Download A Vascular Lesion with Smooth Muscle Differentiation Presenting as

A Vascular Lesion with Smooth Muscle Differentiation
Presenting as a Coin Lesion in the Lung:
Glomus Tumor versus Hemangiopericytoma
BROOKE ALT, M.D., WILLIAM E. HUFFER, M.D., AND DEBORAH A. BELCHIS, M.D.
A 34-year-old black man presented with an asymptomatic coin
lesion in the lung. The diagnosis was narrowed to a differential
between glomus tumor and hemangiopericytoma. The authors
found that the terminology applied to such tumors in the literature
is confusing largely because of lack of consistency in criteria
used to establish the diagnosis. The authors propose that the
term glomus tumor be reserved for tumors composed of endothelial-lined vascular spaces surrounded by smooth muscle cells.
Hemangiopericytoma should be used for similar tumors composed of pericytes with or without other types of perivascular
mesenchymal cells. According to these criteria, this case is the
third glomus tumor reported in the lung. (Key words: Glomus
tumor; Hemangiopericytoma; Smooth muscle cells) Am J Clin
Pathol 1983; 80: 765-771
Department of Pathology, University of Wisconsin
Clinical Sciences Center and William S. Middleton Veterans
Administration Hospital, Madison, Wisconsin, and
Department of Pathology, University of Colorado Health
Sciences Center, Denver, Colorado
hemangiopericytoma was favored by some pathologists,
we have reviewed the literature concerning this differential
diagnosis and present our conclusions herein.
Report of a Case
A 34-year-old black man was admitted to the William S. Middleton
Veterans Administration Hospital in August 1982 for surgical evaluation
of a 2-cm solitary nodule in the right upper lobe,firstnoted in December
1980. At that time, the lesion seen on chest x-ray was a round nodular
density at the level of the right second costochondral junction. Tomograms did not reveal calcification. The nodule had not changed in
size since 1980. Skin testing for tuberculosis, histoplasmosis, and coccidioidomycosis had negative results in 1980 and 1982. In addition,
complement fixation was negative for blastomycosis, histoplasmosis,
and coccidioidomycosis. A CBC and sedimentation rate were normal,
as were pulmonary function tests. The patient had vague complaints of
"tightness" in the right upper thorax for six months before admission.
There was no history of cough, and the patient denied cigarette smoking,
travel, or tuberculosis exposure. The medical history was significant for
mental illness (schizo-affective psychosis) over the previous 15 years.
The patient was treated with psychotropic medications. Four months
before admission the patient underwent bronchoscopy with biopsy, but
the specimens obtained were nondiagnostic. Upon the present admission,
a thoracotomy was performed.
GLOMUS TUMORS AND HEMANGIOPERICYTOMAS were regarded by Stout and Murray as closely related
tumors, both derived from pericytes.21,29,30,31 The principle
distinguishing feature was an organoid (glomus tumor)
or a nonorganoid (hemangiopericytoma) pattern of
growth.29 Hemangiopericytomas also were described
originally as showing a spectrum of differentiation towards
smooth muscle cells,29 which was lacking in glomus tumors.21 Masson earlier had described glomus cells as
showing myofibrils by light microscopy.17
Since that time, ultrastructural studies have shown that
normal glomera9,10 and glomus tumors1'8""'3,16,20'33,35"37
are composed of perivascular cells with light and electron
microscopic features of smooth muscle cells. Some ultrastructural studies of tumors classified by light microscopy as hemangiopericytomas have described perivascular
cells similar to normal pericytes,5,7,19,22,28,34 but other
studies of similar tumors have described cells showing
varying degrees of smooth muscle,15,23,25,26 fibroblastic,3,23
or myofibroblast^23 differentiation as pericytes.
In this report we describe a lesion with light microscopic
features of a glomus tumor and ultrastructural features
of smooth muscle differentiation. Since a diagnosis of
Pathologic Findings
Gross
Received February 25, 1983: received revised manuscript and accepted
for publication April 25, 1983.
Supported in part by a generous gift of the R. J. Reynolds Industries.
Inc., to the Department of Pathology, University of Colorado Health
Sciences Center.
Address reprint requests to Dr. Huffer: Department of Pathology,
University of Colorado Health Sciences Center, Denver, Colorado 80262.
