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Onco Board Review 2 > Histiocytic > Flashcards

Histiocytic Flashcards

1
Q

IHC markers for cutaneous histiocytoma?

A

E-cadherin

CD1a+, CD11c+, MHCII+. CD4-, Thy1/CD90-, Ecad+
Langerhans cells

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2
Q

IHC markers for histiocytic sarcoma?

A

CD1+, CD11c+, MHCII+, CD4-, Thy1-, Ecad-
Differentiate from histiocytoma because Ecad-
Also Iba1
(Interstitial DC)

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3
Q

IHC markers for cutaneous histiocytosis?

A

CD1+, CD11c+, MHCII+, CD4+, Thy1+

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4
Q

IHC markers for systemic histiocytosis?

A

CD1-, CD11c+, MHCII+, CD4+, Thy1+

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5
Q

IHC markers for hemophagocytic histiocytic sarcoma?

A

CD1 (low), CD11c-, CD11d+, MHCII+

Unique one is the CD11d+

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6
Q

What cell type mediates regression in histiocytomas?

A

CD8+ αβ T-cells

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7
Q

Signalment typical for histiocytoma?

A

Often dogs <3 yrs, cranial portion of body; often spontaneously regress in 1-2 months

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8
Q

What is the general outcome for dogs with LN metastatic histiocytoma treated with surgery?

A

Favorable - can spontaneously regress even if metastatic

Faller JSAP 2016

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9
Q

What is the major differentiating factor between the two reactive histiocytoses?

A

cutaneous histiocytosis - Limited to skin and SQ;
systemic histiocytosis - dermal, SQ, LN, BM, spleen, liver, lung, MM can be involved (nasal/ocular)
Both are CD4+ (differentiates from histiocytomas and HS)

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10
Q

How do outcomes for the two reactive histiocytoses vary?

A

Cutaneous - responds to immunosuppressive therapy (steroids)

Systemic - often prolonged but refractory to tx, most dogs euthanized due to relapse or failure to respond

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11
Q

What is the MST for PAHS treated with amputation alone? Metastatic rate for PAHS?

A

MST 6 months, metastatic rate 91%

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12
Q

What is the ORR of canine HS to CCNU? Does pred improve response?

A

46% RR with gross dz
remission duration 85d, MST for responders 172d
pred does not improve response

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13
Q

What is the ORR of canine HS to DOX/CCNU?

A

58% (Cannon JSAP paper)

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14
Q

What are 3 negative prognostic factors for HS?

A
  1. localized vs. disseminated (PAHS may be better)
  2. hemophagocytic variant more aggressive
  3. anemia, thrombocytopenia
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15
Q

What 3 genes are differentially expressed in visceral vs. soft tissue HS in flat coat retrievers? (Boerkamp 2014)

A

C6 unregulated in visceral vs. soft tissue form
CLEC12A down regulated in visceral
CCL5 down regulated in visceral

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16
Q

What medical intervention is associated with DECREASED risk of HS in Berners? (Ruple 2016)

A

Prescribe anti-inflammatory meds for orthopedic dz

orthopedic conditions –> more likely to develop HS

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17
Q

What are the unique MRI characteristics of histiocytic sarcoma in the brain? (Tamura 2009)

A

Tamura - can be confused for meningioma (dural tail, broad base) or encephalitis; doesn’t appear to have unique features

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18
Q

Which bisphosphonate/chemo combinations may be beneficial in canine HS? (Hafeman 2011)

A

Zoledronate + DOX enhanced cell kill (zoledronate increased cell uptake of DOX)
Clodronate + vincristine synergistic cell kill

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19
Q

What is the cell of origin of hemophagocytic HS?

A

Macrophage

- more aggressive form, invariably involves spleen and can also involve liver, BM, LN, and/or lung

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20
Q

What are most common hematologic findings in dogs with hemophagocytic HS?

A

regenerative anemia, thrombocytopenia, hypoalbuminemia, hypocholesterolemia

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21
Q

What is the cell of origin in histiocytoma?

A

Langerhans cells (intraepithelial dendritic cells)

22
Q

What is the prognosis for PAHS vs. synovial cell?

