Julia A Bridge

• MD, FACMG
• Managing Director at The Nebraska Medical Center

Myoid hamartoma of the breast is an uncommon benign breast neoplasm. We describe an unusual example of an in-situ and invasive carcinoma arising in a myoid hamartoma. We also describe the unique molecular findings in the myoid hamartoma and review the pertinent literature. In radiology studies, the mammogram showed increased density/attenuation, an...

Purpose DEK::AFF2 fusion-associated squamous cell carcinoma (DEK::AFF2 SCC), also reported in the literature as low-grade papillary sinonasal (Schneiderian) carcinoma (LGPSC), is a rare, primarily bland-appearing, but locally aggressive neoplasm. Morphologically, these tumors can closely resemble sinonasal papilloma (SP), especially on small or lim...

Xanthogranulomatous epithelial tumor (XGET) and HMGA2::NCOR2 fusion keratin-positive giant cell–rich tumor (KPGCT) are recently described morphologically overlapping rare neoplastic entities characterized by HMGA2::NCOR2 fusions, low-grade biological behavior, and a strong predilection for young females. To date, 47 cases have been reported with on...

Angiomyolipoma (AML) is a neoplasm within the perivascular epithelioid cell tumor family that occurs somewhat frequently in the kidney. Most are indolent and discovered incidentally, with rare tumors demonstrating malignant clinical behavior. A small subset of renal AMLs with epithelioid features are associated with aggressive behavior, and may dem...

Angiomyolipomas (AML) are neoplasms within the perivascular epithelioid cell tumor family that occur somewhat frequently in the kidney. Most are indolent and discovered incidentally, with rare cases demonstrating malignant clinical behavior. A small subset of renal AMLs which are epithelioid are associated with aggressive behavior, and may demonstr...

Intracranial mesenchymal tumor (IMT), FET::CREB fusion-positive is a provisional tumor type in the 2021 WHO classification of central nervous system tumors with limited information available. Herein, we describe five new IMT cases from four females and one male with three harboring an EWSR1::CREM fusion and two featuring an EWSR1::ATF1 fusion. Unif...

Introduction/Objective DEK::AFF2 fusion-associated sinonasal carcinoma (DEK::AFF2 SC) also reported in the literature as low-grade papillary sinonasal carcinoma (LGPSC) is a rare, bland-appearing, but locally aggressive neoplasm. Morphologically, these tumors can closely resemble sinonasal papilloma (SP), leading to misdiagnosis. DEK::AFF2 SC is de...

Mesenchymal neoplasms with GLI1 alterations have recently been reported in several anatomic locations. Their morphology and immunohistochemistry (IHC) are nonspecific, making their recognition a true challenge. To assess the diagnostic value of GLI1 and p16 IHC for identifying GLI1-altered neoplasms, we evaluated 12 such neoplasms (6 GLI1-amplified...

Context.—: Next-generation sequencing-based approaches using RNA have increasingly been used by clinical laboratories for the detection of fusion genes, intragenic rearrangements, and exon-skipping events. Correspondingly, the College of American Pathologists (CAP) has advanced RNA sequencing proficiency testing (PT) to ensure optimal performance...

The histiocytoses comprise a histopathologically and clinically diverse group of disorders bearing recurrent genomic alterations, commonly involving the BRAF gene and mitogen-activated protein kinase pathway. In the current study, a novel CLTC::SYK fusion in 3 cases of a histopathologically distinct histiocytic neoplasm arising as solitary soft tis...

Aims: Intraosseous hibernomas are rarely reported tumours with brown adipocytic differentiation of unknown aetiology, with only 38 cases documented in the literature. We sought to further characterise the clinicopathologic, imaging and molecular features of these tumours. Methods and result: Eighteen cases were identified occurring in eight fema...

A subset of malignant testicular sex cord tumors (TSCTs), heretofore interpreted as Sertoli cell tumors, not otherwise specified, exhibits distinctive morphologic features that partially overlap with those of seminoma. In this study, we evaluated the clinicopathologic and molecular characteristics of 13 such tumors. The patients were 20 to 73 years...

