Plasmacytosis and Smudge Cell Lymphocytes

Abnormal B-cell morphologies have come up several times in the past papers. The college loves to ask about plasma cells in particular.  The usual trend is to ask for four or six different reasons as to why these cells may be seen in a blood film.

Plasmacytosis

Plasma cells swarming in the bloodstream can be a marker of numerous illnesses, and it is difficult to find just one article which might summarise the whole spectrum. In this Nature article, Table 2 lists several plasma cell disorders:

  • MGUS
  • Multiple myeloma
  • Waldenström's macroglobulinemia
  • Solitary plasmacytoma
  • Systemic AL amyloidosis
  • POEMS syndrome

A 1958 article reports on a few more causes:

  • Adenocarcinoma of the colon
  • Pulmonary tuberculosis
  • Cirrhosis of the liver
  • Aplastic anaemia
  • Syphilis

The college answer to one of the recent CICM fellowship questions also includes the following causes, for which there is not much literature:

There are numerous others.

For instance, one article (recording the finding of peripheral plasmacytosis in a patient with Dengue fever) also mentions (and backs with references) the following causes:

  • Primary infection and reactivation of Epstein–Barr virus
  • Acute respiratory infections
  • Parvovirus B19 infection
  • Rubella
  • Hepatitis virus A infection

Hypergammaglobulinaemia and hyperviscosity syndrome

If there is plasmacytoma, there is likely to be a monclonal gammopathy and hypergammaglobulinaemia. These extra gamma globulin molecules will be monoclonal immunoglobulins being produced by berserk out of control plasma cells. Waldenström's macroglobulinemia is the disorder where  clinically significant hyperviscosity occurs most frequently, according to this article by Mehta et al (2003). This is because Waldenström's macroglobulinemia is characterised by the excess production of IgM, which is a massive molecule.

Symptoms of hyperviscosity are presented in Question  7.3 from the first paper of 2016. They are as follows:

Features of the clinical presentation which suggest hyperviscosity:

  • Severe headaches
  • A fluctuating conscious state
  • Stroke, seizures, coma (usually, venous cerebral infarction)
  • Constitutional symptoms: fatigue, malaise, lethargy
  • Haemorrhagic symptoms:  gingival or mucosal bleeding, or epistaxis.
  • Blurred vision due to central retinal vein occlusion
  • Headaches due to increased intracranial pressure (due to venous occlusion)
  • Fundoscopy reveals dilated, tortuous retinal veins, as well as flame-shaped haemorrhages.
  • Renal failure
  • Aggravated heart failure (more difficult to pump the viscous blood)
  • Priapism

Laboratory features:

  • Leukocytosis, which suggests haematological malignancy
  • An elevated plasma cell count
  • An elevated globulin level (it will be mainly monoclonal IgM)

Management of the hyperviscosity syndrome is by plasmapheresis.

Smudge cell lymphocytes

Smudge cells are deformed lymphocytes which are associated with chronic lymphocytic leukaemia. Look, here's a whole bunch of them at the ASH Image Bank.

 

References

Kyle, R. A., and S. V. Rajkumar. "Criteria for diagnosis, staging, risk stratification and response assessment of multiple myeloma." Leukemia 23.1 (2009): 3-9.

Fadem, Robert S., and JOHN E. McBIRNIE. "PLASMACYTOSIS IN DISEASES OTHER THAN THE PRIMARY PLASMACYTIC DISEASES A REPORT OF SIX CASES." Blood 5.2 (1950): 191-200.

Aherne, W. A. "The differentiation of myelomatosis from other causes of bone marrow plasmacytosis." Journal of clinical pathology 11.4 (1958): 326-329.

Constantino, Benie T., and Bessie Cogionis. "Nucleated RBCs—significance in the peripheral blood film." Lab Medicine 31.4 (2000): 223-229.

SCHMIDT, JOHN J., HAROLD J. ROBINSON, and CHARLES S. PENNYPACKER. "Peripheral plasmacytosis in serum sickness." Annals of internal medicine 59.4 (1963): 542-546.

Bäumler, H., et al. "Basic phenomena of red blood cell rouleaux formation."Biorheology 36.5 (1999): 439-442.

Wagner, Christian, Patrick Steffen, and Saša Svetina. "Aggregation of red blood cells: From rouleaux to clot formation." Comptes Rendus Physique 14.6 (2013): 459-469.

REPLOGLE, ROBERT L., HERBERT J. MEISELMAN, and EDWARD W. MERRILL. "SPECIAL ARTICLE Clinical Implications of Blood Rheology Studies." Circulation 36.1 (1967): 148-160.

Ponder, Eric. "On sedimentation and rouleaux formation-I." Experimental Physiology 15.3 (1925): 235-252.

Aslinia, Florence, Joseph J. Mazza, and Steven H. Yale. "Megaloblastic anemia and other causes of macrocytosis." Clinical medicine & research 4.3 (2006): 236-241.

Walker, H. Kenneth, et al. "Peripheral blood smear." (1990). in Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition.

Bessis, Marcel. "Codocytes and Target Cells." Corpuscles. Springer Berlin Heidelberg, 1974. 59-64.

Jones, Kathy W. "Evaluation of Cell Morphology and Introduction to Platelet and White Blood Cell Morphology." I do not know which textbook this is form, but it is a chapter which is available for free online ... for now.

Bull, BRIAN S., J. Breton-Gorius, and E. Beutler. "Morphology of the erythron."New York, McGraw Hill (2001): 271-288. - this is an online re-posting of a chapter of Williams' Haematology, but without the figures.

Corazza, G. R., et al. "Howell‐Jolly body counting as a measure of splenic function. A reassessment." Clinical & Laboratory Haematology 12.3 (1990): 269-275.

Bain, Barbara J. "Diagnosis from the blood smear." New England Journal of Medicine 353.5 (2005): 498-507.

Sakka, Vissaria, et al. "An update on the etiology and diagnostic evaluation of a leukemoid reaction." European journal of internal medicine 17.6 (2006): 394-398.

ul Haque, Anwar, and Noor ul Aan. "Leukemoid Reaction: Unusual Causes." International Journal of Pathology 8.1 (2010): 39-40.

HARLEY, JOHN D., and ALVIN M. MAUER. "Studies on the formation of Heinz bodies. II. The nature and significance of Heinz bodies." Blood 17.4 (1961): 418-433.

JANDL, JAMES H. "The Heinz body hemolytic anemias." Annals of internal medicine 58.4 (1963): 702-709.

Mehta, Jayesh, and Seema Singhal. "Hyperviscosity syndrome in plasma cell dyscrasias." Seminars in thrombosis and hemostasis. Vol. 29. No. 05. Copyright© 2003 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.:+ 1 (212) 584-4662, 2003.