Primary hepatic carcinoma with inhibin positivity is a rare aggressive liver tumor with seven cases described. The tumor presents at a younger age than primary hepatic carcinoma with all cases being ...females. RNA albumin ISH positivity suggests the tumor to be a primary hepatic carcinoma. The tumor is different from hepatocellular carcinoma as well as intrahepatic cholangiocarcinoma because of its distinct morphology, lack of hepatocellular differentiation, strong inhibin staining, and lack of typical mutations. A 26-year-old male presented with a 20-cm liver mass. The tumor progressed on therapy with development of multiple lung metastasis. Currently, the patient is enrolled in phase II clinical trial utilizing nivolumab and ipilumumab. While the tumor has a female preponderance, it is not exclusively found in females. Additional studies are necessary to determine the cause of inhibin staining, driving molecular alterations, natural history of this rare tumor, and to come up with consensus nomenclature.
Epithelioid inflammatory myofibroblastic sarcomas are an aggressive variant of inflammatory myofibroblastic tumor described primarily in the abdomen and less commonly in pulmonary location. The ...anaplastic lymphoma kinase (
ALK
) fusion partners described in this tumor include
RANB2
,
RRBP1
and
EML4
. While rare examples of inflammatory myofibroblastic tumors have been described in the central nervous system, the epithelioid variant has never been described. The
ALK–VCL
fusion has been described in renal cell carcinoma, high-grade glioma and epithelioid fibrous histiocytoma but has not been described in epithelioid inflammatory myofibroblastic sarcoma or even inflammatory myofibroblastic tumor. Herein, we report the first case of epithelioid inflammatory myofibroblastic sarcoma in the central nervous system as well as the first case with
VCL
as the fusion partner for
ALK
.
Abstract Occult infection with the hepatitis C virus (HCV) is defined as the presence of the HCV genome in either liver tissue or peripheral blood monocytes (PBMCs), despite constant negative results ...from tests for HCV RNA in serum. We investigated whether patients who maintained a sustained virologic response 12 weeks after therapy (SVR12) with direct-acting antiviral (DAA) agents for recurrent HCV infection following liver transplantation had occult HCV infections. We performed a prospective study of 134 patients with recurrent HCV infection following liver transplantation who were treated with DAAs, with or without ribavirin, from 2014 through 2016 (129 patients achieved an SVR12). In more than 10% of the patients who achieved an SVR12 (n=14), serum levels of aminotransferases did not normalize during or after DAA therapy, or normalized transiently but then increased sharply after DAA therapy. Of these 14 patients, 9 were assessed for occult HCV infection by reverse transcription quantitative PCR. This analysis revealed that 55% of these patients (n=5) had an occult infection, with the detection of negative strand viral genome, indicating viral replication. These findings indicate the presence of occult HCV infection in some patients with abnormal levels of serum aminotransferases in spite of an SVR 12 to DAAs for HCV infection following liver transplantation.
Purpose
There is debate regarding the definition and clinical significance of margin clearance in pancreatic ductal adenocarcinoma (PDA). A comprehensive archival analysis of surgical resection ...margins was performed to determine the effect on locoregional recurrence and survival, and the impact of adjuvant therapy in PDA.
Methods
We identified 105 patients with resected PDA. Pancreatic, anterior, bile duct, and posterior surgical resection margins (PM; posterior surface, uncinate and vascular groove) were identified. Three pathologists reviewed all archival surgical specimens and recategorized each margin as tumor at ink/transected, <0.5, 0.5–1, >1–2, or >2 mm from the inked surface. The impact of these and other clinical variables was assessed on local control, disease-free survival (DFS), and overall survival (OS).
Results
Among all margins, PM clearance up to 2 mm was prognostic of DFS (
p
= 0.01) and OS (
p
= 0.01). Dichotomizing the PM at 2 mm revealed it to be an independent predictor of local recurrence-free survival hazard ratio HR 0.20, 95% confidence interval CI 0.048–0.881,
p
= 0.033), DFS (HR 0.46, 95% CI 0.22–0.96,
p
= 0.03), and OS (HR 0.31, 95% CI 0.14–0.74,
p
= 0.008). A margin status of >2 mm was also prognostic of OS in patients who received adjuvant chemotherapy (HR 0.31, 95% CI 0.11–0.89,
p
= 0.03), however this difference was mitigated in patients receiving adjuvant chemoradiotherapy (HR 0.40, 95% CI 0.10–1.58,
p
= 0.19).
