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A 28-year-old woman experienced gross hematuria after the administration of the second dose of an messenger ribonucleic acid (mRNA) vaccine (BNT162b2). She was diagnosed with Immunogloblin A nephropathy (IgAN) by a renal biopsy two weeks after vaccination, which revealed a mild increase in mesangial cells and a matrix with co-depositions of galactose-deficient IgA1 and C3 in the mesangial region. The gross hematuria and proteinuria gradually improved without any medication, suggesting that immune activation by the mRNA vaccine may not elicit continuous disease progression of IgAN. Thus, further studies investigating the relationship between mRNA vaccines against COVID-19 and the progression of IgAN should be conducted.

Mucoepidermoid carcinoma (MEC) of the lacrimal gland (LG) is a rare entity. A 47-year-old woman was aware of periorbital swelling for 3 months. At presentation, the patient showed periorbital swelling in the right eye. CT scan showed an isodense mass in the anterior superolateral part of the orbit. MRI delineated the mass as enhancing, extra-conal tumor appearing isointense on T1-weighted sequences, and to be of mixed intensity on T2-weighted sequences. The tumor was totally resected. Microscopically, the tumor tissue was comprised of squamous, epithelioid cells, and cells with plump and clear cytoplasm. Necrosis, neural invasion, or mitotic figures were not observed. Immunohistochemical examination revealed intense staining for cytokeratin 7. A subset of the cells was positively stained with periodic acid–Schiff and mucicarmine stains. Genetic analysis revealed the presence of the CRTC1-MAML2 fusion. The CRTC1-MAML2 fusion may be a useful indicator for the prognosis and planning of adjuvant therapy.

Alveolar hemorrhage presents with severe respiratory failure, requiring prompt diagnosis and treatment. Alveolar hemorrhage is often caused by autoimmune diseases accompanied by progressive renal dysfunction. However, few cases without autoimmune diseases occur, making diagnosis difficult. Here, we report a case of alveolar hemorrhage with hypertensive emergency.A 28-year-old man presented with dyspnea and bloody sputum. His blood pressure was 200/120 mm Hg.The chest computed tomography showed suggestive of alveolar hemorrhage. Renal dysfunction and proteinuria were observed. However, autoantibodies were not detected. Echocardiogram revealed left ventricular function decrease. Ejection fraction was 20% to 30% with no ventricular asynergy or any valvular diseases. Brain magnetic resonance imaging showed hyperintense lesions on fluid-attenuated inversion recovery in the white matter of both cerebral and right cerebellar hemispheres, which were compatible with posterior reversible encephalopathy syndrome. Renal biopsy did not reveal any immune-mediated glomerulonephritis or vasculitis, but hypertensive nephropathy was diagnosed.Blood pressure was controlled with combination therapy using calcium channel blocker, angiotensin II receptor blocker, α1 blocker, and β blocker.Alveolar hemorrhage and proteinuria improved with strict blood pressure control.This case indicates that severe hypertension can possibly cause alveolar hemorrhage. Accumulating these cases is important for general physicians to diagnose the alveolar hemorrhage with hypertensive emergency in its early stage and to avoid unnecessary treatment such as immunosuppressive therapy.

Appendiceal mucinous tumors (AMTs) include low-grade mucinous appendiceal neoplasms (LAMNs), high-grade mucinous appendiceal neoplasms (HAMNs), and mucinous adenocarcinomas (MACs). We collected 51 AMT samples (LAMN: 34, HAMN: 8, MAC: 9). Three of the eight HAMN cases contained LAMN components, and four out of nine MAC cases contained LAMN and/or HAMN components within the tumor. A next-generation sequencing (NGS) cancer hotspot panel was used to analyze 11 pure LAMN, 4 HAMN, and 3 MAC cases. The results revealed KRAS and GNAS as the most frequently mutated genes. Sanger sequencing was then performed to detect KRAS, GNAS, and TP53 mutations in the remaining 31 cases and RNF43 mutations in all cases. KRAS/GNAS and TP53 mutations occurred exclusively in pure LAMNs; however, five LAMN cases had mutations in both KRAS and GNAS. RNF43 mutations almost exclusively occurred with KRAS/GNAS mutations in pure LAMNs. In MAC and HAMN, KRAS/GNAS mutation status was nearly preserved between lower-grade areas. Most of the detected RNF43 mutations was missense type. RNF43 mutations were detected in both components of MAC with lower-grade area; however, RNF43 mutations detected in these two lesions were entirely different. RNF43 mutations were detected in only one of the eight HAMN patients, which was the sole case without pseudomyxoma peritonei (PMP). None of the four MAC patients with RNF43 mutation showed PMP. These findings suggest that RNF43 mutations occur at a later stage of MAC development and do not associate with PMP. Furthermore, a gradual transition from LAMN to MAC via HAMN could be considered.

