子宫内膜异位症相关性卵巢透明细胞癌和卵巢子宫内膜样癌的临床病理特征研究

目的 研究子宫内膜异位症(EM)相关性卵巢透明细胞癌(CCC)和卵巢子宫内膜样癌(EC)的临床病理特征.方法 选取CCC和EC患者共167例,根据是否为EM恶变将患者分为EM组(n=84)和非EM组(n=83).比较两组患者的年龄、生育史、EM病史、临床表现、凝血功能、血清CA125水平、超声检查结果、术中情况及术后病理特点.结果 EM组患者的发病年龄、初潮年龄均明显小于非EM组(P﹤0.01),未绝经患者所占比例明显低于非EM组(P﹤0.01);EM组患者的孕次、产次明显低于非EM组(P﹤0.001),不孕症患者所占比例明显高于非EM组(P﹤0.001);EM组中既往有EM病史的患者所占比例高于非EM组(P﹤0.05);临床表现方面,EM组患者的痛经、月经紊乱发生率均明显高于非EM组(P﹤0.01);EM组患者的PT、APTT明显短于非EM组(P﹤0.001);术后,EM组患者的血清CA125水平低于非EM组(P﹤0.05);两组患者超声检查结果比较,差异无统计学意义(P﹥0.05);EM组患者的肿瘤直径明显大于非EM组(P﹤0.001);两组患者的FIGO分期比较,差异有统计学意义(P﹤0.05),其中EM组患者中Ⅰ~Ⅱ期患者所占比例高于非EM组.结论 EM相关性CCC和EC与单纯CCC和EC存在明显不同的临床病理特征,具有确诊年龄及初潮年龄小、绝经比例更高、孕产次更低、既往有EM病史患者所占比例更高、痛经和月经紊乱表现更多、PT和APTT更短、血清CA125水平较低和临床病理分期较早等特点.     

Different features of angiogenesis between ovarian and breast carcinoma

Angiogenesis assessed by immunohistochemical staining for endothelial cells has been widely accepted as an independent prognostic factor in human breast carcinoma. However, the clinicopathologic significance of angiogenesis is still being argued in ovarian carcinoma. Therefore, we retrospectively analyzed the clinicopathologic significance of angiogenesis in ovarian carcinoma compared with that in breast carcinoma. After vessels were stained with CD34-monoclonal antibody, the areas with the highest number of intratumoral microvessels were assessed in a 200× field in 42 ovarian carcinoma and 41 breast carcinoma. Intratumoral microvessel density (IMD) in ovarian carcinoma was significantly lower than that in breast carcinoma. Further, the difference of IMD from tumor to tumor in ovarian carcinoma was smaller than that in breast carcinoma. IMD was correlated with tumor grade, but not with other clinicopathologic variables in ovarian carcinoma. Although the patients with high-IMD tumor revealed a poorer prognosis than those with low-IMD tumor in breast carcinoma, IMD had no influential effects on the survival of the patients with ovarian carcinoma. Our comparative analysis of IMD in ovarian carcinoma with that in breast carcinoma indicates that angiogenesis may play an important role in the transient of ovarian neoplasms, but not in the progression of ovarian carcinomas, and that the biological roles of angiogenesis might be different, depending on histologic subtype.     

