An autopsy case of fulminant myocarditis after severe acute respiratory syndrome coronavirus 2 vaccine inoculation.

A 61-year-old woman without significant medical history developed fever 3 days after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination and went into shock the next day. She was negative for SARS-CoV-2 mRNA in real-time polymerase chain reaction (PCR). Finally, she died 10 days after vaccination. At autopsy, the heart showed moderate dilatation of both ventricles, and the myocardium showed an uneven color change and decreased elasticity. Histologically, severe myocarditis with extensive myocytolysis was observed. The myocarditis showed severe inflammatory cell infiltration with T-lymphocyte and macrophage predominance, and in addition to the inflammatory cells described above, vast nuclear dust accompanying neutrophilic infiltration was observed. In the bone marrow and lymph nodes, hemophagocytosis was observed. In postmortem examination, nucleic acids of any cardiotropic viruses including SARS-CoV-2 were not detected using multivirus real-time PCR system. We discussed the relationship between the possible immune reaction after vaccination and the myocarditis observed in this case from immunopathological viewpoints. This mRNA vaccine is the first applied nucleic acid vaccine for humans, and its mechanism of efficacy and immune acquisition remain unclear. We hope the accumulation of more detailed analyses of the similar cases to reveal the mechanism of this kind of adverse reaction.

[Perforated upper gastrointestinal ulcers potentially attributable to mycophenolate mofetil after allogeneic hematopoietic stem cell transplantation].

A 46-year-old man with myelodysplastic syndrome/myeloproliferative neoplasm-unclassifiable underwent myeloablative bone marrow transplantation from an HLA-DR-1-antigen-mismatched related donor while receiving tacrolimus and mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis. However, grade III acute GVHD of the gut occurred on day 20 and was treated with prednisolone (PSL) and oral beclomethasone dipropionate while continuing MMF. Subsequently, he presented with progressive epigastric pain. Endoscopy demonstrated multiple stomach and duodenal deep ulcers. The ulcers were suspected to be GVHD; thus, the PSL dose was increased and infliximab was administered; however, the ulcers exacerbated, resulting in repeated perforations and hemorrhagic shock. Furthemore, MMF was suspected as the cause of refractory ulcers and was discontinued on day 156, which resolved the ulcers after 6 months. MMF-induced gastrointestinal (GI) injury resembles anti-inflammatory drug-related ulcers and upper and lower GI tract GVHD, respectively. MMF-induced GI injury has been reportedly resolved after discontinuing or reducing the MMF dose. Several reports suggested that refractory upper GI ulcers and rectal sparing colitis were associated with MMF toxicities rather than GVHD in hematopoietic stem cell transplantations. Physicians should be aware that MMF can induce severe GI injury.

A rare case of high-grade intraductal carcinoma of the upper lip: immunohistochemical and genetic analyses.

Although intraductal carcinoma (IDC) of the salivary glands was previously called low-grade cribriform cystadenocarcinoma, it was newly categorized in the 4th version of the World Health Organization classification. We report a case of IDC of the upper lip and examined it immunohistochemically and genetically. The patient was a 48-year-old Japanese female, who noticed a tiny nodule on her left upper lip. Histologically, the tumor cells, which had eosinophilic cytoplasm, exhibited papillary and solid growth patterns, and regions of suspected microinvasion or intraductal spread were also seen at the periphery of the tumor. Small necrotic foci were noted. Immunohistochemically, the tumor cells were diffusely positive for the androgen receptor, CK19, CK5/6, EGFR, and SOX10, whereas they were focally positive for GCDFP-15, S-100 protein, and mammaglobin. The tumor nests were surrounded by alpha-smooth muscle actin-p63-/calponin-/CK14-positive myoepithelial cells. The Ki-67 labeling index was 51.2%. Genetic analysis showed no evidence of the TRIM27-RET or NCOA4-RET fusion gene. We finally diagnosed the tumor as a high-grade mixed intercalated duct/apocrine-type IDC of the upper lip. IDC of the minor salivary glands is exceedingly rare. We discuss diagnostic problems associated with minor salivary gland lesions, and the "basal-like" phenotype of this case.

