This multicentric, retrospective study conducted within the Italian Rare Cancer Network describes clinical features and explores their possible prognostic relevance in patients with advanced epithelioid haemangioendothelioma (EHE) started on surveillance.
We collected data on adult patients with molecularly confirmed, advanced EHE consecutively referred at five sarcoma reference centres between January 2010 and June 2018, with no evidence of progressive disease (PD) and started on surveillance. Overall survival (OS) and progression-free survival (PFS) univariable and multivariable Cox analyses were performed. In the latter, due to the low number of cases and events, penalized likelihood was applied, and variable selection was performed using a random forest model.
Sixty-seven patients were included. With a median follow-up of 50.2 months, 51 (76%) patients developed PD and 16 (24%) remained stable. PD at treatment start did not meet RECIST version 1.1 in 15/51 (29%) patients. The 3-year PFS and OS were 25.4% and 71.1%, respectively, in the whole population. Tumour-related pain (TRP) was the most common baseline symptom (32.8%), followed by temperature (20.9%), fatigue (17.9%), and weight loss (16.4%). Baseline TRP (P = 0.0002), development of TRP during follow-up (P = 0.005), baseline temperature (P = 0.002), and development of fatigue during follow-up (P = 0.007) were associated with a significantly worst PFS. An association between baseline TRP (P < 0.0001), development of TRP during follow-up (P = 0.0009), evidence of baseline serosal effusion (P = 0.121), and OS was recorded.
Because of the poor outcome observed in EHE patients presenting with serosal effusion, TRP, temperature, or serosal effusion, upfront treatment in this subgroup could be considered.

The objective of this study was to report on a retrospective series of patients with epithelioid hemangioendothelioma (EHE) who received treatment with sirolimus within the Italian Rare Cancer Network.
From January 2005, 38 adult patients with advanced EHE received continuous-dosing sirolimus, 5 mg daily, until they developed either toxicity or disease progression. Disease progression in the 6 months before the start of treatment was required. Each pathologic diagnosis was reviewed. The daily dose of sirolimus was adjusted based on plasma levels. Response was retrospectively assessed by local investigators using Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST). Survival was estimated using the Kaplan-Meier method.
All 38 patients (WW Domain Containing Transcription Regulator 1 [WWTR1]-positive, n = 37; transcription factor E3 [TFE3]-positive, n = 1) had disease progression before starting sirolimus (at baseline, 13 of 38 patients had the presence of serosal effusions and systemic symptoms). Thirty-seven patients were evaluable for response (there was 1 early interruption). The best RECIST responses were a partial response in 4 patients (10.8%), stable disease in 28 patients (75.7%), and disease progression in 5 patients (13.5%). At a 41.5-month median follow-up (interquartile range [IQR], 23.9-56.8 months), the median PFS was 13 months (95% CI, 3.7 months to not estimated [NE]), and the median OS was 18.8 months (95% CI, 10.6 months to NE). In patients who had serosal effusions at baseline, the median PFS was 4.8 months (IQR, 3.5-11.7 months), and the median OS was 10.6 months (IQR, 5.1-13.0 months), compared with 47.8 months (IQR, 11.4 months to NE) and 47.8 months (IQR, 15.7 months to NE), respectively, in patients without serosal effusions. Overall, sirolimus was fairly well tolerated, with 10 patients reporting irregular menstruation/ovary disfunction.
The current results confirm that sirolimus is active in EHE, leading to prolonged stabilization in most patients who present without serosal effusions. Serosal effusions are confirmed as an unfavorable prognostic sign associated with short survival, and sirolimus displays limited activity in this subgroup.

There are limited studies of cytology diagnosis of haematopoietic and lymphoid tumours in serosal effusion except for occasional case reports. We would like to demonstrate an algorithmic approach for accurate diagnosis, especially in patients without previous history.
We reviewed 36 cases of lymphoma diagnosed in serosal effusion following an algorithmic approach. Suspected tumour cells were classified into small, intermediate and large sizes and two characteristic forms of plasmacytoid and Reed Sternberg-like on smears (step 1), followed by utilising panels of immunohistochemical markers and Epstein-Barr encoding region in situ hybridisation on cell blocks (step 2). A panel of CD3, CD20 and Ki-67 formed the basic workup, followed by pertinent batteries of immunostaining. Molecular tests were applied in 22 selected cases by fluorescence in situ hybridisation (step 3).
There were 15 diffuse large B-cell lymphomas; 12 plasma cell myelomas; two mantle cell lymphomas; one anaplastic large cell lymphoma ALK +; one small lymphocytic lymphoma; one plasmablastic lymphoma; one peripheral T-cell lymphoma, not otherwise specified, one extranodal NK/T-cell lymphoma, nasal type and two T-cell lymphoblastic lymphomas. 14 cases with previous history had complete concordance in immunophenotype between cytology and histology. Another 14 cases were primarily diagnosed in patients with initial symptom of effusion based on immunophenotyping and cytogenetic test in selected cases. Eight cases were diagnosed based on morphology alone.
An algorithmic approach based on morphology and immunohistochemistry is the key to making an accurate diagnosis of haematopoietic and lymphoid tumours in effusion. A molecular test is also important for confirmation and prognostic prediction. We reviewed 36 haematolymphoid neoplasms diagnosed in effusion including 14 cases primarily diagnosed in patients without previous history following an algorithmic approach by combining morphology, immunohistochemistry and molecular cytogenetics.

BACKGROUND: Carbohydrate antigen 125 (CA-125) is one of the most common used tumor biomarkers in clinical practice. Previous studies showed an association of increased CA-125 levels with advanced characteristics and inferior outcome in non-Hodgkin lymphoma.
OBJECTIVE: To identify the clinical significance of CA-125 in diffuse large B-cell lymphoma (DLBCL).
METHODS: We retrospectively analyzed 181 patients with DLBCL with measured serum CA-125 concentration at diagnosis and follow-ups during the courses. Clinical significance of CA-125 was evaluated by assessing the association between CA-125 levels and clinical characteristics.
RESULTS: CA-125 levels on admission were positively correlated with serum lactate dehydrogenase, β2-microglobulin (β2-MG), serum ferritin (SF) and cavity effusion, while negatively correlated with serum albumen (ALB). During the courses, CA-125 levels were positively correlated with β 2-MG, SF and effusion, and negatively correlated with ALB. A better correlation between effusion and CA-125 levels was observed. Using a cut-off value > 50.39 U/ml gave a sensitivity of 73.8% and a specificity of 92.1% for the indication of effusion at diagnosis, while during the courses the sensitivity was much lower. On the prognostic role of CA-125, we found prognostic relevance on progression-free survival (PFS) but not on overall survival (OS).
CONCLUSIONS: Our study revealed limited usefulness of CA-125 concentration at diagnosis and follow-ups in DLBCL.