Pathology Of The Lymphoreticular System Flashcards
What organs are in the Lymphoreticular System? (Name the primary and secondary organs)
Primary: Bone marrow and Thymus (in thorax)
Secondary: Lymph nodes, Spleen and MALT
Name the common pathology causes to this system.
- Infection
- Immune-mediated disease
- Neoplasia
Diseases of the Thymus:
What can cause Thymic hypoplasia?
- Developmental abnormalities (associated with primary immunodeficiency) Eg. x-linked SCID
- Systemic viral lymphoid depletion Eg. FeLV, FIV, CDV
this infects the lymphocytes (T cells)
Diseases of the Thymus:
What happens in Feline Thymic lymphoma?
Name the CS, DDx, Tx
- Malignant - infected lymphocytes and thymus reacts
- Usually associated with FeLV - CATS
- Cs:
-Anorexia, Wt loss, dyspnoea (caused by sto mass)
(cats cope well by resting - don’t see breathing issues -discover disease late) - DDx:
-Thoracic rads show soft tissue opacity mass
-Effusion - cytology of pleural fluid, Fine needle aspiration biopsy (FNAB)
(Affects mediastinal LN possible) - Tx:
-Chemotherapy
Diseases of the Thymus:
What is a thymoma?
Name the Cs, DDx, Tx
- Benign - neoplasia of thymic epithelial cells - DOGS
- DOGS - breed disposition - GSDs + Labs
- CS
- Dyspnoea, Dysphagia - space occupying lesion in anterior thorax
- thoracic effusion
- Paraneoplastic sydromes:
a) hypercalcemia (release of PTHrp from tumour cells: ↑bone resorption + distal tubule Ca reabsorption
b) Myasthenia gravis with megaoesophagus - REGURG (autoimmune - muscle weakness) - DDx: Thoracic rads, u/s, cytology of fluid/FNAB
- Tx: Surgical excision of tumour +/- chemo
Good prognosis for Stage 1 Thymoma - no spread from thymic capsule and no paraneoplastic disease
Diseases of Lymph Nodes:
What is the function of
a) Lymphocytes
b) Lymph Nodes
a) Lymphocytes constantly move around body in blood- visiting secondary Lymphoid organs - searching for foreign antigen and APCs
IN: High Endothelial Venules
OUT: Efferent Lymphatic vessels + thoracic duct
(back to blood)
b) Lymph Nodes trap foreign material (prevent systemic spread) and optimise exposure of lymphocytes to Antigen
Best environment for Lymphocytes to activate, proliferate, differentiate (Effector T cells + AB from plasma cells)
-also antigen presentation - interdigitating Dendritic cells to Tcells and follicular DC to B cells
Diseases of the Lymph nodes:
a) Define Lymphadenopathy and name the two types:
b) Common causes of Lymphadenopathy?
a)
1. Localised (regional disease)
2. Generalised (systemic disease- check spread to spleen
b) Infection (↑WBC count with pyrexia) and neoplasia
Diseases of the Lymph nodes:
Name the DDx of generalised lymphadenopathy:
1) Haematology
- Lymphopenia - viral infection ↓L
- Neutropenia + left shift - Bac infection - ↑N
- Eosinophilia - Parasite or allergy - ↑E
2) Lymph node Biopsy: Fine needle, Core, Excisional
Chylothorax:
a) What are the causes of C?
b) What are the CS?
c) What is the definitive DDx?
a) Thoracic duct is damaged/perforated, eroded by a tumour usually causing the efferent lymph to leak out into thoracic cavity
b) Compromised resp function, disrupt lymphocyte migratory function
c) Milky, pink liquid appearance tapped from thorax, lymphopenia
What happens when malignant cells attempt to metastasise via lymphatic system?
-They get stuck in the LNs, trapped - establishing 2° site of tumour formation
Eg. MCT, Malignant melanoma, SCC
- blocked lymphatics can cause peripheral oedema (limbs)
Name the Differential DDx based on histopathology:
- Reactive LN
- Lymphadenitis
- 1° Neoplasia
- 2° Neoplasia (mets)
Describe the histopath appearance of
a) Reactive LN
a) Reactive LN
- Normal architecture with increased cellularity -cloned- reacting to antigenic challenge - therefore enlarged
- 2° follicles with germinal centres
Describe the histopath appearance of
b) Lymphadenitis -
Name the 3 subcategories with appearance and examples
b) Lymphadenitis
- Active infection WITHIN LN - LN trapped antigens but causing disease inside
- Appearance = similar to reactive LN, but with pyogranulomatous inflamm
-3 subcategories
1. Suppurative - yellow green pus, liquid abscess
Eg. Strept equi - Strangles
- Caseous - cottage cheese abscess
-alternate layers of fibrosis and necrosis and abscesses can burst expelling infectious pus
Eg. Corynebacterium pseudotuberculosis (sheep/goats) - Granulomatous - inflamm response
Eg. Mycobacterial infection = TB/Johnes disease
Describe the histopath appearance of
c) 1° Neoplasia
(another name?)
