Clinical and prognostic significance of PD-1 and PD-L1 expression in sarcomas

Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) are new targets in cancer immunotherapy in recent years. The aim of this study is to evaluate the PD-1/PD-L1 expressions in sarcomas and to determine association between PD-1/PD-L1 expressions and clinical/pathological properties in some sarcoma subtypes. Formalin-fixed, paraffin-embedded tissue samples from 65 cases with sarcomas were analyzed. Immunohistochemical staining was performed to detect the PD-1 and PD-L1 expressions in tumor tissue and microenvironment, separately. PD-1 expression in tumor tissue and microenvironment was detected in 11 (17 %) and 8 (12 %) cases, respectively. PD-L1 expression in tumor tissue and microenvironment was detected in 19 (29 %) and 20 cases (30 %), respectively. None of the 5 Ewing sarcomas involving bone showed PD-1/PD-L1 expression, while 2 of 3 cases with Ewing sarcomas involving soft tissue showed PD-1 and PD-L1 expression. Among 5 cases with Kaposi sarcoma, four showed PD-1 and/or PD-L1 expression in tumor or microenvironment. PD-1/PD-L1 expressions were detected 3 of 6 cases with pleomorphic sarcoma, 2 of 4 cases with peripheral nerve sheath tumors and 1 of 4 cases with synovial sarcoma. Interestingly, strongest PD-1/PD-L1 expressions in our study group were detected in 2 sarcoma cases with the history of giant cell tumor. PD-1 and PD-L1 expressions are up to 30 % of the cases with sarcomas. It may be rational to target programmed death pathway in Kaposi sarcoma, pleomorphic sarcoma and peripheral nerve sheath tumors. Strong expression of PD-1/PD-L1 in cases with previous giant cell bone tumor has been found to be interesting and must be studied in giant cell tumor samples.     

Sarcomas in ovarian mucinous tumors: a report of two cases.

Two sarcomas that appeared as distinct solitary nodules in the walls of ovarian mucinous cystic tumors are described. One of the tumors was a fibrosarcoma associated with a mucinous cystadenoma; the other was an undifferentiated sarcoma in a mucinous cystadenocarcinoma. Both patients died within 1 1/2 years of their operations with distant metastasis; one of them had had metastatic sarcoma in the para-aortic lymph nodes at the time of exploration. These two cases are the only well-documented examples of this unusual combination of tumor types.     

Extraskeletal osteosarcoma. A clinicopathologic review of 26 cases

The clinical records and histopathologic features in 26 cases of extraskeletal osteosarcoma (ESOS) diagnosed at M.D. Anderson Cancer Center (Houston) between 1950 and 1987 were reviewed. Presentation was usually that of an enlarging soft tissue mass. The thigh (11 cases), upper extremity/shoulder girdle (three cases), and retroperitoneum (three cases) were the most common anatomic sites. Tumor size ranged from 2.5 to 30 cm. The predominant histologic pattern was osteoblastic in four cases, chondroblastic in two, fibroblastic or pleomorphic malignant fibrous histiocytoma (MFH)-like in four, giant cell type MFH-like in one, and small cell in one. Various mixtures of these patterns were seen in the remaining 14 tumors. The telangiectatic pattern was not seen as the predominant component in any primary tumor but was observed as a minor component. Thirteen tumors recurred locally and 16 metastasized; five patients had distant metastases at presentation. The lungs, bone, and soft tissue were the most frequent metastatic sites. Sixteen patients died of disease at 2 to 54 months, one patient died of unrelated causes at 61 months, seven patients were alive with no evidence of disease (NED) at 30 to 122 months, and two patients were alive with disease at 28 and 54 months, respectively. Tumor size (less than 5 cm versus greater than or equal to 5 cm) was the main prognostic factor; all patients alive with NED for whom accurate tumor measurements were available (six of seven) had neoplasms measuring less than 5 cm that were amenable to complete surgical excision. Histologic pattern and other clinicopathologic features did not significantly affect outcome.     

