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Primary transitional cell carcinoma of the fallopian tube associated with primary carcinomas of the ovary and endometrium
GYNECOLOGIC
ONCOLOGY
4, 138-143 (1976)
Primary Transitional Cell Carcinoma of the Fallopian Tube Associated with Primary Carcinomas of the Ovary and Endometrium PRAPHATHOVADHANAKUL, M.D.,’ STEVEN P. NUERENBERGER, M.D.,* PAUL J. RITTER, M.D.,* HERBERT B. TAYLOR, M.D.,* AND DENIS CAVANAGH, M.D.’ ‘Department of Gynecology and Obstetrics and ?he Department of Pathology, St, Louis University
Hospital,
1325 South Grand Boulevard,
St. Louis,
Missouri
63104
Received December 16, 1976 A patient with primary transitional cell carcinoma of the fallopian tube, primary endometrial adenocarcinoma, and primary endometrioid carcinoma of the ovary is reported. The clinical picture was similar to that of adenocarcinoma of the fallopian tube, but the mode of spread was somewhat different and more aggressive. The patient was treated with surgery and a combination of internal and external radiotherapy.
Primary carcinoma of the fallopian tube is the least common malignancy of the female genital tract. Adenocarcinoma is the most common histologic finding. After an extensive review of the English language literature only one example of primary transitional cell carcinoma of the fallopian tube was found [ 11, and only two instances of primary squamous cell carcinoma. This is probably the first patient ever to be reported with a primary transitional cell carcinoma of the fallopian tube associated with primary endometrioid carcinoma of the ovary, and primary adenocarcinoma of the endometrium. A CASE REPORT
The patient is a 51-year-old white woman who was first seen by her private physician in February 1975 with a history of irregular vaginal bleeding and discharge. The patient had been very healthy up to then. She received a fractional curettage, and a biopsy was taken of a small lesion located on the anterior vaginal wall 3-4 cm from the urethral orifice. The original pathologic interpretation was well differentiated endometrial adenocarcinoma and squamous cell carcinoma of the vagina. The cervical curettings showed no evidence of malignant tumor. The patient was then referred to the Gynecologic Oncology Service, St. Louis University Hospital. On admission to this service, pelvic examination revealed normal external genitalia. There was a small indurated area on the anterior wall of the vagina 3-4 cm from the urethra. The cervix was clean. The uterus was irregularly enlarged with a myoma, being about the size of an S-week pregnancy. There was a 5 x 4 cm mass in the right adnexal area. The left adnexa was normal. Address for reprints: Praphat Hovadhanakul, M.D., Department of Gynecology and Obstetrics, St. Louis University Hospital, 1325 South Grand Boulevard, St. Louis, Missouri 63104. 138 Copyright @ 1976 by Academic F’rcss, IIIF. All righrs of rsproducfion in any form reserved.
CELL
CARCINOMA
OF THE
FALLOPIAN
TUBE
139
There were no intrinsic rectal lesions. Pretreatment evaluation was carried out and the reports were as follows: Complete blood count, urinalysis, SMA12, and VDRL were within normal limits. An EKG was normal. Intravenous pyelogram revealed prompt, normal excretion by both kidneys. A barium enema was normal. A diagnosis of carcinoma of the corpus (adenocarcinoma) Stage Ia Grade I and in addition a squamous cell carcinoma of the vagina Stage I was made. The patient was given external cobalt 60 therapy 4000 rads tumor dose to the whole pelvis. This was followed by a radium implant with a Burnette applicator which delivered 8000 rads to the vaginal mucosa in the area of the lesion. On May 16, 1975 the repeat pelvic examination revealed only slight regression of the vaginal lesion. On June 3, 1975 the patient underwent exploratory laparatomy. The upper abdomen was explored. No evidence of liver metastasis was found. The gallbladder, small and large bowel, stomach, kidneys, spleen, and pancreas were normal to palpation, but a nodular mass, 4 x 5 cm, was