Lymphoplasmacytic lymphoma with IgG-κ paraproteinemia presenting as a hepatic bulky mass.

Lymphoplasmacytic lymphoma (LPL) usually involves bone marrow (BM) and sometimes lymph nodes and spleen. LPL presenting as a hepatic mass lesion is extremely rare, with only one case reported in the English literature. A 70-year-old Japanese female presented to us with a right hypochondriac mass with tenderness. Computed tomography (CT) revealed a 14 cm-sized bulky hepatic mass. Laboratory findings showed a normal white blood cell count of 4.1×109/L with 4% plasmacytoid lymphocytes; normocytic anemia, Hb 9.4 g/dL; high soluble IL-2 receptor level, 2,290 U/mL; and elevated IgG, 10,306 mg/dL. Furthermore, IgG-κ monoclonal protein was detected. 18F-fluorodeoxyglucose-positron emission tomography/CT revealed abnormal uptake in the liver mass; left supraclavicular, parasternal, abdominal, and left inguinal lymph nodes; and bilateral lung bases. Magnetic resonance imaging showed no bone lesions. BM aspiration and liver biopsy showed predominant infiltration of small lymphocytes admixed with plasmacytoid lymphocytes and plasma cells. In the liver specimen, lymphoepithelial lesions were not observed. The small lymphocytes were positive for CD20, CD79a, and bcl-2, and negative for CD5, CD10, cyclin D1, and IRTA1; plasma cells in BM were positive for CD19, CD45, IgG, and κ-chain, and negative for CD20, and CD56. MYD88 L265P mutation, reported in approximately 40% of non-IgM LPL cases, was not detected in the liver specimen and BM cells. The frequency is lower than that of typical IgM LPL. These findings led us to a diagnosis of LPL with IgG-κ paraproteinemia. The patient underwent four courses of R-CHOP and two courses of Bendamustine-R. Partial remission was achieved.

Extremely rare case of H-type gallbladder duplication coexistent with carcinoma: a case report and review of the literature.

INTRODUCTION: Multiple gallbladders represent a rare congenital disorder, and coexistence with carcinoma is extremely rare, leading to a high possibility of misdiagnosis and surgical complications. In this study, a case was reported and the literature was reviewed. CASE PRESENTATION: An 80-year-old woman was diagnosed with acute cholecystitis via ultrasonography and was successfully treated with antibiotics. After the patient's biliary colic relapsed, she was referred to our hospital. Multiple imaging modalities revealed duplication of her gallbladder (H-type) and suggested coexistence with carcinoma. According to preoperative evaluations, we assumed the patient had stage IIIA disease, and cholecystectomy, cholangiography using a near-infrared ray vision system, and sectionectomy of segments 4a and 5 were performed. Contrary to the high standardized uptake values obtained by 18F-fluoro-2-deoxy-D-glucose positron emission tomography, gallbladder carcinoma was pathologically diagnosed as stage 0 mucosal cancer. Seven days after the operation, portal thrombosis of the posterior branch was revealed, and conservative therapy was indicated; satisfactory results were achieved. The patient was discharged 65 days after surgery. No recurrence was observed for 1 year after surgery. CONCLUSIONS: An extremely rare case of malignancy in a duplicated gallbladder was reported, and the literature was reviewed. Accurate estimations are feasible for diagnoses of multiple gallbladders, where correct evaluations are vital, especially in malignant cases. Because of the possibility of malignancy, resected accessory gallbladders should be scrutinized pathologically.

[A Forensic Autopsy Case Applied for Asbestos-Related Disease].

We had a forensic autopsy case that required additive pathological examination for the asbestos-related lung disease compensatory application afterwards. A man in his sixties with a history of occupational asbestos inhalation who had neither visited a hospital nor received a physical examination received forensic autopsy because of his death from unknown cause. An inmate said, "He developed cough and dyspnea, and died in the progression of the symptoms." The autopsy revealed widespread pleural plaques on both sides of the parietal pleura and multiple tumors in both sides of the lungs. The cause of death was diagnosed as lung cancer. Additional pathological examination was asked by his family to certify that he had suffered from asbestos-related lung disease in order to apply to the Asbestos-related Damage Relief Law. The Japanese criteria of the compensation law of asbestos-related lung cancer is the detection of more than 5,000 asbestos bodies per gram of dry lung tissue, while his number of asbestos bodies was 4,860. Asbestos bodies were reported to be accumulated in the distal lung parenchyma with no pathological changes. The present lung samples were collected from proximal section around the tumor, which might have made the number of asbestos bodies less than the criteria. Both the number of patients suffering from asbestos-related lung disease and the number of forensic autopsy cases have increased in Japan. Collecting lung samples from the appropriate lung section is essential and should be noted when the lung cancer is suspected at forensic autopsy in order to apply for asbestos-related lung disease compensation.