Conclusion
These data highlight the clinical significance of the PM and the lack of significance of other resection margins. Clearance in excess of 2 mm should be considered to improve long-term clinical outcomes. The use of adjuvant radiotherapy should be strongly considered in patients with PMs <2 mm.
Single cell and spatially resolved 'omic' techniques have enabled deep characterization of clinical pathologies that remain poorly understood, providing unprecedented insights into molecular ...mechanisms of disease. However, transcriptomic platforms are costly, limiting sample size, which increases the possibility of pre-analytical variables such as tissue processing and storage procedures impacting RNA quality and downstream analyses. Furthermore, spatial transcriptomics have not yet reached single cell resolution, leading to the development of multiple deconvolution methods to predict individual cell types within each transcriptome 'spot' on tissue sections. In this study, we performed spatial transcriptomics and single nucleus RNA sequencing (snRNAseq) on matched specimens from patients with either histologically normal or advanced fibrosis to establish important aspects of tissue handling, data processing, and downstream analyses of biobanked liver samples. We observed that tissue preservation technique impacts transcriptomic data, especially in fibrotic liver. Single cell mapping of the spatial transcriptome using paired snRNAseq data generated a spatially resolved, single cell dataset with 24 unique liver cell phenotypes. We determined that cell-cell interactions predicted using ligand-receptor analysis of snRNAseq data poorly correlated with cellular relationships identified using spatial transcriptomics. Our study provides a framework for generating spatially resolved, single cell datasets to study gene expression and cell-cell interactions in biobanked clinical samples with advanced liver disease.
Succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST) is a subset of wild-type GIST that constitutes approximately 10% of gastric GISTs. SDH-mutated GISTs lack mutations in ...the proto-oncogene receptor tyrosine kinase (also known as KIT, c-KIT, or CD117) or platelet-derived growth factor receptor α (PDGFR-α). These tumors have female predilection, affect children and young adults, and have a spectrum of behavior from indolent to progressive. These tumors have characteristic morphologic features including multinodular architecture, multiple tumors, lymphovascular involvement, and occasional lymph node metastasis. They can be seen in patients with Carney triad or Carney-Stratakis syndrome. Although a mutation in any one of the SDH subunits can be pathogenic, deficiency of a single subunit leads to loss of detectable SDH subunit B by immunohistochemistry, enabling a convenient, tissue-based screening method. The prognosis and the clinical course of these tumors is different from that of KIT- or PDGFR-α-mutated GISTs. Surgical management is considered the main line of treatment. SDH-mutated GISTs do not respond well to the common targeted therapy, with no objective tumor response to imatinib. The role of the pathologist in diagnosing these cases is imperative in management and subsequent follow-up.
Radiation-associated sarcomas are rare and aggressive types of sarcomas that can occur after exposure to ionizing radiation. We examine a case of radiation-associated undifferentiated/unclassified ...soft-tissue sarcoma with primary disease in the chest wall. The optimal treatment of these patients is surgical resection if possible; however, the role of chemotherapy has not been well defined. The patient described herein had a central tumor in the chest wall. Since many of these patients have borderline resectable tumors, the use of neoadjuvant chemotherapy may be helpful to downstage the tumors for possible surgical resection. In this case, doxorubicin plus ifosfamide chemotherapy was employed with a favorable therapeutic effect prior to being resected. To our knowledge this is the first report of greater than 90% necrosis in a patient with radiation-associated undifferentiated/unclassified soft-tissue sarcoma treated with chemotherapy for a borderline resectable mass.
Endometrial stromal sarcomas (ESS) account for 10-15% of uterine malignancies and are classified into four categories: endometrial stromal nodule (ESN), low-grade endometrial stromal sarcoma ...(LG-ESS), high-grade endometrial stromal sarcoma (HG-ESS) and undifferentiated uterine sarcoma (USS). Depending on stage, ESS is treated with surgery, hormone therapy, chemotherapy or targeted therapy. A rare complication of ESS with metastatic pulmonary disease is recurrent, bilateral pneumothoraces. The current literature has reported on patients with ESS who either presented with pneumothoraces at their initial diagnosis, and thus were untreated, or after treatment with surgical resection and hormone therapy. There have been no case reports of patients with ESS who presented with pneumothoraces while receiving chemotherapy. Furthermore, there have been no reported cases of patients with HG-ESS presenting with this rare complication. We would like to expand the literature by reporting on two patients with HG-ESS who presented with pneumothoraces while concurrently receiving chemotherapy.
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