key: cord-0009860-khxb15wp
authors: Foa, C.; Foa, J.; Carcassonne, Y.
title: Morphologic study of virus‐like particles in a case of acute leukemia
date: 2006-06-28
journal: Cancer
DOI: 10.1002/1097-0142(197604)37:4<1718::aid-cncr2820370417>3.0.co;2-x
sha: c5bcf6c3957245b4a27e4cadb72c7f1181fc1a32
doc_id: 9860
cord_uid: khxb15wp

Virus‐like particles, grouped in clusters not bound by a membrane, were seen in electron micrographs of fresh leucoblasts of an acute leukemic patient. They consisted of large (100‐nm diameter), round particles apparently composed of subunits. Tubular structures (30–50‐nm diameter) were also seen in leucoblasts of the same patient. The two types of structures were never seen simultaneously in the same cell. The authors review the literature pertaining to the morphology of virus‐like particles associated with malignant hematologic disease.

At present, these particles do not fall into any of the above categ0ries.~~. 30 Their viral nature has not yet been proved but their ultrastructure suggests that it might be possible. T h e shown structures and those described by Tavassoli and Baughan28 and !%manz5 are in this category.

In the present case, the patient was a 75year-old woman whose white blood cell count was found to be 270,000, of which 98yo were leucoblasts. A diagnosis of acute leukemia was made. T h e patient died several days after admission.

In smears stained with May-Grunwald Giemsa large, round leucoblasts were seen; their nucleocytoplasmic ratio was rather elevated. T h e oval-shaped nucleus was skewed to one side of the cell and limited a rather large, clear cytoplasmic zone. In the nucleus, the chromatin, which was uniform in aspect, was fine and dispersed and there were one or two nucleoli.

T h e cytoplasm was sparse and only slightly basophilic; it did not contain any granules. At this magnification, i t seemed to be rather homogenous (Fig. 1 ).

In view of the poorly differentiated aspect of the blood smears, the white cells were processed for electron microscopy. T h e leucoblasts were round and small (between 8 and 14 pm) and rather monomorphic, with a very large, often kidney-shaped nucleus. Depending on the section, one or two nucleoli were present (Fig. 4) . T h e chromatin was completely dispersed without any margination but the internal nuclear membrane was particularly dense (Fig. 2) .

T h e cytoplasm, more or less abundant, was distributed in fibrillar, very often concentric formations, in most of the cells. These formations were closed and sometimes adjacent to the nucleus and to the numerous mitochondria ( Figs. 2 and 3) . These mitochondria were round or slightly elongated with more or less distortetl cristae. Some of the cells contained rare azurophilic granules (Fig. 3) . In addition* There is no doubt about the existence of subunits. lar particles and tubular structures which were never seen simultaneously.

T h e larger-sized particles (100 nm in diameter) present in 50/, of the leucoblasts were round, though occasionally elongated (Fig. 5 ). Twenty to 50 particles were grouped in clusters, never bound by a membrane. T h e content of each particle was not homogenous and at higher magnifications (Fig. 6 ) seemed to b e composed of juxtaposed subunits.

T h e tubular structures, present in 8% of the leucoblasts, formed clusters measuring 30-50 nm in diameter (Fig. 7) . They were seen most of the time very close to the nucleus. Like the large-sized particle clusters, these tubular arrangements were never bound by a membrane. T h e tubes were twisted and seemed to be entangled with each other. They were found near the endoplasmic reticulum, the diameter of which was much larger than that of the tubules. Sometimes (Fig. 7) these structures seemed to be contiguous to the mitochondria. High magnification (Figs. 8 and 9 ) did not furnish additional data.

T h e leukemia evolved so rapidly that certain classic explorations could not be performed. This is the reason why cytochemical and enzymologic investigations were not carried out. Nevertheless, from the optical and electron microscope images seen, it seems that this case can be classified as an acute, myeloblastic, poorly differentiated leukemia. FIG. 8. Detail of tubular structures (~5 0 , 0 0 0 ) . Vacu oles (v) are present in the heart of these clusters.

FIG . 9. High magnification of the tubules (X150,000) . The tubules are sectioned in various planes. 7. Leucoblast containing tubular structures (~34,500) . Note the close relationships linking the fibrillar structures, the mitochondria, the tubular structures, and the nuclear membrane.

Fibrillar plaques: Vertiginous, more or less concentric fibrillar masses have been frequently found i n cancer cellsl~3 and in lymphoid cells of acute lymphoblastic~3 or myeloblastic leukemia,4 but their significance is not known.

Large particles:

In view o f their size and general aspect, these particles appear to be like those described by Seman.z51z6 However, they seem to be somewhat different because they did not have a dense inner core and were not surirounded by a membrane.

Tubular structures: They look very much like the tubular inclusions referred to before,*lJ5 but the clusters were never bound by a membrane as often described in the literature.

T h e fact that virus-like particles and tubular structures were found in the leucoblasts of the same patient suggests two hypotheses: 1) The tubular structures are required for the manufacture of the virus-like particles, as Oshiro has shown.21 However, we never observed both types of structures simultaneously in the same cells and the size of the particles we observed did not correspond to those described by Oshiro. 2) T h e tubular structures are the response of the cell to a particular stimulus which, in our case, may be the virus-like particles.

T h e structures we describe do not seem very different from certain virus-like particles already seen by some investigators, but it is impossible to be sure that they are identical or that they really represent viruses. ADDENDUM While this article was in press, an article by J. C. Cawley and A. Karpas, "The Ultrastructural Demonstration of Virus-like Particles in Human Leukaemic Cells," was published in European Journal of Cancer 10:559-561, 1975. T h e particles observed by these authors resembled exactly those we describe. They also report that two forms of viruslike particles were present, which corresponds to our observations. Their conclusions agree with our's in that they are purely speculative. It must be noted that these particles have now been observed in several types of leukemia.

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