WBC Pathology Flashcards
Follicular Lymphoma
Differentiated from follicular hyperplasia by:
Disrupted architecture
Lack of a mantle zone w/ polarity
No dark/light zones w/ tangible body macros
Reverse bcl2 staining
Paracortical hyperplasia
Enhanced growth of the T-cell region due to stimulation via infection, drugs (Dilantin), and even dermatopathic lymphadenopathy
-Must correlate w/ clinical findings and TCR rearrangement studies
Sinus histiocytosis
Numerous macrophages within the lymph sinuses thought to be the response to malignant cells
-Will be prominent in nodes draining cancer
Nonspecific lymphadenitis
Follicular hyperplasia that occurs due to the drainage of infections; results in large, tender nodes
-Can be acute or chronic; common in kids
Precursor-B cell ALL
Clinical: Abrupt stormy onset, BONE PAIN (marrow involvement), possible CNS symptoms
Immunophenotype: CD19, CD22, CD10 (+), TdT (+)
Cytogenetics: Can involve t(12;21) mutating ETV6 and RUNX1 genes or t(9;22) mutating BCR-ABL
Treatment: Aggressive chemo including CNS prophylaxis
(Very successful in children; adults can sometimes not handle the chemo)
*Monitor to ensure there is no detection of MDR
Precursor T-cell ALL
Clinical: Abrupt stormy onset, Bone pain, CNS sx, MEDIASTINAL MASS
Diagnosis: MPO(-), disruption of normal architecture
*CD34, TdT, CD1a, CD2, CD5, CD7 (+)
*NOTCH1 mutations seen in 70%
Prognosis: Aggressive chemo and CNS prophylaxis
*Detection of MRD is assoc. w/ bad outcome
CLL/ASL
Clinical: Generalized lymhadenopathy w/ hypogammaglobulinemia (infxns)
Diagnosis: Smudge cells on PS, Increased small and mature lymphs that are hyperclumped,
(SLL)-lymphoid aggregates in BM and white/red pulp in spleen/liver
* Pale areas on lymph node can be indicative * CD19, CD5, CD23, CD20-dim, surface light chain restricted-dim
Prognosis=> Most pts. die of other problems
**Progression to Richter Syndrome possible
Follicular Lymphoma
Clinical: Painless lymphadenopathy, mimics normal architecture
Diagnosis: LN has a nodular pattern w/ lack of an asymmetric mantle zone; liver shows “portal tracks”
* CD10, 19, 20, surface light chain restriction * t(14;18) =>> bcl2 and bcl6 overexpression
Prognosis: Chemotherapy is ineffective but disease is indolent
–transformation to DLBCL occurs later
Bcl2
Inhibits apoptosis via the mitochondrial pathway
-Normally shut off to allow for normal lymphocyte maturation
Bcl6
Encodes for a DNA zinc finger that is normally required for normal germinal center regulation
Mantle Cell Lymphoma
Clinical: Painless lymphadenopathy, lymphomatoid polyposis, BM involvement
Diagnosis: CD5, CD19, CD20, BRIGHT surface light chain
* t(11;14) =>>Increased cyclin D1 expression and increased G1-S phase transition * Tumor cells can resemble that of normal mantle cells
Prognosis: Retuximab and Chemo; possible BM transplant in adolescents
*Most pts. relapse or die of organ failure in 3 yrs
Marginal Zone Lymphoma (nothing special)
Clinical: Assoc. w/ hyperinflammatory states (Hashimotos, Sjogrens); can regress if these states are controlled; cells can resemble normal marginal zone cells
Diagnosis: Pleomorphic population of plasmacytoid and monocytoid B-cells w/ destructive infiltration of host tissue
**Starts off as a reactive polyclonal reaction to inflammation, acquires mutations or t(11;18) to express MALT1 or BCL10 that will not respond to extrinsic signaling =»lymphoproliferation
Causes of lymphadenopathy
AI disorders- Sjogrens, SLE
Iatrogenic- Drugs, silicone
Infection
Malignancy
Sarcoidosis
Dermatopathic lymphadenopathy
Lymphoplasmocytic Leukemia
Resembles SLL only most neoplastic cells are plasma cells; secretes monoclonal IgM =»Waldenstrom’s Macroglobulinemia
-Cryoglobulinemai, visual/neurologic symptoms
- Involves a mutation in the MYD88 gene
- promotes the growth and survival of tumor cells
-Plasmapharesis alleviates symptoms
Hairy Cell Leukemia
Clinical: Monocytopenia, splenomegaly; *assoc. w/ mutations in BRAF
Diagnosis: Diffuse, fried eggs in the BM; dry tap of BM; red pulp involvement w/ obliteration of the white pulp
*CD11c/CD25/CD103 (+) =»CHARACTERISTIC
Prognosis: Indolent course; use chemo w/ BRAF inhibitors
Multiple Myeloma
Pathophysiology: MUST CONTAIN
- M-protein in blood/urine
- Monoclonal plasma cells
