[CANCER RESEARCH 36, 1717-1724, May 1976)
Multilaminar Endoplasmic Reticulum and Abnormal Mitosis
in Hodgkin Tumor Cell&
Richard T. Parmley, Samuel S. Spicer, and Abbott J. Garvin
Departments of Pathology (S. S. S., A. J. G.J and Pediatrics (R. T. P.], Medical University of South Carolina, Charleston, South Carolina 29401
SUMMARY
interphase tumor cells (6, 8, 9, 14), and virally induced
mitotic cells in vitro (21). In other studies, the stacked mem
A multibaminam alteration of endoplasmic reticulum (ER) branes were not noted in phytohemagglutinin-stimulated
has been observed in tumor cells of eight patients with mitotic lymphocytes from either normal individuals (22, 37)
Hodgkin's disease and a patient with histiocytic lymphoma. or Hodgkin patients (10) and were not observed in mabig
These multibaminamstructures are more numerous in divid
nant on normal mitotic plasma cells (11, 12, 16) on cultured
ing cells and thus appear to arise primarily during mitosis. tumor cells (19, 32). This structure has not been encoun
The stacked membranes in the multilaminar structures pos
tened in normal intemphase cells and, although observed on
one occasion in normal dividing mammalian cells in vivo
sibly result from abnormal sticking of organelle mem
bmanes,as evidenced in this study by adherence of ER to (25), is generally thought not to occur in such cells (23, 32,
other elements of ER, nuclear envelope, mitochondnia, on 33). The multilaminam reticulum thus appears primarily con
lipid droplets. Multilaminam ER was identified in all mitotic fined to some tumor cells or cultured cells in mitosis and
occurs rarely in nondividing neoplastic cells (8, 14, 33).
tumor cells, a rare mitotic plasma cell, and numerous inter
phase Hodgkin cells. The paucity of mubtilaminar ER in Although the presence of multilaminar ER has been briefly
normal mitotic cells and its virtual absence for normal inter
noted previously in Hodgkin tumor (26, 28), it has not been
phase cells suggest that this structure represents a patho
observed in several ultmastmuctumab
studies of Hodgkin neo
logical alteration in tumor cells from patients with Hodg
plasms (4, 7, 13, 17, 18) and has not been previously investi
kin's disease and histiocytic lymphoma. The multilaminar
gated. In this study, we demonstrate extensive multilaminam
defect of ER is associated with other atypical features of ER structures involving granular reticulum and nuclear enve
in Hodgkin
tumor cells, including
the excessive
length and
lope of both mitotic and intemphase tumor cells in Hodgkin
curving of ER profiles, the collapse of the ER cistennae, and specimens and mitotic cells in histiocytic lymphoma (meticu
the overall spamsityof this organelbe.
lum cell sarcoma).
Such structures
appear
abnormal
and
Other abnormalities observed in rnitotic Hodgkin tumor are thought possibly to be related to the spamsityof ER and
cells include the presence of disorganized microtububes, greatexcessof unbound mibosomesinthetumor cells(18).
large cytoplasmic vacuoles, and abnormally clumped chno
mosomal material and the persistence throughout mitosis
MATERIALSAND METHODS
of bodies suggestive of nucleoli and of the nuclear bodies
of intenphase cells.
Lymph nodes from 8 patients and a spleen from 1 patient
with Hodgkin's disease and a lymph node from a patient
INTRODUCTION
with histiocytic lymphoma (reticulum cell sarcoma) were
removed surgically. The patients ages ranged from 4.5 to 55
A mubtilaminam structure composed of 4 stacked mem
years, and none had received prior therapy for their cancer.
branes of ER2 or of ER with nuclear envelope has been
A portion of each specimen was fixed in buffered 10%
described previously in various conditions. This multilami
fommalin and processed routinely for light microscopic di
nan ER was initially observed in dividing sarcoma cells as a
agnosis. All specimens from Hodgkin patients revealed tu
double tubular structure which was thought eventually to
mom of the mixed cell variety, as diagnosed by surgical
transform into ER (29). This structure has more recently
pathologists of the University Hospital. Tumor cells me
been interpreted as aggregates of granular reticulum. The
placed normal structure in the node from the patient with
multilaminam ER has been observed in mitotic rat thymo
histiocytic lymphoma.