妊娠期卵巢粘液性囊腺瘤恶变伴肉瘤样囊内结节1例报告

 本文报告一例妊娠期妇女卵巢粘液性肿瘤伴肉瘤样囊内结节。患者年龄29岁，妊娠8个月伴腹部巨大包块，见标本囊内有9个结节，较软、褐色、伴出血。在显微镜下检查上皮成份从良性粘液性囊腺瘤表现到交界恶性。在结节内，可见纤维母细胞、多形性细胞、巨结胞、多核巨结胞，还可见组织细胞。根据此例说明，此型囊内结节，是假肉瘤样改变，可能是对癌肿的一种反应。     

Malignancy in giant cell tumor of bone

BACKGROUND: The term malignant giant cell tumor embraces multiple entities and therefore can be confusing. The goals of the current study were to define the clinicopathologic and histologic features of malignancy in giant cell tumors and to clarify the terminology. METHODS: The authors reviewed all cases from the Rizzoli Institute (Bologna, Italy) of primary (PMGCT) and secondary (SMGCT) malignancy in giant cell tumors. PMGCT is a high-grade sarcoma that arises side by side with benign giant cell tumors. SMGCT is a high-grade sarcoma that occurs at the sites of previously treated giant cell tumors of bone. RESULTS: The authors report 5 PMGCTs and 12 SMGCTs; half of the SMGCTs were postradiation sarcomas. Patient age ranged from 20 to 68 years (median, 62 years) for PMGCT and from 30 to 77 years (median, 40 years) for SMGCT. The average latent period between diagnosis of giant cell tumor and diagnosis of SMGCT was 9 years (range, 3-15 years) for patients with postradiation SMGCT and 19 years (range, 7-28 years) for patients with SMGCT resulting from spontaneous transformation. The histologic classification of high-grade sarcomas in the PMGCT group was osteosarcoma in four cases and malignant fibrous histiocytoma in one case. In the SMGCT group, the histologic classification was osteosarcoma in nine cases, fibrosarcoma in two cases, and malignant fibrous histiocytoma in one case. The outcomes associated with all malignancies in giant cell tumors were poor, with the worst outcome associated with postradiation SMGCT. CONCLUSIONS: Malignancies in giant cell tumors of bone always are high-grade sarcomas with a poor prognosis. These lesions must be distinguished from benign giant cell tumors of bone. SMGCT usually is easy to diagnose upon malignant clinicoradiographic presentation. In contrast, PMGCT often mimics giant cell tumors both clinically and radiographically. In addition, upon histologic examination, PMGCT shows areas of conventional giant cell tumor, which can lead to difficulties in making the correct diagnosis.     

Radiation therapy in the treatment of difficult giant cell tumors

Thirteen patients with giant cell tumors of bone have been treated by radiation therapy because surgery was not feasible or unacceptably disfiguring. Seven patients were treated for primary giant cell tumors of the bone, four for recurrent disease, and three for metastasis (one presented with both distant metastasis and local recurrence after primary surgery). The follow-up time ranged from 18 months to 13 years, with a mean of 6.5 years. All patients except one are alive. Local control was achieved in 11 patients (85%). One patient whose tumor was located in the sacrum had no gross response and at 5 months was subjected to a partial sacrectomy. A second patient had local regrowth 1 year after treatment; salvage surgery was successful. There have been no long-term complications of radiation therapy. This study confirms that for patients with giant cell tumor of bone, radiation therapy offers an effective alternative to complex or difficult surgery and constitutes a good treatment method to medically inoperable patients.     

Benign and malignant fibrous histiocytomas of the soft tissues: functional characterization of the cultured cells

Cell cultures were carried out from fresh tumor tissues obtained from seven cases of histiocytic tumors of the soft tissues including four of malignant fibrous histiocytoma, two of benign fibrous histiocytoma, and one of giant cell tumor of tendon sheath. The cultured cells were studied by light and electron microscopy, rosette formation for surface receptors, immune phagocytosis, and enzyme cytochemistry. The culture of each tumor revealed a mixture of histiocyte-like cells, fibroblast-like cells, amd intermediate forms. Bizarre giant cells were numerous in the early cultures of malignant fibrous histiocytoma, but they were absent in the cultures of benign fibrous histiocytoma and giant cell tumor of tendon sheath. In all the seven cases the cultured cells exhibited several features characteristic of histiocytes: (1) surface receptors for the Fc-portion of immunoglobulin G; (2) surface receptors for the third component of complement; (3) immune phagocytosis of opsonized erythrocytes; and (4) lysosomal enzymes including alpha-naphthyl butyrate esterase, and acid phosphatase. These findings suggest that the histiocytic tumors of the soft tissues in discussion actually comprise the cells that have the functional property of histiocyte. The tumor cells in the surgical specimens presented essentially the same ultrastructural and enzyme histochemical characteristics as those of the cultured cells.     

