Inflammatory myofibroblastic tumor of the mesentery with a SQSTM1::ALK fusion responding to alectinib.

Background: Inflammatory myofibroblastic tumor (IMT) is an ultra-rare soft tissue neoplasm associated with fusion proteins encompassing the anaplastic lymphoma kinase (ALK) protein fused to a variety of partner proteins. Data regarding response to ALK-targeting agents based on fusion partner is limited.

Case: A 30-year-old female sought emergency care after onset of abdominal and lower back pain in 2019.

Myoepithelial carcinoma of the parotid gland with a novel CTCF::NCOA2 fusion.

We describe a case of a myoepithelial carcinoma of the superficial parotid gland in a 46-year-old male harboring a novel CTCF::NCOA2 gene fusion. To our knowledge, this novel gene fusion has not been described previously in myoepithelial carcinoma. A 46-year-old male patient presented with a mass involving the superficial left parotid gland with extension into the external auditory canal (EAC) and erosion of the conchal cartilage.

Droplet Digital PCR (ddPCR) as a Novel Technology in Detecting CTNNB1 Mutations in Desmoid Fibromatosis.

Desmoid fibromatosis (DF) is a locally aggressive soft tissue neoplasm with frequent recurrences. DF is characterized by alterations in the Wnt/β-catenin pathway, with the majority showing sporadic mutations in CTNNB1 , whereas others have germline mutations in APC . Immunohistochemical staining for β-catenin is often difficult to interpret and can be negative in up to 30% of cases.

Prevalence and detection of actionable BRAF V600 and NRAS Q61 mutations in malignant peripheral nerve sheath tumor by droplet digital PCR.

Malignant peripheral nerve sheath tumors ( MPNSTs) are aggressive tumors with poor prognosis that do not typically respond well to standard chemotherapy. Recently, point mutations involving BRAF V600E have been demonstrated in a subset of MPNST, offering the possibility of targeted treatment. However, the reported prevalence of these alterations is variable.

Clinical and Pathologic Characterization of 94 Radiation-Associated Sarcomas: Our Institutional Experience.

Radiation-associated sarcomas are an uncommon complication of therapeutic radiation. However, their prevalence has increased with the more widespread use of this treatment modality. The clinical, pathologic and genetic characteristics of radiation-associated sarcomas are not fully understood.

Neoadjuvant Therapy Induces a Potent Immune Response to Sarcoma, Dominated by Myeloid and B Cells.

Purpose: To characterize changes in the soft-tissue sarcoma (STS) tumor immune microenvironment induced by standard neoadjuvant therapy with the goal of informing neoadjuvant immunotherapy trial design.

Experimental Design: Paired pre- and postneoadjuvant therapy specimens were retrospectively identified for 32 patients with STSs and analyzed by three modalities: multiplexed IHC, NanoString, and RNA sequencing with ImmunoPrism analysis.

Results: All 32 patients, representing a variety of STS histologic subtypes, received neoadjuvant radiotherapy and 21 (66%) received chemotherapy prior to radiotherapy.

Fédération Nationale Des Centres de Lutte Contre Le Cancer (FNCLCC) Grading, Margin Status and Tumor Location Associate With Survival Outcomes in Malignant Peripheral Nerve Sheath Tumors.

Background: Histologic grading using the Fédération Nationale des Centres de Lutte Contre Le Cancer (FNCLCC) system is not universally accepted as applicable to malignant peripheral nerve sheath tumor (MPNST), as its prognostic value is not well established.

Methods: We retrospectively evaluated 99 cases of MPNST to investigate any association between the outcomes overall survival (OS) and progression-free survival (PFS), and predictor variables FNCLCC grade, clinical setting, tumor location, and tumor size at diagnosis using multivariable Cox proportional hazard analysis.

Results: Univariable and multivariable analysis demonstrate a statistically significant association between FNCLCC grade and both OS and PFS when comparing tumors by histologic grade.

Calcified chondroid mesenchymal neoplasms with FN1-receptor tyrosine kinase gene fusions including FGFR2, FGFR1, MERTK, NTRK1, and TEK: a molecular and clinicopathologic analysis.

