Malignancy Flashcards
What causes Kaposi sarcoma?
HHV8 (KSHV)
ACTG staging of KS - good risk
All of the following
Tumor - confined to skin, LN or minimal oral disease
Immune system - cd4 >150
Systemic illness - performance status >70
KS staging - poor risk
Any of the following
Tumour associated oedema or ulceration, extensive oral KS, GI KS, KS in non nodal viscera
Immune - CD4 <150
Systemic - PS <70 or other hiv related illness
Treatment of KS
cART plus
1st line Pegylated liposomal doxorubicin 20mg/m2 every 3 weeks
2nd line - paclitaxel every 2 weeks 100mg/m2
Baseline investigation for ?KS
Clinical exam
HIV serology
Routine bloods
HHV8 viraemia
Cd4 count
Histology
Whole body CT
Bronchoscopy/endoscopy if any suggestive symptoms
Are there local therapies for KS?
Radiotherapy used less now cART is available but may be useful at specific sites
Topical retinoids (not in uk)
Intralesional vinblastine
Cryo
In general local therapies superseded by cART
Who can receive local KS therapies?
Symptomatic or cosmetic improvement in early (stage t0) ks
Ongoing KS follow up
Depends how serious - if severe hiv related then monthly clinical evaluation, 3/12 radiological evaluation
Bloods, cd4, clinical exam. If symptoms - bronchoscopy, endoscopy, Ct whole body
What constitutes a complete response to KS?
Complete resolution with no new lesions for at least 4 weeks. Biopsy needed to confirm resolution in flat pigmented lesions.
Endoscopes must repeated to confirm resolution of previously detected visceral disease
What constitutes partial response to KS?
One or more of the following in absence of new cutaneous or visceral lesions, ks associated oedema, 25% increase of any index lesion:
50% decrease in number measurable lesions
Or 50% decrease defined as - 75% nodular lesions become plaques, flattening of 50% lesion, 50% decrease sum of bidimensional diameters of index lesion
Flattening of 50% lesions
What constitutes progressive KS?
Any of:
25% increase in size of any index lesion
Appearance of new lesions
Where 25% or more of previously flat lesions become raised
New or increased KS associated oedema
Most common subtypes of aids related non Hodgkin lymphoma
Diffuse large B cell lymphoma, burkitt lymphoma/leukaemia
Baseline investigations for DLBCL and BL
Bloods - routine plus esr, blood film, g&s, coag, LDH, urate, CRP, immunoglobs, protein electrophoresis, b2 microglobulin.
Hep b, c, cmv, VZV tests
ECG
CXR
Bone marrow
CT NCAP
Pet Ct
LP NOT ROUTINE
Prognostic factors for aggressive NHL?
1 point for each -
Age >60
Serum LDH > normal
PS > 1
Stage iii/iv
Extranodal site >1
0-1 low risk
2 low intermediate risk
3 high intermediate risk
4 or 5 high up
Should rituximab be used in treatment of DLBCL?
Yes but increased death rate in those with CD4 <50 so need to ensure appropriate antibiotic prophylaxis (fluconazole, aciclovir, septrin, azithromycin), preemptive GCSF, prompt tx of OI
What is the treatment of HIV associated burkitt lymphoma/leukaemia?
CODOX-M/IVAC DA-EPOCH
Rituximab should be added
Prevention of secondary CNS lymphoma in those with ARL?
Cns relapse less likely if improved control of systemic disease
Those at increased risk - disease in testes, paranasal sinuses, paraspinal disease, breast, renal, epidural space, bone
Also advanced stage, elevated LDH
those with DLBCL at high risk to receive CNS prophylaxis - IT or IV methotrexate
All patients with burkitt lymphoma should be offered prophylactic intrathecal chemo
When does tumor lysis syndrome occur (DLBCL/
12-72 hrs after commencement of chemotherapy
What increases risk of tumour lysis syndrome?
Elevated LDH and bulky disease (DLBCL) or stage 3/4 disease (BL)
Management of tumour lysis syndrome
Aggressive hydration and rasburicase
Should patients on chemotherapy continue their cArt?
Yes
May need adjusting if interactions
How is refractory /relapsed aids related lymphoma treated?
Offer second line chemotherapy which may contain platinum
For those who respond (CR or PR) should be considered for high dose therapy and autologous stem cell transplant
How is response evaluated for NHL in HIV+patients?
Assess response halfway through treatment - clinical evaluation, Ct scan, bone marrow
PET CT at least 4-6 weeks after last chemo 8-12 weeks after last radiotherapy
Follow up 3/12ly first year, 4-6/13ly 2nd and 3rd year, 6/12 up to 5 years
I what is a PCNSL?
