The World Health Organization histologic classification system reflects the oncologic behavior of thymoma: a clinical study of 273 patients

BACKGROUND: Although the histologic classification of thymic epithelial tumors has been confusing and controversial, an agreement on the universal classification system for thymic epithelial tumors was achieved by the World Health Organization (WHO) in 1999. The authors previously reported that the WHO histologic classification system reflects invasiveness and immunologic function of thymic epithelial tumors. In this subsequent study, they examined the prognostic significance of this classification system. METHODS: Clinical features as well as postoperative survival of patients with thymoma, but not thymic carcinoma, were examined with reference to WHO histologic classification based on an experience with 273 patients over a 44-year period. RESULTS: There were 18 type A tumors, 77 type AB tumors, 55 type B1 tumors, 97 type B2 tumors, and 26 type B3 tumors. In patients with type A, AB, B1, B2, and B3 tumors, the respective proportions of invasive tumor were 11.1%, 41.6%, 47.3%, 69.1%, and 84.6%; the respective proportions of tumors with involvement of the great vessels were 0%, 3.9%, 7.3%, 17.5%, and 19.2%; and the respective 20-year survival rates were 100%, 87%, 91%, 59%, and 36%. According to the Masaoka staging system, the 20-year survival rates were 89%, 91%, 49%, 0%, and 0% in patients with Stage I, II, III, IVa, and IVb disease, respectively. By multivariate analysis, the Masaoka staging system and the WHO histologic classification system were significant independent prognostic factors, whereas age, gender, association with myasthenia gravis, completeness of resection, or involvement of the great vessels were not significant independent prognostic factors. CONCLUSIONS: This study showed that histologic appearance reflects the oncologic behavior of thymoma when the WHO classification system is adopted. The WHO classification system may be helpful in clinical practice for the assessment and treatment of patients with thymoma.     

Cerebral involvement of metastatic thymic carcinoma

Summary The authors report the clinical presentations, radiological findings, and treatment outcome of thymic carcinoma patients with cerebral metastasis. The authors retrospectively reviewed the medical records of 49 patients with thymic carcinoma and 6 of them (12.2%) developed brain metastasis. There were 4 men and 2 women with a mean age of 48 years (ranging from 33 to 56 years). The pathological types of thymic carcinoma which developed brain metastasis were thymic carcinoma type C of the WHO classification in three patients, type B3 in one and carcinoid tumor in two patients. Surgical resection was performed as an initial treatment for brain lesions in three patients. Five patients received whole brain radiation therapy (WBRT) and radiosurgery was performed in one of them. The survival time was from 2 months in a patient with no treatment for brain lesions to 9 months in a patient who is still alive after surgical resection combined with WBRT and radiosurgery. There is high probability of metastasis particularly in thymic carcinoma type C or carcinoid tumor. Frequent surveillance and aggressive therapeutic approach are necessary to improve survival in these patients with cerebral involvement.     

Diagnostic and clinical significance of KIT(CD117) expression in thymic epithelial tumors in China

Aims: To study KIT (CD117) expression in thymic epithelial tumors in China, and investigate diagnosticand clinical significance. Material and Methods: Thymic epithelial tumors (TETs) from 102 patients (3 type A,29 type AB, 5 type B1, 22 type B2, 29 typeB3 and 16 thymic carcinomas) were examined. Immunohistochemicalstaining with an antic-kit monoclonal antibody was performed on a tissue microarray. Relationships betweenKIT positive expression and the TET clinical characteristics (WHO histologic classification and Masaoka stagesystem) were analysed. Results: The KIT positive expression rate was significantly higher in thymic carcinoma(60%, 9/16) than in thymoma (8%, 7/86), a strong correlation being found with the WHO classification, but notthe Masaoka tumor stage. The overall survival for patients with KIT positive lesions was significantly worse.Conclusions: KIT is a good molecule marker to differentially diagnose thymic carcinoma from thymoma, whilealso serving as a predictor of prognosis for TETs. Further research into KIT mutations in Chinese TETs shouldbe conducted to assess the efficacy of targeted therapy.     

