Feline lymphoma

Question 1

Lymphoma accounts for what % of hematopoeitic tumors?

Answer 1

50% to 90%

Question 2

Despite a sharp drop in FeLV-associated lymphoma, the overall prevalence of lymphoma in cats is increasing

This is due to?

Answer 2

alimentary (and, in particular, the intestinal) and extranodal anatomic forms of lymphoma

Question 3

Commonly affected breeds?

Overrepresented breeds?

Answer 3

domestic shorthair (DSH) cats are most commonly affected and Siamese cats appear overrepresented in some reports

Question 4

Gender predisposition?

Australian cases?

Answer 4

1.5:1 male-to- female ratio was observed in two studies, with no association with gender or neutering status observed in one

male cats and the Siamese/oriental breeds were overrepresented

Question 5

Siamese/oriental breeds, there appears to be a predisposition for a _____ form that is not FeLV-associated and represents a _____ population

Answer 5

mediastinal, younger (median of 2 years)

Question 6

Median age of cats? FeLV era?

Alimentary form and extranodal forms occur most often in?

Answer 6

11 to 12 years (3-5 years in FeLV era)

older, FeLV-negative cats

Question 7

FIV- associated lymphoma is more likely to be of ____ immunophenotype, as opposed to the _____ predominance associated with FeLV

FIV infection may be associated more commonly with _____ lymphoma of _____ origin, and this may be related to chronic dysregulation of the immune system or the activation of oncogenic pathways

Answer 7

B-cell, T-cell

alimentary, B-cell

Question 8

Genetic and Molecular factors

What are factors implicated?

Answer 8

N-ras aberrations have been implicated, although they are rare in cats.

Telomerase activity has been documented in feline lymphoma tissues.

Cyclin-dependent kinase cell-cycle regulators and the Bcl-2 family of proapoptotic and antiapoptotic governing molecules, have also been implicated in feline lymphoma.

Question 9

Environmental factors

In one report, the relative risk of developing lymphoma in cats with any exposure to ETS and with 5 or more years of exposure to ETS was 2.4 and 3.2

Question 10

Alimentary/GI LSA

Lymphoma is the most common tumor type found in the GI tract of cats, representing ____ % of cases

_____ breed is reported at increased risk; however, the majority of cases occur in _____ cats

Mean of ____ years for T-cell alimentary lymphoma and ____ for B-cell lymphoma

Alimentary lymphoma is nearly ___ times more likely to occur in the ___ intestine than the ____ intestine.

Answer 10

55%

Siamese, DSH

10 to 13years, 12 years

4x, small, large

Question 11

Most feline GI lymphomas can be categorized into one of three types based on histopathology and immunohistopathology:

(1) low-grade alimentary lymphoma (LGAL),
(2) intermediate- or high-grade alimentary lymphoma (I/HGAL),
(3) large granular lymphoma (LGL)

Question 12

Low-Grade Alimentary Lymphoma

LGALs represent ____, _____, _____immunophenotypes that arise primarily from MALT

Major differential for LGAL is?

T-cell variants are much more likely to occur in the ____ (94%) and rarely in the _____ or _____

• The majority of T-cell variants are mucosal (equivalent to WHO enteropathy-associated T-cell lymphoma [WHO EATCL] type II), and the majority of B-cell tumors are transmural (equivalent to WHO EATCL type I classification).

Answer 12

mucosal, epitheliotropic, small T-cell

benign lymphocytic-plasmacytic enteritis

SI, stomach or LI

Question 13

Intermediate- or High-Grade Alimentary Lymphoma

Majority of I/HGALs are large or intermediate sized ___ lymphomas

They arise from ___ in the stomach and _____and mucosal lymphoid nodules concentrated in the distal small intestine, cecum, and colon

I/HGAL is more common in the _____, _____, ___, and _____

The majority are transmural (equivalent to WHO EATCL type I classification) and epitheliotropism is rarely observed.

