BCL-2 is consistently expressed in hyperplastic marginal zones of the spleen,abdominal lymph nodes,and ileal lymphoid tissue

BCL-2 is an antiapoptotic protein overexpressed in follicular lymphomas, principally as a result of the t(14;18)(q32;q21), and useful in distinguishing follicular lymphoma (usually BCL-2 positive) from follicular hyperplasia (BCL-2 negative). BCL-2 is also overexpressed in other lymphoma types without the t(14;18), including marginal zone B-cell lymphoma, because of other, poorly understood mechanisms. It has been suggested that BCL-2 immunoreactivity can distinguish between malignant (BCL-2 positive) and reactive (BCL-2 negative) marginal zone B cells. In this study, we evaluated 26 spleen, 10 abdominal lymph node, and 3 ileum specimens with marginal zone B-cell hyperplasia for BCL-2 expression immunohistochemically. We also analyzed these cases using polymerase chain reaction methods to evaluate for the presence of clonal rearrangements of the immunoglobulin heavy chain gene (IgH) using consensus V FRIII and J region primers, and the t(14;18) involving both the major breakpoint and the minor cluster regions of the bcl-2 gene. All (100%) cases of splenic, abdominal lymph node, and ileal marginal zone hyperplasia displayed strong BCL-2 reactivity in the marginal zone B cells. In all cases analyzed, IgH polymerase chain reaction demonstrated a polyclonal pattern, and bcl-2/JH DNA fusion sequences were not detected. Our results indicate that BCL-2 is consistently expressed by reactive marginal zone B cells of the spleen, abdominal lymph nodes, and ileal lymphoid tissue and should not be used as a criterion for discriminating between benign and malignant marginal zone B-cell proliferations involving these sites.     

CD10 and BCL-6 expression in paraffin sections of normal lymphoid tissue and B-cell lymphomas

In this study the authors explored the value of immunostaining for follicular center B-cell markers, BCL-6 and CD10, in paraffin sections as a tool for the differential diagnosis of B-cell lymphomas. The cases studied comprised reactive lymphoid hyperplasia (RLH; n = 19), follicular lymphoma (FL; n = 50), low-grade mucosa-associated lymphoid tissue (MALT) lymphoma (n = 24), mantle cell lymphoma (n = 19), splenic marginal zone lymphoma (n = 13), diffuse large B-cell lymphoma (DLBCL; n = 54), Burkitt's lymphoma (BL; n = 20), nodular lymphocyte predominance Hodgkin's disease (NLPHD; n = 16), and classic Hodgkin's disease (CHD; n = 13). In RLH, CD10 and BCL-6 were expressed almost exclusively by the follicular center cells. In contrast in FL, the expression of CD10 (39/50) and BCL-6 (34/36) was seen in both follicular and interfollicular neoplastic B cells. Marginal zone/MALT lymphomas and mantle cell lymphoma were always negative. In DLBCL the expression was variable for both CD10 (21/54) and BCL-6 (39/47), with some tumors, including cases of transformed follicular lymphoma (9/10), coexpressing CD10 and BCL-6, and others expressing only BCL-6, and a small group expressing neither marker, possibly reflecting the underlying primary pathogenetic events such as the rearrangement of BCL-2 or BCL-6 genes. BL was always both CD10 and BCL-6 positive. In NLPHD the L&H cells expressed BCL-6 (11/13) but not CD10, whereas in CHD BCL-6 expression was seen in half of the cases. This study demonstrates that both CD10 and BCL-6 are reliable markers of follicular center B-cell differentiation. CD10 and BCL-6 immunostaining have an important role in differential diagnosis of FL from RLH and other low-grade B-cell lymphomas. The results also suggest that a CD10/BCL-6 expression pattern may be helpful in identifying main subsets of DLBCL. However, additional studies comparing genotype with immunophenotype are required.     

Primary Lung Small B-Cell Lymphoma versus Lymphoid Hyperplasia: Evaluation of Diagnostic Criteria in 26 Cases.

