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T-zone lymphoma (TZL) is an indolent, nodal lymphoma that has been clinically characterized in detail in dogs, and T-zone hyperplasia (TZH) is a hyperplastic change in lymph nodes associated with antigen processing. In some cases, histopathological features of TZL and TZH are similar, and are difficult to differentiate by morphology alone. Since there have been few publications characterizing their immunohistochemical profiles, histological, immunohistochemical, and clonality examinations were performed using formalin-fixed paraffin-embedded samples of canine lymph nodes with TZL (14 cases) and canine lymph nodes with TZH associated with nonlymphocytic tumors (10 cases). Immunohistochemically, small- to medium-sized lymphocytes of TZL were immunopositive for CD3, CD5, and HLA-DR, and negative for CD45, FOXP3, and granzyme B (GRB) in all cases. Among these 14 cases, 11 were immunopositive for CD8 and 1 was CD20 positive. Paracortical lymphocytes in TZH were diffusely immunopositive for CD3, CD5, and CD45, with scattered immunopositivity for CD8, HLA-DR, FOXP3, and GRB, and negative for CD20 in all cases. A clonal TCR gene rearrangement was detected in 13/14 TZL and none of the TZH cases. The present study revealed that TZL is a clonal proliferation of monomorphic CD8+CD45-GRB- T cells, while TZH consists of an immunophenotypically heterogenous population of CD45+ T cells that are variably positive for CD8 and FOXP3. These results suggest that canine TZL is a clonal proliferation of naïve or premature cytotoxic T cells. Regarding TZH, variable immunopositivity for cytotoxic and regulatory T-cell antigens may reflect immune responses to a variety of regional neoplastic lesions.

Purpose: Flow cytometry (FCM) is used to evaluate cell surface markers of various leukocyte populations quantitatively. However, little is known about the usefulness of FCM in follicular lymphoma (FL) of the ocular adnexa. The aim of this study was to evaluate the clinicopathological features and FCM results in ocular adnexal FL. Materials: This is a retrospective multicenter case study on clinical and immunohistochemical features. All tumors, surgically excised, were diagnosed based on histopathology, immunoglobulin heavy chain gene rearrangement, and FCM. The percentages (%) of B-cell markers, T-cell markers, a natural killer cell marker, and cell surface kappa/lambda measured by FCM analysis in tumor tissues were searched based on medical records. Results: This study enrolled nine tumors in eight FL patients (three men and five women). The median age at the time of initial presentation was 74 years. All the tumors surgically excised histologically exhibited cluster of differentiation (CD)10, CD20, and BCL2-positive cells. At the time of ophthalmic diagnosis, lymphomas were already disseminated throughout the body in five cases. FCM demonstrated high percentage of B-cell markers including CD10, CD19, CD20, and CD23 in all nine tumors. CD10 population was 73.5% ± 11.9% in seven out of nine tumors, while that in the other two tumors was particularly low being 11.7% ± 1.13%, which showed the relatively high T-cell lineages compared to the other seven tumors. Conclusion: For ophthalmologists involving managements of ocular adnexal tumors, FCM can provide useful information for complementing the diagnosis and understanding pathophysiology of FL.

Collision tumors are rare and there have only been a few previously described cases between an intestinal adenoma and a lymphoma. We report the first case of a 74-year-old woman who on investigation for iron deficiency had a tubulovillous adenoma with underlying follicular lymphoma. The atypical lymphoid proliferation showed immunohistochemical positivity for cluster of differentiation 20 (CD20), B-cell lymphoma 2 (BCL2), and B-cell lymphoma 6 (BCL6). Subsequent right hemicolectomy showed a superficially invasive adenocarcinoma.

In this article, we report the case of a 78-year-old woman who consulted our hospital for a right breast mass detected on mammography during her cancer screening. Biopsy specimens showed atypical lymphocytic infiltration with a follicle-like growth pattern, suggesting a follicular lymphoma (FL). Immunohistochemically, the atypical lymphoid cells were diffusely and strongly positive for CD20, BCL2, and BCL6, but negative for CD10. IGH- BCL2 translocation was confirmed by fluorescence in situ hybridization analysis, leading to the diagnosis of primary breast FL. The most important differential diagnosis of this case was marginal zone lymphoma (MZL), which usually shows a CD10−/BCL2+ immunophenotype and is one of the common histological types in primary breast lymphomas. FLs with an atypical immunophenotype exist in a certain percentage of patients. Therefore, FL is considered to be a heterogeneous entity. It is important to distinguish FL from MZL in primary breast lymphomas because FLs may have a worse prognosis than MZLs.

