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Villoglandular adenocarcinoma of the cervix: Clarity is needed on the histological definition for this difficult diagnosis
Gynecologic Oncology 100 (2006) 192 – 194 www.elsevier.com/locate/ygyno
Case Report
Villoglandular adenocarcinoma of the cervix: Clarity is needed on the histological definition for this difficult diagnosisB R.D. Macdonald a,*, J. Kirwan a, K. Hayat b, C.S. Herrington c, H. Shawki d a
c
Department of Gynaecological Oncology, Liverpool Womens Hospital, Liverpool L8 7SS, UK b Clatterbridge Centre for Oncology, Bebington, Wirral, UK Department of Histopathology, Bute Medical School, University of St. Andrews, St. Andrews, UK d Department of Histopathology, Royal Liverpool University Hospital, Liverpool, UK Received 26 February 2005 Available online 2 November 2005
Abstract Background. Villoglandular adenocarcinoma (VGA) of the cervix is reported as a variant of a cervical adenocarcinoma with a good prognosis. Cases. We present two cases histologically reported as a villoglandular adenocarcinoma of the cervix that have recurred and progressed rapidly since initial treatment. External histopathological review suggested both had a prominent villoglandular pattern but with an associated underlying well-differentiated adenocarcinoma. Conclusion. The diagnosis of VGA is difficult. Current literature is not entirely consistent in the presented definition, and further clarity is needed. Because of the rarity of VGA and the difficulty but importance of the diagnosis, we would feel that a central review of all cases of VGA is warranted. This would assist in diagnosis and also in obtaining accurate follow-up data. D 2005 Elsevier Inc. All rights reserved. Keywords: Cervix; Villoglandular adenocarcinoma
Introduction
Case reports
Villoglandular adenocarcinoma (VGA) of the cervix has only been recognised as a separate entity relatively recently; with the initial report was in 1989 [1]. The majority of reports have subsequently described this variant as having a limited metastatic potential and a good long-term prognosis [2– 4]. So far in the literature, there are seven cases of metastases associated with villoglandular tumours and only two deaths [5– 9]. We present here two cases of initially diagnosed and treated as villoglandular cervical tumours, but the histopathological review and poor outcome would suggest that both tumours contained a villoglandular element with an underlying adenocarcinoma.
Case 1
i We present two cases of VGA with a poor outcome. These cases highlight this difficult histological diagnosis where the published reports and definitions are conflicting. * Corresponding author. Fax: +44 151 7024131. E-mail address: [email protected] (R.D. Macdonald).
0090-8258/$ - see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.ygyno.2005.07.133
A 32-year-old woman presented to the colposcopy clinic with a clinically suspicious cervix and persistent post coital bleeding. A cervical smear was reported as ?glandular neoplasia. Biopsies showed a superficial villoglandular adenocarcinoma. In light of the superficial nature of the biopsy, further histology was required for a formal diagnosis, so a cone biopsy was taken 4 weeks later. The cone biopsy was reported as a villoglandular tumour, maximum dimension 24 mm, with 2.4 mm depth invasion and all resection margins clear on a 30 30 20 mm specimen (Fig. 1). Close follow-up rather than further surgery was recommended due to the histology, but at colposcopy 3 months later, an obvious cervical recurrence was noted. MRI staged this as a 1b2 tumour (maximum dimension 47 mm), and a biopsy from the cervix showed a continuum from a well-differentiated adenocarcinoma with a villoglandular pattern to a poorly differentiated carcinoma (Fig. 2). Chemoradiation was initiat-
R.D. Macdonald et al. / Gynecologic Oncology 100 (2006) 192 – 194
193
oped a further pelvic recurrence and is now receiving palliative rather than curative support and treatment. Histological review
Fig. 1. Initial cone biopsy of Case 1: Adenocarcinoma with a villoglandular pattern and mild cytological atypia.