Pro-gastrin-releasing peptide as a marker for the Ewing sarcoma family of tumors.

BACKGROUND: Pro-gastrin-releasing peptide (ProGRP) is an established tumor marker of small cell lung cancer. The purpose of this study was to determine if ProGRP could serve as a tumor marker for the Ewing sarcoma family of tumors (ESFTs). METHODS: Sixteen patients with ESFTs (mean age 32 years) were included in this study. As a control group, 42 patients with other tumor types that clinically or pathologically mimic ESFTs were also analyzed. Pre-treatment serum ProGRP and neuron-specific enolase (NSE) levels, the relationships between these levels, and tumor volume were investigated. In addition, serial changes in the serum or plasma ProGRP (6 patients) and NSE levels (5 patients) were measured over the course of treatment. RESULTS: Pre-treatment serum ProGRP levels were higher than the normal range in 8 of 16 patients; for these eight patients, ProGRP levels positively correlated with tumor volume (R = 0.99). In the control group, ProGRP levels were within the normal range, except for the two patients. Changes in ProGRP levels during treatment were consistent with tumor volume. Serum NSE levels were elevated in 14 of 16 patients with ESFTs and 8 of 42 patients with other tumor types. The range of NSE elevation was much smaller compared to that of ProGRP. Our data indicate that ProGRP is superior to NSE in terms of specificity. CONCLUSIONS: Serum ProGRP levels were elevated in half of the patients with ESFTs and reflected therapeutic response. ProGRP is a reliable tumor marker for the diagnosis of ESFTs and evaluation of treatment response.

Pathological complete response by advanced hepatocellular carcinoma with massive macrovascular invasion to hepatic arterial infusion chemotherapy: a case report.

BACKGROUND: Advanced hepatocellular carcinoma (HCC) with macrovascular invasion has an extremely dismal prognosis. We report a rare case of multiple HCC with tumor thrombosis in the portal vein and inferior vena cava that was initially treated with hepatic arterial infusion chemotherapy (HAIC); later resection revealed pathological complete response. CASE PRESENTATION: A 75-year-old man presented with HCC in his right liver, with tumor thrombosis growing to the right portal vein and the inferior vena cava, and bilateral intrahepatic liver metastases. He underwent HAIC (5-fluorouracil [170 mg/m2] + cisplatin [7 mg/m2]) via an indwelling port. Although the tumor shrank and tumor marker levels decreased rapidly, we abandoned HAIC after one cycle because of cytopenia. We resumed HAIC 18 months later because of tumor progression, using biweekly 5-fluorouracil only [1000 mg] due to renal dysfunction. However, after 54 months, the HAIC indwelling port was occluded. The patient therefore underwent a right hepatectomy to resect the residual lesion. Histopathological findings showed complete necrosis with no viable tumor cells. The patient has been doing well without postoperative adjuvant therapy for more than 10 years after initially introducing HAIC and 6 years after the resection, without evidence of tumor recurrence. CONCLUSIONS: HAIC can be an effective alternative treatment for advanced HCC with macrovascular invasion.

Osteogenic differentiation in dedifferentiated liposarcoma: a study of 36 cases in comparison to the cases without ossification.

AIMS: Ossification is found occasionally in dedifferentiated liposarcoma (DDLPS). The aims of this study were to elucidate whether the formed bone tissue is usually produced by tumour cells or by reactive non-neoplastic cells, and to reveal the clinicopathological characteristics of DDLPS with ossification. METHODS AND RESULTS: We examined 36 cases of ossified DDLPS by comparing them to 31 cases of non-ossified DDLPS. MDM2 amplification was confirmed in osteocytes and/or osteoblastic cells in all but one ossified DDLPS cases (27 of 28) using fluorescence in-situ hybridisation, although the morphological impression of ossification appeared to be mainly metaplastic (27 of 36) or high-grade osteosarcoma-like (six of 36). The bone tissue was often formed predominantly at the periphery of the DDLPS area near the well-differentiated liposarcoma component (18 of 36), and an organised structure such as bone marrow-like differentiation was not uncommon (12 of 36). According to a modified French Fédération Nationale des Centers de Lutte Contre le Cancer (FNCLCC) grading system, ossified DDLPS tended to be lower grade than non-ossified DDLPS (mean grade: 1.88 and 2.15, respectively). Ossification in DDLPS was associated significantly with shorter local recurrence-free survival by multivariate analysis (P = 0.02347), but metaplastic-appearing ossification tended to be associated with longer overall survival (P = 0.1400). CONCLUSIONS: The bone tissue formed in DDLPS was mainly neoplastic regardless of its morphology and maturity, which highlighted the osteogenic differentiation of the tumour cells. DDLPS patients with osteogenic differentiation tended to suffer from earlier local recurrences, which did not necessarily lead to poor life outcomes.

