Intra-abdominal bleeding caused by amyloid transthyretin amyloidosis in the gastrointestinal tract: a case report.

Diagnosis of gastrointestinal (GI) amyloidosis is often very difficult because of its nonspecific symptoms. However, a few reports have indicated that serious symptoms such as fatal GI bleeding and obstruction or perforation sometimes lead to a diagnosis of GI amyloidosis. A 79-year-old man was transported to our emergency department with a 1-week history of worsening abdominal pain. Abdominal contrast-enhanced computed tomography showed extravasation from part of the transverse colon wall and moderate ascites. Because intra-abdominal bleeding was suspected, the patient urgently underwent partial resection of the transverse colon, which was the source of the bleeding. Postoperative pathological examination of the tissue specimens led to a diagnosis of amyloid transthyretin amyloidosis. This is the first reported case in which intra-abdominal bleeding led to a diagnosis of GI amyloidosis. We should consider the possibility of GI amyloidosis when intraperitoneal bleeding is observed in elderly patients.

Primary cardiac angiosarcoma directly invading the right lung: An autopsy report.

We presented a difficult-to-diagnose case of cardiac angiosarcoma. The patient presented pericardial effusion, but cytology of the effusion was negative. Because cytological detection of angiosarcoma cells is difficult, a possibility of malignancy should not be excluded with negative cytological examination. Biopsy of cardiac mass is the best way for diagnosis.

Signet Ring Cell Differentiation in Salivary Duct Carcinoma with Rhabdoid Features: Report of Three Cases and Literature Review.

Salivary duct carcinoma with rhabdoid features (SDCRF) is a rare salivary tumor with poor prognosis and is proposed as a salivary counterpart of pleomorphic lobular carcinoma of the breast (PLCB). Here, we report three cases of SDC with rhabdoid features (SDCRF) mimicking PLCB. Pleomorphic adenoma (PA) component was accompanied in all the cases confirming carcinoma ex PA. One patient had frequent rhabdoid features and showed invasive growth into the surrounding tissue. The other two patients had intracapsular tumor but with rhabdoid features. The patients with intracapsular SDCRF survived for > 5 years after surgery with no evidence of recurrence, whereas the patient with extracapsular SDCRF died 10 months after biopsy, and autopsy revealed disseminated metastasis to the central nervous system. Histologically, tumor cells in all three cases resembled PLCB, with a discohesive appearance, abundant cytoplasm, enlarged hyperchromatic nuclei, and similar immunohistochemical profiles, namely loss of membranous E-cadherin, obscured expression of membranous ß-catenin, diffuse positivity of androgen receptor, gross cystic disease fluid protein-15, mitochondrial adenosine triphosphate synthase subunit ß, MUC1, and INI-1. Estrogen and progesterone receptors were negative, and HER2 immunoreactivities were variable. The tumor cells of extracapsular invasive SDCRF exhibited higher MIB-1 labeling index and more frequent intracytoplasmic lumina than those of intracapsular SDCRF. Ultrastructurally, rhabdoid cells contained intracytoplasmic lumina with microvillous structure, analogous to those reported in PLCB. No intracytoplasmic intermediate filament aggregation was observed. These observations indicate that SDCRF is a salivary counterpart of PLCB and under signet ring cell differentiation.

Cytomegalovirus colitis presented with triserial longitudinal hemorrhage in an autopsy case of adult T-cell leukemia.

Longitudinal mucosal and submucosal hemorrhage along the taeniae coli is a potential colonic manifestation of cytomegalovirus infection in immunocompromised patients. When diagnosing cytomegalovirus colitis in immunocompromised patients, endoscopic biopsy on taeniae coli seems effective for viral detection.

Clinicopathological study of 5 cases of renal cell carcinoma with t(6;11)(p21;q12).

