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HEPATOCELLULAR CARCINOMA IN CAPTIVESLENDER TAILED MEERKATS (SURICATA SURICATTA):5 CASESAuthor(s): Judilee C. Marrow, D.V.M., Puja Basu, B.V.Sc. & A.H., M.Sc.,Timothy F. Walsh, D.V.M., Dipl. A.C.V.P. and Jessica L. Siegal-Willott,D.V.M., Dipl. A.C.Z.M.Source: Journal of Zoo and Wildlife Medicine, 45(1):134-142. 2014.Published By: American Association of Zoo VeterinariansDOI: http://dx.doi.org/10.1638/2013-0142R.1URL: http://www.bioone.org/doi/full/10.1638/2013-0142R.1

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Journal of Zoo and Wildlife Medicine 45(1): 134–142, 2014

Copyright 2014 by American Association of Zoo Veterinarians

HEPATOCELLULAR CARCINOMA IN CAPTIVE SLENDER TAILED

MEERKATS (SURICATA SURICATTA): 5 CASES

Judilee C. Marrow, D.V.M., Puja Basu B.V.Sc. & A.H., M.Sc., Timothy F. Walsh, D.V.M., Dipl.

A.C.V.P., and Jessica L. Siegal-Willott, D.V.M., Dipl. A.C.Z.M.

Abstract: Hepatocellular carcinoma was diagnosed in five slender tailed meerkats (Suricata suricatta) housed at

the Smithsonian Institution’s National Zoological Park between 1980 and 2013. Animals included four females

and one male, ranging from 7 to 15 yr of age. Common clinical signs included weight loss and lethargy. Three of

the neoplasms originated from the right medial liver lobe and were located adjacent to or partially incorporated in

the gall bladder. Three animals had solitary masses, and two animals had multiple hepatic masses; all were

characterized by polygonal to round neoplastic hepatocytes arranged in a trabecular pattern with smaller regions

of varied solid, adenoid, and rarely peliod cell patterns. Hemorrhage and necrosis often with cystic degeneration

was noted in all five cases. There was no evidence of metastatic disease in any of the cases examined.

Key words: Hepatocellular carcinoma, Herpestidae, meerkat, Suricata suricatta.

INTRODUCTION

Hepatic neoplasia is a rare occurrence in a

variety of domestic and wildlife species.3,5–8,10,14,15,18,20,22,24,26,29,30,33,34 Of reported malignant

hepatic neoplasms, hepatocellular carcinoma is

the most common primary hepatic neoplasm in

domestic carnivores.26–28 The morphologic, histo-

pathologic, and clinicopathologic features of

hepatocellular carcinoma have been well de-

scribed in dogs.19,27 In general, limited cases of

neoplasia have been reported in Herpestidae;

characterized neoplasms of meerkats (Suricata

suricatta) include nephroblastoma, pleomorphic

liposarcoma, squamous cell carcinoma, and in-

trahepatic cholangiocarcinoma.1,5,9,11,31 This report

presents the clinicopathologic and histopatholog-

ic findings of five meerkats with hepatocellular

carcinoma housed at the Smithsonian’s National

Zoological Park (NZP) between 1980 and 2013.

CASE REPORTS

Case 1

On 1 September 1984, a female, 940-g, 11-yr-

old, captive-born meerkat was presented for a 24-

hr history of holding the mouth open. The

meerkat had been housed at NZP for 10 yr and

had an unremarkable previous medical history

with the exception of melengestrol acetate (MGA)

implantation (manufacturer and dose not record-

ed) for pregnancy prevention. The animal was

anesthetized with ketamine (KetaVedt, Vedco, St.

Joseph, Missouri 64507, USA; 20 mg/kg i.m.) and

xylazine (Rompunt, Bayer Animal Health, Shaw-

nee Mission, Kansas 66201, USA; 2 mg/kg i.m.),

then maintained on halothane (Fluthanet, Wyeth-

Ayerst Laboratories, Philadelphia Pennsylvania

19101, USA; 0.5–1%) via endotracheal tube in

100% oxygen for examination. Significant physi-

cal exam findings included foreign material (food)

lodged in the molars preventing normal dental

occlusion and a large cranial abdominal mass.

Radiographs revealed a soft tissue opacity mass

occupying the right cranial abdominal quadrant.

