Case report: Amphiphysin-IgG autoimmunity: a paraneoplastic presentation of appendiceal goblet cell carcinoma

Abstract

Background: Appendiceal goblet cell carcinoma (aGCC) is a rare neoplasm with mixed endocrine and exocrine features. No paraneoplastic neurological syndromes or autoantibodies have been identified in cases of aGCC or even appendiceal tumors. Amphiphysin-immunoglobulin G (IgG) autoimmunity was first described in stiff-person syndrome with breast cancer. We firstly described the clinical course and pathological findings of a patient with aGCC-associated amphiphysin-IgG autoimmunity.

Case presentation: A 54-year-old man who developed aGCC was admitted for acute disturbance of consciousness, psychiatric symptoms, cognitive impairment, seizure and hypotension. Amphiphysin-IgG was detected in the patient's serum and CSF by immunoblotting and tissue-based indirect immunofluorescence assay confirming the diagnosis of definite paraneoplastic amphiphysin-IgG-positive encephalitis. Histopathology revealed amphiphysin protein expression and accompanying immune cell infiltration (predominantly CD20+ B cells, CD3+ and CD8+ T cells) within the tumor tissue, suggesting a possible paraneoplastic origin of amphiphysin-associated paraneoplastic neurological syndromes (PNSs) in this case. Although the patient's symptoms resolved after high-dose corticosteroid therapy, he experienced recurrence 6 months later, manifesting as paraneoplastic cerebellar dysfunction. Despite treatment with IV cyclophosphamide and oral mycophenolate mofetil, no improvement was noted.

Conclusions: This case suggests that aGCC may trigger amphiphysin-IgG autoimmunity.

Keywords: amphiphysin; appendiceal goblet cell carcinoma; paraneoplastic neurological syndromes; pathological findings; tremors.

Figure 1

Brain MRI scans obtained from the patient and timeline of his clinical course. Despite there being no specific findings upon an initial T2-weighted MRI (A), mild cerebellar atrophy was observed in the subsequent axial T2-weighted MRI performed seven months later (B, yellow arrow). Timeline of the patient’s clinical course highlighting the manifestation, auxiliary examination, treatment and diagnosis time (C). EEG, electroencephalograph; LE, limbic encephalitis; MMF, mycophenolate mofetil; MRI, magnetic resonance imaging; IVMP, intravenous methylprednisolone; PET/CT, positron emission tomography with computed tomography.

Figure 2

Histopathology of appendiceal goblet cell carcinoma of the patient. Tumor cells exhibit a goblet cell morphology and characteristically form small tight clusters (A). The immunohistochemical staining shows moderate positivity for CK20 (B), CDX-2 (C), and strong positivity for carcinoembryonic antigen (CEA, D). Staining for synaptophysin (Syn, E), and chromogranin (F) is mild. Varying degrees of positivity are also shown in lymphocytes such as CD3+ T cells (G), CD8+ T cells (H) and CD20+ B cells (I). Immunohistochemistry shows positive staining for amphiphysin-IgG (J). Tissue-based indirect immunofluorescence assay (TBA) of the patient’s serum detected fluorescence responses, with specific fluorescence responses in Purkinje cells (red arrows) from the monkey cerebellum brain section (K) as well as dentate gyrus glial cells (white arrows) from the monkey hippocampal tissue. (A,–C, G, J) bar = 50 µm; D, H bar = 250 µm; (E, F, O) bar = 100 µm, (K, L) bar = 20 µm).