胸腺上皮源性肿瘤的WHO组织学分型和CT征象的相关性

背景与目的:胸腺上皮肿瘤的生物学和大体形态学的特征多样化,本文旨在探讨根据1999年WHO组织学分型的各亚型胸腺上皮源性肿瘤的CT征象。方法:对经病理检查证实的94例胸腺上皮源性肿瘤患者螺旋CT征象进行回顾性分析,其中包括A型7例,AB型24例,B1型16例,B2型13例,B3型16例,C型18例。结果:在本组94例患者病灶中,A、AB型的长短径明显小于C型(P<0.05);所有A型肿瘤均表现为轮廓光滑,A→C型出现率逐渐下降,A、AB、B1型更常呈轮廓光滑(P<0.05),B3、C型更常呈轮廓不规则(P<0.05);A型瘤内的坏死灶较其他亚型少见(P<0.001);B2、B3、C型肿瘤较A、AB、B1型的瘤灶内更常见多发钙化灶(P<0.05);瘤灶均匀强化更常见于A、AB、B1、B2型(P<0.001);B3、C型瘤灶浸润纵隔脂肪的发生率明显高于其他亚型(P<0.05)。结论:尽管各亚型肿瘤的CT征象存在一定的重叠,小肿瘤、轮廓光滑、类圆形、密度均匀(无钙化、坏死灶)、均匀强化高度提示A型肿瘤,大肿瘤、轮廓不规则、瘤内出现坏死灶、多发钙化、不均匀强化、浸润纵隔脂肪、浸润大血管等高度提示B3、C型肿瘤。     

82例胸腺瘤新组织学分型与患者临床特征和预后的相关性分析

背景与目的:世界卫生组织(WHO)于1999年制定了新的胸腺瘤组织学分型标准。本研究探讨胸腺瘤WHO组织学分型与临床特征和预后的相关性。方法:回顾性分析82例经外科治疗的胸腺瘤患者的临床资料,经有经验的病理科医生按WHO组织学分型标准重新做出诊断,并结合患者的临床特征和预后进行分析。结果:胸腺瘤A型5例(6.1%),AB型21例(25.6%),B1型14例(17.1%),B2型12例(14.6%),B3型14例(17.1%),C型16例(19.5%)。根据Masaoka临床分期,Ⅰ期29例(35.4%),Ⅱ期13例(15.8%),Ⅲ期32例(39.0%),Ⅳa期8例(9.8%)。临床分期与组织学分型的相关性有显著性意义(χ2=47.29,P<0.001)。肿瘤外侵的程度与组织学分型的相关性也有显著性意义(χ2=30.78,P<0.001)。A﹑AB﹑B1和B2型胸腺瘤合计切除率较B3和C型胸腺瘤合计切除率高(84.6%vs.50.0%,χ2=11.29,P=0.002)。临床Ⅰ、Ⅱ、Ⅲ、Ⅳa期胸腺瘤切除术后5年生存率分别为100%、100%、69.5%和37.5%;10年生存率分别为88.1%、57.1%、47.5%和0。不同临床分期患者生存率的差异(log-rank=40.31,P<0.001)与组织学分型间生存率的差异(log-rank=16.0,P=0.007)均有统计学意义。结论:WHO组织学分型可在一定程度上反映胸腺瘤的生物学行为和临床特征,对临床诊断和治疗胸腺瘤有指导意义。     

Clinical benefit from resection of recurrent glioblastomas: results of a multicenter study including 503 patients with recurrent glioblastomas undergoing surgical resection

Background

While standards for the treatment of newly diagnosed glioblastomas exist, therapeutic regimens for tumor recurrence remain mostly individualized. The role of a surgical resection of recurrent glioblastomas remains largely unclear at present. This study aimed to assess the effect of repeated resection of recurrent glioblastomas on patient survival.

