Acute viral lymphadenitis mimicking low-grade peripheral T-cell lymphoma. A clinicopathological study of nine cases.

Acute viral lymphadenitis, especially infectious mononucleosis (IM), often shows the presence of Reed-Sternberg-like cells, resulting in confusion with Hodgkin's disease. However, acute viral lymphadenitis requiring differential diagnosis from non-Hodgkin's lymphoma is not widely recognized. We describe the clinicopathological and immunohistochemical features of lymph node lesions from nine such patients which pose serious problems of differential diagnosis from low-grade peripheral T-cell lymphoma. There were three males and six females with ages ranging from 21 to 44 years (median 25 years). All patients had "B" symptoms and multicentric lymphadenopathy. The clinical course was also self-limiting. Each lymph node specimen showed an obvious expansion of an interfollicular area by pleomorphic and polymorphous infiltration with an increased number of arborizing postcapillary venules. The infiltrate was composed of variable numbers of small and medium-sized lymphocytes, immunoblasts, plasma cells in various stage of maturation and occasional granulocytes. The small lymphocytes usually had regular round nuclei, whereas the medium-sized lymphocytes occasionally showed nuclear pleomorphism. Hyperreactivity of B-lymphocytes, including hyperplastic germinal centers and/or foci of monocytoid B-cells, was seen in parts of the lesion. The majority of the interfollicular T-lymphocytes, including T-immunoblasts, expressed CD8 antigen. Various numbers of TIA-1-positive small and medium-sized T-cells were observed in the paracortical area. Despite these findings, the overall histological picture of this series posed serious difficulties when differentially diagnosing this condition from low-grade peripheral T-cell lymphomas such as angioimmunoblastic T-cell (AILD) and T-zone types, indicating that viral lymphadenitis occasionally presents with histological features of AILD and T-zone lymphomas. To avoid overdiagnosis and overtreatment, we emphasize the need to pay careful attention to the clinical and laboratory findings as well as the morphological features.

Inflammatory pseudotumor of the submandibular gland: report of a case presenting with autoimmune disease-like clinical manifestations.

We report a rare case of inflammatory pseudotumor arising in the submandibular gland, which presented with autoimmune disease-like clinical manifestations. A 70-year-old Japanese man developed masses in both submandibular regions. Laboratory tests revealed polyclonal hypergammaglobulinemia, high titers of antinuclear antibody, and a positive thyroid test. Histologically, the lesion was composed of multiple nodules separated by thick fibrous bands and contained a few atrophic lymphoid follicles and residual ductal structures. At higher magnification, the nodules contained numerous mature plasma cells mixed with myofibroblasts, lymphocytes, and histiocytes. Occasionally, the myofibroblasts were arranged in poorly formed fascicles and in a storiform pattern. Polymerase chain reaction analysis failed to demonstrated the rearrangement of the immunoglobulin heavy-chain gene. The patient was free of disease after 72 months follow-up. Marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type arising from salivary glands occasionally showed prominent plasma cell differentiation. The present case indicates that inflammatory pseudotumor should be added to the list of different diagnoses for mucosa-associated lymphoid tissue-type lymphoma of the salivary glands.

Lymph node necrosis in systemic lupus erythematosus. A histopathological and immunohistochemical study of four cases.

The lymph node lesions of lupus lymphadenitis are characterized by necrosis sometimes accompanied by hematoxylin bodies, but only a few immunohistological analyses of this unique lesion have been reported. In this study we investigated the immunopathogenesis of these lesions. Lymph node specimens from four patients were analyzed immunohistochemically by applying recently developed monoclonal antibodies to immunocompetent cells. Necrosis occupied almost the entire lymph node in two cases (extensive type), whereas small foci of necrosis were found in the paracortex in the remaining two (localized type). No hematoxylin body formation was detected in any of the samples. Necrosis of the small muscular arteries, arterioles and venules was seen in the necrotic areas in all four cases. In one case of the localized type, necrotizing angitis was seen in a few arterioles and venules in the non-necrotic area. By immunohistology, amorphous depositions of immunoglobulins and C3 were demonstrated in the walls of the arterioles and venules in two cases. Our findings indicate that vasculitis due to local deposition of immune complexes in the blood vessels may play an important role in the pathogenesis of necrosis in lupus lymphadenitis.

