bromochloroacetic-acid and Adamantinoma

Topics: Adamantinoma; Adolescent; Adult; Ameloblastoma; Biomarkers, Tumor; Child; Female; Head and Neck Neoplasms; Humans; Immunohistochemistry; Keratins; Male; RNA-Binding Protein EWS; Sarcoma, Ewing; Young Adult

The archetypal solitary fibrous tumor (SFT) features fibroblastic cells with varying cellularity without any particular architectural arrangement in a collagenous matrix, with staghorn vessels, CD34 and STAT6 expression, and NAB2::STAT6. To date, this fusion is thought to be specific for SFT. With more routine use of fusion gene panels, the histologic diversity of NAB2::STAT6-positive tumors is increasingly appreciated. Here we present four head and neck tumors harboring NAB2::STAT6 but exhibiting remarkably unusual morphologic features for SFT. All cases were pulled from the authors' consultation files. Immunohistochemistry was performed, along with targeted RNA sequencing in all cases, plus DNA next-generation sequencing on two. The cases arose in the nasal cavity (n = 2), retromolar trigone (n = 1) and parapharynx (n = 1), in patients ranging from 39 to 54 (mean, 44). Both nasal cases were biphasic, with a variably cellular collagenized stroma that resembled SFT but also interspersed malignant epithelial and neuroepithelial nests. One of the nasal cases also exhibited overt rhabdomyoblastic differentiation within both components. The two non-nasal cases were comprised of plump, epithelioid cells that were diffusely positive for pan-cytokeratin. One of these cases had prominent cystic change lined by overtly squamous epithelium. STAT6 immunostaining was positive in all cases, although the epithelial/neuroepithelial nests in the sinonasal cases were negative. All cases were confirmed to harbor NAB2::STAT6 by RNA sequencing. The two sinonasal cases were also found to harbor oncogenic mutations. The presented cases highlight a much broader histologic diversity than previously known for neoplasms with NAB2::STAT6. The biphasic nasal cases closely resemble teratocarcinosarcoma, while the epithelioid, cytokeratin-positive cases could be conceptualized as "adamantinoma-like," to borrow terminology already in use for Ewing sarcomas with complex epithelial differentiation. To identify similar cases, pathologists should have a low threshold for using STAT6 immunohistochemistry on any difficult-to-characterize head and neck tumor.

Topics: Adamantinoma; Ameloblastoma; Biomarkers, Tumor; Head and Neck Neoplasms; Humans; Keratins; Repressor Proteins; Solitary Fibrous Tumors; STAT6 Transcription Factor

Five cases of a heretofore unreported rare variant of thymic carcinoma characterized by a striking resemblance to adamantinoma of the mandible are described. The tumors occurred in 4 women and 1 man aged 58 to 76 years (mean: 67.8 y); they arose in the anterior mediastinum and measured from 5.3 to 12.0 cm in greatest diameter (mean: 8.9 cm). Presenting symptoms included chest pain, shortness of breath, and in 2 patients, pleural effusion. One tumor was asymptomatic and discovered incidentally. Histologically, the tumors were extensively desmoplastic, and the cellular proliferation was characterized by multiple islands of squamous epithelium with striking peripheral palisading of nuclei and central areas containing clear cells resembling a stellate reticulum. Areas of preexisting spindle cell thymoma were identified in 2 cases; these areas gradually merged with the higher-grade component of the lesion. Cystic changes were noted in 3 cases. Immunohistochemical studies in 3 cases showed the tumor cells were positive for cytokeratins, p40 and p63, and all showed a high proliferation rate (>50% nuclear positivity) with Ki-67. Next-generation sequencing was performed in 2 cases that showed amplification of the AKT1 gene (copy numbers 6 and 13). Clinical follow-up in 3 patients showed recurrence and metastasis after 1 and 2 years; 1 patient passed away 2 years after diagnosis due to the tumor. Desmoplastic adamantinoma-like thymic carcinoma represents an unusual histologic variant of thymic carcinoma that needs to be distinguished from metastases from similar tumors to the mediastinum.

