DDIT3-amplified or low-polysomic pleomorphic sarcomas without MDM2 amplification: Clinicopathological review and immunohistochemical profile of nine cases.

Several high-grade pleomorphic sarcoma cases that cannot be classified into any existing established categories have been reported. These cases were provisionally classified into undifferentiated pleomorphic sarcoma (UPS). Some dedifferentiated liposarcoma (DDLS) cases may also have been classified into the UPS category due to the absence of MDM2 amplification or an atypical lipomatous tumor/well-differentiated liposarcoma component. We retrieved and reviewed 77 high-grade pleomorphic sarcoma cases, initially diagnosed as UPS in 66 cases and DDLS in 11 cases. Fluorescence in situ hybridization (FISH) analyses of DDIT3 and MDM2 were performed for available cases. Of the cases successfully subjected to DDIT3 FISH (n = 56), nine (7 UPS and 2 DDLS) showed DDIT3 amplification but no MDM2 amplification. Two UPS cases showed both telomeric (5') and centromeric (3') amplification of DDIT3 or low polysomy of chromosome 12, whereas 5 UPS and 2 DDLS cases showed 5'-predominant DDIT3 amplification. Histopathologically, all cases showed UPS-like proliferation of atypical pleomorphic tumor cells. Immunohistochemically, only one case showed focal nuclear positivity for DDIT3, supporting the previous finding that DDIT3 expression was not correlated with DDIT3 amplification. All three cases with focal MDM2 expression involved 5'-predominant amplification, two of which showed DDLS-like histological features. The majority of cases (7/9) showed decreased expression in p53 staining, suggesting that DDIT3 amplification regulates the expression of TP53 like MDM2. From a clinicopathological perspective, we hypothesize that DDIT3-amplified sarcoma, especially with 5'-predominant amplification, can be reclassified out of the UPS category.

Pancreatic mixed acinar-neuroendocrine carcinoma with intraductal growth: A case report with radiologic-pathologic correlations.

Pancreatic mixed acinar-neuroendocrine carcinomas are rare malignant tumors of the pancreas. They are composed histologically of both acinar and neuroendocrine cells. The pancreatic duct is known to be an important site of tumor growth for acinar cell carcinomas, neuroendocrine tumors, and intraductal tubulopapillary neoplasms. To the best of our knowledge, there has been only 1 report of a mixed acinar-neuroendocrine carcinoma growing into the pancreatic duct and no reports detailing imaging findings with this tumor. We here report a 69-year-old man who presented with worsening glycemic control. Multiphase contrast-enhanced computed tomography and magnetic resonance imaging revealed a well-circumscribed mass with poor contrast enhancement in the pancreatic tail region of the pancreatic duct. The intraductal mass showed diffusion restriction on magnetic resonance imaging. These imaging findings are consistent with the expansive, smooth-surfaced polypoid tumor of low vascularity and high cellularity that was diagnosed pathologically. Mixed acinar-neuroendocrine carcinomas should be included in the differential diagnosis of intraductal tumors of the pancreas with poor contrast enhancement and diffusion restriction.

Comparative analyses of tumour immune microenvironment between collecting duct carcinoma and fumarate hydratase-deficient renal cell carcinoma.

AIMS: Collecting duct carcinoma (CDC) and fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) have similar histological morphologies and both show a poor prognosis. Programmed death ligand 1 (PD-L1) inhibitor has been approved for the treatment of RCC. However, tumour-infiltrating neutrophils stimulated by interleukin-8 (IL-8) interfere with PD-L1 inhibitors. Here, we retrospectively analysed PD-L1 and IL-8 expression, and examined its relationship with infiltrating immune cells. METHODS: Nine cases of CDC and seven cases of FH-deficient RCC were selected. We defined PD-L1 and IL-8 expression by the Tumour Proportion Score and Combined Positive Score (CPS). We counted the numbers of CD8+, CXCR2+, CD11b+, CD66b+ and CD33+ immune cells located in the tumour components. RESULTS: A number of CXCR2+ (p=0.0058), CD11b+ (p=0.0070) and CD66b+ (p=0.0067) immune cells infiltrating into CDC were significantly higher than those infiltrating into FH-deficient RCC. In CDC, PD-L1 expression was correlated with a high density of CD8+ lymphocytes (p=0.0389), but was not in FH-deficient RCC (p=0.6985). IL-8 CPS was significantly higher in CDC than in FH-deficient RCC (p=0.0069). In addition, among the CDC cases, IL-8 CPS showed significant positive correlations with CXCR2+, CD11b+ and CD66b+ immune cell densities (p=0.0250, p=0.0104 and p=0.0374, respectively), whereas FH-deficient RCC showed no significant correlations between IL-8 CPS and immune cell densities. CONCLUSIONS: Our results suggest the difference of each tumour microenvironment between CDC and FH-deficient RCC, and IL-8 is a potential therapeutic target for treating CDC, but not FH-deficient RCC.

