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{{CMG}} {{AE}} {{MV}}
{{CMG}} {{AE}} {{MV}}
   
   
{{SK}} Mixed Müllerian tumor; MMMT; Malignant mixed Müllerian tumor
{{SK}} Mixed Müllerian tumor; MMMT; Malignant mixed Müllerian tumor; Carcinosarcoma of the uterus; Sarcomatoid carcinoma of the uterus; Malignant mesodermal mixed tumor; Metaplastic carcinoma
 
==Overview==
==Overview==
'''Malignant mixed mullerian tumor''' (MMMT) is a rare [[uterine sarcoma]] or carcinosarcoma. Mixed Mullerian tumors are normally composed of both carcinomatous (epithelial) and sarcomatous (mesodermal) components. Mixed Mullerian tumor may be classified according to pathology findings into 2 types: epitheloid subtype and sarcomatoid subtype. Mixed Mullerian tumor may also be classified according to anatomical location into 7 types:  [[Uterine corpus cancer|uterine corpus]], [[cervix]], [[ovaries]], [[fallopian tubes]], [[Vaginal Cancer|vagina]], [[peritoneum]], and extragenital sites. Common risk factors in the development of mixed Mullerian tumor are [[Radiation|exposure to radiation]], [[Estrogen|excessive estrogen exposure]], [[obesity]], and nulliparity.<ref name="pmid20642852">{{cite journal |vauthors=Kanthan R, Senger JL, Diudea D |title=Malignant mixed Mullerian tumors of the uterus: histopathological evaluation of cell cycle and apoptotic regulatory proteins |journal=World J Surg Oncol |volume=8 |issue= |pages=60 |year=2010 |pmid=20642852 |pmc=2913917 |doi=10.1186/1477-7819-8-60 |url=}}</ref> Mixed Mullerian tumor is more commonly observed among postmenopausal women  between 50 and 60 years old. Early clinical features include [[Vaginal bleeding|postmenopausal vaginal bleeding]], [[pelvic pain]], and [[vaginal discharge]]. Mixed Mullerian tumors are rare, and they only account for 3 to 4% of all uterine malignancies. The estimated prevalence of mixed Mullerian tumor is 3 cases per 100,000 women in the United States. The diagnosis of mixed Mullerian tumor is made with biopsy. Biopsy findings of mixed Mullerian tumor, include: tumor with carcinomatous and sarcoma-like elements and angiolymphatic invasion. Surgery is the mainstay of therapy for mixed Mullerian tumor. Total hysterectomy in conjunction with surgical staging is the most common approach to the treatment of mixed Mullerian tumor. Prognosis is generally poor, and the 5-year survival rate of patients with mixed Mullerian tumor is approximately 33% to 39%.<ref name="pmid9656116">{{cite journal |vauthors=Clement PB, Zubovits JT, Young RH, Scully RE |title=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 |journal=Int. J. Gynecol. Pathol. |volume=17 |issue=3 |pages=211–22 |year=1998 |pmid=9656116 |doi= |url=}}</ref>


==Historical Perspective==
==Historical Perspective==
*[Disease name] was first discovered by [scientist name], a [nationality + occupation], in [year] during/following [event].
*Mixed Mullerian tumor was first described by Ferriera and colleagues in 1951.<ref name="pmid16051326">{{cite journal |vauthors=Wright JD, Rosenblum K, Huettner PC, Mutch DG, Rader JS, Powell MA, Gibb RK |title=Cervical sarcomas: an analysis of incidence and outcome |journal=Gynecol. Oncol. |volume=99 |issue=2 |pages=348–51 |year=2005 |pmid=16051326 |doi=10.1016/j.ygyno.2005.06.021 |url=}}</ref>
*In [year], [gene] mutations were first identified in the pathogenesis of [disease name].
*In [year], the first [discovery] was developed by [scientist] to treat/diagnose [disease name].
   
