High-grade neuroendocrine carcinoma arising in a gastric duplication cyst: a case report with literature review.

Gastric duplication cysts are rare congenital anomalies that are mostly discovered in children but can remain asymptomatic and undetected into adulthood. Malignant transformation in gastric duplications is extremely rare, with most reported cases being adenocarcinomas. Herein, the authors report the first case of a high-grade neuroendocrine carcinoma arising in a gastric duplication cyst in a 40-year-old Asian male. This case highlights that duplication cysts should be included in the differential diagnosis of cystic masses of the gastrointestinal tract in adult, as well as pediatric, patients and emphasizes the importance of complete surgical resection and meticulous pathologic examination of these congenital anomalies.

Polypoid endometriosis: a clinicopathologic analysis of 24 cases and a review of the literature.

We describe 24 cases of polypoid endometriosis, most of which were referred because of problems in differential diagnosis, particularly distinction from a low-grade müllerian neoplasm. The patients were 23 to 78 years (mean 52.5 years) of age. Seven patients were on unopposed estrogen, four on combined estrogen-progestin therapy, and one patient had a synchronous ovarian thecoma. The most common clinical presentations were a pelvic mass, vaginal polypoid masses, and large bowel obstruction. In some cases, the intraoperative findings suggested a neoplasm. Sites of involvement in order of frequency included colon, ovary, uterine serosa, cervical and/or vaginal mucosa, ureter, fallopian tube, omentum, bladder, paraurethral and paravaginal soft tissue, and retroperitoneum. Multiple sites were involved in seven cases. Five cases occurred within ovarian or extraovarian endometriotic cysts. The lesions ranged up to 14 cm in size and formed polypoid, pink, gray or tan, masses. On microscopic examination, the polypoid masses were composed of an admixture of endometriotic glands and stroma. A variety of glandular architectural patterns were observed, sometimes in combination, most commonly cystic and noncystic simple hyperplasia, but also simple or complex hyperplasia with atypia, disordered proliferative, and cystic atrophy. Various types of epithelial metaplasia (tubal, mucinous, squamous, papillary syncytial metaplasia) were common. Hemorrhage, fibrosis, prominent thick-walled blood vessels, hemosiderin-laden histiocytes, and decidual change were also present in some cases. Eighteen cases were associated with usual (nonpolypoid) endometriosis. In one case, polypoid endometriosis merged with a mucinous borderline tumor of endocervical-type. In all but two cases, polypoid endometriosis lacked periglandular stromal hypercellularity, stromal atypia, and intraglandular stromal papillae, helping distinguish it from adenosarcoma. Focal intraglandular stromal papillae were noted in two cases with focal mild periglandular stromal hypercellularity in one of them, but no stromal atypia was present in either case. Follow-up data in 17 patients indicated that 15 patients were alive without evidence of residual disease, 1 was alive with residual endometriosis, and 1 died of other causes. In conclusion, polypoid endometriosis is a rare manifestation of endometriosis that may be mistaken for a neoplasm on clinical, intraoperative, or pathologic assessment. Some cases may be attributable to exogenous hormones or hyperestrinism and, like conventional endometriosis, some may evolve into a premalignant or, rarely, a neoplastic lesion. The main lesion in the differential is a müllerian (mesodermal) adenosarcoma.

Assessment of interlaboratory variation in the immunohistochemical determination of estrogen receptor status using a breast cancer tissue microarray.

The determination of tumor cell estrogen receptor (ER) expression status by immunohistochemical analysis has become standard practice, yet assay reproducibility has not been assessed adequately. By using a breast cancer tissue microarray, we examined interlaboratory variability in ER reporting. A 2-fold redundant tissue microarray block was created from 29 breast cancers. Unstained slides were distributed to 5 laboratories, and each laboratory immunostained and scored 1 slide for ER. Interlaboratory agreement ranged from moderate to high (overall kappa = 0.54 for 0-3+ grading; overall kappa = 0.84 for negative vs positive assessment of ER status). When 1 observer scored each of the 5 slides, interlaboratory agreement was slightly better (kappa = 0.63 for 0-3+ scoring; kappa = 0.96 for negative vs positive scoring). One laboratory, which had used an antibody and antigen retrieval method different from the others, demonstrated only fair concordance with the other 4 laboratories, but there was substantial intralaboratory interobserver agreement and excellent agreement with an outside observer reviewing the slide stained in that laboratory. The tissue microarray was an efficient and effective tool for identifying variability in ER reporting and should prove valuable in other external quality assurance programs.

Skeletal muscle-like and rhabdoid cells in uterine leiomyomas.

