Nailing the diagnosis
Help your pathology help you
Small Animal Specialist Hospital
Dr Sophia Tzannes
Nailing the diagnosis
Help your pathology help you
• Cytology
• When, how, what and where?
• Advanced cytology and additio...
Nailing the diagnosis
Help your pathology help you
• ‘Hugo’
• ‘Gywna’
• ‘Forster’
• ‘Dudley’
CYTOLOGY
• When?
• How?
• What?
• Where?
CYTOLOGY:
WHEN
Pre-surgical diagnosis is encouraged
• Owners expectations: prognosis and financial considerations
• Determ...
CYTOLOGY:
WHEN
Staging and monitoring when diagnosis known
• Staging
• Monitor for recurrence of lesions cytologically
CYTOLOGY
HOW
• Make sure what you are sampling is what you wish to sample
• Make sure what you have sampled is of diagnost...
CYTOLOGY
HOW
fat
lesion
• Make sure what you are
sampling is what you
wish to sample
• ‘Hugo’ is a 12 y MN Rottweiler X
• ...
CYTOLOGY
HOW:
Make sure what you are sampling is what you wish to sample
• Visualisation is the key
• Superficial lesions:...
CYTOLOGY:
HOW
Make sure what you have sampled is of diagnostic quality
9y FN Irish Setter
Presented with mammary masses
Vu...
CYTOLOGY:
HOW : MAKE SURE WHAT YOU HAVE SAMPLED IS OF DIAGNOSTIC QUALITY
• Equipment needed
• Common problems encountered ...
CYTOLOGY:
HOW : MAKE SURE WHAT YOU HAVE SAMPLED IS OF DIAGNOSTIC QUALITY
• Common problems encountered with slide preparat...
CYTOLOGY:
HOW : MAKE SURE WHAT YOU HAVE SAMPLED IS OF DIAGNOSTIC QUALITY
• Common problems encountered with slide preparat...
CYTOLOGY:
HOW : MAKE SURE WHAT YOU HAVE SAMPLED IS OF DIAGNOSTIC QUALITY
1. Is the slide of diagnostic quality?
2. Are the...
CYTOLOGY:
WHAT IS IT?
Is the slide of
diagnostic quality?
Yes
Are there different
types of cells
present?
Yes
Are inflamma...
CYTOLOGY:
WHAT IS IT?
Is the slide of
diagnostic quality?
Yes
Are there different
types of cells
present?
Yes
Are inflamma...
CYTOLOGY:
WHAT IS IT?
Inflammatory
Neoplastic
Degenerative
MCT: Toluidine blue
CYTOLOGY:
WHAT IS IT?
Neoplastic
• Cytological criteria of malignancy:
• Nuclear criteria
• e.g.: variation in nuclear siz...
CYTOLOGY:
WHAT IS IT?
Neoplastic
CYTOLOGY:
WHAT IS IT?
Is the slide of
diagnostic quality?
Yes
Are there different
types of cells
present?
Yes
Are inflamma...
CYTOLOGY:
WHAT IS IT?
• Limitations
• Mammary > histopathology
• Cannot grade
• May not be definitive
CYTOLOGY: WHERE?
WHERE CAN WE SAMPLE, WHERE SHOULD WE SAMPLE?
• External tissues
• Internal tissues and fluid
• Contra-ind...
CYTOLOGY: WHERE?
WHERE CAN WE SAMPLE, WHERE SHOULD WE SAMPLE?
• Staging
• Performed on patients with malignant lesions
• K...
CYTOLOGY: WHERE CAN WE SAMPLE, WHERE SHOULD WE SAMPLE?
CANINE LYMPHOMA- SPECIAL CONSIDERATIONS
• Multi-centric lymphoma
• ...
• Immunocytochemistry and immunohistochemistry refer to
the process of detecting antigens in tissues or cells by
exploitin...
IMMUNOPHENOTYPING
• The diversity of immunophenotyping markers used in
diagnostic pathology is substantial and more marker...
PARR AND FLOW
What is the difference between flow cytometry and PARR?
