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Background: Chromosomal anomalies are a recognized cause of stillbirth, accounting for 6-17% of the cases. As a diagnostic laboratory method in this setting, conventional karyotyping has two main drawbacks: the need for viable fetal cells in a dead fetus and its limited resolution as compared to alternative techniques., Objective: To assess the effectiveness of cytogenetic analysis in stillbirths between different testing methods and different sampled tissues., Methods: From 2011 to 2017, 145 stillborn fetuses (defined as fetal losses after 22 weeks) were delivered in our center. The stillbirth protocol includes genetic testing by means of a karyotype, QF-PCR, or chromosomal microarray analysis (CMA), depending on the presence of fetal structural anomalies and the study time period. The success rates were compared between tests and between different sampled tissues., Results: Consent was granted for cytogenetic analysis in 136 stillbirths. Test success rate was 100% (38/38) for CMA independent of the sampled tissue, 99% (65/66) for QF-PCR, and 66% (65/98) for karyotyping. The success rate for karyotyping was 48% (69/145) of the total tissues samples, showing great variation according to the tissue sampled: 83% (40/48) in amniotic fluid, 78% (21/27) in the placenta, 13% (7/54) in fetal skin, and 6.3% (1/16) in fetal blood. Four full or partial aneuploidies (trisomy 9, trisomy 22, tetrasomy 18p, and monosomy X) and 2 microdeletions (del2p16.3 and del1q13.2q13.4) were found, resulting in a 3.9% (4/103) prevalence for full or partial aneuploidy and a 5.3% prevalence (2/38) for submicroscopic abnormalities., Conclusions: Amniotic fluid should be the preferred tissue source in the cytogenetic analysis of stillbirth due to its high success rate. Between tests, CMA is a preferable method because of its higher test success rate, independent of the sampled tissue, and higher diagnostic yield including chromosomal and submicroscopic anomalies., (© 2020 S. Karger AG, Basel.)

Objective: To assess the distribution of the parental origin of the retained X chromosome in monosomy X, either in miscarriages or in ongoing pregnancies., Method: The parental origin of the X chromosome was determined in monosomy X pregnancies, either miscarriages or ongoing pregnancies. Microsatellite marker patterns were compared between maternal and fetal samples by quantitative fluorescence polymerase chain reaction. Distributions of maternally and paternally derived X chromosome were assessed in miscarriages and in ongoing pregnancies using two-tailed Fisher exact test., Results: Forty monosomy X pregnancies were included in the study: 26 miscarried at 5-16 weeks, and 14 ongoing pregnancies were diagnosed at 11-20 weeks. The retained X chromosome was maternally derived in 67% of the cases. In miscarriages, maternal and paternal X chromosome were retained in a similar proportion (54% [95% CI: 35-73%] vs. 46% [95% CI: 27-65%]), while in ongoing pregnancies, the maternal rate was 13 times higher (93% [95% CI: 79-100%)] vs. 7% [95% CI: 0-20%])., Conclusions: The retained X chromosome in individuals with monosomy X should theoretically be maternally derived in 2/3 of the cases. Our study suggests a preferential early miscarriage in pregnancies with a retained paternally derived X chromosome. This may explain the observation that 75-90% of individuals with monosomy X retain the maternal X chromosome., (© 2017 S. Karger AG, Basel.)

Low-grade fibromyxoid sarcomas (LGFMS) bear either the t(7,16) (q32-34;p11) or t(11,16) (p11;p11) translocations, resulting in FUS-CREB3L2 or FUS-CREB3L1 fusions, respectively. Heretofore, fusion transcripts were mainly detected in frozen tissues, using reverse transcription-polymerase chain reaction. In this study, we aimed to develop a reliable method to detect these in paraffin-embedded tissues, and to examine the clinicopathologic characteristics of a series of translocation-positive LGFMS. Sixty-three neoplasms with typical morphologic features of LGFMS and 66 non-LGFMS tumors selected for their resemblance to LGFMS (LGFMS-like tumors) were examined. RNA of sufficient quality could be extracted from 111/129 (86%) cases (59 LGFMS, 52 non-LGFMS). Of all, 48/59 (sensitivity, 81%) LGFMS contained detectable transcripts (45 FUS-CREB3L2, 3 FUS-CREB3L1). Most relevant clinicopathologic features of fusion-positive LGFMS included predominance in lower extremities (22/48; thigh: 13/48), deep situation (46/48), and occasional presence of unusual histologic features, for example, hypercellular areas (16/48), foci of epithelioid cells (13/48), and giant rosettes (6/48). Most tumors expressed EMA (41/45), at least focally, CD99 (38/41) and bcl-2 (36/41) while being essentially negative for CD34 (2/45), mdm2 (1/41), smooth muscle actin (1/45), S100 protein (0/46), desmin (0/44), h-caldesmon (0/42), keratins (0/44), and CD117 (0/40). Eleven presumed LGFMS were fusion negative. Of all, 7/52 non-LGMFS neoplasms contained FUS-CREB3L2 transcripts, of which 4 had been diagnosed as sclerosing epithelioid fibrosarcoma. In conclusion, FUS-CREB3L1/L2 fusion transcripts can be detected in paraffin-embedded LGFMS in a sensitive manner, using reverse transcription-polymerase chain reaction. Most fusion-positive LGFMS are EMA-positive and CD34/S100/smooth muscle actin negative. The presence of epithelioid cells and fusion transcripts in both LGFMS and a subset of sclerosing epithelioid fibrosarcoma suggest that these neoplasms might be related.

