Development of a human herpesvirus 8-negative effusion-based lymphoma during treatment with dasatinib for chronic myeloid leukemia.

We present the case of an 85-year-old male patient diagnosed with human herpesvirus 8 (HHV8)-negative effusion-based lymphoma (EBL) that developed from long-lasting pleural effusion (PE) induced by dasatinib treatment for chronic myeloid leukemia (CML). After the onset of this disorder, dasatinib treatment was discontinued and drainage was performed to regress the effusion. The major molecular response (MMR) was thus lost. The patient did not tolerate nilotinib treatment, but bosutinib was successful in restoring MMR. During these clinical courses, the patient suffered from a recurrence of EBL, which was treated with rituximab-based chemotherapy. The PE sample just before the 3rd cycle of chemotherapy revealed the proliferation of CD57-positive T cells, along with the disappearance of lymphoma cells. Anti-tumor immunity may have been activated following the immunochemotherapy in the undisturbed immunological environment when both EBL and CML almost regressed. After four cycles of R-CVP therapy, the patient has been in remission for 16 months and no longer requires drainage.

Double pituitary neuroendocrine tumors in a patient with normal growth hormone level acromegaly: A case report and review of the literature.

Background: Acromegaly is a rare disease caused by growth hormone (GH) hypersecretion caused by a pituitary neuroendocrine tumor (PitNET). However, some acromegaly patients show normal GH levels, and they can be a pitfall in clinical diagnosis. Moreover, rarely, synchronous true double or multiple PitNETs are encountered. Moreover, these PitNETs increase the risk of a left lesion during surgical exploration. Case Description: The patient, who was a 73-year-old female, was referred to our hospital with a chief complaint of headache. Assessment of basal anterior pituitary function revealed a slightly high level of insulin-like growth factor-1 (IGF-1) (standard deviation, 2.4), and her physical findings exhibited mild acromegalic features. The endocrine evaluation confirmed acromegaly and magnetic resonance imaging (MRI) showed a macro PitNET with suprasellar extension. Endoscopic endonasal surgery (EES) was performed to remove the macro PitNET. Although postoperative MRI showed complete removal of the macro PitNET, endocrinological testing indicated no improvement in GH or IGF-1 excess. Pathological examination of the surgical specimen revealed a gonadotropic PitNET. Therefore, we repeated the MRI scan and found a micro PitNET in the thin left normal pituitary gland. A second EES was successfully performed to remove the micro PitNET completely, and both endocrinological and pathological examinations confirmed that the disease was cured. Conclusion: Diagnosing acromegaly with low GH levels requires close monitoring. Double PitNETs are relatively rare and can cause incomplete remission of functional PitNETs.

Transient atelectasis due to hilar lymph node swelling affected by lenalidomide-induced tumor flare reaction.

Tumor flare reaction (TFR) is a unique immune-mediated tumor recognition phenomenon presenting as rapid enlargement of the tumor, which mimics disease progression, developing in the early stage of treatment using immunomodulatory drugs or immune checkpoint inhibitors. A 59-year-old man with follicular lymphoma had residual tumor burden in the left hilar lymph nodes after R-CHOP therapy, and received lenalidomide and rituximab (R2) therapy. He developed respiratory distress on day 11 of R2 therapy. Chest X-ray and CT demonstrated left lung atelectasis due to left hilar lymph node swelling. We performed transbronchial lung biopsy on day 20 of R2 therapy. The biopsied left bronchus tissue exhibited extensive necrosis, which had a B-cell phenotype consistent with that of follicular lymphoma. Neither NK cells nor cytotoxic T cells were detected. It was unclear whether the immune effector cells disappeared at the time of transbronchial lung biopsy. Atelectasis in our patient improved by continuing R2 therapy beyond TFR.

Acquired amegakaryocytic thrombocytopenia after durvalumab administration.

