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iousIy been putting forth to you that chronic disorder of the major joints can frequentIy not be diagnosed accurateIy even by symptomatoIogy, physica findings or roentgen ray findings, and that an incision for biopsy may prevent a greatwaste of time and useIess treatment.

findings, was found by expIoratory operation; and a second knee disorder in which the clinica symptoms had elsewhere Ied to a diagnosis of tubercuIosis, but which turned out to be most probabIy on a neurotic fixation basis. At this time I might reiterate the proposition that I have pre-

INFECTED MYOMA UTERI A REPORT

OF THREE

CASES,

MEYER

M.

WITH

STARK, NEW

B

REMARKS

Y red degeneration, we mean that form of necrosis or necrobiosis, as it is sometimes caIIed, which converts the ordinary hard fibromyoma into a softer, fleshier mass, the change being accompanied by a reddish or other discoIoration which resuIts from the hemoIytic action of excess Iipoids. This red necrosis is an aseptic process, with hemoIysis and tissue autoIysis, bacteria.being present in those few cases which undergo suppuration, the infection being secondary to the degenerative process. There is no round ceI1 infXtration, whereas in infected cases, where it shouId be present, it is not marked. Infection is not onIy singuIarIy rare, but is whoIIy incidenta1, and stands in no reIation to the cause of the degeneration. The proximity in the cervix and vagina of hemoIytic bacteria does not aIter this concIusion, nor does it seem to favor the theory that such bacteria can gain access to the affected myoma through these channeIs. The typica hard fibroma, on cross section, presents a white, gIistening, satinIike, whorIed appearance, which, aIong with its distinct and weII-marked encapsuIation and its contrast with the surround-

M.D.,

ON RED REGENERATION* F.A.C.S.

YORK

ing reddish myometrium, is striking and characteristic. EquaIIy striking is the appearance of a uterine myoma undergoing red degeneration or necrobiosis. This change usuaIIy affects 0nIy one tumor, even if others are present, and generaIIy a Iargesized one. Rarely are two or more so affected. The differing tumor is soft in consistency, has a weII-marked capsule, is conspicuousIy coIored in red, mahogany, yeIIow or grey, and is Ioose textured. In most cases, its appearance is that of raw beef, or of the pink coIor of Tennessee marbIe. The extent of the necrosis is variabIe, sometimes in foci, sometimes in streaks, and at times onIy about the periphery, the pigmentation fading toward the center and Ieaving a grey nucIeus. Necrotic tumors are usuaIIy interstitia1, though at times partiaIIy submucous, and occasionaIIy subperitonea1. PeduncuIated tumors are not subject to this pathoIogy, even though twisting and stranguIation take pIace. Red degeneration was first described by Gebhard in 1899, but it was not unti1 Igo3 that particuIar attention was given it, when Fairbairn pubIished his essay on its etioIogy, pathoIogy and treatment. WhiIe

* From the gyneco!ogicaI services of Dr. T. H. Cherry and Dr. S. DiPaIma at the HarIem Hospital in New York City. Read at the N. Y. Academy of Medicine, Section Obstetrics and GynecoIogy, on October 25, rgq.

