[A case of gastric cancer associated with systemic lupus erythematosus and nephrotic syndrome].

A 72-year-old man with a complaint of lower limb edema was admitted to our hospital. Investigations revealed anemia, a decreased serum albumin level (1.7g/dl), and an increased urinary protein volume (7.4g/day), leading to a diagnosis of nephrotic syndrome. He also tested positive for anti-nuclear antibody and anti-DNA antibody, fulfilling the criteria for systemic lupus erythematosus (SLE). Endoscopy revealed type 2 advanced gastric cancer at the greater curvature of the antrum of the stomach. We performed distal gastrectomy and an open right renal biopsy without preoperative treatment. Histopathological examination of the resected stomach specimens revealed adenocarcinoma. Immunohistochemistry of the kidney specimen suggested membranous lupus nephritis. After surgery, his urinary protein volume gradually decreased and lower limb edema improved in the absence of any specific treatment for nephrotic syndrome or SLE.

[A case of gradually progressive, symptomatic, ectopic gastric pancreas].

A 27-year-old man was admitted to a hospital with a complaint of epigastric discomfort. Upper gastrointestinal endoscopy and endoscopic ultrasonography revealed an elevated lesion on the posterior wall of the upper gastric body, and a diagnosis of ectopic gastric pancreas was made. Follow-up endoscopy performed 5 years later revealed an increase in the size of the mass to approximately 5cm in diameter. The location, shape, and clinical course of the mass aroused a suspicion of malignancy; therefore, partial gastrectomy was performed. Histopathologically, the resected mass was diagnosed as ectopic gastric pancreas with chronic inflammation, fibrosis, and bleeding around the acinar cells.

[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.

[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.

Activity and safety of combination chemotherapy with methotrexate, ifosfamide, l-asparaginase and dexamethasone (MILD) for refractory lymphoid malignancies: a pilot study.

Optimal salvage chemotherapy has not been established for lymphoid malignancy, which is refractory to the conventional cyclophosphamide, doxorubicin, vincristine, and prednisone regimen. To explore an effective regimen, we conducted a phase I pilot study of combination chemotherapy with methotrexate, ifosfamide, l-asparaginase and dexamethasone (MILD), which are unaffected by MDR1-encoded P-glycoprotein. A total of 18 patients with lethal lymphoid malignancy were enrolled over a 2-yr period. The median age was 63 yr. Eleven patients had T/NK-cell malignancies, six had B-cell malignancies, and one was diagnosed with a blastic plasmacytoid dendritic cell neoplasm. Patients aged >/=60 and <60 yr were planned to receive a set of starting doses of methotrexate and ifosfamide, which should induce myelosuppression. Eleven patients completed two courses of MILD therapy. Treatment-related death because of systemic mucormycosis was observed in one patient. Major treatment-related adverse events were grade 3 or more hematologic toxicities, which included lymphopenia corresponding to dose-limiting toxicity. The most common grade 3 non-hematologic toxicity was febrile neutropenia. Of the 14 evaluated patients, three achieved a complete response, and four showed a partial response. The overall response rate was 57%. It was very interesting that all of seven responders had T/NK-cell malignancies. MILD therapy was feasible and presented acceptable toxicity in patients with refractory or lethal lymphoid malignancies. The efficacy for T/NK-cell malignancies should be further evaluated.

Malignant granular cell tumor in the gluteal region with unusual pathologic features.

Malignant granular cell tumors (MGCTs) are very rare soft tissue sarcomas. Definite criteria for pathologic diagnosis and the optimal treatment strategy have not been fully established. Here, we describe a 76-year-old woman with a huge MGCT in the right gluteal region, who developed a local recurrence and died from that tumor 14 months after undergoing an operation for the primary tumor. Although microscopic examination revealed that round and granular tumor cells staining for S-100 protein were dominant, components of the spindle cell sarcoma reacting with alpha smooth muscle actin were partially observed. MGCT is believed to originate from Schwann cells; however, pathologic findings in our case showed both Schwannian and non-Schwannian features. This is the first report on MGCT with these 2 features appearing simultaneously.

[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.

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.

Conversion Surgery for Metastatic Pancreatic Mucinous Carcinoma Responsive to Systemic Chemotherapy with Modified FOLFIRINOX: A Case Report.