- End organ damage
Clinical: Weakness (anemia), recurrent infxn, polyuria (hypercalcemia), renal failure (BJ protein), amyloidosis
* Labs: BJ protein in urine; increased IgG or IgA; anemia; Rouleux and "Blue smear" on peripheral blood slide
- Bony, lytic lesions on x-rays of bone
- Caused by translocations involving IgH, del17p, and rearrangements involving MYC
- Increased IL-6 also increases the activity of osteoclasts
Treatment: Chemo and stem cell transplant may prolong life but not cure
MGUS
“Monoclonal Gammopathy of Unknown Significance”
-Most common cause of monoclonal gammopathy that must be monitored (BJ protein and serum protein M levels) to ensure it doesn’t progress to MM
Plasmacytoma
Soft tissue clonal plasma cell masses that commonly collect on the spine (bone site) or lung/oropharynx (soft tissue site)
-Can progress to MM; treat w/ localized radiation
Diffuse Large B-Cell Lymphoma
Clinical: B-grade symptoms w/ rapidly forming mass; BM involvement later
Diagnosis: Diffuse disruption of BM architecture by large lymphocytes; mitotically active and have indistinct cell borders
*No pathognomic cell markers, just CD10, 19, surface light chain
*Can have bcl2, bcl6, or myc8 gene rearrangement
=»DLBCL w/ two of these is much more aggressive
Treatment: R-CHOP works pretty well; fatal if untreated tho
*Can occur in IC pts. where it is assoc. w/ EBV infection
Burkitt Lymphoma
Clinical: 30% of childhood NHL; usually extranodal w/ mandibular mass and abdominal masses
=»can lead to Tumor Lysis Syndrome
*Assoc. w/ EBV infections in endemic areas
Diagnosis: “Starry Sky” appearance of BM (macros eating dead cells); infiltrate of medium sized cells w/ basophilic cytoplasm; high mitotic activity
- typically has translocation of MYC protein allowing for increased glycolysis by the tumor
* Is bcl2, CD34, and Tdt (-) because the cells are MATURE
***ASSOC. W/ t (8;14)
Treatment: Responds well to systemic chemotherapy as well as intrathecal administration
Tumor Lysis Syndrome
Rapid cell turnover and death causes the release of uric acid, K+, and Ca2+
=»Medical emergency requiring hydration, binding of electrolytes, and hemodialysis
Peripheral T-Cell Lymphoma
Clinical: General lymphadenopathy, eosinophilia
Diagnosis: Large sized malignant cells w/ paracortical effacement; CD34 and TdT (-)
Prognosis: Not good
Anaplastic Large Cell Lymphoma
Clinical: Extranodal infiltrate w/ BM involvement
*Involves ALK translocation which can be stained w/ immunohistochemistry
Diagnosis: *Hallmark= Large anaplastic cells w/ horseshoe appearing nucleus
*Neoplastic cells congregate around sinuses
Prognosis: Favorable unless you are adult and ALK (-)
Adult T-cell Leukemia
Clinical: T-cells infected w/ HTLV-1 that presents as generalized lymphadenopathy, skin lesions, and lymphocytosis
*Skin lesions only=favorable prognosis
Diagnosis: Cloverleaf cells; ^**CD4(+)/CD7(-); HTLV-1 (+)
Mycosis fungoides/Sezary Syndrome
CD4+ tumor in the skin w/ three stages:
- Patch
- Plaque
- Tumor
* Can spread to blood and progress to Sezary syndrome and will see exfoliative erythema
Diagnosis: Dermal plaque, *Cerebriform nuclear contours in neoplastic cells, Sezary cells in the blood
Prognosis: Indolent; death can occur due to immunodeficiency produced
Large Granular Lymphocytic Leukemia
STAT3 mutations =» large, GRANULAR lymphocytes
*Can be T-cell or NK cell (NK type is more aggressive)
Clinical: Neutropenia (decreased myeloid growth in the BM
Felty Syndrome
Anemia
Felty Syndrome
RH arthritis, splenomegaly, and neutropenia
Reed-Sternberg Cell
Characteristic neoplastic cell of Hodgkin’s Lymphoma; makes up the minority of the cell population
- derived from the germinal center and can potentially harbor EBV
- Has appearance of Owl Eyes, Mononuclear, Lacunar (folded due to disruption during fixation), or Popcorn (specific to Nodular Sclerosing HL)
CD15/CD30 (+)
*Except in NSNHL; this will have CD45, B-cell Ag, and Bcl6 (+)
Hodgkin’s Lymphoma Staging
I- One node region
II- Two node regions
III- Has crossed the diaphragm
IV- Dissemination
NSHL
Nodular Sclerosing Hodgkin’s Lymphoma - most common subtype
Involves cervical, supraclavicular, mediastinal nodes that have formation of nodules due to sclerosing collagen
