Malignant Mixed Tumor

Synonyms: Carcinoma Ex Pleomorphic Adenoma, Salivary Gland Carcinosarcoma

Carcinoma (right) with atypical large cells arising in pleomorphic adenoma

Definition

Carcinoma arising in a preexisting pleomorphic adenoma. Carcinosarcoma arising de novo is a distinct type of malignant mixed tumor.

Clinical Features

Malignant transformation of a pre-existing benign mixed tumor:
- clinical features include:
  - sudden increase in growth
  - pain
  - facial paralysis1–3
  - often a history of previous surgery and/or radiation therapy
- may be difficult to obtain history of a preexistent benign mixed tumor
Features said to indicate greater likelihood of malignant transformation of a mixed tumor:
- submandibular location
- older age
- large tumor size
Metastases:
- most common sites:
  - abdominal organs 4

Histopathology

Malignant transformation of a pre-existing benign mixed tumor:
- need microscopic evidence of:
  - a previously existing benign tumor:
    - sometimes represented by only a totally hyalinized round nodule surrounded by carcinoma, or
    - benign and malignant tumor in same neoplasm
  - thorough sampling may be required
- Features said to indicate a greater likelihood of malignant transformation of a mixed tumor:
  - prominent zones of hyalinization
  - moderate mitotic activity5
- Malignant component always has an epithelial appearance (Fig. 1
  Fig. 1: Benign mixed tumor (left) with area of malignant transformation in the form of poorly differentiated carcinoma (right).
  ):
  - rarely appearance of a well-recognized variant of salivary gland carcinoma2,6–8
  - in one series, malignant component was classified as:
    - unclassified in 2 9
  - usually poorly differentiated

Special Stains and Immunohistochemistry

B72.3:
- extensive immunoreactivity more common in malignant than benign mixed tumors10
In malignant areas commonly:
- overexpression of
  - p53 (due to mutation)
  - c-erbB-211,12

Diagnosis

Two major categories:9,13
- more common type:
  - a complication in ≈ 5–10% of these neoplasms 6,14
  - cytologically malignant foci entirely within a benign mixed tumor (i.e. carcinoma in situ) are not associated with clinical malignancy:13
  - behaves in a malignant fashion only when invasion occurs beyond capsule
- the second type:
  - has a biphasic composition similar to that of benign mixed tumor, but both elements have a malignant appearance with:3,14–17
  - the epithelial element often in the form of a ductal carcinoma
  - the mesenchyme-like element in the form of chondrosarcoma
  - aggressive and often rapidly lethal

Differential Diagnosis

Select up to 2 differential diagnoses to compare with Malignant Mixed Tumor

Prognosis

Depends on:
- histologic type
- microscopic grade (related to histologic type)
- proliferative index9,18
Extent of invasion beyond capsule important:
- in one series all patients with extension >8 mm beyond capsule died of tumor 9

References

1 Eneroth C-M. Histological and clinical aspects of parotid tumours. Acta Otolarynol (Stockh). 1964;191(Suppl):1–99.

2 Gnepp DR. Malignant mixed tumors of the salivary glands. A review. Pathol Annu. 1993;28(Pt 1):279–328.

3 Spiro RH, Huvos AG, Strong EW. Malignant mixed tumor of salivary origin. A clinicopathologic study of 146 cases. Cancer. 1977;39:388–396.

4 Thomas WH, Coppola ED. Distant metastasis from mixed tumors of the salivary glands. Am J Surg. 1965;109:724–730.

5 Auclair PL, Ellis GL. Atypical features in salivary gland mixed tumors: Their relationship to malignant transformation. Mod Pathol. 1996;9:652–657.

6 Moberger JG, Eneroth C-M. Malignant mixed tumors of the major salivary glands. Special reference to the histologic structure in metastases. Cancer. 1968;21:1198–1211.

7 Batsakis JG. Carcinoma ex pleomorphic adenoma's “Big Tent” has room for low- and high-grade tumors. Adv Anat Pathol. 1997;4:176–178.

8 Lewis JE, Olsen KD, Sebo TJ. Carcinoma ex pleomorphic adenoma: pathologic analysis of 73 cases. Hum Pathol. 2001;32:596–604.

9 Tortoledo ME, Luna MA, Batsakis JG. Carcinomas ex pleomorphic adenoma and malignant mixed tumors. Histomorphologic indexes. Arch Otolaryngol. 1984;110:172–176.

10 Brandwein MS, Huvos AG, Patil J, Jagirdar J. Tumor-associated glycoprotein distribution detected by monoclonal antibody B72.3 in salivary neoplasia. Cancer. 1992;69:2623–2630.

11 Rosa JC, Fonseca I, Felix A, Soares J. Immunohistochemical study of C-erbB-2 expression in carcinoma ex-pleomorphic adenoma. Histopathology. 1996;28:247–252.

12 Yamamoto Y, Kishimoto Y, Wistuba II, Virmani AK, Vuitch F, Gazdar AF, et al. DNA analysis at p53 locus in carcinomas arising from pleomorphic adenomas of salivary glands: Comparison of molecular study and p53 immunostaining. Pathol Int. 1998;48:265–272.

13 LiVolsi VA, Perzin KH. Malignant mixed tumors arising in salivary glands. I. Carcinomas arising in benign mixed tumors. A clinicopathologic study. Cancer. 1977;39:2209–2230.

14 Nagao K, Matsuzaki O, Saiga H, Sugano I, Shigematsu H, Kaneko T, et al. Histopathologic studies on carcinoma in pleomorphic adenoma of the parotid gland. Cancer. 1981;48:113–121.

15 Bleiweiss IJ, Huvos AG, Lara J, Strong EW. Carcinosarcoma of the submandibular salivary gland. Immunohistochemical findings. Cancer. 1992;69:2031–2035.

16 Stephen J, Batsakis JG, Luna MA, von der Heyden U, Byers RM. True malignant mixed tumors (carcinosarcoma) of salivary glands. Oral Surg Oral Med Oral Pathol. 1986;61:597–602.

17 Yamashita T, Kameda N, Katayama K, Hiruta N, Nakada M, Takeda Y. True malignant mixed tumor of the submandibular gland. Acta Pathol Jpn. 1990;40:137–142.

18 Xin W, Paulino AFG. Prognostic factors in malignant mixed tumors of the salivary gland: correlation of immunohistochemical markers with histologic classification. Ann Diagn Pathol. 2002;6:205–210.

Last updated: 7 Jan 2006