Efficacy and safety of therapeutic procedure for Waldenström's macroglobulinemia with hyperviscosity syndrome.

INTRODUCTION: Hyperviscosity syndrome (HVS) is a significant complication in Waldenström's macroglobulinemia (WM), although the significance of plasmapheresis in clinical practice has not been clarified. To confirm the efficacy and safety of plasmapheresis followed by primary therapy for WM with HVS, we retrospectively conducted this study. METHODS: Untreated WM with HVS, or serum immunoglobulin M (IgM) levels ≥4000 mg/dL, were analyzed. The basic therapeutic flow was conducted as follows: (1) performing plasmapheresis, (2) followed by primary therapy without rituximab, and (3) performing the second cycle. The serum IgM reduction rate and adverse events (AEs) were evaluated. RESULTS: Ten patients were enrolled. The median serum IgM levels at diagnosis, post-plasmapheresis, after the first cycle of primary therapy, and after the second cycle were 5174, 2900, 3286, and 2657 mg/dL, respectively. No patients experienced IgM flare or bleeding AEs. CONCLUSION: The therapeutic flow offers sufficient efficacy and safety in WM with HVS.

A Rare Clinical Case of Secondary Central Nervous System Involvement without Transformation in Hairy Cell Leukemia: Case Report and Literature Review.

Introduction Hairy cell leukemia (HCL) is an indolent B-cell lymphoma characterized by a specific genetic mutation, BRAF V600E, which affects the specific morphology and oncogenesis. For HCL, few reports regarding secondary central nervous system involvement (SCNSI) are available. Herein, we present the case of an 80-year-old woman who had a relapse of HCL with SCNSI. Case presentation The diagnosis of HCL was made in June 2015 after identifying BRAF V600E proteins by immunohistochemical analysis, and the disease was then controlled for 6 years by employing chemoimmunotherapy. In February 2021, the patient was admitted with neurological symptoms such as dizziness. Magnetic resonance imaging of the brain showed abnormal enhancement in the cerebrum, and cerebrospinal fluid analysis revealed neoplastic cells without transformation into large cells. Thus, the patient was diagnosed as having SCNSI in HCL. Conclusion We report a case of a rare clinical presentation of SCNSI in HCL with literature review.

Extramedullary hematopoietic pleural effusion in Waldenström's macroglobulinemia.

Extramedullary hematopoietic effusion (EHE) is one of the extremely rare phenomena associated with extramedullary hematopoiesis, which is caused by serous effusions, including pleural effusion, and may be related to hematologic disorders and neoplasms. Herein, we present the case of an 81-year-old man with EHE accompanying Waldenström's macroglobulinemia (WM). The patient complained of anemia and dyspnea. The chest X-ray and computed tomography showed a massive left pleural effusion, and the aspirates revealed infiltration of the immature myeloid cells and megakaryocytes, in addition to the lymphoma cells. To our knowledge, this is the first report of EHE in WM.

Other iatrogenic immunodeficiency lymphoproliferative disorder induced by corticosteroid used for an autoimmune disorder.

Other iatrogenic immunodeficiency lymphoproliferative disorders (oii-LPD) are defined as lymphoid proliferations or lymphomas that occur in patients taking immunosuppressive agents (ISA) for autoimmune disorders (AID). Although methotrexate and tumor necrosis factor-alpha inhibitors cause oii-LPD, the association between corticosteroids and lymphomagenesis remains unknown. Herein, we present the case of a 51-year-old woman with oii-LPD caused by corticosteroid use for autoimmune hemolytic anemia (AIHA). The diagnosis of AIHA was made in May 2016, and AIHA had been well-controlled for 5 years with oral prednisolone (PSL). During a regular follow-up visit in March 2022, an abnormal increase in atypical lymphoid cells in the peripheral blood was found. The bone marrow biopsy specimens showed local aggregations of large cells that were identified as lymphoplasmacytic cells and plasma cells, and that were positive for cluster of differentiation (CD)19 and CD20, with apparent nucleoli among the diffuse infiltration of atypical small lymphocytes. The large cells were partially positive for the Epstein-Barr encoding region in situ hybridization and latent membrane protein 1, which confirmed Epstein-Barr virus (EBV)-affected lymphomagenesis. To our knowledge, this is the first report of an oii-LPD case shown to be induced by corticosteroid use for AID.

