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Malignant mixed Mullerian tumor of the cervix – case report
Cancer Treatment Communications (2014) 2, 12–15
Malignant mixed Mullerian tumor of the cervix – case report$ Erik Kudelaa,1, Pavol Slavikb, Jozef Visnovskya,n, Pavol Buocika, Jana Sivakovaa, Petra Sumichrastovaa, Lukas Plankb, Jan Dankoa a
Department of Gynecology and Obstetrics, Jessenius Faculty of Medicine, Comenius University, Slovakia Institute of Pathologic Anatomy, Jessenius Faculty of Medicine, Comenius University, Slovakia
b
Received 26 August 2013; received in revised form 21 January 2014; accepted 23 February 2014
KEYWORDS Malignant mixed Mullerian tumor; Cervix
1.
Abstract Objective: To report a rare case of cervical malignancy necessitating complex treatment. Case: A sixty-five year old woman was admitted to the hospital with a diagnosed tumor arising from the upper lip of the cervix. Patient underwent the amputation of the cervix with the curettage of the cervical channel. Because of the diagnosis of malignant mixed Mullerian tumor (MMMT) a radical hysterectomy with pelvic lymphadenectomy was performed afterwards. The composition of the tumor concerning basaloid carcinoma combined with homologous sarcoma was published only in five cases in the known literature. Conclusions: Because of rarity of MMMT there are no consensus guidelines regarding treatment. We present the case with successful management and 4-year disease free survival. & 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BYNC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
Introduction
About 80–90 % of cervical malignancies represent squamous cell carcinomas followed by adenocarcinomas (10–20%) where incidence is on the rise nowadays. Other types of tumors are relatively rare. Malignant mixed Mullerian tumors of the cervix are extremely rare (0.005% of all malignancies of the cervix)
first described in 1951 by Ferriera and colleagues [1,2]. MMMT´s include both malignant epithelial and mesenchymal components. The most common components are squamocellular carcinoma combined with homologous sarcoma. So far only about 50 cases can be found in the literature [3] and from these only a smaller part was thoroughly described. Because of such a number of cases there are no consensus guidelines regarding treatment, prognosis and outcome.
☆
Précis: Malignant mixed Mullerian tumors of the cervix are extremely rare and because of their aggressive behavior appropriate management is vital. n Corresponding author. E-mail addresses: [email protected] (E. Kudela), [email protected] (J. Visnovsky). 1 Tel: +421 902 300 017; fax: +421 43 4203 242.
2.
Case report
A sixty-five year old woman (hypertensive, diabetic, P2) was admitted to the hospital with a diagnosed tumor arising from the upper lip of the cervix. She complained of three months lasting intermittent vaginal bleeding one year after
http://dx.doi.org/10.1016/j.ctrc.2014.02.001 2213-0896 & 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
Malignant mixed Mullerian tumor of the cervix – case report
13
Fig. 1 PAP staining of the cytology sample from the site of cervical tumor. Visible cells with morphologically large atypic nuclei suspicious from malignity.
the menopause. No other symptoms were present. During the vaginal examination at the Department an Exophytic Fragile tumor 3 1.5 cm was confirmed. The cytological sample from the site of the tumor was suspicious from malignity (Fig. 1). Patient underwent the amputation of the cervix with the curettage of the cervical channel. Because of the diagnosis of malignant mixed Mullerian tumor a radical hysterectomy with pelvic lymphadenectomy was performed afterwards. Subsequently whole pelvis irradiation ( 60 Gy in 30 fractions) and cis-platin based adjuvant chemotherapy were carried out without any complications. The patient is now five years after the operation with no signs of recurrence.
2.1.
Pathological findings
Grossly the tumor occupied the anterior lip of the cervix with regressive changes. Microscopically the tumor was composed of two different parts. The epithelial part was composed of basaloid squamocellular carcinoma (HMW CK+, EMA+) whereas the mesenchymal part was represented by homologous high-grade stromal sarcoma (CD 10+, vimentin+, desmin+/ , MSA , SMA , S100 ) (see Figs. 2 and 3) . The endocervix was intact, without the infiltration, and samples from the endocervical curettage were negative as far as the malignancy was concerned. Uterus, fallopian tubes and ovaries were intact. 30 Lymph nodes removed from the iliac and obturatory regions were examined with no sign of metastatic process. In conclusion the tumor was staged as pT1bpN0pMx G3.
