- Email: [email protected]
Malignant ovarian teratomas in the first two decades of life
MALIGNANT
JAMES R.
OVARIAN TERATOMAS IN THE FIRST TWO DECADES OF LIFE*
LISA, M.D., J. WILLIAM HINTON, M.D., SEYMOUR WIMPPHEIMER, M.D. AND JOSEPH D. GIOIA, M.D. New York, New l’ork
T
about 300 to 400 cc. of bloody fluid with clots were found. There was torsion of the right ovary which had a hemorrhagic cyst and a smaI1 perforation. The appendix and smaI1 intestine were normaI. The cyst was resected and the appendix removed. The postoperative course was uneventfu1 and the patient was discharged on December I, 1948. The pathoIogic report was as follows: The cystic right ovary measured 5.4 by 3 by 3.3 cm. and was purpIe in coIor. On the surface there was a raised Ientiform white noduIe. On section the cyst was fiIIed with fluid bIood. The wall was purple-bIack and about 9 mm. thick. The posterior surface had a ragged rent. MicroscopicaIIy, the waI1 was edematous and hemorrhagic. There were norma stroma and some primordia1 foIIicIes. The teratomatous tissues were characterized by an embryonal appearance. The most abundant was the skin and its appendages of hair and sebaceous glands. Sometimes the squamous epithelium merged with gIanduIar structures lined by tall ciliated epitheIium. There was abundant activeIy growing bone, with or without foci of caIcification, fibro-erastic cartilage, glial tissue and Ioose areoIar tissue. Some structures were organoid and resembled bone with synovial cavity in architectural pattern. None of the tissues had any of the histoIogic criteria of maIignancy. The diagnosis was teratoma of CASE REPORTS ovary with torsion. CASE I. The onset of iIIness in this patient, The patient was readmitted five months Iater a seven year oId child, was a sharp attack of on April 24, 1949. One week previousIy she had severe abdomina1 pain simuIating acute appenhad an attack of vomiting and enlargement of dicitis. An emergency Iaparotomy was carried the abdomen was discovered. For the entire out on November 26, 1948, with that preopera- .sI week there was intermittent fever, diarrhea and tive diagnosis. When the abdomen was opened,:! extreme Hatulence. * From Doctors Hospital, New York, N.Y.
of the ovary aIthough inERATOMAS frequent in the first two decades of Iife are not rare. They constitute the most common tumor of the premenstrua1 yearst1s2 usualIy occurring in the first half of the second decade.3 To the middIe of 1949 about 150 authentic cases are found in the Iiterature incIuding those reported as dermoids. ExampIes of the coincidenta invorvement of the same ovary by a maIignant tumor and a non-malignant teratoma such as reported by Goodfriend and Caruso4 are not included. In addition to individua1 case reports there are severa excellent Ionger articIes. 2*5-12Since the pubIications and Agerty’” of WakeIy ’ ’ and Witzberger twenty-four more cases have been found.13-2d Ten are benign and fourteen malignant. Of the total number approximateIy one-third have shown evidence of maIignancy. The earIy literature usuaIIy deaIs with benign tumors. In the more recent publications maIignant disease is more frequent, probabIy, as suggested by Downes, 25 due to more thorough histoIogic examination. The purpose of the present communication is to review the recent Iiterature on maIignant ovarian teratomas of the frrst two decades and to report two additional cases which iIIustrate some of the important features of these tumors.
April,
1951
453
454
Lisa et aI.-MaIignant
FIG. I. Case I. The nodular mass found replacing the right ovarian tissue left at the first operation.
On examination the patient appeared acuteIy ill. Her face was Aushed and her temperature The abdomen was distended, was 103.8%. slightiy tender under the old scar and felt cystic. Laparotomy was performed the next day. The segment of right ovary Ieft at the first operation was repIaced by a mass Iarger than a footbaI1 and adherent to sigmoid and omentum. (Fig. I .) InnumerabIe masses of various sizes were scattered over the peritoneum and omenturn; one, 8 cm. in diameter, was adherent to the sigmoid. The Ieft ovary appeared normaI. The right ovarian, the sigmoida1 and an omenta1 mass were removed. The patient was discharged on May 2nd. The pathoIogic report reveaIed the foIIowing: The right ovarian mass was grossIy noduIar, had a smooth, intact serosa and measured rg by 13 by 6 cm. It feIt soft and cystic. On section there were numerous cysts of various sizes fiIIed with pseudomucinous contents. The centraI portion was soIid and had some amorphous, gritty particIes. The other two masses were similar. MicroscopicalIy, a11 the tumors were simiIar and contained both aduIt and embryona1 tissues. There were connective tissue, adipose tissue, invoIuntary muscIe, young and aduIt voIuntary muscIe, deveIoping bone, fibro-eIastic cartilage, aduIt skin with accessory structures and neurogenic tissue. No pattern was folIowed; a11 the tissues were intermingIed. (Fig. 2.) The cysts were of various types. Skin with hair shafts and sebaceous glands Iined some.