Immune checkpoint inhibitors (ICIs), despite their ability to potentiate antitumor T-cell responses, may cause various immune-related adverse events. Most cases of thrombocytopenia induced by ICIs have revealed a pathophysiologic mechanism of immune thrombocytopenia with increased platelet destruction and preserved megakaryocytes. Acquired amegakaryocytic thrombocytopenic purpura (AATP) is an unusual disorder characterized by thrombocytopenia with markedly diminished bone marrow megakaryocytes in the presence of otherwise normal hematopoiesis. AATP caused by ICIs has not been reported on. Herein, we present the case of a 79-year-old man diagnosed with squamous cell carcinoma of the lung who developed AATP after two courses of durvalumab, a drug targeting programmed death-ligand 1. Two weeks after the second cycle, his platelet count decreased to 2.1 × 104/µL. After the patient underwent platelet transfusion, his platelet count increased to 8.1 × 104/µL the next day but subsequently decreased repeatedly even after the ICI was discontinued. Six weeks after the second cycle, he developed interstitial pneumonia and was administered prednisolone (50 mg/day). However, thrombocytopenia did not improve. Bone marrow biopsy showed scarce megakaryocytes (< 1 megakaryocyte/10 high-power fields) with preservation of myeloid and erythroid series. Myelodysplasia, myelofibrosis, or metastatic lesions were not observed. Cytogenetic analysis showed a normal male karyotype of 46XY. Hence, the patient received eltrombopag, a thrombopoietin receptor agonist, and his platelet count subsequently improved. After recovery, bone marrow aspiration revealed a normal number of megakaryocytes. AATP is rarely the type of thrombocytopenia induced by ICIs and may be successfully treated with thrombopoietin receptor agonists.

Airway Obstruction Caused by Substernal Thyrotoxic Multinodular Goiter.

BACKGROUND: Substernal thyrotoxic multinodular goiter (MNG) shows signs and symptoms as a result of compression of adjacent organs and thyrotoxicosis. However, acute airway obstruction is rarely caused by substernal thyrotoxic MNG. CASE REPORT: We have described a 56-year-old Japanese woman who demonstrated acute airway obstruction because of compression of the airway by substernal thyrotoxic MNG. She had been diagnosed with substernal thyrotoxic MNG 6 years back. However, because she was unwilling to undergo surgery to remove substernal thyrotoxic MNG, she was treated with methimazole. The patient maintained normal thyroid function with this therapy for 6 years. However, after 6 years the patient was admitted to our hospital because of severe dyspnea. Physical examination revealed inspiratory stridor, which indicated an airway obstruction caused by substernal thyrotoxic MNG. Airway intubation and subtotal thyroidectomy were performed. After the surgery, the dyspnea ameliorated. The general condition of the patient remained good 6 months after the surgery. CONCLUSION: This case clearly demonstrates the need for careful monitoring of substernal thyrotoxic MNG, because it may lead to an airway obstruction.

[A Case of Rectal Neuroendocrine Carcinoma with Metachronous Liver Metastasis Treated with Multimodality Therapy].

A 6 2-year-old woman visited our hospital with a complaint of anal bleeding and was diagnosed with rectal cancer. She underwent low anterior resection and D3 lymphadenectomy. The pathological diagnosis was shown as follows: Ra, Circ, type 2, por1, pSS, ly3, v1, pN2, pStage III b, and KRAS wild type. UFT/UZEL with polysaccharide K(PSK)was initiated as adjuvant chemotherapy after the operation. However, multiple liver metastases were found on CT after 3 courses of UFT/UZEL with PSK, and pathological reexamination revealed that the primary tumor was a neuroendocrine carcinoma. She underwent chemotherapy with CBDCA combined with CPT-11, but bone marrow suppression was observed after 4 courses of the treatment. As second-line chemotherapy, FOLFOX4 plus panitumumab(Pmab)was administered. Although the disease remained stable through 10 courses of FOLFOX4 plus Pmab, Grade 3 peripheral neuropathy was observed. Hence, FOLFIRI plus bevacizumab(Bmab)was administered as third-line chemotherapy. Twenty-eight courses of FOLFIRI plus Bmab were administered, and transcatheter arterial chemoembolization(TACE)was performed during chemotherapy. However, her general condition worsened after the therapies, and she died 2 years 3 months after the initial chemotherapy.