Follicular lymphoma (FL) usually has an indolent course and presents with painless, waxing and waning lymphadenopathy in the absence of systemic symptoms. It is uncommon for FL to present outside of lymph nodes, although it can develop in the gastrointestinal tract, skin, thyroid, and testes. Central nervous system (CNS) involvement in FL is rare. Most CNS lymphomas are diffuse large B-cell lymphoma, although Burkitt lymphoma, lymphoblastic lymphoma, and peripheral T-cell lymphoma are also observed. These tumors usually involve white matter but may also involve gray matter. Lymphomas of the dura are very uncommon and are usually mucosa-associated lymphoid tissue lymphomas. Here, we present a case of FL of the dura arising in a 62-year-old woman that was responsive to chemotherapy. According to a literature review, there have been 15 previously reported cases of FL of the dura. Dural FL has been most frequently treated with radiation and chemotherapy. Patients were still alive in all cases in which follow-up was reported. Although the sample size is small, these data suggest that dural FL, like other forms of FL, is an indolent disease that is associated with prolonged survival despite usually being incurable.

Lymphomas are a diverse group of hematologic malignancies that arise from either T cell, B cell or the natural killer cell lineage. B cell lymphomas arise from gene mutations with critical functions during normal B cell development. Recent advances in the understanding of molecular pathogenesis demonstrate that many different recurrent genomic and molecular abnormalities and dysregulated oncogenic regulatory pathways exist for many subtypes of B cell lymphomas, both across and within histological subtypes. Pathogenetic processes such as (1) chromosomal aberrations, for example, t(14;18) in follicular lymphoma, t(11;14) in mantle cell lymphoma, t(8;14) in Burkitt lymphoma; dysregulations in signaling pathways of (2) nuclear factor- κB (NF-κB); (3) B cell receptor (BCR); (4) Janus kinase/signal transducers and transcription activators (JAK-STAT); (5) impaired apoptosis/cell cycle regulation due to mutated, rearranged or amplified MYC, BCL-2, BCL-6 proto-oncogenes; (6) epigenetic aberrations may contribute to pathogenesis. More studies are under way to elucidate the molecular heterogeneity underlying many types of lymphomas that account for variable responses to treatment, generation of subclones and treatment resistance. Although significant research is still needed, targeted therapy promises to provide new options for the treatment of patients with lymphomas. This article provides a non-exhaustive overview on the current understanding on the genetics of pathogenesis of B cell lymphomas and their therapeutic implications.

Bcl-2, an anti-apoptotic protein, is commonly overexpressed in follicular lymphomas in humans. This is usually the result of a chromosomal translocation that transposes the Bcl-2 gene into the immunoglobulin gene locus. The immunohistochemical assessment of this overexpression can be used as a tool for the differentiation of follicular lymphoma and follicular hyperplasia. In cats, little information about the expression of Bcl-2 in follicular lymphoma exists. We investigated 18 follicular lymphomas histologically and immunohistochemically for the expression of Bcl-2, CD3, CD45R, and feline leukemia virus. Clonality was assessed by PCR for antigen receptor gene rearrangements. Although the histology resembled that of their human counterparts, diffuse expression of Bcl-2 within the follicles of the feline lymphomas, as seen in human cases, was not present. Only single cells within the follicles, comparable to the reactive controls, were positive for Bcl-2 expression. The mean survival time of 4.6 y confirmed the indolent character of the tumor. None of the clinical parameters assessed were statistically significant predictors of survival. Furthermore, a statistically significant difference in survival of animals with or without anti-neoplastic therapy was also not demonstrable.

Various non-proportional hazard models have been developed in the literature for competing risks data. The regression coefficients under these models, however, typically cannot be compared directly. We propose new methods to quantify the average of the time-varying cause-specific hazard ratios and subdistribution hazard ratios through two general classes of transformations and weight functions that are chosen to reflect the relative importance of the hazard ratios in different time periods. We further propose an [Formula: see text] -norm type of test statistic that incorporates the test statistics for all possible pairs of the transformation function and weight function under consideration. Extensive simulations are conducted under various settings of the hazards and demonstrate that the proposed test performs well under all settings. An application to a clinical trial in follicular lymphoma is examined in detail.

