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□ CASE REPORT □

Pineal Malignant B-cell Lymphoma with Lower CranialNerve Involvement

Takeshi Yoshida 1, Yukio Tezuka 2, Takanobu Hirosawa 2, Hiroshi Umeki 3, Haruo Obara 2,

Takeshi Sueyoshi 4, Akimasa Yano 5, Kazumitsu Tamaki 6 and Manabu Jonosono 1

Abstract

A 62-year-old man was admitted to our hospital complaining of dysphagia and hoarseness that had per-

sisted for five days. A neurological examination indicated bulbar palsy. Brain magnetic resonance imaging

showed thickening of cranial nerves IX, X and XI, in addition to pineal body enlargement with diffuse con-

trast enhancement. A tumor biopsy overriding the spinal root of the right XIth cranial nerve was performed.

The histologic analysis confirmed a diagnosis of diffuse large B-cell lymphoma. Malignant lymphoma should

be considered in the differential diagnosis of pineal region tumors. Furthermore, obtaining histological confir-

mation is crucial for making proper management decisions.

Key words: malignant lymphoma, pineal gland, bulbar palsy

(Intern Med 53: 1205-1208, 2014)(DOI: 10.2169/internalmedicine.53.1002)

Introduction

Approximately 1-2% of patients with non-Hodgkin’s lym-

phoma (NHL) present with primary central nervous system

(CNS) disease at the initial diagnosis (1). Among them, the

occurrence of malignant lymphoma in the pineal region is

very rare, as only a few such cases have been re-

ported (2-7). We herein report a case of pineal region malig-

nant lymphoma with lower cranial nerve involvement and

review the previous literature.

Case Report

A 62-year-old man was admitted to our hospital com-

plaining of dysphagia and hoarseness that had persisted for

five days. Most pronounced was a difficulty in swallowing

liquids. He denied previously having similar episodes, fever,

night sweats, weight loss, dizziness, altered vision, weakness

or numbness. His past medical history was unremarkable,

except for hypertension. His father had died of malignant

lymphoma at 81 years of age. On a physical examination,

there was no lymphadenopathy or abdominal organomegaly.

A neurological examination revealed a positive curtain sign

(uvula deviated to the left side), hoarseness and a decreased

gag reflex. The remainder of the neurological exam, includ-

ing assessments of other cranial nerves, the motor and sen-

sory systems, the cerebellar function and gait, was normal.

The patient was admitted to the neurology department for a

further investigation of his symptoms. The results of labora-

tory tests were as follows: white blood cell count=5.8×103/

μL (4.8-8.5×103/μL); red blood cell count=4.53×106/μL

(3.70-5.00×106/μL); hemoglobin=14.5 g/dL (12.0-16.0 g/

dL); platelet count=14.1×104/μL (13-37×104/μL); lactate de-

hydrogenase (LDH)=175 IU/L (120-240 IU/L); angiotensin-

converting enzyme (ACE)=6.0 IU/L (8.3-21.4 IU/L); cere-

brospinal fluid (CSF) cell count=120/mm3 (lymphocytes:

99%, neutrophils: 1%) (<5/mm3); CSF protein=54 mg/dL

(15-45 mg/dL); and CSF immunoglobulin G index=0.91.

Blood and CSF cultures for bacteria and acid-fast bacilli

were negative. The levels of serum beta-D-glucan as well as

serum and CSF cryptococcal antigens were within the nor-

mal limits. HIV antibodies were negative. Fiber optic laryn-

goscopy showed a poor soft palate and vocal cord move-

１Department of Neurology, Okinawa Chubu Hospital, Japan, ２Department of Internal Medicine, Okinawa Chubu Hospital, Japan, ３Department of

Otolaryngology, Okinawa Chubu Hospital, Japan, ４Department of Radiology, Okinawa Chubu Hospital, Japan, ５Department of Neurosurgery,

Okinawa Chubu Hospital, Japan and ６Department of Hematology & Oncology, Okinawa Chubu Hospital, Japan