Ovarian T’eratonlas In others the squamous epithelium merged with epitheIium of respiratory type which was associated with mixed seromucous glands. It merged sometimes with non-ciliated epitheIium covering viIIous projections mimicking small bowe1 foids. OccasionaiIy it merged with a cystic Iining of epetidymal nature, lying in aduIt g&al tissue. Other cavities had taI1, ciIiated, mucusproducing ceIIs. Ciliated columnar ceIIs with nests of non-ciIiated mucous ceIIs lined other cavities. Occasionally these cysts had transitional epithelium. There were some structures with Iining similar to large bowe1. A few areas had structures Iike fallopian tube and choroid plexus. The neurogenic tissue was abundant. Chiefly it was aduIt gIia, sometimes embryona1 glia with normal mitoses. Sometimes both were intermingIed. The gIia frequently had small cavities Iined with ependyma resembIing the centra1 canal of the spina cord. Some areas of edema formed cavities. There were some neurones with NissI granuIes. There were a few aduIt nerves and one gangIion simiIar to those of the sympathetic chain. Norma1 ovarian tissue was not found. The diagnosis was recurrent teratoma of the right ovary and metastatic teratoma of the peritoneum. (Fig. 3.) Roentgentherapy was carried out from May 9th to June 10th through two anterior and two posterior portaIs, each 15 by IO cm. The tota dosages measured in air were as follows: anterior right peIvis and abdomen, 1,550 r; anterior Ieft pelvis and abdomen, 1,550 r; posterior right peIvis and abdomen, 1,600 r; and posterior Ieft peIvis and abdomen, 1,600 r. The factors at 50 cm. T.S.D. were KV 200 M A 8 fiIter mm. 45 Cu I AI. When Iast seen in November the patient appeared weI1, was in good heaIth and apparentIy free of metastases. CASE II. The current iIIness of the patient, nineteen years of age, was of two to three weeks’ duration and was characterized by Ieft Iower quadrant pain. It began about five days before the Iast menstrual period and continued after menstruation ceased. The pain was suffrcientIy severe to prevent continuing at work. The menses previousIy had aIways been reguIar. On examination on May 14, 1949, a cystic mass was paIpabIe in the Ieft ovarian area. Laparotomy was performed two days Iater. The Ieft ovary was Iying on the right side, twisted 180 degrees, the size of a grapefruit American Journal of Surgery
Lisa et al.-Malignant
Ovarian
Teratomas
455
2 3 FIG. 2. Cast I. \loderately celIuIar embryonal tissue showing some norma mitoses, found in the recurrent and metastatic lesions. X 600. FIG. 3. Case I. Neurogenic tissue with both adult glial cells and neurones with NissI granules.
and muItiIocuIar. The right ovary was soIid and as Iarge as a basebaIL There were some omenta1 adhesions from a previous appendectomy. The masses were resected Ieaving some ovarian tissue on each side. The pathoIogic report reveaIed the foIIowing: The Ieft ovary was roughly ovoid, had a smooth outer surface with prominent vesseIs, feIt aImost cystic and measured 8 by 7.5 by 6 cm. On section it was made up Iargely of a soIid noduIe of geIatinous appearance with coarse tibrous bands producing the appearance of thyroid tissue. (Fig. 4.) A sIit-like cavity containing miIky fluid separated the centra1 mass from the periphera1 zone. One part of the waI1 was bony hard. The right ovary was smooth, cystic, measured 13 by 9.5 by 6 cm. and had some doughy masses presenting externaIIy. On section there were two cysts separated by a calcified ridge. Both cysts contained Iight yeIIow fluid. At one pole of the Iarger cyst there was a secondary cavity containing sebaceous materia1 and hair and a caIcified mass in the waI1. SeveraI smaI1, soft noduIes in the waI1 had a yeIIow-white cut surface. In the waI1 of the smaIIer cyst there was a secondary cyst containing sebaceous materia1, hair and a caIcifIed mass. MicroscopicaIIy, the most prominent component of the Ieft ovary was glial tissue, mainIy
April,
1951
FIG. .+. Case II. Cut surface of left ovary has a solid gelatinous appearance with coarse fibrosis producing the appearance of thyroid tissue.
very ceIIuIar, embryona1 in type, extremeIy atypica1, rich in norma and abnorma1 mitoses and showing rosette formation. The tissue was extremeIy edematous, particularly in the soIid centra1 mass which resembIed thyroid to the naked eye. A few smaI1 cavities appeared Iined by ependyma. Some areas had aduIt and embryona1 skin with sebaceous gIands and hair foIIicIes. They overIay adipose tissue and canceIIous bone. (Figs. 5 and 6.) The right ovary had aduIt tissues. The smaI1 cyst was Iined by skin with hair, sebaceous and sweat gIands, merging into a muItiIayered ciliated epitheIium which in turn Ied into a gIial-
446
Lisa et al.-MaIignant
Ovarian
Teratomas
6 FIG. 5. Case II. Young emb&nal tissue showing the great cellularity. X 600. FIG. 6. The blastomatous gliaI tissue showing the atypica1 cells, numerous mitoses and rosette formation.
Iined cavity. In the waI1 of the cyst there were structures Iike choroid pIexus, adipose tissue, coIIagenous connective tissue and invoIuntary muscle. The Iarge cyst had skin, sebaceous glands, subcutaneous adipose tissue and aduIt glia. Some of the gIia1 foci had neuronal ceIIs. There was some canceIIous bone with fatty marrow in which foci of myeIocytes and megakaryocytes were scattered. There was some moderateIy ceIIuIar young embryona1 gIia free of signs of rapid growth. A segment of norma ovarian stroma was present. The diagnosis was maIignant teratoma of the Ieft ovary with gIiobIastomatous foci and torsion, and nonmaIignant teratoma of the right ovary. A second Iaparotomy was done on May 25th. A supracervica1 hysterectomy and biIatera1 salpingo-oophorectomy were performed with compIete remova of both broad Iigaments. Microscopic examination showed organizing hematoma of the right ovary. Otherwise both had onIy norma tissue. CarefuI examination faiIed to revea1 any evidence of tumor in any portion of the tissues removed. The patient was discharged on June 5th. After Ieaving the hospita1 the patient received roentgentherapy from June 2Ist to August 12th through four portaIs each IO by 15 cm. The tota dosage measured in air was as follows: right anterior peIvic fieId, 2,075 r;
X 600.