palpable at the level of the left renal artery. The mass was firm and fixed to the posterior abdominal wall. Frozen sections of this lesion revealed metastatic carcinoma. Exploration of the pelvis revealed dilated, very tortuous fallopian tubes, particularly on the left side. Total hysterectomy with bilateral salpingo-oophorectomy was done. An isolated nodule was removed from the serosa of the urinary bladder. An enlarged lymph node was removed from the left hypogastric region grossly suggestive of metastatic involvement. Another enlarged lymph node was noted in the right hypogastric region, but this lymph node was intimately attached to the wall of the hypogastric artery and external iliac vein and was marked with a silver clip as was the positive lymph node on the paraaortic chain; this was done with a view to subsequent radiotherapy. The postoperative course was uneventful. At the time of this report, the patient is receiving additional external cobalt 60 therapy to give 6000 rads tumor dose to the whole pelvis and 5000 rads to the paraaortic chain. Midway through the additional course of teletherapy the vaginal lesion was noted to have undergone further regression. PATHOLOGIC FINDINGS Gross Observations The uterus was symmetrical, 85 g, and 9 x 5 x 4 cm. The ectocervical mucosa was pink-tan, smooth, and glistening. The endometrium was up to 2 mm thick with focal areas of hemorrhage. Within the anterior myometrial wall there was a firm, whitish, whorled, encapsulated lesion 1.2 cm in maximum dimension. There was dilatation of the left tube proximally. There was a grayish white area with focal necrosis extending distally along the tube for a distance of 5 cm. The left ovary was 4 x 2.5 x 1 cm., blue-gray, smooth, and glistening with some focal areas of hemorrhage. The sectioned surface revealed the presence of a grayishwhite ovarian parenchyma. The right fallopian tube was 8.5 x 4 cm covered by blue-gray, smooth, and glistening serosa.
140
HOVADHANAKUL
ET AL.
Microscopic Description
Sections of the left fallopian tube disclosed a transitional cell carcinoma arising from the tubal epithelium (Fig. 1). The tumor was characterized by poorly differentiated epithelium whose nuclei were perpendicular to the surface, the formation of papillary structures with central fibrovascular stalks (Fig. 2), and a stnking propensity to invade lymphatic channels (Fig. 3). Sections of the endometrium revealed focal, residual, moderately well-differentiated adenocarcinoma (Fig. 4). Sections of the right ovary revealed the presence of an ovarian cyst lined by an endometrioid adenocarcinoma with focal stromal invasion (Fig. 5). Sections of the right tube and the left ovary were histologically unremarkable. Sections of the paraaortic node, the nodule from the bladder serosa, and the vaginal nodule all revealed transitional cell carcinoma, similar to the primary lesion of the left fallopian tube. DISCUSSION
Primary carcinoma of the fallopian tube accounts for approximately 0.5% of all gynecologic malignancies. Extensive reviews of the literature indicate that the most common histologic pattern is papillary adenocarcinoma [4,5]. The early diagnosis of carcinoma of the fallopian tube is even more difficult than the early diagnosis of carcinoma of the ovary. In only a few patients is it diagnosed preoperatively. The most common symptoms are metrorrhagia, bloody discharge, pain, or pressure [S]. Our patient complained of vaginal bleeding, but most likely this was from the primary endometrial carcinoma or possibly from the vaginal
FIG. 1. Transitional cell carcinoma arising from tubal epithelium. H & E stain; x 188.
CELL CARCINOMA
OF THE FALLOPIAN
TUBE
141
FIG. 2. Papillary pattern of the tubal carcinoma with fibrovascular core. H L E stain; x 188 obj.
FIG. 3. Lymphatic permeation by transitional cel1 carcinoma. H & E stain; x300.
142
HOVADHANAKUL
ET AL.
FIG. 4. Residual endometrial adenocarcinoma found in surgical specimen. H & E stain; x75.
FIG. 5. Endometrioid adenocarcinoma arising in right ovary. H. & E slightly enlarged; x 188.
