B7 CM Heme/Onc Exam 2

Tumor suppressor genes 🤝 me during exam week: doing absolutely nothing.

•collect and return interstitial fluid, including plasma protein to the blood, and thus help maintain fluid balance

•defend the body against disease by producing lymphocytes

•absorb lipids from the intestine and transport them to the blood

what are the principal functions of the lymphatic system?

thoracic duct

all lymphatics for the rest of the body drain into the:

lymphatic duct

all lymphatics for the right upper quadrant drain into the:

virchow's node

Supraclavicular node enlargement by metastatic carcinoma

chylothorax

presence of chyle in the pleura, caused by disruption or dysfunction in the flow of chyle through the thoracic duct

malignancy, benign tumors, lymphatic disorders

nontraumatic causes of chylothorax

iatrogenic from surgery

traumatic causes of chylothorax

chyle

white or pale yellow substance in lymph that contains fatty substances absorbed by the lacteals

dyspnea without chest pain, as chyle does not invoke an inflammatory response

presentation of chylothorax

-thoracentesis with pleural fluid analysis

-milky appearance, predominantly lymphocytes

-high protein, no glucose, pH 7.4-7.8

-high TGs

diagnostic findings of chylothorax

-fragment of tumors

-infected material

what materials are most commonly spread via the lymph vessels to spread malignancy?

malignancy

if pt presents with lymphadenopathy, what should always be on your ddx?

-strep pharyngitis

-cellulitis or inflammatory conditions of the skin (bug bite, tinea, cat scratch disease)

-inguingal adenopathy of STI: chancre, HSV

-EBV

common etiologies of explained/likely explained lymphadenopathy

tender anterior cervical LAD

lymphadenopathy associated with strep pharyngitis

lymphagitis

infection of lymph vessel walls that occurs in some acute pyogenic infections in which the microbes in the lymph draining from the area infect and spread along the walls of lymph vessels

bilateral posterior cervical LAD

adenopathy associated with EBV

EBV

what disease?

-rash will develop in 90% who are treated with amoxicillin

Primary HIV infection

What disease?

-cause of explained lymphadenopathy

-mucocutaneous ulceration

-rash (48-72 hours after onset of fever)

CMV

What disease?

-mild form of EBV mono

-Elevated LFTs more common

-cause of explained lymphadenopathy

toxoplasmosis

What disease?

-Fever and LAD without pharyngitis

-No pharyngitis,

-Normal LFTs

-cause of explainable lymphadenopathy

generalized or localized

with an unexplained lymphadenopathy , must determine if it is:

generalized lymphadenopathy

> 2 noncontiguous LN regions without an explanation

CBC, CXR, HIV, (+/- monospot)

initial testing if you find unexplained generalized lymphadeopathy

supraclavicular > neck > axilla > groin

most to least likely nodes of lymphadenoapthy

allopurinol, atenolol, captopril, cephalosporins, gold, hydralizine, imatinib, penicillin, phenytoin, sulfonamides

select drugs that can cause lymphadenopathy

determine if it is likely cancer

-if no, follow up in 3-4 weeks for changes

-if yes, biopsy

work up if you find an unexplainable, localized lymphadenopathy?

-age over 40

-size >2cm

-duration over 1 month

risk factors pointing to malignancy in unexplained localized lymphadenopathy

abnormal

supraclavicular lymphadenopathy is always

malignant than infectious (vice versa if <20 years old)

A mass in the neck of a patient greater than 40 years old is much more likely to be

biopsy (preferably core)

-image according to results of biopsy if malignancy is found

first step in work up of unexplained axillary adenopathy is

NO!! If it ends up being breast cancer, and excisional biopsy decreases the yield of a sentinel lymph node biopsy and may unnecessarily commit the patient to an axillary lymph node dissection.

