Masanori Masuda

Hepatoid carcinoma of the pancreas penetrating into the gastric cavity: A case report and literature review

A 79‐year‐old Japanese woman was admitted to our hospital for treatment of a pancreatic tumor measuring approximately 7 × 5 cm. The tumor had invaded the left adrenal gland and gastric wall and had penetrated into the gastric cavity. Surgical resection was performed. The tumor was composed of a brown to whitish solid area and a zone of hemorrhage, necrosis, and cystic degeneration resembling the gross features of solid pseudopapillary tumor (SPT). Histologically, the tumor showed a heterogeneous growth pattern with a combination of seat‐like, trabecular, papillary and hemorrhagic‐necrotic areas in various proportions. The differential diagnoses first considered were acinar cell carcinoma, neuroendocrine carcinoma and SPT with malignant transformation. Immunohistochemistry showed tumor cells were negative for pancreatic exocrine enzymes and endocrine markers. Tumor cells diffusely expressed cytokeratin 19, alpha‐fetoprotein, carcinoembryonic antigen and glypican‐3, but lacked vimentin or β‐catenin expression. Small proportions of tumor cells expressed hepatocyte paraffin‐1. Although typical morphological features of well‐differentiated hepatocellular carcinoma (HCC) were not distinctly apparent, the tumor morphology partly resembled poorly differentiated HCC. Given these findings and considerations, the tumor was finally diagnosed as poorly differentiated hepatoid carcinoma of the pancreas.

The utility of a reusable bipolar sealing instrument, BiClamp®, for pulmonary resection

OBJECTIVE To assess the use of a combination of bipolar sealing and electrosurgical coagulation for pulmonary resection. METHODS The procedure was used in both dogs and humans. Initially, lung wedge resections were performed on six healthy, Beagle dogs using a voltage controlled electrosurgical system. The area of lung tissue to be resected was first coagulated to provide a distinct line of seal. The lung was then resected along the peripheral site of the sealing scar. Efficiency of sealing was assessed using a tracheally applied air pressure of 30cmH(2)O. The electro-cauterized tissue was compared histologically to tissue sealed by a standard stapling technique. In the clinical phase, lung resections were performed after cauterization in 17 patients. Bullectomies were performed using video-assisted thoracic surgery in 4 patients, and thoracotomic procedures in 13 (1 bullectomy, 5 wedge resections, and 7 fissure separations). RESULTS Dogs: Tissue sealing was highly successful, without any air leakage, in all six dogs. Histologically, the clamped lesion showed tissue-fusion probably due to both the compression and thermal effects. The proximal zone adjacent to the clamped lesion revealed both collapsed alveolar spaces and fused alveolar walls. In comparison, the stapled lesions showed no tissue-fusion. Humans: There were no major complications. The median operation time was 189min, and estimated median hemorrhage volume was 67ml. Median chest drainage duration was 3 days (range: 1-7) and no patient suffered from prolonged air leakage (>7 days). CONCLUSIONS Lung parenchymal tissue resection following bipolar sealing and electrosurgical coagulation instead of staples was efficient and simple. Furthermore, the technique reduced the use of staples, reducing the cost of the surgery.

Clinicopathologic features of advanced gallbladder cancer associated with adenomyomatosis

Adenomyomatosis of the gallbladder has not been considered to have malignant potential, but gross features of adenomyomatosis are sometimes encountered in gallbladders resected under a diagnosis of gallbladder carcinoma. The purpose of this study was to determine the clinicopathologic features and survival rates in cases of gallbladder cancer with gross features of adenomyomatosis. The study subjects were 97 surgically treated gallbladder carcinoma patients. Only gallbladder showing typical gross features of adenomyomatosis was judged as adenomyomatosis-positive gallbladder cancer. In terms of gross findings, 25 cases (25.8%) were classified as adenomyomatosis-positive. The status of adenomyomatosis was significantly associated with the T stage (P = 0.0004), lymph node (LN) metastasis (P < 0.0001), distant metastasis (P = 0.008), and stage (P = 0.0005). In the adenomyomatosis-positive group, 16 of the 25 cases (64.0%) were classified as segmental type and 9 cases (36.0%) were classified as fundal type. No diffuse-type cases were present in this series. The status of adenomyomatosis correlated significantly with survival (P = 0.0007). However, the multivariate analysis of significant variables identified from the univariate analysis identified only T stage (P = 0.0178) and LN metastasis (P = 0.0048) as independent prognostic factors. Subset analysis with T stage according to the status of adenomyomatosis showed no significant impact on survival. These results indicate that adenomyomatosis-positive gallbladder cancer is more often diagnosed clinically in the advanced stages. Since preceding adenomyomatosis may prevent the early detection of gallbladder cancer, the usefulness of preventive cholecystectomy in cases of asymptomatic adenomyomatosis should be considered.

