Non-Hodgkin and Hodgkin Lymphomas Select for Overexpression of BCLW.

Purpose: B-cell lymphomas must acquire resistance to apoptosis during their development. We recently discovered BCLW, an antiapoptotic BCL2 family member thought only to contribute to spermatogenesis, was overexpressed in diffuse large B-cell lymphoma (DLBCL) and Burkitt lymphoma. To gain insight into the contribution of BCLW to B-cell lymphomas and its potential to confer resistance to BCL2 inhibitors, we investigated the expression of BCLW and the other antiapoptotic BCL2 family members in six different B-cell lymphomas. Experimental Design: We performed a large-scale gene expression analysis of datasets comprising approximately 2,300 lymphoma patient samples, including non-Hodgkin and Hodgkin lymphomas as well as indolent and aggressive lymphomas. Data were validated experimentally with qRT-PCR and IHC. Results: We report BCLW is significantly overexpressed in aggressive and indolent lymphomas, including DLBCL, Burkitt, follicular, mantle cell, marginal zone, and Hodgkin lymphomas. Notably, BCLW was preferentially overexpressed over that of BCL2 and negatively correlated with BCL2 in specific lymphomas. Unexpectedly, BCLW was overexpressed as frequently as BCL2 in follicular lymphoma. Evaluation of all five antiapoptotic BCL2 family members in six types of B-cell lymphoma revealed that BCL2, BCLW, and BCLX were consistently overexpressed, whereas MCL1 and A1 were not. In addition, individual lymphomas frequently overexpressed more than one antiapoptotic BCL2 family member. Conclusions: Our comprehensive analysis indicates B-cell lymphomas commonly select for BCLW overexpression in combination with or instead of other antiapoptotic BCL2 family members. Our results suggest BCLW may be equally as important in lymphomagenesis as BCL2 and that targeting BCLW in lymphomas should be considered. ©2017 AACR

Indirect induction of radiation lymphomas in mice. Evidence for a novel, transmissible leukemogen.

The transmission of a lymphomagenic agent(s) from the bone marrow of irradiated mice to thymic target cells has been demonstrated by: (a) the induction of T cell lymphomas in nonirradiated thymic grafts implanted in irradiated, Thy-l-congenic mice, (b) the induction of T cell lymphomas of host origin in mice infused with bone marrow from irradiated, Thy-l-congenic donors. The latter procedure also yields an appreciable number of pre-B cell lymphomas of uncertain origin. The results confirm Kaplan's theory that radiation induces thymic lymphomas in mice by an indirect mechanism. However, the previously described radiation leukemia virus is clearly not involved in the majority of transferred lymphomas. We propose that the mediating agent in radiation lymphomagenesis is a novel, transmissible agent induced in the bone marrow, but exerting its transforming activity on cells in the thymus. The nature and mode of action of the agent are under investigation

Perforated small intestine in a patient with T-cell lymphoma; a rare cause of peritonitis

The nontraumatic perforations of the small intestine are pathological entities with particular aspects in respect to diagnosis and treatment. These peculiarities derive from the nonspecific clinical expression of the peritonitis syndrome, and from the multitude of causes that might be the primary sources of the perforation: foreign bodies, inflammatory diseases, tumors, infectious diseases, etc. Accordingly, in most cases intestinal perforation is discovered only by laparotomy and the definitive diagnosis is available only after histopathologic examination. Small bowel malignancies are rare; among them, lymphomas rank third in frequency, being mostly B-cell non Hodgkin lymphomas. Only 10% of non-Hodgkin lymphomas are with T-cell. We report the case of a 57 years’ old woman with intestinal T-cell lymphoma, whose first clinical symptomatology was related to a complication represented by perforation of the small intestine. Laparotomy performed in emergency identified an ulcerative lesion with perforation in the jejunum, which required segmental enterectomy with anastomosis. The nonspecific clinical manifestations of intestinal lymphomas make from diagnosis a difficult procedure. Due to the fact that surgery does not have a definite place in the treatment of the small intestinal lymphomas (for cases complicated with perforation), and beyond the morbidity associated with the surgery performed in emergency conditions, prognosis of these patients is finally given by the possibility to control the systemic disease through adjuvant therapy

Primary Non-Hodgkin's Malignant Lymphoma of the Sinonasal Tract

Primary non-Hodgkin’s lymphomas (NHL) of the sinonasal tract are rather uncommon entities. Morphologically and radiographically, sinonasal lymphomas are difficult to distinguish from other malignant neoplasms or non- neoplastic processes. They have a variable presentation from fulminant destructive manifestations to chronic indolent type of disease and may mimic as carcinomas and invasive fungal infection respectively. We report a case of primary NHL involving sinonasal tract in elderly female, which was clinically and radiologically mimicking as sinonasal malignany and was proven as NHL on histological examination and confirmed by immunohistochemistry. A high index of suspicion, appropriate histopathological examination and immunohistochemistry is necessary to differentiate sinonasal lymphomas from other possibilities. Failure to do so may miss the diagnosis and delay appropriate treatmen

On the crossroad between tolerance and posttransplant lymphoma.