Primary lung non-Hodgkin's lymphoma is a rare neoplasm mostly represented by low-grade B-cell lymphomas of mucosa-associated lymphoid tissue. Their diagnostic criteria are now well defined on surgical specimens, but pathologists may experience difficulties in distinguishing them on exiguous biopsies from benign lymphoid hyperplasia and other lymphomas. Therefore, we examined a series of 26 lung lymphoid lesions to further define the pathologic features of either lymphoma or lymphoid hyperplasia on small specimens. We observed 16 primary lung non-Hodgkin's lymphomas with a large predominance of low-grade mucosa-associated lymphoid tissue-type lymphomas (87.5%, n = 14). There were no autoimmune disorders, but three patients had a concomitant infectious disease (hepatitis C virus and Helicobacter pylori gastritis). One patient presented with a synchronous pulmonary adenocarcinoma. As well as the classical mucosa-associated lymphoid tissue cellular infiltrate, immunohistochemical characterization of the 14 mucosa-associated lymphoid tissue-type lymphomas revealed the CD20+/CD43+ centrocyte-like cell phenotype in 10 cases (71.5%). Although the lymphoepithelial lesions observed in all lymphomatous cases have been reported in lung lymphoid hyperplasia, the determination of B-cell CD20+/CD43+ phenotype of the intraepithelial lymphocytes highly increased the specificity of lymphoepithelial lesions. A monoclonal immunoglobulin heavy chain gene rearrangement was present in 71.4% of the mucosa-associated lymphoid tissue-type lymphoma specimens. Investigation of H. pylori by polymerase chain reaction detection was negative, even for the two cases associated with H. pylori gastritis.     

Cutaneous b-cell lymphomas of follicular and marginal zone types: use of Bcl-6, CD10, Bcl-2, and CD21 in differential diagnosis and classification

Cutaneous follicular lymphomas (FLs) and cutaneous B-cell lymphomas of extranodal marginal zone (MZL)/mucosal-associated lymphoid tissue (MALT) type may have morphologic overlap, despite the fact that they are thought to be of distinct derivation (germinal center vs. postgerminal center). The problem is compounded by the reported absence of bcl-2 expression by many cutaneous FLs, leading to speculation that cutaneous FL may be unrelated to nodal FL. The authors analyzed the expression of the germinal center-associated antigens bcl-6 and CD10 and of bcl-2 in 18 cutaneous B-cell lymphomas (10 FLs and eight MZLs), in relationship to CD21+ follicular structures, to clarify the relationship of nodal to cutaneous FLs and to explore the value of these antigens in differential diagnosis. The authors studied 10 cutaneous FLs (seven primary and three secondary) and eight MZLs (six primary and two secondary). The FLs (found in six men and four women age 45-75 years) involved the trunk (n = 3) and scalp, face and neck (n = 7). The MZLs (found in five women and three men age 34-81 years) involved the trunk (n = 4), face and neck (n = 2), and arm (n = 2). Immunostaining for CD21, bcl-6, CD10, and bcl-2 allowed the delineation of compartments within the tumors and yielded distinct patterns of staining in FL and MZL. In both follicular and interfollicular/diffuse areas of FL the neoplastic cells were bcl-6+ (10 of 10), often CD10+ (seven of 10, four of seven primary), and bcl-2+ (nine of 10, six of seven primary). Only three of seven cases (one of five primary) had bcl-2 rearrangement detectable by polymerase chain reaction. In the MZLs, the neoplastic B-cells were bcl-6-, CD10-, and bcl-2+ (eight of eight). Three patterns of CD21+ follicles were identified in MZL: reactive germinal centers, uniformly bcl-6+, CD10+, and bcl-2- (five of eight MZLs); colonized follicles, both bcl-6-, bcl-2+, and L26+ cells, and bcl-6+ and bcl-2- cells (five of eight MZLs); and expanded/colonized follicular dendritic cell meshworks, bcl-6- and bcl-2+ B cells with rare residual bcl-6+ and bcl-2- cells (four of eight MZLs). The authors conclude that cutaneous FLs express bcl-6 uniformly, usually express CD10 and bcl-2, and have a follicular pattern similar to nodal FL and consistent with a germinal center origin. The immunophenotype of cutaneous FL is distinct from that of cutaneous MZL, which is negative for bcl-6 and CD10. Colonized follicles in MZL, identified by CD21+ follicular dendritic cell meshworks, contained numerous bcl-6- and bcl-2+ B cells, and were readily distinguished from neoplastic follicles in FL. Conversely, CD21- interfollicular and diffuse areas in FLs contained bcl-6+ and CD10+ cells, which were not seen in diffuse areas of MZLs. Thus, the combination of bcl-2, bcl-6, and CD21 staining is useful for the distinction of cutaneous MZL from cutaneous FL.     