Received for publication July 21, 2013; Accepted for publication January 13, 2014

Correspondence to Dr. Takeshi Yoshida, yoshida_okinawahosp@yahoo.co.jp

Intern Med 53: 1205-1208, 2014 DOI: 10.2169/internalmedicine.53.1002

1206

Figure　1.　Magnetic resonance imaging (MRI) findings. Diffusion-weighted images (A, G), T1-weighted image (E), T2-weighted image (D) and contrast-enhanced T1-weighted images (B, C, F, H, I). The initial MRI images showed enlargement of cranial nerves IX, X and XI with partially restrict-ed diffusion and diffuse contrast enhancement (A-C). MRI also showed enlargement of the pineal gland with diffuse contrast enhancement (D-F). Follow-up MRI performed six months after the ini-tiation of chemotherapy showed dramatic improvements in the nerve enlargement with slight con-trast enhancement (G, H) and the disappearance of the pineal lesion (I).

F

A B CD E F G H I

ment on the right side. Brain magnetic resonance imaging

(MRI) revealed thickening of cranial nerves IX, X and XI,

in addition to pineal body swelling with diffuse contrast en-

hancement (Fig. 1). Although CSF cytology demonstrated

few large atypical lymphocytes, a flow cytometric analysis

of the CSF was non-diagnostic. In order to obtain a defini-

tive diagnosis, we attempted to perform a biopsy of the cra-

nial nerve lesion. We observed a whitish and thickened

arachnoid membrane via posterior fossa craniotomy. Upon

incision, soft, pinkish-white tumorous lesions diffusely infil-

trated the subarachnoid space and formed a mass lesion

overriding the spinal root of the right XIth cranial nerve

(Fig. 2). The surface of the lesions was gently removed with

a ring curette. After the procedure, the patient showed no

symptoms suggestive of accessory nerve dysfunction. A his-

tologic analysis of the mass revealed proliferation of large

atypical lymphocytes with prominent nucleoli (Fig. 3).

These atypical cells were positive for CD5, CD20, CD79a

and bcl-2 and negative for CD3, CD10 and cyclin D1. The

rate of Ki-67 positivity was over 95%. Based on these re-

sults, a diagnosis of diffuse large B-cell lymphoma was

made. A whole-body computed tomography scan and bone

marrow biopsy were negative for other sites of disease. The

patient was initially treated with intravenous high-dose

methotrexate, cytarabine and prednisolone. Intrathecal

methotrexate and cytarabine were subsequently added to the

treatment regimen. After four cycles of chemotherapy, the

cranial nerve thickening and pineal gland enlargement on

MRI improved, followed by a gradual recovery from the

dysphagia. The patient was transferred to another hospital

where he successfully received autologous hematopoietic

stem cell transplantation.

Discussion

NHL may involve the CNS with either a primary tumor

or hematogenously with systemic lymphoma. Only 1-2% of

patients with NHL present with primary CNS disease at the

initial diagnosis (1). Furthermore, the occurrence of malig-

nant lymphoma in the pineal region is very rare, and there

are few reports of pineal gland lymphoma (2-7).

Table compares the clinical, radiological and histological

characteristics of our case with those of previous cases

found in the literature that were described in detail. Com-

Intern Med 53: 1205-1208, 2014 DOI: 10.2169/internalmedicine.53.1002

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Figure　2.　Biopsy of the tumor. Via posterior fossa craniotomy, a whitish and thickened arachnoid membrane was observed (A). Upon incision, soft, pinkish-white tumorous lesions diffusely infiltrated the subarachnoid space and formed a mass lesion overriding the spinal root of the right XIth cranial nerve (B). The surface of the lesions was gently removed with a ring curette (C).

BA C

Figure　3.　Histologic analysis. Hematoxylin and Eosin staining (A) and CD20 immunohistochemis-try (IHC) (B). The proliferation of large atypical lymphocytes with prominent nucleoli was observed (A). IHC was positive for various B cell-lineage markers, including CD20 (B).

