JPC SYSTEMIC PATHOLOGY
DIGESTIVE SYSTEM
December 2021
D-V24

 

SIGNALMENT (JPC #2047475):  An adult male Rhesus monkey (Macaca mulatta).

 

HISTORY:  None

 

HISTOPATHOLOGIC DESCRIPTION:  Small intestine: Circumferentially affecting 90% of the section, markedly expanding the serosa, and infiltrating and multifocally effacing the tunica muscularis and to a lesser extent the submucosa are multiple nodular, unencapsulated, densely cellular proliferations of spindle to stellate cells arranged in interlacing streams, haphazard bundles, and perivascular whorls supported by a dense, occasionally hyalinized to sclerotic, collagenous matrix to well-vascularized stroma.  The cells have indistinct borders, a moderate amount of amphophilic to eosinophilic, fibrillar cytoplasm, and a plump, oval to stellate, vesicular nucleus with 0-1 nucleoli.  Mitoses average 1 per 2.37mm² (10 HPFs).  Multifocally, there are few lymphocytes, plasma cells, and rare neutrophils and eosinophils, as well as numerous small caliber blood vessels.  Multifocally the submucosa is infiltrated by similar inflammatory cells and few macrophages, is expanded by edema, and there are increased numbers of dilated lymphatics (edema).

 

MORPHOLOGIC DIAGNOSIS:  Small intestine, serosa: Atypical mesenchymal proliferation, multinodular, moderate (retroperitoneal fibromatosis), Rhesus monkey (Macaca mulatta), nonhuman primate.

 

CAUSE:  Simian retrovirus type D serotype 2 (SRV-2) and retroperitoneal fibromatosis associated herpes virus (RFHV) (gammaherpesvirus, Rhadinovirus)

 

CONDITION:  Retroperitoneal fibromatosis

 

GENERAL DISCUSSION: 

• Retroperitoneal fibromatosis (RF) is characterized by an aggressive proliferation of highly vascular fibrous tissue subjacent to the peritoneum, usually involving the ileocecal junction, and/or the root of the mesentery, and associated mesenteric lymph nodes
• Simian acquired immunodeficiency syndrome (SAIDS) in macaques is associated with three type D retroviruses (oncoviruses): SRV-1, SRV-2, and Mason-Pfizer monkey virus (MPMV); they are unrelated to the type E retrovirus (a lentivirus) (SIV) that can also cause SAIDS
• SRV-2 associated with SAIDS is reported in colonies of macaques to cause a peculiar form of retroperitoneal fibromatosis
  • These are similar to Kaposi’s sarcoma in humans caused by Kaposi’s sarcoma-associated virus

 

PATHOGENESIS: 

• Not well worked out but appears SRV-2 and RFHV act as cofactors to induce RF
  • RFHV is apparently necessary to produce disease but is not alone able to induce the condition
• Cell of origin unknown but thought to be associated with vascular smooth muscle (pericyte)
• IL-6 is an important growth factor for RF

 

TYPICAL CLINICAL FINDINGS: 

• SAIDS: Progressive weight loss, recurrent diarrhea, chronic infections unresponsive to therapy, and unusual opportunistic infections; anemia, neutropenia, and lymphopenia (decreased CD4+ T cells)
• RF:

• occurs under conditions of immune suppression
• Two RF syndromes are recognized:

• Localized form (palpable mass in the ileocecal or inguinal region)
• Progressive form (throughout the abdominal and pleural cavities)

• RF/SAIDS animals develop profound lymphoid depletion, thymic atrophy, and decreased response of peripheral lymphocytes to mitogens

 

TYPICAL GROSS FINDINGS: 

• Occur as single or multiple nodular fibroproliferative lesions forming plaques or nodules on mesothelial surfaces in the abdomen
• Localized syndrome: 1-4 cm single to multiple, firm, pale nodules beneath the peritoneum at the mesenteric attachment of the ileocecal junction and/or adjacent lymph nodes
• Progressive syndrome:
  • Fibrous tissue encircling the intestines and adjacent lymph nodes
  • May extend throughout the abdominal cavity as multiple discrete nodules or as a large continuous mass, and can involve the mesentery, parietal peritoneum, omentum, and encase the gastrointestinal tract
  • Rarely may extend into the inguinal canal, and/or invade through the diaphragm into the pleural cavity
  • May cause obstruction by interfering with peristalsis

 

TYPICAL LIGHT MICROSCOPIC FINDINGS: 

