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Concomitant Well-Differentiated Adenocarcinoma and Leiomyosarcoma of the Uterus.



The occurrence of neoplasms involving different organs or tissues, either concurrently or in succession, is a phenomenon that has long been observed but continues to be little understood.[1] The most frequent concomitant genital tumors reported in the medical literature are ovarian and endometrial cancers.[2] We present the clinical and pathologic findings from a patient initially diagnosed with endometrial endometrial /en·do·me·tri·al/ (en?do-me´tre-il) pertaining to the endometrium.
endometrial,
n relating to the end-ometrium or cavity of the uterus.
 endometrioid adenocarcinoma who later underwent total hysterectomy and was found to have concomitant tumors of endometrium endometrium /en·do·me·tri·um/ (-me´tre-um) pl. endome´tria   the mucous membrane lining the uterus.

en·do·me·tri·um
n. pl.
 and myometrium myometrium /myo·me·tri·um/ (-me´tre-um) the tunica muscularis of the uterus.myome´trial

my·o·me·tri·um
n.
The muscular wall of the uterus.
.

REPORT OF A CASE

A 66-year-old postmenopausal woman (gravida 1, para 1) presented in July of 1998 with vaginal bleeding of approximately 6 months' duration. The patient had a past medical history of essential hypertension, atrial fibrillation, type 2 diabetes mellitus Type 2 diabetes mellitus
One of the two major types of diabetes mellitus, characterized by late age of onset (30 years or older), insulin resistance, high levels of blood sugar, and little or no need for supple-mental insulin.
, hypothyroidism, osteoarthritis, and moderate obesity. A Papanicolaou test performed at the time of clinical examination revealed malignant tumor cells consistent with a papillary papillary /pap·il·lary/ (pap´i-lar?e) pertaining to or resembling a papilla, or nipple.
papillary,
adj similar to a small, nipple-shaped elevation or projection.
 endometrial adenocarcinoma. The patient was referred to the University of Cincinnati Medical Center, where pelvic ultrasound and endometrial biopsy were performed. Pelvic ultrasound revealed a posterior uterine fibroid. Endometrial biopsy showed a well-differentiated endometrial adenocarcinoma. Total hysterectomy with lymph node sampling was performed at the University of Cincinnati Medical Center.

Gross Findings

The specimen from the total abdominal hysterectomy to·tal abdominal hysterectomy
n. Abbr. TAH
An abdominal hysterectomy in which the uterus and cervix are removed.


total abdominal hysterectomy 
 consisted of a 410-g, 12 x 10 x 8-cm uterus; fallopian tubes; and ovaries. Examination of the endometrial cavity revealed a yellow-tan endometrial fungating mass approximately 0.9 cm in the largest dimension. Beneath the endometrial mass but separated by normal-appearing myometrium was a 3-cm, well-circumscribed, soft nodule with irregular margins contained within the myometrium. The cut surface was yellow-gray with areas of softening and necrosis (Figure 1).

[Figure 1 ILLUSTRATION OMITTED]

Histologic Findings

The microscopic appearance of the endometrial portion of the tumor exhibited features of a well-differentiated endometrioid adenocarcinoma with minimal myometrial invasion (Figure 2, a). The sections of the underlying myometrial nodule showed fascicles of very pleomorphic pleomorphic adjective Referring to a variable appearance or morphology  spindle cells with abundant eosinophilic eosinophilic /eo·sin·o·phil·ic/ (-fil´ik)
1. readily stainable with eosin.

2. pertaining to eosinophils.