cytes (25) and mitotic and interphase leukemic cells exhibit
Another portion of each specimen was fixed 1 to 2 hr in
ing viruses in vivo (34) and has been reported in phytohe
3% glutanaldehyde in 0.1 M, pH 7.4, cacodylate buffer at 4°.
magglutinin-stimulated lymphocytes (30), mitotic and mane
The glutamaldehyde-fixed specimens were rinsed with 7.5%
sucrose, buffered with 0.1 M cacodylate at pH 7.4 and then
* This research
was supported
by NIH Grants AM-i 0956 and AM-i 1 028 and
were postfixed 1 hr in 2% osmium tetmoxide, dehydrated,
Veterans Administration Training Grant TA-i 68a.
and embedded in Epon. Thin sections were stained with a
Received September 2, 1975; accepted December 29, 1975.
umanyl acetate and lead citrate sequence and viewed in a
2 The
abbreviation
used
is:
ER,
endoplasmic
reticulum.
MAY 1976
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1717
A. T. Parmley et a!.
Hitachi HS-8 electron microscope at an accelerating voltage
of 50 kV.
composed of 2 outer layers comparable in thickness to the
usual cytoplasmic unit membrane plus an inner, thicker
layer (Figs. 1 and 9). Very sparse particles presumed to be
mibosomes and amorphous material adhered to the cyto
RESULTS
plasmic surface of the outer layers of the mubtilaminam ER.
The multilaminam elements of ER frequently contacted on
The tumor cells in Hodgkin lesions ranged from 20 to 40 enwrapped other cell omganelles such as lipid droplets (Fig.
@m
in diameter and usually enclosed 1 nuclear profile but, 9). ER occasionally was approximated closely to mitochon
occasionally, could be identified as Reed-Stennbeng cells dna in such a way that the 2 mitochondmial membranes and
from their content of 2 or 3 nuclear profiles. Intemphase 2 ER membranes formed a 4-layered structure (Fig. 9) simi
tumor cells were observed in all of the patients studied, and lamto mubtilaminam ER. Some irregular projections of cob
mitotic cells were seen in 6 of the 8 patients with Hodgkin's
lapsed ER appeared folded back upon themselves. Occa
disease and the 1 patient studied with histiocytic lymphoma.
sionally, profiles of ER or multilaminated structures formed
The nuclei of Hodgkin tumor cells measured 10 to 20 @m
in a completecircle
(Figs.
1,and 7 to9).
diameter, and in turn, enclosed bizarre nucleoli measuring
Two mitotic plasma cells in 1 tumor specimen displayed
up to 8@m in greatest dimension (Fig. 1). The nuclear chro
the mubtilaminamER in the 1 or 2 profiles of granular meticu
matin was finely dispensed and the nuclei often contained
bum nearest the nucleus (Fig. 10). These were the only
several nuclear bodies composed of a moderately dense rim dividing plasma cells encountered.
and a less dense cone. The nucleoli consisted mainly of
Cells presumed to be Hodgkin tumor cells were observed
abundant granular component with sparse interspersed
in various
stages of mitosis
(Fig. 2). These dividing
cells
dense component and a few small foci of pans amorpha.
