Gynecologic Oncology 99 (2005) 500 – 503
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Case Report

Paraneoplastic cerebellar degeneration with fallopian tube adenocarcinoma
Yudai Tanaka a, Nao Suzuki b,*, Masaki Takao c, Akiko Ichikawa d,
Nobuyuki Susumu b, Daisuke Aoki baDepartment of Obstetrics and Gynecology, Yamato Municipal Hospital, Kanagawa, Japan
Department of Obstetrics and Gynecology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582, Japanc
Department of Neurology, Mihara Memorial Hospital, Gunma, Japand
Department of Rehabilitation, School of Medicine, Keio University, Tokyo, Japanb

Received 15 April 2004
Available online 29 August 2005

Abstract
Background. Paraneoplastic cerebellar degeneration (PCD) is rarely caused by fallopian tube adenocarcinoma.
Case. We present a patient with PCD and fallopian tube cancer. Anti-Yo antibody, one of an anti-neuronal antibody, was positive inserum and cerebrospinal fluid. She was also positive for HLA A24, which is common in patients with PCD. Radical surgery did not
significantly ameliorate her neurological impairment, although the dysarthria improved slightly.
Conclusion. This case highlights the importance of detecting the underlying malignancy in patients with subacute neurologicalimpairment and shows that fallopian tube cancer can potentially cause PCD.
D 2005 Elsevier Inc. All rights reserved.
Keywords: Anti-Yo antibody; Fallopian tube carcinoma; Paraneoplastic cerebellar degeneration

Introduction
Paraneoplastic cerebellar degeneration (PCD) is a rareneurological disorder that is characterized by the subacuteonset of cerebellar dysfunction and is associated with anunderlying malignancy. Many types of anti-neuronal antibodies have been identified in patients with PCD. Tumors
such as ovarian cancer and breast cancer are commonly
reported to be associated with PCD. Here, we present a rarecase of PCD that occurred in a patient with occult fallopian
tube cancer.

Case report
A 63-year-old woman (G2, P2) began to experience
occasional episodes of dizziness in May 2003. The symptom* Corresponding author. Fax: +81 3 3226 1667.
E-mail address: naos@sc.itc.keio.ac.jp (N. Suzuki).
0090-8258/$ - see front matter D 2005 Elsevier Inc. All rights reserved.
doi:10.1016/j.ygyno.2005.06.064

gradually became more severe and then she complained ofdropping a teacup involuntarily. In June, she developed gait
disturbance and occasional numbness of the extremities.
Slurring of her speech occurred at the same time andsubsequently became worse. She also lost about 8 kg ofweight over 3 months. At the end of June, she was referred to
the Neurology outpatient clinic of our hospital. At the firstvisit, she was alert and well oriented. Neurological examination showed vertical nystagmus, severe dysarthria, truncal
ataxia, and dysdiadochokinesis. Her coordination wassignificantly impaired, but there were no sensory deficits.
Her past medical history was unremarkable, except fortrigeminal neuralgia 6 years earlier.
Brain MRI and CT did not reveal any abnormalities.
Abdominal CT and pelvic MRI were also performed, anddetected a 5  5 cm solid mass in her right pelvic cavity withpara-aortic lymph node swelling, suggesting a gynecologicalmalignancy (Figs. 1A, B). The serum CA125 and CA546
levels were 36 U/ml (normal <35) and 49 U/m (normal <12),
respectively, while other tumor markers (including CA19-9,CEA, and CA602) were within normal limits. Because PCD

Y. Tanaka et al. / Gynecologic Oncology 99 (2005) 500 – 503

501Fig. 1. Pelvic MRI, abdominal CT, and histopathological findings. (A) Pelvic MRI. A solid mass (5  5 cm in diameter) is seen on the right side (arrow). (B)
Abdominal CT. Enlargement of para-aortic lymph nodes is seen (arrow). (C) Histopathological findings. Atypical cells are arranged in a papillary
configuration, suggesting serous adenocarcinoma.

