Heart-tumor
Last revised 25 November 2011
Last major update May 2007
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Cardiac tumors-benign: general, adenomatoid tumor, angiomyolipoma, atrioventricular node tumor, benign fibrous histiocytoma, blood cyst, calcified amorphous tumor, endocardial fibroelastosis, fibroma, granular cell tumor, hamartoma, hemangioma, inflammatory pseudotumor, Lambl’s excrescence, lipoma, lipomatous hamartoma, lipomatous hypertrophy, lipomatous infiltration, mesothelial/monocytic cardiac excrescence, myxoma, necrobiotic xanthogranuloma, papillary fibroelastoma, paraganglioma, rhabdomyoma, schwannoma, sugar tumor, tumor with perivascular myoid differentiation, varix
Cardiac tumors-malignant: angiosarcoma, chondrosarcoma, Ewing’s sarcoma/PNET, fibrosarcoma, germ cell tumor/teratoma, granulocytic sarcoma, hemangioendothelioma, hemangiopericytoma, Kaposi’s sarcoma, leiomyosarcoma, liposarcoma, lymphoma, malignant fibrous histiocytoma, malignant mesenchymoma, malignant peripheral nerve sheath tumor, metastases, osteosarcoma, post-transplant lymphoproliferative disorder, rhabdoid tumor, rhabdomyosarcoma, sarcoma-general, synovial sarcoma, undifferentiated sarcoma
Pericardial tumors: hemangiolymphangioma
Miscellaneous: features to report-tumors
American Journal of Clinical Pathology, (AJCP), January 1975 to May 2007
American Journal of Surgical Pathology (AJSP), March 1977 to May 2007
Archives of Pathology and Laboratory Medicine (Archives), January 1976 to May 2007
Biomed Center, 1 March 1997 to 2 May 2007
Human Pathology (Hum Path), March 1970 to May 2007
Modern Pathology (Mod Path-free full text after 1 year), January 1988 to April 2007
Mills: Sternberg's Diagnostic Surgical Pathology (4th ed), 2004
Rosai: Rosai and Ackerman's Surgical Pathology (9th ed), 2004
Tumors of the Heart and Great Vessels (AFIP Atlas of Tumor Pathology, Series 3, Vol 16); 1996
AFIP images (not copyrighted) courtesy of www.PathologyResources.com
Websites with images: PathoPic, PEIR digital library
Journal search terms: heart and each disease entity listed
Please refer to these primary references for more detailed discussions and additional images
Cardiac tumors-benign
Occur in 1 per 300 to 100,000 autopsies
Common tumors are myxoma (30% of all primary cardiac tumors), papillary fibroelastoma (8%), rhabdomyoma, fibroma, hemangioma, lipomatous hypertrophy, AV nodal tumors, other (5% or less each)
In children, common tumors are rhabdomyoma, fibroma and teratoma (Orphanet J Rare Dis 2007;2:11)
Adenomatoid tumor of the heart
Very rare
Case reports: incidental 1 cm tumor (AJSP 1997;21:1378)
Micro: cords or tubules of large epithelioid cells without atypia that occasionally branch into anastomosing channels
Micro images:
adrenal gland - various images
epididymis - tubules, cords or nests of epithelioid cells in fibrous stroma; cells have large intracytoplasmic vacuoles, but no atypia #1; #2; cytokeratin AE1/AE3
site unknown - tumor has angiomatous-like spaces
Positive stains: AE1/AE3, CAM 5.2, EMA, calretinin, thrombomodulin (paratesticular tumors-Histopathology 2000;36:109, adrenal tumors-AJSP 2003;27:969)
Negative stains: CEA
Very rare
Associated with tuberous sclerosis
Case reports: 48 year old woman with dyspnea and right atrial mass (AJSP 1994;18:1164), massive (34 cm) right atrial tumor (J Formos Med Assoc 1997;96:653)
Gross images: posterior mediastinal tumor is well circumscribed, yellow and fatty
Micro: mixture of blood vessels, smooth muscle and fat
Micro images: kidney - tumor #1; #2; #3; liver - epithelioid angiomyolipoma; mediastinum - mature adipocytes, plump spindle cells and vessels; HHF35+; HMB45+
Positive stains: adipocytes - S100; smooth muscle cells - desmin, actin; most cells - CD117 (diffuse and cytoplasmic, AJSP 2002;26:493), HMB45, NKI-C3/CD63 (Archives 2001;125:751), MelanA/Mart1, microphthalmia transcription factor
EM images: kidney - tumor cells with smooth muscle differentiation adjacent to lipid droplet within an adipocyte (left); various images
DD: renal angiomyolipoma with thrombus extending into right atrium (Urol Int 2001;67:168, Nippon Hinyokika Gakkai Zasshi 1999;90:745)
Atrioventricular node tumor of heart
Also called cystic tumor of AV node or mesothelioma of AV node, but does not appear to have mesothelial origin
Rare; usually identified at autopsy
May be congenital rests of endodermal origin (Archives 1990;114:1057) or ultimobranchial heterotopia identical to solid cell nests of thyroid (AJCP 2005;123:369)
Associated with other congenital anomalies
Often causes heart block and sudden death
Mean age 38 years, 75% female
Should examine conduction system in all patients with sudden death, particularly if a history of arrhythmia or heart block
Case reports: causing heart block for years before death (AJCP 1975;63:377), causing sudden cardiac death #1 (Archives 2001;125:573), #2 (Am J Forensic Med Pathol 2005;26:349), occurring in atrial septum (Cardiovasc Pathol 1999;8:325), congenital tumors (Cardiovasc Pathol 1999;8:233), with multiple endocrine abnormalities (Pathol Res Pract 1996;192:54)
Treatment: pacemaker implantation, anti-arrhythmic drugs, possibly surgical excision (Heart 2000;83:E6)
Gross: may not be visible due to small size (2 to 20 mm); multicystic lesion in area of atrioventricular node and membranous septum
Gross images: tumor outlined by arrowheads (RA-right atrium, RV-right ventricle, TV-tricuspid valve); figures 1/2: nodule of atrioventricular node; fig 3: elastic and trichrome stains
Micro: must sample conduction system; solid and cystic areas lined by nonciliated, epithelial appearing cuboidal cells (main cells), mixed with occasional clear cells (neuroendocrine or C cells); lumina contains PAS+ diastase resistant material which may calcify; may have inflammatory cells and fibrosis; no smooth muscle, no mitotic figures, no atypia
Micro images: normal anatomy (no tumor) with IAS-interatrial septum (tumors are located inferiorly), TV-tricuspid valve and VS-ventricular septum; large cysts filled with proteinaceous debris; multiple small cysts not visible to naked eye; cysts with irregular shape surrounded by fibrous stroma; cyst may have two cell lining, with inner lining composed of small cuboidal cells; tumor nests and cysts replace muscle bundles in inferior interatrial septum; cuboidal cells and clear, sebaceous-type cells; squamous differentiation and calcification of luminal debris; nests of cells resembling urothelium; cysts lined by squamous epithelium; H&E and AE1/AE3+; various images
Atrioventricular node tumor of heart (continued)
Positive stains: main cells - CAM5.2, AE1/AE3, 34βE12, CK7, EMA, CEA, CA19.9, p63, bcl2, galectin 3
neuroendocrine or C cells - CAM5.2, AE1/AE3, CEA, calcitonin, chromogranin, synaptophysin, TTF-1
Negative stains: CK20, vimentin, CD31, factor VIII–related antigen, calretinin, estrogen receptor and progesterone receptor
EM: (a) cells form solid nests with well formed basement membranes, cytoplasmic tonofilaments and desmosomes or (b) glandular structures with desmosomes, electron-dense material and short microvilli
DD: bronchogenic cyst (solitary, grossly visible, on epicardial surface, smooth muscle present), mesothelial cyst (larger, unilocular, on surface of heart), teratoma (has neural or other ectodermal structures, Pediatr Pathol 1994;14:913)
Benign fibrous histiocytoma of heart
Rare in heart
Case reports: 4 month old boy who died due to large cardiac tumor (Z Rechtsmed 1990;103:335)
Micro: storiform pattern of spindle cells and lipid laden histiocytes; no mitotic figures, no pleomorphism
Micro images: cellular tumor without mitotic figures; tracheal tumor
Positive stains: alpha-1-antichymotrypsin, lysozyme, vimentin, factor XIIIa
Negative stains: CD68, CD34
Congenital cyst found on endocardium, particularly along lines of closure of heart valves
More common on mitral and tricuspid valves
Actually diverticula (invagination of atrial endothelium into atrioventricular valves or ventricular endothelium into semilunar valves)
Incidental findings in 50% of infants under age 2 months on cardiac valves; rare after age 2 years
Rarely causes ventricular or valvular obstruction
Case reports: acquired after surgery (J Am Soc Echocardiogr 2003;16:377), on pulmonary valve (Hum Path 1997;28:252)
Gross: usually 3 mm or less; may be blue; 50% are multiple, may have up to 20 cysts
Gross images: 4 mm cyst is incidental finding on tricuspid valve of 4 month old who died of unrelated causes; blood cyst of mitral value; seen with dissecting microscope
Micro: blood filled cystic cavity with fibromyxoid wall lined by flattened or cobblestone-shaped endothelium; filled with nonorganized blood
Micro images: non-organized blood in a sac lined by endothelium; cyst wall (fig 3)
Calcified amorphous tumor of heart
Endocardial based intracavity cardiac mass
Mean age 52 years