We report a case of metastatic pancreatic-head mucinous carcinoma (with multiple lymph node and bone metastases) and review the relevant literature. Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) was useful for diagnosis, and a satisfactory outcome was achieved after systemic chemotherapy with FOLFIRINOX followed by resection of the primary lesion as conversion surgery. The patient was a 55-year-old man. Hematological findings included elevated serum tumor marker levels: CEA 12.7 ng/mL, DUPAN-2 400 U/mL. Findings from several imaging modalities and EUS-FNA confirmed a clinicopathological diagnosis of metastatic pancreatic mucinous carcinoma with multiple bone and lymph node metastases. Five courses of modified FOIFIRINOX (m-FFX) were given as systemic chemotherapy, which had an antitumor effect. Subtotal stomach-preserving pancreaticoduodenectomy and extensive lymph-node dissection were thus performed. Histopathological analysis showed invasive ductal carcinoma, muc (pT3, pN1b, cM1). After surgery, the clinical course was notable for the absence of complications. Tegafur/gimeracil/oteracil (S-1) was started as maintenance adjuvant chemotherapy postoperatively, and no disease progression has been observed at 10 months after surgery.

Pathologic complete response confirmed by surgical resection for liver metastases of gastrointestinal stromal tumor after treatment with imatinib mesylate.

A 39-year-old male underwent distal gastrectomy for a high grade gastrointestinal stromal tumor (GIST). Computed tomography (CT) and magnetic resonance imaging (MRI) 107 mo after the operation, revealed a cystic mass (14 cm in diameter) and a solid mass (9 cm in diameter) in the right and left lobes of the liver, respectively. A biopsy specimen of the solid mass showed a liver metastasis of GIST. The patient received imatinib mesylate (IM) treatment, 400 mg/day orally. Following the IM treatment for a period of 35 mo, the patient underwent partial hepatectomy (S4 + S5). The effect of IM on the metastatic lesions was interpreted as pathologic complete response (CR). Pathologically verified cases showing therapeutic efficacy of IM have been rarely reported.

Primary Pulmonary Mucosa-Associated Lymphoid Tissue Lymphoma with a Nodular Opacity: Report of a Case.

Herein, we describe our experience in treating a case of primary pulmonary mucosa-associated lymphoid tissue lymphoma detected as a nodular opacity. A 79-year-old man was referred to our hospital. Computed tomography showed a nodular opacity measuring 20 mm in diameter with regular margins in segment 5 of the right middle lobe of the lung. Although the bronchoscopic brush cytology result was class III, the patient was tentatively diagnosed with suspected mucosa-associated lymphoid tissue lymphoma. A thoracoscopic right middle lobectomy was performed. The pathological findings showed nodular proliferation of small to medium-sized, mature-appearing atypical lymphoid cells, lymphoepithelial lesions, and vague follicles suggesting follicular colonization in some areas. The patient was diagnosed with low-grade small B-cell lymphoma and mucosa-associated lymphoid tissue lymphoma. He has remained well to date, 23 months after surgery, without evidence of recurrence.

A primary esophageal MALT lymphoma patient with Helicobacter pylori infection achieved complete remission after H. pylori eradication without anti-lymphoma treatment.

Primary esophageal lymphoma is an extremely rare disease. We report a 76-year-old woman with esophageal lymphoma who achieved remission after Helicobacter pylori (HP) eradication. Esophagogastroduodenoscopy (EGD) revealed a mass in the lower esophagus, and she was diagnosed with stage IE mucosa-associated lymphoid tissue (MALT) lymphoma. She rejected any anti-lymphoma treatment except for HP eradication. Follow-up EGD demonstrated the disappearance of the esophageal MALT lymphoma 2 months after HP eradication, and she remained in remission for more than 3 years. Our results demonstrate that HP eradication may be effective as initial therapy in primary esophageal MALT lymphoma patients with HP infection.

Comparative study between DNA copy number aberrations determined by quantitative microsatellite analysis and clinical outcome in patients with stomach cancer.