Histopathological and genetic review of phosphaturic mesenchymal tumours, mixed connective tissue variant.

AIMS: Phosphaturic mesenchymal tumour, mixed connective tissue variant (PMT-MCT), is a tumour of uncertain differentiation, characterised by 'smudgy/grungy' calcification and vitamin D-resistant phosphaturic osteomalacia. Fibroblast growth factor (FGF)23 is recognised as a reliable marker of PMT-MCT, but quantitative evaluation has never been performed. We reviewed cases of tumour-associated osteomalacia or histologically definitive PMT-MCT without osteomalacia using histological, immunohistochemical and genetic methods and evaluated the diagnostic significance of these findings. METHODS AND RESULTS: A total of 19 tumours from 14 cases diagnosed previously as PMT-MCT were retrieved, on which immunohistochemical staining, reverse transcription-polymerase chain reaction (RT-PCR) and fluorescence in-situ hybridisation (FISH) analysis were performed. Histologically, fibrous capsule, calcification and giant cell reaction tended to be observed in soft-tissue PMT-MCT, while PMT-MCT of bone and multiple PMT-MCT showed an infiltrative growth pattern. The immunohistochemical results were as follows: the tumour cells were positive for FGF23 (nine of 12, 75%), FGFR1 (11 of 11, 100%), CD56 (12 of 14, 85.7%) and E26 oncogene homologue (ERG) (5 of 13, 38.4%). The sole malignant tumour was positive for p53. FGF23 mRNA was detected in seven of 14 formalin-fixed paraffin-embedded (FFPE) specimens and all five frozen specimens by RT-PCR. The level of FGF23 mRNA, which was determined by real-time PCR, varied among the phosphaturic cases. Two of 17 tumours were positive for FGFR1 gene rearrangement. CONCLUSIONS: It was considered that PMT-MCT is a histopathological entity with or without phosphaturia, with varying levels of FGF23 mRNA, and with or without fibronectin 1 (FN1)-FGFR1 fusion gene. The authors propose that the histology of PMT-MCT differs depending on its location, such as bone or soft tissue, which could complicate the differential diagnosis.

A new marker, insulinoma-associated protein 1 (INSM1), for high-grade neuroendocrine carcinoma of the uterine cervix: Analysis of 37 cases.

OBJECTIVE: High-grade neuroendocrine carcinoma of uterine cervix (HGNCUC) has been recognized as a highly malignant tumor. Therapeutic strategy specific to neuroendocrine (NE) tumors needs to be considered, but some cases wouldn't allow simple final diagnoses. Insulinoma-associated protein 1 (INSM1), which is a zinc-finger transcription factor related to NE differentiation, is frequently expressed in NE tumors. We investigated the association between INSM1 and HGNCUC, and the possibility of INSM1 as a useful NE marker. METHODS: Thirty-seven cases of formalin-fixed and paraffin-embedded HGNCUCs were evaluated immunohistochemically for conventional NE markers and INSM1. We also surveyed polymerase chain reactions and examined the frequency and the genotype of human papillomavirus (HPV) infections. RESULTS: In HGNCUC, chromogranin A, synaptophysin and neural cell adhesion molecule (NCAM) were expressed in 86%, 86% and 68%, respectively. In addition, INSM1 was detected in 95%. Positivity for INSM1 was clearly evaluated histologically, because the intensity of nuclear staining on positive cells was high and nonspecific reactions were minimal. In uni- and multivariate analyses of prognostic factors on stage I and II surgical cases, the association between INSM1 expression and prognosis was insignificant. We confirmed 72% of 29 examined cases had high risk HPV infections (type 16, 14%; type 18, 86%). CONCLUSIONS: This study has clarified that INSM1 is closely related to the development of HGNCUC, and a useful new NE marker in conducting its correct and rapid diagnosis.