were interpreted as neoplastic cells in mitosis from the
Structural variability was evident among both multinucle
similarity of their cytoplasmic features to those of Hodgkin
ated Reed-Stemnberg cells and uninucleam Hodgkin cells in and Reed-Stemnbemgcells and the atypical appearance of
the same specimen as described previousy (4, 17, 18). Some their chromosomal mass (Fig. 2). The chromosomal mate
tumor cells resembled immunoblasts with sparse collapsed
nab in mitotic cells had an abnormally clumped appearance
ER and abundant free polynibosomes (18) (Fig. 2), whereas and irregular contour. Microtubules associated with this
other tumor cells often contained abundant microfilaments,
chromosomal material often appeared tortuous and diso
a few granules, fairly abundant mitochondnia, and variable
niented rather than linear and aligned perpendicular to
amounts of ER (Fig. 1). The specimen with histiocytic lym
chromosomal material. Remnants of nuclear material me
phoma disclosed numerous interphase tumor cells with fine sembling nucleoli (5) were seen in the cytoplasm of tumor
structural features similar to those previously described for cells in all stages of mitosis (including late tebophase). Also,
these cells (31).
bodies showing a cortex and less dense center and resem
Reed-Stennberg and Hodgkin cells and histiocytic lym
bling nuclear bodies of intemphase tumor cells persisted in
phoma cells exhibited a multilaminam membrane alteration
the cytoplasm of occasional mitotic tumor cells.
(Figs. 1 to 9). This change was observed in mitotic and
intemphase cells of lymph node and spleen from 6 Hodgkin
patients and of the lymph node from the patient with histio
DISCUSSION
cytic lymphoma. In 2 Hodgkin patients, no mitosis was
encountered, and the multilaminar ER was not present in
Since the multilaminam ER has been observed only namely
the intemphase tumor cells observed in this study. The prey
in normal dividing mammalian cells in vivo (25), the pmes
alence of multilaminam ER in tumor cells was not related to ence of the multilaminam structures in all dividing tumor
the age of the patients on the extent of their disease. The cells in Hodgkin specimens and histiocytic lymphoma rep
multilaminar structure frequently consisted of a collapsed
resents, at the least, a pathological increase in this event.
cistemnaof rough ER closely approximated or adherent oven The occurrence of this structure in intemphase Hodgkin cells
a variable distance to another cistemnaof ER (Figs. 1 and 2). would appear to be abnormal, since insofar as we are
aware, it has not been previously described in intemphase
In other profiles, these structures were composed of vania
bly long segments of nuclear envelope of interphase cells on cells in vivo. The presence of multilaminam ER in Hodgkin
persistent nuclear envelope of mitotic cells in similar ap
tumor cells further supports speculation that this structure
pnoximation to rough ER (Figs. 3 and 4). At the point where
is more prevalent in tumor cells in general (6, 8, 9, 29).
adherence of 2 cistennae terminated, the multilaminan netic
The increased prevalence of multilaminar ER in some
ulum appeared to branch into cistemnaeof ER (Figs. 5 and 6) dividing cells, as previously recognized (8, 14, 25), suggests
on nuclear envelope and ER (Figs. 3, 4, and 7). The multilam
that this process occurs primarily, or is accentuated, during
man profiles accounted for a minority of the rough ER and cell division. When observed in normal cells, the multilami
nuclear envelope in approximately 15% of the intemphase nan ER does not appear to persist beyond late tebophase.
tumor cells encountered (Fig. 1), but comprised all on most Multilaminam ER encountered here in intemphase cells am
of the granular reticulum in all of the 15 mitotic tumor cells
gues then against the genesis of the lesion transpiring only
(Fig. 2).
during mitosis, unless it has persisted since cell division.
The approximated cistemnae lay separated by a narrow
For the multilaminan ER in intemphase cells to be a residuum
distance in some areas and exhibited 4 membrane layers. of structures formed during mitosis, however, does seem
Less commonly, the 2 central membranes appeared fused
consistent with the invariable presence of this change in
throughout most or all of the multilaminar ER so that it was mitotic Hodgkin tumor cells and its lessen prevalence in
1718
CANCERRESEARCHVOL. 36
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Multilaminar ER
intemphase cells. The lesion thus appears to occur with
increased frequency in mitotic cells and to persist abnor
mally after mitosis in Hodgkin tumors.