Should you perform an excisional biopsy to start with unexplained axillary adenopathy?

inguinal lymph nodes

primary lymph drainage of anus and genitalia, and distal 1/3 of vagina is

inguinal adenopathy

lymphadenopathy often palpable in healthy people without cancer

-Often palpable in healthy people without cancer perhaps because chronic trauma and infection is so common in the LE; also common in obese pts

Contrast cross-sectional CT

initial study of choice for adult pts with neck mass

normal: hypoechoic cortex and echoic central hilum

abnormal: centrally hypoechoic, lost its hilum

normal vs abnnonrmal LN on ultrasound

•Size (location & context dependent)

•Morphology (loss of hilum)

•Enhancement

•Invasion (aka extracapsular extension)

things to assess on imaging in work up of lymphadenopathy

▪Currently not sufficient for establishing a diagnosis of cancer

disadvantage of liquid biopsy

useful in the following when additional tissue biopsy is not feasible but diagnosis is already established

▪Identifying therapeutic targets

▪Selecting patients at risk of recurrence

▪Monitoring response to therapy

indications for liquid biopsy of lymphadenopathy

-high false negative rate!

-lack of tissue architecture

-limited material

-generally not sufficient info for establishing initial diagnosis

disadvantage of FNA in evaluating lymphadenopathy

core biopsy

what type of biopsy?

•14 to 20 gauge needle

•Typically under image guidance

•Provides enough tissue for special testing and some information on nodal architecture

•Allows for placement of clips/markers into area of interest

more painful, hematomas can form, generally safe tho

disadvantage of core biopsy

•Excisional - entire abnormal LN is removed

•Incisional - part of abnormal LN is removed

what is the difference between excisional and incisional biopsy

•Allows for assessment of nodal architecture

•Preferred biopsy when lymphoma is suspected

advantages of open biopsy

open biopsy

biopsy type that is generally better to avoid if you think you are dealing with a carcinoma

-removes sentinel node, risk of seeding the skin

lymphedema

▪An accumulation of excessive proteins, edema, chronic inflammation, and fibrosis in tissues secondary to the impairment of the lymph vessels.

Chronic condition, generally not cured

▪congenital absense or anomaly of the lymphatic system

pathophysiology of primary lymphedema

obstruction or interruption of lymphatic system

ex: malignancy, infection, trauma, cancer treatment

pathophysiology of secondary lymphedema

-highest risk associated with axillary dissection + axillary radiation

-lowest risk with sentinel biopsy alone

determinant of risk of lymphedema in breast cancer treated pts

•Psychosocial

•Skin infection

•Lymphangiosarcoma: Stewart-Treves syndrome

complications of lymphedema

do NOT overtreat the axilla!

-avoid excisionnal biopsy in initial workup, perform sentinel node biopsy in clinically negative axilla, neoadjuvant therapy for positive axilla

best way to management treatment relatedd lymphedema

-monitoring, elevation, exercist

-compression therapy

-physiotherapy

conservative management of lymphedema

•Lymphatic bypass procedures

•Excision

•Liposuction

surgical management of lymphedema consnists of

•Synthesis of immunoglobulin G (IgG), properdin (an essential component of the alternate pathway of complement activation), and tuftsin (an immunostimulatory tetrapeptide)

immune functions of the spleen

>12 cm across

size definition of splenomegaly

•No symptoms in some cases

•Pain or fullness in the left upper abdomen that may spread to the left shoulder

•Early satiety

•Anemia

•Fatigue

•Frequent infections

•Thrombocytopenia

•Easy bleeding

symptoms associated with an enlarged spleen

ultrasound

best imaging for monitoring size of spleen

•Biopsy is generally not performed due to risk of bleeding

can I biopsy the spleen?

