JUNE, 1973

DIFFUSE CYSTIC ANGIOMATOSIS OF BONE*

REPORT OF TWO CASES

ANNE C. B ROWER, and THEODORE

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By M.D., JAMES E. CULVER, JR., M.1)., E. KEATS, M.D.

CHARLOTTESVILLE, VIRGINIA

T HE patient with diffuse cystic disease At the age of 22 years, a routine chest roent-
of his skeleton presents the radiologist genograrn again revealed the multiple cystic
with an intriguing problem of differential lesions of lien ribs and she was admitted to
another hospital for evaluation. A bone survey
diagnosis, which he is often able to solve in
showed multiple osteolytic lesions of the skull,
the context of the clinical presentation of
vertebrae, pelvis, humeri and femora. Physical
the patient. The final solution is often
examination was within normal limits. Labora-
found with biopsy. However, this intel-
tory studies were all normal except for a mildly
lectually satisfying course of events does
elevated alkaline phosphatase. Biopsies were
not always follow in the patient with dif- taken from the right iliac crest and a rib. These
fuse angiomatosis of his skeleton, in whom were reported as showing hoilow cavities, some
the biopsy is often quite unrevealing, but in ofwhich were lined by a single layer of flattened
itselfis a useful clue. endothelial cells. Hyperactive marrow was seen
This report concerns our recent exper- in the bone surrounding the cavities. Numerous
ience with two such cases. fat cells were also present. No specific dagnosis

Cystic angiomatosis of tile skeletal sys- was made. Both the diagnosis of histiocytosis

tem was first described by Jacobs and

x and the diagnosis of some form of angioma-
tosis were suggested.
Kimmelstiel in 1953. Isolated skeletal in-
No further diagnostic efforts were made until
volvement is extremely rare with only
admission to our hospital. She remained
cases reported.’4 The diagnosis is a diflicult
asymptomatic except for occasional anterior
one to make and is partly one of exclusion. chest pain. Again roentgenograms showed the
It should be considered in patients present- multiple osteolytic lesions involving the skull,
ing with diffuse cystic lesions of the skele- vertebrae, ribs, pelvis, humeri and femora (Fig.
ton on roentgenographic examination and i-6). Roentgenogranls from hen other hospital
with minimal or no associated clinical or admissions were not available to us for coni-
laboratory findings. Biopsy ofa lesion often parison . Physical exanlination was entirely
yields nonspecific histologic material and normal. All laboratory studies, including a bone
marrow and liver biopsy, were normal.
multiple attempts may be necessary before
diagnostic pathologic tissue is obtained. An open biopsy ofthe left
anterior iliac crest
was performed. Multiple small empty cysts
Our 2 patients, seen within the past year,
were noted (Fig. 7). Specimens taken included
illustrate the roentgenographic features of
portions of a cyst wall.
this disease and the inherent difficulties in
Microscopically, only small fragments of the
making the diagnosis.
thin wall of the cavity were seen, but not
REIORT OF CASES enough to identify the wall. A few very large
vascular sinusoids were found about the cysts.
CASE I. A 25 year old Negro female was first
seen in our ilospital in April 1970. Anxiety over
This histologic material, together with the
her known “holes in my bones” brought hen to specimens obtained from her previous hospital-
us for evaluation. She was first told of her dis- izations, were reviewed by the Armed Forces
ease at the years, when
age of 12 multiple cystic Institute of Pathology and were described as
lesions of her ribs were found on a routine chest niost compatible with diffuse cystic angiorna-
roentgenogram. A rib biopsy was performed tosis of the bone (Fig. 8, 4 and B).7
elsewhere at that time, but the patilologic She was reassured, discharged and at last re-
report was lost. port, i year later, was doing well.
* From the I)epartments of Radiology and Orthopedic Surgery, University of Virginia School of Medicine, Charlottesville, Virginia.
Partially supported by NIH Research i’raining Grant IToIAMo56360IAI.