Knowledge of the ER in dividing plasma cells in vivo is too
limited to determine whether multilaminar ER in mitotic
plasma cells is abnormal. However, the structure is absent
from illustrated mitotic plasma cells (12, 16) and plasma
cytoma cells (11) and, to our knowledge, has not been
previously encountered in such cells. Possibly, therefore,
the presence of multibaminar ER in plasma cells in vivo is
abnormal and arises from an influence of the neoplastic
environment on the cell on as an early manifestation of
transformation in the cell line from which the Reed-Stern
berg cells derive (18).
Previous investigators (29) have suggested that these
stacked profiles of ER develop as a consequence of mitosis
induced proliferation of new nuclear envelope or ER. The
formation of the structures may also entail folding of nu
clean envelope on itself as it is pulled toward the spindle
poles in late pmophase (6). Consequently, the term spindle
lamellae has been used (6) to describe the multilaminam
structures. However, normal dividing cells generally lack
multilaminam ER (1, 2, 16, 23, 32, 33, 35) and are not known
to replicate ER by a mechanism entailing formation of such
structures.
The multilaminam structure, on the other hand, conceiva
bly arises through segments of ER paralleling, contacting,
and fusing with nuclear envelope on other ER segments.
The structure might develop from ER or nuclear envelope
folding back and adhering to itself. The intimate approxima
tion or contact of the ER with mitochondria and lipid drop
bets, as well as nuclear envelope on other profiles of ER
observed in intemphase Hodgkin cells, suggests an abnom
mab tendency of the ER membrane to approach other or
ganelle surfaces in these cells. Perhaps the membrane is
altered in such a way as to favor approximation and adhe
sion to other structures. If the adherence occurs mainly
during mitosis, the structure might subsequently pull apart
and reform ER on nuclear envelope or simply degenerate,
as has been suggested previously (8).
The multilaminar ER is a distinctive structure and clearly
differs from the projections of nuclear envelope containing
nuclear material as seen in cultured Burkitt lymphoma cells
(15) or guinea pig thymus (35). The structure has been
interpreted
as a form of annulatelamellae,
but from the
present and previous observations, appears distinct from
the latter entity (20).
A number of the cells in which multilaminar ER has been
observed heretofore were infected with virus (3, 21, 24, 34).
Viral particles and other microorganisms have been ob
served ultnastmucturalby in patients with Hodgkin's disease
(27). Recently, tubular arrays identified in the ER of cultured
Hodgkin cells have been attributed to a possible viral lesion
(36). Although cells with multilaminam reticulum disclosed
no intracellular microorganisms, prior infection or contin
ued infection in an occult form possibly could play a part in
pathogenesis of multilaminar ER in tumor cells and plasma
cells of the same specimen.
The increased prevalence of multilaminar ER in Hodgkin
tumor cells suggested by the present results conceivably
MAY 1976
entails impaired genesis of granular reticulum. Defective
formation of ER could comprise a basis for the failure of
the tumor cells to mature into plasma cells. The lack of ER
in these tumor cells apparently results in production of im
munogbobulin on unbound nibosomes (18) and failure to
secrete the globulins (15). The observation here of small
amounts of multilaminar ER in dividing plasma cells infil
trating tumor of presumed B-cell origin suggests that the
propensity for development of mubtibaminar ER exists
throughout the B-cell series.
ACKNOWLEDGMENTS
The authors would like to express appreciation for the skilled technical
and secretarial assistance of Joanne Wright, Karen Beaufort, and Dorothy
Smith.
REFERENCES
1. Bajer, A., and Mole-Bajer, J. Formation of Spindle Fibers, Kinetochore
Orientation, and Behavior of Nuclear Envelope during Mitosis in Endo
sperm. Fine Structural and in Vitro Studies. Chromosoma, 27: 448-484,
1969.
2. Barer, A., Joseph, S., and Meek, G. A. The Origin of the Nuclear Mem
brane. Exptl. Cell Res., 18: 179-182, 1959.
3. Bernhard, W. Fine Structural Lesions Induced by Viruses. Cellular Injury.
In: A. V. S. de Reuck and J. Knight (eds.), Ciba Foundation Symposium.
