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Metastatic carcinoma in the uterus
METASTATIC
CARCINOMA HERMAN
CHARACHE,
BROOKLYN,
carcinoma in the uterus is very rare. According to Virchow’ those organs which are frequentIy the seat of primary tumors are seldom affected by metastatic growths; and according to Ewing2 the uterus is the first on the list of organs affected by primary cancer. The subject of metastatic tumors in the uterus is hardIy mentioned at a11 in the Iiterature, except in some instances when discussing carcinoma of the ovary and its reIationship to carcinoma of the uterus. Because of the close proximity of the two organs and the intimate reIationship of their lymphatics, it is often diffIcuIt to determine which of the two is the primary seat of the cancer. This is particularly true when the malignancy is Iimited to the peIvic organs. Offutt,3 in 1932, reported 616 cases of papiIIary cyst adenocarcinoma of the ovary from the Mayo CIinic. Eight and six-tenths per cent of the cases were associated with carcinoma of the uterus; and in 52 I cases of adenocarcinoma of the body of the uterus, there was associated carcinoma of the ovary in I I .g per cent. Norris and Murphy4 in the same year reported ninety-three cases of maIignant ovarian neoplasms, I 1.8 per cent of which also invorved the uterus. Metastasis usuaIIy takes place by the Iymphatic route and by contact impIantation. TranstubaI dissemination has been reported by Sampson,” Clark and Norris,G and Offutt. In severa of Offutt’s cases, carcinomatous ceIIs were found in the Iumen of the FaIIopian tubes, whiIe the bIood vesseIs and Iymphatic channeIs of the tubes were apparently normaI. Two similar cases were found by CIark and Norris. The ETASTATIC
IN THE UTERUS*
NEW
M.D.
YORK
Iatter believe that transtuba1 dissemination occurs in many cases of combined ovarian and uterine carcinoma. Ruge’ has demonstrated that 12 to 13 per cent of carcinoma of the FaIIopian tubes metastasizes to the uterus. Sampson advocates the ligation of the fimbriated end of the tubes before proceeding with the remova of the cancerous tissue, and the limitation of uterine curettage for fear that some of the curettings may make their way to the peritonea1 cavity. One other suggestion may be added -the aboIition of the uterine retractors which, when cIamped forcibIy down on the uterus, squeeze its contents through the FaIIopian tubes into the peritoneal cavity. Novak8 strongIy supports the theory of Iymphatic extension in cases of combined ovarian and uterine maIignancy, and he questions the extension of the maIignancy by contact impIantation, aIthough not denying its existence. Metastatic carcinoma in the uterus from extrapeIvic organs is extremeIy rare. Only fifty-six cases have been reported in the Iiterature up to the present writing. Thirty-one cases had their origin in the breast (55.4 per cent). Seventeen of them were reported by Tariick and WitteIshiiferg from the Vienna Pathologica Institute covering a period of sixty-two years (I 8 I 71879). The others were single case reports. Two of the cases, reported by Franqu&‘O and Schaper,” occurred in pregnant women. The former gives a very good discussion on metastatic carcinoma of the uterus. Fourteen cases had their origin in the stomach (25 per cent). One of these cases, reported by Senge,12 metastasized to the pIacenta.
* Frownthe Brooklyn Cancer Institute, Brooklyn, New York. 152
New SERIESVOL. LIII, No. I
Charache-Carcinoma
Nine cases originated in the folIowing organs: lungs three, pIeura one, pancreas one, liver one, gaIIbIadder one and kidney two. Two metastasized from meIanocarcinoma. AI1 cases came to autopsy. Four
additiona
cases
of
metastatic
carcinoma in the uterus are here reported. Three originated in the breast, making a tota of thirty-four cases of metastatic carcinoma of the uterus originating in the breast up to the present writing. The fourth case had its origin in papiIIary adenocarcinoma of the ovary. CASE
REPORTS