d) 2° Neoplasia (mets)
c)
- Lymphoma
- Non-infectious
- Lack of normal architecture (large no of nucleated cells)
- Large no of abnormal lymphocytes (large) with ↑ mitotic figures
d)
- Metastasis
- Areas of normal lymphoid tissue with infiltration of neoplastic cells either focal or diffuse
Haem route goes to Liver/Lung but Lymphatic route to nearest LN
Eg. MCT, ST sarcoma, tonsillar squamous cell carcinoma, Metastatic melanoma
Diseases of the Spleen:
Name potential diseases that can occur to the spleen:
- Trauma/Rupture/haematoma (eg RTA)
- Torsion with GDV
- Infarction (Eg classical swine fever)
- Splenomegaly - diffuse, nodular
Splenomegaly
Explain the difference of diffuse and nodular S and name examples of each one
-Diffuse S is enlargement of the spleen generally whereas only nodules of the spleen are enlarged in Nodular S - found at Clinical Exam
- Diffuse S:
- Venous congestion (eg following torsion and also PM artefact after barbiturate)
- Lymphoid hyperplasia (systemic infectious/inflamm/immune-mediated)
- Systemic amyloidosis
- Neoplasia (lymphocytes, multiple myeloma) - Nodular S:
-Nodular hyperplasia - benign
- Abscess/cyst (infectious agent)
Diff to tell apart from N hyperplasia
- 1° Neoplasia - Lymphoma, Haemangioma, Haemangiosarcoma
-2° Neoplasia - Metastatic disease (eg. MCT)
What infectious agents particularly impact the Lymphoreticular system?
a) Viruses
b) Bacteria
c) Protozoa
a) Malignant Catarrhal Fever (herpes virus) Classical Swine Fever FeLV/FIV/Canine distemper/FIP Equine Infectious Anaemia
b)
Bacillus anthracis (Anthrax)
- haemorrhage from orifices, sudden death
Mycobacterium bovis (TB)/ M. avium paratuberculosis (Johnes disease)
Corynebacterium pseudotuberculosis
-not curable
c) Exotic - Leishmania, Babesia, Ehrlichia, Theileria
Splenic disorders:
1a) Name the 3 important branches of the Splenic A + V?
1b) What do you have to be careful when exteriorising the Spleen in relation to vessels?
1a) Left limb to pancreas, greater curvature of the stomach (gastroepiploic), fundus of the stomach (short gastrics)
1b) Must ligate the main S artery in removal - stop haemorrhage
Must lift the omentum covering the S A + V to see the branch to Pancreas - ligate after branching or P will die
Splenic disorders:
2a) Name the functions of the spleen:
2b) Name the parts of the spleen that makes up the Red pulp and the White pulp
2c) Is it vital?
2a)
Red pulp-
-RBC maintenance (filters), iron metabolism (stores iron from past RBC)
-Blood reservoir - smooth muscle capsule contracts for blood boost
-Haematopoiesis (helps out Bone marrow)
White pulp-
-Immune functions - protects from septicaemia
2b) Red pulp is the venous sinuses and the white pulp is lymphoid tissue
2c) Dogs and cats can survive normally without a spleen - don’t live longer enough to see effects
Splenic disorders:
3) Which is performed more commonly, Total Splenectomy or Partial and why?
