Fryns syndrome phenotype caused by chromosome microdeletions at 15q26.2 and 8p23.1.

BACKGROUND: Fryns syndrome (FS) is the commonest autosomal recessive syndrome in which congenital diaphragmatic hernia (CDH) is a cardinal feature. It has been estimated that 10% of patients with CDH have FS. The autosomal recessive inheritance in FS contrasts with the sporadic inheritance for the majority of patients with CDH and renders the correct diagnosis critical for accurate genetic counselling. The cause of FS is unknown. METHODS: We have used array comparative genomic hybridisation (array CGH) to screen patients who have CDH and additional phenotypic anomalies consistent with FS for cryptic chromosome aberrations. RESULTS: We present three probands who were previously diagnosed with FS who had submicroscopic chromosome deletions detected by array CGH after normal karyotyping with G-banded chromosome analysis. Two female infants were found to have microdeletions involving chromosome band 15q26.2 and one male had a deletion of chromosome band 8p23.1. CONCLUSIONS: We conclude that phenotypes similar to FS can be caused by submicroscopic chromosome deletions and that high resolution karyotyping, including array CGH if possible, should be performed prior to the diagnosis of FS to provide an accurate recurrence risk in patients with CDH and physical anomalies consistent with FS.

Sentinel lymph node biopsy after neoadjuvant chemotherapy for breast cancer.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is a developing alternative to axillary dissection and may prove to be accurate in the detection of micrometastases in lymph nodes of breast cancer patients. Limited studies exist in the use of SLNB after neoadjuvant therapy. This study was undertaken to determine the accuracy of SLNB after neoadjuvant chemotherapy. METHODS: Thirty-one patients with stage I or II breast cancer underwent SLNB after neoadjuvant chemotherapy. RESULTS: Lymphatic mapping was performed by radioisotope, blue dye, or both techniques. Sentinel nodes (SN) were identified in 29 patients (93.5%). The SN was positive in 11 patients (38.0%), and was the only positive node in 5 patients (45.5%). There were no false negative SN by hematoxyin and eosin stain or immunohistochemistry (IHC) studies. CONCLUSIONS: Sentinel node identification rate is similar to that in nonneoadjuvant studies. The sentinel node accurately predicted metastatic disease in the axilla. IHC studies failed to detect any additional micrometastases. This diagnostic technique may provide treatment guidance for patients after neoadjuvant therapy.

Microtubule-associated protein-2: a new sensitive and specific marker for pulmonary carcinoid tumor and small cell carcinoma.

Microtubule-associated proteins (MAPs) are a major component of cytoskeleton family proteins associated with microtubule assembly. MAP-2 has been shown to be specifically expressed in neuronally differentiated cells. Pulmonary neuroendocrine carcinomas such as carcinoid tumors and small cell carcinomas are derived from neuroendocrine cells. We hypothesize that neuroendocrine cells may also express MAP-2, and therefore, MAP-2 may be used as a marker for pulmonary carcinomas of neuroendocrine differentiation. To investigate the utility of using MAP-2 expression to separate pulmonary neuroendocrine from non-neuroendocrine tumors, we examined the expression of MAP-2 immunohistochemically in 100 cases of pulmonary carcinomas. The immunoperoxidase method with antigen retrieval was used to characterize the expression of MAP-2, chromogranin, synaptophysin, and neuron-specific enolase in 25 small cell carcinomas, 25 carcinoid tumors, 25 adenocarcinomas, and 25 squamous cell carcinomas. All tumors were lung primaries. All 25 cases of carcinoid tumors (100%) as well as 23 of 25 cases (92%) of small cell carcinomas were positive for MAP-2. Four of 25 cases (16%) of adenocarcinomas were positive for MAP-2 and synaptophysin. Among the 25 squamous carcinomas, 4 cases (16%) were positive for MAP-2, 2 cases (8%) were positive for synaptophysin, 11 cases (44%) were positive for neuron-specific enolase, and none was positive for chromogranin. In conclusion, MAP-2 is a new sensitive and specific marker for the pulmonary tumors of neuroendocrine differentiation. We recommend that MAP-2 be added to immunohistochemical panels to separate non-neuroendocrine from neuroendocrine lung tumors.

Small-cell variant of synovial sarcoma: fine-needle aspiration with ancillary features and potential diagnostic pitfalls.

We report a small-cell variant of synovial sarcoma examined by fine-needle aspiration (FNA) biopsy. The patient is a 23-yr-old female who had a synovial sarcoma involving the left infratemporal region, diagnosed at 7 yr of age, followed by a metastatic lesion involving the lung and chest wall 16 yr later. The chest wall metastases was sampled by FNA biopsy. The aspirate consisted of numerous, small, round cells with very high nuclear-to-cytoplasmic ratios. The cytomorphologic features could potentially be confused with other pediatric small round cell tumors. Ancillary studies demonstrated positive staining of the neoplastic cells for cytokeratin, epithelial membrane antigen (EMA), and CD99. The differential diagnosis of other small round cell tumors that may be mistaken for the small-cell variant of synovial sarcoma are presented. We believe that this is the first FNA report detailing the cytologic and ancillary features of the small-cell variant of synovial sarcoma.

