CYSTADENOMA L Y M P H O M A T O S I S *
A. W. FRESHMAN AND STANLEY K. KURLAND
From the Laboratory of Pathology of the Mercy Hospital, Denver, Colorado
Since 1910, when Albrecht and Arzt published a report of two
cases in which an unusual tumor was removed from the region
of the parotid gland, quite a number of similar accounts have
appeared in the literature from time to time. A total of fiftyfour cases are found in the bibliography emanating from foreign
and domestic periodicals. In 1933 Kraissl and Stout 1 reviewed
the literature and cited nineteen cases reported by various
authors, the first being dated 1898. In 1935 Carmichael, Davie
and Stewart 2 reviewed the literature and brought the total
number to forty-one. It is difficult to estimate exactly how
many of these tumors bore the title of branchiogenic cysts because
of the conception of many that cystadenoma lymphomatosum
is of branchiogenic origin. Examples of this are new growths
reported by Hildebrandt 13a and Sultan,13 where the former described a neoplasm along with twenty cysts and fistulas of the
neck, all of which were considered of branchiogenic origin. Sultan included his own among twenty-two parotid cysts.
Since 1935, when the review by Carmichael, Davie and Stewart
appeared, several additional cases have been reported. Wood,3
in 1935, described three, all of which occurred in males, 37, 48
and 71 years of age. These tumors were approximately of the
same size and shape and were well encapsulated. Hall4 in the
same year reported one in a 48 year old male. In this instance
the tumor was of one year's duration and was both hard and
tender. In 1937 Harris 5 published a report of two tumors of this
type; both were in elderly individuals and the relation to the
* Read before the Colorado Society of Clinical Pathologists, February 19,
1938.
Received for publication February 25th, 1938.
422
CYSTADENOMA
LYMPHOMATOSUM
423
parotid gland was practically identical to others recorded in
the literature. It is a singular fact that out of all of these growths
only two, as mentioned by Carmichael et al., recurred after
surgical removal.
REPORT OF CASE
The patient was a white male aged 63, who, a year ago, noticed a swelling in
the neck along the anterior edge of the superior portion of the left sternocleido-mastoid muscle. The swelling was approximately the size of a lead pencil
in thickness and 4 cm. in length, not painful, but because of the gradual increase
in size a physician was consulted. Upon physical examination, a mass along
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FIG.
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1. HEMISECTION OF TUMOR ILLUSTRATING NODULARITY AND CYSTIC
APPEARANCE OF SECTION SURFACE
the anterior margin of the left sterno-cleido-mastoid muscle was seen which
was not attached to the surrounding tissue. It was soft and fluctuant and
drained a brown serous material. The tumor was removed by Doctor W. M.
Greig by blunt dissection. No difficulty was experienced in separating the mass
from its environment.
Gross specimen. Examination of the growth revealed a mass measuring
4 x 3 x 1 cm., resembling a pecan in shape, firm in consistency. The tissue is
light gray to dark gray in color and somewhat nodular in outline. Surrounding
the mass is a fibrous capsule. At one pole is a thin-walled cyst 3 mm. in diameter. On cut section, the surface is granular in appearance and varies from
light to dark gray in color. Scattered through the tissues are several small
cystic areas which exude cheesy material on pressure.
424
A. W . FRESHMAN AND S. K.
KURLAND
Histologic findings. The capsule consists of fibrillary connective tissue, continuous with fibrous septa found throughout the mass. Between the septa are
tubular glands supported by a lymphoid stroma. The diameter of the glands
varies from 15 to 500 microns. They are lined by two layers of cells which in
places are growing in papillary formation. The basal layer is formed by a
tall cylindrical cell whose nucleus lies near the basement membrane. Alternating with the basal layer is a shorter cylindrical cell that borders on the
FIG. 2. PHOTOMICROGRAPH OF TUMOK TO SHOW GENERAL TOPOGRAPHY. T H E
CYSTS ARE CLEARLY SEEN. T H E DARK AREAS REPRESENT THE LYMPHOID
STROMA
lumen. The nuclei are large, round and granular and each has a distinct nucleolus. Between the cylindrical epithelium are secretory capillaries that extend along the length of the cells to widen as the lumen is approached. Stained
with Mallory's aniline blue-orange G-fuchsin, the capillaries are shown to be
occupied by a homogenous deep purple red substance. The tubular glands
contain an amorphous material. The stroma is lymphadenoid in type with an
occasional germinal center.
CYSTADENOMA
LYMPHOMATOSUM
425
The purpose of this paper is not to attempt a recapitulation
of the material reviewed by Carmichael, Davie and Stewart,
or Kraissl and Stout, but to bring up to date the literature of
this rare tumor and endeavor to clarify some of the conceptions
regarding its origin.
