Intravenous Leiomyomatosis of the Uterus and Pelvis: '

Case Report

JAMES F. MARSHALL, M.D., DONALD S. MoRms, M.D.

From the Departments of Surgery and Pathology, City Memorial Hospital,Winston-Salem, N. C.

IN INTRAVENOUS leiomyomatosis tumorsarise from the media and permeate the lu-mina of the dilated vessels of the uterus andpelvis. Permeation of tissue in vessels is afeature generally reserved for maligna-nttumors giving rise to distant metastases.In intravenous leiomyomatosis the permea-tion of vessels by tumor masses may extendfar beyond the pelvic veins, but distantmetastases were not demonstrated in thefew cases reported. Longer periods of ob-servation in more cases will be needed toassess this feature further.We have not found a case reported in the

English language. The latest case foundwas reported 27 years ago.

Literature

Birch-Hirschfeld,' in 1896, referred tothree cases, in his textbook of PathologicAnatomy, in which many plexiform myo-matous nodules grew into dilated chan-nels of the uterus. These spaces were con-sidered lymph vessels. No other detailswere given.

Knauer,7 in 1903, reported four cases indetail. His descriptions of the surgical spec-imens were excellent. The patients were52, 50, 39 and 52 years of age. Enlargementof the abdomen was the major complaint inthree patients; the other had had menor-rhagia for one year. Ordinary leiomyomaswere present in the uteri of all cases andin the broad ligaments of three cases. Poly-poid cords, nodules and plexiform masses

were observed in numerous gaping veins ofthe uteri and broad ligaments in all cases.Some of these were inserted into the veinwalls by thread-like strands or with a broadbase. Others were not attached and somemeasuring up to 1.5 x 1 cm. could bepulled from the lumina.

Microscopically the intravenous massesexhibited a covering of endothelium andwere composed of interlacing bundles ofsmooth muscle with some fibrous tissue.Focal areas of hyalinization were present.The intravenous masses appeared to ariseby the proliferation of smooth muscle bun-dles of the media which became invaginatedinto the vessel lumina. There was no evi-dence of invasion by tumor tissue throughall layers of the vessels as seen when malig-nant tumors invade veins. In some areas in-numerable, intravenous, plexiform massesaccumulated in markedly dilated segmentsof vessels to form ovoid nodules. On grossexamination these nodules simulated ordi-nary edematous myomas. The endometriumwas unremarkable in all specimens.Knauer concluded that these widespread

intravenous tumors arose from vein walls.They were adjudged histologically benignin all cases, and the patients were well twoand one-half to three years followingsurgery.

Durck,3 in 1907, reported the case of a43-year-old woman who had had five sur-gical procedures for uterine myomas in 15years. She died three hours after a totalhysterectomy. At autopsy a continuouscolumn of tumor extended from the stump

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INTRAVENOUS LEIMYOMATOSIS OF UTERUS AND PELVIS

of the internal iliac vein into the rightatrium by way of the inferior vena cava.

No pulmonary metastases were found. His-tologically the intravenous tumors were

leiomyomas similar to those from heruterus.Hormann,5 also in 1907, had a very simi-

lar case. Death was attributed to the tumorextending into the right atrium. No micro-scopic evidence of malignancy was found.

Sitzenfrey,11 in 1911, reported three casesin women 47, 50 and 43 years of age. Hisillustrations, prepared from the surgicalspecimens, were excellent. These patientshad had menorrhagia for two to four years.Two of the uteri contained ordinary myo-mas; one harbored a vascular tumor desig-nated an angiomyoma. In addition, in allcases, many dilated veins in the uteri andbroad ligaments were filled with tumorstrands described as up to pencil thick.Some of these masses were translucent or

opalescent and only a few appeared to beattached to the vein walls. Microscopically,the characteristics of benign myomas withareas of hyaline or mucinous degenerationwere demonstrated.

