Immunohistopathological Analysis of Extramedullary Hematopoiesis and Angiogenesis of Spleen in a Case of Primary Myelofibrosis with Huge Splenomegaly.

Although splenomegaly is one of the important signs of primary myelofibrosis, the differential diagnosis varies from malignant disorders to benign disorders, including malignant lymphoma and sarcoidosis. The patient was a 67-year-old male who developed anemia and huge splenomegaly. The laboratory findings include human T-cell leukemia virus type 1 (HTLV-1) antibody, elevated soluble interleukin-2 receptor, hypocellular bone marrow, and uptake in the spleen on positron emission tomography/computed tomography scan. Additionally, we performed laparoscopic splenectomy to alleviate the clinical symptoms and to rule out malignant lymphoma. Histological findings revealed extramedullary hematopoiesis, characterized by the presence of erythroid islands and clusters of dysplastic megakaryocytes with increased reticulin fibrosis. Immunohistochemical staining revealed the presence of von Willebrand factor, dysplastic megakaryocytes, myeloperoxidase, myeloid-predominant proliferations, and CD34 immature myeloid cells. Furthermore, regarding the angiogenesis in the spleen, the endothelial cells of the capillaries and those of the sinusoidal vascular system that were reactive for CD34 and CD8, respectively, were also detected. Consequently, the histological findings revealed both extramedullary hematopoiesis and angiogenesis in spleen. Based on the histological findings and the identification of Janus activating kinase 2 (JAK-2) mutation, the patient was diagnosed with primary myelofibrosis. Splenectomy reduces blood transfusion requirements after surgery. The patient was carefully followed-up without further treatments. Thus, primary myelofibrosis is the crucial differential diagnosis of huge splenomegaly.

Postpartum regression of human papillomavirus-related vulvar cancer: A case report.

We report a case of a 23-year-old pregnant woman (gravida 2 para 0, pregnancy 33 weeks and 3 days) with a history of laser ablation for cervical intraepithelial neoplasia-3 at 22 years. At initial visit, a 2 × 2 × 1-cm elevated mass was found on right labia majora. Biopsy results revealed squamous cell carcinoma of right labia; immunostaining revealed p16 positivity. Patient was diagnosed with human papillomavirus-related vulvar cancer. Selective cesarean section was performed at 36 weeks and 4 days of gestation. Postoperative histopathological diagnosis of squamous cell carcinoma, and 1.7-mm deep infiltrations led to vulvar cancer stage IB diagnosis. Reduction operation was performed, and postoperative follow-up of 1 year and 8 months revealed no recurrence. These results emphasize that small vulvar tumors during pregnancy should not be underestimated and histological examinations should be performed without hesitation. Careful observation and evaluation of tumors is necessary during pregnancy and after delivery because they may shrink postdelivery.

[Analysis of Prognostic Factors Considering Absolute Lymphocyte Count of Metastatic Breast Cancer Patients with Eribulin Mesylate Therapy-A Retrospective Study in a Single Institution].

Recently, a study for eribulin mesylate(ERI), which is a useful drug for metastatic and recurrent breast cancer, reported that the absolute lymphocyte count(ALC)before administration is a useful prognostic factor. We retrospectively examined whether the results were reproducible in the patients with ERI. We examined the effect of ERI on the overall survival(OS)in 21 patients with HER2-negative metastatic and recurrent breast cancer who underwent treatment with ERI at our hospital. The clinical benefit ratio(CBR)was 57.1%. The median time to treatment failure(TTF)was 5.8 months and median OS was 19.9 months, showing a positive correlation between the TTF and OS. The factors that significantly prolonged the OS in univariate analysis were the TTF(<3 months vs ≥3 months, p<0.001), NLR(<3 vs ≥3, p=0.037), and ALC(<1,000/ µL vs ≥1,000/µL, p=0.008). In the multivariate analysis, TTF and ALC were the prognostic factors. The ERI outcome at our institution was good regardless of the subtype. The results of the multivariate analysis showed that TTF and ALC were factors that prolonged OS, and patients who received ERI for >3 months had good OS. Long-term administration of ERI was assumed to affect the immune microenvironment and prolong OS. Additionally, our data showed that the lymphocyte count before ERI administration is a simple and useful prognostic factor.

Giant serous cystadenoma of the pancreas appearing sonographically as a remote pararenal mass.