Answer 13

B-cell

MALT, Peyer’s patches

stomach, distal SI, cecum, and colon

Question 14

Large Granular Lymphoma

These granulated round cell tumors have also been termed globule leukocyte tumors

They are usually _____ positive by immunohistochemistry

This population of cells includes cytotoxic T cells and occasionally NK cells: most are CD3+, CD8+, and CD20− and have T-cell receptor gene rearrangements

Originiate in _____, especially ____, are ____, exhibit epitheliotropism

And at least two-thirds present with other organs involved; most with mesenteric lymph node involvement and many with liver, spleen, kidney, peritoneal malignant effusions, and bone marrow infiltration. Also, thoracic involvement may occur with malignant pleural effusion and a mediastinal mass present.

Answer 14

Granzyme B

Small intestine, jejunum, transmural

Question 15

Common clinical signs with LGAL?

Signs present for how long?

Answer 15

weight loss (>80%), vomiting and/or diarrhea (70%–90%), and hyporexia (70%– 90%), whereas icterus is uncommon (7%)

Median 6 months

Question 16

Intermediate- or High-Grade Alimentary Lymphoma

Progress more acutely and are more likely to present with a palpable abdominal mass originating from the GI tract, enlarged mesenteric lymph nodes, or liver

Large Granular Lymphoma

Cats presented more acutely

Abdominal mass in 1/2 the cases, hepatomegaly, splenomegaly, and renomegaly are common

Abdominal and pleural effusions, and icterus are observed in nearly 10% of cases

Question 17

LGAL

Changes, if present, predominantly involves the ____ and ______ layers, although mucosal thickening can also occur

Answer 17

muscularis propria, submucosal layers

Question 18

Chlorambucil (20 mg/m2 PO every 2 weeks [preferred by the author] or 2 mg PO every other day) and prednisolone (initially 1–2 mg/kg PO daily, reduced to 0.5–1.0 mg/kg every other day over several weeks) results in response rates (i.e., resolution of clinical signs) of greater than _____% and MSTs of approximately _____ years.

Negative prognostic factors for cats with LGAL?

Answer 18

80%, 1.5-3.0 years

Lack of response and transmural extension

Question 19

The use of intraperitoneal-delivered COP in a small number of cats (n = 26) was reported; three-quarters achieved a CR with a MST of 1 year.

This study included only three GI cases and did not histologically or immunophenotypically subtype cases beyond saying all were “large cell”; therefore larger, more controlled studies would be necessary to establish/confirm efficacy of this protocol.

Question 20

Response to multiagent chemo protocols fo I/HGAL

Remission rate?

How may achieve CR?

MST?

Answer 20

Remission rates of 50% to 65% can be expected with approximately one-third achieving CR. Remission and survival are only durable in cases achieving a CR;

MSTs for cats in CR are approximately 7 to 10 months with a subset living to 1 year or longer.

Question 21

7 negative prognostic factors identified for I/HGAL include

Positive prognosis associated with?

Answer 21

transmural extension

FeLV antigenemia

weight loss

elevated LDH, hypoalbuminemia

hypo-cobaliminemia

bicavitary involvement

while stage I disease (rare) is associated with a more favorable prognosis.

Question 22

Large Granular Lymphoma

Approximately one-third of cases will experience a response and MSTs in larger reports of cases were only 21 days; cats receiving CHOP-based or CCNU-based protocols experienced MSTs of 45 to 90 days.

That being said, a small subset (7% in this report) enjoyed more durable (>6 month survivals) responses and, in one small study (n = 6), a MST of 9 months was reported after a variety of interventions.

Question 23

Peripheral nodal lymphoma in cats

Involvement limited to peripheral lymph nodes is unusual in cats with lymphoma, representing approximately _____ of cases

Uncommon and distinct form of nodal lymphoma in cats referred to as “Hodgkin’s-like” lymphoma has been reported

• solitary or regional lymph nodes of the head and neck
• Affected cats generally present with enlargement of one or two mandibular or cervical nodes initially, and tumors are immunophenotypically classified as T-cell–rich, B-cell lymphoma
• lymph nodes can be effaced by either nodular or diffuse small to large lymphocytes with characteristic bizarre or multinucleated cells (Reed–Sternberg-like cells)

Answer 23

4% to 10%

Question 24

Mediastinal LSA

Involves what organs?

Hypercalcemia?

Majority of cats in older reports?

