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Programmed cell death-1 (PD-1) is involved in one of the inhibitory pathways of the B7-cluster of differentiation (CD) 28 family; this pathway is known to be involved in the attenuation of T-cell responses and promotion of T-cell tolerance. PD-1 is known to negatively regulate T-cell receptor-mediated proliferation and cytokine production, lead to alternation in the tumor microenvironment. Although several studies have shown that high levels of PD-1-positive cells in follicular lymphoma (FL) patients influence their prognosis, those studies included patients treated without rituximab, and the prognostic impact of PD-1 positivity in the rituximab era (R-era) has not yet been elucidated. We retrospectively studied 82 patients with FL uniformly treated with standard R-CHOP therapy at six institutions between 2001 and 2009 (median follow-up for survivors: 55 months). We also collected and examined biopsy specimens for diagnosis with respect to PD-1 positivity. The PD-1 positivity was significantly higher in male patients and patients with high beta-2 microglobulin (B2M ≥ 3.0) (P = 0.03 and 0.003, respectively). Three-year progression free survival (PFS) and overall survival (OS) were 60% and 86%, respectively. By univariate analysis, elevated LDH (P = 0.07) worsened PFS. Male gender (P = 0.03), high FLIPI score (P = 0.05), and high B2M levels (P = 0.08) worsened OS. Multivariate analysis detected no significant prognostic factors, including PD-1 positivity. However, in male subgroup, high levels of PD-1-positive cells were found to be a prognostic factor for PFS. Addition of rituximab might have altered the prognostic impact of PD-1-positive cells.

An autopsy case of pigmented dermatofibrosarcoma protuberans (Bednar tumor) with systemic metastasis is reported. No previous example of this tumor showing widespread metastasis has been reported in the literature. The patient, a 45-year-old man, developed a tumor on the right upper arm. The tumor recurred twice and metastasized to other parts of the skin, lungs and brain during the 8-year clinical course. The primary tumor contained melanin-laden tumor cells and showed a storiform growth pattern. Autopsy confirmed multiple metastatic lesions in the skin, lungs, brain, thyroid, pancreas, stomach, small intestine and thigh muscles. The recurrent and metastatic tumors lacked both melanin production and the storiform arrangement, and instead revealed "fibro-sarcomatous" change with a herring-bone or interlacing pattern of growth.

We present a 23-year-old patient with extra-adrenal retroperitoneal paraganglioma with lung metastases who was successfully treated by complete removal of the tumour. Lung metastases were the first manifestation of the disease, and an abdominal computed tomography scan showed a large mass in the retroperitoneum with marked contrast enhancement. Angiography demonstrated a hypervascular mass with many feeding arteries, but vascular invasion was not apparent. The retroperitoneal tumour was resected completely followed by resection of lung metastases after 1 month of observation. The patient was disease free for 13 years after this radical surgery. The survival rate in patients with retroperitoneal paraganglioma with lung metastasis is low, and this case represents the longest surviving period reported in the literature. These tumours are usually large and located in the para-aortic region, and hence resection is sometimes challenging. We believe that a complete and meticulous surgical procedure is a prerequisite for long survival from this rare disease.

横紋筋肉腫は, 小児悪性腫瘍の中では代表的な疾患の一つであり, 組織学的には胎児型, 胞巣型, 多形型に分類されている.その中で胞巣型は10～25歳に多く, 頭頸部や四肢に好発する.今回われわれは15歳の女性の会陰部皮下に発生した胞巣型横紋筋肉腫の症例を経験したので, その細胞像を中心に報告する.腫瘍の穿刺吸引細胞診では, 腫瘍細胞は一部孤立散在性に, 一部ロゼット様に出現していた.細胞質は乏しく泡沫状で, N/C比は増大していた.核の多くは類円型で, 大きさはリンパ球の2～3倍であった.核縁の不整や切れ込みは散見されたが, 核縁の肥厚はみられなかった.核クロマチンは粗大顆粒状に増量しており, 核小体は小型だが複数のものも認められた.鼠径リンパ節の生検で得られた組織像では, 小型, 類円型の異型核を有する腫瘍細胞が胞巣状に配列し,「つるし柿」様の構造を呈しており, これらは細胞診におけるロゼット様の配列と対応していると考えられた.また, 免疫組織化学的にはデスミン, 横紋筋アクチンが陽性でケラチン, EMAが陰性であったため, 非上皮性の腫瘍であることが示唆された.また, フローサイトメトリーではDNA Index: 1.88の位置にDNA異数体が検出された.

