8. Acquired and Genetic Disorders of the Lymphatic Vascular System Flashcards by J L

Lymphatic System Function

• Drainage of interstitial fluid from body tissues and return to bloodstream
• ____ and ____ immune response
– ____ (B, T, and NK cells)
– ____ cells (monocytes, macrophages, neutrophils, etc)

humoral
cell-mediated
lymphocytes
supporting cells

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Lymphatic System Structure
• Closely associated with the \_\_\_\_ system
• \_\_\_\_ to prevent backflow (like veins)
• Components: 
– Lymph nodes
– Lymphatic vessels 
– Lymph

cardiovascular

valves

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Lymph 
Composition
• \_\_\_\_ cells
• \_\_\_\_ proteins
• Extra interstitial fluid
• Can also transport \_\_\_\_ cancer cells

Named for lympha, the Roman deity of ____

• Metastatic cancer can also travel via \_\_\_\_

white blood
large
metastic
fresh water

blood

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Lymphoid Structures in H&N

• Lymphoid structures within the oral cavity
	○ Waldeyer's ring
		§ \_\_\_\_ tonsils
		§ \_\_\_\_ airways

asymmetric

compromised

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Lymphatic System Disorders
• ____
– Abnormal collection of interstitial fluid & fibroadipose tissue

• ____
– Abnormal lymph node enlargement

• Lymphoma and metastatic cancers

lymphedema

lymphadenopathy

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Lymphedema Overview

Primary lymphedema: lymphedema due to ____ etiologies
Secondary lymphedema: lymphedema ____ to acquired conditions

	• Secondary
		○ \_\_\_\_, cancer, infection, etc.
	• Malformation in drainage in one of the fingers
		○ Primary lymphedema
		○ Resolve by surgery

congenital/inherited
secondary
surgical

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Primary Lymphedema
• Primarily affects the ____ extremities, but may be found ____ the body
• May progress ____ or resolve ____ throughout development
• Classified by ____ at onset

lower
throughout
slowly
spontaneously
age

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Malformations of Vessels
• Abnormality resulting in ____ of interstitial fluid
○ Lymphatic malformation

[NOTES]

accumulation

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Primary Lymphedema
• Clinical presentation reflects area affected, for example:

Tongue, mouth, trachea
____, ____, speech disturbance, difficult ____

Orbits
____, diplopia

Bone
Bone ____ or overgrowth

Skin
____, pain, swelling

Chest
____, wheezing, ____

dyspnea
dysphagia
feeding

proptosis

hypertrophy

cellulitis

chest pain/pressure
dyspnea

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Primary Lymphedema
• Lymphatic Malformations
– Rare ____ deformities of the lymphatic system due to abnormal development of the lymphatic vasculature

• Drainage in the lower extremities, resulting in \_\_\_\_ swelling
• Cystic hygroma
	○ \_\_\_\_ that can be resected

congenital
unilateral
cystic structure

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Primary Lymphedema
May occur as part of a syndrome including ____ syndrome

	• \_\_\_\_ of X
	• Presents in \_\_\_\_
	• Webbing of the \_\_\_\_
		○ Primary lymphedema
	• \_\_\_\_ corrected

turner
monosomy
females
neck
surgically

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Secondary Lymphedema
• Etiologies include ____, trauma, ____, inflammatory disorders, cancer and cancer treatments

* More \_\_\_\_
* Primary lymphedemas are rare

infection
burns
common

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Secondary Lymphedema
SVC Syndrome

Obstruction of the superior vena cava (SVC) due to thrombosis or compression by pathologic process in adjacent structure
Associated with ____ and ____ etiologies
Symptoms include ____ and marked interstitial ____ of the head and neck• Swelling of neck and face; shortness of breath; lungs, coughs, shortness of breath and dysphagia
• Large ____ mass
○ Lymphoma
○ Tumors from ____
○ ____ tumors
• Compression of vessels that drain HN region
• Can also be caused by thrombosis (bloot clot)
○ No smooth flow: area is prone to thrombosis
• Blood clot and compression results in significant swelling

benign
malignant
dysphagia
lymphedema

medistinal
thymus
germ cell

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Secondary Lymphedema
Post-surgical Lymphedema