• The PARR assay is a PCR assay in which we are ampl...
PARR AND FLOW
What is the difference between flow cytometry and PARR?
• Flow cytometry (FC) allows identification and quan...
CYTOLOGY:
CANINE LYMPHOMA- SPECIAL CONSIDERATIONS
FLOW CYTOMETRY
• Immunophenotyping lymphoma
• Prognosis
• Treatment guid...
CYTOLOGY:
CANINE LYMPHOMA- SPECIAL CONSIDERATIONS
FLOW CYTOMETRY
• Differentiation of hyperplasia and neoplastic populatio...
CYTOLOGY:
CANINE LYMPHOMA- SPECIAL CONSIDERATIONS
PARR
• Sample factors:
• cell lysis/poor preservation
• low diagnostic y...
HISTOPATHOLOGY
• Pre-op, post-op- when does it matter?
• When do we ask for immunohistochemistry?
HISTOPATHOLOGY
• Definitive diagnosis
Punch
Tru-cut
Grab/pinch
Incisional biopsy
HISTOPATHOLOGY
Pre-op, post-op- when does it matter?
• Pre-operative histopathology especially important when
grading may ...
HISTOPATHOLOGY
Pre-op, post-op- when does it matter?
• Pre-operative histopathology especially important when
grading may ...
HISTOPATHOLOGY
Pre-op, post-op- when does it matter?
• Pre-operative histopathology is not indicated where there
is no inf...
HISTOPATHOLOGY:
When do we ask for immunohistochemistry?
• Diagnosis is inconclusive
• Diagnosis does not fit clinical pic...
HISTOPATHOLOGY:
When do we ask for immunohistochemistry?
•‘Forster’, 12y MN Border Collie
•Presented as a referral for a r...
• Further diagnosis with
histopathology and
immunohistochemistry
Epitheliotropic T cell lymphoma
Amelanotic melanoma
Round...
Lip mass. Extensively infiltrating through the submucosa are myriad
round cells with scant amounts of lightly eosinophilic...
• Histopathology
• 50% (7/14) of oral cases were conclusively diagnosed
with histopathology alone (Nemec et al, 2012)
• ea...
HISTOPATHOLOGY:
When do we ask for immunohistochemistry? Diagnosis
Change in diagnosis
Change in management
Surgical > Med...
HISTOPATHOLOGY:
When do we ask for immunohistochemistry?
•‘Dudley’, 12y MN Staffordshire Bull Terrier
•Presented as a refe...
HISTOPATHOLOGY:
When do we ask for immunohistochemistry?
•Immunohistochemistry requested
•Diagnosis: fibrohistiocytic sarc...
• Histologic and immunohistochemical review of splenic fibrohistiocytic nodules (SFHN) in dogs (Moore
2012)
• Splenic FHN ...
HISTOPATHOLOGY:
When do we ask for immunohistochemistry? Therapy
• Intestinal tumours
• Reclassification of small intestin...
HISTOPATHOLOGY:
When do we ask for immunohistochemistry? Therapy
• Mast cell tumours
• Ki-67 prognostic, may elect adjunct...
HISTOPATHOLOGY:
CANINE LYMPHOMA- SPECIAL CONSIDERATIONS
• Summary of Canine Malignant Lymphoma Revised From the Revised Eu...
• Lymphomas divided into 3 major groups
• high, intermediate, low grade
• Most common lymphoma was centroblastic large B c...
HISTOPATHOLOGY:
CANINE LYMPHOMA- SPECIAL CONSIDERATIONS
(Valli et al, 2010)
Personalised
lymphoma
treatment
• Does the spe...
HISTOPATHOLOGY:
CANINE LYMPHOMA- SPECIAL CONSIDERATIONS
(Valli et al, 2010)
Personalised
lymphoma
treatment
• Does a speci...
• Indolent lymphoma comprises 5- 29% of all canine lymphomas
• Limited information regarding the subtypes and biological b...
• B cell predominant
• Both B and T cell indolent lymphomas share a low mitotic rate,
slow rate of progression
• TZL can b...
