| Diagnostic category | Specific requirement/test | Clinical/laboratory details and what constitutes positive finding | Diagnostic utility/performance | Suggested ontology terms |
|---|---|---|---|---|
| Mandatory criteria | Polyneuropathy | Typically a chronic, progressive, symmetrical, sensorimotor, length-dependent, painful demyelinating polyneuropathy/radiculoneuropathy with distal weakness predominance; often initially labeled CIDP; electrophysiology commonly shows uniform demyelination with marked secondary axonal loss and severe lower-limb involvement (pqac-00000000, pqac-00000001, pqac-00000003, pqac-00000005, pqac-00000006) | Essential diagnostic criterion; present in essentially all classic cases; major source of disability and diagnostic delay; treatment-resistant “CIDP” should trigger POEMS workup (pqac-00000001, pqac-00000005, pqac-00000010) | HP:0009830 Polyneuropathy; HP:0007104 Demyelinating peripheral neuropathy; HP:0031843 Neuropathic pain; NCIT:C38008 Nerve Conduction Study |
| Mandatory criteria | Monoclonal plasma cell disorder | Usually low-level IgAλ or IgGλ monoclonal gammopathy/plasma cell dyscrasia; serum paraprotein may be very small or undetectable on serum protein electrophoresis alone; positive finding may require serum/urine immunofixation, bone marrow biopsy, or lesional biopsy; >95% lambda-restricted in most series (pqac-00000003, pqac-00000005, pqac-00000008, pqac-00000009, pqac-00000010) | Essential diagnostic criterion and therapeutic target; SPEP may miss cases; immunofixation improves yield; in one cohort, all 42/42 had positive serum or urine immunofixation, but only 64.7% had positive serum immunofixation at presentation in another cohort (pqac-00000006, pqac-00000009) | HP:0032113 Monoclonal gammopathy; LOINC:24351-9 Protein electrophoresis panel-serum; LOINC:LAB174 Immunofixation electrophoresis |
| Major criteria | Castleman disease | Histopathologically confirmed Castleman disease in lymph node or tissue; may coexist with mild, painless, or even absent overt neuropathy in some cases (pqac-00000003, pqac-00000005, pqac-00000013) | One of the 3 additional major criteria; important overlap entity; helps explain atypical presentations but does not replace mandatory criteria in standard POEMS diagnosis (pqac-00000003, pqac-00000013) | HP:0002664 Castleman disease; NCIT:C4034 Lymph Node Biopsy |
| Major criteria | Sclerotic bone lesions | Osteosclerotic lesions on CT/PET-CT/MRI; may be densely sclerotic, lytic with sclerotic rim, or mixed “soap-bubble” lesions; often multiple and small; FDG-avid lesions can guide biopsy (pqac-00000001, pqac-00000005, pqac-00000007) | One of the core major criteria; central for distinguishing focal from systemic disease and for treatment planning; CT and FDG-PET/CT are emphasized over skeletal survey in modern workup (pqac-00000005, pqac-00000007) | HP:0030934 Osteosclerosis; NCIT:C17204 Computed Tomography; NCIT:C103430 Positron Emission Tomography |
| Major criteria | Elevated VEGF | Elevated serum or plasma vascular endothelial growth factor above assay-specific normal range; markedly raised levels are typical; example cohort median serum VEGF 6256 pg/mL (range 50-12,852 pg/mL) (pqac-00000001, pqac-00000002, pqac-00000009) | Major diagnostic biomarker; supports diagnosis and follow-up; considered useful and accurate for diagnosis and disease monitoring; normalization/suppression after treatment correlates with improved relapse-free survival and outcomes (pqac-00000001, pqac-00000002, pqac-00000007) | LOINC:34694-0 Vascular endothelial growth factor [Mass/volume] in Serum or Plasma; HP:0033677 Increased circulating VEGF level |
