FIGURE 1
FLAIR	T2
Postcontrast	Perfusion image
DWI with ADC	Spectroscopy

These were our differential diagnoses. Do you want to add any other differential diagnosis?

CT scan of chest, abdomen and pelvis were done in search of primary tumor. On CT chest, there were bilateral asymmetric hilar adenopathy and lower lobe predominant nodular densities. The overall chest findings were not typical for sarcidosis. Bronchoscopy-guided biopsy of the hilar nodes revealed non-caseating granulomas. CT of the abdomen and pelvis were unremarkable.

A diagnosis of sarcoidosis was presumed and the patient was put on steroids. Patient got better clinically and an MRI after 5 days revealed significant improvement of the T2 signal abnormality and mass effect. There was no appreciable change in the size of the enhancing lesion. Patient was discharged home with the diagnosis of sarcoidosis and was advised to continue steroids.

FIGURE 2
T2	Post contrast

2 weeks later the patient came back with new onset diplopia as a result of left 6th nerve palsy. MRI at this point showed interval enlargement of the mass, FLAIR abnormality and enhancement. Central T2 hypointense area was more heterogeneous. At this point of time, atypical infection was on the top of our differential diagnoses.

FIGURE 3
FLAIR	T2
Post contrast

Due to relatively rapid progression of clinical symptoms, the lesion was biopsied. It was fungal abscess due to blastomycosis!!

Blastomyces dernatitidis is the causative agent for blastomycosis. Blastomycosis is an uncommon, but potentially serious fungal infection, endemic in Mississippi and Ohio River basins and in the regions of Great Lakes and the St Lawrence River. Occasionally. it can be found in non-endemic areas as well. There is no predilection for any age, sex, race or occupation but it occurs more frequently in the immunocompromised hosts, particularly in AIDS patients. It primarily affects the lungs. CNS dissemination accounts for 5-10% of extrapulmonary blastomycosis and is usually manifested as intracranial mass lesion, abscess of the spinal cord or epidural abscess and meningitis in rare cases. Cerebellum is most commonly involved, but it can involve any area of brain. Multiple lesions throughout the brain mimicking multiple cerebral metastases has also been described in literature. CSF analysis is not very sensitive for the diagnosis as is the CSF culture. CNS blastomycosis is usually treated with Amphotericine B in combination with oral azoles.

References:

1. Bariola JR, Perry P, Pappas PG, et al. Blastomycosis of the central nervous system: a multicenter review of diagnosis and treatment in the modern era. Clin Infect Dis 2010;50:797-804.

2. Borgia SM, Fuller JD, Sarabia A, El-Helou P. Cerebral blastomycosis: a case series incorporating voriconazole in the treatment regimen. Med Mycol 2006;44:659-64.

Figure 1 - Axial CT image of the head, bone windows, demonstrates lytic lesions in the posterior calvarium with thinning of the inner and outer tables.

She continued to have similar symptoms post-operatively that prompted MR imaging of the brain (Figure 2). The images demonstrate several well-demarcated lesions that were T1 hypointense and T2 hyperintense when compared to bone marrow, with severe thinning of the adjacent cortex.  No intracranial lesions were present.  A T1 hyperintense right subdural collection was due to the recent surgery.

Figure 2 - T1 (left) and T2 (right) weighted axial MR images of the brain demonstrate several calvarial lesions that are T1 hypointense and T2 hyperintense when compared to normal bone marrow.

The differential diagnosis for multiple lytic lesions in the adult skull includes primarily metastatic disease and multiple myeloma.  Others include epidermoids, burr holes and in children, the histiocytoses.

What is your diagnosis?  Are there other rare causes of lytic osseous lesions in the skull?

The patient underwent a right frontal skull biopsy.  Pathology revealed non-caseating granulomatous inflammation, consistent with sarcoidosis.

Sarcoidosis is a multisystemic inflammatory disorder of unknown cause that is best known for pulmonary, lymph node, and cutaneous involvement.  Skeletal involvement is rare, occurring in an estimated 5% of patients.  Most common sites of involvement are the small bones of the extremities and the spine, where characteristic “lacy” lytic lesions are seen.  Primary involvement of the skull is extremely rare.  The first published report was by Nielsen in 1934, with less then 35 cases reported since.  When the skull is involved, the lesions are usually discovered incidentally.  When symptomatic, headaches or tenderness over the skull are the most common complaint.   Lesions in the skull can be solitary or multiple.  They are usually well demarcated, without periosteal reaction or perilesional sclerosis.  The lesions tend to appear less aggressive then metastases, with relative thinning of the inner and outer tables more common then frank destruction.  Also, extra-osseous soft tissue extension is less less likely with sarcoidosis.  For comparison, MR images of a calvarial metastasis from non-small cell lung carcinoma are pictured below (Figure 3).

