Path. Res. Pract. 186, 358-364 (1990)
Papillary Tumour of the Vagina Resembling Transitional Cell Carcinoma F. Fetissof Laboratoire d'Anatomie pathologique, Faculte de Medecine, Tours, France
O. Haillot and Y. Lanson Service d'Urologie, H6pital Bretonneau, Tours, France
B. Arbeille Unite de Microscopie electronique, Faculte de Medecine, Tours, France
J. Lansac Service de Gynecologie, H6pital Bretonneau, Tours, France
SUMMARY A case of a peculiar papillary neoplasia of the vagina resembling a urothelial tumour is presented. Four vaginal tumours were excised from a 76-year-old woman. Five years before this patient had undergone a uretero-nephrectomy for a non-invasive papillary transitional cell carcinoma of the renal pelvis. The four vaginal tumours demonstrated gross and microscopic similarities to low-grade papillary transitional cell carcinoma of the urinary tract. This observation indicates that multicentric, non-invasive, papillary tumours may affect the whole uro-genital area. The vaginal wall was not overlaid by a normal squamous epithelium, but by a peculiar "transitional-like" epithelium. Variegated endocrine cells were documented within this lining, using immunohistochemical and ultrastructural techniques. The eventuality of a histogenetic link between the tumour and the adjacent epithelial lining remains unresolved.
Introduction Several subtypes of papillary cervicovaginal neoplasia have been described 10. Such lesions include condyloma, verrucous carcinoma, and papillary squamous cell carcinoma. On the other hand, certain cervicovaginal epithelia share some features of the transitional cell epithelium of urinary tract with regard to their morphological appearance and to the nature of their endocrine cell components? Interestingly, Brenner tumours of the vagina have been 0344-0338/90/0186-0358$3.50/0
reported4• However, to our knowledge, true primary papillary transitional cell carcinomas resembling those of the urinary tract have not hitherto been observed in the cervix and vagina. We report a case of multifocal, papillary, vaginal tumours showing strong resemblance to urothelial tumours. Light microscopic, immunohistochemical and ultrastructural features of the adjacent vaginal mucosa have been documented. © 1990 by Gustav Fischer Verlag, Stuttgart
Papillary Tumour of Vagina . 359
Material and Methods Four vaginal tumours and four fragments of vaginal mucosa formed the basis of this report. All tissue samples were fixed in aqueous Bouin's fluid, embedded in paraffin and stained with hematoxylin and eosin. GrimeIius method was used to detect argyrophilic cells.
a
:
Fig. 1 a-c. Vaginal tumour. - a: Low-power microphotograph illustrating the papillary configuration with fibrovascular cores (HES X 10). - b: Higher magnification of the field encircled on (a) Papillae are covered by a stratified transitional-type epithelium. (HES x 50). - c: Higher magnification of the field encircled on (b) showing details of this epithelial lining (HES x 120) (a), (b) and (c) demonstrate morphological similarities with urothelial tumour or transitional epithelium.
Immunohistochemical procedures were performed on deparaffinized sections. These techniques employed rabbit polyclonal antisera to calcitonin, gastrin, glucagon, neuron-specific enolase (NSE), human pancreatic polypeptide, serotonin and somatostatin, and mouse monoclonal antibodies to bombesin, free asubunit of human chorionic gonadotropin (a-hCG), chromogranin A. Anti-calcitonin, gastrin, glucagon, pancreatic polypeptide,
360 . F. Fetissof et al. serotonin and somatostatin immune sera were kindly furnished by M. P. Dubois (Station de Physiologie de la Reproduction, Institut National de la Recherche Agronomique, F-37380 Nouzilly, France). Monoclonal antibody against a-hCG (AHT 20) was a generous gift from D. Bellet (Unite d'Immunochimie, Institut Gustave Roussy, F-94805 Villeiuif, France). Antibombesin and antichromogranin antibodies were purchased from Hybritech Laboratory (Institut de Pathologie, CHU, B.23, 4000 Sart-Tilman, Liege I, Belgium) and anti NSE immune serum from Dakopatts. The peroxidase-antiperoxidase (PAP) procedure was used employing rabbit polyclonal immune sera. A three-step indirect immuno-peroxidase procedure (primary antibody; peroxidase-conjugated rabbit anti-mouse immunoglobulin; peroxidase-conjugated swine anti-rabbit immunoglobulin) was employed with monoclonal antibodies. Four fragments of grossly normal appearing vaginal mucosa were fixed immediately in a mixture of 4 % formaldehyde and 1% glutaraldehyde in phosphate buffer for ultrastructural analysis. One specimen came from the lower third, 2 others from the middle third (laterally right and left) and the last from the upper third of the vaginal wall.
