Introduction

Pure oncocytic carcinoma of the endometrium is very rare, and few such cases have been reported [1]. Tumor cells possess oncocytic cytoplasm, which contains many mitochondria, as observed in ultrastructural studies [1]. Immunohistochemistry reveals that these tumors are positive for p53 and negative for estrogen receptor (ER) and progesterone receptor (PgR) [1]. The immunostaining pattern in pure oncocytic carcinoma is different from that in common endometrioid adenocarcinoma [2]. Thyroid transcription factor 1 (TTF-1) expression in some endometrial cancers has been recently reported [3]. The breast cancer of this patient was resected 12 years ago. Breast cancers occasionally metastasize to the endometrium [4]. The immunohistochemical profile differs between breast cancers and oncocytic endometrial carcinoma [1, 5]. Therefore, in this case we could differentiate between endometrial oncocytic carcinoma and endometrial carcinoma metastasized from breast cancer.

Case report

A 80-year-old woman, gravida 2, para 2, was admitted to the Tokai University Hospital with the chief complaint of genital bleeding. She had a history of breast cancer for the last 12 years, which was resected, following which she underwent postoperative chemotherapy (tamoxifen) for 1 year. The cancer was not recurrent until this episode. Endometrial cancer was suggested by ultrasonography and computed tomography scans. No tumor lesions were detected in other sites, such as the thyroid and adrenal glands. There was no local recurrence of breast cancer. The tumor markers CEA, CA19-9, and CA125 were within normal limits. Endometrial biopsy showed malignancy. The FIGO stage of the tumor was clinically diagnosed as stage Ib endometrial carcinoma, and the patient underwent hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node dissection. Ascitic fluid is not found clinically. However, tumor cells are detected by peritoneal wash. The FIGO stage was pathologically diagnosed as stage IIIa.

The patient was treated with chemotherapy (paclitaxel and carboplatin). No recurrence of the tumor was found 5 months after surgery.

Materials and methods

Histological studies included light microscopic, histochemical, and immunohistochemical examinations. Sections were processed and stained simultaneously for each antibody by the indirect immunoperoxidase method using a manual technique or an automatic immunostainer (Ventana, Tucson, AZ). Envision/HRP kits (DAKO, Carpinteria, CA) were used for detection using the manual technique. As shown in Table 1, ten commercially available antibodies were used in this study to analyze the tumors. These included antimitochondrial antigen (AMA), p53, ER, PgR, GCDFP-15, mammaglobin (MMG), c-erbB-2, TTF-1, thyroglobulin, and Ki-67 antibodies. The results of immunostaining for each antibody were evaluated. When fewer than 50% cells were positively stained, the results were classified as + and when more than 50% cells were stained positively they were classified as ++.

Table 1 Primary antibodies used in immunohistochemistry
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Results

Macroscopically, the tumor was a whitish solid mass, 5 cm × 6 cm × 4 cm in size. The tumor was located in the uterine body, focally occupying the cervix (Fig. 1).

Fig. 1
figure 1

Endophytic and exophytic growth of a solid mass was found in the uterine body

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Microscopically, the tumor cells were arranged in loose, solid, or solid-tubular nests in a focal papillary manner. Most of the tumor cells possessed abundant oncocytic cytoplasm and enlarged round or oval nuclei with prominent nucleoli (Fig. 2). The tumor invaded more than half of the myometrium. Intraepithelial extension to the cervical glands was focally observed (Fig. 3). Oncocytic metaplasia was not found in the non-neoplastic endometrial glands. There was no lymph nodal metastasis.

Fig. 2
figure 2

Pathological findings of the endometrial oncocytic carcinoma. a Low-power view showing areas of solid and papillary architecture. Hematoxylin and eosin, original magnification ×20. b The tumor cells had fine oxiphilic cytoplasm. Hematoxylin and eosin, original magnification ×100

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Fig. 3
figure 3

Intraepithelial extension to the endocervical glands. Hematoxylin and eosin, original magnification ×40

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Immunohistochemistry results revealed that the tumor cells were positive for AMA, p53, and TTF-1 and negative for thyroglobulin, ER, PgR, and GCDFP-15 (Fig. 4).