- Total Splenectomy is more common - much easier to remove whole spleen and indicated for cases in neoplasia or trauma
(Check for mets is suspect malignant neoplasia)
Splenic disorders:
4) Describe the procedure of Total splenectomy:
1) Large ventral midline abdominal incision
2) Locate spleen in left abdomen and the tail section
3) Double ligate and transect the hilar vessels (can be in bunches) - until main a + v reached
4) Locate the S a + v - artery is white whereas the vein is wider, thinner, darker (see blood)
5) Separate with haemostats and ligate them separately with ligatures closer to the side staying in body
6) Carry on ligating until short gastric vessels - preserve
7) Transect the gastrosplenic ligament
8) Take out - send off for histopath, give as much for DDX but clots common
Splenic disorders:
5) a) Describe the method of fast total splenectomy
b) Describe the limitations to this surgery
a)
1) Start at tail of spleen
2) Ligate in 3 places - short gastric vessels, left gastroepiploic a + v and splenic a + v distal to pancreas branch
b) Difficult if anatomy distorted by major trauma, ligate wrong vessels
Splenic disorders:
6) Describe indications for partial splenectomy
- Used in cases of accidental lacerations
- Focal and benign disease eg. trauma
1) Ligate hilar vessels and transect ones to the diseased spleen - forming a line of demarcation
2) Place forceps and remove diseased portion
3) place two rows of continuous mattress suturing and then one close to cut end of spleen
4) Use stapling device eg. linear stapler
- Difficult to do because because spleen friable/soft
Splenic disorders:
7a) What are the perioperative considerations for this surgery?
7b) What are the intraoperative considerations?
- Increased risk of cardiac arrhythmias with splenic masses - monitor ECG during surgery/ anti-arrhythmias
- DIC can occur with neoplasia - perform coagulation tests
- Examine whole abdomen for mets
- Check Blood pressure
b) -Will need: Abdominal retractors Lot of swabs (have radio-opaque + remember to count) Suction (measure blood and weigh swabs) Waterproof drapes
- Haemorrhage main concern - deal with hypovolaemic shock - slipped ligatures so can use vascular clips/vessel sealants
- if GDV predisposed - gastropexy
- Gastritis/ pancreatitis
Splenic disorders:
Localised Vs Diffuse Splenectomegaly
8a) Which is more common in dogs and cats?
8b) Name some differentials for Localised S?
a) Localised more common in dogs, Diffuse more common in cats
b) Non-neoplastic:
Haematoma, abscess, nodular hyperplasia, infarcation, cyst
Neoplasia:
Benign - haemangioma, leiomyoma, fibroma, lipoma
Malignant - haemangiosarcoma, fibrosarcoma, leiomyosarcoma
Splenic disorders:
9) Name some differentials for Diffuse S?
10) What are some Diagnostic Methods?
9)
- Infection - Bac, virus, fungal, parasitic
- Congestion - drugs, splenic torsion, GDV, Right sided CHF
- Neoplasia- acute/chronic leukaemia, systemic MCT (esp cats), lymphoma, multiple myeloma, malignant histiocytosis
- Immune mediated thrombocytopaenia - (splenectomy performed if refractory to immunosuppressive drugs)
(histiocyte - macrophages, dendritic cells - Antigen presenting cells)
10)
PE - sometimes hard is deep chested
FNA (not useful in localised haematoma/ haemangiosarcoma - produces blood)
U/s - see masses
Splenic disorders:
11a) How common are Canine Haemangiosarcoma? (name a common breed)
b) What are the issues with diagnosing this?
c) What is the prognosis if this is diagnosed?
11a) Most common malignant splenic tumour in dog (GSD at ↑ risk of haemangiosarcoma/haemangioma)
Very common splenic mass, esp if anaemia/haemoabdomen present - ruptured spleen!
b) FNA usually shows up as blood, hard to distinguish between haemangioma and haematoma (and hard grossly)
c) Very likely metastasize - liver/omentum/mesentry/brain/SQ - right atrial HS common too
- bad prognosis even with surgery - extended 3-12weeks because haemorrhage present is life threatening - combine with post op chemo (extended 6month survival) - only palliative
Splenic disorders:
12a) What happens in Splenic torsion?
b) What breeds is it seen in? (common?)
c) What are the presenting signs?
d) DDX?
e) Is a splenectomy indicated?
f) Prognosis?
a) Spleen twists on vascular pedicle occluding hilar vessels –> causing splenic congestion -> potentially splenic vessel thrombosis
b) Deep chested dogs - Great dane, Irish setters and it is rare
c) Present acutely, progressive abdominal pain, distension, shock
Chronic: non-specific - lethargy, anorexia, +/- pancreatitis
d) U/s - Swollen spleen and snow storm effect - unique pattern of echos
Doppler - absent pulse in S a + v
e) Yes after stabilisation
Donot untwist the pedicle - release toxins and ligate by dividing and ligating sections - mass ligation unsafe
f) Usually excellent
Splenic disorders:
13a) Name some examples of Splenic trauma and describe how severe they are?