Methods

In a multicenter retrospective-design study, patients with primary glioblastomas undergoing repeat resections for recurrent tumors were evaluated for factors affecting survival. Age, Karnofsky performance status (KPS), extent of resection (EOR), tumor location, and complications were assessed.

Results

Five hundred and three patients (initially diagnosed between 2006 and 2010) undergoing resections for recurrent glioblastoma at 20 institutions were included in the study. The patients’ median overall survival after initial diagnosis was 25.0 months and 11.9 months after first re-resection. The following parameters were found to influence survival significantly after first re-resection: preoperative and postoperative KPS, EOR of first re-resection, and chemotherapy after first re-resection. The rate of permanent new deficits after first re-resection was 8%.

Conclusion

The present study supports the view that surgical resections of recurrent glioblastomas may help to prolong patient survival at an acceptable complication rate.     

Tumor recurrence and survival in patients treated for thymomas and thymic squamous cell carcinomas: a retrospective analysis.

PURPOSE: Thymic epithelial tumors (TET) are rare epithelial neoplasms of the thymus with considerable histologic heterogeneity. This retrospective study focused on the correlation of WHO-defined TET histotypes with survival and tumor recurrence in a large cohort of patients receiving different modes of treatment. PATIENTS AND METHODS: Two hundred twenty-eight patients were followed for up to 21 years (median, 60 months; range, 1 to 252 months) after primary surgery. Forty-two patients received adjuvant radiotherapy (mean dose, 53 Gy), and 33 patients received adjuvant chemotherapy. RESULTS: Seventy-six (88%) of 86 patients with WHO type A, AB, and B1 thymomas were treated by surgery alone, with three tumor relapses after 3 to 10 years (median, 3.4 years). Twelve of 67 patients with WHO type B2 and B3 thymomas in Masaoka stages I and II were treated by adjuvant radiotherapy without evidence of tumor recurrence after 1 to 12 years (median, 4 years). Among 75 patients with B2 and B3 thymomas with incomplete resection or a tumor stage III or higher, the recurrence rate was 34% (n = 23) after 0.5 to 17 years (median, 5 years) in patients receiving adjuvant radiochemotherapy, compared to 78% (seven of nine patients) in patients without adjuvant radiochemotherapy. Incomplete tumor resection was associated with a high recurrence rate (65%) and a poor prognosis (P <.01). CONCLUSION: The long-term outcome of TET patients is related to tumor stage, WHO histotype, completeness of surgical removal, and type of treatment. Prospective trials are warranted to formally address the efficacy of adjuvant therapy in the treatment of localized and advanced malignant TETs.     

Surgical outcomes and reevaluation of treatment strategies for thymomas

Improved histological typing systems for thymic tumors and advances in induction and adjuvant therapy have created the need to reevaluate strategies for the management of thymoma. We retrospectively studied 73 patients with completely resected thymomas unassociated with myasthenia gravis. The World Health Organization (WHO) histologic classification, clinicopathological features and surgical outcomes were analyzed. Overall survival was 66.2% at 10 years, and the median survival time was 169 months. According to the Masaoka staging system, overall survival rates at 10 years were 94.7% in stage I, 76.1% in stage II, 30% in stage III and 0% in stage IV. In the WHO classification, overall survival rates at 10 years were 91.9% in types A and AB, 50.9% in type B2 and not achieved in type B3. The disease-free interval was slightly shorter in patients with B2 and B3 disease than in those with type A, AB and B1 disease. Advanced thymomas were significantly associated with type B2 and B3 (p<0.01). In stage III and IV disease, adjuvant or neoadjuvant therapy was associated with better survival as compared to no adjuvant therapy (p=0.07). On multivariate analysis, Masaoka stage III and IV disease and extended thymectomy indicated significant, negative and independent risk factors for survival (p<0.01). Masaoka stage I and II thymomas or WHO type A and AB thymomas have favorable prognoses and do not require postoperative adjuvant therapy. Patients with stage III and IV thymomas require additional therapy after surgery.     