CASE I. Metastatic Carcinoma in the Uterus, Primary in the Ovary. A. K., a white female, aged forty-eight, was admitted to the Brooklyn Cancer Institute on November 3, 1939, for x-ray therapy, folIowing a supracervical hysterectomy and biIatera1 saIpingo-oophorectomy in another hospital. The operative diagnosis was papiIlary adenocarcinoma of the right ovary with metastasis to the uterus. This was confirmed by histoIogica1 study. The preoperative history consisted of abdominaI pain and distention of five months’ duration, irreguIar menses of two to three years, associated with passing of cIots and excessive vaginal bleeding lasting from twelve to eighteen days. She was married and had two chiIdren. Her past history and fan-my history were not relevant. On admission to our institution the patient appeared well nourished but somewhat dyspneic. The abdomen was markedIy distended with fluid. A palpable, freely movable tumor, the size of an orange, was found in the right upper quadrant. Pelvic examination revealed the stump of the cervix fixed by a paIpabIe tumor in the posterior cul-de-sac and a nodular indurated parametrium. FolIowing the removal of I, I oo cc. of straw-coIored fluid by abdominal paracentesis, numerous nodules were felt throughout the abdomen. The rest of the physical examination did not revea1 any noteworthy pathoIogy. The urine showed the presence of two plus albumin and numerous white ceIIs, with some hyaIin casts. The bIood urea was 20 mg., creatinin I mg., and sugar 60 mg. The blood Wassermann test was negative. The blood count showed 3,240,ooo red blood celIs with
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American Journal of Surgery
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56 per cent hemoglobin. The white count was with 89 per cent poIymorphonucIear Ieucocytes and 21 per cent lymphocytes. An 20,100
intravenous pyeIogram revealed no pathological condition of the kidneys. X-ray of the chest showed no pathoIogica1 condition of the Iungs or heart. The patient remained in the hospita1 under supportive treatment with repeated abdomina1 paracentesis and x-ray therapy to the abdomen, She died on ApriI 17, 1940. An autopsy was performed and reported by Dr. Herman Bolker as foIIows: (I) PapilIary adenocarcinoma of ovary with metastasis to the uterus (status postsupracervical hysterectomy and biIatera1 oophorectomy) with (a) peritoneal metastases involving the surfaces of a11 abdomina1 viscera, with ascites, (b) peritoneal fibrosis, with multiple adhesions, (c) metastases to iliac lymphnodes and retroperitoneaI tissues, (d) cervicaI erosion, and (e) subacute urocystitis. (2) Right fibrous pleurisy, (3) chronic cholecystitis with ChoIelithiasis; and (4) aortic ateroscIerosis. CASE 11. 1Uetastatic Carcinoma in the Uterus, Primcq- in the Breast. B. B., a white female, aged Iifty-five, was admitted to the Brooklyn Cancer Institute on November g, 1937, complaining of pain in a postoperative mastectomy scar and pain in the right hip radiating to the back. In February, 1935, she noticed a smal1 lump in her breast associated with pain in her right arm. She was admitted to a hospital where a diagnosis of carcinoma was made. The diagnosis was confirmed histoIogicaIly foIIowing a radical mastectomy. The patient later received postoperative deep x-ray therapy. Two years later, May, 1937, she deveIoped a mass in the right axiIIa associated with pain and diflicuIty in manipuIating her right arm. The tumor disappeared four months Iater folIowing the insertion of twelve radon seeds by a private physician. Two months later she was admitted to our Institution. She had never had any other illness. Her menopause was three years previous to admission. Her family history was irrelevant. Physical examination reveaIed a we11 deveIoped, weI nourished white female, not acutely iI1. A firm fixed gland, measuring 2 cm. in diameter, was found in the right supracIavicuIar region, The right breast was absent. There was no evidence of any recurrence. En cuirasse noduIes were present in the chest wall. The left
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FIG. I. Photomicrograph showing A, papilIary adenocarcinoma of the ovary and B, metastasis in the uterus; E and G, primary carcinoma of the breast; c, D, F and H, metastatic carcinoma in the uterus. I80 X.
NEW SERIES VOL. LIII, No. I
Charache-Carcinoma
breast was free from tumefaction. A moderate amount of induration was found in the right axilla. Her heart and Iungs did not revea1 any evidence of pathoIogica1 conditions. The abdomen was free from any paIpabIe tumor. Pelvic examination revealed a partiaIIy stenosed introitus and an enIarged uterus diagnosed as a fibroid. The blood Wassermann test was negative. The blood count, bIood chemistry and urine examination were within normal limits. Roentgenographic study of the lungs and skeIeton reveaIed a metastatic Iesion and partia1 destruction of the second lumbar vertebra with no other evidence of metastatic invoIvement. The patient received deep x-ray therapy to the right supracIavicuIar area and