Signet-Ring Cell Variant of Large Cell Lymphoma

A diffuse, large cell lymphoma of palatine tonsil was found to contain a considerable number of enlarged tumor cells with prominent, hyaline, Russell body-type cytoplasmic inclusions displacing the nucleus peripherally and, thus, the morphologic features of signet-ring cell lymphoma. Immunoperoxidase staining revealed that the contents of the signet-ring cells were strongly positive for μ heavy chains and κ light chains. Ultrastructurally, Russell body-type inclusions consisted of multiple, angulated, electron-dense crystalloids enclosed within expanded segments of rough endoplasmic reticulum.     

Signet-Ring Cell Lymphoma

In a small cleaved, follicular center cell (poorly differentiated) lymphoma the majority of the cells appeared vacuolated by light microscopy. This is an example of the recently described signet-ring cell lymphoma. lmmunoperoxidase staining demonstrated that the cells contained IgG/K. Ultrastructural observations indicated that small vacuoles coalesce to form the large vacuoles, which contain microvesicles approximately 50 nm in diameter.     

Case 8: T-Cell Lymphoma with Large Multilobated Nuclei

The vestibular nerve of patients with Meniere's disease and vascular cross-compression syndrome of the root entry zone due to the antero-inferior cerebellar artery was studied. All patients underwent vestibular neurectomy using the retrosig-moid approach, which permits the removal of a long nerve segment. CA were found in the cytoplasm of astrocytes that had not shown signs of degeneration at the central portion of the vestibular root entry zone. No membrane intervened between CA and the surrounding cytoplasm, which was rich in filaments, in particular near the CA, and poorly equipped with other organelles. CA were round or oval inclusions measuring 10–12 μm in diameter. The matrix of the CA was composed of low-density amorphous material, with irregular masses displaying a medium density. A network of randomly oriented filaments and bilaminar, osmiophilic lipid fragments with the same structure and thickness of myelin layers were embedded in the matrix. The CA rich in bilaminar fragments were recognizable also at low magnification for their high electron density. In the astrocytic cytoplasm, near the CA, round or oval-shaped, electron-dense bodies with a multilamellar structure were often visible. These results confirm the hypothesis that CA may contain degenerating myelin embedded in a microen-vironment rich in glucose polymers and that CA could be an indicator of neurodegeneration.     

Mucinous Colorectal Adenocarcinoma with Signet-Ring Cells: Immunohistochemical and Ultrastructural Study

A primary mucinous colorectal adenocarcinoma tissue with signet-ring cells, as revealed after histological evaluation, was examined ultrastructurally. The authors also analyzed the immunohistochemical data of the tissue for serotonin, vasoactive intestinal polypeptide (VIP), bombesin, somatostatin, and glucagon, using the peroxidase anti-peroxidase (PAP) method and the immunogold labeling method for light and electron microscope, respectively. Electron microscopically mucinous adenocarcinoma was characterized by the formation of small lumen. Adenocarcinoma cells were full of mucous granules of varying electron density, providing a good environment for the tumor cells to grow. They also exhibited a significant loss of microvilli and intracytoplasmic junctions, which could allow the cells to disseminate. Signet-ring cells were located in the basal site of the ducts or in the lamina propria and appeared neoplastic, with mucin accumulation intracellularly and an eccentric crescent-shaped nucleus. The cytoplasmic organelles were decreased and at the periphery of the cell. The PAP method demonstrated that these cells were strongly positive for bombesin and also positive for vasointestinal polypeptide (VIP). The immunogold method detected bombesin immunoreactivity in the vacuoles as well as in other cytoplasmic membranes, whereas VIP was localized mainly in the plasma membrane. The location of signet-ring cells combined with the immunoreactivity for bombesin and VIP indicated that signet-ring cells were of neuroendocrine origin and probably dedifferentiated enterochromaffin-like endocrine cells. These findings have implications for understanding the biological behavior of these composite malignant tumors and could help in the knowledge of the origin of signet-ring cells.     

