Cases Of Small Lymphocytic Lymphoma Research Articles

Simultaneous occurrence of papillary thyroid carcinoma, medullary thyroid carcinoma, and lymphoma: A case report.

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, the coexistence of PTC and medullary thyroid carcinoma (MTC) is uncommon. While the simultaneous occurrence of both cancers with small lymphocytic lymphoma (SLL) in lymph nodes with PTC metastasis is very rare. This study presents a unique case of concurrent PTC, MTC, and SLL, highlighting the exceptional rarity of these coexisting tumors. A 75-year-old female with a thyroid tumor underwent total thyroidectomy, bilateral central neck lymph node dissection, and right radical neck lymph node dissection. Histopathological examination revealed a low-grade medullary thyroid carcinoma (MTC) in the left lobe and classical papillary thyroid carcinoma (PTC) in the right lobe, with PTC metastasis in the cervical lymph nodes and concurrent SLL in the affected lymph nodes. Coexistence of PTC, MTC and SLL in the same patient is rare, there are currently no standardized treatment guidelines due to the limited literature. However, it is essential to consider not only the treatment for each type of tumor but also the potential risks or conflicts associated with the treatments. In the case reported in this paper, the papillary carcinoma invaded the capsule of the right lobe of the thyroid and metastasized to the cervical lymph nodes, warranting radioactive iodine therapy. However, considering the potential negative impact of radioactive iodine on the pre-existing lymphoma, the radioactive iodine therapy was postponed. Meanwhile, constant monitoring of calcitonin and thyroid globulin should be performed to monitor tumor recurrence as was performed in the present case. Since MTC, PTC, and SLL may coexist, patients with PTC deserve careful surveillance for the other disease entities. This case underscores the need for heightened awareness among clinicians, radiologists, and pathologists regarding the possibility of concurrent thyroid tumors and abnormal lymph nodes, guiding comprehensive pre-operative evaluations and postoperative monitoring strategies. This study aims to provide a warning for routine pathological diagnosis and contribute data for related research.

Small Lymphocytic Lymphoma Presenting as Breast Mass: A Rare Case Report

Abstract: Primary breast lymphoma is rare and it accounts for around 0.5% of malignant breast neoplasms. Small lymphocytic lymphoma (SLL) is a subtype of non-Hodgkin lymphoma originating from a B-cell lineage. This report presents a case of primary SLL of the breast with lung metastasis that had excellent clinical response. We reported a 67-year-old female complained a right breast mass that suddenly appeared after she got massage on her right left arm. The mass was swollen and painless with no systemic complications. The specimen was submitted to histopathology department and it revealed small diffuse lymphocytic lymphoma. Chest X-ray showed a lung metastasis. The patient was then treated with CHOP regimens (Cyclophosphamid, Doxorubicin, Vincristin, and Prednison) and the clinical result was excellent. The side effects of the medication were minimal. In conclusion, primary breast lymphocytic lymphoma is rare and this case highlights the differential diagnosis for a painless breast mass. The treatment must be individualized and multimodal, with chemotherapy being the most accepted treatment. Keywords: breast lymphoma; breast mass; malignancy