A 47-year-old male with macroglossia presented with dyspnea on effort and chest pain at rest. Cardiac MRI revealed diffuse global subendocardial late gadolinium enhancement below the left ventricular endocardium and a dark blood pool of intracardiac contrast medium. Tongue biopsy revealed amyloid deposition, which was limited in the myocardium. He was diagnosed with primary light chain amyloidosis. His condition was stage I according to the Mayo Clinic staging system. He underwent autologous peripheral blood stem cell transplantation. On Day 10, he developed chest pain and died suddenly on Day 11. Postmortem examination revealed amyloid deposition throughout the heart.

A 76-year-man presented with generalized lymphadenopathy. Lymph node biopsy led to the diagnosis of Epstein-Barr virus-encoded small RNA in situ hybridization (EBER)-positive angioimmunoblastic T-cell lymphoma (AITL). He was initiated on treatment with oral prednisolone (PSL) at the dose of 50 mg/day; however, he was diagnosed as having right pleural effusion. He was started on treatment with cyclophosphamide, doxorubicin, vincristine and PSL (CHOP therapy). However, the right pleural effusion increased in size, and thoracentesis was performed. The aspirated pleural fluid was bloody, and since only a very small number of atypical cells were found, no definitive diagnosis could be made. CT revealed multiple nodular lesions in the pleura, and thoracoscopy was performed, which revealed jelly-like white lesions in the right parietal pleura. Biopsy raised the suspicion of undifferentiated pleomorphic sarcoma (UPS). Treatment with carboplatin and pemetrexed was started, but his respiratory symptoms worsened and he died. Autopsy revealed evidence of complete remission of AITL and myxofibrosarcoma (MFS) of the pleura. This is the first reported case of AITL combined with MFS.

In Japan, ibrutinib has been approved as both a front-line and later-line treatment for chronic leukemia/small lymphocytic lymphoma(CLL/SLL). However, little is known about the actual outcomes and adverse events(AEs)associated with the use of ibrutinib in Japanese patients.The outcomes and AEs of patients treated with ibrutinib in a real-world setting were investigated.A retrospective cohort study of all patients with CLL/SLL who were treated with ibrutinib at a single institution was conducted.In total, 10 patients, including 5 treatment-naïve patients(50%), were enrolled. The median follow-up period was 9.8 months(range, 0.2-21.6 months), and the estimated overall response rate (ORR: complete remission plus partial remission)was 60%. The median overall survival and progression-free survival outcomes were not reached. During the follow-up period, 4 patients(40%)had at least one AE and 1 patient(10%)had at least one grade≥3 AE. Ibrutinib was discontinued in 4 patients(40%)because of AEs in 2 patients(20%), the progression of CLL in 1 patient(10%), and financial reasons in 1 patient(10%). Richter's transformation did not occur in any of the cases.The ORR was lower(60%)than that observed in clinical trials. The frequency and severity of AEs were both relatively low, although the discontinuation rate was high(40%). Patient education and medication adherence were considered important.

Dasatinib is the second-generation tyrosine kinase inhibitor used in the treatment of chronic myeloid leukemia. Proteinuria has been reported with this agent. We describe two kidney biopsy–proven cases of dasatinib-induced thrombotic microangiopathy that responded to stoppage of dasatinib and using an alternate tyrosine kinase inhibitor. Certain specific tyrosine kinase inhibitors lead to endothelial injury and renal-limited thrombotic microangiopathy. Hematologists and nephrologists need to be familiar with this off-target effect of dasatinib.

Renal medullary carcinoma (RMC) is a rare and aggressive cancer associated with the sickle cell trait. The diagnosis of RMC depends on recognition of its histologic features and immunohistochemical deficiency of INI1, but correct diagnosis is sometimes difficult, especially if a patient's information on race, past, and family medical history is unclear. At present, this is the first report on RMC in Japan.

