The role of the ThyGeNEXT oncogene panel used in combination with the expanded miRNA panel ThyraMIRv2 in Indeterminate thyroid nodules: A large, blinded, real-world, observational study.

BACKGROUND: Molecular analysis of fine-needle aspiration biopsies (FNAB) improves the diagnostic accuracy of cytologically indeterminate thyroid nodules (ITNs). Recently, the use of MPTXv2 has been shown to further improve the accuracy of risk stratification of ITNs. METHODS: A total of 338 patient samples with atypia of undetermined significance (n = 260) or follicular neoplasm (n = 78) cytology diagnosis and corresponding surgical outcomes or clinical follow-up, collected between 2016 and 2020 were included. All samples underwent multiplatform testing (MPTXv1), which includes an oncogene panel (ThyGeNEXT®) plus a microRNA risk classifier (ThyraMIR®). A blinded, secondary analysis was performed to assess the added utility of MPTXv2 (ThyraMIR®v2). The average length of follow-up for the surveillance group (n = 248) was 30 months. RESULTS: Sensitivity at moderate threshold was 96% and specificity at positive threshold was 99% for MPTXv2. At 14% disease prevalence, the negative predictive value at the moderate threshold was 99% and the positive predictive value at the positive threshold was 89% for MPTXv2. MPTXv2 had fewer patients classified into the moderate-risk group than MPTXv1, which was statistically significant (p < .001). Using surgical resection, the gold standard for outcomes, MPTXv2 showed a statistically greater area under the curve (p = .028) than MPTXv1, demonstrating greater accuracy for MPTXv2. CONCLUSION: Both test versions demonstrated robust performance with low false-positive molecular results. Data suggest that incorporation of MPTXv1, and more recently MPTXv2, into clinical practice within our healthcare network resulted in improved accuracy of ITN risk stratification.

Stem cell induced inflammatory hypertrophy of the cauda equina.

Stem cell therapy can present clinicians with challenging clinical scenarios, as access to such treatments outpaces the research into their efficacy and safety due to the burgeoning trend of international travel to acquire stem cell therapy, or "stem cell tourism." Treatment of neurologic conditions remains an enticing potential application of stem cell therapy, often administered intrathecally. In response to such therapy, multiple adverse events have been described in the literature, including neoplasms, demyelinating disease, and seizures, among others. We present a case of symptomatic inflammatory cauda equina nerve root hypertrophy due to intrathecal stem cell infusion, representing a rare but significant complication.

Schnitzler's Syndrome: A Diagnostic Consideration in Evaluating the Constellation of Monoclonal Gammopathy and Chronic Urticaria.

Schnitzler's syndrome is a rare clinical entity characterized by intermittent, non-pruritic urticarial rash, fevers, arthralgias, myalgias and monoclonal gammopathy, most commonly of the immunoglobulin M (IgM) subtype. Schnitzler's syndrome should be considered in the differential diagnosis of fever of unknown origin. We report a case of a 56-year-old healthy Caucasian female, who initially presented to the primary care physician's office with complaints of severe generalized fatigue and myalgias involving thighs and calves. Patient subsequently underwent extensive rheumatologic workup, and was treated with multiple courses of steroids with temporary resolution of symptoms. During the course of her workup she was found to have IgM kappa monoclonal gammopathy, and was referred to hematology for further evaluation. The constellation findings of fever, arthralgias, chronic intermittent non-pruritic urticaria, myalgias, and a negative rheumatologic workup in the presence of IgM monoclonal gammopathy raised the suspicion of Schnitzler's syndrome. Following completion of additional workup, she was started on anakinra 100 mg daily with prompt resolution of her symptoms. Due to the rarity of the disease, the diagnosis of Schnitzler's syndrome is often delayed, with an average time to diagnosis being approximately 5 years. The symptoms in most cases can be debilitating and add to significant morbidity as noted in our patient, who required bilateral hip arthroplasty at a much younger age than expected. Published reports discuss the poor quality of life associated with the delayed diagnosis and unawareness of potential end organ damage. With our case report we like to highlight the disease characteristics for an early identification to prevent further organ damage believed to be from chronic inflammation. Early diagnosis and treatment with agents such as interleukin-1 (IL-1) inhibitors can promptly provide symptomatic relief, reduce inflammation and prevent organ damage.