Clinical features
Histopathology
Immunohistochemistry
Clonality testing
Clinical follow up and
repeat biopsy
NAILING THE D...
of 54

SASH : Nailing the diagnosis pathology by Dr Sophia Tzannes

Nailing the diagnosis pathology. Veterinary consultancy content from SASH
Published on: Mar 3, 2016
Published in: Health & Medicine      
Source: www.slideshare.net


Transcripts - SASH : Nailing the diagnosis pathology by Dr Sophia Tzannes

  • 1. Nailing the diagnosis Help your pathology help you Small Animal Specialist Hospital Dr Sophia Tzannes
  • 2. Nailing the diagnosis Help your pathology help you • Cytology • When, how, what and where? • Advanced cytology and additional tests • Histopathology • Pre-op, post-op- when does it matter? • When do we ask for immunohistochemistry?
  • 3. Nailing the diagnosis Help your pathology help you • ‘Hugo’ • ‘Gywna’ • ‘Forster’ • ‘Dudley’
  • 4. CYTOLOGY • When? • How? • What? • Where?
  • 5. CYTOLOGY: WHEN Pre-surgical diagnosis is encouraged • Owners expectations: prognosis and financial considerations • Determine whether further information is required prior definitive surgery • Staging • May result in non-surgical treatment as best option • Not considered a substitute for histopathology
  • 6. CYTOLOGY: WHEN Staging and monitoring when diagnosis known • Staging • Monitor for recurrence of lesions cytologically
  • 7. CYTOLOGY HOW • Make sure what you are sampling is what you wish to sample • Make sure what you have sampled is of diagnostic quality • repeat multiple times if necessary, use different techniques • Make sure that you submit an adequate number of slides
  • 8. CYTOLOGY HOW fat lesion • Make sure what you are sampling is what you wish to sample • ‘Hugo’ is a 12 y MN Rottweiler X • Presented August 2014 for oncological and surgical assessment of an infiltrating lipoma • Fine needle aspirates by referring vet had consistently revealed droplets of free fat and adipocytes • CT performed to evaluate pre-operatively
  • 9. CYTOLOGY HOW: Make sure what you are sampling is what you wish to sample • Visualisation is the key • Superficial lesions: estimate trajectory • Deep lesions: consider imaging as guidance
  • 10. CYTOLOGY: HOW Make sure what you have sampled is of diagnostic quality 9y FN Irish Setter Presented with mammary masses Vulval mass detected during prep Fine needle aspirate (FNA)
  • 11. CYTOLOGY: HOW : MAKE SURE WHAT YOU HAVE SAMPLED IS OF DIAGNOSTIC QUALITY • Equipment needed • Common problems encountered with slide preparation: • Blood contamination • Low cellularity • Cell rupture or lysis • Smear too thick • Artefacts
  • 12. CYTOLOGY: HOW : MAKE SURE WHAT YOU HAVE SAMPLED IS OF DIAGNOSTIC QUALITY • Common problems encountered with slide preparation: • Blood contamination • Low cellularity • Cell rupture or lysis • Smear too thick • Artefacts -Lymph nodes -Mast cell tumours -Internal organs Liver, spleen -Vascular tumours -Ulcerated lesions -Mucous membranes Spindle cell tumours Easy to exfoliate: Round cell tumours +/- epithelial cells
  • 13. CYTOLOGY: HOW : MAKE SURE WHAT YOU HAVE SAMPLED IS OF DIAGNOSTIC QUALITY • Common problems encountered with slide preparation: • Blood contamination • Low cellularity • Cell rupture or lysis • Smear too thick • Artefact