throughout its thickness, showing no evidence of progressive squamoid transformation. (Fig. 1b, c). The Grimelius procedure and the immunohistochemical techniques did not reveal any argyrophilic or endocrine cells in these tumours. The four specimens of grossly normal appearing vaginal mucosa were all overlaid by a similar lining (Fig. 2). Morphologically, this lining is not uncommon in a postmenopausal woman. It did not correspond either to a typical stratified squamous epithelium or to a typical urothelium. It was rather ambiguous. The lower layers were composed of basaloid cells, whereas the overlying elements were poorly glycogenated and rather elongated. The superficial layers displayed a tendency to differentiate into squamous cells. A salient feature was the presence of long rete pegs composed of basaloid cells. Some of these cells had ovoid coffee-bean grooved nuclei. This peculiar lining might be regarded as a variety of basal cell hyperplasia. In places, this lining showed a gradual transformation into a fully mature squamous epithelium.
Results
Clinical history In 1969, at the age of 57 years, the patient underwent a hysterectomy with bilateral salpingo-oophorectomy for a conventional endometrial adenocarcinoma. In 1983, at the age of 71 years, a right ureteronephrectomy was performed for a non-invasive papillary transitional cell carcinoma of the renal pelvis. In 1987 and 1988, 4 papillary tumours were successively excised from the vagina. During the last excisional biopsy, 4 fragments of grossly normal appearing vaginal mucosa were removed for routine and electron microscopic examination. Up to now, no recurrences of the endometrial and pelvic carcinomas have developed. Iterative urinary bladder cystoscopies and biopsies have never shown any abnormalities.
" 4' ....
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;
,
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• t
,.
.-
"
I
~
~
l"~.
.
~
.
'I •
,
~:
k
'to:!'"
,
.
..
.. '\
'," ~~Qo ,
•
Microscopic observations The four vaginal tumours had the same architectural growth pattern and microscopic appearance. These features, illustrated in the low-power microphotograph (Fig. 1a), were strongly analogous to those of low-grade (grade I) papillary transitional cell carcinomas of the urinary tract. The resected specimen had a finely fronted pattern with delicate papillary processes. No invasive component was present beneath the papillary excrescences. Papillae were made of 7 to 12 layers of stratified transitional cells. The lining was relatively homogeneous
•
.'
Gross observations The four vaginal tumours had a similar gross appearance. They were exophytic and showed a papillary configuration strongly reminiscent of urothelial cell carcinomas. Each lesion measured about 0.5 cm in diameter. They were all implanted laterally in the upper third of the vagina. The remaining vaginal mucosa had a normal gross appearance and did not resemble bladder mucosa.
#
(
~.
I
•
~
•
.,
• 'J .
.. , , I
• .....
~
.. ...
Fig. 2. Vaginal epithelium. General histological appearance on routine stained preparation. Morphologically this type of lining is not uncommon in a postmenopausal woman. Note the prominent rete pegs composed of basaloid cells (HES x 110).
Papillary Tumour of Vagina· 361
No sign of dysplasia was present. Koilocytotic changes, typical of papilloma virus infection, were not discerned. This vaginal lining showed no gradual transition with the well-demarcated papillary carcinomas. The peculiar epithelium harbored endocrine cells. These cells were essentially confined to the lower "basaloid" layers. They were particularly concentrated within the rete pegs where they were often grouped in aggregates (Fig. 3). The Grimelius procedure revealed an abundance of argyrophilic cells with long cytoplasmic processes. Immunohistochemical techniques demonstrated chromogranin, NSE, serotonin and bombesin immunoreactive cells. All other immune sera gave negative results. Serotonin cells outnumbered by far bombesin elements. True foci of stratified squamous epithelium were devoid of endocrine cells. Ultrastructural analysis of grossly unremarkable vaginal mucosa confirmed the presence of endocrine cells. These cells showed the classic morphological features of endocrine cells. They contained neurosecretory-type granules,
Fig. 4. Vaginal epithelium. Electron microscopic examination identifies a granulate endocrine cell (arrow) at the base of the lining (x 4450).
