Dedifferentiation is a well recognized, if sometimes controversial, form of tumor progression in certain types of soft tissue and bone sarcoma, and confers a worse prognosis when compared with the low-grade counterpart. To date, dedifferentiation has not been described in solitary fibrous tumor (SFT). Among 948 cases of both intrathoracic and extrathoracic SFTs in our files accessioned between 1988 and 2008, we identified 8 cases of conventional SFT with a discrete anaplastic component, which we believe represents dedifferentiation. These occurred in 3 men and 5 women, 40 to 76 years old (median 60 y), and measured 3.4 to 20.0 cm (median 8.5 cm). Two cases were intrathoracic, 2 were located in the deep soft tissue of thigh, and single cases were located in the omentum, scalp, retroperitoneum, and abdominal wall. In addition to typical features of benign-appearing SFT there was an abrupt transition to nondistinctive high-grade sarcoma in all cases. The latter included epithelioid, round cell, and/or spindle cell components with increased mitotic activity, necrosis, and cystic degeneration. By immunohistochemistry, 7 of 8 cases were CD34 positive in the usual SFT areas, whereas 5 showed loss of CD34 in the poorly differentiated component. Six of 7 cases stained for p53 and p16 showed either negative or scattered positive cells in well-differentiated SFT areas, in contrast to positive or stronger and more diffuse staining in the high-grade component. Follow-up information available in 7 patients ranged from 1 to 58 months (mean 24 mo). Three patients with the largest tumors (9.0, 17.0, and 20.0 cm) died of disease, whereas 3 patients whose tumors measured 8.0 cm or less were treated by surgical excision only, and show no evidence of disease but with only limited follow-up. One patient with an 11.5 cm intrathoracic tumor is alive with disease at 58 months after recurrence and metastasis. We describe, apparently for the first time, what seems, at least in our view, to be dedifferentiation in primary SFT. Our results demonstrate that dedifferentiation in SFT, comparable with that in other low grade/intermediate soft-tissue tumors, poses a higher risk of tumor recurrence and/or metastasis, most notably in large and deep-seated tumors. Similar to other dedifferentiated sarcomas, abrupt transition between low grade and high-grade areas is typically observed with loss of CD34 positivity. The p53 and p16 overexpression in the high-grade component is common as in other dedifferentiated lesions, perhaps pertaining to the underlying molecular mechanism.

Expanding the spectrum of malignant progression in solitary fibrous tumors: a study of 8 cases with a discrete anaplastic component--is this dedifferentiated SFT?

“Dedifferentiation” and/or high-grade transformation (HGT) has been described in a variety of salivary gland carcinomas, including acinic cell carcinoma, adenoid cystic carcinoma, epithelial-myoepithelial carcinoma, polymorphous low-grade adenocarcinoma, myoepithelial carcinoma, low-grade mucoepidermoid carcinoma and hyalinizing clear cell carcinoma, although the phenomenon is a rare event. Recent authors tend to preferably use the term HGT instead of “dedifferentiation” in these cases. HGT-tumors are composed of conventional carcinomas juxtaposed with areas of HG morphology, usually either poorly differentiated adenocarcinoma or “undifferentiated” carcinoma, in which the original line of differentiation is no longer evident. The HG component is generally composed of solid nests, sometimes occurring in cribriform pattern of anaplastic cells with large vesicular pleomorphic nuclei, prominent nucleoli and abundant cytoplasm. Frequent mitoses and extensive necrosis is evident. The Ki-67 labeling index is consistently higher in the HG component. p53 abnormalities have been demonstrated in the transformed component in a few examples, but the frequency varies by the histologic type. HER-2/neu overexpression and/or gene amplification is considerably exceptional. The molecular-genetic mechanisms responsible for the pathway of HGT in salivary gland carcinomas largely still remain to be elucidated. Salivary gland carcinomas with HGT have been shown to be more aggressive than conventional carcinomas with a poorer prognosis, accompanied by higher local recurrence rate and propensity for cervical lymph node metastasis, suggesting the need for wider resection and neck dissection.

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“Dedifferentiation” and High-Grade Transformation in Salivary Gland Carcinomas

When adipose-derived stem cells (ASCs) are retrieved from the stromal vascular portion of adipose tissue, a large amount of mature adipocytes are often discarded. However, by modified ceiling culture technique based on their buoyancy, mature adipocytes can be easily isolated from the adipose cell suspension and dedifferentiated into lipid-free fibroblast-like cells, named dedifferentiated fat (DFAT) cells. DFAT cells re-establish active proliferation ability and undertake multipotent capacities. Compared with ASCs and other adult stem cells, DFAT cells showed unique advantages in their abundance, isolation and homogeneity. In this concise review, the establishment and culture methods of DFAT cells are introduced and the current profiles of their cellular nature are summarized. Under proper induction culture in vitro or environment in vivo, DFAT cells could demonstrate adipogenic, osteogenic, chondrogenic and myogenic potentials. In angiogenic conditions, DFAT cells could exhibit perivascular characteristics and elicit neovascularization. Our preliminary findings also suggested the pericyte phenotype underlying such cell lineage, which supported a novel interpretation about the common origin of mesenchymal stem cells and tissue-specific stem cells within blood vessel walls. Current research on DFAT cells indicated that this alternative source of adult multipotent cells has great potential in tissue engineering and regenerative medicine.

