# Paraneoplastic cerebellar degeneration from an isolated nodal clear cell carcinoma of suspected gynecologic origin: case report and literature review

**Authors:** Claire Rose Kissinger, Aashima Gupta, Mina Aiad, Zachary Rothkopf, Melissa Wilson

PMC · DOI: 10.1007/s00432-025-06404-6 · Journal of Cancer Research and Clinical Oncology · 2026-01-27

## TL;DR

A rare case of paraneoplastic cerebellar degeneration linked to an undetected gynecologic cancer is reported, emphasizing the need for thorough evaluation in similar cases.

## Contribution

This case highlights the rare occurrence of anti-Yo PCD associated with an isolated nodal gynecologic malignancy without a primary tumor.

## Key findings

- Anti-Yo antibodies were detected in serum and CSF, indicating a paraneoplastic process.
- FDG-PET/CT identified pelvic lymph node metastasis from a suspected gynecologic origin.
- The patient showed partial improvement with immunotherapy and chemotherapy but remains non-ambulatory.

## Abstract

Paraneoplastic cerebellar degeneration (PCD) is a rare neurologic syndrome that often presents before an underlying malignancy is diagnosed. Patients typically develop subacute cerebellar symptoms—such as vertigo, dysmetria, disconjugate gaze, and dysarthria—before any tumor is detected. Establishing the diagnosis involves ruling out metastatic disease, treatment toxicity, infection, and metabolic disturbances, and often hinges on finding antineuronal antibodies (most commonly anti-Yo, also called type-1 anti-Purkinje cell antibody or PCA-1) in blood or cerebrospinal fluid (CSF). Anti-Yo positivity is classically linked to breast or gynecologic cancers and carries a poor prognosis. We describe a 56-year-old woman with a remote history of parotid basal cell adenocarcinoma who developed gradually worsening cerebellar dysfunction over several months, despite negative initial imaging and routine laboratory tests. When more extensive antibody testing revealed high-titer anti-Yo antibodies in serum and CSF, our suspicion for a paraneoplastic process increased. Subsequent FDG-PET/CT identified FDG-avid pelvic lymph nodes, and surgical pathology confirmed metastatic clear cell carcinoma in two iliac nodes, although the uterus, ovaries, and fallopian tubes were entirely benign. The patient received plasma exchange, intravenous immunoglobulin (IVIG), high-dose steroids, and adjuvant carboplatin/paclitaxel. Although she experienced some improvement in speech and upper-limb coordination, she remains non-ambulatory with persistent cerebellar deficits, three years after initial presentation. This case illustrates how anti-Yo PCD can foreshadow an occult nodal gynecologic malignancy without an identifiable primary tumor, highlighting the need for an extensive workup—including advanced metabolic imaging and, sometimes, empiric surgical exploration—when initial evaluations are unrevealing. Early tumor localization and treatment of both the malignancy and autoimmune response remain crucial to optimizing neurologic outcomes.

## Linked entities

- **Chemicals:** carboplatin (PubChem CID 426756), paclitaxel (PubChem CID 36314)
- **Diseases:** paraneoplastic cerebellar degeneration (MONDO:0018215), basal cell adenocarcinoma (MONDO:0006402)