[Synchronous gastrointestinal stromal tumors of the rectum and duodenum: a case report].

An 85-year-old woman with anemia underwent colonoscopy, which revealed a 25-mm submucosal tumor with ulceration in the lower rectum. Histological examination of a biopsy showed that the lesion was a gastrointestinal stromal tumor (GIST). Subsequent esophagogastroduodenoscopy revealed a submucosal tumor in the duodenum, and examination of a biopsy obtained by endoscopic ultrasound-guided fine-needle aspiration also confirmed that this lesion was a GIST. The rectal lesion was surgically resected to control bleeding and was confirmed as a GIST histologically. Simultaneous development of GISTs in the rectum and duodenum is extremely rare.

[Three cases of pedunculated gastric hamartomatous inverted polyps resected endoscopically].

We report three cases of pedunculated gastric hamartomatous inverted polyps (HIPs) that were successfully treated by endoscopic polypectomy. The first case involved an 87-year-old woman with mild anemia. Esophagogastroduodenoscopy (EGD) revealed a pedunculated, reddish polyp located at the greater curvature of the upper stomach. The second case involved a 34-year-old woman in whom a pedunculated polyp was found at the gastric fundus during routine EGD. The third patient was a 59-year-old woman with epigastric discomfort. EGD revealed a pedunculated polyp in the gastric fundus. Polypectomy was successfully performed in all three cases. Histological examination revealed that the tumors comprised submucosal proliferation of cystically dilated gastric glands and hyperplastic glands;thus, we diagnosed gastric HIPs, which are rare and typically difficult to diagnose. Gastric HIPs should be considered in the differential diagnosis of elevated gastric lesions.

Association of microRNA-21 expression with its targets, PDCD4 and TIMP3, in pancreatic ductal adenocarcinoma.

Since the discovery of small non-coding RNAs, the analyses of microRNA (miRNA) expression patterns in human cancer have provided new insights into cancer biology. miRNA-21 has been suggested to be one of the miRNAs that have an important role in the development or biological behavior of a variety of malignancies, including pancreatic cancer. This study was conducted to evaluate the relationship between the expression of miRNA-21 and that of its molecular targets, programmed cell death 4 (PDCD4) and tissue inhibitor of metalloproteinase (TIMP3), in pancreatic ductal adenocarcinoma. The study included 65 pancreatic ductal adenocarcinomas and 5 normal pancreatic tissue specimens for comparison. The miRNA expression profiling of five selected pancreatic ductal adenocarcinomas and five normal pancreatic specimens was performed using a microarray platform, and was evaluated by a hierarchical clustering analysis. The miRNA most highly expressed in pancreatic ductal adenocarcinomas (ie, miRNA-21) was further assessed by quantitative real-time reverse transcription PCR (RT-PCR) assays in the 65 pancreatic ductal adenocarcinoma cases. The expression pattern of its molecular targets (eg, PDCD4 and TIMP3) in pancreatic ductal adenocarcinoma was examined immunohistochemically. In the microarray analyses, 28 miRNAs were upregulated in pancreatic ductal adenocarcinoma compared with normal pancreatic tissue, whereas 48 miRNAs were downregulated. miRNA-21 was the most significantly overexpressed miRNA in the pancreatic ductal adenocarcinomas analyzed, and was also highly expressed in 75% of the 65 pancreatic ductal adenocarcinomas examined by real-time RT-PCR. High miRNA-21 expression was correlated with a worse prognosis in the pancreatic ductal adenocarcinoma patients (P=0.045). The immunohistochemical expression patterns of PDCD4 (reduced nuclear staining pattern) and TIMP3 (downregulated expression) were significantly associated with both the upregulated miR-21 expression (P<0.05) and the poor survival of the patients (P<0.001 and P=0.001, respectively). Our data suggest that an overexpression of miRNA-21 is, therefore, associated with the biological behavior of pancreatic ductal adenocarcinoma via the downregulation of the expression of tumor suppressors, PDCD4 and TIMP3, thus resulting in tumor progression and the adverse clinical course of pancreatic ductal adenocarcinoma.

Lymphoepithelioma-Like Carcinoma of the Stomach with Epithelioid Granulomas.

