Case 3 -
Nodular Elastosis of the Liver
Michael S. Torbenson
Johns Hopkins University School of Medicine
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Brief clinical history:
A 62 year old female with a
high CA125 underwent exploratory laparotomy to rule out ovarian cancer. The surgeon found no evidence
for cancer but did see a pedunculated lesion of the liver that was near but not connected to the
falciform ligament. The liver was otherwise grossly unremarkable. The lesion was biopsied.
Case 3 - Figure 1
H&E, original magnification 20X. A low power view of the mass lesion shows scattered small islands of hepatocytes surrounded by abundant extracellar material.
Case 3 - Figure 2
H&E, original magnification 40X. A medium power view shows the extracellular material involves the portal tracts. The hepatic artery and bile duct can be seen in the remnant of a portal tract.
Case 3 - Figure 3
H&E, original magnification 40X. A medium power view shows the extracellular material involves the central veins. This central vein is nearly obliterated.
Case 3 - Figure 4
H&E, original magnification 100X. A high power view shows the extracellular material as it abuts the islands of hepatocytes. The hepatocytes show no atypia.
Case 3 - Figure 5
original magnification 100X. H&E. A high power view shows the extracellular material. There are scattered cells throughout the extracellular material but these cells show no atypia. No mitotic figures were observed.
Case 3 - Figure 6
H&E, original magnification 16X. A high power view shows the extracellular material has a basophilic and somewhat fibrillar appearance.
Case 3 - Figure 7
original magnification 100X. Miller's Elastic stain. An elastic stain shows the extracellular material is primarily composed of elastic fibers. Both VVG and Movat stains will also work equally well to highlight the elastic fibers in these cases.
Pathological/Microscopic Findings and any Immunohistochemical or Other Studies:
Three unoriented fragments of pale tan tissue measuring
from 0.5 to 0.8 cm in greatest dimensions.
The biopsy specimens showed extensive
deposition of extracellular material that surrounded nodules of benign hepatocytes. The extracellular
material was finely granular and gray in color. There were scattered benign appearing mesenchymal cells
throughout the extracellular material. Enmeshed in this material were residual portal tracts and central
veins. A biliary cyst was also present on one edge of the lesion. A thrombosed vessel could also be
seen at one edge of the specimen.
The following special stains were performed.
Positive stains: vimentin (cells embedded within the extracellular material)
- Trichrome: negative
- Verhoeff-van Gieson Stain: The extracellular material turned black.
- Reticulin stain: Numerous reticulin fibers were evident in the extracellular material.
- Movat stain: The extracellular material turned yellowish-black. As a reminder, in the Movat stain,
elastic fibers stain black while collagen and reticulin fibers stain yellow.
- Congo red
- smooth muscle actin
The differential includes the following, each of which are discussed in
Cystic disease of the liver.
Cancer associated elastosis.
Nodular Elastosis of the liver.
Nodular elastosis of the liver is a pseudotumor of the liver that can be challenging to diagnose.
Nodular elastosis represents the end stage of a series of changes that are associated with segmental
atrophy of the liver. An entire lobe of the liver can also undergo atrophy, but overall such cases are
more commonly diagnosed by imaging studies and are only rarely seen as surgical specimens. Segmental
atrophy, however, can present as a mass lesion that undergoes biopsy or resection.
Based on our recent experience of 16 cases collected from several institutions, of resected or
biopsied lesions, there appears to be a modest female predominance (70%) and a wide age range at
presentation, from 14 to 91 years (median 65 years). The most common clinical presentation is right
upper quadrant abdominal pain (75%). The mass lesions can be identified either at the time of surgery
(as in our case) or by imaging studies.
The majority of lesions are subcapsular (80%) and range in size from 2 to 10.0 cm. A striking
feature in almost all cases is the presence of abnormally thick-walled vessels that may be thrombosed,
fibrosed, and re-cannulized. They can be found throughout the lesion and both arteries and veins may be
affected. Biliary cysts are also a common finding (35%). Although I am without direct experimental
evidence to support this, I believe most of the cysts are "retention cysts" caused by duct obstruction
and subsequent dilatation and cyst formation within the areas of blocked biliary drainage. In many
cases, smaller cysts are clearly within portal tracts and represent dilatation of the native bile duct.
At times, the larger cysts can rupture and develop a thick rind of inflammed fibrotic tissue. The cyst
epithelium maybe denuded from large sections of these inflammed fibrotic cysts, but can almost always be
seen with sufficient sectioning of the cyst wall. On follow-up, no recurrence has been reported.
Based on seriating a set of 16 cases, there appears to be a defined set of morphological appearances
through which these lesions progress. Early lesions appear to be composed principally of collapsed
hepatic parenchyma with occasional islands of residual hepatocytes and brisk bile ductular
proliferation. These early cases may show no elastosis or only focal elastotic changes. Over time the
ductular reaction diminishes and the elastotic changes increase. The later lesions can be composed
almost solely of elastosis with small scattered islands of unremarkable hepatocytes, as seen in our case,
and diagnosed as "nodular elastosis".
How common in this lesion? It is hard to say with any numerical certainty. Between our combined
in-house and consult services, we see on average a case of segmental atrophy perhaps every year or two.
Nodular elastosis is much less common: we have 2 cases in our files from 1984 to 2009.