Ieft anterior peIvic fieId, 2,075 r; anterior upper mid-abdomina1 fieId, 1,500 r; and posterior upper mid-abdomina1 fieId, 1,500 r. The factors at 50 cm. T.S.D. were KV 200, filter I Cu I AI. Roentgenograms taken of the chest and peIvis before therapy was given were negative. During the course of therapy there were two episodes of bIeeding. On JuIy 15th the patient bIed after voiding. The urine had a faint trace of aIbumin and some erythrocytes. Nothing of note was found on physica examination. On JuIy 29th the patient vomited and passed a dark coIored stoo1. Again nothing of note was demonstrabIe. When Iast seen in November she remained free of symptoms and had returned to work. Examination, incIuding fluoroscopy of the chest, had given no evidence of recurrence or metastasis. COMMENTS
Solid teratomas of the ovary are usuaIIy considered potentiaIIy or definiteIy maIignant and cystic tumors benign. These criteria are Iess vaIuabIe in the first two decades of Iife than at older age periods. SeveraI of the tumors Iisted in TabIe I have shown both soIid and cystic areas. Some, such as the case of Willis, have been chiefly cystic. Some of the soIid teratomas, for exampIe those of Baccarini and of Searby, American
Journal
of Surgery
Lisa et al.-Malignant
Ovarian
TABLE MALIGNANT
-_Author
;
F~rlc” ,914
457
I
OVARIAN
-
Symptoms
Age
Teratomas
TERATOMAS Psthology
Site
^
16
Rapidly enlarging ahdomen for I m”. reaching size of 9-m”. pregnancy; gastrointestinal and urinary disturbances, pain. Sever, tumor; ovariotomy; recurrence in 4 mo.; severe abdominal pain,. vomiting, anemi?, rapidly growing mass; extenswr peritoneal metastases at operation Precocious menstruation for 2 yr.; positive Aschheim-Zondek test Abdominal enl;,rgrment 6-m”. preg:nancy
solid; more
___~___ Trratoma
Death with metastatic chorio-rpithelioma
withchorio-epithelioms
._
ISolid and c.y&c; marked crllularity ;rnd mitosrs; other ovary with non-malignsnt teratoma
I-I.eft
Solid; torsion; all layers abundirnt embryonal glia
-__ Right
Enlarging abdomen for 5 m”.; latesympt”ms”ftorsion.ancmia, hy ogastrium; tumor reaching ovariotomy; no visi tYle metastases
5
cystic and recurrence
.-
Fize of
Three wk. mild xnd severe symptoms of torsion, tumor, precoc’ous sexual development; ovar‘otomy; recurrence of symptoms. tumor and metastases in scar in 2 mo.; postoperative radiation
i -_-
Multilocular sBrc”mitt”“s: anaplastic
Right
with
--_
Cystic
_-
and solid; ectodermal tissues with
mesodermal
_--..
Postoperative
and car-
death
cinoma
._ 13 Meyer
4
1936..
.-
Case of Zoltan and Szathmary Inoperable tumor st laparotomv
-I-
Mnyo and Hutsch
Smrltz?.r
193X
I
Symptomless lower abdominal mass 2% yr.; ovariotomy; no visible metastases; intestinal “bstruction in 6 m”.; inoperable pllravertehral mass st operation
Right
I R
Right ovarian resection for torsion 6 mo. previously; recorrcnt Symptoms, tumor filling pelvis and lower abdomen
; Right 1Ectodtrmal
8
S.ymptoms of torsion 3 II.. tu mar; ovariotomy; no vlslble metastases postoperative radiation; reC”rrence of symptoms in 3 m”.; laparotomy 5 mo. later; extensive peritoneal metnstases
; Kight
Mild symptoms of torsion 2^... wk.; tUrnor; ““ar,“t”my: mass tllllng pelvis and lower abdomen; rccurrencc of symptomless mass in 6 mo.; peritoneal metaStases at laparotomy; postoperative rndi-
;
1938
aCon --___
carcinoma
I _~____
194.1-1942
’ 14
t”rSI”“:
““arI”t”“1y;
3X normill: complicated genital anomalies and j carcinoma of “teT”s Authors.
_.
tissues with grade I
ildcno-
Solid with torsion; embr.yonai Sue< of 011 layers: sarcomi,
suesof all layers: benign; metastases ~ tissues with many
-~ ~~.--.
Opcrxtivc
tis-
Death
rtlcoverv
I yr. ;Iftcr onwt
histologically of embryonal mitoses
onset
_____
_______
Symptomless. rapidly growing tumor for 2 mo., weight 1”~s. fever; ovariotomy: mass shove umbilicus; postoperativr r:ldiation ___-ACUfC
-~~.~histologi-
I
Amputation of leg at 3 yr. for cavernow angiomn: recurrences treated with x-my for 7 yr.; abdominal tumor at 13 yr.; radioresistant; oyariotomy; postoperative radiation; early good results h1rF.lhinnr.v
___---All 1ayers representrd tally benign
I.arge loholared mass with Iibrosarcomil :Ind carcinom:l
Death apparently from metastasl% mo. after onset
9
Riuht
I-Ectodermal
ovary
by conprimary
wrs
and mesodermal tiswith s;wcomat”us weas
-
Acute torsion; resection. no visible metutases; intesbn~l ohstruction in $ mo.; peritoneal metastases: postoperative radiadon
Right
Cystic with torsion;, adu:t and emhryonal tissues; hxstologic~lly benign; mPtutases more embryon;tl with rnitoses
‘9
Incrrasing signs of torqion; bilAtera resection; secondary oprrlrtion for rem”*:4 ol all genital organs; postoperative r;ldiation
.eft
Solid with torsion; adult and embryonal tissues with gliohlasto. matous areas; opposite “vary with non-malignant teratoma
Well 5 m”. operation
;,fter
--.__ We!l
i
5
“I”.
