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Background: Giant cell tumor of soft tissue (GCT-ST) is a rare soft tissue neoplasm that is morphologically similar to but genetically distinct from giant cell tumor of bone. A novel keratin-positive GCT-ST (KPGCT-ST) harboring HMGA2::NCOR2 fusions was recently discovered. Fewer than 30 cases have been described; herein is reported an additional seven., Methods: Cases diagnosed as GCT-ST were retrieved from institutional archives and consultation files. The histopathologic characteristics were assessed, and the electronic medical record was reviewed., Results: Seven tumors were identified in six women and one man with a median age of 23 years. All patients underwent excision; no recurrences or metastases were noted during a median follow-up period of 7 months. Histopathologically, the tumors were characterized by a multinodular proliferation of keratin-positive mononuclear cells with evenly admixed osteoclast-like giant cells and absent neoplastic bone. A fibrous capsule with lymphoid cuffing was frequently seen. Foamy macrophages, inflammation, hemorrhage, and hemosiderin were variably present. The HMGA2::NCOR2 fusion was detected in all cases., Conclusions: Our findings support previously reported hypotheses that KPGCT-ST is a spectrum of the same entity as the recently described xanthogranulomatous epithelial tumor. Although follow-up data are limited, to date, KPGCT-ST appears to follow an indolent course., (© 2023 The Authors. Journal of Cutaneous Pathology published by John Wiley & Sons Ltd.)

Background: In this article on giant cell tumor of tendon sheath (GCTTS), we intend to summarize and analyze the clinical and pathological features of GCTTS hoping to improve clinical management and patient treatment., Methods: The study retrospectively reviewed 216 patients of GCTTS, registered at the Affiliated Hospital of Southwest Medical University from January 2010 to December 2020. These cases were diagnosed by surgical excision. The clinicopathological features and the prognosis were reviewed in the light of the current literature., Results: Of these 216 GCTTS patients, 72 were males (33.3%) and 144 females (66.7%), with a ratio male-to-female of 1:2. The patients' age ranged from 5 to 82, the average being 41.5 years at diagnosis. A total of 96 cases (44.4%) occurred in the hand region, followed by 35 cases (16.2%) in the knee, 32 cases (14.8%) in the foot, 25 cases (11.6%) in the ankle, 12 cases (5.6%) in the wrist, 12 cases (5.6%) in the leg, 2 cases (0.9%) in the head, 1 case (0.5%) in the forearm, and 1 case (0.5%) inside and outside the spinal channel. Histopathology mainly revealed large synovial-like monocytes, small monocytes, and osteoclast-like giant cells., Conclusion: Our results confirm that GCTTS predominantly occurs in the hands of young women. Complete surgical resection with long-term follow-up is the preferred management., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Pigmented villonodular synovitis (PVNS) (also known as diffuse-type giant cell tumor) and tenosynovial giant cell tumors (TGCT) are rare, usually benign neoplasms that affect the synovium and tendon sheaths in young adults. These tumors are driven by the overexpression of colony stimulating factor-1 (CSF1). CSF1 is expressed by a minority of tumor cells, which, in turn attract non-neoplastic inflammatory cells that express CSF1 receptor (CSF1R) through a paracrine effect., Methods: Imatinib mesylate (IM) blocks CSF1R, and previous case reports indicated that it also exerts antitumor activity in PVNS. The authors conducted a multi-institutional retrospective study to assess the activity of IM in patients with locally advanced/metastatic PVNS/TGCT., Results: Twenty-nine patients from 12 institutions in Europe, Australia, and the United States were included. There were 13 men, the median age was 41 years, and the most common site of disease was the knee (n = 17; 59%). Two patients had metastatic disease to the lung and/or bone. Five of 27 evaluable patients had Response Evaluation in Solid Tumor (RECIST) responses (overall response rate, 19%; 1 complete response and 4 partial responses), and 20 of 27 patients (74%) had stable disease. Symptomatic improvement was noted in 16 of 22 patients (73%) who were assessable for symptoms. Despite a high rate of symptomatic improvement and a favorable safety profile, 6 patients discontinued because of toxicity, and 4 patients decided to discontinue IM for no clear medical reason., Conclusions: IM displayed interesting activity in patients with PVNS/TGCT, providing proof of concept for targeting CSF1R in this disease. The authors concluded that the benefits of alleviating morbidity in patients with localized PVNS/TGCT must be balanced against the potential toxicity of chronic drug therapy., (Copyright © 2011 American Cancer Society.)

Background: Soft tissue giant cell tumor (GCT-ST) of low malignant potential is an uncommon neoplasm, considered the soft tissue counterpart of giant cell tumor of bone. GCT-ST mainly affects young to middle-age adults and presents as a painless growing mass mainly located in the lower extremities and trunk. Histologically, this tumor is characterized by a mixture of uniformly scattered osteoclast-like multinucleated giant cells intimately admixed with short fascicles of spindled cells. Complete excision with negative surgical margins is associated with a benign clinical course in most cases., Methods: The authors report the clinicopathological and immunohistochemical features of an unusual GCT-ST of 46 years duration previously histologically misdiagnosed as Kaposi's sarcoma., Results: Histologically, the tumor was characterized by a multinodular growth pattern with osteoclast-like multinucleated giant cells admixed with spindle cells partially arranged in a storiform pattern, fibrosis and foci of haemorrhage and mature bone. Immunohistochemistry revealed CD68 reactivity of the multinucleated giant cells., Conclusion: GCT-ST is a rare neoplasm characterized by benign clinical course if excised adequately, as shown by our case of exceptionally long duration. Emphasis is placed on the importance of differential diagnosis with other giant cell-rich soft tissue neoplasms because clinical behaviour, prognosis and treatment significantly differ.