Iumbar spine, resulting in reIief of her symptoms. She was folIowed up in our clinic. Three months later she was readmitted to the hospita1 complaining of vaginal bleeding, recurrent back pain and inabiIity to move her bowels for ten days. She stated that her rectum was closed and was unabIe to admit the enema tube. At this time the patient appeared jaundiced. The noduIe in the right supracIavicuIar region was twice its former size. The lower portion of her abdomen was distended. A metastatic noduIe measuring 3 cm. in diameter was paIpable near the umbiIicus. She had a Iarge indurated mass in the posterior vaginal waI1 pressing on the rectum. The rectal opening was very smaI1 and constricted. Roentgenographic examination at this time reveaIed metastatic invoIvement of the right femur in addition to the destruction of the second Iumbar vertebra present at her previous admission. The patient was kept comfortabIe under supportive treatment. She died March 8, 1939, Autopsy performed by Dr. BoIker was reported as foIIows: (I) Carcinoma of the right breast (postoperative radica1 mastectomy) with metastasis to the substerna1, tracheobronchial and retroperitoneal Iymphnodes, Iungs, liver, peritoneum, spleen, uterus, ovaries, vagina, rectum, second Iumbar vertebra; and (2) acute puruIent pneumonia. CASE III. Metastatic Carcinoma in the Uterus. Primary in the Breast. P. D., a white female, aged forty-eight, was admitted to the Brooklyn Cancer Institute on January 13, 1940, complaining of pain and sweIIing of her left arm and neck, backache, pain in the Ieft hip and knee. In March, 1936, she had a radical left mastectomy in another hospita1. She received
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preoperative radium treatment and postoperative x-ray and radium therapy. She returned to the same hospita1 three years Iater with metastatic involvement of the dorsa1 spine and was treated with aIcoho1 bIock, cobra venom, and large doses of morphine for intractabIe pain. She was Iater referred to the Brooklyn Cancer Institute for supportive treatment. Examination reveaIed a white aduIt femaIe, chronicaIIy iI1, poorIy nourished, confined to bed. The Ieft pupi was smaIIer than the right, with a drooping of the upper Iid, showing evidence of Horner’s syndrome. The cervical gIands were bilateraIIy enIarged, extending from the supracIavicuIar area to the occiput. The skin of the neck showed marked radiation changes with pigmentation. Similar radiation changes were found over the chest and upper portion of the abdomen. Numerous en cuirasse nodules were present over the chest waI1. The right breast was firm and solid. The nipple was retracted and the skin was covered with en cuirasse noduIes. The left upper extremity was more than twice the normal size. The Iymphedema included the fingers, which were contracted and deformed. The skin of the left upper portion of the abdomen was edematous and noduIar. The Iiver was enIarged to two to three fingers below the Costa1 margin. Both gIutea1 regions were Iymphedematous. The entire course of the spine was very tender on palpation. The bIood count showed 3,860,ooo red ceIIs with 73 per cent hemoglobin and 10,450 white ceIIs with 66 per cent poIymorphonucIear Ieucocytes, 27 per cent Iymphocytes and 7 per cent monocytes. The bIood chemistry was within normal Iimits. The bIood Wassermann test was negative. Roentgenographic examination revealed widespread metastasis of the fourth, fifth, sixth, seventh, eighth and tweIfth thoracic, first, second and third Iumbar vertebrae, sacrum and peIvis. The patient was kept camfortable with supportive treatment untiI April 9, 1940, when she expired. An autopsy was performed and reported by Dr. Balker as follows: (I) Carcinoma of Ieft breast with (a) metastases to skin of chest waI1, tissues of neck, Ieft pleura with effusion and pulmonary ateIectasis, hepatic porta Iymphnodes with diIatation of right hepatic bile duct, omentar nodes, vermiform appendix, Ieft ureter with mild hydronephrosis,
156
American
Journal
01’Surgcry
Charache-Carcinoma
urinary bladder, utcrinc \vall (fundal and cervical), Icft Fallopian tube and round Iigament, gastric and recta1 serosac; (b) edema 01 left upper extremity; (c) radiation changes, skin of chest; (d) status post right radical mastectomy. (2) Acute purulent bronchopneumonia; (3) cavernous hemangioma of liver; (4) adrenal medullary calcification; (5) myoma uteri; and (6) aterosclerosis. CASE IV. Metastatic Carcinoma in the Uterus, F. C., a white femaIe, F’rimarJ. in the Breast.
