Prostatic metastasis of large cell neuroendocrine carcinoma of the lung

Large cell neuroendocrine carcinoma (LCNEC) of the lung is a rare and aggressive tumour with a poor prognosis. Lung cancer metastases to the prostate are also uncommon, and are usually found incidentally during autopsy. Most reported primary lung cancers with prostatic metastases are small cell carcinomas, and prostatic metastases from LCNEC of the lung have not been reported previously. This case report describes a 70-year-old man with LCNEC of the lung and metastases in the prostate, brain, bone, liver and lymph nodes.     

Differential gene and protein expression in primary gastric carcinomas and their lymph node metastases as revealed by combined cDNA microarray and tissue microarray analysis

OBJECTIVE: To gain insight into the molecular events of lymph node metastasis of human gastric carcinoma. METHODS: The gene expression profile of five matched primary gastric carcinomas and their lymph node metastases was analyzed by complementary DNA (cDNA) microarray. Differential genes were identified in the metastatic and corresponding primary tumor pairs. Among the differentially expressed genes, carbonic anhydrase II (CAII) and insulin-like growth factor binding protein 4 (IGFBP 4) genes were detected by RT-PCR. CTTN protein expression was examined by tissue microarray. RESULTS: There was a high expression (over twofold) of 44 genes and a low expression (under twofold) of 32 genes in lymph node metastasis compared with primary gastric carcinoma, respectively. CAII mRNA was downregulated and IGFBP 4 mRNA was upregulated in paired lymph node metastases of gastric carcinomas. The overexpression of CTTN protein was related to the lymph node metastasis and the clinical stage of gastric carcinomas. CONCLUSION: This study showed that there is a low expression of genes relative to growth signal and immune response in lymph node metastases, and a high expression of genes relative to growth factor, cell cycle, cell motility and adhesion in lymph node metastases compared with primary gastric carcinomas. The expression of CTTN was related to the invasion and metastasis of gastric cancer.     

Occult lymph node metastases detected by cytokeratin immunohistochemistry predict recurrence in “node-negative” colorectal cancer

There is controversy about the prognostic significance of occult lymph node metastases detected by immunohistochemistry with the anti-cytokeratin antibody CAM 5.2. The aim of this study was to characterize occult lymph node metastases in colorectal carcinomas that might be associated with a higher risk of recurrence. Three hundred fifty-eight lymph nodes from 10 recurrent and 9 nonrecurrent cases of colorectal carcinoma were examined. All these patients had been reported originally as having no lympho node metastases by routine hematoxylin and eosin staining. Three 10-μm sections or ten 3-μm sections (30-μm total thickness) from each lymph node were stained with CAM 5.2 and examined for the presence of occult lymph node metastases. Occult metastases were detected in 67 of 175 lymph nodes from the recurrent cases, and in 23 of 183 lymph nodes from the nonrecurrent cases. The frequency of positive nodes was significantly higher in the recurrent cases. The recurrent cases had metastases in nodes more distant from the main tumor than did the nonrecurrent cases. Detection of occult lymph node metastases with cytokeratin immunohistochemistry may make it possible to identify patients with a higher risk of recurrence after the removal of a primary colorectal tumor.     

Prognosis in synchronous colorectal carcinomas

The prognosis of synchronous colorectal carcinomas is a matter of controversy. 5-year survival rates are reported to be either better or worse in comparison with single carcinomas. In this study 736 cases with histologically proven malignancies oft the large intestine were reviewed. 22 patients (3 per cent) showed multiple primary tumors. Patients with multiple tumors had associated adenomas in 72 per cent vs 14 per cent of the patients with single cancers (P < 0.01). 77 per cent of the synchronous tumors were located in the left colon. Only in 5 patients (23 per cent) two different lymphatic drainage areas were involved. 15 patients (68 per cent) presented without lymph node or distant metastases. A radical procedure was performed in 82 per cent. The overall 5-year survival rate was 54.5 per cent for multiple and 44.5 per cent for single carcinomas. The better survival rate seems to be due to the higher rate of early detection because of rectal bleeding in patients with synchronous tumors.     