Histology from both cases was sent for external review. Both on review were considered to have a marked villoglandular pattern but with an underlying well-differentiated adenocarcinoma. In both the resection, margins were clear on the initial specimen (cone biopsy in Case 1 and radical hysterectomy in Case 2). Case 1 appeared to show de-differentiation, with the recurrence in this case showing a continuum from a well-differentiated adenocarcinoma through to a poorly differentiated adenocarcinoma. Discussion
ed, but following cisplatin (4 cycles) and external beam radiation, an EUA at the initiation of brachytherapy found further clinical tumour extension, with right parametrial involvement (stage 2b). Rapid tumour progression followed the completion of chemoradiation, and she died 2 months later due to complications of an extensive pelvic tumour. Case 2 A 31-year-old woman presented to the Emergency Room with a watery vaginal loss with some associated heavy bleeding. Examination revealed a 5– 6 cm exophytic cervical tumour with no clinical parametrial involvement, confirmed on MRI (stage 1b2). Histology from a punch biopsy of the cervix showed a well-differentiated adenocarcinoma with a villoglandular pattern. Initially chemoradiation was contemplated, but after review of the histology, it was felt she was suitable for surgery in view of the good prognosis reported in the literature for villoglandular tumours. A radical hysterectomy and pelvic lymph node dissection were performed. Histology was reported as a villoglandular adenocarcinoma, with deep invasion (10 mm), lymphovascular space invasion, and a positive left obturator node. All resection margins of the primary tumour were clear. In light of the single positive node and clear margins, adjuvant radiotherapy was not considered necessary when her case was discussed at the MDT meeting. No problems were found at 3 months, but at a routine review at 6 months following surgery, a suspicious lesion at the vaginal vault was found which was biopsied. Histology demonstrated a deeply invasive well-differentiated adenocarcinoma with a villoglandular pattern. Chemoradiation was offered as second line treatment (4 cycles of cisplatin, 45 Gy in 25 fractions as external beam radiation and two sessions of 7 Gy at 5 mm HDR brachytherapy). A repeat EUA 3 months following the completion of chemoradiation found no abnormality at the vaginal vault, but a nodule at the drain site from the original radical hysterectomy came back showing metastatic adenocarcinoma, again with a villoglandular pattern. She has had the nodule excised and completed post-operative radiotherapy. She has since devel-
The original description of a villoglandular tumour was in 1989 by Young and Scully [1], who described 13 cases of a villoglandular type of papillary adenocarcinoma. Six of these 13 had an invasive adenocarcinoma component (two of which were deeply invasive), with the remainder being associated with CGIN or CIN (described in 1989 as adenocarcinoma in situ and squamous cell carcinoma in situ). In this original series, there were no recurrences, and the suggestion was that less radical surgery may be appropriate in these cases. The authors in that report were careful to note that no lymphovascular space invasion was seen, and cellular atypia would warrant looking for an underlying adenocarcinoma. Young and Clement [10] again suggested that a villoglandular tumour should only be diagnosed in the absence of any underlying invasive conventional adenocarcinoma, and there should be at worst mild to moderate cellular atypia. Our concern has been the importance in making what is potentially a difficult diagnosis, particularly when there is such a marked difference in the prognosis between a villoglandular tumour and a conventional cervical adenocarcinoma. As has been already stated, the original report of a villoglandular tumour found no lymphovascular space invasion, and no associated adeno or squamous carcinoma [1,10], with any invasive component being villoglandular, not adenocarcinoma.
Fig. 2. Biopsy of recurrence of Case 1: This shows a continuum from a well differentiated adenocarcinoma through to a poorly differentiated carcinoma.
