Acute Myloid Leukemia in a Dog
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ISRAEL JOURNAL OF VETERINARY MEDICINE
CASE REPORT: ACUTE M L I LEUKEMIA IN A D G Y OD O
F r a , A., E e - u, Z., a d Kol, A. ak s v nZ r n
A ei a M dc l L b r t re , Herzlia, I r e. m rc n e i a a oaoi s sa l
O p y i a e a i ai n its b d t m eaue ws 3 n h sc l x mn to oy e prt r a Magic, a c sr t d d g m l , 1 y as o a e s a a dee pr t r r t s a d h at r t s w r n r a. T a tae o ae 3 e r f g , m l mxr s iaoy ae n e r ae ee om l h ni d pe e t d v r d pe s d a d w a . r s ne ey e r s e n e k be d 1 kg. re ; 0 Is m c u mm rns w r p l a d icteric. O a d t uo s e ba e ee ae n n b A a n ss nm ei: ap N pe i u hsoy H u e p t wt c re t v c i ai n pnai n n a n r aiy ws r v ae . Is pe c p l r o r vo s i t r . o s e ih ur n a cn to s aldto o b om lt a e e l d t r s a ua p pie l l m h n d s w r si h e l r e . o lt a y p o e ee lg t nag d te t e t . r am ns N n uoo i a a n r aii s w r e i e t d rn t e o e r l gc l b om lte ee vd n ui g h Chief c m l i t o pan: eamn to . xl i ai n a T o d y b f r pe e t to M gc s o e g sr i t si w a s eoe r s nai n a i h wd a tone tn sg s of v mtn a d dar e a d n uoo i a sm t m of in o ii g n i rh a n e r l gc l y p s o h a pe sn a d l c of b l n e ed r s i g n a k aa c .
Sg am n: i nl e t
L b r t r e a i ai n a oaoy x m t s no TABLE 1 Clinical - p t oo i a findings:A L 2 Bo h msr r s ls ah l gc l T BE i c e i ty e ut Rs l e ut Ts et Unit Rfrne rn e eee c a g a Hmt l g ) e ao y o
Prmtr R s l aa ee e ut
WC B RC B HB g HT C MV C MH C MH CC PT L
7. 26 22 . 48 . 1. 5 1 6. 86 2. 18 3. 18 5
x etd a g x ^ ) O U is Epce rne ( l V L nt xO u l VL 801 . . - 70 xO u l VL 5081 .-. Gd /L 1 . - 80 201 . % 3 . - 50 705 . FL 6 . - 70 007 . p g 2 . - 50 002 . Gd /L 3 . - 60 203 . xO u l VL 1 05 0 5-0
b Dfe e ta l u o ye c u t ) if r ni l e k c t o n
Prmtr aa ee Rs l e ut (l V L xO u ) E p ce r n e ( l V L x e t d a g xO u )
Nu et
N u sa e t tb Lm h y p
Mn oo E sn oi Bs ao
2 8
4.6 35 43 .6 00 .0 2.6 48 00 .0 00 .0
36 - 31 . 01 . 0 00 - . 8 . 006 02 - . 0 . 741 01 - . 5 . 813 01 - . 5 . 207 00 - . 7 . 001
Glue Choi Urea TP ALP ALT AST A yo e ml s Ca Crea Pi Alb G bl s l un o i T.Bil GGT Lipase CI K Na
5 7 14 8 1 81 3. 42 .9 95 7 32 6 17 6 99 0 86 .5 21 .8 99 . 12 .4 30 .5 41 .9 3 14 0 17 1 42 . 10 5
m/L gd m/L gd m/L gd g/dL U/L U/L U/L U/L mg/dL mg/dL m/L gd g/dL g/dL m/L gd U/L U/L m o/ m lL m o/ m lL m o/ m lL
6 0 1. 00 1. 00 4.9 8 6 1 0 30 5 91 . 05 . 23 . 10 0 23 . 00 . 4 3 9 7 35 . 19 3
17 4 6. 00 6. 00 72 . 15 5 7 0 4 3 10 30 1. 17 15 . 64 . 30 0 45 . 07 . 2 5 35 7 10 2 54 . 10 5
WEBSITE: w wi r m . r w .sv aog
V L M 6 ( ) 20 OU E 3 1 0
ISRAEL JOURNAL OF VETERINARY MEDICINE
Large mononuclear cell population showing severe atypia. The Severe thrombocytopenia is evident on the slide. A band ne nuclei are highly pleomorphic.The chromatin material appears and normoblast are present phil course to reticular.
