Sandbox leucocytosis

• Leukocytosis is defined as an elevated white blood cell (WBC) count greater than 11,000 per mm3 (11.0 × 109 per L).
• The most common type of leukocytosis is neutrophilia.
  • Neutrophilia can be defined as an increase in the absolute number of mature neutrophils to greater than 7,000 per mm3 [7.0 × 109 per L].

			Differentiating Symptoms	Differentiating physical exam findings	Differentiating Labs
Physiological variation	Birth
	Adult
	Pregnancy
Primary	Congenital	Heridatary neutrophilia
		Chronic idiopathic neutrophilia
		Down syndrome
		LAD
	Acquired	CML
		Polycythemia Vera
Secondary	Infection	Acute
		Chronic
	Connective tissue disorders	RA
		JRA
		IBD
		Chronic hepatitis
	Drug induced	Steriod
		Lithium
		Beta agonists
		Cytokines
	Marrow stimulation	Hemolytic anemia
		Immature thrombocytopenia
	Post splenectomy
	Metabolic	Diabetic coma
		Acidosis
		Thyroid strom
		Acute Gout
		Seizures

Differential diagnosis of Lymphocytosis

	Pathophysiology	Symptoms	History	Physical Examination	Laboratory Findings
					CBC	Blood smear	Immunophenotype
Monoclonal B lymphocytosis	Monoclonal population of B lymphocytes <5000 cells/microL	Without other features of Lymphadenopathy Organomegaly Extra-medullary involvement	Active or prior infections History of hematologic malignancy Medications Family history of chronic lymphocytic leukemia (CLL)	Fever Lymphadenopathy Hepatosplenomegaly Joint redness Abdominal pain Lung findings.	Lymphocytosis ≥4000 lymphocytes/microL	Lymphocytes in MBL have no distinguishing appearance Appear as small, mature mononuclear cells.	CD19, CD20, and CD23	Does not require bone marrow examination or imaging for diagnosis
Congenital B cell lymphocytosis
Large granular lymphocyte leukemia	T-cell (T-LGL) Natural killer cell (NK-LGL)	Recurrent infections Fever Night sweats Unintended weight loss Lymphadenopathy			Pancytopenia Splenomegaly		CD3, CD57, CD56 CD3-, CD56+
Chronic lymphocytic leukemia
Sezary syndrome
Mantle cell lymphoma
Follicular lymphoma
Splenic marginal zone lymphoma
Acute lymphoblastic leukemia
Acute Promyelocytic Leukemia
Diffuse Large Cell Lymphoma		Enlarged painful lymph node	Neurological or gastrointestinal manifestations History of environmental and/or infectious disease exposure	Lymphadenopathy Splenomegaly Low-grade fever Pedal edema:

Differential for Eosinophilia

	Pathophysiology	Symptoms	History	Physical Examination	Laboratory Findings
Parasitic Infections	Egg deposition Liberation of antigens of adult worms and eggs Strong inflammatory response characterized by high levels of pro-inflammatory cytokines Interleukins 1, 6, tumor necrosis factor-α, and circulating immune complexes participates in the pathogenesis of the acute phase of the disease	Vary depending on the organism GI STD Neurological Swollen lymph nodes and muscle aches or pains	Travel History	Rash Fever Lymphadenopathy Ulcers	+Stool examination + Serologic testing Urinalysis
Allergy/ Atopic Diseases	Allergic hypersensitivity Eczema (atopic dermatitis) Allergic conjunctivitis, Allergic rhinitis Asthma
Hypereosinophilic syndromes (HES)	Activation of tyrosine kinases Clonal eosinophilic proliferation Overproduction of eosinophilopoietic cytokines.	Shortness of breath Skin rash Cough Diarrhea Myalgias Fatigue Weight-loss		Skin rash Thickening of the skin (lichenification) Eczema (flexural areas) Dermographism Low-grade fever Raynaud phenomenon Wheezing	Persistently elevated eosinophil count (≥ 1500 eosinophils/mm³) in the blood At least six months without any recognizable cause Involvement of either the heart, nervous system, or bone marrow.
Acute myelogenous leukemias	Mutation of myeloblast freezes the cell in its immature state and prevent differentiation.	Persistent or frequent infections. Anemia leads to fatigue, paleness, and shortness of breath. Thrombocytopenia leads to bruising or bleeding with minor trauma.	History of pre-existing hematological disorder (e.g aplastic anemia, PNH, myelofibrosis) History of exposure to anti-cancer chemotherapy agents especially alkylating agents History of exposure to ionizing radiation History of occupational exposure to benzene and other aromatic hydrocarbons History of any congenital disorders (e.g Down syndrome, Bloom syndrome)	Bone tenderness Skin manifestations	Immature Myeloblasts on blood smear Flow cytometry +Aur Rods
Hodgkin's, T- and B-cell lymphomas)	Reed-Sternberg cell B-cell origin CD30 (Ki-1) and CD15 (Leu-M1) antigens	Painless localized peripheral lymphadenopathy B symptoms	Presence or absence, duration, and severity of other associated systemic symptoms. History of previous malignancy (including other lymphomas) Prior treatment with chemotherapy or radiotherapy Previous immunosuppressive illness Family history of HL or other lymphoproliferative, myeloproliferative, or tissue malignancies.	Palpable, painless lymphadenopathy Superior vena cava Central nervous system (CNS) symptoms Paraneoplastic syndromes including Cerebellar degeneration Neuropathy Guillain-Barre syndrome Multifocal leukoencephalopathy	Fine-needle aspiration Mononucleate and binucleate Reed-Sternberg cells in a background of inflammatory cells Lactate dehydrogenase (LDH) may be increased. ESR elevated Serum creatinine elevated in nephrotic syndrome. Alkaline phosphatase (ALP) increased Hypercalcemia, hypernatremia, and hypoglycemia.
Churg-Strauss (Eosinophilic granulomatosis with polyangiitis)	Complex interaction involving genetic and environmental factors that lead to an inflammatory response involving eosinophils, lymphocytes and giant cells	Prodromal phase: Allergic rhinitis and asthma. Eosinophilic phase: Peripheral eosinophilia and infiltration of eosinophils to lung and GI tract. Vasculitic phase: Small and medium-sized vasculitis and inflammatory granuloma formation. Granulomas can be either vascular or extravascular.	History of allergy	Skin involvement (60%) Nasal polyposis Peripheral neuropathy	P-ANCA positive in most cases Elevated levels of IgE Elevated levels of rheumatoid factor at low titer Hypergammaglobulinemia Biopsy is diagnostic Eosinophilic infiltration Vasculitis of small and medium-sized vessels Granuloma formation.
Systemic mastocytosis	Infiltration of bone marrow by mast cell affecting the peripheral blood and coagulation system. The neoplastic clone of mast cells express abnormal cell surface markers CD25 and/or CD2.	GI Cutaneous Urticaria pigmentosa Musculoskeletal Idiopathic and/or recurrent anaphylactoid reactions	History of/ Associated with Hypereosinophilic syndrome Castleman disease Monoclonal gammopathy Hairy cell leukemia Non-Hodgkin lymphoma Polycythemia vera Primary thrombocythemia	Signs of anemia, Hepatoslenomegaly Lymphadenopathy Urticaria Flushing Osteolysis	CBC Eosinophilia Basophilia Thrombocytosis Monocytosis Total–to–beta-tryptase ratio greater than 20:1 is suggestive. CD117 positive and CD25 and/or CD2 positive. Abnormal mast cells. Larger than normal mast cells Irregularly shaped nuclear outlines Less densely packed mast cell granules