A 42‒year‒old woman. At week 27 of pregnancy, she developed subcortical hemorrhage and underwent open cranial surgery for hematoma evacuation. The platelet(Plt)count was 297,000/μL. At week 34 of pregnancy, she developed subcortical hemorrhage again. The Plt count was 429,000/μL. At week 35 of pregnancy, the ventricular rupture and she underwent drainage and emergency cesarean section. The Plt count was 687,000/μL. Two days after delivery, hemorrhage was detected. The Plt count was 815,000/μL. Six days after delivery, she developed infarction. The Plt count was 915,000/μL. MRI revealed no evidence of aneurysm, arteriovenous malformations or tumor. Ten days after delivery, the Plt count was 1,173,000/μL. Bone marrow examination led to the diagnosis of essential thrombocythemia(ET). JAK2, CARL and MPL was negative. She was rated as"low‒risk"by IPSET‒thrombosis, and as"ultralow"risk by revised IPSET‒thrombosis. von Willebrand factor(VWF)activity was as high as 247%. The bleeding time and platelet aggregation activity were normal. There was no evidence of disseminated intravascular coagulation(DIC)or hypertensive disorders of pregnancy(HDP). She died of cerebral hemorrhage and infarction, 26 days after delivery.

We investigate the current status of screening for essential thrombocythemia(ET)and polycythemia vera(PV), at our hospital.According to the World Health Organization(WHO)diagnostic criteria.All patients who visited Juntendo University Urayasu Hospital between May 1984(when the hospital opened)and January 2019.More than 90% of patients with elevated platelet counts(PLT)(n=25,062)and more than 90% of patients with elevated hemoglobin( Hb)or hematocrit(Ht)levels(n=16,422)did not visit the department of hematology, suggesting that there could be a high percentage of patients with potentially latent ET and PV visiting the hospital. In addition, a large number of patients fulfilling the laboratory criteria for ET/PV visited various departments of the hospital other than the department of hematology.Because ET/PV manifests with diverse symptoms, including non-specific symptoms and symptoms pertaining to other organ systems. Based on the findings, we consider that it is essential to disseminate information about the WHO diagnostic criteria/clinical symptoms and possibility of latent ET/PV to all departments of the hospital, and to establish cooperation between the department of hematology and other departments.

A 53-year-old woman had been diagnosed with rheumatoid arthritis (RA) in X-6. She was started on methotrexate (MTX) in X-1. She developed a cough, and chest computed tomography showed abnormalities. In X, MTX was discontinued, but the cough persisted. A lung biopsy revealed a diagnosis of nodular sclerosis classic Hodgkin lymphoma (CHL-NS). She was considered to have "other iatrogenic immunodeficiency-associated lymphoproliferative disorders" (OIIA-LPD), MTX-associated Hodgkin lymphoma (MTX-HL). She received six courses of brentuximab vedotin (BV) in addition to AVD (BV+AVD). A complete metabolic response was obtained, and the RA went into remission. This is the fourth reported case of BV+AVD for MTX-HL.

A 63-year-old woman was referred to our department in 2015 because of anemia and thrombocytosis. MPL W515/K was positive, JAK-2V617F and CALR exon 9 were negative. Bone marrow(BM)biopsy led to a diagnosis of primary myelofibrosis (PMF)in the prefibrotic/early stage(Grade 1). BMbiopsy performed in 2016 showed overt fibrotic stage(Grade 2). She was classified according to the Dynamic International Prognostic Scoring System(DIPSS)as intermediate(Int)-Ⅱrisk. Ruxolitinib 10 mg daily was initiated. Ruxolitinib was suspended for hepatic dysfunction after the dose was increased to 15 mg. Subsequently, ruxolitinib was resumed at 10 mg. BM biopsy performed in 2017 showed progression of myelofibrosis(MF)to Grade 3. BM biopsy performed in 2018 showed improved to Grade 0-1, however, BM was fatty. Currently in 2019, she continues to be on ruxolitinib. Results of immunohistochemical staining of BM biopsy specimens for cytokines and CD34 suggested the role of cytokines in the pathogenesis of the PMF. It was speculated that ruxolitinib blocked the production of cytokines to ameliorate the MF and restore the hematopoietic function of the BM. Although the pathogenesis of the fatty marrow remained unclear, the possibility of involvement of ruxolitinib cannot be denied.

