Cancer of unknown primary (CUP) is defined as a heterogeneous group of tumours that present with metastasis, and in which attempts to identify the original site have failed. They differ from other primary tumours in their biological features and how they spread, which means that they can be considered a separate entity. There are several hypotheses regarding their origin, but the most plausible explanation for their aggressiveness and chemoresistance seems to involve chromosomal instability. Depending on the type of study done, CUP can account for 2–9% of all cancer patients, mostly 60–75 years old. This article reviews the main clinical, pathological, and molecular studies conducted to analyse and determine the origin of CUP.
The main strategies for patient management and treatment, by both clinicians and pathologists, are also addressed.
Objectives
To clarify the impact of histological grades in follicular lymphoma.
Methods
We retrospectively analysed 250 patients diagnosed with FL treated with chemoimmunotherapy: 188 patients were grades 1‐2 and 62 grade 3A.
Results
In our series, grade 3A FL patients were older, higher proportion of localised disease and lower bone marrow infiltration at diagnosis comparing grades 1‐2 FL patients. Estimated six‐year progression‐free survival and time to progression showed no differences between both groups [grade 3A: 56% (95%CI: 39%‐73%) and 51% (95%CI: 41%‐61%) vs grades 1‐2:55% (95%CI: 46%‐63%) and 57% (95%CI: 49%‐65%), P = .782 and P = .521, respectively]. Estimated six‐year overall survival was lower, 76% (95%CI: 64%‐88%) for the grade 3A group than grades 1‐2 83% (95%CI: 77%‐89%); P = .044. In addition to that, cumulative incidence curves of death not related to lymphoma at 10 years between groups were as follows: [0.26 (95%CI: 0.25‐0.27) and 0.05 (95%CI: 0.04‐0.06) for G3AFL and G1‐2FL, respectively], P = .010. Grade 3A FL showed in PFS curve no relapses after 6 years. These results were absolutely reproduced in 199 patients receiving R‐CHOP regimen as induction.
Conclusions
Our results indicate similar long‐term outcomes in terms of progression‐free survival and time to progression in grades 1‐2 and 3A. No relapses were observed in G3AFL group after 6 years.
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