Verrucous acanthosis--so-called verrucous carcinoma--of the esophagus

Verrucous carcinoma of the esophagus is a rare variant of squamous cell carcinoma with a slow, non-invasive growth without formation of metastases. Until today, only 8 cases of verrucous carcinoma of the esophagus have been reported in the literature. All of these tumours showed infiltration of adjacent mediastinal structures or even lymph node metastases. In therefore seems doubtful, wether these tumours were really verrucous carcinomas rather than squamous cell carcinomas of the papillary type. Several authors have questioned the malignant nature of these tumors recently. We report a case of a verrucous lesion of the esophagus the course of which we were able to observe over a period of several years. Transhiatal esophagectomy without thoracotomy is recommended as treatment of choice for verrucous tumours of the esophagus.     

Occult lymph node metastases as a predictor of tumor relapse in patients with node-negative esophageal carcinoma

BACKGROUND & AIMS: Esophageal carcinoma is an aggressive disease with a very poor prognosis. Early tumor relapse after surgical resection in patients with node-negative esophageal carcinoma suggests that occult metastases may have been missed at the original pathologic examination. The aim of this study was to determine the prevalence of immunohistochemically detected occult lymph node microscopic metastases in patients with pathologic N0 esophageal carcinoma and the impact of these occult metastases on relapse-free survival. METHODS: All patients (n = 124) with pathologic N0 esophageal carcinoma undergoing resection at our institution between January, 1994, and October, 1998, constituted the study population. Esophagectomy specimens were reevaluated by immunohistochemistry (monoclonal antibody against cytokeratin AE1/AE3). Clinical and pathologic features were summarized, and patient relapse-free survival was estimated. RESULTS: Among the total of 124 patients, occult lymph node microscopic metastases were identified by immunohistochemistry in 14 patients (11%) (T1 mucosa, 4%; T1 submucosa, 6%; T2, 22%; and T3, 14%). Patients were followed for a median of 3.2 years. Relapse-free survival was not significantly associated with the presence of occult lymph node microscopic metastases as detected by immunohistochemistry (P = 0.12). Advanced T stage (T3; P < 0.001) and lymphovascular invasion (P < 0.001) were found to be associated with tumor relapse. CONCLUSIONS: In the present study, occult lymph node microscopic metastases in pathologic N0 esophageal carcinoma patients were less frequent than previously reported. T stage and lymphovascular invasion were significantly associated with relapse-free survival, although a significant association with occult lymph node metastases was not detected.     

Immunoexpression of cyclooxygenase-2 in primary gastric carcinomas and lymph node metastases

AIM: To evaluate immunoexpression of cyclooxygenase-2 (COX-2) in primary gastric carcinomas and respective lymph node metastases.METHODS: Immunohistochemistry to analyze COX-2 expression was performed on tissue microarray slices obtained from 36 specimens of gastrectomy and satellite lymph nodes from patients with gastric carcinoma.RESULTS: Immunostaining was seen in most cases, and COX-2 expression was higher in lymph node metastases than in corresponding primary gastric tumors of intestinal, diffuse and mixed carcinomas, with a statistically significant difference in the diffuse histotype (P = 0.0108).CONCLUSION: COX-2 immunoexpression occurs frequently in primary gastric carcinomas, but higher expression of this enzyme is observed in lymph node metastases of the diffuse histotype.     

Paraesophageal lymph node metastasis from prostatic adenocarcinoma in a patient with esophageal squamous carcinoma

SUMMARY. Esophageal squamous carcinomas induce regional immune suppression in the domain of the tumor while the global immune system remains intact. We report a patient with a squamous esophageal carcinoma, who was discovered at esophagectomy to have paraesophageal lymph node metastases from a prostatic adenocarcinoma. No other sites of metastatic disease were identified. This supports the concept that regional immune suppression by esophageal squamous cancers facilitates growth of metastases in the local lymph nodes.     

