Atypical Splenic Abscesses Due to Clostridioides difficile.

BACKGROUND Splenic abscess is a rare infectious disease that occurs after bloodstream infection and trauma. It has become more common due to an increase in the number of immunocompromised patients. They typically present with round cystic lesions demonstrated by ultrasonography, computed tomography (CT), and magnetic resonance imaging (MRI). Clostridioides difficile (formerly Clostridium difficile) is a well-known cause of pseudomembranous colitis, but extraintestinal manifestations are very rare. To the best of our knowledge, only 9 cases of splenic abscess due to C. difficile have been reported in the literature. CASE REPORT A 90-year-old man presented with weight loss, fever, and abdominal pain. Contrast-enhanced CT revealed splenomegaly with irregular hypodense nodules. Image-guided biopsy or drainage was not performed for a technical reason. MRI showed atypical nodules with mixed high and low signals on both T1- and T2-weighted images, which were inconclusive. A laparoscopic splenectomy was performed, which resulted in partial removal due to severe adhesion of the spleen to the surrounding tissues. Cultures of splenic pus yielded C. difficile, Enterococcus faecium, and Bacteroides fragilis. Pathological examination of the spleen showed widespread abscesses with hemorrhage and necrosis, leading to the diagnosis of splenic abscesses. Intravenous administration of vancomycin, clindamycin or metronidazole was ineffective. He died of fatal arrhythmia 5 months after the initial diagnosis of splenic abscess. CONCLUSIONS Splenic abscess can present with atypical imaging findings owing to chronic inflammation, bleeding, and necrosis. Although polymicrobial, this is the tenth reported case of splenic abscess caused by C. difficile.

Prolonged Myelosuppression due to Progressive Bone Marrow Fibrosis in a Patient with Acute Promyelocytic Leukemia.

A 34-year-old woman was diagnosed with acute promyelocytic leukemia. Chemotherapy was administered following the JALSG APL204 protocol. Induction therapy with all-trans retinoic acid resulted in complete remission on day 49. She developed coccygeal pain from day 18, which spread to the spine and cheekbones and lasted 5 weeks. She had similar bone pain on days 7-10 of the first consolidation therapy and on days 4-12 of the second consolidation therapy. Oral loxoprofen was prescribed for pain relief. On day 33 of the third consolidation, white blood cell and neutrophil counts were 320/µL and 20/µL, respectively. After she developed epigastralgia and hematemesis, she developed septic shock. Gastroendoscopy revealed markedly thickened folds and diffusely damaged mucosa with blood oozing. Computed tomography revealed thickened walls of the antrum and the pylorus. Despite emergency treatments, she died. Bacterial culture of the gastric fluid yielded Enterobacter cloacae and enterococci growth. Collectively, she was diagnosed with phlegmonous gastritis. Retrospective examination of serial bone marrow biopsy specimens demonstrated progressive bone marrow fibrosis, which may have caused prolonged myelosuppression. Thus, evaluation of bone marrow fibrosis by bone marrow biopsy after each treatment cycle might serve as a predictor of persistent myelosuppression induced by chemotherapy.

Hemophagocytic Syndrome-Associated Variant of Methotrexate-Associated Intravascular Large B-Cell Lymphoma in a Rheumatoid Arthritis Patient.

A 59-year-old man was treated for rheumatoid arthritis (RA) for 12 years with methotrexate (MTX) and prednisolone. After MTX-associated interstitial pneumonia developed, he was treated with cyclophosphamide and prednisolone for 7 months. Arthritis worsened, and tacrolimus was added to the treatment regimen. One month later, he had fever, loss of appetite, and dyspnea on exertion. Blood tests showed pancytopenia with large, atypical lymphocytes. Computed tomography showed mild splenomegaly. Bone marrow examination demonstrated CD20-positive, EBER-positive atypical lymphocytes, and hemophagocytosis. Random skin biopsy led to the diagnosis of intravascular large B-cell lymphoma (IVLBCL). The final diagnosis was a hemophagocytic syndrome-associated variant of IVLBCL. Complete remission was achieved after seven courses of R-CHOP. However, within a month, he complained of dizziness. Magnetic resonance imaging revealed focal infarctions in the cerebellum and around the left lateral ventricle. Central nervous system relapse was suspected. Although salvage chemotherapy (CHASER), whole brain irradiation, and intrathecal injection of cytarabine and prednisolone were temporarily effective, he died. Autopsy revealed infiltration of lymphoma cells in the brain and adrenal glands. To the best of our knowledge, this is the sixth case of IVLBCL and the first case of the hemophagocytic syndrome-associated variant of IVLBCL in RA patients in the literature.

