Radiology of Castleman disease: the pivotal role of imaging in diagnosis, staging, and response assessment of this rare entity.

Castleman Disease (CD) is a rare entity that typically presents as an enhancing nodal mass in the mediastinum or head and neck region on computed tomography (CT). It may manifest as unicentric or multicentric regions of lymph node enlargement. A key clinical issue in the context of CD is delayed diagnosis, which contributes adversely to patient outcome, given that accurate diagnosis facilitates earlier treatment of this curable disease. This article will address relevant imaging aspects, with reference to typical and atypical imaging features of CD, illustrated using examples from our specialist centre; the imaging journey for patients with CD; and will provide practical pointers to radiologists in differentiating CD from other benign and malignant causes of enhancing lymphadenopathy, including lymphoma and neoplastic adenopathy. We will also review current classification tools and staging challenges with reference to World Health Organization guidelines, International Working Group guidelines as well as the Lugano classification. Finally, we will discuss the potential role of additional imaging techniques in CD, highlighting novel imaging methods and expanded utilities from our specialist centre.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL): a good practice guide, pictorial review, and new perspectives.

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare but emerging T-cell non-Hodgkin lymphoma. It has two distinct subtypes, "effusion-only" or "mass-forming" disease, arising around implants in patients with in situ or previous history of textured-surface breast implants. The clinical, histopathological and imaging features are unique and nuanced as compared to primary breast malignancy and other lymphoma categories. Prompt recognition and diagnosis triggers referral to appropriate BIA-ALCL centres and initiation of treatment, with potential for excellent prognosis. Definitive management of both subtypes involves implant and capsule removal; systemic therapy is reserved for mass-forming disease and advanced-stage disease. There have been recent crucial advances in the diagnostic pathway, with publication of national and international guidelines: from the UK Medicines Healthcare products Regulatory Agency (MHRA) Plastic, Reconstructive and Aesthetic Surgery Expert Advisory Group (PRASEAG), and the United States National Comprehensive Cancer Network (NCCN). This review provides a practical guide to the clinical work-up of BIA-ALCL, enabling optimisation of the diagnostic imaging pathway, with representative cases.

Current and future best practice in imaging, staging, and response assessment for Non-Hodgkin's lymphomas: the Specialist Integrated Haematological Malignancy Imaging Reporting (SIHMIR) paradigm shift.

Non-Hodgkin's lymphoma (NHL) encompasses over 40 different haematological malignancies, including low and high-grade neoplasms, such as follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) respectively. A key clinical issue in the context of NHL is delayed and inaccurate diagnosis, which contributes adversely to patient morbidity and mortality. This article will address relevant imaging aspects, with particular reference to advancements in NHL imaging, including computed tomography (CT), integrated positron-emission tomography (PET)-CT, and magnetic resonance imaging (MRI). We provide multiparametric (anato-functional) imaging display items, including histological correlation. We will also introduce our original concept of "Specialist Integrated Haematological Malignancy Imaging Reporting" (SIHMIR), a paradigm shift in lymphoma radiology.

Development of Peritoneal Carcinoma in women diagnosed with Serous Tubal Intraepithelial Carcinoma (STIC) following Risk-Reducing Salpingo-Oophorectomy (RRSO).

INTRODUCTION: The management of Serous Tubal Intraepithelial Carcinoma (STIC) found at the time of Risk-Reducing Salpingo-Oophorectomy (RRSO) remains unclear. We set out to analyse the incidence of peritoneal carcinomas developed after prophylactic surgery and to formulate further guidance for these patients. METHODS: This is a retrospective study of 300 consecutive RRSO performed at the Royal Marsden Hospital between January 2008 and January 2017. RESULTS: The median age at RRSO was 47.8 years (range 34 to 60 years) and median BMI was 26.2 kg/m2 (range 16 to 51 kg/m2). A total of 273 patients (91%) were tested for BRCA mutations. Of these, 124 (45.4%) had a BRCA 1 mutation, 118 (43.2%) had a BRCA 2 mutation, 2 (0.7%) had both a BRCA 1 and a BRCA 2 mutation and 29 (10.6%) had no BRCA mutation detected. Isolated STIC lesions were identified in 7 cases (2.3%) and p53 signatures in 75 cases (25%). There were five (1.6%) incidental tubal carcinomas and one (0.3%) ovarian carcinoma at the time of surgery. Two (28.6%) of the 7 patients with STIC identified following RRSO had high grade serous peritoneal carcinoma diagnosed at 53 and 75 months. One (0.3%) patient from the other 287 patients from our series with no STIC diagnosis or incidental carcinomas at RRSO developed high grade serous carcinoma of peritoneal origin after 92 months. CONCLUSION: This study demonstrates that when a STIC lesion is identified following RRSO there is a significantly higher risk of a subsequent peritoneal cancer. Although there is no published consensus in literature, we recommend that consideration should be given for long term follow-up if a STIC lesion is identified at RRSO.

