We investigated the clinicopathological features and prognostic factors of patients with peripheral T-cell lymphoma (PTCL) in 13 sites across Spain. Relevant clinical antecedents, CD30 expression and staining pattern, prognostic indices using the International Prognostic Index and the Intergruppo Italiano Linfomi system, treatments, and clinical outcomes were examined. A sizeable proportion of 175 patients had a history of immune-related disorders (autoimmune 16%, viral infections 17%, chemo/radiotherapy-treated carcinomas 19%). The median progression-free survival (PFS) and overall survival (OS) were 7Á9 and 15Á8 months, respectively. Prognostic indices influenced PFS and OS, with a higher number of adverse factors resulting in shorter survival (P < 0Á001). Complete response (CR) to treatment was associated with better PFS (62Á6 vs. 4 months; P < 0Á001) and longer OS (67Á0 vs. 7Á3 months; P < 0Á001) compared to no CR. CD30 was expressed across all subtypes; >15% of cells were positive in anaplastic lymphoma kinase-positive and-negative anaplastic large-cell lymphoma and extranodal natural killer PTCL groups. We observed PTCL distribution across subtypes based on haematopathological re-evaluation. Poor prognosis, effect of specific prognostic indices, relevance of histopathological subclassification, and response level to first-line treatment on outcomes were confirmed. Immune disorders amongst patients require further examination involving genetic studies and identification of associated immunosuppressive factors.

The differential diagnosis of Cushing's syndrome is a major challenge to clinical endocrinologists, especially those infrequent cases referred to as occult ectopic ACTH syndromes. Although bronchial carcinoids are well known to be a cause of Cushing's syndrome due to ectopic ACTH secretion, very few cases of carcinoid tumourlets causing an ACTH ectopic syndrome have been reported, and their origin remains controversial. For some authors, tumourlets and typical carcinoids represent distinct pathological entities, whilst others hold that tumourlets are merely microscopic carcinoid tumours. We report a patient with an aggressive Cushing's syndrome that required bilateral adrenalectomy, diagnosed 22 years before a 3-cm lung nodule became apparent on routine chest X-ray. The biopsy after lung surgery revealed a typical peripheral bronchial carcinoid surrounded by tumourlets. Both tumourlets and carcinoid tumour showed strongly positive ACTH immunostaining. Recently, Arioglu et al. (1998) reported a case of Cushing's syndrome caused by pulmonary carcinoid tumourlets, concluding that this entity should be considered in the differential diagnosis of occult ectopic ACTH syndrome. Furthermore, we consider that the carcinoid tumourlets found in our patient, were the initial source of ACTH, leading to Cushing's syndrome with a rapid onset, and that a loss of cell proliferation control in one of such tumourlets many years later, could have resulted in the development of a typical carcinoid tumour, reinforcing the theory of a common origin of these lesions.

Purpose The objective of this study was to investigate clinicopathologic features and prognostic factors of patients diagnosed with PTCL in 13 sites across Spain. Patients and Methods A multicenter, retrospective study was carried out between September 2015-November 2017.Medical charts of patients diagnosed with PTCLs between January 2008 and December 2013 that have signed the approved informed consent form were reviewed. PTCLs were then classified according to the 2016 revision of the WHO classification of lymphoid neoplasms. Clinical characteristics,history, standard immunohistochemistry (IHC) data, International Prognostic Index (IPI) and Prognostic Index for T-cell lymphoma (TCL) (PIT) were also assessed. Medians (range), mean (standard deviation) and frequency as the number of patients (n) and percentages (%) with confidence intervals at 95% (CI95%) were calculated. Overall Survival (OS) and Progression Free Survival (PFS) were analyzed using the Kaplan Meier method. Results 175 (88.4%) patients were successfully analyzed, the male/female ratio was 1.7:1.0, and the median age was 67.2 years (range: 24.8 years -95.8 years). ECOG performance status >1 was reported for 31.9% patients. Ann Arbor stages were III and IV 27.4% and 45.7%, respectively, and LDH levels were elevated to 92 patients (52.6%). Those with B symptoms accounted for 39.4%, while soft tissue was the most frequent location (23,7%) among the 76 patient with extranodal disease; bone marrow infiltration was confirmed in 18.3% patients. Relevant clinical antecedents related to immunological aspects were also frequently reported, including previous neoplasia (18.9%), autoimmune disease (16%), immunosuppressive treatments (7.3%) and previous viral diseases (HIV, HBV or HCV, 5.7%, 4.6% and 7.4%, respectively). Most patients presented with angioimmunoblastic TCL (31.4%); similar proportions of patients were observed among nodal PTCL with TFH phenotype (13.1%, PTCL not otherwise specified (12.0%) and extranodal NK/TCL nasal type (11.4%). CD30 expression and staining pattern (ranged 1-4) allowed the stratification of patients according CD30 intensity (n= 121; weak: 35, moderate: 57, and intense: 29); Patients were also classified based on CD30 expression considering the median value of quantitative CD30 in our sample (15%) the cut-off point: n=132; Negative <15%: 64; Positive, ≥15%: 68). First-line treatment with a CHOP/CHOP-like regimen was the most common finding (69.7%). Best response was observed after a median of 4 months since the start of first-line treatment (range 0.0 months - 65.2 months). Overall response rate after first-line treatment was 66.9%, with 61/151 patients reaching complete response (CR). Median PFS (n=157) and OS (n=175) of this series were 7.87 months (CI95%: 4.98 months-10.75months) and 15.77 months (CI95%: 10.23 months -21.30 months), respectively. Overall, IPI and PIT scores influenced the PFS and OS (p<0.001). A higher number of adverse factors was associated with a shorter survival. Reaching a CR was associated with a better PFS (CR: 62.6m; CI95%: 20.2 months -105.1 months) than the rest of patients (3.97m: CI95%: 3.08 months -4.85m; p<0.001). Response was also associated with OS; patients with CR showed an average OS of 67.01 months (CI95%: 58.2 months -75.9 months) that were significantly longer than that of patients with No-CR (median: 7.34 months; CI95%: 5.85 months -8.83 months; p<0.001). Conclusion This is the largest series of T cell Lymphoma reported in Spain and has allowed the description of distribution of PTCL subtypes, analyzed through central hematopathologists reanalysis and reclassification of samples from 175 PTCL patients, according to the WHO 2016 classification of lymphoid neoplasms. Our data confirm the poor prognosis of these patients, as well as the impact of prognostic indexes and the response to first line treatment on their outcome. Disclosures Rodriguez-Pinilla: Takeda: Honoraria. Piris:Takeda: Honoraria; Janssen: Honoraria; Gilead: Honoraria; Kura: Honoraria. Ruiz-Zorrilla:Takeda: Employment. Montoto:Takeda: Employment.