A case of osteoclast-like giant cell tumor of the pancreas with ductal adenocarcinoma: histopathological, immunohistochemical, ultrastructural and molecular biological studies.

Osteoclast-like giant cell tumor of the pancreas is a very rare neoplasm, of which the histiogenesis remains controversial. A 63-yr-old woman was hospitalized for evaluation of epigastric pain. An abdominal computerized tomography revealed the presence of a large cystic mass, arising from the tail of pancreas. A distal pancreatectomy with splenectomy was performed. Histologically, the tumor was composed of mononuclear stromal cells intermingled with osteclast-like giant cells. In addition, there was a small area of moderately to well differentiated ductal adenocarcinoma. The final pathologic diagnosis was osteoclast-like giant cell tumor of the pancreas with ductal adenocarcinoma. Here, we describe the histopathological, immunohistochemical, ultrastructural and molecular biological findings of this tumor with review of the literature pertaining to this condition.

Benign giant cell tumour of tendon sheaths in a European Lynx (Lynx lynx).

The histological, histochemical, immunohistochemical and ultrastructural features of a benign giant cell tumour (BGCT) of tendon sheaths in a 12-year-old male European lynx (Lynx lynx) are reported herein. The neoplastic mass involved the subcutaneous and inter-muscular tissues of the first, second, third and fourth digit of the left forelimb, from the phalanxes up to the carpus. The tumour appeared as a grey-whitish tissue mottled with darker areas, along with several scattered foci of orange colour. Histologically, the lesion consisted of a mixed population of numerous, multinucleated giant cells and epithelioid or spindle-shaped mononuclear cells embedded in a loose, highly vascular stroma. Neoplastic cells lined cleft formations and synovial-like projections into cystic spaces. No osteoid matrix could be detected. Haemorrhage and necrosis were also observed. The mononuclear and the giant cells were tartrate-resistant acid phosphatase and periodic acid-Schiff positive, being also immunohistochemically reactive for lysozyme and vimentin, with a few cells showing immunopositivity also for alpha-1-antitrypsin. Ultrastructurally, histiocyte-like cells, fibroblast-like cells and multinucleated giant cells were observed, but no virus-like particles could be detected in any of the above cell types. The BGCT of tendon sheaths, a fairly uncommon neoplasm in animals, has not been previously reported in the lynx.

[Tenosynovial giant cell tumor]. / Tenosynovialer Riesenzelltumor Morphologische, ultrastrukturelle und immunhistochemische Befunde sowie Differenzialdiagnose riesenzellhaltiger Tumoren des Weichgewebes.

Morphological, ultrastructural, and immunohistochemical findings of 12 diffuse type-tenosynovial giant cell tumors/pigmented villonodular synovitis are presented compared to 30 localized tenosynovial giant cell tumors (giant cell tumor of tendon sheath). Diffuse-type-tenosynovial giant cell tumor is characterized by a striking vascularisation pattern composed of densely arranged thin-walled, partly slit-like and partly hyalinized small blood vessels within the papillary synovial fronds. These vessels may show abnormal structures with incompletely arranged endothelial cells/pericytes. The fibrohistiocytic tumor cells probably cause considerable compression/distortion or destruction of the small vessels which might be responsible for an increased blood deposition and massive hemosiderosis. Accompanying multinucleated osteoclast-like giant cells seemingly are recruited from circulating blood monocytes. Microhemorrhagic foci with multinucleated giant cells could be detected in 83% of diffuse-type and 67% of localized-type tumors. Apart from the described vessels, typical morphological findings in diffuse-type tenosynovial giant cell tumors included "giant" hemosiderotic granules, (at least 2-3 times the diameter of an erythrocyte) "giant" siderophages, pseudoalveolar clefts and irregularly anastomosing synovial fronds. Neither mitotic rate nor the amount of giant cells/amount of nuclei of giant cells revealed statistically significant differences between localized-type and diffuse-type of tenosynovial giant cell tumor. Immunohistochemically, the diffuse-type exhibited focal expression of CD31 (in 75% of tumors) and calretinin (in 63%) besides CD68-staining.