Autoimmune disease-associated lymphadenopathy with histological appearance of T-zone dysplasia with hyperplastic follicles. A clinicopathological analysis of nine cases.

Autoimmune disease-associated lymphadenopathy shows marked histopathological and clinical diversity. We describe the clinicopathological and immunohistochemical findings of nine cases of autoimmune disease-associated lymphadenopathy, which posed a serious differential diagnostic problem regarding T-zone dysplasia with hyperplastic follicles. There were two males and seven females aged 25 to 65 years (median 37 years). The patients had multicentric lymphadenopathy in association with clinical and laboratory findings suggestive of an "autoimmune disease". Four patients were diagnosed to have systemic lupus erythematosus (SLE), and the remaining five patients had antiphospholipid antibody syndrome and Sjogren's syndrome (SS), rheumatoid arthritis (RA), chronic thyroiditis, RA and SS, and SLE and SS, respectively. None of the nine patients developed malignant lymphomas during the follow-up periods from 44 to 225 months (median 103 months). The lesions were characterized by paracortical hyperplasia with prominent vascular proliferation and many lymphoid follicles with germinal centers. The paracortical area usually contained numerous small T-lymphocytes without cytological atypia, accompanied by a variable number of plasma cells, B-immunoblasts, and histiocytes. Polymerase chain reaction analysis demonstrated no clonal rearrangement of the T-cell receptor chain gene in four cases examined, although immunoglobulin heavy chain rearrangement was detected in only one case. These findings suggest that autoimmune disease-associated lymphadenopathy, especially SLE, shares the histological features with T-zone dysplasia with hyperplastic follicles. The nine cases presented here should be differentiated from T-zone lymphoma with follicles and angioimmunoblastic lymphoma with hyperplastic germinal centers. To avoid overdiagnosis and overtreatment, we emphasize the need to turn attention to these clinical and laboratory findings as well as to the morphological features.

Morphological spectrum of cyclin D1-positive mantle cell lymphoma: study of 168 cases.

Immunostaining for cyclin D1 is essential for reliable diagnosis of mantle cell lymphoma (MCL). However, a small number of cyclin D1-positive lymphomas other than MCL have been encountered. Our goal was to investigate the morphological spectrum of MCL as a disease entity, based on cyclin D1 overexpression. We reviewed 181 biopsy specimens obtained from 168 cases of cyclin D1-positive MCL. Typical findings were the presence of nodular (53.9% of cases) or diffuse (46.1%) histological patterns, containing mantle zone patterns (16.8%), naked germinal centers (33.5%) and perivascular hyaline deposition (83.2%). Unusual findings of residual germinal centers with a mantle cuff (four cases) and follicular colonization (two cases) were seen. High magnification showed a monotonous proliferation of tumor cells with cytological diversity including small (3.0%), intermediate (43.1%), medium (34.1%), medium-large (13.2%) and large (6.6%) cells. Pleomorphic and blastic/blastoid variants were encountered in 9.6 and 7.2% of cases, respectively. Three cases had foci of cells of considerable size, with a moderately abundant pale cytoplasm resembling marginal zone B cells. Two cases showed an admixture of cells which appeared transformed and mimicked the histology of chronic lymphocytic leukemia/small lymphocytic leukemia. In one, neoplastic mantle zones were surrounded by sheets of mature plasma cells, resembling the plasma cell type of Castleman's disease. An admixture of areas characteristic of MCL and of other larger cells, indicating histological progression or a composite lymphoma, were observed in seven cases. In high-grade lesions of five cases, nuclear staining of cyclin D1 was rarely detected. In our experience, cyclin D1 expression was also found in nine lymphomas other than MCL (five plasma cell myelomas, three Hodgkin's disease and one anaplastic large cell lymphoma). The application of cyclin D1 staining prompted us to recognize the broad morphological spectrum of MCL. MCL can be diagnosed with the application of cyclin D1 immunostaining, if careful attention is given to architectural and cytological features.

