elevation of temperature may be noted. When the disease is firmly
established the fever is a marked feature. It may be of an irregular
hectic type, with morning remissions--this is, I think, the most
common--or it may be continuous, with an evening exacerbation. More
rarely there are ague-like paroxysms, with rigor, hot and sweating
stage (Case I.), and during these the fever may rise to 104° and glands
may become more swollen. The range is never very great, rarely
exceeding 103°.
Digestive System.--Difficulty in swallowing may result from the
enlargement of the lymph-follicles at the base of the lungs and of the
tonsils and pharyngeal adenoid tissue. This may be so great as to
necessitate feeding with a tube. There may be early gastric trouble
when the mesenteric and abdominal glands are first affected--dyspepsia,
nausea, and vomiting. Secondary tumors of the stomach are not common.
The loss of appetite and feeble digestion, prominent symptoms in so
many cases, are largely due to the anæmia.
Diarrhoea is not met with so frequently as in leukæmia; it may come on
toward the close and carry off the patient. New growths in the
intestine may produce severe attacks and sometimes hemorrhage.
Obstinate constipation may be the result of pressure.
The liver is rarely enlarged, and there are not often hepatic symptoms.
The new growths do not produce irregularity in the enlargement.
Pressure of enlarged glands at the hilus may cause jaundice and
ascites.
Genito-urinary System.--The urine is usually clear and presents no
striking changes. Reaction acid; albumen may be present. The testicles
may be the seat of secondary growths.
Nervous System.--Headache, giddiness, and noises in the ear are common,
and are dependent upon the anæmic state. Southey[153] has noticed
delirium and coma in some cases.
[Footnote 153: _Barth. Hospital Reports_, vol. ix.]
Special Senses.--Deafness is not uncommon, caused by pressure of the
large glands in the neck or by the growth of adenoid tissue about the
pharynx, closing the Eustachian tube. Inequality of the pupils has been
noted, from pressure of a gland on the sympathetic. Retinal hemorrhages
are uncommon.
Skin.--There may be definite secondary lymphatic tumors apart from
direct infiltration by continuity.[154] Bronzing may occur (Case IV.).
Papular rashes may be very troublesome. Subcutaneous oedema of feet and
eyelids may occur when the anæmia is very profound.
[Footnote 154: Greenfield, _Path. Soc._, xxvii.]
{926} MORBID ANATOMY.--The Lymph-glands.--Virchow made the division
into the hard and soft varieties, the difference depending on the
proportion between the cells and the adenoid reticulum. Where the cells
predominate the growth is soft--may be semi-fluctuating--but when the
stroma is much hypertrophied the glands are hard, firm, and feel like
organs in a state of chronic induration. The great majority of the
cases are of the soft variety. When first affected the glands may be
hard, and as the development proceeds become less consistent; but there
are cases in which they maintain their firmness and solidity
throughout.
When examined in the early stage the individual glands are more or less
isolated, perhaps not larger than almonds or walnuts, adherent by their
capsules, but readily separated and movable. Even when death has been
caused, some groups may generally be found in this state, as it is rare
for all to be equally developed. When advanced, the glands fuse
together, distinction is lost between them, and the bunch may form a
large tumor the size of an orange or even a cocoanut. When of moderate
size the section may show normal-looking gland-substance, and the
distinction between cortical and medullary portions may be well
preserved. When much enlarged the section has usually a grayish-white
appearance, smooth, and of variable consistence, either firm and dry or
soft and juicy. The vascularity is not often marked, and extravasation
and areas of congestion are not seen so frequently as in some
actively-growing neoplasms of the lymph-glands.
The capsules are thinned, and may disappear in the fusion of contiguous
glands, traces being seen on the section as strands of connective
tissue. About large groups the capsular tissues may be much condensed,
forming a very firm investment. The growth may perforate the capsule
and invade contiguous parts--muscle, skin, or the solid organs.