Figl
Fig 2
Leukocyte changes: • Hypoalbuminemia and low albumimglobulin ratio o e • Severe leukocytosis with a marked left shift including the Hypoalbuminemia and a low alb\glob ratio could b attributed both to a state of hepatic failure (globulins cou appearance of metamyelocytes without toxic changes. WNL u • The mononuclear cell population appeared to be neoplastic d e to globulins secretion by immunocytes) and a sta protei showing severe atypia. The cells were mostly rounded and n loosing pathology most probably the latter which c e 3-7 times that of an erythrocyte. The nucleus w s highlyb verified by the urinary protein to creatinine ratio a pleiomorphic varying from round to kidney-shaped to clover-Hyperbilirubinemia • shaped. The appearance of the chromatin material w s course a • Increased activity of to reticular and it w s often possible to distinguish a nucleolos.Increased ALT andliver enzymes indicated hepatocellu a u AST activities Nucleoli were also large and pleiomorphic. d m g while increased ALP activity and hyperbilirubinem a ae • The cytoplasm w s deeply basophilic in color containingndicated cholestasis a i multiple fine vacuoles. Da n ss ig oi • Many cells s o signs of karyorhexis and karyolysis. hw In light of the hematological results (tables 1 and 2), Erythrocyte c a g s hn e: especialy in view of the blood counts and the morpholo • Normocytic normorchromic anemia with no evidence of appearance of the cells in the blood s e r (figs 1 and ma regeneration. diagnosis of ACUTE MYLOID LEUKEMIA (AML) preferab • Many precursor erythrocytes appeared in the blood s eAML M4 (myelomonocytic) or M2 (AML with maturation) ma r MALIGNANT HISTIOCYTOSIS w s made. a from metarubricytes to basophilic rubricytes. Platelet changes: Afinaldiagnosiscouldonlybemadebyimmunohistochemistry • Severe thrombocytopenia as confirmed in the blood s e r cytochemistry staining. m and a with the appearance of megaplatelets. Ds u so ic si n Bo h msr ( a l 2): i c e i ty T be The presence of an elevated total nucleated cell count, m • Mild azoetmia and hyperphosphatemia of which were blast cells, with concurrent severe anemia o Since urine specific gravity w s not measured, a renal thrombocytopenia w s compatible with the diagnosis of ac a a azotemia could b only speculated since the dog w s not leukemia. Bone marrow aspiration or core biopsy is sometim e a dehydrated on physical examination warranted in order to achieve this diagnosis. • Mild hypocalcemia (Total calcium) Differentiation between a lymphoid or myeloid origin can o When correcting the calcium according to the albumin level, ed on morphologic criteria - lymphocytic cells in or suspect a normocalcemia w s speculated. a tend to be 154 times the size of an erythrocyte, a .VOLUME 6 ( ) 2008 3 1
W B I E w wsv a r E ST : w . r m . g i o
2 9
ISRAEL JOURNAL OF VETERINARY MEDICINE