Secondary Syphilis with Tonsillar and Cervical Lymphadenopathy and a Pulmonary Lesion Mimicking Malignant Lymphoma.

BACKGROUND Syphilis is a sexually transmitted disease caused by the pathogen Treponema pallidum. Prevalence continues to rise, especially among men who have sex with men (MSM). Due to changes in patterns of sexual activity, manifestations of the disease are highly variable. CASE REPORT A 27-year-old male visited the hospital for a low-grade fever and tender 5-cm mass in the right side of his neck. His right tonsil was swollen and covered with a white coating. Levofloxacin was prescribed, but ineffective. The patient's levels of liver function enzymes increased gradually. Systemic magnetic resonance imaging (MRI) revealed bilateral cervical lymphadenopathy with right predominance, a right pulmonary nodule, and a periportal lymph node, suggestive of malignant lymphoma. However, a biopsy of the right cervical lymph node showed nonspecific inflammation. Preoperative rapid plasma reagin (RPR) and T. pallidum latex agglutination (TPLA) tests were positive. The patient was MSM and reported oral sex with many sexual partners. A diagnosis of secondary syphilis was made. Oral amoxicillin was effective, and all symptoms other than periportal lymph node resolved. CONCLUSIONS Tonsillitis, cervical lymphadenopathy, and lung lesions can be manifestations of secondary syphilis. A detailed history, pathology, and serology are crucial for diagnosis.

Bosutinib as a fourth-line therapy for a patient with T315I-positive lymphoid blastic phase chronic myeloid leukemia: A case report.

A 35-year-old male was diagnosed with chronic myeloid leukemia in the chronic phase and was prescribed 100 mg daily dasatinib. However, dasatinib was discontinued due to thrombocytopenia, and within six months, the disease progressed to the lymphoid blastic phase. Hyper-cyclophosphamide, vincristine, adriamycin and dexamethasone chemotherapy combined with 140 mg dasatinib or 600 mg imatinib was prescribed. The two inhibitors were soon discontinued due to severe thrombocytopenia and jaundice, respectively. Myelosuppression persisted subsequent to the nadir. Bone marrow (BM) aspiration and biopsy revealed hypercellular marrow filled with blasts. Sequencing of the leukemia cells revealed overlapping peaks for the wild-type sequence and the T315I mutant sequence. The patient was treated with 500 mg bosutinib (which was later reduced to 300 mg) for pretransplant cytoreduction. After 5 months, the patient's spleen exhibited a reduction in volume and the percentage of blasts in the BM decreased from 96.1 to 17.5%. The patient successfully underwent cord blood transplantation. The patient has been disease-free for 5 months subsequent to transplantation. This case suggests that bosutinib may be effective for cytoreduction prior to stem cell transplantation, unless the leukemia cells consistently harbor the T315I mutation.

Splenic Marginal Zone Lymphoma with Acquired von Willebrand Syndrome Diagnosed via Splenic Bleeding.

An 85-year-old woman underwent emergent splenectomy due to left abdominal pain and active bleeding in a massively enlarged spleen. The histological diagnosis was splenic marginal zone lymphoma (SMZL). A prolonged activated partial thromboplastin time (APTT) was noted, and additional tests led to the diagnosis of type 2A-like acquired von Willebrand syndrome (AVWS). An APTT cross mixing test ruled out the presence of inhibitors. She received eight courses of rituximab monotherapy. The coagulation data showed no improvement, possibly because the lymphoma showed a poor response to the treatment. AVWS rarely causes bleeding in solid organs. This is the first case of SMZL with AVWS diagnosed via splenic bleeding.

Intestinal Intravascular Large B-cell Lymphoma Mimicking Ulcerative Colitis with Secondary Membranoproliferative Glomerulonephritis.

