Prevalence and Factors Associated with Hydatidiform Mole among Patients Undergoing Uterine Evacuation at Mbarara Regional Referral Hospital.

OBJECTIVE: We sought to determine the prevalence of and factors associated with hydatidiform molar gestations amongst patients undergoing uterine evacuation at Mbarara Regional Referral Hospital (MRRH), Mbarara, Uganda. METHODS: This was a cross-sectional study carried out from November 2016 to February 2017. All patients admitted for uterine evacuation for nonviable pregnancy were included. The study registered 181 patients. Data were collected on sociodemographics, medical conditions, obstetrics, and gynecological factors. The evacuated tissue received a full gross and histopathologic examination. Cases of pathologically suspected complete hydatidiform mole were confirmed by p57 immunohistochemistry. Data were analyzed using STATA 13. RESULTS: The prevalence of hydatidiform mole was 6.1% (11/181). All detected moles were complete hydatidiform moles, and there were no diagnosed partial hydatidiform moles. Clinical diagnosis of molar pregnancy was suspected in 13 patients, but only 69.2% (9/13) were confirmed as molar pregnancies histologically. Two cases were clinically unsuspected. Factors that had a significant relationship with complete hydatidiform mole included maternal age of 35 years and above (aOR 13.5; CI: 1.46-125.31; p=0.00), gestational age beyond the first trimester at the time of uterine evacuation (aOR 6.2; CI: 1.07-36.14; p=0.04), and history of previous abortion (aOR 4.3; CI: 1.00-18.57; p=0.05). CONCLUSION: The prevalence of complete hydatidiform mole was high at 6.1%. Associated risk factors included advanced maternal age (35 years and above), history of previous abortions, and gestational age beyond the first trimester at the time of evacuations. RECOMMENDATIONS: We recommend putting in place capacity to do routine histopathological examination of all products of conception especially those at high risk for a molar gestation either by clinical suspicion or by risk factors including advanced maternal age, advanced gestational age, and history of previous abortion because of high prevalence of complete mole.

Elevated viral restriction factor levels in cortical blood vessels in schizophrenia.

BACKGROUND: Higher tissue transcript levels of immune-related markers-including the recently discovered viral restriction factor interferon-induced transmembrane protein (IFITM), which inhibits viral entry and replication-have been reported in the prefrontal cortex in schizophrenia. Interestingly, mouse models of neuroinflammation have higher IFITM levels and deficits in γ-aminobutyric acid (GABA)-related markers that are similar to findings in schizophrenia, suggesting that a shared pathogenetic process might underlie diverse cortical pathology in the disorder. However, the cell types that overexpress IFITM messenger RNA (mRNA) in schizophrenia are unknown, and it is unclear whether higher IFITM mRNA levels are associated with lower GABA-related marker levels in the same schizophrenia subjects. METHODS: We used quantitative polymerase chain reaction and in situ hybridization with film and grain counting analyses to quantify IFITM mRNA levels in prefrontal cortex area 9 of 57 schizophrenia and 57 healthy comparison subjects and in antipsychotic-exposed monkeys. RESULTS: Quantitative polymerase chain reaction and in situ hybridization film analysis revealed markedly elevated IFITM mRNA levels (+114% and +117%, respectively) in prefrontal gray matter in schizophrenia. Interestingly, emulsion-dipped, Nissl-stained sections from schizophrenia and comparison subjects revealed IFITM mRNA expression in pia mater and blood vessels. The IFITM grain density over blood vessels was 71% higher in schizophrenia. The IFITM mRNA levels were negatively correlated with GABA-related mRNAs in the same schizophrenia subjects. CONCLUSIONS: The finding that schizophrenia subjects with higher IFITM mRNA levels in cortical blood vessels have greater disturbances in cortical GABA neurons suggests that these cell-type distinct pathological disturbances might be influenced by a shared upstream insult that involves immune activation.

Metastatic pituitary carcinoma in a patient with acromegaly: a case report.

