Lymphocyte composition and distribution in inflammatory, well-differentiated retroperitoneal liposarcoma: clues to a potential adaptive immune response and therapeutic implications.

To the Editor: Many solid tumors in humans can display a naturally occurring immune response that plays a significant role in shaping disease progression.5,6,16 A recent meta-analysis of studies on tumor-infiltrating immune cells concluded that the presence of CD3 and CD8 T cells within tumors had significant correlation with improved survival across multiple solid tumor types.6 In contrast, tumor-infiltrating immune cells may be hindered in their antitumor effector function by regulatory and suppressive mechanisms, resulting in promotion of tumor growth and poor clinical outcome.5,6,16 Very little is known about the immune response in retroperitoneal liposarcoma. In 1997, an inflammatory subtype of well-differentiated liposarcoma was described in 2 case series by Kraus et al and Argani et al,1 published in the American Journal of Surgical Pathology. These and other, more recent, case reports8,19,20 have suggested that the inflammatory infiltrate consists predominantly of lymphocytes, but the descriptions are often incomplete and at times conflicting. As an example of a naturally occurring immune response in retroperitoneal liposarcoma, we sought to better define this inflammatory component. Formalin-fixed, paraffin-embedded well-differentiated liposarcoma resection specimens collected between 1990 and 2009 were retrieved from the University of Texas M.D. Anderson Cancer Center pathology archives, and available hematoxylin and eosinstained slides were reviewed for the presence of inflammation. For the purposes of this study, only cases of primary, well-differentiated retroperitoneal liposarcoma from 2000 to 2009 were included for review (n=11). Patients were excluded if they had received chemotherapy or radiation before surgery. Further clinical data (eg, patient presentation, operative details, postoperative recurrence) were retrospectively collected on the remaining study patients (n=6). Immunohistochemical analysis for immune cell surface markers was then performed on 4-mm-thick sections prepared from fixed, paraffinembedded tissues from these 6 patients. In our series, patients most commonly presented with symptoms of a palpable mass or fullness (Table 1). No patient had fever or manifested signs of a systemic inflammatory response, and all 6 patients had a normal peripheral white blood cell count before surgery. At the time of surgery, 4 of 6 patients (67%) required en bloc resection of at least one adjacent organ, most commonly the kidney. The median gross tumor size was 36 cm (range, 30 to 40). On the basis of our series and supported by the descriptions by Kraus et al10 the clinical features of patients with inflammatory, well-differentiated liposarcoma appear to be similar to those with conventional, noninflammatory tumors.4 With respect to clinical outcome, recurrence rates after resection were seemingly unaffected by the presence of inflammation in the case series from Kraus et al and Argani et al1. In our series, we found that all patients except one (5 out of 6= 83%) were alive and without recurrence at 3 years (Table 1). The remaining patient developed recurrence at 3 years. Data extrapolated from larger series of conventional, noninflammatory, well-differentiated liposar; coma at our own institution11 and others15 suggest that 3-year recurrence-free survival is typically 60% to 70%. Conclusions regarding improvement in clinical outcome in inflammatory versus conventional, noninflammatory disease, however, are difficult to make, given our limited follow-up time and the overall rarity of this liposarcoma subtype. Histologic analysis of the 6 tumors in our series by hematoxylin and eosin staining demonstrated that the inflammatory component consisted of mononuclear cells that by morphology were, indeed, lymphocytes (Fig. 1A). No polymorphonuclear cells (neutrophils) were seen, and macrophages were rare, except for one case with a florid histiocytic reaction seen in areas of tissue necrosis (data not shown). Consistent across all tumors, the lymphocytes appeared to be distributed in 3 distinct patterns: (1) scattered throughout the tumor, both in fibrous septae and in adipocytic areas; (2) in clusters; or (3) as immature follicles (Fig. 1A). Clusters and follicles were usually perivascular, and vessels seen surrounded by lymphocytes demonstrated no evidence of vasculitis, with an intact endothelial lining and no red blood cell extravasation (Fig. 1B). The density of the inflammatory infiltrate was variable within each individual tumor, with some areas demonstrating little to no immune cells, whereas other areas were densely infiltrated by lymphocytes. With immunohistochemical analysis, Kraus et al10 reported that the tumor-infiltrating immune cells were mostly B cells with <10% T cells. In contrast, Argani et al1 reported that the infiltrate in inflammatory, well-differentiated liposarcoma consisted mostly of T cells, whereas the presence of B cells was much more limited. In our series, we found that in all tumors both T and B cells were equally abundant (Figs. 1C–E). NK cells (not mentioned by either Kraus et al and Argani et al) were absent in all tumors (Fig. 1F). With respect to distribution, CD8 T cells were occasionally found in clusters and follicles but were most commonly seen scattered throughout the tumor (Fig. 1G). LETTER TO THE EDITOR