Sitzenfrey concluded that the intrave-nous shift of adjacent myomatous tissue ledto the formation of these intravascular tu-mor strands. One patient was well 18months after surgery. No postoperative ob-servations on the other patients were

recorded.Lahm,8 in 1915, reported a case in a 61-

year-old woman who had had menorrhagiafor three years. In removing the specimenthe left uterine veins tore away with con-

spicuously little bleeding.A large ordinary myoma was present in

the uterus which also contained plexiformknots. These were adjudged to be in lym-phatic spaces in the uterus. Dilated veinsin the left broad ligament were filled withthick, white tumor masses which extendedbeyond the point of ligation of the infundi-bulopelvic ligament. Intravenous masses

were palpable some distance toward the

kidney. Plexiform myomatous nodules were

demonstrated microscopically in the dilatedvascular spaces.

Lahm noted some cellular changes thathe was inclined to regard as early featuresof malignancy. However, these changeswere present in areas of degeneration.Nevertheless, especially in view of the in-travascular location of the tumors, he ad-judged them to be sarcomas. The case was

reported shortly after surgery, and the finaloutcome is unknown.

Seyler,10 in 1921, reported a case in a 50-year-old woman whose only complaint was

increasing lower abdominal discomfort fora few years. In the surgical specimen ordi-nary myomas were present in the uterusand broad ligaments. Dilated veins con-

taining polypoid tumor masses were alsopresent in these areas. The masses exhibitedhistologic features of leiomyomas. Thick-walled arteries were frequently encounteredbetween the smooth muscle bundles com-

posing the intravascular masses. Seyler fa-vored Setzenfrey's theory of the pathogene-sis of these intravenous tumor masses. Nopostoperative course is recorded.Van Rijssel,13 in 1930, briefly described

two cases. The uteri contained ordinarymyomas. In one case a single intravenouspolypoid mass measuring 7 x 1 cm. was

present. In his second case several intra-venous tumors up to small finger size were

observed. Microscopically, the intravenoustumors were leiomyomas. No postoperativecourses are recorded.Meyers 9 recognized that in rare cases

benign myomatous tumors may grow intovessels.

Case ReportA 40-year-old white female, gravida II, para

II, was admitted to City Memorial Hospital on

September 16, 1956 with a 6 months history ofhypermenorrhea. Her periods occurred every 28to 30 days but with some increased flow lasting7 to 8 days. Spotting was present for several daysfollowing each period.

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Blood pressure was 100 systolic and 64 diastolicin mm. of mercury. Temperature was 37.10 C.Pulse rate was 72. Results of examination of thehead, neck, chest and extremities were negative.An ill defined mass was just palpable above thesymphysis pubis.

Pelvic examination revealed a moderate recto-cele. The uterus was nodular and the size of a 3to 4 months pregnancy. Two 5 to 6 cm. massescould be palpated in the region of the right cornu.The adnexae were not remarkable. Rectal examina-tion was negative except for confirming the vaginalexamination.

Urinalysis gave normal results. The hemoglobincontent was 13.5 Gm. per 100 cc. of blood. Leuko-cytes numbered 13,450 and the differential countwas within normal limits. Result of serological testfor syphilis (VDRL) was negative.

Past History: In December 1954, an area offibrocystic disease was excised from the rightbreast. Pelvic examination disclosed the uterus tobe in mid position and enlarged to twice normalsize with a 4 cm. mass in the region of the rightcornu.

In November 1955, another area of fibrocysticdisease of the right breast was excised. The uteruswas now nodular and enlarged to 3 times normalsize.

Operation: On September 17, 1956 a D & Cwas performed and the rectocele repaired. Theabdomen was entered through a suprapubic inci-sion. The uterus and right broad ligament pre-sented a most unusual picture. Many nodularmasses measuring up to 5 cm. were soft and some-

what fluctuant. On palpation they were sometimes

FIG. 1. Anterior surface of uterus and rightadnexa. Note numerous polypoid tumor massesprotruding from dilated veins of the myometriumand broad ligaments.

FIG. 2. Posterior surface of uterus and rightadnexa. Innumberable opalescent or translucentmasses blossom from cut surfaces and simulatehydatidiform mole.

elusive, slipping up and down the vascular spaces.This feature was best demonstrated in the regionof the thickened infundibulopelvic ligament. Thissame process extended well above the pelvic brimalong the course of the right ovarian vein, anddownward along the right side of the vagina.

