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Table of Contents
Definition / general | Terminology | Epidemiology | Sites | Pathophysiology | Etiology | Clinical features | Diagnosis | Radiology description | Prognostic factors | Case reports | Treatment | Gross description | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Cytology images | Positive stains | Negative stains | Differential diagnosisCite this page: Gera S. Malignant mixed tumor. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/vaginaMMT.html. Accessed May 19th, 2019.
Definition / general
- Primary vaginal biphasic tumor with malignant epithelial and malignant spindle cell elements with atypia and mitoses
- No evidence of another primary malignancy that may give rise to vaginal metastases
Terminology
- Also called vaginal carcinosarcoma (Arch Gynecol Obstet 2005;271:264)
Epidemiology
- Extremely rare
- Postmenopausal women, mean age 66 years, range 61 - 74 years (Gynecol Oncol 1998;70:303)
Sites
- Usually lower and middle vagina (Gynecol Oncol 1998;70:303)
- Most common site of this tumor in the female genital tract is the endometrium, followed by ovary, fallopian tube, cervix and vagina (Pathol Res Pract 2011;207:253)
Pathophysiology
- Not clearly known - theories include collision, combination, composition, metaplastic
- Collision: carcinosarcoma has biclonal origin with two separate but synchronous neoplastic clones fusing to form a "collision" tumor
- Combination: neoplasms are monoclonal and the carcinomatous and sarcomatous elements share a common stem cell
- Composition: mesenchymal component is not truly neoplastic but reactive; not a valid theory because this component is always malignant on histology
- Metaplastic: recent theory that favors a common cell origin like the combination theory but suggests that the epithelial or the mesenchymal component gives rise to the other via metaplasia of a subclonal population (Arch Gynecol Obstet 2005;271:264)
- HPV 16 has been detected in both epithelial and sarcomatous elements, supporting metaplastic theory of histogenesis (Am J Surg Pathol 2001;25:338) although the role of HPV has not been clearly defined
- May originate from any site in Müllerian tract as well as ovary and peritoneum and may arise from glandular or squamous precursors (Gynecol Oncol 1998;70:303)
Etiology
- In one study, in four of seven patients (57%), tumor was preceded by pelvic irradiation (Gynecol Oncol 1998;70:303)
- Associated with high grade vaginal intraepithelial neoplasia (VAIN 3) with koilocytic atypia and HPV infection (Gynecol Oncol 1998;70:303, Arch Gynecol Obstet 2005;271:264, Hum Pathol 2007;38:1282)
- In situ hybridization showed a dot-like positive staining in virtually every nucleus for HPV types 31 / 33 / 51, indicating viral integration into the host genome (Hum Pathol 2007;38:1282)
Clinical features
- Vaginal bleeding, vaginal discharge that is often foul smelling (Gynecol Oncol 1998;70:303, Arch Gynecol Obstet 2005;271:264)
Diagnosis
- Diagnosis of primary MMMT of the vagina should be based on the following:
- Location in the vagina without involvement of the cervix or vulva
- Mixed histological appearance of (a) squamous or glandular and (b) spindle cell elements, showing mitoses and atypia
- Invasion and possible metastasis
- Lack of evidence of other primary malignancy that may have given rise to vaginal metastasis (Gynecol Oncol 1998;70:303, Arch Gynecol Obstet 2005;271:264, South Med J 1975;68:1239)
Radiology description
- Chest Xray, CT scan of the abdomen and pelvis to look for metastases and stage the tumor
Prognostic factors
- Poor prognosis
- According to one study, 57% of the patients died within 23 months and one patient developed a neck node metastasis within 6 months
- Can metastasize to distant sites like supraclavicular nodes (Gynecol Oncol 1998;70:303)
Case reports
- 48 year old perimenopausal woman (Pathol Res Pract 2011;207:253)
- 57 year old woman (Hum Pathol 2007;38:1282)
- 74 year old woman (Arch Gynecol Obstet 2005;271:264)
- 75 year old woman (Pathol Int 2003;53:106)
Treatment
- Depending on patient age, stage and tumor size, includes radiation, wide local excision, hysterectomy with vaginectomy, total pelvic exentration (Gynecol Oncol 1998;70:303, Obstet Gynecol 1985;65:699)
- Surgery followed by radiotherapy is the currently favored management although the prognosis is very poor even after treatment
- Radiation can be given as adjuvant external radiotherapy (Arch Gynecol Obstet 2005;271:264)
- Chemotherapy has a limited role in these tumors (Pathol Res Pract 2011;207:253) and includes cyclophosphamide, vincristine, aclacinomycin A and dacarbazine (J Obstet Gynaecol Res 1998;24:7)
Gross description
- Polypoid or ulcerated mass, up to 8 cm
- Cut surfaces may be variegated, hemorrhagic, gray, yellow or gelatinous (Gynecol Oncol 1998;70:303, Arch Gynecol Obstet 2005;271:264, Hum Pathol 2007;38:1282)
Microscopic (histologic) description
- Tumor is composed of intimately associated epithelial and mesenchymal components
- Epithelial component could be a variety of histological subtypes, alone or in combination, including squamous cell carcinoma, basaloid squamous carcinoma, adenocarcinoma, adenosquamous carcinoma, adenoid basal carcinoma, adenoid cystic carcinoma, undifferentiated carcinoma
- Sarcomatous component may be homologous (fibroblasts and smooth muscle) or heterologous (cartilage, striated muscle, bone, etc.)
- Predominant epithelial component is squamous cell carcinoma, while heterologous elements are rare (Pathol Res Pract 2011;207:253)
- Necrosis can also be present (Gynecol Oncol 1998;70:303)
Microscopic (histologic) images
Images hosted on other servers:
Carcinosarcoma
Various images
Cytology description
- Both epithelial and spindle cells elements can be seen on Pap smear
- Carcinomatous component is poorly differentiated with a high nuclear/cytoplasmic ratio and can be confused with squamous carcinoma in situ
- Atypical spindle cells may represent sarcomatous component
- Necrotic tumor diathesis can be present in the background (Am J Clin Pathol 2004;122:434)
Cytology images
Images hosted on other servers:
Pap stain
Positive stains
- Epithelial elements (squamous and glandular) are positive for broad spectrum keratin and EMA
- Spindle cell component is positive for vimentin and smooth muscle actin (Gynecol Oncol 1998;70:303, Arch Gynecol Obstet 2005;271:264)
Negative stains
- Epithelial elements are negative for vimentin and spindle cell component is negative for keratin
- Both components are negative for ER and PR receptors (Gynecol Oncol 1998;70:303)
Differential diagnosis
- Benign mixed tumor: composed of benign epithelial and stromal elements; presents as a polyp around hymenal ring; no invasion or metastasis (Gynecol Oncol 1998;70:303)
- Endometrial stromal sarcoma (Gynecol Oncol 1998;70:303)
- Metastasis
- Sarcomatoid carcinoma: spindled component retains the staining characteristics of a carcinoma (positive for cytokeratin, negative for vimentin, Hum Pathol 2007;38:1282, Pathol Res Pract 2011;207:253)
- Squamous cell carcinoma with spindle cell sarcoma-like appearance (Arch Gynecol Obstet 2005;271:264)
- Squamous cell carcinoma invading a fibroepithelial polyp with atypical stroma: presence of diffuse atypia and mitotic activity helps in differentiating (Hum Pathol 2007;38:1282)
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