CLL-140: Chronic Lymphocytic Leukemia Presenting as a Solitary Breast Mass

An 80-year-old woman with a past medical history of hypertension and no prior history of malignancy underwent a screening mammogram followed by a breast ultrasound that showed a right breast mass. She remained asymptomatic. The physical exam did not reveal any palpable lymphadenopathy nor hepatosplenomegaly. Peripheral blood smear showed absolute lymphocytosis of 69% with a normal total white blood cell count of 8.1 without dysplastic cells, blasts, anemia, or thrombocytopenia. Breast ultrasound showed an irregular hypoechoic mass measuring 0.7 x 0.5 x 0.5 cm. Subsequent US-guided core biopsy showed non-Hodgkin B-cell lymphoma positive for cluster designation (CD)20 and CD5. Bone marrow aspirate and core biopsy revealed clusters of small-to-medium atypical lymphocytes positive for CD20, CD79a (weak), with a co-expression of CD5 (strong) and CD23CD138, findings that are compatible with Small Lymphocytic Lymphoma (SLL)/Chronic Lymphocytic Leukemia (CLL). Positron Emission Tomography scan showed an uptake within the right breast only. She is being managed with observation and close follow-up. Breast lymphoma (BL) represents around 0.5% of malignant breast neoplasms. Diffuse Large B-Cell Lymphoma (DLBCL) and follicular lymphoma are the predominant subtypes. SLL and CLL are subtypes of non-Hodgkin lymphoma originating from a B-cell lineage. While there have been reported cases of CLL and SLL manifesting as BL, the incidence still is very low and limited to case reports. Moreover, they have been reported to be found concomitantly with breast carcinoma. Most BL are asymptomatic when found incidentally on screening imaging, as in our patient. A hypoechoic round mass is the most common reported appearance. There are no current established guidelines for the treatment of BL. In our patient, we followed the recommendations for managing CLL. Not all breast masses are adenocarcinoma. It is critical to keep in mind the differential diagnosis lymphoproliferative disorders, melanoma, lung cancer, and gynecological malignancies.

Immunohistochemical Expression of BCL10 and Three Markers in Extranodal Marginal Zone Lymphoma and Other Small B-Cell Lymphomas

Abstract Extranodal marginal zone lymphoma (EMZL) is a low-grade B-cell lymphoma representing about the third most common non-Hodgkin lymphoma in the Western world. EMZL shows heterogeneous morphological features and expresses no specific immunohistochemical markers except B-cell markers. BCL10 and MALT mutations causing NF-kB pathway activation play an important role in oncogenesis of EMZL. Aberrant nuclear expression of BCL10 is reported in some EMZLs. Nuclear expression of BCL10 has not been well compared between EMZL and other small B-cell lymphomas. The aim of this study is to evaluate the expression of BCL10 and three markers in different small B-cell lymphomas. Tissue microarray blocks and selected tissue blocks, formalin fixed and paraffin embedded, were selected for immunohistochemical (IHC) studies. More than 100 cases of different small B-cell lymphomas include EMZL, small lymphocytic lymphoma (SLL), mantle cell lymphoma (MCL), follicular lymphoma (FL), lymphoplasmacytic lymphoma (LPL), and hairy cell leukemia (HCL) in the bone marrow biopsy. Commercially available antibodies from DAKO for BCL-10, IRTA-1, LEF-1, and SOX-11 were used according to the protocol. Immunoreactivity in greater than 20% of the tumor cells was considered positive. BCL-10 nuclear expression occurred mostly in EMZL but also in other small B-cell lymphomas except LPL and HCL. Cytoplasmic expression of IRTA-1 was detected in all cases of EMZL and also in SLL, MCL, and FL cases; it was negative in LPL and HCL. Nuclear expression of LEF-1 was detected mostly in SLL cases, a few cases of MZL, and none of the cases of MCL, FL, LPL, and HCL. Nuclear staining of SOX11 was found in most MCL cases; it was negative in all cases of SLL, EMZL, FL, LPL, and HCL. The IHC markers of BCL-10, IRTA-1, LEF-1, and SOX11 increase our ability to make accurate diagnosis of small B-cell lymphomas.

Primary central nervous system small lymphocytic lymphoma in the bilateral ventricles: two case reports