Endoscopic ultrasonography of the mediastinum in the diagnosis of bronchial carcinoma.

Thoracic computed tomography (CT) is an essential component in the preoperative staging of bronchial carcinomas as is mediastinoscopy (MSC) in cases of mediastinal lymphoma. It is known that endoscopic ultrasonography (EUS), as a new diagnostic procedure, can predict lymph-node involvement in cases of tumors in the upper gastrointestinal tract with an 80% probability. In a prospective study, we examined whether EUS could be used to ascertain the presence of mediastinal lymph nodes in cases of bronchial carcinoma. Since 1990, therefore, 32 patients with operable non-small-cell bronchial carcinoma have been examined with an Olympus-Aloka EU-M2 or EU-M3 (frequency 7.5 and 12 MHz) in addition to routine diagnostics. The graded cross-sections of lymph-node dissections obtained during subsequent surgery served as evidence as to the true or false prognosis of the lymph-node status. Endoscopic ultrasonography identifies the presence and estimates the size of subcarinal, tracheobronchial, paraortal and paraesophageal lymph nodes better than computed tomography. Lymph nodes lying behind organs containing air (pretracheal lymph nodes) cannot be identified by ultrasonography. Lymph-node involvement was correctly identified by EUS in 72% of the cases, and the specificity was 86%. The poor sensitivity, at 67%, is explained by the high proportion (37%) of patients with anthracosilicosis, as the latter produces the same echo pattern as malignant infiltration. In 47% of all the cases, CT showed enlarged mediastinal lymph nodes which were not actually infiltrated in 67%. Of these lymph nodes, 33% could be classified as definitely free of metastases on the strength of their echo pattern, the rest were inflamed or really infiltrated by metastases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Seven synchronous early gastric cancer with 28 lymph nodes metastasis

An 85 year male patient complaining epigastric discomfort was admitted.From the esophagogastroduodenoscopy,three early gastric cancer(EGCa)lesions had been identified and these were diagnosed as adenocarcinoma with poorly differentiated cell type.The patient underwent operation.From the post-operative mapping,however,additional 4 EGCa lesions were found,and the patient was diagnosed with 7 synchronous EGCa.Out of the 7 EGCa lesions,6 had shown invasion only to the mucosal layer and one had shown invasion into the 1/3layer of submucosa.In spite of such superficial invasions,28 of 48 lymph nodes had been identified as metastases.The multiple lesions of EGCa do not increase the risk of lymph node metastasis,but if their differentiations are poor or if they have lympho-vascular invasion,multiple lymph node metastases could incur even if the depth of invasion is limited to the mucosal layer or the upper portion of the submucosal layer.     

No correlation between BRAFV600E mutation and clinicopathological features of papillary thyroid carcinomas in Taiwan

OBJECTIVE: Genetic alterations in four oncogenes, namely RAS point mutations, RET rearrangements (RET/PTC), NTRK1 rearrangements (TRK) and BRAF point mutations have been identified in human papillary thyroid carcinomas (PTCs). These oncogenes act along the RET/PTC(TRK)-RAS-BRAF-MEK-MAPK kinase pathway, mediating a number of cellular fates including growth, proliferation and survival in thyroid cells. In this study, we analysed mutations of BRAF in a cohort of PTCs. METHODS: To screen for BRAF mutations, the genomic DNA of 105 PTCs were amplified by polymerase chain reaction (PCR) with primers flanking exon 15 and PCR products were directly sequenced with an automatic sequencer. These results, together with data from our previous studies on RAS, RET rearrangements and NTRK1 rearrangements in the same tumours, were compared to determine their individual significance in the pathogenesis of PTCs in Taiwan. RESULTS: BRAF mutations were detected in 49 of 105 (47%) tumour samples. All mutations involved a thymine-to-adenine transversion at nucleotide 1799 and were heterozygous. There was no overlap between papillary carcinomas harbouring RET rearrangements, NTRK1 rearrangements and BRAF mutations. In this cohort, correlation between BRAF mutations and various clinicopathological parameters in 101 papillary carcinomas did not reveal any association with age at diagnosis, sex, tumour size, histological variants of PTC, multicentricity, cervical lymph node metastases, extrathyroidal invasion, distant metastases and clinical stage. CONCLUSIONS: BRAFV600E mutation is the most prevalent oncogene in PTCs in Taiwan. Our data did not suggest that BRAFV600E mutation could be a potentially useful marker of prognosis in patients with papillary carcinomas in the population studied.     