Nodular lymphoid lesion of the liver: an immune-mediated disorder mimicking low-grade malignant lymphoma

Three cases of unusual lymphoid infiltrate forming nodular macroscopic masses in the liver were studied in the authors' surgical pathology laboratory. These lesions posed difficulty in diagnosis, and their differentiation from low-grade lymphoma was not possible on histopathologic evaluation alone. The liver masses were analyzed histologically and immunohistochemically as well as for clonal immunoglobulin heavy chain (IgH) and T-cell receptor gamma (TCR-gamma) gene rearrangements. The lesions were seen as solitary grossly distinct firm nodules in all three patients, measuring 0.4, 0.7, and 1.5 cm, respectively, in their greatest dimensions. Two were found in livers removed because of end-stage primary biliary cirrhosis at the time of orthotopic liver transplantation, and the third was an incidental finding during laparotomy. Microscopically, these were nodules composed of small lymphocytes, plasma cells, and immunoblasts, with varying degrees of admixed acute inflammatory cells and scattered lymphoid follicles. By immunohistochemistry and molecular studies, these were found to be reactive lymphoid proliferations. All patients are alive and well at 2, 4, and 13 years, respectively. It is concluded that these cases represent a unique type of nodular lymphoid lesion, which is probably an immune-mediated benign reactive hyperplasia. It constitutes an entity by itself and must be distinguished from low-grade lymphoma. For a definitive diagnosis, immunohistochemistry and molecular studies are required.     

Colonic primary large cell lymphoma with marginal zone growth pattern presenting as multiple polyps.

We report a rare case of primary gastrointestinal lymphoma, stage IE, in a 58-year-old white man who had multiple colonic polyps measuring up to 1 x 1.1 cm. The tumor originated in the marginal zone of the follicles infiltrating the interfollicular spaces. Follicular colonization was frequently seen. The mucosa was spared by the infiltrate. Morphologically, the neoplastic cells were monomorph, intermediate-sized blasts. Rare small to intermediate sized cells, some with centrocyte-like morphology, intermingled the blastic infiltrate. The neoplastic cells expressed CD20 and had a monotypic immunoglobulin of cytoplasmic IgM (kappa) on paraffin sections. Tumor cells stained negative for CD45RO, CD5, CD10, IgD, and CD23. Polymerase chain reaction revealed a clonal V-D-J rearrangement. Bcl-1 and bcl-2 rearrangement were not detected. We therefore suggest the diagnosis of primary large cell lymphoma with marginal zone growth pattern mimicking colonic adenomas.     

Lymphoproliferative lesions in patients with common variable immunodeficiency syndrome.

We reviewed our experience with 30 nodal and extranodal lymphoid lesions from 17 patients with common variable immunodeficiency (CVID). Immunohistochemical studies were performed on biopsies from 15 patients, in situ hybridization for Epstein-Barr virus in nine cases, and gene rearrangement analysis on seven lesions. The biopsies were classified into four groups: malignant lymphoma (two cases); atypical lymphoid hyperplasia (eight cases); reactive lymphoid hyperplasia (14 cases); and chronic granulomatous inflammation (six cases). The two malignant lymphomas were diagnosed using histologic criteria; tissue was not available for the assessment of clonality. In one neoplasm, Epstein-Barr virus was identified in the tumor cells by in situ hybridization. The cases of reactive lymphoid hyperplasia and chronic granulomatous inflammation had no atypical architectural, cytologic, or immunohistochemical features. The cases of atypical lymphoid hyperplasia were of particular interest, as these patients had either widespread involvement or massive disease. The diagnosis of lymphoma was considered likely by the clinicians and, in three cases, the histologic slides were originally interpreted as malignant lymphoma by the referring pathologists. Although the architecture of these lesions appeared to be effaced on hematoxylin and eosin-stained sections, immunohistochemical analysis demonstrated preserved architecture with florid expansion of B-cell and T-cell compartments. In addition, clinical follow-up of these patients was benign, and gene rearrangement analysis in three lesions revealed no evidence of clonality. We conclude that the majority of lymphoid lesions in patients with CVID are benign. Immunohistochemical and gene rearrangement studies are particularly helpful in the assessment of cases of atypical lymphoid hyperplasia.     