round nucleus, a d n e and smooth chromatin pattern the could nfinegranules. es contai contain a visible nucleolus and a narrow, basophilic and mostly Acute myeloblastic leukemia and myelomonocytic leukem agranular cytoplasm. are the m s commonly reported as acute myeloid leuke ot On the other hand, myeloid cells in origin tend to b bigger, Cytochemical staining is positive for peroxidase, e of dogs. chlo with a lower N\C ration, a m r indented nucleus and lighterroacetate esterase, leukocyte alkaline phsophatase and oe acid phosphatase which supports and diagnosis of acute and sometimes granular cytoplasm. myl A definitive diagnosis can be m d using advanced techniques omonblastic leukemia (1). ae Malignant histiocytosis is a rapidly progressive, ultimatel such asflowcytometry and immunohistochemestry. fatal, proliferative histiocytic condition affecting older d g a o Acute myeloid leukemias (AML) are u c m o neoplastic In dogs and cats lesions consistently occur in the s s no m n cats. vi myeloproliferative disorders originating from non-lymphoid organs, specifically the lung, liver, spleen, lymph nodes, b hematopoietic stem cells, including granulocytic, monoctic, marrow, intestine and central nervous system, but they m a erythrocytic and megakaryocytic lineages. Viruses, chemicals,present anywhere. Clinico-pathological features are inconsiste ionizing radiation and antineoplastic drugs h v been associated anemia thrombocytopenia and ae but are repor with AML. Clinical signs associated with AML are nonspecifiin 30-50% ,of cases. Phagocytosis ofbilirubinemia leukocyto c. erthrocytes, Lethargy, weakness, inappetance, fever, splenomegaly, hepatomegaly and mild lymphadenopathy are frequently neoplastic cells and hemosiderinare generally prominent. observed. Leukocytosis, severe anemia, and thrombocytopenia Positivity of lysozyme and a-1-antitrypsin (aAT) by are c m o laboratory findings. Blast cells are usually, but not o mn cytochemical staining supports a diagnosis of Malignant always, present in high numbers in the peripheral blood. AMLtiocytosis (2) his blast cells generally have m r abundant cytoplasm that m y oe a
RFRNE EE E CS
1 Raskin, RE. and Valenciiano, A. Cytochemical tests for . diagnosis of leukemia. In Schalm's Veterinary Hematology. Eds: Feldman, BE, Zinkl, JG. And Jain, NC. Lippincott Wiliams and Wilkins, Philadelphia, pp. 755-763. 2000. 2. Deheer, LH. And Grindem, CB. Histiocytic disorders. In Schalm's Veterinary Hematology. Eds: Feldman, BE, Zinkl, JG. And Jain, NC. Lippincott Wiliams and Wilkins, Philadelphia, pp. 696-705. 2000.
3 0
W B I E w wsv a r E ST : w . r m . g i o
VOLUME 6 (1) 2008 3
ISRAEL JOURNAL OF VETERINARY MEDICINE
CASE REPORT: ACUTE M L I LEUKEMIA IN A D G Y OD O
F r a , A., E e - u, Z., a d Kol, A. ak s v nZ r n
A ei a M dc l L b r t re , Herzlia, I r e. m rc n e i a a oaoi s sa l
O p y i a e a i ai n its b d t m eaue ws 3 n h sc l x mn to oy e prt r a Magic, a c sr t d d g m l , 1 y as o a e s a a dee pr t r r t s a d h at r t s w r n r a. T a tae o ae 3 e r f g , m l mxr s iaoy ae n e r ae ee om l h ni d pe e t d v r d pe s d a d w a . r s ne ey e r s e n e k be d 1 kg. re ; 0 Is m c u mm rns w r p l a d icteric. O a d t uo s e ba e ee ae n n b A a n ss nm ei: ap N pe i u hsoy H u e p t wt c re t v c i ai n pnai n n a n r aiy ws r v ae . Is pe c p l r o r vo s i t r . o s e ih ur n a cn to s aldto o b om lt a e e l d t r s a ua p pie l l m h n d s w r si h e l r e . o lt a y p o e ee lg t nag d te t e t . r am ns N n uoo i a a n r aii s w r e i e t d rn t e o e r l gc l b om lte ee vd n ui g h Chief c m l i t o pan: eamn to . xl i ai n a T o d y b f r pe e t to M gc s o e g sr i t si w a s eoe r s nai n a i h wd a tone tn sg s of v mtn a d dar e a d n uoo i a sm t m of in o ii g n i rh a n e r l gc l y p s o h a pe sn a d l c of b l n e ed r s i g n a k aa c .
