Primary carcinoma of the Fallopian tube with report of a case

PRIMARY

CARCINOMA OF THE FALLOPIAN REPORT OF A CASE Lours

E.

PHANEUF,

M.D.,

TUBE WITH

SC.D., F.A.C.S.

Beth IsraeI Hospital BOSTON, MASSACHUSETTS

B

in 1927, pubhshed a comprehensive paper with an extensive review of the Iiterature on primary carcinoma of the FaIIopian tube. Since then pubIications from Smith,2 Kahn and Norris,3 Dannreuther,4 and Robinson5 have appeared. According to Robinson,5 primary carcinoma of the oviduct was first recorded by Raynaud in I 847 and the first pathoIogic description was given by Rokitansky in 1861. Niirnberger shouId be assigned priority to Orthman, who described this condition in 1886. Since Niirnberger published his coIIection of 30 I cases from 1886 to 1931, Robinson has coIIected 48 cases from 193 I to 1935, incIuding those omitted by Ntirnberger and his own additiona two cases. In a11 there are 349 cases of primary tuba1 cancer recorded in the Iiterature up to 1935. From the standpoint of the frequency of the Iesion, Vest, in 1914, found four out of about Ig,ooo gynecoIogic admissions to the Johns Hopkins HospitaI, whiIe Barrows reported three cases seen in 30,000 gynecoIogic patients admitted to the BeIIevue HospitaI from IgI I to 1927. Robinson states that the frequency of this disorder ranges from 0.03 to 0.31 per cent of gynecoIogic affections. The origin of primary tuba1 carcinoma, according to Doran and Fearn, represents a maIignant change occurring in a benign papiIIomatous condition of the tube Iining resuIting from a preexisting sarpingitis, whiIe Sgnger and Barth beIieve that it appears a Iong time subsequent to a chronic, probabIy purulent inff ammation ARROWS,’

of the tubes, usuaIIy occurring about the time of the cIimacteric. 0. FrankI, quoted by Robinson, states : “ If inffammation wouId be a precursor of primary carcinoma of the FaIIopian tube, then the incidence of maIignancy ought to be much higher, for saIpingitis is overwheImingIy frequent.” Previous inflammation as an etioIogic factor, therefore, is disputed. The age of the patients varies considerabIy. Thus two women were found to be 18 and two others 70, whiIe the Iarge majority were found in the years between 40 and 60. Three types of carcinoma of the FaIIopian tube have been described in the Iiterature: the papiIIary, the adenomatous and the aIveoIar. Some pathoIogists beIieve, however, that these are mereIy morphoIogic phases in the deveIopment of the disease, the papiIIary being the earIiest, the aIveoIar the Iatest, and the adenomatous the intermediate stage. Primary carcinoma frequentIy affects the tubes biIateraIIy. In view of this fact, Robinson feeIs that the apparentIy norma appearance of the opposite tube shouId not deter from a radica1 procedure. Metastasis from this maIignant disorder usuaIIy takes place through the Iymphatics. CIinicaI and pathoIogic experience have demonstrated that metastasis may be found in distant Iocations before the tuba1 waI1 has become invoIved; this wouId tend to be against continuity and contiguity as important factors in the spread of the disease. 620

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The diagnosis before operation is extremeIy diff&It, and the Iaparotomy is usuaIIy performed under a different diagnosis. The main symptoms are pain across the peIvis which may be accentuated on one side or the other, and a vagina1 discharge which may be yeIIow, brown, watery or bIoody. The pain frequently takes the form of intermittent cramps which may disappear after the free Aow of the discharge; the distended tube empties its contents in the uterine cavity and the vagina and thus relieves its own interna tension. The usua1 findings on bimanua1 examination are those of tuba1 inflammation from other causes and offer Iittle heIp in arriving at a diagnosis. The treatment shouId consist of the abIation of the entire peIvic structures, that is, panhysterectomy with biIatera1 salpingo-oiiphorectomy, as we11 as the remova of paIpabIe gIands. Deep x-ray therapy shouId be instituted soon after recovery from the surgica1 intervention. The Iiterature discIoses that a number of patients had incompIete operations, since they were operated on for saIpingitis; the diagnosis was onIy subsequentIy made by the pathoIogist. The prognosis is regarded as bad by aImost a11 writers. The mortaIity from coIIected statistics averages 40.2 per cent when the remova is compIete and 59.8 per cent when it is incomplete. (Bower and CIark.) The recent addition of deep x-ray therapy to radica1 surgery may improve these resuIts somewhat in the future. REFORT

