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]


Other findings

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

LITERATURE REVIEW. Anatomic Pathology


Electron Microscopy

Myocardial fibers that appeared normal with the light microscope exhibited only a slightly reduced number of glycogen granules, and mitochondria were uniform in size and often contained small amorphous dense inclusions(14).

The fibers that light microscopically were more granular were less markedly altered than the foamy fibers(4).

The histiocyte-like cells had a increased size(3,21), altered cell shape(more nearly spherical than normal fibers(3,4,8)), smooth borders(3,12,8) with no microvilli or surface projections(3). The plasma membranes of adjacent cells followed parallel courses, but without the interdigitations that are characteristic of intercellular junctions of normal human cardiac muscle cells. These areas of parallel membranes had desmosomes(3,4,12,8), but not nexuses(4). There were occasional findings of junctional complexes relevant to intercalated disks(5,22). Intercalated discs were rare(12) or absent(8), but one was found joining a normal myocyte with transformed cells(12). Basal laminae were thin and inconspicuous(3,8) or exhibited reduplication(8).

Abnormal myocardial cells, in the early stages of the degenerative process(14,4), were enlarged, filled with distorted hyperplastic mitochondria(2,20,14,3,4,12,16,13,22,21,15,8,25,30) that were concentrated centrally in the myocytes(25), and devoid(2,3) or with remnants of disintegrated myofibrils(20,14,3,4, 12,16,13,22,21,15,8) usually peripherally placed(12,13,22,8), and leptofibrils subjacent to cell membranes(12,13,8). The fibrils that were present were not recognizably different from those in normal cells(4). In these cells the Z line, anisotropic bands with mesophragm, and almost obliterated isotropic bands were clearly visible(5,12,16,13,8).

As these changes progressed, the fibers became rounded and enlarged(14). In the most severely affected cells, only a few residual bundles of myofilaments, often severely contracted, could be found in the expanded cytoplasm which contained little other than mitochondria(14,4) and large number of(or a few(4,13,15)) lipid droplets(14).

The vacuoles seen with light microscope appeared to be degenerating mitochondria(2,20). Glycogen particles, lipid droplets and the mitochondria appeared to cause the vacuolization observed in histologic sections(3).

Cytoplasmic glycogen granules were either normal or mildly increased, but lipid vacuoles were mildly to moderately increased(12,8).

There was no significant storage of material between or within the organelles(4).

Mitochondria in affected fibers: More concentrated(3,12). Generally uniform in size(14) and were mildly enlarged(14,22,25). Greater variation in size that those of normal cardiac muscle cells. Matrix swelling and dense amorphous inclusions(also found in normal fibers), which usually exhibited no discernible substructure and which appeared to be agglomerates of matrix fused with cristal membranes(14). These intramitochondrial densities accompany both ischemic injury and autolysis(14).

Still recognizable cristae(20), which appeared normal, but focally they exhibited a dilated saccular(vesicular) configuration(14,3,12,8,25), and less packed(3).

Three types of intramitochondrial inclusions were identified: 1) piles or stacks of closely apposed, parallel, unusually dense lamellar or tubular(22) cristae(3,4,13,22,8); the most unusual and best-preserved of the intramitochondrial abnormalities consisted of stacked paired membranes exhibiting linear, curved and occasionally complete circular profiles. The membranes in these stacks usually were in continuity with saccular cristae and did not exhibit continuity with the outer mitochondrial membrane(14). The stacks of cristae may result form postmortem autolysis(3). 2) Intramitochondrial glycogen deposits(3,12,22,8,25), membrane bound(12); in monoparticular or rosette form(22) similar to those found in cardiac muscle cells in other pathological conditions(3); the accumulation of glycogen inside of mitochondria is related to increased permeability of the outer mitochondrial membranes(3). 3) Rounded, dense inclusions(3,13,22,8,25) that measured from 1,000 to 2,000 in diameter and resembled lipid droplets(3), witout a limiting membrane(22), which significance is unknown(3), probably the result of postmortem autolysis(13) or calcified bodies observed in several conditions(25).

A few mitochondria contained parallel arrays of microtubules 700 nm in length(25)

Distorted mitochrondrial cristae and intramitochondrial vacuoles were very likely the result of the delay in fixation(12).

The outer membranes of adjacent mitochondria often fused to form extremely electron-dense segments, a change which paralleled the other mitochondrial alterations in frequency and which was not seen in control fibers from areas of unaltered myocardium(14).