巨大卵巣嚢腫のため,仰臥位での睡眠が困難な症例の周術期管理を経験した.術前にあらかじめ約35lの嚢腫内容液を排除したところ,仰臥位での睡眠が可能となった.手術を全身麻酔下に開始したが,嚢腫内容液の吸引により血圧は低下し,昇圧薬と急速輸液で対処した.同時に低酸素血症を呈したため,一時的に高濃度酸素吸入を行なった.術前排液量を含めた摘出臓器重量は53kgであった.術後は集中治療部にて管理したが,入室8時間後に血圧低下をきたした以外,呼吸・循環系は安定しており,術後2日目に集中治療部を退室し,後日軽快退院した.

While lichen amyloidosus reportedly may respond to dimethyl sulfoxide (DMSO) application, we present a patient whose lesions were refractory to this agent. This Japanese woman had chronic extensive lichen amyloidosus, mainly on her trunk. Her 10-year history of using nylon towels was the suspected cause. The application of DMSO ointment had no clinical effect, and the amyloid deposits persisted in the histological specimens despite the treatment. The administration of a topical corticosteroid led to gradual clinical improvement.

明細胞が主体に構成される肺大細胞癌の1例を報告する.症例は86歳の男性.増量する喀疾を主訴に近医を受診し, 胸部X線写真上左肺上葉にcoin lesionを指摘された.気管支鏡下の気管支擦過細胞診を行いclassVと診断され, 左肺上葉切除術を施行された.気管支擦過細胞診所見は, 大小不同の著しい腫瘍細胞が, 比較的平面的に出現し, N/C比のばらつきも目立った.粗穎粒状のクロマチンを有し, 核小体の目立つ核と, ライト緑淡染性の淡明な細胞質を示した.切除肺には, 肉眼的に径3cmの黄白色境界明瞭な充実性腫瘍がみられた.病理組織所見では, 血管豊富な充実性腫瘍で, 明らかな扁平上皮癌および腺癌への分化は認めなかった.主体をなす細胞は, 細胞および核の大小不同が目立ち, グリコーゲンの豊富な明るい細胞質が特徴的であった.核の大小不同が非常に目立つ点と併せて, 細胞所見は組織所見をきわめてよく反映しているものと思われる.本邦における肺癌取扱い規約では, 明細胞癌は独立した組織型の存在が確認し難いとの理由で分類からは除外されている.WHO分類では肺明細胞癌は, 大細胞癌の一亜型として分類されており, その構成成分が淡明ないし泡沫状の胞体を有する腫瘍細胞であり, 腺細胞ないし扁平上皮への分化が認められていないものとして定義されており, そこに示されている基準を本例は満たしていると考える.腎細胞癌の肺転移を始め, 良性明細胞腫が鑑別診断として問題となったが, いずれも臨床検査上, また免疫組織化学的検索にて否定された.

Permanent tracheostomy and tracheoesophageal anastomosis were performed as a means of surgical intervention for the treatment of intractable aspiration pneumonia. Conventional methods of tracheoesophageal anastomosis have entailed various problems. The improved method devised by us uses the special histological features and enables safe and reliable anastomosis. By this method, the tracheal perichondrium is retained and the strength of the anastomosed portion of the trachea is maintained, the failure of sutures due to tension on the anastomotic site being prevented. Also, reanastomosis can be performed after the cure of primary disease.

Victoria blue (VB)-hematoxylin and eosin (H&E) staining, originally described by Yokokawa et al in 1983, has been used extensively in our surgical pathology lab as a routine stain for all surgical specimens with cancer. This simple staining sequence is useful for the demonstration of venous invasion by cancer cells as VB dye specifically demonstrates elastic fibers in the background of H&E-stained tissues. (The J Histotechnol 13:271, 1990)