Renal cell carcinoma (RCC) with t(6;11)(p21;q12) has been incorporated into the recent WHO classification. We performed a clinicopathological study of 5 cases with such a tumor. The patients consisted of 4 males and 1 female. The age of patients ranged from 17 to 57 years with a mean age of 38.6 years. Tumor sizes ranged from 2.8 to 11 cm with a mean value of 6.5 cm. Despite immunotherapy and molecular-targeted therapy, one patient died of the disease 28 months after the surgery. Grossly, the cut surface of this tumor showed grayish white color in at least the focal area of all tumors. Furthermore, hemorrhage, daughter nodules and cystic changes were observed in two, three, and two tumors, respectively. Morphologically, all the tumors consisted of two components of large cells and small cells, and the latter surrounded basement membrane-like materials, forming rosette-like structures. Immunohistochemically, nuclei of tumor cells in all cases were positive for TFEB. Fluorescence in situ hybridization study confirmed the TFEB gene break in two tumors. Finally, urologists and pathologists should bear in mind that this tumor may occur in young adults to adults and might behave in an aggressive fashion. Break-apart FISH is useful for the definite diagnosis.

Daily Intake of High-Fat Diet with Lysophosphatidic Acid-Rich Soybean Phospholipids Augments Colon Tumorigenesis in Kyoto Apc Delta Rats.

BACKGROUND: Oral administration of lysophosphatidic acid (LPA) was shown to attenuate gastric ulceration in rats and mice but aggravate intestinal tumorigenesis in mice. AIMS: The present study examined whether dietary LPA induces or prevents development of colorectal tumor in rats. METHODS: Kyoto Apc Delta rats fed high-fat diet with or without an LPA-rich soybean phospholipid mixture (LSP, 0.1 or 1%) were treated with azoxymethane and dextran sodium sulfate to induce colorectal tumorigenesis. Rats were killed 15 weeks after azoxymethane treatment, and size, total number, location, and severity of colorectal tumors were assessed. Expression of mRNA of LPA receptors in rat colon tissue was assayed. RESULTS: Rats fed the diet supplemented with 1% LSP had a higher number of tumors 2-4 mm long compared than those with or without 0.1% LSP. The mean distance of tumors >4 mm long from the anus was significantly higher than those of tumors <2 and 2-4 mm long in rats fed 1% LSP-supplemented diet. Supplementation of the diet with 0.1% LSP decreased mRNA expression of LPA5 in colon tumors of rats. CONCLUSIONS: Dietary supplementation of LPA-rich phospholipids dose-dependently augmented colorectal tumorigenesis. Decreased expression of LPA5 in colon tumors may be relevant to augmented tumorigenesis.

Reduced rat plasma lysophosphatidylglycerol or lysophosphatidic acid level as a biomarker of aristolochic acid-induced renal and adipose dysfunctions.

AIMS: Food products and diet pills containing aristolochic acid (AA) are responsible for a rapid progression of nephropathy associated with reduced body weight in human beings. In this study, we investigated the relationship of dietary NaCl and lysophospholipid (LPL) plasma levels to body weight gain in AA-treated rats. MAIN METHODS: Male rats receiving a salt-deficient chow, normal salt chow or high salt chow were injected intraperitoneally daily with AA for 15days. Body weight, visceral fat mass, food intake, levels of LPL in plasma and its synthesized enzyme were investigated. KEY FINDINGS: Body weight gain, visceral fat mass and daily food intake were smaller in AA-treated rats than those of control rats, regardless of dietary salt concentration. AA treatment decreased plasma levels of major lysophosphatidic acid (LPA) molecular species in rats fed the normal or high-salt chow but not the salt-deficient chow, whereas both the plasma lysophospholipase D activity and kidney mRNA level of autotaxin of AA-treated rats fed chow with defined salt concentrations were lower than those of control rats. Plasma levels of major molecular species of lysophosphatidylglycerol (LPG) in AA-treated rat groups fed chow with defined salt concentrations were lower than those of control rats. SIGNIFICANCE: Plasma levels of LPG and LPA seem to be relevant to the reduced body weight gain and fat mass due to AA treatment.

Fatal Severe Fever with Thrombocytopenia Syndrome: An Autopsy Case Report.