BackgroundPrimary central nervous system (CNS) small lymphocytic lymphoma (SLL), as a type of low-grade lymphoma, is extremely rare. The diagnosis of CNS SLL is challenging due to its variable clinical and radiological features, which may overlap with those of diffuse large B-cell lymphoma (DLBCL). Primary CNS SLL differs from DLBCL in that it has an indolent clinical course and a good prognosis. Thus, it is important to distinguish SLL from DLBCL. By reviewing the literature, only two cases of low-grade SLL, primarily located in the CNS and involving the brain parenchyma and dura, have been reported. To our knowledge, primary CNS SLL in the bilateral ventricles has never been reported. Interestingly, the two cases in our report are identical in terms of the clinical presentations, magnetic resonance imaging (MRI) features, pathological results and prognoses.Case presentationBoth patients presented with headaches. MRI suggested solid lesions located in the bilateral ventricles that were isointense on T1-weighted images and hypointense on T2-weighted images. After the injection of contrast agent (gadolinium, Gd), the intraventricular lesions were homogeneously enhanced and hyperperfused. CSF cytology revealed malignant cells. Brain biopsy revealed diffuse proliferation of small lymphocytes with positive labelling of B-cell immunomarkers. The primary origin in the CNS was confirmed with no evidence of systemic lymphoma. Two patients were given high doses of methotrexate-based chemotherapy and were free from symptoms and progression for more than 1-year of follow-up.ConclusionsThe presence of homogeneously enhanced intraventricular MRI lesions should raise the suspicion of primary CNS SLL.

Massive lymphadenopathy and hypereosinophilia in cd5-negative small lymphocytic lymphoma

Small lymphocytic lymphoma (SLL) is a relatively rare B-cell non-Hodgkin lymphoma that is considered to be the tissue equivalent of the much more common entity chronic lymphocytic leukemia (CLL). Most patients with SLL present with indolent generalized lymphadenopathy, which has frequently been present for several years. We hereby describe an unusual case of SLL in a patient who presented with a huge swelling at the right shoulder region and a single right enlarged axillary lymph node. The other uncommon findings were the presence of peripheral blood hypereosinophilia and CD5 immunonegativity.

XIV. The pathology of transformation of indolent B cell lymphomas.

XIV. The pathology of transformation of indolent B cell lymphomas.

Composite ALK-negative anaplastic large cell lymphoma and small lymphocytic lymphoma involving the right inguinal lymph node

Anaplastic large cell lymphoma and small lymphocytic lymphoma are two lymphoid malignancies with completely distinct morphologies and natural histories. We present a rare case of composite anaplastic large cell lymphoma and small lymphocytic lymphoma in an inguinal lymph node of an otherwise healthy 47-year-old male patient. Immunohistochemical and molecular studies identified the two populations clearly. Their separation is imperative as anaplastic large cell lymphoma can be an aggressive neoplasm and easily overlooked in cases of small lymphocytic lymphoma with a small population of anaplastic large cell lymphoma cells.

Automated Analysis of Multidimensional Flow Cytometry Data Improves Diagnostic Accuracy Between Mantle Cell Lymphoma and Small Lymphocytic Lymphoma

Mantle cell lymphoma (MCL) and small lymphocytic lymphoma (SLL) exhibit similar but distinct immunophenotypic profiles. Many cases can be diagnosed readily by flow cytometry (FCM) alone; however, ambiguous cases are frequently encountered and necessitate additional studies, including immunohistochemical staining for cyclin D1 and fluorescence in situ hybridization for IgH-CCND1 rearrangement. To determine if greater diagnostic accuracy could be achieved from FCM data alone, we developed an unbiased, machine-based algorithm to identify features that best distinguish between the 2 diseases. By applying conventional diagnostic criteria to the flow cytometry data, we were able to assign 28 of 44 (64%) MCL and 48 of 70 (69%) SLL cases correctly. In contrast, we were able to assign all 44 (100%) MCL and 68 of 70 (97%) SLL cases correctly using a novel set of criteria, as identified by our automated approach. The most discriminating feature was the CD20/CD23 mean fluorescence intensity ratio, and we found unexpectedly that inclusion of FMC7 expression in the diagnostic algorithm actually reduced its accuracy. This study demonstrates that computational methods can be used on existing clinical FCM data to improve diagnostic accuracy and suggests similar computational approaches could be used to identify novel prognostic markers and perhaps subdivide existing or define new diagnostic entities.