OF

CASE

M. O., a singIe, white Russian woman, aged 32, was first seen on August 31, 1936. She compIained of having noticed a “Iump in the abdomen” some time previous, although she did not recaI1 exactIy when it had first been brought to her attention. Since August 25, 1936, there had been emesis and diarrhea, but pain was not present at any time. Two years previousIy she had had a similar gastroenteric upset. She had had typhus fever in Russia eighteen years before; a smaI1 tumor had been removed

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from the Ieft breast. Otherwise she had aIways been weI1. Her father had died of pneumonia at the age of 50, her mother of heart disease at 48, and one brother died of cancer, the organ invoIved being unknown. She had three brothers Iiving and weI1. She had begun to menstruate at the age of 14. Her periods were reguIar, of the twenty-eight day type, the duration of the periods was seven days, and the flow was considerabIy more than the normaI, aIthough no cIots were passed. There was occasiona pain, varying in intensity, during the flow, but this was never severe enough to incapacitate her. Her Iast menstrua1 period started on August 13 or 14, 1936. Her appetite was poor, her boweIs were reguIar and she had no diffIcuIty at urination. There had been a vagina1 discharge of late, but this was stated not to be bIoody in character. She had had frequent headaches for the past week; otherwise the history was not remarkabIe. The physica examination reveaIed a we11 deveIoped and nourished woman, weighing I 28 pounds, and having a bIood pressure of 160 systoIic and 90 diastolic. The head and chest showed no abnormalities. The abdomen contained a tumor which was firm, duI1 to percussion, immovabIe and apparentIy originating from the peIvis. The externa1 genitals and the vagina were normaI; the vagina1 introitus and the cervix were those of a nuIIiparous woman and showed no defects. The uterus and the adnexa were invoIved in a Iarge mass fiIIing the peIvis and rising to the IeveI of the umbiIicus. It was impossibIe to paIpate these organs separateIy. The anus, rectum and urethra were normaI. In examining the extremities no abnormahties were discovered. The urine was normaI. The bIood count showed the foIIowing: hemogIobin (Sahli) 61 per cent; red bIood count 3,420,OOO; white bIood count 10,400. The differentia1 count reveaIed 77 per cent poIymorphonucIear Ieucocytes, 19 per cent lymphocytes and 4 per cent The smear demonstrated large monocytes. anisocytosis, achromia and stippIing of some of the red ceIIs. The patient was referred to the private paviIion of the Beth IsraeI HospitaI, with the pre-operative diagnosis of maIignant peIvic tumor. On September 2, 1936, a Iaparotomy was performed under genera1 anesthesia. After the opening of the abdomen and the inspection of the peIvic contents, the diagnosis of bilateral

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malignant ovarian cysts witb metastasis in the pelvis and small myomata uteri was recorded. Operation. The operation consisted of a

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moved and sent to the pathoIogist for a frozen section. On the right the ovary was adherent to the broad Iigament, apparentIy an extension