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an extensive Iiterature has since appeared, IittIe new has been added to his origina contribution. It is acceptabIe that the coIors resuIt from a diffusion of bIood pigment through the tissues after hemoIysis has taken pIace, yet the true nature of the pigments are not expIained, since the products of such change, nameIy hemoIysis, are not found in the specimens. Hemosiderin cannot be demonstrated by the Prussian bIue test, thus eIiminating the presence of free iron, and in onIy one instance have I read of the demonstration by spectrum anaIysis of hemogIobin. StrongIy favoring the theory of hemoIysis is the presence in these specimens of an excess of Iipoids, which we know to be highIy destructive to bIood tissue. This action, however, is usuaIIy checked by the norma bIood pIasma, unIess the Iipoids are in excess, and thus there can be assumed the presence in the specimen of bIood pigments. These Iipoids are specificaIIy considered the cause of thrombosis, and thrombosis, by infection or compression, is to some observers a pIausrbIe cause of degeneration. The acute onset in these cases wouId naturaIIy draw attention to a sudden stoppage of the arteria1 supply, especiaIIy when we consider the rather scanty vascuIature, arteries that are thin-waIIed and not communicating with the vesseIs of the myometrium, and subject to pressure by impaction or crowding, as in pregnancy. It is often noted that intramura1 fibroids Iie IooseIy in their beds and that Iarge spaces are present between them and the surrounding muscuIature. This pecuIiarity affords a pIausibIe basis for disturbed circuIation, as in the uterine contractions incident to menstruation, pregnancy and for there is a sort of foIIowing trauma, rotary motion of the fibroid within its non-extensibIe capsuIe much Iike that of a mass of dough or putty mouIded in the paIms of compressing and sIowIy rotating hands. WhiIe there is a distinct association of Iipoids with degeneration, yet the former

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is not the cause of the Iatter; and whiIe pregnancy is here supposed to offer a cIue to its presence in excess, a numb& of reported cases were not pregnant. The Iipoids are responsibIe for the hemoIysis, and are in excess in the tissues onIy after the degeneration has taken pIace, thus faciIitating the diffusion of the pigments. In other words, the degenerated tissue favors the acceptance of the hemoIyzed bIood. It is the continued action of these Iipoids in excess of inactivating bIood pIasma which is accountabIe for the various hues noticed on section. The presence of thrombi is not typica1, nor can they be proven or surmised to be primary, for degeneration can occur without them and the extent of thrombosis is not proportionate to the amount of degeneration. If the degeneration is presumed to be primary, it is reasonabIe to presume aIso that hemoIysis induces a deposit of fibrin in a vesse1 aIready disintegrated, the thrombus thus appearing secondariIy. In the infected cases, however, it is reaIIy diffIcuIt to deny that thrombi therein arising are the primary factor in the necrosis, the process being simiIar to others eIsewhere in the body. As to frequency of occurrence, degeneration is found as often as 5 to 7 times in every IOO cases, the pregnant ones in the in these majority by far. Suppuration tumors is conspicuousIy infrequent, KeIIy and CuIIen reporting onIy I I in 1428 cases, and Deaver saw his first case in rgzo after over 1200 hysterectomies. Bacteria reported as found are coIon, staphyIo and streptococci. Gonnococcus is not reported in a singIe instance. The demonstration of the bacteria in tissue stains is a very diffIcuIt attainment, and cuItures of tumor tissue are usuaIIy steriIe aIso. The case of Dr. H. Vineberg, reported to these in 1912, is a notabIe exception remarks. The symptoms usuaIIy associated with the onset of degeneration are pain, IocaIized tenderness and a noticeabIe increase in the size of tumors aIready known to be

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present. The pain may not be severe, though with tumors on the right side, associated as the condition is with a Ieucocytosis, an appendicitis is incorrectIy diagnosed. The acute onset, with definite peritonea1 irritation, may misIead the observer into diagnosing such simuIating conditions as twisted ovarian cysts and stranguIated hernias. A toxic phase with nausea and vomiting accompanies the suppurating types. Red degeneration as such cannot be distinguished microscopicaIIy from necrosis in generaI, since the discoIoration simpIy accompanies but does not aIter the pathoIogicaI features. The extent of the changes is determined by the appearance of the ceI1 nucIei, the reaction of the cytopIasm to certain stains, the substitution for the muscIe ceIIs of hyaIine and granuIar materia1 and the presence of fatty substance. Round ceI1 infiItration is not present (Figs. 3 and 4), which emphasizes the noninfectious nature of the troubIe: Fibrin and endotheIia1 debris are found in the bIood and Iymph capiIIaries. The tumors are decidedIy avascuIar. A rare variety of fibroid, described by Virchow and caIIed the angeomatous type, shows a Iarge number of thin-waIIed bIood vesseIs. Two such cases are reported in the EngIish Iiterature. A satisfactory summary of the pathoIogica1 features is the foIIowing, by Lockyear: (I) irreguIar and scanty nucIear staining (nucIear ‘ghosts ’ at times) ; (2) granuIar and hyaIine degeneration; (3) repIacement of muscIe ceIIs by fatty tissue; (4) endotheIiaI shedding, thrombi and deposits of fibrin; and (5) rareIy, pus formation after infection. It wouId appear that the treatment of this condition is myomectomy or hysteromyomectomy, and yet the opinion is stressed by a number of observers, that with the compIication of pregnancy, the patient shouId and can be tided over unti1 such time as an eIective cesarian or myomectomy can be done, or be carried through what might in a11 respects be a fairIy norma Iabor. It is beIieved that most