Adenocarcinoid of the appendix presenting with metastases to the liver

A case of hepatomegalia due to multiple metastases of unknown origin to the liver is described. At autopsy the primary tumor, an adenocarcinoid tumor of the appendix, was identified along with multiple metastases to the lymph nodes and widespread peritoneal carcinoidosis. Hepatic metastases from an appendiceal adenocarcinoid tumor has not been described previously. In the liver and lymph nodes the tumor had an insular growth pattern and was composed predominantly of cells of carcinoid type, whereas the carcinoidosis was composed almost entirely of signet-ring cells. It is suggested that differentiation of the metastases of appendiceal adenocarcinoids is modulated by factors in the recipient organ.     

Human papillomavirus involvement in esophageal carcinogenesis in the high-incidence area of China. A study of 700 cases by screening and type-specific in situ hybridization

BACKGROUND: Human papillomavirus (HPV) DNA has been identified in esophageal precancerous lesions and carcinomas. However, there are marked variations in the prevalence of HPV infection reported in different studies. Most previous studies on HPV and esophageal carcinomas have been based on a limited number of biopsy samples studied by different HPV detection methods with highly variable sensitivity and specificity, making systematic studies of larger series clearly warranted. METHODS: A series of 1876 surgical specimens (primary tumor, adjacent epithelium, regional lymph nodes, resection margins) from 700 patients surgically resected for an invasive squamous cell carcinoma of the esophagus in the high-incidence area of China was analyzed for the presence of HPV DNA with screening in situ hybridization (ISH) using biotinylated HPV DNA probes and followed by type-specific ISH for HPV 6, 11, 16, 18, 30, and 53. RESULTS: Of the 700 esophageal carcinomas, 118 (16.9%) were shown to contain HPV DNA sequences by screening ISH. Positive signals were most frequent in the cancer cells (16.6%), more rare in the surrounding hyperplastic and dysplastic epithelia (5.6%), and infrequently present in the resection margins (0.2%). HPV signals were also detected in cancer cells in 6.9% of the lymph node metastases. HPV types 6, 11, 16, 18, and 30 account for 39.8% of the HPV-positive lesions, of which the high-risk types HPV 16 and 18 were present in 27.1% (32 of 118). Notably, 60.2% of the HPV-positive lesions contained DNA sequences other than HPV types 6, 11, 16, 18, 30, and 53. CONCLUSIONS: This study reports the largest series of esophageal cancers ever analyzed for the presence of HPV DNA. Our results confirm the presence of common mucosal HPV types in esophageal carcinomas but also suggest the involvement of other (novel?) HPV types that are unusually detected in genital cancers in a significant proportion of these lesions. The results further indicate that HVP has an etiologic role in esophageal carcinogenesis, at least in the high-incidence area of northern China.     

Characteristics of variants of colorectal carcinoma that do not metastasize to lymph nodes