Objective This study was conducted with the aim of making the contribution to a decision for treatment and determination of the modalities in patients diagnosed with non-Hodgkın lymphoma which increasingly become widespread in the geriatric population. Materials and methods Ninety-one patients aged over 65 years diagnosed with lymphoma and treated in Bezmialem Vakıf University Medical Faculty Hospital and Haseki Training and Research Hospital between 2008 and 2013 were retrospectively evaluated. Finally, 63 patients for whom data could be reached were included in the study. Results Examining the results, histological diagnoses of our patients were as follows: diffuse large B-cell lymphoma (50.8%), follicular lymphoma (23.8%), marginal zone lymphoma (12.7%), mantle cell lymphoma (4.8%), T-cell lymphoma (4.8%), lymphoplasmacytic lymphoma (1.6%) and small lymphocytic lymphoma (1.6%). Stages at the time of diagnosis were early stage by 33.3% and late stage by 66.7%. Of the patients, 36.5% had a low-intermediate and 63.5% a high-intermediate International Prognostic Index score. According to the Eastern Cooperative Oncology Group scoring, 34.9% of the patients have an Eastern Cooperative Oncology Group score of 2–4. Activities of daily living score of 33.3% patients was under 5. Looking at the responses to treatment, the complete response was found in 50.8%, partial response in 4.8%, stable disease in 1.6% and progressive disease in 9.5% of the patients. The mean follow-up duration of patients was found as 25.2 months and disease-free survival after remission as 20.2 months. Conclusion We found that we have achieved a complete remission in more than half of our patients (50.8%). Based on this, treatment should aim remission in elderly patients.

Objective: To review the mechanism of action, clinical efficacy, safety, dosage, administration, and role of copanlisib in the treatment of relapsed follicular lymphoma (FL). Data Sources: Sources of information were identified through searches of PubMed (August 2014 to January 2019) using the key terms copanlisib, Aliqopa, PI3K inhibitor, and BAY 80-6946. Unpublished abstract information was obtained from the American Society of Clinical Oncology. Study Selection and Data Extraction: Review articles and studies in the English language evaluating the pharmacology, efficacy, and safety of copanlisib were included. Data Synthesis: Copanlisib is the first intravenous phosphatidylinositol 3-kinase (PI3K) inhibitor approved for the treatment of relapsed FL in patients who have received at least 2 prior systemic therapies. The safety and efficacy of copanlisib has been studied in the multicenter, single-arm, phase II CHRONOS-1 study. The results reported for FL patients were an objective response rate of 59%, a complete response of 14%, median duration of response of 22.6 months, and median progression-free survival of 11.2 months. The most common adverse events reported were hyperglycemia and hypertension, which were infusion related and transient. Relevance to Patient Care and Clinical Practice: Copanlisib is unique in that it is a pan–class I PI3K inhibitor with preferential inhibitory activity against the PI3K-α and PI3K-δ isoforms. It has a more favorable safety profile than the other agents in its class with no late-onset toxicities. Conclusions: Copanlisib provides an alternative option for patients with relapsed FL. It is safe and effective and has an acceptable toxicity profile.

Primary colorectal follicular lymphomas are rare indolent lymphoid neoplasms in humans that have not been reported in dogs. We describe 3 cases of primary colorectal follicular lymphoma in dogs with histologic and immunohistochemical features similar to their human counterpart. Initial clinical signs in all dogs included tenesmus, hematochezia, and a palpable rectal mass. Two dogs were castrated males and 1 an intact female, between 9 months and 2 years of age, and of varied breeds. All 3 cases of colorectal follicular lymphoma were characterized by proliferation of follicular germinal centers with no polarity or mantle zone and were composed of centrocytes admixed with fewer centroblasts. By immunohistochemistry, lymphoid cells expressed CD20, BCL2, and BCL6 and lacked expression of CD3, CD5, and cyclin D1. Polymerase chain reaction for rearrangements of the immunoglobulin heavy chain confirmed a monoclonal population in all cases. In 2 of the 3 cases, a solitary nodular colorectal mass was excised and appeared curative; however, the third case had multiple colorectal masses and the animal developed multicentric lymphoma. This case series immunohistochemically characterizes and distinguishes colorectal follicular lymphoma from atypical lymphoid hyperplasia.