Fig. 3. Vaginal epithelium. Endocrine argyrophilic cells are easily found through this type of lining. These cells are disposed either singly through the basal layer or grouped in aggregate (arrow) within the root of a long rete peg (Grimelius X 140).
at times located toward their basal poles. Endocrine cells were found throughout the basal layer of the epithelium (Fig. 4) as well as among basaloid cells of rete pegs (Fig. 5). According to the morphology of neurosecretory granules, two broad types of endocrine cells could be delineated (Fig. 6). Some cells possessed small, round granules of rather uniform shape and size with diameters ranging from 100 to 150 nm. They contained a central dense core surrounded by a narrow lucent halo. In other cells, the
362 . F. Fetissof et al.
granules were more pleomorphic and larger with diameters ranging from 150 to 200 nm. These granules were round, ovoid, angular, elongated or bean-shaped. They consisted of a central or eccentric dense core surrounded by a large poorly osmiophilic halo. In addition, some sparsely granulated endocrine cells were also encountered. Endocrine cells could be elongated with many transverse sections of granulated cytoplasmic processes sandwiched between adjacent cells. No nerve endings were seen in close contact with endocrine cells. Discussion The spectrum of papillary cervicovaginallesions encompasses several varieties of neoplasia. It includes condylo-
rna, squamous papilloma, verrucous carcinoma and papillary squamous cell carcinoma (PSCC). Only papillary squamous cell carcinoma bears some superficial resemblance to urothelial carcinoma. However, according to the report by Randall 10 PSCC does not seem to square exactly with papillary transitional cell carcinoma. PSCC seems rather to correspond to a papillary variant of ordinary squamous cell carcinoma with regard to the clinical behaviour and microscopic appearance. However, at this point, the exact degree of homology connecting PSCC to urothelial-derived tumours remains to be elucidated. Endocrine cells such as serotonin-, calcitonin-, glycoprotein-hormones a-chain-, somatostatin-, bombesin- and TSH-like-immunoreactive cells are normal constituents of all cloacally derived tissues 1,5,8. Transitional epithelium from urethra, urinary bladder, anal transitional zone, and
Fig. 5. Vaginal epithelium. Electron micrograph of a transverse section of rete peg. Note the endocrine cell containing large granules (arrow). In addition, this field contains several small
endocrine cell processes (curved ar-
rows) admixed among basaloid cells (x 2400).
Papillary Tumour of Vagina· 363
Bartholin's glands are particularly well-endowed with these endocrine cells. Again, Brenner tumours which reproduce true urothelium harbor the same endocrine elements2, 6. In contrast, endocrine cells are lacking in low-grade papillary transitional cell carcinomas of the urinary tract 6• As a matter of interest, bronchiolar and bronchial mucosa contains a very similar endocrine cell population3 • Therefore, the similarity of the endocrine cell component from all these non-squamous, "intermediatetype", epithelia (transitional, pseudostratified columnar) must be stressed. In a previous work? it was found that certain varieties of ectocervical and vaginal epithelia bear similarities to these "intermediate-type" epithelia with regard to their morphological appearance and to the nature of their endocrine cell component. The term "transitional-like" was used to refer to these cervicovaginal non-squamous epithelia containing endocrine cells. This kind of lining is usually considered as immature squamous cell metaplasia or basal cell hyperplasia. It
Fig. 6 a-b. Vaginal epithelium. Higher magnification showing the two main types of endocrine cells. - a: small, round granules; b: more pleomorphic and larger granules (x 9000). Insets: detail of both types of neurosecretory granules (x 30000).
contains serotonin and calcitonin cells, in contrast to normal stratified squamous epithelium which is virtually devoid of endocrine cells. Despite the similarities between this type of cervicovaginallining and that of urothelium, distinct differences exist with respect to their cytokeratin expression profiles, reflecting the differences in their tendency to form terminally differentiated cells ("umbrella cells"). Urothelial tumours have a propensity to be associated with tumours elsewhere in the urothelium. Multicentric, independent primary carcinomas have been amply documented. They may occur synchronously or metachronously. These multicentric urothelial tumours always involve the urinary tract. The only associated gynecological manifestations were Paget's disease of the vulva 9 or ovarian tumours ll . The vaginal tumours reported here were grossly and microscopically very close, if not similar to low-grade papillary transitional cell carcinoma of the urinary tract.