The role of the Epstein-Barr virus in the development of post-transplant lymphomas is well established. However, not all lymphomas that arise in these patients contain Epstein-Barr virus, suggesting that other cofactors are involved in tumor pathogenesis. We propose that immunologic interactions that result from the introduction of immunocompetent donor cells during transplantation contribute to a lymphomagenic environment in the host. Murine models of lymphoma that arises following transfer of allogeneic hematopoietic cells are discussed and are related to the transplant setting. One contemporary viewpoint of transplantation immunology holds that interactions between the host and donor components of the immune system determine the ultimate degree of tolerance or reciprocal immunoreactivity (eg, rejection, graft-versus-host disease) within the transplant patient. We conclude that host-donor immunologic microchimerism may also be an over-looked factor in the development of posttransplant lymphomas

Clinicopathological features of extranodal lymphomas: Kuwait experience

A total of 935 patients with extranodal non-Hodgkin lymphoma (NHL) diagnosed in the period between January 1985 and December 2000 in Kuwait Cancer Center, serving the whole population of Kuwait, were used to describe the clinicopathological and epidemiological features of extranodal lymphomas in Kuwait. Extranodal lymphomas accounted for 45% of all NHL observed during this time. All NHL cases from Kuwait Cancer registry were analyzed and pathologically reclassified using the latest WHO ( 2000) classification. The most common lymphoma observed was diffuse large B-cell lymphoma (58.60%) followed by Burkitt's lymphoma (BL) (3.80%). In the pediatric group, BL comprises more than two thirds of all patients (77.20%). The most common extranodal sites were stomach (19.70%) and skin (17.80%) in the adult group, large intestine (29.80%) and small intestine (19.30%) in the pediatric age group. The majority (73.40%) of adult extranodal lymphomas was in stage IE - IIE and had a very good prognosis. On the contrary, the majority of pediatric extranodal lymphomas were found to be in stage III and IV. Variations in treatment policies ( single agent or combined chemotherapy, radiotherapy, combined modality treatment) adopted and changed during the time period of 16 years of this retrospective study were documented. Copyright (C) 2004 S. Karger AG, Basel

Mucosa associated lymphoid tissue lymphoma of the thyroid gland: a case report and literature review = MALT linfoma della tiroide: caso clinico e revisione della letteratura

Mucosa associated lymphoid tissue (MALT) lymphomas are low-grade, non-Hodgkin’s B cell lymphomas, mainly occurring in the gastrointestinal tract, but also in other tissues. We describe the management of a patient with hypothyroidism, tracheoesophageal compressive symptoms and chest tightness affected by a thyroid MALT lymphoma. The patient underwent debulking thyroidectomy and temporary tracheostomy in order to reduce dysphonia and dysphagia, followed by adjuvant chemotherapy and subsequently radiation therapy. A CT scan performed at the end of radiotherapy 6 months after surgery revealed remnants of residual tissue from the thyroidectomy without any pathological findings. I linfomi MALT sono dei linfomi non-Hodgkin a cellule B a basso grado che in genere insorgono a livello del tratto gastrointestinale, ma anche in altri tessuti. Descriviamo in questo articolo il management clinico-chirurgico di un paziente con ipotiroidismo, sintomi da compressione tracheo-esofagea e senso di oppressione toracica, affetto da linfoma MALT della tiroide. Il paziente è stato sottoposto a parziale asportazione della massa tiroidea e tracheostomia allo scopo di ridurre i sintomi compressivi ed in seguito a trattamento chemioterapico e radioterapico. L’esame TC effettuato una volta conclusa la radioterapia, circa 6 mesi dopo l’intervento, ha evidenziato gli esiti della tiroidectomia parziale in assenza di altri reperti patologici

Metagenomic deep sequencing of aqueous fluid detects intraocular lymphomas.

IntroductionCurrently, the detection of pathogens or mutations associated with intraocular lymphomas heavily relies on prespecified, directed PCRs. With metagenomic deep sequencing (MDS), an unbiased high-throughput sequencing approach, all pathogens as well as all mutations present in the host's genome can be detected in the same small amount of ocular fluid.MethodsIn this cross-sectional case series, aqueous fluid samples from two patients were submitted to MDS to identify pathogens as well as common and rare cancer mutations.ResultsMDS of aqueous fluid from the first patient with vitreal lymphoma revealed the presence of both Epstein-Barr virus (HHV-4/EBV) and human herpes virus 8 (HHV-8) RNA. Aqueous fluid from the second patient with intraocular B-cell lymphoma demonstrated a less common mutation in the MYD88 gene associated with B-cell lymphoma.ConclusionMDS detects pathogens that, in some instances, may drive the development of intraocular lymphomas. Moreover, MDS is able to identify both common and rare mutations associated with lymphomas

Prognostic significance of DNA cytometry in cutaneous malignant lymphomas.

The current classification of cutaneous malignant lymphomas (ML) into low-grade and high-grade lymphomas was found to be of limited reproducibility and permitted only a rough prediction about outcome. With this in mind, the relationship between nuclear DNA content and both prognosis and histologic grading according to the Kiel classification was evaluated on Feulgen-stained imprint specimens. In all, 49 cases of malignant non-Hodgkin's lymphoma, primary of the skin or with an involvement of the skin as one of the first symptoms, were studied using a computerized high-resolution image analysis system. The 2c deviation index (2cDI), which reflects the variation of the nuclear DNA values around the normal diploid peak, was found to be the best prognostically relevant criterion. Using the 2cDI, a significant discrimination (P less than 0.001 in the U test) between low-grade and high-grade ML was achieved. The prognostic benefit of the 2cDI was well documented by a significant inverse correlation between the 2cDI and the period of time until the patients progressed at least into one higher stage or died of lymphoma (r equals -0.63, P less than 0.05). In addition, the 2cDI enabled prognosis of the course of disease. In the group with low 2cDI values (2cDI, less than 0.5), no progression of the disease was observed after 1 year. In the groups presenting with a 2cDI between 0.5 and 1.0 and higher than 1.0, a progression was found in 57% and 64% of the cases studied, respectively. In conclusion, these measurements indicate that the determination of DNA distribution patterns in imprint specimens allows a precise and objective prognostic evaluation of cutaneous ML