aged forty-seven, was admitted to the Brooklyn Cancer Institute on February I, 1940, complaining of a lump in a postoperative mastectomy scar. In June, 1936, she had a radical mastectomy in another hospital. The pathological report was duct cell carcinoma, alveolar in origin. The diagnosis was confirmed in our Institution. Following operation she was in exceIIent health for three and one-half years. Three months previous to admission to our Institution, she noticed a Iump in the postoperative scar. This was associated with some Ioss of weight and genera1 weakness. Her menstrua1 periods began at the age of eleven, were always regular, Iasting for four days. For the last six months she had marked dysmenorrhea and profuse menorrhagia, which left her in a very weak, rundown condition. Her past history and famiIy history were uneventful. Examination reveaIed an aduIt white female, somewhat anemic in appearance, moderately well nourished. Several pea-sized nodules were present over the mastectomy scar. The surrounding skin was contracted and firmly adherent to the chest wall. Similar noduIes were present over the manubrium sterni and epigastric region. Th e right arm was lymphedematous, as was the left breast, but there was no paIpable tumor present within the breast. The supraclavicular and axillary glands were not enlarged. Pelvic examination revealed the cervix to be larger than normal and cystic. The fundus was firm and enIarged to the size of an eight months’ gestation. The uterus was freely movable in all directions. The adnexa were free from any tumefaction. The rest of the physical examination did not reveal any evidence of a pathological condition. The urine was not pathologic; the blood chemistry was within normal limits; the blood Wassermann test was negative. The blood count
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JULY. I’)_,’
showed evidence of a lo\\- gratlc anemia, but was otherwise normaI. Roentgenogram of the chest and pelvis showed no evidence of pulmonary or osseous metastasis. A biopsy from one of the chest nodules was reported as metastatic in origin. The curettings from the cervix and fundus were also found to be metastatic carcinoma of mammary origin. The pathological report by Dr. Balker was as follows: Microscopic examination: The endometrium consists of numerous tortuous glands in the secretory phase. There is some swelling of the stroma cells. In spotty areas there is an invasion of groups of atypica1 ceIIs which occur in rows or small alveoli. They occasionally surround the uterine gland without causing its destruction. The individual ceIIs are polygonal in outline, with a deep pink cytoplasm, and vesicular or markedly hyperchromatic irregular nucIei. One area shows an invasion of the uterine musculature. There is a heavy localized infiltrate of lymphocytes and polymorphonucIear leukocytes. The cervix is Iined by intact histoIogicalIy normal layer of stratified squamous epitheIium. Deep in the stroma paravascular are small groups of atypical cells which strongly resemble those of the uterine lesion. They are surrounded by fibrous tissue, the bundles of which are coIlapsed. Diagnosis: Metastatic carcinoma of uterus, fundal and cervical. The patient received 1,500 mg. of radium into the uterus and a similar amount in the form of radium needIes to the nodules of the skin. On June 4, 1940, an explOratOry hparOtOIIIy was performed. Multiple greyish, white nodules were found covering the peritonea1 surface of the uterus, tubes, the serosa of the small intestine (ileum) and the peritoneum of the lower abdominal wall. The para-aortic glands were enlarged. The liver was not involved. Several of the nodules were removed for histological study and were reported as metastatic carcinoma of breast origin. The patient is now convalescing in the hospital and receiving racliation therapy to the pelvis. SUMMARY
AND
CONCLUSION
I. Metastatic carcinoma in the uterus is very rare. When it does occur, the primary Iesions, in order of frequency, are: ovary, Fallopian tubes, breast and stomach. Cases
NEW
SERIES VOL.LIII. No.
I
CharachePCarcinoma
with primary Iesions in the Iungs, pIeura, pancreas, liver, gaIIbIadder and kidney, as we11 as two meIanocarcinomas, are reported. 2. StiII rarer are metastatic tumors in the uterus of extrapeIvic origin. 3. Only fifty-six such cases were reported in the literature. 4. Four additional proven cases of metastatic carcinoma in the uterus are here reported from the BrookIyn Cancer Institute. Three had their origin in the breast and one in the ovary. 5. Of the fifty-nine cases of metastatic tumor in the uterus of extrapelvic origin, thirty-four or 47.6 per cent had their origin in the breast.
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REFERENCES I.
2.
3. 4. 5. 6.
7. 8. 0. IO.
I I.
12.
VIRCHOW. Die Krankhaften Geschwuelste, vo1. I, p. 69. Berlin, 1863. EWING, JAMES. Neoplastic Diseases, 3rd ed., p. 584. Phitadelphia and London, W. B. Saunders Co. OFFUTT, SUSAN R. Surg., Gynec. 0 Obst., 54: 490, 1932. NORRIS, CHARLES C. and MURPHY, DOUGLAS P. Am. J. Obst. &+Gynec., 23: 833, 1932. SAMPSON, J. A. Surg., Gynec. @YObst., 38: 287, 1924. CLARK, J. G. and NORRIS, CHARLES C. Radium in Gynecology, p. 315. Philadelphia, 1927. Lipincott co. Kuti~, II. Arch. Gyniik., 106: 207, 1917. NOVAK, E~~IL. Am. J. Obst. c’~C$~ec., 14: 470, 1927. V. Tii~iic~ and WITTELSH~FER. v. Langenbcck’s Arch., 25 bd., 1880. V. FRANQU~, FELT-STOECKEL. Handbuck dcr Gyngkologie, vo1. 6’, p. 192, 3rd cd. SCHAPER. Vircbows Arch., bd. 129, 1892. SENGE. Zeigler’s Beitr., bd. 53, s. 532, 1895.