An 83-year-old Japanese man was admitted to our hospital for gastric adenocarcinoma mimicking a submucosal tumor in the gastric body. Considering his general condition, partial resection of the stomach and dissection of regional lymph nodes were performed; a dome-shaped tumor that was largely covered by normal mucosa and having a shallow central stellate ulcer was removed. Histopathologically, the carcinoma cell nests were surrounded by prominent lymphoid stroma. Sarcoid-like epithelioid granulomas were noted both in the tumor stroma and in the regional lymph node with metastasis. Epstein-Barr virus (EBV)-encoded RNA (EBER) in situ hybridization showed an intense and diffuse positive reaction in the carcinoma cells and no reaction in the surrounding gastric and lymphoid tissues. While the presence of lymphoid stroma is a characteristic finding in EBV-associated lymphoepithelioma-like carcinoma, sarcoid-like epithelioid granulomas might be associated with latent EBV infection.

[A case of localized malignant pleural mesothelioma].

A 74-year-old man was referred to our hospital for examination of an abnormal chest shadow. A chest computed tomography (CT) scan revealed a 5-cm mass attached to the pleura involving the right upper lobe, and a nodule in the right middle lobe. Transbronchial lung biopsy was performed twice, but no definitive diagnosis was achieved. 18-fluorodeoxyglucose positron emission tomography showed abnormal uptake in the chest lesion. Chemotherapy was initiated for advanced-stage lung cancer, but was not effective. Histopathologic and immunohistochemical examinations after CT-guided needle biopsy revealed malignant mesothelioma. The tumor cells were positive for calretinin and thrombomodulin, and negative for CEA, TTF-1, and SP-A. There was local tumor invasion and metastasis in the lung and brain, without diffuse pleural spread. This is a rare and important case of localized malignant mesothelioma pathologically confirmed by biopsy.

Congenital pulmonary lymphangiectasis: report of an autopsy case masquerading as pulmonary interstitial emphysema.

We describe the clinicopathologic features of a case of congenital pulmonary lymphangiectasis (CPL). A male Japanese infant born prematurely at 34 weeks of gestation developed a severe moaning sound, dyspnea, and prominent respiratory acidosis about 10min after delivery. A chest X-ray film showed bilateral frosted glass-like infiltrates with an air bronchogram and an air leak around the cardiac shadow, suggesting pneumomediastinum. The patient died of hypoxemic respiratory failure 13h after birth. The death was complicated by bilateral pneumothorax, despite the initiation of artificial ventilation and administration of a surfactant. At autopsy, small cystic lesions were noted in the visceral pleura, interlobular septa, and hilum of both lungs. A histologic examination of the lungs showed diffuse and marked dilation of the lymphatic channels in the subpleural, peribronchial, interlobular, and hilar areas. The channels were lined with flattened endothelium, which was immunohistochemically positive for D2-40. In addition, lymphangiectasis was found around the thymus and intra-abdominal organs, but no cardiovascular anomalies were seen. The findings conformed to a primary form of CPL, Noonan Group 3. Although pulmonary interstitial emphysema (PIE) was considered an important differential diagnosis because of the overlapping clinicopathologic features, a giant cell reaction surrounding the interstitial cystic lesions, a histologic hallmark of PIE, was absent in the present case.

[Intravascular lymphoma confirmed by brain biopsy, quickly treated by chemotherapy: a case report].

A 60-year-old female with intravascular lymphoma (IVL) presented with the complaint of urinary dysfunction and gait disturbance. T2 weighted MR imaging of the thoracic spinal cord showed a hyperintense lesion, and brain MR imaging indicated hyperintense lesions in the deep white matter. Multiple sclerosis was assumed, so steroid pulse therapy was administered. However, her level of consciousness decreased and her paraplegia progressed. Laboratory data showed that anemia and thrombocytopenia had worsened with high serum LDH and soluble IL-2 receptor levels. Biopsy of bone marrow indicated hypercellularity associated with hemophagocytic histiocytes, although no atypical lymphocytes were detected. Brain MR imaging indicated a new subcortical lesion in the left parietal lobe. One and a half months after admission, an open brain biopsy of the left parietal cortex was performed. Histopathological diagnosis was IVL, large B cell type. Immediately, she underwent CHOP therapy containing rituximab (R-CHOP therapy). After chemotherapy, spinal and brain MR images showed no new abnormal lesions. Clinically, it is difficult to make a diagnosis of IVL in life as it has no characteristic symptoms or radiological findings. Therefore, if a patient is suspected of having IVL, a biopsy of different organs, including brain, is necessary for making an early diagnosis and initiating chemotherapy.

[Autopsy of a suspected venous circulatory disturbance localized in the medulla oblongata and upper cervical cord accompanied by an aneurysm].

