[Plasmablastic lymphoma presenting with plasmacytosis and polyclonal hypergammopathy].

A 72-year-old woman presented with generalized lymphadenopathies and plasmacytosis accompanied by polyclonal hypergammopathy. 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) showed FDG accumulation in the systemic lymph nodes, spleen, and multiple bones. Human immunodeficiency virus antibody was negative. Lymph node histologic findings showed a monotonous population of plasma cells with a starry-sky appearance. The cells were positive for CD19, λ, and Epstein-Barr virus-encoded RNA, and negative for CD20 and CD56. The MIB-1 index was 80%. A diagnosis of plasmablastic lymphoma with plasmacytosis and polyclonal hypergammopathy was made, and complete metabolic response was achieved after six cycles of dose-adjusted-EPOCH therapy (etoposide, prednisolone, vincristine, cyclophosphamide, and doxorubicin).

[Multiple myeloma with myelofibrosis at diagnosis and aggressive extramedullary relapse after autologous stem cell transplantation].

A 66-year-old man was diagnosed with symptomatic IgG-λ multiple myeloma based on the presence of anemia, thrombocytopenia, renal dysfunction, and a tumor on the right sixth rib. Bone marrow aspiration yielded a dry tap and biopsy revealed myelofibrosis grade 2. Partial response was achieved with Bd (bortezomib and dexamethasone) and VRd (bortezomib, lenalidomide, and dexamethasone). The patient received autologous stem cell transplantation, but the myeloma relapsed 3 months later, and liver tumors developed as well. DKd (daratumumab, carfilzomib, and dexamethasone) was administered, but the patient died due to disease progression. Autopsy revealed multiple extramedullary lesions in the liver, spleen, gallbladder, adrenal glands, kidneys, and multiple lymph nodes, as well as ascites.

[Busulfan/thiotepa followed by autologous peripheral blood stem cell transplantation for refractory diffuse large B-cell lymphoma accompanied by hypopyon].

A 54-year-old male patient, who presented with multiple lymphadenopathies, bilateral leg edema, and oscheohydrocele, was diagnosed with diffuse large B-cell lymphoma (DLBCL) stage IVB. His lymphadenopathies disappeared after six courses of R-CHOP therapy, which consist of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone); however, right hypopyon and partly remaining testicular soft tissue masses with fluorodeoxyglucose accumulation were observed. Lymphoma cell infiltration was observed in the aqueous humor of the right anterior chamber and testis, which indicates DLBCL progression. Hypopyon disappeared after the first course of intrathecal chemotherapy combined with R-HDMA therapy, which consists of rituximab and high-dose methotrexate/cytarabine, but recurred in the third course. The patient then underwent busulfan and thiotepa (BuTT) therapy followed by autologous peripheral blood stem cell transplantation (auto-PBSCT) after four courses of R-HDMA therapy. Hypopyon promptly disappeared after BuTT therapy and no hypopyon recurrence was observed 9 months after auto-PBSCT. Therefore, BuTT therapy is effective for hypopyon associated with refractory DLBCL.

[Successful treatment of HHV8-negative effusion-based lymphoma with drainage of pleural effusion].

Two cases of human herpesvirus 8 (HHV8)-negative effusion-based lymphoma (EBL) involving unilateral pleural effusion that regressed only after drainage are reported. Cases 1 and 2 were 91- and 81-year-old men with right and left pleural effusion, respectively. No chemotherapy was administered to either patient because of their advanced age and the presence of cardiac comorbidities. They completely recovered after effusion drainage alone without relapse till the last observation. Thus, this study suggests that some patients with HHV8-negative EBL can be safely managed with effusion drainage alone.

Immunohistochemical Reactivity of Prostate-Specific Markers for Salivary Duct Carcinoma.

OBJECTIVES: NKX3.1, a transcription factor related to androgen expression, has recently been introduced as a diagnostic marker of prostate adenocarcinoma. Salivary duct carcinoma (SDC) is typically positive for androgen receptor (AR). Therefore, we hypothesized that NKX3.1 is a new immunohistochemical marker for SDC and aimed to investigate whether NKX3.1 staining in combination with other immunomarkers of prostate carcinoma could have a diagnostic or prognostic value in SDC. METHODS: Materials obtained from 42 resected SDCs were examined by immunohistochemistry using antibodies against AR, NKX3.1, α-methylacyl-CoA racemase (AMACR), prostatic acid phosphatase (PAP), and prostate-specific antigen (PSA). RESULTS: In immunoreactivity among SDC cases, 81.0, 35.7, 58.5, 33.3, and 0% were positive for AR, NKX3.1, AMACR, PAP, and PSA, respectively. AMACR and PAP immunoreactivity rates were higher in recurrence cases than in cases with no recurrence. CONCLUSIONS: NKX3.1 expression is useful for SDC diagnosis, but decreased NKX3.1 expression was not correlated with SDC progression. The immunoreactivity of AMACR and PAP could be useful for assessing prognosis in SDC, but immunohistochemical staining of prostate-specific markers should be interpreted with caution when determining whether a metastatic tumor is of prostate origin, especially when patients have a history of SDC.

