bromochloroacetic-acid and Giant-Cell-Tumors

Since the concept of malignant fibrous histiocytoma (MFH) was introduced and subsequently popularized in the 1960's and 1970's, it has become widely regarded as the commonest soft-tissue sarcoma of adulthood. Although the initial notion that MFH was a true histiocytic tumor showing faculative fibroblastic differentiation has been disproved, and despite the lack of definable, reproducible diagnostic criteria and considerable immunophenotypic, ultrastructural and karyotypic heterogeneity, MFH is still accepted widely as a discrete clinicopathologic entity. On the other hand several recent studies have expressed considerable doubts about MFH, or at least pleomorphic MFH, as an "entity" and have suggested that it represents a common morphologic manifestation of a host of poorly differentiated sarcomas and, more rarely, other neoplasms. This article reviews the clinicopathologic features of MFH and its established variants in the context of this debate and considers the evidence for and against their continued acceptance as distinct entities or as a cohesive group. We conclude that the pleomorphic, giant cell and inflammatory variants each represent heterogeneous diagnostic groups which are hard to defend as cohesive entities, while the myxoid ("myxofibrosarcoma") and angiomatoid types are distinct, reproducible tumor types.

Topics: Desmin; Fibrosarcoma; Giant Cell Tumors; Histiocytoma, Benign Fibrous; Humans; Keratins; Leiomyosarcoma; Retroperitoneal Neoplasms; Soft Tissue Neoplasms

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.. 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.. 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.. 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.

Topics: Adult; Diagnosis, Differential; Female; Giant Cell Tumors; Giant Cells; Humans; Keratins; Male; Nuclear Receptor Co-Repressor 2; Soft Tissue Neoplasms; Young Adult

Xanthogranulomatous epithelial tumor (XGET) and keratin-positive giant cell-rich soft tissue tumor with HMGA2-NCOR2 fusion (KPGCT) are two recently described neoplasms with both distinct and overlapping clinical and histopathologic features. We hypothesized that XGET and KPGCT may be related and represent a histologic spectrum of a single entity. To test this, we sought to characterize the clinical, radiographic, immunohistochemical, ultrastructural and molecular features of additional tumors with features of XGET and/or KPGCT, which we refer to descriptively as keratin-positive xanthogranulomatous/giant cell-rich tumors (KPXG/GCT). The archives were searched for potential cases of KPXG/GCT. Clinical and imaging features were noted. Slides were assessed for histologic and immunohistochemical findings. Ultrastructural and next generation RNA sequencing-based analysis were also performed. Nine cases were identified arising in seven women and two men [median age of 33 years (range: 12-87)]. Median tumor size was 4 cm (range: 2.4-14.0 cm) and tumors presented in the thigh (2), buttock (1), forearm (2), groin (1), cranial fossa (1), ilium (1), and tibia (1). Morphologically, tumors were most frequently characterized by a fibrous capsule, with associated lymphoid reaction, enclosing a polymorphous proliferation of histiocytes, giant cells (Touton and osteoclast-types), mixed inflammatory infiltrate, hemorrhage and hemosiderin deposition, which imparted a variably xanthogranulomatous to giant cell tumor-like appearance. One case clearly showed mononuclear cells with eosinophilic cytoplasm characteristic of XGET. All cases expressed keratin and 7 of 9 were found to harbor HMGA2-NCOR2 fusions including cases with xanthogranulomatous appearance. One patient developed local recurrence and multifocal pulmonary lesions, which were radiographically suspicious for metastases. Shared clinical, histologic and immunohistochemical features, and the shared presence of HMGA2-NCOR2 fusions supports interpretation of KPXG/GCT as a single entity which includes XGET and KPGCT. Given limited clinical follow-up to date and rare cases with apparently aggressive findings, we provisionally regard these tumors as having uncertain biologic potential.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Female; Giant Cell Tumors; Giant Cells; Hemosiderin; HMGA2 Protein; Humans; Keratins; Male; Middle Aged; Neoplasms, Glandular and Epithelial; Nuclear Receptor Co-Repressor 2; Oncogene Proteins, Fusion; Soft Tissue Neoplasms; Young Adult