• Intersecting bundles of spindle cells within a well-vascularized collagenous stroma extending along serosal surfaces and that may incorporate normal structures
• Proliferative form:
  • Plump to spindle fibroblasts arranged in ill-formed bundles with occasional swirling or interweaving patterns within a disorganized matrix of collagen and reticulum fibers
  • Stroma is often edematous and contains a rich supply of mature and immature blood vessels
  • Vesicular nuclei with 1-2 nucleoli; occasional mitotic figures
  • Variable numbers of lymphocytes and plasma cells
  • Does not metastasize by lymphatic or hematogenous routes; does not invade epithelial parenchymatous organs
  • Factor VIII-related antigen is present on 25-75% of spindle cells including cells not related to vascular spaces in early proliferative phase of disease
• Sclerotic pattern:
  • Less cellular; nuclei are smaller and less vesicular; no mitoses; lymphocytic infiltration is less prominent; rarely only an acellular mass of collagen; factor VIII related Ag immunoreactivity on less than 25% of spindle cells
• Lymphoid hyperplasia occurs early in RF/SAIDS; atrophy develops as the syndrome progresses
• Increased risk for intestinal amyloidosis

 

ULTRASTRUCTURAL FINDINGS:

• Type D virions form cytoplasmic immature cores (“A” particles) and bud from plasma membranes with complete or crescentic nucleoids
• Outside the cell, virions have a central nucleoid but lack surface spikes

 

ADDITIONAL DIAGNOSTICS:

• Serology or virus isolation for SRV-2
• Immunohistochemistry: RF spindle cells are immunoreactive with vimentin, desmin, and smooth muscle actin

 

DIFFERENTIAL DIAGNOSIS: 

Gross differentials for abdominal mass:

• Endometriosis, fibrosarcoma, leiomyoma, leiomyosarcoma, gastrointestinal stromal tumor (GIST), and intestinal adenocarcinoma
  • Histomorphology and immunohistochemistry to differentiate
  • Absence of mitoses and anaplastic features help differentiate RF from sarcoma

 

COMPARATIVE PATHOLOGY: 

Other selected retroviruses of NHPs:

• Simian immunodeficiency virus (SIV) (P-V19)
  • A highly diverse virus; 40 SIVs have been described both in natural hosts and in heterologous species
  • Non-pathogenic in the vast majority of natural hosts; this is probably a consequence of virus-host adaptation
  • There is a high propensity for cross-species transmission; in the new host, the outcome varies from an incidental infection to a highly pathogenic one
  • There are few reports of RFHV-associated retroperitoneal mesenchymoproliferative lesions in SRV-negative, SIV-positive macaques

 

Selected retroviruses from other veterinary species:

• Feline leukemia virus (FeLV) (H-N02)
  • FeLV can cause tumors (mainly lymphoma), bone marrow suppression syndromes (mainly anemia), and lead to secondary infectious diseases caused by suppressive effects of the virus on bone marrow and the immune system
  • Prevalence is on the decline due to vaccination
• Feline immunodeficiency virus (FIV)
  • Causes an acquired immunodeficiency syndrome that increases the risk of opportunistic infections, neurological diseases, and tumors
  • In most naturally infected cats, FIV itself does not cause severe clinical signs, and FIV-infected cats may live many years without any health problems
• Enzootic bovine leucosis (EBL)
  • A viral disease that affects cattle, characterized by persistent lymphocytosis or lymphosarcoma or both
  • The epidemiological cause of the EBL is the bovine leukosis virus (BLV)
• Equine infectious anemia virus (EIAV) (H-V10)
  • A lentivirus of the Retrovirus family
  • Causes a persistent infection characterized by recurring febrile episodes, fever, thrombocytopenia, and wasting symptoms

 

Other selected causes of mesenchymal proliferations in veterinary species:

• Shope fibroma virus (SFV) (I-V09A), a leporipoxvirus, causes a localized, self-limited, fibroblastic proliferation in adult rabbits
  • In the eastern cottontail, rabbit fibroma virus causes one to multiple cutaneous fibromas that are 1.5–2cm in diameter, raised hairless domes or flat plaques, most often on the feet or legs and not firmly attached to underlying tissues
• Deer fibroma virus (I-V02) causes cutaneous fibromas or fibropapillomas
  • One of the most commonly reported tumors of white-tailed deer
• Equine sarcoid (I-N17) is the most common skin neoplasm of equids
  • Sarcoids are nonmetastatic fibroblastic skin tumors
  • Associated with nonproductive infection with BPV types 1, 2, and 13
• Squirrel fibroma virus (I-V09B), a leporipoxvirus, causes cutaneous and systemic atypical mesenchymal proliferations in red (Tamiasciurus hudsonicus) and gray (Sciurus carolinensis) squirrels

 

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