Neoadjuvant therapy leads to objective response in intrahepatic cholangiocarcinoma.

BACKGROUND: Intrahepatic cholangiocarcinoma (iCCA) is the second most common hepatic malignancy and has a poor prognosis. Surgical resection is the standard of care for patients with resectable disease, representing 30-40% of cases. Increasingly, neoadjuvant systemic therapy is being utilized in patients due to high-risk anatomic or biologic considerations. However, data on the clinical effect of this approach are limited. We performed a cohort study to evaluate the effect of neoadjuvant therapy in patients with oncologically high-risk iCCA. METHODS: iCCA patients (n = 181) between the years 2014-2020 were reviewed for clinical, histopathologic, treatment, and outcome-related data. Tumor regression grade was scored per CAP criteria for gastrointestinal carcinomas. RESULTS: 47 iCCA patients received neoadjuvant therapy and 72 did not. Neoadjuvant treatment led to objective response and tumor regression by CAP score. After adjustment for age, clinical stage, and tumor size, the outcomes of patients who had neoadjuvant therapy followed by surgery were not significantly different from those patients who had surgery first. DISCUSSION: In conclusion, neoadjuvant therapy in iCCA facilitated surgical care. The progression-free and overall survival for surgical patients with and without neoadjuvant therapy were not significantly different suggesting this approach needs further exploration as an effective treatment paradigm.

WITHDRAWN: Neoadjuvant therapy leads to objective response in intrahepatic cholangiocarcinoma.

The Publisher regrets that this article is an accidental duplication of an article that has already been published, https://doi.org/10.1016/j.hpb.2024.04.011. The duplicate article has therefore been withdrawn. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies/article-withdrawal.

NIPBL::NACC1 Fusion Hepatic Carcinoma.

Several reports describing a rare primary liver tumor with histologic features reminiscent of follicular thyroid neoplasms have been published under a variety of descriptive terms including thyroid-like, solid tubulocystic, and cholangioblastic cholangiocarcinoma. Although these tumors are considered to represent histologic variants, they lack classic features of cholangiocarcinoma and have unique characteristics, namely immunoreactivity for inhibin and NIPBL::NACC1 fusions. The purpose of this study is to present clinicopathologic and molecular data for a large series of these tumors to better understand their pathogenesis. We identified 11 hepatic tumors with these features. Immunohistochemical and NACC1 and NIPBL fluorescence in situ hybridization assays were performed on all cases. Four cases had available material for whole-genome sequencing (WGS) analysis. Most patients were adult women (mean age: 42 y) who presented with abdominal pain and large hepatic masses (mean size: 14 cm). Ten patients had no known liver disease. Of the patients with follow-up information, 3/9 (33%) pursued aggressive behavior. All tumors were composed of bland cuboidal cells with follicular and solid/trabecular growth patterns in various combinations, were immunoreactive for inhibin, showed albumin mRNA by in situ hybridization, and harbored the NIPBL::NACC1 fusion by fluorescence in situ hybridization. WGS corroborated the presence of the fusion in all 4 tested cases, high tumor mutational burden in 2 cases, and over 30 structural variants per case in 3 sequenced tumors. The cases lacked mutations typical of conventional intrahepatic cholangiocarcinoma. In this report, we describe the largest series of primary inhibin-positive hepatic neoplasms harboring a NIPBL::NACC1 fusion and the first WGS analysis of these tumors. We propose to name this neoplasm NIPBL:NACC1 fusion hepatic carcinoma.

Clinicopathological and genomic copy number variation analysis in nodular hidradenoma and hidradenocarcinoma with focus on prognostically important features.

Nodular hidradenoma is a cutaneous adnexal tumor of sweat gland origin, characterized by its diverse but overlapping histomorphologic features with other skin tumors. In addition, distinction of benign hidradenoma and its malignant counterpart hidradenocarcinoma can be challenging, especially in prognostic prediction. We retrospectively reviewed pathological features of 29 cases, including benign nodular hidradenoma (n = 17) and hidradenocarcinoma (n = 12), with clinical follow-up ranging from 18 to 216 months. Genomic copy number variation (CNV) was studied in selected cases (n = 18) by single nucleotide polymorphism microarray. None of the benign hidradenomas (0/17) or low-grade hidradenocarcinomas (0/6) had recurrence or metastasis after complete excision, whereas all 6 high-grade hidradenocarcinomas (6/6) showed locally destructive disease, recurrence, or local metastases. In benign hidradenomas, CNV abnormality was absent in all clear cell hidradenomas (0/5) but was detected in a considerable portion of poroid hidradenoma (3/5), with number of abnormalities ranging 2, 4, and 9. In malignant cases, regardless of morphological classification, both low-grade hidradenocarcinomas demonstrated limited CNV abnormalities in 2 areas (2/2), whereas all high-grade hidradenocarcinomas contained 8 or more CNV abnormalities (6/6). No disease-associated death was recorded in the cohort except one case was lost to follow-up after the development of metastatic disease. Overall, the findings support that genomic CNV abnormalities may serve as a sensitive but less specific tool in detecting malignancy in these tumors, and potentially have a role in predicting clinical behavior particularly in the tumors of nonporoid morphology.

Renal neoplasia with papillary architecture involving the pelvicalyceal system.