Context.— Therapy targeted at HER2 (also known as ERBB2) was used initially for breast and gastroesophageal carcinoma and has more recently been adopted for endometrial serous carcinoma (ESC) and colorectal carcinoma (CRC). There is evidence that predictive biomarker testing algorithms for HER2 must be tumor type specific and that an algorithm vali...

Background and objectives: Bone tumours are relatively rare and as a consequence, treatment in a center of expertise is required. Current treatment guidelines also recommend review by a specialized pathologist. Here we report on international consensus-based datasets for the pathology reporting of biopsy and resection specimens of bone sarcomas. T...

Despite the well-established clinical significance of gene fusions, current practices for the representation, communication, and annotation of such events in clinical practice and biomedical literature are largely inconsistent. Consequently, evidence-based interpretation of the functional and clinical significance of fusion variants is laborious, e...

Mesenchymal neoplasms with GLI1 alterations (rearrangements and/or amplification) have been reported recently in several anatomic locations, which include head and neck, soft tissue and gastrointestinal tract. Herein, to the best of our knowledge, we describe the first three cases of superficial/subcutaneous mesenchymal neoplasm with GLI1 amplifica...

Background: Ewing sarcoma (ES) can be confirmed by identifying the EWSR1-FLI1 fusion transcript. This study is to investigate whether immunostaining (IHC) of PRKCB—a protein directly regulated by EWSR1-FLI1 is a surrogate maker for diagnosing ES in routine practice. Methods: Microarray gene expression analyses were conducted. RKCB IHC was applied t...

Background GLI1 is a transcription factor protein that has recently gained recognition in a morphologically distinct group of epithelioid soft tissue tumors characterized by GLI1 fusions or amplifications. The head and neck region, particularly the tongue, is a common location for GLI1-altered tumors. DDIT3 break apart fluorescence in situ hybridiz...

Context.— Integration of molecular data into glioma classification supports diagnostic, prognostic, and therapeutic decision-making; however, testing practices for these informative biomarkers in clinical laboratories remain unclear. Objective.— To examine the prevalence of molecular testing for clinically relevant biomarkers in adult and pediatri...

Myofibroblastoma is a rare, benign stromal tumor with a diverse morphologic spectrum. Mammary-type myofibroblastoma (MTMF) is the extra-mammary counterpart of this neoplasm and its occurrence throughout the body has become increasingly recognized. Similar morphologic variations of MTMF have now been described which mirror those seen in the breast....

Epithelioid fibrous histiocytoma (EFH) is a rare cutaneous neoplasm, which is characterized by the presence of rearrangements involving the ALK gene. Although EFH was long considered a variant of fibrous histiocytoma, the identification of its unique genetic signature confirmed that it represents a distinct entity. The aim of the present study was...

Context.— The diagnosis and clinical management of patients with diffuse gliomas (DGs) have evolved rapidly over the past decade with the emergence of molecular biomarkers that are used to classify, stratify risk, and predict treatment response for optimal clinical care. Objective.— To develop evidence-based recommendations for informing molecular...

Rhabdomyosarcoma (RMS) rarely arises as a primary skin tumor. It is also very rare in older adults, especially the alveolar type. We report an 80-year-old White woman who presented with a painful, erythematous, raised lesion (2 × 3.5 cm) above the left knee that was fixed within the skin, yet mobile about underlying soft tissue. A punch biopsy show...

Cutaneous fibromyxoid neoplasms (CFMN) comprise a vast category of benign and malignant tumors that include, but are not limited to, low-grade fibromyxoid sarcoma, myxofibrosarcoma, myxoid dermatofibrosarcoma protuberans, myxoid solitary fibrous tumor, and myxoid neurofibroma with differing implications for treatment and prognosis. Herein, a case o...

Dermatofibrosarcoma protuberans (DFSP) is a mesenchymal neoplasm that is usually located in the dermis or subcutis and is locally aggressive. Rarely, these lesions may undergo fibrosarcomatous transformation, which is thought to increase their metastatic potential. DFSP is classically associated with a 17;22 translocation (or ring chromosome thereo...

A metastatic spindle‐cell soft‐tissue neoplasm was found to carry a novel ARHGAP23‐FER fusion. The tumor showed a rapid and sustained metabolic response to tyrosine kinase inhibitor lorlatinib.