Topics: Adamantinoma; Aged; Ameloblastoma; Biomarkers, Tumor; Epithelium; Female; Humans; Hyperplasia; Keratins; Male; Middle Aged; Thymoma; Thymus Neoplasms

Adamantinoma-like Ewing Sarcoma (ALES) is a rare subtype of Ewing sarcoma family of tumors (EFTs) which are defined by their EWSR1 gene rearrangements. We present a case of a 15-year old female with a swelling in her anterior neck of 4 months duration which had recently begun to rapidly grow in size. Fine needle aspiration showed a small blue round cell tumor with immunoreactivity for cytokeratin, CD99 and FLI1. Material for molecular testing was available on the resection specimen. Demonstration of t(11;22) (EWS-FLI1) was helpful in establishing the diagnosis.

Topics: 12E7 Antigen; Adamantinoma; Adolescent; Biomarkers, Tumor; Biopsy, Fine-Needle; Diagnosis, Differential; Female; Head and Neck Neoplasms; Humans; In Situ Hybridization, Fluorescence; Keratins; Oncogene Proteins, Fusion; Proto-Oncogene Protein c-fli-1; RNA-Binding Protein EWS; Sarcoma, Ewing; Thyroid Gland; Thyroidectomy

Primary intraosseous myoepithelial tumours, including carcinomas are rare tumours. The concept of histopathological spectrum of these tumours is evolving. We describe clinicopathological and immunohistochemical features of five myoepithelial carcinomas, including molecular cytogenetic results in one case. There were five male patients within age-range of 8-40 years (median = 26). Four tumours occurred in the long bones, including two tumours, each, in the femur and fibula, respectively, while a single tumour occurred in the proximal phalanges. Tumour size (n = 3 cases) varied from 5.6 to 8.6 cm. On radiological imaging, most tumours appeared as expansile, lytic and destructive lesions. Two tumours appeared as sclerotic lesions. Two cases were referred with diagnoses of chondrosarcomas and a single case was referred with two different diagnoses, including an adamantinoma and an osteosarcoma. Histopathological examination in all these cases showed multinodular tumours comprising mostly polygonal cells, exhibiting moderate nuclear atypia and interspersed mitotic figures within a stroma containing variable amount of myxoid, chondroid, hyalinised and osteoid-like material. Three tumours revealed prominent squamous differentiation. By immunohistochemistry, tumour cells were positive for EMA (5/5), pan CK (AE1/AE3) (3/3), CK5/6 (4/4), CK MNF116 (1/1), S100 protein (5/5) and GFAP (3/5). The first tumour revealed EWSR1 rearrangement. The first patient, 10 months after tumour resection and a simultaneous lung metastatectomy, is free-of-disease (FOD). The second patient, 11 months after tumour resection is FOD. The third and fourth patients underwent wide resections and are on follow-up. The fifth patient underwent resections, including a lung metastatectomy. Primary intraosseous myoepithelial carcinomas are rare and mimic conventional primary bone tumours. Some primary intraosseous myoepithelial carcinomas display EWSR1 rearrangement. Squamous differentiation may be considered as an addition to their evolving histopathological spectrum. Immunohistochemical stains constitute as a necessary tool for arriving at the correct diagnosis in such cases, which has treatment implications. Surgical resection remains the treatment mainstay.