Most common etiology is ____ lymph node dissection for ____ cancer
Also seen in patients following ____ and/or radiation• ____ lymph node biopsy
○ Dye injected in area of tumor, and see where it’s draining (radioactive dye)
○ Ultimately resecting the lymph node where the drain is flowing
○ Complication: ____
§ If axillary lymph nodes are all removed: significant swelling
• Compression sleeves allows lymph to recirculation
• OT lymph massages
• Life-long complication
• Treating the lymphedemic arm is ____ (where the dissection was)
○ Do not use the arm for drawing ____, etc
• ____ can mimic the phenotype of lymphedema
○ ____swelling

axillary
breast
chemotherapy

sentinel
lymphedema
limited
blood
thrombosis (DVD)
unilateral

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____ Lymphedema
Lymphatic Filariasis (Elephantiasis)
• ____infection of lymphatics and subcutaneous tissue by filarial worms transmitted by ____
• Can cause disfiguring swelling resulting in pain, disability, and social stigma
• Epidemiology: Over 140 million people infected worldwide

• Common in \_\_\_\_ countries

secondary
parasitic
mosquitoes
tropical

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____ Lymphedema
Obesity

• Would be \_\_\_\_

secondary

bilateral

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Lymphadenopathy Overview
• ____: widespread lymph node enlargement
• ____: lymph node enlargement in one region

generalized

localized

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Lymphadenopathy
• Etiologies include ____, autoimmune conditions (e.g. ____), drug side effects, and ____

• Of note, lymphadenopathy may be ____ or entirely ____

infections
sarcoidosis
cancer

painful
asymptomatic

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Lymphadenopathy
• A “normal” lymph node is about ____ cm – about the size of a fingernail, or pea
– May be slightly larger in ____

adolescents

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Generalized Lymphadenopathy

• Often associated with ____ disease

systemic

____ Lymphadenopathy
Infectious Mononucleosis
“the ____ disease”

* \_\_\_\_ symptoms
* Test for \_\_\_\_
* \_\_\_\_ can be enlarged

generalized
kissing
"B"
EBV
spleen

Generalized Lymphadenopathy
Infectious Mononucleosis (cont.)
• Classic triad of symptoms: ____, ____, ____
– Some patients also present with persistent fatigue, palatal petechiae, hepatosplenomegaly, jaundice, or tonsillar exudate

• 90% of cases associated with Epstein-Barr virus (____ herpesvirus transmitted via ____)
• Reactive lymphocytes demonstrate ____-like morphology (____ cells)
– Hence, mononucleosis

• 70-80% of humans experience EBV at some point in their lifetime

fever
pharyngitis
cervical lymphadenopathy

ubiquitous
saliva
monocyte
Downey

Generalized Lymphadenopathy
Human Immunodeficiency Virus (HIV)
• Retroviral infection characterized by reduced ____ resulting in progressive immunodeficiency

CD4+ Tcells

Generalized Lymphadenopathy
HIV (cont.)

• ____ infection
– Fever, lymphadenopathy, sore throat, rash, joint or muscle pain, and
headache
– Some patients are ____

• Chronic infection
– Many patients are asymptomatic, or present with persistent
generalized ____
– Symptomatic chronic infection includes ____, oral hairy leukoplakia, ____, peripheral neuropathy, and idiopathic thrombocytopenia ____

• Test every patient for \_\_\_\_, may not necessarily be a lymphoma

acute
asymptomatic

lymphadenopathy
thrush
herpes zoster
purpura

Generalized Lymphadenopathy ``` Mycobacterium • Tuberculosis mycobacterium – M. tuberculosis, bovis, and africanum; cause tuberculosis (TB) – 95% of TB patients present with ____ ``` • Nontuberculous mycobacterium – Usually restricted to ____ infection – Cause of 90% of mycobacterium-associated ____

cervical lymphadenopathy localized cervical lymphadenitis

Localized Lymphadenopathy | • Etiologies include local infections/reactions, ____, and ____

implants | cancers

____Lymphadenopathy ``` Streptococcal Pharyngitis • Symptoms: – Sore throat – ____ – Tender cervical adenopathy – ____ • Symptoms respond to ____ therapy; usually resolve within ____ days • Etiology: infection by ____bacteria ```

``` tonsillar exudate fever antibiotic 2-5 group A streptococcus (GAS) ```

Localized Lymphadenopathy Cat Scratch Disease • Infection by ____ transmitted by cat scratch/bite or flea bite • Local infection in up to 90% of cases – Regional ____ and/or acute cutaneous inflammatory reaction near site of bite/scratch • Bloodborne dissemination may cause life-threatening ____ and ____ complications or ____ involvement • About 22,000 cases in the United States annually – Most common among ____ and ____

