Test ID: PNEOE
Paraneoplastic Autoantibody Evaluation, Spinal Fluid
Secondary ID 
A test code used for billing and in test definitions created prior to November 2011
NY State Approved Indicates the status of NY State approval and if the test is orderable for NY State clients.
Useful For Suggests clinical disorders or settings where the test may be helpful
An aid in the diagnosis of paraneoplastic neurological autoimmune disorders related to carcinoma of lung, breast, ovary, thymoma, or Hodgkin's lymphoma
In patients with a history of tobacco use or other lung cancer risk, or if thymoma is suspected, PAVAL/83380 Paraneoplastic Autoantibody Evaluation, Serum is also recommended.
Profile Information A profile is a group of laboratory tests that are ordered and performed together under a single Mayo Test ID. Profile information lists the test performed, inclusive of the test fee, when a profile is ordered and includes reporting names and individual availability.
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| ANN1C | Anti-Neuronal Nuclear Ab, Type 1 | No | Yes |
| ANN2C | Anti-Neuronal Nuclear Ab, Type 2 | No | Yes |
| ANN3C | Anti-Neuronal Nuclear Ab, Type 3 | No | Yes |
| AGN1C | Anti-Glial Nuclear Ab, Type 1 | No | Yes |
| PCA1C | Purkinje Cell Cytoplasmic Ab Type 1 | No | Yes |
| PCA2C | Purkinje Cell Cytoplasmic Ab Type 2 | No | Yes |
| PCTRC | Purkinje Cell Cytoplasmc Ab Type Tr | No | Yes |
| AMPHC | Amphiphysin Ab, CSF | No | Yes |
| CRMC | CRMP-5-IgG, CSF | No | Yes |
Reflex Tests Lists test(s) that may or may not be performed, at an additional charge, depending on the result and interpretation of the initial test(s)
| Test ID | Reporting Name | Available Separately | Always Performed |
|---|---|---|---|
| WBNC | Paraneoplas Autoantibody WBlot,CSF | No | No |
| CRMWC | CRMP-5-IgG Western Blot, CSF | No | No |
| GD65C | GAD65 Ab Assay, CSF | Yes | No |
| NMOC | NMO-IgG, CSF | Yes | No |
| ABLTC | Amphiphysin Western Blot, CSF | No | No |
Testing Algorithm Delineates situation(s) when tests are added to the initial order. This includes reflex and additional tests.
If indirect immunofluorescence assay (IFA) (ANN1C/3852, ANN2C/7472, ANN3C/21633, PCA1C/3988, PCA2C/21632, PCTRC/21631, AMPHC/5906, CRMC/21650, AGN1C/89079) is indeterminate, paraneoplastic autoantibody Western blot is performed at an additional charge.
If IFA pattern is suggestive of neuromyelitis optica (NMO), then NMO-IgG is performed at an additional charge.
If client requests or if IFA patterns suggest CRMP-5-IgG, CRMP-5-IgG Western blot is performed at an additional charge.
If IFA patterns suggest GAD65 antibody, GAD65 antibody radioimmunoprecipitation assay is performed at an additional charge.
If IFA patterns suggest amphiphysin antibody, amphiphysin Western blot is performed at an additional charge.
Method Name A short description of the method used to perform the test
ANN1C/3852, ANN2C/7472, ANN3C/21633, PCA1C/3988, PCA2C/21632, PCTRC/21631, AMPHC/5906, CRMC/21650, AGN1C/89079, NMOC/83936: Indirect Immunofluorescence Assay (IFA)
WBNC/21764, CRMWC/21747, ABLTC/89380: Western Blot
GD65C/84221: Radioimmunoprecipitation Assay
Reporting Name A shorter/abbreviated version of the Published Name for a test; an abbreviated test name
Aliases Lists additional common names for a test, as an aid in searching
ANNA-1, CSF order 80013
ANNA-2, CSF order 80013
ANNA-3, CSF order 80013
Anti-Hu
Anti-Yo
Antineuronal
Cerebellar Antibodies
CRMP-5-IgG, CSF order 80013
Dorsal Root Ganglion Antibody
Hu Antibody
Neuron Restricted Autoantibodies
Neuronal Nuclear Antibody
Neuronal-Anti
Ovarian Cancer-Related Antibodies
Paraneoplastic Autoantibody Western Blot Confirmation, CSF
Paraneoplastic Neurological Autoimmunity
PCA-1, CSF order 80013
PCA-2, CSF order 80013
PCA-Tr, CSF order 80013
Purkinje Cell Cytoplasmic Antibodies
Ri, Anti
Yo-Anti
Specimen Type Describes the specimen type needed for testing
Specimen Required Defines the optimal specimen. This field describes the type of specimen required to perform the test and the preferred volume to complete testing. The volume allows automated processing, fastest throughput and, when indicated, repeat or reflex testing.