  • 14. CYTOLOGY: HOW : MAKE SURE WHAT YOU HAVE SAMPLED IS OF DIAGNOSTIC QUALITY 1. Is the slide of diagnostic quality? 2. Are there different types of cells present? 3. Are inflammatory cells present? 4. Can you identify the cells belonging to the tissue of origin? 5. Unusual cells? a. Shape b. Cluster or occur individually c. Cytoplasmic detail and nuclear detail 6. Extra cellular material/infectious agents
  • 15. CYTOLOGY: WHAT IS IT? Is the slide of diagnostic quality? Yes Are there different types of cells present? Yes Are inflammatory cells present? Yes Can you identify the cells belonging to the tissue of origin? Yes, epithelial cells Unusual cells? No Extra cellular material/infectious agents No
  • 16. CYTOLOGY: WHAT IS IT? Is the slide of diagnostic quality? Yes Are there different types of cells present? Yes Are inflammatory cells present? Yes Can you identify the cells belonging to the tissue of origin? Yes, epithelial cells Unusual cells? No Extra cellular material/infectious agents No Inflammatory Neoplastic Degenerative
  • 17. CYTOLOGY: WHAT IS IT? Inflammatory Neoplastic Degenerative MCT: Toluidine blue
  • 18. CYTOLOGY: WHAT IS IT? Neoplastic • Cytological criteria of malignancy: • Nuclear criteria • e.g.: variation in nuclear size and shape- multinucleation, especially if nuclei within same cell vary in size; increased nuclear:cytoplasmic ratio or variation within same population of cells; coarse and ropey chromatin pattern; nuclear moulding; increased number of mitotic figures; variation in nucleolar size, shape and number, especially within same nucleus- bizarre forms, • Cellular criteria • e.g. variation in cell size and shape (greater in malignancy), cell population in abnormal location • Cytoplasmic criteria • e.g. cytoplasmic basophilia, vacuolation and granulation
  • 19. CYTOLOGY: WHAT IS IT? Neoplastic
  • 20. CYTOLOGY: WHAT IS IT? Is the slide of diagnostic quality? Yes Are there different types of cells present? Yes Are inflammatory cells present? Yes Can you identify the cells belonging to the tissue of origin? Yes, epithelial cells Unusual cells? No Extra cellular material/infectious agents No Inflammatory
  • 21. CYTOLOGY: WHAT IS IT? • Limitations • Mammary > histopathology • Cannot grade • May not be definitive
  • 22. CYTOLOGY: WHERE? WHERE CAN WE SAMPLE, WHERE SHOULD WE SAMPLE? • External tissues • Internal tissues and fluid • Contra-indications include: Vascular lesion Coagulopathy Impaired access Hollow organ Cancer seeding (TCC)
  • 23. CYTOLOGY: WHERE? WHERE CAN WE SAMPLE, WHERE SHOULD WE SAMPLE? • Staging • Performed on patients with malignant lesions • Knowing pattern of metastatic spread is helpful • Less differentiated MCT recommend lymph node, liver and spleen aspirates • Soft tissue sarcoma: haematogenous route to lungs (other soft tissue, liver) common • Subtype dependent: histiocytic/synovial cell sarcoma to regional LN (plus lung, etc) • Carcinoma: lymphatic route
  • 24. CYTOLOGY: WHERE CAN WE SAMPLE, WHERE SHOULD WE SAMPLE? CANINE LYMPHOMA- SPECIAL CONSIDERATIONS • Multi-centric lymphoma • Which lymph nodes? • How many samples? • What should I be requesting to maximise my diagnosis?