364 . F. Fetissof et al.
This warrants their segregation from other papillary cervicovaginallesions. Unfortunately, no fresh samples of tumour have been available. Therefore, it was not possible to determine whether these papillary tumours retained the intrinsic cytokeratin pattern of "authentic" urothelial differentiation. The past history of the patient showed that multifocal, non-invasive, papillary tumours may affect the whole urogenital area. On the other hand, the vaginal wall was not covered with a normal stratified squamous epithelium. This lining fulfilled all the criteria of a "transitional-like" epithelium as previously described 7• It bore some resemblance to other "intermediate-type" epithelia and harbored variegated endocrine cells. The eventuality of a histogenetic link between the tumour and this contiguous, peculiar epithelial lining is a debated point which remains, at this time, unresolved. Acknowledgements The authors are indebted to Miss F. Colliou for the secretarial work, the electron microscopy department, and Mr J. C. Allard and Miss C. Tissier for technical assistance and help with the illustrations.
References I Abrahamsson PA, Wadstrom LB, Alumets J, Falkmer S, Grimelius L (1986) Peptide-hormone- and serotonin-immunoreactive cells in normal and hyperplastic prostate glands. Path Res Pract 181: 675-683
2 Aguirre P, Scully RE, Wolfe HJ, DeLellis RA (1986) Argyrophil cells in Brenner tumors: histochemical and immunohistochemical analysis. lnt J Gynecol Pathol 5: 223-234 3 Becker KL, Monaghan KG, Silva OL (1980) lmmunocytochemical localization of calcitonin in Kulchitsky cells of human lung. Arch Pathol Lab Med 104: 196-198 4 Chen KTK (1981) Brenner tumor of the vagina. Diag Gynecol Obstet 3: 255-258 5 di Sant-Agnese PA, de Mesy Jensen KL (1987) Neuroendocrine differentiation in prostatic carcinoma. Hum Pathol 18: 849-856 6 Fetissof F, Dubois MP, Heitz PU, Lansac J, Arbeille-Brassart B, Jobard P (1986) Endocrine cells in the female genital tract. Review. lnt J Gynecol Pathol 5: 75-87 7 Fetissof F, Arbeille B, Boivin F, Sam-Giao M, Henrion C, Lansac J (1987) Endocrine cells in ectocervical epithelium. An immunohistochemical and ultrastructural analysis. Virchows Arch A 411: 293-298 8 Fetissof F, Arbeille B, Guilloteau D, Lanson Y (1987) Glycoprotein hormone a-chain-immunoreactive endocrine cells in prostate and cloacal-derived tissues. Arch Pathol Lab Med 111: 836-840 9 Fukutani K, Kawabe K, Niijima T, Oohara K (1987) Transitional cell carcinoma of the urinary tract associated with vulvar Paget's disease: a report of two cases. Urol lnt 42: 71-73 10 Randall, ME, Andersen WA, Mills SE, Kim J-AC (1986) Papillary squamous cell carcinoma of the uterine cervix: A clinicopathologic study of nine cases. lnt J Gynecol Pathol 5: 1-10 II Young RH, Scully RE (1988) Urothelial and ovarian carcinomas of identical cell types: problems in interpretation. A report of three cases and review of the literature. lnt J Gynecol Pathol 7: 197-211
Received September 21, 1989 . Accepted in revised form November 27, 1989
Key Words: Vagina - Transitional cell carcinoma - Papillary carcinoma - Endocrine cells Dr. F. Fetissof, Laboratoire d'Anatomie pathologique, Faculte de Medecine, 2 bis Boulevard Tonnelle, F-37032 Tours, France
Papillary Tumour of the Vagina Resembling Transitional Cell Carcinoma F. Fetissof Laboratoire d'Anatomie pathologique, Faculte de Medecine, Tours, France
O. Haillot and Y. Lanson Service d'Urologie, H6pital Bretonneau, Tours, France
B. Arbeille Unite de Microscopie electronique, Faculte de Medecine, Tours, France
J. Lansac Service de Gynecologie, H6pital Bretonneau, Tours, France
