Myeloproliferative Disorder with Intraoral Lesions in an Olive Baboon (Papio anubis)

Abstract

Spontaneous myeloid leukemia is rarely reported in nonhuman primates. We report a case of myeloproliferative disorder suggestive of acute myeloid leukemia with intraoral lesions in an olive baboon (Papio anubis). Clinical pathology, radiology, gross exam (pre-mortem and post-mortem), histopathology, and immunohistochemistry findings are provided.

Introduction

Acute myeloid leukemia (AML) is a myeloproliferative disorder characterized by increased myeloid cells with arrested maturation in the marrow. Myeloid sarcoma (MS) is strongly associated with AML and myelodysplastic syndromes, but rarely affects intraoral tissues.[1 2] We describe a myeloproliferative disorder, suspected to be AML with associated intraoral MS in an olive baboon (Papio anubis).

Case Report

The Southwest National Primate Research Center, Texas Biomedical Research Institute is AAALAC-accredited and all animals are managed under IACUC-approved protocols in accordance with federal animal welfare regulations and the Guide for the Care and Use of Laboratory Animals.[3] A 13.09kg, 5 year-5-month-old, group-housed, female olive baboon presented for facial swelling over the right mandible and weight loss. On clinical exam, there was a round, fluctuant soft tissue swelling at the level of right mandibular premolars. Due to suspected tooth root abscess, two loose premolars were removed. A small amount of caseous material was expressed and the area was flushed with dilute nolvasan. Buprenorphine-SR (0.9mg SC, ZooPharm), meloxicam (2.75mg SC, Henry Schein Animal Health) and cefazolin (350mg IM, WG Critical Care, LLC) were administered.

The following day, the right mandibular canine was loose. Radiographs showed erosion of the caudal cortex of the tooth (Figure 1A); the canine was easily removed. Sodium chloride (0.9%, 18ml/kg, IV) and flunixin meglumine (13mg SC, Merck Animal Health) were given during the procedure. Complete blood count and serum chemistry (Table 1) results showed azotemia, leukocytosis and abnormal electrolytes. NSAID administration was discontinued due to azotemia.

Figure 1:

Image Panel of Radiographic, Gross and Histopathologic Findings. A). Radiograph of cranial mandible. B). Mandibular mass showing removed teeth. Regional swelling consists of soft dark red mass. C)., D). and E). Multiple myeloblasts in blood smear. F). Mandible histopathology showing extensive bone effacement replaced by densely cellular sheet of neoplastic round cells. H&E. G). Higher magnification of mandibular mass shows densely cellular sheet of neoplastic round cells. Three larger round cells with eosinophilic crystalline intracytoplasmic pigment are also present. H&E. H). Histopathology of the iliac crest showing neoplastic effacement of bone marrow, trabecular and cortical bone with regionally extensive periosteal proliferation. H&E.

Table 1.

Complete Blood Count and Serum Chemistry

Parameter	Result, 1d post presentation	Result, 3d post presentation	Reference Range
White Blood Cells (THOUS/MM3)	22.3	25.4	4.5–18.1
Hemoglobin (g/dL)	13.5	12.3	11.0–14.4
Hematocrit (%)	41.5	36.8	33.7–43.7
Neutrophils (THOUS/MM3)	12.3	3.8	2.3–14.9
Bands (THOUS/MM3)	0	4.6	n/a
Lymphocytes (THOUS/MM3)	4.0	12.2	1.0–4.5
Monocytes (THOUS/MM3)	5.5	0.3	0.2–0.8
Eosinophils (THOUS/MM3)	0.1	0	0.0–0.2
Basophils (THOUS/MM3)	0.4	0	0.0–0.1
Glucose (mg/dL)	105	95	60–112
BUN (mg/dL)	119	112	6–20
Creatinine (mg/dL)	4.0	3.3	0.6–1.3
ALT (U/L)	111	151	10–62
AST (U/L)	204	263	17–47
ALP (U/L)	532	599	58–237
Cholesterol (mg/dL)	256	207	57–141
Sodium (meq/L)	133	134	135–147
Potassium (meq/L)	2.5	3.1	2.9–4.2
Chloride (meq/L)	88	90	102–114
Anion Gap (meq/L)	24.5	21.1	6.1–18.4
Total Protein (g/dL)	6.5	5.8	5.9–8.0
Albumin (g/dL)	3.1	2.5	3.1–4.7
Globulin (g/dL)	3.4	3.3	2.2–3.9
LDH (U/L)	n/a	2069	89–332
CPK (U/L)	n/a	16160	108–1020
Calcium (mg/dL)	n/a	14.1	8.1–10.0
Phosphorous (mg/dL)	n/a	7.5	1.7–6.0
Triglycerides (mg/dL)	n/a	1116	11–86

The animal displayed severe inappetence and 3 days after presentation showed continued azotemia, increasing liver enzymes and leukocytosis morphologically consistent with myeloblasts (Figure 1C, D, E). Urinalysis revealed trace protein, blood, bacteria and epithelial cells. Radiographs showed lytic bone lesions within the pelvic iliac crests and both scapulae. Despite supportive care, the animal died 3 days after presentation.