卵巢子宫内膜样腺癌PET/CT影像表现

目的:分析卵巢子宫内膜样腺癌（ovarian endometrioid carcinoma,OEC）的PET/CT影像表现,探讨PET/CT在诊断OEC中的价值。方法:回顾性分析颈手术病例证实的27例OEC患者的PET/CT影像特征,包括位置、大小、密度等解剖学特点及18F-FDG代谢水平特征,两组或多组病灶SUVmax值有无差异采用t检验或单因素方差分析。结果:27例患者中有7例同时合并子宫内膜癌;17例为单侧发生（其中左侧7例,右侧10例）,10为双侧发生,共有病灶37个;肿瘤最大径1.5~24 cm,平均（10.92±5.73） cm。31个为囊实性肿物,6个为实性肿物,实性部分均表现为不同程度18F-FDG高摄取,平均SUVmax值为14.30±5.83（5.93~28.33）。肿瘤临床分期,分化程度,雌激素受体（estrogen receptor,ER）、孕激素受体（progesterone receptor,PR）表达量及合并子宫内膜癌与否之间的SUVmax差异均无统计学意义（P均＞0.05）。结论:OEC在PET/CT上多为单侧或双侧明显高代谢的较大囊实性肿块,可伴有腹盆腔种植转移和淋巴结转移,与其他卵巢恶性肿瘤鉴别较困难。如果患者同时合并子宫内膜癌,可对诊断有一定的提示作用。PET/CT全身显像有助于OEC的分期。     

Microsatellite instability and proliferating activity in sinonasal carcinoma: molecular genetic and immunohistochemical comparison with oral squamous cell carcinoma

Sinonasal carcinomas arise from the respiratory epithelium that lines the nasal and paranasal cavities, and are histologically composed of either squamous or cylindrical cell carcinoma. However, molecular analysis with the purpose of distinguishing sinonasal carcinomas from other head and neck squamous cell carcinomas (HNSCCs), which arise from squamous epithelium, has been limited. Moreover, a wide range of frequency of microsatellite instability (MSI) in HNSCC has been reported. Using high-resolution fluorescent microsatellite analysis (HFRMA), we studied microsatellite alterations in 34 patients with sinonasal carcinoma. As a control, 24 oral squamous cell carcinomas were used. MSI was detected in 14 patients with sinonasal carcinoma (41%), but not in any with oral squamous cell carcinoma (p=0.002). Furthermore, in sinonasal carcinoma, 11 out of 17 (65%) T1-T3 sinonasal carcinomas demonstrated MSI, whereas only 3 out of 15 (20%) T4 tumors demonstrated MSI. Immunohistochemically, sinonasal carcinoma showed a higher MIB-1-labeling index and more frequently showed cytokeratin 18 expression when compared with oral squamous cell carcinoma. These findings suggest that sinonasal carcinoma and HNSCC have quite different molecular backgrounds regarding carcinogenesis, and the role of MSI is relatively minor in cases of advanced sinonasal carcinoma.     

A clinico-pathologic study of clear-cell hepatocellular carcinoma

We reviewed the pathologic and clinical features of 7 cases of clear-cell hepatocellular carcinomas. Tumor cells had a typical clear, empty cytoplasm due to prominent accumulation of glycogen and lipid droplets, as demonstrated by ultrastructural study in one of our cases. Follow-up of the 7 patients did not confirm the better prognosis of this tumor reported by other investigators. The clinical course of our cases was more unfavorable than that of the other 130 cases of usual hepatocellular carcinomas treated at this Institute.     

Breast carcinoma in pregnant women: assessment of clinicopathologic and immunohistochemical features