On sectioning the right broad ligament, smooth,glistening, gray-white, polypoid masses flowedfrom innumerable dilated vascular spaces. Themasses were frequently connected by delicate tis-sue strands, simulating the picture of strung pop-corn. Similar but less marked changes were en-

countered on sectioning the left broad ligament.The ovaries were somewhat enlarged but were

otherwise not remarkable.Frozen sections of intravascular masses showed

smooth muscle bundles and hydropic degenera-tive changes. No features of malignancy were

found.A hysterectomy, right salpingo-oophorectomy

and appendectomy were performed. Tumor tissuewas left along the course of the right ovarianvessels and in the right perivaginal region. In viewof the benign histologic features, a more radicalprocedure was not performed.

The patient was free of symptoms 16 monthsfollowing operation.

Pathology

The uterus measured 13.5 x 7 x 5.3 cm.

The right broad ligament measured up to3.5 cm. in thickness. The surfaces of theuterus and ligament were bosselated. Soft,fluctuant nodules measuring up to 3 cm.

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INTRAVENOUS LEIMYOMATOSIS OF UTERUS AND PELVIS

were palpated in both the uterus and rightbroad ligament. Along the edge of resec-tion of the right broad ligament, numerouspolypoid tumor masses measuring up to1.5 cm. protruded from dilated vascularspaces (Fig. 1). Similar but fewer masses

were present on the left. The endometrialcavity was symmetrical, pink-tan andsmooth except for the curetted area. Thewall of the uterus averaged 2 cm. in thick-ness anteriorly and 3 cm. posteriorly.On sectioning the posterior wall of the

uterus, innumerable gray, translucent or

opalescent, polypoid masses measuring from2 mm. to 2 cm. blossomed from the cutsurfaces (Fig. 2). This process was mostmarked posteriorly and on the right sideof the uterus. These grape-like structureswere grossly suggestive of hydatidiformmole.On sectioning the broad ligament smooth

glistening tumor masses escaped from gap-ing veins measuring up to 2 cm. in diam-eter. Some of the masses were polypoid;others plexiform (Fig. 3). Many of the in-travascular masses were attached to thevein walls by delicate tissue threads or

by broader pedicles.Grossly nodular areas measuring up to

3 cm. were also present in the myometriumand right broad ligament (Fig. 4). Some

6 71

FIG. 3. Posterior surface, region of right ovaryand fallopian tube. The intravenous tumor masseshave escaped from the largest, gaping vein, on theleft.

FIG. 4. Examples of nodules present in theright broad ligament and myometrium. The one onthe left simulates an ordinary myoma. The one onthe right shows a coarsely laminated structure andmeasured 2.5 cm.

had a fine reticulated cut surface andgrossly simulated ordinary myomas. How-ever, distinct clefts were present at the pe-

riphery and some could be lifted out ofvascular spaces. Other nodules had a coarse

laminated appearance with many, large, ir-regular clefts (Fig. 4). A photomicrographof a typical 1 cm. nodule was selected forconvenience of presentation (Fig. 5). How-ever, sections of all nodules, regardless ofsize, showed the same basic architecture.No ordinary leiomyomas were found in thespecimen.The gross features of the nodules were

consistently correlated with the microscopicpictures. The coarsely laminated nodulesshowed loose plexiform intravascular masses(Fig 5). The regular, finely reticulatednodules were composed of very closely ag-

gregated masses separated by narrow slits(Fig. 6).The smaller vessels contained a few

masses or occasionally only a single mass

(Fig. 6). The vessel walls, containing elasticfibers and smooth muscle, exhibited thestructure of veins. Elastic laminae charac-teristic of arteries were not present. Insmaller vessels, focal thickening of themedia was frequently noted.

Various stages in the formation of theintravenous masses were observed. Ini-tially, small peg-like masses were formedby proliferation of the inner portion of the

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MARSHALL AND MORRIS Annals of SurgeryJanuary 1959

FIG. 5. Photomicrograph of a coarsely laminated, 1.0 cm. nodule. (Hematoxylin-Eosin, x 7.1.)