Clinicopathological significance of androgen receptor, HER2, Ki-67 and EGFR expressions in salivary duct carcinoma.

BACKGROUND: Salivary duct carcinoma (SDC) is a highly aggressive disease which often metastasizes to distant sites, and there is no established standard therapy for this systemic disease. Given that SDC is biologically similar to breast and prostate cancer, anti-androgenic receptor (AR) and anti-human epidermal growth factor receptor 2 (HER2) therapies have the potential to exert effects, not only on patients with breast and prostate cancer but also on those with SDC. METHODS: The expression levels of HER2, epidermal growth factor receptor (EGFR), Ki-67, and AR were assessed in 32 patients with SDC, and their correlations with overall survival (OS) and disease-free survival (DFS) were analyzed retrospectively. SDC was classified into five subtypes using a method similar to that used for breast cancer. RESULTS: Anti-AR, HER2, and EGFR were positive in 23 (71.9 %), 14 (43.8 %), and 26 (81.3 %) cases, respectively. One or more of these 3 factors were positive in 30 (93.8 %) cases. The Ki-67 labeling index was greater than 15 % in all cases. While molecular status did not correlate with OS, EGFR and AR positivity were significantly associated with DFS in univariate analysis. Multivariate analysis revealed that EGFR was the only independent predictor of DFS. CONCLUSIONS: The statuses of some molecules are useful to predict DFS in patients with SDC. Ki-67 overexpression suggests that cytotoxic agents are effective for SDC. Since the majority of SDCs express AR, HER2, and/or EGFR, assessing and targeting these molecules are promising strategies to improve the prognosis of unresectable, metastatic or recurrent SDC, and a classification system according to the molecular expression status may be useful to select appropriate therapy.

The current status of tailor-made medicine with molecular biomarkers for patients with clear cell renal cell carcinoma.

Appropriate use of multiple reliable molecular biomarkers in the right context will play a role in tailormade medicine of clear cell renal cell carcinoma (RCC) patients in the future. A total of 11,056 patients from 53 studies were included in this review. The article numbers of the each evidence levels, using the grading system defined by the Oxford Centre for Evidence-based Medicine, in 1b, 2a, 2b, and 3b were 5 (9%), 18 (34%), 29 (55%), and 1 (2%), respectively. The main goal of using biomarkers is to refine predictions of tumor progression, pharmacotherapy responsiveness, and cancer-specific and/or overall survival. Currently, carbonic anhydrase (CA9) and vascular endothelial growth factor (VEGF) in peripheral blood and p53 in tumor tissues are measured to predict metastasis, while VEGF-related proteins in peripheral blood are used to assess pharmacotherapy responsiveness with sunitinib. Furthermore, interleukin 8, osteopontin, hepatocyte growth factor, and tissue inhibitors of metalloproteinases-1 in peripheral blood enable assessment of responsiveness to pazopanib treatment. Other reliable molecular biomarkers include von Hippel­Lindau gene alteration, hypoxia-inducible factor-1a, CA9, and survivin in tumor tissues and VEGF in peripheral blood for predicting cancer-specific survival. In the future, studies should undergo external validation for developing tailored management of clear cell RCC with molecular biomarkers, since individual institutional studies lack the generalization and consistency required to maintain accuracy among different patient series.

World's first telepathology experiments employing WINDS ultra-high-speed internet satellite, nicknamed "KIZUNA".