胸腺上皮性肿瘤中TTF1、Ki-67的表达与WHO分型的关系及临床意义

目的 观察TTF1及Ki-67在胸腺上皮性肿瘤(Thymic epithelial tumors,TET)中的表达情况,探讨其与WHO分型的关系及二者的相关性。方法 收集59例TET标本,其中诊断一致的51例,不一致8例。应用免疫组化技术检测TTF1及Ki-67在诊断一致的 51例TET及30例胸腺增生组织中的表达情况,并分析其与临床病理参数之间的关系。结果 在诊断不一致的8例TET中,4例与AB型有关。在诊断一致的51例TET中,TTF1及Ki-67在TET中的表达均显著高于胸腺增生组(P＜0.05)。TTF1仅在AB型胸腺瘤中表达(11/15),其表达与WHO分型有关。Ki-67标记指数从A型到胸腺癌逐渐增加,且在A型与胸腺癌的表达范围不重叠,其表达与WHO分型及MasaoKa分期均有关。同时TTF1及Ki-67在TET中的表达没有相关性。结论 TTF1是AB型胸腺瘤相对特异性的标记;Ki-67不仅对A型与胸腺癌中的区分有帮助,同时具有很好的指示预后的价值。     

The 2015 World Health Organization Classification of Tumors of the Thymus: Continuity and Changes

This overview of the 4th edition of the World Health Organization (WHO) Classification of thymic tumors has two aims. First, to comprehensively list the established and new tumor entities and variants that are described in the new WHO Classification of thymic epithelial tumors, germ cell tumors, lymphomas, dendritic cell and myeloid neoplasms, and soft-tissue tumors of the thymus and mediastinum; second, to highlight major differences in the new WHO Classification that result from the progress that has been made since the 3rd edition in 2004 at immunohistochemical, genetic and conceptual levels. Refined diagnostic criteria for type A, AB, B1–B3 thymomas and thymic squamous cell carcinoma are given, and it is hoped that these criteria will improve the reproducibility of the classification and its clinical relevance. The clinical perspective of the classification has been strengthened by involving experts from radiology, thoracic surgery, and oncology; by incorporating state-of-the-art positron emission tomography/computed tomography images; and by depicting prototypic cytological specimens. This makes the thymus section of the new WHO Classification of Tumours of the Lung, Pleura, Thymus and Heart a valuable tool for pathologists, cytologists, and clinicians alike. The impact of the new WHO Classification on therapeutic decisions is exemplified in this overview for thymic epithelial tumors and mediastinal lymphomas, and future perspectives and challenges are discussed.     

复发肝癌再手术治疗的体会

目的:探索肝癌术后复发患者再次手术治疗的可行性、安全性及治疗效果。方法:回顾性分析2010年至2016年于我院行手术切除的原发性肝癌术后复发患者的临床资料。结果:共有37例肝癌术后复发患者行再次手术治疗,所有患者均无手术期死亡,术后并发症发生率为32.4%。中位生存期为20个月,1、3和5年生存率分别为83.8%、36.4%和5.6%。结论:对于具有根治性手术切除的复发性肝癌患者,再手术是安全有效的。     

Topoisomerase 2alpha plays a pivotal role in the tumor biology of stage IV thymic neoplasia