Macrocystic serous cystadenoma (MSC) of the pancreas is a rare benign neoplasm with varied imaging appearances. We describe an intriguing case of a surgically resected and histologically proven giant MSC, developed in the pararenal space. Ultrasonography (US) revealed a large, oligocystic mass around the lower pole of right kidney. Like US, computed tomography, and magnetic resonance imaging were unable to detect the origin of the lesion, which was only verified at surgical exploration. A bizarre finding was the unusual location of the pancreatic tumor growing seemingly apart from the pancreas itself, with no obvious connection to it.

Loss of TET2 has dual roles in murine myeloproliferative neoplasms: disease sustainer and disease accelerator.

Acquired mutations of JAK2 and TET2 are frequent in myeloproliferative neoplasms (MPNs). We examined the individual and cooperative effects of these mutations on MPN development. Recipients of JAK2V617F cells developed primary myelofibrosis-like features; the addition of loss of TET2 worsened this JAK2V617F-induced disease, causing prolonged leukocytosis, splenomegaly, extramedullary hematopoiesis, and modestly shorter survival. Double-mutant (JAK2V617F plus loss of TET2) myeloid cells were more likely to be in a proliferative state than JAK2V617F single-mutant myeloid cells. In a serial competitive transplantation assay, JAK2V617F cells resulted in decreased chimerism in the second recipients, which did not develop MPNs. In marked contrast, cooperation between JAK2V617F and loss of TET2 developed and maintained MPNs in the second recipients by compensating for impaired hematopoietic stem cell (HSC) functioning. In-vitro sequential colony formation assays also supported the observation that JAK2V617F did not maintain HSC functioning over the long-term, but concurrent loss of TET2 mutation restored it. Transcriptional profiling revealed that loss of TET2 affected the expression of many HSC signature genes. We conclude that loss of TET2 has two different roles in MPNs: disease accelerator and disease initiator and sustainer in combination with JAK2V617F.

A case of successful CAR-T cell therapy for early isolated CNS recurrence of DLBCL with persistent CAR-T cells.

Secondary central nervous system (CNS) lymphomas typically require CNS-penetrating drugs; however, the available agents are limited with temporary effects and poor outcomes. Chimeric antigen receptor T (CAR-T) cell therapy (lisocabtagene maraleucel; liso-cel) has been used to treat a few cases of isolated secondary CNS lymphoma. Herein, we report the case of a 66-year-old male diagnosed with diffuse large B-cell lymphoma (Ann Arbor grade IV; R-IPI, good risk; CNS IPI: Intermediate risk) who achieved complete remission (CR) after six courses of R-CHOP therapy. Three months later, he presented with ptosis and eye movement disorder. Systemic CT and bone marrow examination revealed no lymphoma. Although cranial-enhanced MRI showed normal findings, an increased number of B-cells (51/µL) with the original lymphoma phenotype (CD19+CD79a+CD5-CD10-CD20-Igλ+) was detected in cerebrospinal fluid (CSF), indicating an isolated CNS relapse. Seven high-dose methotrexate courses led to partial response. Subsequently, the patient received CAR-T cell therapy with tolerable adverse events - cytokine release syndrome treated with tocilizumab, no immune effector cell-associated neurotoxicity syndrome, and bone marrow failure treated with granulocyte-colony stimulating factor and eltrombopag. Sequential flow cytometry revealed a high peak of CAR-T cells and the presence of residual CAR-T cells in the peripheral blood, indicating immune surveillance of CNS lymphoma by CAR-T cells. This treatment led to a second CR. This case is the first to validate the efficacy and safety of CAR-T cell therapy for isolated secondary CNS lymphoma in clinical practice. Future accumulation of evidence on the efficacy and safety of CAR-T cell therapy is essential.

Efficacy of temozolomide in a central nervous system relapse of neuroblastoma with O 6 -methylguanine methyltransferase (MGMT) promoter methylation.

We describe a case of a 5-year-old girl with central nervous system relapse of neuroblastoma after high-dose chemotherapy and autologous stem cell transplantation. Although the brain metastasis was surgically removed, she had a second relapse in the same region with leptomeningeal dissemination despite receiving irinotecan. Administration of temozolomide in addition to irinotecan led to her third complete response and the patient has been in complete response for >24 months. The tumor had no expression of the O -methylguanine methyltransferase (MGMT) gene due to promoter methylation. Temozolomide is an attractive candidate treatment in neuroblastoma with methylated MGMT, especially in central nervous system relapsed cases.

The clinical impact of the ratio of C-reactive protein to albumin (CAR) in patients with acute- and lymphoma-type adult T-cell leukemia-lymphoma (ATL).

