Breast carcinoma with micropapillary features: clinicopathologic study and long-term follow-up of 100 cases

To study the clinicopathologic characteristics and prognosis of invasive micropapillary carcinoma of breast (IMPC), 100 cases of invasive breast carcinoma with an IMPC component were reviewed. Compared with invasive ductal carcinoma, not otherwise specified, with similar histologic grades, carcinomas with IMPC were larger sized, had a higher lymph node metastasis rate with more nodes involved per case, and exhibited increased lymphovascular invasion. The presence of IMPC strongly correlated with the more aggressive behavior. No significant association was established between the proportion of the IMPC component and overall tumor size, histologic grade, lymph node metastasis rate, and distant metastasis, but a trend was noted. Long-term follow-up demonstrated a poorer 5-year and 10-year survival rate for patients with breast carcinoma containing an IMPC component. Breast carcinomas with micropapillary features are more aggressive tumors with a poorer prognosis. This specific structure should be carefully evaluated in the surgical pathology examination of breast carcinoma specimens.     

肾细胞癌的临床病理与免疫表型研究

目的 研究肾细胞癌的临床病理特征、预后及免疫表型特点.方法 复习114例肾细胞癌的临床病理资料、HE切片,按2004年WHO肾肿瘤分类标准重新分类、随访并进行免疫组织化学染色.结果 114例.肾细胞癌包括5个类型,肾透明细胞癌77例(67.5%)、乳头状肾癌11例(9.6%)、肾嫌色细胞癌14例(12.3%)、Xp11.2易位_/TFE3基因融合相关性肾癌10例(8.8%)、未能分类肾肿瘤2例(1.8%).免疫组织化学结果,肾透明细胞癌主要表达CK(93.5%,72/77)、CD10(93.5%,72/77)、波形蛋白(75.3%,58/77),乳头状肾癌主要表达α-甲酰基辅酶A消旋酶(AMACR,11/11),肾嫌色细胞癌主要表达CD117(11/14),Xp11.2易位/TFE3基因融合相关性肾癌TFE3、AMACR、CD10和CK的阳性率分别为10/10、10/10、9/10和7/10.结论 肾癌是一组形态学上各有特征的异质性肿瘤,在形态学基础上,CD10、波形蛋白、CD117、AMACR、CK7、TFE3有助于亚型的诊断.     

具有浆细胞样特征的尿路上皮原位癌:23例临床病理研究

尽管(非腺性)尿路上皮原位癌有5种详细描述的形态学模式,作者收集一种具有浆细胞样特征的扁平尿路上皮癌的新模式,具有特征性形态学表现,包括结构异常伴细胞变圆、核增大偏位、致密的球状嗜酸性胞质。作者收集并回顾23例浆细胞样尿路上皮原位癌(平均年龄:74 1岁,范围:58~91岁)     

Cytologic and clinicopathologic features of abnormal nipple secretions: 225 cases.

A case review of 225 patients with abnormal breast nipple secretions (NS) was done to determine diagnostically useful clinical and cytologic features. The cytologic specimens and medical records from all patients and 45 concurrent breast biopsies were reviewed. Nipple discharge was attributed to fibrocystic disease (FCD) in 81 cases, physiologic disturbances in 62, papillomas in 18, ductal carcinoma (CA) in 5, miscellaneous benign disorders in 14, and unknown causes in 45. Although cytologic examination of NS was very specific in identifying malignancy, the sensitivity of cytology was low. Carcinoma was diagnosed or suspected cytologically in only three of the five CA cases, with no false-positive cytopathologic interpretations. Malignant NS were usually unilateral, hemorrhagic, mass-associated, and in older patients. Males with nipple discharge had a significantly higher incidence of breast cancer (two of nine; 22%) than women with abnormal NS (3 of 216; 1.5%). Papilloma NS were generally unilateral and hemorrhagic; FCD and physiologic NS were mostly serous or milky. Benign NS were not cytologically distinguishable. We conclude that cytologic examination of NS is a specific but insensitive method to identify underlying malignancy. Additional clinical features, including patient age, laterality and character of NS, and radiographic findings, were found to be diagnostically useful.     