Chondroma of soft parts.

The clinical and pathological features of 104 cases of chondroma of soft parts are presented. The tumor occurred predominately in the third and fourth decades, was slightly more common in male (61%) than in female patients, and affected chiefly the soft tissues of the hand (64%) and feet (20%). The presenting symptom was usually a slowly and insidiously growing mass, occasionally causing tenderness or pain. Nearly always the tumor was well demarcated and lobulated and measured between 1 and 2 cm in greatest diameter. Microscopically, most of the tumors were composed of adult-type hyaline cartilage, undergoing calcification in a large percentage of cases. In addition, histologic variants with giant cell proliferation and chondroblastic activity could be distinguished. Despite the slight cellular pleomorphism and the plump appearance of many cartilage cells in the chondroblastic variants, there was no evidence that these tumors behaved differently from the tumors composed predominately of adult-type hyaline cartilage. Of the 56 patients with follow-up information (median follow-up period, 5.7 years) 44 were alive and well with no evidence of recurrence in the follow-up period. In 10 patients the tumor had recurred once. Multiple recurrences or metastatic lesions were no observed. Two patients died of unrelated cause. Complete local excision appears to be the treatment of choice.     

含梭形/巨细胞成分肺癌17例临床病理分析

背景与目的:含梭形/巨细胞成分肺癌(carcinoma with spindle/giant cells,LCSG)是一种少见的恶性上皮肿瘤,相关文献报道较少.本研究目的是探讨LCSG临床病理特点及预后.方法:总结、分析17例手术治疗的LCSG患者的临床和组织病理学资料,并与同期手术的肺癌患者进行比较.利用生存曲线进行生存分析,Cox风险比例模型分析影响预后的独立因素.结果:LCSG患者男女比例为15:2,年龄45～78岁,中位年龄58岁;pTNM分期Ⅰ期5例,Ⅱ期3例,Ⅲ期9例;病理类型梭形细胞癌2例,含梭形细胞癌(均伴一种恶性上皮成分,鳞癌3例、腺癌和大细胞癌各1例)5例,含巨细胞癌(分别有5例伴一种上皮癌、5例伴两种上皮癌)10例;4例Ⅰ期患者术后无瘤生存5年以上;LCSG患者比同期鳞癌的预后差(中位生存36个月和61个月,P=0.027),含巨细胞肺癌患者的预后比含梭形细胞肺癌(包括梭形细胞癌)患者差(中位生存18个月和64个月,P=0.026).多因素分析显示淋巴结分期和含巨细胞癌是影响LCSG患者预后的危险因素.结论:LCSG作为一种独特类型的肺癌,其中含巨细胞的肺癌成分复杂,预后较差.     

膝关节置换治疗膝关节周围骨巨细胞瘤

目的：探讨膝关节置换治疗膝关节周围骨巨细胞瘤的疗效。方法：自2000年5月-2010年2月应用膝关节置换治疗骨巨细胞瘤共14例,男9例,女5例,年龄25岁-56岁,平均37岁。股骨远端6例,胫骨近端8例。Campanacci分级：Ⅱ级1例,Ⅲ级13例。结果：随访时间1年-10年,平均5年,无患者复发,术后患者MSTS功能评定：优8例,良4例,可2例,总体满意率为85.7%。结论：应用瘤段切除＋膝关节置换方法治疗严重骨巨细胞瘤（CampanacciⅢ级）,效果满意。     