According to most authors, dermatofibrosarcoma protuberans (DFSP) and giant cell fibroblastoma (GCF) represent the adult and juvenile forms, respectively, of the same disease entity, as evidenced by similar morphology, an identical chromosomal translocation, and CD34 positivity. It has been shown that DFSP and nuchal-type fibroma (NTF) (which is also CD34-positive) are related lesions, and that there might possibly be a continuum between the two. In addition, NTF exhibits CD99 positivity. It was therefore, hypothesized that both DFSP and GCF would show similar immunopositivity for CD99. Archives of pathology at several institutions were searched for DFSP and GCF tissue blocks. A total of 29 DFSP and 5 GCF were analyzed by immunohistochemistry for expression of CD99. Twenty-three of 29 DFSP (79%) and 2 of 5 GCP (40%) expressed CD99. Comparison of CD99 and CD34 showed that the non-tumoral periphery of DFSP was less probable to be CD99 positive, but this finding was not statistically significant.

Although osteoclast giant-cell-like proliferations have been reported in a diverse range of human malignancies, to the best of our knowledge, they have never been described in cutaneous squamous cell carcinoma (SCC). Histologically, osteoclastic giant cell tumors within extraosseous malignancy resemble their bony and soft tissue counterparts, with round to spindle-shaped cells admixed with osteoclast-like multinucleate cells. These cells should be distinguished from sarcomatoid differentiation within a carcinoma; they have a benign morphology with a low nuclear to cytoplasmic ratio, minimal pleomorphism/mitoses and negative immunohistochemistry for cytokeratin. The authors report the rare occurrence of osteoclast-like giant cells (OGCs) and accompanying epithelioid histiocytes lacking overtly malignant features in association with a poorly differentiated SCC occurring on sun-damaged skin. Immunohistochemically, the area rich in OGCs was strongly positive for CD68 and completely negative for cytokeratin, whereas the poorly differentiated infiltrative area had the reverse immunophenotype and nuclear positivity for p63. The histological differential diagnosis and the origin of the proliferation are discussed in this article.

When human blood monocytes were cocultured with stromal cells derived from human giant cell tumor of bone (GCTSC) and a Millipore filter (0.4 microm) was interposed between monocytes and GCTSC, multinucleated giant cell formation of monocytes was induced. The multinucleated giant cells have characters as osteoclast-like cells, indicating that a soluble osteoclast-inducing factor(s) is secreted from GCTSC expressing RANK, RANKL/ODF/OPGL and TACE mRNA. Furthermore, OCIF/OPG inhibited GCTSC-induced osteoclastogenesis, showing that the RANK-RANKL system is involved in GCTSC-induced osteoclastogenesis and that soluble form of ODF/RANKL induces osteoclasts from monocytes. GCTSC expressed the cytokine mRNAs such as M-CSF, GM-CSF, IL-3, IL-4, IL-6, and IFN-gamma mRNAs. None of IL-1ralpha, IL-1alpha, IL-1beta, IL-2, IL-4, IL-10, IL-18, TNF-alpha, G-CSF and IFN-gamma could be detected in all culture media. A significant amount of IL-6 could be detected in the culture media of all GCTSC. IL-8 was found in the culture media of two GCTSC and two osteosarcoma-derived cells. M-CSF was detected in all culture media. GCTSC express CaSR, and stimulation of GCTSC with either extracellular Ca(2+) or neomycin, agonist of CaSR, augmented the expression of RANKL. Some lines of GCTSC expressed alkaline phosphatase, osteocalcin and Cbfa1, suggesting that GCTSC are intimately related to osteoblastic lineage.

High-pressure paint guns deliver paint at approximately 3000 pounds per square inch. At this pressure, paint will penetrate the skin and spread quickly through fascial planes and tendon sheaths. The present case is that of a lesion from the finger of a 35-year-old white male in whom a history was initially unavailable. Histologic examination revealed diffuse fibrohistiocytic proliferation and giant cells, with numerous darkly pigmented, uniformly small-sized particles throughout the lesion. The initial impression was that of a giant cell tumor of tendon sheath. However, the pigment particles were negative for Perls stain, and polariscopic examination revealed clear refractile fragments. These findings raised the possibility that the lesion was the result of a traumatic event. On further inquiry, it was revealed that the patient had sustained a high-pressure paint-gun injury 1 year earlier. The simulation, histopathologically, of a giant cell tumor of tendon sheath by a high-pressure paint-gun injury has not, to our knowledge, been reported previously, nor has the histologic finding of small, uniformly sized pigment particles and polarizable refractile fragments in this particular type of injury.

Two recently seen patients presenting with large breast lumps that proved to be pure mesenchymal tumors arising from the underlying chest wall are presented. One tumor proved to be a giant cell tumor of soft tissue and the other an osteogenic sarcoma. It is suggested that these two cases may not be unique and that some mesenchymal breast tumors might have their origin in the chest wall. Breast computed tomography (CT) scans would help identify similar cases.