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myomata, even Iow down, wiI1, with advancing gestation, rise out of the pelvis and not be obstructive, and that their proper treatment can be satisfactoriIy conducted near or after fuI1 term. The prognosis, in operation, is uniformIy good, and shouId be no different from the surgery of undegenerated cases. Quite a few cases are recorded of myomectomy in the course of a pregnancy without resuIting miscarriage or abortion. However, in the infected cases, mortaIity is unfortunateIy very high, ranging from 27 per cent in KeIIy’s estimate to 50 per cent in Basso’s and 70 per cent in Berger’s. These high figures wouId make it most important that operation be undertaken early in the degeneration, before infection, if indeed such diagnostic acumen couId be appIied. In a patient known to have myoma, a sudden attack of IocaIized pain and tenderness and a definite increase in the size of the tumor shouId lead one to the diagnosis of degeneration; the advent of toxic symptoms, associated as it wouId be with peritonea1 irritation, high temperature and Ieucocytosis, shouId estabIish the diagnosis of bacteria1 invasion. One of our three cases (Case 11) was correctIy foreseen. SUMMARY

Degeneration of fibroids is associated with the presence of Iipoids, the accumuIation of which may be dependent on the presence and extent of thrombosis or infection. Infection is never primary. The hemoIytic action of the Iipoids is restrained by the blood pIasma, excess of Iipoids giving a red discoIoration, and by its continued action, the red being repIaced by deeper hues; and finaIIy, in extensive changes, by a grey coIor. As degeneration can occur without coIor changes, a better term wouId be simpIy, “Degeneration,” with red or brown or or, “Degeneration grey discoIoration,” whatever the coIor happens to be. The hard consistency of some of these tumors may give no indication, exteriorIy, of the changes noted on section or microscopy. Thrombosis is not

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thought present;

to be primary and is not aIways in infection, it is Iikely to be primary. The microscopy is characterized by the presence of hyahne and granuIar degeneration, repIacing or separating the muscIe fibers remaining by the presence of fat and karyoIysis. The presence of fat is singuIar and probabIy resuIts from muscIe fiber change. There is no round ceI1 i&Itration. Pregnancy is a predisposing factor. Infection gives rise to toxic symptoms and

FIG. ~a.

is fata1; earIy operation, with no resuIting infection, can be successfu1. Operation in degenerated fibroids is indicated, except in such cases complicated by pregnancy where temporizing unti1 fuI1 term may happiIy resuIt. BeIow is reported a case that prompted this brief study, foIIowed by two others, one of which (Case II) was correctIy diagnosed before operation, and the other was an accidenta on for biIatera1

find in a patient operated adnexa1 suppuration. CASE

REPORTS

CASE I. L. G., forty-three years oId, coIored, married. Entered HarIem HospitaI on June 13, 1927, compIaining of pain in Iower abdomen and appearance of a mass, increasing in size, and not known to her to have been present