Non Hodgkin lymphoma confined to cranio-spinal axis.
Characteristically is DLBCL or immunoblastic NHL
Typical presentation of PCNSL?
Rarely B symptoms.
Present with mass lesions - neuropsychiatric signs, raised ICP, seizures
Investigations for PCNSL?
MRI brain with GAD, CT CAP, LP when safe, serum LDH
Brain biopsy only confirmatory test
EBV intumour cells a universal feature of hiv associated PCNSL
Treatment of PCNSL
In normal pop iv methotrexate and cytatabin
I’m HIV+patients iv methotrexate only most utilised
Whole brain radiotherapy may also be used for symptom control
Everyone to start cART
CT findings for PCNSL
May show ring enhancement
Diffuse and multi focal supratentorial brain masses
May involve vitreous, retina and optic nerves
What causes PEL?
HHV8 protea tumorigenedis by enhanced proliferation and impaired apoptosis in cells with latent gene HHV8 expression
EBV plays an unclear role
Presentation of PEL
Commonly - dyspnoea
As a result of pericardial or pleural involvement or abdominal distension from peritoneal involvement
How is PEL diagnosed?
Cytology of fluid
Morphologically- cells large, round to irregular nuclei, conspicuous nucleoli, may have appearance of immunoblasts, plasmablasts and/or anaplastic
Immunohistostaining for LANA-1 expression is standard for detecting HHV8
How to differentiate PEL from other NHL subtype with an effusion
No solid LN masses in PEL
HHV8 required for PEL
Treatment for PEL
Minimal data as low incidence of PEL
cART and CHOP
Advise patients to enter clinical trials
Subtypes of plasmablastic lymphoma
1 oral mucosa - monomorphic population of plasmablasts with minimal plasmacytic differentiation
- More differentiation and usually extra-oral
3rd associated with casteman’s - typically nodal or splenic
How is Plasmablastic lymphoma distinguished from immunoblastic variant of DLBCL
Immunophrnotyping
Low/absent cd45 and b cell markets
Plasma cell markers always present
Tumours almost always EBV positife
Prognosis plasmablastic lymphoma
Poor - 5/12 pre HAART
Median survival 24/12
31% 5 year survival
Treatment for plasmablastic lymphoma?
cART plus systemic anthracycline containing chemotherapy
How often should WLWH have smears?
Aged 25-65 - yearly
Has the incidence of cervical cancer changed with cART?
No but reduced incidence of CIN
Incidence increased in lower CD4 counts.
Higher CD4 associated with reduction of incidence and progression of CIN
CIN 1
Repeat colposcopy 12 months
Unlikely to develop cervical cancer
CIN2/3 management
Higher chance developing cervical cancer
Therefore treatment offered
Risk factors for CIN2/3 treatment failure
CD4 <200, high VL, non use of HAART
Compromised margins on excisional specimen are frequently seen in WLWH and are a risk factor for tx failure
Staging of cervical cancer
FIGO criteria
MRI/PET CT for staging
Treatment for cervical cancer
FIGO IA1 IA2 IB1 - surgery
Anything above that - surgery plus platinum based chemotherapy
Pathogenesis of anal cancer
HPV infection leading to AIN and ensuing progression from low to high grade dysplasia and subsequently invasive cancer
How to diagnose anal cancer
EUA and biopsy in all suspected cases
CT CAP for ?mets and MRI pelvis for LN and tumour extension
PET can have false positives in PLWH
First line treatment
For Anal Cancer
Concurrent chemoradiotherapy (shown to achieve local control and sphincter preservation)
5FU and mitomycin c
How has HAART impacted incidence of anal cancer?