The histological findings tend to fairly distinctive for these cases and after seeing and perhaps
struggling with the first case, subsequent cases tend to be fairly easily identified.
Elastic fibers in the normal and diseased liver
Elastic fibers provide flexibility and recoil-to-stretch in normal tissues and are particularly
prominent in the skin, lungs, and walls of large vessels. Elastic fibers are composed principally of
elastin and microfibrils.  Elastin is encoded by a single gene, ELN, but microfibrils are
composed of a variety of proteins including fibulins and microfibril associated glycoproteins.
 The elastic component of tissues is created during organogenesis and subsequent organ
maturation and forms a complicated 3-diminsional network. Injured tissues in the adult can produce
elastic fibers, but injured tissues have difficulty creating the normal fiber organizational patterns,
often leading to deposition of disorganized and excessive amounts of elastic fibers.  In
response to injury, elastic fibers can be synthesized by fibroblasts as well as smooth muscle cells
 and endothelial cells.
In the normal liver, elastic fibers are found within the portal tracts, the walls of larger vessels,
and in the connective tissue of the central veins.  In the setting of liver injury, elastic
fibers are synthesized by portal myofibroblasts but not activated stellate cells. 
Increased elastic fiber deposition can be seen in a variety of conditions and overall tends to parallel
the amount of fibrosis. For example, in one study of non-alcoholic steatohepatitis, increased elastic
fiber deposition was seen in all cases of advanced fibrosis but only rarely in cases with milder stages
of fibrosis.  Of note, the elastic deposition in such cases do not form discrete lesions
and in general are not seen on H&E stains.
The possibility that a vascular injury leads to the segmental atrophy and subsequent development of
elastosis was outlined above. While this explanation fits well with our histological findings, there
have been clinical reports that have linked segmental atrophy to bile duct injury, 
suggesting there may be more than one pathway of injury that can lead to the same result of segmental
atrophy and eventually to nodular elastosis.
Elastotic polyps of the colon provide some interesting parallels. They can be found
throughout the gastrointestinal tract and are composed of aggregates of elastic fibers found principally
in the submucosal.  The H&E and histochemical staining qualities are essentially
identical to that found in the nodular elastosis of the liver. Of particular relevance, 4/13 cases of
elastotic polyps of the gastrointestinal tract were associated with elastotic submucosal blood vessels,
 suggesting a shared vascular etiology with liver cases.
Cystic disease of the liver. In some cases, multiple small cysts may be
present and this can raise the question of multicystic diseases of the liver. Proper classification can
be assisted by knowing the radiological findings: diffuse cystic change in the liver or cysts within the
kidneys would suggest cystic liver disease. On histological examination, a diagnosis of segmental
atrophy and cystic changes could be based on identifying areas of parenchymal collapse, finding the
thrombosed vessels, or finding the ductular reactions typical of early lesions. The presence of
elastotic changes also will favor a diagnosis of lobar atrophy.
Amyloid . Amyloid deposition can be in the differential in those cases
containing abundant elastosis. A Congo red stain will be negative in elastosis but positive in
Epithelioid hemangioendothelioma. Epitheliod hemanagioendotheliomas
often have a distinctive amphophilic tumor matrix that can resemble nodular elastosis. The neoplastic
cells within this glycoprotein rich tumor matrix are typically more cellular than nodular elastosis, but
in some cases there can be areas that have many fewer cells, leading to an overall cellular density that
resembles nodular elastosis. However, the neoplastic cells of epitheliod hemanagioendotheliomas will
have nuclear pleomorhpism and frequently have cytoplasmic vacuoles that can mimic signet ring cells.
Mitotic figures, which can be seen in many epithelioid hemangioendotheliomas, are lacking in nodular
elastosis. Immunostains for vascular markers factor VIII, CD34, and CD31 are negative in nodular
elastosis but positive in 99%, 70% and 66% of epithelioid hemangioendotheliomas respectively.
Cancer associated elastosis. Irregular dense aggregates of elastic
fibers can also be seen within the stroma of certain types of cancers in other organ systems. For
example, in one study 66% of papillary thyroid carcinomas had stromal elastosis, as did 76% of lung
adenocarcinomas, 50% of lung squamous cell carcinomas, 57% of breast carcinomas, and 22% of gastric
carcinomas.  This same study found no evidence of stromal elastosis with hepatocellular
carcinomas, an observation that fits well with our general experience. Thus, in the liver, nodular
elastosis does not appear to be associated with carcinoma. However, a caveat is that atrophy of the
entire right or left lobe (but typically not segmental atrophy) has been reported in individuals with
hepatocellular or cholangiocarcinomas. 
Systemic conditions. While data is limited, there has
been no clinical evidence of extrahepatic manifestations of lobar atrophy/nodular elastosis changes
to-date. Elastotic polyps of the gastrointestinal tract have rarely been reported to be associated with
other elastotic conditions including elastrofibroma dorsi. 
Review of the Literature/Treatment Options:
Segmental atrophy/nodular elastosis is a
benign lesion that does not require intervention, but since it often presents as a mass lesion, it often
undergoes surgical resection. Once resected, there have been no reports of recurrence.
Nodular elastosis is a histologically distinctive psuedototumor of the liver that is
associated with vascular injury and segmental atrophy of the liver.
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