| Minor criteria | Organomegaly | Hepatomegaly, splenomegaly, and/or lymphadenopathy, often detected by CT rather than palpation (pqac-00000001, pqac-00000003, pqac-00000005) | Minor criterion supporting multisystem nature; helps distinguish POEMS from CIDP and other neuropathy syndromes; organomegaly occurred in 85.7% in one cohort (pqac-00000003, pqac-00000009) | HP:0002240 Hepatomegaly; HP:0001744 Splenomegaly; HP:0002716 Lymphadenopathy |
| Minor criteria | Endocrinopathy | Most characteristic: hypogonadism/hypopituitarism; also thyroid abnormalities and adrenal insufficiency; diabetes or thyroid disease alone are not considered sufficiently specific because common in the general population (pqac-00000001, pqac-00000005) | Minor criterion; combinations of endocrine abnormalities are more diagnostically reliable than isolated diabetes or hypothyroidism; endocrinopathy occurred in 95.2% in one cohort (pqac-00000001, pqac-00000009) | HP:0000818 Abnormality of the endocrine system; HP:0000824 Hypogonadism; HP:0000821 Hypothyroidism |
| Minor criteria | Skin changes | Hyperpigmentation, hypertrichosis, skin thickening, acrocyanosis, flushing/plethora, white nails, hemangiomas/glomeruloid hemangiomata (pqac-00000001, pqac-00000005, pqac-00000006) | Minor criterion and useful visual clue; common in practice; present in 76.5% of one cohort and 95.2% of another (pqac-00000006, pqac-00000009) | HP:0000953 Hyperpigmentation of the skin; HP:0002219 Hypertrichosis; HP:0001065 Skin thickening; HP:0001101 Acrocyanosis |
| Minor criteria | Papilledema | Bilateral optic disc edema/papilledema on ophthalmic examination; may occur with preserved vision early (pqac-00000001, pqac-00000005) | Minor criterion; clinically important because reported as an adverse prognostic marker in prior cohorts; frequency varies by cohort and follow-up duration (pqac-00000001, pqac-00000009) | HP:0001085 Papilledema; NCIT:C38087 Funduscopic Examination |
| Minor criteria | Extravascular volume overload | Peripheral edema, ascites, pleural effusion, and/or pericardial effusion; may coexist with pulmonary hypertension, renal dysfunction, or cardiac insufficiency (pqac-00000001, pqac-00000003, pqac-00000005, pqac-00000009) | Minor criterion; important marker of disease severity and transplant fitness; associated with shorter overall survival in review literature (pqac-00000003, pqac-00000005) | HP:0000969 Edema; HP:0001541 Ascites; HP:0012378 Pleural effusion; HP:0001698 Pericardial effusion |
| Minor criteria | Thrombocytosis / polycythemia | Elevated platelet count and/or increased red cell mass/hematocrit; thrombocytosis is more frequent and contributes to prothrombotic state (pqac-00000001, pqac-00000003, pqac-00000005) | Minor criterion; diagnostically useful because thrombocytosis helps distinguish POEMS from CIDP; also clinically relevant for stroke/thrombosis risk and for thromboprophylaxis decisions with lenalidomide (pqac-00000003, pqac-00000005) | HP:0001873 Thrombocytosis; HP:0001901 Polycythemia; LOINC:777-3 Platelets [#/volume] in Blood |
| Key diagnostic tests and biomarkers | Serum and urine immunofixation electrophoresis | Performed when SPEP is negative or equivocal; detects low-level monoclonal immunoglobulin/light chain; urine immunofixation may be positive when serum testing is negative (pqac-00000003, pqac-00000005, pqac-00000006) | Higher diagnostic yield than SPEP; review data: SPEP positive in as few as 54% vs immunofixation 75-92%; in Wang cohort 64.7% had positive serum immunofixation despite all having clonal plasma cell disorder (pqac-00000005, pqac-00000006) | LOINC:24351-9 Protein electrophoresis panel-serum; LOINC:LAB174 Immunofixation electrophoresis |