Endoglin (CD105) expression and angiogenesis status in small cell lung cancer

It is well established that angiogenesis is crucial for tumor development and progression. Among the angiogenesis immunomarkers defined to date, endoglin (CD105) has been shown to be a useful marker of angiogenesis. To investigate the degree of angiogenesis status in small cell lung cancer (SCLC) tissue, we assessed 35 cases of SCLC at autopsy using immunohistochemical staining of CD31 and CD105. The intratumoral area, peritumoral area, and background pulmonary alveoli were then observed under low magnification, and the microvessel density (MVD) for each area was determined. The MVD-CD31 was the highest in the background alveoli, followed by the intratumoral and peritumoral areas. The MVD-CD105 was highest in the intratumoral area, followed by the peritumoral area and the background lung. The ratio of CD105/CD31 revealed that almost 78% of the intratumoral area, 63% of the peritumoral area, and 4.6% of the background lung alveoli were newly formed and expressed CD105. This result indicated that SCLC is predominantly supported by newly formed vessels that are generated by CD105-mediated angiogenesis. These findings suggest that anti-angiogenic therapy, especially CD105-targeting, may prove an effective form of SCLC treatment.

Analysis of Extrahepatic Multiple Primary Malignancies in Patients with Hepatocellular Carcinoma according to Viral Infection Status

Previous studies have investigated extrahepatic multiple primary malignancy (EHPM) associated with hepatocellular carcinoma (HCC). However, its correlation with viral infection, such as hepatitis B virus (HBV) or hepatitis C virus (HCV), has not been examined. The aim of this study is to investigate the association between EHPM and hepatitis infection in HCC patients. A total of 412 patients who underwent surgical resection for primary HCC were enrolled. Viral infection was evaluated by serum HBV surface antigen (HBs Ag) and HCV antibody (HCV Ab). Sixty-eight (16.5%) patients had one or more EHPM. The most frequent EHPM was gastric cancer (n = 32) in this cohort. No statistical significance was observed in the distribution of viral infection and incidence of entire EHPM. However, HCV Ab, HBs Ag, and negative status for both were correlated with the frequency of gastric (P = 0.0194), urinary tract (P = 0.0067), and breast cancer (P = 0.0036), respectively. Infection of Helicobacter pylori was investigated by immunohistochemistry in gastric EHPM and resulted that 20 out of 21 analyzed cases were negative for Helicobacter pylori. Although it should be verified by well-designed large cohort studies, the current results suggested correlation between HCV infection and gastric cancer, HBV infection and urinary tract cancer and viral hepatitis-free status and breast cancer in HCC patients.

A case of mucosa-associated lymphoid tissue lymphoma of the gastrointestinal tract showing extensive plasma cell differentiation with prominent Russell bodies.

A 73-year-old Japanese woman was hospitalized for detailed examination of nausea, diarrhea and loss of appetite. Atypical erosion in the ileum was found on endoscopy. Biopsy of this erosion showed proliferation of cells containing numerous Russell bodies. Differential diagnoses considered were Russell body enteritis, crystal-storing histiocytosis, Mott cell tumor, immunoproliferative small intestinal disease (IPSID) and mucosa-associated lymphoid tissue (MALT) lymphoma. The cells containing prominent Russell bodies showed diffuse positivity for CD79a and CD138, but negative results for CD20, CD3, UCHL-1, CD38 and CD68. Russell bodies were diffusely positive for lambda light chain, but negative for kappa light chain, and immunoglobulin (Ig) G, IgA and IgM. Based on these findings, Russell body enteritis, crystal-storing histiocytosis and IPSID were ruled out. As the tumor formed no mass lesions and was restricted to the gastrointestinal tract, MALT lymphoma with extensive plasma cell differentiation was finally diagnosed. The patient showed an unexpectedly aggressive clinical course. The number of atypical lymphocytes in peripheral blood gradually increased and T-prolymphocytic leukemia (T-PLL) emerged. The patient died of T-PLL 7 mo after admission. Autopsy was not permitted.

Pathological features of classical polyarteritis nodosa: analysis of 19 autopsy cases.

Classical polyarteritis nodosa (cPN) is a rare autoimmune disease featuring systemic inflammation of middle- and small-sized arteries. Because most of autopsy cases underwent clinical treatment, arterial fibrinoid necrosis, which is the most specific finding of cPN, is often obscure. The aim of this study was to seek morphological characteristics of the middle-sized arteries in autopsy cases of cPN, and to identify immunohistochemical markers for the diagnosis of cPN. Nineteen patients who had undergone autopsy with a diagnosis of cPN were enrolled. Twenty-one autopsy cases without cPN were examined as control group. Arterial fibrinoid necrosis in medium-sized arteries was observed in 8/19 autopsy cases. Elastica van Gieson staining showed an increased number of elastic fiber layers (P<0.0001) and greater distances between elastic fiber layers (P<0.0001) in the renal middle-sized arteries of the cPN group. These findings probably reflected the post-inflammatory remodeling process after necrotizing vasculitis. On immunohistochemical examination, the cPN group showed high matrix metalloproteinase-1 and tumor necrosis factor-α expressions and decreased smoothelin expression in the vascular wall compared to the control group. When uncertain or atypical autopsy cases of cPN are examined, these findings can help to make the pathological diagnosis of cPN.

