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Plasma cell dyscrasias involve the abnormal proliferation of plasma cells . These B-cell clones synthesize and secrete a single monoclonal immunoglobulin or its fragments, e.g., free light chains and free heavy chains. These monoclonal immunoglobulins are termed M proteins and appear as the M spike in the gamma region of SPEP. They can accumulate in tissue and are freely excreted in urine in the absence of glomerular damage
Plasma cell dyscrasias account for 15% of malignant WBC neoplasms and 1% of cancer deaths.
MGUS vs smoldering myeloma vs multiple myeloma
Waldenstrom vs MGUS vs Multiple Myeloma
Waldenstrom MGUS Multiple Myeloma Clinical features Bleeding, hyperviscosity, hepatosplenomegaly None CRAB Age 60-70s Labs Normocytic anemia None Normocytic anemia , Hypercalcemia SPEP M-spike between the beta and gamma regions (IgM) gamma spike (IgG) gamma spike (IgG) Bone marrow biopsy Abnormal lymphocytic infiltration, PAS+ < 10% plasma cells > 10% plasma cells Treatment Plasmapheresis Watch and wait Bortezomib, Thalidomide, Dexamethasone (VTD), then Melphalan → Bone marrow transplant. Other – Daratumumab
Normal morphology of plasma cells
Round Eccentric nucleus
“Clock-face” coarse chromatin
Prominent perinuclear hof (clearing- golgi)
Abundant basophilic cytoplasm- also described as a fried-egg appearance
Morphological patterns seen in plasma cell dyscrasias
Flame cells: Variants that overproduce IgA (Vermillion staining, IgA carbs cytoplasmic projections stain red on Wright stain)
Mott cells/ Morulae cell/ Grape cells: Plasma cells with abundant cytoplasmic inclusions or vacuoles (Russel bodies)
Russel bodies: Hyaline intracytoplasmic inclusions
Dutcher bodies: Pale staining intranuclear inclusions, single and large, most common in IgA myeloma
Plasmablasts
Plasma cells: with perinuclear hof and clockface chromatin
Binucleate plasma cells
Monoclonal gammopathy of undetermined significance (MGUS )
Serum monoclonal proteins <30g
Bone marrow plasma cells <10%
Absence of myeloma-defining events or amyloidosis (or Waldenstrom macroglobulinemia in the case of IgM MGUS )
Smouldering multiple myeloma
Serum monoclonal protein (IgG or IgA) or urinary monoclonal protein and or clonal bone marrow plasma cells 1-60%
Absence of myeloma-defining events (CRAB) or amyloidosis
Multiple myeloma
Evidence of end-organ damage that can be attributed to the underlying plasma cell proliferative disorder, specifically
Any or more of the following biomarkers of malignancy
Clonal bone marrow percentage ≥ 60%
Involved: uninvolved serum-free light-chain ratio ≥ 100
More than 1 focal lesion in MRI studies
Biochemistry
