General
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• 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
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• Also called vaginal carcinosarcoma (Arch Gynecol Obstet 2005;271:264)

Epidemiology
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• Extremely rare
• Postmenopausal women, mean age 66 years, range 61-74 years (Gynecol Oncol 1998;70:303)

Sites
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• 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
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• 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 mullerian tract as well as ovary and peritoneum, and may arise from glandular or squamous precursors (Gynecol Oncol 1998;70:303)

Etiology
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• 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
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• Vaginal bleeding, vaginal discharge that is often foul smelling (Gynecol Oncol 1998;70:303, Arch Gynecol Obstet 2005;271:264)

Diagnosis
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• 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
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• Chest x-ray, CT scan of the abdomen and pelvis to look for metastases and stage the tumor

Prognostic factors
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• 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
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• 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
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• 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
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• 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)

Micro description
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• Tumor is composed of intimately associated epithelial and mesenchymal components
• The 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
• The sarcomatous component may be homologous (fibroblasts and smooth muscle) or heterologous (cartilage, striated muscle, bone, etc.)
• The 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)

Micro images
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Carcinosarcoma

 

Various images

Cytology description
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• Both epithelial and spindle cells elements can be seen on pap smear
• The 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
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Pap stain

Positive stains
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• 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
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• 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
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• 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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