Poorly differentiated adenocarcinoma with signet ring cells of the gallbladder producing a high level of alpha-fetoprotein: A case report.

INTRODUCTION: Alpha-fetoprotein (AFP) can become elevated in hepatocellular carcinoma (HCC), yolk sac tumors and other malignant tumors of various organs. Herein, we present a case of AFP-producing gallbladder carcinoma with signet ring cells successfully treated with laparoscopic whole-layer cholecystectomy. PRESENTATION OF CASE: A 69-year-old woman was found to have increased levels of the tumor marker AFP (16.1 to 1474 ng/mL), and an irregularly shaped mass 22 mm in size in the gallbladder at 5 months follow-up after transcatheter arterial chemoembolization and radiofrequency ablation for HCC in segment 3 of the liver. As no additional metastases were detected, we diagnosed the patient with either AFP-producing gallbladder carcinoma (cT2aN0M0, cStage IIa, UICC 8th) or gallbladder metastasis from HCC. Laparoscopic whole-layer cholecystectomy was performed, and histological examination revealed AFP positive poorly differentiated adenocarcinoma with signet ring cells (pT2bN0cM0, pStage IIb, UICC 8th). AFP levels were remarkably decreased after operation (15 ng/mL), and no residual tumors or distant metastases were observed on contrast enhanced computed tomography (CE-CT), indicating that the tumor was an AFP-producing gallbladder carcinoma rather than metastasis of HCC. DISCUSSION: Due to the similar developmental origin of the liver and gallbladder, gallbladder carcinoma could produce AFP in some cases. Considering that AFP is predominantly synthesized during embryogenesis, the status of cellular differentiation would be associated with the ability to synthesize AFP. CONCLUSION: When no lesions except for in the gallbladder can account for elevated AFP levels, clinicians should consider AFP-producing gallbladder carcinoma.

Liver metastases 2 years after resection of a very-low-risk duodenal gastrointestinal stromal tumor: a case report.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are rare mesenchymal tumors, but are the most common mesenchymal tumors of the gastrointestinal tract. The risk classification of GISTs is based on the tumor size, mitotic index, tumor site, and presence of tumor rupture. Recurrence in the very-low-risk group is extremely rare. We herein report a case of liver metastases 2 years after resection of a very-low-risk duodenal GIST. CASE PRESENTATION: A 57-year-old woman presented to the hospital for evaluation of melena. Esophagogastroduodenoscopy showed bleeding from the exposed blood vessels at the top of a submucosal tumor approximately 20 mm in size located in the second (descending) part of the duodenum, and the bleeding was controlled with electrocoagulation. A GIST was suspected, and the patient underwent wedge resection of the duodenum. The resected specimen contained a 16- × 12-mm (< 20-mm) white submucosal tumor composed of spindle cells with a mitotic count of 4 per 50 high-power fields, and a histologically negative margin was achieved. Immunochemical analysis revealed positive tumor staining for c-kit protein and alpha-smooth muscle actin and negative staining for CD34, desmin, and S-100 protein. Therefore, the tumor was diagnosed as a very-low-risk duodenal GIST based on the Fletcher classification and modified Fletcher classification (Joensuu classification). The postoperative course was uneventful, and the patient was discharged on postoperative day 11. At the follow-up visit 2 years postoperatively, contrast-enhanced computed tomography revealed liver tumors in S8 and S6 measuring 26 × 24 and 10 × 10 mm, respectively. Both lesions showed peripheral dominant hyperenhancement with hypoenhancement inside, indicating tissue degeneration within the tumors. These imaging findings closely resembled those of the duodenal GIST. Hence, the patient was diagnosed with liver metastases of GIST 2 years postoperatively. She was subsequently started on treatment with 400 mg of imatinib. At the time of this writing (2 months after diagnosis), the patient was clinically well and asymptomatic and was continuing imatinib therapy. CONCLUSIONS: Recurrence of very-low-risk GISTs is extremely rare. Even a small GIST with low mitotic activity can never be considered completely benign, and long-term follow-up is necessary.