FIG. 6. Photomicrograph of a finely reticulated nodule. Note narrow slits between plexiform intra-venous tumor masses. Smnaller veins show thickened walls with tumor pegs arising from the media.(H-E, x 7,1.)

130

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INTRAVENOUS LEIMYOMATOSIS OF UTERUS AND PELVIS 131

FIG. 7. Photomicrograph of an intravenous tu-mor mass. Note longitudinally and tangentiallysectioned smooth muscle bundles. Hydropic changesare present on the right. (H-E, X 120)

media (Fig. 6). Stages of transition to bul-bous and finally slender ploypoid structures

were commonly encountered. These poly-poid masses extended for varying distancesalong the vessel lumen. In a given section,many of the masses showed no attachmentssince their pedicles were at a different levelin the vein.The intravascular masses had an endo-

thelial covering and were composed of in-terlacing bundles of smooth muscle as inordinary leiomyomas (Fig. 7). Where bun-dles were sectioned tangentially the nucleioften had a palisaded arrangement. No his-tologic features of malignancy were en-

countered. With differential stains varyingamounts of collagenous fibers were demon-strated among the smooth muscle bundles.The masses were generally well vascular-ized. In some intravenous masses manylarge arteries were present (Fig. 8). Focalareas of hyalinization, a feature common inleiomyomas, were observed. An unusual

FIG. 8. Photomicrograph of an intravenous tumor mass containing many thick-walled arteries.(H-E, X 55)

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MARSHALL AND MORRIS Annals of SurgeryJanuary 1959

FIG. 9. Photomicrograph demonstrating large pools of hydropic change. (H-E, x 55)

feature was the frequent occurrence ofsmall areas (Fig. 7) and large pools ofhydropic degeneration (Fig. 9). Identicalchanges occur in the chorionic villi of hy-datidiform moles which this specimen sim-ulated to some degree.The endometrium showed secretory type

glands and stroma. A few cystic glands were

present in the cervix. No areas of adeno-myosis were found. No notable pathologicchanges were encountered in the fallopiantube. The ovary measured 4.5 cm. in thegreatest dimension and contained multiplesmall cystic follicles. Typical intravenoustumor masses were present in the vessels ofthe hilum of the ovary. The appendix was

unremarkable.This unusual process was designated:

"Intravascular leiomyomatosis." Materialwas subsequently sent to the Armed Forces

Institute of Pathology (Accession 776146)wvhere it was studied by Dr. Hugh Grady.4He interpreted it as "a most peculiar andunusual intravascular leiomyoma." There isonly one other case in the files of the AFIPwhich was submitted by Kimmelstiel andWoltz in 1951 (AFIP Accession 503799).

Kimmelstiel,6 Dockerty 2 and Stewart 12lhave examined our material and concur inour diagnosis.

DiscussionSince intravenous leiomyomatosis is such

a rare entity, it seems remarkable that as

many as four clearly acceptable cases were

reported by a single observer many decadesago. Yet, we have not found a case reportedin the last 27 years. Nevertheless, occasionalcases are being recognized. Kimmelstiel 6kindly gave us sections from an unreported

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Volume 149 INTRAVENOUS LEIMYOMATOSIS OF UTERUS AND PELVIS 133Number 1

case he studied in 1951. Dockerty 2 recallshaving seen two cases which have not beenreported. We have interrogated many otherpathologists and surgeons, and none ofthem recalls having seen such a case.

In discussing this case with other physi-cians, some of them visualized endometrialstromatosis. Intravenous leiomyomatosiscould certainly be confused, on gross in-spection, with endometrial stromatosis sincein both entities there is permeation of vas-cular spaces by tumor tissue. Histologically,however, the smooth muscle bundles of theformer may be definitely differentiatedfrom the neoplastic endometrial stroma ofthe latter. The endometrium in our case,and when described in cases in the litera-ture, showed no notable pathologic changes.Although rare, pathologists and surgeons

should become familiar with this entity.We believe that further information willmore firmly establish distinct differencesbetween intravenous leiomyomatosis andendometrial stromatosis in regard to theirprognosis and perhaps in their surgicalmanagement.The type of vessel harboring the intra-

