L7: The Cytological Evaluation Of Lymphoid Tissue (Black) Flashcards
Where do neoplastic cells usually enter the LN?
Through the afferent lymphatic into the cortex
-early metastatic dz often found in the subcapsular sinus
preferred aspiration/biopsy sites of LN
Popliteal and prescaps
-avoid: submandibular, centers of very large lymph nodes (may be necrotic)
Categories of lymph node
- normal
- reactive (lymphoid hyperplasia)
- inflammation (lymphadenitis)
- lymphoid neoplasia (lymphoma)
- metastatic dz
- edema (lymphedema)
- hemorrhage
Sizing of lymphoid cells
Small: nucleus 1-1.4x RBC, dark purple chromatin
Intermediate: 1.5-2x
Large/lymphoblast: >2x, w/ variable chromatin lighter purple, variable distinct nucleoli
Normal LN has 75-90% small, 5-10% intermediate,
Typical appearance of plasma cells
- royal blue cytoplasm
- perinuclear clearing
- eccentric round nucleus
- cartwheel nucleus
Chars. Of reactive lymphoid hyperplasia
- small, well-differentiated lymphocytes still predominate
- increased intermediates
- increased larges (but
Causes of LN enlargement
- reactive lymphoid hyperplasia (2ary to regional antigenic stim.)
- lymphadenitis (neutrophilic, eosinophilic, pyogranulomatous)
- lymphoma
- metastatic neoplasia
- edema (lymphedema)
Types of lymphadenitis
- neutrophilic
- eosinophilic
- pyogranulomatous
Chars. Of neutrophilic lymphadenitis
> 5% nucleated cells neuts
-Etiology: bacterial, necrosis, draining area of trauma, neoplasia (SCC), immune-mediated
Chars. Of eosinophilic lymphadenitis
> 3% eosinophils
-etiology: parasitic, hypersensitivity, MCT, T cell lymphoma, some carcinomas, feline eosinophilic skin dz, etc.
Chars. Of pyogranulomatous lymphadenitis
- aka histiocytic lymphadenitis
- macs overrepresented
- MNGcs
- etiology: atypical bacteria, fungal, protozoal, salmon fluke poisoning dz, FIP, prototheca, oomycete, neoplastic, vasculitis, hemosiderosis, etc.
Chars. Of Reactive lymphoid hyperplasia
- POLYCLONAL lymphocyte proliferation induced by infectious, auto-immune dz, etc.
- results in PLEOMORPHIC lymphoid pop.
- multiple nodes affected
- many etiologies possible
Chars. Of Lymphoma
-neoplastic transformation and unregulated growth of lymphocytes
-MONOCLONAL/MONOMORPHIC population
-presence of aberrant markers
-loss of polymorphism
-usually >50% lymphoblasts (suspicious when >30%)**
-
Differentiating b/w benign and neoplastic lymphoid proliferation: presence of LGL in circulation could be?
E. Canis or leukemia
lymphocyte-rich thoracic fluid with a mediastinal mass could be?
Chylous effusion
Small cell lymphoma or thymoma
predominance of lymphoblasts in splenic aspirate could be either:
Germinal center of lymphoid follicle or lymphoma
presence of expanded small lymph. Pop. In feline GI aspirate could be either:
Inflamm. Bowel dz.