Container/Tube: Sterile vial
Specimen Volume: 4 mL
Additional Information: Include name, phone number, mailing address, and e-mail address (if applicable) of ordering physician.
Forms: If not ordering electronically, submit a General Request Form (Supply T239) with the specimen.
Specimen Minimum Volume Defines the amount of specimen required to perform an assay once, including instrument and container dead space. Submitting the minimum specimen volume makes it impossible to repeat the test or perform confirmatory or perform reflex testing. In some situations, a minimum specimen volume may result in a QNS (quantity not sufficient) result, requiring a second specimen to be collected.
Reject Due To Identifies specimen types and conditions that may cause the specimen to be rejected
| Hemolysis | Mild OK; Gross reject |
| Lipemia | Mild OK; Gross reject |
| Icterus | Mild OK; Gross reject |
| Other | NA |
Specimen Stability Information Provides a description of the temperatures required to transport a specimen to the laboratory. Alternate acceptable temperature(s) are also included.
| Specimen Type | Temperature | Time |
|---|---|---|
| CSF | Refrigerated (preferred) | 14 days |
| Ambient | 72 hours | |
| Frozen | ||
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Several antineuronal and glial autoantibodies are recognized clinically as markers of a patient's immune response to specific cancers (paraneoplastic autoantibodies). Seropositive patients present with neurologic symptoms and signs in >90% of cases. The cancers are most commonly small-cell lung carcinoma (SCLC), ovarian (or related mullerian) carcinoma, breast carcinoma, thymoma, or Hodgkin's lymphoma. The cancers may be new or recurrent, are usually limited in metastatic volume, and are often occult by standard imaging procedures. Detection of the informative marker autoantibodies allows early diagnosis and treatment of the cancer, which may lessen neurological morbidity and improve survival.
Serum is the preferred specimen for paraneoplastic autoantibodies. However, cerebrospinal fluid (CSF) results are sometimes positive when serum results are negative (especially for CRMP-5 and other inflammatory central nervous system autoimmunity). Additionally, CSF is more readily interpretable because it generally lacks the interfering nonorgan-specific antibodies that are common in serum of patients with cancer. Because neurologists typically perform spinal taps in these patients, we recommend that CSF be submitted with serum, either for simultaneous testing or to be held for testing only if serum is negative.
CRMP-5-IgG Western blot is also performed by specific request for more sensitive detection of CRMP-5-IgG. Testing should be requested in cases of subacute basal ganglionic disorders (chorea, Parkinsonism), cranial neuropathies (especially loss of vision, taste, or smell), and myelopathies.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
ANTINEURONAL NUCLEAR ANTIBODY-Type 1 (ANNA-1)
Negative at <1:2
ANTINEURONAL NUCLEAR ANTIBODY-Type 2 (ANNA-2)
Negative at <1:2
ANTINEURONAL NUCLEAR ANTIBODY-Type 3 (ANNA-3)
Negative at <1:2
ANTI-GLIAL/NEURONAL NUCLEAR ANTIBODY, Type 1 (AGNA-1)
Negative at <1:2
PURKINJE CELL CYTOPLASMIC ANTIBODY, Type 1 (PCA-1)
Negative at <1:2
PURKINJE CELL CYTOPLASMIC ANTIBODY, Type 2 (PCA-2)
Negative at <1:2
PURKINJE CELL CYTOPLASMIC ANTIBODY, Type Tr (PCA-Tr)
Negative at <1:2
AMPHIPHYSIN ANTIBODY
Negative at <1:2
CRMP-5-IgG
Negative at <1:2
Note: Titers lower than 1:2 are detectable by recombinant CRMP-5 Western blot analysis. CRMP-5 Western blot analysis will be done on request on stored spinal fluid (held 4 weeks). This supplemental testing is recommended in cases of chorea, vision loss, cranial neuropathy, and myelopathy. Call the Neuroimmunology Laboratory at 800-533-1710 or 507-266-5700 to request CRMP-5 Western blot.
Neuron-restricted patterns of IgG staining that do not fulfill criteria for the listed autoantibodies may be reported as "unclassified antineuronal IgG." If detected, newly identified autoantibody specificities may be reported. Complex patterns that include non-neuronal elements may be reported as "uninterpretable."