We describe an autopsied case of an 86-year-old woman who presented with acute tetraparesis, bulbar palsy, and respiratory insufficiency. MRI showed a T2 hyperintensity lesion in the medulla oblongata and C1 and C2 level cervical cord, and an unruptured aneurysm in the left posterior inferior cerebellar artery. With an initial diagnosis of Bickerstaffs brainstem encephalitis, we started corticosteroid therapy. Initially, the corticosteroid treatment gradually improved her general condition; however, about two weeks later she died of an acute respiratory insufficiency. From the postmortem pathological examination, we considered a venous circulatory disturbance of the medulla oblongata and upper cervical cord. No arteriovenous shunt was found in the intramedulla and the medulla oblongata was partially compressed on the left side by an unruptured aneurysm. However, neither inflammatory nor malignant cells were found in the lesion. What caused the venous circulatory disturbance was unclear, but the dural arteriovenous fistula could have been responsible. Our case suggested that venous circulatory disturbances accompanied with an aneurysm need rapid consideration by angiography followed by intervention.

Co-occurrence of subchondral insufficiency fracture of the femoral head and contralateral femoral neck fracture in a rheumatic patient receiving steroid treatment.

We describe a 79-year-old woman with rheumatoid arthritis who suffered from subchondral insufficiency fracture of the femoral head (SIF) and contralateral femoral neck fracture. Radiographs obtained two months after the onset of thigh pain showed collapse of the right femoral head and contralateral femoral neck fracture. MRI revealed a subchondral serpiginous low-intensity band in the right femoral head on the T2-weighted image. This case report suggests that SIF should be considered in the differential diagnoses of rheumatic patients who suffer from thigh pain without antecedent trauma.

Prognostic significance of the local expression of interleukin-12 in patients with advanced gastric cancer.

BACKGROUND: Interleukin (IL)-12 is a heterodimeric cytokine that exhibits potent antitumor and antimetastatic activities. Very few studies have so far investigated the local expression of L-12 in tumor specimens of gastric cancer. The purpose of this study was to investigate the immunohistochemical expression of IL-12 in patients with gastric cancer. PATIENTS AND METHODS: IL-12 was immunohistochemically stained using monoclonal antihuman IL-12 antibody (1-1A4) in surgical specimens of 117 gastric cancer patients. The IL-12-positive cell density was calculated. The relationships among the IL-12-positive cell density, clinicopathological factors and 5-year survival rate were evaluated. RESULTS: Among the patients (n=117), the 5-year survival rate after surgery was not statistically different between the patients with high and low IL-12 positive cell-density. However, in the patients with advanced gastric cancer (n=85), those with a high IL-12-positive cell density showed a significantly better prognosis in comparison with those with a low IL-12-positive cell density (p=0.0104). A multivariate analysis indicated that the IL-12-positive cell density and TNM stage are significant prognostic factors. CONCLUSION: IL-12-positive cell density may be a significant independent prognostic factor in surgical specimens of advanced gastric cancer.

Ochronotic arthropathy: pathological evidence of acute destruction of the hip joint.

Alcaptonuria is a hereditary disease, also known as black hip, where there is an accumulation of homogentisic acid pigmentation in joint cartilages. We describe a 74-year-old woman who showed acute destruction of her left hip joint. She received a total hip arthroplasty on her right side in July 2000, and was diagnosed with ochronosis. Her postoperative follow-up was at our institutions outpatient department. She first complained of increasing groin pain in July 2005, after which she had a left total hip arthroplasty in October 2005. Histopathologically, samples from this patient showed "fragmentation and cleft formation" in the cartilage of the femoral head. In addition, the samples revealed a remarkable degradation of proteoglycan, which is the secondary most abundant constituent of extra cellular matrix. These findings suggested that "cleft formation", where cracks develop toward the center, caused an acute destructive arthropathy with morphological fragility suggestive of ochronosis.

Sebaceous carcinoma of the breast: case report and review of the literature.

Sebaceous differentiation has been described in only limited examples of benign and malignant epithelial lesions of the breast. We report a rare case of mammary sebaceous carcinoma to further delineate its morphologic features. Microscopically, the tumor, arising in the right mammary gland of a 63-year-old woman, was composed of well-defined solid sheets or lobules of atypical epithelial cells including many large pale or clear cells with often scalloped nuclei and coarsely vacuolated cytoplasm, in which abundant lipid droplets were identified with oil-red-O staining. Immunohistochemical expressions of cytokeratin, epithelial membrane antigen, and receptors of estrogen and progesterone were detected, whereas GCDFP-15, S-100 protein, vimentin, alpha-smooth muscle actin, p63, androgen receptor, and the HER2/neu protein were not expressed. Besides, a subset of the tumor cells co-expressed synaptophysin, neurofilament, and PGP9.5, suggesting neuroendocrine differentiation that is a hitherto undescribed phenomenon in the mammary tumors with sebaceous features. This case would expand the morphologic diversity of carcinoma of the breast.