[Cotton-Dam Wash Cytology:A Technique for Diagnosis and Prevention of Dissemination during Resection of Metastatic Brain Tumors].

The management of brain metastases has been important in neurosurgical oncology. Resection of a brain metastasis carries an increased risk of leptomeningeal dissemination than other treatment modalities such as irradiation or pharmacotherapy. We have utilized intraoperative wash cytology of cotton patties covering the brain surface. The cytology information contributes to making a decision of postoperative whole brain radiation. We named the method as "cotton dam", that serves as a check and catch of neoplastic cells on the brain surface during resection surgery.

Expansive hematoma in delayed cerebral radiation necrosis in patients treated with T-DM1: a report of two cases.

BACKGROUND: Multiple new targeted agents have been developed for patients with human epidermal growth factor receptor type 2 (HER2) - positive breast cancer. Patients with HER2- positive breast cancer will develop brain metastases with greater incidence than patients with non-HER2 cancers, and many of them will undergo stereotactic radiosurgery (SRS) or other CNS radiotherapy. The interaction between radiation effects and new targeted agents is not well understood. We report two cases suggesting a novel adverse effect of T-DM1 (trastuzumab emtansine) on symptomatic enlargement of radiation necrosis (RN) after SRS. CASE PRESENTATION: Two patients with HER2-positive breast cancer had received SRS for single brain metastasis more than 5-years ago. They had been heavily treated for HER2-positive metastatic breast cancer (trastuzumab and pacritaxel, lapatinib and capecitabine). They initiated T-DM1 therapy for progressive systematic disease 5.5 years after stereotactic irradiation, when a small RN was recognized on brain MR images of each patient. The RN lesions increased in size and became symptomatic during 13 or 14 months of T-DM1 treatment. The patients underwent surgical resection of the lesion. Pathological examination revealed necrosis, hematoma, granulation tissue and telangiectasia without neoplastic cells. CONCLUSIONS: A potential enhancement of RN by T-DM1 in the brain may be one of important adverse events associated with the use of T-DM1 for patients after SRS. These cases highlight the need of careful follow-up when combining new systemic targeted therapies and SRS for brain metastases.

"Comet tail sign": A pitfall of post-gadolinium magnetic resonance imaging findings for metastatic brain tumors.

A highly enhanced cap attached to the surface of metastatic tumors in the brain parenchyma is occasionally encountered on magnetic resonance (MR) images. This atypical enhanced cap tends to occur in severe peritumoral edema and may produce the characteristic bulge of a metastatic mass lesion termed the "comet tail sign" (CTS). The purpose of this study was to demonstrate the features of the CTS using MR imaging and pathological findings, and to clarify its clinical relevance. We selected 21 consecutive cases of newly diagnosed metastases from MR imaging studies that demonstrated the CTS; all had diffuse peritumoral edema. The MR T2-weighted images showed similarly homogenous and high intensity signals in both the tail and peritumoral edema. Fourteen of the 21 patients underwent surgical resection of their tumors, and 12 tails were separately removed for pathological examination, no tumor cells which revealed. We speculate that the CTS does not contain neoplastic tissues but is observed as a result of the leakage of contrast medium from the tumor body into the interstitial space of the white matter. Although CTS is a peculiar and uncommon enhancement pattern, it has clinical significance in determining the extent of the margin for invasive local treatments, such as surgical resection or stereotactic radiotherapy; this is particularly true in and near the eloquent areas.

[Two Surgical Techniques for Metastatic Brain Tumors:Minimum Resection and Removal with Safety Margin].

Successful resection of cerebral metastases is based on good basic neurosurgical techniques, in conjunction with technologies for tumor localization. A clear understanding about the border zone pathology of metastatic lesions leads to two different techniques for safe and effective tumor removal. There is no capsule or pseudocapsule around the metastatic brain tumors. The border zone is widely heterogeneous, especially in lesions after stereotactic irradiation. Resection can be performed in a circumferential and en bloc fashion with sufficient safety margin of the normal brain in non-eloquent area. However, enucleation should be done without surrounding brain damage in and near eloquent areas.