An Asian variant of intravascular large B-cell lymphoma: clinical, pathological and cytogenetic approaches to diffuse large B-cell lymphoma associated with haemophagocytic syndrome.

Diffuse large B-cell lymphoma with haemophagocytic syndrome (BCL-HS) has been reported mainly in Asia and is regarded as a distinct variant of intravascular lymphoma (IVL). However, it is unclear whether all cases of BCL-HS fall within the framework of IVL and available clinical information is limited. We analysed 25 cases with BCL-HS, including 11 autopsied cases (median, 66 years; male-female ratio, 1.1:1). The patients presented with fever, anaemia, thrombocytopenia, hepatosplenomegaly, haemophagocytosis, bone marrow invasion, respiratory disturbance and disseminated intravascular coagulopathy, but usually lacked lymphadenopathy, mass formation, neurological abnormalities and skin lesions. The clinical course was aggressive with a median survival of 7 months. The morphological findings were uniform: large lymphoid cells infiltrated vessels and/or sinusoids of the liver, marrow, lung, kidney and other organs. They were positive for CD19, CD20, CD79a and HLA-DR, but negative for CD10, CD23 and CD30. CD5 was positive in five out of 17 cases. Our critical review indicates that BCL-HS is the equivalent of the Asian variant of IVL.

Insulin resistance in patients with depression and its changes during the clinical course of depression: minimal model analysis.

A high proportion of patients with depression develop glucose intolerance accompanied by hyperinsulinemia, suggestive of reduced insulin sensitivity (insulin resistance). The aim of this study was to evaluate insulin sensitivity in patients with depression and its changes during the clinical course of depression. Twenty nondiabetic patients with depression (13 males and 7 females aged 44+/-14 years; body mass index [BMI] 23.2+/-2.8 kg/m2) were prospectively studied by the frequently sampled intravenous glucose tolerance test (FSIGT) and the oral glucose tolerance test (OGTT) before and after treatment of depression, and an age-, sex-, and BMI-matched control group (n = 13) was examined once by the FSIGT. Metabolic indices measuring glucose effectiveness at basal insulin (SG) and insulin sensitivity (SI) were derived from minimal model analysis. Each patient was treated by cyclic antidepressants with an 1,800 to 2,200 kcal/d food intake and underwent no exercise therapy. SI was significantly lower in patients before treatment versus control subjects (6.0+/-2.5 v 13.8+/-8.6 x 10(-5) min(-1) x mol(-1) x L, P < .01). After treatment of depression, a significant increase in SI (10.7+/-7.5 x 10(-5) min(-1) x mol(-1) x 1, P

Prognostic significance of CD56 expression for ALK-positive and ALK-negative anaplastic large-cell lymphoma of T/null cell phenotype.

