Plasma cell disorders: Pathology review


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Plasma cell disorders: Pathology review

Hematological system


Iron deficiency anemia



Sideroblastic anemia

Anemia of chronic disease

Lead poisoning

Hemolytic disease of the newborn

Glucose-6-phosphate dehydrogenase (G6PD) deficiency

Autoimmune hemolytic anemia

Pyruvate kinase deficiency

Paroxysmal nocturnal hemoglobinuria

Sickle cell disease (NORD)

Hereditary spherocytosis

Anemia of chronic disease

Aplastic anemia

Fanconi anemia

Megaloblastic anemia

Folate (Vitamin B9) deficiency

Vitamin B12 deficiency

Fanconi anemia

Diamond-Blackfan anemia

Heme synthesis disorders

Acute intermittent porphyria

Porphyria cutanea tarda

Lead poisoning

Coagulation disorders


Vitamin K deficiency

Platelet disorders

Bernard-Soulier syndrome

Glanzmann's thrombasthenia

Hemolytic-uremic syndrome

Immune thrombocytopenic purpura

Thrombotic thrombocytopenic purpura

Mixed platelet and coagulation disorders

Von Willebrand disease

Disseminated intravascular coagulation

Heparin-induced thrombocytopenia

Thrombosis syndromes (hypercoagulability)

Antithrombin III deficiency

Factor V Leiden

Protein C deficiency

Protein S deficiency

Antiphospholipid syndrome


Hodgkin lymphoma

Non-Hodgkin lymphoma


Chronic leukemia

Acute leukemia

Leukemoid reaction

Leukemoid reaction

Dysplastic and proliferative disorders

Myelodysplastic syndromes

Polycythemia vera (NORD)

Myelofibrosis (NORD)

Essential thrombocythemia (NORD)

Langerhans cell histiocytosis

Mastocytosis (NORD)

Plasma cell dyscrasias

Multiple myeloma

Monoclonal gammopathy of undetermined significance

Waldenstrom macroglobulinemia

Hematological system pathology review

Microcytic anemia: Pathology review

Non-hemolytic normocytic anemia: Pathology review

Intrinsic hemolytic normocytic anemia: Pathology review

Extrinsic hemolytic normocytic anemia: Pathology review

Macrocytic anemia: Pathology review

Heme synthesis disorders: Pathology review

Coagulation disorders: Pathology review

Platelet disorders: Pathology review

Mixed platelet and coagulation disorders: Pathology review

Thrombosis syndromes (hypercoagulability): Pathology review

Lymphomas: Pathology review

Leukemias: Pathology review

Plasma cell disorders: Pathology review

Myeloproliferative disorders: Pathology review


Plasma cell disorders: Pathology review

USMLE® Step 1 questions

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USMLE® Step 1 style questions USMLE

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A 62 year-old man presents to his outpatient provider’s office because of two months of persistent headaches, blurry vision, and numbness in the hands bilaterally. The headache is unresponsive to over the counter pain-killers. He also reports 10 lbs (4.5 kg) weight loss over the same period. Past medical history is notable for hypertension. Family history is significant for multiple sclerosis in his mother. His temperature is 37.1°C (98.8°F), pulse is 75/min and blood pressure is 148/97 mmHg. Cardiopulmonary examination is noncontributory. Abdominal examination reveals hepatosplenomegaly. On peripheral smear, red blood cells are seen to clump together when placed in a 5°C (41°F) refrigerator. Which of the following best explains the pathophysiology of the patient’s condition? 


Content Reviewers

Yifan Xiao, MD


Samantha McBundy, MFA, CMI

Maria Emfietzoglou, MD

Evan Debevec-McKenney

Kaia Chessen, MScBMC

At the family medicine department, a 70 year old male named Ian came in with progressive fatigue and chronic back pain. His lab tests show anemia with an MCV of 90. as well as increased calcium, blood urea nitrogen and creatinine levels. Peripheral blood smear showed the following. Next to Ian, there’s a 65 year old female named Amanda that complains of progressive fatigue, recurrent nosebleeds and blurred vision. Clinical examination reveals palpable liver and spleen. Her lab tests show anemia with normal MCV, reticulocyte count index over 2%, increased LDH, and a positive Coombs test.

