Pathology Notes

Infectious mononucleosis Updated: 09/10/2020 © Jun Wang, MD, PhD General features Febrile illness EB virus associated Spread by intimate contact, including breast feeding, saliva exchange and other sexual contacts Human likely major reservoir More common in young adults Higher risk for EBV associated malignancies, such as Hodgkin lymphoma , Burkitt lymphoma Clinical presentations Most asymptomatic Incubation 1-2 months Triad of fever , tonsillar pharyngitis , and lymphadenopathy Other nonspecific presentations: fatigue, Hepatomegaly, jaundice, splenomegaly, etc Risk of fatal spontaneous spleen rupture Key pathogenesis EB virus infection of B cells Infects reticular endothelial system (liver, spleen, lymph nodes, etc) through circulation B cells produce antibodies against EBV protein components T cells eliminate infected B cells Inflammatory reactions associated with clinical presentations B cell malignancy may develop due to uncontrolled proliferatio

Reactive leukocytosis Updated: 09/26/2020 © Jun Wang, MD, PhD General features Usually a reaction to physiological (stress, exercise) or pathological (inflammation, underlying neoplasm, allergic reactions, hereditary) processes Results of elevated levels of growth factor, cytokines, etc Specific terms Left shift : Increased circulating immature leukocytes, usually neutrophils, caused by releasing of stored leukocytes, associated with bacterial infection Leukemoid reaction : Neutrophils above 50 x 10 3 /mm 3 , more immature cells, particularly myelocytes, associated with severe infection, intoxications, severe hemorrhage, acute hemolysis, etc Leukoerythroblastic reaction : Nucleated red blood cells and immature myelocytes in circulation, associated with severe marrow function disruption, may be seen in myelofibrosis, may mimic myeloid neoplasms . Neutrophilia Usually associated with acute infection, steroid usage, inflammations, metabolic disorders such as ketoac

Splenomegaly Updated: 07/13/2020 © Jun Wang, MD, PhD General features Enlarged spleen >400 g Massive if > 1000 g Various etiology, usually associated with splenic hyperfunction Etiology Part of systemic presentation of inflammation: Such as in subacute bacterial endocarditis or infectious mononucleosis Local inflammation: Sarcoidosis, abscess, etc RBC destruction: Hereditary spherocytosis, thalassemia Congestive: Portal hypertension Ectopic hematopoiesis: Myeloproliferative neoplasm , etc Neoplastic: Lymphomas, metastatic malignancy, etc Clinical presentations Various Key pathogenesis Splenic hyperfunction Key Laboratory findings Nonspecific Anemia, leukopenia, or thrombocytopenia Less mature white cells, nucleated red cells , teardrop-shaped red cells , etc Diagnostic approaches to identify etiology History CBC and peripheral blood morphology Bone marrow biopsy if hematopoietic disorder suspicious Flow cytometry if lymphocyte pre

Hemophagocytic lymphohistiocytosis Updated: 08/04/2020 © Jun Wang, MD, PhD General features Generalized, non-malignant histiocytosis Rare but aggressive and life threatening Excessive activation of immune activity Familial : infants/young children, autosomal recessive Acquired : EBV+ immunocompromised, or associated with other infections or malignancy May develop from Chediak-Higashi syndrome May involve any organ Repeated biopsy of bone marrow, lymph nodes, etc if necessary for diagnosis Clinical presentations Acute febrile illness Splenomegaly and hepatomegaly Lymphadenopathy Skin rash Key pathogenesis Abnormal activation of macrophages Over expression of calreticulin (CRT) Underexpression of CD47 Key Laboratory findings Pancytopenia Key morphological features Hemophagocytosis Indicators for diagnosis Fever with hepatosplenomegaly and cytopenia, as well as elevated ferritin Genetic abnormalities If familial, associated

Hyposplenism Updated: 08/02/2020 © Jun Wang, MD, PhD General features Reduced splenic function Various etiologies Clinical features Increased risk for infection, especially encapsulated bacteria, such as pneumococcus Etiology Splenectomy Infarction, such as seen in sickle cell disease Others including congenital abnormality, celiac disease, etc Key Laboratory findings Howell-Jolly bodies Pappenheimer bodies Target cells Back to benign white cell disorders Back to contents

Chronic lymphadenitis Updated: 07/23/2020 © Jun Wang, MD, PhD General features Chronic inflammation Various etiology Associated with toxoplasmosis, early HIV infection, rheumatoid arthritis, etc Clinical presentations Painless enlargement of lymph node Key morphological features Follicular hyperplasia with normal architecture Prominent post capillary venules Usually numerous tangible body macrophages Diagnostic approaches Special stains Immunohistochemistry Molecular studies Flow cytometry to rule our monoclonal lymphocytic proliferation Back to benign white cell disorders Back to contents

