Plasma Cell Dyscrasias.pptx

Clinico pathological correlation in plasma cell dyscrasias.

1. PLASMA CELL DYSCRASIAS Dr. ANJALY S IIⁿᵈ YEAR PG INSTITUTE OF PATHOLOGY, MMC

2. CASE HISTORY 64 Years old male patient, presented with fever, vomiting and back pain. He is a known case of systemic hypertension, chronic pancreatitis and CKD on conservative management. History of a lytic lesion in vertebrae present.

3. COMPLETE BLOOD COUNT: WBC : 10.7 × 10³ / microlitre RBC : 2.43 × 10⁶ / mL Hb% : 7.2 g/dL MCV : 94.2 fL MCH : 29.6 pg/dL PC : 178×10³ / microlitre RDW-CV : 19.8% ESR : 28 INVESTIGATIONS(Contd.)

4. INVESTIGATIONS(Contd.) NORMOCHROMIC, NORMOCYTIC ANEMIA. NO ROULEAUX FORMATION

5. PERIPHERAL SMEAR: RBC: Normal count Normocytic, normochromic RBC with some macrocytes No rouleaux formation seen Anisopoikilocytosis present composed of tear drop cells No nRBC / Inclusions / Hemoparasites INVESTIGATIONS(Contd.)

6. PERIPHERAL SMEAR(Contd.): WBC: Normal count NEUTROPHILS - 79% LYMPHOCYTES - 21% EOSINOPHILS - 10% AEC - 1170 cells/mm³ PLATELETS: Normal count Distribution - singles IMPRESSION: Normocytic, Normochromic Anemia with eosinophilia INVESTIGATIONS(Contd.)

7. PLASMA CELLS Identified in bone marrow based on morphology and immunophenotype. Multi parametric flow cytometry that can detect six or more antigens (commonly CD38, CD45, CD56, CD19, KAPPA & LAMBDA)

8. PLASMA CELLS(Contd.) MORPHOLOGIC FEATURES OF PLASMA CELLS DEPENDING ON THEIR MATURITY MATURE PLASMA CELLS IMMATURE PLASMA CELLS Oval with abundant basophilic cytoplasm, nucleus is round and eccentrically located,perinuclear hoff or cytoplasmic clearing, “clock face” or “spoke wheel” chromatin without nucleoli. Dispersed nuclear chromatin, prominent nucleoli and a high nuclear to cytoplasmic ratio. Morphologically indistinguishable from myeloblasts.

9. PLASMA CELLS(Contd.)

10. INVESTIGATIONS(Contd.) BONE MARROW ASPIRATION: Cellular, Adequate Trilineage hematopoiesis present Myeloid Erythroid Ratio - 5:1 ERYTHROID : Present, Reduced Binucleate, Budding Present MYELOID : Present, Increased Neutrophils - 34% Lymphocytes - 7%

11. INVESTIGATIONS(Contd.) BONE MARROW ASPIRATION(Contd.): Band forms - 18% Eosinophilis - 2% Metamyelocytes - 12% Myelocyte - 24% Plasma cells - 3% IMPRESSION: Trilineage hematopoiesis with myeloid hyperplasia with 3% plasma cells.

12. INVESTIGATIONS(Contd.) BONE MARROW BIOPSY (9775/22) : GROSS: Received three grey white, grey brown bony fragments each measuring 0.3 cm in length. MICROSCOPY: Cellular marrow Adequate Trilineage hematopoiesis - present Erythroid - present

13. BONE MARROW BIOPSY(Contd.): MICROSCOPY(Contd.): Myeloid - present Maturing myeloid - present Megakaryocytes - Adequate Blasts - Not increased Lymphocytes - Not increased Plasma cells - Increased Granuloma - Absent Reticulin - Grade I INVESTIGATIONS(Contd.)

14. BONE MARROW BIOPSY(Contd.):

15. BONE MARROW BIOPSY(Contd.): IMMUNO HISTOCHEMISTRY: CD138 - Positive in plasma cells in singles and in clusters INVESTIGATIONS(Contd.)

16. INVESTIGATIONS(Contd.) BONE MARROW BIOPSY(Contd.): DISCUSSION: 64 year old male with lytic lesion in vertebrae with history of anemia and renal failure. Bone marrow aspiration shows trilineage hematopoiesis with myeloid hyperplasia and 3% plasma cells . Bone marrow biopsy shows CD138 positive plasma cells in singles and in clusters. IMPRESSION: Bone marrow plasmacytosis. suggested clinical correlation.

17. INVESTIGATIONS(Contd.) CT GUIDED BIOPSY OF L3 VERTEBRAL BODY(FROM THE LYTIC LESION) GROSS: Received multiple grey white linear bony fragments largest measuring 1.2cm in length, smallest measuring 0.5cm in length. MICROSCOPY: Section studied shows multiple fragments of mature bony trabeculae with intervening marrow spaces exhibiting normal trilineage hematopoiesis along with few plasma cells. IMMUNO HISTOCHEMISTRY: CD38 - Positive in 15% of plasma cells.