Figure 3 (left to right) - T1, T2, and T1 post-gadolinium images of the brain demonstrate a T1 hypointense, T2 hyperintense, enhancing mass centered in the calvarium at the right temporal-parietal junction. There is marked cortical destruction and a prominent extra-osseous soft tissue component.

Corticosteroids are the mainstay of treatment, although when isolated to the skull results can be disappointing.

In this case, the patient had no systemic symptoms of sarcoidosis.  Chest radiograph, and films of the pelvis, hands, and feet were normal.  The patient was treated ith steroids.

References:

1. Fernandez-Ruiz, M et al.  Sarcoidosis presenting as an osteolytic skull lesion: a case report and review of literature on skull sarcoidosis.  Clin Rheumatol, 2007; 26: 1745-1748
2. Landsberger D et al.  The skull in chronic sarcoidosis.  Postgrad Med J, 1998; 64: 875-877
3. Moore, SL et al.  Musculoskeletal sarcoidosis: spectrum of appearances at MR imaging.  RadioGraphics, 2003; 23:1389-1399

Figures 1-3: Non contrast CT, coronal post Gd T1WI, and axial post Gd T1WI.

What is your diagnosis? What should you always consider when a lesion in a cavernous sinus is present?

The imaging studies were re-evaluated and due to the calcifications and the non-enhancing region the possibility of a partially thrombosed aneurysm of the ICA was considered.  An angiogram was done (Fig. 4).

Fig 4.  Nearly lateral 3D DSA view after injection of right ICA.

Giant aneurysms represent 5% of all intracranial ones; the prognosis is not good: mortality is 50-100% depending on location.  The most common type is saccular and they can be further subdivided into those that have concentric layers of clot in their walls and those do not.  In the first subtype, their growth is due to intramural re-bleeding and associated inflammation which also results in significant perilesional edema. When they bleed, SAH is generally small, near the aneurysm, and/or inside its walls.  In the 2nd subtype, a small saccular aneurysm becomes giant and when it bleeds it results in diffuse SAH.  Fusiform giant aneurysm are a second type and they are seen with dissections (like in the posterior circulation), infections, and disorders of the arterial walls (such as collagen-vascular ones).   The 3rd typ- the rarest- are the serpentine ones.  These represent re-canalized channels within the clot inside a giant thrombosed aneurysm and what is typical about them is that they have entry and exit points.

Aneurysms become “giant” when they reach > 25 mm in size.  They are more common in middle age females. They generally produce symptoms by mass effect and tend to spontaneously clot more often than others (about 10%).  Common sites: bifurcation of the ICA, intracavernous ICA, basilar artery (dome and then body), and MCA.  Note that this patient also has a smaller aneurysm in the MCA bifurcation (Fig. 4).  The patient underwent a test balloon occlusion of the right ICA successfully and awaits treatment.

At this point, what is your diagnosis? Meningioma…… right?

Our pre-operative diagnosis was also meningioma. Only concern was that the diffusion restriction was little too much for a meningioma, even for a densely cellular anaplastic meningioma.

There were two surprises for us both from surgeons as well as from pathologists. When the surgeons opened the dura, the mass was intra-axial! When the pathologists saw the tumor under microscope, they found diffuse large B-cell lymphoma with very high proliferative index (90-95%) and officially they called it “Large B-cell lymphoma, diffuse, with high proliferative rate and intermediate features between Burkitt lymphoma and large cell lymphoma (WHO classification 2008)”.

This is a very interesting case because the tumor grew without following the ‘basic rules of neuroradiology’. Though the tumor arose from intra-axial compartment the way it enlarged and its internal morphology gave it a look of an extra-axial mass. This is not an uncommon dilemma of day to day neuroradiology practice. The best way to differentiate between pathologies at a given anatomic location is to execute a mental workout (I call it ‘Curé’s algorithm’) which is consisting of a) correct identification of the compartment from where the lesion arises, b) recall of normal structures of that compartment, c) recall of possible pathologies that can arise from the normal structures of that compartment, d) careful evaluation of the imaging appearances of the lesions in different imaging sequences/modalities and finally e) to perform an intensive mental database search for ‘curve fitting’ of the imaging appearances with the possible pathologies considered before. As the first step of the ‘Curé’s algorithm’ went wrong in this case, we ended up a wrong diagnosis even though there were subtle clues to the right diagnosis.

