Paper # 008 Versión en Español Versión en Español

Purkinje cell hamartoma (Histiocytoid cardiomyopathy). Study of a case in an 18 months infant.

Marcial Garcia-Rojo, Carlos Gamallo, Felipe Moreno

[Title] [Introduction] [Materials & Methods] [Results] [Pictures] [Discussion] [Bibliography]



[Definition] [Clinical] [Gross] [Techniques] [Other findings] [Interpretation]

LITERATURE REVIEW. Anatomic Pathology


Light microscopy



Diameter: about 50 µ(11). 20 to 40 f in greatest dimension(20,3,12). The polygonal cells were up to twice the size of adjacent myocardial cells(9).

These cells appeared particularly large because of the small diameters(5-8 µ) of the uninvolved heart muscle in these patients(3).

The cells had abundant polygonal(3,12,8), ovoid(4,12,8), granular(4,21,9) cytoplasm, pale (21), lightly eosinophilic(3) and resembled storage histyocytes (20,14,26,27,13,21,15), foamy(3,4,16,30) cells or lipid-filled histiocytes(3), epithelioid histiocytes (14), oxyphil cells of parotid oncocytoma(14) and granular cells of "myoblastoma"(14).

Nodular aggregates of Purkinje cells(23) that have lost their normal elongation and linear histological organization and have unusual thick cell membranes(23). At no place in the heart were there normally arranged Purkinje fibers(23).

Individual cells had distinct cytoplasmic borders(9).

Numerous cells distended with vacuoles(11,25) and granular material(11) or coarse eosinophilic granules in the cytoplasm(8,9).

Rounded or oval-shaped myocardial cell with smooth(3) or well defined(12,8) borders and partial or complete loss of contractile elements(2,3,8), as showed by the phosphotungstic acid-hematoxylin stain(5,12), and a finely granular or vacuolated sarcoplasm(2,20,14,3,12), with vacuoles 1-3 f in diameter(3).

Nuclei: Centrally placed(12); one or two(3).Small(20), hyperchromatic(20,8,9), large(8,9); oval to elongate(14),vesicular(12), occasionally exhibited marked angulation and folding(14,3,21,8), and often contained a single prominent(14,8,9), single(12) nucleolus. In the left atrial myocardium (20) or elsewhere(14) large hyperchromatic nuclei with bizarre intranuclear inclusions suggestive of viral origin were seen(20,14). These were found both in the "histiocytoid" cells and also in the adjoining myocardial fibers showing early vacuolar sarcoplasmic degeneration(14). Occasional cells were multinucleate(8). No mitotic figures could be identified(8,9).



The morphology of the large, vacuolated cells was the same regardless of their location in the heart(3).

Granular cells tended to form diffuse sheets in the immediate subendocardial zone and to surround the immediate subendocardial sinusoids and coronary blood(12,16) and/or lymph(16) vessels.

Some of the large cells appeared to be isolated, generally in clusters(4) in the interstitium, other cells, however, where in direct contact with unaltered cardiac muscle cells (and blended directly into them(4,21), only in papillary muscles(16)) and with cells that appeared intermediate forms between normal cardiac muscle cells and the clear cells described(3,23)(Purkinje cells clusters)(23).

The phosphotungstic acid-hematoxylin stain showed a complete lack of myofibrils and cross striations(12) or indistinct cross striation(22) in the granular cells except in a small proportion of myocytes that appeared to be intermediate between normal and transformed cells(12).

In the sections stained for lipid content, the heaviest accumulations of the relatively insoluble lipid was found in the largest polygonal "histiocytoid" cells. Adjacent enlarged elongated myocardial fibers exhibited cross striations and contained lesser amount of insoluble lipid. These fibers represented a transitional stage between the first ones and the myocardial fibers, although in the sections stained with hematoxylin-eosin the abnormal cells were sharply demarcated from adjacent unaltered myocardial fibers(14,23,5,16), except in papillary muscles(16), although there is no encapsulation(23), but the vacuolized fibers were separated from normal neighboring myocardium by interstitial connective tissue through which small vessels could run(5).




The grossly affected parts(11). Histologic study showed the incidence of the valvular changes to be higher than was suspected on gross examination(3).

All chambers and at all levels of myocardium, with numerous random foci(2,3,23,4,12,8,). The myocardium showed a striking foamy transformation of myocardial fibers diffusely (30).

Subendocardium(20,26,27,14,23,5,12,16,8, 24), conforming to the grossly visible yellow plaques(14), most abundant in the left ventricular (11,20,1,26,3,4,5,12,8,25[5 cases],24), but also in the right ventricle(2,26,27,14,3,23,5,8) and septum(5,16,8) in its upper part proximal to the central fibrous body (12). A distinct subendocardial layer of such cells covered papillary muscles and formed a cap over their apices between their fibrotendinous tips and the endocardium(12,16).

Mases of these cells also were observed in left ventricular subepicardium(26,27,3,4,8), and in the right ventricle epicardium, peripheral to the epicardial coronary vessels and distinct from the epicardial nerves(12).

The left atrial myocardium was also a site of lipid-cell replacement(2,20,14,3,23,4,12), as well as the right atrium(2, 7,26,3,23,12) and interatrial septum(23,8).

Discrete nodules on the atrial surface of the tricuspid valve(8).

Isolated atrial lesions have occurred(3).

A sheet of similar cells extended from the base of the mitral valve(11,20,1) inferiorly to the apex of the left ventricle(left ventricular septum (11,20,1,26,14) and partially replaced the papillary and trabecular muscles(20,1), and also in the left ventricular free wall(14). Some narrow discontinuous columns of granular cells were traced subendocardially along the entire length of the chordae tendinae(12,11k) and along the ventricular surface of the mitral or tricuspid valve leaflets to their fibrous ring(12).