  • 25. • Immunocytochemistry and immunohistochemistry refer to the process of detecting antigens in tissues or cells by exploiting the antigen-antibody binding process found in biological tissues. CYTOLOGY: LYMPHOMA- SPECIAL CONSIDERATIONS IMMUNOPHENOTYPING AND FLOW CYTOMETRY
  • 26. IMMUNOPHENOTYPING • The diversity of immunophenotyping markers used in diagnostic pathology is substantial and more markers are becoming available in the veterinary field. Some examples of commonly used markers include: – CD3: T cell lymphoma – CD79a: B cell lymphoma – CD18, 11: Histiocytic disease – CD117: KIT used to identify MCT’s and GIST’s – Vimentin: a marker common to sarcomas
  • 27. PARR AND FLOW What is the difference between flow cytometry and PARR? • The PARR assay is a PCR assay in which we are amplifying DNA to evaluate lymphocyte (LCT) receptor gene length. In a heterogenous LCT population the LCT’s are all genetically distinct so the LCT receptor genes vary in length. • Homogenous or clonal LCT population, is often malignant and have identical gene length throughout the population. • The results tell us if the majority of cells in the sample are derived from the same original clone (most consistent with neoplasia), or from multiple clones (most consistent with a reactive process- inflammation, immune mediated disease or infection)
  • 28. PARR AND FLOW What is the difference between flow cytometry and PARR? • Flow cytometry (FC) allows identification and quantitation of cell surface markers • The FC study involves staining live cells (blood, BM, LCT) with labelled antibodies that bind to proteins expressed on the cell surface • The cells are analyzed on a flow cytometer, which tells us how many cells of each type are present. This information allows us to determine the lineage of the cells present, and whether they are homogeneous (more consistent with neoplasia) or heterogeneous (more consistent with a reactive process • Limitation – sample collection- appropriate cytofixative for FNA samples (48 hours), or blood/bone marrow into EDTA (24 hours)
  • 29. CYTOLOGY: CANINE LYMPHOMA- SPECIAL CONSIDERATIONS FLOW CYTOMETRY • Immunophenotyping lymphoma • Prognosis • Treatment guidance CD3 (T cell marker) CD4 (helper T cells) CD5 (T cell marker) CD8 (cytotoxic T cells) CD21 (B cells, but not their precursors) CD34 (stem cell marker, expressed in acute leukaemia) CD3-e (pan T cell marker) CD79a (pan B cell marker) Myeloperoxidase (expressed by myeloblasts and granulocyte precursors) MAC387 (expressed by monoblasts, and some granulocyte precursors) CD14 (expressed by monoblasts and monocytes)
  • 30. CYTOLOGY: CANINE LYMPHOMA- SPECIAL CONSIDERATIONS FLOW CYTOMETRY • Differentiation of hyperplasia and neoplastic populations • Characterisation of leukaemias CD3 (T cell marker) CD4 (helper T cells) CD5 (T cell marker) CD8 (cytotoxic T cells) CD21 (B cells, but not their precursors) CD34 (stem cell marker, expressed in acute leukaemia) CD3-e (pan T cell marker) CD79a (pan B cell marker) Myeloperoxidase (expressed by myeloblasts and granulocyte precursors) MAC387 (expressed by monoblasts, and some granulocyte precursors) CD14 (expressed by monoblasts and monocytes)
  • 31. CYTOLOGY: CANINE LYMPHOMA- SPECIAL CONSIDERATIONS PARR • Sample factors: • cell lysis/poor preservation • low diagnostic yield • location of sample- e.g. intestinal tract • Disease factors: • equivocal diagnosis- ‘reactive node’ • early diagnosis • certain lymphoma sub-types versus • persistent lymphocytosis
  • 32. HISTOPATHOLOGY • Pre-op, post-op- when does it matter? • When do we ask for immunohistochemistry?
  • 33. HISTOPATHOLOGY • Definitive diagnosis Punch Tru-cut Grab/pinch Incisional biopsy
  • 34. HISTOPATHOLOGY Pre-op, post-op- when does it matter? • Pre-operative histopathology especially important when grading may influence surgical plan • Surgical margins Grade 1 and 2: Minimum 2 cm and one deep fascial plane Grade 3: Minimum 3 cm and one deep fascial plane Mast cell tumour, H+E
  • 35. HISTOPATHOLOGY Pre-op, post-op- when does it matter? • Pre-operative histopathology especially important when grading may influence surgical plan • Surgical approach when surgery may be challenging: • large • localisation
  • 36. HISTOPATHOLOGY Pre-op, post-op- when does it matter? • Pre-operative histopathology is not indicated where there is no influence on surgical plan • Location • renal • spleen • mammary Always obtain post-operative histopathology
  • 37. HISTOPATHOLOGY: When do we ask for immunohistochemistry? • Diagnosis is inconclusive • Diagnosis does not fit clinical picture • Where a more precise diagnosis will influence prognosis or treatment •Round cell neoplasia •Fibrohistiocytic splenic neoplasia •Intestinal neoplasia (sarcoma, other)
  • 38. HISTOPATHOLOGY: When do we ask for immunohistochemistry? •‘Forster’, 12y MN Border Collie •Presented as a referral for a recurrent oral melanoma Forster’s biopsy: Round cell population
  • 39. • Further diagnosis with histopathology and immunohistochemistry Epitheliotropic T cell lymphoma Amelanotic melanoma Round cells Histiocytic cells Mast cells Lymphoma Plasma cells TVT (Melanoma) HISTOPATHOLOGY: When do we ask for immunohistochemistry?
