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Leiomyosarcoma of the Uterus Associated With Ramifying Angiomyoma
LEIOMYOSARCOMA
OF THE UTERUS ASSOCIATED RAMIFYING ANGIOMYOMA
WITH
A. M. GNASSI, M.D., AND H. P. PRICE, M.D., JERSEY CITY, N. J. (From
the Department
of Pathology
of the Jersey
City
Medical
Center)
V ASCULAR
neoplasms of the uterus remain unusual and interesting tumors. There are at present 39 recorded case@ of benign hemangiomas, the majority of which have been associated with leiomyofibromata. This ease is reported as an instance of a peculiar vascular process associated with a leiomyosarcoma of the uterus. Mrs. C. R. (248,281), a 39-year-old white married housewife, was admitted to the Jersey City Medical Center on Oct. 20, 1939, complaining of profuse menstrual bleeding of nine months’ duration. Nine months before admission her menstrual flow became profuse and many clots were passed. This continued for sixteen days and was accompanied by severe cramps. Menorrhagia of a similar nature has persisted, although one or two periods were of three days’ duration with but a moderate flow and less severe cramps. Four months before admission appeared a dull dragging lower abdominal pain which has been progressive. During the past three months mild headaches have accompanied her menses. Two months before admission the patient noted nocturia, two to three times, as well as infrequent dribbling with coughing or sneezing. The patient had previously been in good general health with the exception of the usual childhood diseases, and a tonsillectomy had been performed when she was 14 years of age. Five years ago she experienced an attack of epigastric pain of several days’ duration, and since that time she has noted intolerance to fried or fatty foods. Her menarche occurred at 10 years of age; her periods occurred regularly each twenty-eight days, lasted three to four days, and were accompanied by moderately severe cramps. She has two healthy children and two abortions occurred at two months’ and three months’ gestation, respectively. Physical examination revealed a well-developed and somewhat obese, middleaged white female who did not appear acutely ill. The temperature was 98.6” F., the pulse 78, respiration 22, and blood pressure 112/80. The general physical exThe abdomen was obese and lower abdominal amination was essentially normal. striae were present. There was slight tenderness in the left lower quadrant withA firm irregular, 5 cm. mass was felt directly out rebound tenderness or rigidity. above the symphysis. Pelvic examination disclosed cervical erosions and lacerations. The uterus was grapefruit in size and the ovaries were not felt. The urinary findings were within normal limits. The hemoglobin was 70 per cent, the red blood cells numbered 3.4 million, and the white blood cells 9,200, with 63 per cent polymorphonuclear leucoeytes. Laparotomy was performed on the following day. The uterus was enlarged to three times its usual size, and irregular in contour. A 4 cm. irregular, moderately firm mass extended from the left fundal wall into the broad ligament. A total hysterectomy and bilateral salpingo-oophorectomy were performed. The patient made an uneventful postoperative recovery and was discharged on the fifteenth hospital day. At the present time, eighteen months after her admission, large firm pelvic masses can be felt by bimanual examination. The surgical specimen consisted of a complete uterus, two tubes, and two ovaries. The uterus measured 15 by 6 by 5 cm. Its smooth surface was interrupted by a A somewhat softer, roughly round, 0.5 cm. firm peduneulated subserous mass. lobulated, smooth, 4 cm., light pink mass was broadly attached to the left side between the peritoneal folds of the broad ligament, and smaller portions of similar tissue surrounded the lower portion of the uterus. The myometrium was 2.5 em. 514
GNASSI AND PRICE : in thick cireumsc midport a whorl1
LEIOMYOSARCOMA
515
nes18, firm and light pink. Near the periphery were several quite well:rik bed soft, spongy, honeycombed, 0.5 to 1.5 cm., pink areas. Withi Ln the ion was a 0.3 cm., well-circumscribed, firm, translucent, white ! area with ike ! appearance. The endometrial cavity was compressed by a 3 cm. I*ourid,
Fig. l.- DiI ated tortuous endothelial-lined tubes and a cellulsr stroma supporting well developed arterioles and capillaries.
Fig. %.-Thrombosis
within
one of the large vascular channels.