Complete blood count (CBC) demonstrated leu-

kocytosis (14.43103/ll; reference range, 5.4 6 2.8

3 103/ll), increased red blood cell count (RBC)

(17.83106/ll; reference range, 9.4 6 1.53106/ll)and mildly increased hematocrit (HCT) (54%;

reference range, 41.5 6 6.8%).12 Serum biochem-

ical evaluation was not performed owing to

limited sample volume.

Exploratory laparotomy revealed a 3.5-cm

round mass originating from the right medial liver

lobe adjacent to the gall bladder. Other liver lobes

had multiple, small nodular masses of similar

appearance. A partial liver lobectomy of the right

medial liver lobe was performed, and the mass

was fixed in 10% buffered formalin for histopath-

ologic evaluation. Intraoperatively, the meerkat

received lactated Ringer’s solution (LRS, Hospira

Inc., Lake Forest, Illinois 60045, USA, 44 ml/kg

i.v.), atropine (Atropine sulfate 1/120 grain in-

jectable, Vedco, St. Joseph, Missouri 64507, USA;

0.02 mg/kg i.m.) and penicillin G benzathine/

From the Smithsonian Institution National Zoological

Park, Smithsonian Conservation Biology Institute, Wild-

life Health Sciences, 3001 Connecticut Avenue, Wash-

ington, D.C. 20008, USA (Marrow, Basu, Walsh, Siegal-

Willott). Present address (Marrow): Binder Park Zoo,

7400 Division Drive, Battle Creek, Michigan 49014,

USA. Correspondence should be directed to Dr. Marrow

(judileemarrowdvm@gmail.com).

134

penicillin G procaine (Dual-Pent, TechAmerica

Group Inc., Elwood, Kansas 66024, USA; 75,000

IU/kg s.c.). No anesthetic reversals were admin-

istered. Trimethoprim/sulfadiazine (Tribrissent,

Intervet/Schering-Plough Animal Health, Mills-

boro, Delaware 19966, USA; 50 mg/kg s.c. b.i.d.

for 7 day) was administered postoperatively. No

complications were noted at the time of surgery or

during recovery.

Histopathologic evaluation of the excised liver

mass demonstrated multifocal expansile, nonen-

capsulated, hypercellular nodules, consisting of

sheets and anastomosing cords of neoplastic

hepatocytes that compressed adjacent hepatic

architecture (Fig. 1). The neoplastic cells had

coarsely granular to vacuolated cytoplasm. The

nuclei had up to two variably distinct nucleoli and

moderate anisokaryosis with a mitotic rate of up

to 5 mitotic figures per high powered field (HPF;

3400) (Table 2). Many of the nodules contained

large blood-filled cysts or multifocal areas of

medium-sized cystic spaces filled with proteina-

ceous material. The histologic diagnosis was

hepatocellular carcinoma.

This meerkat represented 8 mo later with

progressive weight loss of 21% body weight.

CBC demonstrated anemia, and biochemical

evaluation revealed elevated liver enzymes and

total bilirubin (2.2 mg/dl; reference range, 0.2 6

0.2 mg/dl) consistent with liver failure (Table 1).12

Euthanasia was elected owing to poor clinical

condition.

At necropsy, the meerkat was in poor body

condition with decreased subcutaneous fat stores

and muscle atrophy. The abdomen was distended

with 25-ml sanguineous fluid. The liver was

diffusely enlarged and pale, with numerous focal

to coalescing, fluctuant to firm nodules, measur-

ing up to 3 cm in diameter. Gross findings were

consistent with progression of hepatocellular

carcinoma, and histopathology was consistent

with previous biopsy results but also included

extensive areas of necrosis. There were numerous

dilated and congested sinusoids surrounded by

areas of necrosis throughout the liver, consistent

with clinicopathologic findings of biliary stasis

and liver failure. There was no evidence of

extrahepatic metastasis.

Case 2

On 19March 1998, a spayed, 12-yr-old, 1,100-g,

female meerkat was evaluated for routine exam-

ination. The animal had a history of uterine

neoplasia (details not recorded), which was suc-

Figure 1. Photomicrograph of the liver from a

meerkat (Suricata suricatta) (case 1) demonstrating the

multinodular interface with nonneoplastic liver and

hepatocellular carcinoma (A) and the hepatic capsule

covered with hemorrhage (B). Bar¼ 2 mm. H&E, 20X.

