Malignant mixed Mullerian tumor of the fallopian tube

GYNECOLOGIC

9,381-393 (1980)

ONCOLOGY

CASE REPORT

Malignant

Mixed Mullerian

Tumor

of the Fallopian

Tube

Report of a Case and Review of Literature PARVIZ

HANJANI,

M.D.,

FACOG,

AND SUSAN Departments Temple

ROBERT

0. PETERSEN,

A. BONNELL,

M.D.,

PH.D.,

R.N.

of Obstetrics and Gynecology, Section of Pelvic Oncology University Health Sciences Center, 3401 North Broad Street, Pennsylvania 19140

and Pathology, Philadelphia,

Received May 23, 1979 Twenty-three cases of malignant mixed Mullerian tumor of the fallopian tube have been reported; we report another such case. Type of therapy and outcome of these 24 cases is reviewed and the histogenesis is presented. Thirteen patients were treated with surgery alone, with a mean survival of 14.7 months; the longest survival was 43 years. Nine patients were treated with surgery followed by radiation therapy, five patients died within 15 months, and the longest survivor was 44 years. Three patients survived 12, 24, and 17 months. Our patient responded well to combination chemotherapy after surgery and survived 26 months. The small number of patients precludes conclusions on optimal therapy. Survival does not improve with postoperative radiation therapy. The potential benefit of combination chemotherapy following surgery awaits further evaluation.

Primary fallopian tube malignancy is a rare occurrence, and as such, no single institution is able to study a large series of patients. Accordingly, the importance of reporting every case has been emphasized [l-4]. These malignancies account for only O.l-0.5% of all gynecologic cancers [1,2]. Although approximately 950 cases of primary carcinoma of the fallopian tube have been described in literature [l-5], only 23 cases of malignant mixed Mullerian tumors have been reported. Malignant mixed Mullerian tumors are, as a group, uncommon. The most frequent site is the endometrium, followed in decreasing incidence by the vagina, the cervix, and the ovary. The fallopian tube is the least common site, accounting for less than 4% of the reported cases [6,7]. The purpose of this paper is to report the 24th case of this unusual Mullerian tumor, and briefly review the literature concerning the outcome of 23 previously reported cases. HISTOGENESIS

By definition, malignant mixed Mullerian tumors contain both malignant epithelial and stromal elements. The stromal component may contain tissues homolo381 OWO-8258/80/030381-13$01.00/O Copyright @ 1980 by Academic Press, Inc. All rights of reproduction in any form reserved.

382

HANJANI,

PETERSEN,

AND

BONNELL

gous and/or heterologous to the Mullerian duct system. Homologous types, such as smooth muscle, endometrial stromal cells, etc., are normally derived from Mullerian tissue. Heterologous elements such as fat, striated muscle, bone, and cartilage are foreign to the Mullerian duct system. It is believed that the origin of both the epithelial and the stromal components is the multipotent mesoderm of the Mullerian system [S]. Malignant mixed Mullerian tumors have been referred to differently in literature. McFarland noted 110 synonyms for this tumor [93. A classification of female genital tract malignancies with sarcomatous components alone or with an epitheha1 component has been formulated only for tumors of endometrial origin [lo]. Norris et al. divided this group of tumors arising from endometrium as carcinosarcoma with homologous sarcomotous elements and malignant mixed mesodermal tumor composed of sarcomatous components foreign to the tissue of origin. They related the better prognosis for the former [I 1,121. To understand this seemingly diverse group of neoplasms, it is important to review the embryology of the female genital tract. In the lo-mm embryo a fold of tissue along each urogenital ridge rolls inward to form the Mullerian duct by invagination of the coelomic epithelium into the vaginal mesenchyme [9]. In the female the caudal portion of the Mullerian duct becomes fused forming the upper vagina and uterus. The cephalad portion of the Mullerian duct remains separated, forming the individual fallopian tubes [7]. In view of a common embryologic origin of these organs, the histologic spectrum of malignant mixed Mullerian tumors becomes understandable. On the basis of multipotentiality of Mullerian stroma (which apparently retains a latent capacity to differentiate into a variety of cell types by a yet unknown stimulus) it is not unreasonable to find this tumor in the vagina, uterus, fallopian tube, or ovaries [7]. Although any benign or malignant tumor including malignant mixed Mullerian tumor noted elsewhere in the paramesonephric system may occur in the tube, the lack of physiological activity of tubal Mullerian stroma has been suggested as the basis for these tumors occurring less commonly in this site than in the endometrium