"Honeycomb" appearance in large-duct type pancreatic ductal adenocarcinoma: Case report with radiologic-pathologic correlation.

Large-duct type pancreatic ductal adenocarcinoma (PDA) is a rare morphologic variant forming large duct elements. This case report, to our knowledge, is the first report of a large-duct type PDA with a "honeycomb" appearance resembling a serous cystic neoplasm (SCN) on CT and MRI. The patient is an 82-year-old woman who presented with upper abdominal pain. Dynamic contrast-enhanced CT revealed a multilocular cyst with honeycomb loculi, in which the cyst walls showed gradual enhancement. On T2-weighted MRI, the mass displayed inhomogeneous hyperintensity characterized by a honeycomb appearance with irregular and thick hypointense cyst walls. The patient underwent distal pancreatectomy; histopathological diagnosis was large-duct type PDA. Although the imaging features of large-duct type PDA may resemble those of SCN, this distinction between PDA and SCN is important because the treatment options are very different.

Approach for reclassification of collecting duct carcinoma and comparative histopathological analysis with SMARCB1/INI1-deficient renal cell carcinoma and fumarate hydratase-deficient renal cell carcinoma.

Collecting duct carcinoma (CDC) is a rare subset of high-grade renal cell carcinoma (RCC). To diagnose CDC, it is necessary to rule out other renal tumors including renal medullary carcinoma and fumarate hydratase (FH)-deficient RCC. However, there is overlap in the morphology of these three tumors, which all have poor outcomes. There is also still a need to sufficiently examine the therapeutic strategies for each of these tumors. In this study, we retrospectively reclassified invasive/infiltrating high-grade RCC and investigated its pathological features. We reviewed 18 cases previously diagnosed as "CDC," "FH-deficient RCC," and "unclassified RCC," which were reclassified as SMARCB1/INI1-deficient RCC, FH-deficient RCC, and CDC by SMARCB1/INI1, FH, and 2SC immunohistochemistry (IHC) and FH gene mutational status. As the result, 18 cases were reclassified into 2 cases of SMARCB1/INI1-deficient RCC, 7 cases of FH-deficient RCC, and 9 cases of CDC. The morphological features of each group overlapped, and no specific immunohistochemical expression except for SMARCB1/INI1, FH, and 2SC was detected. These results suggest that invasive/infiltrating high-grade RCC should be diagnosed by the combination of immunohistochemistry and molecular biological technique.

Myxoid type and non-myxoid type of intimal sarcoma in large vessels and heart: review of histological and genetic profiles of 20 cases.

Intimal sarcoma is one of the most common and well-known primary malignant neoplasms of the aorta and heart. The authors reviewed cases of intimal sarcoma from histological, immunohistochemical and genetic perspectives. Twenty cases of intimal sarcoma were retrieved. Immunohistochemistry and FISH of MDM2 and PDGFRA genes were performed. All 20 tumours were composed of spindle-shaped, stellate, oval or polygonal tumour cells with irregular hyperchromatic nuclei arranged in a haphazard pattern, accompanied by nuclear pleomorphism and frequent mitotic figures. Other histological findings were as follows: abnormal mitosis in 10 cases (50%), necrosis in 15 cases (75%), myxoid stroma in 12 cases (60%), cartilaginous formation in 1 case (5%), haemorrhage in 12 cases (60%) and fibrinous deposition in 14 cases (70%). The tumours were positive for MDM2 in 16 cases (80%), ERG in 4 cases (20%), alpha-smooth muscle actin in 6 cases (30%), desmin in 5 cases (25%) and AE1/AE3 in 4 cases (20%). Immunohistochemical positivity was focal in each case. Loss of H3K27me3 expression was noted in 2 cases (10%). MDM2 and PDGFRA gene amplifications were detected in 11 cases (55%) and 1 case (5%), respectively. Fisher's exact test revealed a significant correlation between MDM2 gene amplification and myxoid stroma (p = 0.0194). No parameters showed any association with the anatomical location of the tumours. It was suggested that myxoid histology of intimal sarcoma may be associated with MDM2 gene amplification and that intimal sarcoma may be divided into myxoid and non-myxoid types.

Histological background of dedifferentiated solitary fibrous tumour.