Table 1. Comparison of signalment, weight loss, select hematologic and biochemical parameters for fivemeerkats (Suricata suricatta) diagnosed with hepatocellular carcinoma between 1980 and 2013.a

Case SexAge(yr)

Weightloss (%)

Hematology and biochemical results

RBC9.4 6 1.53 106/llb

HCT41.5 6 6.8

(%)

WBC5.4 6 2.83 103/ll

AST80 6 39IU/L

ALT103 6 73IU/L

ALP19 6 10IU/L

GGT4 6 4IU/L

ALB3.3 6 0.5

g/dl

1c F 11 21 12.3 27.5 14.0 192 318 699 — 2.2

2 F 12 6 10.14 38 12.5 370 337 517 — 2.8

3 M 15 15 7.75 35 4.1 370 331 517 — 3.1

4 F 7 18 9.64 48.2 6.8 72 142 39 16 1.9

5 F 9 21 7.69 39.2 6.4 104 445 93 53 2.2

a RBC, red blood cell; HCT, hematocrit; WBC, white blood cell; AST, aspartate transaminase; ALT, alanine aminotransferase;

ALP, alkaline phosphatase; GGT, gamma-glutamyl transpeptidase; ALB, albumin; F, female; M, male.b Reference intervals.12

c Clinicopathological data from time of euthanasia as there was insufficient sample available for biochemical evaluation at the

time of diagnosis.

MARROW ET AL.—HEPATOCELLULAR CARCINOMAS IN MEERKATS 135

cessfully treated with ovariohysterectomy, and

had been housed at NZP for 4 yr. The animal

was anesthetized and maintained under anesthe-

sia using isoflurane (Isoflot, Abbott Laboratories,

Animal Health Division, Abbott Park, Illinois

60064, USA; 2.5–3%) in 100% oxygen via face-

mask for examination. On examination, a large

cranial abdominal mass was detected, and a body

weight loss of 6% was documented. The meerkat

had a slight anemia on CBC and elevations in liver

enzymes (Table 1). Exploratory laparotomy re-

vealed a 10-cm diameter soft, purple to red, multi-

lobulated mass filling the abdominal cavity. Eu-

thanasia was elected at the time of surgery owing

to poor prognosis.

Necropsy examination revealed fair body con-

dition with adequate subcutaneous fat stores.

The liver mass weighed 256 g, displaced the

gallbladder and common bile duct ventrally, and

arose from the right medial liver lobe. Approx-

imately 30 ml of serosanguineous fluid and

several clots filled the abdomen. On cut section,

the mass had central cystic areas, measuring up

to 4.5 cm, filled with clear to serosanguineous

fluid. Histopathologically, the round to polygo-

nal neoplastic hepatocytes were arranged in well-

defined cords and trabeculae replacing the nor-

mal hepatic architecture. The cells had moderate

amounts of granular eosinophilic cytoplasm and

finely stippled chromatin with mild to moderate

anisokaryosis. The mitotic rate averaged one

mitotic figure per 3400 field (Table 2). Rare,

multi-nucleate cells contained up to three large

nuclei. There were multifocal cavitations associ-

ated with hemorrhage and necrosis similar to the

previous case. Scant aggregates of hematopoietic

cells were most prominent around the periphery

of the nodules.

Case 3

On 19 October 2000, a male, 712-g, 15-yr-old

meerkat presented for examination after 15%body weight loss of 7 mo duration. The animal

was captive born, had been housed at NZP for 6

yr, and prior medical history included dental

disease and cataracts. The animal was anesthe-

tized with isoflurane (0.5–3%) as previously

described. A large cranial abdominal mass was

palpated and identified on radiographs as a large

soft tissue opacity within the left cranial abdo-

men. The mass had a heterogeneous echogenicity

with a hypoechoic center on ultrasound. The CBC

revealed leukocytosis, and serum biochemistry

revealed elevations in liver enzymes (Table 1).

Euthanasia was elected owing to poor prognosis.

At necropsy, this meerkat was in good body

condition with adequate subcutaneous fat stores

despite recent weight loss. Approximately 2 ml

clear, straw-colored fluid was present in the

abdomen. A green to brown, lobulated, 5.8 3 4.4

3 4.8-cm, 100-g mass projected from the left side

of the liver, with multiple close adhesions between

the diaphragm, stomach, and proximal small

intestine. On cut surface, the mass was soft to

firm with central cysts full of brown-tinged fluid,

measuring up to 1.3 cm. Histologically, the mass

was focally extensive, multinodular, compressive,

and nonencapsulated. The cells were arranged in

dense trabecular and acinar (adenoid) structures.