INTRODUCTION: Asymptomatic pituitary abnormalities occur in about 10% of cranial magnetic resonance imaging scans, but metastatic carcinoma of the pituitary gland is rare: 133 cases have been reported. Two thirds secreted either prolactin or adrenocorticotropic hormone, and another 24% were non-secreting. CASE PRESENTATION: A 42-year-old Caucasian man lived for 30 years after the diagnosis of a pituitary tumor whose clinical and biochemical features were those of acromegaly and hypogonadism. Radiotherapy, totaling 7300 rad, was administered to the sella over two courses. Growth hormone levels normalized, but he developed both thyroid and adrenal insufficiency, and replacement therapy was commenced. Fourteen years later, growth hormone levels again became elevated, and bromocriptine was commenced but led to side effects that could not be tolerated. An attempted surgical intervention failed, and octreotide and pergolide were used in succession. Twenty-seven years after the diagnosis, a mass from an excisional biopsy of below the angle of the mandible proved to be metastatic pituitary carcinoma. Immunohistochemical staining was positive for synaptophysin, growth hormone, and prolactin. One year later, an octreotide scan showed uptake at the sella, neck, and spleen. Our patient declined further active oncology treatment. CONCLUSIONS: Metastatic pituitary carcinoma associated with acromegaly is particularly rare. To the best of our knowledge, this is the eighth such case and is the first report of growth hormone and prolactin present in the metastatic mass.

Deficits in transcriptional regulators of cortical parvalbumin neurons in schizophrenia.

OBJECTIVE: In schizophrenia, alterations within the prefrontal cortical GABA system appear to be most prominent in neurons that contain parvalbumin or somatostatin but not calretinin. The transcription factors Lhx6 and Sox6 play critical roles in the specification, migration, and maturation of parvalbumin and somatostatin neurons, but not calretinin neurons, and continue to be strongly expressed in this cell type-specific manner in the prefrontal cortex of adult humans. The authors investigated whether Lhx6 and/or Sox6 mRNA levels are deficient in schizophrenia, which may contribute to cell type-specific disturbances in cortical parvalbumin and somatostatin neurons. METHOD: The authors used quantitative PCR and in situ hybridization with film and grain counting analyses to quantify mRNA levels in postmortem samples of prefrontal cortex area 9 of 42 schizophrenia subjects and 42 comparison subjects who had no psychiatric diagnoses in life, as well as antipsychotic-exposed monkeys. RESULTS: In schizophrenia subjects, the authors observed lower mRNA levels for Lhx6, parvalbumin, somatostatin, and glutamate decarboxylase (GAD67; the principal enzyme in GABA synthesis), but not Sox6 or calretinin. Cluster analysis revealed that a subset of schizophrenia subjects consistently showed the most severe deficits in the affected transcripts. Grain counting analyses revealed that some neurons that normally express Lhx6 were not detectable in schizophrenia subjects. Finally, lower Lhx6 mRNA levels were not attributable to psychotropic medications or illness chronicity. CONCLUSIONS: These data suggest that in a subset of individuals with schizophrenia, Lhx6 deficits may contribute to a failure of some cortical parvalbumin and somatostatin neurons to successfully migrate or develop a detectable GABA-ergic phenotype.

Cortical opioid markers in schizophrenia and across postnatal development.

Certain cognitive deficits in schizophrenia have been linked to dysfunction of prefrontal cortical (PFC) γ-aminobutyric acid (GABA) neurons and appear neurodevelopmental in nature. Since opioids suppress GABA neuron activity, we conducted the first study to determine 1) whether the µ opioid receptor (MOR), δ opioid receptor (DOR), and opioid ligand proenkephalin are altered in the PFC of a large cohort of schizophrenia subjects and 2) the postnatal developmental trajectory in monkey PFC of opioid markers that are altered in schizophrenia. We used quantitative polymerase chain reaction to measure mRNA levels from 42 schizophrenia and 42 matched healthy comparison subjects; 18 monkeys chronically exposed to haloperidol, olanzapine, or placebo; and 49 monkeys aged 1 week-11.5 years. We found higher levels for MOR mRNA (+27%) in schizophrenia but no differences in DOR or proenkephalin mRNAs. Elevated MOR mRNA levels in schizophrenia did not appear to be explained by substance abuse, psychotropic medications, or illness chronicity. Finally, MOR mRNA levels declined through early postnatal development, stabilized shortly before adolescence and increased across adulthood in monkey PFC. In schizophrenia, higher MOR mRNA levels may contribute to suppressed PFC GABA neuron activity and might be attributable to alterations in the postnatal developmental trajectory of MOR signaling.