Primary cutaneous follicular lymphoma: a clinicopathologic and molecular study of 16 cases in support of a distinct entity

Primary cutaneous B-cell lymphomas displaying a prominent follicular growth pattern are rare and remain poorly defined, particularly in terms of the frequency of detection of t(14;18) and whether or not, as a group, they represent an entity distinct from follicular lymphoma arising in lymph nodes. The morphologic, immunophenotypic, and clinical features of 16 cases of primary cutaneous follicular lymphoma, identified during a review of all PCBCL in the Scotland and Newcastle Lymphoma Group database, were studied and the number of cases harboring t(14;18) assessed by polymerase chain reaction using primers to the major breakpoint cluster region. Comparisons were made with stage I follicular lymphoma arising in lymph nodes and follicular lymphoma secondarily involving the skin. All cases of primary cutaneous follicular lymphoma had undergone thorough staging, including physical examination and CT scans of chest and abdomen, with 15 of 16 cases also having bone marrow aspiration and/or trephine performed. The morphology and immunophenotype of the lesions were similar to that expected in lymph nodes. All cases displayed a follicular architecture complete with follicular dendritic cell networks and comprised an admixture of CD10 and/or bcl-6-positive neoplastic centrocytes and centroblasts with 13 of 16 cases also expressing bcl-2 protein. None harbored t(14;18), a significantly different finding compared with cases of stage I nodal follicular lymphoma (p <0.001) and secondary cutaneous follicular lymphoma (p <0.039). Relapses occurred in five of 15 patients with a median time to first relapse of 20 months (range 1-73 months; mean 27.2 months). These were multiple in two patients and involved extracutaneous sites in two patients. The propensity for relapse was similar to that in a comparative cohort of stage I nodal follicular lymphoma, but the group of primary cutaneous follicular lymphoma were significantly more likely to attain complete remission; all cases of primary cutaneous follicular lymphoma were in complete remission when last seen compared with 49 of 87 patients with stage I nodal follicular lymphoma (p <0.005). No lymphoma-related deaths were encountered in 15 cases with a mean follow-up >60 months (range 5-119 months). These results support the concept of a subtype of follicular lymphoma lacking t(14;18) involving the major breakpoint cluster region, and with a propensity to arise in the skin. Despite a high relapse rate patients with primary cutaneous follicular lymphoma are more likely to achieve complete remission and may ultimately have a more favorable long-term prognosis than those with equivalent nodal disease.     

Micronodular thymoma with lymphoid B-cell hyperplasia: clinicopathologic and immunohistochemical study of eighteen cases of a distinctive morphologic variant of thymic epithelial neoplasm.

We describe 18 cases of a distinctive morphologic variant of primary thymic epithelial neoplasm characterized by a micronodular growth pattern associated with florid lymphoid follicular hyperplasia of the stroma. The tumors occurred in seven women and 11 men aged 41 to 76 years (mean, 58 years). All cases were asymptomatic and discovered incidentally on routine chest radiograph or during coronary artery bypass surgery. The tumors measured from 3 to 10 cm in greatest dimension and were well circumscribed and encapsulated. In seven cases, the lesions were grossly described as cystic or partially cystic masses. Histologically, they were characterized by a proliferation of small tumor nodules separated by abundant lymphoid stroma with prominent germinal centers. The nodules were composed of spindle cells containing oval nuclei devoid of atypia or mitotic activity. Immunohistochemical studies showed strong positivity of the spindle tumor cells for CAM 5.2 and broad spectrum keratin antibodies. The surrounding lymphoid cell population was strongly positive for LCA and L26 and showed a polyclonal pattern of staining for kappa and lambda. Stains for UCHL-1, CD1a, CD3, CD5, and CD99 were negative in the stromal lymphoid cell population. The tumor in one of the patients was associated with active pulmonary tuberculosis, and in another with anemia and splenomegaly of unknown etiology. None of the patients had clinical signs or history of myasthenia gravis or other autoimmune disorders. The present cases are interpreted as an unusual morphologic variant of spindle cell thymoma with prominent B-cell lymphoid hyperplasia. The possible significance of this phenomenon is discussed.     

