[A Case of Sigmoid Colon Cancer with Liver Metastasis and Gastric Infiltration for Which Ileus Surgery Was the Impetus for Surgery].

The case is a woman in her 60s. Sigmoid colon cancer surgery, liver metastasis surgery, and adjuvant chemotherapy were performed at another hospital 2 years ago. Later, she developed a metastasis in her liver and was recommended surgery, but she refused treatment and was transferred. Her liver metastasis had invaded the stomach and formed a giant gastric ulcer. This time she had an adhesive ileus and underwent laparoscopic surgery at our hospital. At that time, we observed the state of liver metastasis and gastric infiltration by laparoscopy, so we thought that palliative surgery was possible and recommended it. Although she initially refused treatment, the relative ease with which her ileus surgery was performed encouraged her to undergo palliative surgery. Laparoscopic-assisted gastrectomy and partial hepatectomy were performed, and she was discharged on hospital day 13 after surgery. She subsequently developed liver metastases and died 8 months after palliative surgery, although she was able to eat and maintain her ADL until the end of life. By staying close to the patient, we were able to lead the patient from refusal of surgery to palliative surgery, and we felt that we were able to make the patient reach a favorable end.

RBM10-TFE3 renal cell carcinoma characterised by paracentric inversion with consistent closely split signals in break-apart fluorescence in-situ hybridisation: study of 10 cases and a literature review.

AIMS: Xp11 rearrangement in renal cell carcinoma (RCC) typically involves gene fusion to the gene encoding transcription factor E3 (TFE3), a member of the microphthalmia-associated transcription factor family on chromosome Xp11.2. Dual-colour break-apart fluorescence in-situ hybridisation (FISH) is recommended to confirm histological diagnoses. Recently, RNA-binding motif protein 10 (RBM10), encoded by a gene on chromosome Xp11.3, was identified as a chimeric partner of TFE3; thus, RBM10-TFE3 fusion results from paracentric inversion. RBM10-TFE3 RCC may yield a false-negative result in FISH analysis of TFE3 expression. The aim of the present study was to investigate the clinicopathological features of RBM10-TFE3 RCC. METHODS AND RESULTS: Ten patients with RBM10-TFE3 RCC aged 31-71 years were investigated. Histological analysis, immunostaining, dual-colour break-apart FISH for TFE3, reverse transcription polymerase chain reaction and sequencing analysis were performed. No patient had a history of exposure to chemotherapy. Two of these patients died of RCC, and three were alive but developed metastases. Microscopically, the tumours were composed of a mixed architecture of tubulocystic and papillary patterns with scattered psammoma bodies. The tumours showed strong nuclear immunoreactivity for TFE3. FISH showed consistent closely spaced split signals in the RCCs of four patients, and polysomic signals with occasional closely spaced split signals in the RCCs of six patients. Of the latter six patients, five had renal failure, and four developed tumours in kidneys subjected to haemodialysis. CONCLUSIONS: The present study suggests that the carcinogenesis of RBM10-TFE3 RCC in some, but not all, patients may be associated with chronic kidney disease. The aggressive nature of RBM10-TFE3 RCC should be considered, as five patients experienced metastases.

Cotyledonoid dissecting leiomyoma of the uterus: report of two cases.

BACKGROUND: Cotyledonoid dissecting leiomyoma (Sternberg tumor) is a rare variant of the uterine smooth muscle tumor. Although this tumor is a benign tumor clinically and pathologically, the appearance and growth pattern is unusual, so it may be misdiagnosed as malignancy. CASE REPORTS: We report two cases of cotyledonoid dissecting leiomyoma of the uterus that occurred in two 44- and 31-year-old women, respectively. Total hysterectomy and bilateral salpingo-oophorectomy were performed in one of the patients, and myomectomy was done in the other one. Macroscopically, both tumors were grape-like exophytic masses resembling placental tissue. The patients were well after surgery, and one patient gave birth. To our knowledge, this is the first case report of a successful delivery after myomectomy of this tumor. CONCLUSION: To prevent aggressive surgery it is important to recognize that this tumor is a benign and unusual appearing variant of leiomyoma. A fertility-sparing surgical procedure should be considered if the patient wishes to preserve her fertility.

