Histiocytic disease Flashcards
Tsai et al. Imaging characteristics of intrathoracic histiocytic sarcoma in dogs
Reviewed studies from 39 dogs
Most common findings noted by 1st and 2nd observer?
Common location in the lung?
Common LNs affected?
Intrathoracic lymphadenopathy - 82% and 87% and Pulmonay mass - 74% and 82%
Ventral aspect of the R middle
Sternal and tracheobronchial more common than cranial mediastinal
Nielsen et al. Investigation of a screening programme and the possible identification of biomarkers for early disseminated histiocytic sarcoma in Bernese Mountain dogs
Construct a screening programe for DHS in Bernese Mountain Dogs
How were dogs identified?
What showed potential as blood borne marker?
MST for early DHS?
Screening program how often and diagnostics?
Diagnostic imaging (n=4)
Serum ferritin (n=1)
226 days (7.5 mo)
Every 6 months for dogs over 4 years including diagnostic imaging and ferritin
Moore et al. 2012. Histologic and Immunohistochemical Review of Splenic Fibrohistiocytic Nodules in Dogs
Composed of malignant and non-malignant disease (SFHN)
32 dogs with SFHN
Median OS?
What was associated with survival time?
What diseases were SHFN reclassified?
Survival for dogs with HS?
387 days (~1yr)
Grade 3 SFHN
Nodular hyperplasia, lymphoma, stromal sarcomas and histiocytic sarcomas
74 days
Kato et al. The Class A Macrophage Scavenger Receptor CD204 is a useful IHC marker of Canine Histiocytic Sarcoma
All the HSs expressed what markers?
Less commonly expressed markers for HS?
Round cell tumor expression for CD204?
CD204, CD18, MHCII
CD163 (27/50) and CD11d (7)
Negative except for 1 grade III MCT
CD204 is a useful marker for canine HS
Barger et al. 2012. Cytologic identification of erythrophagocytic neoplasms in dogs
Identify neoplasms that exhibit erythrophagia
What were the neoplasms that exhibited erythrophagia?
Differentials for erythrophagia?
HSA (12/34), HHS (11), OSA (9), MCT (1), T-cell LSA (1)
Spindle cell sarcoma, OSA, HSA, HHS
Ito et al. 2013. Identification of dasatinib as in vitro potent growth inhibitor of canine HS cells
Dasatinib targets several kinases
Examined effect in 6 HS cell clines and MDCK cells
Result?
Inhibited growth in 4 HS cell lines
Kinase targeted by dasatinib is crucial for growth in some HS
Boerkamp et al. 2013. Gene expression profiling of histiocytic sarcoma in canine model: the predisposed FCR dog
Which genes were upregulated?
Which genes were downregulated?
Analysis revealed 24 pathways were involved in development of HS, most of which involved?
GTSF1, Col3a1, CD90, LUM
PPBP, SpiC, VCAM1, ENPEP, ITGAD
DNA repair and replication
Kuijk et al. 2013. Periarticular Histiocytic sarcoma and previous joint disease in Bernese Mountain Dogs
PAHS may be more frquent around diseased joints in BMD
A significant association between joint disease and PAHS was demonstrated for which joints?
Left elbow, right elbow, right shoulder, left and right stifle, and left carpal joint
Abbondati et al. 2013. An immunohistochemical study of expression of the hypoxia markers Glut-1 and Ca-IC in canine sarcomas
HIF-1 induces trasncription of Glut-1 and Ca-IC- endogenous markers of chronic hypoxia in humans
What was the expression of Glut-1 in HS?
What was positively associated with immunoreactivity score?
High compared to low grade STS
Intratumoral microvessel density
Nielsen et al. 2013. Monocyte chemotactic protein-1 and other inflammatory parameters in BMD with disseminated HS
EValuate the immunological state of untreated BMD with DHS
Significant differences were not between BMD and healthy controls with which factors?
Fibrinogen, CRP, MCP-1 (monocyte chemotactic protein)
Heinrich et al. 2014. Passage-dependent morpholocial and phenotypical changes of a canine histiocytic sarcoma cell line
Early passaged cells were characterized by round cell bodies with small cytoplasmic projections and later passages exhibited spindle shaped morphology with larger processes
The % of CD11c- CD14-, CD18-, CD45-, and CD80 positive cells were decreased in late passages
Expression of CD44, CD86, MHC I, MHC II and ICAm-1 remained unchanged
Erich et al. 2013. Causes of death and the impact of HS on the lide expentancy of the Dutch population of Bernese mountain dogs and FCR
What % of deaths in BMD and FCR is associated with malignant tumors?