12-Year Experience with High-Dose Rituximab-Containing Autologous Stem Cell Transplantation for SOX11-Positive Mantle Cell Lymphoma Patients in First Remission: Emerging Lymphoma-Free Survival Plateau After 3 Years,

Abstract 4138 Background:The addition of high-dose rituximab to conditioning regimens has been shown to improve outcomes of autologous stem cell transplantation (ASCT) for mantle cell lymphoma (MCL) patients (pts) in first partial (PR) or complete remission (CR)(Tam C et al. Blood 2009,113:4144). It has been suggested that absence of SOX11 expression can identify a subtype of indolent MCL with excellent outcomes that might be managed more conservatively than conventional MCL. We now report updated results of ASCT for 40 MCL pts treated at our center between 05/99 and 10/10. We also report on SOX-11 expression in a subset of these pts. Methods and Patients:Pts had a median age of 54 years (range, 38–72), and 30% were older than 60 years. At diagnosis, 60% had IPI>1, 30% had intermediate/high MIPI, 88% had stage IV disease, and 78% had bone marrow involvement. 28% had blastic features and Ki-67 was ≥30% in 11/23 (52%) pts who were tested. Pts were treated with R-CHOP or R-hyper-CVAD × 4 cycles induction in 30% and 45% respectively (Group A). Since 2001, pts were referred to ASCT only if they failed to achieve CR with >4 cycles of R-hyper-CVAD induction (n= 10, 25%) (Group B). Prior to transplant, CR (or CR unconfirmed-CRu) was present in 62% pts; 38% were in PR, and 18% were PET+. Conditioning was R-BEAM and R-Cy-TBI conditioning in 77% and 23% respectively. Pts received R during stem cell collection with R administered at 375 mg/m2 on the day before initiating chemotherapy for stem cell mobilization, and again at 1000 mg/m2, 7 days later. Pts then received additional R at 1000 mg/m2 on days +1 and +8 after ASCT, as previously described. Pts were staged with CT, PET (whenever indicated) scans, bone marrow biopsy, and colonoscopy (if history of GI involvement) every 3 months for the first year, every 6 months for 5 years, then yearly thereafter. Results: a.SOX11: Formalin-fixed, paraffin-embedded tissue biopsy sections were assessed by immunohistochemistry (IHC) using anti-Sox-11 rabbit polyclonal antibody (Abcam, Cambridge, MA; 1:1500). For IHC controls we used a tissue microarray including 13 cases of MCL in addition to one complete section of MCL serving as positive controls, and sections from two cases of small lymphocytic lymphoma involving lymph node serving as negative controls. The 11 cases consisted of five GI biopsies, three lymph node biopsies, two bone marrows and one testis. 10/11 showed positive staining for SOX11. The case with negative staining, a GI biopsy, had scattered positive cells. b.Clinical outcome : Following transplantation, CR/CRu was achieved in 100% pts. With a median follow-up of 37 months (range, 6–145), 10 pts experienced recurrent disease. All progressions occurred within 3 years, with a clear plateau emerging subsequently (Figure). The projected lymphoma-free-survival at 10-year, was 65% (95%CI, 44–80). A tendency for a higher risk of relapse was observed in R-hyper-CVAD resistant pts (Group B) pts [4/10 pts (40%) vs 6/30 (20%) in Group A; HR 2.5 (95%CI, 0.7–9.2), p=0.2)], and in pts with ki-67 ≥30% [HR 2.2 (95%CI, 0.4–11), p=0.3). MIPI, blastic histology, age (> 60 years), disease status at transplant (CR/PR) and conditioning were not found to be of prognostic value in our study. 2 pts (5%) developed myelodysplasia, one of which was concurrent with progression. [Display omitted] Conclusions:ASCT with high-dose rituximab has the potential to cure a proportion of pts with MCL after response to induction chemotherapy. Our results are favorable despite the inclusion of pts who were resistant to R-hyper-CVAD. Randomized studies comparing this strategy to conventional chemo-immunotherapy are warranted. The prognostic significance of Ki-67 level needs to be assessed in a larger cohort of patients. Disclosures:No relevant conflicts of interest to declare.