Cell block preparation in urine cytology: examination of utility and workflow in an academic practice.

INTRODUCTION: Urine cytology is a common non-invasive test to screen for urothelial carcinoma. Urine cell blocks may sometimes be prepared as a diagnostic aid (eg, to characterize architecture or perform immunohistochemistry). The aim of this study was to determine whether routinely preparing cell blocks on urine specimens improves diagnostic sensitivity. MATERIALS AND METHODS: Three time periods were compared: time period 1 (prior to November 2009; 1437 consecutive selected cases), when cell blocks were rarely prepared; period 2 (November 2009 to May 2010; 1230 selected cases), when cell blocks were prepared on all cases; and period 3 (after May 2010; 1499 consecutive selected cases), when cell blocks were made only when indicated (for samples with substantial cellular pellets or when requested by a pathologist). RESULTS: Patient demographics and the type of specimens received were relatively similar during the 3 time periods. Increased preparation of cell blocks was not accompanied by a notable improvement in specimen adequacy rate, given that <1%, 2%, and 1% of samples were unsatisfactory for the 3 periods. Only the proportion of atypical cases differed during the time periods, being highest in period 1 (23%), but lower in periods 2 and 3. Turnaround time was fastest for period 1 (mean: 47 hours, median: 33 hours), and slower for period 2 and period 3. CONCLUSION: These data show that routinely preparing cell blocks for urine samples did not improve our laboratory's specimen adequacy rate. Nonetheless, cell block preparation on urine samples did help lower the proportion of atypical diagnoses, when routinely or selectively prepared. Because preparation of cell blocks on all urine cases can be costly and only provides minimal added clinical benefit, our recommendation is to rather judiciously utilize cell blocks when screening urine cytology samples.

Iatrogenic solid tumors following immunosuppressive therapy.

Immunosuppression induced by chronic medication, such as occurs post-transplantation, may increase a patient's risk of developing solid tumors. These are often rare tumors characterized by odd presentations. This review focuses on commonly encountered iatrogenic, non-hematopoietic solid tumors following immunotherapy and provides a practical approach to their diagnosis. All of the malignancies covered in this review are viral-induced. They include human papillomavirus (HPV)-associated carcinomas, Epstein-Barr virus (EBV)-associated tumors, Merkel cell polyomavirus (MCPyV)-related Merkel cell carcinoma, and Human Herpesvirus 8 (HHV8)-related Kaposi sarcoma. The complementary diagnostic role of ancillary studies, such as immunohistochemistry and in-situ hybridization that target these oncogenic viruses, is addressed.

Correlation of histological grade of dedifferentiation with clinical outcome in 55 patients with dedifferentiated liposarcomas.

In this study the histologic grade of dedifferentiated liposarcomas was correlated with outcome in surgically resected specimens in 55 patients over a 19-year period at the University of Pittsburgh Medical Center. The tumors were located in the retroperitoneum (N=35); the extremities and thigh (N=16), and the remainder involved the spermatic cord and head and neck. Most tumors were large (mean=21 cm.) Follow-up was available in all 55 patients (median=36 months). Forty-one tumors classified as high-grade dedifferentiated liposarcoma (HG-DDLPS) had mitotically active pleomorphic and spindle cells and foci of necrosis. They included tumors with foci of smooth muscle differentiation (N=12), osteosarcoma (N=4), and myxoid areas (N=9). Fourteen tumors classified as low-grade dedifferentiated liposarcoma (LG-DDLPS) displayed a predominantly bland, monomorphic, spindle cell population with few mitoses and scant necrosis. The Kaplan-Meier method and log-rank test were used for statistical analysis. All tumors had unequivocal foci of well-differentiated liposarcoma (WDLPS). Fluorescence in situ hybridization (FISH) detected amplification of MDM2 in 29 cases. Twenty of 41 patients (49%) with HG-DDLPS died of tumor, and two patients died with LG-DDLPS (14%). The overall survival of patients with LG-DDLPS was significantly longer (P=.02). The median survival was 113 months for the LG-DDLPS and 48 months for the HG-DDLPS. Metastases (N=4) occurred only in the high-grade tumors and were independent of the type of heterologous differentiation. Patients with HG-DDLPS were at a greater risk of earlier death. Distinction between the two groups is important for patient selection for possible adjuvant therapy.

