516
LYMPHOID
HYPERPLASIA
OF
THE
APPENDIX
Clinical
Study
By ALFRED
A.
NATHANS, M.D., HYMAN MERENSTEIN,M.D.,
ANt)SAMUEL S. BROWN, M.D. Brooklyn
LTHOUGH
lymphoid
hyperplasia
of
the
appendix
is
a
frequently
encountered
pediatric entity, the standard texts and the literature treat with it sparsely and
emphasize
principally
its
role
in
the
pathogenesis
of
acute
appendicitis.
The
condition,
once diagnosed, is often entertained as a benign disturbance, transient in character with
subsequent
return
of the
appendix
to its normal
state.
This
misconception
on
the
part
of
the physician, with his associated sense of complacency once the diagnosis of lymphoid
hyperplasia of the appendix is made, is to be brought to his attention. Bohrod1 quotes
the late Dr. Brennemann as having regretted describing this syndrome ‘‘since there
were
times
when
clinicians
having
made
that
diagnosis,
neglected
to watch
for
the
de-velopment of a true infective appendicitis.”
The
purpose
of
this
paper
is to focus
attention
on
the
existence
of
this
condition,
to
point out that it is not always a benign self-limiting disease, and to describe its clinical
features.
METHOD
This study consists of an analysis of the clinical history, the physical findings, and the histologic
examination of the removed appendix in 198 cases in which a microscopic diagnosis of lymphoid
hyperplasia of the appendix was made either as the sole diagnosis or in those cases where lymphoid hyperplasia represented an appreciable part of the microscopic picture. The pathologic diagnosis was
based on the presence of many large lymphoid follicles with large active germinal centers (see
Fig. 3).
FnmINGs
In 196 of these cases a preoperative diagnosis of acute appendicitis had been made. One case, an
ectopic pregnancy, had coincidental removal of the appendix. Another appendix was removed during
TABLE 1
AGE DISTRIBUTION
Birth IF 15+ 20± 2H- 30± 4f- 4(;f. 5#{176}4.
5yr. 10 yr. 15 yr. 20 yr. 25 yr. 30 yr. 35 yr. 40 yr. 45 yr. 50 yr. 55 yr. 60 yr. 65 yr. 70 yr.
36 84 43 14 8 3 3 4 2 0 0 0 0 1
l8.2%) (42.4%) (21.2%) (7.1%) (4.1%) (1.5%) (1.5%) (2%) (1%) (O..S)
a herniorrhaphy because of its presence in the hernial sac. There were 97 males and 101 females. The youngest patient was 28 mo. and the oldest 68 yr. The average age was 1 1.3 yr. The age distribution is indicated in table 1.
Initial Symptoms: In 177 (89.4%) of the patients the initial symptom was pain alone. Pain accompanied by vomiting, as an initial symptom, was present in 8 cases and pain associated with
From the Departments of Pediatrics and Pathology, The Jewish Hospital of Brooklyn, Brooklyn.
119(60.1%) 54(27.3%) 17 (8.6%)
None 1+ 2+ 3+ 4+
5(2.5%) 3(1.5%)
TABLE 7
LYMPHOCYTE COUNTS
20% to 30% 1
30%to 40% 5
40%to 50% 1
50%to 60% 14
60% to 70% 41
70% to 80% 57
80%to 90%
90% to 100%
46
20
-Lymph. Counts No.ofCases
0 tolO% 26
10% to 20% 50
20% to 30% 56
30% to 40% 30
40%to 50% 9
50%to 60% 3
60%to 70% 1
70%to 80% 1
80%to 90% 0
90%tolOO%
0
TABLE 2
SPASM
TABLE 3
RIGIDITY
None 1+ 2+ 3+ 4+
178(89.9%) 7(3.5%) 7(3.5%) 4(2%) 2(1%)
nausea and vomiting occurred in one case. In only 10 cases was pain absent initially. In this group
there were 6 cases of initial vomiting and nausea, 2 cases of nausea and one of vomiting. The only
symptomless patient had the appendix removed during a herniorrhaphy.
Character of the Pain: In 161 of the cases (81.3%
)
the pain was noncolicky. Thirty-six hadcolicky pain. In 25 patier’ts the pain was severe, and in 172 the pain was slight to moderate.
Incidence of Other Symptoms: Nausea occurred in 130 (66%) of the patients and vomiting in
105 (53%
)
. Fifteen had diarrhea and 5 were constipated. Previous similar attacks occurred in 26cases (13%).