Topics: Adamantinoma; Adolescent; Adult; Biomarkers, Tumor; Bone Neoplasms; Calmodulin-Binding Proteins; Child; Chondrosarcoma; Diagnosis, Differential; E2F6 Transcription Factor; Femur; Fibula; Finger Phalanges; Gene Expression; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Keratins; Male; Mutation; Myoepithelioma; RNA-Binding Protein EWS; RNA-Binding Proteins; S100 Proteins

Topics: Adamantinoma; Brain Neoplasms; Female; Humans; Keratins; Magnetic Resonance Imaging; Membrane Glycoproteins; Membrane Proteins; Middle Aged; Tibia

Ewing sarcoma family tumors (EFTs) of the head and neck are rare and may be difficult to diagnose, as they display significant histologic overlap with other more common undifferentiated small blue round cell malignancies. Occasionally, EFTs may exhibit overt epithelial differentiation in the form of diffuse cytokeratin immunoexpression or squamous pearls, resembling the so-called adamantinoma-like EFTs and being challenging to distinguish from bona fide carcinomas. Furthermore, the presence of EWSR1 gene rearrangement correlated with strong keratin expression may suggest a myoepithelial carcinoma. Herein, we analyze a series of 7 adamantinoma-like EFTs of the head and neck, most of them being initially misdiagnosed as carcinomas because of their anatomic location and strong cytokeratin immunoexpression, and subsequently reclassified as EFT by molecular techniques. The tumors arose in the sinonasal tract (n=2), parotid gland (n=2), thyroid gland (n=2), and orbit (n=1), in patients ranging in age from 7 to 56 years (mean, 31 y). Microscopically, they departed from the typical EFT morphology by growing as nests with peripheral nuclear palisading and prominent interlobular fibrosis, imparting a distinctly basaloid appearance. Moreover, 2 cases exhibited overt keratinization in the form of squamous pearls, and 1 sinonasal tumor demonstrated areas of intraepithelial growth. All cases were positive for CD99, pancytokeratin, and p40. A subset of cases showed synaptophysin, S100 protein, and/or p16 reactivity, further confounding the diagnosis. Fluorescence in situ hybridization assays showed EWSR1 and FLI1 rearrangements in all cases. Our results reinforce that a subset of head and neck EFTs may show strong cytokeratin expression or focal keratinization, and are therefore histologically indistinguishable from more common true epithelial neoplasms. Thus, CD99 should be included in the immunopanel of a round cell malignancy regardless of strong cytokeratin expression or anatomic location, and a strong and diffuse CD99 positivity should prompt molecular testing for the presence of EWSR1 gene rearrangements.

Topics: 12E7 Antigen; Adamantinoma; Adolescent; Adult; Antigens, CD; Biomarkers, Tumor; Biopsy; Bone Neoplasms; Calmodulin-Binding Proteins; Cell Adhesion Molecules; Cell Differentiation; Child; Diagnosis, Differential; Female; Gene Rearrangement; Head and Neck Neoplasms; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Keratins; Male; Middle Aged; Myoepithelioma; Neuroectodermal Tumors, Primitive, Peripheral; Predictive Value of Tests; Proto-Oncogene Protein c-fli-1; RNA-Binding Protein EWS; RNA-Binding Proteins; Sarcoma, Ewing; Tissue Array Analysis; Young Adult

Topics: Adamantinoma; Adult; Diagnosis, Differential; Female; Femur; Follow-Up Studies; Humans; Humerus; Ilium; Keratins; Male; Middle Aged; Mucin-1; Retrospective Studies; Sarcoma, Ewing; Sarcoma, Synovial; Tibia; Tomography, X-Ray Computed; Young Adult

Adamantinoma is one of the rarest primary bone tumors and is almost exclusively found in the tibia. Because of its scarcity, there are only a handful of reported cases of adamantinoma diagnosed by fine needle aspiration (FNA). We report a case of a 30-year-old woman seen at The Johns Hopkins Hospital for a 2.5-cm lytic lesion in the distal diaphysis of the tibia. A computed tomography-guided FNA of the lesion revealed a moderately cellular lesion consisting of a biphasic admixture of epithelioid cells seen singly and in fragments. These cells had round to oval nuclei with pale chromatin and well-formed nuclear grooves. The other population had more elongated nuclei and spindled appearance. An immunostain for cytokeratin was positive, supporting the diagnosis of adamantinoma. Due primarily to its rarity, the diagnosis of adamantinoma on FNA can be challenging and must be made in the context of its characteristic clinical and radiographic setting.