Ossifying fibromyxoid tumor: a study of 6 cases of atypical and malignant variants.

Ossifying fibromyxoid tumors (OFMT) of soft parts are rare, slow-growing tumors that have potential for local recurrence and may metastasize. While OFMT originally was considered benign, several cases of malignant OFMT have been documented. There is no universally accepted risk stratification, although this study emphasizes the importance of utilizing histology, immunohistochemistry and FISH in establishing the diagnosis. Herein, we describe six cases of atypical and malignant OFMT with differences in morphologic features, 5 of which display the proposed morphological criteria for malignancy. The patients were mostly male (M=5, F=1) with an age range of 33-69 years. The tumors arose from the extremities (3 cases), the shoulder (1 case), the head and neck area (1 case), and the paraspinal area (1 case). One tumor had high grade and overtly sarcomatous changes, while another invaded the underlying clavicle. Two cases showed cytological atypia and necrosis. Fluorescence in situ hybridization (FISH) detected rearrangement of the PHF1 gene in 5 cases. All cases were positive for EAAT4 and actin by immunohistochemistry, while negative for desmin. Three tumors were immunoreactive for S100 protein. INI-1 immunohistochemical staining was conserved in all but 2 cases in which a mosaic loss of expression was noted. All but two patients are currently alive and free of disease.

CT-guided transthoracic needle aspiration biopsy of subsolid lung lesions.

PURPOSE: To assess the diagnostic performance of computed tomography (CT)-guided transthoracic needle aspiration biopsy (TNAB) in the evaluation of persistent subsolid lung lesions. MATERIALS AND METHODS: A retrospective review of all CT-guided TNABs performed at a single institution from January 2002 to November 2012 was conducted to identify patients with persistent subsolid lung lesions. The diagnostic performance of CT-guided TNAB was assessed through comparison of cytologic diagnoses with core needle biopsy, surgical resection, or imaging and clinical follow-up. The cytologic, histologic, and imaging features of each lesion were characterized, and CT-guided TNAB complications were recorded. RESULTS: In 32 patients, a diagnosis of benign or malignant disease was identified through evaluation of pathologic or follow-up data. There were 18 men and 14 women, with a mean age of 67.1 years ± 9.6 (range, 52-86 y). The mean lesion diameter was 21 mm ± 11 (range, 8-62 mm). A final diagnosis of malignancy was made in 28 cases (87.5%); four benign lesions were also diagnosed. The overall sensitivity of CT-guided TNAB in the evaluation of these lesions was 89.2%, and the specificity and positive predictive value were 100%. Two pneumothoraces (6.3%) were identified. CONCLUSIONS: Among patients with subsolid lung lesions, CT-guided TNAB is safe and shows high sensitivity. The high specificity and positive predictive value of the procedure allow for definitive treatment decisions to be made for most patients.

Myxoid solitary fibrous tumor: a study of three cases.

Limited myxoid areas are usually encountered in solitary fibrous tumor (SFT), but SFT with abundant myxoid stroma has only been reported occasionally. Myxoid SFT is defined as having myxoid changes in 50% or more of the tumor. We review the literature on myxoid SFT and add 3 new cases to those previously described. Microscopically, the lesions were composed of spindle cells arranged in a haphazard or storiform pattern in a cellular and hypocellular myxoid background with thin-walled "staghorn" branching vessels. Atypical features (necrosis, hypercellularity, or increased mitotic figures) were not identified. All cases were positive for CD34 and CD99 and had a benign course with a follow-up ranging from 15 to 70 months. Our review suggests that like classical SFT, myxoid SFT is associated with an indolent clinical course and favorable prognosis. Their recognition is crucial to distinguish a variety of myxoid spindle cell neoplasms with different prognoses and treatment options.