[6,7,131. BRIEF REVIEW

OF PREVIOUSLY

REPORTED

CASES

In 1973, Wu et al. [7] summarized 14 cases including one of their own. Acosta, Kaplan, and Kaufman reported three additional cases in 1973 [8]. Manes et al. [ 141 reported four cases in 1976 but two patients from their series had questionable diagnosis (Cases 20 and 22 from Table 1). In these patients hysterectomy was not performed, and it could not be determined whether the tumor was primary in the uterus, which is the most common site for this malignancy. One case was reported by Jain in 1977 [ 151. Henderson et al. reported one additional case in 1977 [5]. The present study is the 24th such recorded case. Table 1 summarizes the 24 recorded cases including the present case. CASE HISTORY

M.K., a 62-year-old white woman was admitted to the gynecologic oncology service on May 11, 1975, following a left inguinal node biopsy which revealed poorly differentiated adenocarcinoma. The patient had noticed a left groin mass 5

FALLOPIAN

TUBE

MIXED

MULLERIAN

TUMOR

383

months prior to biopsy. She was otherwise asymptomatic. She had her last menstrual period 6 years prior to admission with normal menstrual history and no postmenopausal bleeding. The patient’s past history was noncontributary. She was Gravida I, Para I. Examination showed a biopsy site in left inquinal area with a 2 x 2 cm node. No ascites or abdominal distention were noted and no other nodes were palpable. Pelvic examination revealed an 8 x 10 x IO-cm semisolid mass in the region of the left ovary. The hemoglobin was 9 g, red blood count: 4.89 mm3, white blood count: 8,700 mm3, total protein: 7.3 g/dl, albumin: 3.7 g/d], globulin: 3.6 g/dl, alkaline phosphatase 11 IU/liter, serum glutamic oxaloacetic transaminase: 16/IU/liter, chest film, intravenous pyelogram, barium enema, and upper gastrointestinal were normal and pap smear was negative. After transfusion of 2 units of packed cells, an exploratory laparotomy was performed on May 21, 1975, and the following findings were noted: (a) The left adnexal region had a large fungating mass measuring 10 x 8 x 8 cm, taking origin from the fallopian tube. The left ovary was of normal size. No ascites was present. (b) Uterus, right fallopian tube, and ovary appeared normal. (c) The paraaortic area was studded with enlarged firm metastatic lymph nodes. (d) Two large implants of tumor on the omentum and a large 5 x 4 x 5-cm mesenteric node were detected. A total abdominal hysterectomy and bilateral salpingo-oophorectomy, omentectomy, and resection ot mesenteric node were performed. Microscopic examination revealed that throughout the specimen both carcinomatous and malignant stromal components were present in varying proportions. The adenocarcinomatous element was well differentiated with papillary and glandular patterns admixed (Fig 1). Cystic areas of varying sizes, lined by carcinomatous cells evidencing papillary projections were common. Other areas showed a more compact proliferation of neoplastic glands. The malignant stromal component intermingled with the carcinomatous glands. Its appearance throughout the tumor was similar. The stromal cells were undifferentiated and were found in loose bundles which were frequently associated with thin-walled vessels and varying amounts of stromal edema (Fig. 2). The cells were spindle shaped with varying amounts of cytoplasm. The nuclei were hyperchromatic and evidenced significant variation in size. No evidence of rhabdomyoblast or cartilagenous differentiation was observed. The above features were interpreted as that of a malignant mixed Mullerian tumor, homologous type. The patient had an uneventful postoperative course. She was treated with chemotherapy consisting of vincristine, actinomycin D, and cyclophosphamide. Cyclophosphamide, 10 mg/kg/day, and actinomycin, 0.5 mg/day, were administered for 5 days and repeated every 4 to 5 weeks. Vincristine was given in a dose of 2.5 mg weekly. Only eight courses of vincristine were given because the patient developed peripheral neuropathy from which she recovered when vincristine was discontinued. The patient did very well and her response to chemotherapy was excellent. The left inguinal nodes completely disappeared and she was active with no clinical sign of disease. She did well for 20 months until February 1977 when tumor progression was noted. For 4 months prior to this date she had not