Increased - people living longer, more chance for HPV to progress
Also improved SURVIVAL
Management of relapse of anal Cancer
22-25% in general population have persisting primary or recurrent disease
Treated with salvage surgery - abdominoperineal excision of rectum and anal canal with pedicle flap and colostomy
If metastatic disease or local relapse following salvage surgery can sometimes try palliative chemo - best supportive care may be more appropriate
Evaluation of response to tx for anal ca
6-8 weeks after completion - clinical exam, MRI pelvis and EUA
Review every 3-6/12 for 2yes then 6-12 mon this for 5 years
Screening for AIN
Not recommended in current guidelines - current treatments aren’t good enough to make screening worthwhile, tx can be uncomfortable have side effects and don’t always stop AIN from recurring
Diagnosis AIN
If symptomatic
Anal smear or anoscopy or proctoscopy with biopsy
Treatment low grade AIN
Further review in 6-12/12
No immediate treatment
Treatment high grade AIN
Options - surgery to remove lesions that cover a small area, cream eg Aldara or 5FU 2-3x week for 4/12, ablative therapies
In many cases the problem recurs as tx doesn’t get rid of HPV
OI prophylaxis for those undergoing cancer treatment
CD4 changes can be unpredictable with chemo and radiotherapy so OI considered regardless of CD4
KS treated by doxorubicin or paclitaxel not at increased risk so standard guidelines should be followed
1/12 after the end of chemo or radiotherapy repeat CD4 and reconsider
Prophylaxis for -
PCP <200 or at risk
fluconazole 50mg qds for everyone
HSV/VZV prophylaxis
NTM prophylaxis if detectable VL cd4 <50 or risk of dropping below 50
Histology of Hodgkin Lymphoma in PLWH
Predominance of mixed cellularity and lymphocyte depleted types with higher percentage of EBV positivity
Tests for HL in PLWH
Bone marrow biopsy mandatory as higher proportion of BM involvement in PLWH
Whole body PET
Baseline bloods and virology
Staging of HL (Ann arbor/Cotswolds)
- Single LN or lymphoid structure
- 2 or more LNs same side diaphragm
- LN groups both sides diaphragm
IV. Extranodal sites beyond those designated ‘e’
X - bulky disease >10cm
Or >1/3 widening of mediastinum at t5-6
E - Extranodal extension contiguous or proximal to known nodal site of disease
A/B - absence of B symptoms
Management of HL in PLWH
Less risky strategies used as precise Ed higher risk with HIV and less good-risk disease in PLWH
ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)
Number of cycles and addition of radiotherapy depend on risk factors and stage of disease
Early favourable ABVD X2-4 + IFRT 20-30
Early unfavourable ABVD x4 + ifrt 30
Advanced stage - ABVD x6-8 +/- RT
Can AVBD be given with HAART
Yes but increased risk of treatment related toxicities
Avoid PI/r - vinblastine mediated neurotoxicity and neutropenia given with ritonavir
Second line treatment for HL?
Salvage chemo and consolidation with high dose therapy with autologous stem cell rescue
OI prophylaxis in HIV associated lymphomas
PCP, MAI, fungal infection
What should HIV and HL patients requiring blood products be given?
Irradiated products
What is localised castlemans disease?
Usually in young adults
Masses in mediastinum, neck or less commonly intra abdominal
Systemic symptoms rare
What is multicentric castlemans?
Rare lymphopriferatjve disorder presenting with fevers, anaemia, lymphadenopathy
Multi organ systemic features
More aggressive
Symptoms of MCD
Malaise, night sweats, rigours, fever, anorexia, weight loss
Signs of MCD
Widespread lymphadenopathy
Often accompanied by one or more of- hepatosplenomegaly, ascites, oedema, pulmonary and pericardial effusions
May present with pancytopenia, renal or respiratory failure
Polyneuropathy and leptomeningeal and CNS infiltration with central pontine myelinolisis as well as myaesthenia Gravis.
PEL can also develop in presence of MCD
Test findings in MCD
Thrombocytopenia, anaemia, hypoalbuminaemia, hypergammaglobulinaemia.
Haemophagocytic lymphohistiocytosus may be present and confirmed on bone marrow
MCD originates from…
Hhv8 infected extrafollicular B cells
PELs originate from..
HHV8 infected pre terminally differentiated B cells that have traversed the germinal centre
Definition of an MCD ‘attack’
Fever, raised CRP and 3 of the following symptoms -
Peripheral lymphadenopathy, splenomegaly, oedema, pleural effusion, ascites, cough, nasal obstruction, xerostomia, rash, CNS symptoms, jaundice, autoimmune haemolytic anaemia
Things increasing risk of MCD
Nadir CD4 >200
Older age
No previous cART
Non caucasian background
How to diagnose MCD
Ct NCAP to identify lymphadenopathy, organ involvement and direct tissue sampling
Definitive diagnosis by LN biopsy
HHV8 viral load may aid in diagnosis and monitoring response to treatment (cut off >1000)
Histological findings in MCD
Onion skin appearance and interfollicular plasmablasts that express the HHV8 latent nuclear antigen
Recommended - immunocytochemical staining for HHV8 and IgM lambda
Treatment for MCD
Rituximab first line
CHOP chemotherapy should be added to this for aggressive disease
In relapse - rituximab based therapy