Giant cell tumors of soft tissue (GCT-ST) are rare low-grade neoplasms that were at one time thought to represent the soft tissue counterparts of GCT of bone (GCT-B) but are now known to lack the H3F3 mutations characteristic of osseous GCT. We present six distinctive giant cell-rich soft tissue neoplasms that expressed keratins and carried a recurrent HMGA2-NCOR2 gene fusion. Patients were five females and one male aged 14-60 years (median, 29). All presented with superficial (subcutaneous) masses that were removed by conservative marginal (3) or wide (2) local excision. The tumors originated in the upper extremity (2), lower extremity (2), head/neck (1), and trunk (1). Five patients with follow-up (median, 21 months; range, 14-168) remained disease-free. Grossly, all tumors were well-demarcated but not encapsulated with variable lobulation. Histologically, they were composed of bland plump epithelioid or ovoid to spindled mononuclear cells admixed with evenly distributed multinucleated osteoclast-type giant cells. Foci of stromal hemorrhage and hemosiderin were seen in all cases. The mitotic activity ranged from 2 to 14/10 high power fields (median: 10). Foci of necrosis and vascular invasion were seen in one case each. The mononuclear cells were immunoreactive with the AE1/AE3 keratin cocktail and less frequently/less diffusely for K7 and K19 but lacked expression of other lineage-associated markers. RNA-based next-generation sequencing revealed an HMGA2-NCOR2 fusion in all tumors. None of the keratin-negative conventional GCT-ST showed the HMGA2-NCOR2 fusion (0/7). Metaplastic bone (4/9) and SATB2 expression (3/4) were frequent in keratin-negative conventional GCT-ST but were lacking in keratin-positive HMGA2-NCOR2 fusion-positive tumors. The distinctive immunophenotype and genotype of these tumors strongly suggest that they represent a discrete entity, differing from conventional GCT-ST and other osteoclast-rich morphologic mimics. Their natural history appears favorable, although a study of additional cases and longer follow-up are warranted.

Topics: Adolescent; Adult; Aged; Child; Female; Giant Cell Tumors; HMGA2 Protein; Humans; Keratins; Male; Middle Aged; Nuclear Receptor Co-Repressor 2; Oncogene Fusion; Soft Tissue Neoplasms; Young Adult

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.

Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Carcinoma, Pancreatic Ductal; Diagnosis, Differential; Female; Giant Cell Tumors; Humans; Immunohistochemistry; Keratins; Microscopy, Electron; Middle Aged; Mucin-1; Osteoclasts; Pancreatic Neoplasms; Proliferating Cell Nuclear Antigen; Vimentin

Topics: Adult; Cystadenocarcinoma, Mucinous; Female; Giant Cell Tumors; Humans; Immunohistochemistry; Keratins; Lymph Nodes; Lymphatic Metastasis; Neoplasm Recurrence, Local; Osteoclasts; Pancreatic Neoplasms; Tumor Suppressor Protein p53; Vimentin

Undifferentiated carcinomas and osteoclast-like giant cell tumours of the pancreas commonly contain foci of neoplastic ductal glands. To test the hypothesis that undifferentiated carcinomas and osteoclast-like giant cell tumours have a ductal origin, the immunocytochemical cytokeratin pattern and the frequency and type of Ki-ras mutations at colon 12 were studied in a series of 17 undifferentiated carcinomas and two osteoclast-like giant cell tumours. The cytokeratin features of undifferentiated carcinomas and osteoclast-like giant cell tumours were compared with those found in 10 ductal adenocarcinomas, 20 acinar cell carcinomas, 25 neuroendocrine tumours, and 15 solid-pseudopapillary tumours. All undifferentiated carcinomas and osteoclast-like giant cell tumours stained with at least one cytokeratin antibody, and 13/19 of them with antibodies against cytokeratins 7, 8, 18, and 19. The latter cytokeratins were expressed in all ductal adenocarcinomas, but only in 15/20 acinar cell carcinomas, 2/25 neuroendocrine tumours, and 1/15 solid-pseudopapillary tumours. In addition to cytokeratin, 15/19 undifferentiated carcinomas/osteoclast-like giant cell tumours were positive for vimentin. Ki-ras mutations at codon 12 were found in 10 undifferentiated carcinomas and one osteoclast-like giant cell tumour from which DNA could be successfully amplified. The Ki-ras mutation patterns were analysed in six tumours and corresponded to those typical of ductal adenocarcinomas. In tumours with ductal and anaplastic components, both components revealed identical mutation patterns. From these findings, it is concluded that both undifferentiated carcinomas and osteoclast-like giant cell tumours belong to the pancreatic tumours that show a ductal phenotype. Since undifferentiated carcinomas and osteoclast-like giant cell tumours share the same cytokeratin and Ki-ras features, they are probably derived from the same cell lineage.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Carcinoma; Female; Genes, ras; Giant Cell Tumors; Humans; Immunoenzyme Techniques; Intermediate Filaments; Keratins; Male; Middle Aged; Mutation; Neoplasm Proteins; Pancreatic Neoplasms; Polymorphism, Restriction Fragment Length