Sg am n: i nl e t
L b r t r e a i ai n a oaoy x m t s no TABLE 1 Clinical - p t oo i a findings:A L 2 Bo h msr r s ls ah l gc l T BE i c e i ty e ut Rs l e ut Ts et Unit Rfrne rn e eee c a g a Hmt l g ) e ao y o
Prmtr R s l aa ee e ut
WC B RC B HB g HT C MV C MH C MH CC PT L
7. 26 22 . 48 . 1. 5 1 6. 86 2. 18 3. 18 5
x etd a g x ^ ) O U is Epce rne ( l V L nt xO u l VL 801 . . - 70 xO u l VL 5081 .-. Gd /L 1 . - 80 201 . % 3 . - 50 705 . FL 6 . - 70 007 . p g 2 . - 50 002 . Gd /L 3 . - 60 203 . xO u l VL 1 05 0 5-0
b Dfe e ta l u o ye c u t ) if r ni l e k c t o n
Prmtr aa ee Rs l e ut (l V L xO u ) E p ce r n e ( l V L x e t d a g xO u )
Nu et
N u sa e t tb Lm h y p
Mn oo E sn oi Bs ao
2 8
4.6 35 43 .6 00 .0 2.6 48 00 .0 00 .0
36 - 31 . 01 . 0 00 - . 8 . 006 02 - . 0 . 741 01 - . 5 . 813 01 - . 5 . 207 00 - . 7 . 001
Glue Choi Urea TP ALP ALT AST A yo e ml s Ca Crea Pi Alb G bl s l un o i T.Bil GGT Lipase CI K Na
5 7 14 8 1 81 3. 42 .9 95 7 32 6 17 6 99 0 86 .5 21 .8 99 . 12 .4 30 .5 41 .9 3 14 0 17 1 42 . 10 5
m/L gd m/L gd m/L gd g/dL U/L U/L U/L U/L mg/dL mg/dL m/L gd g/dL g/dL m/L gd U/L U/L m o/ m lL m o/ m lL m o/ m lL
6 0 1. 00 1. 00 4.9 8 6 1 0 30 5 91 . 05 . 23 . 10 0 23 . 00 . 4 3 9 7 35 . 19 3
17 4 6. 00 6. 00 72 . 15 5 7 0 4 3 10 30 1. 17 15 . 64 . 30 0 45 . 07 . 2 5 35 7 10 2 54 . 10 5
WEBSITE: w wi r m . r w .sv aog
V L M 6 ( ) 20 OU E 3 1 0
ISRAEL JOURNAL OF VETERINARY MEDICINE
Large mononuclear cell population showing severe atypia. The Severe thrombocytopenia is evident on the slide. A band ne nuclei are highly pleomorphic.The chromatin material appears and normoblast are present phil course to reticular.
Figl
Fig 2
Leukocyte changes: • Hypoalbuminemia and low albumimglobulin ratio o e • Severe leukocytosis with a marked left shift including the Hypoalbuminemia and a low alb\glob ratio could b attributed both to a state of hepatic failure (globulins cou appearance of metamyelocytes without toxic changes. WNL u • The mononuclear cell population appeared to be neoplastic d e to globulins secretion by immunocytes) and a sta protei showing severe atypia. The cells were mostly rounded and n loosing pathology most probably the latter which c e 3-7 times that of an erythrocyte. The nucleus w s highlyb verified by the urinary protein to creatinine ratio a pleiomorphic varying from round to kidney-shaped to clover-Hyperbilirubinemia • shaped. The appearance of the chromatin material w s course a • Increased activity of to reticular and it w s often possible to distinguish a nucleolos.Increased ALT andliver enzymes indicated hepatocellu a u AST activities Nucleoli were also large and pleiomorphic. d m g while increased ALP activity and hyperbilirubinem a ae • The cytoplasm w s deeply basophilic in color containingndicated cholestasis a i multiple fine vacuoles. Da n ss ig oi • Many cells s o signs of karyorhexis and karyolysis. hw In light of the hematological results (tables 1 and 2), Erythrocyte c a g s hn e: especialy in view of the blood counts and the morpholo • Normocytic normorchromic anemia with no evidence of appearance of the cells in the blood s e r (figs 1 and ma regeneration. diagnosis of ACUTE MYLOID LEUKEMIA (AML) preferab • Many precursor erythrocytes appeared in the blood s eAML M4 (myelomonocytic) or M2 (AML with maturation) ma r MALIGNANT HISTIOCYTOSIS w s made. a from metarubricytes to basophilic rubricytes. Platelet changes: Afinaldiagnosiscouldonlybemadebyimmunohistochemistry • Severe thrombocytopenia as confirmed in the blood s e r cytochemistry staining. m and a with the appearance of megaplatelets. Ds