Case 2 -
Saint Louis University
Saint Louis, MO
Click on each slide thumbnail image for an enlarged view
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.
Case 2 - Slide 1
Case 2 - Figure 4
(higher power view of Figure 3) Mass effect adjacent to liver lesion, with portal expansion, edema, ductular proliferation, and mixed inflammation.
Case 2 - Figure 5
Liver mass with cystic area and hemorrhage.
Case 2 - Figure 6
Medium power view of lesion with characteristic biphasic pattern.
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.
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 ).
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
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 . 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
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
There are several hypotheses for the etiology of endometriosis, which are not mutually
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 .
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 .
3. Hematogenous or lymphatic dissemination of endometrial tissue,
which would explain endometriosis in lymph nodes, brain, liver parenchyma, and other distant
4. Direct implantation of endometrium, as in endometriosis in cesarean
section scars .
Fewer than two dozen cases of hepatic endometriosis have been reported, with an age range at diagnosis
of 21 to 64 years
The hepatic endometriomas were usually solitary, unilocular or
multilocular cysts that measured from 3 to 30 cm
Few were correctly diagnosed prior to
excision; these were diagnosed on needle biopsy
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 . Most patients were symptomatic, with right upper quadrant
or vague upper abdominal pain being the most common presenting complaint
half had a prior history of endometriosis, and a similar number also had a history of prior pelvic
surgery or laparoscopy . Exceptional patients presented with signs and symptoms of an acute
abdomen , as obstructive jaundice
with ascites , or with recurrent spontaneous
catamenial pneumothorax  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
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