Woman aged 24 years with fourth ventricular mass.

April 2005. A woman aged 24 years presented with symptoms related to a tumor in the fourth ventricle. Cytologically, the tumor was biphasic with areas typical of a classic ependymoma, including rosettes, and other areas containing grossly atypical giant cells. Many tumor cells were GFAP-positive and ultrastructural examination revealed microvilli and cilia. The histopathologic abnormalities place this tumor among the ependymomas. Its focal giant cell phenotype is very rare, but has been reported in 4 intracranial or filum ependymomas.

Primary de novo malignant giant cell tumor of kidney: a case report.

BACKGROUND: Osteoclast-like giant cell tumors are usually observed in osseous tissue or as tumors of tendon sheath, characterized by the presence of multinucleated giant cells and mononuclear stromal cells. It has been reported in various extraosseous sites including breast, skin, soft tissue, salivary glands, lung, pancreas, female genital tract, thyroid, larynx and heart. However, extraosseous occurrence of such giant cell tumors in the kidney is extremely rare and is usually found in combination with a conventional malignancy. De-novo primary malignant giant cell tumors of the kidney are unusual lesions and to our knowledge this is the second such case. CASE PRESENTATION: We report a rare case of extraosseous primary denovo malignant giant cell tumor of the renal parenchyma in a 39-year-old Caucasian female to determine the histogenesis of this neoplasm with a detailed literature review. CONCLUSION: Primary denovo malignant giant cell tumor of the kidney is extremely rare. The cellular origin of this tumor is favored to be a pluripotential mesenchymal stromal cell of the mononuclear/phagocytic cellular lineage. Awareness of this neoplasm is important in the pathological interpretation of unusual findings at either fine needle aspiration or frozen section of solid renal masses.

Giant cell fibroblastoma in a 3-year-old boy.

Giant cell fibroblastoma (GCF) is a rare soft tissue tumor most often discovered during the first two decades of life. We present a case of a 3-year-old boy with a history of a recurrent lesion in the knee, the tumor growth progressively and enlarged to 2.1 cm in the previous two years before diagnosis. It involved the subcutaneous tissue, had infiltrative borders and extended into the superficial dermis. The tumor was surgically excised with free margins. There was no evidence of local recurrence, and a metastatic workup was negative after 10 years of follow up. We review herein the clinicopathologic features, histogenesis, differential diagnosis and relationship to dermatofibrosarcoma protuberans (DFSP).

Malignant fibrous histiocytoma, giant cell type, of the breast mimicking metaplastic carcinoma. A case report.

BACKGROUND: We report a case of malignant fibrous histiocytoma, giant cell type (MFHGC), of the breast. A review of the literature failed to reveal cytology-based reports on this entity. The cytologic similarity of breast MFHGC on fine needle aspiration biopsy (FNAB) to other malignant breast neoplasms, including carcinoma with osteoclastlike giant cells, metaplastic carcinoma and breast sarcomas, as well as benign reactive processes, makes the recognition of this tumor challenging. CASE: A 72-year-old woman presented with a 5-month history of an enlarging breast mass. FNAB of the mass showed a hypercellular smear composed of cohesive, branching clusters of spindle cells with ovoid, focally hyperchromatic nuclei and inconspicuous nucleoli. Interspersed osteoclastlike giant cells, some associated with clusters of spindle cells, were uniformly seen throughout the smear. The background was hemorrhagic, with cellular debris and occasional spindle cells and lymphocytes. No ductal epithelial or myoepithelial cells were seen. An incisional biopsy was performed, followed by radical mastectomy. The histologic examination was diagnostic of MFHGC. The diagnosis was supported by immunohistochemical and electron microscopic studies. CONCLUSION: MFHGC, also called primary giant cell tumor of soft tissues, is composed of a mixture of histiocytes, fibroblasts and bland-appearing osteoclastlike giant cells with a multinodular growth pattern. Although MFHGC rarely occurs in the breast and the definitive diagnosis is difficult based on cytology alone, the diagnosis can be considered when a cytologic examination reveals a hypercellular, spindle cell smear with osteoclastlike giant cells in the absence of ductal epithelial or myoepithelial cells.

