Keywords facial pain - primary lymphoma of the central nervous system - trigeminal neuropathy
Palavras-chave dor facial - linfoma primário do sistema nervoso central - neuropatia trigeminal
Case Report
A 29-year-old previously healthy male presented with lancinating left facial pain
and paresthesia. The pain involved all divisions of the trigeminal nerve and was worse
in the mandibular division. He received a daily dose of 1,200 mg of carbamazepine
without improvement. The patient was then seen by a dentist and underwent repeated
molar extractions; however, his facial pain became worse. He also suffered from severe
symptomatic diplopia, which was evident on lateral gaze to the left. Clinical examination
revealed an intact corneal reflex with abducent nerve palsy on the left side. There
was hypoesthesia to all sensory modalities, involving the maxillary and mandibular
divisions; however, there were no trigger points. There was no evidence of weakness
of the muscles of mastication on the left side, but the examination showed atrophy
of the temporalis muscle.
Brain magnetic resonance imaging (MRI) revealed a globular lesion straddling the posterior
and middle fossae, which caused uniform enlargement of the trigeminal nerve from its
root at the prepontine cistern unitl the gasserian ganglion at the Meckel cave on
the left side, and extending to the left cavernous sinus without encasement of the
carotid artery ([Fig. 1 ]). It measured 3 × 1.8 × 2.8 cm, showing intermediate T1 and T2 signal intensity,
and intense enhancement with gadolinium without a dural tail. The preoperative diagnostic
hypothesis was schwannoma, based on the site and imaging characteristics. Routine
laboratory investigations were within normal values.
Fig. 1 After discussing the advantages and disadvantages of the available treatment options
with the patient, surgery was decided. The other possible treatment was stereotactic
radiosurgery (SRS) with serial imaging follow-up.
Operative Procedure and Findings
Operative Procedure and Findings
The patient was operated by an anterior petrosal approach. The approach was performed
through a frontotemporal osteomuscular craniotomy. The details of anesthesia, positioning
and craniotomy, drilling of the apex of the petrous bone, dural opening, and division
of the tentorium have been described elsewhere.[1 ] The tumor was evident after exposure of the gasserian ganglion. However, the posterior
fossa part of the tumor was only seen after opening of the dura and division of the
tentorium. At this point, the whole trigeminal nerve was evident from the root entry
zone and all the way until the division of the gasserian ganglion.
The tumor was greyish-brown in color, quite firm in consistency, and adhesive. It
was arising within the plexiform part of the Gasserian ganglion. It was dissected
using sharp dissection from within the Gasserian ganglion and, with difficulty, a
plane of dissection could be established from the medial aspect of the ganglion. At
this point, the sixth nerve became visible and was preserved. We found that the tumor
did not encircle the carotid artery. It was completely resected along with the trigeminal
nerve root due to its complete infiltration by the tumor. Hemostasis was achieved
and the wound was closed in layers.
Postoperatively, the patient was in an excellent condition. The wound was clean and
without cerebrospinal fluid (CSF) collection. The sixth cranial nerve started to regain
function and the diplopia improved considerably, but did not go back to normal. The
trigeminal pain disappeared completely, and the patient stopped taking carbamazepine.
However, there was a persistent hypoesthesia involving all division of the trigeminal
nerve on the left side, but it was not incapacitating. A follow-up brain MRI with
contrast revealed complete excision of the tumor.
Histopathological examination of the excised tumor by light microscopy after hematoxylin
and eosin (H&E) staining revealed mildly fibrotic tissue showing moderate lymphoplasmacytic
infiltrate with moderate lymphoid hyperplasia. The preliminary diagnosis was of an
inflammatory process, but immunohistochemistry revealed neoplastic cells that were
moderately positive for CD20, CD138 and BCL2, and many scattered non-neoplastic cells
positive for CD3. The Ki -67 stain was positive in between 30 and 35% of the neoplastic cells. Accordingly,
the findings were compatible with low grade marginal zone B cell lymphoma ([Fig. 2 ]).
Fig. 2 (A ) Histopathology by light microscopy after hematoxylin and eosin (H&E) staining showing
moderate lymphoplasmacytic infiltrate with moderate lymphoid hyperplasia. Figure 2
B,C,D: Immunohistochemistry revealed neoplastic cells to be moderately positive for
CD20, CD138 and BCL2 in B, C and D, respectively.
Systemic involvement was excluded by whole body positron emission tomography (PET)
scan, and laboratory investigations including CSF cytology and bone marrow biopsy.
