Pathology for Medical Students - Blood and Lymphatics PDF

PATHOLOSIS DR. TAREK Pathology for medical students Helwan UN.  patholosis Dr. TAREK (++) RBC’s count and (++) Hb conc. Types:  Relative: dehydration hemoconcentration  Absolute:  Primar...

PATHOLOSIS DR. TAREK Pathology for medical students Helwan UN.  patholosis Dr. TAREK (++) RBC’s count and (++) Hb conc. Types:  Relative: dehydration hemoconcentration  Absolute:  Primary (polycythemia vera): myeloproliferative (low erythropoietin).  (++) viscosity  HF  Secondary: hypoxia in high altitude and renal diseases: RCC. (high erythropoietin) (--) o2 carrying capacity (--) total Hb conc. (--) RBC's mass Classification of anemia:  Deficiency anemia.  Hemolytic anemia.  Bone marrow hypo-function anemia.  Acute post hemorrhagic anemia. 1  patholosis Dr. TAREK Causes: Aplastic anemia: Bone marrow aplasia with depression in formation of blood elements. Hypocellular bone marrow: (all hematopoietic series)  peripheral pancytopenia Pure red cell aplasia failure: only erythroid series  anemia in the peripheral blood Causes 1-primary: idiopathic 65% 2-secondry: hypersensitivity to drugs, poisons or radiation  Toxic exposures  Total body irradiation  Drugs or chemicals:  Viral infections  Inherited diseases (e.g., Fanconi anemia) MYELOPHTHISIC ANEMIAS: by metastatic tumor cells replacing the bone marrow Megaloblastic anemia: (--) vit B12, folic acid (--) synthesis of thymidine  (--) DNA replication  enlarged hematopoietic precursors (megaloblasts)  ineffective hematopoiesis  , may be pancytopenia Causes: - intestinal malabsorption - liver cirrhosis. - gastric defects e.g., pernicious anemia: autoimmune gastritis and loss of IF production.  megaloblastic anemia  leukopenia and hypersegs  neurologic posterolateral spinal tracts  achlorhydria  LOW serum B12 Morphology 2  patholosis Dr. TAREK Peripheral blood: anisocytosis with abnormal large and oval RBCs (macro ovalo cytes) Bone marrow: lag nuclear maturation; increased apoptosis with compensatory megaloblastic hyperplasia  ineffective erythropoiesis Abnormal granulopoiesis with giant metamyelocytes in marrow and hypersegmented neutrophils in peripheral blood and in marrow FOLATE DEFICIENCY: Decreased Intake: diet, Alcoholism, infancy Impaired Absorption: intestinal disease DRUGS: anticonvulsants, CHEMO Increased Loss: Hemodialysis Increased Requirement: Pregnancy, infancy As Vit B12 deficiency but absence of gastric atrophy and the neurologic defects Iron deficiency anemia (the mother of all anemias)  Negative iron balance - chronic blood loss (GIT, female genital) - nutritional - inadequate absorption - ankylostomiasis THE ONLY WAY to LOSE IRON is by LOSING BLOOD: because Fe is recycled Morphology: Microcytic (low MCV) Hypochromic (low MCHC) central pallor Marrow: erythroid hyperplasia, loss of iron in marrow macrophages. Blood: low serum iron, ferritin (GREAT test), transferrin saturation, hemosedrin levels. Anemia of Chronic Disease: chronic infections chronic immune disorders 3  patholosis Dr. TAREK neoplasms liver, kidney failure very much look like iron deficiency anemia, BUT ABUNDANT STAINABLE HEMOSIDERIN in the marrow. NORMAL iron stores Hemolytic Anemias: Hereditary Membrane abnormalities:  Membrane skeleton proteins: spherocytosis  Membrane lipids: abetalipoproteinemia Enzyme deficiencies  Enzymes of hexose monophosphate shunt: glucose 6 phosphate dehydrogenase, glutathione synthetase  Glycolytic enzymes: pyruvate kinase, hexokinase Disorders of hemoglobin synthesis: Structurally abnormal globin synthesis (hemoglobinopathies):  Sickle cell anemia, unstable hemoglobins  Deficient globin synthesis: thalassemia syndromes Acquired: Membrane defect: paroxysmal nocturnal hemoglobinuria 1. Antibody mediated 2. transfusion reactions, immune hydrops (Rh disease of the newborn) 3. Autoantibodies: idiopathic (primary), drug