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Control #664 - eEdE-97
Implications, Manifestations &
Complications of
HPV, HIV & EBV Infection
Christine Glastonbury, MBBS, Bhavya Rehani, MD,
Alina Uzelac, DO
Disclosures
• Alina Uzelac - None
• Bhavya Rehani - None
• Christine Glastonbury – Received royalties from Amirsys for
Statdx & Books; prior shareholder.
HN Triple Threat: HPV, HIV & EBV
We present a review of the epidemiology, mode of transmission of infection and the
mechanism of action of these three viral agents. More importantly for the radiologist
we illustrate the many head & neck (HN) manifestations of disease associated with
infection with each of these viruses. Human Papilloma Virus (HPV) is well known for
causing anogenital carcinomas and is responsible for a rapid
increase in H&N mucosal malignancies over the
last 10 years – particularly Oropharyngeal SCCa.
Epstein Barr Virus (EBV) is associated with
HPV
nasopharyngeal carcinoma (NPC) and with Burkitt
EBV
lymphoma and post-transplant lymphoproliferative
Disease (PTLD).
In addition we will share common imaging features of
HIV
Human immunodeficiency virus (HIV) infection from
lymphoid hypertrophy to parotid lesions as well as
life-threatening secondary infections from immunodeficiency.
HIV alone – or in combination with EBV or HPV! – is also
associated with malignant disease including
MALIGNANCIES & OTHER NECK
Kaposi sarcoma, SCCa and lymphomas.
MANIFESTATIONS!
What is Human Papilloma Virus?
HPV is a sexually transmitted virus with more than 100 different genotypes. Almost
two thirds of HPV cause cutaneous infections, resulting in warts. Just over one third of
HPV types produce mucosal infections. These viral types may be “low risk” with the
most common being HPV6 and HPV11, resulting in benign mucosal and anogenital
papillomas. There are more than 12 different “high risk” viral types, known as
oncogenic HPVs. The most common of these are HPV16 & HPV18 which are
responsible for cervical cancer in women and
anogenital and oropharyngeal carcinomas in
men and women. It is estimated that
HPV16 & 18 are responsible
for ~33 400 HPV-cancers/year USA.
Oral HPV prevalence = 6.9% USA
One in 15 people in the USA have oral HPV, although only around 1% of the population
has HPV16 infection. Oral swab testing is three times more likely to find HPV in men
than women, and more likely to find HPV in older people, in smokers, and in those
with a greater number of sexual partners. Both men and women currently have an
80% lifetime risk of genital HPV infection – it is the most common STD!
Who gets HPV-SCCa then?
(& Where?)
There is a markedly rising incidence of HPV-related oropharyngeal SCCa (OPSCCa)
over the last 20 years. In the USA up to 80% OPSCCa are due to HPV. Most of these
are HPV16 (87-96%). In countries likes Sweden with lower tobacco use, HPV
accounts for up to 90% OPSCCa.
• Generally younger patients than tobacco SCCa: Age range 31-78yrs
• >90% white patients and 3♂: ♀
• Palatine and lingual tonsils are the most frequent sites
59yr nonsmoker
male presents with
left neck mass.
Large left lingual
tonsil primary
tumor & ipsilateral
involved nodes.
HPV-OPSCCa
cT2N2b.
*Prior infection with HPV 16 is associated with x9 increased risk of SCCa*
Pathologically, what’s going on?
HPV targets the reticulated epithelium of tonsillar crypts which is in distinction to
tobacco-related SCCa which tends to arise from surface epithelium. This means that
small tumors literally hide in the depths of the tonsil and may be very difficult to
appreciate clinically. Pathologically (H&E) there are no specific histologic
characteristics, but there are some suggestive features of HPV tumors:
SCCa is often basaloid, no surface dysplasia
Infiltrating lymphocytes, no keratinization
Direct testing for HPV-DNA can be done by polymerase chain reaction (PCR)
although this is difficult to perform well. In situ hybridization (ISH) is less
sensitive than PCR; both PCR and ISH are expensive and time consuming.
