Neoplastic Diseases by System

Last modified on August 14, 2010

Skin    Genital    Liver   Mammary glands   Gastrointestinal    Urinary    Lymphatic    Musculoskeletal    CNS   

Skin tumors

Melanoma

Melanomas are a frequent tumor in the canine oral cavity, especially small breeds and those with pigmented mucosa. Melanoma is considered a malignant tumor if it occurs in the mouth, with local spread, recurrence and metastasis to local lymph nodes and the lungs. They can be difficult to diagnose accurately; the tumors may not be pigmented, and microscopically they can resemble other tumors. There are some ways to distinguish them using special procedures, although none are foolproof. Melanomas are usually DOPA (dihydroxyphenylalanine oxidase) positive on frozen sections, they react positively with the Masson-Fontana stain, and they are positive for S100 protein. In this review, the relative risk was highest for Anatolian sheepdogs, Chow chows, and Peke-a-Poos, with average survival times of 173 days post-diagnosis.{4063}

Basal cell adenoma

These tumors are composed predominantly of basaloid cells with no recognizable differentiation toward adnexal structures. They are more common in dogs. A reported case involved a 6 yr old male NZW rabbit (a class pet) that developed a dome-shaped nodular growth (2.5 cm) on the back over 6 months. Surgical removal of the mass was done and the animal survived for the next three years with no evidence of recurrence or metastasis. Typical histologic patterns of nests, cords and strands of uniform basaloid cells were observed. Basal cell tumors are rare in rabbits with only 2 reports in the literature.{3670}

Epidermotropic lymphoma (mycosis fungoides)

Epidermotropic lymphoma (mycosis fungoides) is a form of cutaneous T-cell lymphoma present in people, dogs, and cattle. It has also occurred in cats, hamsters, rats, mice, horses, and ferrets. It mimics dermatitis in patches or plaques at first, progressing to nodules or tumors. Neoplastic cells infiltrate the epidermis, dermis and SQ and may spread to peripheral lymph nodes and visceral organs in the later stages. The mechanism may be a histogenesis error, with bone marrow-derived T-cell precursors bypassing the thymus and going directly to the skin.{4120}

A case of epidermotropic lymphoma with systemic spread into lymph nodes and visceral organs was reported in an 8 month old female ICR sentinel mouse. The mouse had progressive, generalized alopecia and lymphadenopathy. The skin was markedly and diffusely thickened, with multiple serous to hemorrhagic crusts, ulcerated plaques, and raised nodules. Microscopically, there was perivascular infiltration of pleomorphic lymphoid cells in skin, lymph nodes, thymus, spleen, lungs and liver. Most infiltrating cells labeled with anti-CD3 (pan-T cell) antibody.{4120}

Genital tract

Testicle

Leydig cells (or interstitial cells) produce testosterone and estrogens, and are required for male reproductive function. Leydig cell tumors are divided into three types: solid, cystic vascular, and pseudoadenomatous. Leydig cell tumors can be induced experimentally in susceptible mouse strains (BALB/c) by the administration of estrogens. Although spontaneous Leydig cell tumors are common in dogs and in some rat strains (80% of aged F344{4757}), they are extremely rare in mice, with a spontaneous incidence of less than 1%. In a large BALB/cJ breeding colony, only six Leydig cell tumors were identified in 6,500 male mice necropsied over a period of 8.5 years. Tumors were unilateral, with no predilection for right or left testis. Histologically all Leydig cell tumors were well differentiated and of the solid, diffuse type.{3646}

Testicular tumors are very rare in macaques, with only 23 published reports. However, in the tree shrew (Tupaia belangeri), social intimidation causes subordinate males to retract their testes into the abdomen. A high incidence (6.3%) of Leydig cell tumors was noted in older male tree shrews (no comparison between stressed and non-stressed given). In humans, germ cell tumors are more common. Tumors in both men and tree shrews are more common in the left testicle, which may be related to fetal gonadogenesis. In the human fetus, the right testicle is larger and descends later, maintaining higher temperature. Leydig cell tumors appear grossly as well defined, yellow to chalk-white, often hemorrhagic, slightly protruding nodules which cause enlargement of the affected testis. Histologically, there are solid trabeculae of large vacuolar or foamy cells having well defined cell borders and round to ovoid nuclei. Sertoli cell tumors, which are sometimes seen in tree shrews, are smaller, and are composed of cells with indistinct borders, large fat vacuoles and regularly sized globoid nuclei. The cells grow around vascular structures or in an irregular way.{4094}