Although their symptoms are very different, both Ian and Amanda have a plasma cell disorder. Plasma cell disorders are a group of hematological malignancies that are characterized by unregulated proliferation of plasma cells in the bone marrow. They include multiple myeloma, monoclonal gammopathy of unknown significance or MGUS(em-gus), and Waldenström’s macroglobulinemia. Each of them produce a monoclonal or M-protein, which is a unique protein of a single type, like a protein “clone”. Because plasma cells normally make immunoglobulins, it’s not surprising that the M-proteins produced are also immunoglobulins

Alright, now let’s take a closer look at these different plasma cell disorders, starting with multiple myeloma, which is the most common primary bone tumor in people older than 40 to 50 years of age. In multiple myeloma, the most common M-protein produced is IgG, followed by IgA, and these immunoglobulins have both a heavy and light chain. More rarely, the myeloma cells can only make the kappa or lambda light chain of the immunoglobulin, and in that situation, the resulting protein is called the Bence-Jones protein.

A high yield concept is the clinical presentation of multiple myeloma, which can be summarized with the mnemonic CRAB (like the animal), “C” is for hypercalcemia, which results from increased osteoclast activity due to the release of osteoclast activating factor from the malignant plasma cells, which resorbs the bone and releases free calcium into the circulation. Remember that your exam might not just give you the lab finding, but instead give you some symptoms of hypercalcemia, such as abdominal pain, psychiatric changes, constipation or fatigue. Okay, “R” is for renal disease, which can be caused by multiple mechanisms. First, the light chains can deposit in and obstruct the renal tubules, and this is called light chain cast nephropathy, or myeloma kidney. Renal disease can also be due to type two renal tubular acidosis, or even hypercalcemia which may cause the formation of calcium phosphate kidney stones. Now, multiple myeloma can also lead to a specific type of amyloidosis called primary amyloidosis. Here, the immunoglobulin light chains leave the circulation and abnormally aggregate in various tissues, resulting in various clinical manifestations These include restrictive cardiomyopathy, a large tongue, also called macroglossia, and nephrotic syndrome to name a few. So on the exam, beware of primary amyloidosis being a presenting feature of multiple myeloma. “A” is for anemia, which causes fatigue and shortness of breath. The anemia occurs because the malignant cells infiltrate the bone marrow, and disrupt the normal production of red blood cells. Finally, “B” is for bone pain, which is due to increased osteoclast activity causing pathologic fractures and lytic bone lesions. So, in the exams, look for an elderly individual with symptoms of anemia and chronic back pain. Other manifestations include spinal cord compression if the tumor infiltrates from the vertebrae, and frequent infections, because although the tumor is making lots of immunoglobulins, they are not functional immunoglobulins and so they are not useful in fighting infections.


  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  3. "Multiple myeloma: 2018 update on diagnosis, risk-stratification, and management" American Journal of Hematology (2018)
  4. "Multiple Myeloma: An Update" Oman Medical Journal (2013)
  5. "Multiple Myeloma: Diagnosis and Treatment" Am Fam Physician (2017)
  6. "Multiple Myeloma: Diagnosis and Treatment" Mayo Clinic Proceedings (2016)
  7. "Waldenström Macroglobulinemia: Review of Pathogenesis and Management" Clinical Lymphoma Myeloma and Leukemia (2017)
  8. "Waldenström Macroglobulinemia" Advances In Anatomic Pathology (2012)
  9. "Diagnosis, risk stratification and management of monoclonal gammopathy of undetermined significance and smoldering multiple myeloma" International Journal of Laboratory Hematology (2016)

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