A

PAHS 9-12 mos (~300d)

Synovial cell 3-4 mos

23
Q

Which breed is over-represented for cutaneous Langerhans Cell Histiocytosis

A

Shar-peis

24
Q

What dog breeds were overrepresented with CNS HS? What was the MST in this study? (Mariani 2015)

A

Retrievers and Pembroke welsh corgis
MST 3 days
(all in this study had histopath CNS diagnosis)

25
Q

Are PDGFRbeta and c-KIT expressed in feline histiocytic diseases? (Treggiari 2015)

A

PDGFR-beta was variable, c-KIT negative in all tumors

15 cases

26
Q

Do feline histiocytic diseases respond to CCNU? Toceranib? (Treggiari 2015)

A

Partial responses were documented to each

27
Q

What % of HS expressed CD204 in Kato 2013?

A

100% (all 50 samples); all other round cell tumors were negative for CD204
Also expressed CD18 and MHCII

28
Q

Are most cases of histiocytic sarcoma in flat coated retrievers disseminated or localized? (Constatino 2011)

A

57% were primary limb lesions
26% were visceral - mainly spleen

All expressed MHCII and CD18, spleen consistently expressed CD11d

29
Q

What population of cells were noted to infiltrate HS lesions of flat coated retrievers? (Marcinowska 2017)

A

FoxP3+ (Tregs) - higher in the soft tissue lesions

30
Q

Does e-cadherin successfully distinguish cutaneous histiocytoma from other round cell tumors? (Ramos-Vera 2011)

A

No

31
Q

What breed was recently determined to be predisposed to HS based on pedigree analysis? (Lenz 2017)

A

Miniature schnauzers

32
Q

What % of dogs with stifle PAHS had prior joint disease?

A

88.2%

Most common was CrCL rupture

33
Q

What are Birbeck’s granules?

A

Found in Langerhans cells

34
Q

Does canine HS express COX-2?

A

No (Heller 2005)

35
Q

What was the ORR and TTP of HS to DOX/CCNU? (Cannon 2015)

A

ORR 58%, TTP 185d

36
Q

How did a survivin suppressor affect HS in a murine model?

A

Enhanced chemosensitivity

37
Q

What is DFI and MST for dogs with localized HS treated with aggressive local therapy + CCNU? (Skorupski 2009)

A 
DFI 248d (8.3 months) MST 568d (18 months)
50% developed mets
38
Q

RR to CCNU of macroscopic HS? MST? (Skorupski 2007)

A 
ORR 46%
MST 106d (3.5 months)
39
Q

ORR of HS to epirubicin? (Mason 2017)

A

29%

very messy study

40
Q

What is the odds ratio for a dog with previous joint disease developing PAHS? (van Kuijk 2013)

A

5.4

41
Q

What gene region encoding for p16 may be associated with HS development? (Ruple 2016)

A

CDKN2A/B

42
Q

Berners have a ___% lifetime risk of developing HS.

A

25%

43
Q

In a study evaluating primary pulmonary histiocytic sarcoma, dogs who had surgery followed by chemo had much longer PFS at ___ and OS at ___. (Marlowe 2018)

A

PFS 276d

OS 374d

44
Q

IHC markers for reactive histiocytosis?

A

CD4, Thy-1 (CD90)

45
Q

IHC marker for hemophagocytic HiSa?

A

CD11d

46
Q

What is unique about many of the IHC stains for histiocytic diseases?

A

must be performed on fresh smears or snap frozen tissues

47
Q

What was discovered regarding miRNA leg-7g in BMDs with disseminated HiSa? (Borresen VCO 2016)

A

significantly down-regulated in dogs with disseminated HiSa compared to healthy controls

48
Q

MST for synovial cell sarcoma (by grade and mets vs. no mets)?

A

mets - <6 months, no mets 36 months
Grade 1: 48 months
Grade 2: 36 months
Grade 3: 7 months

49
Q

Where does hemophagyocytic HiSa originate from?

A

splenic red pulp and bone marrow

CD11d+

50
Q

What two important genes have shown copy number aberrations in HiSa?

A

PTEN

CDKN2A

Onco Board Review 2 (20 decks)

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