INTERACTIVE CASE MANAGEMENT

Transcription

1 INTERACTIVE CASE MANAGEMENT A N U D E P R U N G S I P I P A T, D V M ( H O N S ), P H D, D T B V P, C E R T E S A V S ( O N C O L O G Y ) C O M P A N I O N A N I M A L C A N C E R R E S E A R C H U N I T D E P A R T M E N T O F V E T E R I N A R Y P A T H O L O G Y, O N C O L O G Y C L I N I C, S M A L L A N I M A L T E A C H I N G H O S P I T A L F A C U L T Y O F V E T E R I N A R Y S C I E N C E, C H U L A L O N G K O R N U N I V E R S I T Y

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3 Signalment: TONY Canine, Female, Dalmatian, 8 yr- old, 17 kg Clinical history Anorexia & vomiting for 4 wks Generalized lymphadenopathy Mandibular LN 4x4, 4x3 cm Superficial inguinal LN 2x2.5 cm Popliteal LN 1.5x1.5, 2x2 cm Prefemoral LN 3x3 cm

4 How do you proceed with diagnosis?

5 Give your differential diagnosis!

6 DIFFERENTIAL DIAGNOSIS Inflammation: Acute lymphadenitis Granulomatous lymphadenitis Hyperplasia: reactive hyperplastic lymphadenitis Neoplasia Lymphoma Metastatic tumor to lymph node Etc.

7 Which tests do you want to perform for diagnosis?

8 Cytology Biopsy X-ray CT-scan/ ultrasound Blood profile Bacterial culture & sensitivity Etc..

9 Cytology: majority of pleomorphic lymphoblastic cells, mild anisocytosis, 1-2 mitosis/ HPF Buffy coat smear: Presence of prolymphocytes in peripheral blood Biopsy LN : Lymphoma

10 Moderate bronchointerstitial lung pattern Splenomegaly with soft tissue density at splenic tail

11 Multicentric Bilateral and/symmetrical peripheral lymphadenopathy. ±Tumor metastasis to liver, spleen, tonsil and bone marrow Extranodal Any location outside the lymphatic system such as eyes, central nervous system, bone, testes, kidney, heart, and nasal cavity Cutaneous Multifocal or generalized skin involvement Mediastinal or Thymic Abnormal mediastinal lymph nodes with or without tumor metastasis to bone marrow Alimentary Gut-associated lymphoid tissue involvement

12 CLINICAL STAGES OF CANINE LYMPHOMA Stage I II III IV V Involvement Single lymph node or lymphoid tissue in single organ involvement Regional node involvement Generalized node involvement Hepatic and/or splenic involvement Blood, bone marrow and/or other organs involvement Greenlee et al., 1990; Ettinger, 2003

13 Disseminated (systemic) disease Clinical signs are variable and depend on location of the tumor Generalized lymphadenopathy Hepatosplenomegaly Respiratory distress Pre-caval syndrome Ulcerative dermatitis Skin nodules and plaque Vomit and diarrhea Anorexia Weight loss Ascites PU/PD Fever Emaciation Vail and Young, 2007

14 CLINICAL PATHOLOGY PROGNOSTIC FACTORS Red blood cell count (RBC) and Pack cell volume (PCV): Anemic evaluation Platelet count: Thrombocytopenic evaluation Leukocyte count: Leukocytosis evaluation Serum calcium: Hypercalcemia (Paraneoplastic s syndrome) Circulating lymphoblasts: Blood involvement

15 IMMUNOPHENOTYPE Pax5 positive cells, 400x CD79a positive cells, 400x CD3 positive cells, 400x

16 hpcr for antigen receptor rearrangement Cµ IgH TCRγ1 TCRγ2 IgH TCRγ1 TCRγ2 IgH + TCRγ2 + NC 100 bp cytology Cytology heteroduplex

17 MODIFIED COP AND CHOP PROTOCOLS Treatment A: modified COP L-asparaginase 400 IU/kg SC/IM Vincristine mg/m 2 IV Cyclophosphamide 250 mg/m 2 PO Prednisolone 2mg/kg for 7 days then 1 mg/kg EOD week Treatment B: modified CHOP L-asparaginase 400 IU/kg SC/IM Vincristine mg/m 2 IV Cyclophosphamide 250 mg/m 2 PO Doxorubicin 30 mg/m 2 IV (if < 15kg: 1mg/kg) Prednisolone 2 mg/kg/d week 1 Prednisolone 1.5 mg/kg/d week 2 Prednisolone 1 mg/kg/d week 3 Prednisolone 0.5 mg/kg/d week 4

18 RESCUE PROTOCOLS Protocol Rescue A L-asparaginase Lomustine/CCNU Prednisolone Dosage 400 IU/kg SC/IM week 0 Dog < 15 kg: 60 mg/m 2 PO every 3 wks Dog > 15 kg: 70 mg/m 2 PO every 3 wks 2 mg/kg/d taper down to 1 mg/kg q 48hr Rescue B L-asparaginase Doxorubicin Toceranib phosphate 400 IU/kg SC/IM week 0 Dog < 10 kg: 1 mg/kg IV every 3 wks Dog > 10 kg: 30 mg/m 2 IV every 3 wks 3.25 mg/kg PO EOD taper down to 2.2 mg/kg q 48hr