Boston: Little Brown & Company, 1964.
4. Bover, G. F., Candela, J. B., Vila, J. F., Guillem, E. B., and Candela, A. B. E
Studio de Ia Ultrastrucura de Ia Celula Gigante de Steinberg y de sus
Relacioner con otras Celulas Immunocompetenter. Med. Espan., 59:
429-459,1968.
5. Brinkley, B. A. The Fine Structure of the Nucleolus In Mitotic Divisions of
Chinese Hamster Cells in Vitro. J. Cell Biol., 27:411, 1965.
6. Buck, A. C. Lamellae in the Spindle of Mitotic Cells of Walker 256
Carcinoma. J. Biophys. Biochem. Cytol., 11: 227-236, 1961.
7. Carr, I. The Ultrastructure of the Abnormal Reticulum Cells in Hodgkin's
Disease. J. Pathol., 115: 45-50, 1975.
8. Chang, J. P., and Gibley, C. W., Jr. Ultrastructure of Tumor Cells during
Mitosis. Cancer Res., 28: 521-534, 1968.
9. Chentsov, G. S. An Electron Microscopic Study of Induced Rhabdomyo
blastoma of the Rat. Proc. Acad. Sci. USSR (EngI. Tr.), 132: 447, 1960.
10. Cohnen, G., Douglas, S. D., Konig, E., and Brittinger, G. In Vitro Lympho
cyte Response to Phytohemagglutinin and Pokeweed Mitogen in Hodg
kin's Disease: An Electron Microscopic and Functional Study. Cancer,
31:1346-1353,
1973.
11. Curtis, S. K., Propp, A., Cowden, A. A., and Tartaglia, A. P. Ultrastructure
of a Human Malignant IgA Producing Plasmacytoma. EptI. Molec. Pa
thol.,
22:386-399,1975.
12. de Petris, S., and Karlsbad, G. Localization of Antibodies by Electron
Microscopy in Developing Antibody Producing Cells. J. Cell Biol., 759778,1965.
13. Dorfman, A. F., Rice, D. F., Mitchell, A. D., Kempson, R. L., and Levine, G.
Ultrastructural Studies of Hodgkin's Disease. NatI. Cancer Inst. Mono
graph, 36: 221-238, 1973.
14. Epstein, M. A. Some Unusual Features of Fine Structure Observed in He
La Cells. J. Biophys. Biochem. Cytol., 10: 153-162, 1961.
15. Epstein, M. A., and Achong, B. G. Fine structural organization of human
lymphoblasts of a tissue culture stain (EBI) from Burkitt's Lymphoma. J.
NatI. Cancer Inst., 34: 241-253, 1965.
16. Feldman, J. D. Morphology of Plasma Cells. In: W. J. Williams (ed.)
Hematology, pp. 760-776. New York: McGraw-Hill, Inc. 1972.
17. Frajola, W. J., Greider, M. H., and Bouroncle, B. A. Cytology of the Reed
Sternberg Cell as Revealed by the Electron Microscope. Ann. N. Y. Acad.
Sci.,
73:221-236,1958.
18. Garvin, A. J., Spicer, S. S., Parmley, A. T., and Munster, A. M. Immunohis
tochemical Demonstration of lgG in Reed-Sternberg and Other Cells in
Hodgkin's Disease. J. Exptl. Med., 139: 1077-1083, 1974.
19. George, P., Journey, L. J., and Goldstein, M. Effect of Vincristine on the
Fine Structure of HeLa cells during Mitosis. J. NatI. Cancer Inst., 35: 355361,1965.
20. Harrison, G. A. Some Observations on the Presence of Annulate Lamellae
in Alligator and Sea Gull Adrenal Cortical Cells. J. Ultrastruct. Res., 14:
158-166,1966.
1719
Downloaded from cancerres.aacrjournals.org on June 17, 2017. © 1976 American Association for Cancer Research.
