Anti-Yo Antibody-Mediated Paraneoplastic Cerebellar Degeneration in a Man With Esophageal Adenocarcinoma

Authors: Kai Xia, MD, PhD; John R. Saltzman, MD; David L. Carr-Locke, MD, FRCP Series Editor: David L. Carr-Locke, MD, FRCP

Disclosures

August 05, 2003

Case Report

A previously healthy 58-year-old white man experienced flu-like symptoms 6 weeks prior to his presentation to clinic. He subsequently developed severe dizziness related to head movement and unsteady gait. These symptoms were also associated with nausea and watery diarrhea. Initial neurologic and medical evaluations at a local hospital were normal. He was treated with decongestants and antidiarrheal agents. However, his symptoms worsened over the next several weeks with progressive incoordination, manifesting as difficulty in writing and deteriorating balance. He also reported a 25-lb weight loss within the last 6 months. He denied dysphagia, odynophagia, or excessive alcohol intake. Review of systems was otherwise unremarkable. There was no family history of cerebellar dysfunction.

Physical examination revealed truncal and gait ataxia in the absence of Romberg's sign, horizontal nystagmus on lateral gaze, and dysmetria of all 4 limbs without weakness or sensory loss. The patient also had dysarthria with scanning speech. His cognitive function was intact. Extremity reflexes were normal, and both plantar responses were flexor. The remainder of the physical examination was unremarkable.

Initial laboratory studies revealed normal electrolytes and normal liver function tests. Although both hematocrit and white blood cell (WBC) counts were within normal limits, WBC differential count revealed 66% neutrophils and 15% eosinophils. Stool studies, including stool fecal leukocytes, cultures, ova and parasites, Clostridium difficile toxin, and fecal fat, were all negative. Erythrocyte sedimentation rate was mildly elevated, at 27 mm/hr. Antinuclear antibody, antiendomysial IgA, tissue transglutaminase, angiotensin-converting enzyme, Lyme serology, and HIV serologies were all negative.

Further work-up with head computed tomography (CT) was normal, and cranial magnetic resonance imaging (MRI) showed no evidence of cerebellar mass, metastasis, or atrophy except for a large cisterna magna. The cerebrospinal fluid (CSF) contained 14 erythrocytes, 34 leukocytes with 7% neutrophils, 86% lymphocytes, 7% macrophages, and 0% eosinophils; 0.9g/L protein; and 4.2 mmol/L glucose. Serologies for varicella-zoster virus, cytomegalovirus, human herpes virus type 6, and herpes simplex virus were all negative. CSF cytology was also negative, but oligoclonal bands were present in the serum and CSF.

Paraneoplastic neurologic syndrome was suspected. The CSF and serum were then analyzed for the presence of paraneoplastic antibodies by immunohistochemical analysis. Anti-Hu antibody (also called ANNA I [antineuronal nuclear antibody I]) and anti-Ri antibody (also called ANNA II [antineuronal nuclear antibody II]) were both negative. However, high titers of anti-Yo antibodies (also called APCA I [anti-Purkinje cell cytoplasmic antigen antibody I]) were detected in both the serum and CSF. Therefore, the patient most likely had PCD caused by an occult malignancy.

The patient first underwent chest and abdominal CT scan, the results of which were unrevealing. Because of the associated diarrhea and eosinophilia, he then underwent upper endoscopy. A small single, friable erythematous irregular mass proximal to the gastroesophageal (GE) junction was identified. The lesion was nonobstructing and noncircumferential (Figure 1). Biopsies of this lesion revealed well-formed glands lined by atypical cells, infiltrating through the muscularis propria into the underlying serosa, consistent with well-differentiated invasive adenocarcinoma of the esophagus (Figure 2).

Figure 1.

Endoscopic view of the esophageal mass proximal to the GE junction.

Figure 2.

Photomicrograph of biopsy from the esophageal mass showing well-formed glands infiltrating through muscularis propria, consistent with well-differentiated adenocarcinoma. (H&E; photo taken by Jason Hornick, MD).

Multiple biopsies at and near the GE junction showed no evidence of intestinal metaplasia. Subsequently, the patient underwent endoscopic ultrasound for staging. The lesion measured 1.3 cm in the largest dimension, with the tumor penetrating through the muscularis propria as well as with involvement of adjacent lymph nodes (Figure 3).

Figure 3.

Endosonographic image showing the tumor (labeled as "mass") infiltrating through the muscularis propria and the involvement of an adjacent lymph node (cross-hair in the middle).

The tumor was classified as T3N1M0. The positron emission tomography (PET) scan showed intense uptake at the GE junction, consistent with the patient's known primary esophageal cancer. Therefore, a diagnosis of exceedingly rare PCD caused by esophageal adenocarcinoma was finally made.

Clinical Course and Outcome

The patient's cerebellar symptoms worsened despite chemotherapy with prednisolone, cisplatin, and irinotecan, followed by radiation therapy. Three months after his initial presentation, he became completely wheelchair-bound and lost the ability to speak intelligible words. His cognitive function remained preserved. Because paraneoplastic neurologic syndromes, in general, are thought to be an autoimmune-mediated process, and because there have been some reported cases in which patients were treated with immunosuppressants, IVIG (intravenous immunoglobulins), or plasmapheresis with variable effects, the patient was then treated with each of these modalities. Unfortunately, there was no effect on his cerebellar dysfunction. Finally, he underwent esophagectomy with the goal of destroying the tumor as quickly as possible, as well as to prevent further debilitation. Although he was free of cancer following surgery, his cerebellar degeneration relentlessly progressed. The patient was completely incapacitated and entered a long-term rehabilitation phase with uncertainty of whether his cerebellar function would ever recover.

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