As an alternative, many institutions perform immunohistochemistry (IHC) for
p16 expression . A positive p16 test means that most cells stain strongly for
p16. IHC p16 is a sensitive, cheaper and easier test to perform but is only a
surrogate marker for HPV+ tumors.
In the oropharynx there is 5-10% false + rate [ie p16+ but not HPV+],
and an 8% false – rate [ie p16- tumor but it is actually HPV+]
So what’s this “p16” all about?
A “p16+” tumor does not mean HPV16 DNA! p16 is a protein that is important for cell
cycle regulation, acting as a tumor suppressor, and is up-regulated in HPV-induced
tumors. Specifically, p16 is a cyclin-dependant kinase inhibitor.
HPV E6 oncoprotein degrades p53 tumor suppressor protein*. This interferes
with DNA repair and apoptosis. HPV E7 oncoprotein inactivates the
retinoblastoma protein pRB → leads to further loss of cell cycle control.
E6
E7
p53
pRB
*Tobacco and alcohol-related
SCCa have p53 mutations and
are usually p16-*
To try to restore cell
cycle control, the host
cell over-expresses p16
p16
While p16 is a surrogate marker for HPV,
p16+ OPSCCa have a favorable prognosis
regardless of tumor HPV status!
p16 may be a better predictor of response
to radiation than HPV DNA testing!
56yr male nonsmoker
with a tonsillar mass
noted by his dentist.
Biopsy revealed p16+
OPSCCA. Note the tumor
is largely a bulky
exophytic mass.
Imaging Pearls: HPV+ OPSCCa tend to be
more exophytic than HPV- tumors, and
are more likely to have cystic nodes.
62yr male nonsmoker
with a left neck mass.
Bilateral nodal disease
found to be p16+.
Primary tumor is a large
palatine tumor
extending superiorly to
the left palate. T3N2C.
Note the extranodal
tumor spread also!
Imaging Key Points & Pitfalls
PITFALL #1: Primary tumors occur deep in tonsil & may be very
small / occult with large / multiple nodes.
37yr nonsmoker man presents with a large left neck mass. MRI shows
multiple left neck nodes. Note the subtly asymmetric palatine tonsil!
Left tonsil HPV+ SCCa, T1N2b
KEY POINT #1: Look for /suspect subtle pharyngeal asymmetry.
PET-CT may help!
Imaging Key Points & Pitfalls
PITFALL #2: Metastatic nodes are frequently cystic
69yr nonsmoker man with a large mass at the left tongue base infiltrating
the floor of the mouth has left solid and cystic nodes. FNA reveals p16+
SCCa. Note that the cystic node has no FDG uptake!
KEY POINT #2: Cystic (or solid) new mass in adult = Cancer UPO!
Imaging Key Points & Pitfalls
PITFALL #1 + 2: Cystic node metastases at level 2 mimic BCCs but
don’t be tempted to call them that just bc the primary is occult!
45yr man presents with a left neck mass. CECT: Septated cystic neck mass
behind the left submandibular gland. Called branchial cleft cyst at OSH. FNA
reveals p16+ SCCa. A tiny primary was found at left tonsillectomy.
KEY POINT #1+2: Hold your ground! Cystic mass = Cancer UPO!
45yr female with a right neck
mass which on FNA was shown to
be p16+ SCCa.
Clinical examination did not find
this primary tumor although
asymmetry of the palatine tonsils
was readily evident on MR and
PET-CT. pT2N1 OPSCCa.
59yr male, HIV+ . PET-CT obtained for restaging of his recurrent anal carcinoma
(HPV+) found neck adenopathy and a primary tonsillar mass. T2N2b HPV+ OPSCCa.
Patients with HPV anogenital carcinomas have >x4 risk of OPSCCa.
Patients with HIV are more likely to develop malignancies from HPV.
HPV Vaccine?
Two vaccines are available to prevent HPV infection. Both are a 3-shot IM vaccination
series given at 0, 2, 6 months, and both appear to be safe. The most common
symptoms experienced with injection are syncope, local pain, dizziness, nausea and/or
headache. The vaccine was developed to prevent HPV-cervical cancer and after
initially being recommended for girls, the CDC now recommends the vaccine for both
boys and girls in the prevention of female and male anogenital cancers.