18. LYTIC BONE LESION BIOPSY :

19. IMMUNO HISTOCHEMISTRY: CD38 - Positive in plasma cells. INVESTIGATIONS(Contd.)

20. INVESTIGATIONS(Contd.) Serum Calcium level - 8.1 mg/dL Urine Bence Jones proteins - Negative Serum protein electrophoresis shows normal electrophoretic pattern. No para protein band detected. Free light chain assay - Report awaited

21. REACTIVE PLASMACYTOSIS MULTIPLE MYELOMA SOLITARY PLASMACYTOMA LYMPHOPLASMACYTIC LYMPHOMA MGUS SMOULDERING MYELOMA DIFFERENTIAL DIAGNOSIS

22. Clonality should be established by showing a kappa/lambda light chain restriction on flow cytometry, immuno histochemistry or immuno flureoscence. Bone marrow plasma cell percentage should be estimated from a core biopsy specimen when possible. Approximately 4% of patients may have fewer than 10% bone marrow plasma cells, since marrow involvement maybe focal rather than diffuse.

23. Polyclonal plasma cells Bone Marrow: hypercellularity Trilineage hematopoiesis with normal morphology Immuno histochemistry: Positive for CD38, CD138,CD45,CD19 Kappa and Lambda light chains Negative for CD 56 REACTIVE PLASMACYTOSIS :

24. MULTIPLE MYELOMA : Clonal bone marrow plasma cell percentage ≥10% or biopsy-proven plasmacytoma and ≥1 of the following myeloma-defining events: END ORGAN DAMAGE ATTRIBUTABLE TO THE PLAMSA CELL PROLIFERATIVE DISORDER: Hyper calcemia : Serum calcium >0.25 mmol/L (>1mg/dL) higher than the upper limit of normal or >2.75 mmol/L (>11mg/dL) Renal insufficiency : Creatinine clearance <40 mL/min or serum creatinine >177 micromol/L (>2 mg/dL)

25. Anemia : a hemoglobin value of >20 g/L below the lower limit of normal or a hemoglobin value <100 g/L Bone lesions : ≥ 1 osteolytic lesion on skeletal radiography, CT or PET/CT ≥1 OF THE FOLLOWING BIOMARKERS OF MALIGNANCY: Clonal bone marrow plasma cell percentage ≥60% An involved-to-uninvolved serum free light chain ratio ≥100 >1 focal lesion on MRI MULTIPLE MYELOMA(Contd) :

26. CONDENSED OR CRYSTALLISED IMMUNOGLOBULIN :

27. IMMUNOPHENOTYPE : Immunohistochemical staining, immunofluorescent flow cytometry. Expression of some normal plasma cell markers( eg: CD79a, VS38c, CD138 & CD138) Either kappa or lambda light chains, not both. Absence of surface immunoglobulin. Absence of CD19 in most instances. Variable expression of CD45(usually negative), CD56 (usually positive) The kappa/lambda ratio of more than 4:1 or less than 1:2.

28. SOLITARY PLAMSACYTOMA : Biopsy proven solitary lesion of bone or soft tissue consisting of clonal plasma cells. Normal random bone marrow biopsy with no evidence of clonal plasma cells. Normal skeletal survey and MRI or CT except for the solitary lesion. Absence of end organ damage attributable to a plasma cell proliferative disorder.

29. PLAMSACYTOMA :

30. Single focus of plasma cells occuring in either bone or soft tissue. Males Sixth decade MICROSCOPY: Very vascular with a minimal stromal component and consists of sheets of plasma cells of varying degree of differentiation. SOLITARY PLAMSACYTOMA :

31. Lymphoplasmacytic lymphoma in the bone with an IgM monoclonal gammopathy in blood (Walden Strom macroglobulinemia). Predominant cells are small lymphocytes or a mixture of small lymphocytes and plasma cytoid lymphocytes. Small lymphocytic component that express a clonal surface immunoglobulin, CD19 and CD20. LYMPHOPLASMACYTIC LYMPHOMA

32. MONOCLONAL GAMMOPATHY OF UNDETERMINED SIGNIFICANCE(MGUS) : M protein in serum < 30 g/L Bone marrow clonal plasma cells < 10% No evidence of other B cells proliferative disorders. No myeloma-related organ or tissue impairment (no end organ damage, including bone lesions)

33. SMOULDERING MYELOMA : Serum M protein > 30g/L, Urine M protein > 500 mg per 24 hours and/or clonal marrow plasma cells of 10% - 60%, and Absence of myeloma defining events or amyloidosis

34. THANK YOU