Recently, the ratio of C-reactive protein to albumin (CAR) is used as an inflammatory marker that has been demonstrated to be a simple and reliable prognostic factor in solid tumors and hematological malignancy. However, no studies of the CAR have been performed in patients with adult T-cell leukemia-lymphoma (ATL). We retrospectively analyzed the clinical features and outcomes in 68 newly diagnosed acute- and lymphoma-type ATL [(acute-(n=42) or lymphoma-type (n=26)] patients in Miyazaki Prefecture from 2013 to 2017. Furthermore, we investigated correlations between pretreatment CAR levels and clinical features. The median age was 67 years (range, 44 - 87). Patients were initially treated by either palliative therapy (n=14) or chemotherapy [n=54; CHOP therapy (n=37)/ VCAP-AMP-VECP therapy (n=17)], and showed median survival durations of 0.5 months and 7.4 months, respectively. The factors affecting OS by multivariate analysis were age, BUN, and CAR. Importantly, we revealed that the high CAR group (optimal cut-off point; 0.553) was a significant indicator of worse OS by multivariate analysis (p< 0.001, HR; 5.46). The median survival of patients with a CAR< 0.553 was 8.37 months, while patients with a CAR>0.553 had a median survival of 3.94 months. The different clinical features between high CAR and low CAR groups were hypoproteinemia and the implementation of chemotherapy. Furthermore, in the chemotherapy group, but not the palliative therapy group, CAR was a significant prognostic marker. Our study indicated that CAR may be a new simple and significant independent prognostic marker in acute- and lymphoma-type ATL patients.

Successful treatment with infliximab for inflammatory colitis in a patient with X-linked anhidrotic ectodermal dysplasia with immunodeficiency.

X-linked anhidrotic ectodermal dysplasia with immunodeficiency (X-EDA-ID) is caused by hypomorphic mutations in the gene encoding nuclear factor-κB essential modulator protein (NEMO). Patients are susceptibile to diverse pathogens due to insufficient cytokine and frequently show severe chronic colitis. An 11-year-old boy with X-EDA-ID was hospitalized with autoimmune symptoms and severe chronic colitis which had been refractory to immunosuppressive drugs. Since tumor necrosis factor (TNF) α is responsible for the pathogenesis of NEMO colitis according to intestinal NEMO and additional TNFR1 knockout mice studies, and high levels of TNFα-producing mononuclear cells were detected in the patient due to the unexpected gene reversion mosaicism of NEMO, an anti-TNFα monoclonal antibody was administered to ameliorate his abdominal symptoms. Repeated administrations improved his colonoscopic findings as well as his dry skin along with a reduction of TNFα-expressing T cells. These findings suggest TNF blockade therapy is of value for refractory NEMO colitis with gene reversion.

Lymphomatoid gastropathy: a distinct clinicopathologic entity of self-limited pseudomalignant NK-cell proliferation.

Diagnostic errors in distinguishing between malignant and reactive processes can cause serious clinical consequences. We report 10 cases of unrecognized self-limited natural killer-cell proliferation in the stomach, designated as lymphomatoid gastropathy (LyGa). This study included 5 men and 5 women (age, 46-75 years) without any gastric symptoms. Gastroscopy showed elevated lesion(s) (diameter, ∼ 1 cm). Histologically, medium-sized to large atypical cells diffusely infiltrated the lamina propria and, occasionally, the glandular epithelium. The cells were CD2(+/-), sCD3(-), cCD3(+), CD4(-), CD5(-), CD7(+), CD8(-), CD16(-), CD20(-), CD45(+), CD56(+), CD117(-), CD158a(-), CD161(-), T cell-restricted intracellular antigen-1(+), granzyme B(+), perforin(+), Epstein-Barr early RNA(-), T-cell receptor αß(-), and T-cell receptor γδ(-). Analysis of the 16 specimens biopsied from 10 patients led to a diagnosis of lymphoma or suspected lymphoma in 11 specimens, gastritis for 1 specimen, adenocarcinoma for 1 specimen, and LyGa or suspected LyGa for 3 specimens. Most lesions underwent self-regression. Three cases relapsed, but none of the patients died. According to conventional histopathologic criteria, LyGa is probably diagnosed as lymphoma, especially as extranodal natural killer/T-cell lymphoma, nasal type. However, LyGa is recognized as a pseudomalignant process because of its clinical characteristics. The concept of LyGa should be well recognized.

An Extragastrointestinal Tumor Diagnosed as a Vaginal Mass during Pregnancy.