A 57-year-old male patient presented with a cystic lesion in the tail of the pancreas, which was considered to be a pseudocyst. He was treated by cystojejunostomy but one year later a tumour was found to have invaded the stomach and jejunum. This was an osteoclast-like giant cell tumour containing a small area of typical ductal adenocarcinoma. Immunohistochemical staining revealed that the pleomorphic tumour cells were positive for cytokeratin, epithelial membrane antigen, vimentin and the proliferation marker MIB-1. The osteoclast-like giant cells and some small histiocytic cells stained for leukocyte common antigen and histiocytic markers and were negative for MIB-1. At autopsy, tumour rests were found in the pancreas but there were no metastases. Osteoclast-like giant cell tumours of the pancreas may present as cystic lesions and should be included in the differential diagnosis of pseudocysts.

Topics: Antigens, Nuclear; Biomarkers, Tumor; Diagnosis, Differential; Fatal Outcome; Giant Cell Tumors; Humans; Immunohistochemistry; Jejunum; Keratins; Ki-67 Antigen; Male; Middle Aged; Neoplasm Recurrence, Local; Nuclear Proteins; Pancreatic Neoplasms; Pancreatic Pseudocyst

In view of the different terminology for salivary gland tumours with giant cells, eleven cases were analysed by histopathology and immunocytochemistry. Four cases (three pleomorphic adenomas, one carcinosarcoma in a pleomorphic adenoma) were classified as having a foreign-body giant cell reaction, and five cases (two mucoepidermoid carcinomas, one acinic cell carcinoma, two carcinomas in pleomorphic adenomas) as having a sarcomatoid osteoclast-like giant cell reaction. In two further cases a giant cell tumour and a giant cell granuloma were associated with carcinomas in pleomorphic adenomas. All giant cells showed characteristic expression of CD68 as a typical marker for histiocytes and macrophages with their origin in mononuclear haematopoetic stem cells. There was no evidence for an epithelial origin of the giant cells because all those examined had a negative reaction to cytokeratin. Foreign-body cells were characterized by cytoplasmic vacuoles and irregularly dispersed nuclei. They showed a focally circumscribed reaction mostly outside the connective tissue pseudocapsule of the tumours. The sarcomatoid osteoclast-like giant cell reactions in carcinomas were distinctly intermingled with the carcinomatous patterns. In contrast, the associated osteoclast-like giant cell tumour was distinctly separate from the salivary gland tumour tissue and was composed of numerous larger osteoclast-like giant cells with a greater number of nuclei (more than 20); these giant cells were uniformly distributed throughout the tumour tissue. The giant cell granuloma was also separate from the carcinoma and was composed of nests of smaller, more irregularly distributed giant cells.

Topics: Adenoma, Pleomorphic; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers; Carcinoma; Carcinoma, Acinar Cell; Carcinoma, Mucoepidermoid; Carcinosarcoma; Cell Lineage; Cell Nucleus; Connective Tissue; Epithelial Cells; Foreign-Body Reaction; Giant Cell Tumors; Giant Cells; Giant Cells, Foreign-Body; Granuloma, Giant Cell; Hematopoietic Stem Cells; Histiocytes; Humans; Immunohistochemistry; Keratins; Macrophages; Neoplasms, Multiple Primary; Osteoclasts; Salivary Gland Neoplasms; Sarcoma; Vacuoles

A case of an osteoclastic giant cell tumor of the pancreas is presented. Immunohistochemical studies were performed, which showed keratin (CAM, AE1) and epithelial membrane antigen positivity in the tumor cells. The findings support an epithelial origin for this tumor.

Topics: Aged; Antigens, Neoplasm; Female; Giant Cell Tumors; Humans; Keratins; Mucin-1; Neoplasm Proteins; Osteoclasts; Pancreatic Neoplasms

A case of giant cell tumour of the pancreas with a mixture of pleomorphic giant cells and osteoclast-like cells is described. This association is rare and its histogenesis has been debated. The presence of a small differentiated adenocarcinomatous area at the periphery of the tumour indicates an epithelial origin. Moreover, some pleomorphic cells were positive for keratin (KL1). The osteoclast-like cells strongly expressed CD68 (a marker of histiomonocytic lineage) and did not show proliferative activity. They probably correspond to an unusual reaction of the stroma. Their clinical importance in this type of tumour remains unknown.