A 28-year-old woman who was 34 weeks pregnant was admitted with complaints of cough and blood-stained sputum. After delivery of the baby at 37 weeks gestation, computed tomography and magnetic resonance imaging revealed a tumor in the right lung and a 15-mm brain metastasis. A diagnosis of lung adenocarcinoma was made, cT4N3M1b (stage IV disease) by pleural fluid cytology. Additional testing for anaplastic lymphoma kinase (ALK) fusion protein showed a strongly positive result, which was then confirmed by fluorescence in situ hybridization. The patient was started on treatment with alectinib, and the tumor and brain metastasis had almost vanished by 2 months after the start of this treatment. In the literature, there are 59 reports of lung cancer diagnosed during pregnancy, including two cases of cancer with expression of ALK fusion protein and five cases showing epidermal growth factor receptor mutation. The type of mutation should be taken into consideration while selecting for the appropriate therapeutic strategy.

A 31-year-old woman with systemic lupus erythematosus and lupus nephritis was treated with prednisone and immunosuppressants. After her lupus nephritis symptoms worsened, both high-dose steroid and cyclophosphamide pulse therapy were administered. The patient developed an intestinal perforation, and laparoscopic Hartmann's surgery was performed on the sigmoid colon. Serum Cytomegalovirus (CMV) antigen C7HRP was detected, and the patient was diagnosed with CMV colitis and underwent a colon resection. Severe hematochezia continued despite ganciclovir administration, and the patient underwent laparoscopic total colectomy and partial ileostomy. CMV enteritis should be considered in patients treated with prednisone and immunosuppressants and those who have abdominal pain and hematochezia. Immunocompromised patients with intestinal perforation due to CMV enteritis have a poor prognosis. We report a case with along with the results of a literature review.

Rationale: Anti-glomerular basement membrane (GBM) disease is a T cell-mediated disease that has a poor prognosis with conventional therapy. We tested rituximab as a primary therapy to reduce anti-GBM antibody produced by B cells. Patient concerns: A 53-year old woman with complaints of a fever, headache and abdominal discomfort showed renal failure with elevated anti-GBM antibody, and renal biopsy revealed crescentic necrotizing glomerulonephritis with linear immunoglobulin G (IgG) 1 deposition along GBM. Diagnoses: The patient's plasma contained autoantibodies against Goodpasture antigen, which is the NC domain of collagen IVα3, and CD4-positive helper T cells were found surrounding crescent glomeruli with the coexistence CD20-positive B cells. Interventions: Rituximab with steroid and plasma exchange. Outcomes: The levels of autoantibody for Goodpasture antigen were reduced, and the patient was able to temporarily withdraw from hemodialysis. Lessons: B cell depletion with rituximab is effective as an initial therapy for anti-GBM disease.

Autologous peripheral blood stem cell transplantation(auto-PBSCT)combined with high-dose chemotherapy has been considered as the standard therapy for relapsed or induction therapy-refractory aggressive lymphomas sensitive to chemotherapy. While various regimens have been applied as the conditioning,none has yet been established as the standard. We have begun to employ high-dose ranimustine,cytarabine,etoposide and cyclophosphamide(MCVAC)regimen. The present study was undertaken to review the efficacy and safety of MCVAC. Regimen: We carried out a retrospective analysis of 20 patients diagnosed as diffuse large B-cell lymphoma. The median follow-up duration of 20 patients was 13.05 months(range, 0.57-49.5 months). The 4-year OS and PFS were 57.8% and 30.2%,respectively. Relapse was the most frequent cause of treatment failure(n=7). The major toxicities were anorexia/nausea(95%),diarrhea (75%),hypokalemia (70%). One patient died of hepatic veno-occlusive disease(VOD). The serious adverse events included hypokalemia,arrhythmia,cerebral hemorrhage,and heart failure(1 case[5%]each). There was 1 case of a late-onset adverse event: therapy-related myelo- dysplastic syndrome/acute myeloblastic leukemia(MDS/AML). MCVAC regimen was concluded as effective and well-toler- ated. However,we should carefully monitored for the possible development of VOD and MDS/AML. Further follow-up is needed to evaluate the long-term efficacy and safety.

