T H E AMEBICAN JOURNAL OF CLINICAL PATHOLOGY
Vol. 50, No. 5
Copyright © 1968 by The Williams & VVilkins Co.
Printed in U.S.A.
GRANULAR CELL TUMORS (MYOBLASTOMAS) INVOLVING T H E
BRONCHUS AND SKIN
R E P O R T OF A C A S E
ROBERT W. BUSH, M.D., AND GEORGE L. PLAIN, M.D.
South Bend Medical Foundation and South Bend Clinic, South Bend, Indiana 46601
Granular cell myoblastoma, a tumor of
uncertain histogenesis, is not a rare lesion.
It most frequently involves the tongue, skin,
and subcutaneous tissue, although it has
been observed in nearly every region of the
body. Granular cell myoblastoma involving
the bronchus is unusual. Multiple tumors
involving the bronchus are apparently rare,
there being only three previous reports of
such an occurrence.
Recently we encountered a patient with
multiple granular cell myoblastomas of the
bronchus and of the skin. The case is here
presented as the fourth report of multiple
endobronchial granular
cell myoblastomas.
R E P O R T O F A CASE
The patient, a 38-year-old Negro man,
was initially seen in August 1966- At that
time he complained of cough and fatigue.
The productive cough had been present for
approximately 3 weeks and was not accompanied by fever or chills. Physical examination revealed bilateral rhonchi. The patient
improved with antibiotic therapy, but
roentgenograms of the chest revealed persistence of an area of pneumonia in the lower
lobe of the right lung. He was admitted to
the hospital on October 31, 1966, for further
study.
Past history revealed that he had been
hospitalized in 1965 for right lower lobe
pneumonia. Bronchoscopy at that time revealed a normal appearing larynx, trachea,
carina, and left bronchi. Inflammation of
the mucosa of the bronchus of the lower lobe
of the right lung was observed. Cultures of
bronchial aspirate for bacteria, including myReceived December 6, 1967.
Dr. Bush's present address is Laboratory,
Riverside Methodist, Hospital, Columbus, Ohio
43214.
cobacteria, were negative. Papanicolaou
smears were reported as negative. There was
also a history of multiple skin nodules which
had begun to occur approximately 5 years
before. These enlarged to approximately 2.5
cm. in diameter. They were painless except
for those over the lower back and anal region,
which caused some discomfort.
At the time of physical examination the
patient looked well, was afebrile, and had a
blood pressure of 130/70 and a pulse of 70
per min. Rhonchi were heard bilaterally.
Multiple skin nodules were observed and
thought to be neurofibromas.
A repeat roentgenogram of the chest confirmed persistence of the pneumonia involving the superior segment of the lower
lobe of the right lung. These findings suggested the possibility of a bronchial lesion.
Smears and cultures of sputum were negative for acid-fast bacilli. The red blood cell
count was 4,500,000. The white blood cell
count was 17,700 with the following differential: 67 segmented neutrophils, 2 nonsegmented neutrophils, 22 lymphocytes, 6
monocytes, 2 basophils, and 1 eosinophil.
The hemoglobin was 13.3 Gin, per 100 ml.
Alkaline phosphatase was 13 King-Armstrong units. A Bromsulphalein* dye test,
serum glutamic oxalacetic transaminase,
serum lactic dehydrogenase, serum total
proteins, and protein electrophoresis were
within normal limits. A first strength purified protein derivative tuberculin skin test
was positive.
Bronchoscopy was performed and revealed
a normal appearing trachea, carina, and left
bronchi. The right main bronchus appeared
normal except at the division of the lower
lobe bronchus. In this region there was a
* I-Tynson, Westcott & Dunning, Inc., Baltimore,
Md.
563
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Vol. 50
BUSH AND PLAIN
narrowing of the lumen of approximately
50 to 60 %, due to a bulge in the right lateral
wall. It was impossible to determine whether
this was due to extrinsic pressure or to a
lesion in the submucosa. The mucosa appeared to be intact. A biopsy of the mucosa
in this region was obtained from which a
diagnosis of granular cell myoblastoma of
the bronchus was made.
One week following the bronchoscopic
procedure a right pneumonectomy was performed. Following the surgery, the patient
improved without complications, and at
the present time he is without symptoms.
Pathologic findings. The weight of the right
lung was 4S0 Gm. The pleural surfaces were
translucent, glistening, and wrinkled. Both
the exterior and cut surfaces were mottled
blue-gray to red-gray. Cut surfaces were
relatively dry. All lobes were noncrepitant
and appeared collapsed. The right main
bronchus had been resected near the carina.