3.
Discussion
MMMT of the cervix usually occurs in postmenopausal women, although the age varies from 12 to 93 years [4,5]. Most of the patients complained of vaginal bleeding and had a detectable mass in the uterine cervix. Grossly the cervical tumors ranged between 1.1 and 10 cm [4]. Microscopically the documented epithelial components of tumors were represented by squamocellular carcinoma (keratinizing,
Fig. 2 (A–C) Haematoxilin staining of the tumor with emphasis on the border of two different components (basaloid carcinoma and homologous sarcoma).
non-keratinizing, basaloid, papillary) and adenocarcinoma. Documented mesenchymal components were either homologous or heterologous (rhabdomyosarcoma, chondrosarcoma). One case report described also neuroendocrine component of MMMT. There are various etiologic factors concerning radiation exposure to the pelvic area, previous
14
E. Kudela et al.
HMW CK
CD 10
Vimentin Fig. 3 Immunohistochemical findings. Positive CK staining in basaloid carcinoma (A), and positive vimentin and CD10 staining in sarcomatous component (B, C).
Table 1 Literature review of basaloid MMMT's of the cervix (RT—radiotherapy, CHT—chemotherapy, TAH (total abdominal hysterectomy), BSO (bilateral salpingo-oophorectomy), ACC—adenocarcinoma, SCC—squamocellular carcinoma, NA—not available). Reference Age Presentation [4]
71
[4]
70
[4] [6]
87 68
[6] [6]
55 36
[6]
93
Treatment
Carc. comp.
Cervical mass
Local excision, RT + CHT Abnormal PAP TAH, BSO
Basaloid carcinoma with ACC like pattern Basaloid carcinoma with ACC like pattern Abnormal PAP Local excision, RT Basaloid carcinoma NA NA Basaloid carcinoma, keratinizing SCC NA NA Basaloid carcinoma NA NA Basaloid carcinoma, kratinising SCC NA NA Basaloid carcinoma, kratinising SCC
chemotherapy and HPV infection. The most common HPV types detected in MMMTs are HPV 16 and 18. Grayson et al. detected HPV16-DNA in the nuclei of both epithelial and sarcomatous components in three cases. These observations lend support to metaplastic theory of histogenesis [6].
Sarc. comp
Outcome
Low-grade myxoid fibrosarcoma
NA
Low-grade myxoid fibrosarcoma
NA
Homologous sarcoma Spindle cell sarcoma
NA NA
Spindle/giant cell sarcoma NA Spindle and myxoid cell sarcoma NA Spindle/giant cell sarcoma
NA
Our case represents only seventh documented case in the literature of MMMT (according to the review of Khanna et al.) composed of basaloid carcinoma and homologous sarcoma (see Table 1). MMMTs of the cervix compared to their counterparts in the corpus are more commonly
Malignant mixed Mullerian tumor of the cervix – case report confined to the uterus at presentation and have a better prognosis because of their early detection [4]. Behavior of these tumors is dominated by the carcinomatous component. Cervical MMMTs are according to a review article by Khanna et al. managed with radical hysterectomy, chemotherapy (cisplatin-based) and radiotherapy. According to Table 1 appropriate data concerning treatment modalities and outcome are missing in the literature. Some authors advise the removal of pelvic and aortic lymph nodes, omentectomy and peritoneal cytology in case of abdominal dissemination. The role of adjuvant radiotherapy and chemotherapy is also uncertain, but some authors have shown the advantage of radiotherapy for disease-specific survival in early stage tumors. Aggressive primary therapy can result in curing early-stage tumors whereas extracervical disease has very poor prognosis [7]. Taxanes and cisplatin-based chemotherapy, ifosfamid, along with pelvic irradiation, may lead to increased survival in people with metastatic carcinosaromas [8]. Median follow-up for patients with MMMT was 16 months, median time to death 10.5 months [9]. The follow-up of our patient continues for 60 months (control every 6 months) with negative ultrasound of small pelvis (every 6 moths), negative oncocytology result and negative oncomarkers (Ca125, CEA). In summary, we present a case of MMMT of the cervix with basaloid and high-grade homologous sarcoma components. Despite its aggressive nature, the patient was successfully managed with no signs of recurrence 5 years after the surgery.