Date

1892

1902

1926

1933

1940

1941

1950

Case

1

2

3

4

5

6

7

58

60

54

14

51

Age

Carcinosarcoma, adenocarcinoma, sarcomatous with cartilage and bone Carcinosarcoma, sarcoendothelioma Carcinosarcoma spindle ceil sarcoma; adenocarcinema Carcinosarcoma pleomorphic and spindle cell sarcoma Adenocarcinoma with pleomorphic sarcoma; carcinosarcoma Adenocarcinoma with spindle cell sarcoma; carcinosarcoma Carcinosarcoma, adenocarcinoma, spindle cell sarcoma

Histology

PRIMARYFALLOPIANTUBE

Peritoneum, multiple-nodular

Opposite tube

Opposite tube

Sigmoid, mesentry, ovary, opposite tube

Peritoneum, uterus, opposite tube Peritoneum, left iliac, bone, lungs

Metastasis

Treatment

Survival time (months)

TABLE 1 MALIGNANTMIXEDMLJLLERIANTUMOR:TOTALCASEREPORTIN

Adherent to sigmoid

Resembled hydrosalpinx

History of old salpingitis

Involvement of both tubes Metastasis had sarcoma only

Remarks

LITERATURE

25

24

23

22

16

21

20

Reference

35

69

45

1963

1963

1963

1970

1971

1961

IO

II

12

13

14

15

46

57

64

58

1961

9

65

19.59

8

Mixed Mullerian tumor

Adenocarcinoma, pleomorphic spindle cell sarcoma, and malignant cartilage Adenocarcinoma, pleomorphic and spindle cell sarcoma, and malignant cartilage

Undifferentiated and spindle cell carcinosarcoma with cartilage islands Adenocarcinoma, pleomorphic sarcoma with cartilage and striated muscle Carcinosarcoma

Carcinosarcoma, adenocarcinoma, spindle-cell sarcoma, cartilage Mixed mesodermal tumor, malignant

ovary

radia-

Left oviduct with extension to left ovary with ascites IO cm

TAH/BSO

2

12+

Vaginal hysterectomy LS., and BSO, pelvic radiation 5 I50 rad total pelvis

6.5 8

TAH/BSO

Bilateral involvement One out of 29 pelvic lymph nodes showed carcinoma without sarcomatous elements None

6

54

15

TAHIBSO, BPND, and radiation

Cobalt irradiation and thiotepa

TAH/BSO and external irradiation

TAHIBSO, tion

Peritoneum with secondary bowel obstruction

Peritoneum with secondary small bowel obstruction Pelvic, periaortic, lumbosacral, lung, liver

Homolateral

Ascites, sudden death, no autopsy

Died of generalized metastasis No autopsy

Resembled old hydrosalpinx

Both carcinoma and sarcoma element in metastasis

8

7

I9

27

6

13

18

26

Date

1970

1970

1975

Case

16

17

18

52

62

48

Age

Adenocarcinoma, carcinosarcoma with cartilage like island

Both carcinoma and sarcoma element (homologous)

Mixed Mulletian tumor

Histology

None

Probable lung, brain, and abdomen

Left tube and 15cm polar cystic mass involving tube and ovary

Metastasis

TABLE

Treatment

7

47i

TAHIBSO

5

Survival time (months)

