Cytological Assessment of Desmoplastic Malignant Pleural Mesothelioma in an Autopsy Case.

INTRODUCTION: Desmoplastic malignant pleural mesothelioma (DMPM) is a sarcoma-type mesothelioma, comprising approximately 5% of malignant pleural mesotheliomas. Although effusion cytology is commonly used as the primary diagnostic approach for mesothelioma, it may not be useful for DMPM because of the presence of desmoplasia and bland cellular atypia. We report a case, and previously undescribed cytological features, of DMPM that was diagnosed during autopsy. CASE PRESENTATION: A man in his 60s with a history of occupational asbestos exposure was referred to our hospital with right chest pain. A chest CT scan showed right pleural effusion. Thirteen months later, the patient died of respiratory failure. During autopsy, scrape-imprint smears were prepared and cytology of pleural effusions was performed. The scrape-imprint smear samples showed spindle cells with mild nuclear atypia and grooves with fibrous stroma. Pleural effusion cytology revealed spindle cells with mild nuclear atypia, as well as grooves with loose epithelial connections. Histological examination of the right pleura showed spindle cells proliferating with dense collagen fibers, as seen in the cytological samples, thus indicating a diagnosis of DMPM, which was confirmed by fluorescence in situ hybridization. CONCLUSION: Cytological procedures such as pleural effusion cytology and scrape-imprinting cytology may help in diagnosing rare tumors such as DMPM.

Helicobacter pylori protein that binds to and activates platelet specifically reacts with sera of H. pylori-associated chronic immune thrombocytopenia.

Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by antiplatelet antibodies and/or CD8 + T cells, resulting in the destruction of platelets and decreased platelet counts. Helicobacter pylori that persistently colonizes the stomach causes various disorders, including extragastric diseases such as chronic ITP (cITP). Several studies have reported increased platelet counts in H. pylori-infected cITP patients with eradication treatment and also the pathophysiological pathways involving cross-reaction of antibodies against H. pylori with platelets, the modulation of Fcrγ receptors balance and others. We previously reported an immunocomplex pathway comprising H. pylori low-molecular-weight (LMW) antigens, their antibodies, and platelets, involved in the development of H. pylori-associated cITP; however, the LMW antigens were not identified. In the present study, we demonstrated that the H. pylori LMW antigen of the immunocomplex was identified as Lpp20 of outer membrane proteins. Lpp20 could bind to platelets and specifically react with sera of H. pylori-associated cITP patients.

Capecitabine + Epirubicin + Cyclophosphamide Combination Therapy (CEX Therapy) as Neoadjuvant Chemotherapy for HER-2-Negative Breast Cancer: A Retrospective, Single-Center Study.

BACKGROUND: We modified and administered capecitabine + epirubicin + cyclophosphamide combination therapy (CEX) as neoadjuvant chemotherapy (NAC) for HER-2-negative breast cancer and retrospectively analyzed its effectiveness and tolerability at our center. METHODS: The inclusion criteria were presence of breast cancer negative for HER-2 and positive lymph node metastasis, or negative lymph node metastasis when tumor diameter was 20 mm or greater without distant metastasis. Additional inclusion criteria were a performance status of 0 or 1, an EF >60%, and an age of 75 years or less. Clinical outcomes were evaluated after 4 courses of epirubicin 80 mg/m2, cyclophosphamide 500 mg/m2 (administered every 3 weeks), and capecitabine 1,500 mg/m2 (administered for 2 weeks and withdrawn for 1 week). RESULTS: A clinical benefit was noted in all 18 patients who received CEX as neoadjuvant chemotherapy during the period from 2009 through 2013. The clinical response rate was 83.3% (15/18), and the clinical complete response rate was 50%. Aesthetic outcomes of breast-conserving surgery were positive in all patients. Among patients with satisfactory outcomes, 33.3% had a pathologic complete response (triple-negative: 6, luminal: 0) and 68.8% were n0 (triple-negative: 8, luminal: 3). All patients with a pathologic complete response are presently alive, free of recurrence, and currently undergoing follow-up. Adverse events were classified as grade 2 or lower in all patients. CONCLUSIONS: CEX therapy administered as neoadjuvant chemotherapy could be useful for individualized treatment. In particular, this regimen was effective for triple-negative breast cancer.