Pelvicalyceal system (PS) involvement by renal cell carcinoma (RCC) is staged as pT3a disease (American Joint Committee on Cancer [AJCC], 8th edition). As papillary RCC (PRCC) has been infrequently represented in studies looking at the prognostic impact of PS involvement, we reviewed our institutional cohort of 8225 cases for PS involvement by PRCC. Nine such cases were subjected to histopathologic review and immunohistochemistry. Fluorescence in situ hybridization for TFE3/TFEB alterations was performed if indicated. One case each (1 of 9, 11%) was classified as TFE3-rearranged and FH-deficient RCC. The majority were high grade (World Health Organization/International Society of Urologic Pathology grade 3: 8 of 9, 89%) or had features of aggressive disease, including hilar fat (6 of 9, 67%) and regional lymph node involvement (5 of 7, 71%). One low-grade 3.3-cm tumor with isolated PS involvement with a germline heterozygous FH p.Lys477dup alteration with retained FH, lack of increased S-(2-succino)-cysteine expression, BRAF V600E immunohistochemistry positivity, and lack of trisomy 7/17 on chromosomal microarray was identified, arguing against an FH-deficient and conventional PRCC. Our study shows that PS involvement by renal neoplasia with papillary architecture is a rare event. Aside from PRCC, it is important to note that these may include other aggressive and nonaggressive subtypes of renal neoplasia with papillary architecture. One case of isolated PS involvement by a low-grade, noninvasive tumor that we refer to as nephrogenic papillary neoplasm was identified. At present, there are insufficient data to stage such tumors as pT3a (AJCC, 8th edition), and additional studies are needed to address this question.

Candida auris Direct Detection from Surveillance Swabs, Blood, and Urine Using a Laboratory-Developed PCR Method.

Candida auris is an emerging fungal pathogen with cases reported in countries around the world and in 19 states within the United States as of August 2020. The CDC has recommended that hospitals perform active surveillance upon admission for patients with the appropriate risk factors. Currently, active surveillance requires that local hospitals send surveillance swabs to a public health laboratory for analysis. In this work, a real-time PCR assay was developed for the specific detection of C. auris from surveillance swabs, blood, and urine to enable rapid detection of this pathogen. The assay uses commercially available primers and reporter probes and it was verified on the LightCycler 480 PCR platform. Contrived specimens and prospectively collected composite groin/axilla surveillance swabs were used to validate the assay. The performance of the PCR assay on surveillance swabs was also compared to a second PCR assay targeting C. auris that was performed at the Minnesota Department of Health-Public Health Laboratory (MDH-PHL). Our PCR assay is able to detect and differentiate C. auris from closely related Candida species such as C. duobushaemulonii, C. haemulonii, and C. pseudohaemulonii on the basis of melting curve temperature differences.

Secondary renal neoplasia following chemotherapy or radiation in pediatric patients.

Renal neoplasia occurring as a second malignancy following childhood cancer has been most closely associated with neuroblastoma and Wilms tumor. While some cases have been associated with a genetic predisposition, nearly all are thought to result from "late effects" of therapy-related toxicity that involves chemotherapy or radiation. It is unclear if these tumors are enriched for specific molecular or morphologic characteristics. A query of our institutional nephrectomy registry of 8295 patients for renal neoplasia occurring post-treatment for childhood cancer revealed 6 patients with Wilms tumor, 4 with neuroblastoma, and 1 with acute lymphoblastic leukemia (ALL). Three additional cases of MiT family translocation renal cell carcinoma (RCC), from 2 patients, following chemotherapy for neuroblastoma and systemic lupus erythematosus and another of clear cell RCC post-ALL were included. The most common tumor type was clear cell RCC: 9/19 cases (47.4%), followed by metanephric adenoma and MiT family translocation RCC (3/19, 15.8%). There were no characteristic features to indicate a unique renal neoplasia subtype. Potential syndromic renal neoplasia occurred in 2 patients, metanephric adenomas and oncocytoma in a patient with hyperparathyroidism-jaw tumor syndrome post-treatment of Wilms tumor and a fumarate hydratase-deficient RCC in a patient post-treatment for ALL. The mean age at diagnosis of childhood neoplasia or treatment with chemotherapy or radiation was 4.7 years, and the average time to subsequent renal neoplasia was 31 years. Five (of 14) patients developed metastatic RCC, and there were 2 RCC-related deaths. These results indicate the need for extended clinical follow-up of these patients.

Application of a 5 Marker Panel to the Routine Diagnosis of Peripheral T-Cell Lymphoma With T-Follicular Helper Phenotype.

The 2017 World Health Organization update introduced a new category of nodal peripheral T-cell lymphoma with T-follicular helper phenotype (PTCL-TFH) defined by expression of at least 2 or 3 TFH markers. Our study assesses the utility of an immunohistochemical panel of 5 TFH markers (CD10, BCL6, PD-1, CXCL13, and ICOS) for identification of TFH phenotype in angioimmunoblastic T-cell lymphoma (AITL) and PTCL not otherwise specified (NOS). Immunohistochemical for the 5 markers was performed on 22 cases of AITL and 29 cases of PTCL-NOS. Cases were reviewed for morphologic features characteristic of AITL. All AITL cases showed expression of ≥2 TFH markers. This panel resulted in reclassification of 41% PTCL-NOS cases to PTCL-TFH. Positive percent agreement for the TFH phenotype is 97% for PD1, 94% for ICOS, 44% for CD10 and CXCL13, and 29% for BCL6. Negative percent agreement for TFH phenotype is 100% for CD10, BCL6, and CXCL13, 82% for ICOS and 71% for PD1. AITL cases were more likely than PTCL-TFH cases to contain expanded CD21-positive follicular dendritic cell meshworks, clear cell cytology and polymorphous inflammatory background; however, there was a significant (P<0.005) Kruskal-Wallis trend in all morphologic variables between the 3 groups suggesting a continuum from PTCL-NOS to PTCL-TFH to AITL. The median number of morphologic features of AITL also correlated significantly with number of TFH markers positive (Spearman coefficient ρ=0.759). In summary, the stain panel chosen will have an impact on cases classified as PTCL-TFH. This entity may exist along a spectrum between PTCL-NOS and AITL.