AIMS: Dedifferentiation is a histological phenomenon characterised by abrupt transition of histology to a sarcomatous component with high-grade malignant potential in solitary fibrous tumour (SFT). The authors histologically reviewed SFT cases to reveal the histological background of dedifferentiated SFTs. METHODS: Clinicopathological and histopathological findings of 145 SFT cases were reviewed. Immunohistochemical staining and genetic analysis were also performed. RESULTS: The non-dedifferentiated components showed a cellular component in 45 of 145 (31%), high mitotic rate (≥4/10 high-powered field) in 12 of 145 (8.2%) tumours, necrosis in 7 of 145 (4.8%) tumours, multinodular growth pattern in 39 of 132 (29.5%) available tumours and intratumoural fibrous septa in 37 of 131 (28.2%). Immunohistochemically, the non-dedifferentiated components were positive for CD34 in 128 of 141 (90.7%), bcl-2 in 101 of 133 (75.9%), nuclear pattern of ß-catenin in 64 of 127 (50.3%) and p16 in 22 of 140 (15.7%). Loss of Rb protein expression was detected in 17 of 110 (15.4%) cases. Statistically, cellular component, multinodular structure, p16 overexpression and Rb protein loss were significantly associated with dedifferentiation. Moreover, cellular component and multinodular structure were significantly associated with p16 overexpression and Rb protein loss. All the non-deddifferentiated components showed wild type of p53 expression. The dedifferentiated components of all 10 dedifferentiated tumours presented positivity for p16 in 9 of 10 (90%) and mutational type of p53 in 5 of 10 (50%). Loss of Rb protein expression was detected in 6 of 10 (60%). CONCLUSIONS: The authors propose that cellular or multinodular transformation may be associated with dedifferentiation. They also suggest that cellular and multinodular transformation may be associated with p16 overexpression and Rb downregulation.

Prognostic implication of desmoplastic stroma in synovial sarcoma: A histological review.

Synovial sarcoma (SS) is a malignant soft tissue neoplasm harboring SS18-SSX fusion gene and is histologically characterized by spindle cells and epithelial components. Some investigations have demonstrated that desmoplastic reaction (DR) is an independent prognostic factor of cancers. However, it remains unknown whether DR is of predictive value for the prognosis of synovial sarcoma patients. Here, we reviewed the clinical and histological findings of 88 patients with SS. We defined DR as hyalinized collagenous structures and classified the degree of DR as follows: none, mild, moderate, and severe. Overall, 23 SS cases (24%) showed moderate or severe DR histologically. Statistically, the cases with moderate or severe degree of DR showed poorer prognosis than those with no or mild DR (local recurrence: P = 0.0059, distant metastasis: P = 0.0002, tumor death: P = 0.0382). The findings of the study suggest that the DR of synovial sarcoma could be an important prognostic factor.

Pathological review of cardiac amyloidosis using autopsy cases in a single Japanese institution.

AIM: Amyloidosis is a systemic or localized disease of protein deposition characterized by amorphous eosinophilic morphology and positivity of Congo Red staining. The typing of amyloidosis is becoming increasingly important because therapeutic agents for each amyloidosis type have been developed. Herein, the authors review the autopsy cases at an institution to reveal the putative Japanese characteristics of each amyloidosis type and evaluate the clinicopathological significance of each type. MATERIALS AND METHODS: A total of 131 autopsy cases of systemic and localized amyloidosis were retrieved for classification by immunohistochemistry. Immunohistochemistry for transthyretin, amyloid A (AA), immunoglobulin light-chain kappa and lambda, and ß2-microglobulin was performed for all cases. RESULTS: The 131 amyloidosis cases were classified as follows: 71 cases (54.2%) of transthyretin amyloidosis, 32 cases (24.4%) of AA amyloidosis, 8 cases (6.1%) of light-chain amyloidosis, and 5 cases (3.8%) of ß2-microglobulin amyloidosis, along with 15 equivocal cases (11.5%). All cases showed myocardial involvement of amyloidosis. Histopathologically, the transthyretin type was significantly associated with the interstitial and nodular patterns, and with the absence of the perivascular and endocardial patterns. The AA type was significantly associated with the perivascular and endocardial patterns, and with the absence of the nodular pattern. CONCLUSION: The authors revealed the putative characteristics of cardiac amyloidosis in Japan by using autopsy cases. About 90% of amyloidosis cases were successfully classified using only commercially available antibodies.

Intermittent percutaneous drainage of ovarian tumour.