At surgery, a peripheral nodule in the posterior segment
of the right upper lobe was shelled out. The tissue received
in surgical pathology consisted of a 2 cm in diameter,
round, soft, fleshy, yellow-tan, faintly lobulated mass with
a smooth external surface and a smooth, glistening cut
surface.
Light Microscopy
The tumor was fixed in 10% neutral buffered formalin,
embedded in paraffin, sectioned at 5 n, and stained with
0002-9173/83/1100/0765 $01.15 © American Society of Clinical Pathologists
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ALT, HUFFER, AND BELCHIS
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A.J.C.P. • November 1983
vol. 80. No. 5
CASE REPORTS
767
FIG. 1 (upper, left). Light microscopic photomicrograph showing area of tumor with round to
elongate cells surrounding vascular spaces. Hematoxylin and eosin (X70).
FIG. 2 (upper, right). PAS-positive material surrounding individual cells with distinct borders. Periodic acid-Schiff(X300).
FIG. 3 (lower). Electron micrograph of cells arranged around vascular space (X5.600).
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hematoxylin and eosin, periodic acid-Schiff (PAS), Masson trichrome, toluidine blue, the Fontana-Masson stain,
and Wilder's reticulum stain by standard technics (AFIP
manual). Histologically, the tumor was demarcated
sharply, but not encapsulated. A few alveolar septae focally
surrounded the mass, but there was not sufficient normal
lung parenchyma to determine its relationship to the
whole periphery of the tumor. The tumor was composed
of cells that were round to slightly oval and were around
numerous dilated vascular spaces, some of which had an
angular appearance. In some areas, the cells were arrayed
closely and dispersed fairly evenly. In other areas there
was a loose arrangement with abundant hyalinized stroma
(Fig. 1). A reticulum stain showed a definite reticulum
membrane between the endothelial cells of the blood vessels and the surrounding cells. In addition, there was
abundant reticulum surrounding individual cells as well
as small clusters of cells. The nuclei were predominantly
round with finely granular chromatin, though in some
areas they had a slight spindled configuration. There was
a moderate amount of palely staining to slightly eosinophilic cytoplasm, and cell borders were usually very distinct. PAS-positive material surrounded individual cells
(Fig. 2). In some areas the cells were separated by abundant
hyalinized material, which appeared collagenous by trichrome stain. The latter stain also showed some of the
cells to have slightly granular, reddish cytoplasm.
Another striking feature of this tumor was the presence
of abundant mast cells scattered throughout. Toluidine
blue stain showed prominent metachromatic granules in
these cells.
Fontana-Masson stain for neurosecretory argentaffin
granules was negative. No nerve fibers were identified
either within or surrounding the tumor mass.
Electron Microscopy
Formalin-fixed tissue was minced in 2% glutaraldehyde
in buffer pH 7.5, postfixed in Os0 4 , and embedded in
Epon® 8-12. Thin sections were examined on a Philips
electron microscope. Ultrastructurally, the tumor cells
were arranged concentrically around round or slightly
irregularly shaped vascular spaces continously lined by
endothelial cells having the usual characteristics including
numerous cytoplasmic filaments, Weibel-Palade bodies,
pinocytotic vesicles, and a well-developed endoplasmic
reticulum (Fig. 3). Cell junctions between endothelial cells
were identified. A basement membrane separated the endothelial cells from the surrounding tumor cells.
The tumor cells had round-to-oval nuclei, some of
which had an irregular nuclear outline. The chromatin
was clumped peripherally, and there was an occasional
nucleolus. The cytoplasm contained numerous electrondense attachment bodies around its peripheral membrane.
Myofibrils were identified entering these attachments as
well as entering randomly placed electron dense bodies
within the cytoplasm. A moderate number of pinocytotic
vesicles also were identified around the periphery of the
cytoplasmic membranes (Fig. 4). Other cytoplasmic organelles included scattered mitochondria, sparse profiles
of rough endoplasmic reticulum, only occasional Golgi
apparatus and centrioles, and in one cell a structure resembling a cilia.
Each cell was surrounded completely by a basal lamina.
In addition, there was abundant smudgy, granular material between cells corresponding to the light microscopic
areas of hyalinization. In some areas this resembled basement-membrane-like substance. In other areas the stroma
was fibrillar or had a periodicity suggesting both closely
spaced as well as long-spaced collagen. Numerous mast
cells with abundant dense-core granules were scattered
throughout the tumor (Fig. 5).