primary

sarcoidosis is considered a ______ cause of splenomegaly

RhoGAM

drug highly associated with splenomegaly

neutrophilia

most common form of leukocytosis

viral (EBV)

most common infectious cause of lymphocytosis

Drugs

Addisons/allergy

Worms

Neoplasia

DAWN

mnemonic to rremember the most common causes of eosinophilia

CML

most common neoplasm causing basophilia

-marked increase in neutrophils >50000

-left shift

-severe infection, trauma, bone marrow infiltration

-looks like leukemia

define criteria of a leukemoid reaction

acute myeloid leukemia

bone marrow aspirate

-blasts are large, moderate amount of grayish blue cytoplasm, no distinct nucleoli

acute lymphoblastic leukemia

-most common childhood malignancy

-most common cause of cancer death in pts under 20

2-5 years old

peak incidence of ALL

down syndrome

genetic syndrome related to ALL

children complaining of bone pain

-fatigue, infections, bleeding, dyspnea, petichiae, mucosal bleeding, fever

most common presenting symptoms of ALL

-CNS penetration---> meningeal signs, CN deficits, AMS

these symptoms are a MAJOR issue with ALL, but not that common

testicular swelling, neurologic findings, mediastinal mass

less common findings associated with ALL

-CBC w/ diff, peripheral smear, bone marrow exam

-lymph node if there is one

lab orders for workup of suspected ALL

acute leukemia

a high level of blasts in peripheral blood smears should make you suspicious for

lymphoblast

-no auer rods, positive staining for TdT

myeloblast

-cytoplasmic granules, may see suer rods

-increased prominence of nucleoli

immunophenotyping (flow cytometry)

DIAGNOSTIC lab for determinging lymphoid or myleoid lineage

•L1 small cells with homogeneous chromatin

•L2 large heterogeneous cells, irregular cytoplasm

•L3 large homogeneous cells, deep blue cytoplasm

what are the 3 subtypes of ALL as defined by FAB

TdT (terminal deoxynucleotidyl transferase)

both B cell and T cell ALL are positive for

B cell ALL

type of ALL that is HLA-DR positive

the term lymphoma is used when the disease is confined to a mass lesion with little or no blood and marrow involvement

when to use the terrm lymphoma over leukemia

lymphoma type ALL

Mass & <25% blasts in marrow it is

leukemia type ALL

No mass & >25% blasts in marrow it is

5 year overall survival > 90%

prognosis of ALL

-older age (>35)

-high initial WBC count

-under one year old

-female

poor prognosis indicators of ALL

1-9

age to have ALL with the best prognosis

hyperploidy>hypoploidy

ploidy associated with most cases of ALL

•t(9;22) encodes BCR-ABL (activates TK activity)

translocation associated with very poor prognosis with ALL

•t(12;21) encodes ETV6-RUNX1 (transcription factors)

translocation associated with a favorable prognosis of ALL

-good prognosis if good response to steroids in one week, <5% blasts by day 8 or 15 with therapy

-<.01% minimal residual disease

describe how the treatment is a prognostic test in ALL

<5% blasts in bone marrow

bone marrow finding indicative of complete remission

•Poor predictor of prognosis due to poor sensitivity and interobserver variability

bone marrow eval a good predictor of prognosis?

leukemic cells present after therapy but not detectable by conventional morphological assessment; must be found by FISH, PCR, flow cytometry, etc

-BEST PREDICTOR OF PROGNOSIS

define what it means to be measurable residual disease positive

minimal residual disease

What is the best test to predict progosis with ALL?

-almost 2 years of 4-5 chemo regimens

-CNS prophylaxis

-allogenic transplantation in reaching the 1st remission

describe the therapy for ALL

in 1st remission

when can allogenic transplantation be considered for treatment of ALL

infertility, secondary malignancies, growth/maturation changes

complications of ALL after complete remission

-induction 4-6 weeks

-post remission consolidation

-maintenance therapy

what are the phases of treatment of ALL?

tyrosine kinase inhibitor (imatinib, dasatinib)

treatment to add in casess of ALL that are philadelphia chromosome positive

CD19

-may be treated with anti-CD19 immunotherapies

CD marker that is present in over 90% of ALL cases

-combo therapies typically consisting of methotrexate and/or cytarbine

-cranial radiationn reserved for highest risk pts

-incorporated into every phase of treatment

prophylactic CNS therapy regimens for ALL