   
==Classification==
==Classification==
*[Disease name] may be classified according to [classification method] into [number] subtypes/groups:
*Mixed Mullerian tumors are normally composed of both carcinomatous (epithelial) and sarcomatous (mesodermal) components.
:*[group1]
*Mixed Mullerian tumor may be classified according to pathology findings into 2 types:
:*[group2]
'''Epitheloid subtype'''
:*[group3]
:*[[Adenocarcinoma - endometrium|Endometroid adenocarcinoma]] (most common)
*Other variants of [disease name] include [disease subtype 1], [disease subtype 2], and [disease subtype 3].
:*[[Clear cell tumor|Clear cell carcinoma]]
:*[[Mucinous carcinoma]]
:*Papillary-serous carcinoma
'''Sarcomatoid subtype'''
:*Undifferentiated sarcoma
:*[[Rhabdomyosarcoma]]
 
*Mixed Mullerian tumor may also be classified according to anatomical location into 7 types:
:*[[Uterine corpus cancer|Uterine corpus]]
:*[[Cervix]]
:*[[Ovaries]]
:*[[Fallopian tubes]]
:*Vagina
:*[[Peritoneum]]
:*Extragenital sites
 
==Pathophysiology==
==Pathophysiology==
*The pathogenesis of [disease name] is characterized by [feature1], [feature2], and [feature3].
*The pathogenesis of mixed Mullerian tumor is characterized by epithelial and stromal growth, and the transdifferentiation of uterine carcinoma into sarcoma.<ref name="pato">D'Angelo E, Prat J. Pathology of mixed Mullerian tumours. Best Pract Res Clin Obstet Gynaecol. 2011;25:705-718.</ref>
*The [gene name] gene/Mutation in [gene name] has been associated with the development of [disease name], involving the [molecular pathway] pathway.
*The PIK3CA gene has been associated with the development of mixed Mullerian tumor, involving the PI3K pathway.  
*On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
*Genes involved in the pathogenesis of mixed Mullerian tumor, include: <ref name="MMM">Mutation Profiling in Uterine Carcinosarcoma / Malignant Mixed Mullerian Tumors. Melissa McConechy; David Huntsman, MD. ESUN. http://sarcomahelp.org/carcinosarcoma.html Accessed on April 7, 2016</ref>
*On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
:*PIK3CA (50% of the tumors)
:*[[PTEN gene|PTEN]] (30% of the tumors)
:*PIK3R1 (30% of the tumors)
*On gross pathology, a large cervical mass is a characteristic finding of mixed Mullerian tumor.
*On microscopic histopathological analysis, high-grade stromal sarcoma, poorly differentiated epithelial cells, and angiolymphatic invasion are characteristic findings of mixed Mullerian tumor.<ref name="pmid16813659">{{cite journal |vauthors=Maheshwari A, Gupta S, Shet T, Wuntkal R, Tongaonkar HB |title=Diagnostic dilemma in a case of malignant mixed mullerian tumor of the cervix |journal=World J Surg Oncol |volume=4 |issue= |pages=36 |year=2006 |pmid=16813659 |pmc=1526432 |doi=10.1186/1477-7819-4-36 |url=}}</ref>
 
==Causes==
==Causes==
* [Disease name] may be caused by either [cause1], [cause2], or [cause3].
*The most important cause of mixed Mullerian tumors is the mutation in genes PTEN, ARID1A, PIK3R1, and POLE.<ref name="MMM">Wada H, Enomoto T, Fujita M, et al. Molecular evidence that most but not all carcinosarcomas of the uterus are combination tumors. Cancer Res. 1997;57:5379-5385.</ref>
* [Disease name] is caused by a mutation in the [gene1], [gene2], or [gene3] gene[s].
*Mixed Mullerian tumor may also be caused by chronic estrogen stimulation.
* There are no established causes for [disease name].
 
==Differentiating Mixed Mullerian tumor from other Diseases==
==Differentiating [disease name] from other Diseases==
*Mixed Mullerian tumor must be differentiated from other diseases that cause abnormal vaginal bleeding, abdominal pain, and uterus enlargement such as:
*[Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:
:*[[Leiomyosarcoma|Uterine leiomyosarcoma]]
:*[Differential dx1]
:*[[Adenocarcinoma - endometrium|Adenocarcinoma of the uterus]]
:*[Differential dx2]
:*[[Endometrial cancer differential diagnosis|Endometrial cancer]]
:*[Differential dx3]
 