Discussion
Typical glomus tumors are thought to arise from the
glomus apparatus or Suquet-Hoyer canal, an arteriovenous anastomosis associated with both blood flow and
temperature control. 410 The tumor has been described
as an enlarged "caricature" of the glomus apparatus and
regarded by some as a hyperplastic or hamartomatous
process rather than a neoplasm.21 Glomus tumors are
usually benign, although malignant ones have been reported,16'32 thus supporting the concept that the lesion is
a true neoplasm.
Although glomus tumors most often occur subcutaneously in the hands and fingers," similar tumors occur
elsewhere in superficial and deep soft tissues and visc e r a 1.2,11,14.21 ivt urTa y a n ( j stout suggested that the tumor
has its origin in the pericyte of Zimmerman, which might
be found anywhere in the body.21
Ultrastructural studies have shown that normal glomus
cells 910 and cells of glomus tumors 11112,20-35,36 closely resemble normal smooth muscle cells. They have numerous
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ALT, HUFFER, AND BELCHIS
A.J.C.P. • November 1983
Vol. 80 • No. 5
769
CASE REPORTS
FlG. 4. Electron micrograph of cell with pinocytotic vesicles {arrow), dense attachment plaques and cytoplasmic fibrils {bracketed area, left lower
area) (X29.700). Insert {upper right) shows prominent dense body in cytoplasm with attached fibrils and basal lamina {between arrows) (X28.500).
Insert {lower left) shows higher power of pinocytotic vesicles (X61,200).
cytoplasmic myofibrils approximately 40-80A in diameter; condensation plaques on the cytoplasmic membrane
and electron-dense bodies within the cytoplasm, both associated with myofibrils; numerous pinocytotic vesicles
along the cytoplasmic membranes; and basement membrane and/or abundant osmiophilic basement-membranelike material surrounding individual cells.19 These findings
do not rule out a pericytic origin for glomus cells, but
they indicate that Stout's original concept that glomus
cells were equivalent to Zimmerman's pericytes21 was
incorrect.
Hemangiopericytomas are vascular neoplasms originally described by Stout and Murray29 as nonorganoid
pericytic tumors closely related to glomus tumors. Tumors
classified by light microscopy as hemangiopericytomas
have shown a wide spectrum of ultrastructural
differentiation5'719'22'28,34 leading to confusion in diag-
nosing this neoplasm and the statement that pericytes are
poorly defined cells.719
Ultrastructural studies by Rhodin 27 have described
pericytes as cells with multiple processes surrounding the
endothelial cells and enclosed in the endothelial cell basement membranes of capillaries and veins up to 50 n in
diameter. They have prominent Golgi and rough endoplasmic reticulum, lysosomal granules, and scattered cytoplasmic filaments not organized into bundles. They have
no fusiform dense bodies and only rudimentary plasma
membrane attachment zones. They are distinct from "veil
cells," which resemble fibroblasts and primitive and mature smooth muscle cells. Cells described as venous pericytes by Kuhn and Rosai had small bundles of fibrils and
dense material along the plasma membrane interpreted
as the analogue of smooth muscle attachment sites."
These cells were distinguished from mature smooth mus-
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FIG. 5. Electron micrograph of mast cell located amidst tumor cells. The latter show
numerous attachment plaques and are surrounded completely by basal lamina (X7,500).
770
A.J.C.P. • November 1983
ALT, HUFFER, AND BELCHIS
cle cells because of the smaller size of the attachment
bodies and fibrils. They seem to correspond to cells defined
by Rhodin as primitive smooth muscle cells27 rather than
pericytes.
From the descriptions above, it is clear that pericytes
have their own distinctive ultrastructural features, which
do not include extensive smooth muscle differentiation.
It seems logical to agree with Kuhn and Rosai15 and
others3'5,719-20'22-28 that hemangiopericytomas should be
composed at least in part of perivascular cells with characteristics of normal pericytes.