3. pertaining to or characterized by eosinophilia.
 cytoplasm. The nuclei were fusiform fusiform /fu·si·form/ (-form) shaped like a spindle; tapered at each end.

fu·si·form
adj.
Tapering at each end; spindle-shaped.



fusiform

spindle-shaped.
 with rounded ends and hyperchromatic coarse chromatin (Figure 2, b). Prominent nucleoli nucleoli

plural form of nucleolus.
 were present. Numerous multinucleated multinucleated

characterized by having more than one nucleus per cell.


multinucleated giant cell
see giant cell.
 tumor cells were noted, as well as high mitotic activity (greater than 10 mitotic figures per 10 high-power fields). Tumor cell necrosis was prominent. A zone of histologically normal myometrium separated the myometrial neoplasm from the endometrial carcinoma (Figure 3). No intermixture of epithelial and sarcomatous components was present. There were no features of endometrial stromal sarcoma endometrial stromal sarcoma
n.
A rare sarcoma in which the lesions form multiple foci in the myometrium and in vascular spaces in other sites and the tissue and cells resemble endometrial stroma cells.
. No heterologous heterologous /het·er·ol·o·gous/ (het?er-ol´ah-gus)
1. made up of tissue not normal to the part.

2. xenogeneic.


het·er·ol·o·gous
adj.
1.
 elements were present. Immunohistochemical studies with cytokeratin antibodies to AE1 and AE3/CAM5 (AE1/AE3, Boehringer Mannheim Biochemica, Indianapolis, Ind; CAM5.2, Becton Dickinson, San Jose, Calif) revealed strong immunoreactivity of the endometrial endometrioid adenocarcinoma and no reaction of the high-grade leiomyosarcoma.

[Figures 2-3 ILLUSTRATION OMITTED]

Hyperplasia was present in both ovaries. The fallopian tubes were unremarkable.

COMMENT

Concomitant primary malignancies of the ovary and endometrium, ovary and breast, and breast and cervix have been reported. To our knowledge, no case of a concomitant endometrial endometrioid adenocarcinoma and leiomyosarcoma of the uterus has been reported in the English literature.

The occurrence of a neoplasm involving different organs or tissues in the same patient, either concomitantly or in succession, is a phenomenon that has long been observed but continues to be poorly understood.[1] Billroth[3] reported the first case of multiple primary neoplasms in 1879.

Several hypotheses have been suggested to explain occurrence of multiple primary neoplasms in the female genital tract. One of the theories postulated by Lauchlan[4] and later by Woodruff et al[5] suggested that malignancies arising in spatially separated foci may represent metaplasia occurring in similar histologic epithelia under the same oncogenic oncogenic /on·co·gen·ic/ (-jen´ik) giving rise to tumors or causing tumor formation; said especially of tumor-inducing viruses.

on·co·gen·ic or on·cog·e·nous
adj.
 stimuli.[6]

Sica et al[7] stated that shared hormonal receptors (eg, estrogen receptors) may be responsible for the development of multiple primary malignancies in predisposing tissue.

Carcinosarcomas, although uncommon, have well-defined histomorphologic features. This tumor was the main differential diagnosis in our case. The differentiation of carcinoma into sarcomatous elements (metaplastic or sarcomatoid carcinomas) has created considerable discussion, and its occurrence has been suggested in several organs, including squamous epithelium-lined mucosal surfaces, the breast, and the genitourinary tract.[8] Current evidence suggests that carcinosarcomas are either "metaplastic carcinomas" or that they are neoplasms undergoing bilateral differentiation. The theory that carcinosarcomas are carcinomas undergoing sarcomatous transformation is best supported by light microscopic, immunohistochemical, ultrastructural, and in vitro evidence. By light microscopy, carcinosarcomas are characterized by a mixture of malignant epithelial and mesenchymal elements. Endometrioid carcinoma is the most common epithelial pattern followed by adenosquamous, serous serous /se·rous/ (ser´us)
1. pertaining to or resembling serum.