Though the patient presented with relatively short duration of frontal lobe symptoms and the tumor had prominent diffusion restriction we did not consider primary CNS lymphoma (PCNSL) as our provisional diagnosis because a) we thought the tumor was extra-axial, b) the incidence of primary leptomeningeal lymphoma (LL) is exceedingly rare and typical LL does not look like this, c) the tumor had high rCBV, a perfusion characteristic perfusion characteristic typically not seen in lymphoma and finally d) all imaging appearances other than diffusion restriction was ‘best-fit’ for meningioma.

PCNSL is an extranodal manifestation of non-Hodgkin’s lymphoma limited in central neuraxis including orbit, leptomeninges, spinal cord and cranial/spinal nerves without any other systemic manifestation. PCNSL constitutes 6-15.4% of all brain tumor, more common in men and usually occurs in patients >60 years of age. PCNSL is more commonly supratentorial (87%) and solitary (66%) in immunocompetent patient. Primary leptomeningeal lymphoma is a rare subtype of PCNSL limited to the meninges. Primary ocular lymphoma is another rare subset of PCNSL that involves vitreous, sub-retinal space or anterior chamber without systemic or CNS involvement. Up to 90% of these patients subsequently develop CNS lymphoma. Some authors also consider neurolymphomatosis as a variant of PCNSL. Neurolymphomatosis is very difficult to diagnose on MRI, particularly if the patient has no known lymphoma, either systemic or PCNSL.

The imaging appearance of the tumor depends upon the immune status of the patient. In immune competent patients, PCNSL is solid, T1 hypointense and iso- to slightly hyperintense on T2 weighted sequence. It can involve any area of brain but frontal lobe and basal ganglia are most commonly involved. It enhances brightly and homogenously with contrast. On diffusion weighted imaging, there is prominent diffusion restriction due to intense ‘packing’ of the tumor. Lymphoma is usually cold on perfusion imaging. PCNSLs in immunocompromised patients typically appear as peripherally located ring-enhancing lesions with central necrosis. They are often multiple. There may be diffusion restriction only at the periphery.

Iwamoto FM, DeAngelis LM. An update on primary central nervous system lymphoma. Hematol Oncol Clin North Am. 2006;20:1267-85

Shenkier TN. Unusual variants of primary central nervous system lymphoma. Hematol Oncol Clin North Am. 2005;19:651-64

On surgery, the mass was encapsulated but the capsule was tightly adherent to the cerebellum. On histopathology, the tumor turned out to be a malignant fibrous histiocytoma (MFH) with 40% MIB-1 index.

MFH, the most common soft tissue sarcoma in adults, arises from fibroblasts, myofibroblasts or undifferentiated mesenchymal cells. Most patients are between 50 and 70 years old. Men are affected 2-3 times more commonly than women. Most MFHs arise de novo however, they can occur secondary to prior radiation, trauma, Paget’s disease, chronic osteomyelitis or benign bone tumors. MFH most commonly occurs in lower extremity. Head and neck area is involved up to 10% of cases.  In head neck, nasal cavity and paranasal sinuses are most commonly involved. It has variable appearances on CT and MRI. On CT, this is usually large lobulated sift tissue mass which is isodense to muscles with destruction/remodeling of adjacent bone. There may calcification in up to 5-20% of patients. On MRI, they are isointense to muscle on T1 weighted sequence and heterogeneously hyperintense on T2 weighted sequence. This tumor can have both solid and cystic component. Solid portion enhances intensely. Spontaneous hemorrhage is frequently seen and can obscure the primary tumor. The diagnosis is important because it is a malignant tumor and post-resection radiation therapy is required for better tumor control. MFH also has poor prognosis.

Suggested readings:

Nakayama K, Nemoto Y, Inoue Y, Mochizuki T, Soares SB, Ohata K, Katsuyama J, Onoyama Y and Wakasa K. Malignant fibrous histiocytoma of the temporal bone with endocranial extension.AJNR Am. J. Neuroradiol. 1997; 18: 331 – 4.

Park SW., Kim HJ., Lee JH, and Ko. YH. Malignant Fibrous Histiocytoma of the Head and Neck: CT and MR Imaging Findings. AJNR Am. J. Neuroradiol. 2009; 30: 71 – 6.