A 47-year-old woman with ulcerative colitis (UC) was admitted to our hospital for renal dysfunction and progressive anemia. Colonoscopy revealed intestinal lesions and pathological findings showed intravascular large B-cell lymphoma (IVLBCL). According to the polymerase chain reaction analysis of sequential rectal specimens, we concluded that she suffered from intestinal BCL, not UC. After chemotherapy, her renal function progressed to nephrotic syndrome. The pathological findings of renal biopsy specimens indicated membranoproliferative glomerulonephritis (MPGN). Chemotherapy was continued and led to the remission of BCL and MPGN. We herein describe the first case of intestinal IVLBCL mimicking UC with secondary MPGN.

Esophageal Candidiasis as the Initial Manifestation of Acute Myeloid Leukemia.

A 47-year-old woman presented with persistent dysphagia. A gastroendoscopy revealed massive esophageal candidiasis, and oral miconazole was prescribed. Three weeks later, she returned to our hospital without symptomatic improvement. She was febrile, and blood tests showed leukocytosis (137,150 /µL, blast 85%), anemia and thrombocytopenia. She was diagnosed with acute myeloid leukemia (AML). She received chemotherapy and antimicrobial agents. During the recovery from the nadir, bilateral ocular candidiasis was detected, suggesting the presence of preceding candidemia. Thus, esophageal candidiasis can be an initial manifestation of AML. Thorough examination to detect systemic candidiasis is strongly recommended when neutropenic patients exhibit local candidiasis prior to chemotherapy.

IL-1α induces thrombopoiesis through megakaryocyte rupture in response to acute platelet needs.

Intravital visualization of thrombopoiesis revealed that formation of proplatelets, which are cytoplasmic protrusions in bone marrow megakaryocytes (MKs), is dominant in the steady state. However, it was unclear whether this is the only path to platelet biogenesis. We have identified an alternative MK rupture, which entails rapid cytoplasmic fragmentation and release of much larger numbers of platelets, primarily into blood vessels, which is morphologically and temporally different than typical FasL-induced apoptosis. Serum levels of the inflammatory cytokine IL-1α were acutely elevated after platelet loss or administration of an inflammatory stimulus to mice, whereas the MK-regulator thrombopoietin (TPO) was not elevated. Moreover, IL-1α administration rapidly induced MK rupture-dependent thrombopoiesis and increased platelet counts. IL-1α-IL-1R1 signaling activated caspase-3, which reduced plasma membrane stability and appeared to inhibit regulated tubulin expression and proplatelet formation, and ultimately led to MK rupture. Collectively, it appears the balance between TPO and IL-1α determines the MK cellular programming for thrombopoiesis in response to acute and chronic platelet needs.

Metastatic seminomas in lymph nodes: CD10 immunoreactivity can be a pitfall of differential diagnosis.

Metastatic seminoma can potentially be confused with lymphoma in a lymph node biopsy. Here, we report a case in which the immunohistochemistry of CD10 was a pitfall in the differential diagnosis of a metastatic seminoma, and further present a brief study of CD10 expression in a seminoma series. A 67-year-old man, who had a history of lobectomy of the lung due to squamous cell carcinoma 2 years prior, showed lymphadenopathy of the neck and the paraaorta on follow-up study by fluorodeoxyglucose-positron emission computer tomography scan. The biopsy of the cervical node demonstrated infiltration of large atypical cells. The results of the screening immunohistochemistry were CD20(-), CD3(-), CD10(+), CD30(-), AE1/AE3(-), and placental alkaline phosphatase(-), providing the impression of CD10-positive lymphoma. However, the following studies revealed germ cell characteristics [OCT3/4(+), SALL4(+), and CLDN6(+)], confirming the diagnosis of seminoma. We further evaluated CD10 expression in a series of seminomas (n=16). Strong positivity was observed in 14 cases; partial and weak positivity, in 2 cases. These findings should be considered in the differential diagnosis of seminoma.

Successful treatment of ulcerative colitis associated with hypereosinophilic syndrome/chronic eosinophilic leukemia.

A 23-year-old female was diagnosed as having simultaneous ulcerative colitis (UC) relapse and hypereosinophilic syndrome (HES)/chronic eosinophilic leukemia (CEL) without FIP1L1-platelet-derived growth factor receptor alpha (PDGFRA) (F/P) fusion gene. Pathological findings of colon specimens were compatible with UC, however, focal severe infiltration of eosinophils was observed in the rectum, which is unusual in UC, suggesting eosinophil-mediated organ damage. Although imatinib mesylate (IM) is usually ineffective for the treatment of HES/CEL with negative-F/P fusion gene, in the present case it led to the remission of HES/CEL and UC at a higher drug dosage level (400 mg/day). That suggested the presence of unknown tyrosine kinase abnormalities not yet categorized.