Summary The clinical and pathologic characteristics of colorectal carcinomas that did not metastasize to mesenteric lymph nodes have been compared with the same characteristics of carcinomas that did metastasize to lymph nodes by computer-programmed analysis of significant differences in 420 cancers in the first group and 344 cancers in the second group. Characteristics associated with an increased probability of metastasis to lymph nodes included the past or present association of skin cancers, the existence of metastases outside the field of resection, and the characteristics of the cancer margins (greater stromal and vascular infiltration by cancer and less inflammatory cell infiltration). Factors associated with a decreased likelihood of metastasis to lymph nodes included favorable characteristics of the cancer margins (“pushing” or circumscribed margin and denser infiltration of inflammatory cells), deep local extension through the bowel wall into mesenteric fat and adjacent organs, and absence of distant metastases. The nonmetastasizing variants were found among tumors of all sizes and histologic grades. Further studies of the individual characteristics of both cancers and hosts are necessary for development of an infallible method of identifying tumors that have not metastasized. Such a method could permit the use of localized ablation more frequently. Read at the meeting of the American Proctologic Society, Boston, Massachusetts, June 16 to 18, 1969. Supported in part by USPHS Grants CA-09741 and CA-08023.     

Prognostic implication of isolated tumor cells and micrometastases in regional lymph nodes of gastric cancer

AIM: To determine the prognostic significance of isolated tumor cells (ITCs) and lymph node micrometastases in gastric cancer. METHODS: Hematoxylin and eosin-stained slides of lymph node dissections of 632 consecutive gastric cancers were reviewed. Cytokeratin immunostaining was performed in 280 node-negative cases and 5 cases indefinite for lymph node metastases. Lymph node metastases were divided into ITCs, micrometastases, or macrometastases, according to the sizes of tumor deposits in largest dimension. ITCs were further classified into four groups according to metastasis pattern. RESULTS: Lymph node metastases were identified by immunostaining in 58 of 280 node-negative cases (20.7%) and were not significantly associated with patient survival (P- 0.3460). After cytokeratin immunostaining, 196 cases were classified as pN1, which consisted of 20 cases with micrometastases detected by immunostaining (pNlmi(i+)), 34 cases with only micrometastases (pN1mi),and 142 cases with pN1 with one or more macrometastases (pN1). Cases with pNlmi and pNlmi(i+) had a significantly better prognosis than the cases with pNl (P = 0.0037). ITCs were found in 38 of these 58 cases, and could be divided into four groups: 12 cases with only a single cell pattern, 7 cases with multiple individual cells, 5 cases with single small cluster, and 14 cases with multiple small clusters. Among these four groups, cases with ITCs of multiple individual cell pattern showed the worst survival (median survival: 28 mo, P<0.0001). CONCLUSION: Both size and pattern of lymph node metastases can give prognostic information on the survival of gastric cancer patients.     

Distal intramural spread of rectal carcinomas

Forty-three consecutive specimens of resected rectal carcinomas, 16 abdominoperineal and 27 anterior resections, were examined for distal intramural spread. Thirty-four of the resections were considered curative and nine palliative. Eighteen carcinomas (42 percent) showed no distal spread, and 14 (33 percent) showed very limited distal spread (0–5 mm). In the remaining cases, 11 (25 percent) had distal spread of more than 5 mm and eight of more than 10 mm. The eight carcinomas with distal spread of greater than 10 mm were advanced Dukes' C tumors. Only three were considered curable. All potentially curable carcinomas would have been resected adequately with a distal margin of only 1.5 cm except one signet-ring carcinoma with extensive lymph node metastases located in the lower rectum.     

Hepatoid adenocarcinoma of the stomach: report of five cases and review of the literature

We report on a rare hepatoid adenocarcinoma of the stomach producing alpha-fetoprotein (AFP) in five cases. Definitive features included an aggressive, invasive, and rapidly progressing neoplasm showing areas morphologically comparable to those of hepatocellular carcinomas. All patients had multiple metastases to lymph nodes and/or liver. The serum AFP level of the patients was between 83-87.900 ng/ml. Two subtotal and one palliative gastrectomy was performed. A short duration of chemotherapy was administered only in two patients. The length of survival averaged 4.7 months. Our experience together with what has been reported in literature suggest that the course of hepatoid adenocarcinoma of the stomach is more aggressive than an ordinary adenocarcinoma and that from a diagnostic point of view distinction from an adenocarcinoma may be accomplished histochemically and by measuring serum AFP levels.     