Interfollicular Hodgkin's disease

An unusual pattern of focal involvement of lymph nodes by Hodgkin's disease is described which we have named "interfollicular Hodgkin's disease." It is characterized by florid reactive follicular hyperplasia which overshadows involvement of the interfollicular zones by Hodgkin's disease. The pattern can be mistakenly diagnosed as one of the many causes of reactive follicular hyperplasia. The seven cases studied did not appear to differ clinically from other more recognizable forms of Hodgkin's disease. The importance of this pattern of lymph node involvement by Hodgkin's disease rests on its misdiagnosis as a benign lesion and not on any unusual clinical features.     

CD200 (OX-2 membrane glycoprotein) is expressed by follicular T helper cells and in angioimmunoblastic T-cell lymphoma

CD200, an immunoglobulin superfamily membrane glycoprotein, is expressed in B cells, a subset of T cells, and in a range of B-cell lymphoproliferative disorders. We recently found, by immunohistochemical staining, that follicular helper T cells associated with neoplastic L and H cells in nodular lymphocyte predominant Hodgkin lymphoma, express CD200. Here we show that CD200 is expressed by follicular helper T cells in reactive lymphoid tissue, using single-color and 2-color immunohistochemical staining. Immunohistochemical staining of a range of T-cell lymphoproliferative disorders shows that the neoplastic cells in angioimmunoblastic T-cell lymphoma are immunoreactive for CD200, and the pattern of expression is similar to that of other follicular helper T-cell markers, PD-1 and CXCL13. In contrast, only a minority of cases of T-cell neoplasms other than angioimmunoblastic T-cell lymphoma are immunoreactive for CD200. A subset of CD200-positive peripheral T-cell lymphoma, not otherwise specified, cases may represent evolving angioimmunoblastic T-cell lymphoma or another neoplasm derived from follicular T helper cells. We conclude that CD200 is a useful immunophenotypic marker of angioimmunoblastic T-cell lymphoma and may be a suitable therapeutic target for an anti-CD200 immunotherapy undergoing clinical trial.     

Nodular lymphoid hyperplasia of the lung: a very rare disease entity

Nodular lymphoid hyperplasia of the lung is an uncommon disease that is considered to be a benign lesion of a polyclonal lymphoid proliferation. Because of its rarity, little is known about the clinicopathologic characteristics of nodular lymphoid hyperplasia. Some researchers have questioned whether nodular lymphoid hyperplasias are truly reactive or are marginal zone B-cell lymphomas (low-grade lymphomas of mucosa-associated lymphoid tissue) mimicking reactive lymphoid processes. We present the case of a 67-year-old woman with nodular lymphoid hyperplasia of the lung and discuss the current knowledge concerning nodular lymphoid hyperplasias.     

Follicular colonization in B-cell lymphoma of mucosa-associated lymphoid tissue

The formation of neoplastic B-cell follicles is universally accepted as diagnostic of a follicle centre cell (FCC) lymphoma. Low-grade B-cell lymphomas of mucosa-associated lymphoid tissue (MALT) are characterized by a diffuse infiltrate of cells of uncertain lineage known as "centrocyte-like" cells because of their resemblance to centrocytes (small cleaved cells). Some MALT lymphomas, however, contain numerous follicles and may even have a predominantly follicular appearance. These follicles may be reactive or show immunoglobulin (Ig) light-chain restriction, indicating their neoplastic nature. We have proposed that these neoplastic follicles are not composed of follicle centre cells but result from colonization of reactive follicles by CCL cells. In this study, the immunophenotype and genotype of 10 primary gastrointestinal lymphomas with a follicular component have been determined. One case exhibited the morphological, immunophenotypic, and genotypic features of FCC lymphoma (Ig light-chain restriction, CD10+, KB61 (CDw32)-, Jh, and bcl-2 gene rearrangement). Neoplastic follicles in the remaining nine cases, which showed the features of MALT lymphoma, were of a different phenotype (Ig light-chain restriction, CD10- KB61(CDw32)+), and these lymphomas showed Jh but not bcl-2 gene rearrangement. Taken in conjunction with the morphological features, these findings suggest that in these cases the neoplastic follicles formed as the result of colonization of previously reactive follicles by neoplastic CCL cells. Thus, not all lymphomas containing neoplastic follicles are of FCC origin. Follicular colonization, as seen in low-grade MALT lymphomas, is likely to be a recapitulation of an as yet undescribed normal immunological phenomenon that may involve marginal zone B cells.     