Anaplastic large cell lymphoma (ALCL) is a distinct entity of non-Hodgkin lymphoma, characterized by a proliferation of pleomorphic large lymphoid cells that express CD30. Recent studies have found that a subset of ALCL aberrantly expresses a chimeric anaplastic lymphoma kinase (ALK) protein as a result of t(2;5)(p23;q35) or variant translocations. ALK-positive ALCLs feature good prognosis, but some of them lead to poor outcomes. Since CD56 is expressed in some ALCLs, its clinical significance was examined in a series of T/null cell type ALCLs. Of 143 patients, 83 (58%) showed ALK-positive staining, and of 140 patients, 25 (18%) expressed CD56. The ALK-positive subgroup was characterized by a younger age of onset (P <.0001), lower serum lactate dehydrogenase level (P =.01), better performance status (P =.03), less frequent extranodal involvement (P =.01), lower international prognostic index (IPI) categories (P =.002), and superior survival (P =.0009) in comparison with the ALK-negative group, suggesting that ALK is a specific marker defining a distinct subtype. CD56(+) cases showed a significantly poor prognosis overall (P =.002) as well as in both ALK-positive and ALK-negative subgroups (P =.02 and P =.04, respectively). Multivariate analysis confirmed that CD56 is independent of other prognostic factors, including IPI. Although CD56(+) cases showed a higher incidence of bone involvement, no other differences in clinicopathologic parameters were found between the CD56(+) and CD56(-) groups. These findings suggest that CD56 is not a marker to identify a distinct subtype of ALCL, but a strong clinical prognostic factor. Effective therapeutic approaches should be explored for high-risk ALCL patients, who can be identified by means of a prognostic model, including CD56.

Reactive follicular hyperplasia in the lymph node lesions from systemic lupus erythematosus patients: a clinicopathological and immunohistological study of 21 cases.

To clarify the clinicopathological and immunohistological findings of reactive follicular hyperplasia in systemic lupus erythematosus (SLE) lymphadenopathy, we examined 21 such cases, including four males and 17 females. Three main patterns could be delineated: pattern A, histological features of Castleman's disease (n = 6); pattern B, follicular hyperplasia with pronounced arborizing vasculature in the paracortex resembling T-zone dysplasia with hyperplastic follicles (n = 6); and pattern C, follicular hyperplasia without any other specific findings (n = 9). The patients who showed patterns A and B on histology were all female with a median age of 36 years, and presented with the lymphadenopathy within 4 months, some before a definitive diagnosis could be made. The group with pattern C included four males and five females with an age ranging from 20 to 58 years (mean, 37 years). In seven of them, the lymphadenopathy was noted 6 months or more after the therapy had been initiated. In a virological study, a small to moderate number of the lymphoid cells were positive for the Epstein-Barr virus-encoded small RNA in five of 10 cases examined. Human herpesvius 8 was not detected in the four cases examined by polymerase chain reaction and immunohistochemistry. The present study demonstrated that SLE lymphadenopathy showed histological variety and occasionally represented histopathological findings of multicentric Castleman's disease or findings similar to T-zone dysplasia with hyperplastic follicles in the biopsied specimens. We emphasize that careful attention to these morphological features, together with clinical and laboratory examinations, should allow a firm diagnosis of SLE to be made, providing information that is pertinent to the treatment of the disease. Moreover, disarray of the follicular dendritic cell (FDC) network, which could be easily detected by immunohistochemistry, was found in approximately 60% of our series. SLE lymphadenopathy should be listed as one of the diseases occasionally associated with disarray of the FDC network, although its clinicopathological significance remains unclear.

Significance of cyclin D1 overexpression for the diagnosis of mantle cell lymphoma: a clinicopathologic comparison of cyclin D1-positive MCL and cyclin D1-negative MCL-like B-cell lymphoma.

Mantle cell lymphoma (MCL) is a distinct clinicopathologic entity of non-Hodgkin's lymphoma, characterized by a monotonous proliferation of small to medium-sized lymphocytes with co-expression of CD5 and CD20, an aggressive and incurable clinical course, and frequent t(11;14)(q13;q32) translocation. We examined 151 cases of lymphoma with MCL morphology from a viewpoint of cyclin D1 overexpression, which is now easily detectable by immunohistochemistry. 128 cases (85%) showed positive nuclear staining for cyclin D1, while the remaining 23 (15%) were negative. Except for cyclin D1 immunohistochemistry, current diagnostic methods, including morphological and phenotypical examinations, could not make this distinction. Although both the cyclin D1-positive and -negative groups were characterized by male predominance, advanced stages of the disease, frequent extranodal involvement, and low CD23 reactivity, the cyclin D1-positive group showed a higher age distribution (P =.04), larger cell size (P =.02), higher mitotic index (P =.01), more frequent gastrointestinal involvement (P =.05), higher international prognostic index score (P =.05), and lower p27(KIP1) expression (P <.0001). Of particular interest is that cyclin D1-positive MCL showed significantly worse survival than cyclin D1-negative lymphoma (5-year survival: 30% versus 86%, P =.0002), which was confirmed by multivariate analysis to be independent of other risk factors. These data suggest that cyclin D1-positive and -negative groups may represent different entities and that the former closely fits the characteristics of classical, typical MCL. We therefore propose that cyclin D1-positivity should be included as one of the standard criteria for MCL, and that innovative therapies for this incurable disease should be explored on the basis of the new criteria.