| Key diagnostic tests and biomarkers | Bone marrow aspirate/biopsy with kappa/lambda immunohistochemistry | Evaluates plasma cell burden and light-chain restriction; marrow clonal plasma cells are often sparse; one genomic cohort had median bone marrow plasma cells 1.5% (range 0-10%) (pqac-00000003, pqac-00000008, pqac-00000009) | Fundamental in suspected POEMS when paraprotein is subtle; helps distinguish POEMS from other plasma-cell disorders and from Waldenström macroglobulinemia/amyloidosis (pqac-00000003, pqac-00000012) | NCIT:C17617 Bone Marrow Biopsy; NCIT:C12255 Immunohistochemistry |
| Key diagnostic tests and biomarkers | Nerve conduction studies / EMG | Positive pattern: demyelinating neuropathy with marked secondary axonal loss, severe lower-limb CMAP reduction/absence, less conduction block and less temporal dispersion than CIDP, higher terminal latency index in some studies (pqac-00000000, pqac-00000005, pqac-00000006) | In Wang et al., combination of positive serum monoclonal protein and high TLI discriminated POEMS from CIDP with sensitivity 94.1% and specificity 76.5% if either present; specificity 100% if both present, but sensitivity 47.1% (pqac-00000000) | NCIT:C38008 Nerve Conduction Study; NCIT:C38054 Electromyography |
| Key diagnostic tests and biomarkers | Nerve ultrasound | Ultrasound of median, ulnar, brachial plexus and other nerves; POEMS shows more homogeneous enlargement along nerves and no conduction block, compared with more heterogeneous CIDP enlargement (pqac-00000011) | Two-step protocol using conduction block plus maximum/minimum median nerve CSA ratio differentiated CIDP from POEMS with sensitivity 93% and specificity 79% (pqac-00000011) | NCIT:C17230 Ultrasonography |
| Key diagnostic tests and biomarkers | CT / FDG-PET/CT imaging | CT identifies osteosclerotic lesions, adenopathy, organomegaly, ascites, pleural effusions, and edema; FDG-PET/CT identifies active bone lesions and guides lesional biopsy (pqac-00000003, pqac-00000005, pqac-00000007) | Recommended as part of routine workup in suspected POEMS; FDG-PET/CT is especially useful for target lesion selection and treatment planning (local vs systemic therapy) (pqac-00000005, pqac-00000007) | NCIT:C17204 Computed Tomography; NCIT:C103430 Positron Emission Tomography |
| Key diagnostic tests and biomarkers | Ophthalmologic examination | Direct fundus examination and related ophthalmic assessment for papilledema/optic disc edema (pqac-00000001, pqac-00000005) | Important because papilledema may be overlooked yet contributes to diagnosis and prognosis (pqac-00000001) | NCIT:C38087 Funduscopic Examination; HP:0001085 Papilledema |
| Key diagnostic tests and biomarkers | CBC and routine laboratory screening | Platelet count for thrombocytosis, hemoglobin/hematocrit for polycythemia, endocrine panels, renal/liver function testing, and general multisystem assessment (pqac-00000003, pqac-00000005) | Supports minor criteria and complication assessment; thrombocytosis is a practical discriminator from CIDP and helps estimate thrombotic risk (pqac-00000003, pqac-00000010) | LOINC:57021-8 CBC W Auto Differential panel-Blood; LOINC:777-3 Platelets [#/volume] in Blood |
| Diagnostic rule | Standardized case definition | Diagnosis is confirmed by both mandatory criteria plus at least 1 other major criterion and at least 1 minor criterion (pqac-00000003, pqac-00000006, pqac-00000008) | Standard framework across reviewed literature; integrates neurologic, hematologic, laboratory, and imaging data and reduces misclassification as CIDP or other monoclonal gammopathy-associated neuropathies (pqac-00000003, pqac-00000010) | MONDO: not confirmed from retrieved context; NCIT:C3671 Diagnostic Criteria |


*Table: This table summarizes the standardized diagnostic criteria for POEMS syndrome and the main diagnostic tests used in practice. It is useful for organizing mandatory, major, and minor criteria alongside the most informative laboratory, electrophysiologic, and imaging studies.*