BACKGROUND: Recent advances in information technology have allowed the development of a telepathology system involving high-speed transfer of high-volume histological figures via fiber optic landlines. However, at present there are geographical limits to landlines. The Japan Aerospace Exploration Agency (JAXA) has developed the "Kizuna" ultra-high speed internet satellite and has pursued its various applications. In this study we experimented with telepathology in collaboration with JAXA using Kizuna. To measure the functionality of the Wideband InterNet working engineering test and Demonstration Satellite (WINDS) ultra-high speed internet satellite in remote pathological diagnosis and consultation, we examined the adequate data transfer speed and stability to conduct telepathology (both diagnosis and conferencing) with functionality, and ease similar or equal to telepathology using fiber-optic landlines. MATERIALS AND METHODS: We performed experiments for 2 years. In year 1, we tested the usability of the WINDS for telepathology with real-time video and virtual slide systems. These are state-of-the-art technologies requiring massive volumes of data transfer. In year 2, we tested the usability of the WINDS for three-way teleconferencing with virtual slides. Facilities in Iwate (northern Japan), Tokyo, and Okinawa were connected via the WINDS and voice conferenced while remotely examining and manipulating virtual slides. RESULTS: Network function parameters measured using ping and Iperf were within acceptable limits. However; stage movement, zoom, and conversation suffered a lag of approximately 0.8 s when using real-time video, and a delay of 60-90 s was experienced when accessing the first virtual slide in a session. No significant lag or inconvenience was experienced during diagnosis and conferencing, and the results were satisfactory. Our hypothesis was confirmed for both remote diagnosis using real-time video and virtual slide systems, and also for teleconferencing using virtual slide systems with voice functionality. CONCLUSIONS: Our results demonstrate the feasibility of ultra-high-speed internet satellite networks for use in telepathology. Because communications satellites have less geographical and infrastructural requirements than landlines, ultra-high-speed internet satellite telepathology represents a major step toward alleviating regional disparity in the quality of medical care.

Value of metastin receptor immunohistochemistry in predicting metastasis after radical nephrectomy for pT1 clear cell renal cell carcinoma.

KISS-1 is a metastasis-suppressor gene of human melanoma, and encodes metastin, which was identified as the ligand of a G-protein-coupled receptor (metastin receptor). The precursor protein is cleaved to 54 amino acids, which may be further truncated into carboxy-terminal fragments. Previous studies showed that lack of metastin receptor in clear cell renal cell carcinoma (RCC) is associated with tumor progression, but the prediction of metastasis in patients with pT1 clear cell RCC after radical nephrectomy is difficult. The objective of this study was to evaluate the usefulness of metastin receptor immunohistochemistry in predicting metastasis after nephrectomy for pT1 clear cell RCC. After verification of the correlation between immunostaining and mRNA expression, we evaluated the clinical value of metastin receptor immunohistochemistry. Fifty-four patients were enrolled in this study; following radical nephrectomy, seven patients were found to have lung metastasis. The sensitivity, specificity, positive predictive value, and negative predictive value with negative immunostaining of metastin receptor were 85.7, 97.6, 46.2, and 97.6 %, respectively. Metastasis-free survival rates were significantly higher in patients with positive staining (97.6 %) than in patients with negative staining (53.8 %) (P < 0.001). In univariate analysis for metastasis-free survival, negative immunostaining of metastin receptor was a significant risk factor for metastasis (P = 0.001). Furthermore, negative immunostaining of metastin receptor was an independent predictor for metastasis in multivariate analysis (hazard ratio, 3.735; 95 % CI 0.629-22.174; P = 0.002). In conclusion, our study suggests that negative expression of metastin receptor in clear cell RCC is significantly related to metastasis.

Utility of preoperative chemoradiotherapy for advanced esophageal carcinoma.

