Final Diagnosis:

Multiple Myeloma

Clinical Information:
A55 year old man presents with back pain and cramping in his legs. Routine bioochemistry reveals a raised globulin fraction and a new acute kidney injury. Further testing shows a paraprotein on electrophoresis.

This bone marrow shows the classical appearance of multiple myeloma. This is a rare malignancy, but relatively common to haematologists and should be easily recognisable by trained morphologists. Although plasma cell infiltration varies, often in older patients who present late the bone marrow cells are effaced (completely replaced) with plasma cells. Although plasma cells are found in normal bone marrow, they are rare. If you can find lots of them, you need to undrtake a differential. 

Plasma cells can be recognised by their blue stained cytoplasm - this is the immunoglobulin - and their low NC ratio. They tend to have a noticeably large amount of cytoplasm with an obvious eccentric nucleus. As they are a mature cell, the chromatin is dense and compact. Some plasma cells may be blastic - with open chromatin and much higher NC ratio, and if these are frequent then you may have plasmablastic myeloma, a much more aggressive form of the disease. 

Binucleate plasma cells are noteworthy in your report as these are also a sign of aggresive malignancy - the theory being that these cells have acquired additional dysplastic changes which make them abnormal, i.e. nuclear division failed.

There is an overlap between plasma cell leukaemia and multiple myeloma. Both can have circulating plasma cells in the peripheral blood, although myeloma will be significantly less than PCL (<20% of TNCs). The key way to differentiate PCL from MM though is by flow cytometry. MM will generally express CD56 which is a cell adhesion molecule. Loss of this allows the plasma cells to enter the blood stream more easily, so PCL is generally thought to be CD56 negative. The prognosis for PCL is poor as this is an aggressive malignancy. 

The source of the symptoms from MM is multifactorial. Back pain may be direct, from erosion of the spinal column vertebral bodies by the plasma cells, a crush fracture around a weakened site, or neuropathic damage from the crush fracture or paraprotein. Anaemia is caused by direct replacement of bone marrow cells with plasma cells, and by renal damage which results in low EPO production. Renal failure is caused by high plasma viscosity, anaemia, hypercalcaemia (a feedback loop here) and globulin deposition in the glomeruli - so called myeloma kidney. On a microscopic level, the pathology is called cast nephropathy.

Its worth noting that after treatment, plasma cell morphology can change radically, so while we always want to correlate with bone marrow at diagnosis, don't expect the plasma cells to look identical.

Your report should include all the standard comments and differentials, but the key figure is the plasma cell percentage which must be included. Note that because of the expression of adhesion molecules (like CD56), flow cytometry often underestimates the percentage of plasma cells, and histropathology is quite challenging in edge cases so the bone marrow aspirate might be the place where the diagnosis is made.

It's also a staple in the FRCPath examination.