Catheter Tip-Associated Mass With Continuous Infusion of Sufentanil for Persistent Spinal Pain Syndrome Type 2: A Case Report Including Histopathologic Examination and Review of the Associated Basic and Clinical Research.

OBJECTIVES: Intrathecal opioids delivered by implanted pumps are used to treat malignant or nonmalignant chronic pain. In this study, we 1) review a case in which intrathecal infusions of sufentanil along with other adjuvants were used and after an extended period led to an intrathecal mass and 2) compared and contrasted the potential mechanisms for these phenomena. MATERIALS AND METHODS: A woman aged 66 years with a history of scoliosis and multiple spine surgeries was treated with an implantable drug delivery system for treating persistent pain after laminectomy. The patient received intrathecal medication comprising sufentanil, bupivacaine, and clonidine. RESULTS: Intrathecal therapy over approximately ten years served to reduce pain and improve function over the treatment period. After the extended treatment interval, the patient developed an intrathecal mass that was associated with impairment. The mass was surgically removed. Systematic histopathology revealed the space-occupying mass to largely comprise fibroblasts and some inflammatory cells embedded in a collagen mass located proximally to the catheter tip. CONCLUSIONS: To our knowledge, this is the first published case report of sufentanil causing this complication. The science and mechanism of intrathecal catheter tip-associated mass formation and associated clinical research correlates are reviewed in detail, and explanations for this phenomenon are proposed based on histochemical analysis of the patient's pathology findings.

Rare Mesenchymal Tumors of the Pelvis: Imaging and Pathologic Correlation.

Most pelvic tumors originate from the organs. Less commonly, tumors can arise from the various anatomic pelvic compartments and are comprised of mesenchymal tissue: muscles, connective tissue, vessels, lymphatics, and fat. Among some of the rarer entities are benign tumors (eg, angiomyxoma, cellular angiofibroma, and desmoid fibromatosis), malignant tumors (eg, sarcoma), and tumors that can manifest as benign or malignant (eg, solitary fibrous tumor or nerve sheath tumor). Because these tumors are uncommon and often manifest with nonspecific clinical features, imaging (usually MRI) is an initial step in the evaluation. Radiologists interpreting these images are asked to help narrow the differential diagnosis and assess the likelihood of malignancy for treatment planning. Thus, the MRI report should include the imaging features that would indicate the underlying tissue histology for pathologic diagnosis as well as a description of the anatomic extent and pattern of growth. The authors describe multiple locally aggressive benign and malignant mesenchymal tumors and highlight characteristic clinical and imaging features that enable the radiologist to narrow the differential diagnosis. The anatomic spaces of the pelvis are reviewed with illustrations to aid the radiologist in describing these tumors, which often span multiple pelvic compartments. Tumor appearance at T2-weighted, diffusion-weighted, and postcontrast MRI is summarized and illustrated with correlation at CT or fluorodeoxyglucose PET/CT, when available. MRI features that correspond to specific types of tissue (eg, myxoid, fibrous, or vascular) are highlighted and correlated with images from pathologic evaluation. Online supplemental material is available for this article. ©RSNA, 2021.

Interobserver reproducibility of the diagnosis of differentiated exophytic vulvar intraepithelial lesion (DEVIL) and the distinction from its mimics.