The patient received localized intensity modulated radiation therapy (IMRT) on the
tumor bed with a dose of 36 Gy divided over 20 sessions in 4 weeks. After a 3-month
follow-up interval, there was no recurrence, and the patient was pain-free.
Discussion
The trigeminal nerve is a rare site for primary CNS lymphomas ([Table 1 ]).[2 ]
[3 ]
[4 ]
[5 ]
[6 ]
[7 ]
[8 ]
[9 ]
[10 ]
[11 ]
[12 ] The first case was reported in 1996 by Nakatomi et al.[2 ] The reported cases were in patients with ages ranging from 40 to 77 years old, with
a mean age of 56 years old. The male to female ratio was 2.67: 1. Our male patient
was 29 years old at the time of presentation. In previous reports, the main presenting
symptoms were facial pain followed by diplopia and facial numbness. Our patient also
presented with left-sided facial pain that was more severe in the distribution of
the mandibular division. This was also associated with numbness and diplopia due to
paralysis of the 6th nerve.
Table 1
Reports of Trigeminal Nerve Lymphoma
Authors
Age and gender
Presentation
Site
Preliminary diagnosis
Approach
Histopathology
Fate
Nakatomi 1996(2)
77
Male
Facial hypoesthesia
Lt prepontine cistern- cavernous sinus
Schwannoma or meningioma
Lateral suboccipital
Diffuse large B cell
Death
Abdel Aziz 1999(3)
40
Female
Facial pain, hypoesthesia
Lt Meckel's cave- cavernous sinus
Schwannoma
Frontotemporal craniotomy with orbit zygomatic osteotomy with anterior petrosectomy.
Monocytoid malignant B cell lymphoma
N.A.
Kinoshita 2003(4)
55
Male
Facial pain, diplopia
Lt Meckel's cave- infratemporal fossa
N.A.
Lateral suboccipital
Diffuse large B cell lymphoma Biopsy
Death
Bulsara 2005(5)
52
Female
Facial pain
Lt Meckel's cave- foramen rotundum
N.A.
Subtemporal
Non-Hodgkin lymphoma
N.A.
Iplikcioglu 2006(6)
50
Male
Facial pain, diplopia
Rt prepontine cistern- cavernous sinus
N.A.
Lateral sub occipital
B cell malignant lymphoma
Complete recovery
Akaza 2009(7)
60
Male
Facial pain
Lt prepontine cistern- Meckel's cave
Schwannoma or sarcoidosis
Biopsy from another lesion
Diffuse large B cell lymphoma
Complete recovery
Yamahata
2012(8)
68
Male
Facial pain and numbness
Distal trigeminal root -Lt Meckel's cave
Schwannoma, meningioma, malignant lymphoma, metastasis, or inflammatory disease
Anterior petrosal approach
T cell/histiocyte-rich B cell lymphoma
Complete recovery
Perera 2014(9)
55
Female
Diplopia
Rt cavernous sinus- pterygopalatine fossa
Meningioma
Transsphenoidal and pterional
Non-Hodgkin small B cell lymphoma with plasmacytoid differentiation
N.A.
Jack 2014(10)
57
Male
Facial pain
Lt prepontine cistern- Meckel's cave
N.A.
Lateral suboccipital
Diffuse large B cell lymphoma
Complete recovery
Ogiwara 2015(11)
47
Male
Facial pain, diplopia
Lt prepontine cistern- infratemporal fossa
Schwannoma or neuritis
Lateral suboccipital and subtemporal
Diffuse large B cell lymphomas, nongerminal center B type
Complete recovery
J.W.J 2015(12)
55
Male
Facial pain
Rt cavernous sinus- RtMeckel's cave- infratemporal fossa
Schwannoma or meningioma
Right temporal
Diffuse large B cell lymphoma
Complete recovery
Present case
29
Male
Facial pain
Lt Meckel's
Cave - lt cavernous sinus
Schwannoma
Anterior petrosectomy through frontotemporal craniotomy
Low grade marginal zone B cell lymphoma
As in all the available reports, preoperative diagnosis was not possible. Our proposed
preoperative diagnostic hypothesis was schwannoma. Differential diagnosis of lesions
involving the trigeminal nerve and extending into the cavernous sinus include: schwannoma
of the trigeminal nerve, meningioma, lymphoma, and inflammatory lesions (herpes neuritis
of the trigeminal nerve, idiopathic trigeminal neuropathy, and chronic granulomatous
neuritis).[11 ] It is difficult to distinguish these lesions on pure clinical or radiological basis
alone, but trigeminal lymphoma may be suggested by the short duration of symptoms.[6 ] The duration of symptoms in our case was only 3 months. Our patient had rapidly
progressing abducens palsy. This is rare in trigeminal schwannomas or meningiomas.