Relevance of IgVH Gene Somatic Hypermutation and Interphase Cytogenetics in Lymphomatous Presentation of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma

Chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are regarded as the same entity, with SLL restricted to tissue cases featuring no leukemic phase. In this study, the authors evaluate a group of SLL cases for cytogenetic abnormalities and IgVH gene mutational status to illicit differences between CLL and SLL. IgVH gene polymerase chain reaction amplification and subsequent sequencing were preformed on formalin-fixed, paraffin-embedded archival tissue of 44 patients (SLL n = 34 or CLL n = 10). Cytogenetic data, CD38, and ZAP-70 expression were also evaluated for these cases. The data indicate that 9/34 (26%) SLL cases have somatic hypermutation >2%, which is less than the CLL group where 40% were mutated (4/10). Cytogenetic abnormalities were seen in 58% of the SLL cases with many showing abnormalities associated with favorable to intermediate prognosis. The authors' attempt to compare CLL with SLL with regards to cytogenetic and IgVH mutational status shows no statistically significant difference.

口蓋に発生した小細胞性リンパ腫の1例

The primary development of small lymphocytic lymphoma in the oral cavity is very rare. A review of the literature revealed that no such case has been reported previously in Japan, and only a few cases have been reported overseas. We present a case of small lymphocytic lymphoma arising in the palate. The patient was a 77-year old woman with an elastic, hard, painless mass with a smooth surface measuring 40 × 20 mm in the right palate. No particular abnormality was observed on blood tests or general examinations. A biopsy was performed for a suspected diagnosis of a benign palatal tumor. A proliferation center, which is a characteristic of small lymphocytic lymphoma, was noted on hematoxylin-eosin staining. In addition, immunological staining revealed that CD5, CD10, and cyclin D1 were negative and CD20 and CD23 were positive. Therefore, the lesion was diagnosed to be a small lymphocytic lymphoma. Three courses of R-THP-COP were administeret, and the tumor shrank immediately after the start of therapy. Complete remission with regard to both clinical and imaging findings was achieved by the end of treatment. No recurrence or metastasis has been noted for 1 year 6 months after therapy.

Combined applications of fine needle aspiration cytology and Flow cytometric immunphenotyping for diagnosis and classification of non Hodgkin Lymphoma

Aims and objectivesIn this present study we have evaluated the feasibility of sub-classification of non-Hodgkin's lymphoma (NHL) cases according to World Health Organization's (WHO) classification on fine needle aspiration cytology (FNAC) material along with flow cytometric immunotyping (FCI) as an adjunct.Materials and methodsIn this five years study, only cases suggested or confirmed as NHL by FNAC were selected and FCI was performed with a complete panel of antibodies (CD3, CD2, CD 4, CD5, CD8, CD7, CD10, CD19, CD20, CD23, CD45, κ and λ) by dual color flow cytometry. Both cytologic findings and FCI data were interpreted together to diagnose and sub-classify NHL according to WHO classification. Wherever possible the diagnoses were compared with cytology.ResultsThere were total 48 cases included in this study. The cases were classified on FNAC as predominant small cells (12), mixed small and large cells (5) and large cells (26). In five cases a suggestion of NHL was offered on FNAC material and these cases were labeled as NHL not otherwise specified (NHL-NOS). Flow cytometry could be performed in 45 cases (93.8%) and in rest of the three cases the material was inadequate because of scanty blood mixed aspirate. Light chain restriction was demonstrated in 30 cases out of 40 cases of B-NHL (75%). There were 15 cases each of κ and λ light chain restriction in these 30 cases. With the help of combined FCI and FNAC, it was possible to sub-classify 38 cases of NHL (79%) according to WHO classification. Combined FNAC and FCI data helped to diagnose 9 cases of small lymphocytic lymphoma (SLL), 2 cases of mantle cell lymphoma (MCL), 4 cases of follicular lymphoma (FL), 17 cases of diffuse large B lymphoma (DLBL) and 6 cases of lymphoblastic lymphoma. Histopathology diagnosis was available in 31 cases of NHL out of which there were 14 recurrent and 17 cases of primary NHL. Out of 15 DLBL cases diagnosed on FCI and FNAC, histology confirmed 14 cases and one of these cases was diagnosed as Burkitt's lymphoma on histology. Cases of FL (4), SLL (3) and MCL (2) were well correlated with histopathology. Out of the five cases suggestive of NHL on cytology, histopathology was available in four cases. Histology diagnosis was given as DLBL (1), SLL (1), anaplastic large cell lymphoma (1) and FL transformed into large cell NHL (1). Considering histopathology as gold standard, diagnostic specificity of combined FNAC and FCI was 100% (31/31) and sensitivity in sub-classification was 83.8% (26/31).ConclusionFNAC combined with FCI may be helpful in accurately sub-classifying NHL according to WHO classification. Many of the subtypes of NHL such as FL and MCL which were previously recognized as a pure morphologic entity can be diagnosed by combined use of FNAC and FCI. Other ancillary investigations such as chromosomal changes, cell proliferation markers etc. may be helpful in this aspect.