associated, systemic lupus erythematosus 4. Mechanical trauma to red cells 5. Microangiopathic hemolytic anemias: thrombotic thrombocytopenic purpura, disseminated intravascular coagulation 6. Defective cardiac valves 4  patholosis Dr. TAREK 7. Infections: malaria N.B: Hypersplenism: splenomegaly with destruction of RBC's  normocytic normochromic anemia INTRA-vascular (vessels) & EXTRA-vascular (spleen) Morphology: Life span LESS than 120 days  Marrow hyperplasia  Increased catabolic products, e.g., bilirubin, hemosiderin (prehepatic hemolytic jaundice)  Hemoglobinurin N.B: Hemoglobinuria: hemolytic anemia hepatosplenomegaly: compensatory synthesis of RBCs HEREDITARY SPHEROCYTOSIS Pathogenesis:  Autosomal dominant Genetic defects affecting ankyrin, spectrin  Children, adults  Anemia, hemolysis, jaundice, splenomegaly, gallstones (dark pigmented stones) Morphology:  lack of a central pallor and a microcytosis (low MCV)  marrow erythroid hyperplasia  Marked splenic congestion erythrophagocytosis Hematologic findings:  ↑RBC osmotic fragility  ↑ the mean RBC hemoglobin (Aplastic crisis)  Hemolytic crisis  Gall stone  splenectomy is helpful Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency 5  patholosis Dr. TAREK  A-and Mediterranean are most significant types  More risk to oxidative DAMAGE?  hemolytic anemia FEATURES of G6PD Deficiency  Genetic: X-linked  Can be triggered by foods (fava beans) (favism), oxidant substances drugs (primaquine, chloroquine), or infections  HEINZ bodies Acute intravascular hemolysis can occur:  Hemoglobinuria  Hemoglobinemia  Anemia Sickle Cell Disease Pathogenesis:  Classic hemoglobinopathy  Normal HGB (α2β2): β-chain defects (Valine > Glutamate)  When deoxygenated, HbS: stiff chains  deform (sickle) RBCs  chronic hemolysis, microvascular occlusion, tissue damage. Peripheral blood  irreversibly sickled cells: elongated, spindled, boat-shaped irreversibly sickled red cells  reticulocytosis  Target cells due to RBC dehydration.  In childhood: splenomegaly By adulthood  repeated episodes of vasocclusion  fibrosis and shrinkage (autosplenectomy). Clinical features of HGB-S disease  Chronic hemolytic anemia  Vaso-occlusive crises  Aplastic crisis 6  patholosis Dr. TAREK  sickling more likely in NON-oxygenated blood  Severe anemia  Jaundice  PAIN (pain CRISIS)  Vaso-occlusive disease: EVEREWHERE, but clinically significant bone, spleen (autosplenectomy)  Infections: Pneumococcus, H.influnza, Salmonella osteomyelitis THALASSEMIAS  COMPLEX genetics  Alpha or beta chains deficient synthesis  MAJOR or MINOR, depending on severity Clinical picture: May be silent carriers and “traits”  HEMOLYSIS + microcytic anemia LOW MCV (like iron deficiency anemia)  “crew cut” skull x-ray appearance: in severe erythroid hyperplasia.  Diminished synthesis of one chain  low intracellular hemoglobin (hypochromia)  decreased b-globin synthesis  reduced HbA production: “under-hemoglobinized” RBC hypochromic and microcytic  reduced oxygen carrying capacity.  unbound chain  unstable aggregates  membrane damage: precursor destruction in the marrow (ineffective erythropoiesis) splenic sequestration of mature RBCs.  Severe anemia  marked compensatory expansion of erythropoietic marrow  encroaching on cortical bone  skeletal abnormalities in growing children.  Ineffective erythropoiesis  excessive absorption of dietary iron + repeated blood transfusions  severe iron overload.  “spiculated” or “spiked” appearance of the outer table of the skull due to extreme erythroid hyperplasia Hemoglobin H Disease  Deletion of THREE alpha chain genes  Asian  HGB-H HIGH affinity for oxygen  unstable  hemolysis 7  patholosis Dr. TAREK HYDROPS FETALIS MOST SEVERE form of thalassemia: FOUR alpha chain genes are deleted  die intrauterine  If born  SEVERE hemolytic anemia (erythroblastosis fetalis of Rh disease):  Pallor, jaundice, kernicterus  Edema “hydrops”  Massive hepatosplenomegaly (hemolysis) Paroxysmal Nocturnal Hemoglobinuria (PNH)  ACQUIRED, NOT INHERITED  mutations in phosphatidylinositol glycan A (PIGA): gene controlling complement activation  RBCs hypersensitive  autoimmune response to GPI -linked proteins on hematopoietic stem cells.  