骨外骨肉瘤病理特征与鉴别诊断4例报道并文献复习

目的 探讨骨外骨肉瘤（extraskeletal osteosarcoma, EOS）的临床病理特征、免疫表型及病理诊断与鉴别诊断要点。方法 收集4例EOS,对其临床、病理组织学及免疫表型进行观察并复习相关文献。结果 4例患者均为成年男性,平均年龄35.5岁。主要表现为无痛性或有触痛性软组织肿块。3例发生于下肢,1例发生于上肢。2例为肌纤维母细胞型EOS,1例为小细胞型EOS,1例为恶性纤维组织细胞型EOS。病理检查：(1)肉眼观见瘤体最大径平均为4cm,切面灰白,质软质脆,界限清楚。(2)镜检:肌纤维母细胞型EOS呈小叶状结构,细胞呈梭形或卵圆形。小细胞型EOS瘤细胞形态一致,弥漫分布。恶性纤维组织细胞型EOS瘤细胞多形性,伴多核巨细胞。（3）免疫组织化学：4例均表达Vim,OC,1例表达OCT。4例均不表达S100、desmin、CD34、NSE及SMA。结论 EOS是一种罕见的软组织肿瘤,其诊断主要依靠组织病理学特征,免疫组织化学标记可帮助诊断和鉴别诊断。     

Surgical Management of Parapharyngeal Space Tumors: Our Experience

The purpose of this study is to evaluate parapharyngeal space (PPS) tumors with regards to clinico-pathological features and pre-operative assessment and also to analyze the benefits of transcervical approach in the management of PPS tumors. We performed retrospective analysis of patients who had undergone transcervical resection of PPS tumors from May 2006 to May 2009 at KLES Dr. Prabhakar Kore Hospital and M. R. C, Belgaum. Patients were diagnosed on the basis of clinical examination, FNAC and magnetic resonance imaging. All patients were observed with an annual follow-up of at least 3 years by physical examination and ultrasonographic evaluation. The total number of patients were four; with three males and one female patient. Their age varied from 20 to 55 years with a mean age of 36 years. There were two cases of neurilemomas, one case of carotid body tumor and one case of pleomorphic adenoma. All four patients underwent surgical excision of tumor by transcervical approach. There were no major post-operative complications. All four patients are alive with no recurrence in the 3 year follow-up period. Transcervical approach is versatile, flexible and provides good access to the narrow PPS. This approach also provides good vascular control and reduced risk of post-op complications. We recommend transcervical approach even for large sized pre-styloid and post-styloid compartment benign tumors which are free from deep lobe of parotid.     

全脊椎整块切除术治疗原发性腰椎肿瘤九例

目的探讨全脊椎整块切除术（TES）在治疗原发性腰椎肿瘤中的可行性及疗效。方法2005年6月至2009年7月共使用TES治疗原发性腰椎肿瘤患者9例。行单一后路全脊椎切除7例（L1骨肉瘤和和骨巨细胞瘤各1例,12骨巨细胞瘤、单发浆细胞瘤、软骨肉瘤和脊索瘤各1例,L3组织细胞肉瘤1例）;行后前联合入路全脊椎切除2例（L4骨巨细胞瘤并椎旁巨大肿块和纤维肉瘤各1例）,肿瘤切除后均一期进行脊柱重建。对所有病例进行术前、术后神经功能测评及肿瘤复发情况的追踪。结果所有患者术后均获得随访,随访时间3～49个月,平均19个月。所有患者术后临床症状均明显改善,未出现严重手术并发症。近中期随访未发现肿瘤的局部复发及远处转移。结论对于原发性腰椎肿瘤,行TES加脊柱重建术,方法可靠,近中期随访效果满意,长期结果有待进一步随访。     

Giant cell tumor of the skull.