In a more recent report of 55 cats with mediastinal lymphoma from the United Kingdom, the majority were antigenically FeLV/FIV negative, young (median age, 3 years), male (3.2:1 male-to-female ratio), and nearly one-third were Siamese.

In the largest report, cats with mediastinal lymphoma treated with either COP- or CHOP-based protocols experienced

overall response rate of 95% with a MST of 373 days (980 days if CR was achieved).

In contrast, mediastinal lymphoma in young FeLV-positive cats is generally associated with a poor prognosis and MSTs of approximately 2 to 3 months are expected after treatment with CHOP- or COP-based protocols.

Answer 24

Thymus, mediastinal, sternal LNs. Pleural effusion is common.

Rare

young (median age, 2–4 years), FeLV positive, and had T-cell immunophenotype tumor; however, many reports did not report immunophenotypic data.

Question 25

**Nasal lymphoma** Localized disease but \_\_% can have extension or distant metastasis at necropsy Median age? FIV/FELV? Immunophenotype? Breed? Sex?

Answer 25

20% 9-13 years Negative 3/4 B cell, T-cell and mixed B-cell/T-cell immunophenotypes are reported in 10% to 15% of cases Siamese cats appear overrepresented and a 2:1 male-to-female ratio has also been observed

Question 26

**Nasal lymphoma** If disease is documented to be confined to the nasal cavity (i.e., stage I) after thorough staging, then RT is the treatment of choice. CR rates of \_\_\_\_% are reported with MSTs after RT of ____ years. Cats that do not achieve a CR with RT have an MST of approximately \_\_\_\_. Total radiation dosage does affect STs, and a total dose greater than 32 Gy is recommended. The addition of chemotherapy to RT has not been definitively shown to enhance STs for cats with locally confined disease; combinations of RT and chemotherapy result in similar response rates and STs. Chemotherapy (COP- or CHOP-based protocols) is a reasonable alternative to RT, with CR rates of approximately _\_\_\__ % and MSTs of approximately ____ for cats achieving CR.

Answer 26

75-95%, 1.5-3.0 yrs 4.5 mo 75%, 2 years

Question 27

**Renal LSA** Can extend to what organ? Ultrasonographic imaging usually reveals bilateral (\>80%), irregular renomegaly with hypoechoic subcapsular thickening \_\_\_\_\_ will experience clinical benefit with COP- or CHOP-based protocols with MSTs reported from \_\_\_\_

Answer 27

CNS two-thirds, 4 to 7 months

Question 28

**CNS LSA** Most lesions occur at a thoracolumbar or lumbosacral location and are often multifocal. Bone marrow and renal involvement are often present, and cytologic assessment of these or other more accessible involved organs is generally more easily attainable than from spinal sites. generally fewer than 50% will respond and MSTs of 1 to 4 months can be expected.

Question 29

Cutaneous LSA older cats (median age, 10.0–13.5 years) with no sex or breed predominance, and is not associated with FeLV/FIV Cutaneous lymphoma often affects the head and face and is generally an indolent disease Two forms have been distinguished histologically and immunohistochemically. Most reports in the cat are epitheliotropic and consist of T cells, although, unlike in dogs, adnexal structures are often spared.

Question 30

**Ocular LSA** Presumed solitary ocular lymphoma (PSOL) is rare in cats and was identified in 5 of 110 cases of extranodal lymphoma in one report.559 Cats with ocular lymphoma are presented with uveitis or iridial masses, as well as signs related to systemic involvement of disease. Only sporadic reports appear in the literature with the major- ity (approximately 75%) being B-cell immunophenotyped. One case of LGL PSOL is documented. Intraocular, retinal, and conjunctival locations are reported.

Question 31

**Lymphoid leukemia** Approximately 60% to 80% of cats with ALL are FeLV positive, and most malignant cells have T-cell immunophenotypes Using COP-based protocols, a 27% CR rate has been reported CLL can be treated with chlorambucil (0.2 mg/kg PO or 2 mg/ cat qod; alternatively, 20 mg/m2 q2 weeks) and prednisolone (1 mg/kg PO daily). In 16 cats treated with chlorambucil and prednisolone, approximately 90% responded with a median remission duration of 6 months; however, half achieved CR with a median remission duration of 14 months.