Ectopic pancreatic adenocarcinoma in Meckel's diverticulum: a case report.

BACKGROUND: Malignant neoplasms arising from Meckel's diverticulum are rare and an adenocarcinoma in Meckel's diverticulum originating from ectopic pancreatic tissue is even rarer. Herein, we report a patient with an ectopic pancreatic adenocarcinoma in Meckel's diverticulum who was successfully treated with surgery and chemotherapy. CASE PRESENTATION: A woman in her sixties presented to another hospital with abdominal pain. Plain computed tomography suggested an abdominal tumor and she was referred to our hospital. Enhanced computed tomography revealed a 23-mm low-density tumor in the abdominal cavity. Surgery was performed with a tentative diagnosis of a mesenteric tumor, such as a gastrointestinal stromal tumor, schwannoma, or lymphoma. First, we inspected the peritoneal cavity with a laparoscope. This revealed numerous nodules in the small bowel mesentery, suggesting peritoneal dissemination. A 20-mm-diameter white tumor was found in the small intestine and diagnosed as a small intestinal cancer. The small intestine was partially resected laparoscopically through a small skin incision. The patient's postoperative course was uneventful, and she was discharged on postoperative day 9. Pathological examination revealed well-differentiated adenocarcinoma in the small intestine. The tumor had developed from a sac-like portion protruding toward the serosal side and had a glandular structure lined with flattened atypical cells. Neither pancreatic acinar cells nor islets of Langerhans were evident, suggesting a Heinrich type 3 ectopic pancreas. The final diagnosis was an adenocarcinoma originating from an ectopic pancreas in Meckel's diverticulum. After a smooth recovery, the patient commenced chemotherapy for pancreatic cancer. CONCLUSIONS: We present a very rare case of ectopic pancreatic carcinoma in Meckel's diverticulum.

Gilteritinib as Bridging and Posttransplant Maintenance for Relapsed Acute Myeloid Leukemia with FLT3-ITD Mutation Accompanied by Extramedullary Disease in Elderly.

A 69-year-old woman was diagnosed with acute myeloid leukemia (AML) with an FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD) mutation. Complete remission (CR) was achieved after induction therapy, but AML resulted in a hematological relapse two months after the consolidation chemotherapy. Relapse was accompanied by multiple skin lesions that demonstrated leukemic cell infiltration as well as a drooping right eyelid with extroversion of the eye due to right oculomotor palsy. Gilteritinib was started as salvage therapy, and bone marrow blasts decreased to 0.8% after one month. Two months later, the eye symptoms improved, and the patient underwent cord blood transplantation (CBT). The skin lesions disappeared after the conditioning regimen, and the patient achieved CR status with complete donor chimerism at day 28. Gilteritinib was restarted as posttransplant maintenance therapy on day 53 of CBT. No adverse events other than mild hepatotoxicity were observed, and the patient was alive and in CR status, while continuing gilteritinib at one year and seven months after CBT. Bridging and posttransplant maintenance therapy with gilteritinib may be a promising therapeutic option for relapsed AML with the FLT3-ITD mutation in elderly patients.

Successful treatment with tirabrutinib for relapsed Bing-Neel syndrome following high-dose methotrexate and craniospinal irradiation.

A 63-year-old man was diagnosed with Waldenström's macroglobulinemia (WM). Six courses of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) resulted in complete remission, but WM relapsed three years after R-CHOP. After six courses of BR (bendamustine, rituximab), the serum IgM level and CRP normalized. Four years after BR, the patient presented with muscle weakness, sensory disturbance, and myoclonus of lower limbs. T2-weighted magnetic resonance imaging (MRI) showed areas of signal hyperintensity with contrast enhancement in the right temporal and parietal lobes in brain parenchyma, medulla, bilateral basal ganglia, white matter of occipital lobe, and thoracic spinal cord at the Th2-11 levels. Open brain biopsy revealed diffuse proliferation of small lymphocytes and plasmacytoid lymphocytes on the brain surface and around cerebral blood vessels, resulting in a diagnosis of Bing-Neel syndrome (BNS). Two courses of R-MPV (rituximab, methotrexate, procarbazine, and vincristine) resulted in progressive disease, but the neurological symptoms and MRI findings improved following craniospinal irradiation of 30.6 Gy. Three years after craniospinal irradiation, T2-weighted MRI showed recurrence of BNS with progression of myoclonus of lower limbs and IgM elevation. Tirabrutinib was started for the second recurrence of WM and progression of BNS. Two months after the initiation of treatment with tirabrutinib, the myoclonus of lower limbs disappeared and the MRI findings showed improvement. Serum IgM levels decreased and no adverse events were observed. Tirabrutinib shows promise as a therapeutic option for relapsed BNS.

Highly efficient biodiesel production by a whole-cell biocatalyst employing a system with high lipase expression in Aspergillus oryzae.