Metachronous aortic aneurysms due to sarcoidosis

A 62‐year‐old male developed metachronous aortic aneurysms at different locations over an interval of one year and three months. He was diagnosed to have sarcoid aneurysms due to the presence of noncaseating epithelioid granulomas in the aortic wall and lymph nodes. The patient was treated with steroids, but his sarcoidosis progressed gradually and extended into other major organs, and the lungs and heart were clinically determined to have been involved by sarcoidosis. He died of cardiac tamponade four years after the first operation for an aortic aneurysm.

A case of mucinous cholangiocarcinoma showing features of hepatocellular carcinoma.

To the Editor: Mucinous cholangiocarcinoma is a rare variant of intrahepatic cholangiocarcinoma. The incidence of mucinous cholangiocarcinoma has not been investigated in detail, but Nakajima et al. reported only one case of mucinous cholangiocarcinoma (0.8%) among 102 patients with cholangiocarcinoma. The development of portal invasion is one of the characteristic features of hepatocellular carcinoma (HCC), while protein induced by vitamin K absence or antagonist (PIVKA)-II, which is also termed des-gamma carboxyprothrombin and alpha-fetoprotein (AFP), are wellknown tumor markers of HCC. We encountered a unique case of mucinous cholangiocarcinoma showing oncocytic cytoplasm, marked portal vein invasion and PIVKA-II production. To the best of our knowledge, no such case has been reported in either the English or Japanese literature. A 51-year-old Japanese man had been followed for diabetes mellitus and chronic hepatitis C. After follow-up abdominal ultrasonography revealed a hepatic mass, further clinical examinations were performed. Laboratory tests revealed mild anemia (hemoglobin concentration, 10.4 g/dL), while white blood cell and platelet counts were within normal ranges (6200/μL and 23.8 × 10/μL, respectively). Coagulation tests showed no abnormalities. Results of serological testing were as follows: total protein, 7.0 g/dL; albumin, 2.8 g/ dL; aspartate aminotransferase, 44 IU/L; alanine aminotransferase, 19 IU/L; lactate dehydrogenase, 323 IU/L; alkaline phosphatase, 547 IU/L; γ-glutamyl transpeptidase, 188 IU/L; total bilirubin, 1.0 mg/dL; C-reactive protein, 1.55 mg/dL; and HbA1c, 4.2%. Levels of examined tumor markers were as follows: carcinoembryonic antigen (CEA), 6.4 ng/mL (normal, <5.0 ng/mL); carbohydrate antigen (CA)19-9, 540 U/mL (normal, <37 U/mL); PIVKA-II, 5750 mAU/mL (normal, <40 mAU/mL); AFP, 76.3 ng/mL (normal, <10.0 ng/mL); and AFPL3, 87.3% (normal, <10.0%). Contrast-enhanced abdominal computed tomography (CT) showed a huge mass replacing the right lobe of the liver. Tumor embolus was also identified in the portal vein (Fig. 1a). No metastatic nodules were detected in the left lobe of the liver. The tumor showed signal hypointensity on T1-weighted magnetic resonance imaging (MRI) and marked signal hyperintensity on T2-weighted MRI. Although radiological findings were unusual for HCC, the tumor was clinically diagnosed as HCC based on characteristics such as portal tumor embolus and elevated levels of serum PIVKA-II and AFP. Surgical resection (right hepatectomy) without lymphadenectomy was therefore performed. Although S-1 was administrated as adjuvant chemotherapy, recurrent tumors were found at the left lobe of the liver eight months after the operation. No further chemotherapy and only palliative therapy was performed. He died of

Mitotic count reflects prognosis of gallbladder cancer particularly among patients with T3 tumor

The surgical strategy for gallbladder cancer (GBC) depends on the extent of the disease. Thus, the identification of useful prognostic markers exerting strong prognostic impact for each T stage would be beneficial in the development of rational therapeutic strategies. The purpose of this study was to identify useful prognostic markers of GBC for each T stage. CD8+ tumor-infiltrating lymphocytes (TIL), Ki-67 labeling index (LI), p53 nuclear expression and mitotic count (MC) were investigated as candidate prognostic markers. In total, 86 patients with invasive GBC were included. Of the prognostic markers examined, only MC showed a correlation with reduced survival (P=0.0383) in the univariate analysis of overall T stage. In the univariate analysis of T2 stage (n=31), only high p53 expression correlated with survival showing a positive correlation (P=0.0154). In the univariate analysis of T3 stage (n=40), the only factor showing a significant correlation with survival was MC (P=0.0113). Multivariate analysis, including N and M as factors, identified only MC as an independent prognostic factor in T3 stage GBC (P=0.0419). In conclusion, this study demonstrated the strong prognostic impact of MC in GBC, particularly in patients with T3 tumor.