Catalogue Search | MBRL
Are you sure you want to remove the book from the shelf?
{{itemTitle}}
536
result(s) for
"Hill, Ashley"
Sort by:
DICER1 tumor predisposition syndrome: an evolving story initiated with the pleuropulmonary blastoma
DICER1
syndrome (OMIM 606241, 601200) is a rare autosomal dominant familial tumor predisposition disorder with a heterozygous
DICER1
germline mutation. The most common tumor seen clinically is the pleuropulmonary blastoma (PPB), a lung neoplasm of early childhood which is classified on its morphologic features into four types (IR, I, II and III) with tumor progression over time within the first 4–5 years of life from the prognostically favorable cystic type I to the unfavorable solid type III. Following the initial report of PPB, its association with other cystic neoplasms was demonstrated in family studies. The detection of the germline mutation in
DICER1
provided the opportunity to identify and continue to recognize a number seemingly unrelated extrapulmonary neoplasms: Sertoli-Leydig cell tumor, gynandroblastoma, embryonal rhabdomyosarcomas of the cervix and other sites, multinodular goiter, differentiated and poorly differentiated thyroid carcinoma, cervical-thyroid teratoma, cystic nephroma-anaplastic sarcoma of kidney, nasal chondromesenchymal hamartoma, intestinal juvenile-like hamartomatous polyp, ciliary body medulloepithelioma, pituitary blastoma, pineoblastoma, primary central nervous system sarcoma, embryonal tumor with multilayered rosettes-like cerebellar tumor, PPB-like peritoneal sarcoma,
DICER1
-associated presacral malignant teratoid neoplasm and other non-neoplastic associations. Each of these neoplasms is characterized by a second somatic mutation in
DICER1
. In this review, we have summarized the salient clinicopathologic aspects of these tumors whose histopathologic features have several overlapping morphologic attributes particularly the primitive mesenchyme often with rhabdomyoblastic and chondroid differentiation and an uncommitted spindle cell pattern. Several of these tumors have an initial cystic stage from which there is progression to a high grade, complex patterned neoplasm. These pathologic findings in the appropriate clinical setting should serve to alert the pathologist to the possibility of a
DICER1
-associated neoplasm and initiate appropriate testing on the neoplasm and to alert the clinician about the concern for a
DICER1
mutation.
Journal Article
Hormone Therapy and Other Treatments for Symptoms of Menopause
The results of large clinical trials have led physicians and patients to question the safety of hormone therapy for menopause. In the past, physicians prescribed hormone therapy to improve overall health and prevent cardiac disease, as well as for symptoms of menopause. Combined estrogen/progestogen therapy, but not estrogen alone, increases the risk of breast cancer when used for more than three to five years. Therefore, in women with a uterus, it is recommended that physicians prescribe combination therapy only to treat menopausal symptoms such as vasomotor symptoms (hot flashes) and vaginal atrophy, using the smallest effective dosage for the shortest possible duration. Although estrogen is the most effective treatment for hot flashes, nonhormonal alternatives such as low-dose paroxetine, venlafaxine, and gabapentin are effective alternatives. Women with a uterus who are using estrogen should also take a progestogen to reduce the risk of endometrial cancer. Women who cannot tolerate adverse effects of progestogens may benefit from a combined formulation of estrogen and the selective estrogen receptor modulator bazedoxifene. There is no high-quality, consistent evidence that yoga, paced respiration, acupuncture, exercise, stress reduction, relaxation therapy, and alternative therapies such as black cohosh, botanical products, omega-3 fatty acid supplements, and dietary Chinese herbs benefit patients more than placebo. One systematic review suggests modest improvement in hot flashes and vaginal dryness with soy products, and small studies suggest that clinical hypnosis significantly reduces hot flashes. Patients with genitourinary syndrome of menopause may benefit from vaginal estrogen, nonhormonal vaginal moisturizers, or ospemifene (the only nonhormonal treatment approved by the U.S. Food and Drug Administration for dyspareunia due to menopausal atrophy). The decision to use hormone therapy depends on clinical presentation, a thorough evaluation of the risks and benefits, and an informed discussion with the patient.
Journal Article
Poorly differentiated thyroid carcinoma of childhood and adolescence: a distinct entity characterized by DICER1 mutations
Poorly differentiated thyroid carcinomas (PDTC) in young individuals are rare and their clinical and histopathologic features, genetic mechanisms, and outcomes remain largely unknown. Here, we report a detailed characterization of a series of six PDTC in patients ≤21 years old defined by Turin diagnostic criteria studied for mutations and gene fusions characteristic of thyroid cancer using targeted next-generation sequencing (NGS) and whole-exome sequencing (WES). All tumors had solid, insular, or trabecular growth pattern and high mitotic rate, and five out of six tumors showed tumor necrosis. Targeted NGS assay identified somatic mutations in the
DICER1
gene in five of six (83%) tumors, all of which were “hotspot” mutations encoding the metal-ion binding sites of the RNase IIIb domain of
DICER1
. WES was performed in five cases which confirmed all hotspot mutations and detected two tumors with additional inactivating
DICER1
alterations. Of these two, one was a germline pathogenic
DICER1
variant and the other had loss of heterozygosity for
DICER1
. No other mutations or gene fusions characteristic of adult well-differentiated thyroid cancer and PDTC (
BRAF
,
RAS
,
TERT
,
RET/PTC,
and other) were detected. On follow-up, available for five patients, three patients died of disease 8–24 months after diagnosis, whereas two were alive with no disease. The results of our study demonstrate that childhood- and adolescent-onset PDTC are genetically distinct from adult-onset PDTC in that they are strongly associated with
DICER1
mutations and may herald DICER1 syndrome in a minority. As such, all young persons with PDTC may benefit from genetic counseling. Furthermore, their clinically aggressive behavior contrasts sharply with the indolent nature of the great majority of thyroid tumors with
DICER1
mutations reported to date.