194
R.D. Macdonald et al. / Gynecologic Oncology 100 (2006) 192 – 194
However, subsequent publications have reported finding both lymphovascular space invasion [7,9] and associated adenocarcinoma and squamous cell cancers [3,11,12]. So far over 110 cases of villoglandular adenocarcinoma of the cervix are in the world literature, and only seven metastases and two deaths have been reported up to now. This shows an apparent discrepancy between the original [1] and subsequent reports by other authors of villoglandular tumours [3,11,12]. The two cases reported here would fit with later reports of VGA but would probably not be consistent with the original definition. A villoglandular adenocarcinoma of the cervix is a rare tumour. The diagnosis is difficult and important, in view of the change in prognosis and potentially treatment the diagnosis would bring. Definitions in the literature of villoglandular tumours appear to be inconsistent. Ideally the diagnosis can only be made on complete excision of the primary tumour, rather than on a biopsy. In view of the difficulty of the diagnosis, until this stage of complete excision treatment has to follow the standard management of a cervical adenocarcinoma. Equally, we would advise caution in the light of our experience in following the more recent variations in the definition of a villoglandular tumour and continue to adhere to a limited and conservative definition of a villoglandular carcinoma: only villoglandular components, with no standard adenomatous or squamous features and no high grade nuclear abnormalities. The management of the cervical villoglandular tumour is a significant challenge. Diagnostically, there is a major problem for the pathologist in making a confident and accurate diagnosis in view of the variable definitions in the literature. From a clinical management perspective, although there are reports of this being a tumour with a good prognosis, there are sufficient reports of a poor outcome following the diagnosis to strike a note of caution about treating VGA less aggressively than other variants of cervical adenocarcinomas. Further information, particularly on diagnostic definition and on long-term follow-up, would help future management. A potential way forward would be the creation of a central review of all potential cases of villoglandular adenocarcinomas
and the setting up of a rare tumour database for this and other rare gynaecological cancers. This would provide greater consistency in the diagnosis of villoglandular tumours and also allow for the collection of follow-up data. References [1] Young RH, Scully RE. Villoglandular papillary adenocarcinoma of the uterine cervix. A clinicopathologic analysis of 13 cases. Cancer 1989; 63:1773 – 9. [2] Jones MW, Silverberg SG, Kurman RJ. Well-differentiated villoglandular adenocarcinoma of the uterine cervix: a clinicopathological study of 24 cases. Int J Gynecol Pathol 1993;12:1 – 7. [3] Stanley-Christian H, Heim BK, Hines JF, Hall KL, Willett GD, Barnes WA. Villoglandular adenocarcinoma of the cervix: a report of three cases and review of the literature. Gynecol Oncol 1997;66:327 – 30. [4] Datta CK. Well-differentiated papillary villoglandular adenocarcinoma of the uterine cervix. W V Med J 1997;93:186 – 8. [5] Dede M, Deveci G, Deveci MS, Yenen MC, Goktolga U, Dilek S, et al. Villoglandular papillary adenocarcinoma of the uterine cervix in a pregnant woman: a case report and review of the literature. Tohoku J Exp Med 2004;202:305 – 10. [6] Utsugi K, Shimizu Y, Akiyama F, Umezawa S, Hasumi K. Clinicopathologic features of villoglandular papillary adenocarcinoma of the uterine cervix. Gynecol Oncol 2004;92:64 – 70. [7] Khunamornpong S, Maleemonkol S, Siriaunkgul S, Pantusart A. Welldifferentiated villoglandular adenocarcinoma of the uterine cervix: a report of 15 cases including two with lymph node metastasis. J Med Assoc Thailand 2001;84:882 – 8. [8] Garcea A, Nunns D, Ireland D, Brown L. A case of villoglandular adenocarcinoma of the cervix with lymph node metastasis. BJOG 2003;110:627 – 9. [9] Kaku T, Kamura T, Shigematsu T, et al. Adenocarcinoma of the uterine cervix with predominantly villoglandular papillary growth pattern. Gynecol Oncol 1997;64:147 – 52. [10] Young RH, Clement PB. Endocervical adenocarcinoma and its variants: their morphology and differential diagnosis. Histopathology 2002;41: 185 – 207. [11] Bouman A, Oosterhuis GJ, Naudin ten Cate L, van Doorn GA. Villoglandular papillary adenocarcinoma of the cervix. Beware of a wolf in sheep’s clothing. Eur J Obstet Gynecol Reprod Biol 1999;87:183 – 9. [12] Collinet P, Prolongeau JF, Vaneecloo S. Villoglandular adenocarcinoma of the uterine cervix. Eur J Obstet Gynecol Reprod Biol 199;86: 101 – 3.
