What the EWSR1-ATF1 Fusion has Taught Us About Hyalinizing Clear Cell Carcinoma

Hyalinizing clear cell carcinoma (HCCC) is a unique low-grade tumor composed of cords and nests of clear cells in a hyalinized stroma that was first reported by Milchgrub et al. It was recognized as a separate entity from clear cell variants of epithelial-myoepithelial carcinoma, myoepithelial carcinoma and mucoepidermoid carcinoma. HCCC is included in a long list of clear cell-containing tumors of salivary gland, as well as odontogenic tumors and metastases (renal cell carcinoma). Up until now, it has been considered a diagnosis of exclusion, despite its very distinctive appearance, and labeled as “not otherwise specified” by the World Health Organization. The emergence of molecular data in salivary gland tumors, including HCCC now allow for a more rigorous appraisal of its spectrum. The EWSR1-ATF1 fusion has proven the concept of a “mucinous HCCC” and removes mucin as an exclusion criterion for this tumor. It has also proven a genetic link between clear cell odontogenic carcinoma and HCCC. Molecularly-proven cases have also highlighted variant morphologies and shown that cases with overt squamous differentiation are true HCCC. This gives further weight to the classification of this tumor as squamous or adenosquamous in differentiation and as a specific entity rather than an “NOS” tumor.     

甲状腺透明变梁状肿瘤临床病理观察

目的 探讨甲状腺透明变梁状肿瘤的病理特征.方法 对1例甲状腺肿瘤的临床病理资料进行光镜、电镜和免疫组化标记检查,选用的抗体TTF1、Ki-67、Ki-67(MIB-1)、E-cadherin、calcitonin、CgA、TFE3、Syn、AFP、EMA、CKpan和p53,并复习文献.结果 患者为青年男性,肿瘤位于甲...     

Hyalinizing spindle cell tumor with giant rosettes with pulmonary metastasis after a long hiatus: a case report

Hyalinizing spindle cell tumor with giant rosettes (HSCTGR) is a recently described tumor, which is regarded as an unusual variant of low-grade fibromyxoid sarcoma. Proof of a metastatic potential was lacking. The patient in the report was a 35-yr-old woman who showed multiple bilateral pulmonary nodules with massive pleural effusion in the right side. She had a history of a mass excision in the right thigh 11 yrs ago at another hospital, which was reported as a "leiomyoma". Two years before this presentation, the patient received a routine chest radiograph which demonstrated bilateral multiple pulmonary nodules. A lobectomy of the left upper lung was performed. The histological findings revealed a well-circumscribed nodule that was characterized by a spindle-shaped fibrous to hyalinized stroma with criss-crossing short fascicles and giant collagen rosettes surrounded by a rim of spindle-shaped cells. Electron microscopy confirmed the fibroblastic nature of the tumor. This case, in addition to at least two other cases reported in the literature, demonstrates that the HSCTGR is a malignant neoplasm with the capacity to metastasize after a long hiatus.     

Clear Cell Carcinoma of Palatal Minor Salivary Gland Harboring a Novel EWSR1-ATF1 Fusion Gene: Report of a Case and Review of the Literature

Clear cell carcinoma (CCC) is a rare low-grade malignant salivary gland carcinoma. EWSR1-ATF1 fusion has been characterized as a consistent finding in CCC, with breakpoints described between EWSR1 exon 11 and ATF1 exon 3. So far, over 100 cases of CCC harboring EWSR1 rearrangement arising from salivary gland of the oral cavity have been reported. Although EWSR1 involvement in these cases was confirmed by EWSR1 break-apart FISH indicating the translocation, sequence analysis for EWSR1-ATF1 fusion type has been reported only in three cases of CCC so far. Herein, we report a CCC case with novel EWSR1-ATF1 fusion (EWSR1 exon 15 and ATF1 exon 5) arising in minor salivary gland and review the role of the chimeric variants in some malignancies with EWSR1-ATF1 rearrangement. Current tumor was composed of the small nests of clear tumor cells and hyalized fibrous stroma. Immunohistochemically, the tumor was positive for AE1/AE3, CK5/6 and p63, negative for S100, Melan-A, SMA and CD10. After 8 months of follow-up, there are no evidence of recurrence.     