Primary low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma with polypoid appearance. Polypoid gastric MALT lymphoma: A clinicopathologic study of eight cases.

In the current study, we report eight cases with primary low-grade gastric mucosa-associated lymphoid tissue (MALT) lymphoma endoscopically characterized by polypoid lesions in order to highlight their clinicopathologic significance. Four patients were male, their ages ranging from 40 to 78 years old. The resected specimens revealed a histology of low-grade MALT lymphoma characterized by dense lymphocytic infiltration predominantly in the submucosa and a relatively monotonous proliferation of centrocyte-like cells with reactive follicles and infrequent lymphoepithelial lesions. The tumor cells were of CD5-, CD10-, CD20+, BCL2+ and cycline D1- phenotype, and showed a monoclonal rearrangement of immunoglobulin heavy chain genes in the five of six cases examined. Interestingly, Helicobacter pylori (H. pylori) was detected in three (37.5%) of the eight patients, which was significantly lower than previous reports. Two of the H. pylori-positive cases initially underwent H. pylori eradication, but showed no change in their lymphomas after the cure of H. pylori infection. The clinicopathologic findings of the present cases appeared to closely resemble those of colorectal MALT lymphoma with a polypoid appearance and few association of H. pylori infection in their pathogenesis. These gastric polypoid cases may merit separate consideration because of the therapeutic problems they pose.

Nodal cytotoxic lymphoma spectrum: a clinicopathologic study of 66 patients.

The expression of cytotoxic granule-associated proteins has been reported in some T-cell or natural killer (NK)-cell lymphomas of mostly extranodal origin, but rarely of nodal origin except for anaplastic large cell lymphoma (ALCL) and Hodgkin's disease (HD). This study analyzed 66 nodal lymphomas expressing T-cell intracellular antigen-1 (TIA-1) and/or granzyme B to characterize the clinicopathologic spectrum of these neoplasms. Four main groups could be delineated. The first group consisted of p80/anaplastic lymphoma kinase (ALK)-positive ALCL (n = 35). The patients were 2 to 62 years of age (median age, 16 years), and the lymphomas pursued a relatively indolent clinical course. The tumors were phenotypically of either T- or null-cell type with constant expression of CD30, epithelial membrane antigen (EMA), and p80/ALK, but not CD15 or BCL2. None harbored Epstein-Barr virus (EBV). The second group consisted of peripheral T/NK-cell lymphoma, the nodal high-grade cytotoxic type (n = 13). The patients were 29 to 72 years in age (median age, 55 years), and the tumors pursued an aggressive clinical course. The tumors often showed pleomorphic, anaplastic, or centroblastoid morphology, and were featured by either EBV association or CD56 expression. The third group consisted of peripheral T-cell lymphoma, of the nodal low-grade cytotoxic type (n = 8). The patients, three men and five women, were 31 to 75 years old (median age, 61 years). Notably, six of them exhibited lymphoepithelioid (Lennert's) lymphoma. The fourth group consisted of cytotoxic Hodgkin's-like ALCL/HD (n = 10), included seven cases of Hodgkin's-like ALCL and three cases of HD, and was characterized by the presence of Reed-Sternberg cells and often the CD15+ phenotype. The patients were all men except for one woman, and they ranged in age from 24 to 84 years (median age, 62 years). The link among these four groups was reinforced by the presence of a highly characteristic large cell with horseshoelike or reniform nuclei-the frequent expression of CD30 and EMA-and the often lack of T-cell receptor-alphabeta. In this series, the expression of p80/ALK and CD56 was also associated with favorable and poor prognoses respectively (p<0.001, log-rank test).