BACKGROUND. Most giant cell tumors (GCT) occur at the ends of long bones. There is little information about GCT of the skull bones. METHODS. The authors reviewed the Mayo Clinic files, which contained 546 cases of GCT, and their own consultation files, which contained approximately 1500 cases. RESULTS. Eleven tumors occurred in the sphenoid bone with extension to the surrounding bones and structures in 8 patients. One tumor (in Paget's disease) occurred in the frontal bone, one tumor was in the occipital bone, and one tumor was in the temporal bone. There were 4 men and 11 women whose ages ranged from 8 to 78 years, with a mean of 36.5 years. Radiographic findings were not suggestive of a specific diagnosis, although the features were those of an aggressive lesion. Histologically, the tumors had features typical of GCT. However, a prominent spindle cell component was seen in five tumors. The initial treatment in all patients but one was intralesional excision that was as complete as possible. The last patient had a wide excision and had soft tissue recurrence at 1 year. This was excised and she was free of disease at 2.7 years. Three patients died, one in the immediate postoperative period and the other two at 1.6 and 4 years with progression of tumor. One patient had postoperative radiation therapy and was without evidence of disease for 2 years when he was lost to follow-up. The remaining 10 patients all had postoperative radiation therapy; 6 patients were alive without disease from 4 to 34 years. However, one of these six patients had a recurrence that was treated surgically with additional radiation. Four patients were alive with tumor from 2.1 to 26 years at the time of this report. CONCLUSIONS. GCT of the skull bones is rare but should be distinguished from giant cell reparative granuloma because of the tendency for progression. Surgical ablation (as complete as possible) and postoperative radiation therapy seem to be the treatment of choice for GCT of the skull bones.     

Pleomorphic (giant cell) carcinoma of the intestine. An immunohistochemical and electron microscopic study

Pleomorphic (giant cell) carcinomas have been described in the lungs, thyroid, pancreas, and gallbladder. Two pleomorphic carcinomas of the small bowel and two of the large bowel are presented. On light microscopic study, the carcinomas were solid, without squamous or glandular differentiation. The tumors were composed of the following three cell types: gemistocytic (giant) cells, smaller polygonal cells, and spindle cells, with identical immunohistochemical reactions. A panel of monoclonal and polyclonal antibodies was applied. All tumors were found to coexpress keratin and vimentin. A positive reaction for neuron-specific enolase (NSE) was found in three tumors and a positive reaction for chromogranin was found in one tumor. On electron microscopic study, intracytoplasmic whorls of intermediate filaments were seen in the perinuclear area. Dense core "neurosecretory" granules were rarely seen. Intestinal pleomorphic carcinomas are histologically identical to pulmonary giant cell carcinomas. The prognosis is poor due to early tumor spread, with only a few months of postoperative survival. The pleomorphic carcinomas have some of the differentiation characteristics of carcinoid tumors and are best regarded as poorly differentiated variants of neuroendocrine carcinomas.     

Pleomorphic granular cell astrocytoma of the pineal gland.

BACKGROUND. Primary neoplasms of the pineal gland are uncommon. Two patients with unusual primary pineal tumors that had similar distinctive histologic features are reported. METHODS. The surgically resected neoplastic pineal tissue from these patients were examined by light microscopy, immunohistochemistry, and electron microscopy and correlated with the patients' clinical course. RESULTS. These pineal tumors consisted of a mixture of spindle-shaped cells with fibrillated cell processes and many large lipidized and/or granular pleomorphic cells, some of which were multinucleated. These two tumors superficially resembled pleomorphic xanthoastrocytoma and granular cell tumors of the central nervous system. The pleomorphic tumor cells expressed glial fibrillary acidic protein and some also produced retinal S-antigen, a marker for retinal photoreceptor cells. Long-term follow-up (8 years) on one of these patients suggested a relatively "benign" clinical course. CONCLUSIONS. It is possible that this newly described tumor may be a distinct subset of pineal gland neoplasias with a favorable biologic behavior despite the histologic features that would suggest otherwise.     

骨巨细胞瘤的治疗：附50例报告

Fifty cases of giant cell tumor of bone are reported in this paper. The peak age was 20-40 years (76%). 75% of the tumors occurred in the extremity of long bones, of which 36% were around the knee. These patients were treated by curettage and bone graft or bone cement filling, bloc resection with or without bone graft and amputation. In this series, the follow-up time was 4 months-22 years and 3 months, and recurrence rate was 34%. There was no marked relation between recurrence and grade of tumor (35% for Grade I, 31% for Grade II and 25% for 25% Grade III). Patients with Grade III tumor had much poorer prognosis than those with Grade I or II. The surgical treatment of giant cell tumor of bone, particularly tumor of the spine, is still a challenge for orthopedic surgeons. Bloc resection of the tumor might be the treatment of choice for giant cell tumor of bone.     