An ectopic thymoma arising in the middle mediastinum that was difficult to distinguish from a lymph node metastasis.

BACKGROUND: Ectopic thymomas often occur in the upper mediastinum; however, they rarely arise in the middle mediastinum, especially on the dorsal side of the innominate vein and superior vena cava in the peribronchial region. CASE PRESENTATION: Six years prior, a 27-year-old female presented to our department and was diagnosed with locally advanced left breast cancer. First, we administered chemotherapy including an anti-human epidermal growth factor receptor 2 antibody. The size of the tumor was markedly reduced, and a radical operation involving mastectomy and axillary lymph node dissection was then performed. The patient underwent radiotherapy after the mastectomy, followed by trastuzumab therapy; she continued to receive endocrine therapy thereafter. She underwent computed tomography once a year after the surgery, and a nodule in the middle mediastinum on the dorsal side of the innominate vein and superior vena cava in the parabronchial region was detected at 4 years. We speculated that the nodule was a solitary mediastinal lymph node metastasis from her breast cancer; therefore, we performed thoracoscopic resection of the tumor. We diagnosed the tumor as a thymoma. Currently, the patient visits our hospital to receive continuous hormone therapy for her breast cancer, and the latest computed tomography scan demonstrated no metastases from or recurrence of her breast cancer or thymoma. CONCLUSIONS: We report a case of ectopic thymoma in the middle mediastinum. The tumor, which was detected during systemic therapy for locally advanced breast cancer, was located on the dorsal side of the innominate vein and superior vena cava in the parabronchial region and was indistinguishable from a lymph node metastasis from breast cancer.

An Autopsy Case of Bing-Neel Syndrome: Discrepancy between the Radiological and Pathological Findings.

A 64-year-old man previously diagnosed with Waldenstrom's macroglobulinemia presented to our hospital with confusion. Magnetic resonance imaging (MRI) revealed diffuse meningeal enhancement. The patient was diagnosed with Bing-Neel syndrome (BNS) based on an elevated IgM index and the presence of monoclonal IgM protein, as detected by immunofixation electrophoresis of the cerebrospinal fluid. The patient underwent intrathecal and systemic chemotherapy but ultimately died of pneumonia. An autopsy revealed extensive meningeal and perivascular infiltration by malignant cells throughout the brain and spine. Thus, BNS may cause more extensive malignant infiltration into the central nervous system than is revealed by MRI.

Impact of rituximab and half-dose CHOP as primary therapy for untreated symptomatic Waldenström Macroglobulinemia: review of a combined regimen of rituximab with an alkylating agent.

BACKGROUND: Waldenström Macroglobulinemia (WM) is a rare subtype of indolent B-cell lymphoma, and prospective randomized studies on WM are scarce. The R-CHOP therapy [rituximab (R), cyclophosphamide, hydroxy-doxorubicin, vincristine, and prednisone] is a popular and recommended regimen for primary therapy, prescribed by several treatment guidelines for WM. However, treatment with R-CHOP is accompanied by severe myelosuppression and high rates of peripheral neuropathy. Therefore, we retrospectively evaluated the efficacy and toxicity of half-dose CHOP combined with R as a primary therapy for WM. METHODS: Patients with untreated symptomatic WM, treated at the Disaster Medical Center between April 2011 and September 2016, were retrospectively analyzed after administration of 6 cycles of half-dose R-CHOP for every 3 weeks. The response, median time to response, best response, progression-free survival, overall survival, and toxicities were evaluated. RESULTS: Of the 20 WM patients analyzed, 16 (80%) received half-dose R-CHOP without vincristine, and 13 (65%) responded to the treatment. With a median follow-up duration of 26.3 months, the 2-year progression-free survival and 2-year overall survival rates were 70 and 93.3%, respectively. The median time to response and best response were 6 and 9.9 weeks, respectively. Grade 3/4 leukocytopenia, neutropenia, febrile neutropenia, and Grade 1 peripheral neuropathy developed in 32, 37, 0, and 21% of patients, respectively. CONCLUSION: The half-dose R-CHOP is an effective and well-tolerated primary therapy for WM. To the best of our knowledge, this is the first study reporting the use of a reduced-dose R-CHOP regimen for the primary treatment of WM.