Endometrioid adenocarcinoma arising from endometriosis of the rectosigmoid.

A case of endometrioid adenocarcinoma supposedly arising from endometriosis of the rectum is reported. Malignant transformation is uncommon but a well-known complication of endometriosis. In the present case, it was proved by histopathological findings and immunophenotype such as cytokeratin7+/cytokeratin20-/estrogen receptor+. The cause of rectal endometriosis in this case might have been related with previously received hormone replacement therapy for ovarian endometriosis. Following surgical removal of the lesion, this patient underwent adjuvant chemotherapy with paclitaxel and carboplatin, although this kind of therapy is still controversial as to its effectiveness.

[An autopsy case of alpha-fetoprotein-producing carcinoma of the sigmoid colon resulting in sudden death].

A 63-year-old woman was admitted to our hospital with complaints of abdominal distention and bilateral cervical masses. Her serum AFP was 11700 ng/dl. AFP was confirmed immunohistochemically by biopsy of a sigmoid colon tumor, yielding a diagnosis of AFP-producing carcinoma of the sigmoid colon, accompanied by multiple liver metastases, and systemic multiple lymph node metastases. Due to her poor general condition with mitral regurgitation, the patient began S-1 treatment. The patient's general condition rapidly worsened after 1 course of S-1 had no effect. She died on the 59th hospital day and a pathological autopsy was performed. We examined 67 cases of AFP-producing colon cancer in Japan, including our own, and report the findings with references.

Detection of Epstein-Barr virus-encoded small RNA-expressed myofibroblasts and IgG4-producing plasma cells in sclerosing angiomatoid nodular transformation of the spleen.

Sclerosing angiomatoid nodular transformation (SANT) of the spleen is a rare inflammatory tumor-like lesion composed of vascular nodules and non-neoplastic stroma including spindle cells and inflammatory cells. The focus of our study was on the stromal proliferating process in SANT. Nine cases of SANT were examined. All cases showed alpha-smooth muscle actin (alpha-SMA) and vimentin on the spindle cells but not CD21, CD31, CD34, CD68, desmin, S100, human herpes virus-8, or anaplastic lymphoma kinase-1. In one case, 20-30% of the myofibroblasts in Epstein-Barr-virus (EBV)-positive spindle cells were detected using double-labeling immunohistochemistry for alpha-SMA and EBV-encoded small RNA in situ hybridization. A quantitative analysis of IgG and IgG4-positive plasma cells (pPCs) in SANT was performed. The median densities of IgG-pPCs and IgG4-pPCs in SANT were approximately four-fold and 13-fold higher than those in the normal spleens, respectively. In addition, there was a statistically significant increase of IgG4/IgG-pPCs ratio in SANT in comparison to the control specimens. In conclusion, the fibrogenesis in a subset of SANT may be associated with EBV-infected myofibroblasts in an overlapping immune reaction indicated by the presence of infiltrating IgG4-pPCs. Further investigation is needed to elucidate the association between SANT and IgG4-related sclerosing disease.

[Two cases of gastrointestinal stromal tumor (GIST) of the stomach and a consideration of its malignancy potential and treatment strategy - report of two cases].

We report two cases of large gastrointestinal stromal tumor (GIST) of the stomach both of which were assessed as highly malignant, but took different clinical courses. Case 1: A 72-year-old male. Case 2: A 63-year-old female. The tumor size of Case 1 was suggestive of high malignancy, but only a partial gastrectomy was selected because it did not show any invasive findings. This patient has been followed up for 3 years post-operatively and no recurrence or metastasis has been noted. Case 2 had liver and lymph node metastases, which was consistent with high malignancy. We performed a total gastrectomy with distal pancreatosplenectomy and segmental liver resection. But after surgery, liver metastasis recurred therefore, imatinib mesylate was administered as adjuvant chemotherapy and since then, the tumor has been diminishing in size. No definitive evidence for adjuvant therapy has been established so far, but we suggest that post-operative adjuvant therapy is effective for high-risk GIST.

c-erbB-2 oncoprotein expression related to chemoradioresistance in esophageal squamous cell carcinoma.