UNLABELLED: As of June 2014, among six patients who had severe fever with thrombocytopenia syndrome (SFTS) at our hospital, an 83-year-old man died despite receiving appropriate critical care. An autopsy revealed extensive ischemic damage of the intra-abdominal organs, including the liver, spleen, stomach and gut, due to severe celiac atherosclerotic stenosis and superior mesenteric arterial thrombosis. Many SFTS virus nucleoprotein antigen-immunoreactive cells were detected in a paraaortic node, where necrotizing lymphadenitis was seen, and in the spleen. Fewer such cells were seen in the liver, bone marrow and adrenals. CONCLUSION: Atherosclerosis, in addition to hemophagocytic lymphohistiocytosis syndrome, can be lethal in elderly SFTS patients.

Reduced kidney levels of lysophosphatidic acids in rats after chronic administration of aristolochic acid: Its possible protective role in renal fibrosis.

Aristolochic acid (AA) is considered to be a causative agent for progressive interstitial renal fibrosis, leading to AA nephropathy. Lysophosphatidic acid (LPA) is a mediator in the onset of renal fibrosis. In this study, we analyzed the molecular species of LPA and its precursor lysophospholipids in kidney tissue from rats exposed to AA. Daily intraperitoneal injections of AA for 35 days to rats gave rise to fibrosis in kidney, decreased the kidney levels of LPA, lysophosphatidylserine and lysophosphatidylinositol. In rat renal cell lines (NRK52E and NRK49F), AA-induced cytotoxicity was potentiated by Ki16425, LPA1,3 receptor antagonist. The level of mRNA encording α-smooth muscle actin was significantly increased by AA-treatment only in NRK52E cells, while the mRNA level of collagen III was decreased in both NRK52E and NRK49F cells. These results suggest that endogenous LPA in rat kidney prevents AA-induced renal fibrosis.

A case of a pleomorphic hyalinizing angiectatic tumor of soft parts with intracytoplasmic hemosiderin pigment apparent upon fine-needle aspiration cytology.

Pleomorphic hyalinizing angiectatic tumors of soft parts are extremely rare low-grade mesenchymal lesions that frequently occur subcutaneously, especially in the lower extremity. The tumor is histologically characterized by sheets of plump, spindled or rounded cells, and clusters of ectatic blood vessels. It also has a number of previously characterized cytological features such as pleomorphic cells, intranuclear pseudoinclusion, and intracytoplasmic hemosiderin pigments. However, intracytoplasmic hemosiderin has not been carefully evaluated in cytology specimens. Here, we report the case of a 56-year-old Japanese man with an encapsulated pleomorphic hyalinizing angiectatic tumor of soft parts that included fine and coarse hemosiderin-laden tumor cells. The tumor was clinically followed up as a hematoma, but malignant tumors, including malignant melanoma, were suspected because aspiration cytology specimens contained pleomorphic cells with intracytoplasmic brown pigments. The tumor was closely associated with an intratumoral hematoma and a few microscopic satellite lesions. Pleomorphic hyalinizing angiectatic tumor of soft parts should be included in the differential cytological diagnosis of soft tissue tumors if the three cytological features described earlier are present. Enucleation therapy could facilitate local recurrence, as the tumor may have the potential to infiltrate surrounding soft tissue or form satellite lesions.

The potential protective role of lysophospholipid mediators in nephrotoxicity induced by chronically exposed cadmium.

Cadmium is a hazardous metal whose chronic exposure induces renal failure due to fibrosis, but the mechanisms are not well known. In this study we analyzed the molecular species of lysophosphatidic acid (LPA) and related phospholipids, together with their metabolic enzyme activity, in plasma from Wistar rats exposed up to 300ppm Cd(2+) in drinking water for 114days. Exposure of 300ppm Cd(2+) for 114days enhanced autotoxin (ATX)/lysophospholipase D activity, but significantly lowered the total levels of LPA and lysophosphatidylethanolamine. Interestingly, the total level of sphingosine-1-phosphate (S1P) was elevated dose-dependently by Cd(2+). Cultured rat kidney-derived interstitial fibroblast cells, NRK49F cells and proximal epithelial cells, NRK52E cells, were both responsive to the protective action of LPA or S1P against Cd(2+) toxicity. The former cell expresses ATX RNA. In conclusion, the elevation of LPA-producing enzyme activity and S1P concentrations in plasma after exposure of rats to Cd(2+) would protect from the renal toxicity of Cd(2+).