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20 FELINE GASTROINTESTINAL LYMPHOMA Symptoms of feline intestinal lymphoma include: Loss of appetite Vomiting Diarrhea Weight loss Anorexia (loss of appetite) Lethargy (tiredness) Excessive thirst (polydipsia) More urination (polyuria)

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25 FELINE LYMPHOMA Up to 200 cases / 100,000 at FeLV/FIV endemic areas 62x risk for LSA in FeLV+ cats 6x risk for LSA in FIV+ cats 77x risk for LSA in FeLV/FIV+ cats Alimentary Mediastinal Extranodal Differences exist geographically

26 GASTROINTESTINAL LYMPHOMA Usually low grade lymphoma Full thickness biopsy to differentiate from inflammatory bowel disease Abdominal exploratory surgery Tx with prednisolone and chlorambucil Pred 1mg/kg PO q24h Chlorambucil 4 mg/m 2 PO every 3 days Median survival = years!

27 TREATMENT COP d median 1 st remission Cyclophosphamide, vincristine, prednisone COP + Idarubicin 183d COP + Doxorubicin 281d The bottom line K9 LSA is in a fairly good road to achieve maximum efficacy of standard chemo Common terminology needed (i.e. diffuse vs lymphoblastic) Need for additional treatment options Bone marrow transplants, stem cell transplants, mabs, TKIs Feline LSA diagnosis & treatment is lagging Cats are not small dogs

28 FELINE MEDIASTINAL (THYMIC) LYMPHOMA ASSOCIATED WITH FELV INFECTION IN A YOUNG CAT

29 SIGNALMENT AND HISTORY Canine and Feline lymphoma Feline male, 1-year-old with DSH breed Refered to CU. Vet. Sci. Ani. Tech. Hosp. with chronic regurgitate and severe dyspnea Physical examination: pale mm., more than 7% dehydration, dyspnea and both submandibular enlargement Diagnostic immaging and routine blood check

30 HEMATOLOGIC AND BLOOD CHEMISTRY RESULTS RBC ( / μl) 4.28 x10 6 SGPT(I/U) 162 Hb.(g/dl) 8 PCV(%) 27 Plt.(/μl) 148x10 3 WBC(/μl) 22x10 3 Neu. (/μl) 13,640 Band (/μl) 1,320 Eo. (/μl) 440 Mono. (/μl) 1,320 Lymph. (/μl) 5,280 ALP(I/U) 387 BUN(mg/dl) 30 Creatinine(mg/dl) 1.5 TP(g/dl) 2.85 Calcium(mg/dl) 10.1 Canine and feline lymphoma Page 30

31 RETICULOCYTE COUNT AND RED CELL MORPHOLOGY Microcyte No Macrocyte +2 Anisocytosis +1 Poikilocytosis No Spherocyte No Target cells No Polychromasia No NRC/100WBC No Reticulocytes (0.7%) 29,960 cell/μl

32 CLINICAL PATHOLOGY TERMINOLOGY Non-regenerative anemia Leukocytosis shift to the left Thrombocytopenia Raised liver enzyme ( SGPT and ALP) Hypoproteinemia

33 DIAGNOSTIC IMAGING Increased radiopacity in cranial portion of thorax Strongly suggested for mediastinal mass. H E R E C O M E S Y O U R F O O T E R P A G E 33

34 CYTOLOGIC SMEAR OF PLEURAL FLUID 40X CU VET PATH 100X Cellular morphology : pleomorphic lymphoblastic cells Large irregular nuclei, prominent nucleoli, high N:C ratio. Atypical mitotic figures H E R E C O M E S Y O U R F O O T E R P A G E 34

35 SUGGESTED FOR INVESTIGATION Feline leukemia virus (FeLV) and Feline immunodiefiency virus (FIV) Test Positive (+) only FeLV

36 Postmortem Pathology HISTOPATH. : H&E Mediastinal mass : gross and histopathological lesions

37 positive H&E CD3 CD20 negative Immunohistochemistry CD3 and CD20 Solid sheet of pleomorphic neoplastic lymphoid cells with multiple foci of tumor necrosis (arrow) H E R E C O M E S Y O U R F O O T E R P A G E 37

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39 GENERAL INFORMATION Jacque, an aggressively 9 years, complete vaccinated, male French Bulldog He usually had a clinical signs of allergy previously such as Urticaria, Erythematous skin diarrhea and vomiting Previously, Rt. 1 st digit inflammation and bleeding without bone fracture The clinical signs of 1 st digit was eliminated

40 GENERAL INFORMATION A 1x 0.8x 0.8 cm mass was observed between 3 rd and 4 th digit Redness, dome shaped, firm consistency, loosed and flexible

