Mixed carcinomas

Topic Completed: 1 August 2011

Minor changes: 25 February 2019

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PubMed search: mixed [title] carcinoma uterus

Mohamed Mokhtar Desouki, M.D., Ph.D.
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Cite this page: Desouki M. Mixed carcinomas. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/uterusmixedcarcinoma.html. Accessed August 10th, 2020.
Definition / general
  • Endometrial adenocarcinoma composed of both type I (endometrioid) and type II (serous or clear cell type) tumors, with at least 10% of each component
  • Also called mixed cell adenocarcinoma
  • Sixty percent of patients with uterine papillary serous carcinomas (UPSC) have pure tumors and 40% also have endometrioid or clear cell components
  • Type I tumors are associated with endometrial hyperplasia, mostly due to prolonged estrogenic stimulation or from estrogen secreting tumors
  • Type II tumors are estrogen independent; usually arise on atrophic endometrium or post radiation therapy for cervical carcinoma; are associated with p53 mutations
Clinical features
  • Average age 62 years
  • Poor prognosis if > 25% type II tumor; impact of type II component unclear if < 25%
  • Mixed carcinomas with > 50% serous have 5 year survival of 40%, with 46% of deaths in first year
  • Mixed carcinomas with predominant endometrioid type have 5 year survival of 67%
  • No correlation between the stage and 5 year survival
Prognostic factors
  • Papillary serous component has poor prognosis, but similar 5 year survival of 44% if pure or mixed
Case reports
  • A 46 year old woman with menorrhagia and dysmenorrhea for 2 years presented to the hospital. USG showed a thickened endometrium. A hysterectomy was done (Case of the week #422)
  • Treat patients with pure or mixed serous similarly
  • Systemic chemotherapy if high stage disease
Gross description
  • Usually large uterus due to myometrial invasion, but uterus may be normal / small if primarily high grade type II component
Microscopic (histologic) description
  • Mixture of type I and type II tumors, usually with background of endometrial hyperplasia
  • Type I component usually formed of back to back glands of varying differentiation with minimal to absent intervening desmoplastic stroma, with occasional foamy cells due to tumor necrosis
  • Any variant of classic endometrioid tumor could be seen
  • Type II component may have serous morphology with well formed papillae or tubules with highly pleomorphic tumor cells containing prominent nucleoli, detached buds and tufts, frequent mitotic activity, tumor necrosis and prominent myometrial invasion
  • May resemble villoglandular carcinoma
  • Type II component may have clear cell architecture with atypical large and clear to rarely eosinophilic cells

Mixed carcinoma patterns:
  • 1) Typical serous carcinoma as described above with typical high grade endometrioid carcinoma with sharp, distinct separation (most common pattern)
  • 2) Some of tumor has microscopic features intermediate between serous and endometrioid; for example, papillary architecture typical of serous but without classical cytologic features or glandular architecture with epithelial features suggestive of serous (less common type, Int J Gynecol Cancer 1994;4:7)
  • Lymphovascular space invasion in 31%, myoinvasion in > 50%, adnexal involvement in 19%, cervical involvement in 6%
Microscopic (histologic) images

Images hosted on PathOut server:

Mixed endometrial carcinoma, Case of the Week #422

Mixed endometrial carcinoma, Case of the Week #422

Cytology description
  • Type I component cells are single or in three dimensional clusters; cytoplasm is delicate with a single large vacuole with or without neutrophils; high grade tumors have clumped chromatin with prominent but small nucleoli
  • Type II component has marked variation in nuclear size with irregular nuclear outlines, chromatin clumping, clearing and necrosis
  • Serous carcinoma cells arrange in true papillae lined with many cells with overlapping nuclei; cells are large, better preserved and with indistinct cell borders; nuclear chromatin is coarse with large prominent nucleoli
Board review style question #1
Which of the following does not represent an example of mixed endometrial carcinoma:

A. Villoglandular carcinoma and clear cell carcinoma
B. Mucinous carcinoma and serous carcinoma
C. Chondrosarcoma and rhabdomyosarcoma in a malignant mixed Müllerian tumor
D. High grade endometrioid adenocarcinoma and serous carcinoma
Board review answer #1
C. Chondrosarcoma and rhabdomyosarcoma in a malignant mixed Müllerian tumor
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