PURPOSE: Esophageal carcinoma is a challenging target for radiotherapy. To improve treatment efficacy, an investigation of a predictive factor is desirable. In this study, we evaluated the significance of apoptosis and immunohistochemical staining for p53, Ki-67, c-erbB-2 (HER-2/neu), Ku (p70/p80), and DNA-PKcs for predictive markers of the responsiveness to chemoradiotherapy in esophageal squamous cell carcinoma. MATERIALS AND METHODS: This retrospective analysis consisted of 34 patients with esophageal squamous cell carcinoma in whom tumor biopsy was performed before treatment. They were divided into chemoradiosensitive (n = 13) and chemoradioresistant (n = 21) groups according to the tumor response evaluated at a total radiation dose of 40 Gy. The biopsy samples were examined with immunohistochemical staining for various factors and with an in situ nick end labeling method for apoptosis. The examined data were compared between the two groups. RESULTS: The difference in the Ki-67, p53, Ku (p70/p80), DNA-PKcs labeling indexes and the apoptosis index in tumor cells between the chemoradiosensitive and chemoradioresistant groups was not statistically significant. The expression of c-erbB-2 oncoprotein was statistically significant in the chemoradioresistant group (p = 0.02), although it did not correlate with survival. CONCLUSIONS: c-erbB-2 immunostaining is useful for the prediction of chemoradioresistance in esophageal squamous cell carcinoma.

Loss of heterozygosity analysis shows monoclonal evolution with frequent genetic progression and divergence in esophageal carcinosarcoma.

Carcinosarcoma (spindle cell carcinoma) of the esophagus is a rare neoplasm that shows squamous cell carcinoma (SCC) with a variable component of spindle cell sarcoma. Clinical and pathologic features of this neoplasm have been well documented, but the histogenesis has long been a matter of speculation and dispute. In an attempt to clarify the clonality and genetic relationships in the evolution of this neoplasm, we microdissected a total of 36 carcinomatous and sarcomatous foci from six esophageal carcinosarcoma (CS) and analyzed the allelic status with 25 microsatellite markers on chromosomal arms 3p, 5q, 6q, 8p, 9p, 11q, 13q, 17p, and 18q. In all cases, we found multiple and homogenous allelic losses in both the carcinomatous and sarcomatous components, strongly supporting the concept of monoclonal origin for this neoplasm. Homogeneous allelic losses were detected most frequently on 17p (5 cases), a chromosomal arm that included the p53 locus, followed by 3p, 11q, and 13q (3 cases); 9p (2 cases); and 8p and 18q (1 case). Moreover, five of the six cases showed additional or divergent allelic losses at more than one chromosomal locus at some of the microdissected foci, indicating genetic progression (2 cases) or genetic progression and divergence (3 cases). In four cases, the genetic changes indicated that an original clone of a pure SCC apparently acquired carcinosarcomatous or sarcomatous phenotype by successive genetic changes. On the other hand, we saw no evidence for tumors in which a sarcoma appeared to give rise to a carcinosarcomatous or carcinomatous subclone in the examined cases. In conclusion, our data support the concept that esophageal CS is derived from a single clone originating from a SCC. Furthermore, we showed genetic heterogeneity to accompany the phenotypic divergence, with patterns of genetic alterations that are consistent with both progression and divergence within individual tumors.

Adult-onset familial pulmonary fibrosis in Japanese brothers.

Two Japanese brothers were diagnosed in their 20s with familial pulmonary fibrosis, the pathological findings of which were consistent with usual interstitial pneumonia (UIP). However, an atypical characteristic was observed in the lungs of these brothers; 2-mm areas of 'honeycomb' were identified throughout the lungs, which is smaller than the generally observed 5-10 mm honeycombing seen in UIP. Fibroblastic foci were demonstrated in the second eldest brother, but not in the eldest, which indicates that the lungs of the eldest brother was in a more advanced stage of fibrosis. Their youngest brother and parents have no clinical evidence of pulmonary fibrosis. All five family members had low values for the diffusion capacity of the lung for carbon monoxide (DLCO), suggesting the presence of an inheritable disease and the existence of different phenotypes. The genomic DNA of the affected brothers was sequenced for the reported surfactant protein C (SP-C) gene mutations in patients with familial pulmonary fibrosis, but none was documented. It is necessary to clarify the presence of novel gene mutations of SP-C or other genes to explain these particular pathological findings and the low DLCO observed in this family.