The chief changes which the tumors may undergo are fibroid induration,
suppuration, and caseation. The gradual increase of the stroma may give
a high degree of density, and the gland on section may present a
smooth, glistening appearance. Suppuration is most frequently seen when
the growth reaches the skin; it may point and an abscess discharge. In
the deep glands the formation of pus is not often met with. Caseation
is extremely rare. Hemorrhages may take place from rupture of the
thin-walled vessels.
The chief characters of the lesions in the different groups have been
dealt with in the section on Symptoms. The superficial glands are most
often attacked, and the cervical or axillary may form huge masses
before there are any signs of internal trouble. The superficial and
deep cervical groups may be uniformly affected, the muscles lifted and
wasted, and vessels and trachea surrounded by a solid mass. Sometimes
all distinction between the tissues is lost, and the carotids run in
the midst of the new growth, which may extend far out beneath the
trapezius and down into the chest or over the clavicle on to the
outside. When the neck is not primarily affected the groups are more
isolated, and can be traced as chains of enlarged glands along the
trachea and the carotids continuous with those of the axillæ and
mediastinum.
The axillary group is next involved in the order of frequency, and the
masses when large grow out under the pectorals and back beneath the
scapulæ and high into the fossa, compressing the axillary vessels and
causing great swelling of the arm. In Case VII. the growth infiltrated
the neighboring muscles and eroded the humerus and neck of the scapula,
perforated the blade, and exuded on its outer surface. Though an
enormous mass, the vessels were not infiltrated, and only moderately
compressed. The inguinal glands when very large may obstruct the
femoral artery and vein, and seriously interfere with the circulation
in the legs.
{927} Of the internal groups, those of the thorax are most often
affected, and we may have the chain in the posterior mediastinum along
the aorta and the sides of the trachea and gullet, and along them pass
into the neck (Case V.), or the bronchial group may be primarily
attacked, with the formation of a great bunch at the fork and numerous
small masses along each bronchus at the root of the lung, which may be
extensively involved (Case VI.); or those of the anterior mediastinum
beneath the sternum may be affected, with the production of large
masses extending over the pericardium and passing even to the
diaphragm. In these cases bulging of the sternum and ribs, with erosion
and perforation, may occur. In Case II. the sternum was completely
destroyed to a level with the fourth rib. The heart may be pushed aside
and the aorta and its branches completely surrounded by growths (Cases
II. and VI.). It is remarkable in these cases that great vessels do not
suffer more from compression. When the abdominal glands are involved,
the retro-peritoneal are most frequently enlarged, and form a
continuous chain from the diaphragm to the internal rings on either
side of the aorta and its branches, extending into the pelvis. Pressure
effects are not common, but they may compress the ureter, causing
hydronephrosis, the sacral and lumbar nerves, the iliac veins, and, as
in the case I mentioned, may adhere to the broad ligaments and uterus
in such a way as to deceive the most skilled gynæcologist. The
mesenteric glands may present slight enlargement, but in my experience
they are but little affected, even when the retro-peritoneal are of
large size. When the glands at the portal fissure are involved they may
compress the vein and duct. Phelps of Chateaugay, N.Y., sent me a
specimen in which the glands of this region formed two huge masses the
size of cocoanuts, and, so far as I could ascertain, they were primary
lympho-adenomatous growths. The possibility of ovarian disease had been
discussed by several consultants.
The chief change is an increase of the cells with or without thickening
of the reticulum. The cells correspond to ordinary lymph-corpuscles;
some may be a little larger, with darker granules and more pronounced
nuclei. Giant cells are frequently met with, more often in the small
glands. I have not seen them in the large soft tumors. In the early
stage there may be simple hyperplasia and the relations of the
lymph-paths are maintained, but when the glands are much developed the
normal arrangement is disturbed and they cannot be injected. The
reticulum varies much; in the very soft form it is expanded and can
scarcely be found; the substance may be semi-diffluent. The firmer the
structure the more evident is it, and in the hard forms the network of
fibres in whose meshes the cells are enclosed can be distinctly seen
and by pencilling very clearly brought out. It is not merely a
thickening of pre-existing fibres, but probably there is a new
development of adenoid tissue. In some cases of advanced fibroid change
very few cells can be seen. The vessels passing to the glands are
sometimes dilated.