Background: Primary giant cell tumor of soft tissue, also known as soft tissue giant cell tumor of low malignant potential, is a rare soft tissue tumor located in both superficial and deep soft tissue. Histologically, these lesions bear a close resemblance to their bony counterparts, giant cell tumor of bone, with round to spindle-shaped cells intimately admixed with uniformly scattered osteoclast-like multinucleated giant cells. In 1989 in the dermatology literature, two malignant giant cell tumors of soft parts were described that filled the dermis and extended into the subcutaneous tissue., Methods: The authors report the rare occurrence of a giant cell tumor of soft tissue occurring primarily in the dermis that lacks overtly malignant features and clinically was thought to be an epidermal inclusion cyst., Results: Light microscopy revealed a non-encapsulated cellular dermal tumor containing numerous osteoclast-like giant cells. Cytologic atypia was minimal and the mitotic count averaged 2-3/10 HPF. The histologic differential diagnosis is also discussed., Conclusion: Giant cell tumor of soft tissue is a rare neoplasm of the skin, however, recognition of this tumor is important due to its behavior as a low-grade malignancy.

Dei Tos and colleagues in 1995 reported a series of seven distinctive orbital tumors in adults which they named giant cell angiofibroma (GCA). The morphologic features are intermediate between giant cell fibroblastoma and solitary fibrous tumor with a richly vascularized, patternless spindle cell proliferation forming a collagenous or myxoid stroma with pseudovascular angiectoid spaces. The spindled tumor cells have large, rounded nuclei, sometimes with complex folded shape and pseudoinclusions. There also are multi- or mononuclear giant cells, and these tumor cells partly line so-called angiectoid spaces. Cells express human progenitor cell antigen CD34 and vimentin. One case in the buccinator fascia was also noted by the authors, but similar cutaneous lesions are thus far unknown. We report our experience with a polypoid tumor that ocurred on the thigh of a 49-year-old woman that conforms to the description of GCA. The tumor has variegated vessels admixed with patternless spindle and giant cell stroma with angiectoid spaces as well as areas of dermatofibrosarcoma protuberans (DFSP). Most tumor cells express vimentin and CD34, including giant and spindle cells lining angiectoid spaces. Focally up to 40% of the lesional cells express coagulation factor XIIIa with histiocytoid to highly dendritic cytosomes. The DFSP component is composed of admixed CD34+ and FXIIIa+ dendritic cells arranged in a storiform pattern. Tumor cells are negative for actin, desmin, S-100, and cytokeratin. The Ki67 proliferation index is 1% in GCA areas and 3% in DFSP areas; Ki 67 stains mainly fibroblasts. We conclude that this cutaneous GCA is a fibrohistiocytic tumor closely related to and representing a more organoid angioformative analog of GCF, with both being related histogenetically also to DFSP. These lesions represent part of a greater spectrum of fibrovascular tissue patterns, all probably derived from proliferations of interactive microvascular CD34+ fibroblasts and FXIIIa+ histiocytes.

Background: The proliferation index (PI) and vascular density (VD) in giant cell tumors (GCT) of bone were studied to assess then value as prognostic markers., Methods: Formalin fixed, paraffin embedded tissue from 7 nonrecurrent (NR-GCT) and 13 recurrent (R-GCT) tumors were stained with MIB-1, a monoclonal antibody against Ki-67 (nuclear proliferation antigen), and QBEND-10, a monoclonal antibody against CD34 (endothelial antigen). A minimum of ten fields/case were analyzed on the SAMBA 4000 Image Analyzer. Only mononuclear cell nuclei were analyzed for MIB-1 staining., Results: Mean values +/- 1 Standard deviation (SD) for PI (stained nuclear area/total nuclear area) were: NR-GCT, 10.98 +/- 3.70; R-GCT (initial presentation), 8.94 +/- 3.57; and R-GCT (first recurrence), 9.25 +/- 3.52. In addition, the mean PI +/- 1 SD for mononuclear round-ovoid cells was 8.71 +/- 3.47 and was 9.16 +/- 10 for mononuclear spindle cells. The mean values +/- 1 SD for VD (stained area/total area of structures) were: NR-GCT, 10.61 +/- 6.37; R-GCT (initial curettage), 9.40 +/- 4.94; and R-GCT, (first recurrence), 12.56 +/- 5.88. Comparing the means for PI and VD for both groups of tumors using Student's t test showed no statistically significant differences (P = 0.34). In one case of histologically benign GCT that metastasized to the lungs, the PI of the metastatic tissue was not significantly different from the primary tumor., Conclusions: This study presents evidence that the degree of tumor cell proliferation and vascularity are not useful parameters to predict the recurrence of GCT of bone and that there are no significant differences between the PI of mononuclear round-ovoid cells and mononuclear spindle cells.

An unusual case of a metastasizing dermatofibrosarcoma protuberans with fibrosarcomatous change (DFSP-FS) is reported. The tumor metastasized to unusual sites, including soft tissues of the cheek, forearm, and retroperitoneum 5 years after surgical resection without local recurrence. In addition, the patient had a second, histologically distinct fibrohistiocytic tumor: a malignant giant cell tumor of soft parts. The occurrence of these two tumor types in the same patient highlights the relationship of DFSP to the family of fibrohistiocytic tumors. The late onset of metastases in the absence of local relapse, although a rare event, reflects the potential difficulty in predicting its biologic behavior. DFSP-FS may be a more aggressive tumor than ordinary DFSP.