R. T. Parmley et a!.
21. lkeuchi, T., Sanbe, M., Weinfeld, H., and Sandberg, A. A. Induction of
Nuclear Envelopes around Metaphase Chromosomes after Fusion with
Interphase Cells. J. Cell Biol., 51: 104—115,
1971.
22. Johnson, F. R., and Roberts, K. B. The Growth and Division of Human
Small Lymphocytes in Tissue Culture. An Electron Microscopic Study. J.
Anta., 98: 303-31 1, 1964.
23. Melmed, R. N., Benitez, C. J., and Holt, S. J. An Ultrastructural Study of
the Pancreatic Acinar Cell in Mitosis with Special Reference to Changes
in the Golgi Complex; J. Cell Sci., 12: 163-173, 1973.
24. Morgan, C., Rose, H. M., Holden, M., and Jones, E. P. Electron Micro
scopic Observations on the Development of Herpes Simplex Virus. J.
Exptl. Med., 110: 643-656, 1959.
25. Murray, R. G., Murray, A. S., and Pizzo, A. The Fine Structure of Mitosis in
Rat Thymic Lymphocytes. J. Cell Biol., 26: 601-619, 1965.
26. Oliva, H., Valle, A., Florer, L D., and River, M. C. Intranuclear Mitochon
dna in Hodgkin's Disease. Virchows Arch. Abt. B Zellpathol., 12: 189-194,
1973.
27. Parmley, R. T., Spicer, S. S., Pratt-Thomas, H. A., Morgan, S. K., and
Othersen, H. B. Microorganism-like Structures in Hodgkin Disease. Arch.
Pathol., 99: 259-266, 1975.
28. Parmley, R. T., Spicer, 5. 5., and Wright, N. J. Ultrastructural Identifica
tion of Tissue Basophils and Mast Cells in Hodgkin's Disease. Lab.
Invest., 32: 469-475, 1975.
29. Porter, K. R. The Submicroscopic Morphology of Protoplasm. Harvey
Lectures Ser. 51: 175-228, Acad. Press, 1957.
30. Procicchiani, G., Miggino, V., and Arancia, G. A. Peculiar Structure of
Membranes in PHA-stimulated Lymphocytes. J. Ultrastruct. Res., 22:
195-205, 1968.
31. Rice, R. W., Cabot, A., and Johnston, A. D. The Application of Electron
Microscopy to the Diagnostic Differentiation of Ewings Sarcoma and
Reticulum Cell Sarcoma of Bone. Clin. Orthopaed., 91: 174-185, 1973.
32. Robbins, E., and Sonatos, N. K. The Ultrastructure of a Mammalian Cell
during the Mitotic Cycle. J. Cell Biol., 21: 429—463,
1964.
33, Roos, U. P. Light and Electron Microscopy of Rat Kangaroo Cells in
Mitosis. I. Formation and Breakdown of the Mitotic Apparatus. Chromo
soma, 40: 43-82, 1973.
34, Sanel, F. T. Studies of Neoplastic Myelomonocytic Cells in BALB/c Mice
Producing Infection C-type Viruses. Cancer Res., 33: 671-678, 1973.
35. Toro, I., and Olah, I. Nuclear Blebs in the Cells of Guinea Pig Thymus.
Nature, 212: 315-317, 1966.
36. Uzman, B. G., Saito, H., and Kasac, M. Tubular Arrays in the Endoplasmic
Reticulum in Human Tumor Cells. Lab. Invest., 24: 492-498, 1971.
37, Zucker-Franklin, D. The Ultrastructure of Lymphocytes. Seminars Hema
tol., 6: 4-27, 1969.
Fig. 1. This large binucleate tumor cell (27 @m
in greatest diameter) corresponds to Reed-Sternberg cells observed at the light microscope level. The
nuclei (15.5 @m
in greatest dimension) contain dispersed chromatin and large dense nucleoli with abundant granular component and sparse pars amorpha.