BACKGROUND: Breast carcinoma is one of the most common carcinomas in pregnant women. The incidence of breast carcinoma may increase in the future because of the trend toward delayed childbearing and increased screening. However, very few contemporary studies have attempted to identify the combined histopathologic and immunohistochemical features of breast carcinoma in these patients. METHODS: The authors evaluated 39 patients with breast carcinoma occurring coincident with pregnancy. This was comprised of a critical histologic review and immunohistochemical evaluation to determine the status of prognostic and predictive markers including estrogen receptor (ER), progesterone receptor (PR), HER-2/neu, Ki-67, and p53. RESULTS: The mean age at presentation was 33 years (range, 24-44 years). Densities and/or masses were noted on mammograms in 14 of 16 patients with available radiographic information. The primary tumors were a mean of 4.5 cm in greatest dimension (range, 0.1-13.5 cm). Two of the 39 patients had clinical (American Joint Committee on Cancer) Stage I disease, 19 patients had Stage II disease, 16 had Stage III disease, and 2 patients had Stage IV disease at the time of presentation. Histologically, high-grade invasive ductal carcinomas were found in 32 of 38 patients. The primary tumor was not available for review in one patient. A predominantly solid pattern of growth was observed in nine patients. Lymphovascular invasion was identified in 61% of cases. Ductal carcinoma in situ was identified in 72% of tumors and was high grade in all cases. Of the 25 patients tested, ER positivity was found in 7 patients, PR positivity was found in 6 patients, HER-2/neu positivity was found in 7 patients, and p53 positivity was found in 12 patients. The proliferation rate as shown by Ki-67 staining was high in 60% of the cases. Follow-up information was available for 35 patients and the mean follow-up period was 43 months (range, 2-163 months). Distant metastasis occurred in seven patients. The mean time to disease recurrence was 20.4 months (range, 10-33 months). Of 35 patients, 4 have died, 22 were alive with no evidence of disease, and 9 were alive with disease at the last follow-up. The remaining four patients died of unknown causes. CONCLUSIONS: Pregnant women with breast carcinomas generally present with advanced-stage disease and the tumors have poor histologic and prognostic features. The findings from the follow-up indicated that these tumors do not follow a very aggressive clinical course as was proposed in earlier reports. Breast carcinomas occurring during pregnancy share many histologic and prognostic similarities with breast carcinoma occurring in other young women.     

A case of brain metastasis from advanced ovarian clear-cell carcinoma during maintenance chemotherapy with irinotecan+cisplatin

Clear-cell carcinoma of the ovary is a highly malignant neoplasm. Survival of patients in the advanced stage is poor, and the best treatment is not clear. We report here a case of a 57-year-old woman who had Stage IIIb advanced clearcell carcinoma of the ovary. We performed abdominal hysterectomy, bilateral salpingo-oophorectomy, pelvic lympho adenectomy and partial omentectomy. After the operation she was placed on induction and maintenance chemotherapy with a combination of irinotecan(CPT-11)(60 mg/m2, day 1, 15)plus cisplatin(CDDP)(60 mg/m2, day 1). Four years after surgery, a metastatic tumor was found in the brain. Considering the poor prognosis of clear-cell carcinoma, this regimen is thought to be effective for advanced clear-cell carcinoma of the ovary. It is important to check brain metastases under maintenance chemotherapy.     

Clinicopathologic and immunohistochemical features of surgically resected small cell carcinoma of the esophagus

Esophageal small cell carcinoma (SmC) is considered an aggressive cancer carrying a poor prognosis, although the rarity of this tumor has impeded statistical evaluation. We reviewed records of 457 esophageal cancer patients treated in our department from 1986 to 2000, comparing clinicopathologic factors and post-treatment outcomes, for 9 patients with SmC, most undergoing esophagectomy including lymphadenectomy, with data from 128 patients with esophageal squamous cell carcinoma (SqC) invading to the muscular layer or beyond. Immunohistochemical features were compared between the SmC and 12 consecutive SqC. All patients studied had localized disease according to preoperative staging. SmC showed more ulcerative and infiltrative growth, and more aggressive lymphatic spread, than SqC. All SmC patients had lymph node metastasis (thoracic nodes, 9 patients: abdominal 6; cervical 1). All SmC specimens but no SqC were immunoreactive for neuron-specific enolase. Two and three SmC specimens were reactive for epithelial membrane antigen and keratin, respectively. Survival of SmC patients after esophagectomy (median, 11 months) was worse than for SqC patients (p=0.013). However, 1 SmC patient remains alive at 76 months. Survival was not related to any clinicopathologic or immunohistochemical features. While SmC shows aggressive behavior and worse outcomes than SqC, combining esophagectomy with chemotherapy or radiotherapy may prolong survival.     