Cytotoxic large T-cell lymphoma with fulminant clinical course, CD8+ and CD56- phenotype, and its relation to Epstein-Barr virus: a report of two cases.

Currently, the immunohistochemical evaluation of cytotoxic granule-associated proteins such as TIA-1 and granzyme B can be carried out on paraffin sections. This procedure has broadened our knowledge of cytotoxic lymphoid neoplasms. Their detection is now regarded as a useful adjunctive in some characterizations of cytotoxic T- or natural killer (NK)-cell lymphoma, mostly in lymphoma of extranodal origin. We report two cases of nodal cytotoxic large T-cell lymphoma with identical biologic properties. Both cases presented with systemic lymphadenopathy, lymphomatous bone marrow involvement, and thrombocytopenia. The clinical course was fulminant, and both patients died within 1 week of presentation. The cells had a characteristic immunophenotype of CD2+, CD3+, CD4-, CD5-, CD8+, CD30 -/+, CD56-, CD57-, TCR alpha/beta+, and TCR gamma/delta-. They also expressed the cytotoxic granule-associated proteins of TIA-1 and granzyme B, and exhibited clonal rearrangements of the T-cell receptor beta chain gene. Monoclonal integration of Epstein-Barr virus was also detected. The present cases exhibited clinicopathological features that were distinct from other types of malignant lymphoma expressing cytotoxic granule-associated proteins.

Mast cell sarcoma with tissue eosinophilia arising in the ascending colon.

Mast cell sarcoma is a rare disease. We report an unusual case of this neoplasm arising in the ascending colon of a 32-year-old Japanese woman who presented with abdominal pain. An ulcerating mass in the colon was resected, along with enlarged mesenteric lymph nodes. Two years after surgery, the neoplasm recurred as left cervical lymphadenopathy and an intra-abdominal mass. Despite predonine and radiation therapy, the disease progressed, and the patient died. The tumor cells had abundant fine granular or clear cytoplasm, and oval, lobulated, or indented nuclei. Numerous mature eosinophils were intermingled with the tumor cells. Immunohistologic studies on paraffin sections demonstrated that the majority of the tumor cells were strongly positive for CD45RB, CD68, and mast cell tryptase. They were unreactive, however, with a broad spectrum of antibodies against myelomonocytic and lymphocytic antigens. The mast cell nature of this rare type of tumor can be best identifiable by immunostains for mast cell tryptase.

Insulin resistance in patients with depression and its changes in the clinical course of depression: a report on three cases using the minimal model analysis.

It has been reported that depression and diabetes mellitus often occur together, and insulin resistance has been observed in patients with depression. For further understanding of the relationship of depression to insulin resistance, three patients with depression were given the oral glucose tolerance test (OGTT) and the frequently sampled intravenous glucose tolerance test (FSIGT) with minimal model analysis before and after antidepressant treatment. Depressive patients showed decreased glucose tolerance, enhanced insulin secretion, and diminished insulin sensitively during OGTT and FSIGT. These abnormalities were resolved after their recovery from depression without changes in body weight or diet.

Hodgkin's disease expressing follicular dendritic cell marker CD21 without any other B-cell marker: a clinicopathologic study of nine cases.