This tumor first attracted attention in 1898 when Hildebrandt
discovered a case which he considered to be closely related to
F I G . 3. L o w
P O W E R P H O T O M I C R O G R A P H OF T U M O R TO S H O W T H E
STROMA B E N E A T H T H E G L A N D U L A R
LYMPHOID
EPITHELIUM
branchiogenic cysts and therefore of branchiogenic origin. In
the same year Sultan found one of these tumors and interpreted
it merely as one form of parotid cyst. Lecene and Morestin
also thought that the tumors that they each saw originated from
out-pouching of pharyngeal ectoderm or branchial pouches.
Next in line, according to the date of discovery, came Albrecht
and Arzt,6 who ascribed the origin of the tumor to misplaced
426
A. W. FRESHMAN AND S. K. KTJRLAND
epithelial tissue from the entoderm and mesenchymal germ
layers or to the inclusion of epithelium of the entoderm of the
oral cavity into lymph nodes. Glass took a similar view.
Ribbert, 7 however, interpreted Glass' explanation in the
following way: "The lymphoid tissue and parotid lobule grew
into one another and the mixed portion became separated from
the parotid gland." In so far as this process takes place in
P I G . 4.
H I G H P O W E R P H O T O M I C R O G R A P H O F T U M O R TO S H O W T H E S E C R E T O R Y
CAPILLARIES
BETWEEN
THE
CYLINDRICAL
CELLS
LINING
THE
GLANDS
the development of the branchial cleft, Glass prefers to call the
tumor a branchiogenic eystadeno-lymphoma,
Neumeister at the same time said practically the identical
thing but left the question open as to whether the entodermal
and mesenchymal tissue were misplaced at the same time and
a lymph node developed from the mesenchymal tissue at a later
date, or whether the entodermal epithelium arrived in a site from
CYSTADENOMA
LYMPHOMATOSUM
427
which lymphoid tissue would later develop. Askanazy believed
the most probable origin to be from the branchial clefts. He
thought that the cells closely resembled the eosinophilic cells
of the parathyroid gland. Then according to Carmichael several
investigators, including Nicholson, Menetrier, Peyron, Surmount
and Stober, thought that the tumor might have arisen from
preparotid lymph nodes, in which Neisse had been able to demonstrate scattered acini of salivary tissue and in some cases lobules
of salivary tissue which contained excretory ducts. In explaining the presence of these glands, Neisse showed that early
in the development of the human fetus (120 mm.) there are
lymph nodes in the parotid and submaxillary glands which have
in their substance salivary tissue. At a later date these glands
become the preparotid lymph nodes, at which time they are
encapsulated and free from the parotid. It is entirely possible
that when these lymph nodes moved away from the parotid gland
they might still have retained portions of salivary tissue in
their substance for varying lengths of time. At times these
salivary structures in preparotid lymph nodes have been found
in adult life. The next step in the supposition would be the
development of tumors from these gland structures.
In 1929 Warthin 8 reported two cases. Because of a similarity
that he saw between the epithelium of the tumor and the cells
lining the Eustachian tubes, he thought that the former could
have originated from a dystopia of the pharyngeal ectoderm. In
the following year Wendel9 substantiated Warthin's views.
In 1931 Hamperl advanced the observation that as an individual grows older there is a type of cell found in salivary glands
which resembles the epithelial structure of the tumor more
closely than it does the normal epithelium of salivary glands.
These cells were described by Schaffer (1897) and then studied
by Zimmermann10 and termed pyknocytes. In 1932 Jaff611
reported a case. He felt, after careful study, that the epithelial
cells of the tumor corresponded in every way with the onkocytes
of Hamperl. Because of this Jaffe' proposed the name onkocytoma. His explanation of the lymphoid tissue was that it
was the remnant of a lymph node and the presence of the germinal
428
A. W. FRESHMAN AND S. K. KTJRLAND
centers was in answer to the greater resorptive demands of the
tumor because of its secretory products. This term, onkocytoma,
has met with opposition on the part of Harris who thinks, and
we believe rightly, that because of the fact that onkocytes are
an evidence of senility and are found only in individuals at least
past twenty years of age, the term does not explain the presence
of this tumor in one case of Albrecht and Arzt, which was only
twelve years of age, and in the case of Cunningham12 which was
sixteen years old. The other objection of Harris, which could
probably be overlooked, is that the term onkocytoma would
only add another word to an already overburdened medical
vocabulary.
Peyron removed two cystic structures from the parotid region.
On microscopic examination, the walls were found to contain
Hassall's corpuscles. From this observation and Askanazy's
description, one would have to bear in mind the possibility that
these tumors might arise from any of the branchial clefts. In
this process the supporting structure of the cystic tumor would
thus be characteristic of the structures which normally arise
from the branchial clefts such as the parathyroid gland and
the thymus.