The mucosa at the margin of resection was
raised, irregular, and finely papillated. This
area measured S mm. in diameter and did
not appear to narrow the lumen of the
bronchus significantly. Located approxi-
mately 3 cm. from this area was a similar
patch of altered mucosa which measured 12
mm. in diameter. There was considerable
narrowing of the lumen at this region, most
noticeably involving the origin of the
bronchus to the lower lobe. On cut section
the wall of the mainstem bronchus was observed to be irregularly thickened by pale
yellow-gray to gray-white firm tissue. This
tissue surrounded several of the cartilaginous rings and formed three separate masses
(Fig. 1). Two of these masses were associated
with the areas of altered bronchial mucosa.
The distal mass surrounded approximately
60% of the bronchus, causing marked narrowing of the lumen at the origin of the
middle and lower lobe bronchi. The largest
mass measured approximately 2 cm. in
greatest dimension. No other lesions were
observed in the bronchial tree. The pulmonary blood vessels were unremarkable.
Hilar lymph nodes were enlarged, moderately firm, and mottled blue-black to yellowgray. The larger nodes were 2 cm. in diameter.
Microscopically, the altered mucosa of
the right mainstem bronchus consisted of
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FIG. 1. Longitudinal section of right mainstem bronchus. Arrows indicate the
three separate endobronchial granular cell tumors. The lower lobe bronchi are at
the left of the photograph.
F I G . 2 (upper left). Metaplastic bronchial mucosa lines elevated papillary projections containing
numerous granular cells. Hematoxylin and eosin. Reduced 15% from X 15.
F I G . 3 (upper right). Characteristic arrangement of granular cells intermingled with collagen fibers.
Nuclei are round to oval and eccentrically positioned. Hematoxylin and eosin. Reduced 15% from X IGO.
F I G . 4 (lower left). Typical example of peripheral nerve encircled by numerous granular cells. Hematoxylin and eosin. Reduced 15% from X 160.
F I G . 5 (lower right). Granular cells surrounding mucous glands of the bronchial mucosa. Hematoxylin and eosin. Reduced 15% from X 160.
565
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BUSH AND PLAIN
Vol 50
numerous relatively broad, irregular papil- toma has been of considerable interest.
lary projections (Fig. 2). There was moderate Despite its recognition as an entity with
hyperplasia- and metaplasia of the bronchial characteristic histologic features, no agreeepithelium. Immediately beneath the base- ment exists as to the exact nature and
ment membrane were numerous large histogenesis of the lesion. The view that
granular cells with eosinophilic cytoplasm granular cell myoblastoma is a muscle
and eccentrically placed small, oval, dark tumor is no longer widely held. Pearse10
staining nuclei. Nucleoli were evident in found the granules in the cytoplasm to conmany of the nuclei. Mitoses were not ob- 'tain lipid and regarded the tumor as a lipid
served. The cells varied in shape from round granular cell fibroblastoma. Bangle2 made a
to oval to elongated straplike cells. These morphologic and histochemical study of
cells extended into the deeper connective granular cell myoblastoma and also contissue of the wall of the bronchus and inter- cluded that the tumor cells contained lipid.
mingled with the collagenous tissue (Fig. 3). He considered it to be most likely bound as
In some areas they surrounded mucous lipoprotein or sphingolipid, and he supglands, bundles of smooth muscle, and ported a neural origin for the lesion.
peripheral nerves (Figs. 4 and 5). The
Azzopardi1 doubted the neoplastic nature
granular cells were arranged in three un- of the lesion and suggested that the lipid
encapsulated separate masses. Within the was altered myelin originating from the
masses the cells were arranged in variable nerve elements which are often conspicuous
patterns. In some areas they were numerous in the lesion. He considered the granular
and arranged in tight groups. In other areas
cells to be histiocytes and suggested the
the cells were sparse and intermingled with
name lipoid thesaurismosis. Fisher and
abundant collagenous connective tissue.
Wechsler,7 employing the electron microThe periphery of the lesions were ill-defined,
scope and histochemical technics, concluded
and the granular cells appeared to infiltrate
that the tumor derived from Schwann cells.
adjacent tissue. Several of the cartilaginous
rings were surrounded by granular cells, They suggested the name granular cell
and much of the three masses was beneath schwannoma, the suffix "oma" referring to a
bronchial cartilage. The cytoplasmic gran- tumorous, not necessarily neoplastic, nature.
ules, particularly the more coarse ones, They also questioned whether the lesion was
stained periodic acid-Schiff-positive, both in fact truly neoplastic. I t seemed more likely
before and after diastase digestion. Some to them that the lesion arose from peripheral
of the granules stained weakly positive with nerves through histiocytic transformation of
Schwann cells. Their conclusions were based
Sudan black B and oil red 0.
upon the morphologic and histochemical
Hilar and peribronchial lymph nodes were similarities of the granular cells to Schwann
hyperplastic, contained carbon pigment, cells and on the dissimilarity of the granular
and were without evidence of tumor. Sec- cells to damaged and fetal skeletal muscle.
