was no specific vascular imaging performed in the initial imaging work-up of the case presented here that would have allowed us to rule out occlusive disease within the intracranial arteries.

Due to their highly invasive nature, malignant gliomas (i.e. astrocytomas IDH mutant grade 3 or 4 and glioblastomas IDH wildtype grade 4 were considered in this case) tend to spread along subcortical white matter and intrahemispheric as well as interhemispheric tracts, such as the corona radiata and the corpus callosum [9]. While high-grade IDH mutant astrocytomas mainly affect adults between 30 and 50 years of age [10], the peak incidence for glioblastomas is around 55 years [11]. As in this case, malignant gliomas are usually solitary, hypointense to isointense on T1, hyperintense T2/Fluid attenuated inversion recovery (FLAIR) and predominantly affect the white matter [12]. Although contrast enhancement may be variable, it is most often seen peripherally and surrounding necrotic portions of the tumor [12]; however, invasion of the perivascular spaces has been reported [9] and may lead to a more unusual enhancement pattern. Perifocal vasogenic oedema is seen in most of the larger gliomas but is usually less extensive as seen in the case presented. The solid and enhancing parts of the lesion may show restricted diffusion and an elevated relative cerebral blood volume (rCBV) which tend to correlate with portions within the tumor that are more likely to be high grade [13].

Neural involvement is relatively common among patients suffering from systemic sarcoidosis [14]. The high number of intracranial findings associated with neurosarcoidosis and their subtle manifestation in some cases may pose a challenge in patients who are neither known nor suspected to suffer from sarcoidosis prior to brain imaging. Sarcoidosis usually affects patients between 30 and 40 years of age [15]. An MRI may show enhancement of different intracranial structures including the brain parenchyma (in the form of masses or nodules), the pachymeninges and leptomeninges as well as the cranial nerves [16]. Leptomeningeal enhancement predominantly involves the basal aspects of the brain but may also follow perforating vessels along perivascular spaces leading to a distinct enhancement pattern as seen in this Figs. 1 and 2b–d [17]. Cranial nerve involvement most commonly affects the facial and the optic nerve and may occur in up to three quarters of patients [18, 19]. Pituitary and hypothalamic involvement are usually seen in cases with more extensive leptomeningeal involvement but may also present in isolation [16].

Due to the great variation in imaging appearances brain metastasis present a well-known diagnostic challenge. They roughly represent one third of all intracranial tumors and are most often caused by either lung carcinoma, colorectal carcinoma or breast carcinoma [20]. Cerebral metastasis may be occult at diagnosis and can be solitary in up to 50% of cases [20]. They predominantly occur at the grey-white matter junction or in the arterial watershed areas and may hemorrhage [21]. They may be of variable density on NCCT and often show surrounding edema that is disproportional to the tumor size [21]. On MRI they are usually isointense to hypointense on T1, hyperintense on T2/FLAIR and may show intense, punctate, nodular or ring enhancement depending on their size [21]; however, case reports have shown that brain metastasis can also lead to enhancement along perivascular spaces [22] as seen in this case. Thus, it is wise to consider metastasis as a potential differential diagnosis in all patients with an intra-axial mass lesion, regardless of the enhancement pattern.

Extramedullary plasmactyomas (EMPC) are solitary plasmacytomas manifesting as isolated accumulations of plasma cells at non-osseous sites. They account for less than 5% of all plasma cell disorders and up to one third of solitary plasmacytomas [23]. Patients affected usually present between the fifth and seventh decade of life with a localized submucosal mass in the head and neck region involving either the sinuses, the nasopharynx or the oropharynx [23].

It has also been reported that there is a relevant male predilection [23]. Cross-sectional imaging usually shows homogeneously enhancing soft tissue masses [24]. While literature review provides a few cases describing intracranial plasmocytoma, they have all been reported as extra-axial masses in patients suffering from multiple myeloma [25‐27]. To our knowledge, this is the first case report presenting a patient with an intra-axial solitary plasmacytoma that shows no connection to the dura or skull interface on cross-sectional imaging. Considering the location and the imaging characteristics of the tumor, biopsy and histopathological analyses were essential for making the correct final diagnosis.