Diffuse type of giant-cell tumor of tendon sheath: an ultrastructural study of two cases with cytogenetic support.

Two cases of the diffuse type of giant-cell tumor of the tendon sheath (GCTTS) are described. Both tumors arose in the vicinity of large joints of the lower extremity, showing similar clinical and radiological features. Histologically, a proliferation of polygonal mononuclear cells was seen, together with osteoclastlike giant cells, foam cells, and siderophages. The tumors were poorly delineated, displaying an infiltrative pattern into the neighboring soft tissues. Immunohistochemically, strong expression of vimentin, neuron-specific enolase, A1-antitrypsin, and CD68 was found in both mono- and multinucleated tumor cells. At the ultrastructural level, mononuclear cells revealed a diverse morphology, displaying features of histiocytelike and fibroblastlike cells, with the former being more numerous. Scarce neurosecretorylike granules, made up of electrondense membrane-bound material, were found in the cytoplasm of the mononuclear cells. Cytogenetic analysis of one case shows the presence of a clonal population with 47 chromosomes and two different translocations, t(2;3) and der(8) t(8;12). Present findings provide further support regarding the neoplasic nature of this tumoral entity.

A study of four cases of extra-orbital giant cell angiofibroma with documentation of some unusual features.

AIMS: To document the clinical, light microscopic, immunohistochemical and ultrastructural features of four cases of extra-orbital giant cell angiofibromas. METHODS AND RESULTS: Sections of formalin-fixed paraffin-embedded specimens were studied by haematoxylin and eosin, reticulin and immunohistochemical stains. Electron microscopy was carried out in two cases on tissue fixed in formalin. The age of the patients ranged from 30 to 41 years. Two patients presented with a soft tissue swelling in the left groin, one patient had a left axillary soft tissue lump and one patient presented with a parotid lump. All lesions were well circumscribed and contained variably cellular and vascularized tissue composed of round to spindle cells with a patternless arrangement, scattered multinucleate giant cells and pseudovascular spaces conforming to the description of giant cell angiofibroma. Mononuclear and multinucleate tumour cells were both positive for vimentin and CD34; one tumour exhibited focal S100 protein and GFAP positivity. Both of the tumours examined by electron microscopy showed fibroblastic features, but in addition one contained cells having Schwannian features. All four patients were well without recurrent disease on follow-up (average 25 months). CONCLUSION: Giant cell angiofibroma shares many features with solitary fibrous tumour and giant cell fibroblastoma and shows a wider distribution than initially recognized. Rarely, Schwannian differentiation may be observed in these tumours.

Giant cell tumor of tendon sheath: a light and electron microscopic study.

A neoformation has been surgically withdrawn from third finger extensor tendon of the right hand of a 52 year male subject. Light (LM) and electron microscope (EM) observations from a number of tissue fragments allowed the identification of tumor nature, which appeared a giant cell tendon sheath. Moreover, some structural patterns have been described and compared to the previously reported cases. In areas of major cell density, parenchyma does not show lobular or gland-like organization; on the other hand, wide zones characterized by an amorphous matrix, progressively replacing collagen and containing elongated cells, are present. Giant multinucleated cells, mostly localized close to collagen bundles, can also be revealed. Unexpectedly, no foam cells appear and no phagocytized cell debris can be identified in giant multinucleated cells. Engulfed crystals are, differently, evidentiated by electron microscopy, both in mono- and multinucleated cell cytoplasm. Their electron density and their localization within cytoplasmic vacuoles suggest the presence of calcium. A correlation between giant cells and osteoclasts is then proposed. Multiple variously oriented centrioles support the possible mitotic genesis of multinucleated giant cells, which never show, on the other hand, fusion features. Siderosomes and residual bodies are also present. An unusual, diffuse thickening of nuclear lamina, only interrupted at nuclear pore level, is described and discussed.