Translocations involving FN1 have been described in a variety of neoplasms that share the presence of a cartilage matrix and may also contain a variable extent of calcification. Fusions of FN1 to FGFR1 or FGFR2 have been reported in nine soft tissue chondromas, mostly demonstrated indirectly by FISH analysis. Delineation of FN1 fusions with various partner genes will facilitate our understanding of the pathogenesis and diagnostic classification of these neoplasms.

Spindle cell neoplasm with EML4-ALK gene fusion presenting as an intraosseous vertebral mass.

In this article, we describe a spindle cell neoplasm harboring an EML4-ALK gene fusion presenting as an intraosseous vertebral mass with extension into the adjacent soft tissue in a 65-year-old man. Histologically, the lesion was characterized by the presence of monotonous, cytologically bland spindle cells with loose myxoedematous stroma and interspersed areas of amianthoid-like collagen fiber deposition. Immunohistochemistry demonstrated strong diffuse staining for CD34 and S100, with absent immunoreactivity for SOX10.

Characterization of novel USP6 gene rearrangements in a subset of so-called cellular fibroma of tendon sheath.

Fibroma of tendon sheath (FTS) is an uncommon benign fibroblastic/myofibroblastic neoplasm that typically arises in the tenosynovial tissue of the distal extremities. Histologically, it is a well-circumscribed proliferation of spindle cells within collagenous stroma with peripheral slit-like vessels. Most examples are relatively hypocellular and more densely collagenous than nodular fasciitis; however, a cellular variant has been described, which has considerable morphologic overlap with nodular fasciitis and has been shown to harbor USP6 translocations in a subset of cases.

A novel MBTD1-PHF1 gene fusion in endometrial stromal sarcoma: A case report and literature review.

The classification of endometrial stromal sarcoma (ESS) has been refined and aided by the discovery of various recurrent gene translocations. Low-grade ESS (LG-ESS) is most commonly characterized by JAZF1-SUZ12 fusions followed by rearrangements involving PHD finger protein-1 (PHF1) and multiple fusion partners, including JAZF1, EPC1, EPC2, and MEAF6. In the present study, integrating anchored polymerase chain reaction and paired-end next-generation ribonucleic acid sequencing, we identified the presence of a novel malignant brain tumor domain-containing 1 (MBTD1)-PHF1 gene fusion in a case of LG-ESS.

Primary Sarcomas of the Larynx: A Single Institutional Experience with Ten Cases.

Sarcomas infrequently arise in the larynx where the vast majority of tumors are of epithelial origin. Given their rarity, studies of these lesions are limited in number. In this series, we describe our institutional experience with ten primary sarcomas of the larynx encountered over an 18 year period, comprising 1.

Detecting disease-defining gene fusions in unclassified round cell sarcomas using anchored multiplex PCR/targeted RNA next-generation sequencing-Molecular and clinicopathological characterization of 16 cases.

Detection of disease-defining gene fusions in sarcoma has led to refining their classification, as well as to discover several new entities. The advent of anchored multiplex PCR/targeted RNA next-generation sequencing (AMP/RNA-seq) has allowed for the development of scalable platforms that can simultaneously examine multiple fusion transcripts without prior knowledge of specific fusion partners.In this study, we assess the utility of a FusionPlex sarcoma panel analysis by AMP/RNA-seq to detect disease-defining gene fusions in 16 cases of undifferentiated round cell sarcoma in which prior diagnostic work-up could not establish a definitive diagnosis.

Amplification of DNA damage-inducible transcript 3 (DDIT3) is associated with myxoid liposarcoma-like morphology and homologous lipoblastic differentiation in dedifferentiated liposarcoma.

Dedifferentiated liposarcoma is defined as progression of atypical lipomatous tumor/well-differentiated liposarcoma to a higher grade usually non-lipogenic sarcoma, with amplification of 12q13-15. This region contains several genes involved in liposarcoma pathogenesis, including MDM2, CDK4, and DDIT3. While the former two are thought of as the main drivers in dedifferentiated liposarcoma, DDIT3 is typically rearranged in myxoid liposarcoma.