Anaplastic Large Cell Ki-1 Lymphoma of the Stomach with Villopodial Projections: An Immunocytochemical and Ultrastructural Study and Review of the Literature

The report describes a case of anaplastic large cell Ki-1 lymphoma of the stomach with a rapidly fatal course observed in a 28-year-old woman. By electron microscopy the neoplastic cells presented long projections of the cytoplasmic membrane arranged uniformly along all the cell circumference. The morphology and distribution of these projections were characteristic, and the term villopodial is proposed for them. A review of the literature revealed 18 cases of lymphoma and 7 cases of nonlymphoid neoplasms composed of cells with projections similar to those observed in the present case. It is suggested that such tumors be denominated villopodial lymphomas and villopodial tumors. The present case is the first anaplastic large cell Ki-1 lymphoma with villopodial projections reported in the literature.     

A Case of Adult T-cell Leukemia/Lymphoma, Histologically Presenting CD30-Positive Large Cell Lymphoma

A 48 year old Japanese woman with adult T-cell leuke-mia/lymphoma (ATLL), histologically presenting CD30 positive large cell lymphoma is reported. The patient, who was from an ATLL endemic area in Japan, had cutaneous nodules in the head, trunk, and extremities, and cervical lymph node swelling; these had been found three months before her admission to our hospital. A biopsy specimen of a skin lesion showed diffuse large cell lymphoma; the lymphoma cells were positively stained with CD30 (Ki 1/ Ber H 2), CD4 (helper T), and CD25 (interleukin 2 receptor) antibodies. Anti HTLV-1 antibody (ATLA) was detected in the serum, and molecular cytogenetic studies of lymphoma cells showed both positive T-cell receptor rearrangement and HTLV-1 specific DNA sequences.     

Outcomes of Hematopoietic Cell Transplantation for Diffuse Large B Cell Lymphoma Transformed from Follicular Lymphoma

There are limited data on the outcomes of autologous or allogeneic hematopoietic cell transplantation (HCT) in diffuse large B cell lymphoma transformed from follicular lymphoma. We analyzed transplantation outcomes in 141 subjects with biopsy-proven diffuse large B-cell lymphoma transformed from follicular lymphoma reported to the Center for International Blood and Marrow Transplant Research between 1990 and 2009. Two groups were identified: autologous HCT (auto-HCT; n = 108) and allogeneic HCT (allo-HCT; n = 33). Fewer auto-HCTs were done for transformed follicular lymphoma in 2003 to 2009, with a shift favoring allo-HCT. Auto-HCT was associated with a 1-year nonrelapse mortality (NRM) of 8% (95% confidence interval [CI], 4% to 14%), 5-year progression-free survival of 35% (95% CI, 26% to 45%), and 5-year overall survival of 50% (95% CI, 40% to 59%). In contrast, allo-HCT was associated with a 1-year NRM of 41% (95% CI, 23% to 58%), 5-year progression-free survival of 18% (95% CI, 6% to 35%), and 5-year overall survival of 22% (95% CI, 8% to 41%). Auto-HCT for transformed follicular lymphoma achieves sustained remission in a high proportion of subjects. The high NRM of allo-HCT offset any benefit that might be associated with this transplantation modality.     

Cell Junctions in Lymphomas: Study of a Primary Ovarian T-Cell Lymphoma and Review of Fifty-Six Other Cases of Lymphoma

A case of primary ovarian lymphoma was studied by light microscopy, immunohistochemistry, and electron microscopy. The ultrastructural study revealed the presence of cell junctions of the paired subplasmalemmal densities and tight junctions between adjacent lymphoid cells. Fifty-six cases of non-Hodgkin's lymphoma randomly selected from the files of the Electron Microscopy Facility of the Faculty of Health Sciences, McMaster University, were reviewed. Paired subplasmalemmal densities and tight junctions were identified in five of the cases (9%). This study suggests that the absence of cell junctions should not be considered an essential criterion for the ultrastructural diagnosis of lymphomas.     