==Epidemiology and Demographics==
==Epidemiology and Demographics==
* The prevalence of [disease name] is approximately [number or range] per 100,000 individuals worldwide.
* Mixed Mullerian tumor is rare, it only accounts for 3 to 4% of all uterine malignancies.<ref name="pmid15047237">{{cite journal |vauthors=Brooks SE, Zhan M, Cote T, Baquet CR |title=Surveillance, epidemiology, and end results analysis of 2677 cases of uterine sarcoma 1989-1999 |journal=Gynecol. Oncol. |volume=93 |issue=1 |pages=204–8 |year=2004 |pmid=15047237 |doi=10.1016/j.ygyno.2003.12.029 |url=}}</ref>
* In [year], the incidence of [disease name] was estimated to be [number or range] cases per 100,000 individuals in [location].
* The estimated prevalence of mixed Mullerian tumor is 3 cases per 100,000 women  in the United States.<ref name="pmid15047237">{{cite journal |vauthors=Brooks SE, Zhan M, Cote T, Baquet CR |title=Surveillance, epidemiology, and end results analysis of 2677 cases of uterine sarcoma 1989-1999 |journal=Gynecol. Oncol. |volume=93 |issue=1 |pages=204–8 |year=2004 |pmid=15047237 |doi=10.1016/j.ygyno.2003.12.029 |url=}}</ref>
===Age===
===Age===
*Patients of all age groups may develop [disease name].
*The median age at diagnosis of Mixed Mullerian tumor is 66 years
*Mixed Mullerian tumor is more commonly observed among patients aged between 50 and 60 years old.
*[Disease name] is more commonly observed among patients aged [age range] years old.
*Mixed Mullerian tumor is more commonly observed among postmenopausal women
*[Disease name] is more commonly observed among [elderly patients/young patients/children].
===Gender===
*[Disease name] affects men and women equally.
*[Gender 1] are more commonly affected with [disease name] than [gender 2].
* The [gender 1] to [Gender 2] ratio is approximately [number > 1] to 1.
===Race===
===Race===
*There is no racial predilection for [disease name].
*There is no racial predilection for mixed Mullerian tumor.<ref name="pmid15047237">{{cite journal |vauthors=Brooks SE, Zhan M, Cote T, Baquet CR |title=Surveillance, epidemiology, and end results analysis of 2677 cases of uterine sarcoma 1989-1999 |journal=Gynecol. Oncol. |volume=93 |issue=1 |pages=204–8 |year=2004 |pmid=15047237 |doi=10.1016/j.ygyno.2003.12.029 |url=}}</ref>
 
*[Disease name] usually affects individuals of the [race 1] race.
*[Race 2] individuals are less likely to develop [disease name].
==Risk Factors==
==Risk Factors==
*Common risk factors in the development of [disease name] are [risk factor 1], [risk factor 2], [risk factor 3], and [risk factor 4].
*Common risk factors in the development of mixed Mullerian tumor are [[Radiation|exposure to radiation]], [[Estrogen|excessive estrogen exposure]], [[obesity]], and nulliparity.<ref name="pmid20642852">{{cite journal |vauthors=Kanthan R, Senger JL, Diudea D |title=Malignant mixed Mullerian tumors of the uterus: histopathological evaluation of cell cycle and apoptotic regulatory proteins |journal=World J Surg Oncol |volume=8 |issue= |pages=60 |year=2010 |pmid=20642852 |pmc=2913917 |doi=10.1186/1477-7819-8-60 |url=}}</ref>
   
   
== Natural History, Complications and Prognosis==
== Natural History, Complications and Prognosis==
*The majority of patients with [disease name] remain asymptomatic for [duration/years].
*Early clinical features include [[Vaginal bleeding|postmenopausal vaginal bleeding]], [[pelvic pain]], and [[vaginal discharge]].
*Early clinical features include [manifestation 1], [manifestation 2], and [manifestation 3].
*If left untreated, the majority of patients with mixed Mullerian tumor may progress quickly to develop lymph node invasion, [[metastasis]], and death.  
*If left untreated, [#%] of patients with [disease name] may progress to develop [manifestation 1], [manifestation 2], and [manifestation 3].
*Prognosis is generally poor, and the 5-year survival rate of patients with Mixed Mullerian tumor is approximately 33% to 39%.
*Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
*Findings associated with good prognosis include p16 and Mcl-1 gene expression.<ref name="pmid16813659">{{cite journal |vauthors=Maheshwari A, Gupta S, Shet T, Wuntkal R, Tongaonkar HB |title=Diagnostic dilemma in a case of malignant mixed mullerian tumor of the cervix |journal=World J Surg Oncol |volume=4 |issue= |pages=36 |year=2006 |pmid=16813659 |pmc=1526432 |doi=10.1186/1477-7819-4-36 |url=}}</ref>
*Prognosis is generally [excellent/good/poor], and the [1/5/10­year mortality/survival rate] of patients with [disease name] is approximately [#%].
 