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before this sudden iIIness. Typhoid and pneumonia two years ago. Has had two chiIdren and two miscarriages. Menses began at thirteen, were reguIar and continued from 3 to 3 days, rather more profuse the past two years, and for the past two months accompanied by pre-, per- and postmenstrual pain. The pains were of a bearing-down character, feIt in the Iower abdomen and aIso in the back. Her present iIIness began two weeks ago, with onset of reguIar menses, rather more than usua1 pain in the Iower abdomen and back, occasiona

FIG. Ib.

chiIIy feeling, and a noticeabIe increase in the size of the abdomen, within which she herseIf was abIe to make out a mass of which she was not previousIy cognizant. She ‘did not fee1 at a11 weI1,’ had nausea and vomited once. In spite of her Iast menses having passed onIy ten days prior to admission, she was stiI1 thought to be pregnant, and sought hosowing to her pecuIiarIy sick pitaIization, condition. On admission, she Iooked acuteIy iI1, with temperature loo’, w.B.c. 15,400, polymorphonucIears 78 per cent. The Wassermann was negative. The patient was we11 deveIoped and we11 nourished, and exhibited abdomenaIIy a gIobuIar mass, hard, freeIy movabIe, painfu1 and tender, reaching up to within the umbilicus. VaginaIIy, two other fibroids were made out. A provisiona diagnosis of ovarian cyst and twisted pedicIe was made and operation

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advised; this advice was not accepted; three days thereafter, temperature went to 103, and again on the fifth day to reg. Operation was then undertaken, on June 2 I, 1927, eight days after admission. The specimen shown by supracervica1 hys(Fig. I) was removed, terectomy, Ieaving both the adnexa. In preparing the uterus for removaI, it was Iifted out of the peIvis with a cork-screw. Not suspecting troubIe ahead, the operation proceeded and was speediIy finished. Unaware of what was waiting, the specimen was sectioned

FIG.

2.

in an unsteriIe fashion, and to our great surprise, a quantity of pus flowed away, and the red fibroid was noted. No smear was taken at this time. The fibroid so affected was the Iargest of thirteen, and about the size of a Iarge orange. The fluid had a fishy odor, the capsuIe was we11 defined, though IooseIy attached in pIaces, with minute cIots of bIood appearing in the Ioose areas. The consistency was hard, the coIor that of washed meat. The pathoIogy present was that described above, and is shown in Figures 3 and 4. A contrast with an ordinary fibroid is offered in Figure 2. For the relief of paraIytic iIeus, an enterostomy was performed on the fourth day, and huge quantities of pus were taken from the much-distended smaI1 intestine. The patient died on the morning of the fifth day postoperative, cuItures from the peritoneum showing pure coIon baciIIus.

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CASE II. S. J., aged thirty-seven, operated upon at HarIem HospitaI on June 24, 1927. She was about seven months pregnant (fourth gravidity) and gave the history of sudden iIIness about three weeks ago with severe abdomina1 pain, frequent vomiting, occasiona high fever, and a definite history of a chiI1. Of significance is the fact that at the beginning of her iIIness, though not subsequentIy, she noticed an abnorma1 deveIopment in the size of her pregnancy, and compIained especiaIIy of pain in the Ieft upper quadrant. The pain

FIG. 3.

was severe, aImost constant, giving the patient, who was an unusuaIIy robust and pain-enduring type, the appearance of acute severe iIIness. Temperature on admission was 104, puIse go to 100, Ieucocytes, 16,200, poIynucIears 82 per cent and Iymphocytes 16 per cent. A smaI1, hard, tender mass was paIpabIe, attached to and movabIe with the uterus, situated at the site of acutest tenderness, nameIy, at the fundus of the enIarged uterus, at the Ieft. At operation, on the day foIIowing admission (June 24, Ig27), the tumor was found as outIined, surrounded by recent adhesions which heId down the neighboring intestines and omentum; these adhesions separated, the mass sheIIed out and proper cIosure was affected. The patient never seemed to be abIe to throw off the septic phase she presented before operation, her robustness evidentIy no match