BACKGROUND: Microsatellite studies in histologic types B3 and C thymic neoplasia detected gains on chromosome 17q, which contains the Her-2/neu and its juxtaposed topoisomerase 2alpha (T2alpha) genes. The study aimed to evaluate their impact on tumor biology and survival of advanced thymic neoplasia patients. METHODS: From 1991 to 2005, 36 consecutive stage IV thymic carcinoma patients were treated, 18 men and 18 women, aged 11 to 84 years. There were 22 thymic carcinoma, 13 type B3, and 1 type B2 thymoma. Patients received treatment consisting of surgical resection, combination chemotherapy with the CAP (cyclophosphamide, Adriamycin, cisplatin) regimen, or radiation therapy potentiated by high-dose weekly 5-fluorouracil infusion. Permutations of these 3 treatment modalities were prescribed as necessary. RESULTS: T2alpha gene amplification was detected in 4 of 14 thymic carcinoma and 1 of 15 type B3 thymoma. Three thymic carcinoma patients had Her-2/neu coamplification and these 3 patients had rapidly growing tumor and extensive disease at initial diagnosis. CAP was prescribed in 28 patients and 20 patients responded (response rate, 71.4%, 95% confidence interval [CI]: 52.8% to 85%); all responders overexpressed (> or = 10% nuclei positive) the T2alpha protein, whereas 4 nonresponders had very low expression. T2alpha overexpression predicts CAP response, and its absence predicts resistance (P = .001). Overall survival was significantly prolonged if the tumor was resectable (P = .001), of type B3 histology (P = .0039), and had no Her-2 gene amplification (P = .0081). CONCLUSION: T2alpha and Her-2/neu genes play a pivotal role in the tumor biology, CAP response, and survival of advanced thymic neoplasia patients.     

Relationship Between Computed Tomography Manifestations of Thymic Epithelial Tumors and the WHO Pathological Classification

Objective: To explore the relationship between computed tomography (CT) manifestations of thymoma andits WHO pathological classification. Methods: One hundred and five histopathologically confirmed cases werecollected for their pathological and CT characteristics and results were statistically compared between differentpathological types of thymoma. Results: Tumor size, shape, necrosis or cystic change, capsule integrity, invasionto the adjacent tissue, lymphadenopathy, and the presence of pleural effusion were significantly different betweendifferent pathological types of thymomas (P <0.05). Type B2, B3 tumors and thymic carcinomas were greater insize than other types. More than 50% of type B3 tumors and thymic carcinomas had a tumor size greater than10 cm. The shape of types A, AB, and B1 tumors were mostly round or oval, whereas 75% of type B3 tumorsand 85% of thymic carcinomas were irregular in shape. Necrosis or cystic change occurred in 67% of type B3thymomas and 57% of thymic carcinomas, respectively. The respective figures for capsule destruction were 83%and 100% . Increases in the degree of malignancy were associated with increases in the incidence of surroundingtissue invasion: 33%, 75%, and 81% in type B2, type B3, and thymic carcinomas, respectively. Pleural effusionoccurred in 48% of thymic carcinomas, while calcification was observed mostly in type B thymomas. Conclusions:Different pathological types of thymic epithelial tumors have different CT manifestations. Distinctive CT featuresof thymomas may reflect their pathological types.     

Trends in Incidence and Survival of Patients With Thymic Epithelial Tumor in a High-Incidence Asian Country: Analysis of the Korean Central Cancer Registry 1999 to 2017

IntroductionTo report the trends in incidence and survival associated with thymic epithelial tumors (TETs) in Korea.MethodsData from 1999 to 2017 were obtained from the Korean Central Cancer Registry. Age-standardized incidence rates and average annual percentage changes (AAPCs) were calculated. Net survival (NS) was estimated by the Pohar-Perme method.ResultsAmong 5812 patients diagnosed with having TETs, 58.9%, 38.1%, and 3.0% were diagnosed with having thymoma, thymic carcinoma, and thymic neuroendocrine tumor (NET), respectively. Age-standardized incidence rates were 0.50, 0.30, 0.18, and 0.02 per 100,000 for all TETs and the respective subtypes. There was an increase in incidence of all TETs (AAPC = 6.1%) and subtypes: thymoma (AAPC = 5.6%), thymic carcinoma (AAPC = 7.0%), and thymic NET (AAPC = 3.4%). Proportions of patients with thymoma, thymic carcinoma, and thymic NET were 58.9%, 38.1%, and 3.0%, respectively. For thymoma, the relative proportion of distant stage decreased (19.4% in 2005 to 8.8% in 2017) and low-grade WHO subtype (A, AB, B1) increased faster than high-grade WHO type (B2, B3) (AAPC = 19.8% versus 9.6%). For thymoma, the 5-year NS was 82.3%. This increased from 64.3% in 1999 to 2002 to 90.6% in 2013 to 2017. For thymic carcinoma, the 5-year NS was 46.2% and only slightly increased from 39.4% in 1999 to 2002 to 47.9% in 2013 to 2017.ConclusionsThis study indicates a high incidence of TET and its continuous increase in Korea. The proportion of thymic carcinoma was relatively higher than in the United States or Europe. Survival for thymoma improved during the study period, whereas this was not evident for thymic carcinoma or thymic NET.     