BACKGROUND AND AIMS: The most effective treatment would be neoadjuvant chemoradiotherapy (NACRT) plus surgery with three-field lymphadenectomy, if tolerability and complications are acceptable. The aim of this prospective study was to evaluate the tolerability of NACRT+ systematic three-field lymphadenectomy. METHODS: A total of 127 cases of advanced esophageal carcinoma were objected, among which 32 had NACRT, being the cases suspected to cT3-T4 or, < cT3 with multiple lymph node metastasis. ≥ T2 of 95 cases were treated by surgery alone (NACRT [-] case). The effect of NACRT was evaluated by histological examination and corrected with the clinicopathologic factors, including postoperative prognosis. After reports JCOG9907, we treated eight cases with neoadjuvant chemotherapy at stages II and III. We examined Musashi-1 staining for these eight cases. RESULTS: Histological good response to NACRT group showed good prognosis. Lymph node metastasis is a predictive factor for prognosis. In this additional study, Musashi-1 was positive after neoadjuvant chemotherapy in three cases. The histological response was grade 1 in all of them and recurrence was observed within a short period of time. Two cases of grade 3 were negative staining to Musashi-1 and showed no recurrence. CONCLUSIONS: This study shows that NACRT plus surgery with three-field lymphadenectomy is a feasible therapeutic approach for the cases with multiple lymph node metastases. Prognosis was significantly better in cases with marked histological improvement. It is important to find the predictive factors of histological improvement. Musashi-1 might be a candidate maker for histological response and prognosis, and further studies are needed to prove it.

[Two cases of ileocecal carcinoid found by total colonoscopy and a review of the literature on 16 cases].

We report 2 cases of ileocecal carcinoid with review of the literature recently reported in Japan. Both cases were diagnosed as carcinoid by colonoscopic biopsy after ileocecal tumors had been pointed out by computed tomography. We performed curative operation with lymph node dissection. Since multiple lymph node metastases were shown in both cases pathologically, they were closely followed after surgery, but no recurrence has been shown. Since SSTR2a stain was strongly positive in both cases, octreotide, the effectiveness of which was verified in the PROMID study might be administered if necessary. As ileocecal carcinoid has a tendency to metastasize to other organs, careful surveillance by colonoscopy and early detection are required. Furthermore, development of effective drugs following octreotide and further investigation including biological and histopathological analysis of neuroendocrine tumors including carcinoid are necessary.

Neuroendocrine carcinoma of the stomach: a case study.

Gastric neuroendocrine carcinomas are rare and have a poor prognosis, and the diagnostic criteria for this disease have recently changed. We herein report a case of sporadic gastric neuroendocrine carcinoma. A 75-year-old man was referred to our hospital with epigastric pain. Endoscopic examination revealed a localized ulcerative lesion (diameter, 4 cm) at the upper stomach. The diagnosis on biopsy was neuroendocrine carcinoma. Total gastrectomy with D2 lymphadenectomy, splenectomy, and cholecystectomy was performed. Pathologically, the tumor infiltrated the subserosal layer, and 6/49 lymph nodes were involved. The tumor was uniform in shape and arranged in a rosette-like structure to form solid nests, with medium-sized, round-to-cuboid-shaped tumor cells and intense mitosis 46/10 HPF. It was positive for synaptophysin and chromogranin A, and the Ki-67 labeling index was 70-80%. The diagnosis of neuroendocrine carcinoma was made according to the WHO 2010 criteria. The patient was followed up for three years without recurrence.

Multiple endocrine neoplasia type 1-associated thyrotropin-producing pituitary carcinoma: report of a probable de novo example.

Pituitary carcinomas are exceedingly rare. At present, the sole diagnostic criterion is metastatic spread, either craniospinal or systemic. There is no agreement on a histologic, immunohistochemical, and/or ultrastructural definition. We report a clinically and morphologically well-documented example of pituitary thyrotropin cell carcinoma in a man with multiple endocrine neoplasia type 1 syndrome. The tumor produced thyrotropin, alpha-subunit, and prolactin and, through electron microscopy, was found to consist solely of Thyrotroph cells. Over a protracted course, craniospinal and systemic metastases were noted. The primary and metastatic deposits of this aggressive tumor were studied. To our knowledge, this tumor is the first reported case of thyrotropin cell carcinoma occurring in association with the multiple endocrine neoplasia type 1 syndrome. The literature regarding thyrotropin carcinomas is reviewed. Based on the study of several biopsies during disease progression, we believe that the carcinoma originated de novo without an intermediary adenoma phase.