ACTH P: <80 ng/L ALT P: 5–35 U/L Albumin P: 35–50 g/L Aldosterone P: 100–500 pmol/L Alk. phosphatase P: 30–130 U/L α-Amylase P: 0–180 IU/dL α-Fetoprotein S: <10 kU/L Angiotensin II P: 5–35 pmol/L ADH P: 0.9–4.6 pmol/L AST P: 5–35 U/L Bicarbonate P: 24–30 mmol/L Bilirubin P: 3–17 μmol/L BNP P: <50 ng/L CRP P: <10 mg/L Calcitonin P: <0.1 mcg/L Calcium (ionized) P: 1.0–1.25 mmol/L Calcium (total) P: 2.12–2.60 mmol/L Chloride P: 95–105 mmol/L Cholesterol P: <5.0 mmol/L VLDL P: 0.128–0.645 mmol/L LDL P: <2.0 mmol/L HDL P: 0.9–1.93 mmol/L Cortisol AM P: 450–700 nmol/L Cortisol Midnight P: 80–280 nmol/L CK ♂ P: 25–195 U/L CK ♀ P: 25–170 U/L Creatinine P: 70–100 μmol/L Ferritin P: 12–200 mcg/L Folate S: 2.1 mcg/L FSH P: 2–8 U/L ♂; >25 menopause GGT ♂ P: 11–51 U/L GGT ♀ P: 7–33 U/L Glucose (fasting) P: 3.5–5.5 mmol/L Growth hormone P: <20 mu/L HbA1C (DCCT) B: 4–6% HbA1C (IFCC) B: 20–42 mmol/mol Iron ♂ S: 14–31 μmol/L Iron ♀ S: 11–30 μmol/L Lactate (venous) P: 0.6–2.4 mmol/L Lactate (arterial) P: 0.6–1.8 mmol/L LDH P: 70–250 U/L LH P: 3–16 U/L Magnesium P: 0.75–1.05 mmol/L Osmolality P: 278–305 mosmol/kg PTH P: 0.8–8.5 pmol/L Potassium P: 3.5–5.3 mmol/L Prolactin ♂ P: <450 U/L Prolactin ♀ P: <600 U/L PSA P: 0–4 mcg/mL Protein (total) P: 60–80 g/L Red cell folate B: 0.36–1.44 μmol/L Renin (erect) P: 2.8–4.5 pmol/mL/h Renin (recumbent) P: 1.1–2.7 pmol/mL/h Sodium P: 135–145 mmol/L TBG P: 7–17 mg/L TSH P: 0.5–4.2 mU/L T4 P: 70–140 nmol/L Free T4 P: 9–22 pmol/L TIBC S: 54–75 μmol/L Triglycerides P: 0.50–2.3 mmol/L T3 P: 1.2–3.0 nmol/L Troponin T P: <0.1 mcg/L Urate ♂ P: 210–480 μmol/L Urate ♀ P: 150–390 μmol/L Urea P: 2.5–6.7 mmol/L Vitamin B12 S: 0.13–0.68 nmol/L Vitamin D S: 50 nmol/L
Arterial Blood Gases
pH 7.35–7.45 PaCO₂ 4.7–6.0 kPa PaO₂ >10.6 kPa Base excess ±2 mmol/L
Urine
Cortisol (free) <280 nmol/24h Hydroxyindole acetic acid 16–73 μmol/24h Hydroxymethylmandelic acid 16–48 μmol/24h Metanephrines 0.03–0.69 μmol/mmol cr. Osmolality 350–1000 mosmol/kg 17-Oxogenic steroids ♂ 28–30 μmol/24h 17-Oxogenic steroids ♀ 21–66 μmol/24h 17-Oxosteroids ♂ 17–76 μmol/24h 17-Oxosteroids ♀ 14–59 μmol/24h Phosphate (inorganic) 15–50 mmol/24h Potassium 14–120 mmol/24h Protein <150 mg/24h Protein/creatinine ratio <3 mg/mmol Sodium 100–250 mmol/24h
Haematology
WCC 4.0–11.0 ×10⁹/L RBC ♂ 4.5–6.5 ×10¹²/L RBC ♀ 3.9–5.6 ×10¹²/L Hb ♂ 130–180 g/L Hb ♀ 115–160 g/L PCV ♂ 0.4–0.54 L/L PCV ♀ 0.37–0.47 L/L MCV 76–96 fL MCH 27–32 pg MCHC 300–360 g/L RDW 11.6–14.6% Neutrophils 2.0–7.5 ×10⁹/L (40–75%) Lymphocytes 1.0–4.5 ×10⁹/L (20–45%) Eosinophils 0.04–0.44 ×10⁹/L (1–6%) Basophils 0–0.10 ×10⁹/L (0–1%) Monocytes 0.2–0.8 ×10⁹/L (2–10%) Platelets 150–400 ×10⁹/L Reticulocytes 0.8–2.0% / 25–100 ×10⁹/L Prothrombin time 10–14 s APTT 35–45 s
Paediatric
Pulse Rate (bpm) Neonate 140–160 Infant <1yr 120–140 1–5 years 110–130 5–12 years 80–120 >12 years 70–100 Respiratory Rate (tachypnoea) 0–2 months ≥60/min 2–12 months ≥50/min 1–5 years ≥40/min >5 years ≥30/min Blood Pressure (mmHg) Term 65/45 1 year 75/50 4 years 85/60 8 years 95/65 10 years 100/70 Weight Formulas 3–12 months (a + 9)/2 kg 1–6 years 2a + 8 kg >6 years (7a − 5)/2 kg Haemoglobin (g/dL) Term newborn 13–20 1 month 11–18 2 months 10–15 1–2 years 10–13 >2 years 11–14 MUAC (6 months–5 years) Obese >17.5 cm Normal 13.5–17.4 cm At risk 12.5–13.4 cm Moderate malnutrition 11.5–12.4 cm Severe malnutrition <11.5 cm Developmental Milestones Social smile 1.5 months Head control 4 months Sits unsupported 7 months Crawls 10 months Stands unsupported 10–12 months Walks 12–13 months Talks 18 months CSF WBC (/mm³) Term newborn 0–25 >2 weeks 0–5