Clinically simulates neoplasm
Case reports: 2 cm mass in right ventricular wall involving chordae tendineae of tricuspid valve (Cardiovasc Pathol 2006;15:299), hemodialysis patients (Kyobu Geka 2006;59:851)
Treatment: excision is curative, although residual calcium may persist
Gross: firm, yellow-white, partially calcified
Micro: nodular calcium with degenerating blood elements and chronic inflammation
DD: calcified thrombi
References: Hum Path 1997;28:601
Endocardial fibroelastosis of heart
Rare
Focal or diffuse fibroelastic thickening of mural left ventricular endocardium
Usually ages 0-2 years
Focal cases have no symptoms; diffuse cases may cause rapid cardiac decompensation and death (Transplant Proc 2006;38:1511, Am J Forensic Med Pathol 1999;20:357)
Associated with (a) cardiac anomaly, such as aortic valve obstruction, or response to other chronic prenatal cardiac stress (J Clin Pathol 1991;44:576); (b) congenital heart block and maternal anti-Ro or anti-La autoantibodies (Circulation 2002;105:843), (c) mumps or other viral infection (Circulation 1997;95:133)
Declining incidence, with almost no new cases, may be due to declining incidence of mumps (eMedicine)
Case reports: fibroelastosis in neonate with no other cardiac pathology (J Clin Pathol 1992;45:1042)
Treatment: heart transplant
Gross images: pale opaque endocardium #1; #2; #3; marked endocardial thickening of left ventricle; thickened endocardium; neonate-A: endocardium of left ventricle is grossly thickened, and extends into myocardial sinusoids (arrow); B: von Gieson elastin stain shows endocardium is composed of bands of collagen and elastic fibers
Micro: increased fibroelastic tissue in endocardium and subendocardium; myocardium usually normal
Micro images: low power; von Gieson elastic stain #1; #2; trichrome stain shows marked firous thickening of endocardium
References: OMIM 305300
Rare, but is common among cardiac tumors in children
Benign, congenital, probably a hamartoma; rare cases may represent fibromatosis with aggressive behavior
Presents with heart failure or cyanosis in 1/3, syncope or arrhythmia in 1/3, incidental/asymptomatic in 1/3
Found in 10% of Gorlin’s syndrome patients (nevoid-basal cell carcinoma syndrome)
Case reports: 8 month old boy with nevoid basal cell carcinoma syndrome (Tex Heart Inst J 2006;33:88), sudden death in 7 month old girl (J Forensic Sci 2000;45:731), sudden death in 6 year old boy (Circulation 2000;101:E168), 25 year old woman with sudden death (Case of Week #224)
Treatment: excision, possibly transplant (Curr Opin Cardiol 2000;15:121)
Gross: discrete bulging mass, nearly always solitary, often calcification
Gross images: large septal mass on anterior and right lateral border #1; #2; #3 (homogeneous mass was easily shelled out); large circumscribed mass in lateral right ventricular wall compresses right ventricular cavity; ventricular mass; intraoperative image
Micro: bland fibroblasts and collagen; calcification common; more cellular in infants and children; mitotic figures in infants only; margin is infiltrative; occasionally perivascular lymphocytes and histiocytes, elastic fibers, myxoid stroma
Micro images: cellular lesion in infant with perivascular lymphocytes and minimal collagen; tumor with collagen deposition; prominent fibrous tissue; spindle cells in collagen matrix; fibroblastic cells; trichrome #1 shows abundant collagen (more common in older children/adults); #2 shows infiltrative margin-a; infiltrative margin-b; #3 shows cardiac muscle at periphery, central tumor cells in biopsy; #4; #5; von Gieson elastin stain shows elastic fibers; calcification
EM: fibroblasts with extensive endoplasmic reticulum but few cellular organelles; incompletely developed/absent basement membrane, ramifying cytoplasmic processes, central nucleus with distinct nucleolus; also cells of intermediate differentiation with smooth muscle myofilaments
DD: fibrosarcoma (rare in infants/young children, prominent mitotic activity), inflammatory pseudotumor / myofibroblastic tumor (endocardial lesions covered by fibrin; stellate tumor cells have obvious nucleoli, more prominent inflammation, occasional mitotic figures and necrosis, Ann Diagn Pathol 2001;5:335), fibrous histiocytoma (extremely rare in heart, lipid-laden histiocytes), scar (grossly does not bulge)
Very rare
Usually incidental finding at autopsy that may be overlooked
Benign tumor of Schwann cells, not myocytes (Archives 1976;100:276)
Only rarely has malignant behavior in heart
Case reports: multicentric tumor of skin and heart (Ann Thorac Surg 1994;57:1653), malignant tumor with multiple foci in myocardium (AJSP 1982;6:665)
Gross: epicardial nodules at base of heart in adults; circumscribed, gray-tan, firm; almost never continuous with nervous tissue
Gross images: tumor (arrowheads) overlying left main coronary artery near its origin (AO-aorta, PA-pulmonary artery); circumscribed white tumor of epicardial surface overlying right ventricle
Micro: tumor cells merge with cardiac myocytes; have ill defined cell margins, abundant eosinophilic and granular cytoplasm with bland pyknotic nuclei, similar to granular cell tumors elsewhere
Micro images: well demarcated tumor adjacent to coronary artery (Movat pentachrome stain); tumor adjacent to left anterior descending coronary artery with arterial elastic fibers highlighted by Movat pentachrome stain; tumor has ill defined cell margins, abundant eosinophilic and granular cytoplasm and pyknotic nuclei
Breast - cells have abundant, eosinophilic granular cytoplasm
Esophagus - clusters of granular cells; PAS and S100
Positive stains: S100, PAS+ diastase resistant granules; also neuron specific enolase
Negative stains: neurofilament, GFAP
EM: granules are membrane bound autophagic vacuoles with cellular debris; may have myelinated and nonmyelinated axon-like structures
DD: disseminated granular cell epulis (tumor of gingiva of infants that rarely disseminates)
Hamartoma of mature cardiac myocytes
Rare
Case reports: 24 year old man (Mod Path 1998;11:496), 33 year old man with shortness of breath (Rev Esp Cardiol 2005;58:450), 33 year old patient with tachycardia (Ann Thorac Surg 2001;71:1673)
Gross: resembles hypertrophic cardiomyopathy but has localized masses or multiple discrete masses, usually in right ventricle or atrium; no septal asymmetry (Hum Path 1998;29:904)
Gross images: right ventricular mass
Micro: discrete but unencapsulated nodules of marked myocyte hypertrophy with disorganization (resembles hypertrophic cardiomyopathy), focal scarring and thickened intramural arteries; no myocyte vacuoles
Micro images: disorganized cardiac cells with prominent nuclei; haphazard hypertrophied myocytes and fibrosis
EM: abundant and disorganized myofilaments; normal intercellular junctions
DD: rhabdomyoma (myocyte vacuoles), oncocytic cardiomyopathy
Rare; <5% of benign cardiac tumors
All ages
30% are multiple
Usually asymptomatic, but may cause sudden death or significant cardiac dysfunction by displacing large portions of atria and ventricles
Case reports: necrotic tumor with DIC (Hong Kong Med J 2005;11:308), 49 year old with left atrial tumor (Braz J Cardiovasc Surg 2005;20(4)), with papillary endothelial hyperplasia and liver involvement (Heart 2004;90:e49)
Treatment: complete excision if possible
Gross images: right atrial tumor shows hemorrhage and dilated vessels; left ventricular tumor; tan bosselated mass
Micro: types are capillary (small vessels) or cavernous (multiple dilated thin walled vessels) or arteriovenous (thick walled, dysplastic malformed arteries and veins); no necrosis, no mitotic figures, no atypia; intramural tumors may contain adipose or fibrous tissue
Micro images:
capillary - small vascular channels #1; #2; mixed capillary-cavernous #1; #2; #3; #4; #5; muscle specific actin outlines vascular channels
cavernous - focus of papillary endothelial hyperplasia; dilated vascular channels; intramural tumor
DD: angiomatosis (vessels of various sizes with variable wall thickness, adipose tissue and skeletal muscle, Int Heart J 2006;47:469), myxoma (hemangiomas may have myxoid background, but lack myxoma cells or ring structures), angiosarcoma (atypia present)
References: Radiographics 2000;20:1073, Am J Cardiovasc Pathol 1990;3:283
Inflammatory pseudotumor / inflammatory myofibroblastic tumor of heart
Previously called plasma cell granuloma
Extremely rare
Usually age 2 months to 17 years
May be intravascular in infants (Pediatr Dev Pathol 2002;5:400)
Case reports: 15 year old boy and 5 month old girl (Archives 1996;120:549), 2 month old boy with multiple tumors (Ann Thorac Surg 2006;82:1531), 72 year old woman (Ann Thorac Surg 2003;75:1971), 55 year old woman with sudden death due to tumor (Forensic Sci Int 1991;49:89)
Treatment: excision, possibly steroids (Pediatr Cardiol 2004;25:406); may recur or continue to grow locally, but no distant metastases (AJSP 1995;19:859)