Background: Giant cell tumors (GCT) usually involve the epiphyses of long bones and only rarely involve the metaphysis or diaphysis without epiphyseal extension., Methods: This report presents the clinical and pathologic features of 14 patients with metaphyseal and diaphyseal GCT. Of these tumors, 10 were metaphyseal; 2, metadiaphyseal; and 2, diaphyseal., Results: The sites of involvement included the proximal tibia in six patients, distal radius in three, proximal fibula in one, distal fibula in one, distal ulna in one, proximal humerus in one, and distal femur in one. Radiographically, the tumors were lucent, and the majority were sharply marginated without sclerosis. By contrast with conventional epiphyseal GCT, which generally appear in the mature skeleton, a large proportion (50%) of the GCT in this series were in patients who had open epiphyseal growth plates. Despite the unusual clinical presentation, the behavior of metaphyseal and diaphyseal GCT was similar to that of the typical epiphyseal GCT. There was a 43% recurrence rate after curettage in this series., Conclusions: It is important to distinguish this subset of GCT from other giant cell-rich lesions more common in these sites, including aneurysmal bone cyst, osteosarcoma, and nonossifying fibroma.

Method: A new neoplastic cell line, UISO-GCT-1, was established from a giant cell tumor of the right tibia in an 18-year-old man. Immunohistochemical, cytogenetic, ultrastructural, and growth studies were performed., Results: Multinucleated giant cells (> 4-6 nuclei/cell) persisted in a culture relatively late in passage (passage 17), which is unique in cell lines of giant cell tumor of bone. Mononuclear and multinucleated cells in monolayer culture expressed vimentin and tartrate-resistant acid phosphatase and reacted with monoclonal antibodies to CD13 and CD68, suggesting a monocytic-macrophage origin of these cells. Mononuclear and multinuclear cells also selectively expressed high molecular weight cell membrane antigens specifically associated with soft tissue sarcomas and osteosarcomas. Karyotypically, UISO-GCT-1 cells were hypodiploid, hypotetraploid, and multiploid, with more than 200 chromosomes per mitosis present in some cells. Other chromosomal aberrations observed included ring chromosomes, double minutes, translocations, multiple fragments, and multiradials., Conclusion: Collectively, observations of this study suggest that karyotypically abnormal giant cell tumors of bone arise from a monocyte-macrophage lineage and subsequently express an antigenic profile similar to malignant mesenchymal tumors.

Background: Giant cell reparative granuloma is generally considered to be a benign tumor-like bone lesion. Its involvement of axial skeleton and long bones is rare., Methods: Seven cases of extragnathic giant cell reparative granuloma (GCRG), which arose in the axial skeleton and long bones, were analyzed clinicopathologically and compared with allied lesions consisting of 31 cases of aneurysmal bone cyst (ABC) and 83 cases of giant cell tumor of bone (GCT)., Results: These occurred in patients ranging in age from 8-36 years; two were in the vertebrae; two, in the clavicles; one, in a rib; one, in the humerus; and one in the tibia. None of the patients with GCRG had a recurrence despite incomplete resection. Its skeletal distribution and average associated patient age were similar to those of ABC. Histologically, they were characterized by florid fibroblastic proliferation with osteoclast-like giant cell-rich areas, stromal hemorrhage, and newly formed bone or osteoid trabeculae. The histologic features could be found around either the characteristic aneurysmal cysts or sinuses, although they were lacking any large blood-filled spaces., Conclusions: The overlapping clinical and histologic features between GCRG and ABC and their similar biologic behavior represent related responses to an intraosseous hemorrhage. The authors prefer to use the term "solid variant of aneurysmal bone cyst" to describe this lesion.

Background and Methods: Flow cytometric DNA analysis was performed on 30 cases of giant cell tumor (GCT) of bone with the use of paraffin-embedded sections., Results: According to the criteria of Huvos, they were classified histologically into three groups: Grade 1, 26 cases; Grade 2, 4 cases; and Grade 3, no cases. Among the Grade 1 cases, 21 were diploid and 5 were aneuploid. Of the four Grade 2 cases, three were diploid and one was aneuploid. Nine patients had local relapses. Among four patients with complications by lung metastases, two have remained well at 18 and 157 months with the metastases. The other two patients, who had Grade 1 DNA diploid GCT of the 11th thoracic spine, had malignant transformation (osteosarcoma) resulting from radiation therapy. In one patient, the primary lesion exposed to radiation and the lung lesions were diploid, but in the other patient both were found to be aneuploid at autopsy. No significant differences of S-phase fraction were observed between two different grade groups. There was no significant correlation among DNA ploidy, histologic grade, and the presence or absence of lung metastases., Conclusions: Based on this study, the DNA analysis has a limitation in predicting the biologic behavior of GCT.