Acknowledgments Funding was received from the Comenius University Grants No. 303/2011, 242/2012, 77/2013 and Scientific Grant
15 Agency of the Ministry of Education of the Slovak Republic VEGA 1/0271/12.
References [1] J.D. Wright, K. Rosenblum, P.C. Huettner, D.G. Mutch, J.S. Rader, et al., Cervical sarcomas: an analysis of incidence and outcome, Gynecol. Oncol. 99 (2) (2005) 348–351. [2] H.P. Ferriera, A case of mixed mesodermal tumor of the uterine cervix, J. Obstet. Gynaecol. Br. Emp. 58 (1951) 446–448. [3] A. Maheswari, S. Gupta, T. Shet, R. Wuntkal, H.B. Tonqaonkar, Diagnostic dilemma in a case of malignant mixed mullerian tumor of the cervix, World J. Surg. Oncol. 4 (2006) 36. [4] P.B. Clement, J.T. Zubovits, R.H. Young, R.E. Scully, Malignant mullerian mixed tumors of the uterine cervix: a report of nine cases of a neoplasm with morphology often different from its counterpart in the corpus, Int. J. Gynecol. Pathol. 17 (3) (1998) 211–222. [5] A. Ribeiro-Silva, A. Novello-Vilar, A.M. Cunha-Mercante, L.A. De Angelo Andrade, Malignant mixed Mullerian tumor of the uterine cervix with neuroendocrine differentiation, Int. J. Gynecol. Cancer 12 (2) (2002) 223–227. [6] W. Grayson, L.F. Taylor, K. Cooper, Carcinosarcoma of the uterine cervix: a report of eight cases with immunohistochemical analysis and evaluation of human papillomavirus status, Am. J. Surg. Pathol. 25 (3) (2001) 338–347. [7] S.B. Khanna, K. Dash, D.S. Arora, Malignant mixed Mullerian tumor – case reports and review article, Apollo Med. 6 (3) (2009) 227–241. [8] E. D’Angelo, J. Prat, Pathology of mixed Müllerian tumours, Best Pract. Res. Clin. Obstet. Gynaecol. 25 (6) (2011) 705–718. [9] R. Laterza, A. Seveso, F. Zefiro, G. Formenti, L. Mellana, N. Donadello, et al., Carcinosarcoma of the uterine cervix: case report and discussion, Gynecol. Oncol. 107 (2007) S98–S100.
Malignant mixed Mullerian tumor of the cervix – case report$ Erik Kudelaa,1, Pavol Slavikb, Jozef Visnovskya,n, Pavol Buocika, Jana Sivakovaa, Petra Sumichrastovaa, Lukas Plankb, Jan Dankoa a
Department of Gynecology and Obstetrics, Jessenius Faculty of Medicine, Comenius University, Slovakia Institute of Pathologic Anatomy, Jessenius Faculty of Medicine, Comenius University, Slovakia
b
Received 26 August 2013; received in revised form 21 January 2014; accepted 23 February 2014
KEYWORDS Malignant mixed Mullerian tumor; Cervix
1.
Abstract Objective: To report a rare case of cervical malignancy necessitating complex treatment. Case: A sixty-five year old woman was admitted to the hospital with a diagnosed tumor arising from the upper lip of the cervix. Patient underwent the amputation of the cervix with the curettage of the cervical channel. Because of the diagnosis of malignant mixed Mullerian tumor (MMMT) a radical hysterectomy with pelvic lymphadenectomy was performed afterwards. The composition of the tumor concerning basaloid carcinoma combined with homologous sarcoma was published only in five cases in the known literature. Conclusions: Because of rarity of MMMT there are no consensus guidelines regarding treatment. We present the case with successful management and 4-year disease free survival. & 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BYNC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
Introduction
About 80–90 % of cervical malignancies represent squamous cell carcinomas followed by adenocarcinomas (10–20%) where incidence is on the rise nowadays. Other types of tumors are relatively rare. Malignant mixed Mullerian tumors of the cervix are extremely rare (0.005% of all malignancies of the cervix)
first described in 1951 by Ferriera and colleagues [1,2]. MMMT´s include both malignant epithelial and mesenchymal components. The most common components are squamocellular carcinoma combined with homologous sarcoma. So far only about 50 cases can be found in the literature [3] and from these only a smaller part was thoroughly described. Because of such a number of cases there are no consensus guidelines regarding treatment, prognosis and outcome.