Topics: Antigens, CD; Antigens, Differentiation, Myelomonocytic; Giant Cell Tumors; Humans; Keratins; Male; Middle Aged; Osteoclasts; Pancreatic Neoplasms

The origin of the stromal, stellate and multinucleate cells in oral giant cell fibroma is unclear. Sixteen giant cell fibromas were stained immunocytochemically for keratin (MNF 116), vimentin, S-100 protein, neurofilaments, glial fibrillary acidic protein, alpha-smooth muscle actin, desmin, CD31 (PECAM-1), CD68, Factor XIIIa and prolyl 4-hydroxylase (5B5). In all cases positive staining was found with vimentin and prolyl 4-hydroxylase, indicating a functional fibroblast phenotype. Reactivity for Factor XIIIa was seen in two cases and in only one was a small number of giant cells stained, suggesting that the majority of oral giant cell fibromas are unrelated to the histologically similar fibrous papule of the nose or facial angiofibroma.

Topics: Actins; Adolescent; Adult; Aged; Animals; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Cell Adhesion Molecules; Desmin; Female; Fibroblasts; Fibroma; Giant Cell Tumors; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Mouth Neoplasms; Neurofilament Proteins; Phenotype; Platelet Endothelial Cell Adhesion Molecule-1; Procollagen-Proline Dioxygenase; S100 Proteins; Stromal Cells; Transglutaminases; Vimentin

A case of neuroendocrine lung tumor located beneath the pleura in a 71-year-old woman is reported. At autopsy, the tumor was found to have metastasized to the bones and liver without involving the hilar lymph nodes. Histologically, the tumor cells at the primary site and in the liver metastasis exhibited a carcinoid-like organoid structure, whereas pleomorphic giant cells were noted in the bone metastasis. The argyrophilic tumor cells were immunoreactive for neuron-specific enolase, chromogranin A, serotonin, calcitonin, calcitonin gene-related peptide, gastrin-releasing peptide, neuropeptide Y, gastrin, pancreatic polypeptide, glicentin, the alpha-subunit of human chorionic gonadotropin, keratin, epithelial membrane antigen, Leu M1 and carcinoembryonic antigen. Electron microscopy revealed abundant neurosecretory granules in the cytoplasm. This was considered to be a rare case of neuroendocrine lung tumor showing carcinoid-like histology at the primary site and large-cell transformation in bone metastasis.

Topics: Aged; Autopsy; Bone Neoplasms; Calcitonin; Calcitonin Gene-Related Peptide; Carcinoembryonic Antigen; Carcinoid Tumor; Cell Transformation, Neoplastic; Chorionic Gonadotropin; Chromogranin A; Chromogranins; Female; Giant Cell Tumors; Humans; Immunohistochemistry; Keratins; Lung Neoplasms; Membrane Glycoproteins; Microscopy, Electron; Mucin-1; Phosphopyruvate Hydratase; S100 Proteins; Serotonin

We report two cases of osteoclast-like giant cell tumour of urinary bladder associated with papillary transitional cell tumours. Both cases were morphologically identical to giant cell tumour of bone. The giant cells stained strongly for acid phosphatase which was resistant to tartrate digestion, a staining reaction typical of osteoclasts. In view of the ability of urinary bladder to induce metaplastic and neoplastic bone, we believe that these tumours may represent extraosseous giant cell tumours of bone.

Topics: Acid Phosphatase; Aged; Bone Neoplasms; Carcinoma; Carcinoma, Transitional Cell; Diagnosis, Differential; Giant Cell Tumors; Humans; Immunohistochemistry; Keratins; Male; Membrane Glycoproteins; Mucin-1; Muramidase; Osteoclasts; S100 Proteins; Urinary Bladder Neoplasms; Vimentin

We present a case report of osteoclast-type giant cell tumor of the pancreas and review the literature concerning this rare neoplasm, the histogenesis of which is uncertain. Electron microscopic features have suggested stromal, histiocytic, and epithelial origins to different investigators. Analysis of the present case supports and epithelial origin, with positive immunocytochemical staining for carcinoembryonic antigen and for low molecular weight keratin in the mononuclear and in some osteoclastlike giant cells. These tumor cells did not stain for mesenchymal markers (lysozyme, alpha 1-antitrypsin, alpha 1-antichymotrypsin, S100 protein). Zymogen granules, desmosomes, and zonulae occludentes were identified ultrastructurally and further support an epithelial derivation.

Topics: Carcinoembryonic Antigen; Female; Giant Cell Tumors; Histocytochemistry; Humans; Immunochemistry; Keratins; Microscopy, Electron; Middle Aged; Molecular Weight; Osteoblasts; Pancreatic Neoplasms

Topics: Diagnosis, Computer-Assisted; Giant Cell Tumors; Humans; Infant; Jaw Neoplasms; Keratins; Leukoplakia, Oral; Lichen Planus; Mouth Diseases; Mouth Mucosa; Mouth Neoplasms; Odontogenic Cysts; Odontogenic Tumors; Precancerous Conditions; Tooth; Tooth, Deciduous