Infantile/congenital fibrosarcoma (IFS) is the most common soft tissue tumor in children less than one year of age. The most common anatomic site of IFS is in the extremities or trunk, and rarely in the abdomen or retroperitoneum. Approximately 70-90% of cases are characterized by a distinct t(12;15)(p13;q25) translocation resulting in an ETV6-NTRK...

Thyroid-like follicular renal cell carcinoma is an uncommon kidney tumor with no distinct molecular alteration described to date. This cohort of eight women with mean and median ages of 45 and 46 years, respectively (range 19–65 years), had unencapsulated, well-circumscribed tumors composed of tightly packed anastomosing follicle-like cysts filled...

Inflammatory myofibroblastic tumor (IMT) is a distinctive fibroblastic and myofibroblastic spindle cell neoplasm with an accompanying inflammatory cell infiltrate and frequent receptor tyrosine kinase activation at the molecular level. The tumor may recur and rarely metastasizes. IMT is rare in the head and neck region, and limited information is a...

Objective To evaluate the performance of the Xpert Bladder Cancer Monitor (Xpert; Cepheid, Sunnyvale, CA, USA) test as a predictor of tumour recurrence in patients with non‐muscle‐invasive bladder cancer (NMIBC). Patients and Methods Patients (n = 429) undergoing surveillance for NMIBC underwent Xpert, cytology, and UroVysion testing. Patients wit...

NUT (midline) carcinoma is a rare, highly aggressive, poorly differentiated carcinoma that characteristically harbors a rearrangement of the NUTM1 gene. Most of these tumors occur in adolescents and young adults, arise from the midline structures of the thorax, head, and neck, and are associated with extremely poor outcomes. Rare cases originating...

“Cutaneous melanocytic tumor with CRTC1‐TRIM11 fusion” (CMTCT) is a newly described, potentially novel entity that typically presents as a dermal nodule on the head and neck, extremities and trunk of adults. Histopathologically, it is reported as a nodular or multinodular tumor composed of epithelioid and spindle cells that are variably immunoreact...

To our knowledge, we describe the first mesenchymal tumor with a novel GLI1‐FOXO4 fusion gene. This well‐circumscribed kidney tumor displayed variably myxoid and epithelioid histologic features with a focally nodular growth pattern. The tumor cells showed bland, round to ovoid nuclei, with no overt high‐grade features. The tumor showed focal immuno...

Background: In patients with haematuria, a fast, noninvasive test with high sensitivity (SN) and negative predictive value (NPV), which is able to detect or exclude bladder cancer (BC), is needed. A newly developed urine assay, Xpert Bladder Cancer Detection (Xpert), measures five mRNA targets (ABL1, CRH, IGF2, UPK1B, and ANXA10) that are frequent...

Pseudomyogenic hemangioendothelioma, an uncommon mesenchymal neoplasm composed of plump spindled and/or epithelioid endothelial cells, may present multicentrically and tends to locally recur but rarely metastasizes. Morphologic resemblance to epithelioid sarcoma and other spindle cell neoplasms may result in diagnostic confusion. Molecular characte...

Porocarcinoma is a rare malignant adnexal tumor with predilection for the lower extremities and the head and neck region of older adults. This entity may arise de novo or in association with a benign poroma. Porocarcinoma's non‐specific clinical appearance, immunohistochemical profile and divergent differentiation may occasionally be diagnostically...

Acral fibromyxoma (AF) is a slow growing benign soft tissue tumor with predilection to subungal and periungal region of the hands or feet. CD34 expression is consistently expressed whereas very recently loss of Rb1 expression was described as a possible driver molecular event for this entity. Herein we present two additional cases of AF with loss o...

Primary superficial Ewing sarcoma (psES) cases are exceedingly rare, with less than 150 cases reported in the literature. Small case series have suggested differences between psES and Ewing sarcoma (ES) of bone or deep soft tissues: psES appears to have a more indolent course and a higher 5‐year overall survival rate. PsES is more common in older a...

Epithelioid fibrous histiocytoma (EFH) is a rare, benign, cutaneous neoplasm. This fibrohistiocytic tumor was once believed to be a variant of fibrous histiocytoma, but EFH is now known to be a distinct entity based on the presence of ALK gene rearrangements in most cases. The pattern of immunohistochemical expression of ALK in EFH in the literatur...