Comparison of chemotherapeutic efficacy between LCNEC diagnosed using large specimens and possible LCNEC diagnosed using small biopsy specimens.

BACKGROUND: It is often difficult to diagnose large cell neuroendocrine carcinomas (LCNEC) of the lung using small biopsy specimens. Some recent studies attempted to diagnose LCNEC using biopsy specimens; in 2011, the International Association for the Study of Lung Cancer pathological panels suggested possible LCNEC as a diagnosis for LCNEC by using biopsy specimens. Here, we compared the chemotherapeutic efficacy in possible LCNEC and LCNEC diagnosed using surgically resected specimens. METHODS: We retrospectively reviewed patients who received platinum-based chemotherapy as first-line chemotherapy at our institution during September 2002-September 2011. Further, we compared the clinical characteristics, chemotherapeutic responses, and survival outcomes of patients diagnosed as having "LCNEC definite" with those diagnosed as having "possible LCNEC." RESULTS: We selected 34 patients of whom 10 were diagnosed with LCNEC using surgically resected specimens and 24 patients with possible LCNEC were diagnosed using small biopsy specimens. In both groups, almost all patients were men and were smokers. Small-cell carcinoma-based chemotherapy, such as platinum plus irinotecan or platinum plus etoposide, was used for treating 60 % LCNEC patients (6/10) and 67 % possible LCNEC patients. In the LCNEC and possible LCNEC groups, respectively, the response rate was 70 and 54 % (p = 0.39), median progression-free survival was 2.9 and 4.4 months (p = 0.20), and median survival time was 12.8 and 9.1 months (p = 0.50). CONCLUSION: No statistically significant differences were found in chemotherapeutic responses and survival outcomes between the 2 groups, which suggests that chemotherapeutic efficacy is similar in both possible LCNEC and LCNEC.

Bacillus Calmette-Guérin treatment of urothelial carcinoma arising in the ileal neobladder after radical cystectomy.

In January 2005, a 66-year-old man underwent radical cystectomy and ileal neobladder reconstruction for invasive bladder cancer. A total of 3 years after the cystectomy, left-side ureteral cancer was diagnosed, and a nephroureterectomy was carried out in May 2008. In October 2011, he complained of asymptomatic macroscopic hematuria. We detected multiple papillary pedunculated and broad-based tumors in the left side and the dome of the neobladder. The patient underwent transurethral resection of the bladder tumor, and a pathological diagnosis of high-grade pTa urothelial carcinoma was made. A total of 4 months later, tumors recurred in the right side and anterior wall of the neobladder. We carried out transurethral resection of the bladder tumor again; the pathological diagnosis was high-grade pTa urothelial carcinoma with carcinoma in situ. Bacillus Calmette-Guérin instillation was carried out seven times into the neobladder, without any severe side-effects. Tumor recurrence was not observed up to 8 months after bacillus Calmette-Guérin treatment.

Successful Treatment of Epstein-Barr Virus Reactivation-associated Transverse Myelitis Following Herpes Zoster with Intravenous Rituximab in a Cord Blood Transplant Recipient.

The Epstein-Barr virus (EBV) is associated with many malignancies and autoimmune diseases, including multiple sclerosis. In addition, EBV rarely but occasionally causes central nervous system (CNS) complications. We herein report a case of transverse myelitis (TM) associated with systemic EBV reactivation after herpes zoster infection in a cord blood transplant recipient. Identification of EBV-infected peripheral blood cells revealed a predominance of B cells. Notably, intravenous rituximab ameliorated EBV reactivation and TM. Since the CNS infiltration rate of intravenous rituximab is markedly low, the clinical efficacy of rituximab against TM suggests that EBV reactivation may cause TM via immune-mediated mechanisms.

Predominance of T-bet-positive Th1 cells in infiltrating T-lymphocytes in most of active arteritis lesions of giant cell arteritis.