Follicular lymphoma of the thyroid gland

The majority of lymphomas arising in the thyroid gland are mucosa-associated lymphoid tissue lymphomas and diffuse large B-cell lymphomas, which arise from a background of chronic lymphocytic thyroiditis. Follicular lymphoma may also present in the thyroid gland, but its clinicopathologic features at this site are not well characterized, leading to difficulties in diagnosis and clinical management. We have addressed this problem by studying the clinical, morphologic, immunophenotypic, and genetic features of 22 such cases. All cases showed morphology characteristic of follicular lymphoma, however, in many the interfollicular neoplastic infiltrate was particularly prominent and all lymphomas contained readily identifiable and often striking lymphoepithelial lesions, features heretofore considered indicative of mucosa-associated lymphoid tissue lymphoma at this site. Furthermore, 13 of 18 cases for which sufficient evidence was available had clinical and/or histologic evidence of chronic lymphocytic thyroiditis. Analysis of genetic and immunohistochemical features identified 2 distinct groups. In 1 group, similar to typical adult follicular lymphoma, cases carried a t(14;18)/IGH-BCL2 and/or expressed Bcl-2, and were mostly CD10-positive and of World Health Organization (WHO) grade 1 to 2. Follicular lymphomas in the other group lacked IGH-BCL2 and Bcl-2 expression, were often of WHO grade 3 and were often CD10-negative, similar to the minority of follicular lymphomas previously described that are Bcl-2-negative and are often encountered at other extranodal sites. The 2 groups differed in clinical stage at presentation, 11 patients in the former group but none in the latter group having disease beyond the thyroid gland. Appreciation of the spectrum of morphologic, immunophenotypic, and genetic characteristics of follicular lymphoma presenting in the thyroid gland should aid both diagnosis and clinical management.     

Development of vascular neoplasia in Castleman's disease. Report of seven cases

Seven cases of vascular neoplasia arising within lesions of hypervascular follicular hyperplasia (HFH) fulfilling the criteria of Castleman's disease are described. The patients did not have evidence of acquired immunodeficiency syndrome or other immunologic disorders. The masses were solitary and located in the retroperitoneum (five cases), mediastinum (one case), and axilla (one case). Grossly, they measured up to 20 cm and had a variegated appearance. In each case two morphologically distinct processes were present: a mesenchymal spindle-cell neoplasm with evidence of vascular differentiation and Castleman's disease of hyaline vascular type. The two processes blended with each other, with the neoplasm appearing to be continuous with the interfollicular proliferation of small vessels that is typical of Castleman's disease. The lesions behaved aggressively in two cases, both patients having died with metastatic disease. This remarkable association may be viewed as a pathologic manifestation of the intimate functional relationship that exists between the immune and the vascular systems. Other probable examples of this relationship are systemic Castleman's disease associated with Kaposi's sarcoma, localized Castleman's disease associated with vascular hamartoma, histiocytoid hemangioma/angiolymphoid hyperplasia with eosinophilia, and (possibly) angiomatoid malignant fibrous histiocytoma. Perhaps these associations are mediated by the production of angiogenic factors by the activated lymphoid cells.     

Cutaneous follicular lymphoma

Fifteen cases of cutaneous follicular lymphoma were evaluated clinically, histologically, and immunologically. Nine of the patients presented with skin disease alone, which showed a predilection for the scalp and forehead. The six remaining cases had either concurrent or secondary cutaneous involvement. All of the cases had a nodular configuration which was evident histologically or immunologically. In many cases, the diagnostic microscopic fields were in the deep dermis or subcutis, with nonspecific inflammation in the superficial dermis. The cases consisted of five small cleaved, seven mixed, and three large cell follicular lymphomas. A senior dermatopathologist diagnosed four of the 15 cases as benign, indicating the difficulty of diagnosis by morphology alone when the biopsy is small or the inflammatory component is prominent. This underscores the importance of large, deep biopsies for accurate histologic diagnosis. Immunological studies confirmed the B cell lineage of these lesions. An unexpectedly high proportion of immunoglobulin-negative cases (eight cases) was found, especially among the primary cutaneous follicular lymphomas (six of nine cases). Immunoglobulin-expressing cases exhibited monotypic immunoglobulin light-chain staining of tumor cells. In all cases, the dendritic reticulum cell network within lymphoma follicles lacked the polytypic immunoglobulin complexes characteristic of reactive follicles. As described previously for follicular lymphomas in lymph nodes, many cases exhibited polytypic follicular mantle zones similar to reactive follicles. The low-grade nature of these lymphomas was supported by clinical follow-up. We conclude that given adequate sampling, cutaneous follicular lymphomas can usually be diagnosed by histologic criteria similar to those used for lymph nodes; however, immunohistologic studies are an important adjunct.     