Genetic structure and diversity of the wild Ussurian pear in East Asia.

The Ussurian pear is the most important cultivated pear in the northern part of China. Cultivated Ussurian pears are considered to have derived from Pyrus ussuriensis Maxim. which is native to the northeast of China. In Japan, two varieties of P. ussuriensis, P. ussuriensis var. aromatica and var. hondoensis are native to the northern area and the central area of the main island respectively. In order to reveal the origin of Pyrus ussuriensis var. aromatica distributed in the northern area of main island of Japan, more than 40 explorations have been performed in Japan and in China, and more than 30 natural habitats were recognized. These natural habitats are at risk of extinction because of human development and forest degradation caused by climate change. Population structure and genetic diversity of P. ussuriensis in China and P. ussuriensis var. aromatica in Japan have been investigated using both morphological and molecular markers in order to define appropriate conservation units, and to provide a good focus for conservation management. Distant evolutionary relationships between P. ussuriensis Maxim. in China and P. ussuriensis var. aromatica in Japan inferred from population genetic structure and phylogenetic analysis are also discussed.

Population Structure of and Conservation Strategies for Wild Pyrus ussuriensis Maxim. in China.

Pyrus ussriensis Maxim. is native to the northern part of China, but whose habitats are currently being destroyed by environmental changes and human deforestation. An investigation of population structure and genetic diversity of wild Ussurian pear is a priority in order to acquire fundamental knowledge for conservation. A total of 153 individuals of wild Ussurian pear from the main habitats, Heilongjiang, Jilin, and Inner Mongolia in China, possessed low genetic diversity as a result of habitat fragmentation. The genetic diversity of the populations in Inner Mongolia and north east of Heilongjiang was especially low and there was the possibility of inbreeding. Wild Ussurian pears were divided into 5 groups based on the Bayesian clustering method using 20 nuclear SSRs (nSSRs) and 5 groups by haplotype distributions using 16 chloroplast SSRs (cpSSRs), and the populations in Inner Mongolia and north east of Heilongjiang represented unique genotypes. AMOVA indicated there was a 20.05% variation in nSSRs and a 44.40% variation in cpSSRs among populations. These values are relatively high when compared to those of other tree species. Haplotype E, positioned in the center of the cpSSR analysis network and showed the largest number of connections with other haplotypes, represented the most important haplotype. Inner Mongolia and the north east of Heilongjiang are two areas that need urgent conservation because of their genetic vulnerability and peculiarity. We determined 4 conservation units based on the clustering by nSSRs and cpSSRs, and geographic factor. This information is helpful in deciding the conservation strategies for wild Ussurian pear in China.

A rare case of primary squamous cell carcinoma of the stomach and a review of the 56 cases reported in Japan.

We report an extremely rare case of primary squamous cell carcinoma of the stomach. A 69-year-old man was admitted to our hospital with a 2-month history of dysphagia and tarry stools. Endoscopic examination revealed a cauliflower-shaped protruding mass along the lesser curvature of the gastric cardia. Biopsy of the lesion revealed squamous cell carcinoma of the stomach. Computed tomography revealed a thickened stomach wall and a mass protruding into the gastric lumen. Total gastrectomy with splenectomy, distal pancreatectomy, and Roux-en-Y reconstruction was performed, together with a lower thoracic esophagectomy via a left thoracotomy. Histopathological examination of the specimen revealed well-differentiated squamous cell carcinoma of the stomach. Postoperative follow-up was uneventful for the first 18 months. However, multiple liver metastases and para-aortic lymph node metastasis developed subsequently. Despite systemic combination chemotherapy, the patient died because of progression of the recurrent tumors. Here, we review the characteristics of 56 cases of gastric squamous cell carcinoma reported in Japan.