What is not clear from the literature is whether hemangiopericytomas are composed solely of pericytes. This is
implied by the definition of hemangiopericytomas as a
uniform population of cells without myofibrils by light
microscopy.6 On the other hand, as mentioned above,
several authors have described tumors called hemangiopericytomas, composed of cells with smooth muscle
and other types of differentiation. Some of these have
been referred to as transitional types between glomus
tumors and hemangiopericytomas.15,24
From the discussion above, it is apparent that there is
confusion in the literature regarding the diagnosis of glomus tumors and hemangiopericytomas. Because hemangiopericytomas are usually thought to have a worse prognosis than glomus tumors, it is important to attempt to
distinguish these as separate entities. We suggest that classification would be simplified if the definition of hemangiopericytoma was broadened to include tumors composed of pericytes, with or without other types of perivascular cells such as immature and mature15-23,25,26
smooth muscle cells, fibroblasts,3 endothelial cells,3 and
myofibroblasts.23 This terminology is consistent with and
extends Stout's original description of hemangiopericytomas as a class of tumors showing a spectrum of differentiation from pericytes to smooth muscle cells.29 The
term glomus tumor would be restricted to neoplasms
with endothelial channels surrounded only by smooth
muscle cells and lacking pericytes. Transitional tumors
such as those described by Stout30 and Kuhn and Rosai15,24
would be classified as hemangiopericytomas.
According to the definitions above, our tumor should
be diagnosed as a glomus tumor. Three other tracheal
tumors 8,13,37 and two other peripheral lung tumors 16,33
also fit this definition of glomus tumor. Though there
are at least 24 cases of hemangiopericytoma in the lung,18
we have been unable to find ultrastructural findings to
compare with glomus tumors in the tracheopulmonary
tree.
Acknowledgments. The authors thank G. Reza Hafez, M.D., for his
suggestions in preparing this article. Kenneth Powers and Don Walker
for their technical assistance, John LeBosquet for his photographic contribution, and Debra Mann and Diane Venden for assistance in preparation of the manuscript.
References
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tumor of the stomach. Histologic and ultrastructural features.
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2. Appelman HD, Helwig EB: Glomus tumor of the stomach. Cancer
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3. Battifora H: Hemangiopericytoma: Ultrastructural study offivecases.
Cancer 1973;31:1418-1432
4. Carroll RE, Berman AT: Glomus tumors of the hand. Review of
the literature and report of twenty-eight cases. J Bone Joint Surg
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5. Eimoto T: Ultrastructure of an infantile hemangiopericytoma. Cancer 1977;40:2161-2170
6. Enzinger FM, Smith BH: Hemangiopericytoma. Analysis of 106
cases. Hum Pathol 1976; 7:61-82
7. Enzinger FM, Weiss SW: Soft tissue tumors. CV Mosby Co, St.
Louis, 1983
8. Fabich DR, Hafez GR: Glomangioma of the trachea. Cancer 1980;
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9. Fine G, Morales AR: The ultrastructure of the "normal" human
glomus apparatus of the nailbed. Abstract. Am J Clin Pathol
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10. Goodman TF: Fine structure of the cells of the Suquet-Hoyer canal.
J Invest Dermatol 1972; 59:363-369
11. Hamilton CW, Shelburne JD, Bossen EH, Lowe JE: A glomus
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13. Heard BE, Dewar A, Firmin RK, Lennox SC: One very rare and
one new tracheal tumor found by electron microscopy: Glomus
tumor and acinic cell tumor resembling carcinoid tumors by
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14. Kay S, Callahan, WP Jr, Murray MR, Randall HT, Stout AP: Glomus
tumors of the stomach. Cancer 1951; 4:726-736
15. Kuhn C, Rosai J: Tumors arising from pericytes. Ultrastructure
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16. Mackay B, Legha SS: Coin lesion of the lung in a 19-year-old male.
Ultrastruc Pathol 1981; 2:289-294
17. Masson P: Le glomus neuromyo-arteriel des regions tactiles et ses
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18. Meade JB, Whitwell F, Bickford BJ, Waddington JKB: Primary
hemangiopericytoma of lung. Thorax 1974; 29:1-15
19. Morales AR, Fine G, Pardo V, Horn RC, Jr: The ultrastructure of
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20. Murad TM, vonHaam E, Murthy MSN: Ultrastructure of a hemangiopericytoma and a glomus tumor. Cancer 1968; 22:1239-1249
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24. Osamura RU, Watanabe K, Yoneyama K, Hayashi T: Glomus
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25. Pena CE: Intracranial hemangiopericytoma. Ultrastructural evidence
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34. Tavassoli FA, Weiss SW: Hemangiopericytoma of the breast. Am
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Fatality Due to Paraquat Intoxication: Confirmation
by Postmortem Tissue Analysis
SANDRA E. CONRADI, M.D., LAWRENCE S. OLANOFF, PH.D., M.D., AND WILLIAM T. DAWSON, JR., M.D.