[Pathology of intraductal papillary-mucinous tumor of the pancreas].

Many intraductal papillary-mucinous tumors (IPMTs) have been diagnosed with improvements in diagnostic imaging techniques. The histology of IPMT is various, including hyperplasia to invasive carcinoma. IPMTs are thought to occur multicentrically through the hyperplasia-adenoma-carcinoma sequence. IPMTs are characterized by genetic heterogeneity associated with histologic heterogeneity that may be due to slow growth and favorable prognosis. However, some IPMTs progress to invasive pancreatic cancer through malignant transformation with aggressive clonal progression. Thus some conventional pancreatic cancers may be derived from IPMTs. Although IPMTs and conventional pancreatic cancer initially occur in the ductal epithelium, they are thought to be totally different entities in terms of large or peripheral pancreatic duct origin, developmental style, genetic alterations, and prognosis. In future, differences and/or similarities will be discussed on the basis of molecular analyses of the carcinogensis of both tumors.

A Case of Malignant T-Cell Lymphoma of Gastric Origin Accompanied by Pyothorax.

The patient was a 74-year-old man suffering from tuberculotic chronic pyothorax. He had hematemesis in January 2006. Hb was 6.1 g/dl. A type 2 tumor 3 cm in diameter was found in the vaulted region on the greater curvature side. It was diagnosed as a malignant lymphoma. WBC and differential count were normal, and the patient tested negative for HTVL-1 antibody. sIL2-R was elevated to 1,500 U/ml. The superficial lymph nodes were not palpable. CT examination was not remarkable for the liver and spleen. There was no generalized lymph node enlargement. Based on these findings, a diagnosis of malignant lymphoma of gastric origin was made. As the patient had respiratory disorders, too, wedge-shaped gastrectomy was performed to inhibit invasion. Pathological examination revealed CD3 positive large atypical lymphocytes diffusely, EBV positive, HP negative. As a result, a diagnosis of non-Hodgkin T-cell lymphoma was made. The tumor did not return for 1 year and 8 months after surgery, but the patient died of sudden aggravation of respiratory disorders in September 2007. Pathological anatomy was performed. The gastric remnant was left with lymphoma, and the bone marrow and systemic lymph nodes were negative for a malignant lymphoma. The possibility of stomach metastasis from the preoperative pyothorax-related malignant lymphoma was considered, but was ruled out because the lungs were devoid of a malignant lymphoma. We report a case of an extremely rare malignant T-cell lymphoma of gastric origin.

Invasive ductal adenocarcinoma of the pancreas may originate from the larger pancreatic duct: a study of 13 tumors less than 2 cm in diameter.

BACKGROUND/PURPOSE: We aimed to elucidate the origin/primary site of invasive ductal adenocarcinoma of the pancreas, based on the distribution of intraductal carcinoma components. These components were identified by a mural elastic fiber cuff. METHODS: Thirteen specimens from patients with invasive ductal adenocarcinoma (microscopically, less than 2 cm in diameter) of the pancreas were studied histopathologically. Variants of invasive ductal adenocarcinoma and intraductal papillary-mucinous carcinoma were excluded. RESULTS: Intraductal carcinoma components of invasive ductal adenocarcinoma were found in 12 of the specimens 13 (92%), and were observed within the tumor mass and/or on its boundary, or outside the tumor mass. Intraductal components were characterized by low papillary projections lacking a fibrovascular core, with/without surrounding tubular structures, or by irregular stratification and pleomorphism of the epithelial cells. Invasive components mostly showed a tubular pattern with desmoplasia. The distribution of the intraductal components in the 12 specimens was as follows: in 9 (75%), they were in both the main pancreatic duct and large branch ducts; and in 3, they were in the smaller branch ducts only. CONCLUSIONS: Invasive ductal adenocarcinomas of the pancreas may originate most frequently from the main pancreatic duct or larger branch ducts, while the smaller ducts are less often the site of cancer origin.

Different patterns of p16INK4A and p53 protein expressions in intraductal papillary-mucinous neoplasms and pancreatic intraepithelial neoplasia.