TAH/BSO

TAH/BSO and 5000 rad total pelvis external irradiation

I-Continued

Died of intraperitoneal metastases and bowel obstruction; treated for supraclavicular nodes with 5000 rad external radiation; treated with adriamycin and DTIC for intraperitoneal metastases Left tube only 10 x 12 cm; no autopsy, died at home; left pleural effusion Recurrence noted 30 months post surgery; mass in colon; treated with cytoxan and 5 FU; at time of this report she is still alive with disease

Remarks

15

8

8

Reference

62

62

1976

1976

1977

1975

21

22

23

24

74

58

76

1976

20

47

1916

19

Left mixed Mullerian tumor Mixed Mullerian tumor

Mixed Mullerian tumor

Carcinosarcoma

Carcinosarcoma

Carcinosarcoma

Pelvic metastasis 10 x 8 x 8 left oviduct, and omenturn, metastasis to left inguinal node

Right fallopian tube only Right tube, right hydrosalpinx

Left tube, no metastasis

None, hydrosalpinx

2%

TAH/BSO, pelvic radiation 5000 rad TAH/BSO omentectomy, chemotheraw

26

53+

12

9

24i

RSO

TAHiBSO

TAHIBSO, 5832 rad total pelvis LSO, rad total pelvis 4200 colbalt

Died

No further therapy; 37 months later developed recurrence in pelvis and upper abdomen; alive at last contact with tumor Died

Alive at last contact, bilateral hydrosalpinx 3 Months after surgery had bowel obstruction then 6 months later died from disease No further therapy

Present case

5

14

14

14

14

388

HANJANI,

PETERSEN,

AND BONNELL

FIG. 1. Adenocarcinoma, well-differentiated component in malignant mixed Mullerian tumor. Numerous compact glands lined by pleomorphic cells are present. Focal papillary areas are noted near the right border. Hematoxylin-eosin, x 113.

received chemotherapy on a regular basis due to severe bone marrow suppression. Because she had widespread nonresectable metastasis in the peritoneal cavity she was switched to adriamycin and then to piperazinedione but she did not respond and finally on July 1, 1977 the patient died. Autopsy was refused.

FALLOPIAN

TUBE

MIXED

MULLERIAN

TUMOR

389

‘IG. 2. Undifferentiated sarcomatous component in malignant mixed Mullerian tumor. The SFtindle cells present are in loose bundles with variable amounts of intercellular edema. Thin-walled vess,els are abundant. Hematoxylin-eoxin, x 3 15.

DISCUSSION

To date only 23 cases of primary mixed Mullerian tumor originating in t he fal lopian tube have been reported. Our case is the 24th reported case. It is qu estionable as to whether the fallopian tube was actually the primary site in SOIne

390

HANJANI,

PETERSEN,

AND BONNELL

FIG. 3. Undifferentiated sarcomatous component in malignant mixed Mullerian tumor. Spindle cells with varying amounts of cytoplasm are seen in loose bundles. Hematoxylin-eosin, x620.

of these cases, l), an autopsy tional patients did not have

for example, the patient reported by Motta [ 161 (Case 3 from Table case of a 14-year-old girl with pelvic carcinomatosis. Two addireported by Manes and Taylor [141 (Cases 20 and 22 from Table l), hysterectomy to rule out primary uterine malignancy. Another

