Signalment:  

15-year-old, female sooty mangabey (Cercocebus atys).This adult female sooty mangabey was born at the Field Station of the Yerkes National Primate Research Center. She was found in her social group recumbent, hypothermic and pale with a tense abdomen. Laboratory analysis revealed a moderately elevated blood urea nitrogen, moderate anemia and hyperglycemia. Abdominal ultrasound revealed a large amount of fluid in the abdomen. Fluid collected by abdominocentesis appeared dark brown/red. Due to the poor prognosis, the animal was euthanized.

Gross Description:  

This animal weighed 8.18 kilograms at necropsy. The lung parenchyma had multiple pinpoint red nodules (2-5 mm diameter). Approximately 200 ml unclotted blood, intermixed with extensive adhesions between the mesentery and serosa of the intestines and uterus, was observed in the abdominal cavity. The uterus was enlarged to approximately five times its normal size. When opened, the endometrium was hemorrhagic and thrown into folds. Clotted blood was present in the uterine lumen.

Histopathologic Description:

The lung parenchyma has 1-2 foci consisting of glands and periglandular stroma. These foci resemble the glands and stroma in the uterine endometrium. In other sections, disseminated endometriosis is seen in the mesentery and serosa of gastrointestinal tract, urinary bladder and uterus.

Morphologic Diagnosis:  

Lung, endometriosis.

Lab Results:  

No significant pathogen was isolated from the blood, liver or contents of the colon.

Condition:  

Endometriosis

Contributor Comment:  

Endometriosis is defined as the appearance of endometrial tissue outside the uterine cavity.(5) Theories about its etiology include shedding of viable endometrial cells through retrograde menstruation and implanting onto the peritoneal surface, or decreased immunological clearance of shed endometrial cells within the peritoneal cavity.(6) Endometriosis is an important cause of reproductive failure in both rhesus and cynomolgus macaques due to blocked fallopian tubes or scarred ovaries.(5) Pelvic adhesions and serosal -�-�chocolate cysts are a part of gross appearance of endometriosis.(4) To histologically diagnose endometriosis two of the following three are required: endometrial glands, endometrial stroma, and hemosiderin-laden macrophages.(1) Older lesions may have only hemosiderin deposits and no glands.

Spontaneous endometriosis has been studied in rhesus macaques, cynomolgus macaques and baboons, although the disease has also been reported in other captive and wild species.(3) Risk factors examined for the development of spontaneous endometriosis in nonhuman primates include maternal age, parity, captivity and experimental procedures such as laparoscopies, hysterectomies, and treatment with estradiol implants.(3) Nonprimates (e.g. rats, syngenic mice, nude mice, hamsters and rabbits) do not develop spontaneous disease, but the disease has been experimentally induced in them.(6)

In the present case, metastasis of endometrial cells by lymphatic and/or hematogenous routes could have disseminated the endometriosis to the thorax. To the authors knowledge, endometriosis has not been reported in sooty mangabeys, and only one case of endometriosis in lung has been reported in a rhesus macaque.(5)

JPC Diagnosis:  

Lung: Endometriosis, with uterine stroma, few endometrial glands, and hemosiderin-laden macrophages.

Conference Comment:  

We thank the contributor for providing this captivating example of a classic condition in an unusual anatomical location. In women, endometriosis occurs more commonly in the following sites, in descending order of frequency: 1) ovaries; 2) uterine ligaments; 3) rectovaginal septum; 4) cul du sac; 5) pelvic peritoneum; 6) large and small bowel and appendix; 7) mucosa of the cervix, vagina, and fallopian tubes; and 8) laparotomy scars. (2)

Because foci of endometriosis respond to hormonal stimulation with periodic bleeding, the diagnosis is not always straightforward, as mentioned by the contributor. In some cases, lesions consist only of endometrial stroma and areas of hemorrhage or hemosiderin; longstanding lesions may be obscured by secondary fibrosis.(2) A rather atypical example with decidualized stromal cells from a rhesus macaque on a therapeutic course of Depo-Provera-� (medroxyprogesterone acetate) was reviewed in WSC 2007-2008, Conference 10, case III. In cases lacking the distinctive features of endometriosis described by the contributor, the differential diagnosis may include retroperitoneal fibromatosis and neoplasia of mesenchymal origin. In such cases, immunohistochemistry may be useful; endometriotic stromal cells exhibit markedly upregulated estrogen production due largely to high levels of the aromatase enzyme, which is absent in normal endometrial stroma. Interestingly, high levels of such proinflammatory cytokines as prostaglandin E2, interleukin (IL)-1β, IL-6, and tumor necrosis factor are also noted in endometriosis. Prostaglandin E2 stimulates local estrogen synthesis, and endometriotic tissue is resistant to the antiestrogenic effect of progesterone; therefore, the overall inflammatory and endocrine milieu in endometriotic tissue is characterized by the overproduction of estrogen and prostaglandin and resistance to progesterone.(2)

Conference participants discussed the two predominant theories for the development of endometriosis, i.e. the metastatic theory and the metaplastic theory. The former postulates that endometrial tissue is physically transplanted to extrauterine locations through: retrograde menstruation, with subsequent spread to the peritoneum; surgical procedures, with subsequent spread to the cervix, vagina, and laparotomy scars; or metastasis via blood and lymphatic vessels. The metaplastic theory suggests that endometrial tissue arises directly from cell rests in the mesothelium, from which the M+�-+llerian ducts arise during embryogenesis.(2) The mechanism by which endometriosis developed in the lung of the sooty mangabey in this case is unclear. Participants considered hematogenous dissemination, but based on the generally peripheral distribution of the lesions in the sections examined, many speculated that direct extension from the abdominal cavity through the esophageal hiatus, aortic hiatus, or caval opening could have occurred.

In addition to the microscopic features described by the contributor, conference participants noted individualized round cells scattered throughout the endometrial stroma characterized by round, hyperchromatic nuclei and small amounts of cytoplasm containing brightly eosinophilic globules. The round cells are interpreted as endometrial stromal granulocytes, which are likely large granular lymphocytes that reach peak numbers during the secretory phase, the onset of which is marked by ovulation.(7)

References:

1. Clement PB: The pathology of endometriosis: a survey of the many faces of a common disease emphasizing diagnostic pitfalls and unusual and newly appreciated aspects. Adv Anat Pathol 14:241-260, 2007
2. Ellenson LH, Pirog EC: The female genital tract. In: Robbins and Cotran Pathologic Basis of Disease, eds. Kumar V, Abbas AK, Fausto N, Aster JC, 8th ed., pp. 1028-1029. Saunders Elsevier, Philadelphia, PA, 2010
3. Hadfield RM, Yudkin PL, Coe CL, Scheffler J, Uno H, Barlow DH, Kemnitz JW, Kennedy SH: Risk factors for endometriosis in the rhesus monkey (Macaca mulatta): a case-control study. Hum Reprod Update 3:109-115, 1997
4. Lowestine LJ: A primer of primate pathology: lesions and nonlesions. Toxicol Pathol 31:92-102, 2003
5. McClure HM, Graham CE, Guilloud NB: Widespread endometriosis in a rhesus monkey (Macaca mulatta). Proc 2nd Int Congr Primatol 3:155-161, 1969
6. Story L, Kennedy S: Animal studies in endometriosis: a review. ILAR J 45:132-138, 2004
7. Young B, Lowe JS, Stevens A, Heath JW: Wheaters Functional Histology: A Text and Colour Guide, 5th ed., p. 373. Elsevier Limited, Philadelphia, PA, 2006

Click the slide to view.

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1-1. Lung

1-2. Lung

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