Giant-cell fibroblastoma: a case report emphasising the presence of hyperplastic subplasmalemmal linear densities in continuity with granular matrices in the extracellular space.

The histological, immunohistochemical and ultrastructural features of a case of giant-cell fibroblastoma from the soft tissues of the chest wall in a 48-year-old female are described with special reference to the cell surface and matrix. Subplasmalemmal linear densities (SLDs) characterised cell surfaces, and exhibited excessive development of the dense external component: foci of identical dense material were present in the matrix. The nature of these dense foci, both the external component of the SLD and those free in the extracellular space, was investigated by light microscope immunostaining for fibronectin, laminin and collagen IV. All three proteins stained vessels. There was weaker but positive staining for tumour cell surfaces and matrix, consistent with the widely dispersed nature of the dense foci. Given their fine structural appearance, these dense foci can be referred to as granular matrices. Given also that the matrix protein immunostaining pattern is consistent with the distribution of these granular matrices as observed by electron microscopy, they may be provisionally interpreted as a kind of basement-membrane-related granular matrix. The presence of these proteins emphasises the point that, while giant-cell fibroblastoma fibroblasts lack a lamina, they nevertheless bear basement-membrane-related proteins organised, however, in a non-laminate fashion. The observations reinforce the need to qualify immunostaining results by ultrastructural investigation in order to understand the organisation of immuno-detected proteins and are discussed in terms of their diagnostic and possible biological significance.

Giant cell angiofibroma of the orbit and eyelid.

PURPOSE: To report the clinicopathologic features of a newly recognized tumor, giant cell angiofibroma. DESIGN: Observational case series. MAIN OUTCOME MEASURES: Clinical and histopathologic features of giant cell angiofibroma. METHODS: Light and electron microscopy and immunohistochemistry of five cases of giant cell angiofibroma. RESULTS: A total of five patients (4 women and 1 man) are described: two presented with a painless mass in the eyelid, two with a mass in the orbit, and one presented with a conjunctival lesion. All lesions were well demarcated with no capsule and were composed of blood vessels, a patternless spindle-shaped cell proliferation with a solid and pseudovascular appearance, and multinucleated giant cells. Both spindle-shaped and giant tumor cells were intensely positive for CD34 and vimentin. CONCLUSION: Giant cell angiofibroma resembles solitary fibrous tumor and giant cell fibroblastoma and should be considered in the differential diagnosis of spindle-cell tumors in the eyelid, orbit, and conjunctiva.

Multinucleated giant stromal tumor of the omentum: report of a case with immunohistochemical and ultrastructural investigation.