was suspected, anti-neuronal antibodies were examined,
including anti-Yo antibody, anti-Ri antibody, anti-Hu antibody. Among these, only anti-Yo antibody was positive.
This antibody was also detected in the cerebrospinal fluid,
confirming a diagnosis of PCD associated with assumed
gynecological cancer. After detailed discussion, radical
surgery was scheduled. Before the operation could be done,
her dysarthria became so bad that she could hardly
communicate with the medical staff or her family and she
eventually became completely bedridden.
At operation, a right adnexal mass about 6 cm indiameter was detected to which the appendix was firmlyadherent. There was also massive para-aortic lymph nodeenlargement. Both ovaries appeared to be normal. Total
hysterectomy, bilateral salpingo-oophorectomy, appendectomy, and pelvic and para-aortic lymphandectomy wereperformed. Intraoperative and postoperative pathology
confirmed a diagnosis of serous adenocarcinoma originatingfrom the right fallopian tube (Fig. 1C). Both ovaries wereclear of tumor invasion, but the appendix was macroscopically involved. Tumor invasion was also positive in thepara-aortic lymph nodes and right common iliac lymph
nodes. Thus, the surgical stage of this fallopian tube
adenocarcinoma was FIGO stage IIIc (pT3aN1M0).
The postoperative course was unremarkable with nomajor complications. Her neurological manifestations
showed little change from the preoperative status, exceptthat dysarthria improved slightly. Because of the highrecurrence rate of tubal carcinoma, postoperative chemotherapy (paclitaxel: 180 mg/m2, and carboplatin: AUC 6)
was scheduled. After the first course, however, she refused
additional treatment because of side effects such as emesis

Fig. 2. Brain MRI findings. (A) MRI just before surgery. (B) MRI at 3 months after surgery. Note that the fourth ventricle is dilated and the gyrus is more
prominent, indicating cerebellar atrophy.

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Y. Tanaka et al. / Gynecologic Oncology 99 (2005) 500 – 503

inflammation and degeneration even in the absence of theinitial stimulus. Immunohistochemistry of the Yo antigen
was performed on the tumor tissue but no positive staining
was noted. However, serum antibodies to anti-Yo weredetected. We could not conclude the significance of the antiYo antibody as we could not demonstrate direct lysis oftumor cells with the anti-Yo antibody.
The genetic background seems to be involved in thedevelopment of PCD. Tanaka et al. performed HLA typingof nine PCD patients with anti-Yo antibody, and all of thempossessed HLA A24, which is found in approximately 35%of the Japanese population. Our patient was also positive for
HLA 24A. Thus, HLA typing may be useful to assist in thediagnosis of PCD because anti-neuronal antibody tests cantake several weeks.
There is no established treatment for the neurologicaldeficits of patients with PCD [7]. Resection of theunderlying malignancy may lead to some improvement or
at least stop progression. The interval between the onset ofneurological symptoms and treatment of the underlying
malignancy seems to have no impact on the functionalprognosis. We performed surgery within about 1 month ofthe onset of neurological symptoms, but failed to achieve
functional improvement. Intravenous immunoglobulin-Gand steroids are sometimes tried, but the effects seem tobe limited. Rituximab was reported to dramatically
improve neurological symptoms in a bedridden patient
who regained the ability to walk and remained stable formore than a year [8].
The impact of PCD can be devastating. Shams’ili et al.
reported that the 5-year survival rate of 19 PCD patientswith anti-Yo antibody was less than 25%, with the mediansurvival time from diagnosis being 13 months [5]. Rojas etal. reported that about half of PCD patients die from theircancer, while the rest die because of neurological progression [7]. As the poor prognosis of PCD patients isconcerned, it can be difficult to decide whether or not to
perform radical surgery, since the chance of neurologicalrecovery is rather low and the risk of complications related
to cerebellar ataxia is very high. Thus, decisions regarding
treatment must be made after detailed discussion between
the physician and patient. Rehabilitation might be a treatment option, as Pelmutter et al. reported a PCD patient whoand nausea. She was then given methylprednisolone pulse
therapy, but there was no neurological improvement. At 2
months after surgery, brain MRI showed mild cerebellar
atrophy (Fig. 2), while serum anti-Yo antibody was negative.
At present, 22 months since operation, her neurologicalimpairment is unchanged.