SUMMARY A case of a peculiar papillary neoplasia of the vagina resembling a urothelial tumour is presented. Four vaginal tumours were excised from a 76-year-old woman. Five years before this patient had undergone a uretero-nephrectomy for a non-invasive papillary transitional cell carcinoma of the renal pelvis. The four vaginal tumours demonstrated gross and microscopic similarities to low-grade papillary transitional cell carcinoma of the urinary tract. This observation indicates that multicentric, non-invasive, papillary tumours may affect the whole uro-genital area. The vaginal wall was not overlaid by a normal squamous epithelium, but by a peculiar "transitional-like" epithelium. Variegated endocrine cells were documented within this lining, using immunohistochemical and ultrastructural techniques. The eventuality of a histogenetic link between the tumour and the adjacent epithelial lining remains unresolved.
Introduction Several subtypes of papillary cervicovaginal neoplasia have been described 10. Such lesions include condyloma, verrucous carcinoma, and papillary squamous cell carcinoma. On the other hand, certain cervicovaginal epithelia share some features of the transitional cell epithelium of urinary tract with regard to their morphological appearance and to the nature of their endocrine cell components? Interestingly, Brenner tumours of the vagina have been 0344-0338/90/0186-0358$3.50/0
reported4• However, to our knowledge, true primary papillary transitional cell carcinomas resembling those of the urinary tract have not hitherto been observed in the cervix and vagina. We report a case of multifocal, papillary, vaginal tumours showing strong resemblance to urothelial tumours. Light microscopic, immunohistochemical and ultrastructural features of the adjacent vaginal mucosa have been documented. © 1990 by Gustav Fischer Verlag, Stuttgart
Papillary Tumour of Vagina . 359
Material and Methods Four vaginal tumours and four fragments of vaginal mucosa formed the basis of this report. All tissue samples were fixed in aqueous Bouin's fluid, embedded in paraffin and stained with hematoxylin and eosin. GrimeIius method was used to detect argyrophilic cells.
a
:
Fig. 1 a-c. Vaginal tumour. - a: Low-power microphotograph illustrating the papillary configuration with fibrovascular cores (HES X 10). - b: Higher magnification of the field encircled on (a) Papillae are covered by a stratified transitional-type epithelium. (HES x 50). - c: Higher magnification of the field encircled on (b) showing details of this epithelial lining (HES x 120) (a), (b) and (c) demonstrate morphological similarities with urothelial tumour or transitional epithelium.
Immunohistochemical procedures were performed on deparaffinized sections. These techniques employed rabbit polyclonal antisera to calcitonin, gastrin, glucagon, neuron-specific enolase (NSE), human pancreatic polypeptide, serotonin and somatostatin, and mouse monoclonal antibodies to bombesin, free asubunit of human chorionic gonadotropin (a-hCG), chromogranin A. Anti-calcitonin, gastrin, glucagon, pancreatic polypeptide,
360 . F. Fetissof et al. serotonin and somatostatin immune sera were kindly furnished by M. P. Dubois (Station de Physiologie de la Reproduction, Institut National de la Recherche Agronomique, F-37380 Nouzilly, France). Monoclonal antibody against a-hCG (AHT 20) was a generous gift from D. Bellet (Unite d'Immunochimie, Institut Gustave Roussy, F-94805 Villeiuif, France). Antibombesin and antichromogranin antibodies were purchased from Hybritech Laboratory (Institut de Pathologie, CHU, B.23, 4000 Sart-Tilman, Liege I, Belgium) and anti NSE immune serum from Dakopatts. The peroxidase-antiperoxidase (PAP) procedure was used employing rabbit polyclonal immune sera. A three-step indirect immuno-peroxidase procedure (primary antibody; peroxidase-conjugated rabbit anti-mouse immunoglobulin; peroxidase-conjugated swine anti-rabbit immunoglobulin) was employed with monoclonal antibodies. Four fragments of grossly normal appearing vaginal mucosa were fixed immediately in a mixture of 4 % formaldehyde and 1% glutaraldehyde in phosphate buffer for ultrastructural analysis. One specimen came from the lower third, 2 others from the middle third (laterally right and left) and the last from the upper third of the vaginal wall.