Establishment of pathological quantitative method for determining undifferentiated component ratio in patients with differentiated/undifferentiated mixed-type early gastric cancer and clinical significance of this ratio.

PURPOSES: The purpose of this study was to establish a pathological quantitative method for determining the undifferentiated components ratio (UCR) in patients with differentiated/undifferentiated mixed-type (Mixed-type) early gastric cancer (EGC) and to examine the clinical significance. METHODS: The subjects were 410 patients who underwent surgical resection for EGC with the invasion limited to m or sm1. Analysis 1: In 12 randomly selected patients with Mixed-type cancer, we calculated the area ratio and the ratio of the length ratio using ImageJ and analyzed the correlation between them. Analysis 2: We generated ROC curves, and determined the cutoff UCR on the basis of the predictive risk factors for lymph node metastasis (LNM). Analysis 3: We analyzed the relationship between clinicopathological factors including UCR/length of undifferentiated component (LUC = maximum dimensions of tumor × UCR) and LNM. RESULTS: Analysis 1: The length ratio can be used as a substitute parameter for the UCR (r = 0.996). Analysis 2: The cutoff UCR as a risk factor for LNM was 58% (sensitivity = 1, 1 - specificity = 0.404). Analysis 3: Lymphovascular invasion (p < 0.0001), UCR ≥58% (p = 0.023), and LUC ≥25 mm (p = 0.005) were identified as significant risk factors for LNM. No LNM was observed in patients with invasion limited to m or sm1 and negativity for lymphovascular invasion and UCR <58% (0/215). CONCLUSIONS: In the patients with Mixed-type EGC, the length ratio of undifferentiated components can be a substitute parameter for the UCR. LNM rarely occurs in patients without lymphovascular invasion and with an UCR <58%. The analysis of the UCR has great significance in determining whether additional surgical resection is required after endoscopic resection.

Expression of L-type amino acid transporter 1 in various skin lesions.

L-type amino acid transporter 1 (LAT1) is a Na(+)-independent neutral amino acid transporter that has an essential role in cell proliferation. Although the involvement of LAT1 in human carcinogenesis has been investigated by immunohistochemistry in various organs, LAT1 expression in skin has not been reported yet. Therefore, in the present study, immunohistochemistry for LAT1 was performed in 15 keratoacanthoma (KA), 10 seborrheic keratosis, 16 Bowen's disease, 11 basal cell carcinoma (BCC), and 9 squamous cell carcinoma (SCC) cases as well as 61 normal epidermis as control. It was demonstrated that LAT1 expression limited to the basal layer was occasionally observed in normal epidermis while its expression was significantly decreased in the epithelium of seborrheic keratosis and Bowen's disease (P<0.05). By contrast, a significantly higher rate of LAT1 expression was observed in the epithelium of KA, BCC, and SCC than in normal epidermis (P<0.05). Although LAT1 expression was limited to the basal layer or rim of the nests in KA, LAT1 expression was also observed in the center of the nests in BCC and SCC (P<0.001). Thus, LAT1 is differentially expressed in various skin lesions and may be an especially useful marker to distinguish KA from SCC.

Carcinosarcoma, an atypical subset of gallbladder malignancies.