Topics: Adamantinoma; Adult; Biomarkers, Tumor; Biopsy, Fine-Needle; Bone Neoplasms; Bone Transplantation; Female; Humans; Immunohistochemistry; Keratins; Tibia

Adamantinomas of the long bones are low-grade malignant tumours. They seem to be related to osteofibrous dysplasia with a mesenchymal-to-epithelial transformation. We report a case of an adamantinoma with a revertant sarcomatoid transformation that showed a complete loss of epithelial differentiation. It corresponded to a 41-year-old male presented with an 8-cm multilobated lesion in the centre of the distal tibia. On the en bloc resection specimen, areas of classic adamantinoma were found but most of the tumor corresponded to a high-grade neoplasm with 2 histologic patterns: one made up by epithelial nests with a basaloid arrangement and positive for pankeratins and so-called glandular keratins, and a second sarcomatoid component, negative for these epithelial markers. Five months after surgery the patient had a massive relapse that consisted solely of the second sarcomatous component also negative for epithelial antibodies.Three cases of adamantinomas with sarcomatoid transformation of the epithelial component have been described but the tumours still preserved an epithelial immunophenotype. However, our case represents the extreme end of the sarcomatoid dedifferentiation of a classic adamantinoma with complete sarcomatoid transformation and total loss of epithelial markers. To our knowledge this has not been described previously.

Topics: Adamantinoma; Adult; Biomarkers; Biomarkers, Tumor; Bone Neoplasms; Cell Transformation, Neoplastic; Humans; Keratins; Male; Mesoderm; Neoplasms, Second Primary; Phenotype; Sarcoma; Tibia; Treatment Outcome

To report long term treatment outcomes of osteofibrous dysplasia and association with adamantinoma.. From January 1984 to July 2001, 14 patients with osteofibrous dysplasia were followed for an average of 108 months (78 to 260 months). Our patient group consisted of 6 men and 8 women, with a mean age of 13.9 years (2 to 65 years). We reviewed the clinical and pathological features of all 14 patients.. Thirteen patients had a lesion in the tibia, while one patient had lesions in both the tibia and the fibula. Initial treatments were observation after biopsy (6 patients), curettage with or without a bone graft (3 patients), resection followed by a free vascularized fibular bone graft (4 patients), or resection and regeneration with the Ilizarov external fixation (1 patient). Curettage was performed on 6 patients due to recurrence or progression after the initial treatment. Among these patients, one was diagnosed with AD from the biopsy of the recurrent lesion. This patient was further treated by segmental resection and pasteurization. After the initial pathology slides of the 13 patients were reviewed with immunohistochemical cytokeratin staining, one patient diagnosis was changed from osteofibrous dysplasia to osteofibrous dysplasia-like adamantinoma.. Some patients with osteofibrous dysplasia require close observation because of the high association risk between osteofibrous dysplasia and adamantinoma, Immunohistochemical staining may be helpful in differentiating these two diagnoses.

Topics: Adamantinoma; Adolescent; Adult; Aged; Child; Child, Preschool; Female; Fibrous Dysplasia of Bone; Fibula; Humans; Immunohistochemistry; Keratins; Male; Middle Aged; Radiography; Tibia

Adamantinoma of the long bones is a rare primary bone tumor of uncertain embryogenesis. It tends to involve the tibia almost exclusively. We report on adamantinomas occurring in a 16-year-old male patient, with synchronous tibial and fibular lesions. Histologically, there were characteristic clusters of epithelial cells in a fibrous background, forming a keratin cyst. Immunohistochemically, these cells were strongly positive for cytokeratin. This keratin cyst formation is quite an unusual finding in classic adamantinoma.

Topics: Adamantinoma; Adolescent; Bone Cysts; Bone Neoplasms; Diagnosis, Differential; Fibula; Humans; Keratins; Magnetic Resonance Imaging; Male; Neoplasms, Multiple Primary; Tibia