In the trabecular areas, the neoplastic cells

formed thin to thick plates or cords, separated

by thin vascular spaces. In the adenoid form,

crude acini were separated by minimal to moder-

ate eosinophilic matrix. The round to polygonal

cells had variably distinct borders and eosinophil-

ic cytoplasm. Nuclei varied from small to medium

with scattered giant nuclei, vesicular chromatin,

and numerous nucleoli. A mitotic rate of up to

Table 2. Comparison of mass gross pattern, histologic pattern, mitotic rate, and survival from diagnosis toeuthanasia for five meerkats (Suricata suricatta) diagnosed with hepatocellular carcinoma between 1980 and 2013.

Case

Hepatocellular carcinomaMitotic rate

(per 3400 field)Survivalin daysGross pattern Histologic pattern Differentiation

1 Nodular Trabecular Well 5 248a

2 Massive Trabecular Well 1 N/A

3 Massive Trabecular, adenoid (rare) Moderately well to well 2 N/A

4 Massiveb Trabecular and solid Moderately well to well 0–6 254a,c

Nodulard Trabecular, areas of spindle cells Poor to moderate 10

5 Nodular Trabecular with solid and peliod (rare) Moderate to well Up to 10 28

a Data reflect treatment with partial liver lobectomy.b Data reflect biopsy findings of hepatocellular carcinoma in case 4.c Case 4 was additionally treated with metronomic chemotherapy for 8 mo prior to euthanasia.d Data reflect necropsy findings of hepatocellular carcinoma in case 4.

136 JOURNAL OF ZOO AND WILDLIFE MEDICINE

two mitotic figures per 3400 field was detected

(Table 2). There were minimal multifocal aggre-

gates of hematopoietic cells and multifocal mod-

erate hemorrhage. No evidence of extrahepatic

metastasis was present in the sections reviewed.

Case 4

On 31 October 2011, an 850-g, female, estimated

7-yr-old meerkat presented for lethargy and hesi-

tancy to sit up in ‘‘guard’’ position. This wild-

caught animal had been housed at NZP for 5 yr

with no significant clinical history. The meerkat

was chamber-induced with isoflurane (5%) in

100% oxygen and maintained (1.25–3%) via face

mask as previously described. Examination re-

vealed a thin body condition, weight loss of 18%,

and a large cranial abdominal mass. CBC and

serum biochemical values were unremarkable

other than slight elevations in alkaline phosphatase

(ALP) and gamma-glutamyl transpeptidase (GGT)

(Table 1). Radiographs revealed a large soft tissue

opacity mass in the right cranial abdomen. Ultra-

sound further revealed the mass to be heteroge-

neous with central hypoechoic cavitations.

Ultrasound-guided fine needle aspiration was

performed; however, cytology was inconclusive.

One week later, exploratory laparotomy for

surgical biopsy to determine the definitive diag-

nosis was performed. The animal was anesthe-

tized as previously described and, once at surgical

plane of anesthesia, was intubated and main-

tained on isoflurane (1.75–3%) for the duration

of the procedure. A 4-cm, 60-g liver mass arising

from the right medial liver lobe and adhered to

the apex of the gall bladder was identified. A

partial liver lobectomy was performed just prox-

imal to the visual demarcation between the liver

and the mass with a TA-30 stapler (Covidien

Surgical, Norwalk, Connecticut 06856, USA).

There was no evidence of metastasis within the

liver, abdominal lymph nodes, or other abdominal

viscera. The mass was fixed in formalin for

histopathology. Intraoperative antibiotics, anal-

gesics, and fluids, and surgical closure were

routine; recovery was unremarkable. Postopera-

tively, the animal was treated with supportive

care, including Ursidiol (Ursidiol 300-mg capsule,

Lannett Company Inc., Philadelphia, Pennsylva-

nia 19136, USA; 9 mg/kg p.o. s.i.d. for 45 days).