Apocrine mammary carcinoma. A clinicopathologic study of 72 cases

Apocrine carcinoma (AC) is an uncommon, poorly characterized type of breast tumor. In this review, 55 patients with intraductal (ID) AC and 17 patients with infiltrating (IF) AC were analyzed retrospectively to define the histologic features and clinical course of this neoplasm. Recurrences in the breast occurred in 3 of 20 ID-AC patients treated by biopsy alone, but not in the 2 patients who received local radiation therapy after biopsy. One patient with ID-AC had axillary metastases at the time of treatment by mastectomy and died of disease five years later. The remaining patients with ID-AC treated by mastectomy have remained disease free. One of the three patients with IF-AC treated by biopsy alone died of disease, and one of two patients with IF-AC treated by biopsy and radiotherapy was alive with carcinoma. Twelve patients with IF-AC were treated by mastectomy. Ten of them were recurrence free at the time of last observation. More than one-third of the cases of ID-AC and IF-AC were detected by mammography alone. Survival analysis of IF-AC cases compared with nonapocrine duct carcinoma cases matched for stage revealed no statistical difference in estimated recurrence-free survival or estimated survival probability. AC is a distinct morphologic entity with a natural history similar to that of nonapocrine ductal carcinoma.     

Urethral caruncle: clinicopathologic features of 41 cases

Urethral caruncle is a benign polypoid mass of the urethral meatus in primarily postmenopausal women. Although a conclusive association with malignancy, urologic disorder, or systemic disease has not been established, often the lesion carries a challenging clinical differential diagnosis that includes malignancy. Conversely, unexpected malignancy is identified in some cases resembling caruncle clinically. We examined clinical and histopathologic characteristics in 41 patients. Medical records were assessed for presentation, clinical diagnosis, associated urothelial carcinoma, radiation treatment, tobacco use, immunologic/urologic disorder, and treatment strategy/outcome. Average patient age was 68 years (range, 28-87 years). Presenting symptoms were pain (37%), hematuria (27%), and dysuria (20%), in contrast to asymptomatic (32%). Clinical diagnosis favored malignancy in 10% of cases. Concurrent or subsequent urothelial carcinoma was present for 5 patients (12%), although none developed urethral carcinoma. Histologic features included mixed hyperplastic urothelial and squamous lining, overlying a variably fibrotic, edematous, inflamed, and vascular stroma. Invaginations of urothelium extending into the stroma were common (68%), showing rounded nests with cystic or glandular luminal spaces, similar to urethritis cystica/glandularis, without intestinal metaplasia. Two lesions included an organizing thrombus, 1 with intravascular papillary endothelial hyperplasia. Twenty patients were treated with topical medications without resolution. Three lesions recurred (7%) after excision. A subset of patients had history of smoking or previous pelvic irradiation. Urethral caruncle is an uncommon lesion that may clinically mimic benign and malignant conditions. Awareness of the spectrum of clinical and histologic differential diagnoses is important in dealing with this unusual disease.     

Gallbladder neuroendocrine carcinoma: report of 10 cases and comparision of clinicopathologic features with gallbladder adenocarcinoma

Few cases of neuroendocrine carcinoma (NEC) of the gallbladder (GB-NEC) have been reported. Data obtained from the 10 patients with GB-NEC treated in our hospital between January 2008 and December 2012 were retrospectively analyzed and compared with those of 377 patients with gallbladder adenocarcinoma. GB-NEC accounted for 2.2% of all gallbladder cancers. The patients (8 females and 2 males) were 59.0 ± 10.0 years old. Four patients presented mixed adenocarcinoma, while six had pure NEC. Immunohistochemical examinations showed a positive rate of 100% for CgA, NSE, and CK; the positive rates for Syn, EMA, and CD56 were 88.9, 87.5, and 75%, respectively. TNM grades II, IVA, and IVB were found in 1, 2, and 7 patients, respectively. GB-NEC patients showed significantly higher N2 lymphatic metastasis rates than gallbladder adenocarcinoma patients (70.0 vs. 34.0%; P < 0.05). Two patients were treated with radical resection and the remaining 8 with palliative operation. The 1-, 2-, and 3-year survival rates were 20, 10, and 0%, respectively (median survival time, 3.0 m); the 1-, 2-, 3-, and 5-year survival rates for all gallbladder adenocarcinoma patients were 38.0, 31.0, 30.1, and 28.4%, respectively (median survival time, 6.0 m), the difference was statistically significant (P = 0.038). The results demonstrate that GB-NEC was mainly found in aged females and shows high malignancy. Its prognosis is poorer than that of gallbladder adenocarcinoma, and surgical resection combined with TACE, radiotherapy, and chemotherapy could increase patient survival.     