Case Report
Villoglandular adenocarcinoma of the cervix: Clarity is needed on the histological definition for this difficult diagnosisB R.D. Macdonald a,*, J. Kirwan a, K. Hayat b, C.S. Herrington c, H. Shawki d a
c
Department of Gynaecological Oncology, Liverpool Womens Hospital, Liverpool L8 7SS, UK b Clatterbridge Centre for Oncology, Bebington, Wirral, UK Department of Histopathology, Bute Medical School, University of St. Andrews, St. Andrews, UK d Department of Histopathology, Royal Liverpool University Hospital, Liverpool, UK Received 26 February 2005 Available online 2 November 2005
Abstract Background. Villoglandular adenocarcinoma (VGA) of the cervix is reported as a variant of a cervical adenocarcinoma with a good prognosis. Cases. We present two cases histologically reported as a villoglandular adenocarcinoma of the cervix that have recurred and progressed rapidly since initial treatment. External histopathological review suggested both had a prominent villoglandular pattern but with an associated underlying well-differentiated adenocarcinoma. Conclusion. The diagnosis of VGA is difficult. Current literature is not entirely consistent in the presented definition, and further clarity is needed. Because of the rarity of VGA and the difficulty but importance of the diagnosis, we would feel that a central review of all cases of VGA is warranted. This would assist in diagnosis and also in obtaining accurate follow-up data. D 2005 Elsevier Inc. All rights reserved. Keywords: Cervix; Villoglandular adenocarcinoma
Introduction
Case reports
Villoglandular adenocarcinoma (VGA) of the cervix has only been recognised as a separate entity relatively recently; with the initial report was in 1989 [1]. The majority of reports have subsequently described this variant as having a limited metastatic potential and a good long-term prognosis [2– 4]. So far in the literature, there are seven cases of metastases associated with villoglandular tumours and only two deaths [5– 9]. We present here two cases of initially diagnosed and treated as villoglandular cervical tumours, but the histopathological review and poor outcome would suggest that both tumours contained a villoglandular element with an underlying adenocarcinoma.
Case 1
i We present two cases of VGA with a poor outcome. These cases highlight this difficult histological diagnosis where the published reports and definitions are conflicting. * Corresponding author. Fax: +44 151 7024131. E-mail address: [email protected] (R.D. Macdonald).
0090-8258/$ - see front matter D 2005 Elsevier Inc. All rights reserved. doi:10.1016/j.ygyno.2005.07.133
A 32-year-old woman presented to the colposcopy clinic with a clinically suspicious cervix and persistent post coital bleeding. A cervical smear was reported as ?glandular neoplasia. Biopsies showed a superficial villoglandular adenocarcinoma. In light of the superficial nature of the biopsy, further histology was required for a formal diagnosis, so a cone biopsy was taken 4 weeks later. The cone biopsy was reported as a villoglandular tumour, maximum dimension 24 mm, with 2.4 mm depth invasion and all resection margins clear on a 30 30 20 mm specimen (Fig. 1). Close follow-up rather than further surgery was recommended due to the histology, but at colposcopy 3 months later, an obvious cervical recurrence was noted. MRI staged this as a 1b2 tumour (maximum dimension 47 mm), and a biopsy from the cervix showed a continuum from a well-differentiated adenocarcinoma with a villoglandular pattern to a poorly differentiated carcinoma (Fig. 2). Chemoradiation was initiat-
R.D. Macdonald et al. / Gynecologic Oncology 100 (2006) 192 – 194
193
oped a further pelvic recurrence and is now receiving palliative rather than curative support and treatment. Histological review
Fig. 1. Initial cone biopsy of Case 1: Adenocarcinoma with a villoglandular pattern and mild cytological atypia.