Gross: up to 8 cm
Micro: spindle cells larger than fibroblasts with obvious nucleoli, inflammatory cells, prominent vasculature, variable myxoid stroma; occasional mitotic figures and necrosis
Micro images: polymorphous inflammatory infiltrate (fig 3); breast tumor-various images; liver tumor-various images; lung tumor shows inflammatory cells and myofibroblasts
Positive stains: smooth muscle actin
Negative stains: desmin, S100, CD34, p53 (Ann Diagn Pathol 2001;5:335)
Also called valvular strands
Common finding in elderly patients
Small filiform / papillary processes that are age-related; may be organized mural thrombi at site of minor endothelial damage
Associated with stroke, particularly among younger patients (Stroke 1997;28:2185)
Aortic/pulmonic valves: most common at nodules of Aranti, along lines of closure and free cuspal edges
Tricuspid/mitral valves: at site of valve closure on atrial surface
Case reports: causing embolic stroke (Nervenarzt 2006;77:1492), causing transient ischemic attack (An Med Interna 2006;23:181)
Gross images: aortic valve
Micro: connective tissue / fibrin covered by endothelium
Micro images: fingerlike projection extending from valve surface without branching
DD: papillary fibroelastoma (larger, more gelatinous, located away from lines of closure and free edges and on endocardial surfaces of atria and ventricles)
References: Am J Cardiol 1986;58:1223
8-12% of primary tumors of heart and pericardium
Usually on epicardium and asymptomatic
May create ball-valve obstructions or produce arrhythmia
Called lipomatous hypertrophy if in atrial septum
Case reports: massive left atrial lipoma occupying pericardial space (Jpn Heart J 2004;45:715), symptomatic tumor of right atrial free wall (Tex Heart Inst J 1998;25:152), interventricular septum (ASAIO J 2006;52:e35), hibernoma in right atrium (Heart Surg Forum 2006;9:E623)
Gross: may be poorly encapsulated but often circumscribed; spherical or elliptical mass of homogeneous yellow fat
Gross images: circumscribed tumor at base #1; #2; well circumscribed yellow mass; 5 cm lobulated mass; left ventricular lipoma
Micro: usually encapsulated, composed of mature fat, may contain trapped myocytes; usually no brown fat cells
Micro images: mature adipose tissue with trapped myocytes (fig 5)
References: Hum Path 2006;37:1245
Lipomatous hamartoma of heart valves
Rare
Usually mitral or tricuspid valve
Case reports: tricuspid valve (Clin Cardiol 1991;14:262), fibrolipoma of tricuspid valve (South Med J 1996;89:1018), aortic valve (Jpn J Thorac Cardiovasc Surg 2005;53:577), with blood cysts (J Am Soc Echocardiogr 1998;11:832)
Treatment: may need to replace valve due to involvement of papillary muscle or adjacent atrial tissue
Micro: mature fat and fibrous tissue; no encapsulation
Lipomatous hypertrophy of cardiac intraatrial septum
Rare (0.6% of cardiac tumors); usually age 60+ years
Associated with increased epicardial fat (heart floats in water), mild to severe obesity
Symptoms include congestive heart failure, atrial fibrillation, supraventricular tachycardia, syncope, sudden unexpected cardiac death (Archives 2006;130:397)
Often diagnosed at autopsy (Cesk Patol 2006;42:182)
“Hypertrophy” is a misnomer because mass is due to increased fat cells, not hypertrophied myocytes
Treatment: weight loss, not surgery (Heart 2004;90:e66)
Gross: unencapsulated mass usually confined to atrium; resembles brown fat; associated with cardiac hypertrophy; septal thickness is 2 to 7 cm (normal is < 1 cm); fossa ovalis is usually spared
Gross images: fatty deposit superior to fossa ovalis; huge fatty tumor of atrial septum sparing fossa ovalis; tumor adjacent to epicardial fat
Micro: multivacuolated fatty infiltration more than 2 cm thick in atrial septum; cells have central nuclei without atypia; some fat cells resemble brown fat and fat cells in malnourished patients; usually atypical and hypertrophied myocytes (AJSP 1996;20:678); variable bands of collagen and chronic inflammatory infiltrates; no mitotic figures, no signet ring structures, no enlarged hyperchromatic and indented nuclei in fat cells
Micro images: mixture of normal fat, vesicular fat and hypertrophied myocytes #1; #2; #3; #4; gross and micro images
EM: abundant mitochondria in vesicular fat cells
DD: myxoma (has stellate or globular cells, myxoid areas, no fat, no hypertrophied myocytes), lipoma (encapsulated, no muscle fibers), liposarcoma (lipoblasts have large clear vacuoles and hyperchromatic indented nuclei)
References: AJCP 1979;72:785, Hum Path 2006;37:1245
Lipomatous infiltration of heart
Also called fatty heart
Heart may float in water at autopsy
Associated with obesity and lipomatous infiltration of atrial septum
Usually incidental, rarely causes sudden death
Case reports: massive infiltration of left ventricle (Jpn Heart J 1986;27:273)
Gross: diffuse lipomatous infiltration of epicardial surfaces with focal infiltration into myocardium; no discrete masses; marked increase in fat in atrioventricular sulci and over ventricles
Micro: mature fat that may infiltrate into myocardium
DD: arrhymogenic right ventricular cardiomyopathy (affects right ventricle only, AJR Am J Roentgenol 2007;188:W423)
References: Archives 1982;106:497
Mesothelial / monocytic incidental cardiac excrescence
Benign
Incidental finding of endocardium or pericardium during cardiac valve replacement
Either reactive or an artifact of surgery (AJSP 1994;18:167), although may exist without prior surgery
Case reports: causing acute cardiopulmonary failure (AJSP 2005;29:564), with clusters of metastatic adenocarcinoma cells (AJSP 1997;21:970)
Micro: haphazard mixture of mesothelial cells, histiocytes, fat globules and fibrin; mesothelial cells may form micropapillary or tubular formations; no/minimal stroma, no mitotic activity
Micro images: fat globules, mesothelial cells and histiocytes without stroma #1; #2; keratin+
Positive stains: CD68 (histiocytes), keratin (mesothelial cells, Ann Diagn Pathol 2000;4:39)
DD: metastatic carcinoma (keratin+ cells with atypia)
References: AJSP 1990;14:993, Mod Path 1994;7:9
Most common primary tumor of heart (~40%), although still rare; distinct from soft tissue myxoma
Sporadic or familial (see Carney syndrome below)
90% occur in atria, 80% on left side
Mean age 50 years
Pedunculated tumors may move through AV value at systole; this “wrecking ball” effect may damage valve leaflets
Symptoms of ball-valve obstruction, emboli, fever/malaise due to IL-6 (mediates acute-phase response, Chest 2003;123:1379)
Associated with HSV infection (Am J Pathol 2003;163:2407)
Benign (only rare metastases), but malignant in a sense because often embolizes (30-40%) and may cause death; embolization may be related to overexpression of matrix metalloproteinases (Am J Pathol 2005;166:1619); rarely embolizes in toto (Jpn Heart J 2004;45:359)
Rarely causes aneurysms (Neurol India 2005;53:216)
Stromal cells may arise from multipotent mesenchyme capable of neural and endothelial differentiation, with glands representing entrapped foregut rests (Am Heart J 2000;140:134)
Carney syndrome/complex: 10% of cases; autosomal dominant with multiple cardiac and extracardiac (skin) myxomas, spotty skin pigmentation, endocrine overactivity, schwannomas, epithelioid blue nevus (Orphanet J Rare Dis 2006 Jun 6;1:21); these patients are younger (mean 24 years), usually men (66% vs. 24% in non-familial cases), multicentric (33%, AJSP 1985;9:53); caused by mutations in protein kinase A regulatory subunit 1 alpha (PRKAR1A, Circ J 2005;69:994, Nat Genet 2000;26:89)
Case reports: Case of the Week #78 (glandular differentiation), infected (MJA 2006;185:332), with thymoma / thymic rests (AJSP 2005;29:1208);
metastases - to brain resembling epithelioid hemangioendothelioma (AJSP 1994;18:107), to choroid plexus and scapula (AJSP 1980;4:391), to small intestine (Archives 2003;127:481), to temporal bone (AJCP 1989;91:221)
Treatment: excision; no/rare recurrence (Yonsei Med J 2006;47:367)
Gross: usually solitary at fossa ovalis, up to 10 cm, sessile or pedunculated, 41% have surface thrombus; soft, polypoid (particularly when examined under water), pale, lobulated; rarely petrified due to repeated hemorrhage (Archives 1989;113:742); rarely grows on both sides of fossa ovalis
Myxoma of heart (continued)
Gross images: gelatinous tumor attached to atrial septum by narrow pedicle, tumor has irregular surface and nearly fills left atrium #1; #2; #3; #4; variegated surface; heterogeneous cut surface; irregular surface of this left atrial mass caused transient ischemic attacks; smooth or villous surfaces; portion of atrial septum and tumor with smooth surface #1; #2; #3; #4; cut surface shows marked calcification; embolism at iliac bifurcation; emboli of iliac artery
