Kinase expression in angiomatoid fibrous histiocytoma: panTRK is commonly expressed in the absence of rearrangement.

Angiomatoid fibrous histiocytoma (AFH) is a soft tissue tumour of intermediate (rarely metastasising) malignant potential, which harbours gene fusions. These tumours can express anaplastic lymphoma kinase (ALK) in the absence of gene rearrangement or copy number alteration and can also coexpresses Pan-TRK immunohistochemistry (IHC). All -rearranged AFH were retrieved from the files of three institutions and Pan-TRK (EPR17341), ALK and BRAF V600E IHC were performed.

Improving sarcoma classification by using RNA hybridisation capture sequencing in sarcomas of uncertain histogenesis of young individuals.

Our aim was to utilise a 241-gene RNA hybridisation capture sequencing (CaptureSeq) gene panel to identify unexpected fusions in undifferentiated, unclassified or partly classified sarcomas of young individuals (<40 years). The purpose was to determine the utility and yield of a large, targeted fusion panel as a tool for classifying tumours that do not fit typical diagnostic entities at the time of the original diagnosis. RNA hybridisation capture sequencing was performed on 21 archival resection specimens.

Molecular and immunohistochemical characterisation of mesothelioma of the tunica vaginalis.

Aims: Malignant mesothelioma (MM) of the tunica vaginalis (TV) is a rare and aggressive tumour, and the molecular features and staining profile with contemporary immunohistochemical (IHC) biomarkers are largely unexplored. We characterise the clinicopathological, molecular and IHC features of MM (n = 13) and mesothelial neoplasms of uncertain malignant potential (MUMP) (n = 4).

Methods And Results: Targeted next-generation sequencing was performed on seven MMs and two MUMPs.

Myeloid sarcoma and extramedullary hematopoiesis expand the spectrum of ERG-positive proliferations: an ancillary tool in the diagnosis.

ERG overexpression has been linked to acute myeloid leukemia/myeloid sarcoma (MS). The aim of our study was to identify the frequency of ERG immunohistochemical (IHC) expression in MS (n = 21), blastic plasmacytoid dendritic cell neoplasms (BPDCNs; n = 8), extramedullary hematopoiesis (EMH: n = 9), normal and pathological bone marrow trephine biopsies (BM-TBs, n = 18), and the marrow component of adrenal myelolipomas (n = 15). ERG-positive and ERG-negative immunostains were identified in 68.

Chromosome 8 Polysomy Accounting for MYC Over-Expression in Angiosarcoma Arising as Somatic-Type Malignancy in Metastatic Teratoma. Case Report.

MYC over-expression by immunohistochemistry (IHC) is utilised in routine pathology practice as a surrogate marker for amplification, which plays a key oncogenic role in post-irradiation and chronic lymphedema-associated angiosarcoma. We present the case of a 32-year old male, who presented with high-grade angiosarcoma arising in a background of metastatic testicular teratoma. IHC for MYC showed strong nuclear expression in the angiosarcoma cells prompting the consideration of post-irradiation-induced angiosarcoma but our patient did not undergo radiotherapy.

Lessons learnt from MDM2 fluorescence in-situ hybridisation analysis of 439 mature lipomatous lesions with an emphasis on atypical lipomatous tumour/well-differentiated liposarcoma lacking cytological atypia.

Aims: Amplification of the murine double minute-2 (MDM2) gene, which is usually detected with fluorescence in-situ hybridisation (FISH), is the key driving event for atypical lipomatous tumours (ALTs)/well-differentiated liposarcomas (WDLs). We sought to determine the concordance between the histopathological findings and MDM2 FISH in the diagnosis of ALT/WDL, and to identify the histological features of MDM2-amplified tumours lacking classic atypia.

Methods And Results: We performed a retrospective analysis of all mature lipomatous lesions subjected to MDM2 FISH analysis at our institution.

Expression of the C-terminal region of the SSX protein is a useful diagnostic biomarker for spermatocytic tumour.

Aims: Spermatocytic tumour (ST) is a rare testicular germ cell neoplasm with few confirmatory biomarkers that can be challenging to diagnose. Like normal spermatogonia, STs are known to express SSX proteins. Recently, a novel SSX antibody directed against a conserved C-terminal region of SSX1, SSX2 and SSX4 (SSX_CT) has emerged as a reliable biomarker for these SSX proteins and synovial sarcoma.

Pharmaceutical care issues in lung cancer: can community pharmacists support patients receiving systemic anticancer therapy?

Objectives: Most patients receive systemic anticancer therapy (SACT) as day cases and toxicities, if they occur, are likely to appear first in primary care. Pharmaceutical care can be delivered by community pharmacists, but little is known about the epidemiology of SACT toxicities in the community and potential interventions to address these which raise the following questions: what are the typologies of SACT-associated toxicities experienced by community-based patients and what are the associated pharmaceutical care issues (PCIs)? The aim of this study was to identify toxicities and pharmaceutical care issues of patients prescribed SACT for lung cancer and understand the potential for community pharmacists to deliver aspects of cancer care including toxicity management.