Journal Article
Zika Virus Infection with Prolonged Maternal Viremia and Fetal Brain Abnormalities
Brief Report: Zika Virus Infection and Fetal Brain Abnormalities
In this case report, the association between Zika virus infection and teratogenicity is strengthened, with evidence that the latency period between ZIKV infection of the fetal brain and the detection of microcephaly and intracranial calcifications on ultrasonography may be prolonged.
Zika virus (ZIKV), a mosquito-borne flavivirus and member of the Flaviviridae family, was originally isolated from a sentinel primate in Uganda in 1947.
1
ZIKV was associated with mild febrile disease and maculopapular rash in tropical Africa and some areas of Southeast Asia. Since 2007, ZIKV has caused several outbreaks outside its former distribution area in islands of the Pacific: in 2007 on Yap island in Micronesia, in 2013 and 2014 in French Polynesia, and in 2015 in South America, where ZIKV had not been identified previously.
2
–
5
There are separate African and Asian lineages of the virus,
6
and the latter . . .
Journal Article
Sexually transmitted infections and risk of hypertensive disorders of pregnancy
Hypertensive disorders of pregnancy (HDP) result in maternal morbidity and mortality but are rarely examined in perinatal studies of sexually transmitted infections. We examined associations between common sexually transmitted infections and HDP among 38,026 singleton pregnancies. Log-binomial regression calculated relative risk (RRs) and 95% confidence intervals (CIs) for associations with gestational hypertension, preeclampsia with severe features, mild preeclampsia, and superimposed preeclampsia. All models were adjusted for insurance type, maternal age, race/ethnicity, and education. Additional adjustments resulted in similar effect estimates. Chlamydia was associated with preeclampsia with severe features (RR
adj
. 1.4, 95% CI 1.1, 1.9). Effect estimates differed when we examined first prenatal visit diagnosis only (RR
adj
. 1.3, 95% CI 0.9, 1.9) and persistent or recurrent infection (RR
adj
. 2.0, 95% CI 1.1, 3.4). For chlamydia (RR
adj
. 2.0, 95% CI 1.3, 2.9) and gonorrhea (RR
adj
. 3.0, 95% CI 1.1, 12.2), women without a documented treatment were more likely to have preeclampsia with severe features. Among a diverse perinatal population, sexually transmitted infections may be associated with preeclampsia with severe features. With the striking increasing rates of sexually transmitted infections, there is a need to revisit the burden in pregnant women and determine if there is a link between infections and hypertensive disorders of pregnancy.
Journal Article
Placental Pathology of Zika Virus: Viral Infection of the Placenta Induces Villous Stromal Macrophage (Hofbauer Cell) Proliferation and Hyperplasia
Context.— The placenta is an important component in understanding the fetal response to intrauterine Zika virus infection, but the pathologic changes in this organ remain largely unknown. Hofbauer cells are fetal-derived macrophages normally present in the chorionic villous stroma. They have been implicated in a variety of physiological and pathologic processes, in particular involving infectious agents. Objectives.— To characterize the fetal and maternal responses and viral localization in the placenta following Zika virus transmission to an 11 weeks' gestation fetus. The clinical course was notable for prolonged viremia in the mother and extensive neuronal necrosis in the fetus. The fetus was delivered at 21 weeks' gestation after pregnancy termination. Design.— The placenta was evaluated by using immunohistochemistry for inflammatory cells (macrophages/monocytes [Hofbauer cells], B and T lymphocytes) and proliferating cells, and an RNA probe to Zika virus. The fetal brain and the placenta were previously found to be positive for Zika virus RNA by reverse transcription–polymerase chain reaction. Results.— The placenta demonstrated prominently enlarged, hydropic chorionic villi with hyperplasia and focal proliferation of Hofbauer cells. The degree of Hofbauer cell hyperplasia gave an exaggerated immature appearance to the villi. No acute or chronic villitis, villous necrosis, remote necroinflammatory abnormalities, chorioamnionitis, funisitis, or hemorrhages were present. An RNA probe to Zika virus was positive in villous stromal cells, presumably Hofbauer cells. Conclusions.— Zika virus placental infection induces proliferation and prominent hyperplasia of Hofbauer cells in the chorionic villi but does not elicit villous necrosis or a maternal or fetal lymphoplasmacellular or acute inflammatory cell reaction.