== Diagnosis ==
== Diagnosis ==
===Diagnostic Criteria===
===Diagnostic Criteria===
*The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met:
*The diagnosis of mixed Mullerian tumor is made with biopsy.
:*[criterion 1]
*Biopsy findings of mixed Mullerian tumor, include:<ref name="pmid9656116">{{cite journal |vauthors=Clement PB, Zubovits JT, Young RH, Scully RE |title=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 |journal=Int. J. Gynecol. Pathol. |volume=17 |issue=3 |pages=211–22 |year=1998 |pmid=9656116 |doi= |url=}}</ref>
:*[criterion 2]
:*Tumor with carcinomatous and sarcoma-like elements
:*[criterion 3]
:*Angiolymphatic invasion
:*[criterion 4]
 
=== Symptoms ===
=== Symptoms ===
*[Disease name] is usually asymptomatic.
*Mixed Mullerian tumor may be initially asymptomatic.
*Symptoms of [disease name] may include the following:
*Symptoms of mixed Mullerian tumor may include the following:<ref name="pmid20642852">{{cite journal |vauthors=Kanthan R, Senger JL, Diudea D |title=Malignant mixed Mullerian tumors of the uterus: histopathological evaluation of cell cycle and apoptotic regulatory proteins |journal=World J Surg Oncol |volume=8 |issue= |pages=60 |year=2010 |pmid=20642852 |pmc=2913917 |doi=10.1186/1477-7819-8-60 |url=}}</ref>
:*[symptom 1]
*Early symptoms
:*[symptom 2]
:* Abnormal [[vaginal bleeding]], abnormal menstrual periods
:*[symptom 3]
:* [[Metrorrhagia]] in premenopausal women
:*[symptom 4]
:* Postmenopausal [[vaginal bleeding]] <ref name="pmid22513918">{{cite journal| author=Kong A, Johnson N, Kitchener HC, Lawrie TA| title=Adjuvant radiotherapy for stage I endometrial cancer. | journal=Cochrane Database Syst Rev | year= 2012 | volume= 4 | issue=  | pages= CD003916 | pmid=22513918 | doi=10.1002/14651858.CD003916.pub4 | pmc=PMC4164955 | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22513918  }} </ref>
:*[symptom 5]
:* Postcoital bleeding
:*[symptom 6]
*Advanced symptoms
:* [[Polyuria]] and [[dysuria]], If a tumor places pressure on the bladder or urethra
:* [[Pelvic pain]] and [[dyspareunia]]
:* [[Fatigue]] and unexplained [[weight loss]]
 
=== Physical Examination ===
=== Physical Examination ===
*Patients with [disease name] usually appear [general appearance].
*Patients with mixed Mullerian tumor may have a normal appearance.
*Physical examination may be remarkable for:
*Pelvic examination may be remarkable for:<ref name="pmid9656116">{{cite journal |vauthors=Clement PB, Zubovits JT, Young RH, Scully RE |title=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 |journal=Int. J. Gynecol. Pathol. |volume=17 |issue=3 |pages=211–22 |year=1998 |pmid=9656116 |doi= |url=}}</ref>
:*[finding 1]
:*[[Vaginal bleeding]]
:*[finding 2]
:*[[Enlarged uterus]] (advanced stage)
:*[finding 3]
 
:*[finding 4]
:*[finding 5]
:*[finding 6]
=== Laboratory Findings ===
=== Laboratory Findings ===
*There are no specific laboratory findings associated with [disease name].
*Laboratory findings associated with mixed Mullerian tumor, may include:
:*Anemia
:*Elevated CA-125


