Mojgan Devouassoux-Shisheboran

Mesonephric adenocarcinomas of the uterine cervix: a study of 11 cases with immunohistochemical findings.

Mesonephric adenocarcinoma is a rare variant of cervical carcinoma with relatively few, well-documented cases reported. We describe the clinicopathologic and immunohistochemical features of 11 examples of this neoplasm, which occurred in women between the ages of 35 and 72 years (mean, 52 years). Most (64%) patients had abnormal vaginal bleeding. Eight tumors were stage IB, and one each was stage IIB and IVB; in one, the stage was unknown. Microscopically, the carcinomas showed various morphologies, most commonly a small tubular pattern or a ductal pattern resembling endometrioid adenocarcinoma; one tumor had an associated malignant spindle cell component. Ten neoplasms were adjacent to hyperplastic mesonephric remnants. Follow-up in 10 cases showed six patients to be alive without evidence of recurrence after a mean of 4.8 years. The patients with stage IIB and IVB disease had local recurrences after 2.2 and 0.7 years and died of progressive disease at 3.2 and 0.8 years, respectively. In a patient with stage IB disease, a mediastinal metastasis and a malignant pleural effusion developed 5.6 years after diagnosis, and the patient died of disease at 6.2 years. Another patient with stage IB disease and a positive vaginal cuff margin that recurred locally after 1.7 years received chemotherapy and was alive and clinically free of disease at 2.5 years. Mesonephric adenocarcinomas were immunoreactive for epithelial markers (AE1/3; CK1, CAM 5.2, cytokeratin 7, and epithelial membrane antigen) (100%), calretinin (88%), vimentin (70%), androgen receptor (33%), and inhibin (30%, focal staining). No immunostaining was detected with cytokeratin 20, estrogen receptor, progesterone receptor, and monoclonal carcinoembryonic antigen. This staining profile is similar to that of mesonephric remnants and may be useful in the distinction of mesonephric carcinoma from mullerian endometrioid adenocarcinoma, with which it may be confused.

Wolffian adnexal tumor, so-called female adnexal tumor of probable Wolffian origin (FATWO) : Immunohistochemical evidence in support of a Wolffian origin

Wolffian adnexal tumor (WAT) is a rare neoplasm believed to originate from wolffian remnants on the basis of its location in areas where these remnants are abundant. To study its histogenesis, the immunoprofile of 25 WATs was compared with that of 10 cervical and vaginal mesonephric remnants and 12 rete ovarii. WATs were unilaterally located in the broad ligament (n = 10), mesosalpinx (n = 9), ovarian hilus (n = 5), and pelvis, not otherwise specified (n = 1). They showed varying morphologies with solid (spindle cells), tubular (lined by columnar cells), retiform and multicystic (spaces lined by cuboidal and attenuated cells) patterns. WATs were immunoreactive for pan-cytokeratin (AE1/3, CK1) (100%), CAM 5.2 (100%), cytokeratin 7 (CK7) (88%, focal staining), keratin 903 (17%), epithelial membrane antigen (EMA) (12%), estrogen receptor (28%), progesterone receptor (24%), androgen receptor (78%), inhibin (68%), calretinin (91%), and vimentin (100%). No immunostaining was detected with monoclonal carcinoembryonic antigen and cytokeratin 20. The pattern of staining was nearly identical to that of the rete ovarii and differed somewhat from mesonephric remnants, which were diffusely immunoreactive for CK7, immunopositive for EMA (apical staining), and nonreactive for inhibin. Our findings provide immunohistochemical support for the derivation of WATs from wolffian remnants, in particular from the rete ovarii. Because of immunoreactivity for inhibin and calretinin in a significant number of WATs, our results further show that these immunostains alone do not allow absolute distinction of WATs from sex cord-stromal tumors and adenomatoid tumors, respectively, with which they may be confused.

Fibromatosis of the breast : Age-correlated morphofunctional features of 33 cases

OBJECTIVE To predict if antiestrogenic agents are useful in the treatment of breast fibromatoses, we undertook an immunohistochemical study of sex steroid hormone receptors (estrogen receptor, progesterone receptor, and androgen receptor) and protein pS2 in 33 cases. METHODS The morphologic and immunohistochemical findings were correlated to patient menstrual status, which was categorized as childbearing age (n = 15), perimenopausal (n = 8), and postmenopausal (n = 10). RESULTS Fibromatoses in women of childbearing age were more cellular, more mitotically active, and displayed a larger proportion of cells with mild atypia than those in perimenopausal and postmenopausal women. The hormonal status of these 3 groups does not explain the morphologic variations observed in these groups, inasmuch as no immunostaining for any of the hormone receptors was detected in the tumors. CONCLUSIONS The absence of estrogen receptor and pS2 in breast fibromatoses suggests that antiestrogenic agents are unlikely to be beneficial in the management of these tumors. Assessment of the hormone receptor profile is a useful adjunct in the diagnosis of spindle cell lesions of the breast. Although most spindle cell carcinomas as well as fibromatoses of the breast do not express estrogen or progesterone receptors, the absence of androgen receptor reactivity would favor a diagnosis of fibromatosis over that of myofibroblastoma.