a) Rare
- Blunt trauma - RTA - many haemorrhage self limiting or other injuries too severe to intervene
- Mild haemorrhage from laceration, percutaneous biopsy - S capsule can be sewn with omentum placed on top
- Severe haemorrhage - requires ligation of s vessels + total or partial splenectomy
Haematopoetic Neoplasia:
1. Describe Lymphoma (lymphosarcoma)
- Malignant neoplasms originating from lymphoreticular system
Haematopoietic Neoplasia:
2. What is the aetiology of Canine Lymphoma? (Think genetic and environmental factors)
2.
- Most common malignant tumour
- Affects middle aged to older dogs
- Aetiology:
a) Unknown (or spontaneous)
b) Genetic factors - breed predisposed (eg. Boxers, Scottish terriers, labs, bulldogs, chromosomal abnormalities and mutations in tumour supressor genes (p53) and oncogenes (in some L)
c) Environmental factors - herbicides
Haematopoietic Neoplasia:
3. What is the aetiology of Feline Lymphoma?
3.
- Median age shifted older to 9-11y - in relation with FeLV vacc
a) FeLV (+ve status increases ↑↑risk) - vaccine reduced cases of FeLV and in turn L associated - can be the virus replication or immunosupressed status
b) FIV (+ve status increases ↑risk)
c) Genetic factors - Young Siamese/oriental cats - predisposed to mediastinal L
d) Environmental factors - tobacco smoke
e) Sites of chronic Inflammation - IBD
f) Immunosuppressed patients
g) Spontaneous
Haematopoietic Neoplasia:
- a) What are common predilection sites for Lymphoma in the cat and the dog?
b) How common are these sites specifically for the dog and cat?
a)
- Multicentric - multiple L
- Gastro-intestinal
- Mediastinal/thymic
- Extranodal (1° not in LN) lymphoma (CNS/eye, Renal, Nasopharyngeal)
b)
Dog - Multicentric 80-85%
Gastro and mediastinal next and the extranodal less common
Cat - most common is Gastro-intestinal L (Spleen/liver), then multicentric, mediastinal/thymic and Extranodal (More common than dogs though)
Haematopoietic Neoplasia:
5a) What is the common presentation in dogs with Multicentric Lymphoma?
b) Name some differential DDX for Multicentric Lymphoma?
c) What is the difference between cats and dogs in relation to Multicentric Lymphoma?
5a) Peripheral Lymphadenopathy - painless, moveable and multiple affected
- Often asymptomatic - vague lethargy, malaise, WL, anorexia, pyrexia, PU/PD if hyperca
- +/- Liver/spleen enlargement
b) Differential DDX:
- Disseminated infection causing lymphadentitis (Bac, parasitic, fungal, protozoal, viral, rickettsial)
- Immune mediated
- Other haematopoietic tumours - leukaemia/myeloma
- Met/disseminated neoplasia - histiocytic sarcoma, mast cell
- Generalised skin disease - demodex, ringworm
- Sterile granulomatous lymphadentitis
c) Cats usually get nodular lymphoma (pure)
Cats more systemically unwell than dogs
diseases unique to cats:
-Benign hyperplastic LN syndrome
- Hodgkin’s-like lymphoma/ T-cell rich B-cell lymphoma - affects head/neck LN
Haematopoietic Neoplasia:
6a) What is the common presentation in cats with Gastro-intestinal/Alimentary Lymphoma?
b) What are the two grades of GI Lymphoma in cats? (Differences)
c) Name some differential DDX for GI Lymphoma
d) What do you have to be careful with in cases of old cats and GI lymphoma?
a)
-WL, anorexia, vomiting, diarrhoea ( Jaundice if liver involved
b) High grade - mass lesions (GI mass/mesenteric LN), short history, may have signs of obstruction, median age - 10
Low grade - diffuse thickened loops/ mild lymphadenomegaly, chronic history, median age - 13
c) Differential DDX
- Inflamm Bowel disease ( diffuse thickening)
- other GI tumours
- Foreign Body, intussusception
d) Rule out old cat diseases that can cause WL - HyperT4, renal failure, diabetes mellitus
Haematopoietic Neoplasia:
7a) What is mediastinal Lymphoma?
b) What is the common presentation for Mediastinal Lymphoma?