Micro: complex structures resembling cords, nests, rings or poorly formed glands, often surrounding blood vessels; composed of stellate or globular myxoma cells with abundant eosinophilic cytoplasm, indistinct cell borders, oval nucleus with open chromatin and indistinct nuclei; abundant mucopolysaccharide (myxoid) ground substance containing chondroitin sulfate and hyaluronic acid (Life Sci 2003;73:849); usually inflammation, hemorrhage; often more cellular and mitotic activity near surface; variable fibrosis (41%), calcification (20%), Gamna-Gandy bodies (17%, identical to those in spleen of sickle cell anemia patients), ossification (8%), extramedullary hematopoiesis (7%, more common in children), mucin-forming glands (3%, Indian Heart J 2003;55:182), atypia (3%), thymic rests (1%); may embolize to peripheral arteries
Micro images: short cords or syncytia embedded in myxoid matrix; multilayered rings of myxoma cells around blood vessels are infiltrated by lymphocytes; scattered spindle cells; nests of cells; ring structure with 2 cell layers #1; #2; #3 with atypia; irregular surface fronds are associated with emboli and younger patient age; cellular areas near surface; various images; blood vessels show mucoid degenerative changes; central area of bone; Gamna Gandy bodies; focal calcification; extramedullary hematopoiesis; thymic rest; interface with atrial septum often shows lymphoid aggregates, smooth muscle bundles and thick walled vessels; possible cardiac myxoma (fibrotic mass with myxoma-type cells); A: CD34+ surface cells; B: CD34+ deep cells; C: factor VIII negative myxoma cells (positive vascular control); D: smooth muscle actin+
tumors with glandular component: glandular structures #1; #2; #3; #4; #5; #6; #7; mucicarmine; Alcian blue (pH 2.5); CK7; MNF-116
emboli - intramyocardial coronary artery; pulmonary artery
Myxoma of heart (continued)
Positive stains: CD31, CD34, calretinin (strong, diffuse, cytoplasmic and nuclear staining, AJCP 2000;114:754), S100 (Am Heart J 2000;140:134), vimentin; glandular components may be keratin+; variable Factor VIII (surface cells may be positive, otherwise negative)
Negative stains: CD68, cytokeratin (except for glandular elements)
EM: features of endothelial, smooth muscle and immature mesechymal cells; cells have numerous cytoplasmic filaments (Cancer 1977;40:2216)
EM images: multiple appearing nuclei with little ultrastructural differentiation; bundles of intermediate filaments and rough endoplasmic reticulum; primitive intercellular junction without desmosomes
DD: mural myxoid thrombi (no nests, cords or rings, calretinin negative, image), left atrial appendage thrombus (Circulation 2006;113:e456), metastatic carcinoma if myxoma has glandular structures (carcinoma has anaplasia, mitotic activity), myxoid sarcoma, papillary fibroelastoma (on valve cusps, avascular papillary fronds)
References: AJCP 1993;100:671, eMedicine, Wikipedia, OMIM 255960, Radiographics 2002;22:673
Necrobiotic xanthogranuloma of heart
Rare
Associated with similar lesions in lung and skin; also leukopenia, paraproteinemia and complement deficiencies; also nodular transformation of liver (Pathology 1985;17:533)
Case reports: myocardial lesions at autopsy (Hum Path 1992;23:195), pericardial, pulmonary and cutaneous involvement (Ann Dermatol Venereol 2003;130:341)
Micro: amorphous necrotic tissue, foamy macrophages / giant cells with vacuoles and inclusions, lymphocytes
Micro images: skin - necrobiotic xanthogranuloma #1; #2; various images
Papillary fibroelastoma of heart
Also called giant Lambl’s excrescence
8-10% of all heart tumors; third most common after myxoma and lipoma
Mean age 60 years
Benign
Usually an incidental finding at autopsy, although may embolize (higher risk if large, mobile, left-sided, Circulation 2001;103:2687), or prolapse into coronary artery
More common on valve surface or endocardium
Associated with prior cardiac surgery or thoracic radiation (Hum Path 2002;33:1165)
Case reports: 59 year old woman with atrial mass (Archives 2001;125:1605), arising in right coronary ostium (Archives 1992;116:135), presenting as left ventricular mass (Tex Heart Inst J 2006;33:63), two lesions of aortic valve (Tex Heart Inst J 2004;31:448)
Treatment: either no intervention, excision or warfarin
Gross: distinctive cluster of yellow-white hairlike projections up to 1 cm in diameter covering large portions of valvular surface (usually aortic and mitral); often with adherent thrombus; often multiple
Gross images: mitral valve #1; #2; multiple small fronds resembling a sea anemone #1; #2; #3; #4; actual sea anemone (for comparison); causing sudden death due to occlusion of right coronary ostium; tricuspid valve; tumor in noncoronary sinus
Micro: narrow, elongated and branching papillary fronds composed of central avascular collagen and variable elastic tissue, surrounded by acid mucopolysaccharide and lined by hyperplastic endothelial cells
Micro images: arising from aortic valve cusp; avascular fronds lined by endothelial cells #1 (Movat pentachrome stain); #2; #3; #4 (colloidal iron); #5; papillary configuration may be obscured by scarring, but trapped cores of elastic tissue are usually present; papillary structures with elastic fibers (fig 3)
DD: Lambl’s excrescences (not branched, not gelatinous, smaller, only at lines of closure), myxoma (no elastic tissue)
References: Am Heart J 2003;146:404, Arq Bras Cardiol 2005;85:205
Also called extra-adrenal pheochromocytoma (if secretes catecholamines) or chemodectoma (at carotid body)
Either functional (secretes catecholamine, associated with hypertension, headache, flushing) or non-functional
Very rare
Sites: left atrium or near aortic root, where intrinsic cardiac ganglia (chromaffin cells) are located
Case reports: pigmented tumor causing sudden death in 40 year old man (Archives 2001;125:680), 34 year old woman with 6 cm atrial tumor (Heart Lung Circ 2007;16:116), 25 year old with bone metastases (Circulation 1998;97:1993)
Treatment: excision or transplantation; 5-10% recur or metastasize after excision
Gross: 5-7 cm, unencapsulated; on epicardium but may infiltrate adjacent cardiac tissue
Micro: unencapsulated, organoid appearance (zellballen/nests of cells) surrounded by sustentacular cells; no necrosis, no/minimal mitotic figures
Micro images: nested cells in organoid pattern #1; #2; #3 with chromogranin; pigmented tumor; paraganglia cells within right atrium (normal)
Positive stains: chromogranin, neuron-specific enolase; sustentacular cells-S100
Negative stains: calcitonin
EM: norepinephrine-type granules, few epinephrine-type granules
References: AJSP 1985;9:827
50-90% of primary heart tumors in children
Usually discovered in patients less than 1 year of age, rarely in fetuses (Ital Heart J 2002;3:48)
May obstruct valvular orifice or cardiac chamber; may present with sudden cardiac death (Pediatr Dev Pathol 2007;10:129)
Not a true neoplasm, but a hamartoma or malformation due to mutation in TSC1 and TSC2 genes
50% of patients have tuberous sclerosis; sporadic cases are occasionally associated with congenital heart disease
Case reports: 2 year old boy with tuberous sclerosis (Archives 2002;126:1559), diffuse rhabdomyomatosis in 13 year old boy (Archives 1977;101:78)
Treatment: many tumors regress spontaneously; excision if left ventricular outflow tract obstruction or refractory arrhythmia
Gross: small, firm, gray-white, well-circumscribed myocardial masses (often multiple) that protrude into ventricles; average size is 3-4 cm, up to 10 cm, particularly in sporadic cases
rhabdomyomatosis - numerous miliary nodules less than 1 mm
Gross images: rhabdomyomatosis in patient with tuberous sclerosis and multiple minute tumors studding epicardium; tuberous sclerosis patient with tumor #1; #2; right ventricular mass #1; #2; left ventricular tumor causing sudden death in 1-2 year old child #1; #2; multiple ventricular nodules
Micro: clear cells and large, rounded, polygonal cells (“spider cells”) with glycogen vacuoles separated by strands of cytoplasm extending between cell membrane and nucleus; no mitotic activity
adult tumors: more cellular with smaller cells, few spider cells and more cellular proliferation (Hum Path 2002;33:1092)
Micro images: spider cell (center) and intracellular myofilaments (oil emersion); spider cells and clear cells #1; #2; #3; drawings from 1938 report; fig A: well circumscribed, tan-yellow masses in left atrium and left ventricle; fig B: large cells with clear cytoplasm (spider cells); fig C: spider cells surrounded by normal myocytes; muscle specific actin highlights spider cells and cross striations (arrowheads)
Positive stains: PAS+ diastase sensitive (for glycogen), myoglobin, actin, desmin, vimentin; variable HMB45
Negative stains: S100
EM: altered myocytes with abundant glycogen, small and sparse mitochondria; cellular junctions resembling intercalated disks are extensive and randomly distributed, not just at poles of cell as in normal myocytes (Hum Path 1977;8:700)