How many die from HS?
55% BMD and 64% FCR
1/7 (14%)
Yamazaki et al. 2013. Inhibition of survivin influences the biological activities of canine HS cell lines
Survivin is an apoptotic inhibitor factor
Survivin gene levels in 30 HS specimens?
After transfection with survivin siRNA what happened?
Significantly high
Apoptosis, growth cell inhibition, enhanced chemosensitivity, and weaked phagocytic activities
No effect was seen in normal fibroblasts
Survivin may mediate aggressive biological activites of HS and may be a therapeutic target
Yamazaki et al. 2014. Comparative analysis of mRNA expression of surface antigens between histiocytic and nonhistiocytic sarcoma in dogs
Surface antigens (SA) assesed CD11b, CD11c, MHC class IIa, CD86
SA mRNA expression in HS dogs to non-HS dogs?
Accuracy of the cutoff values were MHC Class IIa 88%, CD11b 86%, CD11c 86%, CD86 85%
Significantly higher in HS dogs
Boerkamp et al. 2014. The two main forms of histiocytic sarcoma in predisposed FCR dogs display variation in gene expression
Microarray analysis of either soft tissue- or visceral HS
Which gene was upregulated in the visceral compared to soft tissue form?
Downregulated compared to soft tissue form?
C6
CLEC12A and CCL5
Kato et al. Immunohistochemical detection of the class A macrophage scavenger receptor 2014 using air-dried cytologic smears of canine HS
Validate an anti-human CD204 Ab
10 dogs with CHS and 45 dogs with other tumors
Results?
All 10 CHS showed intense positive staining in >50% cells the other 45 tumors were negative
Pierezan et al. 2014. Immunohistochemial expression of ionized calcium binding adapter molecule 1 in cutaneous histiocytic proliferative, noeplastic and inflammatory disorders of dogs and cats
Iba1 is marker of glial cells and pan-macrophage marker
Which had strong cytoplasmic expression for Iba1?
Which were negative?
Cutaneous histiocytoma, reactive histiocytosis, HS, feline progressive histiocytosis, macrophage in cutaneous mycobacteriosis.
Melanoma, LSA, MCT, plasmacytomas
Iba1 does not differentiate between macrophage and dendritic antigen presenting cells or histiocytic disorders
Yamazaki et al. 2015. Survivin suppressor (YM155) enhances chemotherapeutic efficacy against canine histiocytic sarcoma in murine transplantation models
HS cells with CCNU resistance, YM155 treatment did what?
Suppressed cell growth and cell resistance to CCNU
Yamazaki et al. 2015. Influence of a survivin suppressor YM155 on the chemoresistance of HS cells
Elevated survivin expression in HS dogs corresponded with?
YM155 treatment?
Reduced DFI anf survival time and increased chemoresistance
Supressed cell growth and resistance to CCNU by inhibiting activity of ATP-binding cassette transporters
Cannon et al. Evaluation of a combination chemotherapy protocol including lomustine and doxorubicin in canine HS
CCNU and DOX alternating every 2 weeks
15/17 dogs had disseminated disease
Side effects?
Overall response rate?
Median time to progression?
Overall MST?
Dose reductions in 18% of cycles
58%
185 days
185 days
Hostettler et al. Post mortem CT and core needle biopsy in comparison to autopsy in eleven BMD with HS
Thongthard et al. 2016. Histological and immunohistochemical studies on primary intracranial canine histiocytic sarcomas
Where were the tumors mainly located?
Predominant clinical sign?
Significant association noted between?
Tumor cells were stongly positive for what IHC markers?
Ki67 proliferative index?
Cerebrum, particularly frontal lobe
Seizures
Tumor cell type and hemophagocytic activity
HLA-DR, Iba-1, CD204 (23 cases), INOS (20), CD163 (17), CD208 (9), Lysozyme (8), S100 (5)
0.5-64%
Primary intracranial HS exhibit both dendritic and macrophage phenotye
Borresen et el. 2017. Circulating let-7g is down-regulated in BMD with disseminated histiocytic sarcoma and carcinomas - a prospective study
miRNA let-7g was downregulated in dogs with cancer and dogs with DHS compared to healthy controls
Known tumor suppressor gene
Tagawa et al. 2016. Evaluation of Costimulatory Molecules in Peripheral Blood Lymphocytes of Canine Patients with HS
Dogs with HS, other tumors, and healthy controls
CTLA-4 expression on CD4+?