Cell Junctions in Lymphomas: Study of a Primary Ovarian T-Cell Lymphoma and Review of Fifty-Six Other Cases of Lymphoma

A case of primary ovarian lymphoma was studied by light microscopy, immunohistochemistry, and electron microscopy. The ultrastructural study revealed the presence of cell junctions of the paired subplasmalemmal densities and tight junctions between adjacent lymphoid cells. Fifty-six cases of non-Hodgkin's lymphoma randomly selected from the files of the Electron Microscopy Facility of the Faculty of Health Sciences, McMaster University, were reviewed. Paired subplasmalemmal densities and tight junctions were identified in five of the cases (9%). This study suggests that the absence of cell junctions should not be considered an essential criterion for the ultrastructural diagnosis of lymphomas.     

Unusual Nonimmunoglobulin-Containing Inclusions in a Case of Follicular Large Cell Lymphoma

Intracytoplasmic inclusion bodies were found in a case of follicular large cell lymphoma. They did not react with anti-immunoglobulin antisera and showed no enzyme reactivity. On electron microscopy the inclusions consisted of loosely packed fibrillar material not surrounded by a membrane or by rough endoplasmic reticulum. They were found only in the large lymphomatous cells. Immunocytochemistry showed a reactivity of these cells with anti-HLA-Dr and the OKT10 monoclonal antibodies.

The nature of the inclusions remains unknown. They differ significantly from those described in the literature in cases of B-cell lymphoproliferative disorders.     

Transformation of “Signet Ring Cell” Lymphoma to Typical Nodular, Poorly Differentiated Lymphocytic Lymphoma: Light Microscopic, Immunohistochemical and Electron Microscopic Observations

Malignant lymphoma with intracellular immunoglobulins giving a “signet ring” appearance to the lymphocytes is a recently described morphologic variant with specific ultrastructural and immunohistochemical characteristics. We report a case that had this distinctive morphology when initially biopsied but on subsequent biopsy 2 1/2 years later had the typical appearance of a poorly differentiated lymphocytic lymphoma without “signet ring” cells. The same monoclonal immunoglobulin class and light chain type was demonstrated in both biopsies using immunohistochemical techniques. Rare cells in the second biopsy showed the characteristic ultrastructural findings. These findings support the concept of a continuum of cell types in malignant lymphoma, with transformation toward a cell line lacking the peculiar characteristics resulting in this unique appearance.     

培门冬酶联合CHOP治疗弥漫大B细胞淋巴瘤的临床观察

目的探讨培门冬酶(pegasparaginase,PEG-Asp)联合CHOP方案治疗弥漫大B细胞淋巴瘤的疗效及对免疫功能的影响。方法选取2014年6月至2017年12月我院住院治疗的120例晚期弥漫大B细胞淋巴瘤患者,随机分为观察组及对照组,各60例,对照组给予CHOP方案化疗,观察组在对照组治疗的基础上加用培门冬酶,比较两组临床疗效、不良反应及免疫功能。结果观察组临床有效率(53/60,88.3%)高于对照组(41/60,68. 3%),差异具有统计学意义;两组治疗后CD3^+T、CD4^+T细胞百分比、CD4^+T/CD8^+T比值比较,差异均有统计学意义;两组的主要不良反应为骨髓抑制和胃肠道反应,不良反应发生率差异无统计学意义。结论培门冬酶辅助治疗弥漫大B细胞淋巴瘤临床疗效显著,不增加化疗毒性,减轻化疗药物对免疫功能的抑制,值得临床进一步推广。     

Ki-1 Lymphoma: A Case Report

A case of Ki-1 lymphoma of the large cell anaplastic type with weak leukocyte common antigen expression is presented. These tumors can sometimes demonstrate confusing immunophenotypes (weak or negative leukocyte common antigen, pan T, pan B, HMB 45, and S-100, and anomalous positive epithelial membrane antigen staining), and ul-trastructural examination may be requested. The tumor consisted of sheets of large malignant cells with large pleomorphic nuclei, prominent nucleoli, and a high mitotic rate. Ultrastructural examination showed pleomorphic tumor cells with irregular nuclei, large nucleoli, and abundant complex cytoplasm with varied organelles.     