Interpretation Provides information to assist in interpretation of the test results
Antibodies directed at onconeural proteins shared by neurons, glia, muscle, and certain cancers are valuable serological markers of a patient's immune response to cancer. They are not found in healthy subjects, and are usually accompanied by subacute neurological symptoms and signs. Several autoantibodies have a syndromic association, but no autoantibody predicts a specific neurological syndrome. Conversely, a positive autoantibody profile has 80% to 90% predictive value for a specific cancer. It is not uncommon for more than 1 paraneoplastic autoantibody to be detected, each predictive of the same cancer.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Not recommended as a general screening test for cancer.
Seronegativity does not exclude malignancy.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Lucchinetti CF, Kimmel DW, Lennon VA: Paraneoplastic and oncological profiles of patients seropositive for type 1 anti-neuronal nuclear antibody. Neurology 1998;50:652-657
2. Graus F, Vincent A, Pozo-Rosich P, et al: Anti-glial nuclear antibody: marker of lung cancer-related paraneoplastic neurological syndromes. J Neuroimmunol 2005;154(1-2):166-171
3. Pittock SJ, Lucchinetti CF, Lennon VA: Anti-neuronal nuclear autoantibody type 2: paraneoplastic accompaniments. Ann Neurol 2003;53(5):580-587
4. Chan KH, Vernino S, Lennon VA: ANNA-3 anti-neuronal nuclear antibody: marker of lung cancer-related autoimmunity. Ann Neurol 2001 September;50(3):301-311
5. Hetzel DJ, Stanhope CR, O'Neill BP, Lennon VA: Gynecologic cancer in patients with subacute cerebellar degeneration predicted by anti-purkinje cell antibodies and limited in metastatic volume. Mayo Clin Proc 1990;65:1558-1563
6. Vernino S, Lennon VA: New Purkinje cell antibody (PCA-2): marker of lung cancer-related neurological autoimmunity. Ann Neurol 2000 March;47(3):297-305
7. Pittock SJ, Lucchinetti CF, Parisi JE, et al: Amphiphysin autoimmunity: paraneoplastic accompaniments. Ann Neurol 2005;58(1):96-107
8. Yu Z, Kryzer TJ, Griesmann GE, et al: CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol 2001 February;49(2):146-154
Method Description Describes how the test is performed and provides a method-specific reference
Indirect Immunofluorescence Assay (IFA):
The patient's sample is tested by a standardized IFA that uses a composite frozen section of mouse cerebellum, kidney, and gut tissues. After incubation with sample and washing, fluorescein-conjugated goat antihuman IgG is applied. Neuron-specific autoantibodies are identified by their characteristic fluorescence staining patterns. Autoantibody of antineuronal nuclear antibody-type 1 (ANNA-1) specificity is pan-neuronal in reactivity; it binds to the cytoplasm and nucleus (sparing nucleolus) of central and peripheral nervous system neurons. Autoantibody of ANNA-2 specificity has a similar binding pattern but reactivity is restricted to neurons of the central nervous system; neurons of the peripheral nervous system are nonreactive. Autoantibody of purkinje cell cytoplasmic antibody (PCA)-1 specificity bind distinctively to endoplasmic reticulum in Purkinje cells, molecular neurons, and other large neurons in the central and peripheral nervous system. Samples that are scored positive for any neuronal nuclear or cytoplasmic autoantibody are titrated to an endpoint on mouse Purkinje cells or peripheral neurons. Interference by coexisting non-neuron-specific autoantibodies can usually be eliminated by serologic absorption. Occasionally Western blot analysis is required.(Yu Z, Kryzer TJ, Griesmann GE, Kim KK, et al: CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol 2001;49:146-154)
Western Blot:
Western blot testing is indicated in the infrequent situation that interference by coexisting nonneuronal-specific autoantibodies precludes IFA interpretation. It is not cost-effective for routine serologic screening. However, results obtained by Western blot analyses in Mayo Clinic's Neuroimmunology Laboratory have shown 100% concordance with IFA results for PCA-1, and superior sensitivity of the IFA for detection of ANNA-1 and ANNA-2.
An aqueous extract of adult rat cerebellar proteins is used as the source of neuronal antigens on the paraneoplastic autoantibody Western blot. Western blot is performed on denatured and reduced proteins separated by electrophoresis on 10% polyacrylamide gel.(Vernino S, Lennon VA: New Purkinje cell antibody [PCA-2]: marker of lung cancer-related neurological autoimmunity. Ann Neurol 2000 March;47[3]:297-305). Full-length recombinant human CRMP-5 antigen is used to confirm CRMP-50IgG.(Yu Z, Kryzer TJ, Griesmann GE, et al: CRMP-5 neuronal autoantibody: marker of lung cancer and thymoma-related autoimmunity. Ann Neurol 2001 February;49[2]:145-154). Denatured full-length recombinant human amphiphysin protein is used to confirm amphiphysin antibody.