Ossifying fibromyxoid tumor (OFMT) is a rare soft tissue neoplasm of uncertain differentiation and intermediate biologic potential. Up to 85% of OFMTs, including benign, atypical and malignant forms, harbor fusion genes. Most commonly, the PHF1 gene localized to 6p21 is fused with EP400, but other fusion partners such as MEAF6, EPC1, and JAZF1 have...

Herein we described the clinical, radiological, histological, and molecular characteristics of seven soft tissue aneurysmal bone cysts (STABCs) diagnosed and managed at a tertiary cancer center and to elucidate their relationship with myositis ossificans (MO). All cases had established imaging and histopathological diagnosis of STABC and were subje...

Context.— As laboratories increasingly turn from single-analyte testing in hematologic malignancies to next-generation sequencing–based panel testing, there is a corresponding need for proficiency testing to ensure adequate performance of these next-generation sequencing assays for optimal patient care. Objective.— To report the performance of lab...

Adenomyoepithelioma is an extremely rare primary cutaneous neoplasm. Although there is ample evidence on the existence of malignant adenomyoepithelioma in the breast, a malignant counterpart in the skin has not been documented. We report a primary cutaneous adenomyoepithelioma (pcAME) with malignant features arising from a spiradenoma in a 39-year-...

Angiofibroma of soft tissue (AFST) is a rare mesenchymal neoplasm of fibroblastic differentiation with abundant vasculature, which was first described in 2012 by Mariño‐Enriquez et al.1 In their study, they described 37 cases of a tumor that consisted of a “vaguely lobular, variably cellular proliferation of bland, uniform spindle cells in an abund...

Context.— Detection of high-risk human papillomavirus (HR-HPV) in squamous cell carcinoma is important for classification and prognostication. In situ hybridization (ISH) is a commonly used HR-HPV–specific test that targets viral RNA or DNA. The College of American Pathologists (CAP) provides proficiency testing for laboratories performing HR-HPV I...

Aneurysmal bone cysts (ABCs) are benign lesions which most frequently occur in the long bones of pediatric patients. Long thought to be reactive, recent molecular advances have demonstrated that the majority of primary ABCs harbor rearrangements of the USP6 gene, confirming their neoplastic nature. Secondary ABCs arising from other lesions do not d...

Background The jaws are an uncommon location for primary aneurysmal bone cysts (ABCs), and few gnathic cases have been tested for USP6 rearrangement. Rearrangements of CDH11 and/or USP6 are identified in approximately 70% of primary extragnathic ABCs. MATERIALS/METHODS Herein, this multi-institutional, IRB-approved study investigates the USP6 stat...

Abstract The companion diagnostic test for checkpoint inhibitor immune therapy is an immunohistochemical test for PD-L1. The test has been shown to be reproducible for expression in tumor cells, but not in immune cells. Immune cells were used in the IMpassion130 trial which showed PD-L1 expression was associated with a better outcome. Two large stu...

Molecular diagnostics of sarcoma subtypes commonly involve the identification of characteristic oncogenic fusions. EWSR1-PATZ1 is a rare fusion partnering in sarcoma, with few cases reported in the literature. In the current study, a series of 11 cases of EWSR1-PATZ1 fusion positive malignancies are described. EWSR1-PATZ1-related sarcomas occur acr...

Nodular fasciitis is a benign proliferation of fibroblasts/myofibroblasts that can be mistaken for an aggressive neoplasm because of its spectrum of appearances and anatomical locations, rapid growth, infiltrative growth pattern, and high mitotic rate. The presence of fusions involving USP6 gene in most cases provides a useful tool for diagnostic c...

Context.—: The performance of laboratory testing has recently come under increased scrutiny as part of important and ongoing debates on regulation and reimbursement. To address this critical issue, this study compares the performance of assay methods, using either commercial kits or assays designed and implemented by single laboratories ("home bre...

Dermatofibrosarcoma protuberans (DFSP) is a low‐grade sarcoma with fibroblastic differentiation characterized, in the great majority of cases, by fusions between the COL1A1 and PDGFB genes. In some instances, transformation to a genetically more complex sarcoma, most commonly fibrosarcoma, is observed. However, the molecular pathogenesis of this tr...