EM images: abundant glycogen, small and sparse mitochondria, fragmented irregular myofilaments with Z bands
DD: lipoma (usually epicardial, no myofibers, no glycogen), granular cell tumor (epicardial, no vacuoles, no myofibers, S100+, desmin-, myoglobin-), glycogen storage disease (no well formed nodules, cells have intercalated disks at poles by EM), histiocytoid myopathy (small tumor nodules, finely granular cells, no large vacuoles, no spider cells; a variant of rhabdomyomatosis)
References: Mod Path 1991;4:70, TheFetus.net
Case reports: incidental finding of schwannoma with focus of metastatic adenocarcinoma from lung (Archives 1984;108:300), 57 year old man with atrial tumor (J Cardiothorac Surg 2007;2:1), 61 year old woman with atrial tumor (Cardiovasc Pathol 2003;12:290)
Gross images: operative image and S100+ staining; right atrial tumor #1; #2
Very rare in heart; more common in lung
Usually benign, but may have malignant histology
Micro: circumscribed; organoid pattern of tumor cells with clear to eosinophilic cytoplasm, abundant glycogen in rich vasculature; no/rare mitotic figures, no necrosis
Micro images: malignant histology; rectal tumor #1; #2; #3 (HMB45+)
Positive stains: HMB45
Negative stains: S100, keratin, neuroendocrine markers, muscle markers
EM: glycogen, abundant mitochondria, premelanosomes
EM images: premelanosomes
DD: paraganglioma, clear cell sarcoma, melanoma, melanocytic clear cell neoplasm of the kidney
References: Mod Path 2001;14:615-free full text
Tumor with perivascular myoid differentiation of heart
Very rare in heart
May recur after surgery, particularly in adults
Case reports: 70 year old woman with right atrial mass (J Clin Pathol 2004;57:1338)
Micro: round, undifferentiated to epithelioid cells surrounding prominent, thin walled, staghorn vessels
Positive stains: alpha smooth muscle actin
Negative stains: CD34
DD: hemangiopericytoma (CD34+, actin-), solitary myofibroma, epithelioid hemangioendothelioma, glomus tumor, vascular leiomyoma
Usually dilated thrombosed vein in right atrium that arises from inferior rim of fossa ovalis
Incidence varies from 0.1% to 2.5% at autopsy
Asymptomatic
Case reports: 3 cm, round, cystic mass attached to lower rim of fossa ovalis in right atrium (Circ J 2006;70:793), 19 year old woman with 8 cm mass compressing right atrium (Ann Thorac Surg 2004;78:e96)
Gross: blue, raised area inferior to fossa ovalis
Gross images: blue discoloration of endocardium (arrowhead) just above coronary sinus (CS) and posterior to rim of fossa ovalis (FO)
Micro: unilocular, blood-filled cyst lined by endothelial cells and filled with organizing thrombus
Micro images: dilated vein with focal attenuation of wall; unilocular cyst lined by flattened endothelium (fig 2)
DD: blood cyst (congenital, along lines of closure of heart valves)
Cardiac tumors-malignant
Common primary malignancy of heart, although still rare
Usually atrium; right sided more common than left
Often men, mean age 40 years
Metastases present at diagnosis in 89%, usually to liver and lung (may present as diffuse hemorrhage, Archives 2001;125:1562)
Case reports: 36 year old man with HIV (Archives 2005;129:943), 54 year old man with persistent pericardial effusion (Archives 2005;129:117), presenting with cutaneous metastases (Archives 1998;122:273)
Treatment: usually no effective treatment; poor prognosis with death commonly in a few months
Gross: large, infiltrating, pink to dark brown, lobulated mass; often invades vena cava and tricuspid valve
Gross images: right atrial papillary tumor; hemorrhagic and necrotic tumor #1; #2; epicardial tumor
Micro: usually poorly differentiated; anastomosing vascular channels forming dilated sinusoids lined by atypical cells; patterns include spindle cell, angiomatous, undifferentiated/solid; prominent mitotic activity; hemorrhage and necrosis common
Cytology: single or clusters of pleomorphic spindle cells in a background of hemorrhage; occasional microacinar or pseudoacinar structures lined by abnormal spindle or polygonal cells (Diagn Cytopathol 2007;35:164)
Micro images: vessels lined by atypical endothelial cells; anastomosing vascular channels #1; #2; right atrial mass in 20 year old woman; atypical papillary fronds lined by hyperchromatic endothelial cells; cellular area with plump, atypical endothelial cells and mitotic activity, but no obvious vascular channels; spindle cell tumor with poorly formed vascular structures and extravasated red blood cells; slitlike vascular structures lined by atypical cells; hemorrhage, necrosis and papillary structures; tumor invades right atrial myocardium; fig 1: mass involves full thickness of right atrial wall; fig 2: neovascular channels contain red blood cells #1; #2; marked nuclear pleomorphism and mitotic figures; fig 1: transesophageal echocardiography shows large echo-dense mass involving interatrial septum and protruding into right atrium; fig 2: anastomosing vascular channels composed of pleomorphic and hyperchromatic spindle cells; CD31+; CD31+; factor VIII related antigen+ within cytoplasm #1; #2; metastasis to lung
Angiosarcoma of heart (continued)
Positive stains: CD31 (most specific); also CD34, reticulin (highlights vascular channels, shows tumor cells on luminal side of vessels), thrombomodulin, Factor VIII (20%)
Negative stains: CD45, cytokeratin, S100
EM: thin and delicate cytoplasmic processes, Weibel-Palade bodies, distorted extracellular fibrous matrix (Eur Rev Med Pharmacol Sci 2005;9:231)
EM images: abundant cytoplasm with membrane bound vesicles and rough endoplasmic reticulum; focal endothelial differentiation
DD: metastatic angiosarcoma (more common than primary tumor, cardiac metastases associated with widely disseminated disease), Kaposi’s sarcoma (usually small and epicardial with minimal myocardial infiltration), hemangioendothelioma (flattened endothelial cells, distinct vascular channels)
References: Radiographics 2003;23:S141
Less than 20 primary cases reported through 2006 (Jpn J Thorac Cardiovasc Surg 2006;54:228)
Chondroid areas in a cardiac tumor are virtually diagnostic of malignancy
Case reports: tumor producing parathyroid hormone-related protein (Circ J 2004;68:715)
Micro: atypical chondroid areas
Micro images: atypical cells within chondroid matrix #1; #2-from metastases to heart (fig 3); various images (fig 3)
DD: metastatic chondrosarcoma (Ann Thorac Surg 1988;45:291)
See also Bone chapter
Rare as either primary tumor or metastasis
Case reports: 63 year old man (Hum Path 1996;27:1365), metastases to heart (Can J Cardiol 2005;21:525)
Micro images: metastases to heart; small blue cell tumor #1 (site unknown); #2
Positive stains: CD99, NSE, synaptophysin, vimentin
Negative stains: keratin, chromogranin, desmin, actin, myoglobin, CD45/LCA
Rare; 5% of cardiac sarcomas
Often left atrium; may present as congestive heart failure
Treatment: aggressive approach may be necessary (Chest 2003;123:1766); usually poor prognosis
Gross: soft, polypoid, gelatinous tumors that fill atrium or infiltrate ventricles or pericardium; often necrotic
Micro: herringbone pattern of compact fibroblastic type cells with tapered nuclei in collagenous or myxoid matrix; no intracytoplasmic glycogen, no perinuclear vacuoles, no pleomorphism, no histiocytoid cells
Micro images: herringbone pattern of spindle cells; spindle cells with tapered nuclei in a collagenous background; monomorphous cell population in collagenized background; cellular fibrosarcoma metastatic to brain (fig G)
Positive stains: vimentin, variable actin
Negative stains: desmin, cytokeratin, S100
EM: fibroblasts with granular or amorphic cytoplasm, dilated rough endoplasmic reticulum, sparse cytoplasmic organelles, infrequent nucleoli; extracellular mature and immature collagen
DD: malignant fibrous histiocytoma (histiocytoid cells and pleomorphism are prominent), malignant solitary fibrous tumor of pericardium (similar histology but infiltrates pericardial space with little myocardial invasion), synovial sarcoma (monophasic tumors have similar histology, but tumor usually has cytokeratin+ epithelioid foci), osteosarcoma (has large areas of fibrosarcoma but also malignant osteoid), mesothelioma (usually is biphasic, spindled areas are cytokeratin+), leiomyosarcoma (fascicles at sharp right angles but not herringbone, intracytoplasmic glycogen, perinuclear vacuoles, prominent myofilaments, basal lamina with EM, multinucleated giant cells occasionally), fibroma in infants
Germ cell tumor / teratoma of heart
Rare
Most cardiac germ cell tumors are teratomas
Most common site is interventricular septum, extending into right ventricle
Benign if pure teratoma, but malignant if other germ cell elements are present (choriocarcinoma, embryonal carcinoma, yolk sac tumor) or if squamous cell carcinoma arises from teratoma