Interim Analysis of a Phase II Study of the Combination of Denileukin Diftitox (Ontak) and Rituximab for Relapsed/Refractory B-Cell Non-Hodgkin's Lymphoma.

Denileukin diftitox (ONTAK, Ligand Pharmaceuticals) is a genetically engineered fusion protein comprising the enzymatically active domain of diphtheria toxin and the full length sequence of interleukin-2 (IL-2) that targets malignancies expressing the IL-2 receptor. The drug has established efficacy in cutaneous T-cell lymphoma and we have previously reported its clinical activity in patients with recurrent B-cell Non-Hodgkin's Lymphomas (B-NHL) (Dang et al. J Clin Oncol 22:4095–4102, 2004). Given the significant activity of rituximab and the non-cross-resistant mechanism of action, we initiated a phase II study at MD Anderson Cancer Center to evaluate the efficacy of the combination of denileukin diftitox and rituximab in relapsed/refractory B-NHL. Patients were required to have prior exposure to rituximab, absolute neutrophil count ≥ 1000/uL, platelets ≥ 40,000/uL, serum creatinine ≤ 1.5 mg/dL, serum albumin ≥ 3.0 g/dL. Rituximab was given as an IV infusion at a dose of 375 mg/m2 on day one of each cycle. Denileukin diftitox was given at a dose schedule of 18 mcg/kg/day by IV infusion once daily for 5 days on days 2–6 of each cycle. Cycles were repeated every 3 weeks. Restaging evaluation of response was performed after every 2 cycles. Patients with stable disease or objective response were allowed to continue until a maximum of 8 cycles. Premedications (corticosteroids, antihistamines and fluids) were given prior to each drug infusion to decrease the risk and severity of acute hypersensitivity reactions. Thirty-three patients have been entered to date, with 30 being evaluable for toxicity and 28 for response. Median age was 67 (range 47–82), and median number of previous treatment was 4 (range 1–9). Among patients evaluable for response, there were 10 cases of diffuse large cell lymphoma (DLCL), 9 cases of follicular lymphoma (FL), 3 cases of transformed lymphoma from FL (T-FL), 3 cases of mantle cell lymphoma (MCL), 2 cases of small lymphocytic lymphoma (SLL), and 1 case of marginal zone lymphoma (MZL). Twenty patients (71%) were refractory to prior treatment with rituximab. The overall response rate was 32% with 3 CR (11%, 2 FL, 1 T-FL) and 6 PR (21%, 3 FL, 1 T-FL, 1 MCL, 1 SLL). Eight patients (29%) had stable disease. All responders but one had disease refractory to previous rituximab treatment and one CR occurred in a patient who had failed 4 prior treatments that included autologous transplantation. Five of the 9 responders had CD25 + histologies. Median time to progression for responders was 6 months, with the 3 CRs still ongoing at 14+, 10+ and 8+ months. Grade 3–4 toxicities were uncommon and included fatigue 9%, fever 6% and infection 6%. Two patients experienced visual changes; one patient had transient changes and has fully recovered, and the other has residual effects. The patient left with residual effects completed 8 cycles and obtained a CR The etiology of these visual changes is unknown. We conclude that the novel combination of denileukin diftitox and rituximab has significant clinical activity in this heavily pretreated population, with toxicities that can be managed with premedications and close monitoring. Accrual is ongoing.

