Liver Pathology

Hepatic Endometriosis

Christine Janney
Saint Louis University
Saint Louis, MO


Click on each slide thumbnail image for an enlarged view
Clinical History:
The patient, a 36 year old woman, was referred to our center for evaluation and possible resection of a painful large hepatic mass, located in the posterior right lobe. She first noted right upper quadrant abdominal pain 2 months earlier; at that time an ultrasound study demonstrated a predominantly cystic area measuring 6 .3cm in the right lobe of the liver. A subsequent CT scan was initially interpreted as a subcapsular hematoma of the liver. The pain was well-controlled with nonprescription pain medications. One week prior to referral, the pain became worse, and the patient went to an outside hospital. Repeat ultrasound showed that the heterogeneous, cystic and solid lesion now measured at least 11 cm. The repeat CT scan and an MRI were interpreted as showing an encapsulated, predominantly solid mass with cystic, blood-containing regions, c/w an adenoma with hemorrhage, which was thought responsible for the previous subcapsular hematoma. She was referred to St. Louis University Medical Center for resection.

In addition to RUQ pain, the patient complained of fever spiking to 102 degrees F, chills, nausea, vomiting and a 5 pound weight loss over the prior 2 weeks. Past medical history was significant for 2 cesarean sections, post partum depression, and oral contraceptive use. She did not smoke or drink alcohol. Her last menstrual period was 2 weeks prior to referral.

On physical examination, the patient had hepatomegaly and was tender to right upper quadrant palpation. The physical exam was otherwise within normal limits. Laboratory values on admission included a white blood cell count of 14,000, hemoglobin 11, hematocrit 33, platelets 121,000 and albumin 2.9. All other laboratory values were normal.

Following preoperative assessment and review of radiographic studies, the patient underwent a right hepatectomy and resection of adherent diaphragm with prosthetic repair. The patient did well postoperatively and was discharged on postoperative day 5.


Slide 1
Click to view with ImageScope
Click to view with a Web-Based Viewer



Figure 1
Low power of mass and adjacent liver
Figure 2
(higher power view of Figure 1) Medium power view of edge of lesion.
Figure 3
Liver lesion with hemorrhage and mass effect.

Figure 4
(higher power view of Figure 3) Mass effect adjacent to liver lesion, with portal expansion, edema, ductular proliferation, and mixed inflammation.
Figure 5
Liver mass with cystic area and hemorrhage.
Figure 6
Medium power view of lesion with characteristic biphasic pattern.

Figure 7
High power view of lesion with characteristic glands and stroma.
Figure 8
Liver mass adherent to diaphragm.

Final diagnosis:
Hepatic Endometriosis

Pathologic findings:
Received for examination was a right lobe of liver measuring 19 X 15 X 8.5 cm and weighing 1320 gm. An 11.5 X 10 cm. piece of diaphragm was firmly attached to the superior surface. The cut surface showed a well-circumscribed, 8.7 X 8.5 X 8 cm cystic and solid, maroon, brown and tan mass with extensive hemorrhage within the mass and adjacent liver parenchyma. A thick fibrous capsule surrounded the mass. The remainder of the liver showed clot in several hepatic veins but was otherwise unremarkable.

On histological examination, the mass consisted of bland proliferative type endometrial stroma containing irregular and often dilated endometrial glands and thick walled blood vessels; there was extensive fresh and remote hemorrhage within the lesion, such that a minority of sections actually contained recognizable endometriosis. The adjacent liver showed necrosis and hemorrhage in the immediate subcapsular region accompanied by exuberant fibroblastic proliferation and scattered microcalcifications. More distant parenchyma had evidence of "mass effect", with portal edema and mixed inflammation, ductular proliferation, and dilatation of sinusoids and central veins. There was no evidence of a hepatic adenoma or other neoplasm.