Case reports: 2 year old girl with fatal teratoma of interventricular septum (Archives 1993;117:739), “cardiac development” in a sacrococcygeal teratoma (Eur J Pediatr Surg 2002;12:278)
Treatment: excision
Gross: teratomas are multicystic with solid areas, up to 15 cm
Gross images: newborn who died at birth has bulging mass in right ventricular outflow tract (arrows), PV - pulmonary valve; multilocular cystic mass
Micro: teratoma - squamous or mucous lined cysts, smooth muscle, cartilage, neuroglial tissue; intestinal, pancreatic, ependymal tissue and bone; often myxoid stroma
Micro images: teratoma - cysts on endocardial surface (trichrome); neural and glandular structures and stroma; various images #1; #2
DD: bronchogenic cyst (no hair, teeth or neurogenic elements), atrioventricular nodal tumor (Pediatr Pathol 1994;14:913)
See also Leukemia or Lymph nodes-not lymphoma chapters
Historically, leukemic infiltrates were found at autopsy in heart or pericardium in 37% of acute leukemia patients, but usually asymptomatic
Mass lesion may precede clinical symptoms (Am J Hematol 1987;25:325)
Case reports: 12 year old girl (Pediatr Hematol Oncol 1987;4:237), 34 year old man with extensive endomyocardial infiltrate (Echocardiography 2003;20:539), 72 year old man with right ventricular failure (Archives 1990;114:983)
See also Soft Tissue chapter
Rare in heart
Vascular tumor of intermediate malignancy
10% of extracardiac tumors metastasize and 1/3 recur
Case reports: 2 month old baby with extensive tumor infiltration but no mass (Ann Thorac Surg 2005;79:1402), 36 year old woman with shortness of breath (Chin Med J (Engl) 2006;119:966), 69 year old woman with rheumatic heart disease and valvular tumor (Pathol Int 2005;55:644), with distant metastases (J Cardiovasc Surg (Torino) 1993;34:529)
Micro: polygonal cells with abundant cytoplasm and intracytoplasmic vacuoles; epithelioid tumors have short strands or solid nests of round/oval endothelial cells with small intracellular lumina; infiltrate muscular walls of vessels
Micro images: left atrial mass in 71 year old woman shows tumor cells with abundant cytoplasm and large, intracytoplasmic vacuoles; CD34+; H&E, CD34 (fig D), Ki-67 (fig E)
Positive stains: factor VIII related antigen, CD34
DD: adenocarcinoma
Rare in heart
May be benign or malignant
Case reports: 41 year old man with malignant tumor (J Cardiovasc Surg (Torino) 2006;47:71), intracranial tumor that metastasized to heart (Radiat Med 1996;14:91)
Micro: highly vascular tumor of tightly packed cells with minimal cytoplasm and round/oval nuclei which surround endothelial lined vascular channels with staghorn shape
Micro images: bone tumors - spindle cells arranged around large, irregularly shaped vessels; reticulin surrounds each tumor cell (reticulin stain)
Positive stains: vimentin, CD34, factor XIIIa
Negative stains: factor VIII, keratin
EM: pericytes with elongated cytoplasmic processes, pinocytotic vesicles, poorly developed desmosomes, few organelles but well developed basal lamina
DD: synovial sarcoma (biphasic), benign fibrous histiocytoma
See also Soft tissue tumor chapter
Occurs in patients with skin and visceral lesions in classic and epidemic forms of disease
Heart involvement in 5% of HIV+ patients historically
Usually epicardial and pericardial involvement with minimal myocardial infiltration
Case reports: myocardial involvement in heart transplant patient (Catheter Cardiovasc Interv 2000;49:208)
Gross: focal, small, firm, red-brown nodules
Micro: slit like vascular spaces with atypical spindle cells, endothelial cells and red blood cell extravasation
Micro images: atypical spindle cells, extravasated red blood cells and slit-like vascular spaces
8% of cardiac sarcomas
Poor prognosis unless low grade (Histopathology 1999;34:295)
Mean age in 30’s
Likely arises from smooth muscle of pulmonary veins and arteries and spreads into heart (Heart Lung Circ 2005;14:121)
Associated with EBV in cardiac transplant or AIDS patients (J Heart Lung Transplant 2007;26:944)
Case reports: Case of the Week #114, myxoid leiomyosarcoma (Archives 1996;120:583), uterine leiomyosarcoma metastatic to heart (Clin Transl Oncol 2006;8:375)
Treatment: excision or transplantation (J Heart Lung Transplant 1998;17:1133)
Clinical images: tumor over ventricle
Gross: 75% in left atrium, may appear to arise from pulmonary vein, sessile lesions may be grossly myxoid (Can J Cardiol 2001;17:331); 30% are multiple
Gross images: myxoid tumor; pleomorphic leiomyosarcoma
Leiomyosarcoma of heart (continued)
Micro: compact bundles or fascicles oriented at right angles to each other; spindled or epithelioid smooth muscle cells with cytoplasmic glycogen, blunted nuclei with moderate/marked pleomorphism, necrosis, mitotic activity; occasionally giant cells, perinuclear vacuoles; may be low grade with few mitotic figures
Micro images: low power shows border with normal cardiac muscle; fascicles intersect at sharp angles and are composed of cells with blunt ended nuclei #1; #2; #3-also slight vacuolar appearance; epithelioid appearance with round/oval nuclei; epithelioid and spindled areas; high power shows hyperchromatic ovoid nuclei with blunt ends; various images; spindle cells with frequent mitotic figures (fig 2); PAS shows diffuse punctate droplets of glycogen; smooth muscle actin; desmin #1; #2
Positive stains: PAS for intracytoplasmic glycogen, trichrome shows longitudinal fibers; actin, desmin (usually)
Negative stains: cytokeratin (may be positive in epithelioid areas), S100
EM: notched or infolded nuclei, thin actin filaments with focal densities, micropinocytotic vesicles, thin but distinct external lamina, dispersed glycogen, rare mitochondria or endoplasmic reticulum
EM images: various images
DD: fibrosarcoma (tapered nuclei, no intracytoplasmic glycogen, no pleomorphism, negative for actin and desmin), metastatic leiomyosarcoma, particularly from the uterus (Clin Transl Oncol 2006;8:375), intravenous extension of tumor (Ann Thorac Surg 2007;84:644)
Very rare
Mean age 53 years
Usually right atrium
Metastasizes to lung, liver, bones, CNS
Mean survival is 8 months
Case reports: encasement of heart by metastatic myxoid liposarcoma (Cardiovasc Pathol 2002;11:322)
Gross: bulky tumors up to 10 cm, often cystic, soft, bosselated; may have multiple tumor implants on surface of great vessels or diffuse pericardial growth
Gross images: tumor nodules over posterior epicardium of left and right ventricles; large right atrial tumor overlying tricuspid valve; tumor obstructing almost entire left ventricle
Micro: pleomorphic liposarcoma resembles MFH or fibrosarcoma, but with lipoblasts containing multiple vacuoles that indent the cell nuclei; myxoid liposarcoma has prominent plexiform vascular pattern and signet ring type lipoblasts
Micro images: pleomorphic liposarcoma with vacuolated cells in 64 year old man with atrial mass; numerous lipoblasts with large cytoplasmic vacuoles that indent the nucleus; numerous lipoblasts with vacuolated cytoplasm; signet ring lipoblast in myxoid background; metastatic myxoid liposarcoma to heart
Positive stains: S100, Oil Red O (myxoid liposarcoma)
Negative stains: Alcian blue
EM: numerous nonmembrane bound lipid droplets fill cytoplasm and are associated with mitochondria; large indented nucleus is at cell periphery
DD: lipomatous hypertrophy of interatrial septum (cells resemble brown fat, but no lipoblasts or myxoid background; also hypertrophied myocytes), myxoid MFH (no plexiform vascular pattern, no signet ring cell lipoblasts, lipid is Alcian blue positive), undifferentiated sarcoma (no lipoblasts)
Rare; associated with HIV or other immunocompromise
Primary if all of tumor is within pericardium; otherwise secondary
Primary tumors are rare
Most common subtype is diffuse large B cell lymphoma (Arch Mal Coeur Vaiss 2005;98:875, Leuk Lymphoma 2004;45:781)
Poor prognosis, since usually advanced disease
Not associated with EBV (Archives 1996;120:555)
Case reports: adult T cell leukemia/lymphoma-massive cardiac involvement (Archives 1991;115:1052), anaplastic large cell lymphoma-presenting with embolic stroke (Blood 2003;101:4708), Burkitt’s lymphoma mimicking acute pulmonary embolism (J Coll Physicians Surg Pak 2006;16:536), diffuse large B cell lymphoma-with hemophagocytic syndrome (Haematologica 2002;87:ECR27), B cell tumor damaging conduction system and causing atrioventricular block (Acta Cardiol 2007;62:55)
Gross: firm nodules within any chamber and often in pericardium
Gross images: diffuse large B cell lymphoma in 24 year old HIV+ drug addict; atrial tumor obstructs superior vena cava; non-Hodgkin’s lymphoma; type unspecified #1; #2; #3
Micro images: anaplastic large cell lymphoma; Burkitt’s lymphoma; diffuse large B cell lymphoma #1; #2; #3; #4; #5; #6; follicular center cell lymphoma #1; #2; #3; infiltration of bundle of His and degeneration of its myofibrils; infiltration of interventricular septum (left) and endocardium (right); infiltration of proximal left bundle branch