/pdf/dedifferentiated-fat-cells-an-alternative-source-of-adult-2509l7fcm9.pdf

Dedifferentiated fat cells: an alternative source of adult multipotent cells from the adipose tissues

Epithelial-myoepithelial carcinoma (EMC) is a rare salivary gland tumor of presumed intercalated duct origin with a low risk of metastasis and mortality. Factors shown to affect behavior include positive margins, vascular invasion, necrosis, and myoepithelial anaplasia. The latter category and dedifferentiated EMCs have been separated on the basis of presumed myoepithelial versus ductal origin, respectively. Three additional cases of typical EMC with transition to high-grade carcinoma are presented. Two of the tumors were stained with CAM5.2, 34betaE12, cytokeratin 14, p63, S100, calponin, smooth muscle actin, and muscle-specific actin. All tumors showed a gradual transition to a high-grade carcinoma from an EMC, each composed of clear cells even in the high-grade regions. One case also showed a discrete area with ductal lumina and another had plasmacytoid morphology. Squamous differentiation was seen in all cases as well. A consistent immunostaining pattern was not noted. Areas with focal lumina were diffusely positive for CAM5.2 only. Areas with clear cells showed patchy S100 positivity only, whereas cytokeratin 14 and 34betaE12-stained squamous pearls. The case with plasmacytoid morphology was diffusely positive for p63. No immunoexpression was noted with smooth muscle actin, muscle-specific actin, or calponin. It was not possible to convincingly separate the high-grade component in these cases into ductal dedifferentiated EMC versus myoepithelial. Recently, there has been a move to abandon the term "dedifferentiation" in favor of "high-grade transformation" in other salivary gland malignancies. We report these 3 such cases, review the literature and propose that these lesions be regarded as "EMC with high-grade transformation."

Epithelial-myoepithelial carcinoma with high grade transformation.

Adenoid cystic carcinoma (AdCC) is among the most common malignant tumors of the salivary glands. It is characterized by a prolonged clinical course, with frequent local recurrences, late onset of metastases and fatal outcome. High-grade transformation (HGT) is an uncommon phenomenon among salivary carcinomas and is associated with increased tumor aggressiveness. In AdCC with high-grade transformation (AdCC-HGT), the clinical course deviates from the natural history of AdCC. It tends to be accelerated, with a high propensity for lymph node metastasis. In order to shed light on this rare event and, in particular, on treatment implications, we undertook this review: searching for all published cases of AdCC-HGT. We conclude that it is mandatory to perform elective neck dissection in patients with AdCC-HGT, due to the high risk of lymph node metastases associated with transformation.

/pdf/cervical-lymph-node-metastasis-in-high-grade-transformation-22oicro3s7.pdf

Cervical Lymph Node Metastasis in High-Grade Transformation of Head and Neck Adenoid Cystic Carcinoma: A Collective International Review.

Dedifferentiation of salivary gland neoplasms is a rare event, unlike bone and soft part sarcomas, which was first described by Stanley et al. in 1988. An additional case of dedifferentiated epithelial-myoepithelial carcinoma (EMC) is reported here. The patient was a 70-year-old Japanese man who requested examination of the rapid growth of a mass in the right parotid region, which he had first noticed 25 years previously. Clinical examination showed an ill-circumscribed, 6.8 x 4.7 x 7.0-cm lesion. Histologically, most parts of the lesion were high-grade carcinoma (HGC) with sheetlike and nestlike growth of markedly atypical cells and comedonecrosis, whereas the minor part consisted of typical EMC. The outer clear cells of EMC were positive for alpha-smooth muscle actin (ASMA), p63, cytokeratin (CK) 14, and vimentin, and the inner ductal cells of EMC were positive for CKs and epithelial membrane antigen. HGC was negative for ASMA, CK14, and vimentin, but diffusely positive for p53 protein and cyclin D1. The Ki-67 labeling index of EMC was 11.5%, whereas that of HGC was 67.1%. These findings and a review of literature indicate that HGC arose from preexisting EMC, and this phenomenon is the dedifferentiation of EMC. Dedifferentiated EMC is extremely rare.

Dedifferentiated epithelial-myoepithelial carcinoma of the parotid gland: a rare case report of immunohistochemical analysis and review of the literature.