``` bartonella henselae lymphadenopathy visceral neurologic ocular immunocompetent young adults ```

Localized Lymphadenopathy Cat Scratch Disease (cont.) - ____ lesion on finger - Enlarged ____ - Ocular involvement (____ star), rare

papular lymph node macular

Lymphoma Risk Factors • Causes are unknown for most people – Genetic • Unclear • No strong ____ patterns (studies in identical twins) – Environmental factors • Some chemicals suspected (pesticides/herbicides/____) • High-dose ____ exposure – Immuno-suppression • Post–organ ____, autoimmune diseases, HIV – Viral and bacterial infections • ____ virus, EBV, ____, Hepatitis C ``` • HTLV-1 ○ Caribbean and japan ○ T cell ____ • HepC ○ Removing the HepC may cause the lymphoma to enter ____ ```

familial benzenes radiation transplant HTLV-1 H. pylori lymphoma remission

Lymphoma • ____ group of blood cancers arising from lymphocytes • Malignant lymphocytes usually accumulate within lymph nodes forming ____ appearing masses • Some extra-nodal forms may infiltrate skin, bone marrow, GI tract, lung, or peripheral blood ``` • Can infiltrate the ____ ○ Bleeding • ____ biopsy ○ Needle in enlarged lymph node ○ Cylindrical piece • Prefer remove ____ ○ Grade the lymphoma, determine severity ```

``` heterogenous solid gums needle whole lymph node ```

Lymphoma Symptoms • B symptoms: systemic symptoms characteristic of lymphomas – ____ – ____ – ____ (10%) • Other characteristic symptoms include: – Painless lymphadenopathy (may be observed during ____) – ____

``` fevers night sweats uninended weight loss dental exam splenomegaly ```

``` Lymphoma Work-up • HPI and physical exam • Labs – Complete blood count – Metabolic panel – ____ (NHL) – ____ rate (HL) • Radiographic imaging studies • Tissue biopsy – Lymph node and/or bone marrow ``` ``` • Staging ○ Observing where the disease is • PET-CT ○ Activity within the structures ○ Injected with ____ § Areas of metabolic activity § Yellow = metabolically ____ • A residual mass would not pick up any of the ____ • PET-MRI ○ No ____ whatsoever ```

lactate dehydrogenase sedimentation FDG (radiolabeled glucose) active FDG radiation

``` Hodgkin Lymphoma: Overview • 8,500 cases in the U.S. annually • ____ of all lymphomas • Common in ____ patients • High ____ rates • Growing number of survivors (over 150,000 in U.S.) ``` • Hodgkin lymphomas are ____ lymphomas • ____ cells ○ Malignant cells in hodgkin's

10% young cure B-cell Reed-Sternberg

Non-Hodgkin Lymphoma • Very ____ group (over 50 subtypes) • Incidence ____ with age • Accurate pathology is ____

heterogenous increases essential

Non-Hodgkin Lymphoma Clinical Classification ``` • Three subtypes: ○ ____ ○ ____ ○ ____ • Depends on behavior of lymphoma within the patient ```

indolent aggressive highly aggressive

Non-Hodgkin Lymphoma Indolent • ____ growing - may take ____ to progress • Often ____, usually ____ • May not require treatment initially or ____ antibodies only • Respond well to therapy, but ultimately ____(“non-curable”) ``` • Small, enlarged lymph nodes ○ Arm pits, etc • ____ waiting: ○ No proof that treating patients early is of any benefit • When to treat: ○ Large lymph nodes ○ Symptoms § Mechanically affecting the patient ○ Cosmetic • The theory of ____ won't necessarily work because they target rapidly dividing cells ○ Use of ____ instead ```

``` slow years asymptomatic advanced monoclonal relapse ``` watchful chemotherapy monoclonal antibodies

Non-Hodgkin Lymphoma Aggressive • ____ growing - ____ to develop • Often associated with ____ symptoms (fevers, night sweats, weight loss) • ____ (with or without radiation therapy) at diagnosis • Most common: ____ has cure rate over 60% in advanced disease • Can be cured at relapse with ____ • ____ (low grade) lymphomas can transform to high grade (aggressive) disease