vascular masses has been a matter of con-troversy. We are convinced that they arosein veins in our case. The ultimate extensionof tumor through the iliac veins and the in-ferior vena cava in some cases supports ourconclusions.The pathogenesis is another area of dis-

agreement. Knauer concluded that the in-travascular masses arose as independent tu-mors from the vein walls. Sitzenfrey be-lieved they resulted from the intravenousshift of adjacent myomatous tissue. In allthe acceptable cases we could find in theliterature, nodules interpreted as ordinaryleiomyomas were also described in theuterus and usually in the broad ligaments.In contrast, we found none in our case, al-though nodules simulating ordinary myo-mas were present. The absence of ordinarymyomas in our case is evidence againstSitzenfrey's theory. After observing, in our

material, innumerable intravenous massesarising from vein walls which are not asso-ciated with adjacent tumor tissue, we areled to a firm acceptance of Knauer's con-clusions.

In our patient and in the cases reportedthere was a paucity of symptoms.We do not have adequate information

about the prognosis. The cases in the litera-ture were reported after short periods ofobservation. The patient of Kimmelstiel andWoltz 6 was free of symptoms when lastseen five and one-half years after surgery.In all cases, with one exception, the histo-logic picture has been that of a benign tu-mor. Since they are also covered with endo-thelium, it does not seem remarkable thatno evidence of distant metastases has beendescribed.The two deaths recorded in the literature

resulted from the tumor masses finally ex-tending into the right atrium. With thelimited information now available it ap-pears that the patients will not die as aresult of the neoplastic process, except on amechanical basis.

SummaryA case of intravenous leiomyomatosis of

the uterus and pelvis is reported. Seventeenacceptable cases found in the literature arereviewed. Although rare it is important thatsurgeons and pathologists become familiarwith this neoplasm. The pathogenesis andproblems in prognosis are discussed.

AcknowledgmentWe wish to thank Drs. Kimmelstiel and Woltz

and Dr. Dockerty for permission to cite their casesas a matter of incidence of this entity.

Bibliography1. Birch-Hirschfeld, F. V.: Lehrbuch der Patho-

logischen Anatomie. 5th Ed. Leipzig. F. C.W. Vogel, 1896. Page 226.

2. Dockerty, M. B., Mayo Clinic, Rochester, Min-nesota: Personal communication to theauthors.

3. Durck, H.: Ueber ein kontinvierlich durch dieentere Hohlvene in das Herz vorwachsendes.

134 MARSHALL AND MORRIS Annals of Surgery

Fibromyom des Uterus. Miinchen Med.Wchnschr., 54:1154, 1907.

4. Grady, H. G., Seton Hall College of Medicineand Dentistry, Jersey City, N. J.: Personalcommunication to the authors.

5. Hormann, Karl: Ueber einen Fall von myoma-tosem Uterustumor. Zentralbl. f. Gynaik., 31:1604, 1907.

6. Kimmelstiel, Paul and J. H. E. Woltz, Char-lotte Memorial Hospital, Charlotte, N. C.:Personal communication to the authors.

7. Knauer, E.: Beitrag zur Anatomie der Uterus-myome. Beitr. z. Geburtsh. u. Gynak., 1:695,1903.

8. Lahm, W.: Zur Frage des malignen Uterus-myoms. Ztschr. f. Geburtsh. u. Gynak., 77:340, 1915.

9. Meyer, Robert, in F. Henke and 0. Lubarsch:Handbuch der Speziellen PathologischenAnatomie Und Histologie. Berlin. JuliusSpringer, 1930. Vol. 7/1, Page 219.

10. Seyler: Histologisch typische und homologeMlyome des Uterus mit "intravenosem"Wachstum. Virchows Arch. f. Path. Anat.,233:277, 1921.

11. Sitzenfrey, Anton: Ueber Venenmyome desUterus mit intravaskularem Wachstum.Ztschr. f. Geburtsh. u. Gynaik., 68:1, 1911.

12. Stewart, F. W.: Memorial Center for Cancerand Allied Diseases, New York: Personalcommunication to the authors.

13. Van Rijssel, E. C.: Metastaseering van gezwel-len. Nederl. Tijdschr. v. Geneesk., 74:720,1930.