Total Body Irradiation Is Safe and Similarly Effective as Chemotherapy-Only Conditioning in Autologous Stem Cell Transplantation for Mantle Cell Lymphoma

Autologous stem cell transplant (ASCT) consolidation has become a standard approach for patients with mantle cell lymphoma (MCL), yet there is little consensus on the role of total body irradiation (TBI) as part of high-dose transplantation conditioning. We analyzed 75 consecutive patients with MCL who underwent ASCT at our institution between 2001 and 2011 with either TBI-based (n?=?43) or carmustine, etoposide, cytarabine, melphalan (BEAM; n?=?32) high-dose conditioning. Most patients (97%) had chemosensitive disease and underwent transplantation in first remission (89%). On univariate analysis, TBI conditioning was associated with a trend toward improved PFS (hazard ratio [HR], .53; 95% confidence interval [CI], .28-1.00; P?=?.052) and similar OS (HR, .59; 95% CI, .26-1.35; P?=?.21), with a median follow-up of 6.3 years in the TBI group and 6.6 years in the BEAM group. The 5-year PFS was 66% in the TBI group versus 52% in the BEAM group; OS was 82% versus 68%, respectively. However, on multivariate analysis, TBI-based conditioning was not significantly associated with PFS (HR, .57; 95% CI .24-1.34; P?=?.20), after controlling for age, disease status at ASCT, and receipt of post-transplantation rituximab maintenance. Likewise, early toxicity, nonrelapse mortality, and secondary malignancies were similar in the 2 groups. Our data suggest that both TBI and BEAM-based conditioning regimens remain viable conditioning options for patients with MCL undergoing ASCT.     

Early Failure of Frontline Rituximab-Containing Chemo-immunotherapy in Diffuse Large B Cell Lymphoma Does Not Predict Futility of Autologous Hematopoietic Cell Transplantation

The poor prognosis for patients with diffuse large B cell lymphoma (DLBCL) who relapse within 1 year of initial diagnosis after first-line rituximab-based chemo-immunotherapy has created controversy about the role of autologous transplantation (HCT) in this setting. We compared autologous HCT outcomes for chemosensitive DLBCL patients between 2000 and 2011 in 2 cohorts based on time to relapse from diagnosis. The early rituximab failure (ERF) cohort consisted of patients with primary refractory disease or those with first relapse within 1 year of initial diagnosis. The ERF cohort was compared with those relapsing >1 year after initial diagnosis (late rituximab failure [LRF] cohort). ERF and LRF cohorts included 300 and 216 patients, respectively. Nonrelapse mortality (NRM), progression/relapse, progression-free survival (PFS), and overall survival (OS) of ERF versus LRF cohorts at 3 years were 9% (95% confidence interval [CI], 6% to 13%) versus 9% (95% CI, 5% to 13%), 47% (95% CI, 41% to 52%) versus 39% (95% CI, 33% to 46%), 44% (95% CI, 38% to 50%) versus 52% (95% CI, 45% to 59%), and 50% (95% CI, 44% to 56%) versus 67% (95% CI, 60% to 74%), respectively. On multivariate analysis, ERF was not associated with higher NRM (relative risk [RR], 1.31; P = .34). The ERF cohort had a higher risk of treatment failure (progression/relapse or death) (RR, 2.08; P < .001) and overall mortality (RR, 3.75; P < .001) within the first 9 months after autologous HCT. Beyond this period, PFS and OS were not significantly different between the ERF and LRF cohorts. Autologous HCT provides durable disease control to a sizeable subset of DLBCL despite ERF (3-year PFS, 44%) and remains the standard-of-care in chemosensitive DLBCL regardless of the timing of disease relapse.     