Carcinoma and dysplastic lesions of the prostate. A histomorphological analysis of 50 total prostatectomies by step-section technique.

50 prostate carcinomas which were totally prostatectomized together with removal of the seminal vesicles in all cases and pelvic lymphadenectomy in 38 cases were studied histologically. The material was cut by step-section technique in 5 mm thick slices and "large area slides" were made. 4 of the 50 carcinomas were morphologically circumscribed (stage I), 6 tumors were limited to the organ (stage II) and 40 prostate carcinomas had already penetrated the capsule, i.e. fascia of Denonvillier (stage III). In 12 cases the seminal vesicles were involved, regional lymph node metastases were seen 8 times. The carcinomas were mainly localized in the peripheral part of the organ (28 X in the periphery, 21 X both peripherally and centrally and only 1 X in the centre). Multifocal tumor growth was found in 30 cases (60%). The main mass of tumor was mostly situated in the middle (25 X) and caudal (15 X) zone of the prostate. During the course of tumor growth the expansion was directed centrally but then mainly longitudinal and parallel to the urethra. By progressing tumor volume there was a noticeable increase in capsular penetration as well as infiltration of the seminal vesicles and lymph node metastases. Histologically 10 carcinomas showed a uniform pattern, a unique solid and/or cribriform tumor architecture was never observed. 90% of the pluriform carcinomas consisted of the morphological stage III.     

结肠多原发癌合并甲状腺癌肺转移一例

随着肿瘤治疗手段的不断改进,肿瘤患者生存时间明显延长,随之而来的第二原发肿瘤的发生率也在增加。双重癌因原发部位及生物学行为不同,治疗的方法和顺序也不尽相同,目前暂无标准治疗模式。本病例为结肠多原发癌合并甲状腺癌肺转移,通过多学科诊疗团队制定个体化治疗方案,在保证患者生活质量的前提下,延长了生存时间。现将该病例诊断和治疗过程中的体会与大家分享。     

Lymph node metastasis as a significant prognostic factor in gastric cancer: a multiple logistic regression analysis

BACKGROUND: In Japan, the standard treatment policy for all potentially curable patients with gastric cancer is radical resection including extensive lymphadenectomy. This treatment strategy has been used for both early and advanced gastric cancers, and substantial increases in survival time have been reported. In advanced gastric cancer, lymphatic spread is reported to be one of the most relevant prognostic factors for gastric cancer resected for cure. The purpose of this study was to determine the factors affecting lymph node involvement and to establish guidelines for the extent of lymph node dissection most appropriate for the treatment of gastric cancer. METHODS: The clinicopathological features of 926 patients with gastric cancer were reviewed. Information on the clinicopathological features was obtained from the database of gastric cancer at the Department of Gastroenterological Surgery, Sendai National Hospital. Univariate and multivariate analyses of data for patients with gastric cancer tumors were performed to evaluate the prognostic significance of clinicopathological features. The independent risk factors influencing lymph node metastasis were determined by multiple logistic regression analysis. RESULTS: The following clinicopathologic factors were found to be correlated with prognosis of gastric cancer: (1) macroscopic type, (2) depth of invasion, (3) cancer-stromal relationship, (4) histological growth pattern, (5) lymph node involvement, (6) lymphatic invasion, (7) vascular invasion and (8) tumor site. However, a multivariate analysis revealed that macroscopic type, depth of invasion, lymph node involvement and tumor site are independent risk factors for the prognosis of gastric cancer patients. Among these factors, the prognosis of patients with gastric cancer was most strongly influenced by lymph node involvement (odds ratio, 4.632). According to a multiple logistic regression model, depth of cancer invasion and lymphatic invasion was significantly correlated with lymph node metastases. CONCLUSIONS: Lymph node involvement has the strongest influence on the prognosis of gastric cancer. Among the clinicopathological factors, depth of invasion and microscopically lymphatic invasion are important factors in predicting lymph node metastases. Thus, the ability to perform gastrectomy with dissection of lymph nodes is a basic requirement for gastric cancer surgeons.