lawr
zd
Lisa et aI.-MaIignant
458
have proven benign. A more vaIuabIe feature in judging the potentiality of an individua1 case is the rapidity of growth. A rapidIy enlarging tumor has usuaIIy proven malignant. The tissues represented in teratomas are usually derivatives of a11 three germinal layers although those of ectoderma1 origin are the most abundant. GIiaI tissue appears to be a very common component. The case of Mayo and Butsch is the onIy one with ectoderma1 tissues 0nIy. Sarcomatous degeneration is more common than carcinomatous, conforming to the recognized incidence in the young of the two types of maIignancy. Carcinoma occurring in a teratoma with ectoderma1 derivatives onIy, usuaIIy seen among older individuals, is represented by the patient of Mayo and Butsch. Sometimes, as in Case I and in a few other instances, the tissues appear embryona1 onIy and not maIignant aIthough the clinica course with recurrence and metastasis has proven the malignant nature of the growth. The presenting symptoms have been classified by Steel into four groups, nameIy, (I) tumor, (2) precocious sexua1 changes, (3) mechanica1 effects on surrounding viscera and (4) torsion. By far the most frequent has been the compIication of torsion. In many instances it has been intermittent. OccasionaIIy a severe attack initiates the course. Precocious sexua1 changes have been present, both as the predominant feature or associated with others more prominent. The mechanical effects are usuaIIy exerted on the gastrointestina1 or urinary systems and consist of diarrhea or constipation and urgency, frequency or dificuIty in voiding. SymptomIess tumor growth does not appear to be very common. The prognosis is poor. Few patients Iive more than one year after the onset of symptoms. Treatment is surgery foIIowed with roentgentherapy. The main features of the more recent cases are summarized in TabIe I. SUMMARY
AND
CONCLUSIONS
Teratomas of the ovary are infrequent in the first two decades of Iife. They comprise the most common tumor of the premenstrual years. ApproximateIy 130 authentic cases are found in the Iiterature incIuding those reported as dermoids. About one-third have proven maIignant. They have both cystic and soIid areas. The rapidity of growth is a more vaIuabIe criterion
Ovarian Teratomas of maIignancy than the gross appearance of solid or cystic tumor. Sarcomatous change is more common than carcinomatous change. Some maIignant tumors have shown onIy embryonal tissue not histoIogicaIIy maIignant. The most common presenting symptoms are due to torsion. Pressure effects on neighboring organs, precocious sexua1 changes and symptomIess tumor growth are Iess common. They tend to recur and metastasize earIy. The prognosis is poor. Therapy is radica1 surgery folIowed with roentgentherapy. Addendum: The fn-st patient, Case I, subsequentIy died with extensive metastases. The second patient appeared in perfect heaIth and free of any evidence of maIignancy twenty-one months after operation. REFERENCES
I. MATTHEWS, F. S. Management of biIatera1 ovarian dermoids. Ann. Surg., 82: 483-485, 1925. 2. POLLACK, Quoted by LANMAN, T. H. Ovarian tumors in chiIdhood. New England J. Med., 201: 555-562. rg2g. 3. STEEL, W. A. Torsion of ovarian cyst in chiIdren. Brit. J. Med., 2: 798-800, 193 I. 4. GOODFRIEND, M. J. and CARUSO, L. J. Ovarian malignancy in a young girl. New York State J. Med., 49: 2178-2180, 1949. 5. DORAN, A: H. G. ClinicaI and PathoIogicaI Observations on Tumours of the Ovarv. FaIIooian Tubes ant Broad Ligament, chap. 5. London, 1884. Smith Eider & Co. 6. SUTTON, J. B. SurgicaI Diseases of the Ovaries and FaIIopian Tubes, chap. 8, pp. 83-1 IO. London, 1891. CasseII. 7. WEIL, H. I. A survey of ovariotomy at extremes of Iife. Bull. Jobns Hopkins Hosp., 16: roz-log, I)*
I
1905. 8. FRANK, R. F. A case of maIignant teratoma of the ovary. Am. J. Obst., 55: 348-375, 1907. g. HARRIS, R. H. Carcinomatous ovarian teratoma with premature puberty and precocious somatic deveIopment. Surg., Gynec. Ed Obst., 24: 6~4-61 I, rg17;41: 191-193, 1925. I o. LOEB, M. J. and LEVY, W. Ovarian cysts and tumors in chiIdren under ten years of age. Arch. Pediat., 49: 651-666, 1932. I I. WAKELY. C. P. G. Ovarian teratomatous cysts occurring in chiIdren. Surg., Gynec. FY Obst., 56: f-3-6951
1933.
12. WITZBERGER, C. M. and AGERTY, H. A. tumors in infancy and chiIdhood. Arch. 54: 339-348, ‘937. 13. BACCARINI, L. Contributo a110 studio dei ovarici nell’infancia. Arch. ital. di cbir.,
Ovarian Pediat., teratomi 36: 161-
172, 1934. 14. WILLIS, R. A. Structure of teratomata. J. Patb. CT Bact., 40: 1-36, 1935; The histogenesis of neura1 tissue in teratomata. J. Patb. CYBact., 42: 41 r-416, 1936; A further study of the structure
American
Journal
of Surgery
Lisa et aI.-Malignant
I 5. I 6. 17. 18.
19.
01’ teratomata. J. Path. ti Bach, 45: 49-65. 1937; Pathology of Tumours, chap. 61, pp. 940-984. St. Louis, 1948. C. V. Mosby. hIEYER, F. W. Teratoma of the ovary with malignant metastases in chiIdhood. J. I’hiZlip+ne Islands M. A., 16: 555-559, 1936. DREYFUS, J. R. Les teratomes de I’ovaire et I’action endocrine des tumeurs de I’ovaire chez Ies enfants. Arch. de med. des Enjants, 39: 71~723, 1936. SEARBY, J. J. Teratoma of the ovary in a child. M. J. Australia, 24: 922923, 1937. ~IAYO, C. W. and BUTSCH, W. L. Ovarian tumors among young girls. Minnesota Med., 2 I : 256-258, 7938. SMELLY,J. A. In: DAHGEON, H. W. Cancer in Childhood. GynecoIogicaI cancer in chiIdren, pp. 58-66. St. Louis, 1940. C. V. Mosby.
Ovarian
Teratomas
20. SMELTZER, M. Solid teratoma of the ovary in the young girl. Am. J. Oh. IY cynec., 41: 616-623, ‘941. 21. MCELHINNEY, W. T. Solid teratoma of the ovary in a fourteen year old girl. Cincinnati J. Med., 22: 194-195, 1g4r-1942. 22. MATZOS. S. A.. FERRAIRA. J. and VIANA. D. Teratoma ‘comphcado na infancia. An. ‘basil. de glnec., 20: 177-188, 1945. 23. FALCO, A. SuI teratoma solid0 dell’ovario. Ann. di ostet. e ginec., 36: 394-440, 1914. 24. FASOLT, H. Ein teratom des ovars mit chorioepitheliomahnlichen metastasen. Ztschr. ,f. Kinde& 51: 319-334, 193’. 25. DOWNES, W. A. Tumors of the ovary in children. J. A. M. A., 76: 443-445, 192 I.
SOME patients with amebic dysentery, even when put on intensive antiamebic therapy, may fail to heal completely and are then often left with a disabhng condition not unIike non-specific uIcerative coIitis. In such instances frequent proctosigmoidoscopic examinations and appropriate treatments are needed for the residua1 uIcerative Iesions in the coIon. To fail to do so, and simpIy relying instead upon a Iong continued antiamebic regimen, often resuIts in “uncured” cases. In short, one shouId not continue to use amebacides when the ameba no Ionger are found in the stools in patients with persistent symptoms. Such patients now need different treatment for their unheaIed uIcerative Iesions. Aureomycin seems ver\ useful for these complications. (Richard A. Leonardo, M.D.)