Breast carcinoma with features of osteosarcoma--a light and electron microscopic and immunohistochemical study

Reported is the case history of a 58-year-old woman with a lump in the left breast. The tumor was composed of two nodules, sharing a common portion. Grossly, one was an irregular hard tumor that was grayish in color, and the other was a well circumscribed cystic tumor that showed necrosis and a hemorrhage that had filled it with a reddish soft mass. Light microscopically, combined features of a scirrhous carcinoma and of an osteosarcoma were observed in each nodule, but the common portion was consistent with a metaplastic carcinoma, with cancer cells and sarcoma-like cells closely mingled. An ultrastructural study showed that the sarcoma-like cells were composed of polymorphic cells that resembled osteoblasts, myofibroblasts, osteoclasts, histiocytes, and undifferentiated tumor cells. Immunohistochemically, vimentin and alpha 1-antitrypsin in the sarcoma-like cells were positive, suggesting these cells were of a mesenchymal rather than of an epithelial origin.     

Microsatellite instability in ovarian neoplasms.

Microsatellite instability has been observed in a variety of sporadic malignancies, but its existence in sporadic ovarian cancer has been the subject of conflicting reports. We have performed a polymerase chain reaction-based microsatellite analysis of DNAs extracted from the neoplastic and non-neoplastic tissues of 41 ovarian cancer patients. Tumour-associated alterations were observed in seven (17%) of these cases. Clinicopathological correlations revealed that: (1) alterations among tumours classified as serous adenocarcinomas occurred with relatively low frequency (2/24 or 8%); (2) most of the tumours with microsatellite alterations (5/7 or 71%) were of less common histopathological types (epithelial subtypes such as endometrioid and mixed serous and mucinous, or non-epithelial types such as malignant mixed Müllerian or germ cell tumours); (3) tumour-associated alterations were observed in 3/4 (75%) of the patients with stage I tumours vs 4/37 (11%) of the patients with stage II, III and IV tumours (P = 0.01); (4) tumour-associated microsatellite instability was found to occur with similar frequencies among patients with and without clinical features suggestive of familial disease, including positive family history, early onset, or multiple primary tumours. In summary, we have observed microsatellite alterations in the neoplastic tissues of ovarian cancer patients with diverse genetic backgrounds and clinicopathological features. The pattern of alterations is consistent with the possibility that multiple mechanisms may be responsible for microsatellite instability in ovarian neoplasms.     

Primary small cell carcinoma of the esophagus: clinicopathological and immunohistochemical features of 21 cases

Background  

Primary small cell carcinoma (SCC) of the esophagus is a rare and aggressive tumor with poor prognosis. In this study, we report the clinicopathological characteristics of 21 cases of small cell carcinoma of the esophagus treated at the Cancer Center of Sun Yat-Sen University, with particular focus on the histologic and immunohistochemical findings.     

A thyroid metastasis revealing an occult renal clear-cell carcinoma

A case of renal clear-cell carcinoma presenting as a nodular thyroid metastasis is reported. The possibility of a metastatic lesion from the kidney should be taken into account in each case of clear-cell thyroid lesion. Fine needle aspiration cytology may be unable to discriminate between the renal or thyroid origin of such lesions unless PAS staining is performed.     

Current status of anti-angiogenic agents in the treatment of ovarian carcinoma

During the last decade we have assisted in the development of new therapeutic strategies for the treatment of ovarian cancer, based on the best knowledge of molecular biology. One of the most promising strategies under investigation is antiangiogenic therapy. Bevacizumab is a monoclonal humanised antibody targeting vascular endothelial growth factor (VEGF), which has shown antitumour activity in ovarian cancer in preclinical models as well as in clinical trials, both in monotherapy and in combination with other therapies. Currently, ongoing phase III trials are testing bevacizumab as a front-line therapy with carboplatin and paclitaxel. Bevacizumab has been generally well tolerated with mild frequent toxicities (proteinuria, hypertension and bleeding). However, the drug may result in other uncommon, but potentially life-threatening side effects, such as arterial thromboembolism, wound healing complications, and gastrointestinal perforation or fistulae, which should be considered when the drug is administered. Other new therapeutic antiangiogenic strategies that include small-molecule tyrosine kinase inhibitors, antibodies neutralising the VEGF receptor (VEGFR) and soluble VEGFR hybrids (VEGF Trap) are being investigated with promising early results.     