Multinucleated giant stromal cells (MGSC) have been described in a variety of lesions of various anatomical sites. They are generally believed to be derived from fibroblasts or myofibroblasts. Their size and bizarre appearance may lead to an erroneous interpretation of infiltrating malignant cells, but they are regarded as reactive in nature. MGSC also seem to participate in a neoplastic process and form a part of tumors called giant cell fibroblastomas (GCF). In GCF, multinucleated giant cells are sparsely scattered throughout the tumor, which is composed of loosely arranged spindle cells. Thus far, no tumor composed of MGSC entirely, to the best of the authors' knowledge, has been reported. This study involved an 80-year-old female with an omental tumor, which is believed to represent the first case of tumor of MGSC. The patient developed abdominal pain; a large abdominal tumor measuring 18 x 15 x 5 cm by computerized tomography was found located between the left lobe of the liver, the transverse colon, and the greater curvature of the stomach. Although the tumor was adherent to the above organs and infiltrating the omentum, it was resectable. Grossly, the tumor was highly vascular and the surface was shaggy with no recognizable capsule. The cut surfaces were red to tan with frequent cystic spaces containing bloody material. Microscopically, the tumor cells were large and multinucleated (2-6 nuclei) with prominent nucleoli. The cytoplasm was abundant and stained amphophilic. These tumor cells formed moderately cellular sheets filling the spaces between the varying sized vessels. There was prominent vascularity throughout the tumor. DNA study by image analysis revealed aneuploidy peaks. On immunohistochemistry, the tumor cells were strongly positive for vimentin, moderately positive for actin along the periphery of the cytoplasm, and negative for cytokeratin, EMA, myoglobin, S-100, CEA, Factor XIIIa, HMB-45, and HAM56 and KP-1. Ultrastructurally, the cytoplasm contained rich profiles of RER with scattered lysosomes. The cell borders were slightly irregular with occasional subplasmalemmal densities facing loosely arranged collagenous stroma. The light microscopic, immunohistochemical, and electron microscopic features of tumor cells were remarkably similar to MGSC. The tumor size and gross appearance suggested a malignancy, but it was a diploid tumor and the patient remains disease free 5 years after a complete resection.

Diffuse tenosynovial giant cell tumor of soft tissues. Report of a case with cytologic and cytogenetic findings.

Extraarticular diffuse tenosynovial giant cell tumor is an unusual lesion the cytologic picture of which has not been discussed much in the literature. Fine needle aspiration biopsy of a nonpainful mass in the right shoulder in an 18-year-old woman revealed a highly cellular lesion consisting of polygonal cells and multinuclear giant cells with scant nuclear pleomorphism and a marked tendency toward xanthomization. Electron microscopy identified two basic cell populations among many intermediate forms: cells with scant filopodia and abundant ribosomes and cells with well-developed prolongations and numerous mitochondria, lysosomes and lipid drops. The karyotype of the tumor cells obtained from a surgically excised specimen showed a clonal population with 45, XX, t(1;2) (pter->p22::q24->pter), t(1:14)(qter->p13::q13->ter). The cytologic differential diagnosis included other tenosynovial lesions containing xanthomatous cells. Cytogenetic findings are discussed in relation to chromosomal alterations previously found in related lesions (nodular tenosynovitis and pigmented articular villonodular synovitis).

Diffuse-variant tenosynovial giant cell tumor: a rare and aggressive lesion.

The diffuse-variant tenosynovial giant cell tumor is rare. Although it shares histologic features with the exclusively intra-articular pigmented villonodular synovitis and local tenosynovial giant cell tumor, its behavior differs dramatically, being locally very aggressive. We report a case of a diffuse-variant aggressive tenosynovial giant cell tumor that, although diploid by flow cytometry, demonstrated trisomy 7 and 5 as well as clonal rearrangements involving chromosomes 1, 3, and 15. These cytogenetic abnormalities may be markers for aggressive behavior and useful for directing treatment.

Giant cell tumor of tendon sheath. An immunohistochemical observation on the characteristics and the capacity of proliferation of tumor cells.

To investigate character and proliferation of tumor cells of giant cell tumor of tendon sheath (GCTTS), we studied 25 cases of GCTTS by light and electron microscopic immunohistochemistry. Mononucleated stromal cells (SC) of GCTTS could be divided into three types according to their antigenic features. The first type was the histiocytic SC expressing antigens recognized by KP1, Mac387 and Ham56. The second type was the fibroblastic SC showing fibronectin immunoreactivity. The third type was the intermediate SC expressing both KP1 and fibronectin. The presence of intermediate SC suggested that the different types of SC of GCTTS would be of common origin, i.e. from the mesenchymal cells of the synovium and represented different functional phases or phenotypic alterations. The expression of proliferating cell nuclear antigen (PCNA) was observed only in SC and occasionally, in binucleated cells, but multinucleated giant cells (GC) were negative for PCNA, suggesting that GC were non-dividing cells.