距骨原发肿瘤的诊断与治疗

目的 探讨距骨原发肿瘤的发病特点﹑外科治疗和预后.方法 回顾性分析1993年1月至2008年12月我科收治的21例距骨原发肿瘤及瘤样病变,从临床、影像和病理分析距骨肿瘤特点,所有病例均进行外科治疗,术后随访按肌肉骨骼系统肿瘤协会(MSTS)标准进行功能评分.结果 21例患者中软骨母细胞瘤10例,骨巨细胞瘤7例,骨样骨瘤、动脉瘤样骨囊肿、单纯骨囊肿、骨纤维结构不良各1例.10例软骨母细胞瘤发病年龄为10～35岁,平均22岁.均行病灶刮除,1例骨水泥填充,9例植骨.9例完整随访均无复发.随访时间为15-87个月,中位随访时间为36个月,功能评分均为30分.7例骨巨细胞瘤发病年龄为20～33岁,平均24岁.影像学均为溶骨性破坏,基质无钙化.4例原发病例,均行病灶刮除术.3例复发病例,2例行距骨切除跟骨胫骨融合术,1例行小腿截肢术.3例完整随访,2例为原发病例,术后10个月和32个月未复发;另1例为复发病例,随访36个月未复发,功能评分分别为29、26和24分.4例其余诊断病例,1例骨样骨瘤行局部切除植骨术,另外3例均行病灶刮除植骨术,术后随访均无复发.结论 距骨好发肿瘤为软骨母细胞瘤和骨巨细胞瘤.距骨软骨母细胞瘤特点:患者发病年龄较大,病灶内钙化提示诊断,刮除植骨术可获得满意治疗效果.距骨骨巨细胞瘤特点:常累及全距骨,病灶刮除有较高复发率,距骨切除可降低局部复发率,但是遗留部分功能障碍.     

高频超声诊断在腮腺肿瘤诊断中的价值及误诊原因分析

目的:探讨高频超声诊断在腮腺肿瘤诊断中的价值及分析其误诊的原因,以期提高高频超声诊断腮腺肿瘤的符合率。方法:回顾性分析经手术及病理证实的12例腮腺多形性腺瘤病例、10例Warthin瘤病例的高频超声特点,分析并观察肿块的大小、形态、性质、解剖部位、内部回声,应用彩色多普勒检测肿块内部血流的丰富程度。结果:高频超声诊断12例腮腺多形性腺瘤患者中,诊断为多形性腺瘤6例,正确诊断率为50%,误诊为淋巴结炎2例,误诊为血肿1例,诊断为混合性占位、性质待定3例,误诊率50%。应用高频超声诊断10例Warthin瘤患者时,诊断为Warthin瘤4例,正确诊断率为40%,误诊为多形性腺瘤3例,误诊为淋巴结炎1例,诊断为混合性占位、性质待定2例,误诊率60%。多形性腺瘤与Warthin瘤的回声强度无差异,P>0.05;后壁回声增强、血流信号强度分级有差异,P<0.05,差异有统计学意义。结论:典型的多形性腺瘤、Warthin瘤有各自的声像图特点,非典型的多形性腺瘤类似于Warthin瘤。高频超声检查在腮腺多形性腺瘤与Warthin瘤的鉴别诊断过程中,有较高应用价值。通过观察肿块的形态、边界、包膜、内部回声、后壁回声增强情况,并运用彩色多普勒检查检测内部血流情况,结合患者一般临床资料,可以提高腮腺多形性腺瘤与Warthin瘤的诊断准确率。     

卵巢原发性多形性脂肪肉瘤病理分析及文献复习

目的：探讨多形性脂肪肉瘤（pleomorphic liposarcoma,PLS）的临床病理学特征.方法：对1例卵巢PLS进行大体、组织病理学和免疫组化染色观察,并复习相关文献.结果：肿瘤发生于一28岁女性患者卵巢.临床主诉为腹部肿块.镜下见肿瘤由多形性的梭形细胞及小圆形细胞组成,混有少量多核巨细胞.免疫组化：肿瘤细胞Vimentin、S-100阳性,desmin、SMA、myoglobin、EMA、AE1/AE3和HMB45均阴性.结论：卵巢PLS是一罕见的高度恶性软组织肿瘤,结合临床病理学特征及免疫组化,可作出正确诊断.