Sternburg mentions two completely opposite views as to the
possible origin of gland-like structures in lymph nodes: one view
is that they arise by metaplasia from the endothelial lining of
the lymph vessels; the other that they arise from embryonal
rests. Still another hypothesis is that the glandular epithelium
is swept into the lymph nodes from the surrounding structures.
One thing in common to all of these theories, however, is that
the glands, once they are in the lymph nodes, may give rise to
papillary cystadenoma lymphomatosum.
In the publication of Kraissl and Stout the authors tried to
explain the origin of the tumor by what they called an orbital
inclusion. In order to justify their hypothesis, these investigators reviewed the development of the orbital glands in some
members of the carnivora. During this investigation they found
that there was a formation of a sulcus from the oral cavity,
which finally develops into the adult parotid gland. As has
CYSTADENOMA
LYMPHOMATOSUM
429
been reported from time to time, tubular structures have been
found in the region of the parotid gland. These were thought
to be a parotid anlage, as shown by Weishaupt, and were therefore thought capable of developing into the cystic structures
which were occasionally found in the region of the parotid gland.
Following this train of thought, Kraissl and Stout then discovered that early investigators in the study of the development
of the salivary gland had found a tubular structure lined by
epithelium and surrounded by mesenchyme in the region of the
parotid gland but not connected with it. They gave this structure the name of orbital inclusion. They pointed out that as
the embryo increases in size the parotid gland grows larger and
larger and finally lies in close contact with the orbital inclusion.
Just exactly what happens to these orbital inclusions in humans
has never been determined, but it is only fair to assume that
a closed vestigial duct lined by epithelial cells derived from oral
ectoderm might at times develop into cystic structures. This
supposition becomes more plausible when it is learned that
Weishaupt had seen dilatation of one of these structures under
the microscope. By this explanation both the lymphoid and
epithelial elements of the tumor in question are accounted for.
In evaluating this explanation, however, we are at a loss to
explain the position of the tumor in our case, which was at the
anterior border of the superior portion of the sterno-cleidomastoid muscle, while the orbital inclusion is situated in an
anterior position in relation to the parotid gland.
SUMMAKY
A case of cystadenoma lymphomatosum is presented. That
it arises from the branchial pouches seems the most probable
explanation after all the evidence is taken into consideration.
From the fact that some investigators saw what, to them, resembled thymic tissue, and others saw tissues closely resembling
acidophylic cells of the parothyroid gland, it would be safe to
assume that, at least in two cases, there is some reason to adduce
the origin of cystadenoma lymphomatosum from branchial
pouches; the particular pouch from which the tumor develops
not being the same in every instance.
430
A. W . FRESHMAN AND S. K. KTJRLAND
We are indebted to Dr. W. M. Greig for his permission in reporting this case
and to Prof. W. C. Johnson, of the University of Colorado Medical School, for
his kindly counsel.
REFERENCES
(1) KRASSL AND STOUT: Orbital inclusion cysts and cysto-adenomas of the
parotid salivary gland.
Archives of Surgery 26: 485-499. 1933.
(2) CABMICHAEL, R., DAVIE, T. B., AND STEWABT, M. J.: Adenolymphoma of
(3)
(4)
(5)
(6)
(7)
(8)
the salivary glands. Jour, of Pathology and Bacteriology 40:
601. 1935.
WOOD, D . H.: Papillary cystadenoma lymphomatosum of the parotid
gland. Am. Jour, of Pathology 11: 889. 1935.
HALL, E. M.: Adenolymphoma (orbital inclusion adenoma) of the parotid
gland. Archives of Path. 19: 756. 1935.
HAEEIS, P . N.: Adenocystoma lymphomatosum of the salivary glands.
*
Am. Jour, of Path. 13: 81. January, 1937.
HENKE, F., AND LUBAESCH, 0 . : Handbuch der Spez. Path. Anat. Hist.,
' Bd., Teil T : 333. 1926.
RIBBERT, H.: Geschwulstlehre fur Aerzte and Studierende. p. 603.
1914.
WAETHIN, A. S.: Papillary cystadenoma lymphomatosum: A rare teratoid of the parotid region. Jour, of Cancer Research 13: 116-125.
1929.
(9) WENDEL, AUGUST, J E . : Papillary cystadenoma lymphomatosum; A rare
teratoid of the submaxillary region. Jour, of Cancer Research
14: 123. 1929.
(10) ZIMMEEMANN, K. W.: Handbuch der Mikr. Anat. of MoUendorff, Bd. V,
Teil I p. 128. 1927.
(11) JAPPE, R. N.: Adenolymphoma (onkocytoma) of the parotid gland. Am.
Jour, of Cancer 16: 1415-1423. November, 1932.
(12) CUNNINGHAM, W. P . : Branchial cysts of the parotid glands. Annals of
Surgery 90: 114. 1929.
(13) SUTTON: Cited by Krassl and Stout.
(13a) WILDEBEANDT: cited by Krassl and Stout.