c) Name some differential DDX for mediastinal Lymphoma
a) Cranial mediastinal mass +/- pleural fluid, T-cell phenotype, in younger cats
b)
- Dyspnoea, coughing (pushing on lungs), RR↑, tachypnoea, lung sounds displaced ventrally,
- Dysphagia, WL, regurgitation,
- Heart sounds displaced, vagus trunk affected (Horner’s, drooping eyelid), caval syndrome - swollen oedematous head - impeded venous return from head - uncommon
c) Differential DDx:
- Other tumours - thymoma, ectopic thyroid tumour, carcinoma, chemodectoma, metastatic neoplasia
- Non-neoplastic mass lesions - abscess, cyst, granulomatous disease
- Other causes of effusion - FIP, pyothorax, chylothorax, heart failure, haemothorax
Haematopoietic Neoplasia:
8a) What is the common presentation for Renal Lymphoma?
b) Is Renal Lymphoma more common in dogs or cats?
c) Name some differential DDX for Renal Lymphoma
a) Large irregular kidneys on palpation (often bilat), signs of kidney disease - PU/PD, anorexia, WL
b) More common in cats, median age - 9
TX cats often develop CNS L - drugs used in tx can also penetrate BBB
c) Differential DDX:
-Polycystic kidney disease
- Pyelonephritis
- FIP
- Acute renal failure
- Hydronephrosis
- Perinephric pseudocyst
- Other renal tumours eg carcinoma
Haematopoietic Neoplasia:
9a) What is the common presentation for CNS/Spinal Lymphoma?
b) Name some differential DDX for CNS/Spinal Lymphoma
a) Insidious/ rapidly progressive neuro signs - paresis and paralysis with spinal involvement
Mixed site involvement
b) Other CNS tumours - meningioma
Trauma, intervertebral disc prolapse/heriniation
Infection - FIP, mycotic infection
Aortic thrombus/embolism
Haematopoietic Neoplasia:
10a) What is the common presentation and some differential ddx for Nasal/nasopharyngeal Lymphoma?
b) What is the common presentation for Laryngeal/ Tracheal Lymphoma?
c) What is the common presentation for Ocular Lymphoma?
a) Older cats, often B cell Chronic nasal discharge (serosanguinous --> mucopurulent) Epistaxis Sneezing Stertor Anorexia Facial deformity Exophthalmos - abnormal protrusion of eyeball Epiphora - expressive watering of eye
Differential ddx- cat flu, neoplasms
b) in older cats
Upper resp tract obstruction
Dyspnoea
c) can be seen alone or generalised disease
Signs- uveitis, blepharospasm, infiltration, haemorrhage, retinal detachment
Haematopoietic Neoplasia:
11a) What is the common presentation for Cutaneous Lymphoma?
b) Name some differential DDX for Cutaneous Lymphoma
a) Epitheliotrophic form ‘Mycosis fungiodes’ (T cell) - superficial epidermis
3 stages: 1. Scaling, alopecia, pruritus–> 2. Erythematous, thickened, ulcerated, exudative—> proliferative plaques and nodules with progressive ulceration
Non-Epitheliotrophic form- T or B cell - mid to deep dermis, spared epidermis
b) Differential ddx: Infectious dermatitis Immune-mediated dermatitis Histiocytic skin disease Other cutaneous neoplasia eg mast cell, metastatic neoplasia
Haematopoietic Neoplasia:
12a) What paraneoplastic syndromes can be seen in Lymphoma?
a) Hormones + mediators affecting distant sites to tumour
- Hypercalcaemia (production of PTHrP acts on kidneys/bones - release of Ca, also from gut from Vit d)
Ddx - separated EDTA plasma on ice - common in dogs (not cats)
Syndrome causes- PU/PD, bradycardia/ bradydysrhythmias, dehydration, malaise, vomiting, muscle tremors, constipation, depression
Need to tx!!