FIG. I. Left FaIlopian tube, Iow power. Below and to the right, papiIIary carcinoma growing into the Iumen of the tube and replacing the normal epithelium seen to its Ieft. Above. large masses of carcinomatous ceIIs distending the Iymphatics of the mucosal foI&. ”

radicaI abdomina1 hysterectomy with biIatera1 saIpingo-o6phorectomy. A median pelvic incision starting at the symphysis and extending two inches (3 cm.) above and to the Ieft of the umbilicus was made. The peritonea1 cavity was entered between the beIIies of the recti muscles. There was found an ovarian cyst the size of a squash which fiIIed the peIvis and had its origin in the left ovary. The right ovary was the seat of an ovarian cyst the size of an orange and a smaI1 myoma was discovered in the uterine waI1. The tubes were edematous, Iarge, hemorrhagic and firmIy adherent to the ovarian masses. The intestines were walled off with moist gauze strips. In order better to expose the deeper structures, the pedicIe of the Iarge cyst on the Ieft was cut between cIamps and the ovarian tumor was removed. The left broad ligament was opened; it was found that there was a metastasis the size of a Iemon encircIing the Ieft uterine artery which was enIarged to the size of a Iead pencil. The Ieft ureter was dissected for an area of about 3 inches (7.5 cm.) and pushed to the side of the peIvis. The artery was Iigated above and beIow the mass, and the mass itself was re-

of the maIignant process. The ovary was separated from the right broad Iigament, the infundibuIopeIvic and round Iigaments on each side were doubIy Iigated with chromic catgut and cut between the Iigature, and a cIamp pIaced mesiaIIy. The bIadder was freely separated from the uterus and vagina. The right uterine vesseIs were doubIy ligated with chromic catgut and cut, as were the Ieft uterine vesseIs beIow the origina Iigatures. The vagina was opened posteriorIy beIow the cervix and a circuIar incision was carried around the cervix, thus removing the entire uterus, a vagina1 cuff, the metastasis on the left, the two ovarian tumors and the tubes. On paIpation, the iIiac glands were found to be not enIarged and were therefore not removed. The vagina on each side was cIosed with a running stitch of chromic catgut, leaving a Iarge centra1 opening through which was introduced a doubIe strip of iodoform gauze, the ends of which were pIaced over the parametria. The anterior and posterior Ieaves of peritoneum were united over the gauze by a running suture of No. I chromic catgut. The sigmoid was Ied into the peIvis and the omen-

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turn was brought down. The appendix was large, but otherwise appeared to be normal and was not disturbed. The abdomina1 incision was

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made on the Iast date: “The incision is well healed, there is a moderate reaction of the skin to x-ray therapy. The vagina1 vault is heaIed

FIG. z. Right ovarian metastatic tumor, Iow power. Portion showing the most highIy differentiated region in the metastatic masses, with tendency to papiIIary growth. To the Ieft, more undifferentiated, more invasive areas.

ciosed in Iayers. During the operation the pathoIogist reported that frozen sections made from the metastatic mass on the left showed the presence of a maIignant condition. Convalescence. The patient made a good recovery from anesthesia and her convalescence, although compIicated by pyelitis, was satisfactory. The temperature rose to IOI degrees F. (38.3 degrees c.) on the first and fourth post-operative days, and again to 103 degrees F. (39.4 degrees c.) on the fourteenth day. Pyelitis was discovered at this time, but rapidly subsided under the administration of urinary antiseptics and forced ffuids. The highest puIse rate was I IO on the third day, whiIe the respirations rose to 24 on the fourth and eighth days. The vaginal iodoform wick was removed on the fourth day and the abdomina1 sutures on the ninth day; the incision had heaIed by first intention. The patient was discharged from the hospital September 1936, and was referred to Dr. Harry 24, Friedman for deep x-ray therapy. She was seen at the of&e on November 2, 16, 30; December 26, 1936, January 23 and February 20, 1937, the foIIowing note being