Serum CA 125 levels in patients with chronic lymphocytic leukemia

Cancer antigen 125 (CA 125) is a glycoprotein expressed in normal tissues originally derived from celomic epithelia and its serum level is elevated in various benign and malignant conditions that involve stimulation of these tissues. Elevated levels have been reported in 40-43% of patients with non-Hodgkin's lymphoma (NHL) at diagnosis and were associated with parameters known to be associated with advanced and disseminated disease, and with event-free and overall survival. No difference in CA 125 level was found between indolent and aggressive lymphomas, and four of six patients with small lymphocytic lymphoma had elevated CA 125 levels. We therefore decided to measure serum CA 125 levels in chronic lymphocytic leukemia (CLL) patients, and evaluated them in 74 consecutive patients. The mean time from diagnosis to test was 74.5 months (range: 0-300). The mean serum CA 125 level was 16.3 U/ml (range: 3.7-133, normal value: <35 U/ml). CA 125 levels were elevated only in two patients (2.7%). To conclude, serum CA 125 levels are rarely elevated in CLL patients. It is possible that serum CA 125 levels can help differentiate between equivocal cases of small lymphocytic lymphoma and CLL.

Intra-oral small lymphocytic lymphoma

Small lymphocytic lymphoma (SLL) belongs to a family of low-grade malignant lymphomas. Its involvement in the oral cavity has not been reported previously. We describe the case of a 43 year-old male patient suffering intra-oral SLL. Microscopic examination of the incisional biopsy specimen revealed a diffuse and monotonous pattern of small lymphocytes with proliferation centers composed of prolymphocytes or para-immunoblasts. Immunohistochemical (IHC) staining demonstrated that these neoplastic lymphoid cells proved to be positive for LCA, CD5, CD20, CD79a, CD23, CD43, Bcl-2, Bcl-6, and negative for CD10, Bcl-1 (cyclin D1), CD3, CD30, as well as negative for CD68, and smooth-muscle actin, kappa and lambda. Based upon the histological features and the IHC assay pattern, a case of intra-oral SLL and its differential diagnosis using immunohistochemistry is reported here.

Intra-oral small lymphocytic lymphoma

Small lymphocytic lymphoma (SLL) belongs to a family of low-grade malignant lymphomas. Its involvement in the oral cavity has not been reported previously. We describe the case of a 43 year-old male patient suffering intra-oral SLL. Microscopic examination of the incisional biopsy specimen revealed a diffuse and monotonous pattern of small lymphocytes with proliferation centers composed of prolymphocytes or para-immunoblasts. Immunohistochemical (IHC) staining demonstrated that these neoplastic lymphoid cells proved to be positive for LCA, CD5, CD20, CD79a, CD23, CD43, Bcl-2, Bcl-6, and negative for CD10, Bcl-1 (cyclin D1), CD3, CD30, as well as negative for CD68, and smooth-muscle actin, kappa and lambda. Based upon the histological features and the IHC assay pattern, a case of intra-oral SLL and its differential diagnosis using immunohistochemistry is reported here.