Spleen.--In about 75 per cent. this organ is hypertrophied or presents
lymphoid growths (Gowers). The enlargement is not often great, rarely
approximating the colossal size of the leukæmic organ. It is due to
either simple hyperplasia or to the presence of the new growths,
sometimes to both. In the 75 cases of enlarged spleen new growths
occurred in 56 (Gowers). Of the 38 cases in Hutchinson's table, 27
presented the splenic tumors. These are grayish-white bodies, ranging
in size from a small pea to a walnut or larger, scattered irregularly
through the substance, usually rounded in outline, but in some
instances irregularly shaped. They contrast by color strongly with the
red spleen-pulp. The numbers may vary from one or two to many dozens,
the spleen-substance being a mere remnant between them. These masses
often resemble the lymph-glands in appearance and consistence. {928}
They are not encapsulated, but in immediate contact with the
spleen-tissue. They originate from the Malpighian corpuscles, and may
be regarded as the enlarged and developed lymph-elements in the spleen.
The larger ones probably arise from the fusion of several small ones.
When uniform in size and scattered throughout the organ, they may
resemble coarse tubercles, but the absence of any caseation may serve
to distinguish them. Their histological characters are those of the
glands, lymph-corpuscles in a fibrous reticulum; the consistence
depends on the preponderating element.
Amyloid degeneration was found by Gowers in two cases in the growths.
The thymus has been found involved in the mediastinal growths, and is
occasionally affected primarily. The thyroid may be attacked by the
cervical tumors.
The suprarenals may contain secondary growths. In Case VII. both were
extensively involved.
The medulla of the long bones has been found converted into red
lymphoid marrow, and in a few instances into the pyoid variety met with
in leukæmia. It has been found normal in other cases.
Digestive System.--In the mouth and pharynx the lymphatic elements are
very commonly affected when the cervical glands are enlarged, sometimes
independently. The tonsils may form large masses, and with the
follicles at the root of the tongue and at the pharynx produce great
obstruction. Sloughing may occur. In the gullet and stomach secondary
tumors have occasionally been seen. In Case VII. there was a flat
elevated mass at the cardia beginning to ulcerate.
The small intestines may be extensively involved; the glands of Peyer
enlarged and even ulcerated. In Case VII. there were over twenty ulcers
in the jejunum and ileum, ranging in size from a split pea to a bean,
edges elevated and indurated and the bases sloughing. The large
intestines may be secondarily affected, the intertubular adenoid tissue
be greatly developed and compress the crypts of Lieberkühn, and lead to
thickening of the mucosa.
The liver is often enlarged, and presents scattered lymphoid tumors,
rarely larger than a pea, of a white or yellow-white color, and may be
readily mistaken for tubercles. They are most common beneath the
capsule and in the interlobular tissue. A diffuse interacinous growth
may also occur. Cirrhosis has been observed in the vicinity of the
growths, and fatty degeneration.
The pancreas may be the seat of secondary masses.
Genito-urinary System.--The kidneys are very often the seat of new
growths, usually small and of a character similar to those in the
spleen and liver. When the disease is very rapid the tumors may be
large and very vascular. The texture of the kidney is usually soft, and
parenchymatous change is common. The testicles may also be the seat of
adenoid growths; this was the case in one of Hodgkin's patients.
The Respiratory System.--Growths in the trachea are rare. The lungs are
frequently affected, either by the direct invasion at the root from the
bronchial glands (Case V.), or by numerous scattered nodules through
the substance. They develop about the bronchi, and may reach the size
of marbles. Intense bronchitis, oedema, and congestion may be secondary
changes induced by pressure on the bronchi or trachea.
The serous membranes occasionally present lymphoid growths. Pleural
effusion is not uncommon.
The heart presents no very constant changes. When the anæmia is
profound it may be very fatty. It may be compressed by mediastinal
growths, and has been found much atrophied. Lymphoid growths may occur
in it.