The cytoplasm contains abundant free polyribosomes, numerous mitochondria, lipid droplets (LO), microfilaments (m), a moderate amount of collapsed ER,
sparse Golgi Iamellae (G), and rare, small cytoplasmic granules. The left inset enlarges the segments of multilaminar ER above and to the left of center. The
right inset enlarges2 segmentsof collapsedERwhich comeinto closecontactwith eachother at thelowerright. Thelowersegmenthasa circular profile. x
8,700; left inset, x 19,600; right inset, x 15,300.
Fig. 2. This mitotic tumor cell measured over 30 @m
in greatest dimension. The chromosomal mass appears abnormally clumped and asymmetrical. Dense
nuclear material distributed around the chromosomal mass possibly represents residual nucleoli (arrows). Numerous segments of laminated ER surround the
chromosomal mass. Other cytoplasmic organelles include numerous mitochondria and lipid droplets (LD). Several cytoplasmic vacuoles (V) occasionally
appear continuous with segments of ER. A large portion of the cell at the upper left is devoid of cytoplasmic organelles other than free polyribosomes. The
upperinset enlargesthe multilaminarreticulumdisclosingthe sparseribosomesboundto its surface(short arrows).Thenucleolus-likestructuresare also
shown in greater detail, as well as the discrete bodies (long arrows), which possess a cortex and more lucent core and resemble nuclear bodies of interphase
Hodgkin cells. The lower inset enlarges centrally located microtubules that appear disoriented. x 8,700; upper inset, x 23,700; lower inset, X 23,700.
Fig. 3. A portion of an interphase Hodgkin tumor cell shows close approximation of ER with the nuclear envelope resulting in a short multilaminar
structure. Periodic fine particles smaller than ribosomes adhere to the cytoplasmic face of the membranes of this ER. A portion of ER on the left appears to
have formed a roll (arrow). x 23,700.
Fig. 4. A segment of rough ER contacts the nuclear envelope of this interphase Hodgkin cell forming multilaminar ER over an extended distance. x
22,400.
Fig. 5. A mitotic tumor cell from the patient with histiocytic lymphoma (reticulum cell sarcoma) shows a multilaminar structure which branches into 2
segments of rough ER. x 24,800.
Fig. 6. In another mitotic tumor cell from the patient with histiocytic lymphoma, a segment of rough ER (arrow) connects at either end with other profiles
of ER to form 2 multilaminar structures. x 15,400.
Fig. 7. A portion of collapsed ER in this interphase Hodgkin tumor cell merges with the nuclear envelope forming a multilaminar structure. Another
segment of ER ends in a loop (arrow). x 12,300.
Fig. 8. In this interphase Hodgkin tumor cell, an unusual cisterna of granular reticulum completely encircles another circular profile presumably
composed of ER. Ribosomes and dense material are attached to membranes of the outer circle. Two loops of granular reticulum extend from opposite poles
of the outer circle through connecting intervals where the reticulum appears pinched into multilaminated structures (arrows). x 17,900.
Fig. 9. This interphase cell from a patient with Hodgkin's disease contains: a segment of ER merged with nuclear envelope to form a multilaminar structure
at the upper left (short arrow); a circular profile of multilaminar ER surrounding lucent material, presumably lipid (lower center), and a segment of ER which
contacts mitochondria (inset, long arrow) and forms a multilaminar structure at a point of contact. Profiles of ER also abut at their termination on nuclear
envelope and mitochondria. x 23,800; inset, x 53,200.
Fig. 10. A mitotic plasma cell from a Hodgkin tumor contains segments of multilaminated ER (arrows) one of which is enlarged in the inset. This aberration
appears confined to the ER nearest the abnormally clumped chromosomal mass. x 17,000; inset, x 30,000.
1720
CANCERRESEARCHVOL. 36
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CANCERRESEARCHVOL. 36
Downloaded from cancerres.aacrjournals.org on June 17, 2017. © 1976 American Association for Cancer Research.
Multilaminar Endoplasmic Reticulum and Abnormal Mitosis in
Hodgkin Tumor Cells
Richard T. Parmley, Samuel S. Spicer and Abbott J. Garvin
Cancer Res 1976;36:1717-1724.
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