Tenderness: Direct abdominal tenderness of varying degree characterized all of the cases except
the one previously mentioned. In 185 (92.4%) there was tenderness in the right lower quadrant, and in 12 cases the tenderness was generalized. Fifty-three patients (26.7%) had rebound
tender-ness. The tenderness was severe in 8 instances and mild to moderate in 179.
Spasm and Rigidity: The frequency of spasm and rigidity and their relative degree is indicated in tables 2 and 3.
TABLE 4
ADMISSION TEMPERATURES
37.0#{176}C. 37.0#{176}+ 37.8#{176}+ 38.3#{176}+ 38.9#{176}+ 39.4#{176}+
orless to37.8#{176} to38.3#{176} to38.9#{176} to39.4#{176} to 40.00
16 71 56 28 10 17
TABLE 5
TOTAl. WHITE COUNTS
No. of
White Count Cases
Below 6,000 9
6,000to 9,000 54
9,000tol2,000 33 12,000tolS,000 46 15,000tol8,000 22 18,000to2l,000 21 21,000to23,000 7 Above23,000 13 TABLE 6 POLYMORPHONUCLEAR COUNTS No. of
Rectal Examinations: In 170 of the patients rectal examination was either not done or was not charted. Twenty-three patients exhibited tenderness to the examining finger on the right side, 2 were tender anteriorly, and 3 were tender on both right and left sides.
Signs of Upper Respiratory Infection: Fifty (25%) of the patients had evidence of upper respira-tory infection. These signs were for the most part reddening of the nasal and pharyngeal mucosae.
Temperature on Admission: The distribution of the admission temperature is shown in table 4.
The average admission temperature was 38.0#{176}C.
White Blood Cell Counts: In 13 cases the leucocyte counts were uncharted. The lowest count was 3,750 and the highest 35,000. The distribution is indicated in table 5.
Polymorphonuclear and Lymphocytic Leucocytes: The lowest polymorphonuclear count was 26%
and the highest 100%. The distribution of these cell counts is shown in table 6. The distribution of the lymphocyte counts is shown in table 7.
Sedimentation Rates: Unfortunately, sedimentation rates were performed in only 13 cases. Two
were normal and 1 1 were elevated.
Pathologic Diagnosis: In 158 (80%) of the cases lymphoid hyperplasia was present as the sole
lesion. In the remainder, this condition was associated with or was the cause of a variety of other
pathologic conditions. These are listed as follows:
Pathology No. of Cases
Enlarged Mesenteric Nodes 76
Lymphoid Hyperplasia and Acute Appendicitis 21
Lymphoid Hyperplasia and Acute Suppurative Appendicitis 5
Lymphoid Hyperplasia plus Pen-appendicitis 4
Lymphoid Hyperplasia and Subacute Appendicitis 2
Lymphoid Hyperplasia and Acute Appendicitis with Fecolith 2 Lymphoid Hyperplasia and Gangrenous Appendix with Perforation 1 Lymphoid Hyperplasia and Acute Suppurative Gangrenous Appendix 1
Lymphoid Hyperplasia and Oxyuris 2
Lymphoid Hyperplasia and Ovarian Teratoma 1
Lymphoid Hyperplasia and Parovarian Cyst 1
DISCUSSION
The amount of lymphoid tissue in the appendix varies with age. Hwang and
Krumh-haar2 studied the appendices in 300 cases of violent death at different ages. They found
that the percentage of lymphoid tissue and its absolute weight are greatest in the first
decade of life and thereafter diminishes steadily with advancing age.
In this series of 198 cases of lymphoid hyperplasia 60.6% occurred in the first decade
of life. This indicates that the propensity for development of appendiceal symptoms due
to lymphoid hyperplasia is greatest during the time when the amount of appendiceal
lymphoid tissue is at its maximum. In earlier studies on the pathogenesis of acute
appen-dicitis various authors tried to implicate lymphoid hyperplasia as an important etiologic
factor. They were, however, unable to reconcile the fact that lymphoid hyperplasia was
at its maximum in the first decade of life, while the greatest incidence of acute
appen-dicitis occurred in the second decade. This paradox was resolved by Bohrod1 by
ana-tomic study of the appendix. The appendix of the newborn is almost devoid of lymphoid
tissue (see Fig. 1) .
As
the
child
grows
the
lymphoid
tissue
increases
progressively
until
at
about
puberty
(see
Fig.
2) .At
this
time
the
muscularis
increases
in thickness to aconsiderable degree causing the lumen of the appendix to become appreciably narrowed.