Peace, a MYB-like transcription factor, regulates petal pigmentation in flowering peach 'Genpei' bearing variegated and fully pigmented flowers.

Flowering peach Prunus persica cv. Genpei bears pink and variegated flowers on a single tree. The structural genes involved in anthocyanin biosynthesis were expressed strongly in pink petals but only very weakly or not at all in variegated petals. A cDNA clone encoding a MYB-like gene, isolated from pink petals was strongly expressed only in pink petals. Introduction of this gene, via biolistics gave magenta spots in the white areas of variegated petals, therefore this gene was named as Peace (peach anthocyanin colour enhancement). Differences in Peace expression determine the pattern of flower colouration in flowering peach. The R2R3 DNA-binding domain of Peace is similar to those of other plant MYBs regulating anthocyanin biosynthesis. Key amino acids for tertiary structure and the motif for interaction with bHLH proteins were conserved in Peace. Phylogenetic analysis indicates that Peace is closely related to AtMYB123 (TT2), which regulates proanthocyanidin biosynthesis in Arabidopsis, and to anthocyanin regulators in monocots rather than to regulators in dicots. This is the first report that a TT2-like R2R3 MYB has been shown to regulate anthocyanin biosynthesis.

A case of carcinosarcoma of the esophagus detected on fluorodeoxyglucose positron emission tomography.

A 56-year-old woman who received surgery for left breast cancer 10 years previously underwent 18F-fluorodeoxyglucose positron-emission tomography (FDG-PET) for postoperative follow-up. FDG-PET revealed high uptake of tracer in the esophagogastric junction. A slightly elevated, lobular lesion was found in the lower third of the esophagus on upper gastrointestinal endoscopy. An endoscopic biopsy revealed squamous cell carcinoma. We performed thoracoscopic subtotal esophagectomy. Histopathological examination showed a polypoid spindle cell tumor arising from superficial squamous cell carcinoma. Immunohistochemically, the spindle cells were immunopositive for vimentin and AE1/AE3, and a carcinosarcoma of the esophagus was diagnosed. MIB-1 labeling indexes estimated by Ki-67 immunostaining showed that the proliferative rate of the sarcomatous component was markedly higher than that of the carcinomatous component. This is the rare reported case of esophageal carcinosarcoma that showed increased accumulation of tracer on FDG-PET.

Diversity of odor-active compounds from local cultivars and wild accessions of Iwateyamanashi (Pyrus ussuriensis var. aromatica) revealed by Aroma Extract Dilution Analysis (AEDA).

Some local cultivars and wilds of Iwateyamanashi (Pyrus ussuriensis var. aromatica) that grows wild in Northern Tohoku, Japan have good aromatic fruit. Iwateyamanashi may be valuable germplasms as a donor of odor compounds in breeding of Japanese pear (Pyrus pyrifolia), because almost all Japanese pear cultivars have faint odor. Fruits odors from a local cultivar 'Sanenashi', a wild accession (i0830) in Iwateyamanashi, cultivars of 'Kosui' and 'La France' were characterized at first with comparative Aroma Extract Dilution Analysis (AEDA). Application of AEDA, based on Gas chromatography/Olfactometry analysis (GC/O), on the odor concentration prepared from 'Sanenashi' indicated the presence of 33 odor-active compounds including methyl and ethyl esters, aldehydes and alcohol. The eleven odor compounds from 16 accessions of Iwateyamanashi showed various combinations and wide range of odor concentrations by Principal Component Analysis (PCA). Especially 2 accessions of local cultivar 'Natsunashi' plotted in the highly ethyl ester group might be useful for Japanese pear breeding.

Clear cell adenocarcinoma of the renal pelvis in a male patient.