Carcinosarcoma represents an atypical subset of gallbladder malignancies, and sonographic imaging features have not yet been precisely defined. Previously reported cases have shown a heterogeneously echogenic solid mass protruding into and filling the gallbladder lumen. We present herein a case of carcinosarcoma and propose another finding suggestive of this tumor. The patient was a woman in her 70s. Abdominal sonography revealed that the gallbladder lumen was half-filled by a large mass (maximum diameter, 68 mm) showing heterogeneous echogenicity slightly higher than that of bile. However, despite the large size of the mass, gallbladder shape was well-preserved. Considering the findings on computed tomography, cholecystectomy was performed under a diagnosis of gallbladder malignancy. Pathological examination revealed two types of malignant histology: a sarcomatous element of malignant spindle cells and a carcinomatous element of adenocarcinoma tissue. Foci of malignant cartilage and bone areas were also found sporadically. Accompanied by immunohistochemical examination, the mass was diagnosed as carcinosarcoma. The present case showed somewhat different imaging findings from those of ordinary gallbladder carcinoma. Carcinosarcoma should be considered when a well-preserved shape of the gallbladder is recognized along with protrusion of a large heterogeneously echogenic mass into and filling the gallbladder lumen.

AP-VAS 2012 case report: a case of systemic MPO-ANCA-associated vasculitis that demonstrated brain infarction and immunohistochemically MPO-positive capillaries.

We present a case of an aged male with myeloperoxidase anti-neutrophil cytoplasmic autoantibody (MPO-ANCA)-associated vasculitis with onset of brain infarction that demonstrated immunohistochemically MPO-positive capillaries at autopsy. The patient initially presented with gait difficulty and right-sided weakness. Since an imaging study revealed brain infarction, he was admitted to our hospital and medicated by antiplatelet agents. Continuous fever and elevated serum C-reactive protein (CRP), hematuria of glomerular origin, renal dysfunction, and high serum titer of MPO-ANCA were detected. Systemic toxicoderma appeared, and skin biopsy revealed small-vessel vasculitis; thus, he was diagnosed with MPO-ANCA-associated vasculitis. Steroid therapy (methylprednisolone 30 mg/day) was started, and general status improved. However, he died of shock 6 days after the start of the therapy. Autopsy revealed massive retroperitoneal hemorrhage with necrotizing small-vessel vasculitis in systemic organs including retroperitoneum, skin, brain, testes, and kidneys. Immunohistochemically, infiltration of MPO-positive white blood cells into the capillaries was occasionally observed, along with the features of MPO-positive capillaries. Cerebrovascular involvement of MPO-ANCA-associated vasculitis is rare compared with renal and pulmonary manifestations, having been reported to occur in up to 4 % of patients. Furthermore, as we have recently reported, MPO-immunopositive capillaries may appear only during the hyperacute stage of the disease. Therefore, the present case represents the unique combination of these two rare manifestations.

Immature teratoma of the ovary with distant metastases: favorable prognosis and insights into chemotherapeutic retroconversion.

We present a case of a young woman with an immature teratoma of the right ovary that showed systemic metastases. The patient initially experienced abdominal distention at the age of 15 years. Radiographic assessment revealed a right ovarian tumor; thus, right salpingo-oophorectomy was performed, and the resected ovarian tumor showed a multilocular cystic lesion with partially solid areas. Pathologic diagnosis was an immature teratoma, grade 2. As brain, lung, and liver metastases were discovered within 2 years after the operation, sequential resections of the metastatic foci were performed before chemotherapy as well as during the early and late stages of chemotherapy. The resected specimens of each metastatic focus contained histologically more mature elements of the primary immature teratoma and exhibited a decrease in the Ki-67 labeling index, the later the resection was performed. As far as we know, this is the first case of brain metastasis stemming from an immature teratoma of the ovary. In addition, it was highly suggestive that chemotherapy itself was the main etiological factor for the promotion of maturation. The favorable prognosis of this malignant tumor even after brain metastasis was verified by the 10-year-survival of the patient.

Unusual sonographic appearance of synovial sarcoma of the anterior abdominal wall.

We report a case of synovial sarcoma in a 58-year-old woman arising from the anterior abdominal wall. Sonography demonstrated a large mass with an unusual complex "honeycomb" echotexture. Doppler imaging displayed increased vascularity in the solid parts of the tumor.

Expression of stem cell factor (SCF), a KIT ligand, in gastrointestinal stromal tumors (GISTs): a potential marker for tumor proliferation.