CTLA-4 expression on CD8+?
PD-1 expression on CD8+?
IFN-g and CD28 expression?
Significantly higher in HS group than in control group
Significantly higher in HS group than in control group
Significantly higher in HS group than in control group
No difference
Ishikawa et al. 2016. Comparison of conventional MRI and nonenhanced 3D time of flight MR angiography findgins between dogs with meningioma and dogs with intracranial HS: 19 cases
14 dogs with meningioma and 5 with IHS
Tumor type was significantly associated with signal intensity on?
Tumor type was not associated with?
Vessel adjacent to meningiomas were displaced in 8/9 dogs and with IHS not displaced
T2-weighted and fluid-attenuated inversion - meningiomas were hyperintense and most IHS were isointense or hypointense
Signal uniformity, tumor location, tumor orignin, edema, midline shift, brain herniation
Ruple et el. 2016. Risk factors associated with development of HS in BMD
Dogs diagnosed with ____ condition were found to be more likely to develop HS?
Dogs receiving prescrition ____ were found to be considerable lower risk?
Orthopedic conditions
Anti-inflammatory medications
Inflammation may be modifiable risk factor for the development of HS
Dervisis et el. 2017. Clincial prognostic factors in canine histiocytic sarcoma
Most comonly represented breed?
Median survival for all dogs?
Negative factors associated with survival?
BMD (53), Labrador retriever (26) and Golden Retreiver (17)
170 days
Palliative treatment, disseminated HS, use of corticosteroids
Faller et al. 2016. Retropsective characterisation of solitary cutaneous histiocytoma with LN metastasis in 8 dogs
Samples were positive for and negative for?
E-cadherin?
Outcome known for 3 dogs?
CD18 postive and CD11d negative
Reactivity varied
1682 days, 570 days, 318 post-diagnosis (1-4 years)
Metastatic histiocytoma is rare but some may have favourable outcome
Moore et al. 2017. Chemotherapy for dogs with LN metastasis from HS
12 dgos with HS metastatic to LN treated with surgery with and without chemotherapy
MST for 8 dogs that received chemotherapy? 1- and 2- year estimated survival?
MST for 4 dogs with LN mets and no chemo?
219 days (7.3 mo), 38%
57 days none alive at 1 year
Marcinowska et al. 2017. T lymphocytes in Histiocytic Sarcomas of Flat-Coated Retriever Dogs
40 tumors to examinat T regulatory cells
Foxp3 expression?
FOXP3 versus CD45RA
Difference in expression may be related to?
95% of infiltrating T cells were positive by IHC
cell positive for FOXP3 were higher in soft tissues, CD45RA positive cells was higher in splenic origin HS
Differences in the tumor microenvironment
Thongthard et al. 2017. Variations in Histiocytic Differentiation of Cell Lines From Canine Cerebral and Articular Histiocytic Sarcomas
2 new cell lines - PWC-HS01 and FCR-HS02 obtained from brain and articular tumors
PWC-HS01 expressed dendritic (S100, CD208, CD1, CD4) and macrophage (CD68, CD163, CD204 markers)
FCR-HS02 negatve for CD204 and CD68 and positive for dendritic cell markers
HS from CNS may have tendency to more undifferentiated compared from other organs
Wada et al. 2017. Comparisons among MRI signs, apparent diffusion coefficient, and fractional anisotropy in dogs with solitary intracranial meningioma or HS
Kezer et al. 2017. Efficacy of dacarbazine as a rescue agent for HS in dogs
17 dogs with disseminated disease prior tx with CCNU
Overall response rate?
Median event free survival?
Median EFS for dogs that experienced objective response?
18% with 3 PR
21 days
70 days
Lenz et al. 2017. Histiocytic sarcoma in 14 minature schnauzers - a new predisposition?