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Ovary

A case of ovarian teratoma occurred in an 8 year old pigtailed macaque (Macaca nemestrina). She had produced 2 live births out of the last 5 matings. At a routine laparoscopy, both ovaries were noted to be enlarged and dark in color. At post-mortem, no other abnormalities were noted grossly. The right ovary was cystic and revealed mature cartilage, glial, adipose, intestinal, endocrine and respiratory tissues. Mitotic figures were not detected. The left ovary contained a dilated hemangioma. Teratomas are rarely diagnosed in NHP, possibly due to the lack of gross abnormalities. It is unknown if it is responsible for infertility in NHP, but accounts for a small percentage of infertility in women.{3681}

Liver

Spontaneous hepatic neoplasia is said to be rare in nonhuman primates, with only a few case reports in the literature: hepatocholangiocellular carcinoma in C. aethiops, malignant tumors in S. boliviensis, C. albifrons, and Lemur catta. Spontaneous hepatic neoplasia was first reported in cynos in 2000{4059}. Both were incidental findings at necropsy. The first animal was almost 5 years old and had an 18mm round, raised, tan mass in the diaphragmatic surface of the left medial lobe. Histologic evaluation termed it a solitary hepatocellular carcinoma. The other animal was the same age, and its liver was abnormally firm, had an irregular cut surface, and the tissue was pale and lobulated with fibrotic parenchyma without discrete masses. Most of the microscopic nodules were hepatocellular carcinoma, but one was termed a mixed hepatocholangiocellular carcinoma because it contained primitive ductlike structures.

The woodchuck (Marmota monax) is a model for hepatocellular carcinoma. Aged male A/JCr mice tend to develop hepatocellular carcinomas when infected with Helicobacter hepaticus.

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Mammary Glands

Mammary gland tumors are very common in rats, especially Sprague-Dawleys. Half of aged female SDs will have tumors, most often benign fibroadenomas. In contrast, the incidence in F-344 rats is only about 15%.{4757}

Gastrointestinal tract

Intestinal adenocarcinoma

Intestinal adenocarcinoma is the most common tumor in macaques at CRPC; other tumors include leiomyoma, leiomyosarcoma, adenomatous polyps, lymphoma and carcinoid tumors. A review of 32 cases indicated that the most common signs were weight loss of >20%, anorexia, palpable mass, hematochezia, emesis, diarrhea, scant feces and bloating. Hematologic signs, if any, were microcytic hypochromic anemia from intermittent tumor bleeding. Hypoproteinemia (hypoalbuminemia) and hypocalcemia were common findings in the serum. The most common site was the ileocecal junction (40%), followed by the colon (31%) and in the jejunum or ileum (25%). Grossly and radiographically there was a constricting segmental (apple core or napkin ring) lesion. Histologically, the tumors are classified according to Duke. Stage A are limited to the mucosa. Stage B1 lesions extend into the muscularis but not through it; stage B2 penetrate the muscularis and invade the serosa. Stage C lesions involve any layer of bowel and have regional lymph node involvement. Stage D have distant metastasis. In this series 62.5% were stage B1. When the tumors metastasize they go to the liver, regional lymph nodes, lungs, pancreas and adrenal. The survival of macaques who had excisional surgery was 83% at 6 months, 58% at 1 year, 50% at 1.5 years, 33% at 2 years, and 8% at 4 years. Additional diagnostic tests in macaques can include carcinoembryonic antigen (CEA) tests, which were all negative in this review, and Hemoccult testing, which was intermittently positive in all cases. Note that this tumor is different in cotton-top tamarins (Saguinus oedipus), which tend to develop colitis progressing to carcinoma and may have an infective cause. Also, their tumors occur at the colorectal junction and are highly invasive.{4112}

A captive mature male opossum (Didelphis virginiana) was presented with chronic diarrhea and severe muscle wasting. At necropsy, there was multifocal gastric, intestinal, and urinary bladder thickening; bilateral hydroureter and hydronephrosis; and extensive fibrous abdominal adhesions. Histology revealed intestinal adenocarcinoma with coelomic metastasis to the stomach and urinary bladder. This unique presentation of intestinal adenocarcinoma has not previously been reported in the opossum or any other animals. Intestinal neoplasia with Paneth cell differentiation is extremely rare and has been reported in humans with familial adenomatous polyposis.{4078}