CELL CARCINOMA
OF THE FALLOPIAN
TUBE
143
lesion. The extreme rarity of transitional cell carcinoma, and the presence of two distinctly different primary lesions, made the diagnosis difficult prior to laparotomy. Federman reported a case of primary transitional cell tumor of the uterine adnexa, arising in a paratubal cyst; in retrospect this may have represented a malignant lesion of the fallopian tube or of a paraovarian cyst. Our patient had a definite transitional cell carcinoma arising from the tubal epithelium with extensive lymphatic invasion and metastasis to the vagina, paraaortic lymph nodes, and serosa of the urinary bladder. In one review, 67 of 232 patients were reported to have metastases. The most frequent site of spread was the peritoneum (35 patients). There were 23 patients with some involvement of the ovary, and 11 women had myometrial involvement. The mechanism of spread is by direct extension through the fimbriated end of the tube to involve the peritoneum, or through the isthmic portion of the tube into the uterine cavity. The tubal musculature is rarely invaded, even after peritoneal spread has already taken place. Lymphatic spread is unusual. According to Ross et al. [6] and Meigs [7], 60% of patients with primary carcinoma of the fallopian tube developed vaginal metastases. In our patient the sections of the tube revealed extensive lymphatic permeation, with definite metastasis to the right hypogastric nodes and paraaortic nodes. The bladder serosa and vaginal metastases may have resulted from lymphatic permeation in our patient, although the former lesion was probably due to retrograde venous spread and the latter to peritoneal spread. The prognosis for this patient is poor mainly because of the tubal carcinoma with high paraaortic nodal involvement. The adenocarcinoma in the uterus and the endometnod carcinoma of the right ovary were so small that they were probably removed completely. The persistence of the vaginal metastatic lesion after irradiation treatment also implies a bad prognosis. Postoperative treatment will include chemotherapy. Boronow 181reported a patient with disseminated tubal adenocarcinema which regressed completely with 1-phenylalanine mustard (Alkeran), but only a few instances of remission have been reported. REFERENCES 1. Federman, Q., and Toker, C. Amer. J. Ubsr. Gynecol. 115, 863 (1973). 2. Block, E. Acta Radiol. 28, 49 (1947). 3. Malinak, L. R., Miller, G. V., and Armstrong, J. T. Amer. J. Obst. Gynecol. 95, 1167 (1966). 4. Hu, C. Y., Taymor, M. L., and Hertig, A. T. Amer. J. Ubst. Gynecol. 59, 58 (1950). 5. Sedlis, A. Obst. Gynecol. Surv. 16, 209 (1961). 6. Ross, W. M., Ward, C. V., and Lindsay, C. C. Amer. J. Obst. Gynecoi. 83, 425 (1962). 7. Meigs, J. V. Tumors of the female pelvic organs, Macmillan, New York (1934). 8. Boronow, R. C. Obst. Gynecol. 42, 62 (1973).
ONCOLOGY
4, 138-143 (1976)
Primary Transitional Cell Carcinoma of the Fallopian Tube Associated with Primary Carcinomas of the Ovary and Endometrium PRAPHATHOVADHANAKUL, M.D.,’ STEVEN P. NUERENBERGER, M.D.,* PAUL J. RITTER, M.D.,* HERBERT B. TAYLOR, M.D.,* AND DENIS CAVANAGH, M.D.’ ‘Department of Gynecology and Obstetrics and ?he Department of Pathology, St, Louis University
Hospital,
1325 South Grand Boulevard,
St. Louis,
Missouri
63104
Received December 16, 1976 A patient with primary transitional cell carcinoma of the fallopian tube, primary endometrial adenocarcinoma, and primary endometrioid carcinoma of the ovary is reported. The clinical picture was similar to that of adenocarcinoma of the fallopian tube, but the mode of spread was somewhat different and more aggressive. The patient was treated with surgery and a combination of internal and external radiotherapy.
Primary carcinoma of the fallopian tube is the least common malignancy of the female genital tract. Adenocarcinoma is the most common histologic finding. After an extensive review of the English language literature only one example of primary transitional cell carcinoma of the fallopian tube was found [ 11, and only two instances of primary squamous cell carcinoma. This is probably the first patient ever to be reported with a primary transitional cell carcinoma of the fallopian tube associated with primary endometrioid carcinoma of the ovary, and primary adenocarcinoma of the endometrium. A CASE REPORT
The patient is a 51-year-old white woman who was first seen by her private physician in February 1975 with a history of irregular vaginal bleeding and discharge. The patient had been very healthy up to then. She received a fractional curettage, and a biopsy was taken of a small lesion located on the anterior vaginal wall 3-4 cm from the urethral orifice. The original pathologic interpretation was well differentiated endometrial adenocarcinoma and squamous cell carcinoma of the vagina. The cervical curettings showed no evidence of malignant tumor. The patient was then referred to the Gynecologic Oncology Service, St. Louis University Hospital. On admission to this service, pelvic examination revealed normal external genitalia. There was a small indurated area on the anterior wall of the vagina 3-4 cm from the urethra. The cervix was clean. The uterus was irregularly enlarged with a myoma, being about the size of an S-week pregnancy. There was a 5 x 4 cm mass in the right adnexal area. The left adnexa was normal. Address for reprints: Praphat Hovadhanakul, M.D., Department of Gynecology and Obstetrics, St. Louis University Hospital, 1325 South Grand Boulevard, St. Louis, Missouri 63104. 138 Copyright @ 1976 by Academic F’rcss, IIIF. All righrs of rsproducfion in any form reserved.