456
 Voi. ii8, No. 2 Diffuse Cystic Angiomatosis of Bone 457
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FIG. I. CaseI. Anteroposterior view of the lumbar

spine and pelvis shows multiple lvtic lesions in-
volving all the bones. Some lesions have sclerotic Fic. Case
3. i. Lateral view of the thoracic spine
borders, but many do not. shows multiple small lytic lesions throughout the
vertebral bodies. There is slight compression (IC-
formity of T
CASE II. A year old white boy was first
seen by us in November 1969, when ile sus-
tamed an injury to his right shoulder. Roent-

FIG. 4. Case I. laterial view of the skull shows lvtic

FIG. 2. Case i. Posteroanterior view of the chest lesions involving the frontal, and occipital
arietd
shows lytic lesions involving all of the ribs. Some areas. The vertebral bodies and spinous processes
appear to have caused expansion of the ribs. of the cervical spine are also involved.
 458 A. C. Brower, J. E. Culver, Jr. and T. E. Keats JUNE, 1973
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11G. . Case I. (A and B) Anteroposterior view of both humeri shows lytic lesions involving
not only the humeri, but both scapulae as well.

genograms of the right humerus showed a limits, as were all his laboratory studies, except
pathologic fracture through multiple cystic for a slightly elevated alkaline phosphatase. A
lesions involving the proximal end of the Craig needle biopsy was attempted on the right
humerus. humerus, but the tissue obtained was insuffi-
Except for his fractured humerus, the pa- cient for diagnosis.
tient’s physical examination was within normal He was again seen in March 1971 when, dun-
 VOL. ii8, No. 2 Diffuse Cystic Angiomatosis of Bone 459
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FIG. 6. Case I. (A and B) Anteroposterior view of both femora shows lytic involvement
of the shafts of the bone. The distal ends appear free of involvement.

ing a respiratory infection, he sustained 3 was within normal limits. The alkaline phos-
pathologic rib fractures in cystic lesions involv- phatase was slightly elevated, but all other
ing the ribs. A bone survey showed multiple laboratory studies were normal. An open biopsy
cystic lesions also involving the pelvis, femona, of the right anterior iliac crest was carried out.
humeri and radii (Fig. 9-12). Except for physi- Multiple large empty cystic cavities were found.
cal findings corresponding with his upper Specimens taken included a portion of the cyst
respiratory infection, his physical examination wall.
 460 A. C. Bnower, J. E. Culver, Jr. and T. E. Keats JINE, 1973

?slicroscopically, very sniall fragments of the

cyst wall were seen. In some areas a single layer
of flattened endothelial cells was found. Some
fat cells were also noted (Fig. 13). The possi-
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l)iiity of sonle forni of dit+use cystic angio-

IllittOsis WitS considered. I’he pathologic niate-
rial was reviewed by the Armed Forces Insti-
tute of Pathology itii(I was described as similar to
the 2 cases described by Jacobs and Kimmel-
stiei.4 The possibility of a diffuse skeletal
liponiatosis as opposed to an angioniatosis was
considered.
He received no treatment and continues to
do well, without systemic symptoms.

DISCUSSION

lilese 2 cases are strikingly similar. Both

have multiple diffuse cystic lesions, involv-

I METRK
I T 1 LL,Ll..lL.TT,
11G. 7. Case
from
i. Gross
the left iliac
specimen
crest
of a cyst
(5X).
removed

11G. 8. Case I. (/1) Photomicrograph of specinien taken from left iliac crest shows multiple cystic spaces
( 25 X ). I) high P\er view SI1OWS en(IOtllelial lining of one cyst (400X).
 \OL. ii8, No. 2 Diffuse Cystic Angiomatosis of Bone 461
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l’IG. 9. Case II. Anteroposterior view of the pelvis

shows a large, multiloculated cyst involving the
right ilium and a smaller one involving the left
ilium. Several small lvtic lesions are seen in the
proximal femoral shafts.

ing tile pelvis, ribs and proximal long bones,

first appearing in childhood. Both have
been relatively asmptomatic. One has suf- I I !
fered pathologic fractures, but the other
FIG. II. Case II. (A and B) Views of both distal
has been followed for 13 years without com- humeri show various size cystic lesions involving
plications. Neither case has any evidence of the entire bone.
visceral involvement. Both have had mul-
tiple biopsies including open biopsies which ments of cyst wall that appeared vascular
showed multiple empty csts, devoid of in nature.
fluid or cellular materiai. Both had frag_ ‘The roentgenographic findings in both
cases were not specific. The differential
di agnoses considered, from the roen tgeno-
graphic findings alone, in tiiese cases were:
metastatic neoplasm ; multifocal primary
neoplasm; multiple myeloma; primary and
secondary hperparathyroidism ; polvostot-
ic fibrous dysplasia; histiocytosis X; and
mastocytosis. However, the clinical course,
the physical examination, the laboratory
findings and the pathologic specimens all
helped to exclude these diagnoses. Both
cases bear striking similanit to those de-
scnibed by Jacobs and Kimmelstiel1 as
cystic angiomatosis of the skeleton.
\Vallis et cil.14 ill an extensive review of
the literature, were able to find 26 cases of
di ffuse skeletal angiom atosi s. However,
FIG. Case II. Posteroanterior
10. view of the chest
only 9 of these patients were free of visceral
shows rib fractures in the lower right ru) cage and
one in the left 4th rib. Small lytic lesions are seen involvement. The 17 with visceral involve-
in several ribs. ment had symptoms related to the organ
 462 A. C. Brower, J. E. Culver, Jr. and T. E. Keats JUNE, 1973
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FIG. 12. Case I!. (A) Anteroposterior and (B) lateral views of the proximal left radius
and ulna show cystic involvement.