[Trends in gastroenteropancreatic neuroendocrine tumors].

Carcinoids were first reported approximately 100 years ago and proposed to be neuroendocrine tumors of hormonal origin some 50 years later. The first edition of the WHO classification included neuroendocrine tumors of the digestive organs and pancreas, but thereafter it was pointed that neuroendocrine cells are distributed throughout the body and thus that carcinoids occur in various other organs. The most recent edition of the WHO classification takes into account the occurrence of neuroendocrine tumors throughout the body. In addition, carcinoids were originally thought to be variants of a benign tumor type with a low malignancy rate, but thereafter metastases were observed. The term "neuroendocrine tumors" is now preferred instead of "carcinoids," and the malignant potential of such tumors is recognized. This paper reviews the classification and treatment of gastroenteropancreatic neuroendocrine tumors.

Preliminary results of a Japanese nationwide survey of neuroendocrine gastrointestinal tumors.

BACKGROUND: We conducted a nationwide survey to estimate the incidence of neuroendocrine gastrointestinal tumors (NETs) newly diagnosed in Japan from 2002 through 2004. METHODS: Data on 1541 patients, 514 pancreatic endocrine tumors (PETs) and 1027 gastrointestinal carcinoids (GICs), were collected and analyzed. RESULTS: Nonfunctioning tumors (NF-PET) constituted 47.7% of PETs. Next in frequency were insulinoma (31.7%) and gastrinoma (8.6%). Malignancy was frequent in NF-PETs (46.1%) and gastrinomas (45.5%), but only 7.4% of insulinomas were malignant. The incidence of multiple endocrine neoplasia type-1 associated with PETs was 7.4%. The incidence of GICs was 28.8%, 5.2%, and 66.0% in foregut, midgut, and hindgut, respectively. Carcinoid syndrome and metastases were observed in only 1.7% and 5.6% of GICs, respectively. CONCLUSIONS: The incidence of NETs in Japan was clarified by this preliminary study. Comparatively large differences in GICs between Japan and Western nations were present with regard to the location, symptomatic status, and prevalence of malignancy.

The pituitary function of androgen receptor constitutes a glucocorticoid production circuit.

Androgen receptor (AR) mediates diverse androgen actions, particularly reproductive processes in males and females. AR-mediated androgen signaling is considered to also control metabolic processes; however, the molecular basis remains elusive. In the present study, we explored the molecular mechanism of late-onset obesity in male AR null mutant (ARKO) mice. We determined that the obesity was caused by a hypercorticoid state. The negative feedback system regulating glucocorticoid production was impaired in ARKO mice. Male and female ARKO mice exhibited hypertrophic adrenal glands and glucocorticoid overproduction, presumably due to high levels of adrenal corticotropic hormone. The pituitary glands of the ARKO males had increased expression of proopiomelanocortin and decreased expression of the glucocorticoid receptor (GR). There were no overt structural abnormalities and no alteration in the distribution of cell types in the pituitaries of male ARKO mice. Additionally, there was normal production of the other hormones within the glucocorticoid feedback system in both the pituitary and hypothalamus. In a cell line derived from pituitary glands, GR expression was under the positive control of the activated AR. Thus, this study suggests that the activated AR supports the negative feedback regulation of glucocorticoid production via up-regulation of GR expression in the pituitary gland.

Demonstration of chimeric DNA of bcl-2 and immunoglobulin heavy chain in follicular lymphoma and subsequent Hodgkin lymphoma from the same patient.