GPI: Glycosyl phos Phatidyl Inositol (lipid rafts) Immuno hemolytic Anemia  antibodies and/or complement on RBC surfaces  NOT all are AUTO immune, some are caused by drugs  Antibodies:  WARM (IgG)  COLD AGGLUTININ (IgM)  COLD HEMOLYSIN (paroxysmal) (IgG) WARM AGGLUTININS: (IgG) will NOT agglutinate at room temp Primary Idiopathic (most common) Secondary (Tumors, leukemia, lymphoma, drugs) COLD AGGLUTININS: (IgM) will agglutinate at low temp Mycoplasma pneumoniae, HIV, mononucleosis COLD HEMOLYSINS: (IgG) Cold Paroxysmal Hemoglobinuria hemo-LYSIS in body ALSO follows mycoplasma pneumoniae 8  patholosis Dr. TAREK HEMOLYSIS/HEMOLYTIC ANEMIAS DUE TO RBC TRAUMA  Mechanical heart valves breaking RBC’s Consequences of Anemia  ↓tissue oxygen tension  ↑erythropoietin (kidney)  hyperplasia of erythroid precursors in the bone marrow  ↑reticulocytes (immature RBCs) in the peripheral blood.  Severe anemia  extra medullary hematopoiesis (liver, spleen, & lymph nodes).  anemia caused by decreased red cell production  ↓reticulocytes (reticulocytopenia).  Intravascular hemolysis  Hemoglobinemia, hemoglobinuria, and hemosiderinuria and iron deficiency Blood loss: post hemorrhagic anemia  Acute: normocytic normochromic anemia  Chronic: microcytic hypochromic anemia 9  patholosis Dr. TAREK Classifications:  Due to platelets abnormalities (decrease number or inadequate function).  Due to vascular damage.  Due to defects in clotting mechanisms. Bleeding profile:  Bleeding time: Vessels/ platelete phase of hemostasis  Prothrombin time: Factor VII (extrinsic cascade)  Activated partial thromboplastin time: All coagulation factor except Factor VII( intrinsic )  Thrombin time: Prothrombin group  Fibrin degradation product (angiopathic thrombocytopenias) (NON-thrombotic cytopenic purpuras)  Infections: meningococcemia, rickettsia  Drug reactions: leukocytoclastic vasculitis  Scurvy, Ehlers-Danlos, Cushing syndrome  Henoch-Schönlein purpura (mesangial IgA deposits too)  Hereditary hemorrhagic telangiectasia (Osler–Weber–Rendu syndrome. AD)  Amyloid Thrombocytosis: (++) platelet count Thrombocytopenia: (--) platelet count (normal: 150,000-300,000)  (--) production  (++) destruction  Sequestration (Hypersplenism)  Dilution Bleeding tendency: petichea, purpura due to (--) platelets 10  patholosis Dr. TAREK  aplastic anemia  acute leukemia  drugs: alcohol, thiazides, chemotherapy  infections: measles, HIV  megaloblastic anemias  myelodysplastic syndromes (pre-leukemias)  autoimmune (ITP)  post-transfusion (neonatal)  Drugs: quinidine, heparin, sulfa  HIV  DIC “consumptive”  TTP/HUS  Microangiopathy Any thrombocytopenia of (++) destruction: INCREASED megakaryocytes in the marrow LIKE hemolytic anemia has an erythroid hyperplasia  ITP (Idiopathic Thrombocytopenic Purpura)  Acute Immune  DRUG-induced  HIV associated  TTP, Hemolytic Uremic Syndrome  At young adults and elderly  acute or chronic  auto-immune Investigations:  anti-platelet antibodies  increased marrow megakaryocytes 11  patholosis Dr. TAREK Treatment: steroids Acute ITP  children  after viral illness (~ 2 weeks)  anti-platelet antibodies  platelets return to normal in a few months  Quinine  Quinidine  Sulfonamide antibiotics  HEPARIN BOTH (--) production AND (++) destruction BOTH are very SERIOUS with a HIGH mortality:  TTP (THROMBOTIC THROMBOCYTOPENIC PURPURA)  H.U.S. (HEMOLYTIC UREMIC SYNDROME) “Consumptive” coagulopathies like DIC 12  patholosis Dr. TAREK Congenital (genetic):  Bernard-Souliersyndrome (Glycoprotein-1-b deficiency)  Glanzmann’s thrombasthenia (Glyc.