involved. The 9 without visceral involve- lymphangiomatosis is unclear. Cases, simi-

ment were usually asvmptomatic except tar to those described above, have been
for fracture and bone pain. Laboratory reported, in which tile cysts contained
studies in those without visceral involve- lymph-like fluid and the histologic sections
ment were usually normal. The roentgen revealed lymph channels, instead of vascu-
featu res included lytic lesions, sclerotic lar channels. Cases have been reported in
areas, expanding cysts and generalized which both lymph channels and vascular
skeletal lucency. On biopsy, multilocular channels were present.’4 However, these
cysts were usually encountered, which were patients also had visceral involvement.
either very vascular or completely empty. The possibility of diffuse skeletal lipo-
Histologically, there was a conglomeration matosis was raised in our second case.7
of vascular channels. In occasional cases, However, to our knowledge, this entity has
while vascular channels were found in some never been reported in the literature. One
areas, other areas showed empty cysts with could postulate that these multiple empty
fragments of endotheliat lining. cysts were once filled with fat, which has
The relationship of angiomatosis to Since degenerated. Single in tramedullary
 VOL. 118, No. 2 Diffuse Cystic Angiomatosis of Bone 463

mal or no associated clinical or laboratory

findings.

Anne C. Brower, MI).

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I)epartment of Radiology
University of Virginia
School of Medicine
Charlottesville, Virginia 22901