Marginal zone lymphoma (MZL) and mantle cell lymphoma (MCL) belong to a subgroup of indolent B-cell lymphomas most commonly reported in the canine spleen. The goal of this study was to characterize the immunophenotype of splenic MZL and MCL in comparison to their human counterparts. Ten MCLs and 28 MZLs were selected based on morphology. A tissue microarray was generated, and expression of CD3, CD5, CD10, CD45, CD20, CD79a, Pax-5, Bcl-2, Bcl-6, cyclin D1, cyclin D3, MCL-1, MUM-1, and Sox-11 was evaluated. Neoplastic cells in all MCLs and MZLs were positive for CD5, CD20, CD45, CD79a, and BCL2 and negative for CD3, CD10, Bcl-6, cyclin D1, and cyclin D3. Positive labeling for Pax-5 was detected in 8 of 10 MCLs and 26 of 28 MZLs. Positive labeling for MUM-1 was detected in 3 of 10 MCLs, and 27 of 28 MZLs were positive for MUM-1. No MCLs but 8 of 24 MZLs were positive for MCL-1. Canine splenic MZL and MCL have a similar immunophenotype as their human counterparts. However, human splenic MCL overexpresses cyclin D1 due to a translocation. A similar genetic alteration has not been reported in dogs. In addition, in contrast to human MZL, canine splenic MZL generally expresses CD5. Following identification of B vs T cells with CD20 and CD3, a panel composed of BCL-2, Bcl-6, MUM-1, and MCL-1 combined with the histomorphological pattern can be used to accurately diagnose MZL and MCL in dogs. Expression of Bcl-2 and lack of MCL-1 expression in MCL may suggest a therapeutic benefit of BCL-2 inhibitors in canine MCL.

Purpose: To present cases of primary lacrimal sac lymphoma in a Japanese population. Methods: In this retrospective case series, five cases (two males and three females; mean age: 49.8 years; age range: 38–62 years) were included. Clinical features, diagnostic findings, and treatment outcomes were collected and reviewed. Results: Most patients presented with a swelling or mass in the medial canthal area. Only one patient presented with epiphora, while another patient also complained of pain which was due to inflammation. Imaging studies revealed a lacrimal sac mass with involvement of the nasolacrimal duct and variable involvement of the nasal cavity. Histopathological findings revealed three cases of diffuse large B-cell lymphoma, one case of extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue, and one case of follicular lymphoma. Four cases were treated with a combination of chemotherapy and immunotherapy, with one case necessitating additional radiotherapy. One case was treated with immunotherapy alone. The mean follow-up was 23 (range: 3–50) months. Four cases showed complete remission, while the remaining patient is still ongoing treatment. Conclusion: Diffuse large B-cell lymphoma is the most common type of lacrimal sac lymphoma in this series. Lacrimal sac tumors should be ruled out in the presence of epiphora, dacryocystitis, or a mass in the medial canthus, even in the absence of pain or bleeding. Combined chemotherapy and immunotherapy is an effective treatment for these cases.

Meta-analysis of interventions usually relies on randomized controlled trials. However, when the dominant source of information comes from single-arm studies, or when the results from randomized controlled trials lack generalization due to strict inclusion and exclusion criteria, it is vital to synthesize both sources of evidence. One challenge of synthesizing both sources is that single-arm studies are usually less reliable than randomized controlled trials due to selection bias and confounding factors. In this paper, we propose a Bayesian hierarchical framework for the purpose of bias reduction and efficiency gain. Under this framework, three methods are proposed: bivariate generalized linear mixed effects models, hierarchical power prior model and hierarchical commensurate prior model. Design difference and potential biases are considered in all models, within which the hierarchical power prior and hierarchical commensurate prior models further offer to downweight single-arm studies flexibly. The hierarchical commensurate prior model is recommended as the primary method for evidence synthesis because of its accuracy and robustness. We illustrate our methods by applying all models to two motivating datasets and evaluate their performance through simulation studies. We finish with a discussion of the advantages and limitations of our methods, as well as directions for future research in this area.