[It is not yet proven that vaccination prevents HPV-oropharyngeal SCCa]
GARDASIL
CERVARIX
Merck (2006)
GlaxoSmithKline (2009)
Effective for HPV 6 & 11*, 16 & 18
Effective for HPV 16 & 18
HPV vaccination is recommended by the CDC for ♀ 11-26yrs, ♂ 11-21yrs,
and
for homosexual or immunocompromised ♂ <26 yrs.
Vaccination must occur prior to HPV exposure and thus the pre-teen recommendation.
The wide recommended age range reflects the “catch up” group who did not have this
vaccine available as a pre-teen.
So, HPV-SCCa. Where else?
HPV-malignancies have been found in other H&N tumor sites, such as the
nasopharynx, hypopharynx and oral cavity. No correlation has yet been proven
between HPV infection and clinical course in other SCCa. Beware that outside of the
oropharynx “p16+” has a much weaker correlation with HPV infection!
Oropharynx is
the most
frequent site
probably b/c
HPV integration
begins in the
tonsillar crypts
after oral
exposure to the
virus.
42yM presenting with multiple cranial neuropathies. Pathologically this was found
to be an invasive poorly differentiated T4N2M0 nasopharyngeal SCCa with focal
keratinization. It tested to be p16+, EBV negative, HPV positive!
VIRAL FAST FACTS
HPV
▪ Most common sexually transmitted virus - HPV16 &18 are oncogenic.
▪ Causecervical cancer, most anogenital cancers.
▪ Rapid increase in HPV-OPSCCa in>; less often other H&N SCCa.
▪ p16 staining is cheaper & often more readily available surrogate
pathological marker than viral PCR / ISH for HPV-DNA.
▪ HPV-OPSCCa show a trend for cystic metastatic nodes & more
exophytic primary tumors; may be occult primary with large nodes.
▪ Currently HPV-OPSCCa staged & managed as for non-HPV OPSCCa*.
▪ Significantly better OPSCCa prognosis if HPV+ and nonsmoker.
▪ HPV vaccine recommended but not yet proven to prevent H&N SCCa.
* HPV-OPSCCa staging is slated to change with the 8th edition AJCC/UICC.
** Many studies already investigating “de-escalation” treatment protocols.
What is HIV?
Human Immunodeficiency Virus (HIV) is a type of retrovirus (lentivirus) that
preferentially infects CD4 T (‘helper’) cells, macrophages and dendritic cells.
Lowered numbers of CD4 T cells results in loss of cell-mediated immunity (CMI)
with a subsequent susceptibility to opportunistic infections and an increased risk of
malignancies. HIV is most often transmitted through sexual acts (semen/vaginal
fluid), exposure to infected blood, or in utero from maternal HIV. Breast milk may
also transmit HIV.
HIV-1 [AKA ‘LAV’ and ‘HTLV-III’] Responsible for most HIV infections worldwide.
HIV-2 is mainly found in west Africa; it is less virulent & less infective than HIV-1.
Lifelong antiretroviral therapy (ART) is recommended for anyone who tests positive
for HIV by ELISA (Enzyme-Linked ImmunoSorbent Assay), to prevent impaired CMI
and to minimize transmissability of the virus. This is monitored by measuring the
CD4 count: Normal CD4 = 500 -1400 cells/mL. Marked loss of CMI when CD4 <200.
DEFINITIONS (CDC 2014)
Stage 0: Discordant HIV tests: Negative test within 180 days of Positive test.
Stage 1: HIV+ & CD4 count ≥500
Stage 2: HIV+ & CD4 count 200-499
Stage 3 (= AIDS): HIV+ AND CD4<200 OR AIDS-defining illness OR if CD4 count is
unknown, CD4 T-cell % of total lymphocyte count is <14% .
Imaging Key Points & Pitfalls
PITFALL #1: Patients may not be known to be HIV positive at the
time of imaging, and their symptoms may be non-specific.
