Integrative analysis of clinicopathological features defines novel prognostic models for mantle cell lymphoma in the immunochemotherapy era: a report from The North American Mantle Cell Lymphoma Consortium.

BACKGROUND: Patients with mantle cell lymphoma (MCL) exhibit a wide variation in clinical presentation and outcome. However, the commonly used prognostic models are outdated and inadequate to address the needs of the current multidisciplinary management of this disease. This study aims to investigate the clinical and pathological features of MCL in the immunochemotherapy era and improve the prognostic models for a more accurate prediction of patient outcomes. METHODS: The North American Mantle Cell Lymphoma Project is a multi-institutional collaboration of 23 institutions across North America to evaluate and refine prognosticators for front-line therapy. A total of 586 MCL cases diagnosed between 2000 and 2012 are included in this study. A comprehensive retrospective analysis was performed on the clinicopathological features, treatment approaches, and outcomes of these cases. The establishment of novel prognostic models was based on in-depth examination of baseline parameters, and subsequent validation in an independent cohort of MCL cases. RESULTS: In front-line strategies, the use of hematopoietic stem cell transplantation was the most significant parameter affecting outcomes, for both overall survival (OS, p < 0.0001) and progression-free survival (PFS, p < 0.0001). P53 positive expression was the most significant pathological parameter correlating with inferior outcomes (p < 0.0001 for OS and p = 0.0021 for PFS). Based on the baseline risk factor profile, we developed a set of prognostic models incorporating clinical, laboratory, and pathological parameters that are specifically tailored for various applications. These models, when tested in the validation cohort, exhibited strong predictive power for survival and showed a stratification resembling the training cohort. CONCLUSIONS: The outcome of patients with MCL has markedly improved over the past two decades, and further enhancement is anticipated with the evolution of clinical management. The innovative prognostic models developed in this study would serve as a valuable tool to guide the selection of more suitable treatment strategies for patients with MCL.

Pure red cell aplasia occurring during ibrutinib therapy for chronic lymphocytic leukemia.

INTRODUCTION: Chronic lymphocytic leukemia (CLL) has long been known for its complications related to immune deregulation, of which autoimmune cytopenias (AIC) were frequently reported. Ibrutinib has dramatically changed the overall prognosis of patients with CLL. However, whether ibrutinib can induce or aggravate AIC in CLL patients is still disputable. Here we report a CLL patient with pure red cell aplasia (PRCA) occurring during ibrutinib treatment and review available data to discuss the possible role of ibrutinib in developing AIC. CASE REPORT: A 70-year-old female was diagnosed with CLL with indications to initiate ibrutinib treatment given progressive bulky disease. She was admitted for advanced fatigue on the 14th day of ibrutinib monotherapy. A complete blood count revealed severe anemia of hemoglobin (Hb) 37 g/L and a meager reticulocyte count. After excluding other conditions that could cause anemia, PRCA was diagnosed as a complication of CLL. MANAGEMENT AND OUTCOME: Ibrutinib was discontinued on the day of admission. At the same time, the patient received prednisone and intravenous immunoglobulin (IVIg). Five days later, the Hb did not improve. Cyclosporine A (CsA) was added; IVIg was discontinued, and prednisone was tapered. Ten days later, the Hb had risen to 92 g/L with a high reticulocyte count of 0.279 × 1012/L. The CLL treatment restarted with Zanbrutinib in combination with a low dose of prednisone and CsA. Her CLL was in partial remission by the latest follow-up with an average Hb count. DISCUSSION: Our case demonstrates a need to evaluate the risk of developing AIC before initiating ibrutinib. For patients with high-risk factors for AIC episodes, the transient addition of other immunosuppressive therapies should be taken into consideration.

Follicular lymphoma with paraneoplastic pemphigus as the first symptom: a case report and review of the literature.