tions of the lung revealed areas of broncho- In the cutaneous and lingual lesions studied
pneumonia and atelectasis.
by Fisher and Wechsler, the electron phoA total of seven skin nodules were removed tomicrographs revealed the presence of
from the patient on several different occa- virus-like particles. Their significance is
sions. Their locations were as follows: three still speculative.
from the back, two from the right arm, one
Electron photomicrographs of several
from the left shoulder, and one from the granular cell myoblastomas recently studied
right thumb. All were histologically charac- by Moscovic and Azar" revealed ultrastructeristic of granular cell myoblastoma. The
tural features similar to those of previously
patient has four remaining skin nodules
studied cases. They felt that granular cell
which have not been excised.
myoblastoma was most likely of mesenchymal derivation and considered that their
DISCUSSION
findings did not support the theory of
Since its recognition by Abrikossoff in Schwann cell derivation. The granules may
1926, the so-called granular cell myoblas- represent the end result of an obscure meta-
Nov. 1968
567
GRANULAR CELL TUMORS
bolic alteration manifested by intracytoplasmic storage of protein and lipoid substances.
Granular cell myoblastomas have been
found in most areas of the body. Over 500
cases have been reported in the literature.
These tumors are most frequently seen in
the tongue, skin, and subcutaneous tissue.
The lesion is usually single, slow growing,
asymptomatic, and varies from 0.5 to 2.5
cm. in diameter. Grossly granular cell myoblastoma is solid, firm, white to yellow and
circumscribed but unencapsulated. The
diagnosis can only be made by histologic
examination.
Although usually occurring as single lesions, granular cell myoblastomas may be
multiple. Colberg and Hubay 6 estimated
the incidence of multiple granular cell myoblastoma to be 4%. More recently Moscovic
and Azar9 have reviewed multiple granular
cell tumors and estimated their incidence
to be between 7 and 16 %.
The bronchus is an unusual site for granular cell myoblastoma. A review of the literature by Rojer11 in 1965 revealed 23 cases
of bronchial granular cell myoblastomas.
The case presented by Rojer, plus five
additional reported cases, 3 ' 4 ' 8 ' 12 now makes
a total of 29 cases. There are only three
reports 3, 6| n of multiple bronchial granular
cell myoblastoma, which indicates the
rarity of such an occurrence. Several of
the 29 patients did, however, have granular
cell myoblastomas involving other areas of
the body.
Of the 29 reported cases, 17 were males,
11 were females, and in one case the sex was
not stated. Granular cell myoblastoma of
the bronchus is usually seen in adults,
although it has occasionally been observed
in teenagers. The average age is 36 years.
Nearly all of the patients present with symptoms of bronchial obstruction and recurrent
pulmonary infection. The preferred treatment consists of complete surgical removal
of the affected bronchus and distal diseased
portion of the lung. Endobronchial resection
appears to be effective if an adequate lumen
can be restored and if the lung tissue distal
to the lesion has not suffered irreparable
damage. Radium or radiation therapy has
not been considered to be effective.
SUMMARY
The clinical and pathologic features of
an adult Negro man with multiple granular
cell myoblastomas are presented. The lesions
involved both the skin and the right mainstem bronchus. The bronchus contained
three separate lesions. There have been only
three previous reports of multiple granular
cell myoblastomas of the bronchus.
REFERENCES
1. Azzopardi, J. G.: Histogenesis of the granularcell " m y o b l a s t o m a . " J. P a t h . & Bact.,
71:85-94, 1956.
2. Bangle, R., J r . : A morphological and histochemical s t u d y of the granular-cell myoblastoma. Cancer, 5: 950-965, 1952.
3. Benson, W. R.: Granular cell tumors (myoblastomas) of the tracheobronchial tree.
J. Thorac. & Cardiov. Surg., 52: 17-30, 1966.
4. Campbell, D . C , J r . , Smith, E . P . , Jr., Hood,
R. I I . , J r . , Dominy, D . E., and Dooley,
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of the bronchus. Review of the literature
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729-733, 1964.
5. Colberg, J. E . , and H u b a y , C. A.: Granular
cell myoblastoma—a problem in diagnosis.
Surgery, 58: 226-237, 1963.
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Sesana, W., and Satuff, A.: Mioblastoma
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41: 197-202, 1961.
7. Fisher, E . R., and Wechsler, H . : Granular cell
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cell
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S. Gallivan, G. J., Dolan, C. T., Stam, R. E.,
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Cancer, 20: 2032-2047, 1967.
10. Pearse, A. G. E . : The histogenesis of granularcell myoblastoma (? granular-cell perineural
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11. Rojer, C. L.: Multicentric endobronchial
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12. Stein, H. F . : Granular cell myoblastoma of
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