Exam 4 - Histiocytic Sarcoma Flashcards
what are the 2 main disease forms seen with histiocytic tumors?
- reactive histiocytosis - NOT neoplastic (autoimmune inflammation driven by T cells) - cutaneous or systemic
- neoplastic histiocytosis - histiocytes are truly neoplastic & drive the disease - cutaneous histiocytoma (benign), solitary histiocytoma (likes the elbows), & disseminated (acts like lymphoma)
T/F: histiocytic cancer is rare, and only 1% of tumors affect lymphoid tissue
true
what are your dendritic cells?
langerhan’s, kupffer, tissue antigen presenting cells, & macrophages
what are the different paths that may be taken from the common progenitor cell that results in the different forms of histiocytic tumors?
- common progenitor cell -> myeloid stem cell CD 34+ -> CD1+ CD14- = langerhans/dendritic cell = HISTIOCYTOMA (benign)
- common progenitor cell -> myeloid stem cell CD 34+ -> CD1- CD14+ -> HISTIOCYTIC SARCOMA CD1+CD11c+MHCII+CD4-Thy-Ecad- = REACTIVE HISTIOCYTOSIS (like lymphoma)
- common progenitor cell -> monoblast CD34- -> blood monocyte -> macrophage -> low CD1 expression, CD11c-CD11d+MHCII+ = HEMOPHAGOCYTIC HISTIOCYTIC SARCOMA WORST PROGNOSIS
what is hemophagocytic histiocytic sarcoma?
the worst type of histiocytic sarcoma - macrophages eat everything in the body (including RBC) - most animals don’t survive past 30 days
what dog breeds are the usual suspects for reactive histiocytosis?
flat coated retrievers
bernese mountain dogs
what are the stats on bernese mountain dogs getting cancer?
92% chance of getting cancer in their life
average life span of 6 years
what breed is worse than golden retrievers when it comes to getting cancer?
bernese mountain dogs
what is the lesion shown? what signalment of animal is often affected by it? where are they often seen?
reactive cutaneous histiocytosis - benign, diffuse aggregation of histiocytes in the skin
signalment - young to middle aged dogs with a possible male predilection
locations - head, pinna, scrotum, nasal planum, & mucosa
how is cutaneous histiocytosis diagnosed? how is it staged?
diagnosed - biopsy (want 2-3 samples, normal & abnormal junction), FNA is often difficult to distinguish between inflammation & granulomas
staging done even if cutaneous is suspected because it could be a worse prognosis if it is the systemic form - baseline blood work, chest rads, & lymph node aspirates (sternal lymph nodes drains skin of ventral chest/abdomen or cranial mediastinal lymph nodes if draining head & neck)
T/F: it is rare to have systemic histiocytosis that doesn’t involve the skin
true
what therapy is used for cutaneous histiocytosis?
tetracycline/doxycycline + niacinamide + vitamin e (helps the skin heal faster) = help suppress t-cell function & drive down the immune response
if that doesn’t work, can try steroids, chemo (lomustine most intense), etc - radiation for local lesions for dogs that are mostly in remission
what is the prognosis for cutaneous histiocytosis?
fair to guarded - spontaneous regression is possible, but chronic relapses & drug failures are common
euthanasia is done due to poor QOL
what breeds are predisposed to getting systemic histiocytosis?
bernese mountain dogs, rottweilers, golden retrievers, flat coated retrievers, & irish wolf hounds
what is systemic histiocytosis?
non-neoplastic disease of proliferating lymphocytes (autoimmune disease)
what animals are predisposed to getting systemic histiocytosis?
male, middle aged dogs
what common locations do we see systemic histiocytosis manifest?
subcutis, lymph nodes, bone marrow, liver, spleen, scrotum, lung, ocular tissue, & mucus membranes
T/F: the clinical signs seen in patients with systemic histiocytosis reflect the organs that are involved
true
what clinical signs are associated with systemic histiocytosis?
signs often wax & wane
anorexia, depression, weight loss, harsh breathing, & PU/PD (hypercalcemia)
what is the etiology of systemic histiocytosis?
dysregulation of the immune system - helper t cells
infiltration of lymphocytes DOES NOT indicate spontaneous regression in this disease!!!
what organ is most likely to be affected in cutaneous histiocytosis?
the liver (maybe spleen)
is PU/PD seen in systemic histiocytosis due to hypercalcemia of malignancy? why?
NO!!!
monocytes produce vitamin D analogue which drives calcium up!
does infiltration of lymphocytes indicate spontaneous regression in systemic histiocytosis? what about in a cutaneous histiocytoma?
systemic - NO!!!!
cutaneous histiocytoma - YES
how is systemic histiocytosis diagnosed? how is it staged?
biopsy - well differentiated benign histiocytomas, multinucleated giant cells, deep lesions in the skin, interstitial dendritic cells instead of langerhan’s (more superficial cell type)
staging - same as cutaneous form
what therapy is used for systemic histiocytosis?
same as cutaneous - start with steroids + tetracycline/niacinamide combo
try leflunomide (arava) before cyclophosphamide
what is the prognosis for systemic histiocytosis?
not great?
periods of response to therapy with recrudescence (relapse quickly)
overall survival times range from 18-24 months with regressive therapy
euthanasia is done due to drug resistance & chronic recrudescence
what differentials should you consider for systemic histiocytosis?
granulomatous disease & cutaneous histiocytosis
what lesion is this? what animals are affected by it?
cutaneous histiocytoma - benign skin lesion, always epidermal in origin, non-haired, pink, rubbery, & fleshy that is derived from langerhan’s cells
occurs most often in younger dogs
what is seen on FNA of a cutaneous histiocytoma?
round cells with abundant clear cytoplasm, vacuoles, eccentrically located nucleus, & small lymphoctes
how are cutaneous histiocytomas diagnosed? what about staging?
