Tumors of histiocytes and dendritic cells are rare hematopoietic neoplasms of myeloid derived macrophages, and myeloid and mesenchymal stem cell derived dendritic cells. Criteria for diagnosis include morphologic and immunophenotypic evidence of histiocytic or dendritic cell differentiation, utilizing a panel of immunohistochemical markers and exclusion of lymphoid, epithelial, stromal and melanocytic phenotype. Clinical course is variably aggressive to indolent based on the tumor type and grade, with limited therapeutic options.
Fifteen consecutive cases with the diagnoses of Histiocytic Sarcoma (7/15), Langerhans Cell Tumor (4/15), Interdigitating Dendritic Cell Sarcoma (2/15), Indeterminate Cell Histiocytosis (1/15), and Reticulum Dendritic Cell Tumor (1/15), evaluated at Moffitt Cancer Center between years 1989 to 2010, were retrieved from the institutional electronic database. Diagnoses were confirmed according to the WHO 2008 classification of hematopoietic neoplasms. Clinical and demographic data, treatment regimens and outcomes were extracted and analyzed.
Seven patients were males and eight were females. Median age at diagnosis was 60 years (range 18–90). The primary sites of involvement included, lymph node (4, 26%), skin or soft tissue (8, 54%), and bone marrow (3, 20%). Three out of seven (42%) patients with histiocytic sarcoma, had bone marrow involvement. Histopathologically, histiocytic sarcoma cases showed sheets of non-cohesive large epitheloid cells with oval to irregular nuclei, vesicular chromatin and abundant eosinophilic cytoplasm, with variable degrees of pleomorphism, with positivity for CD68 and lysozyme immunostains. IDC sarcoma cases were composed of sheets of spindled cells with vesicular chromatin and marked cytologic atypia, positive for S-100 and vimentin. Langerhans cell tumors were composed of large cells with grooved and folded nuclei, fine chromatin, inconspicuous nucleoli, and moderately abundant eosinophilic cytoplasm, with variable degree of nuclear atypia, positive for CD68, CD1a and S-100. Indeterminate cell tumor was composed of cells with abundant cytoplasm and oval to spindle shape nuclei, positive for S-100, CD68, and CD1a. Reticulum Dendritic Cell tumor shows effacement of lymph node architecture with spindle cells in storiform pattern, positive for S100, actin, and CD45. Eleven out of fifteen patients (73%) underwent resection of primary site of disease and seven (47%) of them received adjuvant chemotherapy most frequently antracycline-based. Three patients with histiocytic sarcoma died with a median survival of 48 months (range 12–48); two had disease recurrence and one developed secondary AML. Three patients with localized Langerhans cell histiocytosis involving skin were treated with complete excision of lesion or topical steroids and showed no evidence of local or systemic recurrence. Two out of 15 patients (13%) developed secondary malignancy (AML, MDS) due to prior chemotherapy for their primary disease. Median overall survival was 24 months (range 4 –168).
Accurate diagnosis of histiocytic and dendritic cell neoplasms requires a combination of histomorphologic examination in conjunction with ancillary immunohistochemical study. Clinical course of this very rare group of disorders is heterogeneous, ranging from aggressive behavior with a poor outcome in patients with systemic manifestations to indolent in localized disease. Although a majority of patients with localized disease can achieve durable remission using currently available treatment strategies, patients with systemic or recurrent disease need novel therapeutic approaches based on better understanding of the biology of these disorders.
No relevant conflicts of interest to declare.
Asterisk with author names denotes non-ASH members.