Case 4 -
Lesion of Aggregated Monocytes and Mesothelial Cells (LAMM)
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An 80 year-old man with a history of prostate cancer presented
with fatigue and dysuria. He was found to have a urinary tract infection and was treated with
antibiotics. One month later he developed chills, sweats and cough. He also had been noticing some mild
right-sided weakness. A work up revealed another urinary tract infection and a large vegetation on the
atrial side of the anterior leaflet of the mitral valve, which in addition was moderate to severely
regurgitant. Blood cultures grew out Streptococcus agalactiae. He underwent valve replacement and at
the time of surgery was diagnosed with mitral valve prolapse and vegetations as described above. Two
specimens were submitted to surgical pathology: a myxomatous valve with a focus of subacute endocarditis
and separate "yellow to white purulent appearing "vegetation" measuring 2.5 x 2.0 x 0.2 cm. Sections are
from this latter specimen.
Case 4 - Figure 1 - "Vegetation from" mitral valve. Note vacuoles and focus of dense connective tissue (x 20)
Case 4 - Figure 2 - The "vegetation" is composed predominantly of oval to round cells with abundant pink cytoplasm (x 40)
Case 4 - Figure 3 - Interspersed among the round cells are clusters and strips of columnar cells, some of which have prominent nucleoli (x 200)
Diagnosis: Lesion of aggregated monocytes and mesothelial cells, LAMM (a.k.a. cardiac MICE
mesothelial/monocytic incidental cardiac excrescence)
In 1990, Luthringer, et al reported a lesion originally thought to resemble a histiocytoid (epithelioid
hemangioma) occurring within the cardiovascular system, particularly the heart. The authors suggested
that the lesions, in part, showed mesothelial differentiation. Two additional reports (Veinot, Courtice)
confirmed the presence of mesothelial cells in these lesions. Courtice, et al suggested that the lesions
were best regarded as "pseudotumors" and in most instances, were artifactually produced. Following
publication of this article, several other authors have recognized the histiocytic and mesothelial
components of this lesion.
In the earliest reported examples of this lesion, they were referred to as histiocytoid hemangiomas.
Additional cases were originally diagnosed as "chemoreceptor tissue" and "metastatic adenocarcinoma".
Thus, it is clear that these lesions have caused at least some confusion to experienced surgical and
cardiovascular pathologists and continue to be the subject of case reports. These lesions have been
identified in cardiac chambers, on cardiac valves, in the pericardial sac, in specimen jars submitted to
pathology, in the ascending aorta, in the mediastinum, and in the pleural space. They have also been
identified in microscopic sections of tissue taken by right ventricular endomyocardial biopsy and
transbronchial biopsy. Similar lesions have been identified incidentally at the time of surgery for
pulmonary disease and submitted as lymph nodes, and are similar, if not identical, to lesions described
as "nodular histiocytic/mesothelial hyperplasia" in the general surgical pathology literature.
The lesions are usually identified incidentally and are often described as being "free floating" by
the surgeon. The lesions range in size from microscopic up to 3 cm in diameter. Grossly, they vary from
gray white to dark red to brown and are frequently associated with obvious thrombus.
The nodules are usually discrete and distinct from other tissue submitted at the same time (e.g.
valves, myocardial biopsies, portions of the aorta). The lesions are composed of two predominant cell
types, a histiocytoid cell and a taller columnar or cuboidal cell. The histiocytoid cells are round to
oval and have pink cytoplasm, well-defined nuclei with prominent nuclear grooves and occasional
nucleoli. They have a low nuclear to cytoplasmic ratio and are positive for CD68 and lysozyme. Electron
microscopically, these cells have features typical of histiocytes with convoluted nuclei, prominent
nucleoli, cytoplasm rich in reticulin and surface pseudopodia. The second, less numerous cells, are
usually present in small groups, strips, or tubular arrangements, have smaller amounts of eosinophilic
cytoplasm and have small, round, non-cleaved nuclei with inconspicuous nucleoli. These cells are
reactive with antibodies for keratin, calretinin, CK 5/6 and fail to react with antibodies for CEA, CD15,
Factor VIII related antigen, multiple hematolymphoid markers, CD68, lysozyme and CD45. Electron
microscopically, these cells have haphazardly arranged intermediate filaments and surface microvilli.
Well-developed desmosomes and intercellular connections may also be present. These features are
consistent with mesothelial cells. The cells may be associated with small numbers of neutrophils,
occasional lymphocytes, and eosinophils, and are sometimes arranged around spaces or adipocyte-like
vacuoles. Occasionally, foreign material may be intermixed.
The authors of the original two studies (Luthringer and Veinot) suggested that these lesions might
represent a form of mesothelial hyperplasia, possibly representing a reactive process in response to
previous cardiac catheterization, as 75 percent of patients in one series had such a previous history.
An additional hypothesis has been put forward by Courtice, et al as a result of their examination of
material found in extracorporal bypass pumps and material adherent to mediastinal and pericardial
drains. Based on their study, in which such lesions were found in 82% of bypass pumps and 13% of
mediastinal and pericardial drains following cardiac surgery, they suggested that these lesions were
produced the cardiotomy suction tip. They hypothesized that compaction and agglomeration of friable
mesothelial strips, other tissue, debris, and fibrin could be transported around the operative site and
thus, be found "free floating" by either the surgeon or the pathologist. This hypothesis probably
explains the majority of examples of this lesion. Further support for this hypothesis comes from
Suarez-Vilela and Izquierdo-Garcia who observed aberrant expression of the adhesion molecule CD34 on the
mesothelial cells of an example of nodular histiocytic-mesothelial hyperplasia identified in a hernia
sac. The Courtice hypothesis does not, however, account for material obtained by right ventricular
endomyocardial biopsy or transbronchial biopsy. Therefore, rare examples of this lesion may represent
the result of perforation of a hollow viscus into a mesothelial space which, along with fibrin and
previously circulating macrophages and rare inflammatory cells, may coalesce to form a pseudoneoplasm.
As emphasized by Courtice, et al, the lack of histologic evidence of attachment to underlying tissues
and a lack of supporting fibrovascular stroma highlight the fact that the fibrin meshwork previously
described is not only a prominent feature of such lesions, but is likely an essential element in their
formation and adherence to other tissues. The lack of supporting stroma also makes it unlikely that
these lesions actually have the "capacity to grow" other than by increasing the number of cells which
adhere to the fibrin meshwork.
What is the best name for these lesions? Several authors have proposed the term "nodular
histiocytic/mesothelial hyperplasia". However, this implies that the lesions actually have the capacity
to grow via their own blood supply. Given the fact that the majority of these lesions do not appear to
have a vascular system or blood supply and are most likely artifactually produced in some way, I prefer
the term "lesion of aggregated monocytes and mesothelial cells" (LAMM) when they occur outside of the
heart and MICE when they occur within the heart. Their significance, of course, lies not so much in what
they are called, but what they are not called (e.g. metastatic
adenocarcinoma). The majority of MICE have behaved in a benign fashion. However, there has been one
report of metastatic adenocarcinoma involving a cardiac MICE (Argani et.al). In this particular example,
a 0.8 cm in diameter fragment of cellular debris was found floating in the pericardial cavity which
proved to contain clusters of clearly malignant cells in a patient who had a known adenocarcinoma.
Therefore, not all lesions with this characteristic architecture and cell composition can be dismissed as
benign. This particular case also suggests the possibility that these lesions can form by induction of
This case represents an example of a cardiac pseudoneoplasm, of which there are several (Table 1).
One process which is no longer considered a pseudotumor or pseudoneoplasm is the lesion now best referred
to as inflammatory myofibroblastic tumor
(IMT). IMT should now be regarded as a true neoplasm and the term "inflammatory pseudotumor"
Calcified amorphous tumors of the heart (cardiac CAT). In one report
(Reynolds et al), patients with these pseudoneoplasms ranged in age from 16-75 years (mean, 52 years) and
included 7women and 4 men. The patients presented with a wide variety of symptoms including
embolic phenomenon (50%), shortness of breath, or orthopnea (30%), a "funny sensation" in the chest
(10%), and without symptoms (10%). Table 2 shows the underlying disease states present in the patients.
Interestingly, a few of the associated diseases are conditions known to predispose to thrombosis while
others predispose to calcification. One patient had no known pre-existing condition.
All four cardiac chambers have been the site of these lesions as well as the mitral valve
(Table 2). The lesions range in size from 0.2-6.5 cm. in diameter. The largest one measured
9cm in length and extended down a central line in a patient on total parenteral nutrition.
Microscopically, they are remarkably similar from case to case. All cases have had various amounts of
often nodular calcium deposits set in a background of what appears to be degenerating fibrin. One case
had bony metaplasia. All cases had mild to moderate numbers of chronic inflammatory cells at the base,
often associated with a few capillaries. Hemosiderin deposition was absent in all but two cases. In one
case cholesterol clefts were present in the degenerating fibrin. Giant cells were present surrounding
the calcium deposits in the one lesion from the patient with a history of tumoral calcinosis. In fact
this lesion resembled that of soft tissue tumoral calcinosis. A majority of the cases (60%) had fresh
fibrin on the surface, which may have been the source of some of the emboli, another possibility being
the calcium fragments themselves.
Follow-up was obtained on 9 of the patients reported by Reynolds et al from 4 months to 18 years. All
patients had a benign course with respect to their cardiac lesion. A repeat echocardiogram in two
patients at 11months and 3.5 years showed some residual calcium at the site of the original mass,
but neither patient was symptomatic.
It is tempting to conclude that all of these lesions represent nothing more than calcified mural
thrombi. In fact, most probably are, particularly those occurring in patients with underlying diseases
which might predispose to thrombosis. The fibrin and red cells in these thrombi, appear to undergo
mummification rather than organization. However, not all patients had such underlying conditions and two
had no underlying condition at all. Additional cases will need to be studied in order to determine their
The clinical differential diagnosis for these lesions includes most benign and malignant cardiac
tumors, particularly myxomas, as well as a group of non-neoplastic processes which may give rise to
mass-like lesions. The pathologic differential diagnosis for these lesions includes a more typical
organizing thrombus, non-infectious thrombotic endocarditis, white blood clots of "white blood clot
syndrome", and Echinococcus cysts.
All of the CAT's lack significant fibroblastic proliferation within the majority of the lesion
characteristic of an ordinary thrombus. Non-infectious thrombotic endocarditis is usually characterized
as 1-4 mm diameter granular, pink vegetations. They are most frequent on the undersurface of the
atrioventricular valves but may be scattered on the valvular endocardium, chordae tendineae and on the
mural endocardium. Histologically, the verrucae consist of finely granular eosinophilic fibrous
material. This may be associated with an underlying valvulitis.
White clot syndrome describes the development of spontaneous major
arterial and/or venous thrombosis in patients receiving heparin therapy. It is often preceded by a
declining platelet count and/or increasing resistance to heparin and occurs in a small percentage of
patients who develop heparin-induced thrombocytopenia. The definitive diagnosis of heparin-induced
intravascular thrombosis is obtained by performing platelet aggregation tests. The fibrinogen level and
prothrombin time are usually normal and the fibrin-split products are normal or slightly elevated.
Complications requiring amputation, thrombectomy, or other surgery have occurred in up to 61% of the
patients with mortality as high as 50%. The name comes from the fact that the thrombi ("clots") in the
heparin-induced white blood clot syndrome are composed predominantly of platelet aggregates and are white
Echinococcus also can involve the heart and present similarly, but the
diagnosis rests on the recognition of the wall of the hydatid cyst and the presence of scolices.
Degenerating right ventricular mural thrombi containing degenerating
eosinophils can also occur in the setting of restrictive/eosinophilic heart disease and have also been
reported in association with Churg Strauss Syndrome.
Table 1 - Non-neoplastic cardiac tumors, a.k.a. pseudoneoplasms
| Calcified amorphous tumor (CAT)|
| Atrial varix|
| Chiari's web with thrombus|
| Large Eustachian valve|
| Non-infective thrombotic|
| White clots|
| In setting of restrictive/eosinophilic heart disease|
| Echinococcal "cysts"|
| Wegener granulomatosis|
| Valvular wind-sock deformities|
| Apical Variant of hypertrophic cardiomyopathy|
| Mitral annular calcification|
| Lipomatous hypertrophy of atrial septum|
| Intramyocardial hematoma|
Table 2: Diseases Present in Patients with Cardiac CAT
|Prior chest radiation and chemotherapy for neuroblastoma|| 1|
|SLE with anti-cardiolipin antibodies|| 1|
|Central line for total parenteral nutrition ||1|
|Cardiac valve disease ||2|
|Chronic renal failure with history of tumoral calcinosis ||1|
|Diabetes mellitus ||1|
|Recurrent pulmonary thromboemboli ||2|
|Coronary artery disease, congestive heart failure ||1|
Table 3: Location of Cardiac CAT
| Right atrium ||2|
|Right ventricle ||3|
|Left atrium ||1|
|Left ventricle ||4|
|Mitral valve ||1|
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