☆
Précis: Malignant mixed Mullerian tumors of the cervix are extremely rare and because of their aggressive behavior appropriate management is vital. n Corresponding author. E-mail addresses: [email protected] (E. Kudela), [email protected] (J. Visnovsky). 1 Tel: +421 902 300 017; fax: +421 43 4203 242.
2.
Case report
A sixty-five year old woman (hypertensive, diabetic, P2) was admitted to the hospital with a diagnosed tumor arising from the upper lip of the cervix. She complained of three months lasting intermittent vaginal bleeding one year after
http://dx.doi.org/10.1016/j.ctrc.2014.02.001 2213-0896 & 2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).
Malignant mixed Mullerian tumor of the cervix – case report
13
Fig. 1 PAP staining of the cytology sample from the site of cervical tumor. Visible cells with morphologically large atypic nuclei suspicious from malignity.
the menopause. No other symptoms were present. During the vaginal examination at the Department an Exophytic Fragile tumor 3 1.5 cm was confirmed. The cytological sample from the site of the tumor was suspicious from malignity (Fig. 1). Patient underwent the amputation of the cervix with the curettage of the cervical channel. Because of the diagnosis of malignant mixed Mullerian tumor a radical hysterectomy with pelvic lymphadenectomy was performed afterwards. Subsequently whole pelvis irradiation ( 60 Gy in 30 fractions) and cis-platin based adjuvant chemotherapy were carried out without any complications. The patient is now five years after the operation with no signs of recurrence.
2.1.
Pathological findings
Grossly the tumor occupied the anterior lip of the cervix with regressive changes. Microscopically the tumor was composed of two different parts. The epithelial part was composed of basaloid squamocellular carcinoma (HMW CK+, EMA+) whereas the mesenchymal part was represented by homologous high-grade stromal sarcoma (CD 10+, vimentin+, desmin+/ , MSA , SMA , S100 ) (see Figs. 2 and 3) . The endocervix was intact, without the infiltration, and samples from the endocervical curettage were negative as far as the malignancy was concerned. Uterus, fallopian tubes and ovaries were intact. 30 Lymph nodes removed from the iliac and obturatory regions were examined with no sign of metastatic process. In conclusion the tumor was staged as pT1bpN0pMx G3.
3.
Discussion
MMMT of the cervix usually occurs in postmenopausal women, although the age varies from 12 to 93 years [4,5]. Most of the patients complained of vaginal bleeding and had a detectable mass in the uterine cervix. Grossly the cervical tumors ranged between 1.1 and 10 cm [4]. Microscopically the documented epithelial components of tumors were represented by squamocellular carcinoma (keratinizing,
Fig. 2 (A–C) Haematoxilin staining of the tumor with emphasis on the border of two different components (basaloid carcinoma and homologous sarcoma).
non-keratinizing, basaloid, papillary) and adenocarcinoma. Documented mesenchymal components were either homologous or heterologous (rhabdomyosarcoma, chondrosarcoma). One case report described also neuroendocrine component of MMMT. There are various etiologic factors concerning radiation exposure to the pelvic area, previous
14
E. Kudela et al.
HMW CK
CD 10
Vimentin Fig. 3 Immunohistochemical findings. Positive CK staining in basaloid carcinoma (A), and positive vimentin and CD10 staining in sarcomatous component (B, C).
Table 1 Literature review of basaloid MMMT's of the cervix (RT—radiotherapy, CHT—chemotherapy, TAH (total abdominal hysterectomy), BSO (bilateral salpingo-oophorectomy), ACC—adenocarcinoma, SCC—squamocellular carcinoma, NA—not available). Reference Age Presentation [4]
71
[4]
70
[4] [6]
87 68
[6] [6]
55 36
[6]
93
Treatment
Carc. comp.
Cervical mass
Local excision, RT + CHT Abnormal PAP TAH, BSO
Basaloid carcinoma with ACC like pattern Basaloid carcinoma with ACC like pattern Abnormal PAP Local excision, RT Basaloid carcinoma NA NA Basaloid carcinoma, keratinizing SCC NA NA Basaloid carcinoma NA NA Basaloid carcinoma, kratinising SCC NA NA Basaloid carcinoma, kratinising SCC
chemotherapy and HPV infection. The most common HPV types detected in MMMTs are HPV 16 and 18. Grayson et al. detected HPV16-DNA in the nuclei of both epithelial and sarcomatous components in three cases. These observations lend support to metaplastic theory of histogenesis [6].