Large Cell Variant Ovarian Small Cell Carcinoma: Case Report

Ultrastructural data about large cell variant ovarian small cell carcinoma (LCV-SCC) are scarce and contradictory and the role of transmission electronmicroscopy (TEM) is not clear in the assessment of such tumors. The authors present a case of LCV-SCC without hypercalcemia in a 30-year-old woman. The diagnosis was confirmed by histopathological and immunohistochemical studies. Cytopathological examination of peritoneal washing showed a population of large neoplastic cells. TEM demonstrated that the neoplasia comprised two types of cells: one type showed many coarse secretory granules without dense core, and the other type was without granules and showed dilated endoplasmic reticulum and sometimes indented nuclei. The present case indicates that different underlying ultrastructural patterns, not yet well known, exist in connection with the pathological and clinical behaviour of LCV-SCC. TEM might play a role in the identification of subtypes of LCV-SCC with different prognostic and therapeutic impact.     

Hematopoietic Cell Transplantation for Plasmablastic Lymphoma: A Review

Plasmablastic lymphoma (PBL) is recognized by the World Health Organization as a very aggressive subtype of non-Hodgkin lymphoma. It was initially described in the setting of human immunodeficiency virus (HIV) infection, but it has since been identified in immunocompetent patients, as well. PBL is characterized by CD20 negativity and is associated with Epstein-Barr virus infection. The outcome with available therapy is poor, with median survival of less than 1 year. Multiple adverse prognostic factors have been identified, including HIV-negativity, MYC gene rearrangement, high-risk international prognostic index, and not achieving complete remission after induction therapy. The role of intensification of induction chemotherapy is controversial. Novel agents have shown some activity in relapsed setting and may have a role in upfront line of treatment. The outcome for relapsed PBL is dismal. Autologous hematopoietic cell transplantation (AHCT) appears to be feasible and may produce better results than chemotherapy, but definitive data are sparse. Chemosensitivity before transplantation might be required to benefit from such therapy. Some data suggest a better outcome of PBL if consolidation with AHCT is used in first-line setting, particularly for those with high-risk disease.     

A Filiform Large Cell Lymphoma in the Spleen: A Case Report with Immunohistochemical and Electron Microscopic Study

We describe histological, immunohistochemical, and ultrastructural findings in a filiform large cell lymphoma of the spleen in a 73-year-old man. The spleen weighed 300 g and contained a nodular mass of dimensions 4 × 2.8 × 3 cm that was lobular, raised, and well circumscribed. Light microscopically, the lesion was composed of compact cellular aggregates having large nuclei with evenly dispersed chromatin and a single large nucleolus or occasionally two to three small nucleoli. Immuno histochemically, the tumor cells were reactive to antibodies to leukocyte common antigen and MBI. Electron microscopically, most tumor cells were covered with tall, delicate, filiform cytoplasmic projections resembling microvilli in number and distribution. Filiform cytoplasmic projections varied from 50 to 200 nm in width and were at right or oblique angles to the surface. They appeared to be parallel but were frequently undulated, curved, or branching, forming in places small tufts. The pattern was more clearly noted on thick sections examined at an accelerating voltage of 200 kV.     

A Filiform Large Cell Lymphoma in the Spleen: A Case Report with Immunohistochemical and Electron Microscopic Study

We describe histological, immunohistochemical, and ultrastructural findings in a filiform large cell lymphoma of the spleen in a 73-year-old man. The spleen weighed 300 g and contained a nodular mass of dimensions 4 × 2.8 × 3 cm that was lobular, raised, and well circumscribed. Light microscopically, the lesion was composed of compact cellular aggregates having large nuclei with evenly dispersed chromatin and a single large nucleolus or occasionally two to three small nucleoli. Immuno histochemically, the tumor cells were reactive to antibodies to leukocyte common antigen and MBI. Electron microscopically, most tumor cells were covered with tall, delicate, filiform cytoplasmic projections resembling microvilli in number and distribution. Filiform cytoplasmic projections varied from 50 to 200 nm in width and were at right or oblique angles to the surface. They appeared to be parallel but were frequently undulated, curved, or branching, forming in places small tufts. The pattern was more clearly noted on thick sections examined at an accelerating voltage of 200 kV.