Carcinoma of the renal pelvis is an uncommon renal neoplasm. Clear cell adenocarcinoma in the urinary tract is rare and has a histomorphology resembling that of the female genital tract. We herein present a case of clear cell adenocarcinoma of the renal pelvis, which is the first example in a male patient to our knowledge. A 54-year-old man presented with right flank pain. The tumor was associated with renal stones and hydronephrosis and invaded into the peripelvic fat tissue with regional lymph node metastasis. The patient died of metastatic disease six months postoperatively. Histologically, the tumor showed complex papillary architecture lined with clear and hobnail cells. Clear cell adenocarcinoma of the renal pelvis may pose a diagnostic challenge on histological grounds, particularly in the distinction from renal cell carcinoma. The immunohistochemical stains could help confirm the diagnosis. Due to its rarity, an effective treatment regimen remains to be determined.

[A successful resected case of advanced esophageal cancer with early gastric cancer responding to neoadjuvant chemotherapy of docetaxel, CDDP and 5-FU].

A 72-year-old male with a chief complaint of dysphagia was admitted to our hospital. Upper gastrointestinal endoscopic examination showed double cancers with thoracic esophageal cancer in the middle esophagus and gastric cancer in the antrum. Pathological examinations of the double cancer revealed the first one to be moderately-differentiated squamous cell carcinoma and the second to be well-differentiated adenocarcinoma. Computed tomography (CT) of the chest and abdomen showed no distant or lymph node metastases. Clinical stagings of the double cancer were stage II (T2N0M0)in esophageal cancer and stage I A (T1N0M0) in gastric cancer. The patient received neoadjuvant chemotherapy using docetaxel, CDDP and 5-FU. After 2 courses of chemotherapy, the adverse event was grade 2 in leucopenia and grade 2 in alopecia. Repeated macroscopic and histological examinations after chemotherapy revealed that the esophageal cancer had significant reductions in the size of tumors, leading to a partial response, and the gastric cancer had disappeared, leading to a complete response. He underwent thoracoscopy-assisted esophagectomy in the prone position, and laparoscopy-assisted gastric tube reconstruction. This neoadjuvant chemotherapy of docetaxel, CDDP and 5-FU might be effective and tolerable as with patients with double cancer of esophageal and gastric cancers.

[A successful resected case of far-advanced CA19-9-producing gastric cancer by neoadjuvant chemotherapy with S-1 and Cisplatin].

A 66-year-old male with a chief complaint of dysphagia was admitted to our hospital. Upper gastrointestinal endoscopy revealed a type 3 tumor on the gastric upper body, and pathological examinations of the biopsy specimens revealed a poorly differentiated adenocarcinoma. Computed tomography (CT) of the abdomen showed significant wall thickness of the stomach, and regional and para-aortic lymph node metastases. The CA19-9 level was high: 978 U/mL on admission. He received neoadjuvant chemotherapy using S-1 (120 mg/body, days 1-21) and cisplatin (108 mg/body, days 8) for faradvanced gastric cancer. After neoadjuvant chemotherapy, upper gastrointestinal endoscopy revealed that the gastric carcinoma had significant reductions in the size of its tumors, and CT showed that the lymph node metastases had disappeared, leading to a partial response. He underwent total gastrectomy, distal pancreatectomy, splenectomy and Roux-en Y reconstruction. Pathological examination of the resected specimens showed a small number of cancer cells in the submucosal layer, suggesting a Grade 2 pathological response, and gave a positive reaction to CA19-9 staining. The postoperative CA19-9 level decreased to a normal level. This case is diagnosed as CA19-9-producing gastric cancer. He was treated on an outpatient basis with adjuvant therapy.

Multinational comparison of diagnostic clues for uterine cervical lesions among cytotechnologists in Asian countries.