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for the toxemia with which she was coping. She miscarried on the tenth day postoperative, and died on the tweIfth day. On section the tumor, the size and shape of an egg, was rather soft, grayish in coIor and had at its center a smaI1 cavity, containing a sanguinous pus without speciaI odor. The pathologist’s report foIIows: “The waI1 of the cavity is shaggy and wrinkIed, and of a grey, opaque tissue, simiIar to that which appears, in shreds, in the cavity. No thrombi visibIe. MicroscopicaIIy, a section

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outer waI1 reveaIed muscIe fibers poorIy stained, showing either no nucIei (the more usua1 phase) or the veriest shadow of a Iarge, ovaI, very vascuIar nucIeus. The fibers were smaI1, the ends rounded or frayed, striations very indistinct. A very moderate poIynucIear Ieucocytic intermuscuIar infiItration was present. In neither of the sections examined were any vesseIs thrombosed, thickened or narrowed.” CASE III. A. L., aged twenty-five, operated upon at the HarIem HospitaI on May 2, 1927, for biIatera1 adnexa1 suppuration and multiple smaI1 fibroids of the uterus. There was no hint in the history that she was having any troubIe in the uterus, the symptoms pointing entireIy to the adnexa, from which she had suffered on a previous occasion. Sh e was not considered especiaIIy III, and was operated upon at a seIected time, tweIve days after admission. One of the fibroids contained pus, the smear of which was negative, though the cuIture showed staphyIococcus albus. There was nodiscoloration. The patient got weI1, and was discharged on May 15, 1927. BIBLIOGRAPHY

FIG. 4.

of the cavity waI1 shows the muscle fibers poorIy stained and in genera1 pycnotic and fragmented; moderate amount of edema separating the fibers. Between the muscIe bundles and muscIe fibers, one finds a considerable number of fairIy weII-preserved and aIso much fragmented poIymorphonucIear neutrophiIes, and nucIear debris. These materiaIs occur in i&defined patches that are generaIIy distributed throughout the specimen, aIways apparentIy paraIIeIing the direction of the muscIe fibers, and more noticeabIe near the centra1 edge of the section. A section removed from the

BLAND, P. B. Surg. Gynec. +Y Obst., March, 1925. GILES, A. E. Sterility in Women. Oxford Medical Press, 1922. FAIRBAIRN, J. S. J. Obst. ~Gynaec. Brit. Emp., 1903. iv. GEBHARD. Veit’s Handbuch der GynaecoIogie. VoI. ii. SCHILLER, H. Am. J. Obst., 1918, Ixxvii. BLAND, J. S. Lancet, 1902, i; Lancet, rgoI, i. Tumors, Innocent and Mahgnant. LOCKYEAR, C. Fibroids and AIIied Tumors. 1918. LOCKYEAR and EDEN. New System of GynaecoIogy. ii. MURRAY, 1~. L. J. Obst. ti Gynaec. Brit. Emp., 1910, xvii. FRANK, R. T. GynaecoIogicaI PathoIogy. Macmillan Monographs. MURRAY, H. L. J. Obst. 8Gynaec. Brit. Emp., 1910, xvii. DARNALL, W. E. N. York M. J., 1922, cxvi. BOLDT. H. J. Am. J. Obst., N. Y., 1412. KELLY; H. A. Am. J. Obst:, 1906; Ii;. STEIN, H. E. J. A. M. A., 1923, Ixxxi. VINEBERG, H. N. Am. J. Obst., Igrz, Ixvi. COLLINS, B. K. T. J. Obst. ~Gynaec. Brit. Emp., 1924, xxxi. SMITH, J. L., and SHAW, W. F. J. Obst. ~Gynaec. Brit. Emp., Igog, xv. SCHARLIEB. Proc. Roy. Sot. Med., London, 1908%rgog, ii, Obst. and Gynaec. Section. KELLY and CULLEN. Myomata of the Uterus.