1. Clinicopathological case conference week 1
Case of the week
3rd February 2017
Video linked
Southend , Basildon and Chelmsford University hospitals NHS foundation Trust (ESR). East of England, United Kingdom.
Dr Amin Islam MB, MRCP UK, FRCPath UK
Consultant Haematologist

2. 57 years old lady
Referred by her GP on discharge from a tertiary hospital
Had a fall during inpatient stay
CT head was abnormal
Underwent evaluation of pancreatic duct stricture and pseudo cyst
Advised to refer to haematology locally

4. What do you see? Pepper pot skull Lytic lesion Vascular markings
Widespread metastatic deposits
Brown tumour

5. PMH Recurrent pancreatitis : idiopathic Type 2 diabetes Hypertension
Raised cholesterol
Does not drink alcohol, works for a blood charity
Medication:
Amitriptyline
Omeprazole
Paracetamol
Family history: NIL

6. Haematology reviewed urgently
She does not have any unusual bony aches and pains.
There is no history of recurrent infections or inflammation.
On examination looked well.
no palpable adenoptahy or hepatosplenomegaly.

7. What test would you do in clinic?

8. The blood test Hb 109, WCC 6, platelets 168,
neutrophils 3.0, lymphocytes 2.5,
creatinine 48, LFT normal, calcium normal.
Protein electrophoresis did not reveal any abnormal paraprotein. CRP is less than 1.
Immunoglobulin normal, LDH normal. Uric acid : Normal
Kappa and Lambda light chains are: normal
K/L ratio :Normal
Urine : BJP : Negative

9. Skeletal survey

10. What next test would you do ?

11. Bone marrow test project on microscopy
Aspirate: Haemodiluted but no plasma cells are seen
Trephine:
>90% infiltration with
Plasma cells?

12. Bone marrow liquid aspirate
Multipara metre flow cytometry
Haemodiluted but no clonal plasma cells detected
Cytogenetic : Not done

13. What next steps would you do on trephine ?

14. Immunophenotying
By immunohistochemistry

15. What staining you ask for myeloma?

16. CD 38
CD 138
CD 56 positive in PCM (useful for detecting residual PCM, particularly in morphologically equivocal cases in which light chain restriction cannot be demonstrated, and may serve as a potential response criterion)
CD 20
Kappa and lambda

17. Project the slides on microscope

18. What is the diagnosis

19. Non –secretory plasma cell myeloma
Non secretary myeloma
57 YRS old lady
MDT agreed
6 course of VTD (Valcade/thalidomide/dexamethasone)
Consolidate with Autologous stem cell transplantations in 1st CR
Response assessment by marrow test after 2-3 cycles of VTD agreed

20. Marrow after 3 VTD Worse infiltrations on trephine Almost 90-100%
Suspicious of non- haematopoietic cells infiltrations
Aspirate : normal with no excess of plasma cells noted
Flow : No clonal plasma cells noted

21. Patient reviewed urgently by haematologist and stopped VTD
Involved
Medical oncologist
Clinical oncologist as CUP ( cancer of unknown primary)
Patient reviewed and counselled
Examination : Unremarkable with no palpable mass and patient asymptomatic
PET CT arranged as urgent

22. What next staining to do:
Haemato-histopathologist reviewed the trephine
Agreed : metastatic cancer infiltrations of unknown primary

23. Specialised Immunohistochemical stain to project on microscope
Cytokeratin 7: strongly positive
Pankeratin : strongly positive
CAM5.2 : strongly positive
MNF116: strongly positive
CD 138 strongly positive
CD 38 strongly positive
ER : positive ?
Kappa and lambda : Negative

24. CUP review on going Examination : NAD CT CNAP : NAD Breast : NAD
PET: left SCF : lymph node 2.5 cm

25. Lymph node biopsy LT SCF

26. Treatment Letrozole started Bisphosphonate Asymptomatic
Back to her work in London
Care transferred to a tertiary hospital
Close to her work

27. Learning points CD 38 and CD 138 are not specific for myeloma
Other GI and neuroendocrine tumour can express this marker
Clonality study essential
Myeloma cells are cytoplasmic kapa/lambda restricted plasma cells

28. Non secretory myeloma Only 1-4% of all myeloma Good prognosis?
t (11:14) many harbour
Do not secrete immunoglobulin or its component parts into either the blood or urine
widely used serum free light chain assay, have reduced the number of patients with truly non-secretory

29. Some hypothesis
In addition to the state of nonproduction, several mechanisms are proposed to account for the absence of an M protein in NSMM cases.
Decrease in M protein synthesis secondary to increased cytoplasmic immunoglobulins
Accelerated degradation of abnormal intracellular immunoglobulins,

30. continued Impaired intracellular transport of immunoglobulins
Intermittent excretion of M protein
Altered secretion ability of plasma cell, Reduced plasma cell membrane permeability, and
Rapid degradation of abnormal immunoglobulin following its secretion

31. Questions