Paraneoplastic pemphigus (PNP) is an autoimmune bullous dermatosis associated with tumors, first described by Anhalt et al. in 1990. Reports of paraneoplastic pemphigus complicated by follicular lymphoma (FL) are rare in the medical literature. Here, we retrospectively analyze a case of PNP accompanied by FL. The patient was a 54-year-old woman who suffered from PNP associated with FL at the beginning. She had received a pathological diagnosis and was treated with R-CHOP and other drugs. Her mucosal lesions and cutaneous lesions improved, and the FL was in remission. Eleven months later, she died of BO after receiving the diagnosis of PNP. We also review most of the studies and reports about PNP accompanied by FL. We list the clinicopathologic features, therapeutic schedule, and prognosis in order to improve hematologists' understanding and treatment of the diseases.

Developing a routine lab test for absolute quantification of HER2 in FFPE breast cancer tissues using Quantitative Dot Blot (QDB) method.

Developing immunoassay for absolute quantitation of protein biomarkers in Formalin Fixed Paraffin Embedded (FFPE) samples promises improved objectivity, consistency and accuracy in daily clinical practice. The feasibility of Quantitative Dot Blot (QDB) method for this purpose was explored in this study. We were able to measure HER2 protein levels using 0.5 µg/sample total protein lysate extracted from 2 × 5 µm FFPE slices absolutely and quantitatively using QDB method in 332 breast cancer FFPE samples. HER2 levels measured using two clinically validated antibodies for immunohistochemistry respectively were highly correlated (r = 0.963). We also achieved area under the curve (AUC) at 0.9998 ± 0.0002 (p < 0.0001, n = 224) with IHC analysis, and 0.9942 ± 0.0031 (p < 0.0001, n = 319) with combined results from IHC and Fluorescence in situ hybridization (FISH) analyses when analyzed with Receiver Operative Characteristics analysis (ROC) respectively. When the results were converted dichotomously with optimized cutoffs from ROC analyses, we achieved 99.5% concordance with IHC; and 96.9% with combined results from both IHC and FISH analyses. Therefore, we were able to demonstrate QDB method as the first immunoassay platform for absolute quantitation of protein biomarkers in FFPE samples to meet the need of daily clinical practice, especially for local laboratories or laboratories in developing countries.

Discordant lymphoma consisting of mantle cell lymphoma and angioimmunoblastic T cell lymphoma: homology or heterogeneity?

OBJECTS: To investigate the pathologic characteristic of discordant lymphoma with mantle cell lymphoma and angioimmunoblastic T cell lymphoma. METHODS: The clinicopathologic data of cases of discordant lymphoma were organized and clinicopathologic features were analyzed by literature review. RESULTS: A 49-year-old male was taken to the hospital due to the lymphandenopathy in January 2007 and mantle cell lymphoma was diagnosed in the pathology report. EBV-EBER staining was negative. Active chemotherapy was received and the patient achieved complete response. Seven years later since diagnosis, in 2014 scattered rashes were found. A skin biopsy was taken and the result was not mantle cell lymphoma but angioimmunoblastic T cell lymphoma. EBV-EBER positivity was detected. Clonal T cell receptor gamma locus gene rearrangements were detected while no clonal immunoglobin heavy locus gene rearrangement was detected in the skin sample. CONCLUSIONS: This is the first report on discordant lymphoma consisting of mantle cell lymphoma and angioimmunoblastic T cell lymphoma. There seems to be no relation these two different kinds of lymphoma, and EBV infection might prompt the development of angioimmunoblastic T cell lymphoma after transplantation. Rash is a common clinical manifestation when T cell lymphoma develops after treatment for MCL.

Nasal NK/T cell lymphoma mimicking mucosa-associated lymphoid tissue lymphoma in morphology: A case report.

The objective of the present study was to describe the clinicopathological features of a patient with nasal NK/T cell lymphoma that was similar in morphology to mucosa-associated lymphoid tissue lymphoma (MALToma). The clinicopathological data of a patient diagnosed with nasal NK/T cell lymphoma mimicking MALToma was collected, and the clinicopathological characteristics were discussed. The female patient was 43 years old and had suffered from persistent congestion for ten days. The mucosa in the left nasal cavity was inflamed, resulting in congestion and it was also purulent on the surface, as observed by nasal endoscopy. The disease was considered to be inflammatory based on CT scan. A biopsy after operation showed that the tumor consisted of small lymphoid cells that resembled MALToma in morphology. On the basis of the immunohistochemistry and in situ hybridization laboratory tests, a diagnosis of left nasal NK/T cell lymphoma was made. The patient received chemotherapy and radiotherapy, and remission was achieved six months after diagnosis. The patient was in a good condition at 16 months follow-up. In conclusion, NK/T cell lymphoma composed of small cells may be a type of indolent lymphoma with special characteristics of clinical presentation, image, pathology and prognosis. This case highlights that more attention is required by radiologists, pathologists and hematologists to diagnose this type of lymphoma.