The clinicopathologic and immunohistochemical features of 63 pleomorphic liposarcomas are presented. There were 35 men and 28 women (median age 63 years; range 18-93 years). Tumor size ranged from 2 to 23 cm (median 10 cm). Tumor locations included lower extremity (36.5%), especially the thigh (28.5%), limb girdles (17.5%), upper extremity (16%), thoracoabdominal wall (9.5%), and internal trunk (20.5%). A total of 75% were deep seated and/or extracompartmental. Histologically, lesions show a varying combination of lipogenic and nonlipogenic areas characterized by malignant fibrous histiocytoma-like, round cell liposarcoma-like, and/or epithelioid/carcinoma-like features. A pericytic pattern was focally present in 15 (24%) tumors. Eighteen (29%) lesions were grade 2, and 45 (71%) were grade 3 sarcomas. Tumor necrosis was observed in 51 (81%) cases, vascular invasion in three, and mitotic counts ranged from 3 to 124 per 10 high power fields (median 25). Lipogenic areas were S-100 protein immunoreactive, at least focally, in 20 of 42 (48%) cases. Nonlipogenic areas showed focal reactivity for smooth muscle actin (24 of 49; 49%), desmin (9 of 48; 19%), CD34 (18 of 45; 40%), S-100 protein (5 of 49, 10%), CD68 (6 of 46, 13%), and epithelial membrane antigen (13 of 49, 26.5%). Epithelioid areas showed epithelial membrane antigen (4 of 11; 36%) but not cytokeratin (0 of 11) reactivity. Treatment procedures in 51 patients consisted of simple tumorectomy (16) and wide excision (33). Five and 31 patients received neoadjuvant and adjuvant chemotherapy and/or radiation therapy, respectively. Follow-up (48 patients, range 7-276 months; median 38 months) showed a 45% local recurrence rate and a 42.5% metastasis rate, metastases occurring mostly in lungs and pleura. Seventeen patients (35%) died of disease, of whom none was metastatic at diagnosis. Five-year overall, metastasis-free, and local recurrence-free survivals were 57%, 50%, and 48%, respectively. Patient age > or =60 years, truncal tumor location, deep situation, tumor size >5 cm, vascular invasion, and incomplete tumor excision were significant adverse prognostic factors. Tumor grade and histology did not affect patient outcome. In conclusion, pleomorphic liposarcoma is a rare, often deep-seated and limb-based aggressive and metastasizing neoplasm of late adulthood. It shows a wide range of morphologic appearances, but tumor grade and histology have no effect on patient outcome.

Thirty six cases of clear cell sarcoma of soft tissue are reported. The median age was 44 years (5 to 80 years). The principal sites were the foot (11 cases), the hand and wrist (7 cases) and the knee (6 cases). The architecture was fascicular with lobular arrangement of cells delimited by delicate fibrous septa intimately bound to tendons or aponeuroses. Tumoral cells were round or fusiform with abundant clear cytoplasm sometimes epithelioid with round nuclei and prominent nucleoli. The mitotic rate was evaluated to 9/10 HPF. S100 protein was expressed in 33/36 cases and HMB45 marked 29/31 cases, without expression of cytokeratin. Three-year and 5-year survival rate were respectively 72% and 62%. Prognosis factors for global survival were efficiency of initial treatment with distal location and necrosis and FNCLCC grade. The distinction of clear cell sarcoma from metastatic melanoma is important because of the difference of prognosis.

In a breast cancer cell line (FAM) isolated and characterized in our laboratory, we previously observed that oestradiol (E2) did not affect cell multiplication in vitro. In this work, we examined whether these cells bearing oestrogen and progesterone receptors, were oestrogen (E)-sensitive in spite of their lack of growth response. We observed that E2 administration resulted in an increase in protein synthesis characterized by enhancement of progesterone receptors, creatine-phosphokinase and plasminogen activator. Thus these FAm cells were true E-responsive target cells and we studied their nuclear size and ultrastructure to determine if E2 stimulation induced the same important changes as described in vivo. We observed no significant differences between control and E2-treated cells. In these breast cancer cells in vitro, E does not act on DNA-auto-reproduction but only on transcriptional activity. Thus, there is only a limited number of activated genes and no gross nuclear morphological changes. In these cultured oestrogen target cells, ultrastructural nuclear changes are not a marker of hormone action, unlike the situation in vivo where E also acts in triggering cell multiplication.