Small cell lymphoma
Tests to differentiate lymphoma vs. reactive lymphoid hyperplasia
PARR
Flow cytometry
Histopath
Immunohistochemistry
PARR =
PCR for Ag receptor rearrangement
- determines clonality of lymphocytes present
- detects T cell receptors in T cells and immunoglobulin receptors in B cells
- 75-80% sensitivity in dogs
- 60-65% sensitivity in cats
- chronic Ag stim. Can cause false positives
Immunophenotyping
- IDs phenotype of cells for prognostication
- est. degree of lymphoid diversity and marker abnormalities w/n a population
- includes flow cytometry, IHC, ICC
Hypercalcemia of malignancy
- paraneoplastic syndrome
- assoc. with T cell lymphoma
- tumor cells produce PTHrp
- assoc. with poorer prognosis
Hyperglobulinemia
- paraneoplastic syndrome assoc. w/ myelomas or some B cell lymphomas
- excess prod. Of immunoglobulin heavy chains and/or light chains
Canine lymphoma most often presents as multicentric lymphoma and is most common lymphoma in dogs
:)
Predominant cell type in canine lymphoma
Immature large lymphocytes (lymphoblasts)
- deeply basophilic cytoplasm
- 2-5x size of RBC
- diffuse chromatin
- occasional perinuclear clear zone
Steroids can decrease # of lymphoblasts! Take sample before giving lymphotoxic drugs
:)
Chars. Of FELINE lymphoma
- same dx criteria
- > 50% lymphoblasts
- most DON’T involve peripheral LN
- “distinctive peripheral LN hyperplasia” can mimic
- usually see more well-differentiated lymphs
- forms: alimentary (most common), hepatic, Hodgkin’s-like, and FeLV-associated
3 forms of Feline GI (alimentary) lymphoma
3 forms:
1) Small cell
- older FeLV cats
- FelV
- looks like IBD; requires histopath
2) Large granular
- hepatic involvement
- originates as intestinal intraepithelial lymphocytes (cytotoxic T cell or NK cell)**
- focal accumulation of eccentric granules**
- granules don’t stain in Diff Quick
- may be confused with MCT
3) Large cell
- usually B cell
- may present as a mass
CHars. Of alimentary feline lymphoma
Aspirates of hepatic, mediastinal, internal LN, nasal, KID, CNS, laryngeal and tracheal, ocular, retrobulbar, and skin yields dense pop. Of lymphoid cells
- primarily lymphoblasts
- 3 forms
Chars. Of feline hepatic lymphoma
- usually composed of small, well-diff. Lymphs
- similar to those seen in cats w/ lymphoplasmocytic cholangio-hepatitis
Chars. Of Feline Hodgkin’s-like lymphoma
- better prognosis
- older cats
- affects LN on the head/neck
- may have mediastinal or thoracic mass
- requires histo dx and IHC
- neoplastic are NOT predominant (only 1-5%); look similar to macs
Distinctive Peripheral Lymph Node Hyperplasia (DPLH)
- YOUNG cats
- mimics multicentric lymphoma**
- no specific etiology
- cytology: inc. lymphoblasts, dec. small and intermediate lymphs, few plasma cells
- usually self-limiting
- generalized lymphadenopathy
Chars. Of FeLV-assoc. lymphoma
- uncommon
- younger cats
- usually T cell
Lymphoma in ferrets
- adult and older usually
- diffuse dz
- GI and multicentric more common
- frequently involves SP and mesenteric LN
- T cell more common than B cell
- Hodgkin’s-like lymphoma can occur in ferrets
Lymphoma in horses
- multicentric: thoracic and abd cavities, GI, and cutaneous dz most common
- peripheral lymphadenomegaly NOT common
- dependent edema common
- T cell rich large B cell lymphoma most common form in horses (can cause waxing and waning serum progesterone conc.); requires histo
Lymphoma in ruminants
- either BLV/EBL-related or sporadic
- juveniles more likely to get sporadic multicentric form
- young >6mo - 2yr more likely to get sporadic thymic form –> resp. Distress, weight loss, cervical masses
- cutaneous RARE
Bovine Leukosis (Leukemia) Virus-assoc. malignant lymphoma
-aka “Enzootic Bovine Lymphoma”
-causes enlarged superficial and visceral LN, thymus, skin, abomasum, HT, SP, KID, etc.
-a cell-associated provirus that infects B cells
-integrates into host’s cell genome
-trans. By exposure to infected B lymphs
-
Most common malignancy in pigs
Multicentric lymphoma
Lymphoma in camelids
- multicentric
- aggressive, poor prog.
- B cell > T cell
Lymphoma in birds
- sporadic, oncovirus-assoc.
- T cell lymphoma assoc. w/ Marek’s dz
MCT commonly met to regional LN
:)
Cytology of normal thymus
- small lymphs predominate
- thymic epithelium
- mast cells present in moderate #
Chars. Of thymic lymphoma
- lymphoblasts most commonly the neoplastic cell population
- assoc. with paraneoplastic hypercalcemia
Chars. Of thymoma
- thymic epithelium = neoplastic cell pop.
- assoc. with hypercalcemia, megaesophagus, myasthenia gravis
Normal spleen
- fibrovascular stroma (mesenchymal cells + phagocytes)
- stored iron (hemosiderin)
- mixed lymphoid pop. Similar to LN
- extramedually hematopoiesis
- erythroblastic islands feed iron
Potential pathologic findings in spleen aspirate
- benign hyperplastic splenic change or nodule
- hemorrhage
- hematoma
- inflammation (splenitis)
- increased EV RBC destruction
- neoplasia
Types of neoplasia found in SP
- lymphoma/leukemia
- hemangioma/sarcoma
- other mesenchymal tumors
- histiocytic sarcoma
- PCT
- metastatic tumors (ie. MCT, carcinomas, sarcomas, neuroendocrine)
Evidence of splenic hemorrhage on SP aspirate
Siderocalcific plaques