- Hypergammaglobinaemia (causes hyperviscosity)
Rare - canine lymphoma - have monoclonal gammopathy- due to aberrant (abnormal) ab production - Anaemia (chronic: mild, non-regen) and thrombocytopenia (myelophthisis - bone marrow infiltration)
- Cancer cachexia
- rarely: immune-mediated disease
Other: hypoglycaemia, polyneuropathy
Haematopoietic Neoplasia:
13a) Can you name any DDX tests for Lymphoma?
a)
1) Full PE and history esp LN palpation, mm, abdominal palpation (masses, organomegaly), thoracic auscultation - masses/fluid
2) CYTOLOGY by:
- LN aspirates/biopsies
- U/s guided internal LN
- Abdominal/pleural fluid
If can’t see on cytology:
3) LN, mass, organ biopsy for HISTOPATH
- Tru-cut
- Endoscopic
- Punch biopsy
4) CT scan
5) MRI
6) Grading of Lymphoma
7) Immunophenotyping
8) Haem
9) Biochem
10) Urinalysis
Haematopoietic Neoplasia:
14a) What management techniques are used for Lymphoma?
a)
-Combination chemo best because systemic disease
- Radiation for localised/ nasal lymphoma in cats
- Costicosteriods - best in combo with chemo - lymphocyte apoptosis
Useful for owners if don’t want chemo - alone allows short remission
- Surgery rare
Haematopoietic Neoplasia:
13b) What would you check for in PE and history in regards to Lymphoma?
b) Full PE and history esp LN palpation, mm, abdominal palpation (masses, organomegaly), thoracic auscultation - masses/fluid
Haematopoietic Neoplasia:
Lymphoma
c) Where would you sample for Cytology?
(what is the difference between sampling for cytology and histopath?)
c) CYTOLOGY by:
- LN aspirates/biopsies - 23gauge needle
- U/s guided internal LN
- Abdominal/pleural fluid
(Lymphocytes in neoplastic LN - large - same size as RBC)
- internal organs (see involvement)
Haematopoietic Neoplasia:
Lymphoma
d) Where would you sample for Histopath?
e) What are the techniques to sample the GI tract and skin?
If can’t see on cytology:
d) LN, mass, organ biopsy for HISTOPATH (see whole structure)
- Tru-cut
e) - Endoscopic - GI tract
- Punch biopsy - Skin
Haematopoietic Neoplasia:
Lymphoma
f) What are CT scans most useful at finding in regards to lymphoma?
f) CT scan - nasal masses (Soft tissue), lost turbinates
Haematopoietic Neoplasia:
Lymphoma
g) What is MRI most useful at looking for?
g) MRI - CNS Lymphoma
Haematopoietic Neoplasia:
Lymphoma
h) Describe the difference of cell morphology in low grade and high grade lymphoma?
h) Grading of Lymphoma - High grade - large cells/blasts, low grade - small cells
Haematopoietic Neoplasia:
Lymphoma
i) How does Immunophenotyping help with diagnosing lymphoma?
(What cells are most common in a dog lymphoma?)
i) Immunophenotyping - FNA into cytocheck medium (cloudy) - Flow cytometry
- Distinguishing from T cell or B cell (better prognosis in B) - by surface markers - affects tx
Dogs - mainly B cell Lymphoma
Haematopoietic Neoplasia:
Lymphoma
j) What does Haem access?
k) What diseases can Haem show up in Lymphoma?
j) Haem - cell counts and smears - patient status pre-chemo tx
k)
- Anaemia
- Cyptopenias (multiple cell lines affected - suspect bone marrow infiltration)
- Atypical circulating lymphocytes (suspect bone marrow involvement)
Haematopoietic Neoplasia:
Lymphoma
l) What is Biochem used to test for?
m) What biochem changes can be seen with Lymphoma?
l) Access organ function in preparation for chemo, paraneoplastic syndromes, extent of the disease
m)
- ↑ Liver enzymes / bilirubin - hepatic infiltration
- azotemia - renal infiltration, hypercalcaemic neuropathy, pre-renal
- Hypoproteinaemia - GI loss in Alimentary L
- Hypercalcaemia
- Hyperglobulinaemia
Haematopoietic Neoplasia:
Lymphoma
n) What is useful about Urinalysis in Lymphoma treatment?
Urinalysis - accessing azotemia, baseline info before chemo - esp cyclophosphamide
Cyclophosphamide can cause haemorrhagic cystitis
Haematopoietic Neoplasia:
18) What are the basic tests before starting chemotherapy?
Biochem, Haem and Urinalysis
Haematopoietic Neoplasia:
19) Why is the WHO staging not useful for cats but only useful for dogs?
19) WHO staging is useful for multicentric lymphoma and this is most common in dogs. GI lymphoma is most useful in cats.
Haematopoietic Neoplasia:
20) What are the 5 stages with WHO grading for canine lymphoma?