April, 1931
459
JAMES R.
OVARIAN TERATOMAS IN THE FIRST TWO DECADES OF LIFE*
LISA, M.D., J. WILLIAM HINTON, M.D., SEYMOUR WIMPPHEIMER, M.D. AND JOSEPH D. GIOIA, M.D. New York, New l’ork
T
about 300 to 400 cc. of bloody fluid with clots were found. There was torsion of the right ovary which had a hemorrhagic cyst and a smaI1 perforation. The appendix and smaI1 intestine were normaI. The cyst was resected and the appendix removed. The postoperative course was uneventfu1 and the patient was discharged on December I, 1948. The pathoIogic report was as follows: The cystic right ovary measured 5.4 by 3 by 3.3 cm. and was purpIe in coIor. On the surface there was a raised Ientiform white noduIe. On section the cyst was fiIIed with fluid bIood. The wall was purple-bIack and about 9 mm. thick. The posterior surface had a ragged rent. MicroscopicaIIy, the waI1 was edematous and hemorrhagic. There were norma stroma and some primordia1 foIIicIes. The teratomatous tissues were characterized by an embryonal appearance. The most abundant was the skin and its appendages of hair and sebaceous glands. Sometimes the squamous epithelium merged with gIanduIar structures lined by tall ciliated epitheIium. There was abundant activeIy growing bone, with or without foci of caIcification, fibro-erastic cartilage, glial tissue and Ioose areoIar tissue. Some structures were organoid and resembled bone with synovial cavity in architectural pattern. None of the tissues had any of the histoIogic criteria of maIignancy. The diagnosis was teratoma of CASE REPORTS ovary with torsion. CASE I. The onset of iIIness in this patient, The patient was readmitted five months Iater a seven year oId child, was a sharp attack of on April 24, 1949. One week previousIy she had severe abdomina1 pain simuIating acute appenhad an attack of vomiting and enlargement of dicitis. An emergency Iaparotomy was carried the abdomen was discovered. For the entire out on November 26, 1948, with that preopera- .sI week there was intermittent fever, diarrhea and tive diagnosis. When the abdomen was opened,:! extreme Hatulence. * From Doctors Hospital, New York, N.Y.
of the ovary aIthough inERATOMAS frequent in the first two decades of Iife are not rare. They constitute the most common tumor of the premenstrua1 yearst1s2 usualIy occurring in the first half of the second decade.3 To the middIe of 1949 about 150 authentic cases are found in the Iiterature incIuding those reported as dermoids. ExampIes of the coincidenta invorvement of the same ovary by a maIignant tumor and a non-malignant teratoma such as reported by Goodfriend and Caruso4 are not included. In addition to individua1 case reports there are severa excellent Ionger articIes. 2*5-12Since the pubIications and Agerty’” of WakeIy ’ ’ and Witzberger twenty-four more cases have been found.13-2d Ten are benign and fourteen malignant. Of the total number approximateIy one-third have shown evidence of maIignancy. The earIy literature usuaIIy deaIs with benign tumors. In the more recent publications maIignant disease is more frequent, probabIy, as suggested by Downes, 25 due to more thorough histoIogic examination. The purpose of the present communication is to review the recent Iiterature on maIignant ovarian teratomas of the frrst two decades and to report two additional cases which iIIustrate some of the important features of these tumors.
April,
1951
453
454
Lisa et aI.-MaIignant
FIG. I. Case I. The nodular mass found replacing the right ovarian tissue left at the first operation.
On examination the patient appeared acuteIy ill. Her face was Aushed and her temperature The abdomen was distended, was 103.8%. slightiy tender under the old scar and felt cystic. Laparotomy was performed the next day. The segment of right ovary Ieft at the first operation was repIaced by a mass Iarger than a footbaI1 and adherent to sigmoid and omentum. (Fig. I .) InnumerabIe masses of various sizes were scattered over the peritoneum and omenturn; one, 8 cm. in diameter, was adherent to the sigmoid. The Ieft ovary appeared normaI. The right ovarian, the sigmoida1 and an omenta1 mass were removed. The patient was discharged on May 2nd. The pathoIogic report reveaIed the foIIowing: The right ovarian mass was grossIy noduIar, had a smooth, intact serosa and measured rg by 13 by 6 cm. It feIt soft and cystic. On section there were numerous cysts of various sizes fiIIed with pseudomucinous contents. The centraI portion was soIid and had some amorphous, gritty particIes. The other two masses were similar. MicroscopicalIy, a11 the tumors were simiIar and contained both aduIt and embryona1 tissues. There were connective tissue, adipose tissue, invoIuntary muscIe, young and aduIt voIuntary muscIe, deveIoping bone, fibro-eIastic cartilage, aduIt skin with accessory structures and neurogenic tissue. No pattern was folIowed; a11 the tissues were intermingIed. (Fig. 2.) The cysts were of various types. Skin with hair shafts and sebaceous glands Iined some.
Ovarian T’eratonlas In others the squamous epithelium merged with epitheIium of respiratory type which was associated with mixed seromucous glands. It merged sometimes with non-ciliated epitheIium covering viIIous projections mimicking small bowe1 foids. OccasionaiIy it merged with a cystic Iining of epetidymal nature, lying in aduIt g&al tissue. Other cavities had taI1, ciIiated, mucusproducing ceIIs. Ciliated columnar ceIIs with nests of non-ciIiated mucous ceIIs lined other cavities. Occasionally these cysts had transitional epithelium. There were some structures with Iining similar to large bowe1. A few areas had structures Iike fallopian tube and choroid plexus. The neurogenic tissue was abundant. Chiefly it was aduIt gIia, sometimes embryona1 glia with normal mitoses. Sometimes both were intermingIed. The gIia frequently had small cavities Iined with ependyma resembIing the centra1 canal of the spina cord. Some areas of edema formed cavities. There were some neurones with NissI granuIes. There were a few aduIt nerves and one gangIion simiIar to those of the sympathetic chain. Norma1 ovarian tissue was not found. The diagnosis was recurrent teratoma of the right ovary and metastatic teratoma of the peritoneum. (Fig. 3.) Roentgentherapy was carried out from May 9th to June 10th through two anterior and two posterior portaIs, each 15 by IO cm. The tota dosages measured in air were as follows: anterior right peIvis and abdomen, 1,550 r; anterior Ieft pelvis and abdomen, 1,550 r; posterior right peIvis and abdomen, 1,600 r; and posterior Ieft peIvis and abdomen, 1,600 r. The factors at 50 cm. T.S.D. were KV 200 M A 8 fiIter mm. 45 Cu I AI. When Iast seen in November the patient appeared weI1, was in good heaIth and apparentIy free of metastases. CASE II. The current iIIness of the patient, nineteen years of age, was of two to three weeks’ duration and was characterized by Ieft Iower quadrant pain. It began about five days before the Iast menstrual period and continued after menstruation ceased. The pain was suffrcientIy severe to prevent continuing at work. The menses previousIy had aIways been reguIar. On examination on May 14, 1949, a cystic mass was paIpabIe in the Ieft ovarian area. Laparotomy was performed two days Iater. The Ieft ovary was Iying on the right side, twisted 180 degrees, the size of a grapefruit American Journal of Surgery
Lisa et al.-Malignant
Ovarian
Teratomas
455
2 3 FIG. 2. Cast I. \loderately celIuIar embryonal tissue showing some norma mitoses, found in the recurrent and metastatic lesions. X 600. FIG. 3. Case I. Neurogenic tissue with both adult glial cells and neurones with NissI granules.