Histology from both cases was sent for external review. Both on review were considered to have a marked villoglandular pattern but with an underlying well-differentiated adenocarcinoma. In both the resection, margins were clear on the initial specimen (cone biopsy in Case 1 and radical hysterectomy in Case 2). Case 1 appeared to show de-differentiation, with the recurrence in this case showing a continuum from a well-differentiated adenocarcinoma through to a poorly differentiated adenocarcinoma. Discussion
ed, but following cisplatin (4 cycles) and external beam radiation, an EUA at the initiation of brachytherapy found further clinical tumour extension, with right parametrial involvement (stage 2b). Rapid tumour progression followed the completion of chemoradiation, and she died 2 months later due to complications of an extensive pelvic tumour. Case 2 A 31-year-old woman presented to the Emergency Room with a watery vaginal loss with some associated heavy bleeding. Examination revealed a 5– 6 cm exophytic cervical tumour with no clinical parametrial involvement, confirmed on MRI (stage 1b2). Histology from a punch biopsy of the cervix showed a well-differentiated adenocarcinoma with a villoglandular pattern. Initially chemoradiation was contemplated, but after review of the histology, it was felt she was suitable for surgery in view of the good prognosis reported in the literature for villoglandular tumours. A radical hysterectomy and pelvic lymph node dissection were performed. Histology was reported as a villoglandular adenocarcinoma, with deep invasion (10 mm), lymphovascular space invasion, and a positive left obturator node. All resection margins of the primary tumour were clear. In light of the single positive node and clear margins, adjuvant radiotherapy was not considered necessary when her case was discussed at the MDT meeting. No problems were found at 3 months, but at a routine review at 6 months following surgery, a suspicious lesion at the vaginal vault was found which was biopsied. Histology demonstrated a deeply invasive well-differentiated adenocarcinoma with a villoglandular pattern. Chemoradiation was offered as second line treatment (4 cycles of cisplatin, 45 Gy in 25 fractions as external beam radiation and two sessions of 7 Gy at 5 mm HDR brachytherapy). A repeat EUA 3 months following the completion of chemoradiation found no abnormality at the vaginal vault, but a nodule at the drain site from the original radical hysterectomy came back showing metastatic adenocarcinoma, again with a villoglandular pattern. She has had the nodule excised and completed post-operative radiotherapy. She has since devel-
The original description of a villoglandular tumour was in 1989 by Young and Scully [1], who described 13 cases of a villoglandular type of papillary adenocarcinoma. Six of these 13 had an invasive adenocarcinoma component (two of which were deeply invasive), with the remainder being associated with CGIN or CIN (described in 1989 as adenocarcinoma in situ and squamous cell carcinoma in situ). In this original series, there were no recurrences, and the suggestion was that less radical surgery may be appropriate in these cases. The authors in that report were careful to note that no lymphovascular space invasion was seen, and cellular atypia would warrant looking for an underlying adenocarcinoma. Young and Clement [10] again suggested that a villoglandular tumour should only be diagnosed in the absence of any underlying invasive conventional adenocarcinoma, and there should be at worst mild to moderate cellular atypia. Our concern has been the importance in making what is potentially a difficult diagnosis, particularly when there is such a marked difference in the prognosis between a villoglandular tumour and a conventional cervical adenocarcinoma. As has been already stated, the original report of a villoglandular tumour found no lymphovascular space invasion, and no associated adeno or squamous carcinoma [1,10], with any invasive component being villoglandular, not adenocarcinoma.
Fig. 2. Biopsy of recurrence of Case 1: This shows a continuum from a well differentiated adenocarcinoma through to a poorly differentiated carcinoma.