Twenty-four hours after surgery, the meerkat

had dramatic ventral abdominal bruising and mild

oozing from the incision. The animal was anesthe-

tized with isoflurane as described previously and

maintained on a face mask. Examination revealed

subcutaneous hemorrhage, and CBC revealed

anemia with a low hematocrit (25%; reference

range, 41.5 6 6.8%).12 The meerkat was treated

with supportive care, including phytonadione (Vit-

K1, Sparhawk Laboratories Inc., Lenexa, Kansas

66215, USA; 0.5 mg/kg p.o. s.i.d. for 14 days) for

possible coagulopathy. The subcutaneous hemor-

rhage resolved over the next week, and no further

complications were noted. The animal was singly

housed during convalescence and returned to its

normal enclosure with a single male companion

without event 2 wk postoperatively.

Histopathologic evaluation of the liver mass

revealed discrete but infiltrative nodular regions

of neoplastic cells compressing the normal hepat-

ic tissue. The nodular regions were composed of

cells, arranged in densely packed sheets or wide

trabeculae, interspersed with cystic areas of

hemorrhage and necrosis (Fig. 2). The small to

large, round to polygonal cells had abundant

coarsely granular to vesicular cytoplasm. Nuclei

were round to ovoid, medium to rarely large.

Isolated small patches of cells had dense eosino-

philic cytoplasm and occasional giant cells. Mi-

totic rate was highly variable from 0 to 6 figures

per HPF (Table 2). Scattered megakaryocytes and

small areas of extramedullary hematopoiesis were

numerous within sinusoids of some nodules while

absent in others. The remaining hepatic capsule

was intact, and the adjacent rim of normal

compressed gall bladder and liver tissue was less

than 1-mm thick at the surgical margin.

Based on the narrow surgical margin, this

animal was started on a metronomic chemother-

Figure 2. Photomicrograph of the liver from a

meerkat (Suricata suricatta) (case 4) demonstrating

prominent trabeculae pattern, with moderately well-

differentiated neoplastic cells, (A) transitioning to a

more compact region (B) within the hepatocellular

carcinoma. Bar ¼ 200 lm. H&E, 100X.

MARROW ET AL.—HEPATOCELLULAR CARCINOMAS IN MEERKATS 137

apy protocol with meloxicam (Metacam, Boeh-

ringer Ingelheim Vetmedica, Inc., St Joseph,

Missouri 64506, USA; 0.05 mg/kg p.o. s.i.d.),

cyclophosphamide (1.4 mg compounded cap-

sules, Taylor’s Pharmacy, Winter Park, Florida

32789, USA; 1.5 mg/kg p.o. s.i.d.), and milk

thistle (Herbal Authorityt, Holbrook, New York

11741, USA; 33 mg/kg p.o. s.i.d.) for hepatopro-

tective effects until the time of euthanasia. The

meerkat was evaluated under anesthesia for

radiographs, ultrasound, CBC, and serum bio-

chemistry at 1-mo intervals for the first 3 mo

then every 3 mo thereafter for evaluation of

tumor reoccurrence. No clinical abnormalities

were noted until the animal presented 8 mo after

mass removal for recheck examination. The

animal was anesthetized with isoflurane as pre-

viously described. Exam revealed a weight loss of

9% and serum biochemistry elevations in aspar-

tate aminotransterase (AST 137 IU/L; reference

range, 80 6 39 IU/L), alanine aminotransferase

(ALT 235 IU/L; reference range, 103 673 IU/L),

and ALP (159 IU/L; reference range, 19 6 10

IU/L).12 Radiographs and ultrasound demon-

strated liver enlargement, and ultrasound re-

vealed multiple hypoechoic masses within the

liver lobes measuring up to 3.5 cm in diameter.

The animal recovered normally, but because of

continued clinical decline over the next month,

euthanasia was ultimately elected.