throughout its thickness, showing no evidence of progressive squamoid transformation. (Fig. 1b, c). The Grimelius procedure and the immunohistochemical techniques did not reveal any argyrophilic or endocrine cells in these tumours. The four specimens of grossly normal appearing vaginal mucosa were all overlaid by a similar lining (Fig. 2). Morphologically, this lining is not uncommon in a postmenopausal woman. It did not correspond either to a typical stratified squamous epithelium or to a typical urothelium. It was rather ambiguous. The lower layers were composed of basaloid cells, whereas the overlying elements were poorly glycogenated and rather elongated. The superficial layers displayed a tendency to differentiate into squamous cells. A salient feature was the presence of long rete pegs composed of basaloid cells. Some of these cells had ovoid coffee-bean grooved nuclei. This peculiar lining might be regarded as a variety of basal cell hyperplasia. In places, this lining showed a gradual transformation into a fully mature squamous epithelium.
Results
Clinical history In 1969, at the age of 57 years, the patient underwent a hysterectomy with bilateral salpingo-oophorectomy for a conventional endometrial adenocarcinoma. In 1983, at the age of 71 years, a right ureteronephrectomy was performed for a non-invasive papillary transitional cell carcinoma of the renal pelvis. In 1987 and 1988, 4 papillary tumours were successively excised from the vagina. During the last excisional biopsy, 4 fragments of grossly normal appearing vaginal mucosa were removed for routine and electron microscopic examination. Up to now, no recurrences of the endometrial and pelvic carcinomas have developed. Iterative urinary bladder cystoscopies and biopsies have never shown any abnormalities.
" 4' ....
••
,.
. .. ~
;
,
'.,;
• t
,.
.-
"
I
~
~
l"~.
.
~
.
'I •
,
~:
k
'to:!'"
,
.
..
.. '\
'," ~~Qo ,
•
Microscopic observations The four vaginal tumours had the same architectural growth pattern and microscopic appearance. These features, illustrated in the low-power microphotograph (Fig. 1a), were strongly analogous to those of low-grade (grade I) papillary transitional cell carcinomas of the urinary tract. The resected specimen had a finely fronted pattern with delicate papillary processes. No invasive component was present beneath the papillary excrescences. Papillae were made of 7 to 12 layers of stratified transitional cells. The lining was relatively homogeneous
•
.'
Gross observations The four vaginal tumours had a similar gross appearance. They were exophytic and showed a papillary configuration strongly reminiscent of urothelial cell carcinomas. Each lesion measured about 0.5 cm in diameter. They were all implanted laterally in the upper third of the vagina. The remaining vaginal mucosa had a normal gross appearance and did not resemble bladder mucosa.
#
(
~.
I
•
~
•
.,
• 'J .
.. , , I
• .....
~
.. ...
Fig. 2. Vaginal epithelium. General histological appearance on routine stained preparation. Morphologically this type of lining is not uncommon in a postmenopausal woman. Note the prominent rete pegs composed of basaloid cells (HES x 110).
Papillary Tumour of Vagina· 361
No sign of dysplasia was present. Koilocytotic changes, typical of papilloma virus infection, were not discerned. This vaginal lining showed no gradual transition with the well-demarcated papillary carcinomas. The peculiar epithelium harbored endocrine cells. These cells were essentially confined to the lower "basaloid" layers. They were particularly concentrated within the rete pegs where they were often grouped in aggregates (Fig. 3). The Grimelius procedure revealed an abundance of argyrophilic cells with long cytoplasmic processes. Immunohistochemical techniques demonstrated chromogranin, NSE, serotonin and bombesin immunoreactive cells. All other immune sera gave negative results. Serotonin cells outnumbered by far bombesin elements. True foci of stratified squamous epithelium were devoid of endocrine cells. Ultrastructural analysis of grossly unremarkable vaginal mucosa confirmed the presence of endocrine cells. These cells showed the classic morphological features of endocrine cells. They contained neurosecretory-type granules,
Fig. 4. Vaginal epithelium. Electron microscopic examination identifies a granulate endocrine cell (arrow) at the base of the lining (x 4450).
