Registry case number TARZ-10121_1 (Pathologist: Dr Lydia Tong)
This aged (25 years), captive, male lizard (weight 623 g) was found to have an oral mass on the right side of the maxilla resulting in tooth displacement. When touched, teeth easily fell out. The mass was reported to have developed within a two week period. Two weeks prior, the shingleback was reported to develop a weeping eye and display rapid breathing after a short period of handling. The animal had a history of conjunctival swelling and depression.
Mandibular Mass: Aspirates from the mandibular mass include erythrocytes, mixed circulating leukocytes, and large numbers of diffuse and clumping abnormal small to medium sized round cells with no or scant cytoplasm (lymphocytes). The abnormal cells exhibit marked anisokaroysis, with karyomegaly, and bizarre nuclei with indentations. Occasional mitoses are seen.
Blood Smear: Amongst erythrocytes and expected mixed circulating leukocytes are single or clustering medium sized round cells with no to scant cytoplasm, exhibiting cellular atypia, anisokaryosis, and nuclear indentation. Occasionally they are binucleate or have karyomegaly.
External Findings: There is a white, soft, well defined, irregular, 20 x 10 mm mass displacing the maxillary teeth. There is a 3 mm diameter, solitary, yellow nodule in the right nasopharynx. Hydration and body condition are good.
Oral cavity (upside down) showing displacement of the maxillary teeth on the right side by a mass
Internal Findings: The liver is peppered with variably sized, soft white raised nodules up to 6 mm diameter. The liver is generally black. There is a moderate amount of thin, opaque fluid in the coelom. Heart ventricle is small.
Coelomic fluid and liver containing multiple variably sized nodules
The mid-stomach and pylorus have well defined, soft, cream, intramural swellings, 18 x 14 x 7 mm and 8 mm diameter.
The left testicle appears red and twice the size of the right testicle. There is a firm, spherical, 5 mm mass associated with testicle. Kidneys markedly affected by nodular, coalescing, soft – firm, white nodules which are obliterating normal kidney parenchyma.
Kidney masses replacing much of the normal architecture
The tissues are in good condition. The following tissues exhibit no significant histopathological changes: Lung (B), Small intestine (C)
Kidney (A): There is a highly cellular proliferation of pleomorphic round cells forming multinodular to coalescing broad-fronted, non-encapsulated, well defined, irregularly edged, invasive nodules which are effacing and replacing the majority of normal renal parenchyma. The proliferative cells are found in large clusters in many blood vessels. There are multifocal areas of haemorrhage. In areas of residual parenchyma, there is degeneration of tubular structures, sometimes with wedge shaped interstitial fibrosis affecting the cortex and medulla. The proliferating cells form vast amorphous sheets within nodules, and invade between pre-existing fine fibrovascular stromal structures. There is marked cellular clumping. The cells are small to medium sized round cells, with scant pale eosinophilic cytoplasm, showing marked anisocytosis and anisokaryosis. The nuclei are rounded, fusiform, indented, ovoid, or rectangular with smudged pale to moderately basophilic chromatin. The mitotic rate is 45 per 10 HPF, most mitoses are bizarre. There is frequent individual cell karyolysis.
Liver (A): There is a highly cellular, multifocal, coalescing, invasive, destructive proliferation of abnormal round cells effacing the liver. Cellular morphology and behaviour of the proliferation is as described in the kidney. Surrounding hepatic parenchyma is compressed by the nodules.
Heart (B): Multifocally within myocardium are proliferative and invasive nodules of round cell infiltrates of the same appearance as those seen in the kidney.
Spleen (B): The spleen is uniformly enlarged, and has both white and red pulp present with normal cells. Also present throughout multifocally in small coalescing clusters and nodules, consisting of around 60% of total splenic cellularity, are abnormal medium sized round cells as per the description of those seen in the kidney.
Testicle (C): There is marked intertubular oedema and some haemorrhage. There are multifocal coalescing abnormal proliferative round cell infiltrates invading within interstitial tissue throughout the testicle. The cells have the same appearance as those in the kidney.
Pancreas (C): The majority of a section of pancreas is expanded and effaced by proliferative round cells of the description of those seen in the kidney. Associated with the pancreas are large dilated ductal structures (cystic dilation). One is filled with amorphous eosinophilic acellular debris (presumed pancreatic secretions), and there is a large nodule of the proliferative round cells in the subepithelial tissue of the dilated duct.
Oesophagus (C): There are increased small mature lymphocyte infiltrates in the submucosa, forming clusters in the subepithelial tissue and associated with a vessel.
Stomach (D): Expanding within the muscle layers of the stomach is a vast, broad fronted, expansile, pseudoencapsulated, highly cellular proliferation of dual cellularity. The majority of the proliferative cells are spindloid cells forming a large irregular nodule with short streams and whorls in a chaotic manner. The cells are short spindle to fusiform, to ovoid, with moderate vacuolated, pale eosinophilic to myxomatous cytoplasm with poorly defined cell margins. There is mild anisocytosis. The nuclei are round, oval or triangular, with moderate anisokaryosis and one mitosis per 10 HPF. Within the mass are multiple large, well differentiated venous structures. These proliferating cells do not invade into surrounding gastric parenchyma. The second cell type within this mass closely resemble the proliferative round cells as described in the kidney. They form multifocal coalescing nodules within the spindle cell proliferation. Focally the spindle cell proliferation meets the submucosa and there is a focal ulceration of the mucosa. Otherwise the submucosa and mucosa are unaffected.
Mandible (AA,BB): Sections across a mandibular mass reveal vast invasive, expansile, coalescing multinodular sheeting masses of proliferative round cells as per the description of those seen in the kidney. The proliferation has invaded and effaced mandibular osteoid, and is seen invading and filling the medullary cavity, replacing bone marrow. The proliferation extends to cutaneous and buccal mucosa, which is not ulcerated although there are focal areas of intraepithelial proliferative cell migration, associated with epithelial hyperplasia and vesicle formation.
Addendum: Immunohistochemistry (A): CD3 and CD79a markers were applied to sections of liver and kidney. Positive and negative controls showed normal staining however a reptile control was not available. The neoplastic cells were negative for both CD3 and CD79a.
Multicentric lymphosarcoma, Stage V
The shingleback had a severe multisystemic lymphosarcoma which was demonstrated to be in circulating blood, warranting a Stage V classification.
It is not possible to determine the primary site of the tumour as so many tissues are now consumed - although it presumably arose in a pre-existing lymphoid structure. There was lymphosarcoma present in the medullary bone marrow cavity in the mandible, although this could have been local invasion rather than representative of widespread bone marrow invasion.
The extent of this malignancy is surprising given the relatively mild or subclinical nature of this disease in the run up to his diagnosis. One explanation is that there was a very high mitotic rate in the visceral masses - and it is likely that this tumour was growing/progressing very rapidly.
Interestingly, this animal also had a stromal tumour in his stomach of the appearance of a gastric leiomyoma, which was itself invaded by lymphosaroma. The presence of the two tumours is most likely a coincidence. Co-occurrence of gastric lymphosarcoma and a gastric stromal tumour has been reported in humans on two occasions - and have been said to be associated with Helicobacter infection. No spiral organisms were observed in stomach sections.
Immunohistochemistry with CD3/CD79a markers were negative. A negative result in this case is not conclusive as use of these markers in reptiles is not validated.