and muItiIocuIar. The right ovary was soIid and as Iarge as a basebaIL There were some omenta1 adhesions from a previous appendectomy. The masses were resected Ieaving some ovarian tissue on each side. The pathoIogic report reveaIed the foIIowing: The Ieft ovary was roughly ovoid, had a smooth outer surface with prominent vesseIs, feIt aImost cystic and measured 8 by 7.5 by 6 cm. On section it was made up Iargely of a soIid noduIe of geIatinous appearance with coarse tibrous bands producing the appearance of thyroid tissue. (Fig. 4.) A sIit-like cavity containing miIky fluid separated the centra1 mass from the periphera1 zone. One part of the waI1 was bony hard. The right ovary was smooth, cystic, measured 13 by 9.5 by 6 cm. and had some doughy masses presenting externaIIy. On section there were two cysts separated by a calcified ridge. Both cysts contained Iight yeIIow fluid. At one pole of the Iarger cyst there was a secondary cavity containing sebaceous materia1 and hair and a caIcified mass in the waI1. SeveraI smaI1, soft noduIes in the waI1 had a yeIIow-white cut surface. In the waI1 of the smaIIer cyst there was a secondary cyst containing sebaceous materia1, hair and a caIcifIed mass. MicroscopicaIIy, the most prominent component of the Ieft ovary was glial tissue, mainIy
April,
1951
FIG. .+. Case II. Cut surface of left ovary has a solid gelatinous appearance with coarse fibrosis producing the appearance of thyroid tissue.
very ceIIuIar, embryona1 in type, extremeIy atypica1, rich in norma and abnorma1 mitoses and showing rosette formation. The tissue was extremeIy edematous, particularly in the soIid centra1 mass which resembIed thyroid to the naked eye. A few smaI1 cavities appeared Iined by ependyma. Some areas had aduIt and embryona1 skin with sebaceous gIands and hair foIIicIes. They overIay adipose tissue and canceIIous bone. (Figs. 5 and 6.) The right ovary had aduIt tissues. The smaI1 cyst was Iined by skin with hair, sebaceous and sweat gIands, merging into a muItiIayered ciliated epitheIium which in turn Ied into a gIial-
446
Lisa et al.-MaIignant
Ovarian
Teratomas
6 FIG. 5. Case II. Young emb&nal tissue showing the great cellularity. X 600. FIG. 6. The blastomatous gliaI tissue showing the atypica1 cells, numerous mitoses and rosette formation.
Iined cavity. In the waI1 of the cyst there were structures Iike choroid pIexus, adipose tissue, coIIagenous connective tissue and invoIuntary muscle. The Iarge cyst had skin, sebaceous glands, subcutaneous adipose tissue and aduIt glia. Some of the gIia1 foci had neuronal ceIIs. There was some canceIIous bone with fatty marrow in which foci of myeIocytes and megakaryocytes were scattered. There was some moderateIy ceIIuIar young embryona1 gIia free of signs of rapid growth. A segment of norma ovarian stroma was present. The diagnosis was maIignant teratoma of the Ieft ovary with gIiobIastomatous foci and torsion, and nonmaIignant teratoma of the right ovary. A second Iaparotomy was done on May 25th. A supracervica1 hysterectomy and biIatera1 salpingo-oophorectomy were performed with compIete remova of both broad Iigaments. Microscopic examination showed organizing hematoma of the right ovary. Otherwise both had onIy norma tissue. CarefuI examination faiIed to revea1 any evidence of tumor in any portion of the tissues removed. The patient was discharged on June 5th. After Ieaving the hospita1 the patient received roentgentherapy from June 2Ist to August 12th through four portaIs each IO by 15 cm. The tota dosage measured in air was as follows: right anterior peIvic fieId, 2,075 r;
X 600.