A 59-year-old female was diagnosed as pulmonary aspergillosis(IPA)while remission induction therapy for Philadelphia chromosome-positive acute lymphoblastic leukemia. Liposomal amphotericin B improved the fungal serodiagnostic markers, however,the IPA worsened. She also developed an Aspergillus brain abscess,which, while being undetectable on CT,was detected as multiple nodular lesions by MRI. A definitive diagnosis was made by polymerase chain reaction(PCR)of brain biopsy specimens. Voriconazole(VRCZ)was effective,and cord blood transplantation was performed. She has received VRCZ for a long time. There are no relapse of either the IPA or the Aspergillus brain abscess.

The clinical features(CF), laboratory data, disease transformation pattern and drug metabolism in essential thrombocythemia(ET)differ between Japan and Western countries. The CF of ET in clinical practice(CP)are more diverse than in prospective clinical studies. We should conduct retrospective analyses in CP. The present study was aimed at evaluating the efficacy, safety and tolerability of anagrelide(ANA)monotherapy and combined ANA plus hydroxycarbamide(HC)in Japanese ET.We have a total of 35 cases. Sixteen patients received ANA monotherapy, 10 received ANA plus HC, and 9 received ANA plus other drugs.Comparison among three groups revealed the absence of differences in response rate(platelet count C60×10 / / 4/mL, platelet count C40×104/mL)(43.8%, 6.3% vs. 50.0%, 10.0% vs. 44.4%, 11.1%), treatment continuation rate(81.3% vs. 40.0% vs. 55.6%), median daily dose of ANA(1.00 mg in all three groups)or median treatment period(days)(259 vs. 198.5 vs. 161.0), the treatment continuation rate tended to be lower in the combined ANA plus HC. The incidence of all adverse events(AEs)was higher in the ANA monotherapy(45.7%)than ANA plus HC(28.6%)or ANA plus other drugs(25.7%), the AEs were mild in all groups.The tolerability of ANA monotherapy, ANA plus HC, and ANA plus other drugs were good.

Background: Amyloidosis is a spectrum of disorders characterized by the deposition of amyloid that causes severe damage to many organ systems. However, conjunctival amyloidosis is thought to be the manifestation of a local immunologic disorder and rarely affects the organ systems. We present two cases of conjunctival amyloidosis found as unilateral ptosis at initial visit. Case 1: 43-year-old-woman presented with unilateral ptosis and discomfort for the left eye. She had been treated with topical antihistamines and corticosteroids for allergic conjunctivitis. However, as symptoms persisted she was referred to us. At initial visit, unilateral ptosis, subconjunctival hemorrhage and waxy-yellow mass were found. Incisional biopsy was performed and histpathological examination revealed amyloid in the conjunctival stroma. Case 2: 31-year-old woman presented with unilateral ptosis and discomfort of palpebral superior conjunctiva in the left eye. At initial visit, the examination of the left superior palpebral conjunctiva showed waxy-yellow mass and hemorrhage. Incisional biopsy was performed and histopathological examination revealed amyloid in the conjunctival stroma. Conclusion: Unilateral ptosis may be an indication of conjunctival amyloidosis.

A 28-year-old woman who was 34 weeks pregnant was admitted with complaints of cough and blood-stained sputum. After delivery of the baby at 37 weeks gestation, computed tomography and magnetic resonance imaging revealed a tumor in the right lung and a 15-mm brain metastasis. A diagnosis of lung adenocarcinoma was made, cT4N3M1b (stage IV disease) by pleural fluid cytology. Additional testing for anaplastic lymphoma kinase (ALK) fusion protein showed a strongly positive result, which was then confirmed by fluorescence in situ hybridization. The patient was started on treatment with alectinib, and the tumor and brain metastasis had almost vanished by 2 months after the start of this treatment. In the literature, there are 59 reports of lung cancer diagnosed during pregnancy, including two cases of cancer with expression of ALK fusion protein and five cases showing epidermal growth factor receptor mutation. The type of mutation should be taken into consideration while selecting for the appropriate therapeutic strategy.