Journal Article
Pleuropulmonary blastoma-like peritoneal sarcoma: a newly described malignancy associated with biallelic DICER1 pathogenic variation
Since the original description of pathogenic germline
DICER1
variation underlying pleuropulmonary blastoma (PPB), the spectrum of extrapulmonary neoplasms known to be associated with
DICER1
has continued to expand and now includes tumors of the ovary, thyroid, kidney, eye, and brain among other sites. This report documents our experience with another manifestation: a primitive sarcoma that resembles PPB and
DICER1-
associated sarcoma of the kidney. These tumors are distinguished by their unusual location in the peritoneal cavity, associated with visceral and/or parietal mesothelium. A total of seven cases were identified through pathology review in children presenting at a median age of 13 years (range 3–14 years). Primary sites of origin included the fallopian tube (four cases), serosal surface of the colon (one case), and pelvic sidewall (two cases). One case had pathologic features of type I PPB, another type Ir (regressed) PPB, and the remaining five had features of type II or III PPB with a mixed primitive sarcomatous pattern with or without cystic elements. All had a pathogenic
DICER1
variation identified in germline and/or tumor DNA. PPB-like peritoneal tumors represent a newly described manifestation of
DICER1
pathogenic variation whose pathologic features are also recapitulated in
DICER1
-related renal sarcoma, cervical embryonal rhabdomyosarcoma, and some Sertoli–Leydig cell tumors with heterologous elements. Tumors arising from the fallopian tube or elsewhere in the abdomen/pelvis, especially those with heterogeneous rhabdomyosarcomatous and/or cartilaginous differentiation, should prompt consideration of germline and tumor
DICER1
testing.
Journal Article
Dyspareunia in Women
Dyspareunia is recurrent or persistent pain with sexual intercourse that causes distress. It affects approximately 10% to 20% of U.S. women. Dyspareunia may be superficial, causing pain with attempted vaginal insertion, or deep. Women with sexual pain are at increased risk of sexual dysfunction, relationship distress, diminished quality of life, anxiety, and depression. Because discussing sexual issues may be uncomfortable, clinicians should create a safe and welcoming environment when taking a sexual history, where patients describe the characteristics of the pain (e.g., location, intensity, duration). Physical examination of the external genitalia includes visual inspection and sequential pressure with a cotton swab, assessing for focal erythema or pain. A single-digit vaginal examination may identify tender pelvic floor muscles, and a bimanual examination can assess for uterine retroversion and pelvic masses. Common diagnoses include vulvodynia, inadequate lubrication, vaginal atrophy, postpartum causes, pelvic floor dysfunction, endometriosis, and vaginismus. Treatment is focused on the cause and may include lubricants, pelvic floor physical therapy, topical analgesics, vaginal estrogen, cognitive behavior therapy, vaginal dilators, modified vestibulectomy, or onabotulinumtoxinA injections.
Journal Article
Embryonal rhabdomyosarcoma of the uterine cervix: a report of 14 cases and a discussion of its unusual clinicopathological associations
Embryonal rhabdomyosarcoma of the uterine cervix is an uncommon presentation of the most common soft-tissue sarcoma in the first decades of life. Unlike embryonal rhabdomyosarcoma in other anatomic sites, in which 70–80% of cases present before 9 years of age, the average age in our series of 14 cervical cases was 12.4 years (median, 13 years), with an age range of 9 months to 32 years at diagnosis. Of the 14 cases, 12 presented as a polyp at the cervical os; two patients had an infiltrative mass in the cervix without a botryoid polyp. The polyps measured 1.5–5 cm and all had the histopathological pattern of the sarcoma botryoides variant of embryonal rhabdomyosarcoma, with condensations of primitive and differentiated rhabdomyoblasts beneath the surface epithelium and around endocervical glands. Nodules of benign-appearing cartilage were present in the stroma of six cases (43%). One of the embyronal rhabdomyosarcomas from the youngest patient, 9 months old, also had a distinctive microscopic focus of immature tubular profiles in a primitive stroma; these tubules expressed epithelial and neuroendocrine markers. Two patients had a pleuropulmonary blastoma, one diagnosed 9 years before the embryonal rhabdomyosarcoma of the cervix and the other recognized synchronously. This latter 9-year old had a
DICER1
germline mutation. One patient presented with hirsutism and had a Sertoli–Leydig cell tumor, an incidentally detected cervical embryonal rhabdomyosarcoma, and nodular hyperplasia of the thyroid. Although a pleuropulmonary blastoma was not documented in the latter patient, ovarian sex-cord stromal tumors and nodular hyperplasia of the thyroid are manifestations of the pleuropulmonary blastoma family tumor and dysplasia syndrome (OMIM 601200). Embryonal rhabdomyosarcoma of the cervix must be distinguished from other rare entities, including adenosarcoma, malignant mixed Mullerian tumor and low-grade stromal sarcoma, as the former has a better prognosis; 12 of our 14 patients remain disease-free following conservative surgery and chemotherapy. Our study suggests that cervical embryonal rhabdomyosarcoma may be another pathological manifestation in the spectrum of extrapulmonary pathology in the setting of pleuropulmonary blastoma.
Journal Article