(P 159) IN BETWEEN OF LYMPHOMAS AND SARCOMAS: WHERE DO HISTIOCYTIC AND DENDRITIC CELL NEOPLASMS (HDCN) STAND? A RETROSPECTIVE, MULTI-INSTITUTIONAL STUDY FROM THE ITALIAN SARCOMA GROUP (ISG)

Objective: HDCNs encompass heterogeneous, ultra-rare neoplasms, arising from cells of haematological or mesenchymal derivation. Consistently, their clinical behaviour recognises features of both haematological cancers and soft tissue sarcomas (STS), with many unresolved questions on the best treatment strategy.

Methods: In the framework of the ISG, we retrospectively reviewed all consecutive cases of HDCNs (histiocytic sarcoma, HS; Langerhans cell sarcoma, LC-S; interdigitating dendritic cell sarcoma, IDC-S; indeterminate dendritic cell tumour, IDC-T; follicular dendritic cell sarcoma, FDC-S; fibroblastic reticular cell tumour, FRC-T) patients (pts) diagnosed between 2000 and 2022 in 7 centers. All diagnoses were confirmed by dedicated pathologists according to the WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues (2017). Radiological response was assessed retrospectively using RECIST1.1 threshold for complete response (CR), partial response (PR), stable disease (SD), progressive disease (PD). Median (m) follow up (FUP) and overall survival (OS, defined as interval between diagnosis and death by any cause) were computed by Kaplan-Meier.

Results: Overall, 56 consecutive HDCNs pts were identified and included in the study (characteristics in table 1): 34 presented with local disease (LD; 7 HS, 17 FDC-S, 3 LC-S, 3 IDC-S, 4 FRC-T), 3 with locally advanced disease (LAD; 1 HS, 1 LC-S, 1 IDC-S), 19 with distant metastases (DM; 7 HS, 6 FDC-S, 1 LC-S, 2 IDC-S, 2 FRC-T, 1 IDC-T). The m-FUP was 86 mos, with a 5-yr OS estimate of 0.97 in pts with LD and 0.5 in pts with LAD or MD.
For pts with LD, all HS underwent surgery with radical intent, 1/7 adjuvant (adj) radiotherapy (RT, 56 Gy), 2/7 adj chemotherapy (CT). The 5-yr OS estimate was 0.87: 1 pt developed local recurrence (LR), 2 DM. All FDC-S pts underwent surgery, 7/17 adj RT (range: 50-66 Gy) and 4/17 adj CT. The 5-year OS estimate was 0.94: 2 pts developed LR, 3 DM. Similarly, all patients with LC-S, IDC-S, FRC-T underwent surgery, 2 pt (LC-S, IDC-S) adj RT (60 Gy, 56 Gy), none CT. None of them recurred. Regardless the HDCNs type, all pts recurring locally did not receive adj RT nor those who developed DM received adj CT (details in table 2).
For pts with MD, the 5-yr OS estimate in HS was 0.50, in FRC-T, IDC-S, IDC-T 0.8. In FDC-S the m-OS was 8 mos, with all pts dead at last FUP. The LC patient died of a B-lymphoma after LC CR on CT.
All pts (4) managed with sequential, definitive anthracycline-based CT and RT (range: 30-55 Gy) are alive and achieved prolonged CR: 2 pts (HS and LC-S) treated for LAD (figure 1) are ADF at 6 and 3 yrs, respectively; 1 patient with a thoracic LR of FDC-S and 1 pt with HS of the gluteus with a single paravertebral metastasis are ADF at 1 and 7 yrs, respectively.
As for CT activity, overall, 20 pts evaluable for response received anthracycline-based CT (LD, LAD, MD included), achieving as best response CR in 7/20 (35%), PR in 6/20 (30%), SD in 4/20 (20%), PD in 3/20 (15%), with a global ORR of 65%. In FDC-S and HS, the ORR was 34% and 78% respectively. Details on response to systemic regimens are reported in table 3.

Conclusion: In this series, the outcome in primary, resected HDCNs is favorable, with an estimated 5-yr OS higher than 80%. Advanced FDC-S remains an unmet need with a m-OS < 12 mos. Similarly to what reported in lymphomas, long lasting CR were achieved in different HDCN types treated with definitive CT/RT, which can be an option for cases unmanageable with surgery. Also, anthracyclines showed a relevant activity in HDCNs, especially in HS, with an ORR superior to those observed in STS. Taken together, these data suggest a possible role for definitive CT/RT and perioperative CT and RT in LD, which needs to be confirmed in a larger series.