A brief case report is presented describing a patient who unknowingly ingested a fatal amount of paraquat, presumably mixed
in some illicit moonshine alcohol. Despite an initial clinical presentation typical of paraquat intoxication, the herbicide was
absent upon analysis of multiple urine and blood specimens, and
the diagnosis was comfirmed only postmortem after determination of high paraquat tissue concentrations in all the major
organs. Autopsy results are presented along with a discussion
of the histopathologic changes observed in the lungs, liver, and
kidneys. Because the combination of toxicologic sequelae attributable to acute paraquat poisoning is fairly unique to this
agent, the diagnosis must be suspected highly early in the clinical
course of such cases and appropriate therapy initiated, despite
the inability to isolate paraquat on preliminary laboratory
screening. (Key words: Paraquat; Signs and symptoms; Autopsy
findings) Am J Clin Pathol 1983; 80: 771-776
PARAQUAT, a bipyridilium herbicide, produces multiple
organ system injury in humans. After exposure, by ingestion or by significant skin contact, toxic changes have
been demonstrated in the lungs,6,7 kidneys,28 liver,20
heart,4 adrenals,25 central nervous system," skin,30 oral
mucosa,26 and esophagus.' Mortality rates following paraquat ingestion have been estimated at 33-50%,2 and
fatal cases have been reported resulting from ingestion
or by direct exposure of the skin to concentrated solutions
of the herbicide.3,21
A report of a fatality secondary to paraquat ingestion
is presented.
Report of a Case
A 39-year-old black man, with a history of 1 pint to 1 quart of alcohol
ingestion per day for the last 1 to 2 months, was otherwise in good
medical health until six days prior to admission, when he reported
Received March 8, 1983; received revised manuscript and accepted
for publication May 2, 1983.
Address reprint requests to Dr. Conradi: Department of Pathology,
Medical University of South Carolina, Charleston, South Carolina 29425.
Departments of Pathology, Pharmacology and Pulmonary
Medicine, Medical University of South Carolina,
Charleston, South Carolina
developing acute left lower quadrant abdominal pain, nausea, and vomiting after drinking an unknown quantity of illicit "moonshine" alcohol.
On the following day, he developed a severe pharyngitis and began to
expectorate small quantities of blood and tissue from the roof of his
oral cavity and abruptly ceased urinating. The patient entered a local
hospital four days after ingestion of the substance, where his initial
examination was remarkable only for glossitis and pharyngitis. Laboratory
results at that time are presented in Table 1 (preadmission). Urinalysis
demonstrated proteinuria. Chest x-ray was interpreted as consistent with
"mild interstitial inflammatory changes." A rudimentary drug screen
was sent, which had negative results for acidic, basic, or neutral drug
substances. No specific analysis for paraquat was performed. He was
transferred to the Medical University Hospital in Charleston on the
sixth day following his toxic ingestion, where physical examination revealed an alert, afebrile black man, with a supine blood pressure of 140/
100 mmHg and a pulse of 92 beats per minute. His sclerae were markedly
icteric, and examination of his oral cavity revealed extensive palatal,
lingual, and posterior pharyngeal ulcerations covered with clotted blood.
Chest examination revealed scattered bibasilar rales and shallow respirations. Abdominal examination was significant for voluntary guarding
to the right upper quadrant (with moderate shock tenderness) and liver
span of 10-12 cm by percussion. Stool was heme positive by guaiac
testing. Laboratory hematologic and chemistry values essentially were
unchanged from initial determinations. Arterial blood gas results determined while the patient inspired room air were as follows: pH, 7.42;
Po;, 55 mmHg; PCOi, 25 mmHg; serum bicarbonate, 16 mEq/L; and
an oxygen saturation, 90%.
A repeat chest x-ray demonstrated a bilateral basilar reticular pattern
of unknown origin, and repeat serum and urine drug screen was remarkable only for the presence of nicotine. Other pertinent laboratory
studies included a negative urine myoglobin, negative Hepatitis B surface
antigen, a urinary fractional sodium excretion of 12.3%, and negative
urine and blood cultures. An abdominal ultrasound revealed slightly
increased kidney size bilaterally, with no obvious obstruction, and normalappearing pancreas and liver. A nasogastric tube was placed to ensure
esophageal patency, and intravenous aqueous penicillin G and dexamethasone were started. Because of his acute renal failure and rapidly
0002-9173/83/1100/0771 $01.10 © American Society of Clinical Pathologists