Review of renal carcinoma with t(6;11)(p21;q12) with focus on clinical and pathobiological aspects.

Recently, a new category of MiTF/TFE family translocation carcinomas of the kidney has been proposed. This category includes Xp11.2 renal cell carcinoma (RCC) and the t(6;11) RCC. These tumors share clinical, morphological, immunohistochemical and molecular genetic features. In this article, we review t(6;11) RCC. This tumor predominantly affects children and young adults. Macroscopically, the tumor generally forms a well circumscribed mass. Satellite nodules may be observed. Histologically, the tumor comprises large cells and small cells surrounded by basement membrane material. Immunohistochemically, tumor cells show nuclear immunolabeling for TFEB and usually express Cathepsin-K in the cytoplasm. Karyotyping detects the rearrangement between chromosome 6p21 and chromosome 11q12. Alpha-TFEB fusion can be detected by reverse transcriptase polymerase chain reaction (RT-PCR) or fluorescence in situ hybridization (FISH). Most cases affecting children and young adults seem to be indolent, but some adult cases have presented with metastasis or caused death. As previously reported cases remain limited to date, further examination in a large scale study will be needed in order to elucidate clinical behavior and molecular characteristics.

Renal carcinoma with (6;11)(p21;q12) translocation: report of an adult case.

An extremely rare adult example of renal carcinoma with t(6;11)(p21;q12 or q13) is presented here. The tumor of a 45-year-old Japanese male, excised under the diagnosis of renal cell carcinoma, was a well circumscribed 7 cm mass with light brown sectioned surfaces. Histologically, it was composed of a major population of large polygonal epithelioid cells in a nested alveolar growth and a subpopulation of smaller cells clustering around hyaline basement membrane material. The former cells possessed ample, clear to eosinophilic granular cytoplasm with well-defined cell borders and the latter was frequently accompanied by psammomatous calcification. These tumor cells exhibited immunoreactivity for melanoma markers, transcription factor EB and cathepsin K, but were not reactive for epithelial markers and transcription factor E3. While pulmonary metastatic foci that were noted preoperatively progressed rapidly following interferon-based therapy, subsequent sunitinib malate yielded a partial response and stabilized the lung metastasis for 6 months after surgery. We could trace 20 cases of 6p21 translocation renal carcinoma, among which only four were in individuals older than 40 years. Description of a new case like this is important since little is known about the prognosis and treatment of adult patients with this condition.

[Assessment of chemoradiation therapy for advanced rectal cancer invaded the pelvic organ].

We assess the effect of chemoradiation therapy for four cases of advanced rectal cancer. The radiation therapy consisted of 40-50 Gy delivered in fraction of 2 Gy/day. A treatment of 5-fluorouracil (500 mg/body) with l-leucovorin (100 mg/body) intravenously once a week, or oral S-1 (100 mg/day/body) for four weeks, was given during radiation therapy. Efficacy for primary carcinoma was evaluated as partial response in all four cases. We performed a curative operation in two cases. Histological efficacy for primary tumors was diagnosed as Grade 2 and Grade 3. Grade 3 adverse effect for neutropenia occurred in one patient, and Grade 3 adverse effect for appetite loss occurred in 2 patients. All cases survived without a recurrence for a period of 4 months-5 years and 3 months. Chemoradiation therapy was safe and an effective treatment prior to curative operation for advanced rectal cancer which invaded the pelvic organ.

[A case of advanced accessory breast cancer effectively treated with trastuzumab and paclitaxel].