Immunological mechanisms through the activation of CD4-positive T-cells have been assumed to be involved in the pathogenesis of giant cell arteritis (GCA). Many studies employing frozen tissues of temporal artery biopsy, peripheral blood lymphocytes, and plasma of GCA patients have revealed the contribution of interferon-γ and interleukin-17 in both protein and mRNA levels. However, the analyses using formalin-fixed and paraffin-embedded (FFPE) tissue specimens, in which the correlation between histopathologic pictures and immunological circumstances would be elucidated, have been limited. Here, we performed the immunohistochemical analyses of infiltrating small lymphocytes in GCA lesions using FFPE specimens, especially of the subsets of CD4-positive T-cells by immunohistochemistry with antibodies against T-bet, GATA-3, RORγT, and Foxp3, which is the differentiation-specific transcription factor for Th1, Th2, Th17, and Treg cells, respectively. In these slides, the nuclear-positive staining is much more clearly and easily identifiable than the cytoplasmic staining for cytokines. The results indicate the predominance of T-bet-positive Th1 cells in infiltrating T-cells in most of active arteritis lesions of GCA. Furthermore, our data suggest the possible immunosuppressive microenvironment induced by T-reg cells and M2-type macrophages in the arteritis lesions throughout the course of GCA inflammation.

Large cell neuroendocrine carcinoma of the lung: is it possible to diagnose from biopsy specimens?

OBJECTIVE: We have recently proposed new diagnostic criteria for high-grade non-small cell neuroendocrine carcinoma, i.e. possible large cell neuroendocrine carcinoma, in biopsy specimens and have started a clinicopathological comparative study of high-grade neuroendocrine carcinomas in an advanced stage. This study aimed to elucidate the usefulness of our diagnostic criteria for inoperable advanced large cell neuroendocrine carcinoma and to know the true incidence of large cell neuroendocrine carcinoma among lung cancers. METHODS: We reviewed all cancer lesions (1040 specimens) obtained by transbronchial lung biopsies in our hospital from 2002 to 2009 and selected 38 biopsy specimens that satisfied our diagnostic criteria for high-grade non-small cell neuroendocrine carcinoma. All 38 cases were clinicopathologically investigated and all biopsy specimens were precisely studied for their morphological characteristics. RESULTS: Clinicopathological information about the selected 38 cases was very similar to the clinicopathological characteristics of large cell neuroendocrine carcinoma reported. Of 38 cases, six were at Stage I, II or IIIA, underwent surgery, and the diagnosis was confirmed to be large cell neuroendocrine carcinoma using surgical tumor specimens. In the 38 biopsy specimens, features of neuroendocrine morphology such as organoid nesting, peripheral palisading and rosette formation were not frequent histological features and the majority of tumor cells contained nuclei with a fine chromatin pattern. Mitoses were difficult to find; however, immunohistochemical Ki-67/MIB1 labeling indices were quite useful for evaluating proliferative activity, which ranged from 43.4 to 99.0%. CONCLUSIONS: Our study showed the diagnostic potential of using biopsy specimens for large cell neuroendocrine carcinoma, and we herein proposed more simplified diagnostic criteria for possible large cell neuroendocrine carcinoma in practical diagnostic use.

Immunohistochemical analysis-based proteomic subclassification of newly diagnosed glioblastomas.

Recent gene expression and copy number profilings of glioblastoma multiforme (GBM) by The Cancer Genome Atlas (TCGA) Research Network suggest the existence of distinct subtypes of this tumor. However, these approaches might not be easily applicable in routine clinical practice. In the current study, we aimed to establish a proteomics-based subclassification of GBM by integrating their genomic and epigenomic profiles. We subclassified 79 newly diagnosed GBM based on expression patterns determined by comprehensive immunohistochemical observation in combination with their DNA copy number and DNA methylation patterns. The clinical relevance of our classification was independently validated in TCGA datasets. Consensus clustering identified the four distinct GBM subtypes: Oligodendrocyte Precursor (OPC) type, Differentiated Oligodendrocyte (DOC) type, Astrocytic Mesenchymal (AsMes) type and Mixed type. The OPC type was characterized by highly positive scores of Olig2, PDGFRA, p16, p53 and synaptophysin. In contrast, the AsMes type was strongly associated with strong expressions of nestin, CD44 and podoplanin, with a high glial fibrillary acidic protein score. The median overall survival of OPC-type patients was significantly longer than that of the AsMes-type patients (19.9 vs 12.8 months). This finding was in agreement with the Oncomine analysis of TCGA datasets, which revealed that PDGFRA and Olig2 were favorable prognostic factors and podoplanin and CD44 were associated with a poor clinical outcome. This is the first study to establish a subclassification of GBM on the basis of immunohistochemical analysis. Our study will shed light on personalized therapies that might be feasible in daily neuropathological practice.