45yr man, not known to be HIV+, presents with a parotid mass. MRI: Left
cystic/solid mass, but note also adenoidal hypertrophy. FNA determined the parotid
lesion to be a lymphoepithelial lesion. Patient later determined to be HIV+.
KEY POINT #1: “Incidental imaging findings” may be the first
clue that directs clinicians to determine HIV infection!
‘Benign’ HN HIV manifestations?
As many as 70% of HIV-infected patients eventually develop HN conditions and
these may be imaged. Non-neoplastic HIV conditions include a wide variety of
infectious diseases / agents and also inflammatory diseases.
56yM, known HIV+ and new dysphagia. CECT shows inflammation of inferior tonsillar pole to
left pyriform sinus. Biopsy proved this to be ulceration with herpes simplex.
HN INFECTIOUS CONDITIONS
Sinusitis : Wide variety pathogens including
acute invasive fungal sinusitis
Otitis media → Coalescent mastoiditis
Pharyngitis and neck abscesses with wide
variety pathogens
CN7/8: H.Simplex; VZV-Ramsay-Hunt
HN INFLAMMATORY CONDITIONS
Nasal allergies
Salivary gland dysfunction: Dry mouth
Parotid lymphoepithelial lesions
Reactive adenopathy
Lymphoid hyperplasia (especially
adenoids)
54yM with known
stage 3 HIV (AIDS),
and right palatal
lesion. Biopsy of
this subtle lesion
proved to be
cryptococcal
infection with
reactive nodes.
49yM HIV+ presents with left
eye blindness and sinus
infection. This not so subtle
case of invasive fungal
(aspergillus) infection
demonstrates extensive sinus,
orbital and cerebral invasion
with destruction and marked
left proptosis.
What are AIDS-Defining Illnesses?
The Centers of Disease Control (CDC) defines the Acquired Immune Deficiency
Syndrome (AIDS) as stage 3 HIV infection. This means HIV+ AND a CD4 count <200
[OR if this is unknown, CD4 T-cell % total lymphocytes <14%] OR HIV+ & “AIDSdefining illness”. These “illnesses”, also defined by the CDC, are numerous but are
categorized into opportunistic infections, neoplasms, & other effects of HIV infection.
INFECTIONS
NEOPLASMS
DIRECT HIV
Candidiasis (lung/esoph)
Cryptococcosis or
Coccidioidomycosis (extrapulmonary)
CMV retinitis
Chronic Herpes Simplex
Histoplasmosis (non-lung)
Chronic Isosporiasis
MAI or M.kansasii
MTB anywhere
Pneumocystis pneumonia
Cerebral toxoplasmosis
Salmonella septicemia
Kaposi sarcoma
Burkitt lymphoma
Lymphoma
(CNS or immunoblastic)
Invasive cervical cancer
HIV encephalopathy
Wasting syndrome
REACTIVATION
PML
AGE-SPECIFIC INFECTIONS
Multiple or recurrent bacterial infections <6yr age
Recurrent pneumonia >6yr age
“Advanced HIV infection” is defined when CD4 <50.
The patient is at risk for more severe opportunistic
infections such as disseminated MAI and CMV.
Imaging Key Points & Pitfalls
PITFALL #2: HN cancer occurs more frequently in HIV patients
and may be mediated by viruses.
48yF, known HIV+ & CD4 171 presents with palatal mass.
Biopsy = Kaposi sarcoma. IHC for HHV8: Scattered + cells.
28yM, HIV+ & CD4 114 presents
with nasopharyngeal mass and
necrotic adenopathy. Biopsy of both = Kaposi sarcoma.
KEY POINT #2: Beware destructive processes or large &/or
necrotic nodes - this is unlikely to be HIV reactive changes!
What viruses cause tumors with HIV?
HIV-LYMPHOPROLIFERATIVE DISEASE
About 60% of HIV-related
lymphomas are linked to
EBV infection. HIV+
patients have a
HHV8
x60-200 risk of
developing
lymphoma.
These tumors are
the AIDS-defining
illness in 3-5%of
HIV patients.
EBV-lymphomas
will be further discussed
in the following section.