Cytology images: diffuse large B cell lymphoma
References: Angiology 2003;54:599
Malignant fibrous histiocytoma of heart
See also undifferentiated sarcoma (some authors consider them the same entity)
#2 most common cardiac sarcoma after angiosarcoma, but still rare
Mean age 44 years, rare in children
90% occur in left atrium, often on posterior wall
Poor prognosis; metastasizes to lung, bones, lymph nodes, serosal surfaces, kidney, thyroid, skin
Case reports: tumor within thrombi (Hum Path 1985;16:1279), left atrial tumor #1 (Archives 1992;116:872), #2 (Gen Thorac Cardiovasc Surg 2007;55:29), #3 (Taiwan J Obstet Gynecol 2006;45:86), metastases to left ventricle (Tumori 2006;92:76), recurrence after heart transplant (J Heart Lung Transplant 2004;23:1447), 16 year old boy (Surg Today 2002;32:270), IL-6 producing tumor (Jpn J Clin Oncol 1999;29:382)
Treatment: excision, possibly chemotherapy or radiation therapy
Gross: lobulated polypoid mass, often multiple; sessile or pedunculated; soft or creamy texture; up to 10 cm
Gross images: tumor of right atrium, tricuspid valve and right ventricle #1; #2-tumor is tan-white and gelatinous; fig A: lobulated tumor in right ventricular outflow tract
Micro: usually pleomorphic-storiform or myxoid subtypes; atypical fibroblasts, pleomorphic histiocytoid cells and giant cells with esosinophilic cytoplasm and fibromyxoid stroma
Giant cell MFH: numerous osteoclast-like giant cells; also called osteoclastoma
Micro images: storiform pattern of fibrohistiocytic cells; spindled fibroblasts and mitotic figures; fibrohistiocytic tumor with giant cells (arrow) and spindle cells (circle); pleomorphic tumor cells with atypical mitotic figures; prominent vessels and myxoid stroma; pleomorphic tumor cells
Positive stains: vimentin, alpha-1-antitrypsin, variable CD68
Myxoid MFH of heart
Definition: bland spindle cell sarcoma with diffuse myxoid background
Previously called myxosarcoma or fibromyxosarcoma
Benign myxomas do NOT transform to myxoid MFH
Usually left atrium
Poor prognosis
Case reports: 21 year old man with widespread systemic metastases (J Korean Med Sci 2001;16:111)
Gross: gelatinous, multilobated, usually sessile endocardial tumor; may be multiple or infiltrate myocardium
Micro: loose storiform pattern, aggregates or single cells that are bland, spindled and resemble myxoma cells; diffuse background of amphophilic proteoglycan; prominent arborizing vessels; foci of atypical hyperchromatic cells with mitotic figures; may infiltrate myocardium
Micro images: hyperchromatic spindle cells in myxoid background, but no ring or cord structures #1; #2; #3; #4; focal infiltration of atrial muscle; cellular area #1; #2; atypical spindle cells in hyalinized background
DD: myxoma (cord and ring structures infiltrated by mononuclear inflammatory cells, less cellular and pleomorphic than MFH; no extensive branching vasculature, no myocardial infiltration; must sample extensively to rule out myxoid MFH)
Malignant mesenchymoma of heart
Definition: sarcomatous tumor with two or more distinct types of cellular differentiation other than fibrosarcoma
AFIP Third Fascicle (soft tissue) and WHO (soft tissue) dislike this terminology, and recommend (a) describing as mixed mesenchymal neoplasm and specifying the components or (b) classifying based on predominant mode of differentiation and mentioning the other component(s)
Rare
Mean age 42 years, 2/3 female
Usually left atrium or mitral valve
Mean survival is 20 months
Case reports: 41 year old woman with left atrial tumor (Eur J Cardiothorac Surg 2002;21:124), 46 year old woman with left atrial tumor (Acta Pathol Jpn 1982;32:851), tumor arising in atrial septum (Acta Pathol Jpn 1975;25:241)
Micro: common components are osteosarcoma, chondrosarcoma, rhabdomyosarcoma, angiosarcoma and liposarcoma
Malignant peripheral nerve sheath tumor of heart
Definition: tapered spindle cells of neurogenic origin by morphology, ultrastructure or immunohistochemistry
Also called malignant schwannoma
Very rare
Case reports: intrapericardial tumor (Eur J Cardiothorac Surg 1997;12:144)
Gross images: metastatic right ventricular tumor
Micro images: spindle cell tumor with sweeping, plexiform growth pattern and a neural appearance; large epicardial nodule, focally S100+, with spindle cells showing irregular nuclear contours
Metastases / tumor extension to heart
30 times more common than primary malignancies (Archives 1993;117:1027)
Distant primaries are often melanoma, breast, lung or renal cell carcinoma, choriocarcinoma, childhood rhabdomyosarcoma
Case reports of metastases: carcinoid tumor of terminal ileum metastatic to conducting system (Archives 2002;126:1538), carcinoid-bronchial (J Clin Pathol 2004;57:778), cervical carcinoma (Jpn Circ J 2001;65:761), chordoma (Jpn Circ J 2000;64:627), gallbladder carcinoma (World J Gastroenterol 2005;11:2048), hepatocellular carcinoma (Chest 1994;105:945), melanoma (Radiographics 2005;25:249), Merkel cell carcinoma (J Clin Oncol 2004;22:1153), myelodysplastic syndrome (BMC Blood Disord 2006;6:4), myeloma (Archives 2000;124:910), osteosarcoma #1 (Br J Radiol 1998;71:336), #2 (Archives 2005;129:241), #3 (Can J Cardiol 2005;21:63), synovial sarcoma (Jpn Heart J 2001;42:387), testicular mixed germ cell tumor (Hum Path 2003;34:1074), thymoma (Intern Med 1993;32:257), thyroid carcinoma-anaplastic (Endocr Relat Cancer 2001;8:71), thyroid papillary carcinoma (Jpn Circ J 2000;64:890)
Extension to heart through venous system or by continuous spread: adrenocortical carcinoma-Cardiovasc Ultrasound 2003 May 16;1:5, J Korean Med Sci 2006;21:572, mesothelioma-Intern Med 1998;37:614, renal cell carcinoma-Anesth Analg 2000;91:1137, synovial sarcoma-renal-Int J Urol 2003;10:657, thyroid carcinoma-anaplastic-Acta Med Okayama 2006;60:135, Wilm’s tumor-Ann Surg 2001;234:116
Gross images: breast carcinoma (atrial epicardium); carcinoid tumor of right atrium; colon carcinoma; gallbladder carcinoma; leiomyosarcoma-right atrium; leukemic biventricular infiltrates; lung carcinoma; lymphoma involving right atrium and atrial septum #1; #2; melanoma #1; #2; #3 (left ventricular outflow tract); #4; #5; #6; #7; #8; mesothelioma extending from pleura to epicardium; myeloma encircling coronary artery; renal cell carcinoma #1; #2 extending to heart; thymoma-malignant extending into right atrium and ventricle; epicardial lesions (unspecified)
Micro images: acute lymphoblastic lymphoma; carcinoid tumor; cervical carcinoma (fig 2); chordoma (fig 2); gastric adenocarcinoma; lung carcinoma #1; #2; melanoma #1; #2; Merkel cell carcinoma-synaptophysin; myeloma encircling coronary artery; myeloma infiltrating coronary sinus; osteosarcoma metastatic from humerus; osteosarcoma from pelvis extending into right atrium; renal cell carcinoma; rhabdomyosarcoma (embryonal); synovial sarcoma-monophasic (fig 3); thyroid carcinoma-anaplastic, extending to heart (fig 5)
myelodysplastic syndrome - epicardial involvement; infiltration by hemopoietic precursors #1; #2-myeloperoxidase positive precursors
Virtual slides: metastatic breast carcinoma
References: J Clin Pathol 2007;60:27, Ann Oncol 2004;15:375, G Ital Cardiol 1997;27:1252
Mean age 38 years
3-9% of cardiac sarcomas
Clinically resembles myxoma
Aggressive, usually causes death or metastases (AJSP 1991;15:289); metastasizes to lymph nodes, thoracotomy incision, lung, thyroid, skin
Treatment: excision, possibly heart transplantation (Bol Asoc Med P R 1999;91:98)
Case reports: 31 year old with left atrial tumor, osteosarcoma #1 (Br J Radiol 1998;71:336), #2 (Archives 2005;129:241), #3 (Can J Cardiol 2005;21:63),
Gross: usually attached to wall of left atrium as a 4-10 cm sessile mass; may extend into pulmonary vein; gritty and calcified areas
Micro: malignant bone forming cells within a spindled or pleomorphic sarcoma; may also have chondroid differentiation or myxoid areas; bone forming areas may be minor with most of tumor resembling MFH or fibrosarcoma
Micro images: atypical cells within osteoid matrix; spindled area in left atrial tumor of 16 year old boy; lung metastasis resembles fibrosarcoma; right ventricular outflow tract tumor; left atrial tumor (figure 1)
Positive stains: vimentin, actin (focal), S100 (chondrosarcomatous areas)
Negative stains: cytokeratin, desmin
DD: myxoma (no osteoid or chondroid malignant cells, has rings or cords of cells, no atypia)
Post-transplant lymphoproliferative disorder of heart
See also Lymphoma-non B cell chapter
Rarely involves the heart allograft
Case reports: involvement of mitral valve (Ann Thorac Surg 1997;64:1822)
Micro images: widespread lymphoid aggregates in endocardium and epicardium
Definition: highly malignant undifferentiated tumor of infants and children