*A  [positive/negative] [test name] is diagnostic of [disease name].
*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].
===Imaging Findings===
===Imaging Findings===
*There are no [imaging study] findings associated with [disease name].
*Enhanced CT scan and MRI is the imaging modalities of choice for mixed Mullerian tumor.
*On MRI,  findings of mixed Mullerian tumor, may include:<ref name="pmid4705156">{{cite journal |vauthors=Abell MR, Ramirez JA |title=Sarcomas and carcinosarcomas of the uterine cervix |journal=Cancer |volume=31 |issue=5 |pages=1176–92 |year=1973 |pmid=4705156 |doi= |url=}}</ref>
*[Imaging study 1] is the imaging modality of choice for [disease name].
:*T1: predominantly isointense to both myometrium (75%) and endometrium (70%)
*On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
:*T2: hyper-intense to myometrium (90%) either hypo-intense (55%) or isointense (41%) to endometrium.  
*[Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].
*On enhanced CT, findings of mixed Mullerian tumor, may include: 
:*Heterogeneously hypodense and ill defined mass
:*Dilatation of uterine cavity
=== Other Diagnostic Studies ===
=== Other Diagnostic Studies ===
*[Disease name] may also be diagnosed using [diagnostic study name].
*Mixed Mullerian tumor may also be diagnosed using [[laparoscopy]], and FDG PET/CT.  
*Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].
   
   
== Treatment ==
== Treatment ==
=== Medical Therapy ===
=== Medical Therapy ===
*There is no treatment for [disease name]; the mainstay of therapy is supportive care.
*There is no treatment for mixed Mullerian tumor; the mainstay of therapy is supportive care.
*The medical management for mixed Mullerian tumor, include:<ref name="pmid4705156">{{cite journal |vauthors=Abell MR, Ramirez JA |title=Sarcomas and carcinosarcomas of the uterine cervix |journal=Cancer |volume=31 |issue=5 |pages=1176–92 |year=1973 |pmid=4705156 |doi= |url=}}</ref>
*The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
:*[[Chemotherapy]] [[ifosfamide]]-based regimen
*[Medical therapy 1] acts by [mechanism of action1].
:*[[Radiotherapy]] (vaginal brachytherapy)
*Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].
:*Chemotherapy plus radiation therapy
 
=== Surgery ===
=== Surgery ===
*Surgery is the mainstay of therapy for [disease name].
*Surgery is the mainstay of therapy for mixed Mullerian tumor.
*[Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
*Total hysterectomy in conjunction with surgical staging is the most common approach to the treatment of mixed Mullerian tumor.
*[Surgical procedure] can only be performed for patients with [disease stage] [disease name].
*Different surgical procedures for the treatment of  mixed Mullerian tumor, include:<ref name="pmid4705156">{{cite journal |vauthors=Abell MR, Ramirez JA |title=Sarcomas and carcinosarcomas of the uterine cervix |journal=Cancer |volume=31 |issue=5 |pages=1176–92 |year=1973 |pmid=4705156 |doi= |url=}}</ref>
:*[[Hysterectomy|Total hysterectomy]]
:*Bilateral salpingo-oophorectomy
:*Pelvic and para-aortic lymph node dissection
:*Cytology of peritoneal washings
:*Omentectomy
:*Biopsies of peritoneal surfaces
 
=== Prevention ===
=== Prevention ===
*There are no primary preventive measures available for [disease name].
*There are no primary preventive measures available for mixed Mullerian tumor.
*Once diagnosed and successfully treated, patients with mixed Mullerian tumor are followed-up every 6 or 12 months.
*Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
*Follow-up testing include pelvic examination, ultrasound, and biomarker monitorization.  
 
*Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3].  


==References==
==References==

Latest revision as of 23:32, 23 May 2019

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Maria Fernanda Villarreal, M.D. [2]

Synonyms and keywords: Mixed Müllerian tumor; MMMT; Malignant mixed Müllerian tumor; Carcinosarcoma of the uterus; Sarcomatoid carcinoma of the uterus; Malignant mesodermal mixed tumor; Metaplastic carcinoma