The Nervous System.--The brain itself is rarely affected, but growths
have been found in the dura mater. In Case VI. a secondary mass
compressed the spinal cord, as in Hutchinson's case, producing
paraplegia.
{929} The skin may be the seat of adenoid growths, as in Greenfield's
case.[155] The growing tumors may involve it (Case IV.), and ulceration
may occur.
[Footnote 155: _Loc. cit._]
COURSE, DURATION, AND TERMINATION.--Trousseau and other French writers
have divided the disease into different stages--the latent and period
of early development, the period of generalization, and the cachectic
state; but the course of the disease is very variable, and depends much
upon the position of the glandular enlargements, the rapidity of
development of secondary growths, and also the constitutional
peculiarities of the patient. Early and rapid growth in the mediastinal
groups may produce pressure effects, and cause death before any marked
anæmia--much less cachexia or the development of secondary masses in
important organs, as the cord, may prove quickly fatal. In some cases
the glandular enlargement rapidly spreads, and group after group is
involved in the space of a few months; in others there may be
hyperplasia of a single set, as the cervical on one side, for months,
or even years, before the glands on the other side or in other regions
become involved. The most acute cases may run a course in three or four
months, the most chronic in as many years. Periods of quiescence are
not uncommon, and the tumors may not only cease to grow, but actually
diminish, or even disappear in a region, and this without any special
treatment.
The mode of death is commonly by asthenia; cachexia is gradually
developed, the anæmia becomes more profound, and finally, with local or
even general dropsy, the end comes from heart failure. Very frequently
the patient is cut off before grave constitutional disturbance is
established, particularly by asphyxia from the pressure of enlarged
glands on the trachea and bronchi or occlusion of the pharynx.
Hemorrhage and diarrhoea, such common symptoms in leukæmia, are rarely
seen. Coma has been the cause of death in a few cases. Oedema of the
lungs, pneumonia, extensive pleuritic effusions, may hasten, and in
some instances cause, the fatal result.
The DIAGNOSIS is in most cases easy; in others time alone will decide
the true nature of the glandular enlargement. Of the chronic forms of
adenitis which are liable to be confounded, the scrofulous is the most
common. The points to be attended to in the diagnosis are--the age;
scrofulous glands affecting chiefly the young and individuals
presenting other signs of the so-called scrofulous habit, or there may
be a well-marked family history of phthisis. In the question of age,
however, it is to be remembered that there is a condition known as
adult or senile scrofula, in which there may be general enlargement of
the glands. Of all groups the cervical are most frequently involved in
scrofula, and the submaxillary set more often than those of the
anterior and posterior triangles, while in Hodgkin's disease the latter
are usually affected first. The enlargement in scrofula is rapid at
first, and may last for years in a group without extending; the bunches
are often, even when small, welded together, and, most important of
all, they tend to suppurate--a feature scarcely ever seen in true
lymphadenosis. Size is an uncertain criterion. I have seen masses of
scrofulous glands in the neck as large as two fists and without
suppuration. A single large bunch in the neck, particularly if
submaxillary, persisting for over a year or eighteen months without
involvement, however slight, of the glands in the same or the opposite
side or in the axillæ, is almost certainly not malignant lymphoma. On
the other hand, a group of slowly-enlarging glands in the anterior
cervical triangle, with gradual affection of those of the opposite side
of the axillæ, particularly if in a person between twenty and thirty
and becoming anæmic, would render the suspicion of Hodgkin's disease
strongly probable.
In connection with this it may be mentioned that occasionally in acute
{930} phthisis there may be great swelling of the glands, from a growth
of miliary tubercles in them. A case of the kind was admitted into my
wards in the General Hospital, Montreal: a man aged twenty-four, with
great swelling of the cervical glands in both sides, tonsillitis, and
sloughing pharyngitis, irregular fever, and diarrhoea, and for a time
the case was believed to be one of Hodgkin's disease.