and high in the peIvis. The recta1 examination shows the parametria to be soft and supple. There is a sIight amount of scar tissue on the Ieft but no sign of recurrence. Thus far, 6200 Roentgens have been administered in thirty-one sessions, this treatment having been compIeted on November 6, 1936.” Pathologic Report. The materia1 removed at operatioy was sent to Dr. M. J. Schlesinger, pathologrst at the Beth IsraeI Hospital, who submitted the foIIowing report: The specimen consists of a fusiform mass, IabeIIed A, a Iarge gIobuIar mass with tube attached, IabeIIed B, a uterus with tube and ovary attached. The fusiform mass, A, is said to be taken from between the two leaves of the broad ligament on the Ieft side. The mass measures 7 by 3 by 3 cm., and aIong the length of this mass runs an artery which measures 4 by 0.3 cm. Its Iumen, which is lined by a gray waI1, is easily patent to a probe. The surface is pink-gray in coIor. The mass is pink-red on the outside and the surface is lifted up in many places by pea-sized to bean-sized masses. Cut surface reveaIs a gray surface on which can be seen numerous soft, yeIIow ffecks and inter-

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lacing pink-blue strands. There is no reguIar arrangement of these structures. The surface is somewhat hard and gritty to the cut. The

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moves as a mass to the knife point and which fades into the surrounding tissue. The cut surface is pink-gray in color with numerous

FIG. 3. Right ovarian metastatic tumor, high power. MarkedIy undifferentiatedceils

with scant stroma, numerousmitoses, tumor giant ceils, and much irregularity of the size of the nuclei.

whoIe surface moves as one in the gray areas when touched, whereas the yeIIow areas are very soft to the touch and depressed. In some areas the mass appears to be distinct from the surrounding tissue; in others it fades into them. Frozen section of this mass reveaIs carcinoma. This specimen is IabeIIed A. The largest mass is gIobuIar in shape, very much distorted by &id under pressure. It measures 14 cm. in diameter. When punctured, it is found to contain about 700 to 800 C.C. of brown, thin, fluid which contains inspissated, amorphous, light brown coIIections of tissue. The surface of this mass is attached to the parovarium aIong one side of which runs the tube, IabeIled B. The surface is otherwise graypink in coIor and numerous vesseIs under the surface, which resembIe diIated veins, can be seen. In one spot, near the proxima1 end of the tube, the surface is irreguIar and red-yeIIow in coIor. Adjacent is a larger gIobuIar thickening of the waII of the mass; from this, smaIIer gIobuIes project. These smaIIer gIobuIes aIso project from the waI1 at varying distances from this Iarger gIobuIe. This Iargest globule is 3.5 cm. in diameter and the cut surface reveaIs a tissue which cuts with a gritty sensation, which

yeIIow flecks. On the inside of the Iarge cystic mass one surface of the gIobuIar mass, which is pink-gray in color, can be seen. The rest of the inner wal1 of the cystic mass is brown-green in coIor, gray in other pIaces, and it is quite irreguIar, made so by the presence of numerous, variousIy arranged, amorphous coIIections of materia1, such as have been previousIy described in the fluid of the Iarge cystic mass. From the surface of the gIobuIar area arise a few papuIar excrescences which are firm, greenbrown in coIor and varying from 0.1 cm. to I cm. in diameter. The thickness of the greater part of the waI1 is 1.4 cm. Frozen section of the gIobuIar mass in the Iarge cyst reveaIs carcinoma. The specimen of the Ieft tube and ovary is IabeIIed B. This consists of a Ieft tube which measures 6 cm. in Iength and 0.8 cm. in diameter. It is gray-red in coIor, patent to a probe from the fimbriated extremity to a point I cm. from the proxima1 extremity. The right ovary is IobuIated, forms a Iarge mass, rough, gIobuIar in shape, measuring g by 7.5 by 6 cm. The surface is made grossIy irregular by numerous cystic diIatations which vary in size from 0.8 cm. in diameter to the