Overview

Malignant mixed mullerian tumor (MMMT) is a rare uterine sarcoma or carcinosarcoma. Mixed Mullerian tumors are normally composed of both carcinomatous (epithelial) and sarcomatous (mesodermal) components. Mixed Mullerian tumor may be classified according to pathology findings into 2 types: epitheloid subtype and sarcomatoid subtype. Mixed Mullerian tumor may also be classified according to anatomical location into 7 types: uterine corpus, cervix, ovaries, fallopian tubes, vagina, peritoneum, and extragenital sites. Common risk factors in the development of mixed Mullerian tumor are exposure to radiation, excessive estrogen exposure, obesity, and nulliparity.[1] Mixed Mullerian tumor is more commonly observed among postmenopausal women between 50 and 60 years old. Early clinical features include postmenopausal vaginal bleeding, pelvic pain, and vaginal discharge. Mixed Mullerian tumors are rare, and they only account for 3 to 4% of all uterine malignancies. The estimated prevalence of mixed Mullerian tumor is 3 cases per 100,000 women in the United States. The diagnosis of mixed Mullerian tumor is made with biopsy. Biopsy findings of mixed Mullerian tumor, include: tumor with carcinomatous and sarcoma-like elements and angiolymphatic invasion. Surgery is the mainstay of therapy for mixed Mullerian tumor. Total hysterectomy in conjunction with surgical staging is the most common approach to the treatment of mixed Mullerian tumor. Prognosis is generally poor, and the 5-year survival rate of patients with mixed Mullerian tumor is approximately 33% to 39%.[2]

Historical Perspective

  • Mixed Mullerian tumor was first described by Ferriera and colleagues in 1951.[3]

Classification

  • Mixed Mullerian tumors are normally composed of both carcinomatous (epithelial) and sarcomatous (mesodermal) components.
  • Mixed Mullerian tumor may be classified according to pathology findings into 2 types:

Epitheloid subtype

Sarcomatoid subtype

  • Mixed Mullerian tumor may also be classified according to anatomical location into 7 types:

Pathophysiology

  • The pathogenesis of mixed Mullerian tumor is characterized by epithelial and stromal growth, and the transdifferentiation of uterine carcinoma into sarcoma.[4]
  • The PIK3CA gene has been associated with the development of mixed Mullerian tumor, involving the PI3K pathway.
  • Genes involved in the pathogenesis of mixed Mullerian tumor, include: [5]
  • PIK3CA (50% of the tumors)
  • PTEN (30% of the tumors)
  • PIK3R1 (30% of the tumors)
  • On gross pathology, a large cervical mass is a characteristic finding of mixed Mullerian tumor.
  • On microscopic histopathological analysis, high-grade stromal sarcoma, poorly differentiated epithelial cells, and angiolymphatic invasion are characteristic findings of mixed Mullerian tumor.[6]

Causes

  • The most important cause of mixed Mullerian tumors is the mutation in genes PTEN, ARID1A, PIK3R1, and POLE.[5]
  • Mixed Mullerian tumor may also be caused by chronic estrogen stimulation.

Differentiating Mixed Mullerian tumor from other Diseases

  • Mixed Mullerian tumor must be differentiated from other diseases that cause abnormal vaginal bleeding, abdominal pain, and uterus enlargement such as:

Epidemiology and Demographics

  • Mixed Mullerian tumor is rare, it only accounts for 3 to 4% of all uterine malignancies.[7]
  • The estimated prevalence of mixed Mullerian tumor is 3 cases per 100,000 women in the United States.[7]

Age

  • The median age at diagnosis of Mixed Mullerian tumor is 66 years
  • Mixed Mullerian tumor is more commonly observed among patients aged between 50 and 60 years old.
  • Mixed Mullerian tumor is more commonly observed among postmenopausal women

Race

  • There is no racial predilection for mixed Mullerian tumor.[7]

Risk Factors

Natural History, Complications and Prognosis

  • Early clinical features include postmenopausal vaginal bleeding, pelvic pain, and vaginal discharge.
  • If left untreated, the majority of patients with mixed Mullerian tumor may progress quickly to develop lymph node invasion, metastasis, and death.
  • Prognosis is generally poor, and the 5-year survival rate of patients with Mixed Mullerian tumor is approximately 33% to 39%.
  • Findings associated with good prognosis include p16 and Mcl-1 gene expression.[6]

Diagnosis

Diagnostic Criteria

  • The diagnosis of mixed Mullerian tumor is made with biopsy.
  • Biopsy findings of mixed Mullerian tumor, include:[2]
  • Tumor with carcinomatous and sarcoma-like elements
  • Angiolymphatic invasion

Symptoms

  • Mixed Mullerian tumor may be initially asymptomatic.
  • Symptoms of mixed Mullerian tumor may include the following:[1]
  • Early symptoms
  • Advanced symptoms

Physical Examination

  • Patients with mixed Mullerian tumor may have a normal appearance.
  • Pelvic examination may be remarkable for:[2]