Neuronal damage in hydrocephalus and its restoration by shunt insertion in experimental hydrocephalus: a study involving the neurofilament-immunostaining method.

OBJECT: The morphological and functional impairments of neurons and their connections caused by hydrocephalus, and their restoration by ventricular shunt placement were investigated in experimental hydrocephalus by the immunostaining of neurofilaments, which constitute the major component of the neuronal cytoskeleton. METHODS: Progressive hydrocephalus was induced in 15 young mongrel dogs 1 to 2 months of age, 3 to 4 weeks after cisternal injection of kaolin. The dogs were divided into three groups of five animals each, a "preshunt," "post-shunt," and "nonshunt" group, depending on whether the hydrocephalic animals underwent a procedure to insert a ventriculoperitoneal shunt. Neurofilament, glial fibrillary acid protein (GFAP), and synaptophysin immunostaining were performed using samples of brain tissue from each hydrocephalic group and a fourth "control" group (five animals). In the cortex, morphological deformation and heterogeneous neurofilament immunoreactivity of the apical dendrites became pronounced in accordance with the progression of hydrocephalus (from the preshunt to the nonshunt group), and these changes remained after shunt insertion (postshunt group). In the periventricular white matter, swollen and fragmented axons increased in number along with hydrocephalic progression and were incompletely repaired by ventricular shunt placement. The GFAP-positive astrocytes observed around repaired axons in the postshunt group were seen more prominently than in the untreated hydrocephalic groups. In the internal capsule, fairly good recovery from axonal damage caused by the hydrocephalic condition was achieved by insertion of a ventricular shunt, compared with that seen in the periventricular white matter. CONCLUSIONS: Cytoskeletal damage of neurons in hydrocephalus and its incomplete restoration by shunt placement were most significant in the periventricular white matter. This finding may account for the impaired cognitive function seen in children who have shunts and an apparently reconstituted cerebral mantle; therefore, neuronal protection in the early hydrocephalic state should be considered.

Primary pulmonary collision cancer consisting of large cell carcinoma and adenocarcinoma.

A case of pulmonary collision tumor is herein reported. An abnormal shadow was discovered in the right lung of a 53-year-old man. A right upper lobectomy with a mediastinal lymph node dissection was performed. Based on the findings of a postoperative pathologic examination, this tumor was considered to be a collision tumor of large cell carcinoma and adenocarcinoma, as the distribution of each tumor was clearly separated. This case is the first report of a primary pulmonary collision tumor consisting of large cell carcinoma and adenocarcinoma.

Primary leiomyosarcoma of the vertebra: Case report and review of the literature.

A case of primary leiomyosarcoma of a thoracic vertebra associated with a compression fracture in a 75-year-old woman was preoperatively thought to be granulation tissue. Surgical decompression was performed and the histological and immunohistochemical studies established the diagnosis of leiomyosarcoma. Based on the clinical and radiological examinations, metastases were ruled out. Primary leiomyosarcoma of the vertebra is extremely rare and in that site it is considered to have a relatively poor prognosis.

Pathologic evidence of degeneration as a primary cause of rotator cuff tear.

Histopathologic, histochemical, and morphometric studies were done on 80 medial stumps of torn rotator cuff tendons to clarify the cause of tears. A high prevalence and diffuse distribution of degenerative changes were observed in the rotator cuff tendons including thinning and disorientation of collagen fibers, myxoid degeneration, hyaline degeneration, chondroid metaplasia, calcification, vascularproliferation, and fatty infiltration. No distinct inflammatory reaction was observed. Thinning and disorientation of collagen fibers, myxoid degeneration, and hyaline degeneration were seen in all cases. All changes except vascular proliferation and fatty infiltration were more pronounced in the middle to deep layers of the tendons than in the superficial layer. The collagen fibers were disoriented in the deep layer of the tendons, shown by microscopic image analysis. The frequency and distribution of thinning and disorientation of collagen fibers, myxoid degeneration, and hyaline degeneration suggest that these are early degenerative processes. Chondroid metaplasia and calcification may be chronic pathologic changes that occur after tearing regardless of the type of tear. Preexisting degenerative change in the middle and deep layers of the tendon in association with microtrauma seems to be the main cause of rotator cuff tears.