-IIB/IIIA deficiency)  Storage pool disorders: platelets misfunction AFTER they degranulate ACQUIRED: ASPIRIN, ASPIRIN, ASPIRIN  NOT spontaneous but following surgery or trauma  Factor VIII and IX: classic X-linked recessive hemophilia A and B  ACQUIRED disorders often due to Vitamin-K deficiencies (II, VII, IX, X)  von Willebrand disease the most common, 1%  1% (most common bleeding disorder)  Spontaneous and wound bleeding  Autosomal dominant  Prolonged BLEEDING TIME, normal platelet count  vWF complexes with Factor VIII,  BOTH platelet and Factor VIII-vWF disorders are present 13  patholosis Dr. TAREK  “classic” HEMOPHILIA  Sex-linked recessive  (--) Factor VIII: Co-factor of Factor IX to activate Factor X  Hemorrhage NOT spontaneous  Wide variety of severities  Prolonged PTT (intrinsic) only  Treatment: Recombinant Factor VIII  “Christmas” HEMOPHILIA  Sex-linked recessive  (--) Factor IX  Hemorrhage NOT spontaneous  Wide variety of severities  Prolonged PTT (intrinsic) only  Treatment: Recombinant Factor IX  endothelial injury  wide spread fibrin deposition  high mortality  all major organs are involved  Extremely SERIOUS condition  NOT a disease in itself but secondary to many conditions  Obstetric: toxemia, sepsis, abruption  Infections: Gm-, meningococcemia, RMSF, fungi, Malaria  Many neoplasms: acute promyelocytic leukemia  Massive tissue injury: trauma, burns, surgery  “Consumptive” coagulopathy 14  patholosis Dr. TAREK Common Coagulation TESTS  PTT (intrinsic)  PT& INR (extrinsic)  Platelet count, aggregation  Bleeding Time, so EASY to do  Fibrinogen  Factor Assays Clinical picture of bleeding disorders Vessel Wall Abnormalities: only petechial and purpura without serious bleeding Thrombocytopenia:  100,000/mL or less  spontaneous bleeding does not occur until platelet 20,000/mL  between 20,000 and 50,000/mL  post traumatic hemorrhage.  spontaneous bleeds of small vessels of the skin and mucous membranes Hemophilia: Massive hemorrhage after trauma or operative procedures Spontaneous hemorrhages in regions of the body normally subject to trauma (e.g. joints)  progressive, crippling deformities 15  patholosis Dr. TAREK  (--) number of WBC'S more common (neutropenia, granulocytopenia) less common (lymphopenia)  Causes:  Congenital immunodeficiency disease  Bone marrow failure at acute leukemia  Viral infections  Glucocorticoid or cytotoxic therapy  Autoimmune  Hypersplenism Typhoid, T.B, malaria Hypersplenism Aplasia of bone marrow Radiation  C/P:  Life threatening Recurrent infections, invasive bacterial or fungal infections of lungs or urinary tract  Neutrophils 500 /mm3 or less  (++) number of WBC'S  Types:  Neutrophilic leukocytosis (neutrophilia) Infection by bacteria, fungi or viruses Suppurative lesions as abscess, appendicitis Lead poisoning Bone marrow neoplasia PMNL leukocytosis (acute inflammation)  Eosinophilia (allergy, parasite, drug reactions, dermatological disorders)  Basophilia is rare 16  patholosis Dr. TAREK  Monocytosis (chronic disorder: TB, malaria, bacterial endocarditis) or collagen vascular disorder (SLE)  Agranulocytosis: below 2000 /cmm, the same causes of aplastic anaemia, bad prognosis.  Lymphocytosis: with monocytois at chronic immunological diseases Whooping cough, T.B, syphilis. Infectious mononucleosis. Some viral infection, especially in children.  Neoplastic proliferation of WBC's precursors in bone marrow  Diffuse replacement of normal bone marrow by neoplastic leukemic cells with accumulation of abnormal immature cells at peripheral blood  Infiltration of organs by leukemic cells (liver, spleen, LNs, meninges and gonads)  Total white cell count is normal, or even low but immature series present in peripheral blood = aleukemic leukemia. Predisposing factors:  Irradiation, chemotherapy  Viral infections: (HTLV-1), HHV-8 and EBV  Genetic (with Down syndrome)  Drugs (treatment of lymphoma by alkylating agents)  Chemicals: benzene derivatives, tobacco smoking Types:  Young age  Abrupt stormy onset (rapid and fulminating course).  