Ieft anterior peIvic fieId, 2,075 r; anterior upper mid-abdomina1 fieId, 1,500 r; and posterior upper mid-abdomina1 fieId, 1,500 r. The factors at 50 cm. T.S.D. were KV 200, filter I Cu I AI. Roentgenograms taken of the chest and peIvis before therapy was given were negative. During the course of therapy there were two episodes of bIeeding. On JuIy 15th the patient bIed after voiding. The urine had a faint trace of aIbumin and some erythrocytes. Nothing of note was found on physica examination. On JuIy 29th the patient vomited and passed a dark coIored stoo1. Again nothing of note was demonstrabIe. When Iast seen in November she remained free of symptoms and had returned to work. Examination, incIuding fluoroscopy of the chest, had given no evidence of recurrence or metastasis. COMMENTS
Solid teratomas of the ovary are usuaIIy considered potentiaIIy or definiteIy maIignant and cystic tumors benign. These criteria are Iess vaIuabIe in the first two decades of Iife than at older age periods. SeveraI of the tumors Iisted in TabIe I have shown both soIid and cystic areas. Some, such as the case of Willis, have been chiefly cystic. Some of the soIid teratomas, for exampIe those of Baccarini and of Searby, American
Journal
of Surgery
Lisa et al.-Malignant
Ovarian
TABLE MALIGNANT
-_Author
;
F~rlc” ,914
457
I
OVARIAN
-
Symptoms
Age
Teratomas
TERATOMAS Psthology
Site
^
16
Rapidly enlarging ahdomen for I m”. reaching size of 9-m”. pregnancy; gastrointestinal and urinary disturbances, pain. Sever, tumor; ovariotomy; recurrence in 4 mo.; severe abdominal pain,. vomiting, anemi?, rapidly growing mass; extenswr peritoneal metastases at operation Precocious menstruation for 2 yr.; positive Aschheim-Zondek test Abdominal enl;,rgrment 6-m”. preg:nancy
solid; more
___~___ Trratoma
Death with metastatic chorio-rpithelioma
withchorio-epithelioms
._
ISolid and c.y&c; marked crllularity ;rnd mitosrs; other ovary with non-malignsnt teratoma
I-I.eft
Solid; torsion; all layers abundirnt embryonal glia
-__ Right
Enlarging abdomen for 5 m”.; latesympt”ms”ftorsion.ancmia, hy ogastrium; tumor reaching ovariotomy; no visi tYle metastases
5
cystic and recurrence
.-
Fize of
Three wk. mild xnd severe symptoms of torsion, tumor, precoc’ous sexual development; ovar‘otomy; recurrence of symptoms. tumor and metastases in scar in 2 mo.; postoperative radiation
i -_-
Multilocular sBrc”mitt”“s: anaplastic
Right
with
--_
Cystic
_-
and solid; ectodermal tissues with
mesodermal
_--..
Postoperative
and car-
death
cinoma
._ 13 Meyer
4
1936..
.-
Case of Zoltan and Szathmary Inoperable tumor st laparotomv
-I-
Mnyo and Hutsch
Smrltz?.r
193X
I
Symptomless lower abdominal mass 2% yr.; ovariotomy; no visible metastases; intestinal “bstruction in 6 m”.; inoperable pllravertehral mass st operation
Right
I R
Right ovarian resection for torsion 6 mo. previously; recorrcnt Symptoms, tumor filling pelvis and lower abdomen
; Right 1Ectodtrmal
8
S.ymptoms of torsion 3 II.. tu mar; ovariotomy; no vlslble metastases postoperative radiation; reC”rrence of symptoms in 3 m”.; laparotomy 5 mo. later; extensive peritoneal metnstases
; Kight
Mild symptoms of torsion 2^... wk.; tUrnor; ““ar,“t”my: mass tllllng pelvis and lower abdomen; rccurrencc of symptomless mass in 6 mo.; peritoneal metaStases at laparotomy; postoperative rndi-
;
1938
aCon --___
carcinoma
I _~____
194.1-1942
’ 14
t”rSI”“:
““arI”t”“1y;
3X normill: complicated genital anomalies and j carcinoma of “teT”s Authors.
_.
tissues with grade I
ildcno-
Solid with torsion; embr.yonai Sue< of 011 layers: sarcomi,
suesof all layers: benign; metastases ~ tissues with many
-~ ~~.--.
Opcrxtivc
tis-
Death
rtlcoverv
I yr. ;Iftcr onwt
histologically of embryonal mitoses
onset
_____
_______
Symptomless. rapidly growing tumor for 2 mo., weight 1”~s. fever; ovariotomy: mass shove umbilicus; postoperativr r:ldiation ___-ACUfC
-~~.~histologi-
I
Amputation of leg at 3 yr. for cavernow angiomn: recurrences treated with x-my for 7 yr.; abdominal tumor at 13 yr.; radioresistant; oyariotomy; postoperative radiation; early good results h1rF.lhinnr.v
___---All 1ayers representrd tally benign
I.arge loholared mass with Iibrosarcomil :Ind carcinom:l
Death apparently from metastasl% mo. after onset
9
Riuht
I-Ectodermal
ovary
by conprimary
wrs
and mesodermal tiswith s;wcomat”us weas
-
Acute torsion; resection. no visible metutases; intesbn~l ohstruction in $ mo.; peritoneal metastases: postoperative radiadon
Right
Cystic with torsion;, adu:t and emhryonal tissues; hxstologic~lly benign; mPtutases more embryon;tl with rnitoses
‘9
Incrrasing signs of torqion; bilAtera resection; secondary oprrlrtion for rem”*:4 ol all genital organs; postoperative r;ldiation
.eft
Solid with torsion; adult and embryonal tissues with gliohlasto. matous areas; opposite “vary with non-malignant teratoma
Well 5 m”. operation
;,fter
--.__ We!l
i
5
“I”.