Signet Ring B Cell Lymphoma: A Potential Diagnostic Pitfall.

Signet ring B cell lymphoma is an unusual non-Hodgkin lymphoma. It is similar to signet ring cell carcinoma and liposarcoma in morphology which should be distinguished. We treated a 63-year-old male patient who suffered from abdominal pain for two months. Multiple enlarged lymph nodes were found in the retroperitoneum by CT scan. The needle biopsy showed neoplastic cells distributed uniformly with clear cytoplasm and the nucleus squeezed to the side mimicking the appearance of signet ring in morphology. By special staining, the neoplastic cells were positive for CD45, Vimentin, Bcl-2 and CD20 but negative for AE1/AE3, S-100, CD3, EMA, CD5, CD10, Bcl-6, MUM1 , Kappa, Lambda and PAS . Ki67 proliferation index was much more than 80%. Based on the histological characters, a diagnosis of signet ring B cell lymphoma was made. Although the patient received six courses of R-CHOP therapy, he died of tumor recurrence at the 34th month after diagnosis.

Chondroid gastrointestinal stromal tumor in the stomach with early adenocarcinoma.

OBJECTIVE: To explore the pathologic features of gastric chondroid gastrointestinal stromal tumors. METHODS: The clinicopathologic data of one case of gastric chondroid gastrointestinal stromal tumor were collected and the features were analyzed by literature review. RESULTS: The male patient was 64 years old and had suffered from upper abdominal fullness discomfort without obvious cause for 5 years. Gastroscopic examination showed a rough area located in the lesser curvature of the gastric antrum, measuring 6 cm × 4 cm. CT scan showed the stomach wall was unevenly thick at the gastric antrum and stomach outlet. Multiple enlarged lymph nodes were seen nearby. The biopsy pathology showed adenocarcinoma of gastric antrum. The patient underwent laparoscopic gastrectomy and gastric chondroid gastrointestinal stromal tumor was found with adenocarcinoma of the stomach. Asp842Val mutation was found in the PDGFRα 18 exon. CONCLUSION: Gastric chondroid gastrointestinal stromal tumors are rare and low risk. Tumor cells express CD117 and Asp842Val mutation in the PDGFRα 18 exon revealed by genetic sequencing suggesting this kind of tumor might be resistant to imatinib.

Expression and clinical significance of H-caldesmon in gastrointestinal stromal tumor: is it a specific marker for myogenic differentiation?

OBJECTS: To investigate the expression and clinical significance of H-caldesmon which is considered a myogenic marker in GIST. METHODS: The clinical information of 105 patients diagnosed with GIST was obtained from Yantai Yuhuangding Hospital and Rambam Health Care Campus. Morphology, the results of immunohistochemical staining and available molecular detection were reviewed. The expression of H-caldesmon was detected for each specimen by immunohistochemical staining. Comparative analysis was carried out between H-caldesmon expression and clinicopathologic parameters. RESULTS: H-caldesmon was expressed in all patients with GIST including tumors outside the gastrointestinal tract and with CD117-negative expression. Although the pattern of expression was different, the positive rate in our study group was 100%. There was no statistically difference between H-caldesmon expression and parameters such as gender, age, location, morphology, risk, immunologic markers, and molecular mutation. CONCLUSIONS: H-caldesmon is expressed positively in GIST and might not be a specific marker for smooth muscle and associated tumors. GIST outside the gastrointestinal tract or with CD117-negative expression should not be misdiagnosed assmooth muscle tumor because of the positive expression of H-caldesmon in the differential diagnosis. Comprehensive analysis combined with other immunological markers and molecular detection is needed.