CARCINOMA HERMAN
CHARACHE,
BROOKLYN,
carcinoma in the uterus is very rare. According to Virchow’ those organs which are frequentIy the seat of primary tumors are seldom affected by metastatic growths; and according to Ewing2 the uterus is the first on the list of organs affected by primary cancer. The subject of metastatic tumors in the uterus is hardIy mentioned at a11 in the Iiterature, except in some instances when discussing carcinoma of the ovary and its reIationship to carcinoma of the uterus. Because of the close proximity of the two organs and the intimate reIationship of their lymphatics, it is often diffIcuIt to determine which of the two is the primary seat of the cancer. This is particularly true when the malignancy is Iimited to the peIvic organs. Offutt,3 in 1932, reported 616 cases of papiIIary cyst adenocarcinoma of the ovary from the Mayo CIinic. Eight and six-tenths per cent of the cases were associated with carcinoma of the uterus; and in 52 I cases of adenocarcinoma of the body of the uterus, there was associated carcinoma of the ovary in I I .g per cent. Norris and Murphy4 in the same year reported ninety-three cases of maIignant ovarian neoplasms, I 1.8 per cent of which also invorved the uterus. Metastasis usuaIIy takes place by the Iymphatic route and by contact impIantation. TranstubaI dissemination has been reported by Sampson,” Clark and Norris,G and Offutt. In severa of Offutt’s cases, carcinomatous ceIIs were found in the Iumen of the FaIIopian tubes, whiIe the bIood vesseIs and Iymphatic channeIs of the tubes were apparently normaI. Two similar cases were found by CIark and Norris. The ETASTATIC
IN THE UTERUS*
NEW
M.D.
YORK
Iatter believe that transtuba1 dissemination occurs in many cases of combined ovarian and uterine carcinoma. Ruge’ has demonstrated that 12 to 13 per cent of carcinoma of the FaIIopian tubes metastasizes to the uterus. Sampson advocates the ligation of the fimbriated end of the tubes before proceeding with the remova of the cancerous tissue, and the limitation of uterine curettage for fear that some of the curettings may make their way to the peritonea1 cavity. One other suggestion may be added -the aboIition of the uterine retractors which, when cIamped forcibIy down on the uterus, squeeze its contents through the FaIIopian tubes into the peritoneal cavity. Novak8 strongIy supports the theory of Iymphatic extension in cases of combined ovarian and uterine maIignancy, and he questions the extension of the maIignancy by contact impIantation, aIthough not denying its existence. Metastatic carcinoma in the uterus from extrapeIvic organs is extremeIy rare. Only fifty-six cases have been reported in the Iiterature up to the present writing. Thirty-one cases had their origin in the breast (55.4 per cent). Seventeen of them were reported by Tariick and WitteIshiiferg from the Vienna Pathologica Institute covering a period of sixty-two years (I 8 I 71879). The others were single case reports. Two of the cases, reported by Franqu&‘O and Schaper,” occurred in pregnant women. The former gives a very good discussion on metastatic carcinoma of the uterus. Fourteen cases had their origin in the stomach (25 per cent). One of these cases, reported by Senge,12 metastasized to the pIacenta.
* Frownthe Brooklyn Cancer Institute, Brooklyn, New York. 152
New SERIESVOL. LIII, No. I
Charache-Carcinoma
Nine cases originated in the folIowing organs: lungs three, pIeura one, pancreas one, liver one, gaIIbIadder one and kidney two. Two metastasized from meIanocarcinoma. AI1 cases came to autopsy. Four
additiona
cases
of
metastatic
carcinoma in the uterus are here reported. Three originated in the breast, making a tota of thirty-four cases of metastatic carcinoma of the uterus originating in the breast up to the present writing. The fourth case had its origin in papiIIary adenocarcinoma of the ovary. CASE
REPORTS