PURPOSE: We detected the relative DNA copy numbers (RCNs) at target loci in patients with stomach cancer with quantitative microsatellite analysis. We additionally clarified the relationship between DNA copy number aberrations and the clinical outcome of the patients. EXPERIMENTAL DESIGN: Fresh frozen samples were obtained from 30 patients who had undergone surgery for stomach cancer. Seven microsatellite loci in chromosomes 8q, 16q, and 20q and one gene-specific locus (ZNF217) were selected as the target loci. The DNA copy number was obtained relatively to a pooled reference consisting of six microsatellite primer sets selected from the regions where few aberrations have been reported in comparative genomic hybridization analysis. On the basis of the TaqMan PCR system, the internal probes used were carrying donor (6-carboxyfluorescein) and acceptor (6-carboxytetramethylrhodamine) fluorescent molecules complementary to CA repeats in the microsatellite markers and to one gene-specific oligomer in the gene-specific marker. RESULTS: Chromosome 8q gain, 20q gain, and 16q loss were detected in 18 (60.0%), 8 (26.7%), and 13 (43.3%) cases, respectively. Gains in the RCNs of D8S1801 and D8S1724 were most frequently found (36.7%). There was a significant correlation between the loss of D16S3026 and reduced survival duration (P = 0.0158), and the simultaneous aberrations of D8S1801 gain and D16S3026 loss (double marker positive) was significantly associated with reduced survival duration (P = 0.0008). According to Cox proportional hazards model, the double marker positive was a significant and independent factor indicating an unfavorable prognostic factor (relative risk, 17.176; 95% confidence interval, 2.782-106.026; P = 0.0022). CONCLUSION: RCN aberrations in tumor tissues determined by quantitative microsatellite analysis enable identification of the prognostic factors that correlate with clinical outcome of the patients with stomach cancer.

[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.

A case of primary pulmonary diffuse large B-cell lymphoma diagnosed by transbronchial biopsy.

A 76-year-old man took a chest X-ray for his medical checkup and an abnormal shadow was detected in the right lower lung field. For more detailed examination, he was referred to our hospital. Chest computed tomography showed a 20-mm nodule with relatively regular margins in the right lower lobe. A compact proliferation of circular to polygonal cells with a high nucleus-cytoplasm ratio was evident in a transbronchial lung biopsy. Based on pathological findings, a mature large B-cell lymphoma was diagnosed. Thoracoscopic right lower lobectomy and mediastinal lymphadenectomy were performed. The post-surgical pathological examination showed that the tumor consisted of diffuse to compact proliferation of medium to large atypical lymphocyte-like cells. Immunohistochemical staining yielded positive results for B-cell lineage markers. Five months after surgical resection, neither local recurrence nor accumulation in remote organs was observed on gallium scintigraphy. The diagnosis of primary pulmonary diffuse large B-cell lymphoma was established.

Utility of immunohistochemistry with an antibody against MYC at the initial diagnosis of follicular lymphoma, grade 3A, for predicting a more aggressive clinical course: a case report and review of the literature.

Follicular lymphoma (FL) is the most common indolent lymphoma, and associated with the chromosomal translocation t(14;18)(q32;q21). While, FL harboring both BCL2 and MYC translocation at diagnosis is very rare. The evaluation of MYC expression in typical FL at presentation using southern blot, G-banded karyotyping or fluorescence in situ hybridization (FISH) analyses has been described so far. However, there are no reports about the use of immunohistochemistry (IHC) to evaluate MYC protein expression in FL at presentation. Here, we present a FL patient who transformed to a B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt's lymphoma, accompanied by concurrent BCL2, BCL6, and MYC translocations; i.e., triple-hit lymphoma. Paraffin-embedded tissue section-FISH analysis demonstrated that the FL was negative for MYC, but MYC protein expression was subsequently detected in the lymph node specimen obtained at the initial diagnosis using IHC. This case revealed aggressive clinical course and central nervous system involvement. In the literature concerning MYC positive FL five out of 8 patients were dead within 24 months. The detection of MYC protein expression in FL using IHC might be useful to predict more aggressive clinical course.

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.

Spontaneous regression of cutaneous blastic plasmacytoid dendritic cell neoplasm followed by acute monocytic leukemia evolving from myelodysplastic syndrome.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy arising from plasmacytoid dendritic cell precursors. BPDCN typically manifests in the skin, but it can also evolve into a leukemic form or be complicated by acute myeloid leukemia, some cases with a preceding myelodysplastic syndrome (MDS). We herein report the first case of complete spontaneous regression of cutaneous BPDCN followed by acute monocytic leukemia evolving from MDS. This is also the first reported case of gastric BPDCN invasion.