Three patients under hemodialysis (HD) with relapsed/refractory multiple myeloma (MM) were administered panobinostat/bortezomib/dexamethasone (FVD). Case 1: The patient was a 66-year-old male with BJP-κ. FVD was effective, but HD could not be discontinued. He developed Grade 3 adverse events (AEs), including nausea, dehydration, and fatigue, following the common terminology criteria for adverse events v4.0. FVD was discontinued after the third course, while HD was continued. Case 2: The patient was a 65-year-old female with IgG-λ + BJP-λ. Amyloidosis was complicated. The first course of FVD was effective, but HD could not be discontinued. She developed G2 AEs, including nausea and fatigue. The cardiac amyloidosis worsened, and she died of heart and renal failure. Case 3: The patient was a 79-year-old male with BJP-κ. FVD was effective, and the HD could be discontinued on day 12 of treatment. No AEs were noted. However, he declined continuation of the FVD and died of MM relapse and renal failure. We analyzed the pharmacokinetics of panobinostat. There were no correlations between dose level and blood level of panobinostat or between blood level, efficacy, and incidence of AEs. We additionally measured the rate of elimination of the drug by HD.

The aim of this study was to investigate the expression pattern of manganese superoxide dismutase (MnSOD) in relation to inflammatory factors in ulcerative colitis (UC) and characterize this enzyme as a newly identified biomarker potentially linked to disease pathogenesis of UC. MnSOD expression was analyzed immunohistochemically in 48 formalin-fixed and paraffin-embedded specimens from patients with UC who had undergone endoscopical biopsy. MnSOD expression was observed in vascular endothelium, macrophages, and polymorphonuclear leukocytes within lamina propria of inflamed mucosa. The patients who did not express MnSOD tended to have stabilization of symptoms, but accompanied with status of inflammation. The MnSOD expression pattern was strongly correlated with disease type. MnSOD was expressed in polymorphonuclear leukocytes of all disease types, but cases of chronically counting and exacerbation type had particularly high frequency of immunopositive cells. MnSOD expression in macrophages was frequently observed in cases of symptom remaining type. The cases with MnSOD expression in the vascular endothelium showed a tendency to express in relapse-remission and exacerbation of symptoms. Immunohistochemical evaluation for MnSOD expression may be useful for predicting disease severity and activity in patients with UC.

Objective: Colorectal cancer patients bearing wild-type KRAS benefit from anti-epidermal growth factor receptor (EGFR) antibody treatment. Since clinical studies showed the efficacy of anti-EGFR antibody treatment for metastatic colorectal cancer (mCRC), we analyzed KRAS mutations in mCRC to gain insight into the association between these mutations and clinicopathological characteristics. Methods:KRAS mutations were analyzed in 109 tissue samples of mCRC using amplification refractory mutation system-Scorpion (ARMS/S) assay (68 samples) and direct sequencing (41 samples). Results: In the ARMS/S assay, 36.5 and 7.4% of mCRCs harbored mutations at codons 12 and 13, respectively. In direct sequencing, corresponding values were 24.4 and 19.5%. Overall, 37.6% (codon 12/13, 25.7/11.9%) of mCRCs harbored KRAS mutations. No significant differences were found between KRAS mutations and clinicopathological variables. Among mCRC patients KRAS mutations at codon 13 was significantly higher in female than male patients (p = 0.035). Conclusion: The incidence of KRAS mutations in mCRC was similar to that of non-mCRC as previously reported. KRAS codon 13 mutations might be associated with younger female patients with mCRC, but further investigation is necessary to clarify the association between this type of mutation and metastatic potential in female CRC patients.

We previously reported a relationship between depth of submucosal invasion of early colorectal carcinomas and desmoplastic reaction (DR). However, poor inter-observer agreement on the histopathological diagnosis of DR in biopsy specimens with hematoxylin and eosin (H&E) staining has been the major critique of this tool. In this study, reproducibility of the histopathological diagnosis of DR was evaluated. Furthermore, we investigated the possible improvement of the reproducibility after education about histological characteristics and tried to identify histological characteristics that are most important in the recognition of DR. A total of 34 H&E stained slides were included in this study and analyzed by three pathologists. Slides were reviewed before and after education about histological characteristics of DR. Kappa statistics were used to compare the inter-observer variability. We investigated the relationship between DR and histopathological factor. The inter-observer agreement during the first session varied between 0.30 and 0.63, which improved during the second session toward an agreement between 0.58 and 0.71. Myofibroblast proliferation associated with cancer invasion was found to be the most useful in the diagnosis of DR. In conclusion, the correct detection of myofibroblasts may facilitate the standardization of diagnosis of DR.