Discussion
PCD is one of the disorders categorized among paraneoplastic syndromes, and is a unique form of neurologicaldysfunction due to the remote effect of malignancy on thenervous system. The neurological features include ataxia,
gait disturbance, dysarthria, vertigo, diplopia, and nystagmus. These symptoms sometimes precede discovery of theunderlying neoplasm by more than a year, and may lead tosevere disability while the tumor remains asymptomatic [1].
Ovarian cancer, lung cancer, breast cancer, and Hodgkin’s
lymphoma are the neoplasm most commonly associatedwith PCD. Review of the world literature showed that only
four cases of PCD associated with fallopian tube adenocarcinoma have been reported previously (Table 1) [1– 3].
The current hypothesis about the mechanism of PCD isthat expression of neuronal proteins by the patient’s tumor
provokes an immune response that eventually causes
neurological disorders [4]. So far, nine associated autoantibodies have been identified. Anti-Yo antibody is the mostfrequently detected (38%), followed by anti-Hu (32%), antiTr (14%), and then anti-Ri (12%) [5]. Anti-Yo antibody is apolyclonal IgG antibody that reacts with a cytoplasmic
component of cerebellar Purkinje cells.
The precise role of anti-Yo antibody in the pathogenesisof PCD is unclear and there is no direct evidence that thepresence of this antibody causes the loss of cerebellar
Purkinje cells in PCD patients. The observation that anti-Yo
antibodies activate T cells which can lyse target cells
presenting the Yo antigen (also called cdr2) in vitro
indicates that T cell responses have an important role in
PCD [6]. In our patient, cerebellar degeneration was notarrested even after anti-Yo antibody became negative,
suggesting that the assault of anti-Yo antibody-mediatedimmune complexes against Purkinje cells leads to ongoing
Table 1
Previous case reports of PCD associated with fallopian tube adenocarcinoma
Author (year)

AgeFirst symptoms

Time interval
until diagnosis

Positive
antibodyPathology(FIGO stage)

Treatment

Neurologicalimprovement

Tanaka et al. (1995)

70

Diplopia, dizziness4 months

Anti-Yo

Surgery, chemotherapy(+)

Matsushita et al. (1998)

57

Dysarthria, diplopia

13 months

Anti-YoSurgery, chemotherapy(++)

Matsushita et al. (1998)

70

Diplopia

3 months

Anti-Yo

Surgery, chemotherapy(+)

Levite et al. (2001)
Presented case (2003)

81
63

Diplopia, tinnitus
Gait, disturbance,dysarthria

1 – 2 months
1 monthAnti-YoAnti-Yo

Poorly differentiatedadenocarcinoma (II)Poorly differentiatedadenocarcinoma (Ic)
Poorly differentiatedadenocarcinoma (Ic)
Serous adenocarcinoma
Serous adenocarcinoma(IIIc)

Surgery
Surgery, chemotherapy

( )
(+/ )

Y. Tanaka et al. / Gynecologic Oncology 99 (2005) 500 – 503

showed functional improvement after 3 weeks of comprehensive inpatient rehabilitation [9].
In summary, we presented a rare case of PCD associatedwith fallopian tube adenocarcinoma. Anti-Yo antibody waspositive in the serum and cerebrospinal fluid and theneurological symptoms stabilized after complete surgicalresection. In patients with subacute onset of neurologicalimpairment suggesting PCD, investigation of the underlying
malignancy and anti-neuronal antibodies may help to makea definitive diagnosis.

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