Fig. 3. Vaginal epithelium. Endocrine argyrophilic cells are easily found through this type of lining. These cells are disposed either singly through the basal layer or grouped in aggregate (arrow) within the root of a long rete peg (Grimelius X 140).
at times located toward their basal poles. Endocrine cells were found throughout the basal layer of the epithelium (Fig. 4) as well as among basaloid cells of rete pegs (Fig. 5). According to the morphology of neurosecretory granules, two broad types of endocrine cells could be delineated (Fig. 6). Some cells possessed small, round granules of rather uniform shape and size with diameters ranging from 100 to 150 nm. They contained a central dense core surrounded by a narrow lucent halo. In other cells, the
362 . F. Fetissof et al.
granules were more pleomorphic and larger with diameters ranging from 150 to 200 nm. These granules were round, ovoid, angular, elongated or bean-shaped. They consisted of a central or eccentric dense core surrounded by a large poorly osmiophilic halo. In addition, some sparsely granulated endocrine cells were also encountered. Endocrine cells could be elongated with many transverse sections of granulated cytoplasmic processes sandwiched between adjacent cells. No nerve endings were seen in close contact with endocrine cells. Discussion The spectrum of papillary cervicovaginallesions encompasses several varieties of neoplasia. It includes condylo-
rna, squamous papilloma, verrucous carcinoma and papillary squamous cell carcinoma (PSCC). Only papillary squamous cell carcinoma bears some superficial resemblance to urothelial carcinoma. However, according to the report by Randall 10 PSCC does not seem to square exactly with papillary transitional cell carcinoma. PSCC seems rather to correspond to a papillary variant of ordinary squamous cell carcinoma with regard to the clinical behaviour and microscopic appearance. However, at this point, the exact degree of homology connecting PSCC to urothelial-derived tumours remains to be elucidated. Endocrine cells such as serotonin-, calcitonin-, glycoprotein-hormones a-chain-, somatostatin-, bombesin- and TSH-like-immunoreactive cells are normal constituents of all cloacally derived tissues 1,5,8. Transitional epithelium from urethra, urinary bladder, anal transitional zone, and
Fig. 5. Vaginal epithelium. Electron micrograph of a transverse section of rete peg. Note the endocrine cell containing large granules (arrow). In addition, this field contains several small
endocrine cell processes (curved ar-
rows) admixed among basaloid cells (x 2400).
Papillary Tumour of Vagina· 363
Bartholin's glands are particularly well-endowed with these endocrine cells. Again, Brenner tumours which reproduce true urothelium harbor the same endocrine elements2, 6. In contrast, endocrine cells are lacking in low-grade papillary transitional cell carcinomas of the urinary tract 6• As a matter of interest, bronchiolar and bronchial mucosa contains a very similar endocrine cell population3 • Therefore, the similarity of the endocrine cell component from all these non-squamous, "intermediatetype", epithelia (transitional, pseudostratified columnar) must be stressed. In a previous work? it was found that certain varieties of ectocervical and vaginal epithelia bear similarities to these "intermediate-type" epithelia with regard to their morphological appearance and to the nature of their endocrine cell component. The term "transitional-like" was used to refer to these cervicovaginal non-squamous epithelia containing endocrine cells. This kind of lining is usually considered as immature squamous cell metaplasia or basal cell hyperplasia. It
Fig. 6 a-b. Vaginal epithelium. Higher magnification showing the two main types of endocrine cells. - a: small, round granules; b: more pleomorphic and larger granules (x 9000). Insets: detail of both types of neurosecretory granules (x 30000).
contains serotonin and calcitonin cells, in contrast to normal stratified squamous epithelium which is virtually devoid of endocrine cells. Despite the similarities between this type of cervicovaginallining and that of urothelium, distinct differences exist with respect to their cytokeratin expression profiles, reflecting the differences in their tendency to form terminally differentiated cells ("umbrella cells"). Urothelial tumours have a propensity to be associated with tumours elsewhere in the urothelium. Multicentric, independent primary carcinomas have been amply documented. They may occur synchronously or metachronously. These multicentric urothelial tumours always involve the urinary tract. The only associated gynecological manifestations were Paget's disease of the vulva 9 or ovarian tumours ll . The vaginal tumours reported here were grossly and microscopically very close, if not similar to low-grade papillary transitional cell carcinoma of the urinary tract.