-RS lacunar cells present
MCHL
Mixed Cellularity Hodgkin’s Lymphoma- second most common subtype
- See diffuse effacement of lymph nodes w/ many RS cells
- EBV ASSOCIATED
- Causes eosinophilia
Possible causes of suppression of granulocytic precursors
Drugs: Phenothiazines, thiouracil, sulfonamides, aminopyrine, and chemotherapy
Infection
Large Granulocytic Lymphocytic Leukemia
-Bone marrow suppression can also be due to aplastic anemia, Kostmann syndrome
Consequences of neutropenia
(Infections)
- mucosal ulcers
- invasive infxns of bladder, kidney, lung
- sites of infxn show numerous organisms w/ little response
AML Morphology
Myelocytic: *Auer rods can be present
CD15/CD33/CD34 (+); MPO (+); NSE (-)
Monocytic: CDllb/CD14/HLADR (+); MPO (-); NSE (+)
APML
Caused by t(15;17) =» PML/RARA; blocks differentiation at the promyelocyte stage
*Can cause DIC; look for schistocytes on PB; WBCs can have Auer rods
Treatment: Anthracycline chemo + ATRA
(All-trans Retinoic Acid/Vitamin A)
*Arsenic can promote degradation of the PML/RARA protein product
AML Clinical Features
Similar to ALL; bleeding is much more striking
Prognosis: Allogenic BM transplants; prior MDS; del11q23 =» BAD
Granulocytic Sarcoma
Tissue mass of erythroid blasts w/o BM or PB involvement
=»Treat before it progresses to AML
Myelodysplastic Syndrome
Clonal stem cell abnormality characterized by ineffective erythropoesis; seen in older pts. a few years post-chemo or idioapathic and presents as pancytopenia
PM: Will see NRBCs w/ ringed sideroblasts and some megakaryocytes
BM: Packed w/ trilineage precuros BUT > BM transplant
Elderly=» Supportive therapy
CML
Characterized by excess effective hematopoesis; MUST HAVE Philadelphia Chromosome to call it this
*CML disorder is in the pluripotent stem cell; can give rise to multiple erythroid and lymphoid cell lines
CML Morphology
PB: Leukocytosis w/ left shift; eosinophilia; ⭐️BASOPHILIA
BM: Packed w/ prominent hyperplasia but NO DYSPLASIA; sea-blue histiocytes
Hepatosplenomegaly to to EMH
CML Treatment
Gleevac (TK inhibitor)
-some resistance occurs w/ altered BCR-ABL protein
*Disease often discovered accidentally; may feel LUQ symptoms due to EMH
Polycythemia Vera
Caused by a JAK-2 mutation; increased cells of mulitple lineage (mostly RBC) alongside DECREASED EPO
-Has minimal reticulin fibrosis; may cause a dry tap
Clinical: Headache, dizziness, parasthesias (due to increased RBC mass); hyperuricemia (gout); DVT in weird sites (mesenteric/hepatic circulation)
Treatment: Therapeutic phlebotomy; JAK-2 inhibitors
Essential Thrombocytosis
Caused by JAK-2 mutations; platelet counts of greater than >450K w/ abnormally large platelets in the PB
Diagnosis: Must exclude iron deficiency anemia and reactive thrombocytosis; inflammatory process
Clinical: Erythomelalgia, unusual sites of thrombosis; BM will have large hyperlobated megakaryocytes
Treatment: Indolent; myelosuppressive therapy
Primary Myelofibrosis
Neoplastic megakarocytes release PDGF and TGF-B =» Proliferation of fibroblasts resulting in increased reticulin and a fibrotic BM =» EMH
Clinical: Early Pre-Fibrotic: Hypercellular marrow w/ cloudy megakaryocytes
Late Fibrotic: Hypocellular marrow w/ fibrosis, NRBCs and teardrop cells due to EMH, osteosclerosis, splenomegaly causing early satiety
Hypersplenism
Splenomegaly causing pancytopenia due to excess removal of blood products by the spleen
Correct w/ splenectomy
Congestive Splenomegaly
Intrahepatic: Right heart failure; hepatic cirrhosis
Extrahepatic: Portal vein thrombosis; splenic vein thrombosis
Clinical: Spleen becomes firm w/ increased congestion over time; increased pressure =» intraparenchymal hemorrhage
*Sugar icing occurs due to fibrosis of the outer capsule when it is trying to contain the size of the spleen
Splenic Infarct
Pale, wedge-shaped, and subcapsular
- Could be abscess formation if assoc. w/ infective endocarditis
- Common in splenomegaly
Thymic Hyperplasia
Appearance of secondary B-follicles usually assoc. w/ Myasthenia Gravis
Thymoma
Non-hematopoetic neoplasm that is a tumor of the thymic epithelial cells; forms of a small mass in the anterior superior mediastinum (similar to NSHL)
Benign, encapsulated: Medullary
Malignant: Epithelial cells or SCC (lymphoepithelioma-like)