Intermediate degrees of myofibrillar dissolution and mitochondrial abnormality were found(2,21).

Membrane-limited dense granular bodies were prominent in fibers exhibiting early myofibrillar loss(14,3), subjacent to plasma membranes(3); the individual granules within these bodies were 7 to 9 mf in diameter, and linear or parallel organization of the granules could occasionally be detected, suggesting the presence of crystalline substructure(14). This material was amorphous in some cells, while in others it formed well defined masses that had a periodic substructure and were associated with filaments that measured from 60 to 80 in diameter(3). The nature and origin of these bodies was not determined, although they seemed to be spatially related to the earliest phase of myofibrillar degeneration, Z-band disintegration(14,3).

The periphery of the histiocyte-like cells also contained clusters of ribosomes, many of which were associated with the Z-band-like material, and a small meshwork of microtubules that measured 200 in diameter(3).

Perinuclear osmiophilic bodies were prominent in affected fibers and were rarely seen in normal fibers(14).

A few scattered clusters of small, deeply osmiophilic spherical homogeneus particles of uncertain nature were seen in the sarcoplasm(4).

Empty vesicles probably resulting from extracted lipids(16).

The numbers of lipid droplets, glycogen particles and lipofucsin granules varied considerably from one cell to another(3). Glycogen particles, demonstrated selectively by the Thiéry method, were very abundant in some cells, sometimes arranged into elongated strands(3).

Lipid vacuoles, often with a double limiting membrane, seemed to correspond with the oil red O positive material seen on frozen sections. They were interpreted as mitochondria with dissolution of the cristae(25).

Tubules of sarcoplasmic reticulum, T tubules, Golgi zones, and cisterns of rough-surfaced endoplasmic reticulum were not present in any of the histiocyte-like cells(3,12), and lisosomes were rarely or not clearly identified(3,8).

Nuclei: The nuclear membranes showed irregular indentations and convolutions(3).

The nuclei of most of the altered myocardial cells were not distinctive(14,3,12) except for prominent large nucleoli(14). Nucleoli were small(3).

Those with large inclusions were examined for virus particles, but none were found(20,14,3), either in the nuclei or in the cytoplasm(3). Occasionally, the nuclear chromatin exhibited a delicate pattern of uniform interwoven fibrils 250 to 300 Angstroms in diameter that resembled that of published electron micrographs of myxovirus tubules(14). The fibrils, however, more significantly, were identical in size and configuration to individual chromosome fibers, and they were solid rather than tubular(14). Such nuclear changes have been observed in myocardium of patients receiving anthracycline drugs(3). The chromatin was in part marginated and in part finely dispersed(3).

Many of the foamy cells were directly adjacent to and in close contact with endothelial channels(16).

The interstitial cells of the myocardium were not increased in either size or number and did not exhibit mitochondrial alterations, lipid accumulation, or evidence of phagocytic activity(14).

Bundles of collagen separating oncocytic myocytes(12).

Numerous foci of reticulin fiber synthesis(20).

Interstitial collagen was not increased and there was very little tendency for the intercalated disks to separate(14).

Hug and Schubert (1970) described a constellation of organellar alterations in a sample of left ventricular muscle obtained via open biopsy from a child with idiopathic cardiomyopathy. The most prominent changes were bizarre cristal configurations in enlarged and unusually numerous mitochondria. The authors observed no increase of lipid droplets(14).



Small amount of desmin and myosin have been found in the cells of the Purkinje hamartoma(29).

A perimembranous positivity for muscular specific actin has been described(17) as well as a lack of reactivity with the histiocytic markers CD68 and lisozyme(17).


Biochemical findings:

The left ventricular endocardium contained relatively more phosphatidyl serine, phosphatidyl ethanolamine plus polyglycerol phosphatide that the patient's right ventricular endocardium(20). This is probably a reflection of the large numbers of mitochondria in these abnormal cells(20).

The level of carnitine in the heart muscle and three different skeletal muscles was normal(22).

Biochemical studies showed markedly decreased succinate-cytochrome c reductase and rotenone-sensitive NADH-cytocrome c reductase activities, while other mitochondrial enzymes were normal(15). In isolated mitochondria, cytochrome spectra showed a severe defect of reducible cytochrome b and a less marked defect of cytochrome cc1, while the content of cytochrome aa3 (cytochrome c oxidase) was normal. Histiocytoid cardiomyopathy appears to be a defect of complex III (reduced coenzyme Q-cytochrome c reductase) in the respiratory chain of heart mitochondria(15).


Other findings