Background: Most giant cell tumors (GCT) occur at the ends of long bones. There is little information about GCT of the skull bones., Methods: The authors reviewed the Mayo Clinic files, which contained 546 cases of GCT, and their own consultation files, which contained approximately 1500 cases., Results: Eleven tumors occurred in the sphenoid bone with extension to the surrounding bones and structures in 8 patients. One tumor (in Paget's disease) occurred in the frontal bone, one tumor was in the occipital bone, and one tumor was in the temporal bone. There were 4 men and 11 women whose ages ranged from 8 to 78 years, with a mean of 36.5 years. Radiographic findings were not suggestive of a specific diagnosis, although the features were those of an aggressive lesion. Histologically, the tumors had features typical of GCT. However, a prominent spindle cell component was seen in five tumors. The initial treatment in all patients but one was intralesional excision that was as complete as possible. The last patient had a wide excision and had soft tissue recurrence at 1 year. This was excised and she was free of disease at 2.7 years. Three patients died, one in the immediate postoperative period and the other two at 1.6 and 4 years with progression of tumor. One patient had postoperative radiation therapy and was without evidence of disease for 2 years when he was lost to follow-up. The remaining 10 patients all had postoperative radiation therapy; 6 patients were alive without disease from 4 to 34 years. However, one of these six patients had a recurrence that was treated surgically with additional radiation. Four patients were alive with tumor from 2.1 to 26 years at the time of this report., Conclusions: GCT of the skull bones is rare but should be distinguished from giant cell reparative granuloma because of the tendency for progression. Surgical ablation (as complete as possible) and postoperative radiation therapy seem to be the treatment of choice for GCT of the skull bones.

Methods: The immunoreactivity of bone GLA protein (BGP) in primary bone tumors, including osteosarcoma, chondrosarcoma, malignant fibrous histiocytoma of bone (MFH), and giant cell tumor of bone (GCT), was investigated with anti-BGP rabbit serum and peroxidase-antiperoxidase complex., Results: As to intracellular localization, BGP antigenicity was detected in 33 of 35 cases of osteosarcoma and 12 of 25 cases of chondrosarcoma. However, there were no positive findings in all 15 cases of MFH or 20 cases of GCT. In chondrosarcoma, the frequency of positively stained cases increased according to pathologic grading (i.e., 3 of 14 cases of Grade 1, 7 of 9 cases of Grade 2, and 2 of 2 cases of Grade 3). Although the multinucleated cells in MFH or GCT were not immunostained, BGP antigenicity was observed in the multinucleated cells of osteosarcoma (12 of 15 cases). In the matrix of osteosarcoma, BGP immunoreactivity of the tumorous osteoid was observed in 28 of 32 cases. However, in the matrices of chondrosarcoma, MFH, and GCT, BGP immunoreactivity was not observed., Conclusion: These results suggest that the immunohistochemical study of BGP is useful for the differential diagnosis of bone tumors.

A cholangiocarcinoma of the hepatic hilus with an element of giant cell tumor that occurred in a 59-year-old man is reported. His medical history included systemic cholelithiasis and repeated operations on the biliary passages. Four years after the last operation, which was a hepatic segmentectomy, he was readmitted because of persistent fever. A computed tomography scan showed a low-density area and stones in the hepatic hilus. He died of hepatic failure approximately 1 month later. At autopsy, a fist-sized tumor and gallstones were found at the hepatic hilus. Histologically, the tumor mainly showed sarcomatoid features and some tubular adenocarcinoma. An element of giant cell tumor consisting of many osteoclast-type giant cells also was noted. The results of immunohistochemical studies showed a positive reaction to cytokeratin and vimentin in some of the spindle-shaped sarcomatoid cells. Sarcomatoid bile duct carcinomas are rare, as are those with osteoclast-type giant cells. The authors also discuss the histogenesis of these giant cells.

Although "rudimentary meningocele" (RM) or "meningothelial hamartoma" of the skin is a seemingly recently described entity, it has been included in past reports as a variant of primary cutaneous meningioma. We document our experience with four such lesions and compare the histologic and immunohistochemical features of these cases with those of seven classic meningoceles (CM) and four giant cell fibroblastomas (GCF). Although all of these entities share significant points of microscopic similarity, RM and CM are lesions composed of meningothelial cells, whereas GCF is probably of myofibroblastic origin. Rudimentary and classic meningoceles demonstrate cellular immunoreactivity for vimentin and epithelial membrane antigen, whereas the cells of GCF lack the latter determinant and may express muscle-specific actin. Our observations suggest that RM and CM represent closely related developmental malformations; however, RM becomes clinically apparent in a somewhat older patient population than CM and is not associated with major skeletal anomalies as may be found with CM. The distinction between various cutaneous meningothelial proliferations has prognostic importance, as does their separation from GCF. RM and CM are adequately treated by simple excision, whereas GCF, a probable form of fibromatosis, has the potential for local recurrence.

Flow cytometric DNA analysis was performed on 60 cases of giant cell tumor of bone and the results were correlated with the clinicopathologic features. Tumors studied were from 31 men and 29 women whose ages ranged from 18 to 62 years (median, 29 years). The most common sites were the distal end of the femur and proximal end of the tibia, accounting for 75% of the lesions. Treatment consisted of resection in 29 patients (48%), curettage with bone chip packing in 15 patients (25%), or curettage with cement packing in 16 patients (27%). Ten patients (17%) had local relapse within 1 to 3 years, and two had lung metastases. Forty-two patients (70%) exhibited tumors with a diploid DNA content, 16 aneuploid (27%), and two tetraploid (3%). Six (37.5%) of the aneuploid patients had relapses: one of those had been treated by resection of the tumor and five by curettage. Of the remaining ten (62.5%) unrelapsed aneuploid patients, nine had been treated by resection of the tumor and one by curettage. Four of the 42 diploid patients (9.5%) had relapses; all had been treated by curettage of the tumor. The two tetraploid tumors were treated by resection and none relapsed. Histologic parameters did not correlate with relapse rate or DNA pattern. Although relapse was more common among aneuploid tumors, our study shows that this appears to be influenced by the treatment modality rather than the ploidy status. Based on this study the DNA analysis of giant cell tumor of bone has a limited utility for predicting the tumor's biologic behavior.