Catalyzed Signal Amplification for Cyclin D1 Detection in Mantle Cell Lymphoma

Mantle cell lymphoma is characterized by a t(11;14)(q13;q32) translocation resulting in cyclin D1 protein overexpression. Immunohistochemical detection of the latter, therefore, is a useful marker for the diagnosis of mantle cell lymphoma. Nevertheless, interpretation of results is often hampered by the weak immunoreactivity obtained with routine detection techniques. This problem can be overcome by resorting to highly sensitive catalyzed signal amplification methods based on peroxidase-catalyzed deposition of a biotinylated phenolic compound. The present study compares the results obtained with catalyzed signal amplification, labeled streptavidin biotin, and dextran polymeric conjugate (EnVision+) techniques in cyclin D1 demonstration in mantle cell lymphoma. The study was performed on formalin-fixed, paraffin-embedded archival tissue from 20 mantle cell lymphoma cases. Ten cases of small lymphocytic lymphoma and 10 instances of follicular center cell lymphoma were used as controls. Antigen retrieval was done by autoclaving under controlled pressure (2 bar) and temperature (120° C) conditions. The best results were obtained after 1 minute of exposure with catalyzed signal amplification and after 6 minutes with other detection systems. Regarding cyclin D1 expression in mantle cell lymphoma cases, 17 (85%) were weakly positive and 3 (15%), moderately positive with labeled streptavidin biotin, whereas 15 (75%) were weakly positive and 5 (25%) moderately positive with EnVision+. In contrast, all 20 mantle cell lymphoma cases were strongly cyclin D1 positive with catalyzed signal amplification. No evidence of cyclin D1 immunostaining was obtained in any of the small lymphocytic lymphoma and follicular center cell lymphoma instances with any of the three methods used. In conclusion, catalyzed signal amplification methods provide a very useful tool for cyclin D1 demonstration in cases in which other immunohistochemical techniques yield inconclusive results.

Bcl-3/IgH translocation (14;19)(q32;q13) in Non-Hodgkin's Lymphomas

The recurrent cytogenetic (CG) abnormality t(14;19)(q32;q13) involving the oncogene BCL3 is described in patients with atypical chronic lymphocytic leukemia (CLL). We report four patients with non-Hodgkin's lymphoma (NHL) bearing t(14;19). All cases were female and their age ranged from 62 to 91. Histologically, there were two cases of small lymphocytic lymphoma (SLL), both CD11c positive with atypical morphology, one case of Burkitt like lymphoma (BLL), and one case of diffuse large cell lymphoma (DLC-L). One SLL patient showed t(14;19) as the sole abnormality and experienced a benign course for 8 years. The other three cases showed secondary CG progression, including tetraploidy, del(6q), t(8;22) and del(13q). These cases were aggressive in clinical behavior, including an SLL case which transformed to DLC lymphoma in 4 months. Southern analysis and long distance PCR confirmed BCL3/IgH C α translocation in one case. We propose that NHLs with t(14;19) may have evolved from the same spectrum of disease as atypical CLL. The poor prognosis of t(14;19) disease is associated with the occurrence of recurrent secondary CG changes, commonly found in B cell lymphoproliferative diseases.

The circulating auto-antibodies to p53 protein in the follow-up of lymphoma patients.

Mutant p53 proteins may be targets of the host immune system - consequently a certain proportion of cancer patients (the percentage varies according to the type of cancer) with tumors that carry p53 missense mutations develop circulating p53 antibodies. The present study was aimed at defining the occurrence of circulating antibodies to p53 protein in patients with various types of non-Hodgkin's lymphomas (NHL). Altogether, the sera of 108 cases with various histological types of NHL and of 20 healthy controls were assessed for the presence of antibodies to p53 protein with an ELISA method. In 73 cases of NHL, also the immunohistochemical staining for p53 antigen was performed to make a rough estimation of the frequency of mutational events. The development of autoantibodies to p53 protein was observed in approximately 7% of NHL patients (predominantly in the more aggressive variants of the disease, but also in one case of small lymphocytic lymphoma). This proportion represents roughly one third of the number of patients assessed (immunohistochemically) to carry a missense p53 mutation in their tumors. The autoantibodies to p53 protein can be used as a tumor marker (early appearance, high specificity) in the follow-up of a subset of NHL patients, but, unfortunately, this subset comprises only approximately 7% of NHL patients.