  • 40. Lip mass. Extensively infiltrating through the submucosa are myriad round cells with scant amounts of lightly eosinophilic to clear cytoplasm and no obvious pigment. The cells have atypical lymphoid appearance with round nuclei containing granular to branched chromatin and 1 nucleolus. Some of the nuclei are indented while occasional cells have a slightly larger nucleus. The cells show aggregation around vessels as well as infiltration into bundles of nerve and skeletal muscle. The mitotic index is 5. There are scattered interstitial eosinophils, small dark lymphocytes, occasional plasma cells and macrophages. Within the overlying haired skin is a similar population of round cells showing epitheliotropism, and also affecting hair follicles, sebaceous glands and sweat glands. These cells often have clear cytoplasm and infiltrate epithelium as individual cells and small clusters. Affected regions of the epithelium are subtended by plasma cells, small dark lymphocytes and a few of the atypical lymphocytes. Distribution of this change within the affected haired skin is not uniform. The mucosal surface is affected but to a lesser extent. Neoplastic cells are not seen at mucosal and haired skin margins. IMMUNOHISTOCHEMISTRY REPORT The neoplastic lymphocytes within epithelium and deeper tissue are strongly and uniformly labelled with CD3 Lip mass. Extensively infiltrating through the submucosa are myriad round cells with scant amounts of lightly eosinophilic to clear cytoplasm and no obvious pigment. The cells have atypical lymphoid appearance with round nuclei containing granular to branched chromatin and 1 nucleolus. Some of the nuclei are indented while occasional cells have a slightly larger nucleus. The cells show aggregation around vessels as well as infiltration into bundles of nerve and skeletal muscle. The mitotic index is 5. There are scattered interstitial eosinophils, small dark lymphocytes, occasional plasma cells and macrophages. Within the overlying haired skin is a similar population of round cells showing epitheliotropism, and also affecting hair follicles, sebaceous glands and sweat glands. These cells often have clear cytoplasm and infiltrate epithelium as individual cells and small clusters. Affected regions of the epithelium are subtended by plasma cells, small dark lymphocytes and a few of the atypical lymphocytes. Distribution of this change within the affected haired skin is not uniform. The mucosal surface is affected but to a lesser extent. Neoplastic cells are not seen at mucosal and haired skin margins. IMMUNOHISTOCHEMISTRY REPORT The neoplastic lymphocytes within epithelium and deeper tissue are strongly and uniformly labelled with CD3 • IMHC: CD3 +(CD8+) HISTOPATHOLOGY: When do we ask for immunohistochemistry? Epitheliotropic lymphoma
  • 41. • Histopathology • 50% (7/14) of oral cases were conclusively diagnosed with histopathology alone (Nemec et al, 2012) • early stages can have marked mixed inflammatory infiltrate, late stages > B lymphocytes • >50% there is a mix of lymphocyte cell size reported • IMHC • humans: 5-10% lymphoid neoplasia cannot be diagnosed with use of histopathology and IMHC • PARR • T cell receptor (TCR) gamma rearrangement • Sensitivity 80-95%, Specificity 96-100% Clinical features Histopathology Immunohistochemistry Clonality testing Clinical follow up and repeat biopsy HISTOPATHOLOGY: When do we ask for immunohistochemistry? Epitheliotropic lymphoma: diagnosis