WBC's count over 100,000/mm3  Immature (blast) cells  Anemia, thrombocytopenia, leucopenia C/P:  Anemia (normocytic normochromic)  Fatigue, infections  fever, bleeding tendency  petichea, ecchymosis, epistaxis, bleeding per gums 17  patholosis Dr. TAREK  bone marrow expansion  Bone pain  dissemination of leukemic cells  Generalized lymphadenopathy (small, discrete), splenomegaly, hepatomegaly  meningeal spread  CNS manifestations (headache, vomiting, paralysis) – more at children and ALL  The most common cause of death of malignant tumor at children (2-4 years)  Hypercellular bone marrow with number of lymphoblasts and areas of necrosis  80% of children achieve cure with chemotherapy but it is fatal if untreated  +Incidence increase with age  Granulocytic or monocytic  FAB calcification (M0-M7) according to degree of differentiation  Bone marrow infiltration by granulocytic or monocytic  Gums infiltration is a feature of monocytic AML  Gradual onset  Increase mature WBC's count in blood  No longer course but fatal  male, Old age  Philadelphia chromosome  TLC markedly increased up to 800,000/cmm  Weakness, easy fatigability, weight loss  Blast crisis final phase resembling acute leukemia  Gout as a part of tumor lysis syndrome  Bone marrow infiltration by myeloid cells esp. granulocytes 18  patholosis Dr. TAREK  Normocytic normochromic anemia and thrombocytopenia are late.  B.M is hypercellular and leucoblastic.  Massive enlargement of spleen due to infiltration by CML cells  infarctions (growth exceeds blood supply)  Liver enlarged: diffuse infiltration of portal tracts and sinusoids with leukemic cells  The lymph node affected late  Chronic lymphoproliferative disease  It is less common.  Occur in middle age and elderly persons.  TLC increased between 25,000 /cmm to 250,000 / cmm( mature lymphocytes and some lymphoblasts)  Similar to low grade lymphoma but predominant blood and bone marrow affection  B.M shows late absolute increase in lymphocytic series.  mature lymphocytes and generalized lymphadenopathy Pathological findings:  Spleen: slightly enlarged with hyperplasia of lymphoid follicles.  Liver enlarged: infiltration of portal tracts.  generalized enlargement of the lymph node.  Anemia, hemorrhage, hypogammaglobulinemia  increased susceptibility to bacterial infections and autoantibodies against erythrocytes or platelets(10% to 15%)  Nodules of leukemic cells in the skin and mucous membranes. Fate  Untreated = fatal  CML more rapidly fatal due to acute exacerbation  CLL slower course 19  patholosis Dr. TAREK  Enlargement of one LN or group of LNs or generalized secondary to disease Acute:  Acute lymphadenitis  infectious mononucleosis (EBV)  Typhoid fever  Post vaccine  Plague Chronic:  Non specific infection  T.B, Sarcoidosis, Syphilis  Cat scratch disease  AIDS  Lymphoma, Leukemia  Metastasis (more common than lymphoma) Localized: direct microbial drainage (cervical LNs draining dental or tonsillar infections) Systemic: bacteremia or viral infection at children Gross:  Enlarged tender LNs (fluctuant at pus formation)  Red skin with draining sinuses Microscopic:  Large germinal center  If pus formation: neutrophilic infiltration and necrosis  Abscess formation follicles Lymph node enlargement 20  patholosis Dr. TAREK  Nonspecific: as reactive follicular hyperplasia  Specific: TB (caseous), atypical mycobacteria, leprosy, syphilis FNA: Rich in neutrophils (acute) Lymphocytes (chronic) Causative organism: Epstein-Barr virus (EBV). Clinical picture:  Fever, sore throat, generalized lymph node enlargement & splenomegaly. Pathology:  Lymph nodes enlargement  Paracortical transformation in the form of immunoblasts (monocytoid B cells)  Peripheral blood: lymphocytosis with many abnormal T lymphocytes.  