616
AMERICAN
JOURNAL
OF
OBSTETRICS
AXD
GYNECOLOGY
submucous mass which was partially covered with fair1 y well-circumscribed, endo lmetrium and had a whorled, yellowish white cut surface with small, irn dark red areas of hemorrhage, The endometrium was smooth and yellowish with a blood-tinged surface. The cut surfaces of the parauterine mas2 ogeneous
Fig. I.-An
Fig.
and
light
intravascular
4.-EIongated
pink
with
small
areas
of hemorrhage.
process of elongated hyperchromatic capillaries and small arterioles.
cells
with
intact agular, white 1 were
hyperchromatic
nuclei
cells
and
supporting
mitotic
figures
dilated
GNA861 AXD PRICE : 4.5 cm. in length Each tub #e measured the musculares were furtoot1n, On section, intact.
Fig.
Fig.
B.-Elongated
cells
5.-Bizarre
with Small
scanty capillary
517
LE10MYO%\R&%iA and were
multinucleated
cytoplasm vessels
0.8 em. in diameter. well
giant
preserved,
The and
the
SW nfaces mu eosae
cells.
and oval nuclei are numerous.
rich
in
chromatin.
518
AMERICAN
JOURNAL
OF
OBSTETRICS
AND
GYXECOLOGY
One ovary nieasured 2.5 by 2 by 1 cm. On section, it presented several 0.5 cm., smooth lined cysts containing clear straw-colored fluid and a 0.5 cm. yellowish lined body filled with clotted blood supported by firm, white, ovarian stroma. The other ovary measured 3.5 by 2.5 by 2 cm. and contained similar cysts. Microscopically, the myometrium is interrupted by several circumscribed areas composed of numerous dilated vascular channels lined by small endothelial cells (Fig. 1). Many of these spaces contain thrombi (Fig. 2). The supporting stroma contains short spindle-shaped cells, numerous small capillaries, well-developed arterioles, and areas of well-differentiated smooth muscle. Within larger channels are intravascular projections of elongated spindle-shaped cells (Fig. 3). The margin of the tumor is quite well demarcated from the myometrium. The single submucous mass is composed of closely related spindle-shaped cells with hyperchromatic nuclei which are occasionally seen in mitosis (Fig. 4) and numerous large bizarre multinucleated giant cells (Fig. 5). Sections of the parauterine mass reveal chaotically arranged, moderately acidophilic, short spindle-shaped cells with oval or elongated nuclei rich in chromatin and with a moderate number of mitotic figures. Small capillary vessels are numerous (Fig. 6). There is hyperplasia of the endometrium, the ovaries contain hemorrhagic follicular and lutein cysts, and there is moderate fibrosis of the tubes. COMMENT
Horganz distinguishes true cavernous hemangiomas from hemangiomatous fibromyomas in which circumscribed areas of greatly enlarged vessels occur only within the smooth muscle tumor. Gardner3 uses the term “fibromyoma angiomatosum” to indicate an abundance of normally developed arteries within cellular fibromyomas. The present case has many features similar to the ramifying angiomyoma of the uterus published by Puschd in 1932. He described a 0.1 to 1.5 cm., branching, truncated mass of soft pink tissue ramifying through the myometrium from cornu to cornu and readily separated from the myometrial bed. A small, soft, red, globular structure bulged from the cut surface of the left broad ligament,. Histo1ogicalIy the tumor was composed of conspicuous blood vessels and smooth muscle fibers arranged in cordlike structures which frequently occupied dilated venous channels. There was no fusion of the neoplasm to the adjacent myometrium. The angiomatous tissue in our case could not be directly traced to the sarWe are prejudiced to the opinion that the vascular process is comatous nodule. independent of the leiomyosarcoma. REFERENCES
(I) lievorlcian, A. I’.: New England J. Med. Surg., Gynec. & Obst. 50: 990, 1930. (3) Gardner, 40: 822, 1940. (4) Pusch, L. C.: Ibid. 24: 907,1932.
Findley, Ct. M.: Chemotherapeutic Investigations uloma Venereum, Lancet 2: 682, 1940.
223: 1, 1940. G. IT.: AM.
(2) Borgan, E.: J. OBST. & GYNEC.