Influencing surgical management in patients with carcinoma of the cervix using a T2- and ZOOM-diffusion-weighted endovaginal MRI technique.

BACKGROUND: Endovaginal MRI (evMRI) at 3.0-T with T2-weighted (T2-W) and ZOnal Oblique Multislice (ZOOM)-diffusion-weighted imaging (DWI) potentially improves the detection of stage Ia/Ib1 cervical cancer. We aimed to determine its sensitivity/specificity, document tumour-to-stromal contrast and establish the effect of imaging on surgical management. METHODS: Following ethical approval and written informed consent, 57 consecutive patients with suspected stage Ia/Ib1 cervical cancer underwent evMRI at 3.0-T using T2-W and ZOOM-DWI. Sensitivity/specificity were calculated against histopathology for two independent observers. Tumour-to-stromal contrast was determined on T2-W, and diffusion-weighted (b=800 s mm(-2)) images and apparent diffusion coefficients (ADCs) were recorded. In patients due for radical vaginal trachelectomy (RVT), change of surgical management based on imaging findings was documented. RESULTS: Sensitivity/specificity for detecting tumour was the following: reporting read 88.0/81.8%, anonymised read 92.0/81.8% (observer 1); 84.0/72.7% (observer2; median tumour volume=1.7 cm(3)). Intraobserver agreement was excellent (kappa=0.89) and the interobserver agreement was good (kappa=0.65). Tumour-to-stromal contrast was greater on ZOOM-DWI compared with T2-W images (3.35±2.36 vs 1.39±0.95; P<0.0004). Tumour and stromal ADCs were significantly different (P<0.00001). In 31 patients due for RVT, evMRI altered surgical management in 12 (38.7%) cases (10 cone-biopsy, 2 chemoradiotherapy). CONCLUSION: T2-W+ZOOM-DWI evMRI has high sensitivity/specificity for detecting stage Ia/Ib1 cervical tumours; in patients due for RVT, the surgical management was altered in ∼39%.

Overexpression of Syk tyrosine kinase in peripheral T-cell lymphomas.

Peripheral T-cell lymphomas (PTCLs) are fatal in the majority of patients and novel treatments, such as protein tyrosine kinase (PTK) inhibition, are needed. The recent finding of SYK/ITK translocations in rare PTCLs led us to examine the expression of Syk PTK in 141 PTCLs. Syk was positive by immunohistochemistry (IHC) in 133 PTCLs (94%), whereas normal T cells were negative. Western blot on frozen tissue (n=6) and flow cytometry on cell suspensions (n=4) correlated with IHC results in paraffin. Additionally, western blot demonstrated that Syk-positive PTCLs show tyrosine (525/526) phosphorylation, known to be required for Syk activation. Fluorescence in situ hybridization showed no SYK/ITK translocation in 86 cases. Overexpression of Syk, phosphorylation of its Y525/526 residues and the availability of orally available Syk inhibitors suggest that Syk merits further evaluation as a candidate target for pharmacologic PTK inhibition in patients with PTCL.

Distinguishing angioimmunoblastic T-cell lymphoma from peripheral T-cell lymphoma, unspecified, using morphology, immunophenotype and molecular genetics.

AIMS: To identify distinguishing histological, immunophenotypic and molecular genetic features between angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma (PTL). METHODS: Nodal T-cell lymphomas examined (n =137), included AITL (n = 89), PTL (n = 22), anaplastic large cell lymphoma (n = 16) and 'AITL/PTL indeterminate' (n = 10) with overlapping features between AITL and PTL, showing morphology typical of AITL but lacking follicular dendritic cell expansion. Immunohistochemistry for CD3, CD20, CD21 and CD10, in situ hybridization for Epstein-Barr virus encoded RNA (EBER) and polymerase chain reaction for T-cell and B-cell clonality analysis were performed. RESULTS: Of the AITLs, 74/89 showed typical morphology, whereas 15/89 showed hyperplastic follicles. AITL and 'AITL/PTL indeterminate' showed a polymorphous infiltrate and prominent vascularity in all cases. In both groups, CD10 was present in the majority and clear cells and EBER positivity were specific (but not universal) features lacking in PTL. Detection of T-cell clonality was significantly higher in AITL (90%) compared with PTLu (59%). CONCLUSION: Clear cells and EBV infection (when present) are useful distinguishing features and CD10 a sensitive and specific marker of AITL. Hyperplastic follicles are present in a significant minority of AITL. AITL/PTL indeterminate probably falls within the spectrum of AITL rather than PTL.