u so ic si n Bo h msr ( a l 2): i c e i ty T be The presence of an elevated total nucleated cell count, m • Mild azoetmia and hyperphosphatemia of which were blast cells, with concurrent severe anemia o Since urine specific gravity w s not measured, a renal thrombocytopenia w s compatible with the diagnosis of ac a a azotemia could b only speculated since the dog w s not leukemia. Bone marrow aspiration or core biopsy is sometim e a dehydrated on physical examination warranted in order to achieve this diagnosis. • Mild hypocalcemia (Total calcium) Differentiation between a lymphoid or myeloid origin can o When correcting the calcium according to the albumin level, ed on morphologic criteria - lymphocytic cells in or suspect a normocalcemia w s speculated. a tend to be 154 times the size of an erythrocyte, a .VOLUME 6 ( ) 2008 3 1
W B I E w wsv a r E ST : w . r m . g i o
2 9
ISRAEL JOURNAL OF VETERINARY MEDICINE
round nucleus, a d n e and smooth chromatin pattern the could nfinegranules. es contai contain a visible nucleolus and a narrow, basophilic and mostly Acute myeloblastic leukemia and myelomonocytic leukem agranular cytoplasm. are the m s commonly reported as acute myeloid leuke ot On the other hand, myeloid cells in origin tend to b bigger, Cytochemical staining is positive for peroxidase, e of dogs. chlo with a lower N\C ration, a m r indented nucleus and lighterroacetate esterase, leukocyte alkaline phsophatase and oe acid phosphatase which supports and diagnosis of acute and sometimes granular cytoplasm. myl A definitive diagnosis can be m d using advanced techniques omonblastic leukemia (1). ae Malignant histiocytosis is a rapidly progressive, ultimatel such asflowcytometry and immunohistochemestry. fatal, proliferative histiocytic condition affecting older d g a o Acute myeloid leukemias (AML) are u c m o neoplastic In dogs and cats lesions consistently occur in the s s no m n cats. vi myeloproliferative disorders originating from non-lymphoid organs, specifically the lung, liver, spleen, lymph nodes, b hematopoietic stem cells, including granulocytic, monoctic, marrow, intestine and central nervous system, but they m a erythrocytic and megakaryocytic lineages. Viruses, chemicals,present anywhere. Clinico-pathological features are inconsiste ionizing radiation and antineoplastic drugs h v been associated anemia thrombocytopenia and ae but are repor with AML. Clinical signs associated with AML are nonspecifiin 30-50% ,of cases. Phagocytosis ofbilirubinemia leukocyto c. erthrocytes, Lethargy, weakness, inappetance, fever, splenomegaly, hepatomegaly and mild lymphadenopathy are frequently neoplastic cells and hemosiderinare generally prominent. observed. Leukocytosis, severe anemia, and thrombocytopenia Positivity of lysozyme and a-1-antitrypsin (aAT) by are c m o laboratory findings. Blast cells are usually, but not o mn cytochemical staining supports a diagnosis of Malignant always, present in high numbers in the peripheral blood. AMLtiocytosis (2) his blast cells generally have m r abundant cytoplasm that m y oe a
RFRNE EE E CS
1 Raskin, RE. and Valenciiano, A. Cytochemical tests for . diagnosis of leukemia. In Schalm's Veterinary Hematology. Eds: Feldman, BE, Zinkl, JG. And Jain, NC. Lippincott Wiliams and Wilkins, Philadelphia, pp. 755-763. 2000. 2. Deheer, LH. And Grindem, CB. Histiocytic disorders. In Schalm's Veterinary Hematology. Eds: Feldman, BE, Zinkl, JG. And Jain, NC. Lippincott Wiliams and Wilkins, Philadelphia, pp. 696-705. 2000.
3 0
W B I E w wsv a r E ST : w . r m . g i o
VOLUME 6 (1) 2008 3
Journal:
