Download COTM0114 - California Tumor Tissue Registry

“A Newborn with Multiple Cardiac
Tumors”
California Tumor Tissue Registry’s
Case of the Month
CTTR COTM Vol. 16:4
January, 2014
www.cttr.org
Immediately following delivery to a healthy young woman, a baby boy was intubated for
respiratory distress. An echocardiogram was performed on the child, revealing left
ventricular enlargement with multiple ventricular masses that partially obstructed the
outflow tract. Given the severity of his condition and the extent and location of the
masses, the boy was deemed to be a poor surgical candidate. Ventilatory support was
withdrawn and the boy expired shortly thereafter.
Gross examination of the heart at autopsy revealed numerous firm, white-tan ventricular
mural nodules up to 1.8 cm.
Although unencapsulated and apparently wellcircumscribed, the nodules involved a substantial portion of the myocardium with some
protruding into the ventricular cavity and approximating the mitral and aortic valves.
Microscopically, the tumors were comprised of large, polygonal clear cells which were
distinct from the surrounding normal myocardiocytes (Figs. 1, 2, 3). The lesional cells
were distended by cytoplasmic vacuoles which surrounded the nuclei (Fig. 3 & 4).
Delicate wisps of pink cytoplasm emanated from the small, central nuclei extending to
the periphery (Fig. 5). Significant atypia, mitotic figures, and necrosis were not
encountered.
Diagnosis: Cardiac Rhabdomyoma
Elif L. Akin, M.D. and Donald R. Chase, M. D.
Department of Pathology & Human Anatomy
Loma Linda University Medical center, Loma Linda, California
Cardiac rhabdomyoma (CR) is the most common cardiac neoplasm in the pediatric
population, comprising about 60% of cardiac tumors in pediatric autopsy series and an
overwhelming 90% of cardiac neoplasms diagnosed in utero. Considered to be a benign
hamartoma which has no predilection for either gender, this neoplasm most frequently
arises in the ventricles.
Grossly, cardiac rhabdomyomas are distinct, well-circumscribed white-tan nodules which
contrast with surrounding myocardium. They can occur as solitary or multiple lesions,
ranging in size from a few millimeters up to 10 cm. Although they usually arise in the
CTTR’s COTM
January, 2014
Page 1
left ventricular free wall, they can involve the muscle surrounding any of the cardiac
chambers.
Microscopically, CR are characterized by nodules of round or polygonal clear cells that
are much larger than myocardiocytes and swollen with glycogen-rich vacuoles. Nuclei
are small and centrally located and have delicate connections to the perimeter of the cell
comprised of eosinophilic wisps of cytoplasm, which are thought to represent
invaginations of the cytoplasmic membrane. These so-called “spider cells” are
characteristic of cardiac rhabdomyomas. Their peripherally vacuolated, clear appearance
is a result of glycogen deposition, which is lost during routine processing. Striations may
also be seen. While some CR may show degenerative change, significant nuclear
pleomorphism, mitotic activity, and necrosis are not typically present.
Many CR occur as asymptomatic lesions that eventually spontaneously regress. As the
regression rate is an estimated 50 to 70%, surgical intervention is often unnecessary,
making CR the second most common cardiac tumor in pediatric surgical series (behind
cardiac fibroma). When symptomatic, the clinical presentation of children with CR
varies considerably depending on the size, extent, and location of the tumor(s). It is not
altogether surprising that lesions involving the conduction system may cause arrhythmias
and that large CR projecting into the ventricular cavity may cause flow abnormalities and
mechanical obstruction. Potential clinical manifestations of problematic CR include
murmurs, arrhythmias, and heart failure and may necessitate partial surgical resection,
depending on symptom severity.
Although CR can occur as a solitary, isolated lesion, it is most frequently seen in the
context of tuberous sclerosis complex (TSC). When associated with TSC, lesions tend to
be multifocal and extend into the ventricular cavity. Because of the strong link to TSC,
patients with a diagnosis of CR must be assessed for other signs of this disease. Cardiac
rhabdomyomas are less often associated with congenital cardiac malformations including
tetralogy of Fallot, Ebstein anomaly, and hypoplastic left heart syndrome.
There are several entities (including non-neoplastic lesions) which may be considered in
the differential diagnosis of cardiac rhabdomyoma.

Glycogen storage disease (Pompe disease) is also characterized by vacuolated
myocytes. However, the cytoplasmic vacuoles tend to be central, with myofibrils
at the periphery. In contrast to CR, glycogen storage disease does not form
distinct nodules and lacks spider cells.

Purkinje cell hamartoma (histiocytoid cardiomyopathy) is a rare pediatric
cardiac tumor which also presents as multiple intramural nodules. Although this
condition also has a predilection for the left ventricle, the nodules tend to be
subendocardial. Unlike CR, the cells of histiocytoid cardiomyopathy (as the
name would suggest) resemble histiocytes, are quite a bit smaller than spider
cells, and show finely vacuolated cytoplasm filled with mitochondria, rather than
glycogen.
CTTR’s COTM
January, 2014
Page 2

As the most commonly excised pediatric cardiac tumor, the shear frequency of
cardiac fibroma makes it another important consideration in the differential
diagnosis. While CR may be multifocal, cardiac fibromas are typically solitary
mural lesions which resemble fibromatoses. Characterized by bland spindled
cells interspersed with collagen bundles, fibromas tend to have infiltrative
borders. Additionally, cardiac fibromas may demonstrate focal calcification, a
feature not ordinarily observed in CR.

Lipomatous hypertrophy, in contrast to the above conditions, affects older,
usually obese adults. It preferentially involves the atrial septum and is
distinguished from CR by the presence of three cell populations including brown
and white adipocytes as well as hypertrophic myocytes.
In summary, CR is a benign hamartomatous neoplasm of infancy which typically arises
in the left ventricular wall. It is characterized by spider cells: large cells with cytoplasmic
vacuolization and central nuclei with strands of eosinophilic cytoplasm extending to the
cell borders. While these lesions are usually asymptomatic and spontaneously regress,
they can cause serious clinical problems (e.g., heart failure) and may require surgical
intervention. Appropriate recognition and diagnosis of CR is important to determine
whether surgery is required and to initiate further evaluation for possible tuberous
sclerosis complex.
Suggested Reading:
Burke A, Tavora F. Practical Cardiovascular Pathology. Wolters Kluwer Health
Lippincott Williams & Wilkins. 2011: 375-380.
Stocker JT, Dehner LP, Husain AN. Stocker & Dehner’s Pediatric Pathology: 3rd ed.
Wolters Kluwer Health Lippincott Williams & Wilkins. 2010: 566-569.
Virmani R, Burke A, Farb A. Atlas of Cardiovascular Pathology. W. B. Saunders
Company. 1996: 82-91.
Weiss SW, Goldblum JR. Enzinger & Weiss’s Soft Tissue Tumors: 5th ed. Mosby
Elsevier. 2008: 583-592.
CTTR’s COTM
January, 2014
Page 3