AIMS: Most vulvar squamous cell carcinomas are human papillomavirus (HPV)-associated or TP53-mutant. A third category of HPV-independent TP53-wild-type lesions is uncommon and not fully understood. Differentiated exophytic vulvar intraepithelial lesion (DEVIL) has been characterised as a precursor of this latter category. The reproducibility of the diagnosis of DEVIL and its distinction from lesions with overlapping morphology has not been studied. Our aim was to establish the interobserver agreement in the diagnosis of DEVIL and its distinction from neoplastic and reactive conditions of the vulva on haematoxylin and eosin evaluation. METHODS AND RESULTS: A set of 35 slides was evaluated by eight reviewers (two trainees and six practising gynaecological pathologists). The set included DEVIL, condyloma, established vulvar precursors [high-grade squamous intraepithelial lesion (HSIL) and differentiated vulvar intraepithelial neoplasia (dVIN)] with superimposed acanthosis or verruciform growth, lichen simplex chronicus (LSC), and psoriasis. Kappa (κ) values were calculated. Overall, interobserver agreement was moderate (κ = 0.56), improving to substantial (κ = 0.7) when evaluation was performed by practising pathologists. Agreement was strong for the diagnosis of HSIL (κ = 0.88), and substantial for the diagnosis of DEVIL (κ = 0.61), condyloma (κ = 0.79), and LSC (κ = 0.72). Agreement was moderate for the diagnosis of dVIN (κ = 0.59) and psoriasis (κ = 0.53). Perfect agreement (6/6) among practising pathologists was observed in 43% of cases, and majority agreement (5/6 or 4/6) was observed in 48% of cases. CONCLUSIONS: Reproducibility in the diagnosis of verruciform vulvar lesions, including the novel DEVIL, is acceptable overall. Reproducibility is higher for well-known lesions such as HSIL and condyloma than for more challenging diagnoses such as DEVIL, dVIN, and psoriasis. Agreement is higher among practising gynaecological pathologists, suggesting that training and experience improve reproducibility. Our findings support the inclusion of DEVIL as a diagnostic entity in the classification of vulvar squamous lesions.

Is excision biopsy of fibroadenomas based solely on size criteria warranted?

Fibroadenomas (FA) are the most common benign tumor in the female breast. Most are managed conservatively provided there is clinical, radiologic, and pathologic concordance. However, surgical excision is typically recommended for cellular fibroepithelial lesions or those lesions with clinical, radiologic, or pathologic features concerning for phyllodes tumor (PT). Some studies have suggested surgical excision in all FA >30 mm to reduce core needle biopsy (CNB) sampling errors. The aim of our study was to evaluate, in the absence of any other concerning clinicopathologic features, whether surgical excision of FA was warranted based on size criteria alone. Cork University Hospital is a large academic center in Southern Ireland. Its breast cancer center provides both a screening and symptomatic service and diagnoses approximately 600 cancers per year. The breast histopathological data base was reviewed for all CNBs from January 1, 2010, to June 30, 2015, with a diagnosis of FA that went on to have excision at our institution. We excluded all cellular fibroepithelial lesions and those cases with co-existent lobular neoplasia, ductal carcinoma in situ, invasive carcinoma, atypical ductal hyperplasia, or lesions which would require excision in their own right. Cases in which the radiologic targeted mass was discordant with a diagnosis of FA were also excluded. Patient demographics and preoperative radiologic size and the radiologic target were recorded in each case. All radiology was reviewed by a breast radiologist prior to inclusion in the study, and there was histologic radiologic concordance with a diagnosis of FA in all cases. A total of 12,109 consecutive radiologically guided CNB were performed January 2010-June 2015; 3438 with a diagnosis of FA were identified of which 290 cases went on to have surgical excision. Of those 290 cases; 98.28% (n = 285) were confirmed as FA on excision. The remaining 1.72% (n = 5) had atypical features-FA with LCIS (n = 1), benign PT (n = 3), and invasive ductal carcinoma (n = 1). Our study suggests that, excision based solely on size is not warranted in clinical and radiologically concordant cases with a diagnosis of FA on CNB.

Low incidence of BRAF and NRAS mutations in a population with a high incidence of melanoma.

Reported rates of BRAF mutation in Irish cutaneous melanoma cohorts are lower than the reported international data. We aimed to assess the mutational status of a cohort of primary cutaneous melanomas and to correlate it with clinical follow-up data.A total of 92 cases of primary cutaneous melanoma diagnosed at a single institution in 2012 were analyzed. Regions containing common mutations in the BRAF, NRAS, KIT, and KRAS genes were investigated by PCR amplification followed by Sanger sequencing. Demographic details, tumor characteristics, and 10-year outcome data were also obtained.Ten cases with BRAF V600E mutations (11.6%) and five (5.49%) NRAS mutations (4 at Q61R, 1 at Q61K) were detected. No statistically significant differences were noted between groups for age, gender, depth of invasion, nodal status, or recurrence status (p ≥ 0.05).These findings suggest that the Irish population has a markedly lower incidence of BRAF and NRAS mutations in melanoma than those reported in other cohorts.