As in reported cases, the laboratory investigations were all within the normal parameters.
Eight reported cases involved location in the Meckel cave. In our case, the lesion
spanned the whole trigeminal nerve, starting from its root until the Gasserian ganglion
at the Meckel cave.
The treatment choices for these cases include surgical excision and stereotactic radiosurgery
(SRS). SRS is widely used for lesions of this size. Stereotactic radiosurgery has
the advantage of being a noninvasive modality to achieve control or even resolution
of the lesion. Nevertheless, pain may not be relieved in cases of trigeminal neuralgia
due to tumors.[13 ] It is risky to perform SRS without definite histopathological diagnosis in trigeminal
lymphomas, as in the case reported by Nakatomi et al. Their preliminary diagnosis
was meningioma of the cavernous sinus. The patient received Gamma knife radiosurgery
leading to improvement of ptosis but not of the facial pain. The imaging obtained
1 year after SRS showed resolution of the cavernous sinus lesion; however, enlargement
of the lesion in the prepontine cistern compressing the brain stem was evident, requiring
surgical excision.[2 ] Additionally, early empirical radiotherapy of lymphomas can render biopsies obtained
at a later stage nondiagnostic.[9 ] In our case, after discussing the available options of treatment, we opted to operate
on the patient. The pain was unbearable despite receiving maximum carbamazepine dosage,
and he already had neurological deficits at presentation. Surgery had several advantages
over SRS, including: obtaining a histopathological diagnosis, relieving the diplopia
caused by the compression of the 6th nerve and achieving immediate pain relief. Moreover, surgery was a better option
in younger patients, and SRS is a better option in elderly patients.
The surgical approaches performed in the reported literature include: lateral suboccipital,
subtemporal, transsphenoidal followed by pterional, anterior petrosectomy through
frontotemporal craniotomy, and combined lateral suboccipital and subtemporal. The
most common approach used was the lateral suboccipital. The surgical approach should
be tailored according to the location, to the extent of the lesion, and to the comfort
level of the surgeon. The approach used in our case was anterior petrosectomy through
a frontotemporal craniotomy. This approach allowed radical excision of the tumor.
The most common histopathological variant of primary lymphoma of the trigeminal nerve
reported in the literature is diffuse large B-cell lymphoma. Our case is distinct,
as the pathological type of the lymphoma was marginal zone B-cell lymphoma (MZBL).
To our best knowledge, this is the first case of this variant to be reported. Primary
marginal zone lymphomas have been reported elsewhere in other intraparenchymal sites
only six times in the literature.[14 ]
[15 ]
[16 ]
[17 ]
[18 ]
[19 ] Marginal zone B-cell lymphomas usually give rise to dural based lymphomas. Marginal
zone lymphoma is a non-Hodgkin lymphoma that occurs more commonly in the gastrointestinal
tract. So, it is sometimes called the “mucosa-associated lymphoid tissue” (MALT) lymphoma.
Patients with marginal zone lymphomas have a more promising outcome, with a 5-year
overall survival rate exceeding 86%.[20 ]
Chemotherapy regimens incorporating high-dose methotrexate (HD-MTX) are considered
the standard of care as induction therapy for newly-diagnosed PCNSLs.[21 ] Following introduction of HD-MTX-based chemotherapy, whole brain radiotherapy (36–45Gy)
has continued to be employed to consolidate responses and to provide more durable
disease control.[22 ] These data are primarily for treating high grade B cell PCNSLs. But, in this case,
our patient had low grade MZBL stage Iea (stage I extra-nodal without B symptoms).
Extrapolation of data in treating early stage MZL in solitary extranodal location
indicates that local treatment is the preferred treatment and, therefore, we followed
surgery with 36Gy of localized irradiation to the tumor bed and, for fear of late
toxicity in a young patient with an early stage indolent lymphoma, we used IMRT.
Conclusion
This is a single case report of a known pathological entity found in an unusual location.
Lesions in the gasserian ganglion are usually benign tumors such as meningiomas or
schwannomas. The message we convey is the importance of clinical correlation. The
short duration of symptoms, severe constant pain and involvement of other cranial
nerves, for example, the abducens nerve, should raise the suspicion of a different
pathology. The administration of SRS in a lymphoma without definite pathological diagnosis
would be hazardous, owing to the systemic and malignant nature of lymphomas. Surgery
and histopathological examination should be the first option, whenever the primary
diagnosis is doubtful.