A unique association of uterine malignant giant cell tumor (MGCT) with leiomyosarcoma (LMS) is described. Contrary to the true mixed sarcomas, they appeared as two adjacent tumors with distinctly different gross, histologic, ultrastructural, and immunohistochemical features and little intermixing at their border. The dissemination of MGCT resulted in the fatal outcome 81 days after hysterectomy. Malignant giant cell tumor and LMS were coexistent neoplasms, which derived probably from different progenitor cells. It is suggested that MGCT could develop in association with preexisting LMS.

Between 1979 and 1987 12 patients with chondroblastoma underwent fine needle aspiration (FNA). There were eight female and four male patients (age range, 11-35 years) with lesions of the proximal humerus (three cases), distal femur (two cases), proximal tibia (two cases), proximal femur, distal tibia, talus, navicular bone, and fifth metacarpal (one case each). The radiologic features of the tumors were not entirely typical of chondroblastoma in the majority of patients. The aspirate was diagnosed as chondroblastoma in seven cases, was considered strongly suggestive of chondroblastoma in one case, was found to be diagnosable as chondroblastoma on review in one case, and was nondiagnostic in two cases. The remaining case, which showed giant cell tumor-like areas in addition to typical chondroblastoma on histologic sections from the curettage, was interpreted as giant cell tumor on FNA. There was no case in which an aspirate was erroneously diagnosed as chondroblastoma. On FNA, chondroblastoma had three dominant cytologic components: neoplastic mononuclear cells (chondroblasts), multinucleated osteoclast-like giant cells, and chondroid matrix fragments. The chondroblasts tended to lie individually in smears creating a pebbled appearance. They most commonly had round to oval nuclei with fine, evenly distributed chromatin and distinct longitudinal grooves, but indented, lobulated, and pyknotic nuclei were also observed. Their cytoplasm was dense and opaque with rounded well-defined borders. Multinucleated osteoclast-like giant cells were randomly admixed and were indistinguishable from those seen in other bone neoplasms. Chondroid matrix stained magenta with the Diff-Quik stain and green to violet with Papanicolaou. The cytologic features of the chondroblasts are the diagnostic hallmark of chondroblastoma and may allow FNA to become a valuable preoperative technique in the management of these patients.

A variety of reactive, benign and malignant soft tissue lesions have been stained for fibronectin using the immunoperoxidase technique. Two patterns of mesenchymal staining have emerged. The first has a diffuse stromal collagen and basement membrane distribution within normal and neoplastic mesenchyme and the second a more specific intracytoplasmic granular staining pattern. The latter is seen only in lesions derived from fibrous-histiocytic and synovial cells, a finding which may be of diagnostic use. The possible significance of intracellular fibronectin in neoplastic mesenchyme is discussed.

A rare, osteoclastoma-like giant cell tumor developed in the macronodular cirrhotic liver of an 87-year-old man. Histogenetically, the tumor was considered to be of reticuloendothelial cell (Kupffer cell) origin. A brief review of the literature concerning the extraosseous giant cell tumors is included in this report.

Four patients with biopsy proven small cell carcinoma of the lung died rapidly following radiotherapy. At autopsy areas of prominent tumor giant cell formation were found at the primary site in all four and in the metastatic sites in three. Giant cell formation in a tumor may be from the development of another tumor, sublethal damage to the original tumor cells or presence of the two components from the outset. The light and electron microscopic appearances of the giant tumor cells and their existence in the nonradiated sites in our cases suggest that small cell carcinoma, as adenocarcinomas and squamous cell carcinomas, may be associated with giant cell carcinoma-like components.

A case of basal cell epithelioma (BCE) with multiple large nuclei on the right buttock of a 69-year-old woman is reported, and the skin was studied by light and electron microscopy. This represented the only case (0.85%) of giant tumor cells with multiple nuclei among 117 patients with BCE. Ultrastructural studies revealed that giant tumor cells were not different from ordinary tumor cells of BCE, except for large convoluted nuclei. In the cytoplasms of giant tumor cells, we observed autophagic vacuoles which were derived from autophagocytosis. Scattered among the giant tumor cells, there were many degenerate tumor cells, some of which were phagocytized by giant tumor cells with multiple nuclei (referred to as macrophagocytosis). It is indicated that tumor cells have considerable phagocytic activities, and degrade the autophagic vacuoles or the degenerate tumor cells with the lysosomes. These findings suggest that the presence of the giant tumor cells with multiple nuclei does not indicate a increased malignant potential or anaplasia of the tumor, and that autophagocytosis or macrophagocytosis is a factor in initiating giant tumor cell formation.