OBJECTIVES: To examine aberrations and differences of cell cycle regulatory proteins between intraductal papillary-mucinous neoplasms (IPMNs) and pancreatic intraepithelial neoplasias (PanINs). METHODS: In total, 47 IPMN lesions and 42 PanIN lesions were obtained from 26 patients with IPMN and 16 patients who underwent pancreatic surgery for invasive pancreatic ductal cancer or other diseases. They were subjected to conventional hematoxylin-eosin staining and immunostaining for p16INK4A and p53. The percentages of immunohistochemical positivity or negativity were compared between IPMN and PanIN, in accordance with the same histological grade of atypia. The Ki-67 labeling index was also counted in each lesion. RESULTS: Either the loss of p16INK4A expression or the overexpression of p53 was much more frequently observed among PanIN-3 than among carcinoma in situ in IPMN (P = 0.046 and 0.008, respectively). The Ki-67 labeling index was correlated with the histological grades of both PanINs and IPMNs (P = 0.0001 and P = 0.0001, respectively). CONCLUSIONS: There are different immunohistochemical expression patterns of p16INK4A and p53 between IPMNs and PanINs. These may substantiate their different genetic progressions to invasive carcinoma.

Intraductal low papillary histological pattern of carcinoma component shows intraductal spread in invasive carcinoma of the pancreas.

BACKGROUND/PURPOSE: We attempted to discriminate between carcinoma in situ (CIS) and the intraductal invasion/cancerization of invasive ductal carcinoma (IDC) of the pancreas, by comparing the histological patterns of the intraductal components and those of venous invasion. METHODS: Specimens from 30 patients with IDC were examined histopathologically. Intraductal components and blood vessel invasion in IDC were assessed in specimens stained with hematoxylin & eosin and elastica van Gieson (EVG). RESULTS: Intraductal components of IDC were found in 28 of the 30 cases of IDC, in 261 ducts, and in 2.3 ducts per one section of one case, on average. The intraductal components of IDC were classified into three histological patterns, as follows: low papillary (including flat), tubular (including solid and cribriform), and mixed (low papillary plus tubular). The incidences of the low papillary, tubular, and mixed patterns in the 261 ducts, were 39% (102 ducts), 56% (145 ducts), and 5% (14 ducts), respectively. The histological pattern of venous invasion was tubular in all but 1 of the 26 cases, and this 1 case showed low papillary patterns as well as a tubular pattern. CONCLUSIONS: A tubular pattern of intraductal components in IDC of the pancreas indicates intraductal invasion, while a low papillary pattern indicates CIS or carcinoma in another location to which it has spread.

Primary pleomorphic liposarcoma of bone: MRI findings and review of the literature.

Primary liposarcoma of bone is exceedingly rare. We report a case of primary pleomorphic liposarcoma in the humerus of a 38-year-old female. Radiographs demonstrated an expansile and osteolytic lesion extending from the head to the proximal part of the shaft in the right humerus. MR study showed a defined lesion in the humerus. The lesion had an iso-signal intensity and partial high-intensity lesion on T1-weighted images and a heterogeneous high signal intensity on T2-weighted images. Wide resection and proximal humeral endoprosthesis replacement were performed. Final pathological diagnosis of the lesion was pleomorphic liposarcoma. This is the second reported case of pleomorphic liposarcoma of the bone, and the first case presenting MRI findings for liposarcoma of bone.

Pancreatic, hepatic, splenic, and mesenteric mucinous cystic neoplasms (MCN) are lumped together as extra ovarian MCN.

Mucinous cystic neoplasms (MCN) of the pancreas are mucin-producing cystic tumors with an ovarian-like stroma (OLS). In the present study MCN were obtained from 27 patients. These MCN were derived from 22 pancreas, three livers, spleen, and mesentery. MCN in various organs have common clinicopathological profiles, being unilocular or multilocular cystic tumors, with a fibrous capsule and lined by mucin-secreting epithelium associated with an underlying subepithelial OLS. The OLS showed strong positivity for alpha-smooth muscle actin (alpha-SMA) and vimentin and weak, focal positivity for desmin. Both estrogen receptors and progesterone receptors were expressed in the nuclei of OLS cells. In addition, 20 ovarian MCN and 13 normal ovaries were studied with particular attention to the stroma. The stroma of ovarian MCN was strongly immunopositive for alpha-SMA and vimentin and focally positive for desmin, whereas normal ovarian stroma was immunonegative for both alpha-SMA and desmin. The OLS of MCN mentioned here was similar to the septa of ovarian MCN but not to ovarian stroma. In conclusion, MCN in various organs should be lumped together as 'extra ovarian' MCN. The OLS was identified on the basis of myofibroblastic proliferation both in response to neoplastic development and dependent on hormones.

