Histiocytic sarcoma

Question 1

Define Histiocytic Sarcoma

Answer 1

a malignant neoplasm arising from the histiocytes (macrophages, dendritic cells).
Several forms; localized, disseminated and hemophagocytic.

Question 2

What is HHS?

Answer 2

Haemophagocytic Histiocytic Sarcoma. It is a distinct, aggressive form in which neoplastic cells demonstrate erythrophagocytosis.

Question 3

Mutations that inactivate tumour suppressor genes

Answer 3

CDKN2A/B
RB1
PTEN
TP53

Question 4

mutations that activate oncogenes

Answer 4

PTPN11
KRAS

Question 5

breed associated with genetic mutations that inactivate tumour suppressor genes and/or active oncogenes

Answer 5

Bernese Mountain Dog

Question 6

HS common sites of metastasis

Answer 6

lymph nodes, liver and lungs

Question 7

Haemophagocytic HS pathophysiology

Answer 7

1.Originates from macrophages; within spleen or bone marrow.
2. Rypically infiltrates organs diffusely rather than forming a discrete mass.
3. Neoplastic cells often exhibit marked erythrophagocytosis that results in anaemia.
4. Diffuse bone marrow infiltration is common and can cause cytopaenias.

Question 8

Pathophysiology of HS

Answer 8

Most forms arise from interstitial dendritic cells. HS can occur in any organ. Spleen, lungs, bone marrow, central nervous system (CNS), skin/subcutis, and periarticular/articular tissues of the limb are common sites. The neoplasm primarily causes destructive mass formation in the organ(s) involve. Common sites of metastasis are lymph nodes, liver and lungs.

Question 9

Expected biochemistry changes

Answer 9

• specific organ involvement
• haemophagocytic HS often have hypoalbuminaemia and hypocholesterolaemia

Question 10

Cytology of HS

Answer 10

• often shows round cell tumour or carcomatous cells.
• presence of multinucleated giant cells and erythrophagia by macrophages suggestive of HS
• erythrophagocytosis by neoplastic cells within spleen, liver, lung and/or bone marrow is seen with haemophagocytic HS

Question 11

Histopathology of HS

Answer 11

• definitive diagnosis
• HS is typically composed of sheets of large, pleomorphic, mononuclear cells
• cellular atypica, bizarre mitotic figures and multinucleated giant cells are common
• some masses may consist partially or entirely of spindle cells that lack discrete cell borders

Question 12

HS immunohistochemistry

Answer 12

• positive staining with 5 markers is typical, including CD1 and CD11c (ID cell of dendritic origin), CD18 and CD45 (ID leukocytes) and MHC11 (ID APCs)
• other supportive markers; vimentin, lysozyme

Question 13

Commonly affected breeds

Answer 13

Bernese Mountain Dog, Rottweilers, Retrievers, mini schnauzer, corgis

Question 14

Prognosis of HS

Answer 14

guarded to grave; response rates to treatment are poor and survival times short (3-6mnths)
- HHS: median survival time of 7.1weeks
- LHS: surgery + chemo; 1.5-2.7yrs. No chemo - 57 days.

Question 15

Surgical tx of LHS

Answer 15

• recommended when no signs of metastasis on staging
• dependent on location; limb amputation, lung lobectomy

Question 16

Chemotherapy for HS

Answer 16

• doxorubicin
• lomustine
• epirubicin, dacarbazine, vinorelbine

Question 17

Recommended monitoring for HS

Answer 17

• CXR and abdo US q2m
• dependent on chemo protocol; if lomustine CBC and ALT prior to each dose