Pleomorphic carcinoma of the pancreas is a well defined histopathological entity characterized by non-cohesive, sarcoma-like growth pattern, and bizarre mono- and multinucleated tumor giant cells with abundant eosinophilic cytoplasm. Fifteen cases are identified in autopsy files of the Department of Pathology, Washington University School of Medicine, which represent 7.1% of all the non-endocrine pancreatic malignancies found at autopsy. Pleomorphic carcinoma is comparable to pancreatic adenocarcinoma in clinical features such as age, sex, and presenting symptoms except that it is more likely to occur in the body and tail of the pancreas, metastases invariably develop, hematogenous spread is more common, and the median survival is worse. Pleomorphic carcinoma could be distinguished from the pancreatic tumors that resemble giant cell tumor of the bone. Differential diagnostic features between it and amelanotic melanoma, hepatocellular carcinoma, choriocarcinoma, pleomorphic liposarcoma, pleomorphic rhabdomyosarcoma, fibroxanthosarcoma, poorly differentiated epidermoid carcinoma, and giant cell carcinomas of the lung and thyroid are discussed.

A study of 31 cases of giant-cell tumor of vertebrae above the sacrum indicates that this unusual diagnosis is sometimes appropriate. Several entities, especially aneurysmal bone cyst and osteoblastoma, should be considered in the diffferential diagnosis. Evidence indicates that excision, sometimes with ancillary irradiation, provides a better chance for cure than would be expected with giant-cell tumor in other sites--sites where recurrent, generally large tumors develop in nearly half of the cases. Giant-cell tumors of vertebrae may affect vertebral bodies or arches and may cause irreversible damage to the spinal cord or to the emerging roots.

Fibro-osseus lesions of the paranasal sinuses, especially those that contain multinucleated giant cells, demonstrate a significant histopathologic overlap although they manifest themselves throughout a wide range of clinical behavior. They routinely require a critical clinical and pathologic interpretation. Often, the clinical course of the disease is the only guide to diagnosis and mode of treatment. This study presents the case of a 4-year-old boy with an osteoid-producing tumor of the ethmoid sinus. Despite an original diagnosis of fibrous dysplasia, the lesion followed a relentless course. Eventually, maxillectomy, orbital exenteration, and craniotomy were required to control the disease. The literature of fibro-osseous lesions of the paranasal sinuses is reviewed and an attempt is made to classify these lesions according to their clinical behavior.

Eighty-six cases of giant cell bone tumor were reviewed with particular attention to frank sarcomatous changes, abnormal mitoses, permeation of vascular channels, and the number of mitoses per square millimeter, and the results were analyzed in relation to malignancy, aggressiveness, and recurrence. There were 4 cases of malignant (Grade III) tumor (about 5%) showing frank sarcomatous changes. Eight (9%) were considered cases of borderline (Grade II+) tumor, without frank sarcomatous changes but showing abnormal mitoses or vascular permeation. Seventy-four (86%) were cases of conventional giant cell tumor (Grades I and II). Mitotic counts did not categorically distinguish the three groups because of overlap. Recurrence essentially reflected the inadequacy of treatment. Metastases were observed only in the malignant group. About a quarter of conventional giant cell tumors were considered aggressive on clinical or radiologic grounds, but these could not be identified on a histologic basis. Tumors with minimal mitotic activity (1/mm2 or less) were almost exclusively nonaggressive. Post-irradiation sarcomas, best regarded as independent new tumors, developed in 4 cases (about 5%).

A 57-year-old man underwent a right pneumonectomy for a bronchogenic carcinoma following bronchoscopy and bronchial biopsy. The tumor was a polypoid mass arising from the lower lobe bronchus. Microscopically it was characterized by mononuclear cells mixed with randomly distributed multinucleated giant cells similar to those seen in giant-cell tumor of bone. Also found were portions showing typical squamous cell and spindle cell carcinoma. Based on the light and electron microscopic findings, we suggest that the current case represents a metaplastic squamous carcinoma showing mesenchymal cell differentiation. A hypothesis on the histogenesis of pleomorphic carcinomas was presented. The problems of histological diagnosis generated by such a tumor should be emphasized.

Three human testicular teratocarcinomas were serially passaged following subcutaneous transplantation into nude mice. Tumor cell suspensions from selected passages were injected intraperitoneally. The subcutaneous transplants of each tumor conserved the morphological characteristics of one component of the primary tumor, namely an embryonal carcinoma in one case and a yolk sac tumor in two. The latter maintained the capacity to synthesize alpha-fetoprotein (AFP). After intraperitoneal injection of cell suspensions, tumors, either attached to or even invading abdominal organs or in the form of free-floating tumor spheroids, were observed. AFP could be localized within the attached growths but not in the spheroids. A critical tumor volume and/or vascularization seemed to be necessary for AFP production in tumor cells. In spheroids from one tumor, cytogenetic analysis revealed both human and murine cells. Thus, these spheroids, apparently composed of tumor cells in the center and murine cells at the periphery, can not be considered to be embryoid bodies.

The histologic features of aggressive Stage 3 benign giant cell tumor of bone were correlated with their radiologic staging studies. Our series includes 24 patients treated at the University of Florida, Department of Orthopaedic Oncology, from January 1979 to July 1983. Particularly in 13 cases, results of routine specimen histologic as well as of the histologic study of macrosections containing the entire resected specimen (the tumor and surrounding bone and soft tissue) were evaluated. Surgical staging studies including plain radiographs, bone scintigrams, computerized axial tomography scans, tomography, and angiography were used to delineate the anatomic location of the lesion. Within this group of giant cell tumors, the general histologic features resemble those of the classic giant cell tumor. However, certain aggressive features best demonstrated on the macrosections, such as cortical and subchondral invasion, capsular and reactive bony zone infiltration, "digital extension" of the tumor, and neovascularity correlated well with the anatomic localization and aggressiveness found on the staging studies. Those findings emphasize the value of staging studies in the delineation of the histologic potential of these benign aggressive lesions.