on the Virus of Lgmghogran-
Experiments on mice, infected intracerebrally with the virus of lymphogranuloma venereum and treated daily by mouth with 10 mg. per 20 Gm. mouse, showed that under the experimental conditions employed the most active compound was sulfamethylthiazole, followed by sulfapyridine, aulfathiazole, sulfanilamide, lutazeol and d&sodium 4:4’-bis-o-carboxylbenzoylamidodiphenylsulphone. Unfortunately in man sulfamethylthiazole may occasionally cause polyneuritis so that sulfapyridine remains the most effective drug clinically available. With sulfapyridine 50 of 100 inoculated animals survived in comparison to 13 survivals among 100 control inoculations. CARL P. HUBER
OF THE UTERUS ASSOCIATED RAMIFYING ANGIOMYOMA
WITH
A. M. GNASSI, M.D., AND H. P. PRICE, M.D., JERSEY CITY, N. J. (From
the Department
of Pathology
of the Jersey
City
Medical
Center)
V ASCULAR
neoplasms of the uterus remain unusual and interesting tumors. There are at present 39 recorded case@ of benign hemangiomas, the majority of which have been associated with leiomyofibromata. This ease is reported as an instance of a peculiar vascular process associated with a leiomyosarcoma of the uterus. Mrs. C. R. (248,281), a 39-year-old white married housewife, was admitted to the Jersey City Medical Center on Oct. 20, 1939, complaining of profuse menstrual bleeding of nine months’ duration. Nine months before admission her menstrual flow became profuse and many clots were passed. This continued for sixteen days and was accompanied by severe cramps. Menorrhagia of a similar nature has persisted, although one or two periods were of three days’ duration with but a moderate flow and less severe cramps. Four months before admission appeared a dull dragging lower abdominal pain which has been progressive. During the past three months mild headaches have accompanied her menses. Two months before admission the patient noted nocturia, two to three times, as well as infrequent dribbling with coughing or sneezing. The patient had previously been in good general health with the exception of the usual childhood diseases, and a tonsillectomy had been performed when she was 14 years of age. Five years ago she experienced an attack of epigastric pain of several days’ duration, and since that time she has noted intolerance to fried or fatty foods. Her menarche occurred at 10 years of age; her periods occurred regularly each twenty-eight days, lasted three to four days, and were accompanied by moderately severe cramps. She has two healthy children and two abortions occurred at two months’ and three months’ gestation, respectively. Physical examination revealed a well-developed and somewhat obese, middleaged white female who did not appear acutely ill. The temperature was 98.6” F., the pulse 78, respiration 22, and blood pressure 112/80. The general physical exThe abdomen was obese and lower abdominal amination was essentially normal. striae were present. There was slight tenderness in the left lower quadrant withA firm irregular, 5 cm. mass was felt directly out rebound tenderness or rigidity. above the symphysis. Pelvic examination disclosed cervical erosions and lacerations. The uterus was grapefruit in size and the ovaries were not felt. The urinary findings were within normal limits. The hemoglobin was 70 per cent, the red blood cells numbered 3.4 million, and the white blood cells 9,200, with 63 per cent polymorphonuclear leucoeytes. Laparotomy was performed on the following day. The uterus was enlarged to three times its usual size, and irregular in contour. A 4 cm. irregular, moderately firm mass extended from the left fundal wall into the broad ligament. A total hysterectomy and bilateral salpingo-oophorectomy were performed. The patient made an uneventful postoperative recovery and was discharged on the fifteenth hospital day. At the present time, eighteen months after her admission, large firm pelvic masses can be felt by bimanual examination. The surgical specimen consisted of a complete uterus, two tubes, and two ovaries. The uterus measured 15 by 6 by 5 cm. Its smooth surface was interrupted by a A somewhat softer, roughly round, 0.5 cm. firm peduneulated subserous mass. lobulated, smooth, 4 cm., light pink mass was broadly attached to the left side between the peritoneal folds of the broad ligament, and smaller portions of similar tissue surrounded the lower portion of the uterus. The myometrium was 2.5 em. 514
GNASSI AND PRICE : in thick cireumsc midport a whorl1
LEIOMYOSARCOMA
515
nes18, firm and light pink. Near the periphery were several quite well:rik bed soft, spongy, honeycombed, 0.5 to 1.5 cm., pink areas. Withi Ln the ion was a 0.3 cm., well-circumscribed, firm, translucent, white ! area with ike ! appearance. The endometrial cavity was compressed by a 3 cm. I*ourid,
Fig. l.- DiI ated tortuous endothelial-lined tubes and a cellulsr stroma supporting well developed arterioles and capillaries.
Fig. %.-Thrombosis
within
one of the large vascular channels.
616
AMERICAN
JOURNAL
OF
OBSTETRICS
AXD
GYNECOLOGY
submucous mass which was partially covered with fair1 y well-circumscribed, endo lmetrium and had a whorled, yellowish white cut surface with small, irn dark red areas of hemorrhage, The endometrium was smooth and yellowish with a blood-tinged surface. The cut surfaces of the parauterine mas2 ogeneous
Fig. I.-An
Fig.
and
light
intravascular
4.-EIongated
pink
with
small
areas
of hemorrhage.
process of elongated hyperchromatic capillaries and small arterioles.
cells
with
intact agular, white 1 were
hyperchromatic
nuclei
cells
and
supporting
mitotic
figures
dilated
GNA861 AXD PRICE : 4.5 cm. in length Each tub #e measured the musculares were furtoot1n, On section, intact.
