Masahiro Ushijima

Giant cell tumor of the tendon sheath (nodular tenosynovitis): A study of 207 cases to compare the large joint group with the common digit group

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 be 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.

Detection of SYT-SSX Fusion Transcripts in Synovial Sarcoma by Reverse Transcription-Polymerase Chain Reaction Using Archival Paraffin-Embedded Tissues

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.

Detection of TLS/FUS-CHOP fusion transcripts in myxoid and round cell liposarcomas by nested reverse transcription-polymerase chain reaction using archival paraffin-embedded tissues.

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 p-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.

Activating Gsα mutation in intramuscular myxomas with and without fibrous dysplasia of bone

Abstract Activating missense mutations in the Arg 201 codon of the gene encoding the α subunit of Gs, the G protein that stimulates cAMP formation, have been recognized as the cause of many endocrine diseases, McCune-Albright syndrome and isolated fibrous dysplasia of bone. On the other hand, intramuscular myxomas with fibrous dysplasia, so-called Mazabraud’s syndrome, have been sporadically reported, but it has not been confirmed whether intramuscular myxoma, with or without fibrous dysplasia, is associated with the Gsα mutations. We investigated the presence of the Gsα mutations in intramuscular myxomas with or without fibrous dysplasia by a PCR-SSCP assay, using formalin-fixed, paraffin-embedded tissues. In five of the six intramuscular myxomas (three with and two without fibrous dysplasia), point mutations were detected as aberrant bands by SSCP, which were confirmed by a subsequent sequence analysis (three Arg to His and two Arg to Cys). This result suggests that the Gsα mutations are related to tumorigenesis in intramuscular myxoma and that intramuscular myxoma is one of the diseases induced by abnormal Gsα protein.

FIBROMA OF TENDON SHEATH: A TUMOR OF MYOFIBROBLASTS

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.

MALIGNANT GIANT CELL TUMOR OF TENDON SHEATH Report of a Case

In a patient with pigmented villonodular synovitis of the right knee joint, there occurred a malignant giant cell tumor of tendon sheath. There was clinical evidence of metastasis after the second local recurrence and the recurrent tumors were studied enzyme cytochemically and electron microscopically. Ultrastructurally, the malignant tumor consisted of three principal cell types; histiocyte‐like cells, fibroblast‐like cells, and intermediate cells, with unique attendance of myofibroblasts. This may be the first report of the presence of myofibroblasts in malignant giant cell tumor of tendon sheath. Enzyme cytochemistry revealed various functional properties of histiocytes. ACTA PATHOL. JPN. 35 : 699–709, 1985.

Molecular detection of EWS-FLI1 chimeric transcripts in Ewing family tumors by nested reverse transcription-polymerase chain reaction : application to archival paraffin-embedded tumor tissues

Chromosomal translocations generating unique chimeric genes are highly characteristic of specific sarcomas, and their use as diagnostic markers has been suggested. From a diagnostic pathologic point of view, detection of such cytogenetic or molecular aberrations applicable to routinely processed archival tissue specimens is considered a powerful tool for tumor diagnosis. To assess the feasibility and reliability of the molecular detection of the transcript originating from the chimeric gene in paraffin‐embedded tumor specimens, we performed a nested reverse transcription‐polymerase chain reaction (RT‐PCR)‐based assay to detect the EWS‐FLI1 chimeric message in a series of Ewing family tumors. Of 24 paraffin‐embedded tumor specimens from 23 cases analyzed, the chimeric message was detectable in 20 (83%) specimens from 20 cases (87%) by this nested RT‐PCR assay, whereas none of 7 small round cell tumors not from this family (3 alveolar rhabdomyosarcomas, 2 neuroblastomas, 2 malignant lymphomas) showed detectable chimeric messages. In the sequence analysis of the PCR products, the amplified chimeric messages contained the junctions between exon 7 of the EWS gene and any one of exons 5, 6 and 8 of the FLI1 gene. The detection process was usually completed within 3 days, except for the subseqent sequence analysis. Our results endorse the use of this molecular assay as an ancillary technique in the diagnosis of Ewing family tumors using paraffin‐embedded material.

PIGMENTED VILLONODULAR SYNOVITIS A Clinicopathologic Study of 52 Cases

Clinicopathologic, enzyme histochemical and electron microscopic findings in 52 patients with pigmented villonodular synovitis (PVS) are reported. The lesion was by far the most common in the knee joint (48%), followed by the ankle joint (25%). As to sex incidence, there seemed to be no predilection (46% in men, 54% in women). Microscopically, the PVS showed thin or thick villous projections of the involved synovial membrane, associated with or without nodular formation. The nodule of PVS consisted essentially of a proliferation of histiocyte‐like cells with phagocytic activities. Another characteristic feature was large clefts and pseudoglandular or alveolar spaces lined by synovial cells. Enzyme histochemical studies revealed that the lesional cells had functional properties of macrophages. Electron microscopically, the lesion consisted essentially of histiocyte‐like and flbroblast‐like cells, together with intermediate cells and myofibroblasts.

Dermatofibrosarcoma protuberans and its fibrosarcomatous variant with areas of myoid differentiation: a report of three cases

We describe three examples of dermatofibrosarcoma protuberans which demonstrated focal myofibroblastic differentiation, and discuss the nature of myofibroblastic differentiation.

Tenosynovial fibroma arising from the posterior cruciate ligament

In a 16-year-old girl, a locking and effusion of the left knee occurred without a history of any specific trauma. Arthroscopic examination of the knee revealed a soft tissue mass arising from the posterior cruciate ligament. The mass was completely excised, arthroscopically. The microscopic diagnosis was tenosynovial fibroma, a new entity reported by Chung and Enzinger in 1979. After a follow-up study of 20 months, the patient was asymptomatic.