FALLOPIAN

TUBE

MIXED

MULLERIAN

TUMOR

391

patient reported by Acosta et al. [8] (Case 16 from Table 1) is also questionable since the tube and ovary were both involved with tumor and no definite diagnosis of primary tubal tumor could be made. There is clinical similarity in all of the reported cases with adenocarcinoma of the uterine tube. The age incidence is between 14 and 76 with a mean age of 55 at the time of diagnosis. This is similar to age incidence of adenocarcinoma of fallopian tube and malignant mixed Mullerian tumor of other sites [ 1,2,4,5,17]. In the early stage, the tumor does not produce any clinical symptoms even when it attains large size. The late manifestations are nonspecific such as vaginal spotting, cramping, abdominal pain, and abdominal enlargement. Seldom is a preoperative diagnosis made. In the majority of cases the diagnosis is achieved by microscopic examination. The tumor usually develops intraluminally as a polypoid mass and may produce unilateral or bilateral hydrosalphinx. The routes of metastasis are similar to that of carcinoma of the fallopian tube. It may spread via intraperitoneal surface dissemination, lymphatic dissemination, or blood-borne metastasis. The neighboring structures such as ovaries, contralateral fallopian tube, lymph nodes, bowel, and peritoneal surfaces are the most common metastatic sites. Distant metastasis are rare and may include liver, lung, and bones. Metastatic lesions may contain stromal or epithelial elements, or both. The longest reported survival to date has been 54 months. The 23 patients recorded survived between 1 and 54 months after operation with a mean survival of 17.1 months. The cause of all deaths was metastasis. The present case lived 26 months after operation and responded well to chemotherapy consisting of vincristine, actinomycin D, and cyclophosphamide. The mean age of patients with mixed Mullerian tumor of the endometrium is 5 1 and mean survival was reported to be 8.4 months [ 171. This is similar to the incidence of mixed Mullerian tumors of the fallopian tube. The mean survival for mixed Mullerian tumors of the tube was slightly higher but is not significant due to the small number of reported cases. Therefore, in both the tube and endometrium this tumor occurs at the same mean age and it seems that they have the same biologic behavior and fatal outcome. All patients had partial or complete removal of the tumor including total abdominal hysterectomy and bilateral salpingo-oophorectomy. Radiation was used as a therapeutic agent in nine patients [5-8,13,14,18,19]. One patient lived for 44 years after therapy, and five died within 15 months [6,8,14,18,19]. Three patients survived for 12, 24, and 27 months, respectively, after their cases were reported [5,7,141.

Thirteen patients were treated with surgery alone (see Table 1). Seven of these patients were lost to follow-up [20-261. The remaining six patients had a mean survival rate of 14.7 months [8,13-15,271. One of these patients lived 4+ years without evidence of recurrent disease [ 141. Our patient received a total abdominal hysterectomy and bilateral salpingo-oophorectomy, omentectomy, and removal of all resectable gross tumor followed by chemotherapy. Her response was good and she survived for 26 months. Due to the small number of reported cases with this neoplasm, no definite conclusions regarding the best method of therapy can be reached. Because the