-.-. ...
. .
. - -I
‘
,i
LYMPHOID
HYPERPLASIA
OF
THE
APPENDIX
enough to obliterate the lumen and the train of events leading to acute appendicitis is
initiated (see Fig. 4).
The lability of the lymphatic system and its ready response to a wide variety of stimuli,
especially infection, is well known. Abdominal symptoms suggestive of and frequently
in-distinguishable from acute appendicitis occur in association with upper respiratory
infec-tions.. Varicella, oxyuriasis and perhaps a high fat diet may evoke a lymphoid response
in the appendix. Of considerable clinical interest is the appendiceal syndrome in
pre-eruptive rubeola. The removed appendix in addition to the lymphoid hyperplasia exhibits
the Warthin-Finkeldey cell that enables the pathologist to predict the occurrence of
FIG. 1. Appendix of newborn infant (>< 16). Note thinness of wall and almost complete absence of lymph follicles. Lumen is relatively wide.
rubeola. In 1950 Raftery, Trafas and McClured reported a 5% incidence of Histoplasma
capsulatum in an unselected series of 2,135 cases in which appendectomy had been
per-formed. In their series, 30 cases of mescnteric adenitis were reported to have had a 43%
incidence of histoplasmosis. In the present authors’ series it was not possible to identify
any structures resembling Histoplasma capsulatum on the routine hematoxylin and eosin
stained section. A recent study7 of 100 appendices employing special staining and special cultural technics failed to show any Histoplasma capsulatum in any of the appendices,
although these cases occurred in a presumably endemic area. Further study
of
1,307appendices stained with hematoxylin and eosin were negative for this organism.
The clinical picture of lymphoid hyperplasia of the appendix is one which is hardly
distinguishable from that of acute appendicitis. The patient is usually a child below the
age of 1 5 years. Abdominal pain of varying degree is generally the first complaint. This
is soon followed
by
nausea and vomiting. The temperature is usually below 38.1#{176}C. The520
A.
A.
NATHANS,
H.
MERENSTEIN
AND
S.
S.BROWN
4)51
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Pain 89% 95%
Nausea 66% 85%
Right Lower Quadrant Tenderness 92% 99%
Spasm 46% Not reported
Rigidity 10% 68%
Rebound 22% 22%
Av. Temperature 38.0#{176}C. 38.3#{176}C.
WBC 3,700 to 35,000
(Av. 12,900)
3,100 to 60,000 (Av. 16,700)
Polys. 74% (av.) Not reported
In both series pain is an outstanding complaint. Nausea is common to both. Right
lower quadrant tenderness is present in over 90% of the cases in each series. Ridity
is much less prevalent in lymphoid hyperplasia ( 10% ) as compared to acute
appen-dicitis (68% ) , but it is obvious that this cannot be used as a differentiating factor in the
-...
#{149}..-,‘
- - - - - -
-
-Fic. 4. Lymphoid hyperplasia and acute appendicitis
(x
16). Microscopic features are similar to those in Fig. 3. Inflammatory reaction is seen on higher magnification in Figs. 5 and 6.LYMPHOID
HYPERPLASIA
OF
THE
APPENDIX
Varying degrees of tenderness, most often in the right lower quadrant, may be elicited.
Rigidity is mostly not present, but some degree of spasm of the right rectus muscle may
be elicited. In this study 40% of the patients were noted to have spasm. The authors
feel that spasm is present much more frequently, and often can only be detected when
comparing the difference in resistance of the right and left rectus muscles on very
super-ficial palpation. Somewhat deeper palpation will also elicit some tenderness on the right
side.
In an attempt to evaluate the significance of the data in arriving at a differential
diag-nosis between lymphoid hyperplasia of the appendix and acute appendicitis the authors
have compared these cases with Norris’8 series of
1,000
cases of acute appendicitis inchildren.
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- .4-LYMPHOID
HYPERPLASIA
OF
THE
APPENDIX
523
individual case. The presence or
abea#{231}ef a
leucocytosis
or polynucleosis
is also
of little
help. The frequency with which a lymphoid hyperplasia progresses to an acute
appen-dicitis, 18% in this series, tends to further complicate the picture. Although there is no
certain way in which to differentiate lymhoid hyperplasia of the appendix from acute
appendicitis, in the authors’ experience, careful observation of the patient every 6 to 12
hours
has
been
helpful
in
avoiding
operation
in
many
cases
and
also
in
bringing
to
earlier surgery those cases which have developed an acute appendicitis. Perhaps the most
important indication for operation is any increase in the local signs, such as spasm or
tenderness.