Autoimmune hepatitis in primary Sjogren's syndrome: pathological study of the livers and labial salivary glands in 17 patients with primary Sjogren's syndrome.

Although primary Sjogren's syndrome (pSS) is an autoimmune exocrinopathy, the involvement of liver has been reported. Because no study focusing on autoimmune hepatitis (AIH) in pSS has been published, the purpose of the present study was to perform a clinical and histological examination of the liver, focusing on AIH, in 17 pSS patients. The patients had liver enzyme abnormalities without hepatitis virus infection. In all cases, biopsied livers were examined, and in 10 cases biopsied labial salivary glands were also examined histologically. Based on the authors' diagnostic criteria for AIH in pSS, the liver diseases consisted of AIH (eight cases, 47%), primary biliary cirrhosis (PBC; six cases, 35%), non-specified chronic hepatitis (two cases, 12%) and acute hepatitis (one case, 6%). Lymphoplasmacytic infiltrate, with predominancy of CD3(+) T cells, was noted in both the liver and salivary glands in the patients with AIH. The patients with AIH with severe interface hepatitis had a good response to immunosuppressive therapy. The comparison of liver histology between the PBC with pSS group and the PBC without pSS group showed that the incidence of lymphoid non-suppurative cholangitis was higher in PBC with pSS. In conclusion, the present study offers new information on the relatively common occurrence, diagnostic criteria and treatment effects of AIH in pSS.

Intraductal spread of pancreatic cancer. Clinicopathologic study of 54 pancreatectomized patients.

BACKGROUND: Invasive ductal adenocarcinoma of the pancreas (IDAP) also spreads through the pancreatic ductal tree. The aim of this study was to clarify the clinicopathologic features of IDAP with intraductal spread. METHODS: We studied the intraductal spread of IDAP and its correlation with clinicopathologic parameters in a surgical series of 54 patients. The pancreatic ducts were analyzed by confirmation of mural elastic fibers with elastica van Gieson stain. RESULTS: Intraductal spread of carcinoma was identified in 37 patients (69%). Such spread was frequent in well-differentiated IDAP (93%), and the number of intraductal carcinoma foci was correlated with the grade of tumor differentiation (p < 0.001). The large branch ducts were the main route of intraductal spread (64.1%). The proliferation index, evaluated using Ki67, was lower in the intraductal carcinoma components than in the associated infiltrating carcinoma components (p < 0.001). The presence or absence of intraductal spread was not correlated with age, sex, tumor location, tumor size, or stage. IDAP with intraductal spread showed a tendency, although it was not significant (p = 0.092), to be associated with longer survival compared with IDAP without intraductal spread. CONCLUSION: IDAP, especially of the well-differentiated type, has a tendency to spread intraductally. The difference between the Ki67 labeling indexes in the intraductal and associated infiltrating carcinoma components suggests that these components show different biological behaviors.

Prevalence of human papillomavirus infection and correlation with cervical lesions in Japanese women.

PURPOSE: To investigate the prevalence of human papillomavirus (HPV) infection in patients attending a gynecologic outpatient department, and to correlate the infection status with the presence or absence of uterine cervical lesions and the grades assessed by cytological or histological examinations. METHODS: Five hundred and seventy-two subjects were studied. In all subjects, HPV detection by the hybrid capture method and a cervical cytological examination were performed RESULTS: The HPV-positive rate in subjects with normal cytology was 12.3%. The detection rate was high (21.7%) in subjects aged in the twenties and low in the forties, and HPV was not detected in subjects aged in the sixties and seventies. When HPV-positive rates were examined according to cytological or histological grades, the rates were higher in subjects with abnormal cytology (P < 0.01) or cervical intraepithelial neoplasia (CIN) or squamous cell carcinoma compared with those with normal cytology. CONCLUSION: Diagnosis of HPV infection is also important for the prediction of progression to CIN and cervical cancer.