Cutaneous syncytial myoepithelioma (CSM) is a recently recognized, histopathological variant of myoepithelial (ME) tumors of the skin. It is characterized by a syncytial arrangement of spindled, ovoid and/or epithelioid cells forming a well‐circumscribed, unencapsulated dermal nodule. There is a paucity of intervening stroma, and absent duct or gla...

Dermatofibrosarcoma protuberans (DFSP) is a low‐grade spindle cell tumor of the skin commonly arising on the trunk and extremities which tends to be slow growing yet locally aggressive. DFSPs are associated with a good prognosis when surgical excision with negative margins is achieved. Although local recurrences occur up to 50% of incompletely rese...

Poorly differentiated neoplasms lacking characteristic histopathologic features represent a significant challenge to the pathologist for diagnostic classification. Classically, NUT carcinoma (previously NUT midline carcinoma) is poorly differentiated but typically exhibits variable degrees of squamous differentiation. Diagnosis is genetically defin...

Anastomosing hemangioma (AH) is a relatively novel variant of benign vascular tumors originally described in the genitourinary tract. Although AH was subsequently documented in various anatomic locations, a primary AH of the skin has not been reported in the literature. The current case report documents a vascular lesion with histologic features re...

Fluorescence in situ hybridization (FISH) has been a revolutionary adjunct tool to traditional histopathological approaches for detecting genomic abnormalities in neoplasia that aid in diagnosis, prognosis, or prediction of response to therapy. With the rise of minimally invasive procedures for obtaining lesional material for evaluation, FISH studi...

Melanoma ex blue nevus (MEBN) is a rare, aggressive, and potentially lethal neoplasm. Distinguishing MEBN from an atypical cellular blue nevus can be very challenging. We report a diagnostically difficult case of MEBN with lymph node metastases, in which single nucleotide polymorphism array and fluorescence in situ hybridization were used to arrive...

Background: A fast, noninvasive test with high sensitivity (SN) and a negative predictive value (NPV), which is able to detect recurrences in bladder cancer (BC) patients, is needed. A newly developed urine assay, Xpert Bladder Cancer Monitor (Xpert), measures five mRNA targets (ABL1, CRH, IGF2, UPK1B, and ANXA10) that are frequently overexpressed...

Inflammatory myofibroblastic tumor (IMT) is a rare spindle cell neoplasm with admixed inflammatory cells which occurs mainly in the abdomen or thoracic cavity of children or young adults. Primary CNS IMT is exceedingly rare with roughly 100 reported cases in the world literature, most of which are extra-axial and occur as a dural-based mass. Herein...

A subset of soft tissue sarcomas often harbor recurrent fusions involving protein kinases. While some of these fusion events have demonstrated utility in arriving at a precise diagnosis, novel fusions in otherwise difficult to classify sarcomas continue to be identified. We present a case of a 40‐year‐old female who noted a lower back nodule in 201...

Context: - Fluorescence in situ hybridization (FISH) and brightfield in situ hybridization (ISH) are 2 clinically approved laboratory methods for detecting ERBB2 (HER2) amplification in breast cancer. Objective: - To compare the performance of FISH and brightfield ISH on proficiency testing administered by the College of American Pathologists La...

Purpose: A comprehensive analysis of the genomics of undifferentiated sarcomas (UDS) is lacking. We analyzed copy number alterations and fusion status in patients with UDS prospectively treated on Children's Oncology Group protocol ARST0332. Experimental design: Copy number alterations were assessed by Oncoscan FFPE Express on 32 UDS. Whole-exom...

Dedifferentiated liposarcoma is typically a nonlipogenic high-grade sarcoma that arises from well-differentiated liposarcoma. It most commonly presents as a large mass in the retroperitoneum. Significant involvement of the gastrointestinal tract by dedifferentiated liposarcoma is uncommon. We present a unique case of dedifferentiated liposarcoma ra...

Perivascular epithelioid tumors (PEComas) are a family of mesenchymal neoplasms that have smooth muscle and melanocytic differentiation. They can be sporadic or associated with Tuberous Sclerosis Complex and commonly present in the kidney as angiomyolipoma or in the lung as pulmonary clear cell sugar tumors or lymphangioleiomyomatosis. However, the...

