Case report: A rare case of pulmonary mucormycosis caused by Lichtheimia ramosa in pediatric acute lymphoblastic leukemia and review of Lichtheimia infections in leukemia.

Mucormycosis caused by Lichtheimia ramosa is an emerging and uncommon opportunistic infection in patients with hematological malignancies, with high mortality rates. Herein, we first report a case of pulmonary mucormycosis with Lichtheimia ramosa in a 3-year-old girl recently diagnosed with B-cell acute lymphoblastic leukemia. The diagnosis was made using computerized tomography of the lung, metagenomic next-generation sequencing (mNGS) of blood and sputum specimens, and microscopic examination to detect the development of Lichtheimia ramosa on the surgical specimen. She was effectively treated after receiving prompt treatment with amphotericin B and posaconazole, followed by aggressive surgical debridement. In our case, the fungal isolates were identified as Lichtheimia ramosa using mNGS, which assisted clinicians in quickly and accurately diagnosing and initiating early intensive treatment. This case also indicated the importance of strong clinical suspicion, as well as aggressive antifungal therapy combined with surgical debridement of affected tissues.

Activation of Janus kinase 1 confers poor prognosis in patients with non-small cell lung cancer.

The activation of Janus kinase 1 (JAK1) has been reported to occur in non-small cell lung cancer (NSCLC), activating the JAK/signal transducers and activators of transcription cascade. However, the association between JAK1 activation and the prognostic value in NSCLC remains unclear. The present study initially investigated the association between expression of the activated form of JAK1 (p-JAK1) and prognosis in patients with NSCLC. A cohort of 142 resected primary NSCLC tissue samples, including 74 adenocarcinoma (ADCC) and 68 squamous cell carcinoma samples, were analyzed. p-JAK1 expression status was determined by immunohistochemistry. Evaluation of epidermal growth factor receptor (EGFR) gene amplification by fluorescence in situ hybridization was subsequently performed in 74 ADCC samples. The prognostic significance of p-JAK1 expression and EGFR gene amplification were evaluated with univariate and multivariate survival analyses. Compared with normal lung tissue, p-JAK1 expression level was significantly increased in NSCLC (P<0.001). Positive p-JAK1 expression indicated a poor prognosis, particularly for patients in early stages (stage I/II, including tumor size <3 cm, Lymph node invasion N0/1; all P<0.05). p-JAK1 expression was an independent predictor of a poor prognosis (P=0.022). The overall survival time for patients with positive p-JAK1 expression and EGFR-amplified tumors was significantly shortened compared with patients with tumors negative for one or both features (both features present vs. neither feature present, P<0.001). The results provided clinical evidence that the activation of JAK1 was an independent prognostic factor, particularly in early stage NSCLC. The combination of EGFR gene amplification and p-JAK1 expression may be a novel target for the selection of individual therapy strategies and predicting the effects of therapy for NSCLC.

Immunohistochemical screening and fluorescence in situ hybridization confirmation of ALK translocation in lung adenocarcinoma and its clinicopathological significance: a single-center large-scale investigation of Chinese patients.

Anaplastic lymphoma kinase (ALK) translocation-positive adenocarcinoma of the lung is a newly recognized molecular subgroup. Limited data on the clinicopathological features of this entity in the Chinese population are available. We performed immunohistochemical staining for the ALK protein and fluorescence in situ hybridization detection of the ALK translocation. We enrolled 793 Chinese patients with lung adenocarcinoma and identified 54 ALK translocation-positive patients (6.8%) in the group. Compared with the entire group of patients, ALK translocation-positive patients were younger (P < .01) and more likely to be nonsmokers (P = .017), but presented with a higher percentage of advanced-stage disease (P = .022) and lymph node metastases (P = .006). ALK translocation-positive patients more commonly exhibited poorly differentiated tumor histology and a predominantly solid tumor growth pattern relative to the ALK translocation-negative patients. Morphologically, ALK translocation was associated with extracellular mucus secretion, a mucinous cribriform structure, and signet ring cell (SRC) components. ALK translocation was present in 42.5% and 34.0% of adenocarcinomas with SRC components or wild-type EGFR, respectively. ALK translocation, occurring at a frequency of 6.8% in Chinese patients, defines a unique molecular subgroup of lung tumors. Fluorescence in situ hybridization should be performed in each case of lung adenocarcinoma with SRC components or wild-type EGFR to identify ALK translocation-positive patients.

Extranodal nasal type natural killer/T-cell lymphoma of testis: report of seven cases with review of literature.