The disease is self-limiting. Nonspecific reaction to any foreign material (infectious or not) reaching the lymph node  Gross:  Enlarged, smooth surface, firm  Cut section: homogenous pale grey  Types:  Increase size of cortical follicles  Pale large germinal center (maturing B cells, other cells like macrophages) surrounded by mantle zone  toxoplasmosis, Collagen vascular diseases, Systemic toxoplasmosis, Syphillis  Enlargement of paracortical zone  viral infections (Infectious mononucleolosis) 21  patholosis Dr. TAREK  Enlargement of sinusoids + macrophages  E.g. nonspecific but it is seen at LNs draining epithelial cancers Primary malignant tumor of lymphoid tissue (nodal or extranodal) N.B: If the CBC should blasts > 20000, then its leukemia  at the sites of normal lymphoid homing: - Lymph nodes - Spleen - Mucosa associated lymphoid tissue (MALT).  Or extranodal lymphomas (intestine, spleen, thyroid, thymus, skin) Types: Hodgkin or non-Hodgkin 22  patholosis Dr. TAREK  Neoplasm of germinal center B cells  EBV may contribute to tumor development  Bimodal: late adult and 60 years old Microscopic:  Classical Reed Sternberg (RS) cells: large bilobed nucleus (mirror image) + large acidophilic nucleolus + abundant cytoplasm  Mononeuclear cells: single rod like nucleus + large nucleolus  Lacunar cells: folded or multilobate nuclei surrounded by empty space  Lymhohistiocytic (L&H) cells: multilobate puffy nuclei (popcorn cells) with abundant cytoplasm These cells secrete cytokines (++) lymphocytes, macrophages and granulocytes that constitute more than 90% of tumor cellularity Types of HL: Classical HL or nodular lymphocytic predominant type  The most common 75%  Lacunar variant and collagen bands that divide LN to nodules  Excellent prognosis  25% of cases and at older ages B symptoms (fever, weight loss)  EBV  RS cells and mononuclear cells  Good prognosis 23  patholosis Dr. TAREK  Uncommon  Reactive lymphocytes + RS and mononuclear cells  Good prognosis  Least common  RS cells and are infected by EBV  Worst prognosis  5% of all cases  nodal effacement and infiltration by lymphocytes + macrophages + RS + L & H cells  expression of germinal center B markers  excellent prognosis  CD 20 +ve Gross pic. Of HL:  LNs:  Starts at one LN group esp. cervical then spread to other in contiguous group  Enlarged fixed discrete LNs  Then fused firm hard in consistency  Cut sec.: pale white pink  Spleen:  One or more nodules  Firm hard in consistency  Cut sec.: grey pink Hodgkin's Lymphoma respond well to therapy important to determine: 1-Stage of the disease 2-Histologic type in order to provide the most appropriate therapy 24  patholosis Dr. TAREK Staging: extent of disease determines therapy and prognosis Classic HL: + CD15 and +CD30 antigens in golgi and on cell membrane in RS cells of except NLPHL --- +CD20. Spread: via lymphatics. Therapy: Curable malignancy with a high overall cure rate.  B or T cell tumor  Wide dissemination so only systemic therapy is curative  CD 15, CD 3 Microscopic:  Effacement of node architecture  Replacement by neoplastic lymphocytes (diffuse or follicular lymphoma) 25  patholosis Dr. TAREK  Diffuse small lymphocytic (SLL)  Follicular lymphoma  Mantle lymphoma  Marginal lymphoma  Low grade T lymphoma  Diffuse large B cell lymphoma  Large cell immunoblastic lymphoma  Anaplastic large cell lymphoma  Lymphoblastic lymphoma  Burkitt's and Burkitt's like lymphoma  Secondary in origin  Most common lymph node tumor  Carcinoma more than sarcoma  Effacement can be partial or complete Microscopic:  similar to primary tumor  If undifferentiated: IHC  Enlarged palpable hard left supraclavicular lymph node  Due to tumor embolization through thoracic duct  Thoracic outlet syndrome, Horner syndrome, unilateral phrenic neuropathy the commonest malignant tumors at LNs 26