乳腺导管内二态性乳头状癌的形态及免疫表型特征

目的探讨乳腺导管内二态性乳头状癌的形态及免疫表型特征。方法收集具有二态性形态学特征的乳腺导管原位癌7例,观察其组织形态学特点,并采用EnVision免疫组化法检测CK5/6、CK34βE12、CK8、CD10、p63、SMA、ER、E-cad、Syn、CgA、GCDFP-15和AR的表达。结果二态性导管内乳头状癌4例,具有二态性特征的筛状型导管原位癌3例;其中4例伴有导管内非典型增生。二态性乳头状癌有两种形态不同的肿瘤细胞:一种是普通性肿瘤细胞,多为柱状细胞,胞质不透明,核为低或中间级别。此类细胞分布于乳头或筛状结构的浅层;第二种细胞是二态性肿瘤细胞,多呈多角形或立方形,胞质透明或淡染,核级别及形态与普通性肿瘤细胞相同。此种细胞位于柱状肿瘤细胞内侧,排列呈条带状、筛状、实性巢状或单个细胞播散分布,其胞质及细胞分布位置类似增生的肌上皮细胞。两种肿瘤细胞均显示CK8、ER阳性,基底高分子量角蛋白(CK5/6、CK34βE12)、肌上皮(CD10、p63、SMA)、Syn和CgA阴性;E-cad阳性5例,另2例部分细胞呈胞膜胞质型微弱阳性而大部分细胞不表达;1例GCDFP-15及AR阳性。结论二态性导管内乳头状癌的两种肿瘤细胞均呈腺系上皮分化,两种肿瘤细胞的形态及胞质染色不同,但核的异型性及其形态相同,免疫组化结果也相同。二态性肿瘤细胞在HE切片内与肌上皮细胞很相似,易被误认为肌上皮,从而导致诊断不足或误诊,宜予高度重视。     

套细胞淋巴瘤的临床病理特征及预后因素分析

目的探讨套细胞淋巴瘤（MCL）的临床病理特征及预后因素。方法对102例经形态学及免疫表型检测确定的MCL进行分析,组织病理制片和链霉素抗生物素蛋白过氧化物酶法或EnVision法染色,并进行了随访。结果102例患者中位年龄59岁（30～79岁）,男女之比约2．92：1。淋巴结是最常受累的部位（98／98,100％）,结外常受累的部位：骨髓（29／45,64．4％）、脾脏（36／57,63．2％）、咽淋巴环（15／48,31．3％）、外周血（15／51,29．4％）、肝脏（12／53,22．6％）及胃肠道（15／102,14．7％）;87．7％（71／81）初次就诊时处于临床Ⅲ～Ⅳ期,45．5％（25／55）患者有B症状;48．7％（19／39）患者血清乳酸脱氢酶升高。除7例（6．9％）因组织取材小无法区分病变模式外,余95例中12例（11．76％）为套区增生型,41例（40．2％）结节型,42例（41．2％）弥漫型。75．5％（77）经典型,24．5％（25例）瘤细胞呈母细胞样变型。102例均表达B细胞标记而不表达T细胞标记,96例（94．1％）肿瘤细胞表达细胞周期蛋白D1,70例（71．4％）CD5弱阳性。68例获得随访,中位生存时间10个月（0～89个月）。套区增生型＋结节型、经典型的核分裂象≤15／10HPF,增殖指数≤15％;骨髓无受累,提示患者预后好,而其他临床病理因素对患者生存未见影响。结论国内MCL患者病征与国外患者基本一致,其病变模式、细胞变型、核分裂象、增殖指数、骨髓是否受累及受累程度与预后有关。     