CASE I. Metastatic Carcinoma in the Uterus, Primary in the Ovary. A. K., a white female, aged forty-eight, was admitted to the Brooklyn Cancer Institute on November 3, 1939, for x-ray therapy, folIowing a supracervical hysterectomy and biIatera1 saIpingo-oophorectomy in another hospital. The operative diagnosis was papiIlary adenocarcinoma of the right ovary with metastasis to the uterus. This was confirmed by histoIogica1 study. The preoperative history consisted of abdominaI pain and distention of five months’ duration, irreguIar menses of two to three years, associated with passing of cIots and excessive vaginal bleeding lasting from twelve to eighteen days. She was married and had two chiIdren. Her past history and fan-my history were not relevant. On admission to our institution the patient appeared well nourished but somewhat dyspneic. The abdomen was markedIy distended with fluid. A palpable, freely movable tumor, the size of an orange, was found in the right upper quadrant. Pelvic examination revealed the stump of the cervix fixed by a paIpabIe tumor in the posterior cul-de-sac and a nodular indurated parametrium. FolIowing the removal of I, I oo cc. of straw-coIored fluid by abdominal paracentesis, numerous nodules were felt throughout the abdomen. The rest of the physical examination did not revea1 any noteworthy pathoIogy. The urine showed the presence of two plus albumin and numerous white ceIIs, with some hyaIin casts. The bIood urea was 20 mg., creatinin I mg., and sugar 60 mg. The blood Wassermann test was negative. The blood count showed 3,240,ooo red blood celIs with
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American Journal of Surgery
‘53
56 per cent hemoglobin. The white count was with 89 per cent poIymorphonucIear Ieucocytes and 21 per cent lymphocytes. An 20,100
intravenous pyeIogram revealed no pathological condition of the kidneys. X-ray of the chest showed no pathoIogica1 condition of the Iungs or heart. The patient remained in the hospita1 under supportive treatment with repeated abdomina1 paracentesis and x-ray therapy to the abdomen, She died on ApriI 17, 1940. An autopsy was performed and reported by Dr. Herman Bolker as foIIows: (I) PapilIary adenocarcinoma of ovary with metastasis to the uterus (status postsupracervical hysterectomy and biIatera1 oophorectomy) with (a) peritoneal metastases involving the surfaces of a11 abdomina1 viscera, with ascites, (b) peritoneal fibrosis, with multiple adhesions, (c) metastases to iliac lymphnodes and retroperitoneaI tissues, (d) cervicaI erosion, and (e) subacute urocystitis. (2) Right fibrous pleurisy, (3) chronic cholecystitis with ChoIelithiasis; and (4) aortic ateroscIerosis. CASE 11. 1Uetastatic Carcinoma in the Uterus, Primcq- in the Breast. B. B., a white female, aged Iifty-five, was admitted to the Brooklyn Cancer Institute on November g, 1937, complaining of pain in a postoperative mastectomy scar and pain in the right hip radiating to the back. In February, 1935, she noticed a smal1 lump in her breast associated with pain in her right arm. She was admitted to a hospital where a diagnosis of carcinoma was made. The diagnosis was confirmed histoIogicaIly foIIowing a radical mastectomy. The patient later received postoperative deep x-ray therapy. Two years later, May, 1937, she deveIoped a mass in the right axiIIa associated with pain and diflicuIty in manipuIating her right arm. The tumor disappeared four months Iater folIowing the insertion of twelve radon seeds by a private physician. Two months later she was admitted to our Institution. She had never had any other illness. Her menopause was three years previous to admission. Her family history was irrelevant. Physical examination reveaIed a we11 deveIoped, weI nourished white female, not acutely iI1. A firm fixed gland, measuring 2 cm. in diameter, was found in the right supracIavicuIar region, The right breast was absent. There was no evidence of any recurrence. En cuirasse noduIes were present in the chest wall. The left
‘$4
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JULY, ,941
FIG. I. Photomicrograph showing A, papilIary adenocarcinoma of the ovary and B, metastasis in the uterus; E and G, primary carcinoma of the breast; c, D, F and H, metastatic carcinoma in the uterus. I80 X.