原发性肝癌术后肝内复发与肝外转移再手术切除疗效分析

[目的]探讨原发性肝癌术后肝内复发与肝外转移再手术切除的疗效.[方法]回顾性分析267例再切除的复发性肝癌患者的临床资料,其中205例行再次肝切除,51例行肝外转移癌切除,11例行肝内复发和肝外转移癌联合切除,比较其临床病理特征和生存率.[结果]肝内复发组第二次手术后1年,3年,5年和10年生存率为81.7%,42.2%,20.0%和10.0%,第三次手术后为78.3%,30.4%,13.0%和8.7%.中位生存时间为44个月.肝外转移组第二次手术后为80.4%,32.0%,16.0%和4.3%,第三次手术后为76.0%,27.9%,13.6%和0.中位生存时间为43个月.肝内复发联合肝外转移切除组总的1年,3年,5年和10年生存率为100.0%,72.7%,36.4%和0.肝内复发组与肝外转移组再切除术后生存率的比较差异无显著性(P＞0.05).[结论]再手术切除不仅适用于肝内复发,还可有选择适用于肝外转移.肝外转移再切除也能延长生存期.     

World Health Organization histologic classification: an independent prognostic factor in resected thymomas

The histologic classification of thymoma remained controversial since 1999, when the World Health Organization (WHO) Consensus Committee published a histologic typing system for tumours of thymus. Clinical features, postoperative relapsing rates, and survival of patients with thymoma were evaluated with reference to the WHO histologic classification, based on a series of 178 patients, submitted to surgery between 1988 and 2000.There were 21 type A, 49 type AB, 45 type B1, 50 type B2 and 13 type B3 tumours. The invasiveness of tumours was 23.8%, 51%, 73.3%, 82% and 100% for types A, AB, B1, B2 and B3 tumours, respectively. The frequency of invasion of the great vessels increased according to the tumour type in the order A (0%), AB (4%), B1 (6.6%), B2 (22%), and B3 (23%). The 10-year disease-free survival was 95%, 90%, 85%, 71% and 40% for types A, AB, B1, B2 and B3, respectively. According to the Masaoka staging system, the disease-free survival rates were 94%, 88% and 66% for stages I, II and III, respectively, at 10 years. No stage IVA thymomas reached 10 years follow-up. Overall survival at 10 years were 88% and 25% when complete and incomplete resection were considered. By multivariate analysis, Masaoka staging system, WHO histologic classification and complete resection were significant independent prognostic factors, whereas age- and sex-associated myasthenia gravis were not. The present study demonstrated the World Health Organization histologic classification a good prognostic factor, such as completeness of surgical resection and Masaoka staging system.     