Laboratory Findings

  • Laboratory findings associated with mixed Mullerian tumor, may include:
  • Anemia
  • Elevated CA-125

Imaging Findings

  • Enhanced CT scan and MRI is the imaging modalities of choice for mixed Mullerian tumor.
  • On MRI, findings of mixed Mullerian tumor, may include:[9]
  • T1: predominantly isointense to both myometrium (75%) and endometrium (70%)
  • T2: hyper-intense to myometrium (90%) either hypo-intense (55%) or isointense (41%) to endometrium.
  • On enhanced CT, findings of mixed Mullerian tumor, may include:
  • Heterogeneously hypodense and ill defined mass
  • Dilatation of uterine cavity

Other Diagnostic Studies

  • Mixed Mullerian tumor may also be diagnosed using laparoscopy, and FDG PET/CT.

Treatment

Medical Therapy

  • There is no treatment for mixed Mullerian tumor; the mainstay of therapy is supportive care.
  • The medical management for mixed Mullerian tumor, include:[9]

Surgery

  • Surgery is the mainstay of therapy for mixed Mullerian tumor.
  • Total hysterectomy in conjunction with surgical staging is the most common approach to the treatment of mixed Mullerian tumor.
  • Different surgical procedures for the treatment of mixed Mullerian tumor, include:[9]
  • Total hysterectomy
  • Bilateral salpingo-oophorectomy
  • Pelvic and para-aortic lymph node dissection
  • Cytology of peritoneal washings
  • Omentectomy
  • Biopsies of peritoneal surfaces

Prevention

  • There are no primary preventive measures available for mixed Mullerian tumor.
  • Once diagnosed and successfully treated, patients with mixed Mullerian tumor are followed-up every 6 or 12 months.
  • Follow-up testing include pelvic examination, ultrasound, and biomarker monitorization.

References

  1. ↑ 1.0 1.1 1.2 Kanthan R, Senger JL, Diudea D (2010). "Malignant mixed Mullerian tumors of the uterus: histopathological evaluation of cell cycle and apoptotic regulatory proteins". World J Surg Oncol. 8: 60. doi:10.1186/1477-7819-8-60. PMC 2913917. PMID 20642852.
  2. ↑ 2.0 2.1 2.2 Clement PB, Zubovits JT, Young RH, Scully RE (1998). "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): 211–22. PMID 9656116.
  3. ↑ Wright JD, Rosenblum K, Huettner PC, Mutch DG, Rader JS, Powell MA, Gibb RK (2005). "Cervical sarcomas: an analysis of incidence and outcome". Gynecol. Oncol. 99 (2): 348–51. doi:10.1016/j.ygyno.2005.06.021. PMID 16051326.
  4. ↑ D'Angelo E, Prat J. Pathology of mixed Mullerian tumours. Best Pract Res Clin Obstet Gynaecol. 2011;25:705-718.
  5. ↑ 5.0 5.1 Mutation Profiling in Uterine Carcinosarcoma / Malignant Mixed Mullerian Tumors. Melissa McConechy; David Huntsman, MD. ESUN. http://sarcomahelp.org/carcinosarcoma.html Accessed on April 7, 2016
  6. ↑ 6.0 6.1 Maheshwari A, Gupta S, Shet T, Wuntkal R, Tongaonkar HB (2006). "Diagnostic dilemma in a case of malignant mixed mullerian tumor of the cervix". World J Surg Oncol. 4: 36. doi:10.1186/1477-7819-4-36. PMC 1526432. PMID 16813659.
  7. ↑ 7.0 7.1 7.2 Brooks SE, Zhan M, Cote T, Baquet CR (2004). "Surveillance, epidemiology, and end results analysis of 2677 cases of uterine sarcoma 1989-1999". Gynecol. Oncol. 93 (1): 204–8. doi:10.1016/j.ygyno.2003.12.029. PMID 15047237.
  8. ↑ Kong A, Johnson N, Kitchener HC, Lawrie TA (2012). "Adjuvant radiotherapy for stage I endometrial cancer". Cochrane Database Syst Rev. 4: CD003916. doi:10.1002/14651858.CD003916.pub4. PMC 4164955. PMID 22513918.
  9. ↑ 9.0 9.1 9.2 Abell MR, Ramirez JA (1973). "Sarcomas and carcinosarcomas of the uterine cervix". Cancer. 31 (5): 1176–92. PMID 4705156.
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