Gastrointestinal stromal tumors (GISTs) show a high incidence of gain-of-function mutations of the c-kit gene, which encodes a receptor tyrosine kinase KIT. This mutation is seen independently of metastasis and/or recurrence of tumors; thus, the factors involved in tumor proliferation rate and malignancy are still not known. Some mesenchymal and epithelial tumors have been reported to co-express KIT and its ligand, stem cell factor (SCF), for autonomous proliferation by the autocrine mechanism. The purpose of this study is to clarify whether GIST cells produce SCF, despite mutated KIT with constitutive activation. Immunohistochemically, we examined the co-expression of KIT and SCF in 36 GIST cases. All cases were found to be KIT-positive, and of these, 21 cases, including four recurrent or metastatic GISTs, showed co-expression of SCF. MIB-1 labeling index was significantly higher, and the average tumor size was larger in SCF-positive cases. By confocal microscopy, KIT was expressed on the cellular membrane, around which SCF was distributed less densely. Western blot analysis revealed that the membrane-bound SCF of 31 kDa was found to be approximately 10 times more abundant than the soluble SCF of 18.5 kDa, suggesting continuous KIT activation. These results indicate that proliferation of GIST cells can be caused not only by the gain-of-function mutation of c-kit, but also by the autocrine mechanism of the SCF/KIT system. Thus, SCF expression would be a useful marker for tumor proliferation.

Multiple aortic aneurysms complicated by a rupture in the systemic lupus erythematosus: a case report.

We report the case of a 61-year-old female who suffered from systemic lupus erythematosus (SLE) and died of a ruptured abdominal aortic aneurysm (AA). She was diagnosed to have SLE at 39 years of age, and was administrated steroids and prostaglandin E(2). From 52 years of age, AA, peripheral arterial occlusion, and multiple organ infarctions appeared repeatedly. At 59 years of age, she was found to be affected by antiphospholipid antibody syndrome (APS). In the following year, expansion of an abdominal AA was identified, but she was given only conservative treatment. In the next year, sudden epigastralgia and dyspnea occurred, and she died. An autopsy revealed multiple AAs up to 11 cm in diameter, one of which showed ruptures, forming a retroperitoneal hematoma. Marked atherosclerosis of the aorta was noted, and she also had aortic dissection accompanied by cystic medial necrosis (CMN). An old myocardial infarction and brain infarction were also confirmed. Although SLE with APS is common, a complication of the disease by CMN, multiple AAs, or ruptured AA has been described in several cases to date. Regarding the etiology of this complicated presentation, we presume synergistic involvement of various factors, such as atherosclerosis and CMN associated with SLE, thrombosis due to APS, and prolonged steroid therapy.

Leiomyosarcoma with dedifferentiation in a premenopausal patient discovered after uterine artery embolization.

Although a hysterectomy is the most common treatment for relieving the symptoms attributable to uterine leiomyomas, uterine artery embolization (UAE) is now being used more frequently as an alternative to a hysterectomy. However, it is difficult to differentiate a leiomyoma from a leiomyosarcoma without performing a pathological examination. Reported herein is a rare case of leiomyosarcoma that showed dedifferentiation of the tumor cells after UAE. A premenopausal 48-year-old woman had been suffering from hypermenorrhea for 4 years before visiting the clinic. She underwent UAE for suspected symptomatic leiomyoma. Two months later, dilatation and curettage was performed because of genital bleeding and a necrotic mass was submitted for pathological examination. Three months after curettage, with renewed symptoms, endometrial biopsy was done, which confirmed pleomorphic sarcoma. Metastatic nodes to the lung were also found at that time. Multiple leiomyosarcomas and a leiomyosarcoma showing dedifferentiation of the uterine body were found on pathological examination. The patient had metastatic nodes to the brain later and died of metastatic disease 20 months in total after UAE. This is a rare case of leiomyosarcoma with dedifferentiation and multiple metastases occurring after UAE, suggesting that dedifferentiation could be derived from ordinary leiomyosarcoma and that the traumatic effect of curettage might cause early metastasis. The present case is a warning that careful and detailed evaluation of the uterine tumor are needed before UEA.