Postmortem examination revealed a 3cm diameter, soft mass overlying the exterior two-thirds of the cranial right mandible (Figure 1B). In addition to all vital organs, multiple bone samples corresponding to areas of radiographic lucency were collected, fixed in 10% neutral buffered formalin, processed conventionally, stained with hematoxylin and eosin and evaluated by light microscopy by a board-certified veterinary pathologist.

Filling the marrow cavity, replacing the cancellous bone and replacing and variably extending through the cortical bone of the mandible, left scapula, right scapula, left ilium, and right ilium (and replacing the bone marrow in the left and right femurs) was an un-encapsulated, poorly demarcated, infiltrative and expansile mass composed of sheets of cells supported by a fine to unapparent stroma (Figure 1 F, G, H). The cells had distinct cell margins, amphophilic to eosinophilic cytoplasm (sometimes with eosinophilic granules), indented to bean shaped nuclei, with stippled chromatin, and generally a single nucleolus. Mitoses were variable, but rare (0–2/HPF). Within the mandible were extensive areas of necrosis. Similar neoplastic cells were observed expanding hepatic sinusoids where they were associated with degeneration, necrosis, and loss of hepatocytes and within the sinusoidal spaces of the hilar lymph node. Neoplastic cells were also observed surrounding and infiltrating the wall of large veins in the liver, as well as in blood vessels of hilar lymph nodes.

Immunohistochemistry (CD3-negative, CD34-non-contributory, CD68-positive, CD79a-negative, lysozyme-positive, myeloperoxidase (MPO)-positive, MUM-1-negative, PAX5-negative and IBA1-non-contributory) was performed on the mandibular mass. Rabbit anti-human monoclonal (CD3, CD79a, MUM-1, PAX5), rabbit anti-human polyclonal (lysozyme, MPO, IBA1) or mouse anti-human monoclonal (CD34, CD68) antibodies from Ventana or Wako (IBA1 only) were used. Antigen retrieval conditions were 37°C except for CD79a (36°C) at 32min (CD34, MPO, PAX5), 37min (CD79a), 40min (lysozyme, MUM-1), 48min (CD3, CD68) or 60min (IBA1). Neoplastic cells were diffusely immunopositive for myeloid markers: lysozyme and CD68. Scattered neoplastic cells were immunopositive for MPO.

Discussion

Clinicopathologic findings are highly suggestive of acute myeloid leukemia (AML). The lesion in the mandible shares some features of intraoral myeloid sarcoma, a rare tumor that often occurs concurrently in humans with AML. Other myeloproliferative disorders such as myeloproliferative neoplasm, myelodysplastic/myeloproliferative neoplasm and myelodysplastic syndromes cannot be fully ruled out.

The most common malignant tumors of monkeys are hematopoietic neoplasms (lymphomas and leukemias).[3 4] Lymphoma has been associated with Simian T-Lymphotropic Virus (STLV-1) in baboons.[3 4] The baboon in this case report was part of a STLV-1 negative SPF colony and her most recent STLV-1 screening was negative 5 months before death. AML has been experimentally induced in macaques with procarbazine administration and spontaneous myeloid leukemia is rarely reported in NHPs.[5–8]To our knowledge, this is the first report of myeloid leukemia with a mandibular myeloid sarcoma in a baboon.[4 9]

AML is the most common leukemia in adult humans.[10] Clinical presentation of AML is diverse and nonspecific.[11] It is often associated with cytopenias and may include fatigue, hemorrhage, infection, pallor and dyspnea.[11] A variety of other symptoms may be attributed to leukemic infiltration of various tissues.[11] There have been rare reports of AML in humans associated with bone marrow necrosis and osteolytic lesions as seen in this baboon.[10] Adverse prognostic indicators in humans include age over 60y, white blood cell count > 20,000/mm³ or an elevated serum LDH level at presentation.[11 12] This baboon had a white blood cell count of >25,000/mm³ and LDH of 2069U/L (normal range 89–332U/L).

Myeloid sarcoma (MS), previously known as “granulocytic sarcoma” or “chloroma”, is a rare tumor strongly associated with AML and myelodysplastic syndromes.[1 2] A variety of tissues may be affected by MS, including the skin, bones, gastrointestinal tract and upper respiratory tract.[1] Rarely, intraoral MS develops.[1] There have been few reports of MS developing in a socket following dental extraction.[1] The majority of intraoral MS occurs in patients with known AML, but it can be the first sign of AML.[1 2] There have been few case reports of MS in domestic animals involving the lung, gastrointestinal tract, lymph nodes, liver or skin in dogs and cats and the skeletal muscle in cattle.[13] MS has presented as a mediastinal mass in dogs and the common marmoset.[13 14]

On initial presentation, it was presumed that this animal had a tooth root abscess. Tooth root abscesses are commonly observed in NHP and treatment options include lancing, flushing, extraction or root canal of affected teeth and systemic medications.[15 16] MS associated with AML should be considered a differential in NHPs with suspected tooth root abscess or gingival swelling and ulceration that is accompanied by unexpected hematologic abnormalities.[2]