Acute lymphadenitis Updated: 07/13/2020 © Jun Wang, MD, PhD General features AKA suppurative lymphadenitits Most commonly due to S. aureus infection Also associated with cat-scratch disease, intravenous drug use, lymphogranuloma venereum Clinical presentations Acute inflammatory changes of involved lymph nodes, including enlargement of node, erythematous and edematous changes of covering skin Key morphological features Neutrophilic infiltrate Microabscesses formation Diagnostic approach Stains: Gram, silver Culture Serology studies for suspicious infection, such as cat scratch Back to benign white cell disorders Back to contents

Morphological abnormalities of white cells Updated: 07/22/2022 © Jun Wang, MD, PhD Alder-Reilly anomaly Metachromatic granules surrounded by clear zone in lymphocytes Associated with the genetic mucopolysaccharidoses Lack the lysosomal enzymes necessary to break down mucopolysaccharides Döhle bodies Single o r multiple blue cytoplasmic inclusions in neutrophils Remnants of rough endoplasmic reticulum retained from a more immature state Associated with myeloid "left shifts" Hypersegmentation Abnormally increased nuclear lobulation in granulocytes Associated with megaloblastic anemia May-Hegglin anomaly Autosomal dominant Dohle-like bodies and background giant platelets May be associated with thrombocytopenia and bleeding Pelger-Huet anomaly Autosomal dominant Less segmentation of granulocyte nuclei Round (homozygote) or bilobed nuclei (heterozygote) in neutrophils Normal cell function Pseudo-Pelger-Huet change Associated with ine

Neutropenia Updated: 08/03/2020 © Jun Wang, MD, PhD General features Heterogeneous group of disorders of decrease in circulating neutrophils Grading by absolute neutrophil count: Mild (1000-1500/mm 3 ), Moderate (500-1000/ mm 3 ), and severe (<500/ mm 3 ) Risk of serious infection, especially when absolute neutrophil count (ANC)  (< 500/ mm 3 ) Agranulocytosis : Absence of neutrophils in peripheral blood, usually applied if ANC < 100/ mm 3 Granulocytopenia : Reduced number of blood granulocytes, namely neutrophils, eosinophils, and basophils Clinical features Risk of infection Key pathogenesis Reduced production: Toxicity of medication or other substances probably to stem cells, or immune response Ineffective hematopoiesis: MDS, megaloblastic anemias, etc Increased destruction or sequestration: Immune mediated neutrophilic injuries, splenomegaly Increased peripheral utilization: Infection, etc   Congenital: Isolated neutropenia, etc Benign ethni

Benign white cell disorders Updated: 08/03/2020 © Jun Wang, MD, PhD 1. Leukopenia Neutropenia Chediac-Higashi syndrome Lymphocytopenia (lymphopenia): ALC <1000 cells/microL for adults, may be associated with HIV infection, primary immunodeficiency , malnutrition, chemotherapy, etc 2. Leukocytosis Neutrophilia Eosinophilia Basophilia Monocytosis Lymphocytosis: infectious mononucleosis 3. Morphological abnormalities Alder-Reilly anomaly Döhle bodies Hypersegmentation May-Hegglin anomaly Pelger-Huet anomaly Pseudo-Pelger-Huet change Toxic granulation 4. Benign lymph node disorders Acute lymphadenitis Chronic lymphadenitis Hemophagocytic lymphohistiocytosis 5. Benign disorders of spleen Hyposplenism Splenomegaly 6. Practice questions Back to contents

Hematology terms A Alder-Reilly anomaly :   Metachromatic granules surrounded by clear zone in lymphocytes, associated with the genetic mucopolysaccharidoses, due to lack the lysosomal enzymes necessary to break down mucopolysaccharides Amyloid : Amorphously deposited fibrillary protein, non-branching fibrils in a beta-pleated sheet conformation; can be monoclonal immunoglobulin; positive for Congo Red; suggestive of B cell disorder Anisocytosis : Red cells unequal in size , commonly seen in anemia Auer rod : N eedle shaped cytoplasmic azurophilic granular material, associated with APL with PML-RARA , and AML with t(8;21)(q22;q22.1) B Bence Jones proteins : Free light chains without attached heavy chains C Cloverleaf/flower cells : Neoplastic T cells with agranular basophilic cytoplasm, multilobated nuclei, in the appearance of clover leaf , seen in adult T cell leukemia/lymphoma Coombs test Direct : Detect antibodies/complements attached to surface of pat