Hyalinizing Clear Cell Carcinoma: Report of Eight Cases and a Review of Literature

Hyalinizing clear cell carcinoma (HCCC) is an extremely rare neoplasm with a female predominance, composed of nests of monomorphic clear cells within a hyaline stroma. This tumor often follows an indolent course and treatment includes wide surgical excision with or without adjuvant radiotherapy. We report eight cases of HCCC identified at two academic institutions in six women and two men, ranging in age from 25 to 86 years. Histologically, all cases demonstrated cords, trabeculae, and nests of monomorphic clear cells as well as cells with eosinophilic granular cytoplasm. Mild cellular atypia was occasionally seen and mitoses were very rare. Seven cases demonstrated a hyalinized stroma, and one case, a myxoid stroma. Immunohistochemically, the tumor cells were positive for epithelial markers and negative for desmin and actin. Seven cases were negative for S-100. Cells were also positive for periodic acid-Schiff and negative for mucin. The important clinicopathologic features and the differential diagnoses of HCCC, as well as a review of the literature are discussed.     

Hyalinizing spindle cell tumor with giant rosettes and low-grade fibromyxoid sarcoma: an immunohistochemical and ultrastructural comparative investigation

Hyalinizing spindle cell tumor with giant rosettes (HSCTGR) and low-grade fibromyxoid sarcoma (LGFMS) are 2 variants of fibrosarcoma, which share several clinicopathologic features. This study compares the light microscopic, immunohistochemical, and ultrastructural features of 2 examples of HSCTGR and 3 of LGFMS to determine the degree of overlap of these 2 tumors. HSCTGR were composed of bland spindle cells within hyalinized to myxoid stroma. Scattered throughout the lesions were characteristic rosette-like structures, formed by a central collagenous core surrounded by spindled neoplastic cells. LGFMS consisted of a mixture of fibrous and myxoid areas, composed of fibroblast-like cells arranged in a swirling, whorled growth pattern. Immunohistochemical analysis showed diffuse positivity for vimentin in all cases, while few scattered tumor cells stained for CD57, CD34, factor XIIIA, and actin. The extracellular matrix showed intense positivity for type IV collagen, laminin, and fibronectin, with the exception of myxoid areas of LGFMS and the central core of the giant rosettes in HSCTGR. Ultrastructurally, both tumor types were composed of cells with the features of fibroblasts, embedded in a collagenous stroma with irregular deposits of amorphous basal lamina-like substance. In conclusion, HSCTGR and LGFMS share similar immunophenotypic and ultrastructural features, and together with other fibrosing fibrosarcomas, like sclerosing epithelioid fibrosarcoma, may constitute a subset of fibrosarcomas formed by fibroblasts capable of producing large amounts of basal lamina-like material.     

Hyalinizing Spindle Cell Tumor with Giant Rosettes of the Hand. A Surgical and Histopathological Rarity

Hyalinizing spindle cell tumor with giant rosettes is a recently described biphasic neoplasm of soft tissue that shares mesenchymal and neuroendocrine features. The tumors have quite distinctive histopathological features with the presence of hyalinized paucicellular foci that are defined as rosettes. Only a few cases of this rare tumor have been described so far. We present an additional case of hyalinizying spindle cell tumor with giant rosettes in a 51 year old female patient who was succesfully treated after radical surgical resection.     

Hyalinizing Spindle Cell Tumor with Giant Rosettes: Report of a Case Showing Remarkable Myofibroblastic Differentiation

We examined the proliferative activity and the differentiation line of tumor cells in a case of "hyalinizing spindle cell tumor with giant rosettes" (HSCGR). A 6 cm tumor within the right deltoid muscle of a 58-year-old female was found by physical and radiographical examinations. A biopsy revealed the histological features of a spindle cell tumor with rosette-like structures. Wide excision was done under the diagnosis of HSCGR. The tumor presented as a gray-whitish, solid mass with focal pseudocystic degeneration. Immunohistochemically, the tumor cells were diffusely positive for vimentin and were also focally positive for S-100, but negative for desmin and alpha-smooth muscle actin. The cells stained positively for Ki-67 with even distribution, there being a correlation with the cellularity of the areas, with a labeling index ranging from 0.3 to 0.5%. In addition, flow cytometry revealed an almost normal diploid DNA pattern and 5.8% S-phase fraction, indicating low proliferative activity. Ultrastructurally, many tumor cells displayed discontinuous basal lamina, pinocytotic vesicles, dilated rough endoplasmic reticulum, and microfilaments with focal dense bodies. The main component of the rosette was collagenous fibrils with normal diameter and normal periodic banding. We interpreted this case of HSCGR as a low grade fibrosarcoma with remarkable differentiation of myofibroblastic lineage, and with focally accumulated, morphologically normal collagenous fibrils.