A total of 17 (10 adrenal and 7 extraadrenal) pheochromocytomas were examined immunohistochemically for the localization of catecholamine-synthesizing enzymes-tyrosine hydroxylase (TH), dopamine β-hydroxylase (DBH), and phenylethanolamine N-methyltransferase (PNMT)-as well as the marker peptides for pheochrornocytomas (i.e., met-enkephalin-arggly-leu [MEAGL]). Normal adult, fetal, and newborn human adrenal medullas were also examined. Six adrenal pheochromocytomas showed immunohistochernically positive staining for PNMT; 5 of these cases demonstrated elevated serum adrenalin levels, This indicated morphofunctional correlation. PNMT-positive cells were mostly positive for TH but did not show co-localization of MEAGL except in 1 case, Absence of co-localization was considered to reflect the physiological condition of the specimen, based on the similar staining in the normal adult adrenal medulla. Primary culture and immunoelectron microscopy suggested the processing and synthesis of adrenalin and MEAGL in the secretory granules.Seven extraadrenal pheochromocytornas were negative for PNMT and suggested the lack of adrenalin synthesis.

Nonspecific cross-reacting antigen (NCA) immunoreactivity was localized in normal and neoplastic human tissues using a monoclonal antibody to 55, 90 and 95 kDa molecules of NCA. This was compared to the localization of immunoreactive carcinoembryonic antigen (CEA) as demonstrated by polyclonal and monoclonal antibodies. In frozen sections, CEA was localized in normal surface epithelium of the stomach and colon where NCA was only weakly detected. Type 1 and type 2-like pneumocytes were positive for NCA, while CEA was localized only in type 2-like pneumocytes. CEA and NCA were both demonstrated in ductal cells of frozen pancreatobiliary and mammary tissues. The antigenicity of CEA and NCA in normal tissues was significantly lost after paraffin embedding as compared to frozen sections. NCA was consistently demonstrated in eccrine sweat glands embedded in paraffin. In various tumor tissues, CEA and NCA were colocalized and expression increased sufficiently to be detected in paraffin sections. Adenocarcinomas of the stomach and colon and cystadenocarcinoma of the pancreas, as well as neuroendocrine carcinomas of the lung and thyroid, showed a CEA predominance over NCA. In ductal adenocarcinomas of the pancreas and breast and in cholangiocarcinoma, NCA reactivity was greater than CEA. Keratinizing foci of most squamous cell carcinomas of mucosal origin and some adenocarcinomas equally expressed both. Hepatocellular carcinoma, lobular mammary carcinoma and papillary thyroid carcinoma were positive only with unabsorbed polyclonal antibody which widely recognizes CEA-related substances. Renal cell carcinoma, prostatic adenocarcinoma, transitional cell carcinoma, anaplastic carcinomas, choriocarcinoma and basal cell carcinomas showed little or no immunoreactivity. Hence the relative ratio of CEA/NCA expression in tumors was dependent on the tissue of origin and histologic type. The cytoplasmic granular staining of NCA in cancer cells was a noteworthy difference from the plasma membrane-associated localization of CEA.

Vascular endothelial growth factor A (VEGF-A) plays an essential role in tumor progression through stromal neovascularization in malignant solid tumors. Neuropilin (NRP) is considered to be the specific receptor for limited types of VEGF-A isoform, VEGF165. The clinicopathological implications of NRP are not well understood in colon cancer, while almost all colon cancers overexpressed VEGF-A. We examined the expression levels of NRP1 and NRP2 genes in 54 colon cancer cases and paired extraneoplastic tissue with quantitative real-time polymerase chain reaction. The gene expression levels of NRP1 in the tumor (0.431+/-0.583) were significantly decreased compared to those in the extraneoplastic tissue (0.754+/-0.799) (paired t-test, p=0.0208). On the other hand, the gene expression levels of NRP2 in the tumor (0.763+/-0.791) were not decreased compared to those in the extraneoplastic tissue (0.508+/-0.386) (paired t-test, p=0.0511). Twenty cases, with preserved expression of the NRP1 gene in the tumor, showed a better prognosis as compared to the 34 cases with decreased NRP1 expression (p=0.0258, log-rank test). No significant relationship was noted between NRP2 gene expression and prognosis. The results suggested that preserved NRP1 expression provides colon cancer patients with a better prognosis.

We reviewed fine-needle aspiration (FNA) cytology cases for breast lesions in order to improve the reliability of cytological diagnoses. We analyzed the results of 1,019 FNA cytology cases of patients with breast lesions for five years in our hospital. One hundred and ninety-seven (19.3%) of the 1,019 cases were examined using histological sections, in addition to cytological specimens, and included 27 cytologically suspicious cases. Of the 1,019 cytology cases, 606 (59.5%) were benign, 41 (4.0%) suspicious, 149 (14.6%) malignant and 223 (21.9%) inadequate/nondiagnostic. We also performed immunostaining against smooth muscle actin (SMA), using 19 cytological specimens and 88 histological specimens. We observed myoepithelial cells positive for SMA, which were valuable for cytological or histological diagnosis. To improve the reliability of cytological diagnoses and decrease the false-positive and false-negative cases, it is very important to obtain sufficient aspirates and to understand the cytological characteristics of various benign and malignant breast lesions.