CELL
CARCINOMA
OF THE
FALLOPIAN
TUBE
139
There were no intrinsic rectal lesions. Pretreatment evaluation was carried out and the reports were as follows: Complete blood count, urinalysis, SMA12, and VDRL were within normal limits. An EKG was normal. Intravenous pyelogram revealed prompt, normal excretion by both kidneys. A barium enema was normal. A diagnosis of carcinoma of the corpus (adenocarcinoma) Stage Ia Grade I and in addition a squamous cell carcinoma of the vagina Stage I was made. The patient was given external cobalt 60 therapy 4000 rads tumor dose to the whole pelvis. This was followed by a radium implant with a Burnette applicator which delivered 8000 rads to the vaginal mucosa in the area of the lesion. On May 16, 1975 the repeat pelvic examination revealed only slight regression of the vaginal lesion. On June 3, 1975 the patient underwent exploratory laparatomy. The upper abdomen was explored. No evidence of liver metastasis was found. The gallbladder, small and large bowel, stomach, kidneys, spleen, and pancreas were normal to palpation, but a nodular mass, 4 x 5 cm, was palpable at the level of the left renal artery. The mass was firm and fixed to the posterior abdominal wall. Frozen sections of this lesion revealed metastatic carcinoma. Exploration of the pelvis revealed dilated, very tortuous fallopian tubes, particularly on the left side. Total hysterectomy with bilateral salpingo-oophorectomy was done. An isolated nodule was removed from the serosa of the urinary bladder. An enlarged lymph node was removed from the left hypogastric region grossly suggestive of metastatic involvement. Another enlarged lymph node was noted in the right hypogastric region, but this lymph node was intimately attached to the wall of the hypogastric artery and external iliac vein and was marked with a silver clip as was the positive lymph node on the paraaortic chain; this was done with a view to subsequent radiotherapy. The postoperative course was uneventful. At the time of this report, the patient is receiving additional external cobalt 60 therapy to give 6000 rads tumor dose to the whole pelvis and 5000 rads to the paraaortic chain. Midway through the additional course of teletherapy the vaginal lesion was noted to have undergone further regression. PATHOLOGIC FINDINGS Gross Observations The uterus was symmetrical, 85 g, and 9 x 5 x 4 cm. The ectocervical mucosa was pink-tan, smooth, and glistening. The endometrium was up to 2 mm thick with focal areas of hemorrhage. Within the anterior myometrial wall there was a firm, whitish, whorled, encapsulated lesion 1.2 cm in maximum dimension. There was dilatation of the left tube proximally. There was a grayish white area with focal necrosis extending distally along the tube for a distance of 5 cm. The left ovary was 4 x 2.5 x 1 cm., blue-gray, smooth, and glistening with some focal areas of hemorrhage. The sectioned surface revealed the presence of a grayishwhite ovarian parenchyma. The right fallopian tube was 8.5 x 4 cm covered by blue-gray, smooth, and glistening serosa.
140
HOVADHANAKUL
ET AL.