``` fast months B chemotherapy DLBCL stem cell transplant indolent ```

Non-Hodgkin Lymphoma Highly Aggressive • ____ progression/cell doubling time • May present as oncologic emergency (spontaneous tumor ____, cord compression, obstruction) • High ____ at diagnosis, but respond well to chemotherapy and curable (up to 80%) • Require CNS ____, inpatient chemotherapies ``` • ____ lymphoma ○ Jaw tumors ○ HIV-related • ____ dividing tumor in human body ○ Very sensitive to chemotherapy • 20% of those uncured: ○ Spontanteous tumor lysis ○ ____ failure due to K+ levels (and arrythemias) • As long as you treat properly highly curative (80%) ```

rapid lysis mortality prophylaxis burkitt's fastest renal

Lymphoma Treatment • Important Factors for Consideration ``` – ____ of lymphoma – Stage – Prognostic characteristics – ____ – ____ of treatment – Other health issues (“co-morbidities”) ``` • Treatment depends on ____ and health • Treatment is currently not tailored to patients ○ ____ § ABVD • Future: individualized treatment ○ Send tumor for molecular signature and determine the best course of action

subtype symptoms toxicity profile age chemo-cocktails

``` Lymphoma Chemotherapy -Short term side effects - Fatigue • Nausea • Low blood counts (risk of neutropenic fevers, bleeding) • Hair ____ • Neuropathy • Cognitive changes: “____” • Constipation/diarrhea • ____ ulcers ``` * Long term side effects * Organ impairment (lungs, heart, fertility, bone marrow, peripheral nerves) * Secondary malignancies (leukemia, another lymphoma, solid organ cancers) ``` • Side effects in mouth are common ○ Lining of ____ ○ Cells with high turnover • Mucositis ○ Difficulty eating, swallowing • "____" ○ Viscous lidocaine ○ Soothing liquid • Immuno-suppressed ○ ____-related issues in mouth ○ ____ thrush ```

loss chemo-brain mouth mouth magic mouthwash HSV oral

Lymphoma Monoclonal Antibodies “Most of the B-cell lymphoma have expression of ____ and ____ works on attacking the cells in different ways and mobilizing the immune system to work on lymphoma.”

CD20 | rituxan

``` Lymphoma Targeted Therapies • Radioimmunotherapy (RIT) – ____antibody labeled with a ____ delivers targeted radiation directly to the tumor site ``` • "____" ○ Goes to area with____-positive B cells ○ Delivers radiation directly to the tumor in small amounts

monoclonal radionuclide liquid radiation CD20

Lymphoma Cellular Therapies • Stem Cell Transplantation – Autologous stem cells – Allogeneic stem cells * Chimeric Antigen Receptor modified T-cells (CAR T cells) * Genetically modified, ____ (patient’s own) ____ specifically directed to attack tumor cells

autologous | Tcells

Targeting Tumors with Chimeric Antigen Receptors Native TCR * CARs combine an recognition piece of an antibody with signaling (activating) domain into ____ protein. * Gene transfer to stably express CAR on T cells confers novel Ag specificity. • Express receptors on T-cell that can attach to CD-19 on tumor cells: ○ Specifically target the tumor cells • Remove T-cells; • Modify them and use a ____to induce change in the DNA of the T-cells; • Now begins to express receptors; • And introduce the modified T-cells back into the patient • CART ○ ____ storm § T-cells are ____ and cause inflammatory issues (fevers, ICU)

single chimeric viral vector cytokine release overactive

``` Oral Complications of Cancer Treatment • Oral mucositis • Alteredtaste • Salivary gland dysfunction • Deferred/delayed dental care • Osteonecrosis of the jaw • Radiation caries ``` • Oral mucositis as a result of both ____ and ____ • SC transplant ○ Auto: patient's own SC are modified (high dose of chemo killing last cancer cell) ○ Allogenic: transplant from ____else § Various immune issues: graft vs host disease □ Dry mouth, lesions within mouth (sickle syndrome…?) • Anti-mimetics/anti-nausea medicine • ONJ ○ Due to ____ used in solid tumors (bone metastases)

chemotherapy radiation someone bisphosphonates

Summary • Disorders of the lymphatic system commonly involve impaired immune function or abnormal lymphatic vasculature • ____ and ____ are often associated with both acquired and congenital disorders

lymphedema | lymphadenopathy

Summary, cont. • Genetic/congenital disorders often manifest at ____ or during ____ • Acquired disorders include ____ and ____ etiologies • Malignancies like lymphoma may present as ____ or ____disease – Complications involving the head and neck may be ____ or due to ____ itself

``` birth puberty infectious non-infectious nodal extra-nodal treatment-related malignancy ```