See also Kidney tumor chapter
Originally described in kidneys; very rare in heart (one case report)
Case reports: 6 month old infant (Cancer 1985;55:2850)
Negative stains: desmin, actin
EM: masses of intermediate filaments
DD: rhabdomyosarcoma (desmin+)
Definition: sarcoma with striated muscle differentiation
Rare, 4-7% of cardiac sarcomas, but most common cardiac malignancy in infants and children
Occurs throughout heart, not just in left atrium as with other sarcomas
Usually children/young adults
Metastases to lung, regional nodes, CNS, GI tract, kidney, other
Case reports: 28 year old with huge biatrial tumor (Cardiovasc Pathol 2006;15:354), associated with hypereosinophilia (Am J Hematol 2003;74:64)
Treatment: resection with atrial reconstruction; possibly chemotherapy
Gross: bulky, invasive, central necrosis; often 10 cm or more; almost always myocardial involvement; may involve mitral valve or atrial wall
Gross images: fleshy tumor with cystic degeneration
Micro images: tumor in one year old child that studded the epicardial surfaces and infiltrated both atria, rhabdomyoblasts were scarce; rhabdomyoblasts have abundant eosinophilic cytoplasm; metastatic tumor to brain; desmin+
Cytology: tumor cells have cross striations
Positive stains: PAS+ diastase sensitive (glycogen), desmin
EM: thick and thin filaments; well formed Z bands; frequent glycogen granules in clumps and mitochondria; nuclei are lobulated with variable condensed chromatin; variable A and I bands
EM images: Z bands indicate myofibrils within tumor cells #1; #2
DD: undifferentiated sarcoma (desmin negative), leiomyosarcoma (spindle cells with dispersed glycogen, although also desmin+)
Alveolar rhabdomyosarcoma of heart
Cardiac cases usually represent metastases
Case reports: metastatic tumor (Circulation 1976;54:837)
Micro: collagenous stroma, few rhabdomyoblasts
Embryonal rhabdomyosarcoma of heart
Usually infants, children and young adults
Case reports: left atrial tumor (Tex Heart Inst J 2000;27:206)
Gross: grape-like structures (sarcoma botyroides variant)
Gross images: left atrial tumor with hemorrhage and necrosis
Micro: cambium layer may be present; small cell tumor with rhabdomyoblasts; variable tadpole-shaped rhabdomyoblasts; some cells have cross striations on high power
Micro images: spindle cells with abundant cytoplasm (left atrial mass); cross striations in some tumor cells #1; #2; rhabdomyoblasts are scattered cells with abundant cytoplasm in an otherwise undifferentiated embryonal sarcoma; tadpole shaped rhabdomyoblasts and large cells with abundant eosinophilic cytoplasm and pleomorphic nuclei; desmin+
EM images: band of filaments
See also individually described sarcomas
Sarcoma is most common primary tumor of heart after myxoma, but still is rare (0.2% of autopsies or less)
Often not diagnosed until autopsy due to rarity and nonspecific signs/symptoms
Primary if neoplasm is confined to heart or pericardium or bulk of tumor is within pericardial cavity
Most sarcomas as surgical specimens are primary, but must rule out metastatic tumor of soft tissue, bone or retroperitoneum, which are more common
Usually occurs in left atrium, except for rhabdomyosarcoma
Poor prognosis overall, with survival of 12-24 months due to advanced stage at presentation (Eur J Cardiothorac Surg 2006;29:925, Ann Cardiol Angeiol (Paris) 2003;52:370)
Poor prognostic factors: necrosis (in groups of cells with an inflammatory infiltrate), frequent mitotic figures (5 per 400x field with an average of 10 in most active area)
Treatment: radical excision or autotransplantation (surgery ex situ) may cause longer survival (Tex Heart Inst J 2006;33:495, Thorac Cardiovasc Surg 2004;52:77), transplantation may not prolong survival (Rev Esp Cardiol 2003;56:408)
Gross: bulky, infiltrating, nodular, firm white masses with variable hemorrhage and calcification
References: eMedicine
Definition: usually biphasic tumor with spindled and epithelioid cells and t(X;18)
Very rare in heart; usually right sided
Young and middle aged adults; 75%+ men (Pathologica 2004;96:29, J Am Soc Endochardiogr 2007;20:197.e1)
Symptoms: dyspnea, fatigue, chest pain, congestive heart failure
Treatment and prognosis: excision; usually poor prognosis due to inability to completely excise; often chemotherapy and radiation therapy
Case reports: 14 year old boy with tricuspid valve tumor (Heart Lung Circ 2006;15:278), 36 year old man with biatrial tumor (J Am Soc Echocardiogr 2007;20:197.e1), 37 year old woman with pericardial mass (Case of Week #150), 42 year old man (Mod Path 2004;17:1434), 66 year old man with mitral valve tumor (Cardiovasc Pathol 2005;14:331), atrial tumor presenting as transient ischemia attacks due to patent foramen ovale (Ann Thorac Surg 2000;69:1949)
Gross: bulky tumor infiltrates myocardium and pericardial surfaces
Gross images: mediastinum, not heart - mass adherent to lung; multicystic mass abuts pleura; cystic mass along pleural surface; well circumscribed suprahilar mass with fibrous capsule; solid tan pleural mass
Micro: biphasic spindle cell and epithelioid tumor or monophasic with spindle cells; spindle cell component resembles fibrosarcoma and has cellular and edematous areas; spindle cells are small, compact, often with lymphocytic infiltration; epithelioid areas may form glands or nests; often has hemangiopericytoma-like vascular pattern
Cytology: high grade tumor with intimate admixture of spindle and epithelial cells; need ancillary studies to confirm (Acta Cytol 2006;50:683)
Gross images: Case of Week #150 - #1
Micro images: various images; spindle cell tumor with cellular and hypocellular foci; nests of epithelioid cells; cytokeratin+ epithelioid cells
Case of Week #150: 10X; 20x; 20x; 40x; 40x; 60x; BCL2; CD99; EMA
mediastinum, not heart - ectatic vascular spaces; biphasic tumor; tumor cells with adjacent areas of myxoid change; fascicles of tumor cells #1; #2
Positive stains: bcl2, CD99, keratin (epithelioid component), vimentin, PAS+ diastase resistant mucin
Molecular: t(X;18)(p11.2; q11.2) in 90% leading to SSX1-SYT, SSX2-SYT or SSX4-SYT fusion genes Clin Lung Cancer 2008;9:257, Mod Pathol 2002;15:679).
Molecular images: COBRA-FISH karyogram with t(X;18) as part of complex karyotype; RT-PCR fusion transcript
Differential diagnosis (none have t(X;18) or fusion gene:
• Mesothelioma - larger spindle cells with more pleomorphism, usually no infiltration of myocardium
• Malignant peripheral nerve sheath tumor - 50% associated with neurofibromatosis, also associated with major nerve or continuous with neurofibroma; often palisading with monomorphic serpentine cells, geographic necrosis with tumor palisading at the edges, frequent mitotic figures, often bizarre tumor cells, usually CD99+, variable S100 (62%), CD57, p53, CD57
• Fibrosarcoma - often left atrium, herringbone pattern of compact fibroblastic type cells with tapered nuclei in collagenous or myxoid matrix; no intracytoplasmic glycogen, no perinuclear vacuoles, no pleomorphism, no histiocytoid cells
• Myxoma - tumor is dominated by myxoid matrix; also complex structures resembling cords, nests, rings or poorly formed glands, often surrounding blood vessels; composed of stellate or globular myxoma cells with abundant eosinophilic cytoplasm, indistinct cell borders, oval nucleus with open chromatin and indistinct nuclei
References: AJSP 2005;29:569
Undifferentiated sarcoma of heart
See also malignant fibrous histiocytoma (some authors consider them the same entity)
Rare, but common subtype of sarcoma in heart (Histopathology 1999;34:295)
Case reports: 3 year old boy with mitral valve tumor (J Cardiovasc Surg (Torino) 2003;44:621), 13 year old girl with widespread disease (Clin Med Res 2003;1:233), 33 year old woman with clinical atrial myxoma (Yonsei Med J 2003;44:530), 37 year old woman with left atrial mass (Yonsei Med J 2007;48:131)
Gross images: one year old girl with congestive heart failure; involving left atrial appendage and mitral valve; 70 year old man with pedunculated mass attached to infundibulum (base of pulmonary artery); 28 year old woman with left atrial mass
Micro images: undifferentiated pleomorphic and giant cells; epithelioid features; small round cells in myxoid background; small round cell tumor of right atrium
EM images: bipolar cells with tapering cell processes; abundant rough endoplasmic reticulum and well-formed intercellular junctions
Pericardial tumors
Miscellaneous
Features to report for cardiac tumors
* Specimen type
* Tumor site
* Tumor size (greatest dimension)
* Histologic tumor
* Histologic grade
* Extent of invasion, as appropriate
* Margins, as appropriate
Recommended but not required
Additional tumor dimensions
Additional pathologic findings
* mandatory to report for accreditation purposes by American College of Surgeons Committee on Cancer
End of Heart-tumor chapter