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Urinary Tract

Renal cell carcinoma

Renal cell carcinomas arise from the renal tubular epithelium. There are two major histologic types: papillary-tubular carcinoma (more common in domestic animals), and clear-cell carcinoma (prevalent in humans, especially men). Mixed types may develop. A viral cause has been identified in leopard frogs (Lucké renal adenocarcinoma), chickens, and gray squirrels. Environmental toxicants (lead) have been implicated in rodents. Renal cell carcinoma is a rare condition in Siberian hamsters.{3789}

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Lymphatic System

Carcinoma

Ten sea lions, all found stranded on the beach, were found to have metastatic carcinoma in the sublumbar lymph nodes. This had been seen before and occurs with very high prevalence, about 18%, and is one of the most common diseases of the species. Histologically, there was intraepithelial neoplasia (a noninvasive neoplastic proliferation of epithelium that is a precursor to invasive metastatic carcinoma) and intranuclear inclusion bodies. Immunohistochemistry was positive for Epstein-Barr virus in one animal. Four animals from which they had fresh tissue had the DNA examined, and they found a new rhadinovirus most closely related to human herpesvirus 8, thought to be the cause of Kaposi's sarcoma. Cervical carcinoma of humans also starts this way, as intraepithelial neoplasia.{4054}

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Plasma Cells/ Gammopathies

Waldenstrom's macroglobulinemia is a dyscrasia constituting about 5% of monoclonal gammopathies. It is characterized by a lack of bone involvement, soft tissue neoplastic infiltrates in lymph nodes, spleen, bone marrow, liver, and kidney, and blood hyperviscosity. The predominant associated immunoglobulin is IgM. The neoplastic infiltrate is varied with recognizable lymphocytoid and plasmacytoid cells admixed with hybrid forms.{3798}

A 13-year-old castrated male Rhesus monkey had a clinical course characterized by weight loss, malaise, and anorexia. Laboratory findings included anemia, hyperproteinemia, and hyperglobulinemia, with a prominent M spike in the gamma globulin region. The animal was positive for simian retrovirus 2. Necropsy findings included generalized lymphadenopathy and bilateral renal enlargement with disseminated solid tumor nodules. No skeletal lesions were noted. Microscopically, a pleocellular neoplastic lymphoid infiltrate with prominent plasmacytoid differentiation was present in the kidney, lymph nodes, bone marrow, spleen, and other viscera. Distinctive renal tubular cast material was present with associated macrophage response. The clinical laboratory and pathologic findings were similar to Waldenstrom's macroglobulinemia. Primary amyloid deposition related to plasma cell tumors has not been reported in NHPs. SRV-2 (type D retrovirus) infection leads to prominent lymphoid hyperplasia especially in the kidney as well as other organs, but has not been reported to cause lymphoma.{3798}

Multiple myeloma causes lytic lesions of the skeleton which may progress to pathologic fractures, anemia secondary to hematopoietic cell replacement by plasma cell infiltrate, hypercalcemia, diffuse depositions of paraproteins in the kidney and excretion of light chains leading to renal failure. IgG is the prominent immunoglobulin.{3798}

Monoclonal Gammopathy of Undetermined Significance [MGUS]: Increased IgG, IgA, or IgM in the serum with no other detectable clinical or pathologic findings that usually occurs in elderly people. Progression to myeloma and other plasma cell dyscrasias is common.{3798}

Amyloidosis is the progressive deposition of abnormal fibrillary proteins in the extracellular spaces of many organs. AL amyloid is resistant to permanganate treatment and is derived from light chains. AA amyloid loses Congo Red staining when treated with permanganate and is secondary to chronic inflammation. Amyloidosis is seen in NHPs in connection with chronic disease, usually diarrhea.{3798}

A new lymphocryptovirus has been incriminated as the cause of B cell proliferation in 16 marmosets (Callithrix jacchus).  Typical signs were weight loss, inappetance and diarrhea; in some there was a palpable abdominal mass (enlarged mesenteric lymph nodes). Neoplastic B cells were found in large numbers in mesenteric nodes, jejunum, duodenum, ileum and colon. The virus bears similarity to Epstein-Barr virus, the cause of several neoplastic diseases in humans including Hodgkin's disease, Burkitt's lymphoma, and nasal carcinoma.{3780}

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Musculoskeletal System

Leiomysosarcoma

Pituitary adenomas (usually chromophobe adenomas) are common in Sprague-Dawley (75%) and Wistar rats. Dietary restriction significantly reduces the incidence of tumors of all types in rats. Chromophobe adenomas can grow to 5mm in diameter, causing compression of adjacent brain tissue and hydrocephalus.{4757}