  • 42. HISTOPATHOLOGY: When do we ask for immunohistochemistry? Diagnosis Change in diagnosis Change in management Surgical > Medical
  • 43. HISTOPATHOLOGY: When do we ask for immunohistochemistry? •‘Dudley’, 12y MN Staffordshire Bull Terrier •Presented as a referral for haemabdomen •Diagnosed with splenic mass •Splenectomy after staging •Diagnosis: splenic sarcoma The splenic masses reflect a malignancy which consists of variably pleomorphic spindloid to histiocytic cells admixed with lymphoid nodules and extramedullary haematopoiesis, consisting with a fibrohistiocytic nodule. The regions of necrosis and areas with a relatively high mitotic rate warrants a diagnosis of malignancy. Diagnosis: splenic sarcoma
  • 44. HISTOPATHOLOGY: When do we ask for immunohistochemistry? •Immunohistochemistry requested •Diagnosis: fibrohistiocytic sarcoma Vimentin Desmin Smooth muscle actin Factor VIII CD3 CD79a CD18
  • 45. • Histologic and immunohistochemical review of splenic fibrohistiocytic nodules (SFHN) in dogs (Moore 2012) • Splenic FHN cases were re-evaluated in 32 dogs • Histopathology Grade I(2) Grade II (9) Grade III(21) dogs • CD3, CD20, CD79a, CD18, CD11d, K1-67 used to reclassify • Grade I- MZL and lymphoid nodular hyperplasia • Grade II-MZ hyperplasia(1), MZL (1), complex hyperplasia (2), LNH(1), stromal sarcoma (3) • Grade III- MZH(1), diffuse large B cell LSA(1), MZL(1)CNH (6),LNH (1), SS (5), HS (6) • Prognosis: HISTOPATHOLOGY: When do we ask for immunohistochemistry? Prognosis HS- poor 74 days Stromal sarcoma 488 days, 56% alive 1 year CNH MST 387 days 70% alive 1 year LNH MST 570 days 60% alive 2 years
  • 46. HISTOPATHOLOGY: When do we ask for immunohistochemistry? Therapy • Intestinal tumours • Reclassification of small intestinal and cecal smooth muscle tumours in 72 dogs (Maas et al, 2007) • Retrospective study of 47 dogs with a prior diagnosis of leiomyoma or leiomyosarcoma • 85% reclassified as gastrointestinal stromal tumour (GIST) or GIST-like • Therapeutic relevance • GIST + c-kit, target for tyrosine kinase inhibitors (TKIs) • Diagnosis is inconclusive • Diagnosis does not fit clinical picture • Where a more precise diagnosis will influence prognosis ortreatment •Round cell neoplasia •Fibrohistiocytic splenic neoplasia •Intestinal neoplasia (sarcoma, other)
  • 47. HISTOPATHOLOGY: When do we ask for immunohistochemistry? Therapy • Mast cell tumours • Ki-67 prognostic, may elect adjunctive treatments if high • KIT (CD 117) if use of TKIs considered C-Kit staininghigh Ki-67low Ki-67
  • 48. HISTOPATHOLOGY: CANINE LYMPHOMA- SPECIAL CONSIDERATIONS • Summary of Canine Malignant Lymphoma Revised From the Revised European-American Classification of Lymphoid Neoplasms/ World Health Organization Classification of Lymphoid Neoplasms B Cell Neoplasms Precursor B cell neoplasms Precursor B lymphoblastic leukemia/lymphoma Mature (peripheral) B cell neoplasms B cell chronic lymphocytic leukemia/prolymphocytic Leukemia/small lymphocytic lymphoma B cell prolymphocytic leukemia Lymphoplasmacytic lymphoma Splenic marginal zone B cell lymphoma Plasma cell myeloma/plasmacytoma Extranodal marginal zone B cell lymphoma of mucosa-associated lymphoid tissue type Nodal marginal zone lymphoma Follicular lymphoma Mantle cell lymphoma Diffuse large B cell lymphomaa Mediastinal large B cell lymphoma Burkitt’s lymphoma/Burkitt’s cell leukemia Provisional entity: high-grade B cell lymphoma Burkitt’s-likea Primary effusion lymphoma T