We describe eight unusual uterine leiomyomas characterized by a component of cells that suggested skeletal muscle differentiation or resembled the rhabdoid cells of extrarenal rhabdoid tumors. All of the tumors were referred because of problems in differential diagnosis, particularly distinction from an epithelioid smooth muscle tumor, a smooth muscle tumor of uncertain malignant potential, or a tumor with skeletal muscle differentiation. The patients were aged 27 to 50 (mean, 38) years, and the presenting clinical features and gross appearance of the tumors were similar to those of typical uterine leiomyomas. On microscopic examination, seven of the tumors were well circumscribed, whereas one showed slight irregularity of its margin. The characteristic feature of the tumors was a variable number of rounded, polygonal, or strap-shaped cells with abundant deeply eosinophilic cytoplasm and fibrillar, or occasionally hyaline, intracytoplasmic globules. Cytoplasmic cross-striations were not identified. The cells usually had eccentric, round-to-oval nuclei with conspicuous nucleoli. A variable number of the rhabdoid/skeletal muscle-like cells, as well as cells without these features, contained multiple or multilobed, pleomorphic, hyperchromatic nuclei, thus qualifying the tumors as leiomyomas with bizarre nuclei. Foci of hydropic change were present in all of the tumors. The mitotic index was low (<1 mitotic figure/10 high-power fields) and necrosis was absent in all the tumors. The rhabdoid/skeletal muscle-like cells were immunoreactive for desmin and h-caldesmon, but not for cytokeratin (AE1/AE3) or skeletal muscle markers (myoglobin, Myo-D1, or myogenin). Intracytoplasmic whorls of intermediate filaments were observed in the cells of one case examined by electron microscopy; there was no ultrastructural evidence of skeletal muscle differentiation. The histologic, immunohistochemical, and ultrastructural features indicated that the peculiar cells in these leiomyomas likely represented smooth muscle cells with an unusual phenotype rather than the cells of uterine tumors with skeletal muscle differentiation, extrarenal rhabdoid tumors, or epithelioid smooth muscle tumors. An association with leiomyomas with bizarre nuclei also was suggested.

Assessment of Her-1, Her-2, And Her-3 expression and Her-2 amplification in advanced stage ovarian carcinoma.

The human epidermal growth factor receptor (Her) family of receptor tyrosine kinases includes Her-1, Her-2, and Her-3. The overexpression of Her-1 and Her-2 have been reported previously in surface epithelial ovarian cancer. Although up to one-third of ovarian carcinomas have been found to have amplification or overexpression of Her-2, responses to trastuzumab therapy in these patients have been disappointing. In this study, we examined Her-1, Her-2, and Her- 3 protein expression as well as the frequency of Her-2 amplification in a series of 103 high-grade, advanced-stage (FIGO stage III or IV) ovarian surface epithelial carcinomas. Immunohistochemical staining using commercially available antibodies against Her-1-3 and fluorescence in situ hybridization (FISH) using probes against Her-2 and chromosome 17 centromere (CEP) were performed on a tissue microarray containing cores of tumor from 103 surface epithelial carcinomas (85 serous, 6 mixed surface epithelial, 5 clear cell, 3 endometrioid, 3 undifferentiated, 1 mucinous). Nine of 99 (9.1%) tumors were positive for Her-1 expression and 5 of 102 (4.9%) tumors were positive for Her-2 expression, with 1 showing strong immunoreactivity. None of the Her-1 positive tumors exhibited Her-2 immunoreactivity. There was no correlation between Her-1 or Her-2 expression and survival. Using Her-2:centromere fluorescence ratios of 2.0 or 1.5 as cutoffs in assessment of Her-2 amplification, 8 of 75 (10.7%) and 25 of 75 (33.3%) tumors, respectively, showed Her-2 amplification. Two of eight tumors that showed higher level (>2) Her-2 amplification by FISH also were positive for Her-2 by immunohistochemistry. Only 3 of 103 tumors expressed Her-3. Immunoreactivity for Her-1 and Her-2 was less frequently observed in this series than has been previously reported. The strong correlation between Her-2 immunostaining and amplification characteristic of breast carcinoma is not seen in ovarian carcinoma. These results indicated that few patients with ovarian carcinoma have tumors that would benefit from therapy targeted specifically against Her-1, Her-2, or Her-3.

Early recurrence of ovarian serous borderline tumor as high-grade carcinoma: a report of two cases.

Ovarian serous borderline tumors (SBTs) are characteristically associated with an indolent course. Recurrences are often delayed and usually show morphologic features of SBT or low-grade serous carcinoma. Transformation to high-grade carcinoma has rarely been documented. We report 2 cases of ovarian SBTs that recurred early as high-grade carcinomas. The first was a 50-year-old woman treated surgically and with chemotherapy for a FIGO stage 1C SBT with microinvasion, who experienced a recurrence in an axillary lymph node at 27 months. The recurrent tumor consisted of well-differentiated papillary serous tumor that resembled the primary tumor and poorly differentiated serous carcinoma. The patient died of progressive disease 43 months after her initial presentation. The second case was a 61-year-old woman treated surgically and with chemotherapy for a stage 3C micropapillary SBT with noninvasive implants. Eighteen months later, an incisional hernia was found that contained high-grade sarcomatoid-type carcinoma with microscopic foci of better differentiated tumor that resembled the primary SBT. This patient is alive with disease 24 months after her initial presentation. Whereas the malignant potential of SBTs remains controversial, the cases described herein demonstrate that SBTs can behave unpredictably and may rarely transform into high-grade carcinoma.