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AND BONNELL

prognosis is generally poor, an aggressive mode of therapy is recommended even though some of the patients reported showed a relatively slow course of disease with late recurrences. The primary therapy is surgery. Malignant mixed Mullerian tumors of the endometrium [28], cervix [29], and ovary have been relatively radioresistant. Also, this seems to be a fact in the management of this tumor arising in the fallopian tube as it has little effect on the natural course of this disease when compared to the mean survival between surgery followed by radiation therapy versus surgery alone. Surgery followed by chemotherapy may have a potential benefit. REFERENCES 1. Gusberg, S. B., and Frick, H. C. (Eds.) Corscaden’s gynecologic cancer, Baltimore, Williams & Wilkins, p. 510, (1970). 2. Green, T. H., Jr., and Scully, R. E. Tumor of the fallopian tube, C/in. O&et. Gynecol. 5, 886, (1%2). 3. Israel, S. L., Crisp, W. E., and Adrian, C. Preoperative diagnosis of primary carcinoma of the fallopian tube, Amer. J. Obstet. Gynecol. 68, 1589, (1954). 4. Jones, V. 0. Primary carcinoma of the uterine tube, Obstet. Gynecol. 26, 122, (1965). 5. Henderson, S. R., Harper, R. C., Salzar, 0. M., and Rudolph, J. H. Primary carcinoma of the fallopian tube, Gynecol. Oncol. 5, 168, (1977). 6. McQueeney, A. J., Carswell, B. L., and Sheehan, W. J. Malignant mixed Mullerian tumor primary in uterine tube. A review of the literature and report of an additional case, Obstet. Gynecol. 23, 388, (1964). 7. Wu, J. P., Tanner, W. S., and Fardal, P. M. Malignant mixed mesodermal tumor of the uterine tube, Obstet. Gynecol. 41, 707, (1973). 8. Acosta, A. A., Kaplan, A. L., and Kaufman, R. H. Mixed Mullerian tumors ofthe oviduct, C&ret. Gynecol. 44, 84, (1974). 9. McFarland, J. Dysontogenetic and mixed tumors of the urogenitol region, Surg. Gynecol. Obstet. 61, 42, (1935). 10. Kempson, R. L., and Bari, W. Uterine sarcoma, classification, diagnosis, and prognosis, Human Pathol. 1, 331, (1970). Il. Norris, H. J., Roth, E., and Taylor, H. B. Mesenchymal tumors of the uterus. II. A clinical pathological study of 31 mixed mesodermal tumors, Obstet. Gynecol. 28, 57, (1966). 12. Norris, H. J., and Taylor, H. B. Mesenchymal tumors of the uterus. III. A clinical and pathological study of 31 carcinosarcomas, Cancer 19, 1459, (1966). 13. Williams, T. J., and Woodruff, J. D. Malignant mixed mesenchymal tumor of the uterine tube. Report of a case, Obstet. Gynecol. 21, 618, (1963). 14. Manes, J. L., and Taylor, H. B. Carcinosarcoma and mixed mullerian tumors of the fallopian tube. Report of 4 cases, Cancer, 38, 1687, (1976). 15. Jain, U. Mixed mesodermal tumor of the fallopian tube. Report of a case and review of literature, M. State

Med.

J. 43, 46, (1977).

16. Motta, G. Contributto alla conoscenza dei tumori misti rari dell’ apperato genitale fimminile (Carcinosarcoma della salpinge), Ann. Obstet. Ginecol. 48, 611, (1926). 17. Sternberg, W. H., Clark, W. H., and Smith, R. C. Malignant mixed mullerian tumor. (mixed mesodermal tumor of the uterus) 1, A study of twenty-one cases, Cancer 7, 704, (1964). 18. Bochner, K. Primary uterine tube malignancy, Obstef. Gyneco/. 18, 767, (1961). 19. Dequerioz, A. C., and Roth, L. M. Malignant mixed mullerian tumor of the fallopian tube, Obstet. Gynecol. 36, 554, (1970). 20. Amann, J. A. Zentralbl. Gynaekol. 33, 1684, (1909). 21. Franque, 0. Carcino-sarko-endotheliuma tubae, Z. Geburtsh. Gynaeko/. 47, 211, (1902). 22. Leuret, J. Epithelioma et sarcome de la trompa uterine, Ann. Anat. Parhol. 10, 1220, (1933). 23. Platz, J. Uber sets weitere falle von primarem tuber carcinom, Arch. Gynaekol. 170,604, (1940).

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24. Laudadio, E. Contributto allo studio dei tumori maligni primitivi della tuba, rarissimo case di neoplasia combinata carcinosarcomatosa, Ann. Obstet. Ginecol. 63, 1017, (1941). 25. Ferrando, M. Su di urn raro case di carcinosarcoma primitivo della salpinge uterina, Miner\u Ginecol. 2, 442, (1950). 26. Cavallero, G., and Rossi, R. Contributo allo studio dei tumori misti malingni della tuba di fallopio (carcinosarcoma), Pathologica 51, 443, (1959). 27. Malnasy, J., and Gaal, M. Primary carcinosarcoma of the fallopian tube, Gynaecologia 156, 203, (1963). 28. Mortel, R., Hess, L. G., Lewis, J. L., and D’Urso, J. R. Mesodermal mixed tumors of the uterine corpus, Obstet. Gynecol. 43, 248, (1974). 29. Abel, M. R., and Ramirez, J. A. Sarcomas and carcinosarcomas of the uterine cervix, Cancer, 31, 1176, (1973).