RE FERENCES
I. CASTLEMAN, B., and MCNEELY, B. U. Case
records of Massachusetts General Hospital:
case 2-I97I. New England 7. Afed., 1971,
284, 1314-1322.
2. COHEN, J., and CRAIG, J. NI. Multiple lymphan-
giectases bone.
of 7. Bone & Joint Surg., 1955,
37-A, 585-596.
3. HAYES, J. T., and BRODY, G. L. Cystic lymph-
angiectasis of bone. 7. Bone & 7oint Surg.,
1961,43-A, 107-117.
4. JACOBS, J. E., and KIMMELSTIEL, P. Cystic an-
giomatosis ofskeletal system. 7. Bone & joint
Surg., I 953, 35-A, 407420.
5. JOHNsON, L. C. General theory of bone tumors.
Ru/I. New York Acad. Med., 1953, 29, 164-17 I.
FIG. 13. Case u. Photomicrograph ofspecimen taken 6. JOHNSON, L. C., and KINDRED, R. G. Anatomy
from the right ilium shows I cyst. Normal fatty of bone cysts. 7. Bone & joint Surg., 1958,
marrow is present near the cyst (I6oX). go-A, 1440.
7. JOHNSON, L. C. Personal communication.
8. MO5ELEY, J. E., and STAROBIN, S. G. Cystic
lipomas of bone have been reported.9 These angiomatosis ofbone: manifestation of hamar-
are thought to undergo degeneration leav- tomatous disease entity. AM. J. ROENTGENOL.,
RAD. THERAPY & NUCLEAR MED., 1964, 9!,
ing an empty benign cyst wall.6 Fat cells
I I 14-I 120.
were found in the pathologic specimen of 9. MUELLER, M. C., and R0BBIN5, J. L. Intra-
the second case, but whether these had medullary lipoma of bone: report of case.
come from marrow fat could not be deter- 7. Bone & joint Surg., 1960, 42-A, 5 17-520.
mined. Therefore, we have left the second 10. RITCHIE, G., and ZEIER, F. G. Hemangiomatosis
ofskeleton and spleen. 7. Bone & joint Surg.,
case classified as a case of angiomatosis.
1956, 38-A, I 15-122.
II. SECKLER, S. G., H., and RABINOWITZ,
RUBIN,
SUMMARY
J. G. Systemic cystic angiomatosis. Am. 7.
Two patients with diffuse cystic angio- Med., 1964, 37, 976-986.
I 2. SPJUT, H. J., and LINDBOM, A. Skeletal angioma-
matosis ofthe skeleton are reported.
tosis. Ada path. et microbiol. scandinar., i 962,
The difficulties encountered in making 55, 4958.
this diagnosis are discussed. 13. SZWEDA, J. A., and ABRAHAM, J. P. Systemic
Despite the rarity of the disease, cystic mast cell disease: review and report of three
angiomatosis should be considered in the cases. Am. 7. Med., 1962,32, 227-239.
14. WALLIS, L. A., ASCH, T., and MAISEL, B. W.
differential diagnosis of a patient presenting
Diffuse skeletal hemangiomatosis: report o
with diffuse cystic lesions of his skeleton on two cases and review of literature. Am. 7.
roentgenographic examination, with mini- Med., 1964,37, 545-563.
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Ducou Lepointe, Jane Languepin, Jeanne Wagnon, Ralph Epaud, Brigitte Fauroux, Jean Donadieu. 2010. Retrospective French
nationwide survey of childhood aggressive vascular anomalies of bone, 1988-2009. Orphanet Journal of Rare Diseases 5:1. . [Crossref]
10. Jürgen Freyschmidt, Helmut Ostertag, Gernot Jundt. Vaskuläre Tumoren 603-649. [Crossref]
11. E.K. Hughes, S.L.J. James, S. Butt, A.M. Davies, A. Saifuddin. 2006. Benign primary tumours of the ribs. Clinical Radiology
61:4, 314-322. [Crossref]
12. Donald Resnick, Michael Kyriakos, Guerdon D. Greenway. Tumors and Tumor-Like Lesions of Bone: Imaging and Pathology
of Specific Lesions 1120-1198. [Crossref]
13. Iftikhar A. Mukhtar, Merv Letts. 2004. Hemangioma of the Radius Associated With Kasabach-Merritt Syndrome. Journal of
Pediatric Orthopaedics 87-91. [Crossref]
14. Iftikhar A. Mukhtar, Merv Letts. 2004. Hemangioma of the Radius Associated With Kasabach-Merritt Syndrome. Journal of
Pediatric Orthopaedics 24:1, 87-91. [Crossref]
15. Mario Campanacci. Lymphangioma, Cystic Angiomatosis 619-622. [Crossref]
16. F J Ballina-Garcia, M R Queiro-Silva, R Molina-Suarez, J Fernandez-Martinez, M Rivela-Vazquez, A Rodriguez-Perez. 1996.
Multiple painful bone cysts in a young man. Annals of the Rheumatic Diseases 55:6, 346-349. [Crossref]
17. P.C. Goutoudi, N.K. Sferopoulos, V. Papavasiliou, A. Konstantinidis. 1996. Cystic angiomatosis of bone. Oral Surgery, Oral
Medicine, Oral Pathology, Oral Radiology, and Endodontology 81:1, 89-92. [Crossref]
18. Kenneth Devaney, Tuyethoa N. Vinh, Donald E. Sweet. 1994. Skeletal-Extraskeletal Angiomatosis. A Clinicopathological Study of
Fourteen Patients and Nosologic Considerations. The Journal of Bone and Joint Surgery-American Volume 76:6, 878-891. [Crossref]
19. Tsuyoshi Ishida, Howard D. Dorfman, German C. Steiner, Alex Norman. 1994. Cystic angiomatosis of bone with sclerotic changes
mimicking osteoblastic metastases. Skeletal Radiology 23:4, 247-252. [Crossref]
20. Fritz Schajowicz. Vascular Tumors 369-402. [Crossref]
21. Maria Luisa Brandi. Bone endothelial cells: A tool for analyzing cell to cell interactions in the skeletal tissue 250-254. [Crossref]
22. Jürgen Freyschmidt, Helmut Ostertag. Vaskuläre Tumoren 503-532. [Crossref]
23. Hubert A. Sissons, Ronald O. Murray, H. B. S. Kemp. Exercises 1–57 1-397. [Crossref]
24. Gary L. Ellis, Robert B. Brannon. 1980. Intraosseous lymphangiomas of the mandible. Skeletal Radiology 5:4, 253-256. [Crossref]
25. Jane L. Ross, Roger Schinella, Louis Shenkman. 1978. Massive osteolysis. The American Journal of Medicine 65:2, 367-372.
[Crossref]
 26. David Y. Graham, Jorge Gonzales, Shirish M. Kothari. 1978. Diffuse skeletal angiomatosis. Skeletal Radiology 2:3, 131-135.
[Crossref]
27. F. Heuck. Allgemeine Radiologie und Morphologie der Knochenkrankheiten 3-303. [Crossref]
28. . Vaskuläre Tumoren 299-311. [Crossref]
29. . Knochentumoren 215-446. [Crossref]
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