Reliable and cost-effective paraffin section immunohistology of lymphoproliferative disorders

We studied 110 neoplastic and reactive lymphoid proliferations with three monoclonal antibodies--CD20 (L26), CD43 (Leu22), and CD45RO (UCHL1)--on B5-fixed, paraffin-embedded tissue to evaluate the utility of this panel as an immunotypic screen of such lesions. All cases were initially immunotyped by conventional methods. Genotyping by Southern blot hybridization was also done in 54 cases. Seventy-four of 79 malignant lymphomas and both of two hairy cell leukemias were of B-cell origin; and five lymphomas were defined as T-cell lineage. Lineage assignment was identical for paraffin section immunohistology and conventional immunotyping in 73 of 76 B cell and all of five T-cell tumors. CD20 was reactive with 73 of 76 B-cell tumors. CD43 was reactive with 12 of 74 B-cell lymphomas, and CD20/CD43 coexpression was seen in 11 of these cases. CD43 and CD45RO marked all of five and three of five T-cell lymphomas, respectively. Lineage assignment was identical for paraffin immunohistology and genotyping in 48 of 50 cases with identifiable gene rearrangements. Twenty-four nonneoplastic and five Hodgkin's disease cases that were studied also showed similar immunoreactivity patterns by both paraffin and conventional immunotypic methods. This panel of three monoclonal antibodies is an efficient, cost-effective approach for immunotyping most lymphoid proliferations in paraffin sections. Nevertheless, the pathologist should always try to obtain fresh or frozen tissue to aid in resolving occasional discrepant cases, to establish clonality in morphologically ambiguous ones, and to profile prognostically important phenotypic deletions.     

Nodular lymphoid hyperplasia: rare case of lymphoproliferative disease in the lung

We report a rare case of nodular lymphoid hyperplasia in the lung. An 18-year-old woman had an abnormal shadow found on chest radiography images. Positron-emission tomography showed an uptake of ¹⁸F-fluorodeoxyglucose in the mass lesion, with a maximum standardized uptake value of 2.4. The lesion gradually enlarged, and surgical removal was performed. Histopathological examination of the resected lung revealed polyclonal proliferation of lymphoid tissue, leading to a diagnosis of nodular lymphoid hyperplasia.     

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.     

Epstein-Barr virus-associated polymorphic B-cell lymphoproliferative disorders in the lungs of children with AIDS: a report of two cases.

Patients infected with HIV experience a spectrum of lymphoproliferative disorders, including generalized reactive lymphadenopathy to atypical lymphoproliferative lesions and lymphomas. Polymorphic B-cell lymphoproliferative disorders are rare and not well documented. We studied lung lesions from two children infected with HIV: an atypical polymorphic B-cell hyperplasia in a 14-year-old boy and a malignant polymorphic B-cell lymphoma in a 21-month-old girl. Morphologically, both lung lesions revealed similar polymorphic lymphoid infiltrations with numerous mitoses in case 1 and extensive necrosis and architectural distortion in case 2. Immunophenotypic examination showed no predominance of kappa or lambda light chain in case 1 and a predominance of kappa light chain in case 2. Genotypic analysis demonstrated an absence of immunoglobulin and T-cell receptor gene rearrangements in case 1 and the presence of biallelic immunoglobulin heavy chain rearrangement and a single clonal Epstein-Barr virus (EBV) in case 2. The clinical course was indolent in case 1 and aggressive in case 2. The clinicopathologic features were similar to those of posttransplantation lymphoproliferative disorders suggesting that these lung lesions might represent an immunosuppression-related spectrum of benign to malignant diseases. EBV infection may play a role in the pathogenesis of these lesions. This study highlights the importance of the molecular characterization of AIDS-associated lymphoproliferative disorders in children in establishing a definitive diagnosis.