Malignant giant cell tumor of the tendon sheath: an autopsy report and review of the literature.

A case of malignant giant cell tumor of the tendon sheath of the right hip, which developed in a 72-year-old Japanese woman, is described. The tumor exhibited histological similarities to a benign giant cell tumor of the tendon sheath (localized nodular tenosynovitis). The resected tumor, measuring 9 x 9 x 11 cm, was located in the adductor muscle and invaded the proximal femur and acetabulum. The nodule was encapsulated with a thin membrane which was soft and gelatinous in consistency and varied in color from yellow to brown. The synovium of the hip joint was normal. The primary lesion was composed of plump polyhedral and spindle-shaped cells. The nuclei were large, irregular and hyperchromatic, and contained prominent nucleoli. A moderated number of multinucleated giant cells was scattered throughout the lesion. There was little stromal collagen. In the majority of the specimens, pseudoglandular or alveolar spaces were predominant. An ultrastructural study demonstrated three cell types: fibroblast-like, histiocyte-like and an intermediate. The patient underwent reconstructive surgery with a Dacron fabric-enveloped alumina ceramic pelvic prosthesis and total hip components after resection of the primary lesion. Unfortunately, because of a local recurrence, a hemipelvectomy was required 10 months after the initial operation. At that time the intestines were involved with the recurrent tumor, and the patient subsequently died of perforative peritonitis. An autopsy revealed distant metastases to the right pelvis, urinary bladder, right ureter, ilium, mesenterium and lungs.

Establishment of a cell line from a human giant cell tumor of bone.

A cell line (CG-1) was established from a specimen of a 21-year-old woman with giant cell tumor of bone. Inverted-phase microscopic analysis showed that the cultured cells were spindle-shaped in appearance. Multinucleated giant cells and macrophagelike round cells characterizing the histology of giant cell tumor of bone were not found. It is believed that the spindle-shaped cells were the neoplastic element of this tumor, because they were cultured more than 40 passages over the course of one year and subsequent cytogenetic analysis with a G-band technique showed constant loss of chromosomes 14 and 19. The cell line was found to produce several cytokines: M-CSF, IFN-gamma and TNF-alpha, as demonstrated by Western blotting analysis. These cytokines are known to show chemotactic, differentiation-inducing, and activating effects on macrophages. Because it has been recently reported in the literature that there are many infiltrated macrophages in giant cell tumor of bone, and because multinucleated giant cells are formed by fusion of macrophages, the newly established cell line may prove a useful system in studying the nature of giant cell tumor of bone.

Crystalline inclusions in a subependymal giant cell tumor in a patient with tuberous sclerosis.

Unusual crystalline cytoplasmic inclusions were encountered in tumor cells in a subependymal giant cell tumor (SEGT) in a 16-year-old girl with tuberous sclerosis. By electron microscopy, the tumor cells demonstrated typical features previously described in SEGT, including abundant dense bodies, prominent Golgi complexes, abundant mitochondria, rough and smooth endoplasmic reticulum, scattered intermediate filaments and microtubules, glycogen, and rare synaptic contacts as well as primitive intercellular junctions. The dense bodies were bound by a single membrane and were round, ovoid, irregular, or cylindric in appearance with electron-dense homogenous content or fingerprint profiles. Of note was the presence of numerous cytoplasmic rhomboidal or rectangular crystalline inclusions akin to those seen in alveolar soft part sarcoma. These inclusions measured as much as 8 microns in length and had 7-nm periodicities, often with intersecting lamellae. Rarely, the membrane-bound dense bodies showed areas of similar periodicities, indicating that the crystalline inclusions are related to and might originate from the dense bodies. While crystalline inclusions have previously been described in one patient with SEGT (Bender and Yunis, Ultrastruct Pathol 1980; 1:287-299), the inclusions in the present case were a striking feature and add to the spectrum of the ultrastructural pathology of SEGT.