SUM MARY
One hundred ninety-eight cases of lymphoid hyperplasia of the appendix, some of
which had other associated pathology, have been analyzed.
Comparison has been made with an analogous series of acute appendicitis in children.
There is no precise differential diagnosis between acute appendicitis and lymphoid
hyperplasia of the appendix. Each case has to be watched carefully, and any increase
in
local signs is an indication for surgery.
Lymphoid hyperplasia is frequently the precursor of acute appendicitis.
Ri:FERE NCES
I. Bohrod, M. G., Pathogenesis of acute appendicitis, Am. J. Clin. Path. 16:752, 1946.
2. Hwang, J. M. S., and Krumbhaar, E. B., Amount of lymphoid tissue of human appendix and its
weight at different age periods, Am. J. M. Sc. 199:75, 19-40.
3. Brennemann, J., Abdominal pain in throat infections in children and appendicitis, J.A.M.A.
89:2183, 1927.
4. Lowenstein, P., Respiratory diseases that mimic appendicitis, J. Missouri M. A. 29:563, 1932. 5. Simon, M. A., and Ballon, H. C., Appendiceal lesions in prodromal stage of measles, J. Clin.
Path. 18:796, 1948.
6.
Raftery, A., Trafas, P. C., and McClure, R. D., Histoplasmosis: Common cause of appendicitis and mesenteric adenitis, Ann. Surg. 132:720, 1950.7. Christopherson, W. M., Miller, M. P., and Kotcher, E., Examination of human appendixes for
histoplasma capsulatum, J.A.M.A. 149:1648, 1952.
8. Norris, W. J., Appendicitis in children, West. J. Surg. 54: 183, 1946.
SPANISH ABSTRACT
Hiperplasia Linfoide del Ap#{233}ndice: Estudio Clmnico
A
pesar de Ia frecuencia de Ia hiperplasia linfoide del ap#{233}ndice como entidad pedi#{225}trica, Ia literatura medica trata ocasionalmente y principalmente poi su papel en Ia patogenia de la apendicitis aguda, consider#{225}ndola como un trastorno benigno y transitorio con regresiOn pronto del ap#{233}ndice a su normalidad y ci paciente a su estado previo de salud. Este artIculo trata de analizardicho estado liiperpl#{225}sico linfoide, recalcar que no siempre es benigno y se#{241}alar sus caracterIsticas clInicas bas#{225}ndose en 198 casos con diagnOstico o bien #{252}nicode hiperplasia linfoide o bien con presencia predominante de folIculos linfoideos con centros germinales activos, en el ap#{233}ndice.
En 196 de estos casos se habIa hecho el diagnOstico pre operatorio de apendicitis aguda; en otro cast) el ap#{233}ndice se d)pero por embarazo ectOpico y en el #{252}ltimo durante una hernioplastla. 97 fueron hombres y 10 1 mujeres ; Ia edad promedio fu#{233}de 1 1 .3 aflos, siendo el paciente m#{225}sjoven de 28 meses y ci m#{225}sviejo de 68 aiIos de edad. Las manifestaciones clmnicas se iniciaron con dolor abdominal, 6 n#{225}useas, 6 vOmitos, hiperestesia cut#{225}nea y profunda, defensa muscular, fiebre,
in-fecciOn de vIas respiratorias altas, todos o en parte presentes en grado variable de frecuencia e intensidad; los datos de laboratorio tambi#{233}n fueron variables.
A.
NATHANS,
H.
MERENSTEIN
AND
S.
S. BROWN
Ia vida, lo que indica Ia propensiOn de smntomas apendiculares debidos a hiperplasia linfoide en
edades en que la cantidad de tejido linfoideo apendicular es mayor. El cuadro clInico de Ia
hiperplasia linfoide del ap#{233}ndice es difIcil de diferenciar de Ia apendicitis aguda ; el dolor, signo
predominante, las n#{225}useasy Ia hiperestesia de Ia fosa iliaca derecha son comunes a ambos ; los
dem#{225}ssignos y smntomas no inclinan a uno u otro diagnOstico por lo que los autores recomiendan
Ia observaciOn cuidadosa del paciente cada 6 o 12 horas a fin de evitar operaciones innecesarias 0
realizar #{233}stasm#{225}astempranamente si asI conviene, en particular cuando hay un aumento en Ia intensidad de las manifestaciones locales. Para ellos la hiperplasia linfoide es con frecuencia el antecedente de
Ia apendicitis aguda.