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largest which measures 6 cm. in diameter. Some of these dilatations are cystic and are bIue-gray in coIor. Others are solid, firm in consistency and yellow-pink in coIor. Cross section reveaIs a surface which is partIy cystic and partIy soIid. The soIid portion resembIes that found in the cross section of the soIid mass which made a gIobuIar thickening in the waI1 of the Iarge cystic mass previously described. This section, which is vellow-gray in coIor with an occasiona fleck on it and which fades in the surrounding tissue, cuts with a gritty sensation. The cystic structures contain from a straw to a serosanguineous fluid and the waIIs are browngray in color. On the otherwise smooth surface of the Iargest cyst can be seen irregular masses of amorphous material. The right tube measures 5.5 cm. in Iength and 0.5 cm. in diameter and is patent to a probe to a point 2 cm. from the proxima1 extremity. The tube is pink-red in color and the distal extremity has on it a cyst of Morgagni. The uterus, which measures 10.5 by 6 by 4 cm. to 2.5 cm., has been removed by panhysterectomy and is triangular in shape. The external OS is smaI1. The mucosa about it is pink-gray in coIor and smooth. The surface of the uterus is covered by a pink-gray serosa which has numerous puncture marks on it and is lifted up in one area by a pink, bean-shaped area, measuring 0.8 cm. in diameter. Cross section of this shows a paIe gray, whorIed surface. The uterus is rough aIong the sides where it is opened. The cervica1 cana contains a gIairy, mucoid materia1. The endometrium is paIe yeIIow in coIor and is shaped up in pIaces. The myometrium is of uniform consistency, except in isolated, occasiona areas where the resistance is increased by some pea-shaped masses which on cross section revea1 a whorIed pink-gray surface. The myometrium measures I cm. to 2 cm. in thickness. The above three are a11 IabeIIed c. Microscopic Examination. Sixteen slides were prepared. Microscopic examination of sections marked A, revea1 sections of artery, not unduly thickened and showing no evidence of inflammation. Sections of the fusiform mass revea1 that the background of rather IooseIy arranged connective tissue is much invaded by an abnorma1 type of cell. This type of ceI1 is arranged in many sections in cIumps with no tendency to papiIIae formation. In other sections the

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arrangement is distinctIy papilhform. These ceIIs stain darkIy. The ceI1 boundaries are reIativeIy indistinct, but the nucIei are very distinct, occupying most of the ceI1. Numerous mitotic figures and occasionaIIy a giant ceI1 are seen. The cytopIasm in the papiIIae stains biue. The connective tissue core is very thin. The tumor ceIIs are very much piIed up and the papiIIiform arrangement in some pIaces is very compIex. Numerous areas are seen where necrosis of the tumor ceIIs and stroma has taken pIace. This necrosis is characterized by the presence of a homogeneousIy staining, gritty material, ceIIuIar debris, and nuclear debris. In some pIaces there are poIymorphonucIear and round ceIIs. The Iymphoid tissue is prominent, with an occasiona aggregation. In sections marked B, the Ieft tube shows numerous bIunted, papiIIary infoldings, Iined by reIativeIy norma coIumnar epitheIium in places, but in other pIaces the epithelium appears to be piIed up and takes a rather dark stain. The connective tissue core of the papiIIae is thickened and shows marked round ceI1 infiItration. The Iymphatics in the connective tissue core are wideIy diIated and most of them contain cIumps of tumor ceIIs which have no definite arrangement, but are poIarized and appear similar to those previousIy described in the fusiform mass. Sections of the left ovary, also marked B, reveaIs one surface which is Iined by a connective tissue stroma, containing Iarge ceIIs whose cytopIasm is fiIIed with a tan pigment. The ovarian stroma is invaded by tumor ceIIs which appear in pIaces in the arrangement of cIumps. In other pIaces true papiIIae are formed. In the stroma numerous areas where singIe tumor ceIIs have invaded the interfibriIIary space can be seen. Examination of sections marked c reveaIs the presence of endometrium Iined by coIumnar epitheIium. Endometrial gIands are most abundant, are Iined by coIumnar epitheIium, piIed up in the form of papi1Iary projections in the lumen. The stroma is composed of smaI1 and large round ceIIs. An occasiona poIymorphonuclear ceI1 is seen. Sections of tissue composed of very denseIy arranged whorIs of smooth muscIe, surrounded by a capsuIe of flattened smooth muscIe, are aIso studied.