Peripheral T-cell lymphoma that developed during the follow-up of IgG4-related disease.

IgG4-related disease is a recently recognized fibroinflammatory disorder characterized by extensive IgG4-positive plasma cell and lymphocyte infiltration of various organs. The pancreatic manifestation of IgG4-related disease is called autoimmune pancreatitis (AIP), in which autoimmune mechanisms are likely involved. On the other hand, some autoimmune and chronic inflammatory disorders, such as Sjögren's syndrome and rheumatoid arthritis, are associated with increased risks of non-Hodgkin lymphoma (NHL). There have been a few reports of cases with IgG4-related disease that had subsequently developed NHL, however, all of them suffered from B-cell lymphoma. We describe the first case of NHL, compatible with a subtype of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), which arose in IgG4-related sclerosing cholangitis. As patients with IgG4-related disease may be at an increased risk of developing NHL, such presentation during the follow-up of IgG4-related disease should be carefully scrutinized to exclude NHL.

A case of syphilis presenting with initial syphilitic hepatitis and serological recurrence with cerebrospinal abnormality.

We present the case of an immunocompetent 50-year-old Japanese man with a cerebrospinal fluid (CSF) abnormality relevant to syphilis; his original presentation was liver dysfunction, the etiology of which was uncertain until positive serology for syphilis was identified. Liver dysfunction was promptly resolved after oral penicillin therapy; however, serological recurrence developed. CSF abnormality associated with syphilis was confirmed by subsequent lumbar puncture. Syphilis should be included in the differential diagnosis of patients with liver dysfunction of unknown etiology, and possible neurosyphilis should be considered when the treatment becomes refractory, even when there is no evidence of neurological manifestations.

[A case of HIV infection associated with ulcerative colitis].

We describe a 42-year-old-man with HIV infection who developed ulcerative colitis. Ulcerative colitis was diagnosed on the basis of clinical symptoms, and the findings of colonoscopy, pathology and culture. Although remission of ulcerative colitis was induced by PSL and SASP, HIV infection progressed. Treatment with highly active antiretroviral therapy (HAART) was started. HIV viral load decreased to less than 50copies/ml and CD4 counts increased to over 400/microl. After discontinuance of PSL and SASP, he is still in good condition. This is the first report of HIV infection associated with ulcerative colitis in Japan. A relationship between immune disorder in advanced HIV infection and inflammatory bowel disease was suggested. Ulcerative colitis might be an important complication in HIV infection.

Thrombopoietin-producing hepatocellular carcinoma.

A 66-year-old man with hepatocellular carcinoma (HCC) showed marked thrombocytosis (110.7 x 10(4)/microl). Bone marrow (BM) aspirates demonstrated an increase of mature megakaryocytes (MgK). The serum thrombopoietin (TPO) level was increased to about 100-fold that of the normal level in the terminal stage. However, the platelet count gradually decreased to 13.5 x 10(4)/microl. The autopsy specimen revealed normoplastic BM with decreased MgK, mainly consisting of the immature type, and it was negative for tumor cells. Liver specimen showed markedly fatty metamorphosis. Immunohistochemical staining of TPO demonstrated that hepatocytes were weakly stained and HCC cells strongly stained, suggesting TPO-producing HCC.

[Primary cardiac lymphoma: a case report].

A 83-year-old woman was admitted because of pretibial edema. Echocardiography demonstrated a huge tumor in the right atrium and ventricle. Transvenous biopsy failed to obtain sufficient specimens for the histological diagnosis. The tumor progressed rapidly and heart failure was intractable. The diagnosis was primary cardiac lymphoma on the basis of elevated soluble interleukin-2 receptor and solitary accumulation of gallium-67 in the heart. Chemotherapy was immediately started. After two courses of chemotherapy, the intracardiac tumor disappeared. However, one month later, the tumor relapsed in the anterior mediastinum. Needle biopsy disclosed diffuse B-cell non-Hodgkin's malignant lymphoma. Additional irradiation reduced the tumor. Early diagnosis and immediate chemotherapy are important for the treatment of primary cardiac lymphoma.