194
R.D. Macdonald et al. / Gynecologic Oncology 100 (2006) 192 – 194
However, subsequent publications have reported finding both lymphovascular space invasion [7,9] and associated adenocarcinoma and squamous cell cancers [3,11,12]. So far over 110 cases of villoglandular adenocarcinoma of the cervix are in the world literature, and only seven metastases and two deaths have been reported up to now. This shows an apparent discrepancy between the original [1] and subsequent reports by other authors of villoglandular tumours [3,11,12]. The two cases reported here would fit with later reports of VGA but would probably not be consistent with the original definition. A villoglandular adenocarcinoma of the cervix is a rare tumour. The diagnosis is difficult and important, in view of the change in prognosis and potentially treatment the diagnosis would bring. Definitions in the literature of villoglandular tumours appear to be inconsistent. Ideally the diagnosis can only be made on complete excision of the primary tumour, rather than on a biopsy. In view of the difficulty of the diagnosis, until this stage of complete excision treatment has to follow the standard management of a cervical adenocarcinoma. Equally, we would advise caution in the light of our experience in following the more recent variations in the definition of a villoglandular tumour and continue to adhere to a limited and conservative definition of a villoglandular carcinoma: only villoglandular components, with no standard adenomatous or squamous features and no high grade nuclear abnormalities. The management of the cervical villoglandular tumour is a significant challenge. Diagnostically, there is a major problem for the pathologist in making a confident and accurate diagnosis in view of the variable definitions in the literature. From a clinical management perspective, although there are reports of this being a tumour with a good prognosis, there are sufficient reports of a poor outcome following the diagnosis to strike a note of caution about treating VGA less aggressively than other variants of cervical adenocarcinomas. Further information, particularly on diagnostic definition and on long-term follow-up, would help future management. A potential way forward would be the creation of a central review of all potential cases of villoglandular adenocarcinomas
and the setting up of a rare tumour database for this and other rare gynaecological cancers. This would provide greater consistency in the diagnosis of villoglandular tumours and also allow for the collection of follow-up data. References [1] Young RH, Scully RE. Villoglandular papillary adenocarcinoma of the uterine cervix. A clinicopathologic analysis of 13 cases. Cancer 1989; 63:1773 – 9. [2] Jones MW, Silverberg SG, Kurman RJ. Well-differentiated villoglandular adenocarcinoma of the uterine cervix: a clinicopathological study of 24 cases. Int J Gynecol Pathol 1993;12:1 – 7. [3] Stanley-Christian H, Heim BK, Hines JF, Hall KL, Willett GD, Barnes WA. Villoglandular adenocarcinoma of the cervix: a report of three cases and review of the literature. Gynecol Oncol 1997;66:327 – 30. [4] Datta CK. Well-differentiated papillary villoglandular adenocarcinoma of the uterine cervix. W V Med J 1997;93:186 – 8. [5] Dede M, Deveci G, Deveci MS, Yenen MC, Goktolga U, Dilek S, et al. Villoglandular papillary adenocarcinoma of the uterine cervix in a pregnant woman: a case report and review of the literature. Tohoku J Exp Med 2004;202:305 – 10. [6] Utsugi K, Shimizu Y, Akiyama F, Umezawa S, Hasumi K. Clinicopathologic features of villoglandular papillary adenocarcinoma of the uterine cervix. Gynecol Oncol 2004;92:64 – 70. [7] Khunamornpong S, Maleemonkol S, Siriaunkgul S, Pantusart A. Welldifferentiated villoglandular adenocarcinoma of the uterine cervix: a report of 15 cases including two with lymph node metastasis. J Med Assoc Thailand 2001;84:882 – 8. [8] Garcea A, Nunns D, Ireland D, Brown L. A case of villoglandular adenocarcinoma of the cervix with lymph node metastasis. BJOG 2003;110:627 – 9. [9] Kaku T, Kamura T, Shigematsu T, et al. Adenocarcinoma of the uterine cervix with predominantly villoglandular papillary growth pattern. Gynecol Oncol 1997;64:147 – 52. [10] Young RH, Clement PB. Endocervical adenocarcinoma and its variants: their morphology and differential diagnosis. Histopathology 2002;41: 185 – 207. [11] Bouman A, Oosterhuis GJ, Naudin ten Cate L, van Doorn GA. Villoglandular papillary adenocarcinoma of the cervix. Beware of a wolf in sheep’s clothing. Eur J Obstet Gynecol Reprod Biol 1999;87:183 – 9. [12] Collinet P, Prolongeau JF, Vaneecloo S. Villoglandular adenocarcinoma of the uterine cervix. Eur J Obstet Gynecol Reprod Biol 199;86: 101 – 3.