We report a case of an extragastrointestinal stromal tumor diagnosed as a vaginal mass during pregnancy. The mass was detected during routine examination at 24 weeks of gestation. At 26 weeks, the patient underwent transvaginal ultrasonography and magnetic resonance imaging, which revealed a blood flow-rich mass of approximately 50 × 30 mm in the rectovaginal septum. At 29 weeks of gestation, we resected the mass vaginally and the pathological diagnosis was a gastrointestinal stromal tumor. Chemotherapy was withheld until after full-term birth because the proliferation index of the tumor cells was low. The patient delivered a healthy infant. Imatinib was commenced at 1 month postpartum, with no recurrence or metastasis after 2.5 years. An extragastrointestinal stromal tumor as a vaginal mass in pregnancy has not been reported; however, our case suggests that the tumor should be considered a differential diagnosis of a vaginal mass in pregnancy.

Pneumocystis Pneumonia in a Patient with Ovarian Cancer Receiving Olaparib Therapy.

We herein report a case of pneumocystis pneumonia (PCP) in a 77-year-old woman with ovarian cancer who was receiving olaparib therapy. After the patient's second relapse of ovarian cancer, she was administered olaparib as maintenance therapy following successful completion of docetaxel and carboplatin therapy. On receiving olaparib, she showed symptoms of a fever and malaise. Based on laboratory and imaging findings, she was diagnosed with PCP. After treatment with corticosteroids and trimethoprim/sulfamethoxazole followed by atovaquone, the patient's general condition improved. The lymphocytopenia observed after olaparib administration may have been associated with the development of PCP.

A rare case of synchronous multiple primary malignancies of breast cancer and diffuse large B-cell lymphoma that responded to multidisciplinary treatment: a case report.

BACKGROUND: Multiple primary malignancies of breast cancer and diffuse large B-cell lymphoma (DLBCL) are rare. Here, we report a case of advanced breast cancer and DLBCL managed with multidisciplinary therapy preceded by surgery with a successful outcome. CASE PRESENTATION: During a medical examination, a 71-year-old woman was diagnosed with a right breast mass, enlarged lymph nodes throughout the body, and a splenic tumor. The results of the clinical examination and imaging were suggestive of widely spread breast cancer with lymph node metastasis and malignant lymphoma with systemic metastasis. The histological evaluation of the biopsied breast tissue revealed human epidermal growth factor receptor 2 (HER2)-positive breast cancer, whereas the histological evaluation of the excised inguinal lymph node revealed DLBCL. 18F-FDG PET/computed tomography was performed, and it was determined that both breast cancer and DLBCL were in an advanced stage. Thus, mastectomy was performed, and the axillary lymph nodes showed mixed metastasis of breast cancer and DLBCL. Soon after, the R-CHOP therapy was initiated (375-mg/m2 rituximab, 2-mg/m2 vincristine, 50-mg/m2 doxorubicin, 750-mg/m2 cyclophosphamide, and 125-mg methylprednisolone). After irradiation of the spleen, trastuzumab was administered for 1 year. CONCLUSIONS: We experienced a case of combined breast cancer and DLBCL, which was difficult to treat because both were in advanced stages. Thorough staging of the malignancy and discussion by a multidisciplinary team are necessary to determine the optimal treatment strategy.

C-MYC rearrangement may induce an aggressive phenotype in anaplastic lymphoma kinase positive anaplastic large cell lymphoma: Identification of a novel fusion gene ALO17/C-MYC.

Anaplastic lymphoma kinase (ALK) positive anaplastic large cell lymphoma (ALCL) is usually associated with a favorable prognosis. We describe an 11-year-old girl patient with ALK positive ALCL bearing t(2;5)(p23;q35) and t(8;17)(q24;q25) translocations who had an aggressive clinical course despite various combinations of intensive chemotherapy. Southern blot analysis identified C-MYC rearrangement. Immunohistochemistry and Northern and Western blot analyses revealed cmyc overexpression. A new fusion between ALO17 (ALK lymphoma oligomerization partner on chromosome 17) and C-MYC was identified by the 50-rapid amplification of cDNA ends. This new fusion may have possibly provoked the poor prognosis in this patient with ALK positive ALCL, and C-MYC rearrangement may indicate poor prognosis in ALCL.

So-called 'adenosarcoma' of the kidney a novel adult renal tumor with a cystic appearance.