Physical examination showed no chemosis, vision loss or cranial nerve palsies.  Because of this the patient was brought back for repeat contrast enhanced CT of the orbits with Valsalva maneuver.  This study showed mild additional enlargement of the already prominent left superior ophthalmic vein and also of the right sided one (see below).  The combination of imaging and clinical findings was thought to be most compatible with orbital varices.  The patient opted for conservative management.

Orbital varices are hamartomas composed of slow flow, low pressure and thinned walled and distensible blood vessels.  As they communicate with the rest of the circulation, they enlarge with Valsava, bending or prone position, and coughing and straining.  They produce proptosis which may be painful and because they may bleed, their symptoms may become acutely exacerbated.  They may also erode adjacent bone.  Treatment is very difficult and is reserved for those with repeated hemorrhages, thrombosis, optic nerve compression and disfigurement.  Orbital vascular processes included in the differential diagnosis are carotid cavernous fistulas of both types and less likely, venous thrombosis.

In CC fistulas, the ipsilateral cavernous sinus may be enlarged particularly in the direct ones (see below).  Extra-ocular muscles may also be large and the retro-ocular fat may have a “dirty” appearance.  In most patients with direct CCFs, chemosis, decreased vision and cranial nerve palsies are present.  Acute thrombosis of the superior ophthalmic vein may present with symptoms that are similar to those of a direct CCF.  Indirect CCFs may have less acute symptoms and be clinically similar to varices.  The diagnosis is confirmed with catheter angiography as shown here.

Suggested readings:

YO Arat, ME Mawad, M Boniuk. Orbital Venous Malformations: Current Multidisciplinary Treatment Approach. Arch Ophthalmol 2004; 122: 1151 – 1158

N Islam, K Mireskandari, GE Rose. Orbital varices and orbital wall defects. Br J Ophthalmol 2004; 88: 1092 – 1093

A Weill, C Cognard, L Castaings, G Robert, J Moret. Embolization of an orbital varix after surgical exposure. AJNR Am. J. Neuroradiol. 1998; 19: 921 – 923

Further questioning of patient disclosed that the symptoms had had a sudden onset 7 days earlier.  The diagnosis of subacute infarction of the right posterior inferior cerebellar artery territory was considered as the most likely cause of the findings.  The patient was followed and repeat MRI three months later demonstrated only malacia and atrophy in the location.

Llermitte-Duclos disease (a.k.a. dysplastic gangliocytoma of the cerebellum) is the CNS hallmark of Cowden syndrome.  It is probably a malformative hamartoma of the cerebellum seen nearly exclusively in this syndrome.  The typical lesion has a “corduroy” or “tiger striped” appearance, does not enhance after contrast, has restricted diffusion (presumably due to its high cellularity), and normal-to-increased perfusion. MRS shows low NAA, decreased Cho/Cr, elevated lactate and high myoinositol and at times the spectra may be near normal (see below).  PET shows increased FDG accumulation.  Thus to differentiate it from an infarct with similar appearance perfusion and PET studies are best when in doubt.  Additionally, contrast enhancement in Llermitte-Duclos is extremely rare.

Suggested readings:

Klish J, JUengling F, Spreer J, Koch D, et la. Llhermitte-Duclos disease: assessment with MR imaging, positron emission tomography, single photon emission CT, and MR spectroscopy. AJNR Am J Neuroradiol 2001; 22: 824-30

Moonis G, Ibrahim M, Melhem ER. Diffusion-weighted MRI in Llermitte-Duclos disease: report of two cases. Neuroradiology 2004; 46: 351-54

Awwad EE, Levy E, Martin DW, Merenda GO. Atypical MR appearance of Lhermitte-Duclos disease with contrast enhancement. AJNR Am J Neuroradiol 1995; 16: 1719-20

Before surgery, a chest radiograph was obtained and showed bilateral hilar nodularities.  Surgery was postponed and a chest CT confirmed the hilar abnormalities and showed parenchymal abnormalities (see below).  Based on the findings a work up for sarcoidosis was performed and was positive.  The patient received steroids and her vision improved.  Follow-up brain MRI showed the lesion to be smaller.