INTRODUCTION: Abdominal pain and distention are common in ovarian tumours. When the ovarian tumour grows too large, the tumour can cause these symptoms. Percutaneous drainage from ovarian tumours, which can alleviate symptoms, is traditionally discouraged for its potential risk of peritoneal tumour seeding. CASE: A 73-year-old woman with a multilocular ovarian tumour reporting abdominal fullness and pain was referred to the palliative care outpatient department. The multilocular tumour occupied most of the intra-abdominal space, which was determined to cause her symptoms. To alleviate her symptoms, we performed intermittent percutaneous drainage for 1.5 years. A clinical autopsy revealed the tumour was an ovarian mucinous carcinoma. Despite iterative tumour drainage, we observed no feature of peritoneal dissemination. CONCLUSION: Intermittent percutaneous drainage of ovarian tumours could reduce tumour-related abdominal symptoms without pathological evidence of peritoneal dissemination. This procedure can be a new palliative treatment option for ovarian tumour-related abdominal symptoms.

Parosteal osteosarcoma with a manifestation of subperiosteal low-grade central osteosarcoma.

We report the peculiar case of a parosteal osteosarcoma arising beneath the periosteum in a 12-year-old boy. He complained of difficulty in left knee flexion. Plain radiography showed a uniformly dense mineralized mass in the bone cortex and parosteal ossified nodules at the metaphysis and diaphysis of the left distal femur. Periosteal reaction was not evident. Uniquely, plain radiography had a smooth outline and revealed gradually thickening mass toward the center. Histologically, the tumor showed a proliferation of spindle-shaped cells with parallel-oriented dense bone trabeculae and hyaline cartilaginous tissue disclosing mild atypia. The periosteum was inverted along the polypoid mass, but there was no periosteum at the top. Immunohistochemically, the spindle cells, including those at the top of the polypoid mass, and cartilaginous cells were positive for MDM2 and CDK4. MDM2 gene amplification was detected in these cells by fluorescence in situ hybridization. Despite the peculiar feature of plain radiography, the lesion was diagnosed as parosteal osteosarcoma. This case report presents a case of parosteal osteosarcoma arising beneath the periosteum, although it is postulated to arise in the outer layer of the periosteum. The unique radiographic findings in this case suggest an association of parosteal osteosarcoma with vigorous bone growth before closure of the growth plate.

Three cases of synovial sarcoma of gastric wall: A case report and review of the literature.

Synovial sarcoma (SS) is a malignant soft tissue neoplasm that occurs in various parts of the human body, but most commonly affects the extremities. Its diagnosis of synovial sarcoma often requires adjunctive techniques such as immunohistochemical staining and molecular studies, especially for synovial sarcoma at unusual locations. SS at a gastrointestinal location is exceedingly rare. We report here three cases of primary gastric synovial sarcoma. Malignant gastric mesenchymal tumor has many differential diagnoses other than synovial sarcoma, such as gastrointestinal stromal tumor (GIST), leiomyosarcoma, schwannoma, malignant peripheral nerve sheath tumor (MPNST) and so on. In our three cases, using reverse transcription polymerase chain reaction (RT-PCR) and direct sequencing, we detected an SS18-SSX1 fusion gene, which is specific to synovial sarcoma. In addition, we found the reduced expression of SMARCB1/INI1 in the tumor cells in two of the three cases. Through histopathological, immunohistochemical, and molecular analyses, we confirmed the diagnosis of primary gastric synovial sarcoma.

Anisotropic Self-Oscillating Reaction in Liquid Crystalline Nanosheet Hydrogels.

Anisotropic chemical wave propagation of self-oscillating Belousov-Zhabotinsky (BZ) reaction was demonstrated in the poly( N-isopropylacrylamide) gel films embedded with macroscopically aligned liquid crystalline inorganic nanosheets. Although the average propagation rate of chemical wave v̅ was 3.56 mm min-1 in the gels without nanosheets, the propagation was retarded in the gels with 1 wt % of nanosheets: [Formula: see text] = 1.89 mm min-1 and [Formula: see text] = 1.33 mm min-1 along the direction parallel and perpendicular to the nanosheet planes, respectively. Thus, the wave propagation is anisotropic with the anisotropy ratio [Formula: see text] = 1.42 in these gels and the periodic patterns formed by the BZ reaction were concentric ellipses, different from circles seen in isotropic gels. Furthermore, the propagation rate and degree of anisotropy were controllable by nanosheet concentration. These phenomena can be explained that the diffusion of molecules inside the gel is effectively hindered along the direction perpendicular to the nanosheet planes due to the very large aspect ratio of the aligned nanosheets. The present systems will be applicable for anisotropic self-oscillating soft actuators with one-dimensional motions as well as for ideal model system of BZ reactions.