NEW SERIES VOL. LIII, No. I
Charache-Carcinoma
breast was free from tumefaction. A moderate amount of induration was found in the right axilla. Her heart and Iungs did not revea1 any evidence of pathoIogica1 conditions. The abdomen was free from any paIpabIe tumor. Pelvic examination revealed a partiaIIy stenosed introitus and an enIarged uterus diagnosed as a fibroid. The blood Wassermann test was negative. The blood count, bIood chemistry and urine examination were within normal limits. Roentgenographic study of the lungs and skeIeton reveaIed a metastatic Iesion and partia1 destruction of the second lumbar vertebra with no other evidence of metastatic invoIvement. The patient received deep x-ray therapy to the right supracIavicuIar area and Iumbar spine, resulting in reIief of her symptoms. She was folIowed up in our clinic. Three months later she was readmitted to the hospita1 complaining of vaginal bleeding, recurrent back pain and inabiIity to move her bowels for ten days. She stated that her rectum was closed and was unabIe to admit the enema tube. At this time the patient appeared jaundiced. The noduIe in the right supracIavicuIar region was twice its former size. The lower portion of her abdomen was distended. A metastatic noduIe measuring 3 cm. in diameter was paIpable near the umbiIicus. She had a Iarge indurated mass in the posterior vaginal waI1 pressing on the rectum. The rectal opening was very smaI1 and constricted. Roentgenographic examination at this time reveaIed metastatic invoIvement of the right femur in addition to the destruction of the second Iumbar vertebra present at her previous admission. The patient was kept comfortabIe under supportive treatment. She died March 8, 1939, Autopsy performed by Dr. BoIker was reported as foIIows: (I) Carcinoma of the right breast (postoperative radica1 mastectomy) with metastasis to the substerna1, tracheobronchial and retroperitoneal Iymphnodes, Iungs, liver, peritoneum, spleen, uterus, ovaries, vagina, rectum, second Iumbar vertebra; and (2) acute puruIent pneumonia. CASE III. Metastatic Carcinoma in the Uterus. Primary in the Breast. P. D., a white female, aged forty-eight, was admitted to the Brooklyn Cancer Institute on January 13, 1940, complaining of pain and sweIIing of her left arm and neck, backache, pain in the Ieft hip and knee. In March, 1936, she had a radical left mastectomy in another hospita1. She received
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preoperative radium treatment and postoperative x-ray and radium therapy. She returned to the same hospita1 three years Iater with metastatic involvement of the dorsa1 spine and was treated with aIcoho1 bIock, cobra venom, and large doses of morphine for intractabIe pain. She was Iater referred to the Brooklyn Cancer Institute for supportive treatment. Examination reveaIed a white aduIt femaIe, chronicaIIy iI1, poorIy nourished, confined to bed. The Ieft pupi was smaIIer than the right, with a drooping of the upper Iid, showing evidence of Horner’s syndrome. The cervical gIands were bilateraIIy enIarged, extending from the supracIavicuIar area to the occiput. The skin of the neck showed marked radiation changes with pigmentation. Similar radiation changes were found over the chest and upper portion of the abdomen. Numerous en cuirasse nodules were present over the chest waI1. The right breast was firm and solid. The nipple was retracted and the skin was covered with en cuirasse noduIes. The left upper extremity was more than twice the normal size. The Iymphedema included the fingers, which were contracted and deformed. The skin of the left upper portion of the abdomen was edematous and noduIar. The Iiver was enIarged to two to three fingers below the Costa1 margin. Both gIutea1 regions were Iymphedematous. The entire course of the spine was very tender on palpation. The bIood count showed 3,860,ooo red ceIIs with 73 per cent hemoglobin and 10,450 white ceIIs with 66 per cent poIymorphonucIear Ieucocytes, 27 per cent Iymphocytes and 7 per cent monocytes. The bIood chemistry was within normal Iimits. The bIood Wassermann test was negative. Roentgenographic examination revealed widespread metastasis of the fourth, fifth, sixth, seventh, eighth and tweIfth thoracic, first, second and third Iumbar vertebrae, sacrum and peIvis. The patient was kept camfortable with supportive treatment untiI April 9, 1940, when she expired. An autopsy was performed and reported by Dr. Balker as follows: (I) Carcinoma of Ieft breast with (a) metastases to skin of chest waI1, tissues of neck, Ieft pleura with effusion and pulmonary ateIectasis, hepatic porta Iymphnodes with diIatation of right hepatic bile duct, omentar nodes, vermiform appendix, Ieft ureter with mild hydronephrosis,
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urinary bladder, utcrinc \vall (fundal and cervical), Icft Fallopian tube and round Iigament, gastric and recta1 serosac; (b) edema 01 left upper extremity; (c) radiation changes, skin of chest; (d) status post right radical mastectomy. (2) Acute purulent bronchopneumonia; (3) cavernous hemangioma of liver; (4) adrenal medullary calcification; (5) myoma uteri; and (6) aterosclerosis. CASE IV. Metastatic Carcinoma in the Uterus, F. C., a white femaIe, F’rimarJ. in the Breast.