lawr
zd
Lisa et aI.-MaIignant
458
have proven benign. A more vaIuabIe feature in judging the potentiality of an individua1 case is the rapidity of growth. A rapidIy enlarging tumor has usuaIIy proven malignant. The tissues represented in teratomas are usually derivatives of a11 three germinal layers although those of ectoderma1 origin are the most abundant. GIiaI tissue appears to be a very common component. The case of Mayo and Butsch is the onIy one with ectoderma1 tissues 0nIy. Sarcomatous degeneration is more common than carcinomatous, conforming to the recognized incidence in the young of the two types of maIignancy. Carcinoma occurring in a teratoma with ectoderma1 derivatives onIy, usuaIIy seen among older individuals, is represented by the patient of Mayo and Butsch. Sometimes, as in Case I and in a few other instances, the tissues appear embryona1 onIy and not maIignant aIthough the clinica course with recurrence and metastasis has proven the malignant nature of the growth. The presenting symptoms have been classified by Steel into four groups, nameIy, (I) tumor, (2) precocious sexua1 changes, (3) mechanica1 effects on surrounding viscera and (4) torsion. By far the most frequent has been the compIication of torsion. In many instances it has been intermittent. OccasionaIIy a severe attack initiates the course. Precocious sexua1 changes have been present, both as the predominant feature or associated with others more prominent. The mechanical effects are usuaIIy exerted on the gastrointestina1 or urinary systems and consist of diarrhea or constipation and urgency, frequency or dificuIty in voiding. SymptomIess tumor growth does not appear to be very common. The prognosis is poor. Few patients Iive more than one year after the onset of symptoms. Treatment is surgery foIIowed with roentgentherapy. The main features of the more recent cases are summarized in TabIe I. SUMMARY
AND
CONCLUSIONS
Teratomas of the ovary are infrequent in the first two decades of Iife. They comprise the most common tumor of the premenstrual years. ApproximateIy 130 authentic cases are found in the Iiterature incIuding those reported as dermoids. About one-third have proven maIignant. They have both cystic and soIid areas. The rapidity of growth is a more vaIuabIe criterion
Ovarian Teratomas of maIignancy than the gross appearance of solid or cystic tumor. Sarcomatous change is more common than carcinomatous change. Some maIignant tumors have shown onIy embryonal tissue not histoIogicaIIy maIignant. The most common presenting symptoms are due to torsion. Pressure effects on neighboring organs, precocious sexua1 changes and symptomIess tumor growth are Iess common. They tend to recur and metastasize earIy. The prognosis is poor. Therapy is radica1 surgery folIowed with roentgentherapy. Addendum: The fn-st patient, Case I, subsequentIy died with extensive metastases. The second patient appeared in perfect heaIth and free of any evidence of maIignancy twenty-one months after operation. REFERENCES
I. MATTHEWS, F. S. Management of biIatera1 ovarian dermoids. Ann. Surg., 82: 483-485, 1925. 2. POLLACK, Quoted by LANMAN, T. H. Ovarian tumors in chiIdhood. New England J. Med., 201: 555-562. rg2g. 3. STEEL, W. A. Torsion of ovarian cyst in chiIdren. Brit. J. Med., 2: 798-800, 193 I. 4. GOODFRIEND, M. J. and CARUSO, L. J. Ovarian malignancy in a young girl. New York State J. Med., 49: 2178-2180, 1949. 5. DORAN, A: H. G. ClinicaI and PathoIogicaI Observations on Tumours of the Ovarv. FaIIooian Tubes ant Broad Ligament, chap. 5. London, 1884. Smith Eider & Co. 6. SUTTON, J. B. SurgicaI Diseases of the Ovaries and FaIIopian Tubes, chap. 8, pp. 83-1 IO. London, 1891. CasseII. 7. WEIL, H. I. A survey of ovariotomy at extremes of Iife. Bull. Jobns Hopkins Hosp., 16: roz-log, I)*
I
1905. 8. FRANK, R. F. A case of maIignant teratoma of the ovary. Am. J. Obst., 55: 348-375, 1907. g. HARRIS, R. H. Carcinomatous ovarian teratoma with premature puberty and precocious somatic deveIopment. Surg., Gynec. Ed Obst., 24: 6~4-61 I, rg17;41: 191-193, 1925. I o. LOEB, M. J. and LEVY, W. Ovarian cysts and tumors in chiIdren under ten years of age. Arch. Pediat., 49: 651-666, 1932. I I. WAKELY. C. P. G. Ovarian teratomatous cysts occurring in chiIdren. Surg., Gynec. FY Obst., 56: f-3-6951
1933.
12. WITZBERGER, C. M. and AGERTY, H. A. tumors in infancy and chiIdhood. Arch. 54: 339-348, ‘937. 13. BACCARINI, L. Contributo a110 studio dei ovarici nell’infancia. Arch. ital. di cbir.,
Ovarian Pediat., teratomi 36: 161-
172, 1934. 14. WILLIS, R. A. Structure of teratomata. J. Patb. CT Bact., 40: 1-36, 1935; The histogenesis of neura1 tissue in teratomata. J. Patb. CYBact., 42: 41 r-416, 1936; A further study of the structure
American
Journal
of Surgery
Lisa et aI.-Malignant
I 5. I 6. 17. 18.
19.
01’ teratomata. J. Path. ti Bach, 45: 49-65. 1937; Pathology of Tumours, chap. 61, pp. 940-984. St. Louis, 1948. C. V. Mosby. hIEYER, F. W. Teratoma of the ovary with malignant metastases in chiIdhood. J. I’hiZlip+ne Islands M. A., 16: 555-559, 1936. DREYFUS, J. R. Les teratomes de I’ovaire et I’action endocrine des tumeurs de I’ovaire chez Ies enfants. Arch. de med. des Enjants, 39: 71~723, 1936. SEARBY, J. J. Teratoma of the ovary in a child. M. J. Australia, 24: 922923, 1937. ~IAYO, C. W. and BUTSCH, W. L. Ovarian tumors among young girls. Minnesota Med., 2 I : 256-258, 7938. SMELLY,J. A. In: DAHGEON, H. W. Cancer in Childhood. GynecoIogicaI cancer in chiIdren, pp. 58-66. St. Louis, 1940. C. V. Mosby.
Ovarian
Teratomas
20. SMELTZER, M. Solid teratoma of the ovary in the young girl. Am. J. Oh. IY cynec., 41: 616-623, ‘941. 21. MCELHINNEY, W. T. Solid teratoma of the ovary in a fourteen year old girl. Cincinnati J. Med., 22: 194-195, 1g4r-1942. 22. MATZOS. S. A.. FERRAIRA. J. and VIANA. D. Teratoma ‘comphcado na infancia. An. ‘basil. de glnec., 20: 177-188, 1945. 23. FALCO, A. SuI teratoma solid0 dell’ovario. Ann. di ostet. e ginec., 36: 394-440, 1914. 24. FASOLT, H. Ein teratom des ovars mit chorioepitheliomahnlichen metastasen. Ztschr. ,f. Kinde& 51: 319-334, 193’. 25. DOWNES, W. A. Tumors of the ovary in children. J. A. M. A., 76: 443-445, 192 I.
SOME patients with amebic dysentery, even when put on intensive antiamebic therapy, may fail to heal completely and are then often left with a disabhng condition not unIike non-specific uIcerative coIitis. In such instances frequent proctosigmoidoscopic examinations and appropriate treatments are needed for the residua1 uIcerative Iesions in the coIon. To fail to do so, and simpIy relying instead upon a Iong continued antiamebic regimen, often resuIts in “uncured” cases. In short, one shouId not continue to use amebacides when the ameba no Ionger are found in the stools in patients with persistent symptoms. Such patients now need different treatment for their unheaIed uIcerative Iesions. Aureomycin seems ver\ useful for these complications. (Richard A. Leonardo, M.D.)
April, 1931
459