Fig.
Fig.
B.-Elongated
cells
5.-Bizarre
with Small
scanty capillary
517
LE10MYO%\R&%iA and were
multinucleated
cytoplasm vessels
0.8 em. in diameter. well
giant
preserved,
The and
the
SW nfaces mu eosae
cells.
and oval nuclei are numerous.
rich
in
chromatin.
518
AMERICAN
JOURNAL
OF
OBSTETRICS
AND
GYXECOLOGY
One ovary nieasured 2.5 by 2 by 1 cm. On section, it presented several 0.5 cm., smooth lined cysts containing clear straw-colored fluid and a 0.5 cm. yellowish lined body filled with clotted blood supported by firm, white, ovarian stroma. The other ovary measured 3.5 by 2.5 by 2 cm. and contained similar cysts. Microscopically, the myometrium is interrupted by several circumscribed areas composed of numerous dilated vascular channels lined by small endothelial cells (Fig. 1). Many of these spaces contain thrombi (Fig. 2). The supporting stroma contains short spindle-shaped cells, numerous small capillaries, well-developed arterioles, and areas of well-differentiated smooth muscle. Within larger channels are intravascular projections of elongated spindle-shaped cells (Fig. 3). The margin of the tumor is quite well demarcated from the myometrium. The single submucous mass is composed of closely related spindle-shaped cells with hyperchromatic nuclei which are occasionally seen in mitosis (Fig. 4) and numerous large bizarre multinucleated giant cells (Fig. 5). Sections of the parauterine mass reveal chaotically arranged, moderately acidophilic, short spindle-shaped cells with oval or elongated nuclei rich in chromatin and with a moderate number of mitotic figures. Small capillary vessels are numerous (Fig. 6). There is hyperplasia of the endometrium, the ovaries contain hemorrhagic follicular and lutein cysts, and there is moderate fibrosis of the tubes. COMMENT
Horganz distinguishes true cavernous hemangiomas from hemangiomatous fibromyomas in which circumscribed areas of greatly enlarged vessels occur only within the smooth muscle tumor. Gardner3 uses the term “fibromyoma angiomatosum” to indicate an abundance of normally developed arteries within cellular fibromyomas. The present case has many features similar to the ramifying angiomyoma of the uterus published by Puschd in 1932. He described a 0.1 to 1.5 cm., branching, truncated mass of soft pink tissue ramifying through the myometrium from cornu to cornu and readily separated from the myometrial bed. A small, soft, red, globular structure bulged from the cut surface of the left broad ligament,. Histo1ogicalIy the tumor was composed of conspicuous blood vessels and smooth muscle fibers arranged in cordlike structures which frequently occupied dilated venous channels. There was no fusion of the neoplasm to the adjacent myometrium. The angiomatous tissue in our case could not be directly traced to the sarWe are prejudiced to the opinion that the vascular process is comatous nodule. independent of the leiomyosarcoma. REFERENCES
(I) lievorlcian, A. I’.: New England J. Med. Surg., Gynec. & Obst. 50: 990, 1930. (3) Gardner, 40: 822, 1940. (4) Pusch, L. C.: Ibid. 24: 907,1932.
Findley, Ct. M.: Chemotherapeutic Investigations uloma Venereum, Lancet 2: 682, 1940.
223: 1, 1940. G. IT.: AM.
(2) Borgan, E.: J. OBST. & GYNEC.
on the Virus of Lgmghogran-
Experiments on mice, infected intracerebrally with the virus of lymphogranuloma venereum and treated daily by mouth with 10 mg. per 20 Gm. mouse, showed that under the experimental conditions employed the most active compound was sulfamethylthiazole, followed by sulfapyridine, aulfathiazole, sulfanilamide, lutazeol and d&sodium 4:4’-bis-o-carboxylbenzoylamidodiphenylsulphone. Unfortunately in man sulfamethylthiazole may occasionally cause polyneuritis so that sulfapyridine remains the most effective drug clinically available. With sulfapyridine 50 of 100 inoculated animals survived in comparison to 13 survivals among 100 control inoculations. CARL P. HUBER