41 Parameter Normal value 25 Jan Feb 2013 RBC x 10 6 per ul Hemoglobin g/dl Hct % Platelet x10 3 per ul WBC x 10 3 per ul Neutrophil % Eosinophils % Basophils % Lymphocytes % Monocytes % Blood parasite NF NF ALT units ALP units BUN mg% Creatinine mg% Total protein g% Albumin g% Calcium meq/ L Phosphorus meq/ L

42 RADIOGRAPHIC DIAGNOSIS

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44 ELECTROCARDIOGRAPHIC DIAGNOSIS

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46 DIFFERENTIAL DIAGNOSIS Cutaneous plasmacytoma Mast cell tumor Cutaneous lymphoma Histiocytoma ETVT

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48 TREATMENT PROTOCOL Medical treatment (first visited) Prednisolone 0.74 mg/kg bid pc for 10 days Cephalexine 22 mg/kg bid ac for 14 days Surgical treatment (14 days later) Surgical excision of the mass Biopsy was done

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51 Signalment Coco An 8-year-old, male, Shih Tzu, dog History 7/11/2011 -> Splenic mass and splenectomy Biopsy -> Hemangiosarcoma 18/10/2012 -> abdominal mass near splenectomy site and hepatic mass Cytology -> Histiocytic sarcoma

52 CYTOLOGY Fig 1. Giemsa stain, 400X

53 HEMATOLOGY Parameter 26/10/12 (1 st chemo.) 2/11/12 9/11/12 20/11/12 (2 nd chemo.) 3/12/12 Normal value WBC (μl) 17,700 32,200 24,200 25,800 38,400 6,000-17,000 Neutrophils 12,775 17,388 19,118 19,350-3,000-11,500 Bands - 5, Eosinophils 1, ,250 Basophils rare Lymphocytes 2,450 14, ,290-1,000-4,800 Monocytes 350 4,733 2,904 4, ,350 RBCx10 6 /μl Hb (g/dl) Hct % MCV (fl) MCH (pg)

54 SERUM CHEMISTRY Parameter 26/10/12 (1 st chemo. ) 2/11/12 9/11/12 20/11/12 (2 nd chemo.) 3/12/12 Normal value ALT ALP , BUN Creatinine Calcium Phosphorus

55 HEMATOLOGY Parameter 13/12/12 20/12/12 (3 rd chemo.) 28/12/12 (4 th chemo.) 16/1/13 24/1/13 30/1/13 Normal value WBC (μl) 34,100 33,900 22,300 40,500 40,100 30,000 6,000-17,000 Neutrophils ,164-29,674-3,000-11,500 Bands Eosinophils ,250 Basophils ,604 - rare Lymphocytes - - 3,345-1,203-1,000-4,800 Monocytes - - 3,568-7, ,350 RBCx10 6 /μl Hb (g/dl) Hct % MCV (fl) MCH (pg) MCHC (g/dl) Plateletx10 3 /μ 1,355 1,249 1,260 1,223 1,

56 SERUM CHEMISTRY Parameter 13/12/1 2 20/12/12 (3 rd chemo) 28/12/12 (4 rd chemo.) 16/1/1 3 24/1/13 30/1/13 Normal value ALT ALP BUN Creatinine Leukocytosis neutrophilia monocytosis Normocytic hypochromic anemia Increased ALP

57 BUFFY COAT SMEAR Fig 2. Dip quick stain, 400X

58 RADIOGRAPHIC FINDINGS Normal heart size and shape Normal lung opacity, no evidence of pulmonary nodules

59 Note: cellular fluid in peritoneal cavity ULTRASONOGRAPHIC FINDINGS Organs 18/10/12 20/11/12 24/1/13 A large heterogeneous mass at left liver lobe 3.79x3.15 cm 4.76x3.57x4.14 cm 8.5x8.4 cm With multiple hepatic nodules Splenectomy site -splenic lymph node -mass near splenic lymph node 0.8x1 cm 1.78x2 cm 1.2x1.4 cm 3.16x1.82 cm 1.90x2.25 cm

60 TREATMENT ( ) ( ) ( ) ( )

61 Histiocytic disease Reactive histiocytosis Cutaneous histiocytosis Systemic histiocytosis Cutaneous histiocytoma Histiocytic sarcoma complex Localized histiocytic sarcoma Disseminated histiocytic sarcoma

62 HISTIOCYTE LINEAGE

63 HISTIOCYTIC SARCOMA Chemotherapy Overall remission rate Median survival time (days) References Chlorambucil 4 mg/m 2 daily 11% 153 Leach et al., 2012 CCNU 90 mg/m 2 q 4 weeks 29% 96 Rassnick et al., 2010 CCNU mg/m 2 q3-4 weeks Liposomal doxorubicin 1 mg/kg q 3 weeks 46% 106 Skorupski et al., % - Vail et al., 1997

64 Thank your for your attentions