Response to PD1 inhibition in conventional chondrosarcoma.

Background: Chondrosarcoma is one of the most common malignant bone tumors in adults. Conventional chondrosarcoma represents around 85% of all chondrosarcomas and is notoriously difficult to treat with chemotherapy.

Case Presentation: We describe a 67-year-old man with metastatic conventional chondrosarcoma who was treated with nivolumab.

High amplification levels of MDM2 and CDK4 correlate with poor outcome in patients with dedifferentiated liposarcoma: A cytogenomic microarray analysis of 47 cases.

Dedifferentiated liposarcoma (DDLS) is characterized at the molecular level by amplification of genes within 12q13-15 including MDM2 and CDK4. However, other than FNCLCC grade, prognostic markers are limited. We aim to identify molecular prognostic markers for DDLS to help risk stratify patients.

T-cell infiltration and clonality correlate with programmed cell death protein 1 and programmed death-ligand 1 expression in patients with soft tissue sarcomas.

Background: Patients with metastatic sarcomas have poor outcomes and although the disease may be amenable to immunotherapies, information regarding the immunologic profiles of soft tissue sarcoma (STS) subtypes is limited.

Methods: The authors identified patients with the common STS subtypes: leiomyosarcoma, undifferentiated pleomorphic sarcoma (UPS), synovial sarcoma (SS), well-differentiated/dedifferentiated liposarcoma, and myxoid/round cell liposarcoma. Gene expression, immunohistochemistry for programmed cell death protein (PD-1) and programmed death-ligand 1 (PD-L1), and T-cell receptor Vβ gene sequencing were performed on formalin-fixed, paraffin-embedded tumors from 81 patients.

Head and Neck Rhabdomyosarcoma: Clinical and Pathologic Characterization of Seven Cases.

Head and neck rhabdomyosarcoma occurs frequently in children and adolescents, and has been well studied in that population. In contrast, it is rare in adults and is not as well characterized clinically and pathologically. Seven cases of adult rhabdomyosarcoma occurring in head and neck were retrieved from the archives of Department of Pathology and Division of Oral Pathology at University of Washington.

Glandular differentiation in dedifferentiated chondrosarcoma: molecular evidence of a rare phenomenon.

Epithelial glandular differentiation in dedifferentiated chondrosarcoma has not been described. Our patient was a 64-year-old man with a history of prostate cancer status post-radiation and hormonal therapy. On screening bone scan, he was found to have increased uptake in his right femoral shaft.

Surgical pathology of skeletal coccidioidomycosis: a clinical and histopathologic analysis of 25 cases.

Skeletal coccidioidomycosis is a rare complication of pulmonary coccidioidomycosis that remains incompletely characterized, and its histopathologic features have not been systematically evaluated. All skeletal coccidioidal infections (2000 to 2012) were retrieved from the University of Arizona and Mayo Clinic in Arizona pathology archives. Clinical history and histologic features were reviewed.

Surgical pathology of pleural coccidioidomycosis: a clinicopathological study of 36 cases.

Most pulmonary coccidioidal infections are intraparenchymal; the pleurae are rarely involved. Pleuritis is a recognized complication of ruptured cavitary infections and occasionally occurs in other settings but has not been fully characterized. To define the clinical and histopathologic characteristics of pleural coccidioidomycosis as encountered by surgical pathologists, we reviewed the clinical history, imaging, and histology of 36 biopsy-, resection-, or autopsy-confirmed cases (with coccidioidal spherules present in pleural tissue; median age, 39 years; 22 men).

The outcome of abstracts presented at the United States and Canadian Academy of Pathology annual meetings.

Many abstracts presented at scientific meetings are never published as articles in peer-reviewed journals. Using PubMed search and custom computer programs, we retrospectively reviewed all 4824 abstracts presented at the United States and Canadian Academy of Pathology annual meetings from 2005 to 2007, and found an overall publication rate of 36% for a 3-year maximal follow-up. This rate is comparable with that of other medical societies with published data.