Reed-Sternberg (RS) and Hodgkin's (H) cells are considered to be the neoplastic cells in Hodgkin's disease (HD). Although most data suggest their lymphoid origin, the nature of these cells still remains a subject of controversy. Recently, a number of RS cells have been found to express an antigen that is also present on follicular dendritic cells (FDCs), asserting FDCs as the possible progenitor cells of H-RS cells. This prompted us to investigate whether these CD21-positive cases had distinct clinicopathologic characteristics. In a series of 94 examined cases of HD, we identified 9 CD21-positive ones (4 of 37 cases of nodular sclerosis, 1 of 41 mixed cellularity, and 4 of 12 lymphocyte depletion HD) without any other B-cell marker on paraffin sections. The patients varied in age from 16 to 82 years (median, 50 years) and included six men and three women. They had superficial or mesenteric lymphadenopathy without hepatosplenomegaly. Peripheral blood leukocytosis was seen in three patients. The clinical course was indolent, and all patients but one achieved an initial complete response with HD-based treatment regimens, although three of them relapsed. Morphologically, two subgroups could be delineated. Six of the cases were characterized, besides by the classic RS cells, by a varying number of the cells with the distinctive walnutlike or cerebrumlike nuclei and cytologically with cytoplasmic processes. Their fine structural examination also revealed villous processes, but no desmosomes. The other three cases had multinucleated RS cells often with triangular nuclei, but not cytoplasmic processes. The percentage of CD21-positive tumor cells ranged from less than 10% to 60% among the H-RS cells. These RS cells were positive for CD30 (9 of 9), CD15 (7 of 9), CD68 (1 of 8), fascin (8 of 8), S-100 protein (1 of 7), and epithelial membrane antigen (2 of 8) on paraffin sections. Notably, of eight cases examined on frozen sections, two showed immunostaining for DRC1, CD35, R4/23, and Ki-M4p. Only CD35 was also detected in the other two cases. Genotypic investigation showed germline configuration of the T-cell receptor beta and gamma chain genes and the immunoglobulin heavy chain gene in all eight cases examined. In situ hybridization showed Epstein-Barr virus sequences in four cases, three of which were examined by the terminal region analysis and showed the Epstein-Barr virus to be monoclonal. We concluded that in a small proportion (9.6%) of HD, H-RS cells might be derived from FDCs and that they appear to represent a distinct pathologic variant based on morphologic and phenotypic traits within the framework of HD.

Imprint cytology of large B-cell lymphoma with high content of epithelioid cells. A report of two cases.

An association of epithelioid cell reaction in follicular center cell lymphomas seems to be a rare phenomenon. The cytological features of this type of B-cell lymphoma from two patients are presented. In both cases, immunohistochemistry applied to paraffin sections revealed reactivity of tumor cells for CD10, 20 and 79a. The first patient, a 77-year-old male, presented with bilateral inguinal bulky masses. The second patient, a 76-year-old female, revealed left supraclavicular bulky masses. Imprint cytological specimens of these two cases showed large lymphoid cells interspersed with epithelioid histiocytes, which were present in small aggregated clusters or in isolated forms. Most tumor cells showed centroblastic morphology, whereas the minority of them looked like immunoblasts. Occasionally, a monotonous proliferation of these large atypical blastic cells was also detected. On the other hand, in some parts of the imprint specimens, numerous epithelioid cells obscured the underlining tumor cells. Reactive cells other than epithelioid cells were not prominent. These cytologic features closely resembled the histologic patterns of this rare follicular center cell lymphoma. Careful examination of the cytological specimens is needed to detect the monotonous proliferation of tumor cells to establish the diagnosis of malignant lymphoma.

Occurrence of monocytoid B-cells in reactive lymph node lesions.