Morphological, immunohistochemical and biochemical characterization of 6 newly established human ovarian carcinoma cell lines.

Six permanent human tumor cell lines (OV-MZ-1 to 6) were established from 6 patients with serous adenocarcinomas of the ovary. These cell lines were derived from both solid tumors and ascites, from pre-treated and untreated patients, and are available over a range of in vitro passage numbers. The tumor cells grow as monolayers and develop foci of "piled-up' cells in confluent cultures. Flow cytophotometry showed that all the lines exhibited DNA hyperdiploidy with DNA tetraploidy in one cell line and DNA aneuploidy in the other cell lines. The mean population doubling time ranged from 24 to 52 hr. Transmission electron microscopy demonstrated that the tumor cells of all cell lines exhibited features of epithelial differentiation such as desmosomes and intracellular gland-like lumina. Immunocytochemical analysis showed that the co-expression of cytokeratins and vimentin, which is a feature of ovarian serous cystadenocarcinomas in situ, was fully preserved in the majority of cell lines. The main cytokeratin polypeptides expressed were numbers 7, 8, 17, 18 and 19. The tumor-associated antigen CA-125, but not CEA, was shed in the culture supernatant. This was in accordance with FACScan analysis of the cell lines and the level of CA-125 and CEA in the patients' serum. The estrogen and progesterone receptors were negative both in the cell lines and in the original tumors. These new ovarian carcinoma cell lines will be valuable models for further investigations into a variety of biological properties.     

Primary branchiogenic carcinoma - immunohistochemical and ultrastructural features - a case-report and review of the literature

A case with histological evidence of malignancy developed in a branchial cleft cyst (BCC), which conforms with the criteria for primary branchiogenic carcinoma (PBC) was analyzed by electron microscopy and immunchistochemistry; our findings reveal peculiar analogies between PBC and BBC, further supporting the primitive nature of the lesion.     

The prognostic significance of epidermal growth factor receptor expression in clear-cell renal cell carcinoma: a call for standardized methods for immunohistochemical evaluation

Background

Epidermal growth factor receptor (EGFR) is overexpressed in the majority of clear-cell renal cell carcinomas (RCCs). The prognostic significance of EGFR overexpression after nephrectomy, however, is controversial because of different methods used in the immunohistochemical (IHC) evaluation of EGFR expression.

Patients and Methods

In this study, we evaluated EGFR expression and its prognostic significance using 3 IHC evaluation methods. A tissue microarray composed of 44 cases of clear-cell RCC was stained for the patterns of EGFR overexpression, including membranous, cytoplasmic (EGFR-c), and total (membranous and cytoplasmic), and the percentage of cells positive for EGFR overexpression were recorded. An EGFR composite score was calculated by multiplying the total EGFR overexpression score (0-3) and percentage of positive cells.

Results

Membranous EGFR overexpression was detected in 38 of 44 cases (93.2%), with moderate to strong staining (scores 2 and 3) in 35 cases (79.5%). EGFR-c was detected in 28 cases (63.6%), with moderate to strong staining (scores 2 and 3) in 16 cases (36.4%). EGFR-c was significantly associated with pathologic stage (P = 0.003) and Fuhrman nuclear grade (P = 0.042). Epidermal growth factor receptor composite score correlated with pathologic stage (P = 0.045) but not Fuhrman nuclear grade. However, EGFR expression did not correlate with overall survival or disease recurrence.

Conclusion

This study demonstrates that the prognostic value of EGFR overexpression differs significantly when different methods are used to evaluate EGFR expression by IHC. Future studies should use standardized methods to evaluate the EGFR staining pattern and intensity and the percentage of positive cells in order to clarify the prognostic significance of EGFR overexpression in clear-cell RCC.