aged forty-seven, was admitted to the Brooklyn Cancer Institute on February I, 1940, complaining of a lump in a postoperative mastectomy scar. In June, 1936, she had a radical mastectomy in another hospital. The pathological report was duct cell carcinoma, alveolar in origin. The diagnosis was confirmed in our Institution. Following operation she was in exceIIent health for three and one-half years. Three months previous to admission to our Institution, she noticed a Iump in the postoperative scar. This was associated with some Ioss of weight and genera1 weakness. Her menstrua1 periods began at the age of eleven, were always regular, Iasting for four days. For the last six months she had marked dysmenorrhea and profuse menorrhagia, which left her in a very weak, rundown condition. Her past history and famiIy history were uneventful. Examination reveaIed an aduIt white female, somewhat anemic in appearance, moderately well nourished. Several pea-sized nodules were present over the mastectomy scar. The surrounding skin was contracted and firmly adherent to the chest wall. Similar noduIes were present over the manubrium sterni and epigastric region. Th e right arm was lymphedematous, as was the left breast, but there was no paIpable tumor present within the breast. The supraclavicular and axillary glands were not enlarged. Pelvic examination revealed the cervix to be larger than normal and cystic. The fundus was firm and enIarged to the size of an eight months’ gestation. The uterus was freely movable in all directions. The adnexa were free from any tumefaction. The rest of the physical examination did not reveal any evidence of a pathological condition. The urine was not pathologic; the blood chemistry was within normal limits; the blood Wassermann test was negative. The blood count
of Uterus
JULY. I’)_,’
showed evidence of a lo\\- gratlc anemia, but was otherwise normaI. Roentgenogram of the chest and pelvis showed no evidence of pulmonary or osseous metastasis. A biopsy from one of the chest nodules was reported as metastatic in origin. The curettings from the cervix and fundus were also found to be metastatic carcinoma of mammary origin. The pathological report by Dr. Balker was as follows: Microscopic examination: The endometrium consists of numerous tortuous glands in the secretory phase. There is some swelling of the stroma cells. In spotty areas there is an invasion of groups of atypica1 ceIIs which occur in rows or small alveoli. They occasionally surround the uterine gland without causing its destruction. The individual ceIIs are polygonal in outline, with a deep pink cytoplasm, and vesicular or markedly hyperchromatic irregular nucIei. One area shows an invasion of the uterine musculature. There is a heavy localized infiltrate of lymphocytes and polymorphonucIear leukocytes. The cervix is Iined by intact histoIogicalIy normal layer of stratified squamous epitheIium. Deep in the stroma paravascular are small groups of atypical cells which strongly resemble those of the uterine lesion. They are surrounded by fibrous tissue, the bundles of which are coIlapsed. Diagnosis: Metastatic carcinoma of uterus, fundal and cervical. The patient received 1,500 mg. of radium into the uterus and a similar amount in the form of radium needIes to the nodules of the skin. On June 4, 1940, an explOratOry hparOtOIIIy was performed. Multiple greyish, white nodules were found covering the peritonea1 surface of the uterus, tubes, the serosa of the small intestine (ileum) and the peritoneum of the lower abdominal wall. The para-aortic glands were enlarged. The liver was not involved. Several of the nodules were removed for histological study and were reported as metastatic carcinoma of breast origin. The patient is now convalescing in the hospital and receiving racliation therapy to the pelvis. SUMMARY
AND
CONCLUSION
I. Metastatic carcinoma in the uterus is very rare. When it does occur, the primary Iesions, in order of frequency, are: ovary, Fallopian tubes, breast and stomach. Cases
NEW
SERIES VOL.LIII. No.
I
CharachePCarcinoma
with primary Iesions in the Iungs, pIeura, pancreas, liver, gaIIbIadder and kidney, as we11 as two meIanocarcinomas, are reported. 2. StiII rarer are metastatic tumors in the uterus of extrapeIvic origin. 3. Only fifty-six such cases were reported in the literature. 4. Four additional proven cases of metastatic carcinoma in the uterus are here reported from the BrookIyn Cancer Institute. Three had their origin in the breast and one in the ovary. 5. Of the fifty-nine cases of metastatic tumor in the uterus of extrapelvic origin, thirty-four or 47.6 per cent had their origin in the breast.
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REFERENCES I.
2.
3. 4. 5. 6.
7. 8. 0. IO.
I I.
12.
VIRCHOW. Die Krankhaften Geschwuelste, vo1. I, p. 69. Berlin, 1863. EWING, JAMES. Neoplastic Diseases, 3rd ed., p. 584. Phitadelphia and London, W. B. Saunders Co. OFFUTT, SUSAN R. Surg., Gynec. 0 Obst., 54: 490, 1932. NORRIS, CHARLES C. and MURPHY, DOUGLAS P. Am. J. Obst. &+Gynec., 23: 833, 1932. SAMPSON, J. A. Surg., Gynec. @YObst., 38: 287, 1924. CLARK, J. G. and NORRIS, CHARLES C. Radium in Gynecology, p. 315. Philadelphia, 1927. Lipincott co. Kuti~, II. Arch. Gyniik., 106: 207, 1917. NOVAK, E~~IL. Am. J. Obst. c’~C$~ec., 14: 470, 1927. V. Tii~iic~ and WITTELSH~FER. v. Langenbcck’s Arch., 25 bd., 1880. V. FRANQU~, FELT-STOECKEL. Handbuck dcr Gyngkologie, vo1. 6’, p. 192, 3rd cd. SCHAPER. Vircbows Arch., bd. 129, 1892. SENGE. Zeigler’s Beitr., bd. 53, s. 532, 1895.