Malignant mixed tumor

Vagina
Malignant tumors
Malignant mixed tumor

Author: Shweta Gera, M.D. (see Authors page)
Editor: Arzu Buyuk, M.D.

Revised: 28 September 2017, last major update July 2014

Copyright: (c) 2002-2017, PathologyOutlines.com, Inc.

PubMed Search: Malignant mixed tumor vagina

Table of Contents

Cite this page: Gera, S. Malignant mixed tumor. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/vaginaMMT.html. Accessed April 26th, 2018.

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:
1. Location in the vagina without involvement of the cervix or vulva
2. Mixed histological appearance of (a) squamous or glandular and (b) spindle cell elements, showing mitoses and atypia
3. Invasion and possible metastasis
4. 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)