Microscopic Description
Sections of the left fallopian tube disclosed a transitional cell carcinoma arising from the tubal epithelium (Fig. 1). The tumor was characterized by poorly differentiated epithelium whose nuclei were perpendicular to the surface, the formation of papillary structures with central fibrovascular stalks (Fig. 2), and a stnking propensity to invade lymphatic channels (Fig. 3). Sections of the endometrium revealed focal, residual, moderately well-differentiated adenocarcinoma (Fig. 4). Sections of the right ovary revealed the presence of an ovarian cyst lined by an endometrioid adenocarcinoma with focal stromal invasion (Fig. 5). Sections of the right tube and the left ovary were histologically unremarkable. Sections of the paraaortic node, the nodule from the bladder serosa, and the vaginal nodule all revealed transitional cell carcinoma, similar to the primary lesion of the left fallopian tube. DISCUSSION
Primary carcinoma of the fallopian tube accounts for approximately 0.5% of all gynecologic malignancies. Extensive reviews of the literature indicate that the most common histologic pattern is papillary adenocarcinoma [4,5]. The early diagnosis of carcinoma of the fallopian tube is even more difficult than the early diagnosis of carcinoma of the ovary. In only a few patients is it diagnosed preoperatively. The most common symptoms are metrorrhagia, bloody discharge, pain, or pressure [S]. Our patient complained of vaginal bleeding, but most likely this was from the primary endometrial carcinoma or possibly from the vaginal
FIG. 1. Transitional cell carcinoma arising from tubal epithelium. H & E stain; x 188.
CELL CARCINOMA
OF THE FALLOPIAN
TUBE
141
FIG. 2. Papillary pattern of the tubal carcinoma with fibrovascular core. H L E stain; x 188 obj.
FIG. 3. Lymphatic permeation by transitional cel1 carcinoma. H & E stain; x300.
142
HOVADHANAKUL
ET AL.
FIG. 4. Residual endometrial adenocarcinoma found in surgical specimen. H & E stain; x75.
FIG. 5. Endometrioid adenocarcinoma arising in right ovary. H. & E slightly enlarged; x 188.
CELL CARCINOMA
OF THE FALLOPIAN
TUBE
143
lesion. The extreme rarity of transitional cell carcinoma, and the presence of two distinctly different primary lesions, made the diagnosis difficult prior to laparotomy. Federman reported a case of primary transitional cell tumor of the uterine adnexa, arising in a paratubal cyst; in retrospect this may have represented a malignant lesion of the fallopian tube or of a paraovarian cyst. Our patient had a definite transitional cell carcinoma arising from the tubal epithelium with extensive lymphatic invasion and metastasis to the vagina, paraaortic lymph nodes, and serosa of the urinary bladder. In one review, 67 of 232 patients were reported to have metastases. The most frequent site of spread was the peritoneum (35 patients). There were 23 patients with some involvement of the ovary, and 11 women had myometrial involvement. The mechanism of spread is by direct extension through the fimbriated end of the tube to involve the peritoneum, or through the isthmic portion of the tube into the uterine cavity. The tubal musculature is rarely invaded, even after peritoneal spread has already taken place. Lymphatic spread is unusual. According to Ross et al. [6] and Meigs [7], 60% of patients with primary carcinoma of the fallopian tube developed vaginal metastases. In our patient the sections of the tube revealed extensive lymphatic permeation, with definite metastasis to the right hypogastric nodes and paraaortic nodes. The bladder serosa and vaginal metastases may have resulted from lymphatic permeation in our patient, although the former lesion was probably due to retrograde venous spread and the latter to peritoneal spread. The prognosis for this patient is poor mainly because of the tubal carcinoma with high paraaortic nodal involvement. The adenocarcinoma in the uterus and the endometnod carcinoma of the right ovary were so small that they were probably removed completely. The persistence of the vaginal metastatic lesion after irradiation treatment also implies a bad prognosis. Postoperative treatment will include chemotherapy. Boronow 181reported a patient with disseminated tubal adenocarcinema which regressed completely with 1-phenylalanine mustard (Alkeran), but only a few instances of remission have been reported. REFERENCES 1. Federman, Q., and Toker, C. Amer. J. Ubsr. Gynecol. 115, 863 (1973). 2. Block, E. Acta Radiol. 28, 49 (1947). 3. Malinak, L. R., Miller, G. V., and Armstrong, J. T. Amer. J. Obst. Gynecol. 95, 1167 (1966). 4. Hu, C. Y., Taymor, M. L., and Hertig, A. T. Amer. J. Ubst. Gynecol. 59, 58 (1950). 5. Sedlis, A. Obst. Gynecol. Surv. 16, 209 (1961). 6. Ross, W. M., Ward, C. V., and Lindsay, C. C. Amer. J. Obst. Gynecoi. 83, 425 (1962). 7. Meigs, J. V. Tumors of the female pelvic organs, Macmillan, New York (1934). 8. Boronow, R. C. Obst. Gynecol. 42, 62 (1973).