CD44 is a family of transmembrane glycoproteins expressed in hematopoietic and epithelial cells, and associated with diverse physiological functions such as cell-cell and cell-matrix interactions. CD44 exists in a standard form, CD44s, and in multiple isoforms which are produced by alternative splicing of the variant exons (exon v1 to exon v10) encoding parts of the extracellular domain. Recently, CD44 was shown to play a role in the invasive and metastatic properties of tumor cells. In this study, we demonstrated CD44 immunoreactivities in 74 primary lung carcinomas. CD44s was noted in 38% (28 out of 74) of primary lung carcinomas. CD44v3 (38%, 28 out of 74) and CD44v6 (41%, 30 out of 74) were less frequently expressed in the primary lung carcinomas, compared with non-neoplastic lung tissues (CD44v3, 100%, p0.001; CD44v6, 73%, p0.05), respectively. CD44v3 and CD44v6 were more frequently found in squamous cell carcinomas than the other histological types (p0.05. CD44s, CD44v3 and CD44v6 were noted in 33% (6 out of 18), 44% (8 out of 18) and 33% (6 out of 18) of cytology-positive cases, and in 46% (6 out of 13), 38% (5 out of 13) and 31% (4 out of 13) of cytology-negative cases, respectively. It is suggested that decreased CD44v3 and CD44v6 might be correlated with sputum cytology-negative cases of lung adenocarcinoma.

This randomized double-blind trial was designed to evaluate the antiemetic effect of continuous epidural analgesia with droperidol mixed with bupivacaine and buprenorphine. We studied 78 patients for abdominal gynecological surgery under general-epidural anesthesia. After recovery from anesthesia, they received epidural administration of 0.25% bupivacaine 40 ml and buprenorphine 0.4 mg with or without droperidol 2.5-5.0 mg at a rate of 2 ml.h-1 for 24 hours. The addition of droperidol 5.0 mg led to serious undesirable effects. Droperidol 2.5 mg, however, showed not only significant antiemetic effect without any adverse action, but also the reduction of rescue analgesics. We conclude that the addition of a small dose of droperidol to epidural analgesics reduces the incidence of postoperative emesis and the requirement of rescue analgesics.

Bcl-2 is one of the cytoplasmic oncoproteins, and has been shown to suppress apoptotic cell death. In this study, we investigated the relationship between Bcl-2 expression and effects of chemotherapeutic agents on human breast cancer cells. We examined 26 surgically resected breast tumors with preoperative trans-arterial administration of chemotherapeutic agents and 30 control cases using immunohistochemical methods. In all 26 cases in the chemotherapy group, the breast cancer cells were focally degenerated to various degrees, associated with inflammation and stromal desmoplastic changes. Bcl-2 expression was found in 46% (12/26) of the chemotherapy group and in 67% (20/30) of controls. Of the 12 Bcl-2-positive cases in the chemotherapy group, 5 were diffusely positive [Bcl-2(2+)] and 7 were focally positive [Bcl-2(+)]. Of the 20 Bcl-2-positive cases in the control group, 18 were diffusely positive and 2 were focally positive. We speculate that Bcl-2 expression was down-regulated by trans-arterial administration of chemotherapeutic agents and was associated with apoptosis and degeneration of breast cancer cells.

Interleukin 10 (IL-10) is an immuno-suppressive cytokine produced by T-lymphocytes, and a regulatory molecule for angiogenesis in various cancers. We examined IL-10 gene expression in 53 colon cancer patients who underwent surgical resection. IL-10 gene expression was correlated with TSP1 and TSP2 gene expression (P=0.0049, P=0.0285). Colon cancer with IL-10 gene expression (19/53) showed significantly decreased venous involvement (P=0.0433). The mean vessel counts in the colon cancers with IL-10 gene expression were significantly lower than those without IL-10 gene expression (P