Differential diagnosis:
The clinical differential diagnosis of a solitary mass lesion in a relatively young, previously healthy woman with a history of oral contraceptive use would not generally include the actual diagnosis in the case, given its rarity. Most of these lesions are easily distinguished from endometriosis by simple examination of hematoxylin and eosin stained sections. Hepatocellular adenoma would top the list, especially given the pain, intralesional hemorrhage and rapid increase in size. Characteristically, hepatocellular adenoma is composed of poorly delineated cords of benign, often hydropic, hepatocytes without acinar architecture or portal tracts, occurring in a non-cirrhotic liver. In cases with extensive hemorrhage, multiple sections may be required to demonstrate viable, diagnostic tumor. Focal nodular hyperplasia, while common in adult women, is usually discovered incidentally during imaging or surgery performed for unrelated conditions. The nodular proliferation of benign hepatocytes with its central stellate scar, abnormal thick arteries, and proliferating ductules usually make FNH diagnosable by imaging or histology; confusion with cirrhosis is a pitfall on needle biopsy if the history of mass lesion is not provided. The fibrolamellar variant of hepatocellular carcinoma, unlike typical HCC, tends to occur in a younger population, occurs equally in both genders as opposed to male predominant, and has no known association with chronic liver disease or other risk factors. The classic findings are of nests and trabeculae of large tumor cells with abundant granular eosinophilic cytoplasm and vesicular nuclei with prominent nucleoli, set in abundant fibrous stroma with parallel bundles of collagen. Many cases have "pale bodies", which are ground glass-like cytoplasmic inclusions of fibrinogen. And finally, hepatobiliary cystadenoma could cause diagnostic confusion, both radiographically and pathologically. It is usually a single multilocular mass in an adult woman that may be painful and may have intralesional hemorrhage, though it more commonly is filled with clear fluid or thin mucus. Microscopically, hepatobiliary cystadenomas have a biphasic pattern, with the cyst walls formed by "mesenchymal stroma" that resembles ovarian stroma (and to some extent endometrial stroma as well), however they are lined by benign simple mucinous columnar epithelium. A small proportion of these develop dysplasia or frank invasive carcinoma of the epithelial component, these then being called hepatobiliary cystadenocarcinomas. Other common and rare differential diagnostic considerations from a clinical standpoint, and which we at SLU have personally observed in adult women of reproductive age, include angiomyolipoma, vascular lesions such as hemangioma and epithelioid hemangioendothelioma, embryonal sarcoma, inflammatory pseudotumor, malignant lymphoma, metastatic malignancies, echinococcal cyst, focal steatosis, lipoma, and schwannoma. These either can be suspected or diagnosed from history and imaging, or can only be diagnosed by examination of microscopic sections.

The microscopic features in this case can be readily attributed to endometriosis once intact lesional tissue is identified among all the hemorrhage and reactive changes. Theoretically, the histologic differential diagnosis could include other biphasic stromal and glandular proliferations in the liver such as hepatobiliary cystadenoma and cystadenocarcinoma, carcinosarcoma, and synovial sarcoma (although the few reported primary hepatic synovial sarcomas tend to be monophasic not biphasic [8]). Attention to the histologic type of epithelium and stroma, the lack of significant mitotic activity or atypical mitoses, and the lack of frank cytologic atypia or anaplasia should make the distinction fairly straightforward. More problematic is evaluating for the presence of malignancy developing within endometriosis. Adenocarcinoma, especially of endometrioid and clear cell types, and endometrial stromal sarcoma, including Mullerian adenosarcoma, as well as other cancers common to the endometrium, have all been reported to arise within foci of endometriosis [2, 6, 19].

Discussion:
Endometriosis is common; hepatic endometriosis is rare. Endometriosis is simply defined as the ectopic occurrence of endometrial tissue, in other words, endometrial glands and stroma in one or more sites outside the endometrial cavity and muscular uterine wall. It primarily affects women of reproductive age, although some cases are identified in postmenopausal women, often associated with hormone supplementation. The true incidence of endometriosis is difficult to assess, since it can be asymptomatic and identified only microscopically, for example at the time of tubal ligation. However, the cited incidence is up to 10% of all women of reproductive age [25]. It is more common in infertile women and those with significant pelvic pain. Other symptoms vary depending on the site of disease. Sites of pathologically confirmed involvement by endometriosis include ovary, cul de sac, uterine ligaments, peritoneum of pelvis (including serosa of tubes, rectosigmoid colon and urinary bladder), less commonly, colon, bladder, cervix, vagina, vulva, abdominal scars, small intestine, appendix, umbilicus, hernia sacs, lymph nodes, and rarely, lungs, pleura, kidney, stomach, pancreas, soft tissue of extremities, brain, breast, heart, and liver [4, 14]. Endometriotic implants can vary in size from sub-millimeter sized red or rusty discolorations of the peritoneum (so-called "powder burn" lesions) to very large, complex , hemorrhagic, cystic masses with extensive adhesions and destruction of parenchymal organs. Definitive diagnosis requires the presence of both endometrial glands and stroma, however some implants may exhibit sufficient hemorrhage, fibrosis, and hemosiderin-laden macrophages that the characteristic stroma or epithelium is obscured. The endometrium in endometriosis is usually proliferative phase, but can show secretory changes or marked decidualization under the influence of ovulation, progesterone therapy or pregnancy [4, 19].