中国胃癌患者HER2蛋白表达与临床病理学参数及预后的关系

目的 评估中国胃癌人群中HEB2蛋白表达的流行病学情况,分析其与患者临床病理学参数之间的关系,探讨HEB2蛋白表达与胃癌患者预后的关系.方法 使用免疫组织化学方法检测胃癌患者中HER2蛋白的表达,以修订后HereepTest评分标准进行评分.x2检验分析HEB2蛋白表达与胃癌患者临床病理学参数之间的关系.生存分析应用Kaplan-Meier法,生存率比较采用Logrank 检验.结果 860例患者中位年龄59岁,男女比例为2.06∶1,其中进展期胃癌患者为774例.使用修订后的HercpTest评分标准评判HER2蛋白阳性表达(3+)的患者为77例(9.0%,77/860),其中进展期胃癌中的HER2阳性表达患者是69例,占进展期胃癌的8.9%(69/774).HEB2蛋白在胃癌中的阳性表达与肿瘤分化、Lauren分型及WHO分型相关,与年龄、性别、肿瘤发生部位及临床分期不相关.生存分析提示HER2蛋白阳性表达的胃癌患者生存率与阴性表达者无明显差异.结论 虽然胃癌HER2蛋白的阳性表达与肿瘤分化及组织学类型相关,但其可能不是胃癌患者的独立预后因子;HER2蛋白在胃癌中的阳性表达可能不影响胃癌患者的预后.

Abstract：

Objective To evaluate the epidemiological status of HER2 protein expression in Chinese patients with gastric carcinoma,and to study its clinical and prognostic significance and the association with the clinicopathological features.Methods The clinical data were reviewed in 860 patients with gastric carcinoma admitted to Guangdong General Hospital from 2003 to 2010.The HER2 status Was evaluated using immunohistochemistry(IHC).The modified Heroep Test scoring criterion Was used to assess HER2 protein expression.The association between HER2 expression and clinicopathological features was analyzed by X2 test.Kaplan-Meier analysis,log-rank test and Cox regression model were used for the survival analysis.Results The median age of the patients Was 59 years, and the male-to-female ratio was 2.06∶1.Positive expression of HER2 protein(3+)was found in 77(9.0%)cases of gastric carcinoma,and in 69(8.9%)edvanced gastric cancers.There waS significantly positive association between HER2 overexpression and tumor differentiation, Lanren claasification and WHO classification.No significant association Was observed between HER2 protein expression and patients'age,gender,tumor location and clinical stage.There waS no statistically significant difference in survival rate between patients with positive HER2expression and negative ones. Conclusion Though there WaS significantly positive association between HER2 expression status and tumor differentiation,histological type,it may be of limited prognostic value in gastric cancer patients.     

中国胃癌患者HER2蛋白表达与临床病理学参数及预后的关系

Objective To evaluate the epidemiological status of HER2 protein expression in Chinese patients with gastric carcinoma,and to study its clinical and prognostic significance and the association with the clinicopathological features.Methods The clinical data were reviewed in 860 patients with gastric carcinoma admitted to Guangdong General Hospital from 2003 to 2010.The HER2 status Was evaluated using immunohistochemistry(IHC).The modified Heroep Test scoring criterion Was used to assess HER2 protein expression.The association between HER2 expression and clinicopathological features was analyzed by X2 test.Kaplan-Meier analysis,log-rank test and Cox regression model were used for the survival analysis.Results The median age of the patients Was 59 years, and the male-to-female ratio was 2.06∶1.Positive expression of HER2 protein(3+)was found in 77(9.0%)cases of gastric carcinoma,and in 69(8.9%)edvanced gastric cancers.There waS significantly positive association between HER2 overexpression and tumor differentiation, Lanren claasification and WHO classification.No significant association Was observed between HER2 protein expression and patients'age,gender,tumor location and clinical stage.There waS no statistically significant difference in survival rate between patients with positive HER2expression and negative ones. Conclusion Though there WaS significantly positive association between HER2 expression status and tumor differentiation,histological type,it may be of limited prognostic value in gastric cancer patients.     