Methods: Retrospective analysis of clinical records of patients prescribed oral and parenteral SACT in 2013-14, to describe patient characteristics; SACT toxicity; PCIs and episodes of unscheduled care.

Genome wide methylation profiling of selected matched soft tissue sarcomas identifies methylation changes in metastatic and recurrent disease.

In this study we used the Illumina Infinium Methylation array to investigate in a cohort of matched archival human tissue samples (n = 32) from 14 individuals with soft tissue sarcomas if genome-wide methylation changes occur during metastatic and recurrent (Met/Rec) disease. A range of sarcoma types were selected for this study: leiomyosarcoma (LMS), myxofibrosarcoma (MFS), rhabdomyosarcoma (RMS) and synovial sarcoma (SS). We identified differential methylation in all Met/Rec matched samples, demonstrating that epigenomic differences develop during the clonal evolution of sarcomas.

Monotypic Plasma Cell Proliferation of Uncertain Clinical Significance Mimicking Interstitial Cystitis: An Early Lesion of MALT Lymphoma?

We prospectively studied our institutional experience of bladder extranodal marginal zone (mucosa-associated lymphoid tissue [MALT]) lymphoma including bladder biopsies in which the possibility of MALT lymphoma was considered. We identified a subset of cases primary to the urinary bladder, presenting with prominent plasma cell infiltrates and symptoms mimicking bladder pain syndrome/interstitial cystitis. These proliferations were designated for this study as "monotypic plasma cell proliferation of uncertain clinical significance" (MPCP-US), as the features were insufficient for diagnosis of MALT lymphoma.

Chromosomal imbalances detected in NTRK-rearranged sarcomas by the use of comparative genomic hybridisation.

Aims: NTRK-rearranged sarcomas are emerging as a distinct class of sarcomas of particular importance in the era of targeted therapy. The aim of this study was to use array comparative genomic hybridisation (aCGH) to explore the cytogenetic profile of six adult soft tissue sarcomas harbouring NTRK gene fusions.

Methods And Results: aCGH was performed on six adult soft tissue sarcomas with proven NTRK rearrangements [NTRK1, n = 1 (TPM3-NTRK1); NTRK2, n = 1 (MTMR2-NTRK2); NTRK3, n = 4 (two ETV6-NTRK3; two with unknown partners).

Prevalence of PD-L1 expression in matched recurrent and/or metastatic sarcoma samples and in a range of selected sarcomas subtypes.

We assessed the frequency of programmed death-ligand 1 (PD-L1) expression by immunohistochemistry (IHC) in a cohort of 522 sarcomas from 457 patients, incuding a subset of 46 patients with 63 matched samples from local recurrence or metastases with primary tumours and/or metachronous metastases. We also investigated the correlation of PD-L1 with the presence and degree of tumour-infiltrating lymphocytes (TILs) in a subset of cases. IHC was performed using the PD-L1 SP263 companion kit (VENTANA) on tissue microarrays from an archival cohort.

A Clinicopathologic and Molecular Analysis of Fumarate Hydratase-deficient Renal Cell Carcinoma in 32 Patients.

Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare and recently described entity associated with hereditary leiomyomatosis and RCC syndrome. FH-deficient RCC may show variable clinical and pathologic findings, but commonly presents with locally advanced and metastatic disease and carries a poor prognosis. We identified 32 patients with FH-deficient RCC, confirmed by FH immunohistochemistry (IHC) and/or FH mutation analysis, and performed a retrospective review of the clinical and pathologic features.

Challenges in Pathologic Staging of Renal Cell Carcinoma: A Study of Interobserver Variability Among Urologic Pathologists.

Staging criteria for renal cell carcinoma differ from many other cancers, in that renal tumors are often spherical with subtle, finger-like extensions into veins, renal sinus, or perinephric tissue. We sought to study interobserver agreement in pathologic stage categories for challenging cases. An online survey was circulated to urologic pathologists interested in kidney tumors, yielding 89% response (31/35).

Thirty-years of screening for cystic fibrosis in East Anglia.

Background: Newborn screening for cystic fibrosis (CF) relies on the measurement of immunoreactive trypsinogen (IRT) originating from the pancreas. The Norfolk, Suffolk and Cambridgeshire screening programme initially exploited the persistent increase in IRT seen in CF (IRT-IRT protocol) and later changed to include mutation analysis as a second tier test (IRT-DNA-IRT protocol).

Results: During a 30 year period 582 966 babies have been screened by IRT-IRT and 147 764 by IRT-DNA-IRT (total 730730), resulting in 296 screen positive cases of CF and 29 false negatives (including 10 false negatives with meconium ileus).

Epithelioid and spindle cell haemangioma of bone.

A case of epithelioid and spindle cell haemangioma of bone occurring in the proximal femur is presented. The tumour had typical microscopic features with a striking lobular pattern comprising spindled and epithelioid areas with admixed inflammatory cells. The case represents only the eighth reported example of this rare tumour, which appears to fit in the spectrum of epithelioid haemangioma.