EBV
HPV
KAPOSI SARCOMA
is caused by Human Herpes
Virus-8 AKA Kaposi
sarcoma-associated herpes
virus (KSHV). Uncommon
viral infection but typically
does not cause tumors until
immune-compromised,
especially with AIDS.
SQUAMOUS CELL CA
As presented previously, HIV
patients have increased risk
of HPV anogenital tumors &
OPSCCa. HPV vaccine is
recommended for immunecompromised <26yrs age.
43yM HIV+, v. unwell &
noncompliant with ART
presents with facial
mass. Biopsy proved it
to be plasmablastic
lymphoma. EBV+, Ki-67
(proliferation index)
>80%. Mets to spine
also found and patient
underwent palliative Rx.
34yM presents with
rapidly enlarging left neck
mass. HIV status unknown
Biopsy = High-grade
lymphoma consistent
with Burkitt; EBV+
Found: HIV+, CD4 265.
Successfully treated with
chemo. Now well on ART
& most recent CD4 620.
VIRAL FAST FACTS
HIV
▪ Lentivirus (type of retrovirus) transmitted through some bodily fluids.
▪ Predominantly HIV-1; HIV-2 less virulent, found in West Africa
▪ Primarily infects T helper lymphocytes (CD4 cells), macrophages &
dendritic cells which results in loss of cell-mediated immunity (CMI).
▪ Use of oral antiretroviral therapy (ART) recommended for all HIV+.
▪ ART can prevent loss of CMI, minimizes transmissibility of virus.
▪ HIV+ & CD4 <200 OR HIV+ & “AIDS-defining illness” = Stage 3 = AIDS.
▪ Rising HIV infection rate but ART has led to decline in HN diseases.
▪ Imaging may be performed b/c of suspected HIV complication OR HIV
status may be unknown: Be alert for adenoid, parotid, node changes!
▪ HIV+ patients are at risk for unusual infections & their complications.
▪ HIV+ associated with increased risk of malignancy from HPV & EBV!
What is Epstein-Barr Virus?
Epstein-Barr virus (EBV) is a human herpes virus (HHV-4) which is transmitted orally
through saliva & genital secretions. This incredibly common virus [90% of USA adults
have prior EBV infection] primarily infects oral /oropharyngeal epithelial cells & B
lymphocytes. After initial infection is controlled by the immune system, EBV remains
latent in B cells for the rest of the person’s life. Most infections are ‘EBV type 1’, except
in Africa where EBV type 1 & EBV type 2 have equal prevalence.
EBV causes multiple diseases with many HN manifestations.
Infectious Mononucleosis
Nasopharyngeal Ca (NPC)
& multiple Lymphomas
Post-Transplant (PTLD) &
HIV-Lymphoproliferative Disease
*EBV has also been associated with auto-immune disorders including
SLE, MS and Rheumatoid arthritis.
EBV within us!
free virus particles
EBV-Plasma cells that go
to multiple sites
Occas.
Oral
Epithelial
cells
B CELLS
LATENT
B CELL
LYTIC
B CELL
PERIPHERAL
BLOOD
Infected Memory
B cells. FOR LIFE
..germ
Waldeyer’s ring &
center
Lymph Nodes
where proliferation
occurs in the …
Cytotoxic
T Cells
Acute EBV infection in HN
Acute EBV infection has several names including infectious mononucleosis (“mono”),
glandular fever and “the kissing disease” due to its occurrence in teens acquiring (and
spreading!) EBV through saliva. Infection is most common in teens & young adults with
a flu-like illness with adenopathy, sore throat and fever, but may occur in childhood
with minimal or no symptoms. Most acute infections are self-limited.
4yr febrile boy underwent extensive work-up for malignancy [incl neck/chest/abdo/pelvis CT +
bone marrow bx, LP and incisional neck & adenoid bx under GA] following OSH CT report of bone
erosion from a nasopharyngeal mass. CECT: Diffuse lymphoid and nodal hyperplasia without
skull base erosion. Biopsy showed this to be EBV infection (Mononucleosis)*.