Dedifferentiated adenoid cystic carcinoma: a clinicopathologic study of 6 cases.

Dedifferentiated adenoid cystic carcinomas are a recently defined, rare variant of adenoid cystic carcinomas characterized histologically by two components: conventional low-grade adenoid cystic carcinoma and high-grade "dedifferentiated" carcinoma. We examined six cases and analyzed their clinicopathologic profiles, including immunohistochemical features and p53 gene alterations. The 6 patients (3 men and 3 women) had a mean age of 46.8 years (range, 34-70 y). The mean size of the tumors was 3.5 cm (range, 1.7-6 cm). The submandibular gland, maxillary sinus, and nasal cavity were involved in 2 cases each. Postoperatively, 5 patients had local recurrence and 5 developed metastatic disease. Five patients died of disease at a mean of 33.7 months after diagnosis (range, 6-69 mo), and one other was alive with disease at 60 months. Histologically, the conventional low-grade adenoid cystic carcinoma component of the tumors consisted of a mixture of cribriform and tubular patterns with scant solid areas. The high-grade dedifferentiated carcinoma component was either a poorly differentiated adenocarcinoma (4 cases) or undifferentiated carcinoma (2 cases). Three tumors were studied immunohistochemically. Myoepithelial markers were expressed in low-grade adenoid cystic carcinoma but not in the dedifferentiated component. In 2 cases, diffusely positive p53 immunoreactivity together with HER-2/neu overexpression was restricted to the dedifferentiated component. Loss of pRb expression was demonstrated only in the dedifferentiated component of the 1 other case. The Ki-67-labeling index was higher in the dedifferentiated component than in the low-grade adenoid cystic carcinoma component. Furthermore, molecular analysis of 2 cases demonstrated the loss of heterozygosity at p53 microsatellite loci, accompanied by p53 gene point mutation, only in the dedifferentiated carcinoma component of 1 case, which was positive for p53 immunostaining. These results indicate that dedifferentiated adenoid cystic carcinoma is a highly aggressive tumor. Because of frequent recurrence and metastasis, the clinical course is short, similar to that of adenoid cystic carcinomas with a predominant solid growth pattern. Limited evidence suggests that p53 abnormalities in combination with HER-2/neu overexpression or loss of pRb expression may have a role in dedifferentiation of adenoid cystic carcinoma.     

乳腺肌上皮癌3例临床病理特征分析

目的探讨乳腺肌上皮癌的临床表现、组织形态学改变和免疫表型特征。方法采用HE及免疫组化Leica BOND-MAX全自动染色仪Bond Polymer Refine Detection法,对3例乳腺肌上皮癌进行染色,并复习相关文献。结果乳腺肌上皮癌的癌组织多由梭形细胞组成,部分病例可见上皮样细胞、浆样细胞和透明细胞,呈实性片状、肺泡样、条索状排列;核分裂象易见;无坏死;可发生腋窝淋巴结转移。免疫表型:3例均表达CK、EMA、CD10、p40、actin、Calponin、p63;2例表达CK5/6、CK14、SMA;1例表达S-100蛋白、D2-40、CAM5.2;CD117、CD34、ER、PR、C-erb B-2/HER-2和desmin均不表达;Ki-67增殖指数为10%~20%。结论肌上皮癌细胞形态多样,结合免疫组化组合标记可做出明确诊断,治疗方式以乳腺癌根治术为主。     

RIN1在膀胱尿路上皮癌中的表达及临床特征

目的探讨膀胱尿路上皮癌中RINl蛋白的表达与临床病理学特征的关系。方法用sP免疫组化法检测手术切除的88例原发性膀胱尿路上皮癌标本和20例癌旁正常组织标本。所有组织用10％福尔马林固定。石蜡包埋,连续切片,厚度4μm。所有上述患者术前均未接受放疗,化疗。通过卡方检验,分析RINl表达与膀胱尿路上皮癌的临床病理学特点。结果免疫组化法发现,88例膀胱尿路上皮癌中有49例RINl表达升高,20例癌旁组织的RINl表达正常。RINl的表达与肿瘤的病理分级（P〈0．05）和临床分期（P〈0．05）呈正相关,与年龄、性别、肿瘤大小、是否多发则无相关性（P〉0．05）。结论RINI在膀胱尿路上皮癌中存在高表达,且在膀胱癌中发挥着重要作用。     