Placenta Accreta Spectrum: Evaluation of classic and non-classic presentations, pathologic grading, and uterine scar dehiscence features in a modern institutional series.

INTRODUCTION: The aim of this study is to document the distribution of classic versus non-classic presentation of Placenta Accreta Spectrum (PAS) disorders as well as grading categories by the Society for Pediatric Pathology (SPP) and FIGO systems in an institutional cohort of gravid hysterectomies. We also document the prevalence of uterine scar as a histologic correlate for uterine scar dehiscence, a phenomenon raised by some as central to PAS pathogenesis. METHODS: PAS cases were assigned grade and designated as classic (anterior lower uterine segment implantation, prior C-section) or non-classic (implantation away from anterior lower uterine segment and/or no prior C-section). Features of dehiscence (uterine window, histologic evidence of scar) were recorded. RESULTS: Sixty-two patients were included: 76 % had prior C-section; 55 % had other forms of uterine instrumentation. Classic PAS was recorded in 52 % patients; notably, 48 % had non-classic presentation; of these, all but one had prior instrumentation (curettage, myomectomy, laparoscopy). Uterine window was described in 53 % classic and 23 % non-classic PAS. Scar was demonstrated in 31 % classic and 23 % non-classic PAS; trichrome/reticulin stains were confirmatory. 32 % cases were SPP grade 1, 18 % grade 2, 18 % grade 3a and 32 % grade 3d. Grade 3 was significantly more common in classic (72 %) than non-classic (27 %) PAS. DISCUSSION: While most PAS patients have classic presentation, a large subset does not; in addition, scar tissue is not identified histologically in most PAS hysterectomies; in these settings, PAS cannot be fully attributed to scar dehiscence. Uterine instrumentation often precedes non-classic PAS reinforcing the concept of decidual disruption as central to PAS pathogenesis. PAS grading as defined correlates with presentation (classic vs non-classic).

Prostatic Metaplasia of the Vagina and Uterine Cervix: An Androgen-associated Glandular Lesion of Surface Squamous Epithelium.

Prostatic-type differentiation in the lower female genital tract is encountered rarely and its causes and clinical associations are not well established. Within the vagina, reports to date have invariably described ectopic prostatic-type differentiation as restricted to the lamina propria. We recently encountered a patient receiving testosterone for gender dysphoria whose vaginectomy specimen showed a prostatic glandular proliferation within the surface epithelium. To elucidate its potential association with androgen exposure, we sought similar lesions, resected over a 26-year period, from patients with exogenous or endogenous androgen excess. Thirteen cases were identified, involving the vagina (n=12) and exocervix (n=1). The most common clinical context was gender dysphoria with long-term testosterone therapy; the lesion was present in 7 of 8 gender-dysphoric patients examined. Four other patients had congenital disorders of sexual development associated with endogenous androgen excess (congenital adrenal hyperplasia, 46,XY disorder of sexual development, and ovotesticular disorder of sexual development). Two had no known exposure to androgen excess. Immunohistochemically, glands stained for NKX3.1 (100% of cases), androgen receptor (100%), CK7 (92%), and prostate-specific antigen (69%). Follow-up (median duration, 11 mo) showed no masses or neoplasia. We propose the designation "androgen-associated prostatic metaplasia" for this form of prostate tissue with distinctive clinical, histologic and immunohistochemical features. It is novel and previously unrecognized within the vagina. It is strikingly prevalent among patients undergoing gender-affirming surgery, an increasingly common procedure. Recognition is important to distinguish it from other potentially neoplastic glandular lesions and facilitate accrual of more follow-up data to better understand its natural history.

Rounded intraplacental hematoma - A high risk placental lesion as illustrated by a prospective study of 26 consecutive cases.