14 MS with HS
10 had localized disease and 4 had disseminated disease
9 had primary pulmonary HS (7) without intrathorathoracic metastasis (2), 1 had gatric HS with nodal metastasis
Pedigree analysis revealed common ancestor - inherited risk factor
Mason et al. 2017 Epirubicin in the treatment of canine HS: sequential, alternating and rescue chemotherapy
29 dogs alternating epirubin and lomustine - ORR? BRR? Median time to progression? MST?
Dogs treated in resceue setting with epirubin - ORR? BRR? Median TTP?
29%, 71%, 69 days, 185 days
19%, 63%, 62 days
Manor et al. 2017. Prior joint disease is associated with increased eisk of periarticular HS in dogs
Study included variety of dog breeds
Dogs with PAHS were more likely to have ____ in the tumor affected joint compared with control population?
A total of ___% with stifle PAHS had prior joint disease
Joint disease
88%
Association with joint disease and PAHS also applies to other breeds
Thaiwong et al. 2017. Gain of function mutation in PTPN11 in HS of BMD
Nakano et al. 2017. Flourescein sodium-gated resection of intracranial lesions in 22 dogs
Adverse effect was vomiting in 2 dgos
Pattern between preoperative Gd enhancement and intraoperative FS?
High grade glioma and HS had more ____ FS staining
Lesions with strong Gd enhancement, meningiomas and choroid plexus tumors, also had ___ FS staining
Agreed
Intense
Intense
Pinto da Cunha et al. 2014. Cytologic and Immunohistochemical characterization of feline progressive histiocytosis
Neoplatic cells expressed?
E-cadherin expression?
Absent birbeck granules in 1 case
CD1a, CD1c, CD11b, CD18, MHC II
Positive except for 1
Treggiari et al. Clinical outcome, PDGFRB and KIT expression in feline histiocytic disorders: a muticenter study
5 FPH, 8 HS, 2 HemoHS
PGFRB and KIT expression?
PR noted with TKI and CCNU, and RT
Survival time shortest with?
Variably positive in most and KIT negative in all
HemoHS
PDGFRB may represent therapeutic target but not KIT
Fayyad et al. 2018. Matric metalloproteinases expression in spontaneous canine HS and its xenograft models
Marlowe et al. 2018. Primary pulmonary HS in dogs: a retropsective analysis of 37 cases
37 dogs: 13 CCNU alone, 18 Sx and CCNU, 3 medical management, 3 surgery alone
Median PFS and OS?
Measurable responses noted in dogs receicinv?
Which group had prolonged survival?
What negatviely impacted PFS?
197 (6.6 mo) and 237 days (8 mo)
chemotherapy - not durable with PFS 91 days and OV 131 days
Surgery and chemotherapy - PFS 276 days (9.2 mo)
Clincial signs or metastasis at time of diagnosis
Toyoda et al. 2019. Clinicopathological characteristics of HS affecting the CNS in dogs
100 dogs with HS and 62 with meningiomas
Predisposition of CNS HS in what breeds?
Corgis and Shetlands had what type? Rotties?
Primary was characterized by?
What was noted in all dogs relative to controls?
WHat resulted in improved survival time?
BMD, Goldens, Rottie, Corgis, Shetland Sheepdogs
Primary tumors. Disseminated.
Marked CSF inflammation and neoplastic cells noted 52% in CSF
Increased neutrophil to lymphocyte ratio
Definitive versus palliative treatment
Quinci et al. 2019. Ultrasonographic Honeycomb pattern of the spleen in Cats: Correlation with Pathological Diagnosis in 33 Cases
33 cats - 15 lymphoid hyperplasia, 8 LSA (4 B and 3 T and 1 LG), 6 splenitis, 3 EMH, 1 HS
Presence of LSA with HCP in spleen?
Most common feature with HCP in cats LSA?
Visualization with linear and micro-convex transducers?
24%
Splenomegaly
100% and 62.5%
Asada et al. 2019 Effect of two-base insertion mutation of the TP53 gene on expression of p53 protein in canine histiocytic sarcoma cells
Effect of common 2-base insertion mutation in exon 5 of TP53 gene
Expression of p53 protein and its function as TF were lost after mutation in canine histiocytic tumor cells
Igase et al. 2019. Anti-tumor activity of oncolytic veovirus against canine histiocytic sarcoma cells
Reovirus can replicater and induce caspace-dependent apoptosis in canine HS cell lines
A single intratumoral injection suppressed growth of SQ grafted tumors in NOD/SCID mice
Cell death attributed to type I IFNA induced by reovirus