In the present study, a system with high lipase expression in Aspergillus oryzae was developed using an improved enolase promoter (P-enoA124) and the 5' untranslated region of a heat-shock protein (Hsp-UTR). P-enoA142 enhanced the transcriptional level of a heterologous lipase gene and Hsp-UTR improved its translational efficiency. Fusarium heterosporum lipase (FHL) was inserted into a pSENSU-FHL expression vector harboring P-enoA142 and Hsp-UTR and was transformed into an A. oryzae NS4 strain. Transformants possessing pSENSU-FHL in single (pSENSU-FHL#1) and double copies (pSENSU-FHL#2) were selected to evaluate the lipase activity of the whole-cell biocatalyst. The two strains, pSENSU-FHL#1 and #2, showed excellent lipase activity in hydrolysis compared with the strain transformed with conventional expression vector pNAN8142-FHL. Furthermore, by using pSENSU-FHL#2, methanolysis could proceed much more effectively without deactivation, which allowed a swift addition of methanol to the reaction mixture, thereby reducing reaction time.

Colon adenoma and adenocarcinoma with clear cell components - two case reports.

BACKGROUND: Diagnoses reflect clear cell morphologies when tumor cells have clear cytoplasm in many organs, and the nature of such clear cells is typically identified. Colorectal tubular adenoma or adenocarcinoma, conversely, rarely show clear cells, the reason for which remains uncertain. We report 2 colon tumors with clear cell components (Case 1: adenoma; Case 2: adenocarcinoma) and investigate the nature of the clear cells. CASE PRESENTATION: Case 1 was a 75-year-old man with a superficial elevated polyp detected in the rectum for whom endoscopic submucosal dissection was performed. Microscopically, 10% of the tumor showed dysplastic columnar epithelium with clear cytoplasm forming tubular structures accompanied by conventional tubular adenoma. Case 2 was a 58-year-old man with a pedunculated polyp found in his sigmoid colon for which polypectomy was performed. Microscopically, 90% of the tumor showed dysplastic columnar epithelium with clear cytoplasm forming fused glands or cribriform structures adjacent to the ordinal tubular adenocarcinoma. In both cases, clear and ordinary tumor cells were negative for CK7 and positive for CK20 and CDX2, consistent with findings of colorectal origin. Different results were found for CEA and CD10 staining. CEA was positive on the luminal side of the conventional area in contrast diffuse cytoplasmic staining of the clear cell area in both cases. CD10 was only positive for the clear cell component of case 2. The clear cell components were negative for Periodic acid-Schiff (PAS), Alcian blue, and mucicarmine staining and AFP immunohistochemistry. An ultrastructural examination found multiple cytoplasmic lipid-like vacuoles in the clear cell component that were predominantly negative for adipophilin by immunoelectron microscopy. CONCLUSIONS: We investigated tubular adenoma and tubular adenocarcinoma with clear cell components. The accompanying conventional tubular adenoma or adenocarcinoma cells helped us to evaluate the atypia of the clear cells. Diffuse cytoplasmic staining of CEA and CD10 suggested that the clear cell component might harbor malignant potential. We were unable to verify the well-known causes of clear cytoplasm, such as an accumulation of glycogen, lipid, or mucin and enteroblastic differentiation. The causes of clear cells in the colorectal region remain uncertain; however, possible explanations include autolysis and carbohydrate elution.

Difference in transducin-like enhancer of split 1 protein expression between basal cell adenomas and basal cell adenocarcinomas - an immunohistochemical study.

BACKGROUND: Basal cell adenoma (BCA) and basal cell adenocarcinoma (BCAC) are benign and malignant, basaloid salivary gland neoplasms, respectively. These tumors show a dual-cell proliferation of inner luminal/ductal cells and outer abluminal/myoepithelial or basal cells. The only difference between them is defined as a malignant morphology such as invasion. Recently, the nuclear expression of ß-catenin and a catenin beta-1 (CTNNB1) mutation were found in BCA. Transducin-like enhancer of split 1 (TLE1) belongs to the Groucho/TLE family, and it functions in the "off" state in the Wnt/ß-catenin signaling pathway. We hypothesized that if the dysregulation of the Wnt/ß-catenin signaling pathway could be attributed to the tumorigenesis of BCA/BCAC, there might be differences in TLE1 expression between BCA and BCAC. METHOD: The study included 35 BCA and 4 BCAC cases. We performed immunohistochemistry to detect TLE1 and ß-catenin and investigated the catenin beta-1 (CTNNB1) mutational profile among BCA and BCAC cases. RESULTS: In BCA, the expression of TLE1 was confined to luminal cells of glandular structures, in contrast to the expression of ß-catenin in abluminal cells. The BCA cases harbored CTNNB1 gene mutations (12/35). In BCAC, luminal cell staining of TLE1 was identical to BCA in non-invasive areas (4/4) but indistinct in invasive areas (3/4). The BCAC cases were ß-catenin positive for abluminal cells in both areas. The BCAC cases had CTNNB1 mutation (2/4) and the laser-captured microdissection allowed the separate collection of infiltrative and non-infiltrative areas to detect the same mutation. CONCLUSIONS: Immunohistochemical analysis for TLE1 can identify BCA and BCAC by luminal cell staining difference, especially indistinct luminal cell expression for TLE1 in invasive areas of BCAC. Moreover, TLE1 can be luminal/ductal cell markers.