Azacitidine is a first-in-class demethylating agent, and it is widely used globally as a first-line treatment for higher-risk myelodysplastic syndrome (MDS). Here, we report the case of a patient with MDS who suffered from a rare adverse event, an acute lung injury (ALI), which was suspected to have been caused by azacitidine and was successfully treated with corticosteroids. As it is a rare, but critical, adverse event, clinicians should consider ALI as one of the differential diagnoses in cases where 1) pneumonia and fever of unknown etiology arise in MDS patients treated with azacitidine, 2) antimicrobial agents are not effective, and 3) microbiological tests produce negative results.

Composite lymphomas consist of 2 or more distinct lymphomas occurring in a single anatomical site or simultaneously in different sites and can be composed of any combination of B-cell non-Hodgkin lymphoma (NHL), T-cell NHL, or Hodgkin lymphoma (HL). Cases of composite lymphomas with more than 2 lymphomas are extremely rare, with only 4 reports in the literature. We report the case of a 49-year-old man with a triple composite lymphoma in a single lymph node, consisting of small lymphocytic lymphoma, follicular lymphoma, and mantle cell lymphoma in situ. The patient received multiple courses of chemotherapy and an autologous stem cell transplant, which resulted in complete remission. Then, 6 years after the stem cell transplant, he developed classical HL. This unique case is, to our knowledge, the first report of a patient with triple composite lymphoma consisting of 3 small mature B-cell NHLs, who subsequently developed a fourth lymphoma.

Purpose A large number of new therapeutic agents have been studied for patients with relapsed/refractory follicular lymphoma (FL). Among new therapies, idelalisib, a novel PI3K inhibitor, shows promising results in the management of this disease. Case report We describe the case of a 39-year-old patient with a diagnosis of grade 3a FL and a Follicular Lymphoma International Prognostic Index score of 2, who underwent several lines of therapy (including autologous stem cell transplant) with transient responses or no response at all. The patient was subsequently treated with 5 courses of idelalisib monotherapy, achieving a partial response. No relevant toxicities occurred. The patient underwent allogeneic stem cell transplant (allo-SCT) from an unrelated donor and obtained a complete response, which was confirmed after 3, 6, 9, and 12 months, and is still ongoing. Conclusions As previously reported, the achievement of a good response is predictive for a better outcome after allo-SCT: idelalisib represents an effective treatment option for patients with relapsed/refractory FL, which can also be adopted as a bridge to allo-SCT.

Purpose The higher sensitivity of new diagnostic tools makes it easier to detect relapse in asymptomatic stages when classic procedures of lymph node biopsies are difficult to perform. The aim of this article is to describe the combination of gamma probe and 18F-FDG positron emission tomography-computed tomography (PET-CT) images in combination with sentinel lymph node biopsy technique for detection of nonpalpable lymph nodes. Methods After a dose of 18F-FDG was administered and PET-CT images that showed the location of suspected pathologic lymph nodes were obtained, transcutaneous localization of the lymph nodes with the highest captation of the tracer was done. The gamma probe was programmed to detect the radioactive signal from the F18, instead of the Tc99m that is usual in the sentinel node biopsy technique. Once the hottest point was detected, a short incision was made on this area, and suspicious nodes with the highest uptake registered by the gamma probe were localized and removed. After the surgical removal from the operating field, the surgical pieces stood positive to the gamma probe. Lymph node involvement, and subsequent relapse, was diagnosed before their clinical manifestation. Conclusions This methodology confirms new horizons for the surgical approach of lymph node biopsies in patients with previous tumors with 18F-FDG avidity and suspicion of relapse.

We encountered a patient with a tongue base lymphoma that we initially diagnosed as a lingual tonsil in view of its benign appearance. We established the correct diagnosis of Waldeyer ring lymphoma by histology. This case led us to conduct a study of all cases of Waldeyer ring lymphoma that had been treated at our center during a 10-year period. We retrospectively examined our case records and found 35 such cases. From this group, we excluded 5 cases because of incomplete data. Thus our final study group was made up of 30 patients—14 males and 16 females, aged 14 to 76 years (mean: 51.6; median 54). The primary presenting signs and symptoms were dysphagia (n =17 [57%]), a neck mass (n = 7 [23%]), nasal symptoms (n = 5 [17%]), and pain (n = 1 [3%]). Only 4 patients (13%) had B symptoms. A total of 20 patients (67%) presented with tonsillar involvement, 8 (27%) with nasopharyngeal involvement, 1 (3%) with tongue base lymphoma, and 1 with anterior tongue involvement. Most patients (77%) presented at an early stage. Histologically, 25 patients (83%) had high-grade diffuse large B-cell lymphoma, 4 (13%) had T-cell lymphoblastic lymphoma, and 1 (3%) had follicular lymphoma. Twenty-one patients (70%) were treated with chemotherapy, 4 (13%) received adjuvant chemotherapy with either radiotherapy or surgery, 3 (10%) resorted to other forms of treatment (primarily traditional remedies), and 2 (7%) declined treatment altogether. There were 14 patients (47%) alive at the end of the study period.

