Clinicopathologic, enzyme histochemical, and electron microscopic findings in 207 cases (208 lesions) of giant cell tumor of tendon sheath (GCTTS) are presented. The GCTTS could he divided into two groups according to the anatomic location, the first occurring in the digits (digit group, 182 cases) and the second, in the larger joints (large joint group, 25 cases). In the majority of cases of the digit group, the tumor occurred in one of the fingers (158 cases), whereas in the large joint group, the tumor was common in the ankle (10 cases) and knee joints (8 cases). The lesion was more common in women (67%) than in men (33%). Microscopically, the GCTTS in both groups consisted of a mixture of abundant histiocyte-like, foam, and multinucleated giant cells of the osteoclast type. However, worthy of special mention were the large clefts or wide pseudoglandular spaces lined by synovial cells and that were more striking in the large joint group than in the conventional digit group. The component cells had functional properties of macrophages, as determined in the enzyme histochemical study. Electron microscopically, the tumors consisted essentially of histiocyte-like, fibroblast-like, and intermediate cells, together with myofibroblasts.Cancer 57:875-884,1986.IANT CELL TUMOR of tendon sheath (GCTTS) (nod-G ular tenosynovitis) and pigmented villonodular synovitis (PVS) have long been studied. The conditions are considered to be benign growths of round or polygonal histiocyte-like cells associated with multinucleated giant cells, foam cells, and hemosiderin-laden cells. Although these two conditions are considered related entities, there is a practical difference. Most lesions of GCTTS produce one or more discrete nodules commonly on the tendon sheath or in the small joints of the fingers and toes. '-9 Less common sites include large joints, such as the ankle or knee PVS is identified by a diffusely proliferated synovial membrane bearing a villous aspect with or without nodular formation, and most frequently involves the knee joint. 2-1 Jaffe and associates,I6 who studied the histologic characteristics of these lesions, concluded that the lesions were in reality multiple manifestations of a single disease, including GCTTS (localized

The reciprocal translocation t(X;18)(p11;q11) is known to be highly characteristic of synovial sarcoma, and its consequence, an SYT-SSX fusion gene, is expected to be a diagnostic molecular marker. In this study, we conducted a reverse transcription-polymerase chain reaction-based assay to detect the SYT-SSX fusion gene transcripts using archival formalin-fixed, paraffin-embedded tumor specimens from a series of 32 synovial sarcoma cases including 6 tumors found in unusual anatomical sites. The SYT-SSX fusion transcripts could be detected in 30 of 32 paraffin-embedded specimens (94%). A subsequent sequence analysis using the polymerase chain reaction products confirmed that the detected messages were derived from either the SYT-SSX1 (22 cases) or SYT-SSX2 (8 cases) fusion gene. Of 23 SYT-SSX-positive monophasic tumors, 16 tumors had an SYT-SSX1 fusion transcript. Fusion transcripts were detectable in all the 7 biphasic tumors analysed, one of which had an SYT-SSX2 fusion transcript. All of the six tumors at unusual locations (lung; 3, metastasis to the abdominal cavity from a tumor of retroperitoneal origin; 1, sacral region; 1, iliopsoas muscle; 1) contained detectable messages. Our results indicate that this molecular assay can be applied to archival formalin-fixed, paraffin-embedded tumor tissues as a feasible and reliable molecular technique for the diagnosis of synovial sarcoma.

Mutations of DOCK8 in humans cause a combined immunodeficiency characterized by atopic dermatitis with high serum IgE levels. However, the molecular link between DOCK8 deficiency and atopic skin inflammation is unknown. Here we show that CD4+ T cells from DOCK8-deficient mice produce large amounts of IL-31, a major pruritogen associated with atopic dermatitis. IL-31 induction critically depends on the transcription factor EPAS1, and its conditional deletion in CD4+ T cells abrogates skin disease development in DOCK8-deficient mice. Although EPAS1 is known to form a complex with aryl hydrocarbon receptor nuclear translocator (ARNT) and control hypoxic responses, EPAS1-mediated Il31 promoter activation is independent of ARNT, but in collaboration with SP1. On the other hand, we find that DOCK8 is an adaptor and negative regulator of nuclear translocation of EPAS1. Thus, EPAS1 links DOCK8 deficiency to atopic skin inflammation via IL-31 induction in CD4+ T cells.

A clinicopathologic study of 18 cases of fibroma of tendon sheath included an immunohistochemical survey of 7 cases and an electron‐microscopic examination of one. The age of the patients ranged from 1 to 77 years, with a median of 34 years. The most common site of the tumors was the finger (7 cases), followed by the knee (3), the hand (2), and the foot (2). The median greatest diameter of the tumor was 2 cm. The tumors were attached or closely related to the tendon or tendon sheath, and usually well circumscribed, and multinodular or tabulated. Microscopically, spindle or stellate tumor cells with fuchsinophilic cytoplasm were embedded in a dense fibrous stroma with scattered small blood vessels. Most tumor cells have immunoreaction products for actin in the cytoplasm with accentuation along the cell membrane. Ultrastructurally, many of the tumor cells proved to be myofibroblasts.

The reciprocal translocation t(12;16)(q13;p11) has been shown to be highly characteristic of myxoid and round cell subtypes of liposarcoma, and the TLS/FUS-CHOP fusion gene that resulted from the translocation is expected to be a diagnostic molecular marker of these sarcomas. In this study, we conducted a nested reverse transcription-polymerase chain reaction (RT-PCR)-based assay to detect the TLS/FUS-CHOP fusion gene transcripts using archival formalin-fixed, paraffin-embedded tumor specimens. Of 18 paraffin-embedded specimens from 16 myxoid and round cell liposarcoma cases, the fusion transcripts could be identified in 16 (89%) specimens from 15 (94%) cases. A sequence analysis using the PCR products confirmed that the detected messages were derived from either type I or type II TLS/FUS-CHOP fusion gene, the latter of which was predominant (80%). The results were consistent in primary and recurrent lesions of the same patients and in paraffin-embedded and snap-frozen samples from the same tumors. In two negative specimens, transcripts of the beta-actin gene could not be detected by RT-PCR, and intact mRNA including the fusion messages might have been degraded. No fusion transcripts were detected in snap-frozen or paraffin-embedded material of other types of tumors with myxoid morphology (seven myxoid malignant fibrous histiocytomas and four lipomas with myxoid change). These results indicate that this molecular assay can be applied to formalin-fixed, paraffin-embedded tumor tissues as a diagnostic aid for these subtypes of liposarcoma.