Microdissection-Based Analysis of Mature Ovarian Teratoma

The genotypic features of mature ovarian teratomas (MOTs) are controversial. Early studies detected a homozygous genotype in MOTs suggesting that these tumors are composed of germ cells that have undergone meiosis I. Other studies, however, revealed a heterozygous genotype in a substantial proportion of MOTs suggesting an origin either from premeiotic germ cells or from a somatic cell line. In view of the complex morphology of MOTs and to increase the sensitivity of teratoma genotyping, we applied tissue microdissection before genetic analysis of teratomatous tissue. This approach allowed selective analysis of different heterotopic tissue elements as well as the lymphoid tissues within MOTs the origin of which is unknown. After DNA extraction, the tissue samples were polymerase chain reaction amplified using a random panel of highly informative genetic markers for different chromosomes to evaluate heterozygosity versus homozygosity. In all seven cases that were analyzed, heterotopic tissues consistently revealed a homozygous genotype with several markers; in two cases, heterozygosity was detected with a single marker, indicating a meiotic recombination event. Lymphoid aggregates within MOTs were heterozygous and derived from host tissue rather than from teratomatous growth. However, well differentiated thymic tissue was consistently homozygous, suggesting lymphoid differentiation capability of MOTs. We conclude that potential pitfalls in genotyping of teratomas including meiotic recombination and host cell participation can be avoided by a microdissection-based approach in combination with a panel of genetic markers.

Ovarian hepatoid yolk sac tumours: morphological, immunohistochemical and ultrastructural features.

The clinicopathological, immunohistochemical and ultrastructural features of two ovarian hepatoid yolk sac tumours (H‐YST) from our files are reviewed.

Teratomatous Genotype Detected in Malignancies of a Non-Germ Cell Phenotype

Originating from post-meiotic germ cells, mature ovarian teratomas (MOT) are genetically homozygous tumors within heterozygous hosts. MOT may be associated with malignant tumors of a non-germ cell phenotype (so-called malignant transformation). Based on the presence of in situ changes, some cases have been hypothesized to arise from teratomatous tissue. However, other malignancies associated with mature teratomas, such as sarcomas, may originate from either teratomatous elements or preexisting somatic ovarian tissue. Eight cases of MOT containing various histologic types of malignancy, including four squamous cell carcinomas, two sarcomas, one thyroid carcinoma, and one carcinoid tumor, were selected for study. Using selective tissue microdissection and PCR-based analysis of the extracted DNA, we compared the genotypic pattern of the mature teratomatous components to the associated malignant neoplasm with a random panel of highly informative genetic markers for different chromosomes. In all eight cases, genetic analysis of the malignant component revealed a homozygous genotype. In seven cases, the genetic profiles of mature teratomas and the associated malignant tumors were identical, suggesting a direct pathogenetic relationship between these lesions. In one case, the malignant component revealed homozygosity of different alleles compared with mature teratoma, suggesting independent teratomatous growth processes. This finding indicates that some ovarian malignancies of the non-germ cell phenotype arise in teratoma and fall into the spectrum of germ cell tumors.

Endobronchial variant of sclerosing hemangioma of the lung: histological and cytological features on endobronchial material

We report two cases of a rare presentation of pulmonary sclerosing hemangioma as an endobronchial polyp resulting in clinical symptoms of bronchial obstruction. We describe the histological and cytological description of this entity based on material obtained during bronchoscopic examination. In both cases, bronchoscopy revealed a polypoid mass protruding into the left lower lobar bronchus, with a smooth and hemorrhagic surface, reminiscent of a carcinoid tumor. On bronchial washing in case 1, numerous small round cells were seen with uniform nuclei and inconspicuous nucleoli, arranged in clusters with a pavement-type pattern and papillary configuration. The presence of a few reactive pneumocytes gives a dual cell proliferation, in a background of numerous foamy macrophages. Although the four architectural patterns of sclerosing hemangioma were present in the resected tumors, the papillary and solid patterns predominated in the endobronchial component of the tumors and these were seen on the bronchial biopsies. Recognition of the papillary pattern, the typical round cells coexpressing thyroid transcription factor-1 and epithelial membrane antigen without cytokeratin immunoreactivity, are helpful clues for the diagnosis on bronchial biopsy. Finally, hopefully awareness by clinicians and pathologists that sclerosing hemangioma can present as an endobronchial mass will facilitate diagnosis when this rare event occurs.

DICER1 and FOXL2 mutations in ovarian sex cord–stromal tumours: a GINECO Group study

FOXL2 mutation has been consistently identified in adult granulosa cell tumours (A‐GCTs). DICER1 mutations have been described predominantly in Sertoli–Leydig cell tumours (SLCTs). The prognostic implication of these mutations remains uncertain, as moderately sized studies have yielded variable outcomes. Our aim was to determine the implications of DICER1 and FOXL2 mutations in 156 ovarian sex cord–stromal tumours (SCSTs).

Pathobiology of ovarian carcinomas

Ovarian tumors comprise a heterogeneous group of lesions, displaying distinct tumor pathology and oncogenic potentiel. These tumors are subdivided into three main categories: epithelial, germ cell, and sex-cord stromal tumors. We report herein the newly described molecular abnormalities in epithelial ovarian cancers (carcinomas). Immunohistochemistry and molecular testing help pathologists to decipher the significant heterogeneity of this disease. Our better understanding of the molecular basis of ovarian carcinomas represents the first step in the development of targeted therapies in the near future.

Somatic DICER1 gene mutation in sporadic intraocular medulloepithelioma without pleuropulmonary blastoma syndrome

Germline DICER1 gene mutation has been described in ocular medulloepithelioma associated with pleuropulmonary blastoma family tumor and dysplasia syndrome. We present a case of sporadic ocular medulloepithelioma in an 18-year-old woman with D1709N somatic mutation in DICER1 gene, which has not been previously described. This case highlights the potential use of DICER1 gene sequencing to resolve the diagnostic challenge in recurrent and metastatic malignant medulloepithelioma, when morphology and immunohistochemistry are inconclusive. Further studies in larger series of this type of tumor are needed to confirm the relevance of this molecular abnormality in the tumorigenesis of this embryonic-type ocular tumor.