An 11-year-old, spayed female domestic shorthair cat was presented for a right flank wound. On clinical examination, a single non-painful skin tear lesion with irregular edges was detected. During the examination, star-shaped cigarette paper-like skin lesions appeared spontaneously. An abdominal mass was also palpated. Feline skin fragility syndrome (FSFS) was suspected and a multicentric lymphoma was diagnosed by fine needle aspiration. The cat’s condition declined and it died spontaneously. Post-mortem examination confirmed the diagnosis of lymphoma. Neoplastic lymphocytes were not observed in the skin. Histological analysis of the skin was consistent with the morphological aspects of FSFS. A possible direct link between the two conditions remains a matter of speculation, but this case report provides the first description of FSFS associated with multicentric follicular lymphoma. Thus, multicentric follicular lymphoma should be considered as a differential diagnosis in cats presenting with FSFS.

Cutaneous lymphoid hyperplasia (CLH) is a reactive polyclonal benign lymphoproliferative process predominantly composed of B cells or T cells, either localized or disseminated. The authors report histomorphologic, immunophenotypic, and genotypic findings of 2 cases of B-cell CLH demonstrating progressive transformation of germinal center (PTGC). Histologically, most of the lymphoid follicles were PTGCs with a few hyperplastic germinal centers. PTGC was characterized by enlarged but well-circumscribed follicles without clear demarcation of the germinal center and mantle zone, which contained a predominance of small lymphocytes and variable numbers of centrocytes, centroblasts, and immunoblasts. However, there were no centroblasts and immunoblasts resembling lymphocytic and/or histiocytic Reed—Sternberg cell variants in nodular lymphocyte—predominant Hodgkin lymphoma (NLPHL) in either lesion. These unusual CLHs should be differentiated from the primary cutaneous marginal zone B-cell lymphoma, primary cutaneous follicular lymphoma, particularly “floral variant,” or NLPHL. To avoid overdiagnosis and overtreatment, immunophenotypic and genotypic studies are required along with careful morphologic examination.

T.M. is a 61-year-old man with a medical history significant for type 2 diabetes mellitus, rheumatoid arthritis, hypothyroidism, and hyperlipidemia. For these, he had been prescribed (via physicians other than the authors) levothyroxine, metformin, glyburide, and fenofibrate. Regarding the diagnosis of follicular lymphoma, T.M. first presented to his primary care provider in April 2004 complaining of enlarged bilateral cervical and inguinal lymph nodes. Shortly before he noticed the lymph nodes, T.M. had experienced a period of profound situational stress followed by a case of Bell palsy. In June 2004, after an initial workup, histological examination of an excised left cervical node revealed follicular lymphoma, grade 1/3 with focal areas of grade 2/3, bcl-2 positive. T.M. was promptly referred to medical oncology by his primary physician, and a chemotherapeutic regimen was prescribed. Fearing the side effects, T.M. declined treatment. The medical oncologist offered no other therapeutic options except for observation. T.M. remained symptomatic with noticeably enlarging lymph nodes. On November 28, 2005, 17 months after the initial medical presentation and 15 months after diagnosis, T.M. presented to the Integrative Medical Center of New Mexico (medical office authors B.M.B. and A.J.B.). There, T.M. revealed a chief complaint of multiple large and enlarging cervical and inguinal lymph nodes. Physical examination revealed the greatest dimension of the largest cervical node (left side) at approximately 7.62 cm and that of the left inguinal region at approximately 12.7 cm. The latter node was particularly symptomatic and painful. The positron emission tomography (PET)/ computed tomography (CT) imaging from December 13, 2005, read as follows