2. producing or containing serum.


se·rous
adj.
Containing, secreting, or resembling serum.
, and clear-cell carcinoma. Homologous sarcoma has the typical appearance of spindle-cell sarcoma, resembling high-grade endometrial stromal sarcoma, leiomyosarcoma, fibrosarcoma fibrosarcoma /fi·bro·sar·co·ma/ (-sahr-ko´mah) a malignant, locally invasive, hematogenously spreading tumor derived from collagen-producing fibroblasts that are otherwise undifferentiated. , malignant fibrous histiocytoma malignant fibrous histiocytoma
n.
A deeply situated tumor, especially on the extremities of adults, frequently recurring after surgery and metastasizing to the lungs.
, or undifferentiated sarcoma. Heterologous foci ordinarily merge with the undifferentiated homologous sarcoma and, in decreasing order of frequency, include rhabdomyosarcoma rhabdomyosarcoma /rhab·do·myo·sar·co·ma/ (mi?o-sahr-ko´mah) a highly malignant tumor of striated muscle derived from primitive mesenchymal cells. , chondrosarcoma, osteosarcoma osteosarcoma /os·teo·sar·co·ma/ (os?te-o-sahr-ko´mah) a malignant primary neoplasm of bone composed of a malignant connective tissue stroma with evidence of malignant osteoid, bone, or cartilage formation; it is subclassified as , and liposarcoma. Immunohistochemical studies have shown markers of epithelial differentiation in stromal cells and coexpression of several immunohistochemical markers by both components. These features seen in carcinosarcoma were not present in our case and immunohistochemical studies did not support the diagnosis of malignant mixed-mullerian tumor. Therefore, we concluded that our case represents a concomitant occurrence of an endometrial endometrioid adenocarcinoma and leiomyosarcoma as separate tumors and not a malignant mixed-mullerian tumor as most frequent is the case.

In summary, the development of concomitant neoplasms in the uterus is an event that can be observed.

References

[1.] Porta RP, Lalle M, Palazzetti PL, Villani C, Pachi A, Stentella P. Multiple primary neoplasms. Consideration on 42 cases. Eur J Gynaecol Oncol. 1995;6: 482-487.

[2.] Eisner RF, Nieberg RK, Berek JS. Synchronous primary neoplasms of the female reproductive tract. Gynecol Oncol. 1989;33:335-339.

[3.] Billroth T. Wien 1871-6; nebs einem gesamnt-bericht uber die chirurgischen kliniken in Zurich und Wien wahrend der jarhe 1870-6: erfahrungen auf dem gebiete der praktischen chirurgie [Experiments in a field of practical surgery]. Chirurgische Klinik. 1879; 258.

[4.] Lauchlan SC. Conceptual unity of the mullerian tumor group. Cancer. 1968; 22:601-610.

[5.] Woodruff D, Solomon D, Sullivant H. Multifocal multifocal /mul·ti·fo·cal/ (mul?te-fo´k'l) arising from or pertaining to many foci.

mul·ti·fo·cal
adj.
Relating to or arising from many foci.
 disease in the upper genital canal. Obstet Gynecol. 1985;65:695-698.

[6.] Lauchlan SC. The secondary mullerian system revisited. Int J Gynecol Pathol. 1994;13:543-557.

[7.] Sica V, Nola E, Contieri E, et al. Estradiol and progesterone receptors in malignant gastrointestinal tumors. Cancer Res. 1984;44:4670-4674.

[8.] Mira JL, Fenoglio-Preiser CM, Husseinzadeh N. Malignant mixed mullerial tumor of the extraovarian secondary mullerian system. Report of two cases and review of the English literature. Arch Pathol Lab Med. 1995;119:1044-1048.

Accepted for publication March 6, 2000.

From the Departments of Pathology (Drs Sheyn and Blanco) and Obstetrics and Gynecology (Drs Walton and Husseinzadeh), University of Cincinnati Medical Center, Cincinnati, Ohio, and the Department of Pathology, Texas Tech University, Lubbock, Tex (Dr Mira).

Reprints: Jose L. Mira, MD, Director of Surgical Pathology and Cytopathology, Department of Pathology, Texas Tech University Health Science Center, 3601 4th St, Lubbock, TX 79430 (e-mail: pthjilm@ttuhsc.edu).
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Author:Sheyn, Irena; Mira, Jose L.; Blanco, Ramon; Walton, Mava B.; Husseinzadeh, Nader
Publication:Archives of Pathology & Laboratory Medicine
Date:Oct 1, 2000
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