A 53-year-old woman was admitted for left axillary mass. The computed tomography showed an invasive mass in the left axilla and left supraclavicular lymph node swelling. Histological findings of axillary mass revealed infiltrating ductal carcinoma of scirrhous type. We diagnosed advanced accessory breast cancer, and the patient was treated by combination chemotherapy with paclitaxel and trastuzumab. The lesions disappeared after 4 courses of chemotherapy and was clinically diagnosed as complete response (CR).

[Fulminant strongyloidiasis successfully treated by subcutaneous ivermectin: an autopsy case].

We report a 49-year-old man who was a human T-cell leukemia virus type 1 (HTLV-1) carrier, born in Okinawa prefecture where both strongyloidiasis and HTLV-1 are endemic. He presented with fever, headache and urinary retention. On the basis of CSF examination and MRI findings, his condition was diagnosed as myelitis. He received methylprednisolone pulse therapy. He was transferred to our hospital due to severe paralytic ileus. Strongyloides stercoralis (S. stercoralis) was found in the duodenal stained tissue of a biopsy specimen. Ivermectin applied both orally and through enema were ineffective because of severe ileus and intestinal bleeding. Nine mg (200 microg/kg) of ivermectin solution was administered subcutaneously every other day for five days (total amount 45 mg). The S. stercoralis burden in the stool decreased and paralytic ileus gradually resolved. Three weeks after the resolution of S. stercoralis infection, purulent meningitis developed and acute obstructive hydrocephalus appeared. The hydrocephalus improved by ventricular drainage. Approximately three months after drainage, he died of incidental aspiratory pneumonia. Autopsy showed neither eggs nor larvae of S. stercoralis in the organs. In this case, the fourth reported case in the world, subcutaneous ivermectin injection was dramatically effective. We should consider a diagnosis of strongyloidiasis for any patient from Okinawa prefecture who was an HTLV-1 carrier presenting with unknown origin ileus after treatment of steroid therapy.

[A 6-year-survival case of esophageal adenosquamous cancer with liver metastases cured by multidisciplinary therapy].

A 65-year-old man was diagnosed as esophageal cancer with multiple liver metastases (S2 10 mm, S7 10 mm, S8 15 mm). The preoperative diagnosis was stage IV (T 3 N 3 M 1 Pl 0), and he was operated palliatively by esophagocardiofundectomy and intrathoracic anastomosis for oral food intake. The postoperative histological diagnosis was adenosquamous carcinoma. One month after the operation he was administered orally UFT-E (300 mg/day) and PSK (3g/day). He was also treated by hepatic arterial infusion therapy with CDDP (10 mg/week). After 180 mg of CDDP, liver metastases were evaluated for PR. This therapy was discontinued after 410 mg of CDDP by vomiting and hypotension. 16 months after, DOC (20 mg/week) was given by arterial infusion and CR of liver metastases was achieved 18 months after. Then he was given 840 mg of DOC and oral administration of UFT-E and PSK was performed for about 5 years. He was free from the recurrence of cancer as an outpatient and had a good QOL. We think that esophageal cancer with liver metastasis should be aggressively treated surgically so as to allow oral food intake, and liver metastasis should be treated with chemotherapy because postoperative hepatic arterial infusion therapy is effective and provides a good QOL.

Ovarian pregnancy: report of four cases and review of the literature.

Ovarian ectopic pregnancy is rarely seen; it constitutes only 0.5-3% of all ectopic pregnancies and the incidence is only 1 for every 7000-40,000 deliveries. We herein report four cases of primary ovarian pregnancy encountered during the last 10 years in Miyazaki prefecture, Japan. The patients in all of these cases were admitted to their local hospitals with increased lower abdominal pain and intraperitoneal bleeding, and had surgery for total or partial oophorectomy. Grossly and microscopically, chorionic villi were exclusively found in the ovary but not in the fallopian tube, so that we diagnosed these cases as primary ovarian pregnancies. None of the patients were known to have used an intrauterine contraceptive device, which have been suggested as the cause of ovarian pregnancies in several studies. The incidence of ovarian pregnancy is recently increasing, and pathologists will have increased chances to diagnose this disease.