Sarc. comp
Outcome
Low-grade myxoid fibrosarcoma
NA
Low-grade myxoid fibrosarcoma
NA
Homologous sarcoma Spindle cell sarcoma
NA NA
Spindle/giant cell sarcoma NA Spindle and myxoid cell sarcoma NA Spindle/giant cell sarcoma
NA
Our case represents only seventh documented case in the literature of MMMT (according to the review of Khanna et al.) composed of basaloid carcinoma and homologous sarcoma (see Table 1). MMMTs of the cervix compared to their counterparts in the corpus are more commonly
Malignant mixed Mullerian tumor of the cervix – case report confined to the uterus at presentation and have a better prognosis because of their early detection [4]. Behavior of these tumors is dominated by the carcinomatous component. Cervical MMMTs are according to a review article by Khanna et al. managed with radical hysterectomy, chemotherapy (cisplatin-based) and radiotherapy. According to Table 1 appropriate data concerning treatment modalities and outcome are missing in the literature. Some authors advise the removal of pelvic and aortic lymph nodes, omentectomy and peritoneal cytology in case of abdominal dissemination. The role of adjuvant radiotherapy and chemotherapy is also uncertain, but some authors have shown the advantage of radiotherapy for disease-specific survival in early stage tumors. Aggressive primary therapy can result in curing early-stage tumors whereas extracervical disease has very poor prognosis [7]. Taxanes and cisplatin-based chemotherapy, ifosfamid, along with pelvic irradiation, may lead to increased survival in people with metastatic carcinosaromas [8]. Median follow-up for patients with MMMT was 16 months, median time to death 10.5 months [9]. The follow-up of our patient continues for 60 months (control every 6 months) with negative ultrasound of small pelvis (every 6 moths), negative oncocytology result and negative oncomarkers (Ca125, CEA). In summary, we present a case of MMMT of the cervix with basaloid and high-grade homologous sarcoma components. Despite its aggressive nature, the patient was successfully managed with no signs of recurrence 5 years after the surgery.
Acknowledgments Funding was received from the Comenius University Grants No. 303/2011, 242/2012, 77/2013 and Scientific Grant
15 Agency of the Ministry of Education of the Slovak Republic VEGA 1/0271/12.
References [1] J.D. Wright, K. Rosenblum, P.C. Huettner, D.G. Mutch, J.S. Rader, et al., Cervical sarcomas: an analysis of incidence and outcome, Gynecol. Oncol. 99 (2) (2005) 348–351. [2] H.P. Ferriera, A case of mixed mesodermal tumor of the uterine cervix, J. Obstet. Gynaecol. Br. Emp. 58 (1951) 446–448. [3] A. Maheswari, S. Gupta, T. Shet, R. Wuntkal, H.B. Tonqaonkar, Diagnostic dilemma in a case of malignant mixed mullerian tumor of the cervix, World J. Surg. Oncol. 4 (2006) 36. [4] P.B. Clement, J.T. Zubovits, R.H. Young, R.E. Scully, Malignant mullerian mixed tumors of the uterine cervix: a report of nine cases of a neoplasm with morphology often different from its counterpart in the corpus, Int. J. Gynecol. Pathol. 17 (3) (1998) 211–222. [5] A. Ribeiro-Silva, A. Novello-Vilar, A.M. Cunha-Mercante, L.A. De Angelo Andrade, Malignant mixed Mullerian tumor of the uterine cervix with neuroendocrine differentiation, Int. J. Gynecol. Cancer 12 (2) (2002) 223–227. [6] W. Grayson, L.F. Taylor, K. Cooper, Carcinosarcoma of the uterine cervix: a report of eight cases with immunohistochemical analysis and evaluation of human papillomavirus status, Am. J. Surg. Pathol. 25 (3) (2001) 338–347. [7] S.B. Khanna, K. Dash, D.S. Arora, Malignant mixed Mullerian tumor – case reports and review article, Apollo Med. 6 (3) (2009) 227–241. [8] E. D’Angelo, J. Prat, Pathology of mixed Müllerian tumours, Best Pract. Res. Clin. Obstet. Gynaecol. 25 (6) (2011) 705–718. [9] R. Laterza, A. Seveso, F. Zefiro, G. Formenti, L. Mellana, N. Donadello, et al., Carcinosarcoma of the uterine cervix: case report and discussion, Gynecol. Oncol. 107 (2007) S98–S100.