Primary pulmonary thymoma.

Primary thymomas arising in an intrapulmonary location without an associated mediastinal component are rare entities. The origin of thymomas in this unusual location remains unknown. Knowledge of the natural history and the prognosis of these tumors is also limited because of their rarity.

Expression of alpha-fetoprotein by ovarian Sertoli-Leydig cell tumors. Case report and review of the literature.

A 17-year-old girl had an ovarian Sertoli-Leydig cell tumor associated with elevation of the serum alpha-fetoprotein level. On microscopic examination, the tumor had a predominantly spindled cellular stroma containing open and solid tubules, focal clusters of hepatoid cells, and heterologous carcinoid. Alpha-fetoprotein was demonstrated within the hepatoid cells by immunohistochemical techniques. After surgery, serum alpha-fetoprotein level fell to normal, and the patient is still free of tumor 8 months later.

Fat deposits in the placenta following maternal total parenteral nutrition with intravenous lipid emulsion.

Total parenteral nutrition with parenteral lipid emulsion is being used with increased frequency in malnourished pregnant women. Placentas examined in 20 reported cases of maternal hyperalimentation with lipid emulsions have been described as normal. We report a case of a 31-year-old pregnant woman who received total parenteral nutrition with daily lipid emulsions for 8 weeks. Intrauterine fetal death was diagnosed at 22 weeks' gestation. The tan-yellow, pale placenta showed vacuolated syncytial cells and Hofbauer cells, which stained for fat by the oil red O stain, in the chorionic villi. To our knowledge, this is the first reported case of fat deposits in the placenta associated with intravenous lipid emulsions.

Thyroid hormone receptor messenger ribonucleic acid in human granulosa and ovarian stromal cells.

OBJECTIVE: To examine whether mRNA for thyroid hormone receptors alpha and beta is present in human granulosa cells in nonstimulated ovaries. DESIGN: Paraffin-embedded sections of ovaries from normally cycling women were analyzed by in situ hybridization with oligonucleotide probes for thyroid hormone receptors alpha and beta. The sense strand oligonucleotide was used as a control for each of the probes. RESULTS: Granulosa cells from the preovulatory antral follicles examined showed positive staining for both the thyroid hormone receptor alpha and beta probes. Positive staining of ovarian stromal cells also was observed for both probes. CONCLUSION: Thyroid hormone receptor mRNAs are expressed in both granulosa cells and ovarian stromal cells found in nonstimulated ovaries. It is, therefore, conceivable that thyroid hormone may play a direct role in human ovarian physiology.

Congenital complete absence (bilateral agenesis) of the diaphragm: a rare variant of congenital diaphragmatic hernia.

Although congenital diaphragmatic hernia is one of the most common congenital anomalies, complete bilateral absence of the diaphragm is a very rare variant, with six cases reported in the literature. A 1040 g black male infant was born at 27 weeks' gestation to a 28-year-old black woman with a history of minimal prenatal care and cocaine abuse during pregnancy. Apgar scores were 2/1/1/0/1 at 1, 5, 10, 15, and 20 minutes, respectively and efforts to resuscitate him were unsuccessful. He died at 2 1/2 hours of age. Autopsy showed complete absence of the diaphragm, pulmonary hypoplasia, and an atrial septal defect of the heart. Cytogenetic studies showed normal male karyotype. We suggest that decreased or interrupted blood supply to the developing diaphragm of this infant may have interrupted normal embryogenesis in the early developmental stages.

Fatal Clostridium perfringens and Escherichia coli sepsis following urea-instillation abortion.

Intraamniotic instillation of urea is a common mode of legal second-trimester pregnancy termination. Associated mortality rarely occurs and is most commonly due to amniotic fluid embolism, pulmonary thromboembolism, infection, hemorrhage, and disseminated intravascular coagulation (DIC). We present the case of an 18-year-old gravida 2, para 1 white woman at 18 weeks' gestation who underwent intraamniotic instillation of hyperosmolar urea and intracervical insertion of laminaria tents; 19 h later, she became unresponsive, academic, and went into shock. Coagulation studies were diagnostic of DIC. Bacilli were seen on peripheral blood smear. Autopsy showed marked subcutaneous emphysema of the anterior abdominal wall, necrosis and emphysema of the uterus, diffuse pulmonary alveolar damage, and renal cortical necrosis. Antemortem blood cultures grew Clostridium perfringens and Escherichia coli. Postmortem culture of the uterus grew E. coli. The source of infection was most likely the introduction of vaginal organisms via laminaria insertion. This is apparently the first reported case of death caused by Clostridium perfringens and E. coli sepsis following urea instillation.