The nm23 gene was originally identified by differential hybridization of metastatic murine melanoma cell lines. Some experimental studies demonstrated a significantly low metastatic potential of melanoma cell lines transfected with the nm23 gene. In this study, we clarified the relationship between intracellular nm23-immunoreactivity and lymph nodal status of human breast cancer. We analyzed 82 surgically removed breast tumors including 67 invasive carcinomas (ductal, lobular and mucinous carcinomas). The nm23 expression was diffusely positive in the benign tumors and non-invasive carcinomas. Of the invasive ductal carcinomas, lymph node metastasis was found in 67.7% (21/31) of the focally positive/negative cases and in 18.2% (4/22) of the diffusely positive cases (p

Abstract 2645 Background Programmed cell death-1 (PD-1) is involved in one of the inhibitory pathways of the B7-cluster of differentiation (CD) 28 family; this pathway is known to be involved in the attenuation of T cell responses and promotion of T cell tolerance. PD-1 is known to negatively regulate T cell receptor-mediated proliferation and cytokine production, lead to alternation in the tumor microenvironment. Carreas et al. (J Clin Oncol. 2009; 27: 1470–1476) examined 100 follicular lymphoma (FL) patients and reported better prognosis in the group that had high levels of PD-1-positive cells. In contrast, in the study performed by Richendollar et al. (Human Pathol. 2011; 42: 552–557), which involved 91 FL patients, high levels of PD-1-positive cells were found to have a poor prognostic impact. Although these studies have shown that high levels of PD-1-positive cells in FL patients influence their prognosis, both studies included patients treated without rituximab, and the prognostic impact of PD-1 positivity in the rituximab-era (R-era) has not yet been elucidated. Materials and methods We retrospectively analyzed data for 91 FL patients uniformly treated by standard rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) therapy in 5 institutions between 2001 and 2009. The median age of the entire cohort was 58 years (range, 34–85 years), and 46 (51%) of the patients were men. We also collected and examined biopsy specimens for diagnosis with respect to PD-1 positivity. The PD-1-positive cells were counted using computer analysis at the Cancer Institute, Japanese Foundation for Cancer Research. Results The FL grade on diagnosis was grade 1 for 34 (37%) patients, grade 2 for 41 (45%) patients, and grade 3 for 16 (18%) patients. The median positivity for PD-1 staining was 16.0% (range, 0.01–51.9%) and was significantly higher in the high beta-2 microglobulin (B2M; at least 3) group (P = 0.009); the men had a high tendency for PD-1 positivity (P = 0.08). After a median follow-up of 29.1 months, the 3-year progression-free survival (PFS) and overall survival (OS) were 61.1% and 88.6%, respectively. Stage 4 FL at diagnosis (P = 0.02) and bone marrow involvement (P = 0.05) resulted in worse PFS, and an Eastern Cooperative Oncology Group (ECOG) performance status of 2–4 (P = 0.04), high Follicular Lymphoma International Prognostic Index (FLIPI; P = 0.02), B symptoms (P = 0.04), and high B2M levels (P = 0.005) worsened OS. Multivariate analysis showed that age over 60 years (P = 0.04) and high B2M levels (P = 0.07) were prognostic factors for PFS. PD-1 positivity was not found to be a prognostic factor with respect to both PFS and OS. Because the addition of rituximab to therapy regimens has altered the clinical course and prognosis of FL, some new prognostic factors have been proposed, and the impact of known prognostic factors has been changing. Rituximab might also have changed the prognosis of FL patients with high levels of PD-1-positive cells. Conclusion High levels of PD-1-positive cells were not found to be a prognostic factor in this study, indicating that the prognostic impact of PD-1 positivity might be eliminated in the R-era. Disclosures: No relevant conflicts of interest to declare.

A 44-year-old male suffered epistaxis and headache of sudden onset and was diagnosed as having suppurative meningitis due to streptococci. Four days after the onset of symptoms, he died despite treatment with antibiotics. Destruction and ballooning of the sella turcica was revealed by a plain head X-ray examination during the clinical course. At autopsy, a massive tumorous lesion extended from the ballooned sella turcica to the paranasal cavities, nasopharynx and facial bone, and this had resulted in suppurative meningitis. The tumor was also disseminated to the basal skull. The tumor cells possessed prominent nuclear atypia and were immunohistochemically positive for prolactin. This was diagnosed as a case of pituitary adenoma with markedly invasive pathological findings and a rapid and fatal clinical course.