20)
I - Solitary LN or lymphoid tissue in a single organ
II - Multiple LN in singe region (1 side of diaphragm)
III- Generalised LN involvement (both sides of Diaphragm)
IV) Liver and/or spleen involvement
V) Bone marrow involvement +/- other organs
Haematopoietic Neoplasia:
Lymphoma
o) What is useful about Rads and U/s?
o) Thoracic Rads - lymphadenopathy, lung patterns, masses, pleural effusion
Abdominal Rads - Hepatomegaly, splenomegaly, renomegaly, lymphadenopathy
U/s - masses, changes in echogenicity in organs, enlarged organs, lymphadenopathy
Haematopoietic Neoplasia:
Lymphoma
p) What is the best diagnostic test to distinguish between the two grades of GI lymphoma in cats?
q) Describe the differences seen in this DDX test in cats with low grade and high grade GI lymphoma:
p) Ultrasound - thickening of gut wall/masses/loss of layering
q) Low grade - muscularis propria layer often thickened - esp in IBD
High grade - loss of normal gut layering + mass lesions
Haematopoietic Neoplasia:
Lymphoma
21) What needs to be discussed when choosing Chemo as the main tx for lymphoma?
Chemotherapy is the main tx but:
- usually only palliative - not usually a cure (relapse will occur)
- potential adverse effects - quality of life
- owner’s commitments (costs/travel/frequent appointments/patient temperament)
Haematopoietic Neoplasia:
c) Name some current chemo protocols for Lymphoma
b) High grade T-cell Lymphoma responds to alklyating agents eg. Lomustine
RVC protocol: modified LOPP protocol: lomustine, vincristine, procarbazine, prednisolone
COP- based protocol: cyclophosphamide, vincristine, prednisolone) induction phase then oral maintenance - chlorambucil, methotrexate, pred (after in remission for 8 weeks)
- for Dogs
Doxorubicin- containing CHOP-type protocols - v intensive initially (adverse effects), no maintenance
D has to be IV infused over 20-30mins
Modified version of Madison-Wisconsin protocol: Vin, Pred, Cyclophosphamide, Dox
Haematopoietic Neoplasia:
14d) What protocols are there for cats?
COP protocol but cannot split the cyclophosphamide - pulse dose instead
Haematopoietic Neoplasia:
14e) What drug is vital for tx of renal/CNS lymphoma?
e) Cytosine arabinoside incorporated into COP protocol - IV infusion over 4-12hr
Haematopoietic Neoplasia:
14f) What is the maintenance protocol for cats?
f) Chlorambucil and Prednisolone
Haematopoietic Neoplasia:
14g) What is the chemotherapy protocol for low grade GI lymphoma in a cat? (what is the route?)
g) Chlorambucil, Pred (cyclophosphamide or lomustine at relapse), supplement with B12 inj
Oral
Good prognosis
Haematopoietic Neoplasia:
15a) What are the 4 different grades of response to tx?
a) CR - complete response
PR- partial response
PD- progressive disease
SD- stable disease
Haematopoietic Neoplasia:
15b) What tests are required to monitor patients receiving chemo?
b) PE Haem Biochem Urinalysis Echocardiography
Haematopoietic Neoplasia:
15c) What does Haem check in regards to patients with lymphoma?
c) - check for myelosupression
- Neutropenia - delay tx
- Marked Neutropenia but asymptomatic - consider broad spec AB eg. TMS, enroflaxacin
- low Neutropenia (<1x10^9) - reduce dose?
Haematopoietic Neoplasia:
15d) What does Biochem check in regards to patients with lymphoma?
d) Abnormal parameters, renal parameters with nephrotoxic drugs, ALT for hepatotoxicity with lomustine
Haematopoietic Neoplasia:
15e) Why do you perform Urinalysis in regards to patients with lymphoma?
e) Immunosuppression means UTI very common
Monitor haemorrhagic cystitis caused by cyclophosphamide (dogs)
Nephrotoxic drugs used
Haematopoietic Neoplasia:
15f) What does Echo check in regards to patients with lymphoma?
f) Offer before doxorubicin - risk of DCM - screen for heart disease- access contractility - this drug accumulates
Haematopoietic Neoplasia:
16) What are some adverse effects of Chemo?