Necropsy revealed good body condition with

adequate subcutaneous fat stores. No ascites was

noted. The liver contained multiple firm, off-

white nodules measuring up to 3.1 cm in diameter,

which encompassed approximately 60% of the left

middle and lateral lobes and 5% of the right

lateral lobe. On cut surface, the masses were

diffusely firm and occasionally contained soft

necrotic centers. The left caudal lung lobe con-

tained a 3-mm, firm, off-white nodule of similar

appearance to those in the liver. Histopathologi-

cally, the liver masses differed from the previous

biopsy; multiple scattered nodules contained

wide, closely opposed, trabeculae. The small to

rarely giant cells were densely packed and varied

from ovoid to polygonal to rarely fusiform, often

with indistinguishable cytoplasmic borders. Cells

had increased amphophilic cytoplasm (increased

basophilia) and nuclear pleomorphism with ve-

sicular and marginated chromatin with a promi-

nent eosinophilic nucleolus. The mitotic rate of

these cells was increased, with up to 10 mitotic

figures per 3400 field (Table 2). Rare nodular

areas transitioned to streaming fusiform cells

predominantly at the periphery. There were

frequent sites of vascular invasion and occasional

intravascular rafts of neoplastic cells (described

above). The surrounding liver had mild periportal

infiltrates of hematopoietic cells and lympho-

cytes. Occasional bile ducts contained clusters of

neutrophils. The pulmonary mass had multifocal

discrete but infiltrative nodules of tightly packed

cords of neoplastic cells palisading along thin

capillaries. The cuboidal neoplastic cells had

uniformly round, apical nuclei and basal cyto-

plasmic clearing. The mitotic rate of the pulmo-

nary mass varied from one to six mitotic figures

per 3400 field. Because of the different histologic

features compared with the hepatic tumors, the

lung mass was considered a primary pulmonary

neoplasm and not a metastasis from the liver.

Case 5

On 21 November 2012, an 869-g, female,

estimated 9-yr-old meerkat was presented for

21% body weight loss of approximately 8-mo

duration. This wild-caught animal had been

housed at NZP for 6 yr prior to presentation.

Clinical history included clinically unapparent

cardiomegaly (diagnosed 1 yr earlier) and admin-

istration of medroxyprogesterone acetate (Depo-

Provera, Pharmacia & Upjohn Company, New

York, New York 10017, USA; 5 mg/kg s.c.) to

treat intraspecific aggression presumed related to

reproductive cyclicity. The meerkat was chamber-

induced with isoflurane (5%) in 100% oxygen and

maintained (3–4%) via face mask as previously

described. Examination and abdominal ultra-

sound were unremarkable, while radiographs

demonstrated a slightly enlarged hepatic silhou-

ette extending just beyond the caudal aspect of the

ribs. CBC and bile acids were unremarkable;

serum biochemical values were unremarkable

other than an elevated GGT (Table 1). Empirical

treatment with amoxicillin trihydrate/clavulanate

potassium and milk thistle was prescribed.

Three and a half months later, the meerkat

represented for an additional 9% weight loss. The

meerkat was anesthetized as described above, and

examination revealed moderate hepatomegaly.

Radiographs revealed rounded hepatic margins

and generalized decreased abdominal detail. The

CBC remained unremarkable, while serum bio-

chemical values were elevated for iron (337 lg/dl;reference range, 186 6 64 lg/dl) and liver

enzymes (Table 1).12 Ultrasonography revealed

multifocal heterogeneous masses, measuring up

to 2 cm, affecting all liver lobes. Needle biopsy

(Tru-cutt, Cardinal Health, Dublin, Ohio 43017,

USA; 18 ga, 3 in) samples were submitted for

138 JOURNAL OF ZOO AND WILDLIFE MEDICINE

histopathologic evaluation, yielding small aggre-

gates of hepatocytes with moderate pleomor-

phism, anisocytosis, and lacking normal

architectural features such as portal triads or

central veins (suggestive of hepatocellular carci-

noma). The meerkat received meloxicam (0.1 mg/

kg s.c.) and lactated Ringer’s solution (11 ml/kg

s.c.) during the exam and was started on a course

of denosyl (Zentonilt, Vetoquinol USA, Fort

Worth, Texas 76137 USA; 200-mg tablet, 70

mg/kg p.o. s.i.d. for 16 days).

Two months after diagnosis, the meerkat pre-

sented for euthanasia because of continued weight

loss (34% weight loss compared with historic

weights). At necropsy, the meerkat was in fair

body condition with adequate stores of adipose

tissue. No ascites was noted. Multiple tan to red

masses, measuring 1–4 cm, with occasional cystic

centers and omental adhesions, were present in

the left medial and right medial liver lobes. Rare

minute nodules were also present in other lobes.

Histopathology revealed distinct cords and tra-

beculae of polygonal cells with moderate amounts

of eosinophilic cytoplasm and medium round

nuclei forming coalescing, compressive, nonen-

capsulated nodules of different staining intensity.

Some smaller areas were characterized by solid

sheets of cells or rarely small tubules or acini.