BACKGROUND: A rounded intraplacental hematoma (RIH) is a recently delineated placental lesion. Following the observation of two cases of RIH in placentas associated with stillbirth in 2012, we postulated that RIHs were associated with a higher risk obstetric phenotype when compared to other lesions characteristic of maternal vascular malperfusion (MVM). We aimed to investigate this further by reviewing the associated maternal and fetal characteristics in a series of prospectively identified cases. METHODS: Pregnancies where a RIH was identified on placental examination were prospectively collected from February 2014-July 2016. Comparison was made with pregnancies with placental evidence of MVM but without RIH. RESULTS: 26 placentas with a RIH were identified and 26 placentas with MVM were selected for comparison. There was a statistically significantly increased incidence of stillbirth in the RIH group as compared with the MVM-only group (p = 0.022). Also, pregnancies with RIHs had a lower maternal age (p = 0.041), decreased incidence of antenatally diagnosed growth restriction (p = 0.023), a trend to increased incidence of clinical abruption (p = 0.051) and heavier mean infant birthweight (p = 0.034). Both groups had a high incidence of pre-eclampsia, Caesarean section and preterm delivery when compared with the general population. DISCUSSION: This is the first study to prospectively identify and collect RIHs using standardised pathological criteria and more than doubles the number of reported cases to date. We present 2 comparable, high-risk cohorts but with a significantly increased incidence of stillbirth in those in which RIHs were seen. Further study of these lesions is justified with an emphasis on the potential for antenatal detection using ultrasound evaluation of placental texture.

Vitamin D status and fertility outcomes during winter among couples undergoing in vitro fertilization/intracytoplasmic sperm injection.

OBJECTIVE: To assess the vitamin D status of men and women undergoing in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI), and to investigate associations between vitamin D status and fertility variables. METHODS: A cross-sectional prospective study was undertaken of men and women attending a fertility clinic in Ireland for IVF/ICSI between January and March 2014. Vitamin D status was determined by measurement of serum 25-hydroxyvitamin D (25(OH)D). Questionnaires examined knowledge and practices concerning vitamin D. Fertility variables and pregnancy outcomes were assessed in relation to vitamin D status. RESULTS: Overall, 73 men and 64 women provided blood samples. Among men, no correlation was found between 25(OH)D and total motility (ρ=0.069, P=0.562), progressive motility (ρ=0.066, P=0.576), count (ρ=0.001, P=0.996), or morphology (ρ=-0.034, P=0.774) of sperm. Additionally, there was no association between 25(OH)D and ongoing pregnancy rates (P=0.158). There was no difference in 25(OH)D between men with and without male factor subfertility issues (P=0.856). Among women, there was no significant correlation between 25(OH)D and anti-Müllerian hormone (P=0.629) or number of collected (P=0.198) and fertilized oocytes (P=0.136). There was no difference in 25(OH)D between women with and without ongoing pregnancy (P=0.222). CONCLUSION: No correlation was found between fertility variables or pregnancy outcomes and male or female vitamin D status.

'Miracle baby': an outcome of multidisciplinary approach to neurotrauma in pregnancy.

Traumatic brain injury (TBI) warranting neurosurgical intervention in the pregnant population is a rarity. We describe a case of a 27-year-old woman who at 13 weeks of gestation presented with multiple traumas having been involved in a near fatal road traffic accident. Glasgow Coma Scale was 6/15. CT brain showed extensive haemorrhagic contusions, diffuse brain swelling and multiple skull and facial fractures. Decompressive craniectomy was performed to control her intracranial pressure during her management in the intensive care. A viable intrauterine pregnancy was confirmed and progressed as maternal stabilisation and rehabilitation continued. At 35+3 weeks a 2770 g male child was delivered via emergency caesarean section after spontaneous onset of labour. The child had no detectable abnormalities and is clinically well. Eight months post-TBI the patient continues to make gradual improvements but is left with severe cognitive impairment and currently undergoing rehabilitation. A multidisciplinary approach was adopted in the management of this patient.