A B

pared to the previous reports, our case was characteristic,

with the absence of headaches and hydrocephalus and the

presence of lower cranial nerve signs on the initial presenta-

tion. Furthermore, meningeal dissemination was confirmed

intraoperatively. The patient in Case 6 presented with a

similar clinical course involving cranial nerve dysfunction

(VIth cranial nerve), and a diagnostic endoscopic biopsy re-

vealed disseminated lesions along the third ventricle. The

patient in Case 4 also demonstrated dissemination along the

ventricular wall, as well as subarachnoid spread at autopsy.

In contrast, the patient in Case 1 showed involvement in the

suprasellar region and dorsal medulla, which resulted in hy-

popituitarism. Case 5 included diffuse leptomeningeal in-

volvement, which produced meningitis-like symptoms.

Meanwhile, the patient in Case 2 developed a mass lesion in

the cauda equina 10 months after radiotherapy of a pineal

tumor.

According to these data, it is likely that pineal malignant

lymphoma is able to easily disseminate through the CSF and

may present with neurological symptoms originating at sites

distant from the pineal gland. Because less than 20% of

cases of primary central nervous system lymphoma

(PCNSL) are associated with meningeal dissemination, the

close proximity of the pineal gland to the third ventricle

may be responsible for the high rate of meningeal dissemi-

nation. In fact, other types of pineal region tumors, such as

germ cell tumors, are known to spread locally and metasta-

size to the CSF (8). As observed in Case 1, germ cell tu-

mors and malignant lymphoma may be indistinguishable

clinically and radiologically (9). Obtaining a histologic diag-

nosis is thus very important for making appropriate manage-

ment decisions.

In the present case, MRI revealed multiple cranial nerve

abnormalities. There are previous reports of cranial nerve

neurolymphomatosis in which the patient presented with

MRI abnormalities that are quite similar to those observed

Intern Med 53: 1205-1208, 2014 DOI: 10.2169/internalmedicine.53.1002

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Table.　Summary of Clinical, Radiological and Histological Characteristics of Pineal Gland Lym-phoma

Case Age / sex

Clinical feature Peripheral nerve involvement

MRI (CT) MD Histology

Case 1(2)

21/M Headache, emesis,hypopituitarism, Parinaud’s sign

None HydrocephalusGd-enhancement

Dorsal medulla and suprasellar lesion

+ (?) Malignant T-cell lymphoma

Case 2(3)

15/M Headache, gait disturbance, Parinaud’s

sign

Cauda equina HydrocephalusGd-enhancement

+ Immunoblasticlymphoma

Case 3(4)

52/M Headache, obnubilation ND No hydrocephalusHomogenous

enhancement on CT

ND Lymphoma (no detail)

Case 4(5)

72/F Confusion, visual and gait disturbance

None Gd-enhancementBrain parenchyma and subependymal lesion

+ High grade, large B-cell lymphoma

Case 5(6)

4/M Seizure, fever, headache, emesis, neck stiffness, altered mental status

None No hydrocephalusGd-enhancement

Bilateral frontal and leptmeningeal spread

+ ALK-1 positiveALCL

Case 6(7)

31/M Diplopia, headache, nausea

Cranial nerveVI

HydrocephalusCystic mass with Gd-

enhanced nodule

+ Malignant B-cell lymphoma

Our case 62/M Dysphagia Cranial nerve IX, X, and XI

No hydrocephalusGd-enhancement

+ Diffuse large B-cell lymphoma

MD: meningeal dissemination, Gd: gadolinium, ALCL: anaplastic large cell lymphoma, ND: no description

in the present case (10-12). Although there is ongoing con-

troversy regarding the use of cranial nerve biopsies due to

the high risk of adverse events (13), the intraoperative find-

ings and results of the histopathological analysis confirmed

the presence of meningeal dissemination in our patient.

The authors state that they have no Conflict of Interest (COI).

AcknowledgementThe authors are deeply grateful to Dr. Kenneth N. M. Sumida,

University of Hawaii, for his insightful suggestions regarding this

case.

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