Vaccination has been underway in several countries for sexually inactive young girls or women against HPV 16 and 18 to prevent them from infection of these HPV types and concurrent cancer development. However, uterine cervical cancers may remain uncontrolled among some Asian countries, where other types of HPV infection are more frequent. A sensitive cancer screening system would remain important for detection of the earlier stage cervical cancers in Asian countries. In this study, 130 cytotechnologists (CTs) in Asian countries (Taiwan 80, Japan 18, Korea 15, Thailand 11, Singapore 3, Bhutan 2, and Mongolia 1) participated in the vote. Selected 10 cervical Pap smears that would be adequate to identify the diagnostic clues especially for atypical squamous cells (ASC) with two or three representative pictures for each case were displayed on the website. The percentages of consistent diagnosis voted by certified CTs with ≥5 years of experience were compared among 10 cervical cases or among Asian countries enrolled. As results, low consistency for ASC cases and high consistency for squamous intraepithelial lesion (SIL) were observed. Examining specimens for the diagnostic clues of ASC in TBS is crucial to maintain the high sensitivity and positive predictive value of SIL in Asian countries.

[Cytology of soft tissue tumors].

In the diagnosis of soft tissue tumors, an incomplete biopsy for malignancy interferes with subsequent therapy. Therefore, we perform fine needle aspiration cytology (FNAC) for soft tissue tumors and consider the following four issues: 1) Is the tumor benign or malignant?; 2) In malignancy, is the tumor primary or metastatic? Furthermore, if possible; 3) In a primary malignant tumor, the histological type and degree of malignancy; 4) In a metastatic malignant tumor, the histological type and the primary site. In FNAC, we diagnose soft tissue tumors based on the pattern of cytological findings, such as small round cells, pleomorphic cells, spindle cells, and epithelioid cells, and furthermore based on the findings of the background, such as mucin, vessels, multinucleated giant cells, and inflammatory cells while referring to clinical information. In soft tissue tumors that are difficult to diagnose only by cytology, immunochemical staining for multiple antibodies using the cell block method and/or cell transfer method is useful to make a definitive diagnosis. If necessary, rapid cytological diagnosis is currently performed for soft tissue tumors in our department.

[Usefulness of rapid cytological diagnosis at autopsy].

The aim of this study was to evaluate the diagnostic value of rapid cytological examinations at autopsy. Rapid cytological diagnosis was performed for nine cases at autopsy using Papanicolaou and/or Giemsa staining. Material was obtained by imprint or needle-aspiration. Among 9 cases, 5 cases were sarcoma, 3 cases carcinoma and 1 case infectious disease. All cases were reported to the physicians during autopsies. Precise medical informations including rapid cytological examination were informed immediately to bereaved family members. The present study showed that rapid cytological examination in conjunction with autopsy is an easy procedure and is not only useful in the concrete diagnosis of death by unknown causes but also helpful in deciding appropriate management of materials for the next steps such as electron microscope diagnosis.

Deciduoid mesothelioma in the pelvic cavity.

A very rare case of deciduoid mesothelioma in the pelvic cavity is presented. A 24-year-old woman (gestational stage: 28 weeks and 6 days) was admitted because of a tumor mass in the abdominal cavity. A well-circumscribed and fibrously encapsulated tumor mass was revealed in the Douglas cavity. Histologically, tumor cells were arranged in a solid sheet with deciduoid appearance and showed partial glandular and papillary structures. The tumor cells contained PAS positive and diastase-digested granules in the cytoplasm as well as alcian-blue positive and hyaluronidase-digested substances in the stroma. The cellularity of the tumor cells was moderate and mitoses were rare. There was partial tumor necrosis and tumor cells had infiltrated through the fibrous capsule. Immunohistochemically, the tumor cells were reactive for pancytokeratin, cytokeratin5/6, vimentin, HBME-1, calretinin and thrombomodulin. Ultrastructurally, numerous, long microvilli, tonofilaments and desmosome junctions could be seen. Consequently, this case was diagnosed as deciduoid mesothelioma and 2 years and 4 months after operation, the patient's clinical course has been good. This case is considered to be the first reported in Japan.