Seven cases of testicular extranodal natural killer (NK)/T-cell lymphoma, nasal type, are reported, with a literature review. Two patients had a testicular lesion as the initial presentation, four had a history of nasal NK/T-cell lymphoma and the remaining patient had concomitant involvement of an adrenal gland. All patients underwent orchiectomy followed by chemotherapy (CT) and/or radiotherapy (RT). Follow-up data showed that two patients with non-primary tumors died of disease within 6 and 11 months, respectively. Histologically, the tumor had a diffuse growth pattern largely replacing the interstitial tissues. Neoplastic cells showed prominent angiocentric and angioinvasive features with focal coagulative necrosis and apoptotic bodies. Immunohistochemically, all cases were positive for cytoplasmic CD3ε and CD56. Epstein-Barr virus infection was demonstrated in all cases. Testicular NK/T-cell lymphoma, whether primary or secondary, was generally very aggressive with a poor outcome despite multimodality therapy. Novel molecular therapeutic targets and more effective treatments are needed, especially for disseminated or recurrent cases.

[Expressions of CXCL13, CD10 and bcl-6 in angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma, not otherwise specified].

OBJECTIVE: To study the value of immunomarkers CXCL13, CD10, bcl-6 in pathologic diagnosis of angioimmunoblastic T-cell lymphoma (AITL). METHODS: One hundred and fifteen cases of AITL, 30 cases of peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) and 30 cases of reactive lymph nodes with paracortical hyperplasia (RH) encountered during the period from January, 1990 to January, 2008 were retrieved from the archival files of the Department of Pathology, West China Hospital of Sichuan University, China. The morphologic features were reviewed and compared. Immunohistochemical study was performed by SP method for CXCL13, CD10, bcl-6, CD21, CD3epsilon, CD3, CD45RO, CD20 and Ki-67. TCR-gamma gene rearrangement study was also carried out. RESULTS: Regressed follicles were evident in 7.8% (9/115) of AITL cases, 6.7% (2/30) of PTCL, NOS cases and 83.3% (25/30) of RH cases, respectively. A marked increase of number of arborizing venules was shown in 98.3% (113/115) of AITL cases, 63.3% (19/30) of PTCL, NOS cases and 76.7% (23/30) of RH cases, respectively. In lymph nodes with paracortical hyperplasia, the expression of CXCL13, CD10 and bcl-6 were restricted to the germinal centers. In AITL, 96.5% (111/115) of cases showed CXCL13 expression, in contrast to 26.7% (8/30) of PTCL, NOS. Expression of CD10 and bcl-6 were found in the neoplastic cells in 50.4% (58/115) and 78.3% (90/115) of AITL, and 3.3% (1/30) and 3.3% (1/30) of PTCL, NOS, respectively. Irregular meshworks of CD21-positive follicular dendritic cells were found in all the AITL cases. Clonal TCR-gamma rearrangement was detected in 83% (83/100) of the AITL cases. CONCLUSIONS: AITL is a type of lymphoma originated from the follicular helper T cells. Detailed morphologic assessment and use of immunohistochemical markers are essential for accurate diagnosis.

[Lymphoplasmacytic lymphoma with Waldenström's macroglobulinemia: a clinicopathological and immunophenotypic study of 40 Chinese patients].

OBJECTIVE: To investigate the clinicopathologic features of lymphoplasmacytic lymphoma (LPL) with Waldenström's macroglobulinemia (WM) and to evaluate the usefulness of immunophenotype analysis in diagnosis and differential diagnosis of the tumor. METHODS: A total of 40 cases of LPL with WM diagnosed according to the 2008 World Health Organization classification of tumors of hematopoietic and lymphoid tissues were analyzed using immunophenotype and follow-up information. RESULTS: The mostly common initial clinical presentations were non-specific symptoms, such as fatigue, anemia and hemorrhage. Lymphadenopathy, splenomegaly and hepatomegaly were found in 42.5%, 20.0% and 12.5% of the patients respectively. The pattern of bone marrow involvement included mixed type (47.2%), diffuse type (41.7%) and interstitial type (11.1%). The nodal architecture was completely destroyed in one case and partially effaced with residual germinal centers and dilated sinuses in 8 cases. All of the neoplastic cells expressed CD20 and CD79a. Neoplastic plasma cells were positive for CD138 and CD79a. No cases expressed CD5. Four cases weakly expressed CD23. No significant prognosis related factors were identified in the survival analysis. CONCLUSIONS: LPL with WM is a rare indolent small B-cell lymphoma, which is commonly seen, in older male patients. The tumor frequently involves bone marrow and shows various clinical manifestations. Combination analyses of the bone marrow biopsy histology, immunophenotypic study and clinical data, especially the serum examination are important for the diagnosis of LPL with WM.