Extrapulmonary lymphangioleiomyomatosis (LAM): clinicopathologic features in 22 cases

We describe the lesions of extrapulmonary lymphangioleiomyomatosis (LAM) affecting the lymph nodes of the mediastinum and retroperitoneum in 22 women (mean age +/- SD, 42.4+/-10.5 years). In most of these patients, the diagnosis of extrapulmonary LAM preceded that of pulmonary LAM, usually by 1 to 2 years. Eleven patients had distinct symptoms, including chylous pleural effusion and/or ascites, abdominal pain, and palpable abdominal masses. In the other 11 patients, the masses caused no symptoms. Well-circumscribed, encapsulated masses, measuring up to 20 cm in size, occurred in the mediastinum in 2 patients, the upper retroperitoneum in 15, extensive areas of the retroperitoneum in 2, and the pelvis in 3. The masses exceeding 3 cm in diameter contained large, multiple cysts filled with yellow-tan chylous fluid. Histologically, the masses were characterized by a proliferation of smooth muscle cells (LAM cells) arranged in fascicular, trabecular, and papillary patterns, which were associated with slit-like vascular channels. The LAM cells varied from small, spindle-shaped cells to large epithelioid cells. Immunohistochemical studies showed a strong reactivity of most LAM cells for alpha-smooth muscle actin and smooth muscle myosin heavy chain and a weak to moderate reactivity of a lesser number of cells for desmin and nonmuscle myosin heavy chain II-B. A reaction for HMB-45 and estrogen and progesterone receptors was observed mainly in epithelioid LAM cells. These patterns of reactivity are similar to those observed in pulmonary LAM. However, the chylous cysts are not a feature of pulmonary LAM and are thought to result from obstruction of lymphatics.     

Clear cell odontogenic carcinoma: a clinicopathologic and immunocytochemical study of 5 cases.

CONTEXT: Odontogenic tumor composed predominantly of clear cells is a rare neoplasm of the jaws that was initially designated as clear cell odontogenic tumor. Subsequent reports in the literature, however, all have indicated that this tumor exhibits an aggressive behavior characterized by infiltrative local growth, recurrence, or metastases. OBJECTIVE: To ascertain the clinicomorphologic features and biologic behavior of this tumor group, we present 5 additional cases using the term clear cell odontogenic carcinoma. DESIGN: Histologic and immunohistochemical examinations were performed on clear cell odontogenic carcinomas from 5 patients. Clinical and follow-up data were recorded, and the literature was reviewed. RESULTS: The patients were 1 man and 4 women with an average age of 42.4 years at diagnosis. Three tumors occurred in the mandible and the other 2 in the maxilla. Four of the 5 cases occurred in the anterior or premolar areas of the jaws, appearing as poorly marginated radiolucencies. All cases consisted of islands and sheets of large clear cells and small basaloid cells with scanty eosinophilic cytoplasm, which were separated by thin, mature, fibrous septae. The tumors were unencapsulated and showed aggressive infiltration of the surrounding muscle and perineural tissues. Most of the clear cells contained cytoplasmic glycogen. Immunocytochemically, the tumor cells were positive for pan-keratin, cytokeratin 19, and epithelial membrane antigen, but were negative for vimentin, S100 protein, desmin, smooth muscle actin, human melanoma antigen (HMB-45), and alpha(1)-antichymotrypsin. Follow-up data showed 4 of 5 patients to have multiple local recurrences, and 1 of these 4 had submandibular lymph node metastasis and a fatal outcome due to uncontrollable tumor growth. CONCLUSION: These results suggest that odontogenic clear cell neoplasms are at least low-grade malignancies and should be classified as carcinomas.