16)
-GI disturbances (Maropitant, bland diet)
-Anorexia
-Myelosuppression -Febrile (fever) neutropenic crisis
-Haemorrhagic cystitis - switch cyclophosphamide
-Hypersensitivity/histamine release- Dogs urticaria/vomiting and Cats - resp distress/vomiting
(Stop drug and give antihistamines)
-Extravasation - could result in amputation- use heat/cold packs, topical steroid cream
Haematopoietic Neoplasia:
17) What happens in patients starting chemo protocols having already been treated with NSAIDS?
17) Induce resistance to Chemo
Remember no NSAID and steroids together
Haematopoietic Neoplasia:
19a) What is Leukaemia?
b) What are the two broad categories?
a) Leukaemias are malignant neoplasms originating from Haematopoietic precursor cells in bone marrow (sometimes spleen)
- Neoplastic cells circulate in bloodstream or
- proliferate in bone marrow causing cytopenias, but don’t spill into circulation (aleukaemic leukamia)
b) Lymphoid and Myeloid
Haematopoietic Neoplasia:
20a) What is Myeloma?
b) What are the clinical signs of myeloma?
c) What are the DDX tests for myeloma and what do they show?
d) What is the treatment for Myeloma?
a) Myeloma is a plasma cell tumour affecting bone marrow in older animals
b) CS- mild pyrexia, lymphadenopathy, hepatosplenomegaly, signs of hyperviscosity eg. neuro signs, retinal detachment, bleeding tendencies, lameness/bone pain
c) Bone marrow aspirate/biopsy - ↑ plasma cells
Haem - anaemia
Biochem - hyperglobulinaemia (↑AB production - monoclonal spike) +/- hyperca
Rads
Urine - Immunoglobulin light chains in urine
d) TX- melphalan and pred (prognosis worse in cats)
Haematopoietic Neoplasia:
18) What is the treatment for hypercalcemia?
-Saline diuresis 0.9% NaCl - 6mls/kg/hr
-Once rehydrated, - give Furosemide at 1-2mg/kg - promote calciuresis
- Treat underlying cause
(supplement to reduce calcium with calcitonin, bisphosphonates)
Haematopoietic Neoplasia:
19f) What are the clinical signs of leukaemia?
g) What are the signs in relation to myelophthisis?
h) How would you diagnose Leukaemia?
i) What is the treatment for Leukaemia? (name the difference between acute and chronic)
f) Non-specific - Lethargy, weakness, malaise, GI signs, lymphadenopathy
g) Fever, petechial, haemorrhages, pallor (anaemia)
h) Abnormal cells - flow cytometry (cell type)
BM biopsy
i) Poor prognosis with acute - ALL - same as lymphoma, AML - cytosine arabinoside
Chronic better prognosis - CLL- Chlorambucil and pred - affects older animals
Haematopoietic Neoplasia:
19b) What is the difference between acute and chronic Leukaemia?
Acute - Aggressive biological behaviour, very progressive, severe CS
DDX- immature cells (blasts) in marrow/blood - poorly differentiated + high capacity to rapidly cell divide
Prognosis = POOR
Chronic - slow and mild CS
Neoplastic cells - well differentiated late precursor cells, less capacity to divide
Prognosis reasonable
Haematopoietic Neoplasia:
19c) What are the Lymphoid leukaemias?
- Acute Lymphoblastic leukaemia and Chronic lymphoblastic leukaemia
Small L and then T or B cell (plasma cell)
Haematopoietic Neoplasia:
19d) What is the difference between ALL and Stage V L?
ALL and Stage V L very similar -
- ALL starts in bone marrow and spreads and in Stage V L neoplasia spreads peripherally and spreads to bone marrow
- ALL -sicker animals, profound cytopenias with milder lymphadenopathy than Stage V L
- DDX- flow cytometry - ALL cells +ve for CD34 marker
- ALL poor prognosis than Stage V L
Haematopoietic Neoplasia:
19e) What are myeloproliferative disorders?
e) Neoplastic or pre- or non-neoplastic conditions of all non-lymphoid cells in marrow
Uncommon
Haematopoietic Neoplasia:
21a) What is Polycythaemia Vera/ Primary Erythrocytosis?
b) What are the CS?
c) What is the DDx?
d) What is the tx?
a) Proliferation of erythroid cell series in marrow with differentiation to mature RBC
b) Bright red MM, neuro signs (hyperviscosity)
c) Persistently high PCV (65-85%) with low or normal erythropoietin activity
d) Phlebotomies and replacement of blood with colloids/electrolytes - alleviate hyperviscosity