Clinical Characteristics of Posttransplant Lymphoproliferative Disorder After Cord Blood Transplantation Without Antithymocyte Globulin.

BACKGROUND: CBT with ATG use is a well-known PTLD risk factor. However, little is known regarding the clinical features of PTLD after ATG-free CBT. PATIENTS AND METHODS: We analyzed the incidence, risk factors and prognosis of PTLD in 183 adults undergoing ATG-free CBT. RESULTS: Fifteen patients (diffuse large B-cell lymphoma, n = 9, mucosa-associated lymphoid tissue lymphoma, n = 2 nondestructive PTLD, n = 1, T-cell lymphoma, n = 3) developed PTLD. The 2-year CuI of PTLD was 8.0% (95% CI: 4.6-12.7). Pathologically, all 12 B-cell PTLD patients had Epstein-Barr virus (EBV), compared with 1 of 3 T-cell PTLD patients. All patients, excluding one with nondestructive PTLD, showed extranodal involvement. In the univariate analysis, the 2-year CuI of PTLD was significantly higher in patients who received mycophenolate mofetil to prevent graft-versus-host disease than in nonrecipients (11.2%/2.9%, P = .0457). However, multivariate analysis revealed no independent PTLD risk factors. All 11 PTLD patients who received specific therapy achieved complete remission. The 1-year overall survival of PTLD patients was 70.9%. CONCLUSION: Although we found a higher CuI of PTLD than previously reported, the prognosis was generally good. In CBT recipients, many factors, including MMF use, may be associated with the clinical features of PTLD.

Case report: Common clonal origin of concurrent langerhans cell histiocytosis and acute myeloid leukemia.

Langerhans cell histiocytosis (LCH) and acute myeloid leukemia (AML) are distinct entities of blood neoplasms, and the exact developmental origin of both neoplasms are considered be heterogenous among patients. However, reports of concurrent LCH and AML are rare. Herein we report a novel case of concurrent LCH and AML which shared same the driver mutations, strongly suggesting a common clonal origin.An 84-year-old female presented with cervical lymphadenopathy and pruritic skin rash on the face and scalp. Laboratory tests revealed pancytopenia with 13% of blasts, elevated LDH and liver enzymes, in addition to generalised lymphadenopathy and splenomegaly by computed tomography. Bone marrow specimens showed massive infiltration of MPO-positive myeloblasts, whereas S-100 and CD1a positive atypical dendritic cell-like cells accounted for 10% of the atypical cells on bone marrow pathology, suggesting a mixture of LCH and AML. A biopsy specimen from a cervical lymph node and the skin demonstrated the accumulation of atypical cells which were positive for S-100 and CD1a. LCH was found in lymph nodes, skin and bone marrow; AML was found in peripheral blood and bone marrow (AML was predominant compared with LCH in the bone marrow). Next generation sequencing revealed four somatic driver mutations (NRAS-G13D, IDH2-R140Q, and DNMT3A-F640fs/-I715fs), equally shared by both the lymph node and bone marrow, suggesting a common clonal origin for the concurrent LCH and AML. Prednisolone and vinblastine were initially given with partial response in LCH; peripheral blood blasts also disappeared for 3 months. Salvage chemotherapy with low dose cytarabine and aclarubicin were given for relapse, with partial response in both LCH and AML. She died from pneumonia and septicemia on day 384. Our case demonstrates a common cell of origin for LCH and AML with a common genetic mutation, providing evidence to support the proposal to classify histiocytosis, including LCH, as a myeloid/myeloproliferative malignancy.