We performed single cell polymerase chain reaction (PCR) amplification of the t (14 ; 18) translocation from paraffin embedded sections in a case of follicular lymphoma (FL) with subsequent development of Hodgkin lymphoma (HL). The lymphoma cells of FL were positive for CD20, CD10 and BCL-2, and negative for CD3, CD30 and CD15. Hodgkin and Reed-Sternberg (HRS) cells of HL were positive for CD20, CD30 and CD15, and negative for CD3 and CD10. EBER-1 RNA in situ hybridization failed to stain with both lymphomas. HRS cells manipulated and FL cells micro-shaved from individual neoplastic follicles were subjected to single-cell PCR. The t (14 ; 18) translocation, a chimeric DNA containing portions of the bcl-2 and the immunoglobulin heavy chain (IgH) genes, was amplified from four of 27 isolated HRS cells and two individual FL follicles. All t (14 ; 18) PCRs yielded products of the same size, and an identical nucleotide sequence including the t (14 ; 18) translocation was found in both FL and HRS samples. Thus, the data demonstrate the common clonal origin of FL cells and HRS cells in subsequent HL, and that both FL and HL were derived from germinal center B cells with the t (14 ; 18) translocation.

Acceleration of the proliferative activity of esophageal carcinoma with invasion beyond the muscularis mucosae; immunohistochemical analysis using MIB-1 for the Ki-67 antigen.

Squamous cell carcinoma of the esophagus with cancer invasion beyond the muscularis mucosae is known to have lymph node metastasis and lymphatic or blood vessel invasion compared with intramucosal carcinoma. In submucosal and T2-3 carcinoma, lymph node and lymphatic/vascular involvement are shown more frequently, leading to a poor prognosis. Therefore, we examined proliferative activity of esophageal squamous cell carcinoma including early carcinoma in relation to clinicopathological findings. 77 cases of esophageal squamous cell carcinoma, including 23 cases of mucosal carcinoma (Tis+T1a), 35 cases of submucosal carcinoma (T1b) and 19 cases of advanced invasive carcinoma (T2+T3) undergoing surgical resection without preoperative treatment were studied using monoclonal antibody MIB-1 for Ki-67 antigen immunohistochemically, and the labeling index (LI) was calculated. The LI of MIB-1 positive nuclei correlated with the depth of cancer invasion was significantly increased in the cancer invading beyond the musculais mucosae. The LI at the invasive tip was significantly higher than that at the core of differentiated carcinoma. The LI values at both invasive tip and core of poorly differentiated carcinoma were higher than those of differentiated carcinoma with significant difference. The LI at the invasive tip of the carcinoma with lymph node metastasis or lymphatic invasion was significantly higher than that without them. Proliferative activities of esophageal cancer cell, immunostaining with MIB-1, had correlations to depth of tumor invasion, differentiation, lymph node metastasis and lymphatic invasion with significant difference. But if invading deeper than m3, the proliferative activity did not increase anymore.

Ovarian carcinomas with neuroendocrine differentiation: Review of five cases referring to immunohistochemical characterization.

AIM: To review five ovarian carcinomas with varying degrees of neuroendocrine differentiation (ND) using an immunohistochemical study focused on the relationship with morphological features. METHODS: ND was immunohistochemically analyzed using 21 antibodies by an indirect immunoperoxidase method, and ploidy pattern was analyzed using paraffin sections. RESULTS: The tumors were divided according to tumor cell size into 'small-sized' for case 1, 'intermediate-sized' for cases 2 and 3, and 'large-sized' for cases 4 and 5. Expressions of neuroendocrine markers and argyrophil reaction tended to be strengthened as tumor cell size increased. Cases 1, 2 and 3 showed diploid pattern and cases 4 and 5 showed aneuploid pattern. CONCLUSION: ND of ovarian carcinomas is closely related to morphological features represented by the cell size. Therefore, ovarian carcinomas with ND should be defined because the disease entity is not successfully integrated irrespective of the highly malignant potential.