Benign monocytoid B-cells are a peculiar subset of B-cells. They are closely related to marginal zone B-lymphocytes, show cytological diversity and may be recognized in a variety of reactive lymph node conditions. To analyze the incidence, cytological spectrum and phenotypic features of benign monocytoid B-cells, we investigated a series of 301 consecutively biopsied and unselected cases of reactive lymph node change from 1988 and 1995. A monocytoid B-cell reaction was identified in 46 (15%) cases and could be cytologically subclassified into two groups: 31 (67%) cases with common-type cells and 15 (33%) cases with large, transformed cells, according to the description by Plank et al. [19]. These reactions were regularly associated with follicular hyperplasia (95%) and were part of an epithelioid cell response in 24 cases (50%). Immunohistologically, both types of benign monocytoid B-cells were negative for bcl-2 protein expression, which was in contrast to the bcl-2 positive reaction in marginal zone B-lymphocytes and their neoplastic counterpart in monocytoid B-cell lymphoma. An association of Epstein-Barr virus (EBV) with monocytoid B-cells was investigated by in situ-hybridization. EBV genomes were detected in five (15%) of 31 cases tested. In each of these five cases, positive cells were represented in both high and low numbers. The morphologic features of the EBV-positive cells were not consistent with monocytoid B-cells, but rather with medium-sized to large lymphoid cells. It appeared that the occurrence of monocytoid B-cell reaction in reactive lymph node lesions was not related to EBV infection in the majority of cases.

Florid reactive follicular hyperplasia in elderly patients. A clinicopathological study of 23 cases.

Florid reactive follicular hyperplasia (FRFH) of the enlarged lymph node in elderly patients requiring biopsy is a relatively uncommon phenomenon as compared with younger age groups. We experienced 23 patients, aged 60 years or more, from whom the biopsied lymph node specimens histologically showed inappropriate FRFH for their age, in the period between 1982 and 1996. These cases were morphologically subdivided into three groups, FRFH with interfollicular plasmacytosis, that with progressive transformation of germinal center, and FRFH without additional specific findings. FRFH with interfollicular plasmacytosis were observed in 11 cases, all of whom were accompanied with several immunological abnormalities (six with rheumatoid arthritis, three with multicentric Castleman's disease and one each with myoepithelial sialoadenitis and autoimmune hemolytic anemia). Three men with uncertain etiology exhibited an unusual histology of progressive transformed germinal centers which were clinically characterized by a bulky neck mass. Among the nine cases with nonspecific FRFH, only four had a specific etiology (one each with adult onset Still's disease, chronic sinusitis, Epstein-Barr virus infection and infectious lateral cervical cyst), while the other five with unknown etiology showed abnormal laboratory findings suggestive of an abnormal humoral immune response, i.e. hypergammaglobulinemia and seropositivities for some autoantibodies. None of our patients developed malignant lymphoma during the follow-up period. Of note, 16 (70%) of the 23 cases were found to be associated with various types of imbalances of the immune system, some of which appeared to be currently ill-defined as clinicopathological entities that were simply categorized as autoimmune disease.

Multiple polypoid lesions of primary mucosa-associated lymphoid-tissue lymphoma of colon.

AIMS: This study was focused on unusual cases of mucosa-associated lymphoid tissue (MALT) lymphoma presenting with multiple polypoid lesions of the colon and rectum with a special reference to the differential diagnosis of mantle cell lymphoma. METHODS AND RESULTS: The lesions of these five cases grossly showed a segmental distribution of nodular protrusions in three patients and of innumerable small polyps in two. These patterns of involvement simulated those of multiple lymphomatous polyposis, known as the gastrointestinal presentation of mantle cell lymphoma (MCL), and caused a differential diagnostic problem between MALT lymphoma and MCL, which have different prognostic and therapeutic implications. Their histological features are almost indistinguishable from each other, especially in the small biopsy specimens via endoscope. The most important procedure for their differentiation is cyclin D1 immunohistochemistry and its negative reaction provides strong indication of MALT lymphoma. Of interest, one case showed a rare karyotypic abnormality of t(11;18)(q21;q21), which has been reported specifically in MALT lymphoma. CONCLUSIONS: This study has indicated that the multiple polypoid lesions of the colon occur not only in MCL, but also in MALT lymphoma, making differential diagnosis between the two entities necessary, and cyclin D1 immunohistochemistry is indispensable for distinguishing between them.