Florid basal cell hyperplasia of the prostate: a histological, ultrastructural, and immunohistochemical analysis.

Basal cell proliferation is a common finding in a benign hyperplastic prostate gland. Occasionally, basal cell hyperplasia is so florid that it can be mistaken for prostatic adenocarcinoma. We characterized histological, ultrastructural, and immunohistochemical features of florid basal cell hyperplasia from transurethral resections (n = 11) and prostatectomy specimens (n = 4). Fifteen cases of prostatic adenocarcinoma were used as comparison. Intraluminal calcification was present in 40% of florid basal cell hyperplasia cases (6 of 15) and a unique finding of intracytoplasmic hyaline globules was detected in 53.3% of florid basal cell hyperplasia cases (8 of 15). Ultrastructural analysis revealed luminal calcification and intracytoplasmic electron-dense globules in foci of basal cell hyperplasia. Crystalloids, a frequent finding in low-grade prostate cancer, were absent in all 15 cases of florid basal cell hyperplasia. By immunohistochemistry, the basal cell-specific 34betaE12 and p63 as well as glutathione-s-transferase pi were positive in all basal cell hyperplasia cases but negative in all prostatic adenocarcinomas. These distinguishing features of florid basal cell hyperplasia are helpful in differential diagnosis from prostatic adenocarcinoma. Cytokeratins 8 and 18 were both positive in basal cells, benign secretory cells, and carcinoma cells, failing to be of discrimatory value. Immunostaining for alpha-methylacyl-coenzyme racemase, a new prostate cancer marker, was negative in hyperplastic basal cells but detected a distinct minor benign cell population in basal cell hyperplasia of possible neuroendocrine origin.

Pathogenesis and significance of collagenous micronodules of the prostate.

Collagenous micronodules, also known as mucinous fibroplasia, are microscopic structures characterized by the presence of small eosinophilic nodules in areas immediately adjacent to prostatic glandular epithelium. The pathogenesis of collagenous micronodules is unknown, although their relation with mucin has been suggested. The objective of our study was to analyze the structural characteristics of collagenous micronodules by using histochemistry, immunohistochemistry, and electron microscopy to elucidate the pathogenesis of this lesion. We analyzed 15 cases of prostate adenocarcinoma (12 prostatectomy specimens and 3 biopsy specimens) with collagenous micronodules. The collagenous micronodules were closely associated with well-formed malignant glands, where tumor cells exhibited basophilic to amphophilic cytoplasm. Occasionally, intraluminal collagen fragments were observed within malignant but not benign glands. Collagenous micronodules were not associated with mucin, confirmed by negative stainings of mucicarmin or alcian blue in all the collagenous micronodules analyzed in this study. Therefore, the term "mucinous fibroplasia" may not be accurate. Collagenous micronodules stained weakly positive for periodic acid-Schiff. Trichrome stain highlighted the presence of collagenous micronodules as distinct blue structures. Collagen IV and laminin immunostaining performed in 12 cases outlined the micronodules with minimal staining in the center. These findings indicated that collagenous micronodules consisted of predominantly collagen fragments admixed with basement membrane material. Ultrastructurally, they were composed of fragmented banded collagen fibrils surrounded by the basement membrane material. Collagenous micronodules are formed by subepithelial accumulations of fragmented collagen fibers, possibly related to the digestion by collagenase produced by prostatic adenocarcinoma cells.