Hypocellularity

Abstract: The dominant lymphocytes in human and murine implantation sites are transient, pregnancy-associated uterine natural killer (uNK) cells. These cells are a major source of interferon (IFN)-γ. Implantation sites in mice lacking uNK cells (alymphoid recombinase activating gene [RAG]-2−/− common cytokine receptor chain γ [γc]−/−) or IFN-γ signaling (IFN-γ−/− or IFN-γRα−/−) fail to initiate normal pregnancy-induced modification of decidual arteries and display hypocellularity or necrosis of decidua. To investigate the functions of uNK cell–derived IFN-γ during pregnancy, RAG-2−/−γc−/− females were engrafted with bone marrow from IFN-γ−/− mice, IFN-γ signal-disrupted mice (IFN-γRα−/− or signal transducer and activator of transcription [Stat]-1−/−), or from mice able to establish normal uNK cells (severe combined immunodeficient [SCID] or C57BL/6). Mated recipients were analyzed at midgestation. All grafts established uNK cells. Grafts from IFN-γ−/− mice did not reverse host vascular or decidual pathology. Grafts from all other donors promoted modification of decidual arteries and decidual cellularity. Grafts from IFN-γRα−/− or Stat-1−/− mice overproduced uNK cells, all of which were immature. Grafts from IFN-γ−/−, SCID, or C57BL/6 mice produced normal, mature uNK cells. Administration of murine recombinant IFN-γ to pregnant RAG-2−/−γc−/− mice initiated decidual vessel modification and promoted decidual cellularity in the absence of uNK cells. These in vivo findings strongly suggest that uNK cell–derived IFN-γ modifies the expression of genes in the uterine vasculature and stroma, which initiates vessel instability and facilitates pregnancy-induced remodeling of decidual arteries.

Abstract: Low-grade fibromyxoid sarcoma (LGFMS) is a rare sarcoma characterized by bland histologic features and a paradoxically aggressive clinical course. The hyalinizing spindle cell tumor with giant rosettes (HSCT) is a closely related tumor characterized by the presence of giant collagen rosettes. Only a single example of a metastasizing HSCT has been reported. A small subset of both LGFMS and HSCT display areas of increased cellularity and atypia which qualify as intermediate- to high-grade sarcoma; the significance of these features has not been definitively assessed. We present the clinicopathologic features of 77 cases of LGFMS and HSCT to determine the degree of overlap of these two lesions, their biologic behavior, and the significance of the occasional presence of intermediate- to high-grade sarcoma within both. The patients (33 female, 40 male) ranged from 3 to 78 years of age (median, 34 yrs). Fourteen cases occurred in patients less than 18 years of age. The tumors measured from 1 to 23 cm (median, 4.5 cm) and occurred predominantly in the trunk and lower extremities in both the deep (66 cases) and superficial (7 cases) soft tissues. In 15 cases, the tumor was present > 1 year before diagnosis. All tumors showed predominantly the typical hypocellularity and bland cytologic features of typical LGFMS; however, areas of hypercellularity and nuclear enlargement and hyperchromatism were identified in 12 of 73 (16%) and 7 of 73 (10%), respectively. Necrosis and mitotic activity >5/50 high-powered fields (HPF) were present in 6 of 73 (8%) and 5 of 73 (7%), respectively. Epithelioid areas were present in 33 of 73 (45%) and rosettes in 22 of 73 (30%). Follow up (54 cases; range, 2-192 mos; median, 24 mos; mean, 38 mos) showed 5 recurrences, 3 metastases, and 1 death. The diagnosis of LGFMS or HSCT was made prospectively in 51 patients; none had metastatic disease. Two of the metastatic tumors were LGFMS and one was a HSCT. LGFMS may occur more often in the pediatric population and show a much wider histologic spectrum than previously thought. A significant number of LGFMS possess inconspicuous collagen rosettes characteristic of HSCT, indicating that these two tumors are ends of a common spectrum rather than distinct entities. HSCT, like LGFMS, are low-grade sarcomas with metastatic potential. The presence of focal areas of intermediate- to high-grade sarcoma does not portend a worse outcome in the short term. The better prognosis reflected in this study compared with previous ones might reflect the fact that all were initially diagnosed as sarcomas and treated with aggressive surgery. The fact that the only three patients to develop metastatic disease were patients whose LGFMS or HSCT was identified retrospectively supports this concept.