There are several hypotheses for the etiology of endometriosis, which are not mutually exclusive [4, 6, 19]. These include:

1. Retrograde menstruation, with regurgitation of endometrial tissue out of the fallopian tubes into the peritoneal cavity, where it implants on peritoneal surfaces, predominantly in the pelvis. This theory is consistent with the observed distribution of endometriosis, and is currently thought to be the major pathogenetic mechanism of the disease [24].

2. Metaplasia of coelomic peritoneum or embryonic rests (Wolffian or Mullerian duct remnants), which competes with retrograde menstruation as a theory consistent with the common distribution of implants [21].

3. Hematogenous or lymphatic dissemination of endometrial tissue, which would explain endometriosis in lymph nodes, brain, liver parenchyma, and other distant sites [14].

4. Direct implantation of endometrium, as in endometriosis in cesarean section scars [14].

Fewer than two dozen cases of hepatic endometriosis have been reported, with an age range at diagnosis of 21 to 64 years [7, 18]. The hepatic endometriomas were usually solitary, unilocular or multilocular cysts that measured from 3 to 30 cm [1, 3, 22]. Few were correctly diagnosed prior to excision; these were diagnosed on needle biopsy [10, 15] or had pain that cycled with menses, suggesting the diagnosis, but in most cases the diagnosis of endometriosis was made only on pathologic evaluation following resection [10]. Most patients were symptomatic, with right upper quadrant or vague upper abdominal pain being the most common presenting complaint [1, 5, 7, 17]. At least half had a prior history of endometriosis, and a similar number also had a history of prior pelvic surgery or laparoscopy [9]. Exceptional patients presented with signs and symptoms of an acute abdomen [23], as obstructive jaundice with ascites [11], or with recurrent spontaneous catamenial pneumothorax [13] complicating their hepatic endometriosis. The consensus appropriate therapy is surgical excision of the endometrioma, for control of pain, to manage or prevent significant lesional bleeding, and because of the small but real risk of the development of endometriosis-associated malignancy [12, 16, 20].

References:
  1. Bohra, AK, and Diamond, T. Endometrioma of the liver. Int J Clin Pract. 2001;55:286-287.

  2. Brooks, JJ and Wheeler, JE. Malignancy arising in extragonadal endometriosis: a case report and summary of the world literature. Cancer 1977;40:3065-3073.

  3. Carbone, A, Prete, FP, Sofo, L, Alfieri, S, Rotondi, F, Zannoni, GF, and Doglietto, GB. Morphological and immunohistochemical characterization of an endometriotic cyst of the liver: diagnostic approach to endometriosis. Histopathology. 2004;45:420-422.

  4. Clement, PB. Pathology of endometriosis. Pathology Annual. 1990;25:245-295.

  5. Cravello, L, DErcole, C, LeTreut, YP, and Blanc. Hepatic endometriosis: a case report. Fertility and Sterility. 1996;66:657-659.

  6. Czernobilsky, B, and Fox, H. Endometriosis, In: Fox, H, and Wells, M, eds. Haines and Taylor's Obstetrical and Gynaecological Pathology, 5th ed. Churchill Livingstone, 2003:963-987.