## Full-text entities

- **Genes:** NAPSA (napsin A aspartic peptidase) [NCBI Gene 9476] {aka KAP, Kdap, NAP1, NAPA, NR1H2-AS1, SNAPA}, ADA2 (adenosine deaminase 2) [NCBI Gene 51816] {aka ADGF, CECR1, IDGFL, PAN, SNEDS, VAIHS}, ESR1 (estrogen receptor 1) [NCBI Gene 2099] {aka ER, ESR, ESRA, ESTRR, Era, NR3A1}, CD68 (CD68 molecule) [NCBI Gene 968] {aka GP110, LAMP4, SCARD1}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, S100A1 (S100 calcium binding protein A1) [NCBI Gene 6271] {aka S100, S100-alpha, S100A}, CALR (calreticulin) [NCBI Gene 811] {aka CALR1, CRT, HEL-S-99n, RO, SSA, cC1qR}, PAX8 (paired box 8) [NCBI Gene 7849] {aka PAX-8}, MPL (MPL proto-oncogene, thrombopoietin receptor) [NCBI Gene 4352] {aka C-MPL, CD110, MPLV, THCYT2, THPOR, TPOR}, WT1 (WT1 transcription factor) [NCBI Gene 7490] {aka AWT1, GUD, NPHS4, WAGR, WIT-2, WT-1}, CA9 (carbonic anhydrase 9) [NCBI Gene 768] {aka CAIX, MN}, CALB2 (calbindin 2) [NCBI Gene 794] {aka CAB29, CAL2, CR}, KRT7 (keratin 7) [NCBI Gene 3855] {aka CK7, K2C7, K7, SCL}, PCAT1 (prostate cancer associated transcript 1) [NCBI Gene 100750225] {aka PCA1, PCAT-1, PiHL}, IL9 (interleukin 9) [NCBI Gene 3578] {aka HP40, IL-9, P40}, ERBB2 (erb-b2 receptor tyrosine kinase 2) [NCBI Gene 2064] {aka CD340, HER-2, HER-2/neu, HER2, MLN 19, MLN-19}, MME (membrane metalloendopeptidase) [NCBI Gene 4311] {aka CALLA, CD10, CMT2T, NEP, SCA43, SFE}, KRT20 (keratin 20) [NCBI Gene 54474] {aka CD20, CK-20, CK20, K20, KRT21}
- **Diseases:** sclerotic (MESH:C538213), pleomorphic adenoma (MESH:D008949), erythrocytosis (MESH:D011086), metastatic disease (MESH:D000092182), lung adenocarcinoma (MESH:D000077192), endometrial carcinoma (MESH:D016889), lymphadenopathy (MESH:D008206), dysarthria (MESH:D004401), lacunar infarct (MESH:D059409), lung (MESH:D008171), Breast cancer (MESH:D001943), mastectomy (MESH:D000072656), immune-mediated disorder (MESH:C567355), dysmetria (MESH:D002524), clear cell carcinoma (MESH:D002292), encephalopathy (MESH:D001927), PCD (MESH:D020362), cerebellar tremor (MESH:D014202), vertigo (MESH:D014717), gait instability (MESH:D043171), cerebellar atrophy (MESH:D002526), ataxia (MESH:D001259), nodal disease (MESH:D004194), adrenal lesions (MESH:D000307), cognitive impairment (MESH:D003072), parotid adenocarcinoma (MESH:D010309), metastases (MESH:D009362), fallopian tube serous carcinoma (MESH:D005185), disconjugate gaze (MESH:D015835), cholangiocarcinoma (MESH:D018281), neurologic deficits (MESH:D009461), cerebellar degeneration (MESH:D013132), nausea (MESH:D009325), primary peritoneal serous carcinoma (MESH:D010534), metabolic disturbances (MESH:D024821), hypokalemia (MESH:D007008), sided hearing loss (MESH:D034381), PNS (MESH:D010523), adenocarcinoma (MESH:D000230), nystagmus (MESH:D009759), paraneoplastic neurological syndrome (MESH:D020361), toxicity (MESH:D064420), atrophy (MESH:D001284), pleural empyema (MESH:D016724), nodal (MESH:D013611), lower extremity paralysis (MESH:D010264), carcinoma (MESH:D009369), neuronal loss (MESH:D009410), ovarian cancer (MESH:D010051), Paraneoplastic (MESH:D010257), aphasia (MESH:D001037), lung cancer (MESH:D008175), endometrial abnormalities (MESH:D014591), neurologic conditions (MESH:D019636), primary malignancies (MESH:D001932), oncologic (MESH:D000072716), neutropenia (MESH:D009503), cerebellar infarction (MESH:D007238), diplopia (MESH:D004172), vomiting (MESH:D014839)
- **Chemicals:** pertuzumab (MESH:C485206), meclizine (MESH:D008468), prednisone (MESH:D011241), scopolamine (MESH:D012601), carboplatin (MESH:D016190), bilirubin (MESH:D001663), lapatinib (MESH:D000077341), azathioprine (MESH:D001379), steroid (MESH:D013256), paclitaxel (MESH:D017239), capecitabine (MESH:D000069287), Yo (-), taxane (MESH:C080625), FDG (MESH:D019788), platinum (MESH:D010984), methylprednisolone (MESH:D008775), trastuzumab (MESH:D000068878), cyclophosphamide (MESH:D003520), ado (MESH:C110027)
- **Species:** Homo sapiens (human, species) [taxon 9606]
- **Mutations:** P504S, JAK2 V617F

## Full text

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Source: https://tomesphere.com/paper/PMC12847610