Cells in these areas were polygonal with small to

moderate amounts of eosinophilic to amphophilic

cytoplasm, and variably small to large, irregularly

spaced, ovoid to round nuclei with clumped

chromatin. There were small to medium cysts,

more prominent in the central regions of the

nodules, containing flocculent eosinophilic mate-

rial with blood and lined predominantly with

proliferative hepatocytes (peliod-type differentia-

tion) with numerous larger areas of necrosis. In

areas with uniform trabeculae, mitotic figures

were rare or absent in a 3400 field; however, in

areas dominated by solid sheets of neoplastic

cells, characterized by giant ovoid nuclei with

vesicular chromatin and large magenta nucleoli,

there were up to 10 mitotic figures per 3400 field

(Table 2). Aggregates of hematopoietic tissue

were within the masses surrounding liver.

DISCUSSION

Hepatocellular carcinoma has not been previ-

ously reported in meerkats or Herpestidae but has

been reported in a number of other carnivore

species in addition to being the most common

malignant hepatic neoplasm in domestic carni-

vores.6,14,15,22,27,30,33 Meerkats were formerly classi-

fied in the family viverridae, and hepatocellular

carcinoma has been reported in a single member

of this taxonomic family.15 Between 1980 and

2013, 5 of 28 adult meerkats (.1 yr of age) in

the NZP collection were diagnosed with hepato-

cellular carcinoma on biopsy or at the time of

necropsy; a prevalence of 17.8%. No other cases

of hepatic neoplasia were documented during this

time period in this population, and none of the

cases appeared to be genetically related. The

average age of presentation was 10.8 yr, similar

to reported age ranges seen in domestic dogs.28 In

cases that underwent surgical resection (cases 1

and 4), life expectancy was similar to reported

ranges for domestic dogs.17 Four of the five cases

occurred in female meerkats, which may represent

an overrepresentation of females in this popula-

tion. Review of the larger population of captive

meerkats would help elucidate if there is a

generalized predilection for hepatocellular carci-

noma and if females are more predisposed to this

tumor type in this species.

The most common presenting clinical finding in

meerkats with hepatocellular carcinoma was a

palpable cranial abdominal mass (n¼ 5), followed

by weight loss of 10% body weight or greater (n¼4), and lethargy (n ¼ 2). In three cases, where

tumor weight was recorded, the masses ranged in

size from 8.2 to 23.2% total body weight. Weight

loss could have initially been masked by corre-

sponding increases in tumor size or excessive

body condition, which can be common in captive

meerkats. Given the social structure of meerkats,

weak or ill animals instinctively mask clinical

signs of disease to avoid conspecific aggression;

this behavior may have contributed to delayed

detection of signs by animal care staff and the

presence of advanced disease in affected animals

at the time of diagnosis.21 In case 4, successful

reintroduction without reported conspecific ag-

gression post surgery was attributed to this

animal being housed with one male conspecific.

In domestic species, commonly reported clinical

signs include anorexia, ascites, vomiting, and

jaundice; cases 1, 2, and 3 had ascites at the time

of necropsy.27 One animal showed no clinical signs

prior to presentation; however, all animals were

noted to have palpable cranial abdominal masses

on examination.

All meerkats had some degree of clinicopatho-

logic abnormality at the time of diagnosis; how-

ever, findings were not consistent among all

animals. The most consistent findings included

elevated ALT (n ¼ 4), low serum albumin (n ¼ 3),

elevated AST and ALP (n¼3), elevated WBC (n¼2) and anemia (n ¼ 2). In domestic carnivores,

MARROW ET AL.—HEPATOCELLULAR CARCINOMAS IN MEERKATS 139

liver enzyme values are not consistently elevated

in cases of hepatocellular carcinoma; however,

ALT is often elevated disproportionally more

than AST as was seen in these meerkats.19,27 In

general, clinicopathologic findings may be helpful

in interpreting the severity of disease, as animals

with advanced hepatocellular carcinoma and large

tumor size tended to have the greatest deviations

in values from reference ranges.