The aim of our study was to evaluate the diagnosis of desmoplastic reaction (DR) by immunostaining for α-smooth muscle actin (αSMA) and desmin, for predicting the depth of submucosal invasion in biopsy specimens of early colorectal carcinomas (CRCs). Thirty-eight cases of non-pedunculated early CRCs were included in this study. Positive for DR was defined as αSMA-positive and desmin-negative stroma in the CRC. The depth of submucosal invasion was measured in endoscopically or surgically resected specimens and the lesions were subsequently divided into two groups: Group A (carcinoma in situ/intramucosal carcinoma and submucosal invasive carcinoma with a depth

The use of antibodies against epidermal growth factor receptor( EGFR) in conjunction with conventionalchemotherapy for metastatic colorectal cancer (CRC) in patients with KRAS wild-type tumors has beenproven to be efficacious. Recently, KRAS testing prior to anti-EGFR therapy has become mandatory formetastatic CRC patients. Although newly developed pyrosequencing is expected to be one of the highthroughput procedures detecting such mutations, the accuracy of the procedure has not been well evaluated.In the present study, we aimed to validate the accuracy, especially the potential for a false-negative result,in detecting KRAS mutations by pyrosequencing using cultured tumor cells. DNA extracted from culturedìNOZî gallbladder cancer cells( known to contain KRAS mutation G12V) at concentrations of 1%, 5%, 10%, and 25%, as well as 2 DNA samples extracted from a resected CRC specimen( known to contain anotherKRAS mutation, G12C) at concentrations of 5% and 25%, were prepared. We analyzed KRAS mutationalstatus and nonexistent and/or nonfunctional mutations of these 6 samples using pyrosequencing. TheKRAS mutation detection rates in the 4 NOZ samples( 1%, 5%, 10%, and 25%) were 0.37%, 2.79%, 5.28%,and 13.85%, respectively. Some artifacts of KRAS mutations unlikely to be present were detected in 1%samples of NOZ at a rate similar to that of the G12V mutation( G12C, 0.29%;G13C, 0.42%). Although theKRAS mutation G12C was detected at rates of 1.26% and 6.49% in samples with 5% and 25% DNA extractedfrom resected CRC specimen, respectively, no other type of KRAS mutation was detected in suchsamples. Pyrosequencing could not detect KRAS mutations correctly in the sample containing 1% DNA.This might cause false negatives. A sample mutated DNA concentration of at least 5% was necessary forprecise analyses by this procedure.

Objective:Oral lichen planus( OLP) is a chronic inflammatory oral mucosal disease of unknown etiology.Due to similar histological features of OLP with other oral diseases. IgG4-related disease has been identified,but whether or not there are organ-specific characteristics related to the etiologic factors is still unknown.In the present study, we investigated the significance of IgG4-positive plasma cells as a marker for OLP.Methods:Biopsy specimens from 63 patients with white papules, erythema and erosive mucosa in theoral cavity were obtained. The lesions were evaluated for inflammatory cell spreading pattern classified ashorizontal superficial type and/or expanding type(s), for lymphoid-plasma cell markers (CD3, CD20,CD79a), Immunoglobulin G( IgG, IgG4) immunoreactivity, and for monoclonality.Results:In the horizontal superficial type with only CD3-positive lymphocytic inflammatory cells wererestricted to the epithelial layer of connective tissue without presence of IgG4-positive plasma cells. Lesionswere further demonstrated to contain CD3-, CD20- and CD79a-positive lympho-plasma cells with focal cytoplasmicIgG4 expression. However, in IgG4-rich cases, there were no monoclonality. The inflammatorycell spreading pattern differed significantly between the horizontal superficial type with only CD3-positivelymphoid cells and expanding types, and was significantly associated with IgG4-positive plasma cells.Conclusions:Detection of IgG4-positive plasma cells and inflammatory cell spreading pattern may beuseful for differential diagnosis and selection of treatable cases in OLP.