50% EBV exposure occurs in childhood, although most EBV-tumors present in adulthood. This
is possible because of the lifelong viral persistence of EBV in Memory B cells.
How does EBV → Solid Tumors?
Plasma cells releasing EBV in
tissues likely cause epithelial
malignancies such as
Nasopharyngeal Carcinoma
(NPC) and gastric carcinoma, in
addition to mesenchymal tumors
like follicular dendritic cell tumor/
sarcoma and in immune –
suppressed patients leiomyomas
& leiomyosarcomas.
The EBV virus is detected within
these tumors!
NPC and EBV
NPC is the most common cancer in Asian males. It is a primary mucosal
malignancy and the most common nasopharyngeal adult tumor. EBV DNA is found in
tumor cells and also in premalignant (dysplastic, in situ) lesions . This tumor most
often occurs in adults 40-60 yrs ( ♂>♀) and is rare in children, where a predominance
in African-Americans is noted. NPC is endemic in southern China (Guangdong province
- 800 per million). Throughout the rest of the world the incidence is roughly <10 per
million, with a moderate increase in the Inuits of Alaska and Canada.
28yF with 4 month weight loss, fatigue & epistaxis. She was also 9 weeks pregnant so
was consented for a non-contrast MRI, which showed a large tumor with large bilateral
retropharyngeal nodes and extensive neck adenopathy.
EBV NPC is a non-keratinizing carcinoma. [Keratinizing SCCa occurring in the
nasopharynx is not EBV-related but associated with tobacco and alcohol
abuse.] NPC is however radiosensitive and has a better 5-year overall survival
than Nasopharyngeal SCCa.
49yr Asian man presents with a right neck mass. CECT and PET/CT demonstrates FDGavid bilateral neck adenopathy with a small right nasopharynx primary tumor. This
proved to be EBV-positive NPC* [undifferentiated non-keratinizing carcinoma].
*Epstein-Barr encoding region (EBER) in situ hybridization (ISH) is the method of
choice for detecting EBV in tissue sections. EBER1 & EBER2 are short nuclearenriched non-coding RNAs.
Imaging Key Points & Pitfalls
PITFALL #1: EBV-Lymphomas are “shape shifters”. They can have
nodal, lymphoid (adenoid/ tonsil) and non-nodal, extralymphatic manifestations.
84yr woman with epistaxis and nasal mass. MRI demonstrates large left nasal cavity mass
extending in to left premaxillary tissues. There was no adenopathy. The tumor was determined
to be EBV+, NK T Cell lymphoma. This is an aggressive extranodal lymphoma. Necrosis with
bone / soft tissue destruction is common. Almost all Nasal-type NKT cell lymphomas are EBV+
KEY POINT #1: Lymphomas are frequently intermediate to low T2-SI
and often have restricted diffusion. This may help your DDx!
How is EBV related to lymphomas?
Germinal center B Cell Blasts
become stuck in the
proliferative phase because of
activated c-myc oncogene →
Burkitt Lymphoma
Cellular mutation at the
germinal center
→ Hodgkin Lymphoma
..and in immune-suppressed pts?
Absence of cytotoxic T cells or
altered T cell function results in
infected B cells not being
destroyed in the germinal centers.
This is thought to give rise to
lymphoproliferative disease in
immune-suppressed patients
including HIV-associated
lymphomas , post-transplant
lymphoproliferative disease
(PTLD) , EBV-lymphoma in the
Elderly.
16y girl with a history of Granulomatosis with Polyangiitis (“Wegener”), for which she had been
on methotrexate and long term steroids. Now neutropenic and with adenopathy which was
thought to be cat-scratch disease. CECT reveals necrotic bilateral adenopathy without
surrounding inflammatory changes. Biopsy revealed Diffuse Large B cell Lymphoma with strong
staining for EBV. In light of
the therapy and neutropenia
this was favored to be an
immunosuppression-related
lymphoma.
IMMMUNE-SUPPRESSED LYMPHOPROLIFERATIVE DISEASE: The abnormal
proliferation of lymphoid cells ranges from benign hyperplasia with a
mononucleosis-like syndrome to aggressive malignant lymphoma. EBV
positivity is found in 80% post-transplant lymphomas and is variable with HIV
lymphoma types (30-100%). Improving EBV-specific immunity (immunesuppressant therapy / CD4 ) is key to successful management.