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covered by Sections of cervical tissue, squamous stratified epithelium, are studied. The basiIar membrane is intact and there are a few round cells in the subepitheIia1 tissue. Section of right tube, aIso caIIed c is studied. PapiIIary infoIdings are numerous but somewhat clubbed. They are Iined by coIumnar epithelium. The connective tissue stroma in the core is increased and infiItrated with round ceIIs. Section of right ovary, marked c, is also studied. This stroma is replaced in many pIaces by tumor cells arranged in cIumps, and also in papiIIiform formation. The coIIagenous connective tissue can be seen to be invaded by the polarized cells. Diagnosis. Papillary carcinoma of left Fallopian tube; metastatic carcinoma of both ovaries and left mesosalpinx; hemorrhagic cyst of left ovary; chronic salpingitis; leiomyoma of uterus; hyperplastic endometrium; negative cervix. SUMMARY

Primary carcinoma of the FaIIopian tube is an infrequently found pathologic condition. Up to 1934, Robinson had found but 349 cases in the Iiterature. It frequentIy, though not aIways, fohows chronic inffammationof the tubes, from which it is usuahy not differentiated if the tube is removed intact. The diagnosis, as a ruIe, is estabIished by the pathoIogist on microscopic examination of the oviduct. The opening of a11 tubes after their abIation and their inspection for papillary projections, as advised by Gupta and recommended by Kahn and Norris, would not infrequentIy prove helpful in estabIishing the diagnosis. The Iast named authors suggest that, in the presence of a brownish or bIoody discharge, not accounted for by a curettage, in a woman beyond 40, tuba1 carcinoma shouId be suspected and the oviducts shouId be carefuIIy palpated for enIarged areas. Because a number of patients have been

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operated on with the diagnosis of chronic pelvic inflammatory disease, incomplete operations, which are not a satisfactory method of treatment, have been performed. This may account, in part at least, for a number of poor results reported in the Iiterature. The treatment shouId consist of a panhysterectomy with biIatera1 saIpingooophorectomy and the excision of paIpabIe glands. The operation shouId be folIowed by deep x-ray therapy. This form of treatment may improve the resuIts of the future. In my own case, the diagnosis of primary carcinoma of the FaIIopian tube was not estabIished even at operation. The ovarian metastases appeared so much more important than the tuba1 Iesion that an operative diagnosis of ovarian carcinoma was made. The histoIogic examination of the excised peIvic organs reveaIed the true diagnosis. WhiIe the patient has made a good operative recovery and has been subjected to deep x-ray therapy, the prognosis should be guarded and onIy time wiI1 revea1 the ultimate resuIt. I am indebted to Dr. M. .I. Schlesinger, pathoIogist at the Beth Israel HospitaI for the photomicrographs iIIustrating this articIe. REFERENCES BARROWS, DAVID N. Primary

tube, with report

carcinoma of FalIopian of three cases. Am. J. Obst. TV

Gynec., 13: 710-719, 1927. SMITH, W. S. Primary carcinoma a report

of two cases.

Am.

of the oviduct, with J. Obst. CT Gynec.,

24: 267-270, 1932. KAHN, M. E., and NORRIS, S. Primary

carcinoma of the FaIIopian tubes. Am. J. Obst. @ Gynec., 28: 392-

402, 1934. DANNREUTHER,

W. T. Primary carcinoma of the FaIIopian tube, with report of a case. Am. J. Obst.

@ GyW., 30: 724-727, 1935. ROBINSON. M. R. A reoort of three

cases of Drimarv cance; of the FaIIopian tubes, with a sumkary df the cases omitted from Nurnberger’s Report (I 93 I) and those recorded to 1935. Am. J. Obst. CYGynec. 32: 84-90, 1936.