PATHOLOGY.--Local benign lymphomata occur, identical in histological
characters with the tumors of Hodgkin's disease, and differing only in
the absence of any tendency to extend in the neighborhood or to
generalize. They are not uncommon about the neck, may grow slowly, and
last for years.
The lymphatic growths of leukæmia are not in any essential particular
different from those of Hodgkin's disease, and the diagnosis rests upon
the examination of the blood. There are, however, certain broad
differences when any considerable number of cases of the two diseases
are compared. Thus the lymphatic element in leukæmia is less
pronounced, the splenic and medullary forms predominate; in Hodgkin's
disease exactly the reverse prevails. It is rare in leukæmia for the
internal glands to be much involved, and patients do not often die from
the pressure effects of the tumors. The hemorrhages so common in
leukæmia, and the diarrhoea, are rare symptoms. The bone-marrow is more
generally affected, and, lastly, the tendency to generalize seems
greater in the growths of Hodgkin's disease.
From other forms of malignant growths in the lymph-glands there may be
difficulty in the diagnosis, and even a microscopical examination may
not serve to make the distinction.
Thus there is a true lympho-sarcoma, a small-celled growth of the
lymph-glands, which must be distinguished, though it is hard in some
cases, from the general lymphadenoma. The distinctions laid down by
some writers, such as a special tendency to attack contiguous parts,
and a more general distribution of the metastatic growths, will not
hold, as we have seen that cases of lymphadenosis or Hodgkin's disease
may attack neighboring structures, and the secondary tumors, though
preferably in lymphatic textures, may occur in every organ. In the
retro-peritoneum, for example, true lympho-sarcoma is not uncommon,
forming large tumors which may press forward the viscera and produce a
very prominent mass in the abdomen. They are not uncommon in children,
and with renal sarcomas make up three-fourths of the abdominal growths
of early life. But they may occur in adults and attain large size,
involving adjacent organs, such as the kidneys, or, as in a case I saw
a short time since, grow into the colon and cause death by gradual
hemorrhage. These are local growths as regards the lymphatic system,
not involving distant glands, and not often, indeed, producing
metastasis.
We may recognize in the lymphatic glands--1st, the local benign growth
which seems nothing more than hypertrophy, lymphadenoma, and which may
persist for years; 2d, a local malignant growth, lympho-sarcoma, which
invades contiguous structures and may be followed by metastasis, but
there is not general involvement of the lymphatic tissues; and 3d,
there is a generalized lymphoma involving groups of glands in
succession, and the adenoid tissue throughout the body, usually
accompanied by anæmia alone, in which case we term it Hodgkin's
disease--sometimes by an excess of colorless corpuscles as well, when
we call the affection lymphatic leukæmia.
PROGNOSIS.--When established sufficiently to make a sure diagnosis, the
prognosis is in the great majority of cases bad; true examples of the
disease rarely if ever recover. A hopeful prognosis may be given in
those cases in which only a few glands are involved, and where there is
any suspicion of a scrofulous habit or where the enlargement has
persisted for years without {931} extending. The presence of profound
anæmia, the existence of swelling in distant groups and in internal
glands, are grave indications. High, irregular fever, rapid growth, and
the development of cachexia are symptoms of the full establishment of
the disease. The physician must not be deceived by intervals of
improvement, with perhaps subsidence of the glandular swelling in
places. Such breaks in the onward progress are not uncommon.
TREATMENT.--When small and localized, the question of the removal of
the glands may be raised. If they persist after appropriate remedies,
and if there is not grave anæmia, and other groups and the spleen are
not affected, excision should certainly be performed. Circumscribed
lymphadenoma, particularly of the neck, may exist for years before the
glands in other regions become involved; and in such cases removal
affords the best guarantee that the disease will not extend.
Local applications are of doubtful benefit. I have never seen any
permanent improvement follow the persistent use of iodine, biniodide of
mercury ointment, or friction with oil. Galvano-puncture has not been
successful, and the same may be said of the various substances injected
into the glands--iodine, arsenic, chromic acid, etc.