A group of 639 bone lesions was reviewed in order to study the features of the aneurysmal bone cyst and its association with other conditions. A diagnosis of primary aneurysmal bone cyst not associated with any other bone lesion was made in 87 patients. In 36 additional patients the gross and microscopic changes of aneurysmal bone cyst were identified as part of some other solid bone lesion. Fourteen of these additional cases were associated with giant cell tumor (96 cases studied), six with chondroblastoma (41 cases studied), three with chondromyxoid fibroma (45 cases studied), two with nonossifying fibroma (68 cases studied), four with osteoblastoma (61 cases studied), one with fibrosarcoma (50 cases studied), three with fibrous histiocytoma (45 cases studied), two with osteosarcoma (100 cases studied), and one with fibrous dysplasia (42 cases studied). The age, site, and sex distribution of the cases associated with another lesion compares closely with that of the solid lesion concerned, supporting the concept that the aneurysmal bone cyst component is secondary.

Approximately 2% of histologically benign giant cell tumors (BGCT) of bone are complicated by lung metastases, which can progress despite their benign histologic appearance. Almost all BGCT studied by DNA flow cytometry (FCM) have been reported to be diploid. However, the very few cases with lung metastases previously analyzed were all aneuploid. To assess the usefulness of DNA FCM in predicting the metastatic potential of BGCT, seven metastasizing BGCT were studied by DNA FCM using paraffin-embedded tissue. Five were purely diploid, one was tetraploid, and one was aneuploid. The primary and the metastasis showed the same DNA distribution in all but the tetraploid case, in which the metastasis was purely diploid. A single patient, who was in the diploid group, had unresectable tumor in the lungs; she remains alive with stable disease at 30 months. The other six patients, who underwent complete resections of their lung metastases, are free of disease. These results suggest that DNA FCM is not a sensitive method for predicting the metastatic potential of BGCT since most metastasizing cases appear to be diploid.

Electron microscopy of two cases of anaplastic giant cell tumor of the thyroid revealed that these neoplasms consisted of pleomorphic cells with large, bizarre-shaped nuclei and relatively little cytoplasm rich in rough endoplasmic reticulum. The presence of various intercellular junctions, the resemblance of tumor cells to non-neoplastic epithelial cells of the thyroid follicles and the observation that follicular remnants were identified in the tumor, support the assumption that these tumors derive from the follicular epithelium and can be regarded as carcinomas. Aggregates of cytoplasmic spherical bodies, ultrastructurally similar to virus particles, were detected in some tumor cells. Further investigation is required to determine the nature of these structures and establish their pathogenetic role. In some tumor cells, tubuloreticular arrays were noted within the dilated cisternae of the endoplasmic reticulum; these may represent ultrastructural manifestations of nonspecific injury.

An unusual malignant thyroid neoplasm with a morphologic resemblance to giant cell tumor of the bone is reported in a patient who presented with a rapidly growing thyroid mass and a history of pre-existing goiter. The light and electron microscopic studies disclosed areas of differentiated follicular carcinoma with gradual transition to undifferentiated carcinoma. Pleomorphic spindle-shaped cells and giant cells were accompanied by numerous osteoclast-like multinucleated giant cells. Desmosomes and interdigitating cell surfaces were apparent in the differentiated as well as undifferentiated areas on electron microscopy. These findings support an epithelial rather than a mesenchymal origin for this neoplasm.

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.

The pretreatment biopsy specimens from 184 cases of malignant gliomas from The National Brain Tumor Study Group were reviewed in order to determine which, if any, of nine histologic factors were useful in subdividing the glioblastoma multiforme. In the smaller group of cases treated with surgery and supportive care only, there was a strong negative correlation between cellularity and survival. For those cases treated with surgery and radiation only, and for the study as a whole, there was a positive relationship between survival and the presence of a giant cell neoplasm. We have concluded, on the basis of this limited sample of this select group of patients, that this latter features offers a potential basis of subclassification of the glioblastoma multiforme.

Giant melanosomes were identified in lentigines and nevi of 4 patients from 3 kindreds with the B-K mole syndrome. They were present in some dysplastic lesions but not in malignant melanomas. In one case examined in the electron microscope, characteristic ultrastructural features were observed.

Carcinomas of the pancreas with giant cells are not rare, but those containing osteoclast-like tumor cells are quite unusual. This report documents a pancreatic neoplasm comprising both easily recognizable well-differentiated adenocarcinoma and osteoclast-like tumor. The literature on the "osteoclastoma" of the pancreas is reviewed. Evidence for its epithelial deviation is supported strongly by the present case.

Three patients with a giant-cell tumour of bone were studied clinically, roentgenologically and morphologically, using cytological, histopathological and electron microscopic methods. The tumours were composed of giant cells possessing a great number of mitochondria and stromal cells exhibiting prominent endoplasmic reticulum and Golgi complex. Mitotic activity was only found among the stromal cells. Autophagic vacuoles, lysosomal bodies and degenerative changes of varying severity were found mainly or exclusively among the giant cells, which may indicate that these cells represent an involutionary form of tumour cell. The giant-cell tumours of bone are believed to arise from undifferentiated cells of the bone marrow. Fine-needle aspiration biopsy represents a valuable complement to histopathological examination in the identification of giant cell lesions and diagnosis of genuine cell tumours of bone.