FNA cytology is all you need
staging is generally not necessary as these often regress on their own
what may happen to cutaneous histiocytomas as they regress?
may become reddened/ulcerated (lymphocyte mediated regression) - why owner’s bring their pet in
when may you remove a cutaneous histiocytoma?
can be removed with narrow margins if it is causing the patient any discomfort - like on the eye or between the toes
what clinical signs are seen with the visceral form of histiocytic sarcomas? what is the prognosis?
general malaise, anorexia, weight loss, cough/dyspnea
worse prognosis than periarticular
what clinical signs are seen with the periarticular form of histiocytic sarcomas? what is the prognosis?
pain, swelling - can be super subtle (not palpable)
loves the elbows!!!
how are histiocytic sarcomas diagnosed?
FNA is all you need - usually super characteristic appearance
can do special stains for CD18 & CD11
what differentials should you consider for histiocytic sarcomas?
other round cell tumors, undifferentiated sarcomas, poorly differentiated synovial cell sarcomas
what staging is done for histiocytic sarcomas?
generally same as the others
may see hemophagic syndrome on bloodwork - neutropenia, anemia, thrombocytopenia)
ultrasound to look at the liver & spleen - target lesion!!!!
lymph node & bone marrow aspirates if indicated
what is the preferred treatment for histiocytic sarcomas?
surgery if possible!!! remove the primary lesion (don’t do it if there is already disseminated disease) - splenectomy, amputation, lung lobectomy
> 90% metastatic rate!!!
what chemo is used for histiocytic sarcomas?
lomustine every 21 days as many times as needed to control disease - this is the most immunosuppressive therapy!!!
what are the risks of treating a patient’s histiocytic sarcoma with lomustine?
this drug will drop platelets into the spontaneous bleeding range (like 35,000) & neutrophils to about 0
will cause hepatic fibrosis - give denamarin concurrently!!!
what is the prognosis for histiocytic sarcoma?
poor!!!!
aggressive treatment with surgery & chemo MST 6 months
periarticular lesions or completely excised lesions maybe get 9 months
what clinical signs are associated with disseminated histiocytic sarcoma? what organs are typically involved?
depression, anorexia, weight loss, vomiting, diarrhea, respiratory distress, jaundice - may have acute onset with rapid deterioration (cough to oxygen dependent & dying within a few weeks)
liver, spleen, lungs, lymph nodes, bone marrow, & skin
how is disseminated histiocytic sarcoma diagnosed?
FNA, biopsy, special stains
CADET histiocytic sarcoma test (like BRAF) - on a cytology or biopsy sample (sensitivity 78% specificity 95%)
when is a bone marrow aspirate indicated for disseminated histiocytic sarcoma?
only done if 1 lesion is seen - if more than 1 lesion, we assume it is everywhere
why no steroids for disseminated histiocytic sarcoma?
shortens survival time
what therapy is used for treating disseminated histiocytic sarcoma?
chemo - same as histiocytic sarcoma, lomustine every 21 days, l-doxorubicin every 12-21 days
what is a negative prognostic factor for patients with disseminated histiocytic sarcoma?
thrombocytopenia is bad
what is the prognosis for disseminated histiocytic sarcoma?
lomustine is the best drug we have & about 50% of cases actually respond…median survival time of 106 days & average remission time of 2 months
what is hemophagic syndrome? what clinical signs are seen?
disseminated histiocytic sarcoma of macrophages where they eat all of the RBC (like 20 RBC inside 1 macrophage)
severe anemia (like 7%), jaundice, weakness/depression, anorexia, & collapse
T/F: you should give blood to a dog that presents with hemophagic syndrome
false - it will just eat up the blood
what organ is always involved if a dog has hemophagic syndrome?
the spleen
what is seen on FNA that is supportive of hemophagic syndrome?
many criteria of malignancy are met + extreme phagocytosis
what is the therapy used for hemophagic syndrome? what is the prognosis?
lomustine - really only 1 dose
extremely grave prognosis - only days
T/F: feline histiocytic sarcoma is rare but when apparent is often disseminated in the spleen
true
what organs are affected by histiocytic sarcomas in cats?
CNS, spleen, liver, lymph nodes, mediastinum, kidney, bladder, & bone marrow
very aggressive
what therapy is used for histiocytic sarcomas in cats? what is the prognosis?
lomustine + l-doxorubicin
super poor prognosis!!!!
what is malignant fibrous histiocytoma?
histologic description for a tumor consisting of malignant fibroblasts & histiocytes that are poorly differentiated from soft tissue sarcomas (more aggressive course)
T/F: malignant fibrous histiocytomas are of histiocytic origin
FALSE - not of histiocytic origin
how are dogs & cats affected by malignant fibrous histiocytomas?
dogs - subcutis & spleen
cats - feline injection site sarcomas
what do you think this FNA sample came from?
cutaneous histiocytoma
what do you think this FNA sample came from?
histiocytic sarcoma
this lesion seen on ultrasound of the liver is associated with what disease?
histiocytic sarcoma!!!