  7. Finkel, L, Marchevsky, A, and Cohen, B. Endometrial cyst of the liver. Am J Gastroenterology. 1986;81:576-578.

  8. Holla, P, Hafez, GR, Sluvkin, I, and Kalayoglu, M. Synovial sarcoma, a primary liver tumor- a case report. Pathology Research and Practice. 2006;202:385-387.

  9. Huang, W-T, Chen, W-J, Cheng, Y-F, Wang, J-H, and Eng, H-L. Endometrial cyst of the liver: a case report and review of the literature. J Clin Pathol. 2002;55:715-717.

  10. Inal, M, Bicakci, K, Soyupak, S, Oguz, M, Ozer, C, Demirbas, O, and Akgul, E. Hepatic endometrioma: a case report and review of the literature. Eur. Radiol. 2000;10:431-434.

  11. Jeanes, AC, Murray, D, Davidson, B, Hamilton, M, and Watkinson, AF. Case report: hepatic and retro-peritoneal endometriosis presenting as obstructive jaundice with ascites: a case report and review of the literature. CLincial Radiology. 2002;57:226-9.

  12. Jelovsek, JE, Winans, C, Brainard, J, and Falcone, T. Endometriosis of the liver containing mullerian adenosarcoma: case report. Am J Obstet Gynecol. 2004;191:1725-1727.

  13. Klein, F, Doehnert, G, and Zeidler, D. [Recurrent spontaneous pneumothorax complicating endometriosis of the liver. German with English abstract. Praxis und Klinik der Pneumologie. 1979;33:810-814.]

  14. Markham, SM, Carpenter, SE, and Rock, JA; Extrapelvic endometriosis. Obstet Gynecol Clin North Am. 1989;16:193-219.

  15. Nehzhat, C, Kazerooni, T, Berker, B, Lashay, N, Fernandez, S, Marziali, M; Laparoscopic management of hepatic endometriosis: Report of two cases and review of the literature. J Minimally Invasive Gynecol. 2005;12:196-200.

  16. N'Senda, P, Wendum, D, Balladur, P, Dahan, H, Tubiana, J-M, and Arrive, L. Adenosarcoma arising in hepatic endometriosis. Eur Radiol. 2000;10:1287-1289.

  17. Rao, M, Yeluri, S, Ching, SS, and McMahon, MJ; An unusual cystic lesion of the liver. Gut. 2006;55:742-743.

  18. Reid, GD, Kowalski, D, Cooper, MJW, and Kaloo, P. Hepatic endometriosis: A case report and review of the literature. Austral and NZ J of Obstet and Gynecol. 2003;43:87-89.

  19. Robboy, SJ, Anderson, MC, and Russell, P. Endometriosis. In: Robboy, SJ, Anderson, MC, and Russell, P, eds. Pathology of the Female Reproductive Tract. Churchill Livingstone. 2003:445-473.

  20. Sanchez-Perez, B, Santoyo-Santoyo, J, Suarez-Munoz, MA, Fernandez-Aguilar, JL, Aranda-Narvaez, JM, Gonzalez-Sanchez, A, and de la Fuente-Perucho, A. [Hepatic cystic endometriosis with malignant transformation. Spanish with English abstract. Cirugia Espanola. 2006;79:310-312.]

  21. Suginami, H, A reappraisal of the coelomic metaplasia theory by reviewing endometriosis occurring in unusual sites and instances. Am J Obstet and Gynecol. 1991;165:214-218.

  22. Tuech, JJ, Rousselet, M-C, Boyer, J, Descamps, P, Arnaud, J-P, and Ronceray, J. Endometrial cyst of the liver:case report and review. Fertility and Sterility. 2003;79:1234-1236.

  23. Verbeke, C, Harle, M, and Sturm, J. Cystic endometriosis of the upper abdominal organs: report on three cases and review of the literature. Pathology Research and Practice. 1996;192:300-304.

  24. Vercellini, P, Abbiati, A, Vigano, P, Somigliana, ED, Daguati, R, Meroni, F, and Crosignani, P. Asymmetry in distribution of diaphragmatic endometriotic lesions: evidence in favor of the menstrual reflux theory. Human Reproduction. 2007;22:2359-2367.

  25. Wheeler, JM. Epidemiology of endometriosis-associated infertility. J Reproductive Med 1982;34:41.