Sarcoidosis is more common in younger (average age: 35 years) African American women.  Over one half of patients will have neurological complaints, generally longstanding.  In about 10% of patients, sarcoidosis is isolated to the CNS.  The most common symptoms are headaches and cranial nerve palsies (mostly affecting the V, VII, VIII and III).  Approximately 15% of patients have dural disease (which is often accompanied by leptomeningeal involvement).  Dural disease responds well to treatment.  Conversely, intra-axial disease leads to seizures and is more difficult to control.  Angiotensin converting enzyme test is positive in 50% of patients.  The MRI findings on our case are typical of sarcoidosis.  The very low T2 signal can be seen in up 20% of meningiomas (particularly of the fibroblastic or transitional types).  Remember that most meningiomas are isointense to gray matter on T2WI (see below).

Suggested readings:

Chirstoforidis GA, Spickler EM, Recio MV, Mehta BM. MR of CNS sarcoidosis: correlation of imaging features to clinical symptoms and response to treatment. AJNR Am J Neuroradio 1999; 20: 655-669

Shag R. Roberson GH, Cure JK. Correlation of MR imaging findings and clinical manifestations in neurosarcoidosis. AJNR AM J Neurodiol 2009; 30: 953-961

Smith JK, Matheus MG, Castillo M. Imaging manifestations of neurosarcoidosis. AJR 2004; 182: 289-295

Analysis of axial images showed that the mass involved the spinal canal but extended out into the paraspinal regions, including the right psoas muscle, via several neural foramina.  The diagnosis was reconsidered to include giant invasive spinal schwannoma (histologically confirmed later).

Schwannomas are the most common primary spinal tumor occurring predominantly in the cervical and thoracic regions.  Tumors of the cauda equina region represent only 6% of all spinal masses; most are schwannomas. “Giant” schwannomas are rare, long lesions that expand, remodel or destroy adjacent bones.  When they extend to extra-spinal myofascial planes, they are considered “invasive”.  Symptoms vary from severe to mild. Total excision is advocated but not always feasible.  Spinal fusion after tumor resection is needed in most patients.  Perhaps, fewer than 20 cases of giant schwannomas are found in the modern literature nearly all of them in the lumbosacral region. They are not associated with NF-2. The main differential diagnosis is that of myxopapillary ependymoma. Giant ependymomas are more common in younger individuals and despite attaining large size they do not tend to produce the focal bone scalloping and paraspinal involvement that giant schwannomas typically show (see illustration below). Mutiple schwannomas, as seen in NF-2 could also have a similar appearance.

References:

Sridhar K, Ramamurthi R, Vasudevan MC, Ramamurthi B. Giant invasive spinal schwannomas: definiation and surgical management. J Neurosurg (Spine) 2001; 94: 210-215

Hung CH, Tsai TH, Lin CL et al. Giant invasive schwannoma of the cauda equina with minimal neurologic deficit: a case report and literature review. Kaohsiung J Med Sci 2008; 24: 212-217

Guyotat J, Fishcer G, Remond J et al. Giant ependymoma of the cauda equine. Long-term development apropos of 7 cases. Neurochirurgie 1993; 39: 85-91

Analysis of images showed an artifact involving the right lower side of the skull seen only on the DWI, ADC and a T2* sequence.  This magnetic susceptibility artifact was found out to have been due to a metal chain.  Upon arrival in our CT scanner, the technologists removed the chain to prevent artifacts.

Discussion:

In FLAIR images, an inversion pulse is applied to suppress the normal signal intensity from CSF.  Multiple causes result in T2 prolongation of CSF signal making it bright on FLAIR and include: inhaled oxygen, increased proteins due to presence of blood or infection, tumor, propofol, and hyperdynamic pulsations such as those seen in the basilar cisterns particularly around arteries.  Artifacts resulting in hyperintense CSF include: motion, inhomogeneity in amplitude of initial inversion pulse, chemical shift, cross-talk, truncation, suboptimal inversion time, overlapping of imaging planes and as in this patient, magnetic susceptibility artifact.  Metals may result in incomplete nulling of CSF signal simulating hemorrhage or increased CSF proteins.  This is commonly seen in the frontal regions in patients with dental braces.

References:

1. Cianfoni A, Martin MGM, Hesselink JR, et al. Artifact simulating subarachnoid and intraventricular hemorrhage on single-shot, fast spin-echo fluid-attenuated inversion recovery imaging caused by head movement: a trap for the unwary. AJNR Am J Neuroradiol 2006; 27: 843-849
2. Tha KK, Terae S, Kudo K, Miyasaka K. Differential diagnosis of hyperintense cerebrospinal fluid on fluid-attenuated inversion recovery images of the brain. Part 2: non-pathological conditions. British J Radiol 2009; 82: 610-614