Frequent recurrence and progression in pilocytic astrocytoma in adults

BACKGROUND: Most pilocytic astrocytomas (piloA) are benign growths (World Health Organization [WHO] grade 1) of the deep midline structures, the brainstem, and the cerebellum. To the authors' knowledge, the literature contains only scarce data regarding piloA in adults. METHODS: Between 1995 and 2005, 44 patients (26 women and 18 men) underwent surgery for a primary or recurrent piloA at the authors' institution. All patients were aged > 16 years (mean +/- standard deviation: 31 +/- 14 years) at the time of their first surgery. The histopathologic diagnoses were reviewed, and relevant clinical information was obtained through a chart review and telephone interviews. The mean follow-up was 76 +/- 59 months (range, 1-227 months). RESULTS: There were 20 patients (45%) with supratentorial lobar piloA (including 10 temporal/temporomesial tumors, 5 parietal tumors, 3 insular tumors, 1 frontal tumor, and 1 occipital tumors), 12 patients with cerebellar piloA, 7 patients with brainstem piloA, 2 patients with opticochiasmatic PiloA, 1 patient with intramedullary piloA, and 2 patients with piloA of the basal ganglia. All but 1 patient with a lobar tumor presented with epilepsy. In 6 of 44 patients (14%), increased proliferative activity was revealed. WHO grade 3 primary anaplastic piloA was diagnosed in 2 patients (5%), and WHO grade 3 secondary anaplastic piloA was diagnosed in 4 patients (9%). Tumor recurrence or disease progression was observed in 13 of 44 patients (30%). Eight of 44 patients (18%) died from their disease. Histologic grading and extent of surgical resection proved to be important predictors of survival. CONCLUSIONS: PiloA in adult patients, surprisingly, often was not a benign disease. The degree of surgical resection was found to be of major importance for the patient's further clinical course; therefore, an aggressive surgical resection should be attempted whenever possible.     

Recurrence of Breast Cancer following local excision alone for ductal carcinoma in situ

OBJECTIVE: To assess recurrence of breast cancer following local excision alone for ductal carcinoma in situ. METHODS: Eighteen patients who received complete resection for noninvasive ductal carcinoma between 1982 and 1997 were investigated in this study. The mean age of the patients was 45 (29-78) years old. The initial presentation was a clinically palpable tumor in 4 patients, nipple discharge in 6, and microcalcification on mammograms in 8. Patients with palpable tumor underwent wide excision with at least a 2-cm free margin. Patients whose mammograms showed microcalcification underwent lumpectomy, and those who showed nipple discharge underwent duct-lobular segmentectomy. Five patients who underwent lymph node dissection up to level I or II had no lymph node metastasis. The mean follow-up period was 86 months. RESULTS: Local recurrence in the conserved breast was seen in five (27.8%) of 18 patients. The actuarial five-year event-free survival was 76.2%. The histological type of the recurrent tumor was ductal carcinoma in situ in three patients and invasive carcinoma in two. There was no difference in age at initial operation or histological subtype between patients with and without recurrent disease, but patients presenting with nipple discharge initially had a significantly shorter ipsilateral disease-free interval than those presenting with tumor or microcalcification on mammograms. All patients with local recurrence in the conserved breast were treated with breast-conserving surgery or subcutaneous mastectomy. CONCLUSION: Local recurrence frequently occurs in patients presenting with nipple discharge treated by duct-lobular segmentectomy for noninvasive ductal carcinoma. Either wide excision with a larger free margin or adjuvant radiation therapy following duct-lobular segmentectomy should be considered for these patients.     

Risk of Lung Cancer among Cigarette Smokers in Relation to Tumor Location

To evaluate the effect of cigarette smoking on lung cancer by tumor location and histological type, we compared the smoking history obtained from medical records of 605 patients with squamous cell carcinoma (194 males and 10 females) or adenocarcinoma (219 males and 182 females) of the lung and 183 patients with metastatic lung cancer (82 males and 101 females) who had been aged 40 years or over at the time of surgical resection at the Cancer Institute in Tokyo from 1973 –1991. The tumors which developed in a main or segmental bronchus were classified as central type, and those in a subsegmental or more distal bronchi were categorized as peripheral type. Cases with adenocarcinoma were classified by a pathologist into two histological subtypes, papillary and tubular types, according to the WHO lung carcinoma classification. Risk of squamous cell carcinoma was strongly associated with cigarette smoking for both central (OR (odds ratio) = 10.3 in males and 4.4 in females) and peripheral sites (OR = 10.7 in males and 6.5 in females). There was no significant association between cigarette smoking and adenocarcinoma for any tumor site or histological subtype in both sexes.