Imaging Key Points & Pitfalls
PITFALL #2: While most lymphomas can’t be distinguished from
each other by imaging, PTLD can mimic aggressive infections!
19y man, 3 months post allogeneic bone marrow transplant for aplastic anemia. While this was
first interpreted as pharyngitis with a suppurative retropharyngeal node, biopsy showed Diffuse
large B-cell lymphoma. Patient responded to chemotherapy with drop in EBV titers also.
KEY POINT #2: Beware the immune-suppressed patient with
“pharyngitis” or invasive fungal sinusitis – it may be PTLD!
88yr man presented with an enlarging right parotid mass and right facial nerve
paralysis. MRI reveals an ill-defined infiltrating and necrotic mass in the superficial and
deep lobes of the right parotid extending to the stylomastoid foramen, suggestive of a
malignant parotid primary tumor. FNA suggested carcinoma, and had normal flow
cytometry. The tumor was subsequently resected and determined to be
EBV-associated Non-Hodgkin Lymphoma of the Elderly.
Senile EBV-associated Lymphoproliferative Disease
These B Cell tumors tend to be aggressive lesions that occur in elderly
patients and invade blood vessels, appearing largely necrotic. They are rare in
the parotid gland and more often present as a necrotizing lung mass.
VIRAL FAST FACTS
EBV
▪ Double-stranded DNA human herpes virus (HHV-4) spread orally and
infecting epithelial cells and B lymphocytes.
▪ Around 90% adults demonstrate prior EBV infection.
▪ Acute EBV: Asymptomatic → flu-like illness with adenopathy (“mono”).
▪ After infection, EBV remains in Memory B cells for life.
▪ Persistent EBV allows for EBV-associated malignancies in adults.
▪ Epithelial tumors: Nasopharyngeal carcinoma (NPC).
▪ EBV is also associated with many different lymphoproliferative diseases
in immune-competent and immune-suppressed.
▪ Immune-competent: Burkitt, Hodgkin, DLBCL, lymphomatoid
granulomatosis, NK/T Cell lymphoma, angioimmunoblastic lymphoma.
▪ Immune-suppressed: PTLD, HIV-associated lymphoproliferative disease.
KEY RADIOLOGY TAKE HOME POINTS
HPV
HIV
EBV
▪ HPV16 &18 are oncogenic.
▪ In USA HPV responsible for
more OPSCCa than tobacco;
rapidly rising incidence over
last 10 years.
▪ HPV-OPSCCa show a trend
for cystic nodes and more
exophytic primary tumors.
▪ HPV-OPSCCa frequently
presents as small or occult
primary.
▪ New cystic/solid neck mass
in adult = carcinoma until
proven otherwise.
- even if primary not readily
apparent
- even if young / nonsmoker
▪ Stage as for all OPSCCa.
▪ HIV-1 infection is rising.
▪ HIV+ & CD4 <200 = AIDS.
▪ Antiretroviral therapy(ART)
recommended for all pts.
▪ ART has resulted in decline
in ENT manifestations of HIV
▪ “Incidental” findings of
adenoid/ parotid/ nodal
changes may be key to first
HIV diagnosis.
▪ HIV+ : ↑risk for unusual
aggressive & infections
- look for complications!
▪ HIV+ : ↑risk for cancers
including tumors associated
with HPV & EBV.
- Beware of aggressive
masses, necrotic nodes!
▪ Herpes virus – HHV-4.
▪ Prior infection evident in
90% adults, 50% children.
▪ Acute infection may be
asymptomatic → “mono”.
▪ EBV persists for life in
memory B cells.
▪ Epithelial and
mesenchymal tumors may
occur with immune
competent patients.
- In HN NPC is most frequent
▪ Lymphoproliferative (LP)
diseases occur in immunecompetent and suppressed.
- Many lymphoma types
- PTLD & HIV-assoc’d LP
disease
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