We present 3 patients with a sclerosing variant of follicular lymphoma that arose from the submandibular gland and resembled "Kiittner tumor." All 3 patients developed a painless unilateral tumor in the submandibular region. Histologically, all 3 lesions were categorized as follicular lymphoma grade 2. The neoplastic follicles were found to be separated by thick connective tissue, and periductal chronic inflammation with periductal fibrosis and duct ectasia was found in the residual atrophic gland. Immunohistochemistry revealed that all of the lesions contained a monoclonal tumor cell population. The immunophenotyopes of the lymphoma cells were CD 10+, CD 20+, CD 79a+, BCL-6+, CD 3-, CD 5-, CD 21-, CD 23-, CD 43-, CD 45RO-, BCL-2-, and Cyclin DI -. Two of the 3 patients exhibited clonal bands for the IgH gene by polymerase chain reaction assay. "Kiittner tumor," which is a common fibrosing, chronic inflammatory lesion of the submandibular gland, is sometimes diagnosed as a malignant tumor. This study indicates that this sclerosing variant of follicular lymphoma should be added to the list of different diagnoses for “Kuittner tumor.”

PURPOSE. Paraneoplastic neurological syndromes are well-known sequelae of some malignancies. To our knowledge, a syndrome mimicking progressive external ophthalmoplegia had never been reported preceding the diagnosis of a lymphoma. CASE REPORT. A 63-year-old man developed progressive external ophthalmoplegia, without any other neurological symptoms, as the initial manifestation of a follicular lymphoma grade III. The ophthalmoplegia resolved after two cycles of combination chemotherapy. CONCLUSIONS. The ophthalmologist, when confronted with a progressive extemal ophthalmoplegia, should consider a neurological paraneoplastic syndrome associated with a tumor as a possible diagnosis.

A case of centroblastic centrocytic follicular lymphoma arising within a bilateral adenolymphoma of the parotid glands with Involvement of the adjacent lymph nodes is reported. The patient was treated with combination chemotherapy and three years after the first cycle of therapy there was no evidence of disease. The occurrence of primary malignant lymphomas in the lymphoid stroma of an adenolymphoma has seldom been discussed in literature. All cases reported of follicular centre cell type were characterized by an indolent clinical course.

T-cells are an integral part of normal follicular centers and many follicular center-cell (FCC) lymphomas. Because the functional role of these cells remains imprecisely determined and because ultrastructural localization of the T-cell antigen receptor-associated CD3 antigen has not been previously reported, an immunoultrastructural study of four tonsils and four FCC lymphomas was performed using an anti-CD3 antibody (UCHT-1). Normal interfollicular CD3-positive T-cells always demonstrated surface membrane positivity, as did 94% of normal and 88% of neoplastic FCC-associated CD3-positive cells. Conversely, whereas only 5% of normal interfollicular CD3-positive cells showed perinuclear positivity, 58% of normal and 38% of neoplastic FCC-associated CD3-positive cells did (p less than 0.001). Definite endoplasmic reticulum (ER) staining for CD3 was identified in 4% and 8% of cells associated with normal or neoplastic FCC, respectively, but in none of the T-zone lymphocytes. Because the perinuclear space is reported to be a site of protein synthesis in cells with little ER, and because of the occasional ER staining observed in cells with perinuclear staining, perinuclear CD3 positivity probably represents CD3 synthesis in mature tonsillar T-cells. The frequency of perinuclear positivity in the FCC-associated T-cells, together with the loss of surface positivity in some cells at this site, suggests that this could represent in vivo T-cell "activation" in follicular centers, with modulation and resynthesis of the CD3 antigen. Furthermore, the results demonstrate a similar phenomenon in the T-cells associated with neoplastic follicular center cells.

The authors describe the results of histological, cytomorphological, cytochemical and immunological studies carried out in two cases of follicular lymphoma characterized at onset by an exceptional degree of splenomegaly. Although several different histological types seem to be capable of giving rise to prominent splenic involvement, the authors, on the basis of the reported findings, suggest the possibility that some cases of follicular lymphoma presenting with conspicuous splenomegaly and which at present are classified in the group of the so-called intermediate lymphocytic lymphoma, might be an expression of proliferation of a cell type normally recognizable in the marginal zone of the splenic follicles.