Diagnosis of hepatocellular carcinoma in meer-

kats was confirmed by needle biopsy (case 5),

excisional biopsy (cases 1 and 4), or necropsy

(cases 2 and 3). Fine needle aspiration was

inconclusive for diagnosis of hepatocellular car-

cinoma in case 4. Meerkats with liver lobectomy

for the purpose of excisional biopsy (cases 1 and

4) had longer survival times than cases without

surgical mass removal. In dogs with solitary

hepatic masses, partial or complete liver lobecto-

my can result in long survival times and resolution

of clinical signs.17 Case 4 additionally received

metronomic chemotherapy aimed at slowing

tumor growth and angiogenesis. This animal

tolerated medications well, and no adverse clini-

cal signs were reported during the 8-mo period

before euthanasia. Further investigation is needed

to determine if metronomic chemotherapy is a

useful modality in extending survival times of

meerkats with hepatocellular carcinoma.

The morphologic appearance of hepatocellular

carcinoma in meerkats was similar to reports in

other domestic and nondomestic carnivores. Two

animals presented with nodular tumors in multiple

lobes of the liver, but the majority of cases

presented with massive tumors of one liver lobe,

corresponding with the most commonly reported

presentation in dogs.19,27 In meerkats most (4 of 5)

tumors at least initially arose from the right side

and impinged on the gall bladder. In dogs, left-

sided origin has been reported to be more

common.27 Histologically, the trabecular pattern

predominated in all cases; though other patterns,

including solid (n¼ 2), adenoid (n¼ 2), and peliod

(n ¼ 1), could be found in some areas. Some

variation of microscopic patterns is considered

common, which may complicate accurate charac-

terization of cytologic or small surgical biopsy

specimens.4,13 Cavitation associated with hemor-

rhage and necrosis was present in all cases. Of

interest, four of the cases (2, 3, 4, and 5) were noted

to have some foci of extramedullary hematopoie-

sis. Extrahepatic metastasis is fairly common in

domestic species.19,27 Despite invasion of hepatic

vasculature by the neoplastic cells in cases 1, 4, and

5 with intrahepatic spread, no extrahepatic metas-

tasis was found. Additionally, in case 4, there was

significant morphologic variation between the

original surgically resected mass and the subse-

quent intrahepatic masses sampled at necropsy.

Whether the more poorly differentiated cytologic

features of the necropsy nodules represent pro-

gressive anaplastic differentiation of the primary

intrahepatic metastasis or development of an

altogether different neoplasia is speculative. There

has been some evidence that, at least in humans,

progression to more poorly differentiated pheno-

types is common with time and increase in tumor

size.16 The small number of cases reported here

may not represent the true metastatic potential of

hepatocellular carcinoma in meerkats.

In humans, the most common etiology is

cirrhosis, while in veterinary species, suggested

etiologies have included viral infections, hemoc-

romatosis, or toxins, but often no underlying

cause can be determined.2,3,7,8,20,28,29,32,34 No com-

mon etiologies of hepatocellular carcinoma have

been reported in nondomestic carnivores; how-

ever, hemochromatosis has been determined as

the underlying etiology in bats.8,14,15,20,22,30,32,33 The

liver of these animals did not have severe

chronic inflammatory or fibrotic changes sug-

gestive of viral infection, cirrhosis, or other

toxic insults. The single animal treated with an

MGA implant demonstrated vacuolar hepatitis,

which can be consistent with chronic steroid

stimulation; insufficient evidence exists to de-

termine if chronic steroid exposure can predis-

pose meerkats to developing hepatocellular

carcinoma. Melengestrol acetate implants have

been linked to neoplasia in carnivores; however,

no cases of hepatic neoplasia have been linked

to these implants.23,25 An underlying etiology for

hepatocellular carcinoma was not evident in the

meerkats examined.

CONCLUSION

With the exception of extrahepatic metastasis,

hepatocellular carcinomas in meerkats are similar

in clinical signs, clinicopathologic presentation,

and histopathologic findings to those reported in

domestic species. Propensity to obesity in captive

animals and the social structure of this species

may mask initial clinical signs. Regular weights,

routine examination, hematologic and biochemi-

cal tests, and diagnostic imaging in addition to

necropsy evaluation of the larger captive and wild

populations of meerkats is necessary to determine

if there is an increased prevalence of this tumor

type in female meerkats or in the general popu-

lation and if a common underlying etiology exists.

140 JOURNAL OF ZOO AND WILDLIFE MEDICINE

Acknowledgments: The authors would like to

thank the past and present veterinary and animal

care staff from the Smithsonian Institution’s

National Zoological Park for their care of the

animals and contributions to the medical care of

the animals presented in this manuscript.

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Received for publication 26 June 2013

142 JOURNAL OF ZOO AND WILDLIFE MEDICINE