Immunoprecipitation Assay:
(125)I-labeled recombinant human GAD65 and nonimmune human serum are incubated with the patient's diluted cerebrospinal fluid. Antihuman IgG and IgM are then added to form an immunoprecipitate. After washing the precipitated immune complexes, specific antibodies are detected by counting gamma-emission from the pellet's bound I-GAD65.(Walikonis JE, Lennon VA: Radioimmunoassay for glutamic acid decarboxylase [GAD65] autoantibodies as a diagnostic aid for stiff-man syndrome and a correlate of susceptibility to type 1 diabetes mellitus. Mayo Clin Proc 1998 December;73[12]:1161-1166)
Day(s) and Time(s) Test Performed Outlines the days and times the test is performed. This field reflects the day and time the sample must be in the testing laboratory to begin the testing process and includes any specimen preparation and processing time required before the test is performed. Some tests are listed as continuously performed, which means assays are performed several times during the day.
ANNA-1: Monday through Friday; 11:30 a.m.
ANNA-2: Monday through Friday; 11:30 a.m.
ANNA-3: Monday through Friday; 11:30 a.m.
AGNA-1: Monday through Friday; 11:30 am
PCA-1: Monday through Friday; 11:30 a.m.
PCA-2: Monday through Friday; 11:30 a.m.
PCA-Tr: Monday through Friday; 11:30 a.m.
Amphiphysin: Monday through Friday; 11:30 a.m.
CRMP-5-IgG: Monday through Friday; 11:30 a.m.
Paraneoplastic autoantibody Western blot confirmation: Monday through Friday; 8 a.m.
NMO-IgG: Monday through Friday, 8 a.m.
CRMP-5-IgG Western blot: Monday through Friday; 8 a.m.
GAD65 antibody assay: Monday through Friday; 6 a.m.
Amphiphysin Western blot: Monday through Friday, 8 a.m.
Analytic Time Defines the amount of time it takes the laboratory to setup and perform the test. This is defined in number of days. The shortest interval of time expressed is "same day/1 day," which means the results may be available the same day that the sample is received in the testing laboratory. One day means results are available 1 day after the sample is received in the laboratory.
Maximum Laboratory Time Defines the maximum time from specimen receipt at Mayo Medical Laboratories until the release of the test result
Specimen Retention Time Outlines the length of time after testing that a specimen is kept in the laboratory before it is discarded
Performing Laboratory Location The location of the laboratory that performs the test
Test Classification Provides information regarding the medical device classification for laboratory test kits and reagents. Tests may be classified as cleared or approved by the US Food and Drug Administration (FDA) and used per manufacturer's instructions, or as products that do not undergo full FDA review and approval, and are then labeled as an Analyte Specific Reagent (ASR), Investigation Use Only (IUO) product, or a Research Use Only (RUO) product.
CPT Code Information Provides guidance in determining the appropriate Current Procedural Terminology (CPT) code(s) information for each test or profile. The listed CPT codes reflect Mayo Medical Laboratories interpretation of CPT coding requirements. It is the responsibility of each laboratory to determine correct CPT codes to use for billing.
86256-AGNA-1
86256-Amphiphysin
86256-ANNA-1
86256-ANNA-2
86256-ANNA-3
86256-CRMP-5-IgG
86256-PCA-1
86256-PCA-2
86256-PCA-Tr
84182-Amphiphysin Western blot (if appropriate)
84182-CRMP-5 Western blot confirmation (if appropriate)
84182-Paraneoplastic autoantibody Western blot confirmation (if appropriate)
86255-NMO-IgG (if appropriate)
86341-GAD65 confirmation (if appropriate)
LOINC® Code Information Provides guidance in determining the Logical Observation Identifiers Names and Codes (LOINC) values for the result codes returned for this test or profile.
| Result ID | Reporting Name | LOINC Code |
|---|---|---|
| 89079 | AGNA-1, CSF | 53714-2 |
| 5906 | Amphiphysin Ab, CSF | 35142-9 |
| 3852 | ANNA-1, CSF | 24400-4 |
| 7472 | ANNA-2, CSF | 24401-2 |
| 21633 | ANNA-3, CSF | 35144-5 |
| 21650 | CRMP-5-IgG, CSF | 35385-4 |
| 3988 | PCA-1, CSF | 14248-9 |
| 21632 | PCA-2, CSF | 35143-7 |
| 21631 | PCA-Tr, CSF | 51748-2 |
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