We describe a novel cystic renal tumor consisting of benign epithelial and malignant stromal components in a 56-year-old woman who was admitted to hospital with macroscopic hematuria. Enhanced computed tomography revealed a multilocular 3.4 × 2.7-cm tumor in the center of the left kidney. After total left nephrectomy, the excised tumor appeared extensively cystic with a well defined border on the cut surface. Histologically, the tumor was composed of biphasic a benign epithelial lining on tubules or cysts with a typically hobnailed appearance, and anaplastic sarcomatous stroma with frequent mitosis. Periepithelial cuffing of the sarcoma cells was evident without an epithelial-stromal transition. Carcinomatous nests, blastemic elements, ovarian-like stroma or differentiated mesenchyme were not evident in the stroma. The epithelial cells were reactive with cytokeratins, epithelial membrane antigen (EMA), vimentin and transducin-like enhancer protein 1 (TLE1). Stromal cells were reactive with vimentin, CD99 and TLE1, partly reactive with CD34 and CD10, and non-reactive with cytokeratins, EMA, Wilm's tumor protein (WT-1), estrogen receptor (ER), progesterone receptor (PgR), CD57, HMB45 or Bcl2. SYT-SSX fusion gene was not detected with reverse transcription polymerase chain reaction. Because these findings did not coincide with established descriptions of cystic renal neoplasms, we preferred the term, 'adenosarcoma'. This could become a new classification for adult cystic renal tumors.

Hemangioma of the umbilical cord with pseudocyst.

A case of umbilical cord hemangioma with a large cystic mass, diagnosed by ultrasound at 18 weeks of gestation, is reported. A normal female infant was born at 39 weeks of gestation. The umbilical cord was 32 cm long with a cystic mass (10 × 10 × 8 cm). Histopathologic examination of the umbilical cord revealed a hemangioma with myxomatous degeneration, presenting as a large cyst with thinning of the umbilical venous wall. A total of 33 umbilical cord hemangioma cases have been reported in detail, and only seven cases had a pseudocystic degeneration. The associated pathologic findings of umbilical cord hemangioma are reviewed.

Snowball-like appearance on radial endobronchial ultrasonography in a patient with invasive mucinous adenocarcinoma.

Invasive mucinous adenocarcinoma (IMA), which is a relatively rare lung adenocarcinoma, is considered a high-grade subtype and is associated with a poor prognosis. IMA is difficult to diagnose by computed tomography because it requires differentiation from inflammatory diseases, such as atelectasis, infectious pneumonia, and organizing pneumonia. Thus far, no reports of radial endobronchial ultrasonography (EBUS) findings in IMA have been published. This article presents a case of IMA with a characteristic shadow, snowball-like appearance on radial EBUS in a 67-year-old Japanese man.

Tracheal Mucoepidermoid Carcinoma Mimicking Deteriorated Bronchial Asthma during Pregnancy.

Primary bronchial tumors are extremely rare. However, symptoms, such as coughing and wheezing, are not specific to this disease, and primary bronchial tumors are often misdiagnosed as bronchial asthma. This report describes the case of a pregnant patient with a bronchial tumor that mimicked deteriorating bronchial asthma. A 37-year-old female patient suffered from repeated episodes of pneumonia since 26 weeks of gestation. Despite treatment, she suffered from another episode of pneumonia at 28 weeks of gestation. This was considered as deteriorating asthma. Bronchoscopy performed at 34 weeks of gestation showed a tumor in the left main lung bronchus, obstructing nearly 100% of the trachea. After cesarean delivery at 34 weeks, she underwent endoscopic bronchial tumor resection. Because of recurrent bronchial obstruction and the possibility of malignant disease, subsequent left main lung bronchial resection and bronchoplasty were performed. The pathological diagnosis was low-grade mucoepidermoid carcinoma. In conclusion, if pneumonia develops repeatedly during pregnancy, the possibility of bronchial tumor should be considered.

Bronchial mucoepidermoid carcinoma, recurrent asthmatic symptoms, and pneumonia presenting in pregnancy.

We report the case of a 37-year-old pregnant Japanese woman (34th week of gestation) with a left main bronchus mucoepidermoid carcinoma. She had left lower lung pneumonia episodes for eight weeks that had been associated with bronchial asthma. Bronchoscopy revealed a membranous endobronchial tumour obstructing most of the left main bronchus. We delivered the baby without any problems by caesarean section, followed by tumour cauterization using a rigid bronchoscope under general anaesthesia. After that, we performed a sleeve resection of the main left bronchus. At one-year follow-up, the patient was disease-free and her baby was growing well.