Mammary analog secretory carcinoma is a primary salivary gland neoplasm with histologic, immunophenotypic, and molecular features identical to those of secretory carcinoma of the breast. Similar neoplasms have now been reported to occur in various nonmammary sites including the parotid gland, submandibular gland, sinuses, lip, skin, thyroid gland,...

Context: - Detection of acquired variants in cancer is a paradigm of precision medicine, yet little has been reported about clinical laboratory practices across a broad range of laboratories. Objective: - To use College of American Pathologists proficiency testing survey results to report on the results from surveys on next-generation sequencing...

Purpose: Despite suboptimal sensitivity, urine cytology is often performed as an adjunct to cystoscopy for bladder cancer diagnosis. We aimed to develop a non-invasive, fast molecular diagnostic test for bladder cancer detection with better sensitivity than urine cytology while maintaining adequate specificity. Materials and methods: Urine speci...

Optimal treatment of rhabdomyosarcoma (RMS) requires multidisciplinary approach, incorporating chemotherapy with local control. Although current therapies are built on cooperative group trials, a comprehensive standard of care to guide clinical decision making has been lacking, especially for relapsed patients. Therefore, we assembled a panel of pe...

Salivary gland-type tumors have been rarely described in the thyroid gland. Mammary Analog Secretory Carcinoma (MASC) is a recently defined type of salivary gland carcinoma characterized by a t(12;15)(p13;q25) resulting in an ETV6-NTRK3 fusion gene. We report 3 cases of MASC involving the thyroid gland without clinical evidence of a salivary gland...

Importance: Four assays registered with the US Food and Drug Administration (FDA) detect programmed cell death ligand 1 (PD-L1) to enrich for patient response to anti-programmed cell death 1 and anti-PD-L1 therapies. The tests use 4 separate PD-L1 antibodies on 2 separate staining platforms and have their own scoring systems, which raises question...

When pediatric, adolescent, and young adult patients present with a bone sarcoma, treatment decisions, especially after relapse, are complex and require a multidisciplinary approach. This review presents scenarios commonly encountered in the therapy of bone sarcomas with the goal of objectively presenting a consensus, multidisciplinary management a...

Perivascular epithelioid cell neoplasms (PEComas) are a family of mesenchymal tumors with features of both smooth muscle and melanocytic differentiation, with or without true melanin pigment. The highly variable morphology of PEComas results in a broad differential diagnosis that is also dependent on anatomic site. A subset demonstrates rearrangeme...

Dedifferentiated liposarcoma can arise de novo or as a complication of a preexisting well-differentiated liposarcoma. We describe the radiologic and pathologic features of a long-standing liposarcoma with multiple recurrences in a 59-year-old male. Imaging demonstrated a heterogeneous fat-containing mass in the anterior thigh. The adjacent proximal...

Fully updated throughout, the second edition of this bestselling book provides a comprehensive guide to the pathology of soft tissue tumors and tumor-like lesions. Reflecting the latest WHO classification throughout, this new edition incorporates advances in clinicopathologic, biologic and genetic studies. As such, detailed coverage of immunohistoc...

Objectives: Primary carcinoid tumor of the renal pelvis is a rare neoplasm with few cases reported in the literature. Here we present the clinical and histopathologic findings of a primary carcinoid tumor arising in the left renal pelvis of a horseshoe kidney in a 61-year-old female patient. Materials and methods: Pathologic features were evalua...

CIC-rearranged sarcomas comprise a recognized subset of the so called "undifferentiated small round cell sarcomas" that lack the traditional EWSR1 fusion to one of the ETS family members.(1) A smaller percentage have demonstrated BCOR gene rearrangements.(2) The CIC gene is most commonly fused with the DUX4 or DUX4L10 genes through t(4;19)(q35;q13)...

The introduction of molecular testing into cytopathology laboratory practice has expanded the types of samples considered feasible for identifying genetic alterations that play an essential role in cancer diagnosis and treatment. Reverse transcription-polymerase chain reaction (RT-PCR), a sensitive and specific technical approach for amplifying a d...