364 . F. Fetissof et al.
This warrants their segregation from other papillary cervicovaginallesions. Unfortunately, no fresh samples of tumour have been available. Therefore, it was not possible to determine whether these papillary tumours retained the intrinsic cytokeratin pattern of "authentic" urothelial differentiation. The past history of the patient showed that multifocal, non-invasive, papillary tumours may affect the whole urogenital area. On the other hand, the vaginal wall was not covered with a normal stratified squamous epithelium. This lining fulfilled all the criteria of a "transitional-like" epithelium as previously described 7• It bore some resemblance to other "intermediate-type" epithelia and harbored variegated endocrine cells. The eventuality of a histogenetic link between the tumour and this contiguous, peculiar epithelial lining is a debated point which remains, at this time, unresolved. Acknowledgements The authors are indebted to Miss F. Colliou for the secretarial work, the electron microscopy department, and Mr J. C. Allard and Miss C. Tissier for technical assistance and help with the illustrations.
References I Abrahamsson PA, Wadstrom LB, Alumets J, Falkmer S, Grimelius L (1986) Peptide-hormone- and serotonin-immunoreactive cells in normal and hyperplastic prostate glands. Path Res Pract 181: 675-683
2 Aguirre P, Scully RE, Wolfe HJ, DeLellis RA (1986) Argyrophil cells in Brenner tumors: histochemical and immunohistochemical analysis. lnt J Gynecol Pathol 5: 223-234 3 Becker KL, Monaghan KG, Silva OL (1980) lmmunocytochemical localization of calcitonin in Kulchitsky cells of human lung. Arch Pathol Lab Med 104: 196-198 4 Chen KTK (1981) Brenner tumor of the vagina. Diag Gynecol Obstet 3: 255-258 5 di Sant-Agnese PA, de Mesy Jensen KL (1987) Neuroendocrine differentiation in prostatic carcinoma. Hum Pathol 18: 849-856 6 Fetissof F, Dubois MP, Heitz PU, Lansac J, Arbeille-Brassart B, Jobard P (1986) Endocrine cells in the female genital tract. Review. lnt J Gynecol Pathol 5: 75-87 7 Fetissof F, Arbeille B, Boivin F, Sam-Giao M, Henrion C, Lansac J (1987) Endocrine cells in ectocervical epithelium. An immunohistochemical and ultrastructural analysis. Virchows Arch A 411: 293-298 8 Fetissof F, Arbeille B, Guilloteau D, Lanson Y (1987) Glycoprotein hormone a-chain-immunoreactive endocrine cells in prostate and cloacal-derived tissues. Arch Pathol Lab Med 111: 836-840 9 Fukutani K, Kawabe K, Niijima T, Oohara K (1987) Transitional cell carcinoma of the urinary tract associated with vulvar Paget's disease: a report of two cases. Urol lnt 42: 71-73 10 Randall, ME, Andersen WA, Mills SE, Kim J-AC (1986) Papillary squamous cell carcinoma of the uterine cervix: A clinicopathologic study of nine cases. lnt J Gynecol Pathol 5: 1-10 II Young RH, Scully RE (1988) Urothelial and ovarian carcinomas of identical cell types: problems in interpretation. A report of three cases and review of the literature. lnt J Gynecol Pathol 7: 197-211
Received September 21, 1989 . Accepted in revised form November 27, 1989
Key Words: Vagina - Transitional cell carcinoma - Papillary carcinoma - Endocrine cells Dr. F. Fetissof, Laboratoire d'Anatomie pathologique, Faculte de Medecine, 2 bis Boulevard Tonnelle, F-37032 Tours, France