Cell and Putative Natural Killer Cell Neoplasms Precursor T cell neoplasm Precursor T lymphoblastic Lymphoma/leukemia Mature (peripheral) T cell and natural killer cell neoplasms T cell prolymphocytic leukemia Large granular lymphocyte leukemia (LGL) Aggressive natural killer (NK) cell leukemia Peripheral T cell lymphomas, unspecifieda Adult T cell lymphoma/leukemia Intestinal T cell lymphoma (+enteropathy associated) Hepatosplenic gdT cell lymphoma Subcutaneous panniculitis-like T cell lymphoma Mycosis fungoides/Sezary syndrome Anaplastic large cell lymphoma, T and null cell primary cutaneous type Peripheral T cell lymphoma not otherwise specified Angioimmunoblastic T cell lymphoma Angiocentric T cell lymphoma a Peripheral T cell lymphomas are those that are not otherwise specified (NOS) to a specific subtype by further definition Personalised lymphoma treatment
  • 49. • Lymphomas divided into 3 major groups • high, intermediate, low grade • Most common lymphoma was centroblastic large B cell CANINE LYMPHOMA- SPECIAL CONSIDERATIONS (Valli et al, 2010)
  • 50. HISTOPATHOLOGY: CANINE LYMPHOMA- SPECIAL CONSIDERATIONS (Valli et al, 2010) Personalised lymphoma treatment • Does the specific diagnosis of lymphoma subtype have a similar impact on survival time in dogs as it did in humans? Low grade T cell (T zone) lymphoma Longest survival time (622 days) T cell high grade (peripheral T cell) lymphoma Shortest survival time (162 days) Clinical signs Low grade often none High grade frequently unwell
  • 51. HISTOPATHOLOGY: CANINE LYMPHOMA- SPECIAL CONSIDERATIONS (Valli et al, 2010) Personalised lymphoma treatment • Does a specific diagnosis in a dog influence the chemotherapy required? High Grade B and T cell lymphoma Effective chemotherapy increased survival time T zone lymphoma Chemotherapy decreased survival time (13 dogs with no treatment had longest survival of 687 days)
  • 52. • Indolent lymphoma comprises 5- 29% of all canine lymphomas • Limited information regarding the subtypes and biological behavior. • Canine indolent lymphoma consists of a group of diseases that are histopathologically similar to subtypes of non-Hodgkin’s lymphoma identified in people. • Histopathological subtypes: B cell- marginal zone (MZL), follicular lymphoma (FL) and mantle cell lymphoma (MCL ), T-zone lymphoma (TZL). HISTOPATHOLOGY: CANINE LYMPHOMA- SPECIAL CONSIDERATIONS (Valli et al, 2010)
  • 53. • B cell predominant • Both B and T cell indolent lymphomas share a low mitotic rate, slow rate of progression • TZL can be difficult to recognize as malignancy given the small mature –appearing cell type and low mitotic activity. • Detection of clonality is useful adjunct to histologic examination HISTOPATHOLOGY: CANINE LYMPHOMA- SPECIAL CONSIDERATIONS INDOLENT LYMPHOMA
  • 54. Clinical features Histopathology Immunohistochemistry Clonality testing Clinical follow up and repeat biopsy NAILING THE DIAGNOSIS: MAKING THE MOST OF OUR PATHOLOGY Cytology • Make sure what you are sampling is what you wish to sample • Make sure what you have sampled is of diagnostic quality • Make sure that you submit an adequate number of slides • Diagnosis is inconclusive • Diagnosis does not fit clinical picture • Where a more precise diagnosis will influence prognosis ortreatment •Round cell neoplasia •Immunophenotyping •Clonality testing •Fibrohistiocytic splenic neoplasia •Intestinal neoplasia (sarcoma, other)

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