Objective Salivary giant cell tumor (GCT) is exceedingly rare. This article presents an additional rare case of salivary GCT with salivary duct carcinoma (SDC). Study design and results The patient was a 40-year-old Japanese male. The peripheral region of the tumor showed SDC and partly revealed a mucin accumulation with cancer nests, which was a mucin-rich variant of SDC. In the central region of the tumor, mononuclear ovoid tumor cells contained osteoclastic-type giant cells. SDC showed immunopositivity for gross cystic disease fluid protein-15 (GCDFP-15), androgen receptor (AR), and Her-2, whereas the giant cell lesion was negative for GCDFP-15, AR, and Her-2. Mononuclear cells in salivary GCT showed immunopositivity for epithelial membrane antigen and p53. Conclusion The salivary GCT was thought to be neoplastic and derived from epithelial cells. The present case is the first de novo case of intraoral salivary GCT with a mucin-rich variant of SDC.

Osteoclast-type giant cell tumor of minor salivary gland with mucin-rich salivary duct carcinoma: a case report of unusual histology with immunohistochemical analysis.

Background. Alveolar soft part sarcoma (ASPS) is a rare mesenchymal neoplasm of uncertain origin. In this article, we report a case of ASPS occurring in the larynx, an extremely rare location for this rather unusual tumor. Methods and Results. The patient was a 34-year-old Japa- nese woman who requested an examination for hoarseness. The tumor showed a proliferation of large polygonal cells with periodic-acid-Schiff-positive diastase-resistant intracytoplasmic granules, arranged in an alveolar growth pattern. The cytoplasm of the tumor cells was eosinophilic. Tumor cells were positive for vimentin and titin. Nuclear immunoreactivity for TFE3 was observed, and the Ki-67 labeling index was 14.7%. Ultrastruc- turally, electron-dense rod-shaped crystals were infrequently observed in the cytoplasm. This case was finally diagnosed as ASPS of the larynx. Conclusion. We discuss the histogenesis and differential di- agnosis of ASPS with immunohistochemical and ultrastructural

Alveolar soft part sarcoma of the larynx: A case report of an unusual location with immunohistochemical and ultrastructural analyses

近年，多くの施設で咽喉食摘術に対して遊離空腸移植術が第一選択とされ，安定した成績が得られるようになってきた。当院の遊離空腸移植術の術後合併症について検討したので報告する。対象：2002年12月から2008年12月までの6年間に当院で咽喉食摘術に対して遊離空腸移植術を施行した90症例を対象とした。内訳は年齢41～85歳（中央値65歳），男性78例，女性12例であった。結果：術後合併症がみられたのは48症例（53%）であった。晩期合併症である気管孔狭窄19例（21%），吻合部狭窄12例（13%），腸閉塞8例（9%）を多く認めた。縫合不全は2例（2%）に認めた。空腸壊死は1例（1%）に認めた。結語：遊離空腸移植術は安全な術式であるとされているが，晩期の気管孔狭窄，吻合部狭窄，術後腸閉塞は多く認められ長期の経過観察が必要と考えられた。

Complications of free jejunal transfer reconstruction for total pharyngolaryngoesophagectomy

副神経を保存した保存的頸部郭清術においても，鉤などの術中操作により術直後はその多くに副神経麻痺が生じている。今回は副神経支配の僧帽筋が最も関与する上肢自動外転角度を計測し，僧帽筋麻痺の程度，回復過程を評価した。副神経を保存した保存的頸部郭清術10例を術後2ヶ月以内でみると，上肢外転角度100度未満の重度の僧帽筋麻痺4例，100～150度未満の中等度の麻痺3例，150度以上のほぼ麻痺のない3例であり，様々な程度の僧帽筋麻痺に分かれた。これは術中の副神経の牽引操作や電気メスなどの影響によって，副神経損傷の程度にばらつきが生じるためと考えられた。術後6ヶ月前後では，全例150度以上に上肢外転角度は改善した。副神経を保存した頸部郭清術においても，一過性の副神経麻痺を来たしている可能性が高く，僧帽筋麻痺による肩関節，肩甲帯の癒着性関節包炎を避けるために，副神経障害の程度に応じたリハビリテーションが必要である。

Rie Asano

Papers

Dedifferentiated epithelial-myoepithelial carcinoma of the parotid gland: a rare case report of immunohistochemical analysis and review of the literature.

Osteoclast-type giant cell tumor of minor salivary gland with mucin-rich salivary duct carcinoma: a case report of unusual histology with immunohistochemical analysis.

Alveolar soft part sarcoma of the larynx: A case report of an unusual location with immunohistochemical and ultrastructural analyses

Complications of free jejunal transfer reconstruction for total pharyngolaryngoesophagectomy

Recovery of trapezius muscle paralysis in neck dissection in which the spinal accessory nerve was preserved