AIDs related Malignancies

Question 1

5 AIDs defining cancers

Answer 1

kaposi sarcoma peripheral lymphoma primary CNS lymphoma primary effusion lymphoma (PEL) squamous cell carcinoma of the cervix

Question 2

kaposi sarcoma

Answer 2

purple/red/brown blotches/tumors on skin due to disrupted endothelium that lines vessels strongly related to immune deficiency (HIV) caused by KSHV (kaposi sarcoma herpes virus) or HHV8 (human herpes virus 8) shed in the saliva (transmission) does NOT integrate, remains episomal

Question 3

factors present in kaposi sarcoma that are set up for malignancy but cells themselves are not transformed

Answer 3

LANA1 - inhibits p53 tumor suppressor and induces angiogenesis vCyclin - induces entry to cell cycle by blocking cyclin D kinase inhibitors vFLIP - inhibits apoptosis

Question 4

biopsy of kaposi sarcoma will show

Answer 4

spindle cells (lymphatic endothelial cells) near disrupted vessels they are LANA+

Question 5

treatment when KSHV infection is lytic and cells are transformed

Answer 5

ART wont work use sytotoxic chemotherapy = liposomal adriamycin, doxorubicin or paclitaxel

Question 6

biopsy of burkitt lymphoma will show

Answer 6

starry sky = macrophages amongst packed lymphocytes

Question 7

endemic burkitt is associated with what virus

epidemic burkitt is associated with what virus

Answer 7

endemic –> EBV +, africa

epidemic –> HIV associated

Question 8

diffuse centroblastic vs diffuse immunoblastic large B cell lymphomas

Answer 8

Diffuse immunoblastic are 100% EBV+ and immune suppressed patients

diffuse centroblastic are 30% EBV and in people with relatively good immune systems (CD4 count is still good)

Question 9

treatment for peripheral lymphomas

Answer 9

EPOCH or CHOP

etoposide

prednisone

vincristine (oncovin)

cyclophasphamide

doxorubicin (hydroxydaunorubicin)

AND all patients receive CNS prophylaxis to prevent meningeal disease with subarachnoid/intrathecal methotrexate or cytosine arabinoside

Question 10

what is used for CNS prophylaxis in peripheral lymphoma patients

Answer 10

subarachnoid/intrathecal methotrexate or cytosine arabinoside

Question 11

primary CNS lymphoma

Answer 11

BAD prognosis

usually diffuse large B cell immunoblastic

anti-CD20 to indicate B cells

anti-EBER stain indicates EBV (always EBV+)

occurs in longstanding HIV ifx (<<200 CD4 count)

Question 12

treatment for primary CNS lymphoma

Answer 12

optimize ART

radiation of 4000 cGy to the brain

multi chemotherapy with high dose methotrexate and leucovorin rescue, temozolomide and rituimab

followed by

ARA-C and etoposide

***very harsh treatment; these patients get very sick

Question 13

PEL

primary effusion lymphoma

Answer 13

B-cell lymphoma, presenting with a malignant effusion without a tumor mass caused by KSHV and often coexists with kaposi sarcoma

• Pulsus paradoxus is present (abnormally large decrease in systolic blood pressure during inspiration = worry for heart issue)
  
  • Pleural and/or pericardial effusion à heart cant expand
  • usually restricted to the pleura, pericardium, or peritoneum
• Rare, Usually in young, homosexual men with advanced HIV
• Survival < 6 months; tumor is refractory to chemotherapy
• Tumor cell is B cell lineage:
  
  • Uniformly express KSHV; frequently EBV
  • Ig heavy chain rearrangement
  • Kappa and lambda light chain restriction
  • CD20 negative

Question 14

squamous cell carcinoma of the cervix

Answer 14

associated with high risk HPV16 and HPV18

in intact immune systems, HPV infection is cleared but in immune deficient women, HPV becomes persistent –> the longer it persists the more likely it will turn from episomal to integrated

Question 15

in SCC of the cervix, why is there a low risk of malignancy when virus is episomal and why higher risk when integrated?

Answer 15

• Low risk of malignancy when episomal because E2 suppresses the expression of E6 and E7 (which block p53 and Pb tumor suppression)
• Persistence –> disrupts E2 and E6 and E7 can be expressed (carcinogenic)

Question 16

what do these agent infect

KSHV

EBV

HPV

Answer 16

KSHV - lymphatic endothelial cells and B cells

EBV - B cells

HPV - squamous epithelial cells

Question 17

when does cART work to control KS and CIN?

Answer 17

• cART works well to control KS and CIN before the target cells are transformed. Once transformed, the patient will need more than cART to prevent or control malignancy.