Fig. 4
figure 4

Immunohistochemistry of the endometrial oncocytic carcinoma. a Hematoxylin and eosin, original magnification ×40. b Immunostaining for antimitochondrial antibody showing granular positive reaction in tumor cytoplasm. c Expression of TTF-1 was occasionally observed in tumor nuclei. d Expression of p53 was frequent in tumor nuclei

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Immunostainings were performed on the previous breast cancer to confirm whether the tumor was a primarily endometrial oncocytic carcinoma or whether it had metastasized from the breast cancer. Results of immunostainings are summarized in Tables 2 and 3.

Table 2 Immunohistochemical profiles of the present endometrial cancer
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Table 3 Immunohistochemical profiles of the previously operative breast cancer
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Tumor cells in the breast cancer were arranged in solid nests with stromal invasion, and possessed eosinophilic cytoplasm and enlarged nuclei with prominent nucleoli (Fig. 5). Immunohistochemistry revealed that the tumor cells were negative for AMA, TTF-1, TG, MMG, ER, PgR, and GCDFP-15.

Fig. 5
figure 5

Pathological findings of previously operated breast carcinoma. a Low-power view showing areas of large solid nest and adjacent invasive small nests. Hematoxylin and eosin, original magnification ×20. b Tumor cells had granular oxiphilic cytoplasm. Hematoxylin and eosin, original magnification ×100

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When the tumor cells of the endometrial cancer and breast cancer were compared, both were found to possess oxiphilic cytoplasm; however, they had different immunostaining patterns.

The endometrial tumor was diagnosed as primary endometrial oncocytic carcinoma because of the presence of intraepithelial extension to the endocervical glands and immunohistochemical profiles different from those of the breast cancer.

Discussion

Oncocytic tumors are generally known to contain oxiphilic cytoplasm, and these tumors occur in various organs such as the thyroid, salivary, and adrenal glands, kidney, and breast. However, pure oncocytic carcinoma of the endometrium is very rare [1].

In the clinicopathologic features of oncocytic endometrial carcinoma about the present and reviewed cases, mean of patient age is 67.6 years and the tumor is mainly composed of oncocytic cancer cells, which are arranged in glandular, solid nests in a papillary manner (Table 4) [1].

Table 4 Clinicopathologic features, treatment and outcome of the present case and review of the literature
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In general, oncocytic cytoplasm contains many mitochondria or eosinophilic granules [1, 6–9]. Tumor cells in endometrial oncocytic carcinoma contain many mitochondria in the cytoplasm [1]. Commonly occurring breast tumors possess eosinophilic cytoplasm, which contains apocrine or other secretory granules. However, oncocytic breast cancer with numerous cytoplasmic mitochondria has also been reported [10].

In immunohistochemical analyses, oncocytic carcinomas are frequently positive for p53, and rarely positive for ER and PgR [1]. Therefore, these tumors are classified as type 2 endometrial cancers (Table 5).

Table 5 Immunohistochemical profiles of oncocytic carcinoma of endometrium in the present case and review of the literature
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In the present case, endometrial tumor cells were positive for antimitochondrial antibody and negative for mammaglobin and GCDFP-15. On the other hand, the breast tumor was negative for antimitochondrial antibody. These results indicate that the breast tumor did not contain many mitochondria.

The present tumor was also positive for TTF-1. TTF-1 is generally expressed in non-neoplastic and neoplastic thyroid and lung tissues. However, TTF-1-positive tumors are rarely reported in other sites. TTF-1 expression is detected in approximately 20% of cases of endometrioid adenocarcinoma [3]. However, the relation between TTF-1 and the endometrial glands is unknown. Breast cancers are generally negative for TTF-1 [11, 12].

Tamoxifen was used for postoperative chemotherapy in this patient for 1 year. Long-term treatment with tamoxifen frequently induces endometrial cancer. In this case, adjuvant chemotherapy with tamoxifen was used for a short time. Therefore, the risk of endometrial cancer caused by this treatment is low [13].

Breast tumors frequently metastasize to the endometrium [4]. Therefore, endometrial oncocytic carcinoma must be distinguished from metastasis of breast cancers. In general, expression of mammaglobin and GCDFP-15 is important in distinguishing breast cancer from endometrial cancers. However, some breast cancers, such as the present case, are negative for these markers. Immunohistochemistry for antimitochondrial antibody and TTF-1 is useful to distinguish between endometrial oncocytic carcinoma and endometrial carcinoma metastasized from breast cancer.