Throughout the left ventricular subendocardium there were many separate small tumors which had no connection with the left bundle branch, and similarly occurred in the right ventricle(23).

The right ventricle and anterior wall of the left ventricle were not involved(20,16), except in some cases (2,1,26,3,12).

Histiocytoid cells in the upper third of mitral valve leaflets (11,20,7,3), tricuspid valve(3), base of aortic valve(11,20), and near the base of the tricuspid valve(3).

Selective involvement of left papillary muscles was not found in any patient(3).


Cardiac conduction system

Step sections showed no conduction-system lesions(2,3).

There was no evidence of preferential involvement or sparing of conduction tissues, that had the same character and extent of alteration that the adjacent nonspecialized myocardial fibers(14).

Multiple samples from the sinoatrial node were normal(14).

Sinoatrial node(11,20,23,12) and atrial appendage(11) showed focal collections of swollen lipid-filled (Purkinje) cells in the vicinity of the nodal tissue(20,23,8).

Within all three internodal pathways there were Purkinje cell tumors(23).

The A-V node was affected(26,14,23,12,8).

The atrioventricular node was entirely normal, as was the bundle of His, up to its penetration of the fibrous ring(20).

The bundle of His, after its penetration of the fibrous ring, showed groups of enlarged, vacuolated cells within the His fibers(20,1,14,23,5).

Large masses of histiocytoid cells in the atriventricular ring near bundle of His(3,16).

None of the patients, however, developed A-V block(3), but a patient had intermittent A-V dissociation(23).

The left bundle branches were also affected as they passed between the subendocardial nodule and the fibrous septum(20,27,14,23,5,24).

Both bundle branch affected(14,23), and they were composed exclusively of these polygonal Purkinje cells(23).

Cytoplasmic continuity between the vacuolated cells and the Purkinje fibers is seen. The right bundle branch was not involved(20).

Typical normal Purkinje cells could nor be discerned in regions containing foam cells(16).

An abnormal potential conducting pathway was shown, bridging between the origin of the left bundle and the crest of the ventricular septum. This pathway consisted of foamy myocytes and could have acted as the route for a re-entry dysrhythmia(24).


Special Stains:


PAS positive(11,7,26,3,23,22).

The material stained blue with alcian blue(11) and was partly periodic acid-Schiff positive(11) and stained(11,23) lightly(11) with Best's carmine for glycogen(11,23). Some particles were glycogen-positive(PAS-diastase)(20,23)(weakly (4)) and others were positive for mucopolysaccharide with Alcian blue(20).

The cytoplasm did not stain for glycogen(Best'Carmine)(25).

The sections from the affected areas were negative for these methods: PAS(14,4,5), PAS diastase, Alcian blue (14).

Glycogen content of the Purkinje cells exceeded that of the adjacent myocardial cells, as it normally does(23).

The granules gave negative or equivocal reactions for acidic groups and for carbohydrate content(14).

The large abnormal cells contained variable amounts of glycogen and lipofucsin(3).



Reaction for fat positive(11,2,20,7,27,14,3).

The sections from the affected areas were negative for these methods: Cholesterol(Schultz)(14).

Histochemical studies from the affected areas yielded the following positive stainings: Nile blue sulfate(the predominance of blue and blue-purple droplets with this method suggested accumulation of free fatty acids), Acid hematin(Baker), Osmium Tetraoxide-Ó-Naphthylamine(Adams)(that persisted after treatment with alcohol) (14).


The abundant cytoplasmic (simple membrane-limited) vacuoles (granules) stained for lipid with Sudan Black B(2,20,14,3,4,12,16), Sudan IV(14), Sudan III(5) and Oil Red O(14,3,4,12,25); and resisted further extraction by prolonged treatment with acetone, alcohol-chloroform, and pyridine(14).

The minute cytoplasmic particles stained irregularly with Sudan black(20).

Lipid droplets in those cells were sparse in patient(3) and absent in patient(3).

Cytoplasmic granules positive for Sudan Black stain were absent is striated myocardiocytes(16).

The bulk of the adventitious material appear to be lipid(11,20).

The histochemical examination reported that the adventitious material was a complex lipid insoluble in ordinary fat solvents(11).

Sudan black B showed many droplets consistent with mitochondria in the sarcoplasm in the altered cells, and not in the normal cells(2).

The reactions were interpreted as strongly suggestive of accumulation of a poorly soluble phospholipid(14).

The granular cytoplasm gave positive reaction with the mitochondrial stains(Altmann's acid fuchsin-picric acid technique and a block staining method( adapted from Swank-Davenport method for degenerate myelin fibers))(25)

Severely affected fibers exhibited prominent accumulation alcohol-extractible lipid presumed to be triglyceride or fatty acids residing in simple membrane-limited vacuoles, and moderate accumulation of a pyridine-insoluble phospholipid, possibly residing in peculiar intramitochondrial stacks of paired membranes(14).



Myofibrils are normally sparse and contain few myofilaments in normal Purkinje cells(23).

The granules were positive in the phosphotungstic adic-hematoxylin stained sections(PTH)(20,12).


Enzimes: Cholinesterase

Sections processed by direct thiocholine method for activity of cholinesterase exhibited scattered foamy cells with a spotty or granular, cytoplasmic brown reaction product, comparable to that found in normal skeletal muscles. Only a fraction of "arachnocytes" presented this reaction, probably due to partial inactivation of cholinesterase by fixation. Myocardiocytes completely lacked this activity(16).


The sections from the affected areas were negative for these methods: Aldehyde fuchsin and Acid-fast(14).



The affected areas had a pale yellow fluorescence in the frozen sections, but it was nonpolarizable(14).